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Sample records for disc degeneration disease

  1. Intervertebral disc degeneration in dogs

    NARCIS (Netherlands)

    Bergknut, N.

    2011-01-01

    Back pain is common in both dogs and humans, and is often associated with intervertebral disc (IVD) degeneration. The IVDs are essential structures of the spine and degeneration can ultimately result in diseases such as IVD herniation or spinal instability. In order to design new treatments halting

  2. Intervertebral disc degeneration in dogs

    NARCIS (Netherlands)

    Bergknut, Niklas

    Back pain is common in both dogs and humans, and is often associated with intervertebral disc (IVD) degeneration. The IVDs are essential structures of the spine and degeneration can ultimately result in diseases such as IVD herniation or spinal instability. In order to design new treatments halting

  3. Familial history, age and smoking are important risk factors for disc degeneration disease in Arabic pedigrees

    International Nuclear Information System (INIS)

    Livshits, Gregory; Cohen, Zvi; Higla, Orabi; Yakovenko, Konstantin

    2001-01-01

    The present study used computed tomography imaging to evaluate the extent and pattern of the intergenerational transmission of spinal disc degeneration disease (DDD) in complex pedigrees. Contribution of a number of the potential covariates was also studied using univariate and multivariate logistic regression analysis, as well as two types of complex segregation analysis models. Among 161 individuals studied, DDD was diagnosed in 60 individuals. The number of protruded discs varied from 1 to 4, mostly in lumbar or lumbosacral regions. The average age at onset of the disease was similar for both women (36.0 years) and men (34.8 years). The proportion of the individuals affected by the DDD status of their parents ranged from 10% in families of two healthy parents to 55.5% of two affected parents (p < 0.01). The results of the logistic regression analyses and complex segregation analysis were qualitatively the same: DDD status of parents, age and smoking were the main risk factors for disc herniation in the Arabic families we examined. All analyses showed a predominating role of the family history as a risk factor for DDD in offsprings. It showed, for example, four times higher risk at age 50 for individuals with two affected parents vs. those who have two non-affected parents. However, the results of models-fitting genetic analysis, did not confirm a monogenic Mendelian pattern of inheritance

  4. Disc degeneration: current surgical options

    Directory of Open Access Journals (Sweden)

    C Schizas

    2010-10-01

    Full Text Available Chronic low back pain attributed to lumbar disc degeneration poses a serious challenge to physicians. Surgery may be indicated in selected cases following failure of appropriate conservative treatment. For decades, the only surgical option has been spinal fusion, but its results have been inconsistent. Some prospective trials show superiority over usual conservative measures while others fail to demonstrate its advantages. In an effort to improve results of fusion and to decrease the incidence of adjacent segment degeneration, total disc replacement techniques have been introduced and studied extensively. Short-term results have shown superiority over some fusion techniques. Mid-term results however tend to show that this approach yields results equivalent to those of spinal fusion. Nucleus replacement has gained some popularity initially, but evidence on its efficacy is scarce. Dynamic stabilisation, a technique involving less rigid implants than in spinal fusion and performed without the need for bone grafting, represents another surgical option. Evidence again is lacking on its superiority over other surgical strategies and conservative measures. Insertion of interspinous devices posteriorly, aiming at redistributing loads and relieving pain, has been used as an adjunct to disc removal surgery for disc herniation. To date however, there is no clear evidence on their efficacy. Minimally invasive intradiscal thermocoagulation techniques have also been tried, but evidence of their effectiveness is questioned. Surgery using novel biological solutions may be the future of discogenic pain treatment. Collaboration between clinicians and basic scientists in this multidisciplinary field will undoubtedly shape the future of treating symptomatic disc degeneration.

  5. Notochord Cells in Intervertebral Disc Development and Degeneration

    Science.gov (United States)

    McCann, Matthew R.; Séguin, Cheryle A.

    2016-01-01

    The intervertebral disc is a complex structure responsible for flexibility, multi-axial motion, and load transmission throughout the spine. Importantly, degeneration of the intervertebral disc is thought to be an initiating factor for back pain. Due to a lack of understanding of the pathways that govern disc degeneration, there are currently no disease-modifying treatments to delay or prevent degenerative disc disease. This review presents an overview of our current understanding of the developmental processes that regulate intervertebral disc formation, with particular emphasis on the role of the notochord and notochord-derived cells in disc homeostasis and how their loss can result in degeneration. We then describe the role of small animal models in understanding the development of the disc and their use to interrogate disc degeneration and associated pathologies. Finally, we highlight essential development pathways that are associated with disc degeneration and/or implicated in the reparative response of the tissue that might serve as targets for future therapeutic approaches. PMID:27252900

  6. Notochord Cells in Intervertebral Disc Development and Degeneration

    Directory of Open Access Journals (Sweden)

    Matthew R. McCann

    2016-01-01

    Full Text Available The intervertebral disc is a complex structure responsible for flexibility, multi-axial motion, and load transmission throughout the spine. Importantly, degeneration of the intervertebral disc is thought to be an initiating factor for back pain. Due to a lack of understanding of the pathways that govern disc degeneration, there are currently no disease-modifying treatments to delay or prevent degenerative disc disease. This review presents an overview of our current understanding of the developmental processes that regulate intervertebral disc formation, with particular emphasis on the role of the notochord and notochord-derived cells in disc homeostasis and how their loss can result in degeneration. We then describe the role of small animal models in understanding the development of the disc and their use to interrogate disc degeneration and associated pathologies. Finally, we highlight essential development pathways that are associated with disc degeneration and/or implicated in the reparative response of the tissue that might serve as targets for future therapeutic approaches.

  7. Magnetic resonance imaging of intervertebral disc degeneration

    International Nuclear Information System (INIS)

    Maeda, Hiroshi; Noguchi, Masao; Kira, Hideaki; Fujiki, Hiroshi; Shimokawa, Isao; Hinoue, Kaichi.

    1993-01-01

    The aim of this study was to correlate the degree of lumbar intervertebral disc degeneration with findings of magnetic resonance imaging (MRI). Seventeen autopsied (from 7 patients) and 21 surgical (from 20 patients) intervertebral discs were used as specimens for histopathological examination. In addition, 21 intervertebral discs were examined on T2-weighted images. Histopathological findings from both autopsied and surgical specimens were well correlated with MRI findings. In particular, T2-weighted images reflected increased collagen fibers and rupture within the fibrous ring accurately. However, when severely degenerated intervertebral discs and hernia protruding the posterior longitudinal ligament existed, histological findings were not concordant well with T2-weighted images. Morphological appearances of autopsy specimens, divided into four on T2-weighted images, were well consistent with histological degeneration. This morphological classification, as shown on T2-weighted images, could also be used in the evaluation of intervertebral disc degeneration. (N.K.)

  8. Magnetic resonance imaging of intervertebral disc degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Maeda, Hiroshi; Noguchi, Masao (Kitakyushu City Yahata Hospital, Fukuoka (Japan)); Kira, Hideaki; Fujiki, Hiroshi; Shimokawa, Isao; Hinoue, Kaichi

    1993-02-01

    The aim of this study was to correlate the degree of lumbar intervertebral disc degeneration with findings of magnetic resonance imaging (MRI). Seventeen autopsied (from 7 patients) and 21 surgical (from 20 patients) intervertebral discs were used as specimens for histopathological examination. In addition, 21 intervertebral discs were examined on T2-weighted images. Histopathological findings from both autopsied and surgical specimens were well correlated with MRI findings. In particular, T2-weighted images reflected increased collagen fibers and rupture within the fibrous ring accurately. However, when severely degenerated intervertebral discs and hernia protruding the posterior longitudinal ligament existed, histological findings were not concordant well with T2-weighted images. Morphological appearances of autopsy specimens, divided into four on T2-weighted images, were well consistent with histological degeneration. This morphological classification, as shown on T2-weighted images, could also be used in the evaluation of intervertebral disc degeneration. (N.K.).

  9. New treatment strategies for canine intervertebral disc degeneration

    NARCIS (Netherlands)

    Smolders, L.A.

    2013-01-01

    Degeneration of the intervertebral disc (IVD) is a common problem in dogs and humans. IVD degeneration can lead to herniation of the IVD with subsequent compression of neural structures and various clinical signs, including back pain. Current treatment of IVD disease is conservative or surgical.

  10. Degenerated human intervertebral discs contain autoantibodies against extracellular matrix proteins

    Directory of Open Access Journals (Sweden)

    S Capossela

    2014-04-01

    Full Text Available Degeneration of intervertebral discs (IVDs is associated with back pain and elevated levels of inflammatory cells. It has been hypothesised that discogenic pain is a direct result of vascular and neural ingrowth along annulus fissures, which may expose the avascular nucleus pulposus (NP to the systemic circulation and induce an autoimmune reaction. In this study, we confirmed our previous observation of antibodies in human degenerated and post-traumatic IVDs cultured in vitro. We hypothesised that the presence of antibodies was due to an autoimmune reaction against specific proteins of the disc. Furthermore we identified antigens which possibly trigger an autoimmune response in degenerative disc diseases. We demonstrated that degenerated and post-traumatic IVDs contain IgG antibodies against typical extracellular proteins of the disc, particularly proteins of the NP. We identified IgGs against collagen type II and aggrecan, confirming an autoimmune reaction against the normally immune privileged NP. We also found specific IgGs against collagens types I and V, but not against collagen type III. In conclusion, this study confirmed the association between disc degeneration and autoimmunity, and may open the avenue for future studies on developing prognostic, diagnostic and therapy-monitoring markers for degenerative disc diseases.

  11. Human disc degeneration is associated with increased MMP 7 expression.

    Science.gov (United States)

    Le Maitre, C L; Freemont, A J; Hoyland, J A

    2006-01-01

    During intervertebral disc (IVD) degeneration, normal matrix synthesis decreases and degradation of disc matrix increases. A number of proteases that are increased during disc degeneration are thought to be involved in its pathogenesis. Matrix metalloproteinase 7 (MMP 7) (Matrilysin, PUMP-1) is known to cleave the major matrix molecules found within the IVD, i.e., the proteoglycan aggrecan and collagen type II. To date, however, it is not known how its expression changes with degeneration or its exact location. We investigated the localization of MMP 7 in human, histologically graded, nondegenerate, degenerated and prolapsed discs to ascertain whether MMP 7 is up-regulated during disc degeneration. Samples of human IVD tissue were fixed in neutral buffered formalin, embedded in paraffin, and sections stained with hematoxylin and eosin to score the degree of morphological degeneration. Immunohistochemistry was performed to localize MMP 7 in 41 human IVDs with varying degrees of degeneration. We found that the chondrocyte-like cells of the nucleus pulposus and inner annulus fibrosus were MMP 7 immunopositive; little immunopositivity was observed in the outer annulus. Nondegenerate discs showed few immunopositive cells. A significant increase in the proportion of MMP 7 immunopositive cells was seen in the nucleus pulposus of discs classified as showing intermediate levels of degeneration and a further increase was seen in discs with severe degeneration. Prolapsed discs showed more MMP 7 immunopositive cells compared to nondegenerated discs, but fewer than those seen in cases of severe degeneration.

  12. Phenotype variations affect genetic association studies of degenerative disc disease: conclusions of analysis of genetic association of 58 single nucleotide polymorphisms with highly specific phenotypes for disc degeneration in 332 subjects.

    Science.gov (United States)

    Rajasekaran, S; Kanna, Rishi Mugesh; Senthil, Natesan; Raveendran, Muthuraja; Cheung, Kenneth M C; Chan, Danny; Subramaniam, Sakthikanal; Shetty, Ajoy Prasad

    2013-10-01

    Although the influence of genetics on the process of disc degeneration is well recognized, in recently published studies, there is a wide variation in the race and selection criteria for such study populations. More importantly, the radiographic features of disc degeneration that are selected to represent the disc degeneration phenotype are variable in these studies. The study presented here evaluates the association between single nucleotide polymorphisms (SNPs) of candidate genes and three distinct radiographic features that can be defined as the degenerative disc disease (DDD) phenotype. The study objectives were to examine the allelic diversity of 58 SNPs related to 35 candidate genes related to lumbar DDD, to evaluate the association in a hitherto unevaluated ethnic Indian population that represents more than one-sixth of the world population, and to analyze how genetic associations can vary in the same study subjects with the choice of phenotype. A cross-sectional, case-control study of an ethnic Indian population was carried out. Fifty-eight SNPs in 35 potential candidate genes were evaluated in 342 subjects and the associations were analyzed against three highly specific markers for DDD, namely disc degeneration by Pfirrmann grading, end-plate damage evaluated by total end-plate damage score, and annular tears evaluated by disc herniations and hyperintense zones. Genotyping of cases and controls was performed on a genome-wide SNP array to identify potential associated disease loci. The results from the genome-wide SNP array were then used to facilitate SNP selection and genotype validation was conducted using Sequenom-based genotyping. Eleven of the 58 SNPs provided evidence of association with one of the phenotypes. For annular tears, rs1042631 SNP of AGC1 and rs467691 SNP of ADAMTS5 were highly significantly associated (p<.01) and SNPs in NGFB, IL1B, IL18RAP, and MMP10 were also significantly associated (p<.05). The rs4076018 SNP of NGFB was highly

  13. Effect of Interbody Fusion on the Remaining Discs of the Lumbar Spine in Subjects with Disc Degeneration.

    Science.gov (United States)

    Ryu, Robert; Techy, Fernando; Varadarajan, Ravikumar; Amirouche, Farid

    2016-02-01

    To study effects (stress loads) of lumbar fusion on the remaining segments (adjacent or not) of the lumbar spine in the setting of degenerated adjacent discs. A lumbar spine finite element model was built and validated. The full model of the lumbar spine was a parametric finite element model of segments L 1-5 . Numerous hypothetical combinations of one-level lumbar spine fusion and one-level disc degeneration were created. These models were subjected to 10 Nm flexion and extension moments and the stresses on the endplates and consequently on the intervertebral lumbar discs measured. These values were compared to the stresses on healthy lumbar spine discs under the same load and fusion scenarios. Increased stress at endplates was observed only in the settings of L4-5 fusion and L3-4 disc degeneration (8% stress elevation at L2,3 in flexion or extension, and 25% elevation at L3,4 in flexion only). All other combinations showed less endplate stress than did the control model. For fusion at L3-4 and degeneration at L4-5 , the stresses in the endplates at the adjacent level inferior to the fused disc decreased for both loading disc height reductions. Stresses in flexion decreased after fusion by 29.5% and 25.8% for degeneration I and II, respectively. Results for extension were similar. For fusion at L2-3 and degeneration at L4-5 , stresses in the endplates decreased more markedly at the degenerated (30%), than at the fused level (14%) in the presence of 25% disc height reduction and 10 Nm flexion, whereas in extension stresses decreased more at the fused (24.3%) than the degenerated level (5.86%). For fusion at L3-4 and degeneration at L2-3 , there were no increases in endplate stress in any scenario. For fusion at L4-5 and degeneration at L3-4 , progression of degeneration from I to II had a significant effect only in flexion. A dramatic increase in stress was noted in the endplates of the degenerated disc (L3-4 ) in flexion for degeneration II. Stresses are greater

  14. Heme oxygenase-1 modulates degeneration of the intervertebral disc after puncture in Bach 1 deficient mice.

    Science.gov (United States)

    Ohta, Ryo; Tanaka, Nobuhiro; Nakanishi, Kazuyoshi; Kamei, Naosuke; Nakamae, Toshio; Izumi, Bunichiro; Fujioka, Yuki; Ochi, Mitsuo

    2012-09-01

    Intervertebral disc degeneration is considered to be a major feature of low back pain. Furthermore, oxidative stress has been shown to be an important factor in degenerative diseases such as osteoarthritis and is considered a cause of intervertebral disc degeneration. The purpose of this study was to clarify the correlation between oxidative stress and intervertebral disc degeneration using Broad complex-Tramtrack-Bric-a-brac and cap'n'collar homology 1 deficient (Bach 1-/-) mice which highly express heme oxygenase-1 (HO-1). HO-1 protects cells from oxidative stress. Caudal discs of 12-week-old and 1-year-old mice were evaluated as age-related models. Each group and period, 5 mice (a total of 20 mice, a total of 20 discs) were evaluated as age-related model. C9-C10 caudal discs in 12-week-old Bach 1-/- and wild-type mice were punctured using a 29-gauge needle as annulus puncture model. Each group and period, 5 mice (a total of 60 mice, a total of 60 discs) were evaluated. The progress of disc degeneration was evaluated at pre-puncture, 1, 2, 4, 8 and 12 weeks post-puncture. Radiographic, histologic and immunohistologic analysis were performed to compare between Bach 1-/- and wild-type mice. In the age-related model, there were no significant differences between Bach 1-/- and wild-type mice radiologically and histologically. However, in the annulus puncture model, histological scoring revealed significant difference at 8 and 12 weeks post-puncture. The number of HO-1 positive cells was significantly greater in Bach 1-/- mice at every period. The apoptosis rate was significantly lower at 1 and 2 weeks post-puncture in Bach 1-/- mice. Oxidative stress prevention may avoid the degenerative process of the intervertebral disc after puncture, reducing the number of apoptosis cells. High HO-1 expression may also inhibit oxidative stress and delay the process of intervertebral disc degeneration.

  15. Developments in intervertebral disc disease research: pathophysiology, mechanobiology, and therapeutics.

    Science.gov (United States)

    Weber, Kathryn T; Jacobsen, Timothy D; Maidhof, Robert; Virojanapa, Justin; Overby, Chris; Bloom, Ona; Quraishi, Shaheda; Levine, Mitchell; Chahine, Nadeen O

    2015-03-01

    Low back pain is a leading cause of disability worldwide and the second most common cause of physician visits. There are many causes of back pain, and among them, disc herniation and intervertebral disc degeneration are the most common diagnoses and targets for intervention. Currently, clinical treatment outcomes are not strongly correlated with diagnoses, emphasizing the importance for characterizing more completely the mechanisms of degeneration and their relationships with symptoms. This review covers recent studies elucidating cellular and molecular changes associated with disc mechanobiology, as it relates to degeneration and regeneration. Specifically, we review findings on the biochemical changes in disc diseases, including cytokines, chemokines, and proteases; advancements in disc disease diagnostics using imaging modalities; updates on studies examining the response of the intervertebral disc to injury; and recent developments in repair strategies, including cell-based repair, biomaterials, and tissue engineering. Findings on the effects of the omega-6 fatty acid, linoleic acid, on nucleus pulposus tissue engineering are presented. Studies described in this review provide greater insights into the pathogenesis of disc degeneration and may define new paradigms for early or differential diagnostics of degeneration using new techniques such as systemic biomarkers. In addition, research on the mechanobiology of disease enriches the development of therapeutics for disc repair, with potential to diminish pain and disability associated with disc degeneration.

  16. Gender difference in genetic association between IL1A variant and early lumbar disc degeneration

    DEFF Research Database (Denmark)

    Eskola, Pasi J; Kjær, Per; Sorensen, Joan S

    2012-01-01

    The purpose of the present study was to analyze the associations between specific genetic markers and early disc degeneration (DD) or early disc degeneration progression (DDP) defined by magnetic resonance imaging (MRI)....

  17. Are animal models useful for studying human disc disorders / degeneration?

    NARCIS (Netherlands)

    Alini, M.; Eisenstein, S.M.; Ito, K.; Little, C.; Kettler, A.A.; Masuda, K.; Melrose, J.; Ralphs, J.; Stokes, I.; Wilke, H.J.

    2008-01-01

    Intervertebral disc (IVD) degeneration is an often investigated pathophysiological condition because of its implication in causing low back pain. As human material for such studies is difficult to obtain because of ethical and government regulatory restriction, animal tissue, organs and in vivo

  18. Correlation of radiographic and MRI parameters to morphological and biochemical assessment of intervertebral disc degeneration

    OpenAIRE

    Benneker, Lorin M.; Heini, Paul F.; Anderson, Suzanne E.; Alini, Mauro; Ito, Keita

    2004-01-01

    Degenerative disc disease (DDD) is a common finding in MRI scans and X-rays. However, their correlation to morphological and biochemical changes is not well established. In this study, radiological and MRI parameters of DDD were assessed and compared with morphological and biochemical findings of disc degeneration. Thirty-nine human lumbar discs (L1–S1), age 19–86 years, were harvested from eight cadavers. Within 48 h postmortem, MRIs in various spin-echo sequences and biplanar radiographs of...

  19. Human Amniotic Tissue-derived Allograft, NuCel, in Posteriolateral Lumbar Fusions for Degenerative Disc Disease

    Science.gov (United States)

    2017-09-14

    Lumbar Degenerative Disc Disease; Spinal Stenosis; Spondylolisthesis; Spondylosis; Intervertebral Disk Displacement; Intervertebral Disk Degeneration; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Spondylolysis

  20. Intervertebral disc (IVD): Structure, degeneration, repair and regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Whatley, Benjamin R.; Wen Xuejun, E-mail: xjwen@clemson.edu

    2012-02-01

    Low back pain affects a large portion of the population, resulting in high care costs for therapy and treatment. One primary cause of low back pain is the degeneration of the intervertebral disc (IVD) resulting in the compression of the spinal nerves and adjacent vertebrae. Exact causes of degeneration are unknown, but it is thought that natural aging, and both biological and genetic factors may play a significant role in the degenerative process. Conventional methods to alleviate low back pain include spinal fusion and artificial disc replacement. Traditional treatments through spinal fusion may eliminate pain yet do not restore disc function and lead to further degeneration of adjacent levels by altering disc biomechanics and natural kinematics. Recently, artificial IVD replacements have started to gain interest, with two IVD implants currently approved in the United States. Although these implants facilitate the preservation of motions and disc space height, they are unable to sustain compressive forces due to their lack of elasticity. In addition, the implants may produce wear debris that can cause osteolysis and other deleterious effects. As an alternative to these conventional approaches, tissue engineered IVD constructs offer the advantage of biointegration while preserving the essential attributes of natural motion and disc space restoration. There is a great need for the development of tissue engineered scaffolds that simulate the natural 3D morphology and microenvironment of the targeted tissue. Scaffolds should facilitate biological transport to satisfy nutrition and waste removal requirements within the IVD. The discrete tissue architectures of the nucleus pulposus (NP) and annulus fibrosus (AF) have posed great challenges to IVD tissue engineering. Current attempts have not been able to satisfy the biological functions and/or mechanical properties of native tissue. Therefore, these current scaffolds are far from satisfactory. This review highlights the

  1. [Partial nucleotomy of the ovine disc as an in vivo model for disc degeneration].

    Science.gov (United States)

    Guder, E; Hill, S; Kandziora, F; Schnake, K J

    2009-01-01

    The aim of this study was to develop a suitable animal model for the clinical situation of progressive disc degeneration after microsurgical nucleotomy. Twenty sheep underwent standardised partial anterolateral nucleotomy at lumbar segment 3/4. After randomisation, 10 animals were sacrificed after 12 weeks (group 1). The remainder was sacrificed after 48 weeks (group 2). For radiological examination X-rays, MRI and post-mortem CT scans were performed. Lumbar discs L 3/4 with adjacent subchondral trabecular bone were harvested and analysed macroscopically and histologically. An image-analysing computer program was used to measure histomorphometric indices of bone structure. 17 segments could be evaluated. After 12 weeks (group 1) histological and radiological degenerative disc changes were noted. After 48 weeks (group 2), radiological signs in MRI reached statistical significance. Furthermore, group 2 showed significantly more osteophyte formations in CT scans. Histomorphometric changes of the disc and the adjacent vertebral bone structure suggest a significant progressive degenerative remodelling. The facet joints did not show any osteoarthrosis after 48 weeks. Partial nucleotomy of the ovine lumbar disc leads to radiological and histological signs of disc degeneration similar to those seen in humans after microsurgical nucleotomy. The presented in vivo model may be useful to evaluate new orthopaedic treatment strategies.

  2. In Vivo Mouse Intervertebral Disc Degeneration Model Based on a New Histological Classification.

    Directory of Open Access Journals (Sweden)

    Takashi Ohnishi

    Full Text Available Although human intervertebral disc degeneration can lead to several spinal diseases, its pathogenesis remains unclear. This study aimed to create a new histological classification applicable to an in vivo mouse intervertebral disc degeneration model induced by needle puncture. One hundred six mice were operated and the L4/5 intervertebral disc was punctured with a 35- or 33-gauge needle. Micro-computed tomography scanning was performed, and the punctured region was confirmed. Evaluation was performed by using magnetic resonance imaging and histology by employing our classification scoring system. Our histological classification scores correlated well with the findings of magnetic resonance imaging and could detect degenerative progression, irrespective of the punctured region. However, the magnetic resonance imaging analysis revealed that there was no significant degenerative intervertebral disc change between the ventrally punctured and non-punctured control groups. To induce significant degeneration in the lumbar intervertebral discs, the central or dorsal region should be punctured instead of the ventral region.

  3. Association between intervertebral disc degeneration and the Oswestry Disability Index.

    Science.gov (United States)

    Middendorp, Marcus; Vogl, Thomas J; Kollias, Konstantinos; Kafchitsas, Konstantinos; Khan, M Fawad; Maataoui, Adel

    2017-01-01

    Low back pain and lumbar intervertebral disc degeneration (IDD) are common findings. Valid data on correlation between clinical pain scores and grades of IDD are not available. To investigate the correlation of intervertebral disc degeneration (IDD) at lumbar levels L4/5 and L5/S1 and the Oswestry Disability Index (ODI). The lumbar discs L4/5 and L5/S1 of 591 patients were evaluated according to the 5-point (Grade I to Grade V) grading system as published by Pfirrmann et al. Functional status was assessed using the Oswestry Disability Index. Spearman's coefficient of rank correlation was used for statistical analysis (p disability (ODI score between 21 and 40%). There was a weak, but statistically significant positive correlation between IDD and ODI for both evaluated lumbar levels. Increased lumbar IDD in MRI goes along with an increased ODI. Thus, MRI is a strong indicator of a patient's clinical appearance. However, low back pain cannot be explained by imaging alone. Clinical correlation is imperative for an adequate diagnostic advance in patients with low back pain.

  4. Degeneration and height of cervical discs classified from MRI compared with precise height measurements from radiographs

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    Kolstad, Frode [National Centre of Spinal Disorders, Norwegian University of Science and Technology, University Hospital of Trondheim, 7006 Trondheim (Norway)]. E-mail: frode.kolstad@medisin.ntnu.no; Myhr, Gunnar [Department of Radiology, University Hospital of Trondheim, 7006 Trondheim (Norway); Kvistad, Kjell Arne [Department of Radiology, University Hospital of Trondheim, 7006 Trondheim (Norway); Nygaard, Oystein P. [National Centre of Spinal Disorders, Norwegian University of Science and Technology, University Hospital of Trondheim, 7006 Trondheim (Norway); Leivseth, Gunnar [Department of Neuromedicine, Faculty of Medicine, Norwegian University of Science and Technology, University Hospital of Trondheim, 7006 Trondheim (Norway)

    2005-09-01

    Study design: Descriptive study comparing MRI classifications with measurements from radiographs. Objectives: 1.Define the relationship between MRI classified cervical disc degeneration and objectively measured disc height. 2.Assess the level of inter- and intra-observer errors using MRI in defining cervical disc degeneration. Summary of background data: Cervical spine degeneration has been defined radiologically by loss of disc height, decreased disc and bone marrow signal intensity and disc protrusion/herniation on MRI. The intra- and inter-observer error using MRI in defining cervical degeneration influences data interpretation. Few previous studies have addressed this source of error. The relation and time sequence between cervical disc degeneration classified by MRI and cervical disc height decrease measured from radiographs is unclear. Methods: The MRI classification of degeneration was based on nucleus signal, prolaps identification and bone marrow signal. Two neuro-radiologists evaluated the MR-images independently in a blinded fashion. The radiographic disc height measurements were done by a new computer-assisted method compensating for image distortion and permitting comparison with normal level-, age- and gender-appropriate disc height. Results/conclusions: 1.Progressing disc degeneration classified from MRI is on average significantly associated with a decrease of disc height as measured from radiographs. Within each MRI defined category of degeneration measured disc heights, however, scatter in a wide range. 2.The inter-observer agreement between two neuro-radiologists in both defining degeneration and disc height by MRI was only moderate. Studies addressing questions related to cervical disc degeneration should take this into consideration.

  5. Degeneration and height of cervical discs classified from MRI compared with precise height measurements from radiographs

    International Nuclear Information System (INIS)

    Kolstad, Frode; Myhr, Gunnar; Kvistad, Kjell Arne; Nygaard, Oystein P.; Leivseth, Gunnar

    2005-01-01

    Study design: Descriptive study comparing MRI classifications with measurements from radiographs. Objectives: 1.Define the relationship between MRI classified cervical disc degeneration and objectively measured disc height. 2.Assess the level of inter- and intra-observer errors using MRI in defining cervical disc degeneration. Summary of background data: Cervical spine degeneration has been defined radiologically by loss of disc height, decreased disc and bone marrow signal intensity and disc protrusion/herniation on MRI. The intra- and inter-observer error using MRI in defining cervical degeneration influences data interpretation. Few previous studies have addressed this source of error. The relation and time sequence between cervical disc degeneration classified by MRI and cervical disc height decrease measured from radiographs is unclear. Methods: The MRI classification of degeneration was based on nucleus signal, prolaps identification and bone marrow signal. Two neuro-radiologists evaluated the MR-images independently in a blinded fashion. The radiographic disc height measurements were done by a new computer-assisted method compensating for image distortion and permitting comparison with normal level-, age- and gender-appropriate disc height. Results/conclusions: 1.Progressing disc degeneration classified from MRI is on average significantly associated with a decrease of disc height as measured from radiographs. Within each MRI defined category of degeneration measured disc heights, however, scatter in a wide range. 2.The inter-observer agreement between two neuro-radiologists in both defining degeneration and disc height by MRI was only moderate. Studies addressing questions related to cervical disc degeneration should take this into consideration

  6. Potential regenerative treatment strategies for intervertebral disc degeneration in dogs

    NARCIS (Netherlands)

    Bach, Frances C; Willems, Nicole; Penning, Louis C; Ito, Keita; Meij, Björn P; Tryfonidou, Marianna A

    Pain due to spontaneous intervertebral disc (IVD) disease is common in dogs. In chondrodystrophic (CD) dogs, IVD disease typically develops in the cervical or thoracolumbar spine at about 3-7 years of age, whereas in non-chondrodystrophic (NCD) dogs, it usually develops in the caudal cervical or

  7. Mechanical deformation and glycosaminoglycan content changes in a rabbit annular puncture disc degeneration model.

    Science.gov (United States)

    Chan, Deva D; Khan, Safdar N; Ye, Xiaojing; Curtiss, Shane B; Gupta, Munish C; Klineberg, Eric O; Neu, Corey P

    2011-08-15

    Evaluation of degenerated intervertebral discs from a rabbit annular puncture model by using specialized magnetic resonance imaging (MRI) techniques, including displacement encoding with stimulated echoes and a fast-spin echo (DENSE-FSE) acquisition and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). To evaluate a rabbit disc degeneration model by using various MRI techniques. To determine the displacements and strains, spin-lattice relaxation time (T1), and glycosaminoglycan (GAG) distribution of degenerated discs as compared to normal and adjacent level discs. Annular puncture of the intervertebral disc produces disc degeneration in rabbits. DENSE-FSE has been previously demonstrated in articular cartilage for the measurement of soft tissue displacements and strains. MRI also can measure the T1 of tissue, and dGEMRIC can quantify GAG concentration in cartilage. METHODS.: In eight New Zealand white rabbits, the annulus fibrosis of a lumbar disc was punctured. After 4 weeks, the punctured and cranially adjacent motion segments were isolated for MRI and histology. MRI was used to estimate the disc volume and map T1. DENSE-FSE was used to determine displacements for the estimation of strains. dGEMRIC was then used to determine GAG distributions. Histology and standard MRI indicated degeneration in punctured discs. Disc volume increased significantly at 4 weeks after the puncture. Displacement of the nucleus pulposus was distinct from that of the annulus fibrosis in most untreated discs but not in punctured discs. T1 was significantly higher and GAG concentration significantly lower in punctured discs compared with untreated adjacent level discs. Noninvasive and quantitative MRI techniques can be used to evaluate the mechanical and biochemical changes that occur with animal models of disc degeneration. DENSE-FSE, dGEMRIC, and similar techniques have potential for evaluating the progression of disc degeneration and the efficacy of treatments.

  8. Experimental model of intervertebral disc degeneration by needle puncture in Wistar rats

    Energy Technology Data Exchange (ETDEWEB)

    Issy, A.C.; Castania, V.; Castania, M. [Departamento de Morfologia, Fisiologia e Patologia Básica, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Salmon, C.E.G. [Departamento de Física, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Nogueira-Barbosa, M.H. [Divisão de Radiologia, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Bel, E. Del [Departamento de Morfologia, Fisiologia e Patologia Básica, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Defino, H.L.A. [Departamento de Biomecânica, Medicina e Reabilitação do Sistema Locomotor, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2013-03-15

    Animal models of intervertebral disc degeneration play an important role in clarifying the physiopathological mechanisms and testing novel therapeutic strategies. The objective of the present study is to describe a simple animal model of disc degeneration involving Wistar rats to be used for research studies. Disc degeneration was confirmed and classified by radiography, magnetic resonance and histological evaluation. Adult male Wistar rats were anesthetized and submitted to percutaneous disc puncture with a 20-gauge needle on levels 6-7 and 8-9 of the coccygeal vertebrae. The needle was inserted into the discs guided by fluoroscopy and its tip was positioned crossing the nucleus pulposus up to the contralateral annulus fibrosus, rotated 360° twice, and held for 30 s. To grade the severity of intervertebral disc degeneration, we measured the intervertebral disc height from radiographic images 7 and 30 days after the injury, and the signal intensity T2-weighted magnetic resonance imaging. Histological analysis was performed with hematoxylin-eosin and collagen fiber orientation using picrosirius red staining and polarized light microscopy. Imaging and histological score analyses revealed significant disc degeneration both 7 and 30 days after the lesion, without deaths or systemic complications. Interobserver histological evaluation showed significant agreement. There was a significant positive correlation between histological score and intervertebral disc height 7 and 30 days after the lesion. We conclude that the tail disc puncture method using Wistar rats is a simple, cost-effective and reproducible model for inducing disc degeneration.

  9. Experimental model of intervertebral disc degeneration by needle puncture in Wistar rats

    International Nuclear Information System (INIS)

    Issy, A.C.; Castania, V.; Castania, M.; Salmon, C.E.G.; Nogueira-Barbosa, M.H.; Bel, E. Del; Defino, H.L.A.

    2013-01-01

    Animal models of intervertebral disc degeneration play an important role in clarifying the physiopathological mechanisms and testing novel therapeutic strategies. The objective of the present study is to describe a simple animal model of disc degeneration involving Wistar rats to be used for research studies. Disc degeneration was confirmed and classified by radiography, magnetic resonance and histological evaluation. Adult male Wistar rats were anesthetized and submitted to percutaneous disc puncture with a 20-gauge needle on levels 6-7 and 8-9 of the coccygeal vertebrae. The needle was inserted into the discs guided by fluoroscopy and its tip was positioned crossing the nucleus pulposus up to the contralateral annulus fibrosus, rotated 360° twice, and held for 30 s. To grade the severity of intervertebral disc degeneration, we measured the intervertebral disc height from radiographic images 7 and 30 days after the injury, and the signal intensity T2-weighted magnetic resonance imaging. Histological analysis was performed with hematoxylin-eosin and collagen fiber orientation using picrosirius red staining and polarized light microscopy. Imaging and histological score analyses revealed significant disc degeneration both 7 and 30 days after the lesion, without deaths or systemic complications. Interobserver histological evaluation showed significant agreement. There was a significant positive correlation between histological score and intervertebral disc height 7 and 30 days after the lesion. We conclude that the tail disc puncture method using Wistar rats is a simple, cost-effective and reproducible model for inducing disc degeneration

  10. MR imaging of degenerative disc disease

    International Nuclear Information System (INIS)

    Farshad-Amacker, Nadja A.; Farshad, Mazda; Winklehner, Anna; Andreisek, Gustav

    2015-01-01

    Highlights: • This systematic literature review summarizes the current knowledge on MR imaging in degenerative disc disease. • Different classification systems for segmental spine degeneration are summarized. • It outlines the diagnostic limitations of MR imaging. - Abstract: Magnet resonance imaging (MRI) is the most commonly used imaging modality for diagnosis of degenerative disc disease (DDD). Lack of precise observations and documentation of aspects within the complex entity of DDD might partially be the cause of poor correlation of radiographic findings to clinical symptoms. This literature review summarizes the current knowledge on MRI in DDD and outlines the diagnostic limitations. The review further sensitizes the reader toward awareness of potentially untended aspects of DDD and the interaction of DDD and endplate changes. A summary of the available classifications for DDD is provided

  11. MR imaging of degenerative disc disease

    Energy Technology Data Exchange (ETDEWEB)

    Farshad-Amacker, Nadja A., E-mail: nadja.farshad@usz.ch [Institute of Diagnostic and Interventional Radiology, University Hospital of Zurich, Zurich (Switzerland); Farshad, Mazda [Department of Orthopaedic Surgery, Balgrist University Hospital, Zurich (Switzerland); Winklehner, Anna; Andreisek, Gustav [Institute of Diagnostic and Interventional Radiology, University Hospital of Zurich, Zurich (Switzerland)

    2015-09-15

    Highlights: • This systematic literature review summarizes the current knowledge on MR imaging in degenerative disc disease. • Different classification systems for segmental spine degeneration are summarized. • It outlines the diagnostic limitations of MR imaging. - Abstract: Magnet resonance imaging (MRI) is the most commonly used imaging modality for diagnosis of degenerative disc disease (DDD). Lack of precise observations and documentation of aspects within the complex entity of DDD might partially be the cause of poor correlation of radiographic findings to clinical symptoms. This literature review summarizes the current knowledge on MRI in DDD and outlines the diagnostic limitations. The review further sensitizes the reader toward awareness of potentially untended aspects of DDD and the interaction of DDD and endplate changes. A summary of the available classifications for DDD is provided.

  12. Increased MMP-2 activity during intervertebral disc degeneration is correlated to MMP-14 levels

    NARCIS (Netherlands)

    Rutges, J. P. H. J.; Kummer, J. A.; Oner, F. C.; Verbout, A. J.; Roestenburg, H. J. A.; Dhert, W. J. A.; Creemers, L. B.

    Intervertebral disc (IVD) degeneration is associated with the increased expression of several matrix metalloproteinases (MMPs), in particular MMP-2. However, little is known about the actual activity of MMP-2 in healthy and degenerated discs, or what mechanisms are involved in its activation. A

  13. Matrix Remodeling During Intervertebral Disc Growth and Degeneration Detected by Multichromatic FAST Staining

    Science.gov (United States)

    Leung, Victor Y.L.; Chan, Wilson C.W.; Hung, Siu-Chun; Cheung, Kenneth M.C.; Chan, Danny

    2009-01-01

    Various imaging techniques have been used to assess degeneration of the intervertebral disc, including many histological methods, but cartilage-oriented histological stains do not clearly show the comparatively complex structures of the disc. In addition, there is no integrated method to assess efficiently both the compartmental organization and matrix composition in disc samples. In this study, a novel histological method, termed FAST staining, has been developed to investigate disc growth and degeneration by sequential staining with fast green, Alcian blue, Safranin-O, and tartrazine to generate multichromatic histological profiles (FAST profiles). This identifies the major compartments of the vertebra-disc region, including the cartilaginous endplate and multiple zones of the annulus fibrosus, by specific FAST profile patterns. A disc degeneration model in rabbit established using a previously described puncture method showed gradual but profound alteration of the FAST profile during disc degeneration, supporting continual alteration of glycosaminoglycan. Changes of the FAST profile pattern in the nucleus pulposus and annulus fibrosus of the postnatal mouse spine suggested matrix remodeling activity during the growth of intervertebral discs. In summary, we developed an effective staining method capable of defining intervertebral disc compartments in detail and showing matrix remodeling events within the disc. The FAST staining method may be used to develop a histopathological grading system to evaluate disc degeneration or malformation. (J Histochem Cytochem 57:249–256, 2009) PMID:19001641

  14. A computational study of intervertebral disc degeneration in relation to changes in regional tissue composition and disc nutrition

    OpenAIRE

    Ruiz Wills, Carlos

    2015-01-01

    Up to 85% of the world population suffers from low back pain, a clinical condition often related to the intervertebral disc (IVD) degeneration (DD). Altered disc cell nutrition affects cell viability and can generate catabolic cascades that degrade the extracellular matrix (ECM). Also, a major degenerative biochemical change in the disc is the proteoglycan (PG) loss, which affects the osmotic pressure and hydration that is critical for cell nutrition. However, the relationship between biochem...

  15. Correlations between radiographic, magnetic resonance and histological examinations on the degeneration of human lumbar intervertebral discs

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    Delio Eulalio Martins

    Full Text Available CONTEXT AND OBJECTIVE: There is controversy regarding which imaging method is best for identifying early degenerative alterations in intervertebral discs. No correlations between such methods and histological finds are presented in the literature. The aim of this study was to correlate the thickness of intervertebral discs measured on simple radiographs with the degree of degeneration seen on magnetic resonance images and the histological findings relating to nerve ends inside the discs. DESIGN AND SETTING: Cross-sectional correlation study on the lumbar spines of human cadavers, at Universidade Federal de São Paulo (Unifesp, São Paulo, Brazil. METHODS: Ten lumbar spinal columns were extracted from human cadavers and subjected to magnetic resonance imaging and simple radiography. They were classified according to the degree of disc degeneration seen on magnetic resonance, and the thickness of the discs was measured on radiographs. The intervertebral discs were then extracted, embedded in paraffin and analyzed immunohistochemically with protein S100, and the nerve fibers were counted and classified. RESULTS: No correlation was observed between the thickness of the intervertebral discs and the degree of degeneration seen on magnetic resonance images. Only the uppermost lumbar discs (L1/L2 and L2/L3 presented a correlation between their thickness and type I and IV nerve endings. CONCLUSION: Reduced disc thickness is unrelated to increased presence of nerve ends in intervertebral discs, or to the degree of disc degeneration.

  16. Stem-cell treatment in disc degeneration: What is the evidence?

    Directory of Open Access Journals (Sweden)

    Manuela Peletti-Figueiró

    2013-01-01

    Full Text Available To review the potential role of stem cells in treating degenerative disc disease of the intervertebral disc (IVD. A review was performed of articles from the Medline database concerning stem cells and degenerative disc disease (DDD. To discuss the data, the papers were classified as: review, in vitro, experimental, and clinical. The currently available treatments were basically for symptom reduction, not to revert the IVD degenerative process. The use of mesenchymal stem cells (MSC is being proposed as an option of treatment for DDD. In vitro studies have shown that the MSC are able to differentiate into NP cells and that the MSC also reduce the inflammatory levels of the degenerated IVD. Besides, experimental studies demonstrated that the MSC remained viable when injected into the IVD, and that they were able to regenerate partially from the degenerated IVD and its structure. The few clinical studies found in the literature presented diverging results. The use of MSC is being widely studied and shows promising results for the treatment of DDD. Although many advances are being achieved in studies in vitro and experimental, there is a lack of clinical studies to prove the role of MSC in DDD management.

  17. REHABILITATION THERAPY VERSUS DRUG THERAPY IN PATIENTS WITH LUMBAR DISC DEGENERATION

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    BROSCATEAN, Emanuela-Flavia

    2013-12-01

    Full Text Available Lumbar disc degeneration is a disorder whose clinical manifestations are represented by episodic pain in the lumbar spine, without lumbar blockage and minor muscle contraction. Because lumbalgia caused by lumbar disc degeneration is not always very high intensity pain, the easiest to apply treatment is drug therapy. The aim of this study was to analyze the potential role of rehabilitation treatment in the recovery of patients and the prevention of complications compared to drug therapy alone. The study included 28 patients (17 women and 11 men aged between 23-60 years, assigned to two groups: 20 patients who received rehabilitation treatment (consisting of massage, kinesiotherapy, hydrokinesiotherapy, electrotherapy and medication and 8 patients who received drug treatment consisting of anti-inflammatory and analgesic drugs. The treatment duration was 10 days. For the evaluation of pain, the visual analogue scale was used, for the degree of disability, the Oswestry questionnaire, and for joint mobility and muscle strength, articular and muscular testing. At the end of treatment, the study group compared to the control group had a statistically significant result for pain (p=0.001, as well as for the Oswestry score (p=0.030. The mean age of the patients was 35.51±3.026, which shows an increased incidence among young adults. A possible connection between the development of the disease in women and age less than 45 years was also investigated, but the result was not statistically significant, p=0.22. Our data suggest the fact that rehabilitation treatment plays an important role in the reduction of pain and the improvement of the quality of life of patients with lumbar disc degeneration by decreasing the degree of disability. In the future, it can be proposed to monitor patients with lumbar disc degeneration over a longer time period in order to see the effects of kinetic rehabilitation programs in relation to the delay of chronicization. As

  18. Prognosis of intervertebral disc loss from diagnosis of degenerative disc disease

    Science.gov (United States)

    Li, S.; Lin, A.; Tay, K.; Romano, W.; Osman, Said

    2015-03-01

    Degenerative Disc Disease (DDD) is one of the most common causes of low back pain, and is a major factor in limiting the quality of life of an individual usually as they enter older stages of life, the disc degeneration reduces the shock absorption available which in turn causes pain. Disc loss is one of the central processes in the pathogenesis of DDD. In this study, we investigated whether the image texture features quantified from magnetic resonance imaging (MRI) could be appropriate markers for diagnosis of DDD and prognosis of inter-vertebral disc loss. The main objective is to use simple image based biomarkers to perform prognosis of spinal diseases using non-invasive procedures. Our results from 65 subjects proved the higher success rates of the combination marker compared to the individual markers and in the future, we will extend the study to other spine regions to allow prognosis and diagnosis of DDD for a wider region.

  19. Genetic susceptibility of intervertebral disc degeneration among young Finnish adults

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    Kelempisioti Anthi

    2011-11-01

    Full Text Available Abstract Background Disc degeneration (DD is a common condition that progresses with aging. Although the events leading to DD are not well understood, a significant genetic influence has been found. This study was undertaken to assess the association between relevant candidate gene polymorphisms and moderate DD in a well-defined and characterized cohort of young adults. Focusing on young age can be valuable in determining genetic predisposition to DD. Methods We investigated the associations of existing candidate genes for DD among 538 young adults with a mean age of 19 belonging to the 1986 Northern Finland Birth Cohort. Nineteen single nucleotide polymorphisms (SNP in 16 genes were genotyped. We evaluated lumbar DD using the modified Pfirrmann classification and a 1.5-T magnetic resonance scanner for imaging. Results Of the 538 individuals studied, 46% had no degeneration, while 54% had DD and 51% of these had moderate DD. The risk of DD was significantly higher in subjects with an allele G of IL6 SNPs rs1800795 (OR 1.45, 95% CI 1.07-1.96 and rs1800797 (OR 1.37, 95% CI 1.02-1.85 in the additive inheritance model. The role of IL6 was further supported by the haplotype analysis, which resulted in an association between the GGG haplotype (SNPs rs1800797, rs1800796 and rs1800795 and DD with an OR of 1.51 (95% CI 1.11-2.04. In addition, we observed an association between DD and two other polymorphisms, SKT rs16924573 (OR 0.27 95% CI 0.07-0.96 and CILP rs2073711 in women (OR 2.04, 95% CI 1.07-3.89. Conclusion Our results indicate that IL6, SKT and CILP are involved in the etiology of DD among young adults.

  20. Qualitative and quantitative assessment of degeneration of cervical intervertebral discs and facet joints.

    Science.gov (United States)

    Walraevens, Joris; Liu, Baoge; Meersschaert, Joke; Demaerel, Philippe; Delye, Hans; Depreitere, Bart; Vander Sloten, Jos; Goffin, Jan

    2009-03-01

    Degeneration of intervertebral discs and facet joints is one of the most frequently encountered spinal disorders. In order to describe and quantify degeneration and evaluate a possible relationship between degeneration and biomechanical parameters, e.g., the intervertebral range of motion and intradiscal pressure, a scoring system for degeneration is mandatory. However, few scoring systems for the assessment of degeneration of the cervical spine exist. Therefore, two separate objective scoring systems to qualitatively and quantitatively assess the degree of cervical intervertebral disc and facet joint degeneration were developed and validated. The scoring system for cervical disc degeneration consists of three variables which are individually scored on neutral lateral radiographs: "height loss" (0-4 points), "anterior osteophytes" (0-3 points) and "endplate sclerosis" (0-2 points). The scoring system for facet joint degeneration consists of four variables which are individually scored on neutral computed tomography scans: "hypertrophy" (0-2 points), "osteophytes" (0-1 point), "irregularity" on the articular surface (0-1 point) and "joint space narrowing" (0-1 point). Each variable contributes with varying importance to the overall degeneration score (max 9 points for the scoring system of cervical disc degeneration and max 5 points for facet joint degeneration). Degeneration of 20 discs and facet joints of 20 patients was blindly assessed by four raters: two neurosurgeons (one senior and one junior) and two radiologists (one senior and one junior), firstly based on first subjective impression and secondly using the scoring systems. Measurement errors and inter- and intra-rater agreement were determined. The measurement error of the scoring system for cervical disc degeneration was 11.1 versus 17.9% of the subjective impression results. This scoring system showed excellent intra-rater agreement (ICC = 0.86, 0.75-0.93) and excellent inter-rater agreement (ICC = 0

  1. Magnetic resonance imaging of diseased cervical and lumbar intervertebral discs

    International Nuclear Information System (INIS)

    Kadoya, Satoru; Nakamura, Tsutomu; Takarada, Akira; Yamamoto, Itaru; Sato, Shuji.

    1989-01-01

    Magnetic resonance images (MRI) of diseased cervical and lumbar intervertebral discs involving both intrinsic and extrinsic cord lesions were examined using either a 0.15 T resistive or a 0.5 T superconductive magnetic imaging system. The vertebrae, intervertebral discs, and spinal cord were delineated on spin-echo (SE) images with a long repetition time (TR) and a short echo time (proton density-weighted image). Protrusion of degenerated intervertebral discs into the spinal canal was clearly demonstrated not only on sagittal but also on parasagittal and transverse views. The location of protruded discs and compression of the spinal cord, caudal sac, and nerve roots were well visualized three-dimensionally. Pathological features of intervertebral discs were well appreciated on T 2 -weighted images with long TR and SE pulse sequences. Degeneration of intervertebral discs resulted in decreased signal intensity in cases of lumbar disc involvement. For suspected myelomalacia, the intrinsic cord lesion resulting from traumatic disc protrusion appeared as focal low signal intensity on T 1 -weithed images and as somewhat high intensity on T 2 weighted images. The inversion recovery sequence with median inversion time displayed an inferior image of low contrast and was judged uninformative in comparison to SE imags. The findings showed MRI to be an essential diagnostic technique for spinal cord disorders. It clearly pinpoints the anatomic structures of the spine and the features of disc degeneration. Both extrinsic and intrinsic cord abnormalities can be identified with MRI. The selection of proper pulse sequences is required for the differentiation of the object of interest. (Namekawa, K)

  2. Magnetic resonance imaging of diseased cervical and lumbar intervertebral discs

    Energy Technology Data Exchange (ETDEWEB)

    Kadoya, Satoru; Nakamura, Tsutomu; Takarada, Akira; Yamamoto, Itaru; Sato, Shuji.

    1989-02-01

    Magnetic resonance images (MRI) of diseased cervical and lumbar intervertebral discs involving both intrinsic and extrinsic cord lesions were examined using either a 0.15 T resistive or a 0.5 T superconductive magnetic imaging system. The vertebrae, intervertebral discs, and spinal cord were delineated on spin-echo (SE) images with a long repetition time (TR) and a short echo time (proton density-weighted image). Protrusion of degenerated intervertebral discs into the spinal canal was clearly demonstrated not only on sagittal but also on parasagittal and transverse views. The location of protruded discs and compression of the spinal cord, caudal sac, and nerve roots were well visualized three-dimensionally. Pathological features of intervertebral discs were well appreciated on T/sub 2/-weighted images with long TR and SE pulse sequences. Degeneration of intervertebral discs resulted in decreased signal intensity in cases of lumbar disc involvement. For suspected myelomalacia, the intrinsic cord lesion resulting from traumatic disc protrusion appeared as focal low signal intensity on T/sub 1/-weithed images and as somewhat high intensity on T/sub 2/ weighted images. The inversion recovery sequence with median inversion time displayed an inferior image of low contrast and was judged uninformative in comparison to SE imags. The findings showed MRI to be an essential diagnostic technique for spinal cord disorders. It clearly pinpoints the anatomic structures of the spine and the features of disc degeneration. Both extrinsic and intrinsic cord abnormalities can be identified with MRI. The selection of proper pulse sequences is required for the differentiation of the object of interest. (Namekawa, K).

  3. The non-invasive investigation of lumbar disc degeneration in patients with chronic low back pain

    International Nuclear Information System (INIS)

    Buirski, G.

    1989-01-01

    The painful degenerate disc is a recognised cause of low back pain. Magnetic Resonance Imaging (MRI) has now replaced discography in the non-invasive assessment of disk degeneration. However, the prohibitive capital expense of MRI and the small number of MR units in Australia produce limitations in clinical access. In contrast, Computed Tomography (CT) is readily available and is performed in most patients prior to MRI referral. This prospective study was undertaken to determine whether preliminary CT could offer any information about disc degeneration and so reduce the demand on a MRI scanner. 30 consecutive patients were studied all of whom had both CT and MRI examinations. Of a total 107 discs examined by both techniques, MRI was able to identify 37 degenerate discs. Conclusive evidence of degeneration (i.e. the presence of intervertebral gas) was only seen in 3 discs at CT (1 patient). Of the 29 posterior disc bulges found on CT, all were both bulging and degenerate on MRI. Indications for MRI based on the CT findings are recommended. Using these criteria, 13% (4 patients) of this study group could have avoided an expensive and unnecessary MR investigation. A useful algorithm for the investigation and assessment of patients with chronic low back pain is discussed. 8 refs., 5 figs., 1 tab

  4. Angiogenesis in the degeneration of the lumbar intervertebral disc

    OpenAIRE

    David, Gh; Ciurea, AV; Iencean, SM; Mohan, A

    2010-01-01

    The goal of the study is to show the histological and biochemical changes that indicate the angiogenesis of the intervertebral disc in lumbar intervertebral disc hernia and the existence of epidemiological correlations between these changes and the risk factors of lumbar intervertebral disc hernia, as well as the patient's quality of life (QOL). We have studied 50 patients aged between 18 and 73 years old, who have undergone lumbar intervertebral disc hernia surgery, making fibroblast growth ...

  5. Protective effects of cannabidiol on lesion-induced intervertebral disc degeneration.

    Directory of Open Access Journals (Sweden)

    João W Silveira

    Full Text Available Disc degeneration is a multifactorial process that involves hypoxia, inflammation, neoinnervation, accelerated catabolism, and reduction in water and glycosaminoglycan content. Cannabidiol is the main non-psychotropic component of the Cannabis sativa with protective and anti-inflammatory properties. However, possible therapeutic effects of cannabidiol on intervertebral disc degeneration have not been investigated yet. The present study investigated the effects of cannabidiol intradiscal injection in the coccygeal intervertebral disc degeneration induced by the needle puncture model using magnetic resonance imaging (MRI and histological analyses. Disc injury was induced in the tail of male Wistar rats via a single needle puncture. The discs selected for injury were punctured percutaneously using a 21-gauge needle. MRI and histological evaluation were employed to assess the results. The effects of intradiscal injection of cannabidiol (30, 60 or 120 nmol injected immediately after lesion were analyzed acutely (2 days by MRI. The experimental group that received cannabidiol 120 nmol was resubmitted to MRI examination and then to histological analyses 15 days after lesion/cannabidiol injection. The needle puncture produced a significant disc injury detected both by MRI and histological analyses. Cannabidiol significantly attenuated the effects of disc injury induced by the needle puncture. Considering that cannabidiol presents an extremely safe profile and is currently being used clinically, these results suggest that this compound could be useful in the treatment of intervertebral disc degeneration.

  6. Treatment of the degenerated intervertebral disc; closure, repair and regeneration of the annulus fibrosus

    NARCIS (Netherlands)

    Sharifi, Shahriar; Bulstra, S.K.; Grijpma, Dirk W.; Kuijer, R.

    2015-01-01

    Degeneration of the intervertebral disc (IVD) and disc herniation are two causes of low back pain. The aetiology of these disorders is unknown, but tissue weakening, which primarily occurs due to inherited genetic factors, ageing, nutritional compromise and loading history, is the basic factor

  7. Functional disability of occupational-related lumbar disc degeneration: Evaluation by magnetic resonance imaging with surgical correlation

    Directory of Open Access Journals (Sweden)

    Alsiagy A. Salama

    2017-03-01

    Conclusion: Disability of occupational-related lumbar disc degeneration is a grave health problem between construction workers. MR imaging is a reliable tool for grading nerve root compromise in disc degeneration. Nerve root compromise is a significant factor to explain pain than the morphologic extension of disc material outside the intervertebral space.

  8. Assessment of Intervertebral Disc Degeneration With Magnetic Resonance Single-Voxel Spectroscopy

    Science.gov (United States)

    Zuo, Jin; Saadat, Ehsan; Romero, Adan; Loo, Kimberly; Li, Xiaojuan; Link, Thomas M.; Kurhanewicz, John; Majumdar, Sharmila

    2014-01-01

    This study examined the feasibility of using short-echo water-suppressed point-resolved spectroscopy (PRESS) on a clinical 3T magnetic resonance (MR) scanner for evaluating biochemical changes in degenerated bovine and cadaveric human inter-vertebral discs. In bovine discs (N = 17), degeneration was induced with papain injections. Degeneration of human cadaveric discs (N = 27) was assessed using the Pfirrmann grading on T2-weighted images. Chemicals in the carbohydrate region (Carb), the choline head group (Cho), the N-acetyl region (N-acetyl), and the lipid and lactate region (Lac+Lip) were quantified using 1H PRESS, and were compared between specimens with different degrees of degeneration. The correlation between the spectroscopic findings and glycosaminoglycan (GAG) quantification using biochemical assays was determined. Significant differences were found between the ratios (N-acetyl/Cho, N-acetyl/Lac+Lip) acquired before and after papain injection in bovine discs. For human cadaveric discs, significant differences in the ratios (N-acetyl/Carb, N-acetyl/Lac+Lip) were found between discs having high and low Pfirrmann scores. Significant correlations were found between N-acetyl/Lac+Lip and GAG content in bovine discs (R = 0.77, P = 0.0007) and cadaveric discs (R = 0.83, P < 0.0001). Significant correlation between N-acetyl/Cho and GAG content was also found in cadaver discs (R = 0.64, P = 0.0039). This study demonstrates for the first time that short-echo PRESS on a clinical 3T MR scanner can be used to noninvasively and can reproducibly quantify metabolic changes associated with degeneration of intervertebral discs. PMID:19780173

  9. Degeneration of the cervical disc: histology compared with radiography and magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Christe, A.; Vock, P. [University of Berne, Department of Radiology, Inselspital, Berne (Switzerland); Laeubli, R.; Berlemann, U. [University of Berne, Department of Orthopaedic Surgery, Inselspital, Berne (Switzerland); Guzman, R.; Schroth, G. [University of Berne, Department of Neuroradiology, Inselspital, Berne (Switzerland); Moore, R.J. [Institute of Medical and Veterinary Science, Adelaide (Australia); Loevblad, K.O. [University of Berne, Department of Neuroradiology, Inselspital, Berne (Switzerland); Geneva University Hospital, Neuroradiology SRRI, Geneva 14 (Switzerland)

    2005-10-01

    Decisions about the treatment of neck pain are largely made on the basis of information gained from plain X-rays and magnetic resonance imaging (MRI), which are used routinely as part of preliminary investigation. We performed a descriptive cadaveric study to compare histology with radiography and MRI. We correlated plain radiography, disc height [Farfan index (FI)] and MRI findings with histology to assess the ability of radiology to detect significant pathologic lesions. The study included 52 motion segments from nine subjects over the age of 50, who underwent routine hospital autopsy. Disc degeneration was assessed by histology, radiography, disc height (FI: anterior disc height plus posterior disc height divided by anterioposterior diameter) and MRI using established grading systems. Most of the discs were classified radiologically as grade 1 (19/52), grade 2 (13/52), grade 3 (9/52) or grade 4 (3/52). Eight of the discs were graded as normal. The distribution of MRI grades was grade 0 (9/36), grade 1 (9/36), grade 2 (7/36), grade 3 (8/36) and grade 4 (3/36). Half of the discs (26/52) showed advanced (grade 4) degeneration histologically. FI correlated with histological grade (P=0.013), MRI grade (P=0.02) and radiological grade (P<0.001) of degeneration. Radiological and histological grade of degeneration showed a weak correlation (r=0.3, P=0.033). MRI correlated with overall histological grade (r=0.41, P=0.015, n=34). Histological features (e.g., tears, rim lesions, prolapse of nucleus material) were poorly recognised by MRI, which had a sensitivity for disc material prolapse and annulus tears of less than 40%. Our study showed that discs from patients over 50 years are histologically severely degenerated; however, these changes may not be detected by conventional radiography and MRI. (orig.)

  10. Degeneration of the cervical disc: histology compared with radiography and magnetic resonance imaging

    International Nuclear Information System (INIS)

    Christe, A.; Vock, P.; Laeubli, R.; Berlemann, U.; Guzman, R.; Schroth, G.; Moore, R.J.; Loevblad, K.O.

    2005-01-01

    Decisions about the treatment of neck pain are largely made on the basis of information gained from plain X-rays and magnetic resonance imaging (MRI), which are used routinely as part of preliminary investigation. We performed a descriptive cadaveric study to compare histology with radiography and MRI. We correlated plain radiography, disc height [Farfan index (FI)] and MRI findings with histology to assess the ability of radiology to detect significant pathologic lesions. The study included 52 motion segments from nine subjects over the age of 50, who underwent routine hospital autopsy. Disc degeneration was assessed by histology, radiography, disc height (FI: anterior disc height plus posterior disc height divided by anterioposterior diameter) and MRI using established grading systems. Most of the discs were classified radiologically as grade 1 (19/52), grade 2 (13/52), grade 3 (9/52) or grade 4 (3/52). Eight of the discs were graded as normal. The distribution of MRI grades was grade 0 (9/36), grade 1 (9/36), grade 2 (7/36), grade 3 (8/36) and grade 4 (3/36). Half of the discs (26/52) showed advanced (grade 4) degeneration histologically. FI correlated with histological grade (P=0.013), MRI grade (P=0.02) and radiological grade (P<0.001) of degeneration. Radiological and histological grade of degeneration showed a weak correlation (r=0.3, P=0.033). MRI correlated with overall histological grade (r=0.41, P=0.015, n=34). Histological features (e.g., tears, rim lesions, prolapse of nucleus material) were poorly recognised by MRI, which had a sensitivity for disc material prolapse and annulus tears of less than 40%. Our study showed that discs from patients over 50 years are histologically severely degenerated; however, these changes may not be detected by conventional radiography and MRI. (orig.)

  11. Poroelastic behaviour of the degenerating human intervertebral disc: a ten-day study in a loaded disc culture system

    NARCIS (Netherlands)

    Emanuel, K. S.; Vergroesen, P.-P. A.; Peeters, M.; Holewijn, R. M.; Kingma, I.; Smit, T. H.

    2015-01-01

    The intervertebral disc (IVD) allows flexibility to the vertebral column, and transfers the predominant axial loads during daily activities. Its axial biomechanical behaviour is poroelastic, due to the water-binding and releasing capacity of the nucleus pulposus. Degeneration of the intervertebral

  12. Aging and degeneration of the intervertebral disc: review of basic science

    Directory of Open Access Journals (Sweden)

    Josemberg da Silva Baptista

    2015-06-01

    Full Text Available Currently there is a growing interest in the study of intervertebral discs due to loss of manpower brought to society by low back and neck pains. These papers seek to delineate the difference between normal aging and disc degeneration, trying to understand what factor would be determining for the second condition. Thus, the morphology field was expanded and knowledge on the structure of intervertebral discs currently uses the research field of cell and molecular biology, and genetics. The results indicate that regardless of age or condition, the intervertebral disc undergoes long and extensive remodeling of its constituents, which are influenced by several factors: environmental, soluble, cell growth and extracellular matrix. In this literature review we describe the biological characteristics of the cervical and lumbar intervertebral disc with a focus on basic science of aging and degeneration, selecting the latest findings and discussions of the area, which influence future research and clinical thoughts.

  13. Spondylolisthesis adjacent to a cervical disc arthroplasty does not increase the risk of adjacent level degeneration.

    Science.gov (United States)

    Kieser, David Christopher; Cawley, Derek Thomas; Roscop, Cecile; Mazas, Simon; Coudert, Pierre; Boissiere, Louis; Obeid, Ibrahim; Vital, Jean-Marc; Pointillart, Vincent; Gille, Olivier

    2018-03-31

    To understand whether a spondylolisthesis in the sub-axial spine cranial to a cervical disc arthroplasty (CDA) construes a risk of adjacent level disease (ALD). A retrospective review of 164 patients with a minimum 5-year follow-up of a cervical disc arthroplasty was performed. Multi-level surgeries, including hybrid procedures, were included. Multiple implant types were included. The two inter-vertebral discs (IVD) cranial of the CDA were monitored for evidence of radiologic degeneration using the Kettler criteria. The rate of ALD in CDA found in this series was 17.8%, with most affecting the immediately adjacent IVD (27.4 and 7.6%, respectively p = 0.000). Pre-operative mild spondylolisthesis adjacent to a planned CDA was not found to be a risk factor for ALD within 5 years. Those with a degenerative spondylolisthesis are at higher risk of ALD (33%) than those with a non-degenerative cause for their spondylolisthesis (11%). Post-operative CDA alignment, ROM or induced spondylolisthesis do not affect the rate of ALD in those with an adjacent spondylolisthesis. Patients with ALD experience significantly worse 5-year pain and functional outcomes than those unaffected by ALD. A pre-operatively identified mild spondylolisthesis in the sub-axial spine cranially adjacent to a planned CDA is not a risk factor for ALD within 5 years. These slides can be retrieved under Electronic Supplementary Material.

  14. Are the determinants of vertebral endplate changes and severe disc degeneration in the lumbar spine the same? A magnetic resonance imaging study in middle-aged male workers

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    Korpelainen Raija

    2008-04-01

    Full Text Available Abstract Background Modic changes are bone marrow lesions visible in magnetic resonance imaging (MRI, and they are assumed to be associated with symptomatic intervertebral disc disease, especially changes located at L5-S1. Only limited information exists about the determinants of Modic changes. The objective of this study was to evaluate the determinants of vertebral endplate (Modic changes, and whether they are similar for Modic changes and severe disc degeneration focusing on L5-S1 level. Methods 228 middle-aged male workers (159 train engineers and 69 sedentary factory workers from northern Finland underwent sagittal T1- and T2-weighted MRI. Modic changes and disc degeneration were analyzed from the scans. The participants responded to a questionnaire including items of occupational history and lifestyle factors. Logistic regression analysis was used to evaluate the associations between selected determinants (age, lifetime exercise, weight-related factors, fat percentage, smoking, alcohol use, lifetime whole-body vibration and Modic type I and II changes, and severe disc degeneration (= grade V on Pfirrmann's classification. Results The prevalences of the Modic changes and severe disc degeneration were similar in the occupational groups. Age was significantly associated with all degenerative changes. In the age-adjusted analyses, only weight-related determinants (BMI, waist circumference were associated with type II changes. Exposure to whole-body vibration, besides age, was the only significant determinant for severe disc degeneration. In the multivariate model, BMI was associated with type II changes at L5-S1 (OR 2.75 per one SD = 3 unit increment in BMI, and vibration exposure with severe disc degeneration at L5-S1 (OR 1.08 per one SD = 11-year increment in vibration exposure. Conclusion Besides age, weight-related factors seem important in the pathogenesis of Modic changes, whereas whole-body vibration was the only significant determinant

  15. Quantitative analysis of disc degeneration using axial T2 mapping in a percutaneous annular puncture model in rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Chai, Jee Won; Kim, Su Jin [Dept. of Radiology, SMG-SNU Boramae Medical Center, Seoul (Korea, Republic of); Kang, Heung Sik; Lee, Joon Woo [Dept. of Radiology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Hong, Sung Hwan [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of)

    2016-02-15

    To evaluate T2 relaxation time change using axial T2 mapping in a rabbit degenerated disc model and determine the most correlated variable with histologic score among T2 relaxation time, disc height index, and Pfirrmann grade. Degenerated disc model was made in 4 lumbar discs of 11 rabbits (n = 44) by percutaneous annular puncture with various severities of an injury. Lumbar spine lateral radiograph, MR T2 sagittal scan and MR axial T2 mapping were obtained at baseline and 2 weeks and 4 weeks after the injury in 7 rabbits and at baseline and 2 weeks, 4 weeks, and 6 weeks after the injury in 4 rabbits. Generalized estimating equations were used for a longitudinal analysis of changes in T2 relaxation time in degenerated disc model. T2 relaxation time, disc height index and Pfirrmann grade were correlated with the histologic scoring of disc degeneration using Spearman's rho test. There was a significant difference in T2 relaxation time between uninjured and injured discs after annular puncture. Progressive decrease in T2 relaxation time was observed in injured discs throughout the study period. Lower T2 relaxation time was observed in the more severely injured discs. T2 relaxation time showed the strongest inverse correlation with the histologic score among the variables investigated (r = -0.811, p < 0.001). T2 relaxation time measured with axial T2 mapping in degenerated discs is a potential method to assess disc degeneration.

  16. Quantitative evaluation of lumbar intervertebral disc degeneration by axial T2* mapping.

    Science.gov (United States)

    Huang, Leitao; Liu, Yuan; Ding, Yi; Wu, Xia; Zhang, Ning; Lai, Qi; Zeng, Xianjun; Wan, Zongmiao; Dai, Min; Zhang, Bin

    2017-12-01

    To quantitatively evaluate the clinical value and demonstrate the potential benefits of biochemical axial T2* mapping-based grading of early stages of degenerative disc disease (DDD) using 3.0-T magnetic resonance imaging (MRI) in a clinical setting.Fifty patients with low back pain and 20 healthy volunteers (control) underwent standard MRI protocols including axial T2* mapping. All the intervertebral discs (IVDs) were classified morphologically. Lumbar IVDs were graded using Pfirrmann score (I to IV). The T2* values of the anterior annulus fibrosus (AF), posterior AF, and nucleus pulposus (NP) of each lumbar IVD were measured. The differences between groups were analyzed regarding specific T2* pattern at different regions of interest.The T2* values of the NP and posterior AF in the patient group were significantly lower than those in the control group (P T2* value of the anterior AF was not significantly different between the patients and the controls (P > .05). The mean T2*values of the lumbar IVD in the patient group were significantly lower, especially the posterior AF, followed by the NP, and finally, the anterior AF. In the anterior AF, comparison of grade I with grade III and grade I with grade IV showed statistically significant differences (P = .07 and P = .08, respectively). Similarly, in the NP, comparison of grade I with grade III, grade I with grade IV, grade II with grade III, and grade II with grade IV showed statistically significant differences (P T2 values decreased linearly with increasing degeneration based on the Pfirrmann scoring system (ρ T2* value can signify early degenerative IVD diseases. Hence, T2* mapping can be used as a diagnostic tool for quantitative assessment of IVD degeneration. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  17. Quantitative evaluation of lumbar intervertebral disc degeneration by axial T2∗ mapping

    Science.gov (United States)

    Huang, Leitao; Liu, Yuan; Ding, Yi; Wu, Xia; Zhang, Ning; Lai, Qi; Zeng, Xianjun; Wan, Zongmiao; Dai, Min; Zhang, Bin

    2017-01-01

    Abstract To quantitatively evaluate the clinical value and demonstrate the potential benefits of biochemical axial T2∗ mapping-based grading of early stages of degenerative disc disease (DDD) using 3.0-T magnetic resonance imaging (MRI) in a clinical setting. Fifty patients with low back pain and 20 healthy volunteers (control) underwent standard MRI protocols including axial T2∗ mapping. All the intervertebral discs (IVDs) were classified morphologically. Lumbar IVDs were graded using Pfirrmann score (I to IV). The T2∗ values of the anterior annulus fibrosus (AF), posterior AF, and nucleus pulposus (NP) of each lumbar IVD were measured. The differences between groups were analyzed regarding specific T2∗ pattern at different regions of interest. The T2∗ values of the NP and posterior AF in the patient group were significantly lower than those in the control group (P T2∗ value of the anterior AF was not significantly different between the patients and the controls (P > .05). The mean T2∗values of the lumbar IVD in the patient group were significantly lower, especially the posterior AF, followed by the NP, and finally, the anterior AF. In the anterior AF, comparison of grade I with grade III and grade I with grade IV showed statistically significant differences (P = .07 and P = .08, respectively). Similarly, in the NP, comparison of grade I with grade III, grade I with grade IV, grade II with grade III, and grade II with grade IV showed statistically significant differences (P T2∗ values decreased linearly with increasing degeneration based on the Pfirrmann scoring system (ρ T2∗ value can signify early degenerative IVD diseases. Hence, T2∗ mapping can be used as a diagnostic tool for quantitative assessment of IVD degeneration. PMID:29390547

  18. Impaired intervertebral disc development and premature disc degeneration in mice with notochord-specific deletion of CCN2.

    Science.gov (United States)

    Bedore, Jake; Sha, Wei; McCann, Matthew R; Liu, Shangxi; Leask, Andrew; Séguin, Cheryle A

    2013-10-01

    Currently, our ability to treat intervertebral disc (IVD) degeneration is hampered by an incomplete understanding of disc development and aging. The specific function of matricellular proteins, including CCN2, during these processes remains an enigma. The aim of this study was to determine the tissue-specific localization of CCN proteins and to characterize their role in IVD tissues during embryonic development and age-related degeneration by using a mouse model of notochord-specific CCN2 deletion. Expression of CCN proteins was assessed in IVD tissues from wild-type mice beginning on embryonic day 15.5 to 17 months of age. Given the enrichment of CCN2 in notochord-derived tissues, we generated notochord-specific CCN2-null mice to assess the impact on the IVD structure and extracellular matrix composition. Using a combination of histologic evaluation and magnetic resonance imaging (MRI), IVD health was assessed. Loss of the CCN2 gene in notochord-derived cells disrupted the formation of IVDs in embryonic and newborn mice, resulting in decreased levels of aggrecan and type II collagen and concomitantly increased levels of type I collagen within the nucleus pulposus. CCN2-knockout mice also had altered expression of CCN1 (Cyr61) and CCN3 (Nov). Mirroring its role during early development, notochord-specific CCN2 deletion accelerated age-associated degeneration of IVDs. Using a notochord-specific gene targeting strategy, this study demonstrates that CCN2 expression by nucleus pulposus cells is essential to the regulation of IVD development and age-associated tissue maintenance. The ability of CCN2 to regulate the composition of the intervertebral disc suggests that it may represent an intriguing clinical target for the treatment of disc degeneration. Copyright © 2013 by the American College of Rheumatology.

  19. Poroelastic behaviour of the degenerating human intervertebral disc: a ten-day study in a loaded disc culture system

    Directory of Open Access Journals (Sweden)

    KS Emanuel

    2015-06-01

    Full Text Available The intervertebral disc (IVD allows flexibility to the vertebral column, and transfers the predominant axial loads during daily activities. Its axial biomechanical behaviour is poroelastic, due to the water-binding and releasing capacity of the nucleus pulposus. Degeneration of the intervertebral disc presumably affects both the instantaneous elastic response to the load on the IVD and the subsequent interstitial flow of fluid. This study aims to quantify the poroelastic behaviour of the IVD and its change with degeneration, as defined by the magnetic resonance imaging-based Pfirrmann Score (PS. For a period of ten days, 36 human lumbar IVDs were loaded with a simulated physiological axial loading regime, while deformation was monitored. The IVDs responded to the loads with instantaneous elastic and slow poroelastic axial deformation. Several mechanical parameters changed throughout the first five days of the experiment, until the IVDs settled into a dynamic equilibrium. In this equilibrium, degeneration was significantly related to a decrease in disc height loss during the daytime high load phase (ρ = -0.49, and to a decrease in the rate of this deformation during the final half hour of each day (ρ = -0.53. These properties were related to the nucleus glycosaminoglycan/hydroxyproline (GAG/HYP ratio, rather than GAG content alone, indicating that remodelling of the extracellular matrix reduces poroelastic properties of the IVD. This implies that the degenerated discs have a reduced capacity to bind water and/or a reduced resistance against fluid flow. The resulting loss in hydrostatic pressure may further change cell behaviour in the nucleus pulposus.

  20. [Epidemiology investigation and biomechanics analyses for the correlation between sacroiliac joint disorder and lumbar intervertebral disc degeneration].

    Science.gov (United States)

    Shi, Ning-Ning; Shen, Guo-Quan; He, Shui-Yong; Guo, Ru-Bao

    2014-07-01

    To study the correlation between lumber disc degeneration and sacroiliac joint disorder, in order to provides a new understanding concepts and therapeutic approach for the prevention and treatment of chronic intractable low back pain. From August 2009 to October 2010,129 cases with lumbar disc herniation were studied with epidemiological methods. Among them, 61 patients with L4, disc herniation included 37 males and 24 females, ranging in aged from 20 to 75 years old, duration of the disease ranged from 1 to 144 months; The other 68 patients with L5S1 disc herniation included 32 males and 36 females,ranging in aged froml8 to 76 years old,duration of the disease ranged from 0.5 to 240 months. The clinical data, symptoms and signs,X-ray characteristics of lumbar spine and pelvis of the patients were investigated by epidemiological. The risk of lumbar disc herniation was calculated with case-control study; independent variables were screened with single factor analysis; the risk factors for lumbar disc herniation were determined with logistic regression analysis, and biomechanics analyses were taken. Among 129 patients with lumbar disc herniation, 88 cases associated with sacroiliac joint disorders, sacroiliac joint disorder was a risk factor of lumbar disc herniation (OR = 4.61, P = 0.00); 47 cases associated with sacroiliac joint disorders in 61 patients with L4,5 disc herniation, iliac crest uneven caused by iliac rotational displacement was a high risk factor of L4,5 disc herniation (OR = 11.27, P = 0.00); 41 cases associated with sacroiliac joint disorders in 68 patients with L5S1 disc herniation, lumbar sacral angle abnormalities caused by sacral tilt shift was a high risk factor L5S1 disc herniation (OR = 2.31, P = 0.03). Lumbar disc herniation and sacroiliac joint disorder are two of fallot, the two factors affect each other and there is a causal relationship. They are common exists in low back pain.

  1. Matrix metalloproteinase-3, vitamin D receptor gene polymorphisms, and occupational risk factors in lumbar disc degeneration.

    Science.gov (United States)

    Zawilla, N H; Darweesh, H; Mansour, N; Helal, S; Taha, F M; Awadallah, M; El Shazly, R

    2014-06-01

    Lumbar disc degeneration (LDD) is a process that begins early in life, contributing to the development of low back pain. LDD is a consequence of a variety of factors, and its etiology remains poorly understood. Objectives to investigate occupational and genetic risk factors inducing lumbar disc degeneration, and to evaluate the possible association of genetic polymorphisms of matrix metalloproteinase 3 (MMP-3) and vitamin D receptor (VDR) with the severity of LDD in an Egyptian population. A case control study involving 84 LDD and 60 controls was carried out. Five types of work related factors were investigated by questionnaire, complete neurological examination for all subjects and MRI for the cases. Polymerase chain reaction and restriction fragment length polymorphism methods were applied to detect polymorphisms in MMP-3 Promoter (-1,171 6A/5A) (rs 731236) and VDR-Apa (rs 35068180). We found that family history, back injury, smoking, high level of sitting, bending/twisting, physical workload, lifting, whole body vibration, mutant allele 5A of MMP-3 and mutant allele T of VDR were significantly associated with LDD (OR = 2.9, 3.1, 2.1, 11.1, 15.9, 11.7, 8.2, 12.6, 2.5 and 3.1 respectively, p < 0.05). Cases that carry allele 5A and/or allele T were associated with LDD severity. LDD is closely associated in occurrence and severity with occupational, environmental risk factors and susceptibility genes namely MMP-3, and VDR (ApaI). This study throws light on the importance of screening for early detection of susceptible individuals and disease prevention.

  2. Does elite swimming accelerate lumbar intervertebral disc degeneration and increase low back pain?

    DEFF Research Database (Denmark)

    Folkvardsen, Steffen; Magnussen, Erland; Karppinen, Jaro

    2016-01-01

    PURPOSE: The aim was to elucidate elite swimming's possible influence on lumbar disc degeneration (DD) and low back pain (LBP). METHODS: Lumbar spine MRI was performed on a group of elite swimmers and compared to a matched Finnish population-based no-sport group. RESULTS: One hundred elite swimmers...

  3. Genetic Alterations in Intervertebral Disc Disease

    Directory of Open Access Journals (Sweden)

    Nikolay L. Martirosyan

    2016-11-01

    Full Text Available Background: Intervertebral disc degeneration (IVDD is considered a multifactorial disease. The last two decades of research strongly demonstrate that genetic factors contribute about 75% of the IVDD etiology. Recent total genome sequencing studies have shed light on the various single nucleotide polymorphisms (SNPs that are associated with IVDD.Aim: This review explores and presents updated information about the diversity of genetic factors in the inflammatory, degradative, homeostatic, and structural systems involved in the IVDD.Results: SNPs in the genes coding for structural proteins linked with IVDD or disc bulging include the Sp1 polymorphism of COL1A1, Trp3 polymorphism of COL9A3, several polymorphisms of COL11A1 and COL11A2, and a variable number tandem repeat polymorphism of ACAN. The rs4148941 SNP of CHST3 coding for an aggrecan sulfation enzyme is also associated with IVDD. The FokI, TaqI, and ApaI SNPs of the vitamin D receptor gene that is involved in chondrocyte functioning are also associated with IVDD. SNPs relevant to cytokine imbalance in IVDD include 889C/T of IL1a and 15T/A, as well as other SNPs (rs1800795, rs1800796, and rs1800797, of IL6, with effects limited to certain genders and populations. SNPs in collagenase genes include -1605G/D (guanine insertion/deletion of MMP1, -1306C/T of MMP2, -1562C/T and a 5-adenosine (5A variant (in the promotor region of MMP3, -1562C/T of MMP9, and -378T/C of MMP-14. SNPs in aggrecanase genes include 1877T/U of ADAMTS-4 and rs162509 of ADAMTS-5. Among the apoptosis-mediating genes, 1595T/C of the caspase 9 gene, 1525A/G and 1595T/C of the TRAIL gene, and 626C/G of the death receptor 4 gene (DR4 are SNPs associated with IVDD. Among the growth factors involved in disc homeostasis, the rs4871857 SNP of GDF5 was associated with IVDD. VEGF SNPs -2578C/A and -634G/C could foster neovascularization observed in IVDD.Conclusion: Improved understanding of the numerous genetic variants behind various

  4. Association between menopause and lumbar disc degeneration: an MRI study of 1,566 women and 1,382 men.

    Science.gov (United States)

    Lou, Chao; Chen, Hongliang; Mei, Liangwei; Yu, Weiyang; Zhu, Kejun; Liu, Feijun; Chen, Zhenzhong; Xiang, Guangheng; Chen, Minjiang; Weng, Qiaoyou; He, Dengwei

    2017-10-01

    The aim of this study was to revisit and further investigate the association between menopause and disc degeneration in the lumbar spine using a magnetic resonance imaging-based eight-level grading system. This study cohort comprised of 1,566 women and 1,382 age-matched men who were admitted for low back pain from June 2013 to October 2016. Data on age, weight, height, body mass index, age at natural menopause, and years since menopause (YSM) were obtained. Lumbar disc degeneration was assessed using a magnetic resonance imaging-based eight-level grading system. After adjustment for the confounding factors of age, height, and weight, young age-matched men were more susceptible to disc degeneration than premenopausal women (P menopause, postmenopausal women had a significant tendency to develop more severe disc degeneration than their age-matched men (P  0.05). Menopause is associated with lumbar disc degeneration. The association occurred in the first 15 YSM, suggesting estrogen deficiency might be a risk factor of disc degeneration of the lumbar spine. Further studies need to be carried out for deciding whether age or menopause plays a more important role in the progression of disc degeneration in the lumbar spine.

  5. Longitudinal Comparison of Enzyme- and Laser-Treated Intervertebral Disc by MRI, X-Ray, and Histological Analyses Reveals Discrepancies in the Progression of Disc Degeneration: A Rabbit Study

    Directory of Open Access Journals (Sweden)

    Marion Fusellier

    2016-01-01

    Full Text Available Regenerative medicine is considered an attractive prospect for the treatment of intervertebral disc (IVD degeneration. To assess the efficacy of the regenerative approach, animal models of IVD degeneration are needed. Among these animal models, chemonucleolysis based on the enzymatic degradation of the Nucleus Pulposus (NP is often used, but this technique remains far from the natural physiopathological process of IVD degeneration. Recently, we developed an innovative animal model of IVD degeneration based on the use of a laser beam. In the present study, this laser model was compared with the chemonucleolysis model in a longitudinal study in rabbits. The effects of the treatments were studied by MRI (T2-weighted signal intensity (T2wsi, radiography (IVD height index, and histology (NP area and Boos’ scoring. The results showed that both treatments induced a degeneration of the IVD with a decrease in IVD height and T2wsi as well as NP area and an increase in Boos’ scoring. The enzyme treatment leads to a rapid and acute process of IVD degeneration. Conversely, laser radiation induced more progressive and less pronounced degeneration. It can be concluded that laser treatment provides an instrumental in vivo model of slowly evolving IVD degenerative disease that can be of preclinical relevance for assessing new prophylactic biological treatments of disc degeneration.

  6. Observations on morphologic changes in the aging and degenerating human disc: Secondary collagen alterations

    Directory of Open Access Journals (Sweden)

    Hanley Edward N

    2002-03-01

    Full Text Available Abstract Background In the annulus, collagen fibers that make up the lamellae have a wavy, planar crimped pattern. This crimping plays a role in disc biomechanical function by allowing collagen fibers to stretch during compression. The relationship between morphologic changes in the aging/degenerating disc and collagen crimping have not been explored. Methods Ultrastructural studies were performed on annulus tissue from 29 control (normal donors (aged newborn to 79 years and surgical specimens from 49 patients (aged 16 to 77 years. Light microscopy and specialized image analysis to visualize crimping was performed on additional control and surgical specimens. Human intervertebral disc tissue from the annulus was obtained in a prospective morphologic study of the annulus. Studies were approved by the authors' Human Subjects Institutional Review Board. Results Three types of morphologic changes were found to alter the crimping morphology of collagen: 1 encircling layers of unusual matrix disrupted the lamellar collagen architecture; 2 collagen fibers were reduced in amount, and 3 collagen was absent in regions with focal matrix loss. Conclusions Although proteoglycan loss is well recognized as playing a role in the decreased shock absorber function of the aging/degenerating disc, collagen changes have received little attention. This study suggests that important stretch responses of collagen made possible by collagen crimping may be markedly altered by morphologic changes during aging/degeneration and may contribute to the early tissue changes involved in annular tears.

  7. A role for TNFα in intervertebral disc degeneration: A non-recoverable catabolic shift

    International Nuclear Information System (INIS)

    Purmessur, D.; Walter, B.A.; Roughley, P.J.; Laudier, D.M.; Hecht, A.C.; Iatridis, James

    2013-01-01

    Highlights: ► TNFα induced catabolic changes similar to human intervertebral disc degeneration. ► The metabolic shift induced by TNFα was sustained following removal. ► TNFα induced changes suggestive of cell senescence without affecting cell viability. ► Interventions are required to stimulate anabolism and increase cell proliferation. -- Abstract: This study examines the effect of TNFα on whole bovine intervertebral discs in organ culture and its association with changes characteristic of intervertebral disc degeneration (IDD) in order to inform future treatments to mitigate the chronic inflammatory state commonly found with painful IDD. Pro-inflammatory cytokines such as TNFα contribute to disc pathology and are implicated in the catabolic phenotype associated with painful IDD. Whole bovine discs were cultured to examine cellular (anabolic/catabolic gene expression, cell viability and senescence using β-galactosidase) and structural (histology and aggrecan degradation) changes in response to TNFα treatment. Control or TNFα cultures were assessed at 7 and 21 days; the 21 day group also included a recovery group with 7 days TNFα followed by 14 days in basal media. TNFα induced catabolic and anti-anabolic shifts in the nucleus pulposus (NP) and annulus fibrosus (AF) at 7 days and this persisted until 21 days however cell viability was not affected. Data indicates that TNFα increased aggrecan degradation products and suggests increased β-galactosidase staining at 21 days without any recovery. TNFα treatment of whole bovine discs for 7 days induced changes similar to the degeneration processes that occur in human IDD: aggrecan degradation, increased catabolism, pro-inflammatory cytokines and nerve growth factor expression. TNFα significantly reduced anabolism in cultured IVDs and a possible mechanism may be associated with cell senescence. Results therefore suggest that successful treatments must promote anabolism and cell proliferation in

  8. Axial Creep Loading and Unloaded Recovery of the Human Intervertebral Disc and the Effect of Degeneration

    Science.gov (United States)

    O'Connell, Grace D.; Jacobs, Nathan T.; Sen, Sounok; Vresilovic, Edward J.; Elliott, Dawn M.

    2011-01-01

    The intervertebral disc maintains a balance between externally applied loads and internal osmotic pressure. Fluid flow plays a key role in this process, causing fluctuations in disc hydration and height. The objectives of this study were to quantify and model the axial creep and recovery responses of nondegenerate and degenerate human lumbar discs. Two experiments were performed. First, a slow compressive ramp was applied to 2000 N, unloaded to allow recovery for up to 24 hours, and re-applied. The linear-region stiffness and disc height were within 5% of the initial condition for recovery times greater than 8 hours. In the second experiment, a 1000 N creep load was applied for four hours, unloaded recovery monitored for 24 hours, and the creep load repeated. A viscoelastic model comprised of a “fast” and “slow” exponential response was used to describe the creep and recovery, where the fast response is associated with flow in the nucleus pulposus (NP) and endplate, while the slow response is associated with the annulus fibrosus (AF). The study demonstrated that recovery is 3-4X slower than loading. The fast response was correlated with degeneration, suggesting larger changes in the NP with degeneration compared to the AF. However, the fast response comprised only 10-15% of the total equilibrium displacement, with the AF-dominated slow response comprising 40-70%. Finally, the physiological loads and deformations and their associated long equilibrium times confirm that diurnal loading does not represent “equilibrium” in the disc, but that over time the disc is in steady-state. PMID:21783103

  9. Ultrastructure of inclusion bodies in annulus cells in the degenerating human intervertebral disc.

    Science.gov (United States)

    Gruber, H E; Hanley, E N

    2009-06-01

    The rough endoplasmic reticulum (rER) of the cell has an architectural editing function that checks whether protein structure and three-dimensional assembly have occurred properly prior to export of newly synthesized material out of the cell. If these have been faulty, the material is retained within the rER as an inclusion body. Inclusion bodies have been identified previously in chondrocytes and osteoblasts in chondrodysplasias and osteogenesis imperfecta. Inclusion bodies in intervertebral disc cells, however, have only recently been recognized. Our objectives were to use transmission electron microscopy to analyze more fully inclusion bodies in the annulus pulposus and to study the extracellular matrix (ECM) surrounding cells containing inclusion bodies. ECM frequently encapsulated cells with inclusion bodies, and commonly contained prominent banded aggregates of Type VI collagen. Inclusion body material had several morphologies, including relatively smooth, homogeneous material, or a rougher, less homogeneous feature. Such findings expand our knowledge of the fine structure of the human disc cell and ECM during disc degeneration, and indicate the potential utility of ultrastructural identification of discs with intracellular inclusion bodies as a screening method for molecular studies directed toward identification of defective gene products in degenerating discs.

  10. MRI histogram analysis enables objective and continuous classification of intervertebral disc degeneration.

    Science.gov (United States)

    Waldenberg, Christian; Hebelka, Hanna; Brisby, Helena; Lagerstrand, Kerstin Magdalena

    2018-05-01

    Magnetic resonance imaging (MRI) is the best diagnostic imaging method for low back pain. However, the technique is currently not utilized in its full capacity, often failing to depict painful intervertebral discs (IVDs), potentially due to the rough degeneration classification system used clinically today. MR image histograms, which reflect the IVD heterogeneity, may offer sensitive imaging biomarkers for IVD degeneration classification. This study investigates the feasibility of using histogram analysis as means of objective and continuous grading of IVD degeneration. Forty-nine IVDs in ten low back pain patients (six males, 25-69 years) were examined with MRI (T2-weighted images and T2-maps). Each IVD was semi-automatically segmented on three mid-sagittal slices. Histogram features of the IVD were extracted from the defined regions of interest and correlated to Pfirrmann grade. Both T2-weighted images and T2-maps displayed similar histogram features. Histograms of well-hydrated IVDs displayed two separate peaks, representing annulus fibrosus and nucleus pulposus. Degenerated IVDs displayed decreased peak separation, where the separation was shown to correlate strongly with Pfirrmann grade (P histogram appearances. Histogram features correlated well with IVD degeneration, suggesting that IVD histogram analysis is a suitable tool for objective and continuous IVD degeneration classification. As histogram analysis revealed IVD heterogeneity, it may be a clinical tool for characterization of regional IVD degeneration effects. To elucidate the usefulness of histogram analysis in patient management, IVD histogram features between asymptomatic and symptomatic individuals needs to be compared.

  11. Diffusion-Weighted MRI Assessment of Adjacent Disc Degeneration After Thoracolumbar Vertebral Fractures

    Energy Technology Data Exchange (ETDEWEB)

    Noriega, David C., E-mail: dcnoriega1970@gmail.com [Valladolid University Hospital, Spine Department (Spain); Marcia, Stefano, E-mail: stemarcia@gmail.com [SS. Trinità Hospital ASL 8 Cagliari, Department of Radiology (Italy); Ardura, Francisco, E-mail: fardura@ono.com [Valladolid University Hospital, Spine Department (Spain); Lite, Israel Sanchez, E-mail: israelslite@hotmail.com [Valladolid University Hospital, Radiology Department (Spain); Marras, Mariangela, E-mail: mariangela.marrasmd@gmail.com [Azienda Ospedaliero Brotzu (A.O.B.), Department of Radiology (Italy); Saba, Luca, E-mail: lucasaba@tiscali.it [Azienda Ospedaliero Universitaria (A.O.U.), Department of Radiology (Italy)

    2016-09-15

    ObjectiveThe purpose of this study was to assess, by the mean apparent diffusion coefficient (ADC), if a relationship exists between disc ADC and MR findings of adjacent disc degeneration after thoracolumbar fractures treated by anatomic reduction using vertebral augmentation (VAP).Materials and MethodsTwenty non-consecutive patients (mean age 50.7 years; range 45–56) treated because of vertebral fractures, were included in this study. There were 10 A3.1 and 10 A1.2 fractures (AO classification). Surgical treatment using VAP was applied in 14 cases, and conservative in 6 patients. MRI T2-weighted images and mapping of apparent diffusion coefficient (ADC) of the intervertebral disc adjacent to the fractured segment were performed after a mean follow-up of 32 months. A total of 60 discs, 3 per patient, were analysed: infra-adjacent, supra-adjacent and a control disc one level above the supra-adjacent.ResultsNo differences between patients surgically treated and those following a conservative protocol regarding the average ADC values obtained in the 20 control discs analysed were found. Considering all discs, average ADC in the supra-adjacent level was lower than in the infra-adjacent (1.35 ± 0.12 vs. 1.53 ± 0.06; p < 0.001). Average ADC values of the discs used as a control were similar to those of the infra-adjacent level (1.54 ± 0.06). Compared to surgically treated patients, discs at the supra-adjacent fracture level showed statistically significant lower values in cases treated conservatively (p < 0.001). The variation in the delay of surgery had no influence on the average values of ADC at any of the measured levels.ConclusionsADC measurements of the supra-adjacent discs after a mean follow-up of 32 months following thoracolumbar fractures, showed that restoration of the vertebral collapse by minimally invasive VAP prevents posttraumatic disc degeneration.

  12. Gene expression profile identifies potential biomarkers for human intervertebral disc degeneration.

    Science.gov (United States)

    Guo, Wei; Zhang, Bin; Li, Yan; Duan, Hui-Quan; Sun, Chao; Xu, Yun-Qiang; Feng, Shi-Qing

    2017-12-01

    The present study aimed to reveal the potential genes associated with the pathogenesis of intervertebral disc degeneration (IDD) by analyzing microarray data using bioinformatics. Gene expression profiles of two regions of the intervertebral disc were compared between patients with IDD and controls. GSE70362 containing two groups of gene expression profiles, 16 nucleus pulposus (NP) samples from patients with IDD and 8 from controls, and 16 annulus fibrosus (AF) samples from patients with IDD and 8 from controls, was downloaded from the Gene Expression Omnibus database. A total of 93 and 114 differentially expressed genes (DEGs) were identified in NP and AF samples, respectively, using a limma software package for the R programming environment. Gene Ontology (GO) function enrichment analysis was performed to identify the associated biological functions of DEGs in IDD, which indicated that the DEGs may be involved in various processes, including cell adhesion, biological adhesion and extracellular matrix organization. Pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) demonstrated that the identified DEGs were potentially involved in focal adhesion and the p53 signaling pathway. Further analysis revealed that there were 35 common DEGs observed between the two regions (NP and AF), which may be further regulated by 6 clusters of microRNAs (miRNAs) retrieved with WebGestalt. The genes in the DEG‑miRNA regulatory network were annotated using GO function and KEGG pathway enrichment analysis, among which extracellular matrix organization was the most significant disrupted biological process and focal adhesion was the most significant dysregulated pathway. In addition, the result of protein‑protein interaction network modules demonstrated the involvement of inflammatory cytokine interferon signaling in IDD. These findings may not only advance the understanding of the pathogenesis of IDD, but also identify novel potential

  13. Trends analysis of surgical procedures for cervical degenerative disc disease and myelopathy in patients with tobacco use disorder.

    Science.gov (United States)

    Grisdela, Phillip; Buser, Zorica; D'Oro, Anthony; Paholpak, Permsak; Liu, John C; Wang, Jeffrey C

    2017-09-01

    This study defined the incidence and trends of surgeries performed for patients with cervical disc degeneration with and without tobacco use disorder (TUD). This study utilized the Humana Inc. database between 2007 and 2013 to identify patients with cervical disc degeneration with or without myelopathy. International Classification of Diseases, ninth revision (ICD-9) and Current Procedural Terminology (CPT) codes determined the initial diagnosis of disc degeneration, myelopathy status and TUD, whether patients received surgery, and TUD status at surgery. The prevalence of disc degeneration with myelopathy increased by 32.8% between 2007 and 2013, while disc disease with myelopathy and TUD increased by 91.6%. For patients without myelopathy, the prevalence of disc degeneration alone increased by 65.4%, and disc degeneration with myelopathy increased by 148.7%. Of myelopathy patients, 1717 (6.4%) had TUD and 1024 (59.6%) received surgery, compared to 6508 patients without TUD (26.1%). For patients without myelopathy, 11,337 (3.5%) had TUD and 787 (6.9%) underwent surgery, compared to 9716 patients (3%) without TUD. Of surgical patients, 781 (76.3%) with myelopathy and TUD still had a TUD diagnosis at surgery, and 542 (68.9%) of patients without myelopathy still had a TUD diagnosis at surgery. The prevalence of degenerative disc disease and TUD has increased more than disc disease alone. Patients with TUD were more likely to get surgery, and to have surgeries earlier than patients without TUD. Patients with TUD at the time of the diagnosis of their disc degeneration likely still had a TUD diagnosis at the time of surgery.

  14. Safety of intradiscal injection and biocompatibility of polyester amide microspheres in a canine model predisposed to intervertebral disc degeneration

    NARCIS (Netherlands)

    Willems, Nicole; Mihov, George; Grinwis, Guy C M; van Dijk, Maarten; Schumann, Detlef; Bos, Clemens; Strijkers, Gustav J; Dhert, Wouter J A; Meij, Björn P; Creemers, Laura B.; Tryfonidou, Marianna A

    Repair of degenerated intervertebral discs (IVD) might be established via intradiscal delivery of biologic therapies. Polyester amide polymers (PEA) were evaluated for in vitro cytotoxicity and in vivo biocompatibility, and thereafter intradiscal application of PEA microspheres (PEAMs) in a canine

  15. Safety of intradiscal injection and biocompatibility of polyester amide microspheres in a canine model predisposed to intervertebral disc degeneration

    NARCIS (Netherlands)

    Willems, Nicole; Mihov, George; Grinwis, Guy C. M.; van Dijk, Maarten; Schumann, Detlef; Bos, Clemens; Strijkers, Gustav J.; Dhert, Wouter J. A.; Meij, Björn P.; Creemers, Laura B.; Tryfonidou, Marianna A.

    2017-01-01

    Repair of degenerated intervertebral discs (IVD) might be established via intradiscal delivery of biologic therapies. Polyester amide polymers (PEA) were evaluated for in vitro cytotoxicity and in vivo biocompatibility, and thereafter intradiscal application of PEA microspheres (PEAMs) in a canine

  16. Hyaluronic Acid (HA)-Polyethylene glycol (PEG) as injectable hydrogel for intervertebral disc degeneration patients therapy

    Science.gov (United States)

    Putri Kwarta, Cityta; Widiyanti, Prihartini; Siswanto

    2017-05-01

    Chronic Low Back Pain (CLBP) is one health problem that is often encountered in a community. Inject-able hydrogels are the newest way to restore the disc thickness and hydration caused by disc degeneration by means of minimally invasive surgery. Thus, polymers can be combined to improve the characteristic properties of inject-able hydrogels, leading to use of Hyaluronic Acid (a natural polymer) and Polyethylene glycol (PEG) with Horse Radish Peroxide (HRP) cross linker enzymes. The swelling test results, which approaches were the ideal disc values, were sampled with variation of enzyme concentrations of 0.25 µmol/min/mL. The enzyme concentrations were 33.95%. The degradation test proved that the sample degradation increased along with the decrease of the HRP enzyme concentration. The results of the cytotoxicity assay with MTT assay method showed that all samples resulted in the 90% of living cells are not toxic. In vitro injection, models demonstrated that higher concentration of the enzymes was less state of gel which would rupture when released from the agarose gel. The functional group characterization shows the cross linking bonding in sample with enzyme adding. The conclusion of this study is PEG-HA-HRP enzyme are safe polymer composites which have a potential to be applied as an injectable hydrogel for intervertebral disc degeneration.

  17. Human cartilaginous endplate degeneration is induced by calcium and the extracellular calcium-sensing receptor in the intervertebral disc

    Directory of Open Access Journals (Sweden)

    MP Grant

    2016-07-01

    Full Text Available The cartilaginous endplates (CEPs are thin layers of hyaline cartilage found adjacent to intervertebral discs (IVDs. In addition to providing structural support, CEPs regulate nutrient and metabolic exchange in the disc. In IVD pathogenesis, CEP undergoes degeneration and calcification, compromising nutrient availability and disc cell metabolism. The mechanism(s underlying the biochemical changes of CEP in disc degeneration are currently unknown. Since calcification is often observed in later stages of IVD degeneration, we hypothesised that elevations in free calcium (Ca2+ impair CEP homeostasis. Indeed, our results demonstrated that the Ca2+ content was consistently higher in human CEP tissue with grade of disc degeneration. Increasing the levels of Ca2+ resulted in decreases in the secretion and accumulation of collagens type I, II and proteoglycan in cultured human CEP cells. Ca2+ exerted its effects on CEP matrix protein synthesis through activation of the extracellular calcium-sensing receptor (CaSR; however, aggrecan content was also affected independent of CaSR activation as increases in Ca2+ directly enhanced the activity of aggrecanases. Finally, supplementing Ca2+ in our IVD organ cultures was sufficient to induce degeneration and increase the mineralisation of CEP, and decrease the diffusion of glucose into the disc. Thus, any attempt to induce anabolic repair of the disc without addressing Ca2+ may be impaired, as the increased metabolic demand of IVD cells would be compromised by decreases in the permeability of the CEP.

  18. Upper thoracic-spine disc degeneration in patients with cervical pain.

    Science.gov (United States)

    Arana, Estanislao; Martí-Bonmatí, Luis; Mollá, Enrique; Costa, Salvador

    2004-01-01

    To study the relationship of upper thoracic spine degenerative disc contour changes on MR imaging in patients with neck pain. The relation between upper thoracic and cervical spine degenerative disc disease is not well established. One hundred and fifty-six patients referred with cervical pain were studied. There were 73 women and 77 men with a mean age of 48.6 +/- 14.6 years (range, 19 to 83 years). All MR studies were performed with a large 23-cm FOV covering at least from the body of T4 to the clivus. Discs were coded as normal, protrusion/bulge or extrusion. Degenerative thoracic disc contour changes were observed in 13.4% of patients with cervical pain. T2-3 was the most commonly affected level of the upper thoracic spine, with 15 bulge/protrusions and one extrusion. Upper degenerative thoracic disc contour changes presented in older patients than the cervical levels (Student-Newman-Keuls test, P < 0.001). Degenerative disc contour changes at the C7-T1, T1-2, T2-3 and T3-4 levels were significantly correlated ( P = 0.001), but unrelated to any other disc disease, patient's gender or age. Degenerative cervical disc disease was closely related together ( P < 0.001), but not with any thoracic disc. A statistically significant relation was found within the upper thoracic discs, reflecting common pathoanatomical changes. The absence of relation to cervical segments is probably due to differences in their pathomechanisms.

  19. Upper thoracic-spine disc degeneration in patients with cervical pain

    Energy Technology Data Exchange (ETDEWEB)

    Arana, Estanislao; Marti-Bonmati, Luis; Costa, Salvador [Department of Radiology, Clinica Quiron, Avda Blasco Ibanez 14, 46010, Valencia (Spain); Molla, Enrique [Department of Radiology, Clinica Quiron, Avda Blasco Ibanez 14, 46010, Valencia (Spain); Department of Morphological Sciences, University of Valencia, Valencia (Spain)

    2004-01-01

    To study the relationship of upper thoracic spine degenerative disc contour changes on MR imaging in patients with neck pain. The relation between upper thoracic and cervical spine degenerative disc disease is not well established. One hundred and fifty-six patients referred with cervical pain were studied. There were 73 women and 77 men with a mean age of 48.6{+-}14.6 years (range, 19 to 83 years). All MR studies were performed with a large 23-cm FOV covering at least from the body of T4 to the clivus. Discs were coded as normal, protrusion/bulge or extrusion. Degenerative thoracic disc contour changes were observed in 13.4% of patients with cervical pain. T2-3 was the most commonly affected level of the upper thoracic spine, with 15 bulge/protrusions and one extrusion. Upper degenerative thoracic disc contour changes presented in older patients than the cervical levels (Student-Newman-Keuls test, P<0.001). Degenerative disc contour changes at the C7-T1, T1-2, T2-3 and T3-4 levels were significantly correlated (P=0.001), but unrelated to any other disc disease, patient's gender or age. Degenerative cervical disc disease was closely related together (P<0.001), but not with any thoracic disc. A statistically significant relation was found within the upper thoracic discs, reflecting common pathoanatomical changes. The absence of relation to cervical segments is probably due to differences in their pathomechanisms. (orig.)

  20. Upper thoracic-spine disc degeneration in patients with cervical pain

    International Nuclear Information System (INIS)

    Arana, Estanislao; Marti-Bonmati, Luis; Costa, Salvador; Molla, Enrique

    2004-01-01

    To study the relationship of upper thoracic spine degenerative disc contour changes on MR imaging in patients with neck pain. The relation between upper thoracic and cervical spine degenerative disc disease is not well established. One hundred and fifty-six patients referred with cervical pain were studied. There were 73 women and 77 men with a mean age of 48.6±14.6 years (range, 19 to 83 years). All MR studies were performed with a large 23-cm FOV covering at least from the body of T4 to the clivus. Discs were coded as normal, protrusion/bulge or extrusion. Degenerative thoracic disc contour changes were observed in 13.4% of patients with cervical pain. T2-3 was the most commonly affected level of the upper thoracic spine, with 15 bulge/protrusions and one extrusion. Upper degenerative thoracic disc contour changes presented in older patients than the cervical levels (Student-Newman-Keuls test, P<0.001). Degenerative disc contour changes at the C7-T1, T1-2, T2-3 and T3-4 levels were significantly correlated (P=0.001), but unrelated to any other disc disease, patient's gender or age. Degenerative cervical disc disease was closely related together (P<0.001), but not with any thoracic disc. A statistically significant relation was found within the upper thoracic discs, reflecting common pathoanatomical changes. The absence of relation to cervical segments is probably due to differences in their pathomechanisms. (orig.)

  1. MRI T2* mapping correlates with biochemistry and histology in intervertebral disc degeneration in a large animal model

    NARCIS (Netherlands)

    Detiger, Suzanne E. L.; Holewijn, Roderick M.; Hoogendoorn, Roel J. W.; van Royen, Barend J.; Helder, Marco N.; Berger, Ferco H.; Kuijer, Joost P. A.; Smit, Theo H.

    2015-01-01

    To evaluate intervertebral disc (IVD) degeneration and treatments, an objective diagnostic tool is needed. Recently, T2* relaxation time mapping was proposed as a technique to assess early IVD degeneration, yet the correlation with biochemical content and histological features has not been

  2. MRI T2* mapping correlates with biochemistry and histology in intervertebral disc degeneration in a large animal model

    NARCIS (Netherlands)

    Detiger, S.E.L.; Holewijn, R.M.; Hoogendoorn, R.J.W.; van Royen, B.J.; Helder, M.N.; Berger, F.H.; Kuijer, J.P.A.; Smit, T.H.

    2015-01-01

    Purpose: To evaluate intervertebral disc (IVD) degeneration and treatments, an objective diagnostic tool is needed. Recently, T2* relaxation time mapping was proposed as a technique to assess early IVD degeneration, yet the correlation with biochemical content and histological features has not been

  3. Relationship of modic type 1 change with disc degeneration: a prospective MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Luoma, Katariina [Helsinki University Central Hospital, Helsinki and Uudenmaa District University Hospitals, Helsinki (Finland)]|[Peijas Hospital, Helsinki University Central Hospitals, Department of Radiology, Vantaa (Finland); Vehmas, Tapio [Institute of Occupational Health, Helsinki (Finland); Groenblad, Mats; Kaeaepae, Eeva [Helsinki and Uudenmaa District University Hospitals, Helsinki University Central Hospital, Department of Physical Medicine and Rehabilitation, Helsinki (Finland); Kerttula, Liisa [Helsinki University Central Hospital, Helsinki and Uudenmaa District University Hospitals, Helsinki (Finland)

    2009-03-15

    The objective was to study the natural course of Modic type 1 change (M1) in relation to lumbar disc degeneration. Twenty-four chronic low back pain (LBP) patients with M1 on lumbar spine were selected from 1,015 patients with magnetic resonance imaging from a follow-up study lasting for 18-74 months. Exclusion criteria were any other specific back disorder, age {>=}60 years, or a recent spine operation. The association between the development of M1 and degenerative disc changes was studied using multivariate modeling (complex samples logistic regression). At baseline, 20 of 28 (71%) disc spaces with M1 had a decreased disc height (DH) and 16 of 28 (57%) a dark nucleus pulposus, but ten of 28 (36%) a very dark annulus fibrosus and a paradoxically bright nucleus pulposus albeit decreased DH. During follow-up, DH decreased in 13 of 28 (46%) and signal intensity of nucleus pulposus (DSI) in eight of 28 (29%) disc spaces with M1, but it increased in four (14%) discs. In those without M1, only few changes occurred. The larger the M1, the more likely was the DH low or decreased further. Both the presence and changes in M1 were associated with a decrease in DH and changes in DSI and bulges. The degenerative process in discs with adjacent M1 seems to be accelerated and leads to advanced and deforming changes with special morphologic features. M1 may be a sign of a pathologic degenerative process in the discovertebral unit. (orig.)

  4. Relationship of modic type 1 change with disc degeneration: a prospective MRI study

    International Nuclear Information System (INIS)

    Luoma, Katariina; Vehmas, Tapio; Groenblad, Mats; Kaeaepae, Eeva; Kerttula, Liisa

    2009-01-01

    The objective was to study the natural course of Modic type 1 change (M1) in relation to lumbar disc degeneration. Twenty-four chronic low back pain (LBP) patients with M1 on lumbar spine were selected from 1,015 patients with magnetic resonance imaging from a follow-up study lasting for 18-74 months. Exclusion criteria were any other specific back disorder, age ≥60 years, or a recent spine operation. The association between the development of M1 and degenerative disc changes was studied using multivariate modeling (complex samples logistic regression). At baseline, 20 of 28 (71%) disc spaces with M1 had a decreased disc height (DH) and 16 of 28 (57%) a dark nucleus pulposus, but ten of 28 (36%) a very dark annulus fibrosus and a paradoxically bright nucleus pulposus albeit decreased DH. During follow-up, DH decreased in 13 of 28 (46%) and signal intensity of nucleus pulposus (DSI) in eight of 28 (29%) disc spaces with M1, but it increased in four (14%) discs. In those without M1, only few changes occurred. The larger the M1, the more likely was the DH low or decreased further. Both the presence and changes in M1 were associated with a decrease in DH and changes in DSI and bulges. The degenerative process in discs with adjacent M1 seems to be accelerated and leads to advanced and deforming changes with special morphologic features. M1 may be a sign of a pathologic degenerative process in the discovertebral unit. (orig.)

  5. Histological, magnetic resonance imaging, and discographic findings on cervical disc degeneration in cadaver spines. A comparative study

    Energy Technology Data Exchange (ETDEWEB)

    Maruyama, Yuichiro [Juntendo Univ., Tokyo (Japan). School of Medicine

    1995-11-01

    A total of 210 cervical intervertebral discs were taken at autopsy from 36 cadavers, and underwent both magnetic resonance imaging (MRI) and discography to compare their diagnostic efficacies for investigating degenerative changes in the cervical spine. The age of the subjects had ranged from 43 to 92 years with an average of 68.1 years. Following the autopsy, MRI and discography were performed on the excised cervical spinal column, and the specimen was then prepared for histological examination. The findings were compared with those of the lumbar spine that had previously been reported by Yasuma et al. on 1238 lumbar discs from 197 cadavers ranging in age from 11 to 92 years. The results were as follows: Low intensity in the T2-weighted MRI was well correlated with histological degeneration in the cervical disc. The rate of appearance of the posterior protrusion of the cervical disc on the MRI was in accordance with the degree of histological disc degeneration, but it did not always correspond with histological posterior protrusion. There was a remarkably high incidence for false-positive posterior protrusion on the MRI, which should be kept in mind on reading the MRI. In the comparison of the MRI with the discography, a certain positive correlation was found as for disc degeneration, but not in complete accordance. There was a considerable difference in the patterns of degeneration and in posterior protrusion of the discs between the cervical spine and the lumbar spine. The posterior protrusion in the cervical disc was more likely related to horizontal fissure and hyalinization of the posterior annulus, while posterior protrusion in the lumbar disc was often related to reversed orientation of the bundles and myxomatous degeneration of the posterior annulus. This difference was attributed to the difference in the mechanical properties of the cervical and lumbar spines. (author).

  6. Histological, magnetic resonance imaging, and discographic findings on cervical disc degeneration in cadaver spines. A comparative study

    International Nuclear Information System (INIS)

    Maruyama, Yuichiro

    1995-01-01

    A total of 210 cervical intervertebral discs were taken at autopsy from 36 cadavers, and underwent both magnetic resonance imaging (MRI) and discography to compare their diagnostic efficacies for investigating degenerative changes in the cervical spine. The age of the subjects had ranged from 43 to 92 years with an average of 68.1 years. Following the autopsy, MRI and discography were performed on the excised cervical spinal column, and the specimen was then prepared for histological examination. The findings were compared with those of the lumbar spine that had previously been reported by Yasuma et al. on 1238 lumbar discs from 197 cadavers ranging in age from 11 to 92 years. The results were as follows: Low intensity in the T2-weighted MRI was well correlated with histological degeneration in the cervical disc. The rate of appearance of the posterior protrusion of the cervical disc on the MRI was in accordance with the degree of histological disc degeneration, but it did not always correspond with histological posterior protrusion. There was a remarkably high incidence for false-positive posterior protrusion on the MRI, which should be kept in mind on reading the MRI. In the comparison of the MRI with the discography, a certain positive correlation was found as for disc degeneration, but not in complete accordance. There was a considerable difference in the patterns of degeneration and in posterior protrusion of the discs between the cervical spine and the lumbar spine. The posterior protrusion in the cervical disc was more likely related to horizontal fissure and hyalinization of the posterior annulus, while posterior protrusion in the lumbar disc was often related to reversed orientation of the bundles and myxomatous degeneration of the posterior annulus. This difference was attributed to the difference in the mechanical properties of the cervical and lumbar spines. (author)

  7. An intervertebral disc whole organ culture system to investigate proinflammatory and degenerative disc disease condition.

    Science.gov (United States)

    Lang, Gernot; Liu, Yishan; Geries, Janna; Zhou, Zhiyu; Kubosch, David; Südkamp, Norbert; Richards, R Geoff; Alini, Mauro; Grad, Sibylle; Li, Zhen

    2018-04-01

    The aim of this study was to compare the effect of different disease initiators of degenerative disc disease (DDD) within an intervertebral disc (IVD) organ culture system and to understand the interplay between inflammation and degeneration in the early stage of DDD. Bovine caudal IVDs were cultured within a bioreactor for up to 11 days. Control group was cultured under physiological loading (0.02-0.2 MPa; 0.2 Hz; 2 hr/day) and high glucose (4.5 g/L) medium. Detrimental loading (0.32-0.5 MPa, 5 Hz; 2 hr/day) and low glucose (2 g/L) medium were applied to mimic the condition of abnormal mechanical stress and limited nutrition supply. Tumour necrosis factor alpha (TNF-α) was injected into the nucleus pulposus (100 ng per IVD) as a proinflammatory trigger. TNF-α combined with detrimental loading and low glucose medium up-regulated interleukin 1β (IL-1β), IL-6, and IL-8 gene expression in disc tissue, nitric oxide, and IL-8 release from IVD, which indicate a proinflammatory effect. The combined initiators up-regulated matrix metalloproteinase 1 gene expression, down-regulated gene expression of Type I collagen in annulus fibrosus and Type II collagen in nucleus pulposus, and reduced the cell viability. Furthermore, the combined initiators induced a degradative effect, as indicated by markedly higher glycosaminoglycan release into conditioned medium. The combination of detrimental dynamic loading, nutrient deficiency, and TNF-α intradiscal injection can synergistically simulate the proinflammatory and degenerative disease condition within DDD. This model will be of high interest to screen therapeutic agents in further preclinical studies for early intervention and treatment of DDD. Copyright © 2018 John Wiley & Sons, Ltd.

  8. Disc degeneration and chronic low back pain: an association which becomes nonsignificant when endplate changes and disc contour are taken into account

    International Nuclear Information System (INIS)

    Kovacs, Francisco M.; Arana, Estanislao; Royuela, Ana; Estremera, Ana; Amengual, Guillermo; Sarasibar, Helena; Martinez, Carmen; Asenjo, Beatriz; Galarraga, Isabel; Alonso, Ana; Casillas, Carlos; Muriel, Alfonso; Abraira, Victor

    2014-01-01

    The objective of this study was to assess the association between severe disc degeneration (DD) and low back pain (LBP). A case-control study was conducted with 304 subjects, aged 35-50, recruited in routine clinical practice across six hospitals; 240 cases (chronic LBP patients with a median pain duration of 46 months) and 64 controls (asymptomatic subjects without any lifetime history of significant LBP). The following variables were assessed once, using previously validated methods: gender, age, body mass index (BMI), lifetime smoking exposure, degree of physical activity, severity of LBP, disability, and findings on magnetic resonance (MRI) (disc degeneration, Modic changes (MC), disc protrusion/hernia, annular tears, spinal stenosis, and spondylolisthesis). Radiologists who interpreted MRI were blinded to the subjects' characteristics. A multivariate logistic regression model assessed the association between severe DD and chronic LBP, adjusting for gender, age, BMI, physical activity, MC, disc protrusion/hernia, and spinal stenosis. Severe DD at ≥1 level was found in 46.9 % of the controls and 65.8 % of the cases. Crude odds ratio (95 % CI), for suffering chronic LBP when having severe DD, was 2.06 (1.05; 4.06). After adjusting for ''MC'' and ''disc protrusion/hernia,'' it was 1.81 (0.81; 4.05). The association between severe DD and LBP ceases to be significant when adjusted for MC and disc protrusion/hernia. These results do not support that DD as a major cause of chronic LBP. (orig.)

  9. Imbalanced Protein Expression Patterns of Anabolic, Catabolic, Anti-Catabolic and Inflammatory Cytokines in Degenerative Cervical Disc Cells: New Indications for Gene Therapeutic Treatments of Cervical Disc Diseases

    Science.gov (United States)

    Mern, Demissew S.; Beierfuß, Anja; Fontana, Johann; Thomé, Claudius; Hegewald, Aldemar A.

    2014-01-01

    Degenerative disc disease (DDD) of the cervical spine is common after middle age and can cause loss of disc height with painful nerve impingement, bone and joint inflammation. Despite the clinical importance of these problems, in current publications the pathology of cervical disc degeneration has been studied merely from a morphologic view point using magnetic resonance imaging (MRI), without addressing the issue of biological treatment approaches. So far a wide range of endogenously expressed bioactive factors in degenerative cervical disc cells has not yet been investigated, despite its importance for gene therapeutic approaches. Although degenerative lumbar disc cells have been targeted by different biological treatment approaches, the quantities of disc cells and the concentrations of gene therapeutic factors used in animal models differ extremely. These indicate lack of experimentally acquired data regarding disc cell proliferation and levels of target proteins. Therefore, we analysed proliferation and endogenous expression levels of anabolic, catabolic, ant-catabolic, inflammatory cytokines and matrix proteins of degenerative cervical disc cells in three-dimensional cultures. Preoperative MRI grading of cervical discs was used, then grade III and IV nucleus pulposus (NP) tissues were isolated from 15 patients, operated due to cervical disc herniation. NP cells were cultured for four weeks with low-glucose in collagen I scaffold. Their proliferation rates were analysed using 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide. Their protein expression levels of 28 therapeutic targets were analysed using enzyme-linked immunosorbent assay. During progressive grades of degeneration NP cell proliferation rates were similar. Significantly decreased aggrecan and collagen II expressions (P<0.0001) were accompanied by accumulations of selective catabolic and inflammatory cytokines (disintegrin and metalloproteinase with thrombospondin motifs 4 and 5, matrix

  10. Intradiscal injection of simvastatin results in radiologic, histologic, and genetic evidence of disc regeneration in a rat model of degenerative disc disease

    Science.gov (United States)

    Than, Khoi D.; Rahman, Shayan U.; Wang, Lin; Khan, Adam; Kyere, Kwaku A.; Than, Tracey T.; Miyata, Yoshinari; Park, Yoon-Shin; La Marca, Frank; Kim, Hyungjin M.; Zhang, Huina; Park, Paul; Lin, Chia-Ying

    2014-01-01

    BACKGROUND CONTEXT A large percentage of back pain can be attributed to degeneration of the intervertebral disc (IVD). Bone morphogenetic protein-2 (BMP-2) is known to play an important role in chondrogenesis of the IVD. Simvastatin is known to up-regulate expression of BMP-2. Thus, we hypothesized that intradiscal injection of simvastatin in a rat model of degenerative disc disease (DDD) would result in retardation of DDD. PURPOSE To develop a novel conservative treatment for DDD and related discogenic back pain. STUDY DESIGN/SETTING Laboratory investigation. METHODS Disc injury was induced in 272 rats via 21-gauge needle puncture. After 6 weeks, injured discs were treated with simvastatin in a saline or hydrogel carrier. Rats were sacrificed at predetermined time points. Outcome measures assessed were radiologic, histologic, and genetic. Radiologically, the MRI index (number of pixels multiplied by corresponding image densities) was determined. Histologically, disc spaces were read by 3 blinded scorers employing a previously described histological grading scale. Genetically, nuclei pulposi were harvested and polymerase chain reaction was run to determine relative levels of aggrecan, collagen type II, and BMP-2 gene expression. This project was supported by Grant No. R01 AR056649 from NIAMS/NIH. There are no other financial conflicts of interest to report. RESULTS Radiologically, discs treated with 5 mg/mL simvastatin in hydrogel or saline demonstrated MRI indices that were normal through 8 weeks post-treatment, although this was more sustained when delivered in hydrogel. Histologically, discs treated with 5 mg/mL simvastatin in hydrogel demonstrated improved grades in comparison to discs treated at higher doses. Genetically, discs treated with 5 mg/mL of simvastatin in hydrogel demonstrated higher gene expression of aggrecan and collagen type II than control. CONCLUSIONS Degenerate discs treated with 5 mg/mL simvastatin in a hydrogel carrier demonstrated

  11. Posteriorly directed shear loads and disc degeneration affect the torsional stiffness of spinal motion segments; a biomechanical modeling study

    NARCIS (Netherlands)

    Homminga, Jasper Johan; Lehr, A.M.; Meijer, Gerdine; Janssen, M.M.A.; Schlösser, T.P.C.; Verkerke, Gijsbertus Jacob; Castelein, R.M.

    2013-01-01

    Objective. To analyze the effects of posterior shear loads, disc degeneration, and the combination of both on spinal torsion stiffness. Summary of Background Data. Scoliosis is a 3-dimensional deformity of the spine that presents itself mainly in adolescent girls and elderly patients. Our concept of

  12. Nucleoplasty as a therapeutic option for lumbar disc degeneration related pain: a retrospective study of 396 cases

    Directory of Open Access Journals (Sweden)

    José Lourenço Kallás

    2013-01-01

    Full Text Available OBJECTIVES: To make a retrospective analysis and evaluate a clinical response to the control of disc degeneration related pain of 396 patients submitted to percutaneous lumbar nucleoplasty; and to make a record of visual analogical scale (VAS up to a three-year follow-up after the surgical procedure. METHODS: Analysis of VAS score in 396 patients with lumbar disc degeneration related pain, according to anamnesis, clinical examination and magnetic resonance imaging (MRI, without improvement of previous clinical treatment, submitted to percutaneous nucleoplasty. RESULTS: A total of 26% of the patients presented 100% remission of pain or paresthesia, of whom 75% showed at least 50% of pain improvement. The median VAS pain improvement was about 67%. CONCLUSIONS: The median VAS improvement in inferior disc levels was higher than four points. The VAS showed improvement of the pain and paresthesia up to a three-year follow up after the surgical procedure.

  13. Prevalence and pattern of radiographic intervertebral disc degeneration in Vietnamese: a population-based study.

    Science.gov (United States)

    Ho-Pham, Lan T; Lai, Thai Q; Mai, Linh D; Doan, Minh C; Pham, Hoa N; Nguyen, Tuan V

    2015-06-01

    Intervertebral disc degeneration (IDD) is one of the most common skeletal disorders, yet few data are available in Asian populations. We sought to assess the prevalence and pattern of radiographic IDD in a Vietnamese population. This population-based cross-sectional investigation involved 170 men and 488 women aged ≥40 years, who were randomly sampled from the Ho Chi Minh City (Vietnam). Anthropometric data, clinical history and self-reported back and neck pain were ascertained by a questionnaire. Plain radiographs (from the cervical spine, thoracic spine to the lumbar spine) were examined for the presence of disc space narrowing and/or osteophytosis using the Kellgren-Lawrence (KL) grading system. The presence of radiographic IDD was defined if the KL grade was 2 or greater in at least one disc. The prevalence of radiographic IDD was 62.4% (n = 106) in men and 54.7% (n = 267) in women. The most frequently affected site was the lumbar spine with prevalence being 50.6 and 43.2% in men and women, respectively. The prevalence of IDD increased with advancing age: 18.8% among those aged 40-49 years, and increased to 83.4% in those aged ≥60 years. Self-reported neck pain and lower back pain were found in 30 and 44% of individuals, respectively. There was no statistically significant association between self-reported neck pain and cervical spine OA. These data suggest that radiographic IDD is highly prevalent in the Vietnamese population, and that self-reported back pain is not a sensitive indicator of IDD.

  14. Acidic pH promotes intervertebral disc degeneration: Acid-sensing ion channel -3 as a potential therapeutic target.

    Science.gov (United States)

    Gilbert, Hamish T J; Hodson, Nathan; Baird, Pauline; Richardson, Stephen M; Hoyland, Judith A

    2016-11-17

    The aetiology of intervertebral disc (IVD) degeneration remains poorly understood. Painful IVD degeneration is associated with an acidic intradiscal pH but the response of NP cells to this aberrant microenvironmental factor remains to be fully characterised. The aim here was to address the hypothesis that acidic pH, similar to that found in degenerate IVDs, leads to the altered cell/functional phenotype observed during IVD degeneration, and to investigate the involvement of acid-sensing ion channel (ASIC) -3 in the response. Human NP cells were treated with a range of pH, from that of a non-degenerate (pH 7.4 and 7.1) through to mildly degenerate (pH 6.8) and severely degenerate IVD (pH 6.5 and 6.2). Increasing acidity of pH caused a decrease in cell proliferation and viability, a shift towards matrix catabolism and increased expression of proinflammatory cytokines and pain-related factors. Acidic pH resulted in an increase in ASIC-3 expression. Importantly, inhibition of ASIC-3 prevented the acidic pH induced proinflammatory and pain-related phenotype in NP cells. Acidic pH causes a catabolic and degenerate phenotype in NP cells which is inhibited by blocking ASIC-3 activity, suggesting that this may be a useful therapeutic target for treatment of IVD degeneration.

  15. The comparative study of radiograph, MRI and pathology in degeneration of lumbar intervertebral disc

    International Nuclear Information System (INIS)

    Shang Tiesong; Wang Yunzhao

    2002-01-01

    Objective: To investigate the pathology, and MRI features of the degeneration of lumbar intervertebral discs (IVD). Methods: Thirteen human lumbar spine segments with 31 IVDs were harvested from fresh cadavers. High quality radiographs were taken for all specimens. Five segments with 20 IVD underwent MRl. Then, the radiographic and MRI findings were correlated with corresponding 87 pathologic sections. Results: Variant degeneration was observed in pathologic sections in all 31 IVDs. With MRI T 2 WI images, 20 IVDs showed linear and spotty high signal in the annular fibers, or most of the IVD showed high signal. On pathologic cuts, 22 of 31 IVDs showed infolding of annular fibers, 18 of 31 showed outfolding of annular fibers. On MRI T 1 WI and T 2 WI images, infolding and outfolding of annular fibers were seen as low signal. 20 of 31 IVDs had necrotic debris of cells in the nucleus pulposus. 14 of 20 demonstrated spotty low signal areas on MRI T 2 WI images. 7 Schmorl nodules were found. On pathologic sections Schmorl nodules were seen as IVD tissue protruding into vertebral endplates, they were seen as high signal on T 2 WI images. Two large fissures found on sections were seen as low signal on T 2 WI. Degenerative fibrosis seen on 6 IVD, which showed intermediate signal on T 2 WI images. However, radiographs only demonstrated osteophytes on 3 vertebrae, 7 Schmorl's nodules. Sclerotic, concave and irregular endplates were seen in 11 IVDs, the tatter is the indication of cartilaginous endplate disruption, Conclusion: MRI is very useful in demonstrating the degeneration of IVD, radiograph is able to indirectly show the disappearance of cartilaginous endplate

  16. Lumbar disc degeneration was not related to spine and hip bone mineral densities in Chinese: facet joint osteoarthritis may confound the association.

    Science.gov (United States)

    Pan, Jianjiang; Lu, Xuan; Yang, Ge; Han, Yongmei; Tong, Xiang; Wang, Yue

    2017-12-01

    A sample of 512 Chinese was studied and we observed that greater disc degeneration on MRI was associated with greater spine DXA BMD. Yet, this association may be confounded by facet joint osteoarthritis. BMD may not be a risk factor for lumbar disc degeneration in Chinese. Evidence suggested that lumbar vertebral bone and intervertebral disc interact with each other in multiple ways. The current paper aims to determine the association between bone mineral density (BMD) and lumbar disc degeneration using a sample of Chinese. We studied 165 patients with back disorders and 347 general subjects from China. All subjects had lumbar spine magnetic resonance (MR) imaging and dual- energy X-ray absorptiometry (DXA) spine BMD studies, and a subset of general subjects had additional hip BMD measurements. On T2-weighted MR images, Pfirrmann score was used to evaluate the degree of lumbar disc degeneration and facet joint osteoarthritis was assessed as none, slight-moderate, and severe. Regression analyses were used to examine the associations between lumbar and hip BMD and disc degeneration, adjusting for age, gender, body mass index (BMI), lumbar region, and facet joint osteoarthritis. Greater facet joint osteoarthritis was associated with greater spine BMD (P osteoarthritis entered the regression model, however, greater spine BMD was associated with greater facet joint osteoarthritis (P  0.05). No statistical association was observed between spine BMD and lumbar disc degeneration in patients with back disorders (P > 0.05), and between hip BMD and disc degeneration in general subjects (P > 0.05). BMD may not be a risk factor for lumbar disc degeneration in Chinese. Facet joint osteoarthritis inflates DXA spine BMD measurements and therefore, may confound the association between spine BMD and disc degeneration.

  17. Disc degeneration and chronic low back pain: an association which becomes nonsignificant when endplate changes and disc contour are taken into account

    Energy Technology Data Exchange (ETDEWEB)

    Kovacs, Francisco M. [Fundacion Kovacs, Departamento Cientifico, Palma de Mallorca (Spain); Fundacion Kovacs, Spanish Back Pain Research Network, Palma de Mallorca (Spain); Arana, Estanislao [Fundacion Kovacs, Spanish Back Pain Research Network, Palma de Mallorca (Spain); Fundacion Instituto Valenciano de Oncologia, Servicio de Radiologia, Valencia (Spain); Royuela, Ana [CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid (Spain); Hospital Ramon y Cajal, Unidad de Bioestadistica Clinica, IRYCIS, Madrid (Spain); Estremera, Ana; Amengual, Guillermo; Sarasibar, Helena; Martinez, Carmen [Fundacion Kovacs, Spanish Back Pain Research Network, Palma de Mallorca (Spain); Hospital Son Llatzer, Palma de Mallorca (Spain); Asenjo, Beatriz [Fundacion Kovacs, Spanish Back Pain Research Network, Palma de Mallorca (Spain); Hospital Carlos Haya, Malaga (Spain); Galarraga, Isabel [Fundacion Kovacs, Spanish Back Pain Research Network, Palma de Mallorca (Spain); Hospital de Manacor, Manacor, Mallorca (Spain); Alonso, Ana [Fundacion Kovacs, Spanish Back Pain Research Network, Palma de Mallorca (Spain); Fundacion Jimenez Diaz, Madrid (Spain); Casillas, Carlos [Fundacion Kovacs, Spanish Back Pain Research Network, Palma de Mallorca (Spain); Instituto de Traumatologia Union de Mutuas, Castellon (Spain); Muriel, Alfonso; Abraira, Victor [Hospital Ramon y Cajal, Unidad de Bioestadistica Clinica, IRYCIS, Madrid (Spain); CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid (Spain)

    2014-01-15

    The objective of this study was to assess the association between severe disc degeneration (DD) and low back pain (LBP). A case-control study was conducted with 304 subjects, aged 35-50, recruited in routine clinical practice across six hospitals; 240 cases (chronic LBP patients with a median pain duration of 46 months) and 64 controls (asymptomatic subjects without any lifetime history of significant LBP). The following variables were assessed once, using previously validated methods: gender, age, body mass index (BMI), lifetime smoking exposure, degree of physical activity, severity of LBP, disability, and findings on magnetic resonance (MRI) (disc degeneration, Modic changes (MC), disc protrusion/hernia, annular tears, spinal stenosis, and spondylolisthesis). Radiologists who interpreted MRI were blinded to the subjects' characteristics. A multivariate logistic regression model assessed the association between severe DD and chronic LBP, adjusting for gender, age, BMI, physical activity, MC, disc protrusion/hernia, and spinal stenosis. Severe DD at ≥1 level was found in 46.9 % of the controls and 65.8 % of the cases. Crude odds ratio (95 % CI), for suffering chronic LBP when having severe DD, was 2.06 (1.05; 4.06). After adjusting for ''MC'' and ''disc protrusion/hernia,'' it was 1.81 (0.81; 4.05). The association between severe DD and LBP ceases to be significant when adjusted for MC and disc protrusion/hernia. These results do not support that DD as a major cause of chronic LBP. (orig.)

  18. Evaluation of Lumbar Intervertebral Disc Degeneration Using T1ρ and T2 Magnetic Resonance Imaging in a Rabbit Disc Injury Model.

    Science.gov (United States)

    Ishikawa, Tetsuhiro; Watanabe, Atsuya; Kamoda, Hiroto; Miyagi, Masayuki; Inoue, Gen; Takahashi, Kazuhisa; Ohtori, Seiji

    2018-04-01

    An in vivo histologic and magnetic resonance imaging (MRI) study of lumbar intervertebral disc (IVD) degeneration was conducted. To clarify the sensitivity and efficacy of T1ρ/T2 mapping for IVD degeneration, the correlation between T1ρ/T2 mapping and degenerative grades and histological findings in the lumbar IVD were investigated. The early signs of IVD degeneration are proteoglycan loss, dehydration, and collagen degradation. Recently, several quantitative MRI techniques have been developed; T2 mapping can be used to evaluate hydration and collagen fiber integrity within cartilaginous tissue, and T1ρ mapping can be used to evaluate hydration and proteoglycan content. Using New Zealand White rabbits, annular punctures of the IVD were made 10 times at L2/3, 5 times at L3/4, and one time at L4/5 using an 18-gauge needle (n=6) or a 21-gauge needle (n=6). At 4 and 8 weeks post-surgery, MRI was performed including T1ρ and T2 mapping. The degree of IVD degeneration was macroscopically assessed using the Thompson grading system. All specimens were cut for hematoxylin and eosin, safranin-O, and toluidine blue staining. Disc degeneration became more severe as the number of punctures increased and when the larger needle was used. T1ρ and T2 values were significantly different between grade 1 and grade 3 IVDs, grade 1 and grade 4 IVDs, grade 2 and grade 3 IVDs, and grade 2 and grade 4 IVDs ( p T2 quantitative MRI could detect these small differences. Our results suggest that T1ρ and T2 mapping are sensitive to degenerative changes of lumbar IVDs and that T1ρ mapping can be used as a clinical tool to identify early IVD degeneration.

  19. The Effect of Electroacupuncture on the Extracellular Matrix Synthesis and Degradation in a Rabbit Model of Disc Degeneration

    Directory of Open Access Journals (Sweden)

    Guo-fu Huang

    2014-01-01

    Full Text Available The present study was aimed at determining if the electroacupuncture (EA is able to protect degenerated disc in vivo. New Zealand white rabbits (n=40 were used for the study. The rabbits were randomly assigned to four groups. EA intervention was applied to one of the four groups. Magnetic resonance imaging and Pfirrmann’s classification were obtained for each group to evaluate EA treatment on the intervertebral disc degeneration. Discs were analyzed using immunofluorescence for the labeling of collagens 1 and 2, bone morphogenetic protein-2 (BMP-2, matrix metalloproteinase-13 (MMP-13, and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1. For protein expression analysis, western blot was used for biglycan and decorin. Outcomes indicated that EA intervention decreased the grades compared with the compressed disc. Immunofluorescence analysis showed a significant increase of collagens 1 and 2, TIMP-1, and BMP-2 positive cells, in contrast to MMP-13 after EA treatment for 28 days. The protein expression showed a sign of regeneration that decorin and biglycan were upregulated. It was concluded that EA contributed to the extracellular matrix (ECM anabolic processes and increased the ECM components. MMPs and their inhibitors involved in the mechanism of EA intervention on ECM decreased disc. It kept a dynamic balance between ECM synthesis and degradation.

  20. Correlation of matrix metalloproteinase-3 expression with patient age, magnetic resonance imaging and histopathological grade in lumbar disc degeneration.

    Science.gov (United States)

    Canbay, Suat; Turhan, Nesrin; Bozkurt, Melih; Arda, Kemal; Caglar, Sukru

    2013-01-01

    The purpose of the present study is to analyze the expression of matrix metalloproteinase-3 (MMP-3), magnetic resonance imaging (MRI) grading and histopathological alterations of the intervertebral disc (IVD) for correlations with each other and with the age, gender and low back pain duration of the patients who had undergone operations for lumbar disc herniation (LDH). Forty-two patients were admitted to our clinic with signs of LDH and underwent surgery for LDH at 48 IVD levels. In all cases, specimens for histological and immunohistochemical analyses were removed from the IVD space. Lumbar IVD degeneration on MRI of the 48 IVDs from which surgical specimens had been obtained was classified into five grades using the Pfirrmann classification. In the degenerated IVD, the expression of MMP-3, MRI grading and histopathological alterations of the IVD displayed significant correlation. Increased age is closely related with aforementioned alterations. There was no correlation between MMP-3 expression and age, gender and duration of the pain. For evaluating and treating IVD degeneration, MRI is a good and non-invasive diagnostic tool to determine the severity of degeneration. MMP-3 may be a therapeutic target of the degenerated IVD.

  1. Mechanoreceptors in Diseased Cervical Intervertebral Disc and Vertigo.

    Science.gov (United States)

    Yang, Liang; Yang, Cheng; Pang, Xiaodong; Li, Duanming; Yang, Hong; Zhang, Xinwu; Yang, Yi; Peng, Baogan

    2017-04-15

    We collected the samples of cervical intervertebral discs from patients with vertigo to examine the distribution and types of mechanoreceptors in diseased cervical disc. The aim of this study was to determine whether mechanoreceptors are distributed more abundantly in cervical discs from patients with cervical spondylosis, and whether they are related to vertigo. Previous limited studies have found that normal cervical intervertebral discs are supplied with mechanoreceptors that have been considered responsible for proprioceptive functions. Several clinical studies have indicated that the patients with cervical spondylosis manifested significantly impaired postural control and subjective balance disturbance. We collected 77 samples of cervical discs from 62 cervical spondylosis patients without vertigo, 61 samples from 54 patients with vertigo, and 40 control samples from 8 cadaveric donors to investigate distribution of mechanoreceptors containing neurofilament (NF200) and S-100 protein immunoreactive nerve endings. The immunohistochemical investigation revealed that the most frequently encountered mechanoreceptors were the Ruffini corpuscles in all groups of cervical disc samples. They were obviously increased in the number and deeply ingrown into inner annulus fibrosus and even into nucleus pulposus in the diseased cervical discs from patients with vertigo in comparison with the discs from patients without vertigo and control discs. Only three Golgi endings were seen in the three samples from patients with vertigo. No Pacinian corpuscles were found in any samples of cervical discs. The diseased cervical discs from patients with vertigo had more abundant distribution of Ruffini corpuscles than other discs. A positive association between the increased number and ingrowth of Ruffini corpuscles in the diseased cervical disc and the incidence of vertigo in the patients with cervical spondylosis was found, which may indicate a key role of Ruffini corpuscles in the

  2. In vitro assessment of biomaterial-induced remodeling of subchondral and cancellous bone for the early intervention of joint degeneration with focus on the spinal disc

    Science.gov (United States)

    McCanless, Jonathan D.

    Osteoarthritis-associated pain of the spinal disc, knee, and hip derives from degeneration of cartilagenous tissues in these joints. Traditional therapies have focused on these cartilage (and disc specific nucleus pulposus) changes as a means of treatment through tissue grafting, regenerative synthetic implants, non-regenerative space filling implants, arthroplasty, and arthrodesis. Although such approaches may seem apparent upon initial consideration of joint degeneration, tissue pathology has shown changes in the underlying bone and vascular bed precede the onset of cartilaginous changes. It is hypothesized that these changes precedent joint degeneration and as such may provide a route for early prevention. The current work proposes an injectable biomaterial-based therapy within these subchondral and cancellous bone regions as a means of preventing or reversing osteoarthritis. Two human concentrated platelet releasate-containing alginate hydrogel/beta-tricalcium phosphate composites have been developed for this potential biomaterial application. The undertaking of assessing these materials through bench-, in vitro, and ex vivo work is described herein. These studies showed the capability of the biomaterials to initiate a wound healing response in monocytes, angiogenic and differentiation behavior in immature endothelial cells, and early osteochondral differentiation in mesenchymal stem cells. These cellular activities are associated with fracture healing and endochondral bone formation, demonstrating the potential of the biomaterials to induce osseous and vascular tissue remodeling underlying osteoarthritic joints as a novel therapy for a disease with rapidly growing healthcare costs.

  3. Kaempferol slows intervertebral disc degeneration by modifying LPS-induced osteogenesis/adipogenesis imbalance and inflammation response in BMSCs.

    Science.gov (United States)

    Zhu, Jun; Tang, Haoyu; Zhang, Zhenhua; Zhang, Yong; Qiu, Chengfeng; Zhang, Ling; Huang, Pinge; Li, Feng

    2017-02-01

    Intervertebral disc (IVD) degeneration is a common disease that represents a significant cause of socio-economic problems. Bone marrow-derived mesenchymal stem cells (BMSCs) are a potential autologous stem cell source for the nucleus pulposus regeneration. Kaempferol has been reported to exert protective effects against both osteoporosis and obesity. This study explored the effect of kaempferol on BMSCs differentiation and inflammation. The results demonstrated that kaempferol did not show any cytotoxicity at concentrations of 20, 60 and 100μM. Kaempferol enhanced cell viability by counteracting the lipopolysaccharide (LPS)-induced cell apoptosis and increasing cell proliferation. Western blot analysis of mitosis-associated nuclear antigen (Ki67) and proliferation cell nuclear antigen (PCNA) further confirmed the increased effect of kaempferol on LPS-induced decreased viability of BMSCs. Besides, kaempferol elevated LPS-induced reduced level of chondrogenic markers (SOX-9, Collagen II and Aggrecan), decreased the level of matrix-degrading enzymes, i.e., matrix metalloprotease (MMP)-3 and MMP-13, suggesting the osteogenesis of BMSC under kaempferol treatment. On the other hand, kaempferol enhanced LPS-induced decreased expression of lipid catabolism-related genes, i.e., carnitine palmitoyl transferase-1 (CPT-1). Kaempferol also suppressed the expression of lipid anabolism-related genes, i.e., peroxisome proliferators-activated receptor-γ (PPAR-γ). The Oil red O staining further convinced the inhibition effect of kaempferol on BMSCs adipogenesis. In addition, kaempferol alleviated inflammatory by reducing the level of pro-inflammatory cytokines (i.e., interleukin (IL)-6) and increasing anti-inflammatory cytokine (IL-10) via inhibiting the nucleus translocation of nuclear transcription factor (NF)-κB p65. Taken together, our research indicated that kaempferol may serve as a novel target for treatment of IVD degeneration. Copyright © 2016 Elsevier B.V. All rights

  4. A selective inhibition of c-Fos/activator protein-1 as a potential therapeutic target for intervertebral disc degeneration and associated pain.

    Science.gov (United States)

    Makino, Hiroto; Seki, Shoji; Yahara, Yasuhito; Shiozawa, Shunichi; Aikawa, Yukihiko; Motomura, Hiraku; Nogami, Makiko; Watanabe, Kenta; Sainoh, Takeshi; Ito, Hisakatsu; Tsumaki, Noriyuki; Kawaguchi, Yoshiharu; Yamazaki, Mitsuaki; Kimura, Tomoatsu

    2017-12-05

    Intervertebral disc (IVD) degeneration is a major cause of low back pain. The transcription factor c-Fos/Activator Protein-1 (AP-1) controls the expression of inflammatory cytokines and matrix metalloproteinases (MMPs) that contribute to the pathogenesis IVD degeneration. We investigated the effects of inhibition of c-Fos/AP-1 on IVD degeneration and associated pain. A selective inhibitor, T-5224, significantly suppressed the interleukin-1β-induced up-regulation of Mmp-3, Mmp-13 and Adamts-5 transcription in human nucleus pulposus cells and in a mouse explant culture model of IVD degeneration. We used a tail disc percutaneous needle puncture method to further assess the effects of oral administration of T-5224 on IVD degeneration. Analysis of disc height, T2-magnetic resonance imaging (MRI) findings, and histology revealed that IVD degeneration was significantly mitigated by T-5224. Further, oral administration of T-5224 ameliorated pain as indicated by the extended tail-flick latency in response to heat stimulation of rats with needle-puncture-induced IVD degeneration. These findings suggest that the inhibition of c-Fos/AP-1 prevents disc degeneration and its associated pain and that T-5224 may serve as a drug for the prevention of IVD degeneration.

  5. The impact of generalized joint laxity (GJL) on the posterior neck pain, cervical disc herniation, and cervical disc degeneration in the cervical spine.

    Science.gov (United States)

    Lee, Sun-Mi; Oh, Su Chan; Yeom, Jin S; Shin, Ji-Hoon; Park, Sam-Guk; Shin, Duk-Seop; Ahn, Myun-Whan; Lee, Gun Woo

    2016-12-01

    Generalized joint laxity (GJL) can have a negative impact on lumbar spine pathology, including low back pain, disc degeneration, and disc herniation, but the relationship between GJL and cervical spine conditions remains unknown. To investigate the relationship between GJL and cervical spine conditions, including the prevalence of posterior neck pain (PNP), cervical disc herniation (CDH), and cervical disc degeneration (CDD), in a young, active population. Retrospective 1:2 matched cohort (case-control) study from prospectively collected data PATIENT SAMPLE: Of a total of 1853 individuals reviewed, 73 individuals with GJL (study group, gruop A) and 146 without GJL (control group, Group B) were included in the study according to a 1:2 case-control matched design for age, sex, and body mass index. The primary outcome measure was the prevalence and intensity of PNP at enrollment based on a visual analogue scale score for pain. The secondary outcome measures were (1) clinical outcomes as measured with the neck disability index (NDI) and 12-item short form health survey (SF-12) at enrollment, and (2) radiological outcomes of CDH and CDD at enrollment. We compared baseline data between groups. Descriptive statistical analyses were performed to compare the 2 groups in terms of the outcome measures. The prevalence and intensity of PNP were significantly greater in group A (patients with GJL) than in group B (patients without GJL) (prevalence: p=.02; intensity: p=.001). Clinical outcomes as measured with NDI and SF-12 did not differ significantly between groups. For radiologic outcomes, the prevalence of CDD was significantly greater in group A than in group B (p=.04), whereas the prevalence of CDH did not differ significantly between groups (p=.91). The current study revealed that GJL was closely related to the prevalence and intensity of PNP, suggesting that GJL may be a causative factor for PNP. In addition, GJL may contribute to the occurrence of CDD, but not CDH. Spine

  6. Degenerative disc disease as a cause of back pain in the thalassaemic population: a case-control study using MRI and plain radiographs

    Energy Technology Data Exchange (ETDEWEB)

    Desigan, S.; Hall-Craggs, M.A.; Ho, C.-P. [Department of Imaging, University College London Hospitals NHS Foundation Trust, London (United Kingdom); Eliahoo, J. [University College London Hospitals NHS Trust, Research and Development Directorate, London (United Kingdom); Porter, J.B. [University College Hospital, Department of Haematology, University College London Hospitals NHS Trust, London (United Kingdom)

    2006-02-15

    The aim of this study was to test our observation that back pain in thalassemic patients could be caused by premature and extensive lumbar degenerative disc disease, when compared to non-thalassemic patients with back pain. Sixteen thalassemic patients with their sex- and age-matched controls were recruited into the study, 12 with thalassemia major, and 4 with thalassemia intermedia. Both the thalassemia patients and control subjects suffered from back pain, which was subjective rather than measured/pain scored. All subjects underwent magnetic resonance (MR) imaging of the lumbar spine, and 11 of the cases and 8 controls had lumbar spine radiographs. Each lumbar disc was scored for radiographic appearances and MR features of disc degeneration and disc protrusion. Proportion values for these parameters and median scores were derived at each disc level, and were analyzed and compared. There was a statistically-significant difference between proportion values of cases and controls for the MR features (P value=0.01, n=16) and the radiographic features (P value=0.01, n=11 cases, n=8 controls) of disc degeneration. The median disc level scores for the thalassemic group were uniformly high across all lumbar discs, and at all levels except at L 4/5. The control group conversely demonstrated a predilection for disc degeneration at L4/5 level. The distribution of lumbar disc degeneration in thalassemic patients with back pain is more extensive, severe and multi-level in nature compared to matched controls, and disc degeneration should be considered as a significant cause of back pain in this population group. (orig.)

  7. Degenerative disc disease as a cause of back pain in the thalassaemic population: a case-control study using MRI and plain radiographs

    International Nuclear Information System (INIS)

    Desigan, S.; Hall-Craggs, M.A.; Ho, C.-P.; Eliahoo, J.; Porter, J.B.

    2006-01-01

    The aim of this study was to test our observation that back pain in thalassemic patients could be caused by premature and extensive lumbar degenerative disc disease, when compared to non-thalassemic patients with back pain. Sixteen thalassemic patients with their sex- and age-matched controls were recruited into the study, 12 with thalassemia major, and 4 with thalassemia intermedia. Both the thalassemia patients and control subjects suffered from back pain, which was subjective rather than measured/pain scored. All subjects underwent magnetic resonance (MR) imaging of the lumbar spine, and 11 of the cases and 8 controls had lumbar spine radiographs. Each lumbar disc was scored for radiographic appearances and MR features of disc degeneration and disc protrusion. Proportion values for these parameters and median scores were derived at each disc level, and were analyzed and compared. There was a statistically-significant difference between proportion values of cases and controls for the MR features (P value=0.01, n=16) and the radiographic features (P value=0.01, n=11 cases, n=8 controls) of disc degeneration. The median disc level scores for the thalassemic group were uniformly high across all lumbar discs, and at all levels except at L 4/5. The control group conversely demonstrated a predilection for disc degeneration at L4/5 level. The distribution of lumbar disc degeneration in thalassemic patients with back pain is more extensive, severe and multi-level in nature compared to matched controls, and disc degeneration should be considered as a significant cause of back pain in this population group. (orig.)

  8. Connective Tissue Degeneration: Mechanisms of Palmar Fascia Degeneration (Dupuytren's Disease)

    NARCIS (Netherlands)

    Karkampouna, S.; Kreulen, M.; Obdeijn, M. C.; Kloen, P.; Dorjée, A. L.; Rivellese, F.; Chojnowski, A.; Clark, I.; Kruithof-de Julio, Marianna

    2016-01-01

    Dupuytren's disease is a connective tissue disorder of the hand causing excessive palmar fascial fibrosis with associated finger contracture and disability. The aetiology of the disease is heterogeneous, with both genetic and environmental components. The connective tissue is abnormally infiltrated

  9. Dynamic Stabilisation in the Treatment of Degenerative Disc Disease with Modic Changes

    Directory of Open Access Journals (Sweden)

    Olcay Eser

    2013-01-01

    Full Text Available Objective. Posterior dynamic stabilization is an effective alternative to fusion in the treatment of chronic instability and degenerative disc disease (DDD of the lumbar spine. This study was undertaken to investigate the efficacy of dynamic stabilization in chronic degenerative disc disease with Modic types 1 and 2. Modic types 1 and 2 degeneration can be painful. Classic approach in such cases is spine fusion. We operated 88 DDD patients with Modic types 1 and 2 via posterior dynamic stabilization. Good results were obtained after 2 years of followup. Methods. A total of 88 DDD patients with Modic types 1 and 2 were selected for this study. The patients were included in the study between 2004 and 2010. All of them were examined with lumbar anteroposterior (AP and lateral X-rays. Lordosis of the lumbar spine, segmental lordosis, and ratio of the height of the intervertebral disc spaces (IVSs were measured preoperatively and at 3, 12, and 24 months after surgery. Magnetic resonance imaging (MRI analysis was carried out, and according to the data obtained, the grade of disc degeneration was classified. The quality of life and pain scores were evaluated by visual analog scale (VAS score and Oswestry Disability Index (ODI preoperatively and at 3, 12, and 24 months after surgery. Appropriate statistical method was chosen. Results. The mean 3- and 12-month postoperative IVS ratio was significantly greater than that of the preoperative group (P0.05. Furthermore, the mean preoperative and 1 and 2 postoperative angles of lumbar lordosis and segmental lordosis were not significantly different (P>0.05. The mean VAS score and ODI, 3, 12, and 24 months after surgery, decreased significantly, when compared with the preoperative scores in the groups (P=0.000. Conclusion. Dynamic stabilization in chronic degenerative disc disease with Modic types 1 and 2 was effective.

  10. Early UV emission from disc-originated matter (DOM) in Type Ia supernovae in the double-degenerate scenario

    Science.gov (United States)

    Levanon, Naveh; Soker, Noam

    2017-09-01

    We show that the blue and UV excess emission in the first few days of some Type Ia supernovae (SNe Ia) can be accounted in the double-degenerate (DD) scenario by the collision of the SN ejecta with circumstellar matter that was blown by the accretion disc formed during the merger process of the two white dwarfs (WDs). We assume that in cases of excess early light, the disc blows the circumstellar matter, that we term disc-originated matter (DOM), hours to days before explosion. To perform our analysis, we first provide a model-based definition for early excess light, replacing the definition of excess light relative to a power-law fit to the rising luminosity. We then examine the light curves of the SNe Ia iPTF14atg and SN 2012cg, and find that the collision of the ejecta with a DOM in the frame of the DD scenario can account for their early excess emission. Thus, early excess light does not necessarily imply the presence of a stellar companion in the frame of the single-degenerate scenario. Our findings further increase the variety of phenomena that the DD scenario can account for, and emphasize the need to consider all different SN Ia scenarios when interpreting observations.

  11. The radiological diagnosis of thoracolumbar disc disease in the Dachshund

    International Nuclear Information System (INIS)

    Kirberger, R.M.; Roos, C.J.; Lubbe, A.M.

    1992-01-01

    The accuracy of survey radiographs in the diagnosis of acute thoracolumbar disc disease in 36 Dachshunds was determined by comparison with lumbar myelographic findings using iohexol. The value of making radiographs immediately after injection of contrast medium and the effectiveness of oblique radiographs in determining the exact circumferential distribution of extruding or protruding disc material were assessed. The presence of a double contrast medium column, resistance to injection and the presence of cerebrospinal fluid flow during needle placement was also evaluated. The location of the affected disc was accurately determined on survey radiographs in only 26 dogs. The myelographic technique used in this study resulted in the correct intervertebral space being identified, together with the exact circumferential distribution of disc material, in 35 dogs. Survey radiographs alone are inadequate for localization of protruding or extruding disc material

  12. Computer aided vertebral visualization and analysis: a methodology using the sand rat, a small animal model of disc degeneration

    Directory of Open Access Journals (Sweden)

    Hanley Edward N

    2003-03-01

    Full Text Available Abstract Background The purpose of this study is to present an automated system that analyzes digitized x-ray images of small animal spines identifying the effects of disc degeneration. The age-related disc and spine degeneration that occurs in the sand rat (Psammomys obesus has previously been documented radiologically; selected representative radiographs with age-related changes were used here to develop computer-assisted vertebral visualization/analysis techniques. Techniques presented here have the potential to produce quantitative algorithms that create more accurate and informative measurements in a time efficient manner. Methods Signal and image processing techniques were applied to digitized spine x-ray images the spine was segmented, and orientation and curvature determined. The image was segmented based on orientation changes of the spine; edge detection was performed to define vertebral boundaries. Once vertebrae were identified, a number of measures were introduced and calculated to retrieve information on the vertebral separation/orientation and sclerosis. Results A method is described which produces computer-generated quantitative measurements of vertebrae and disc spaces. Six sand rat spine radiographs illustrate applications of this technique. Results showed that this method can successfully automate calculation and analysis of vertebral length, vertebral spacing, vertebral angle, and can score sclerosis. Techniques also provide quantitative means to explore the relation between age and vertebral shape. Conclusions This method provides a computationally efficient system to analyze spinal changes during aging. Techniques can be used to automate the quantitative processing of vertebral radiographic images and may be applicable to human and other animal radiologic models of the aging/degenerating spine.

  13. Rabbit model of intervertebral disc degeneration by external compression device characterized by X-ray, MRI, histology, and cell viability

    Directory of Open Access Journals (Sweden)

    Ismail Ismail

    2006-12-01

    Full Text Available Appropriate experimental animal models, which mimic the degenerative process occurring in human intervertebral disc (IVD breakdown and can be used for new treatment studies such as tissue engineering or disc distraction are lacking. We studied the external compression device that used by Kroeber et al to create intervertebral disc degeneration in rabbit model characterized by X-ray, MRI, Histology, and Cell Viability. Ten NZW rabbit were randomly assigned to one of five groups. Intervertebral disc VL4-L5 are compressed using an external loading device, 1.9 MPa. First group rabbit are loaded for 14 days, second loaded for 28 days, thirth group are loaded for 14 days, and unloaded for 14 days, fourth group loaded for 28 days and unloaded for 28 days. The fifth group, rabbits underwent a sham operation. Additional, rabbits were used as sample for cell viability study. In disc height : sample in group one have biggest decreasing of disc height, that is 23.9 unit. In MRI assessment, the worst grade is grade 3. In histological score, the worst group is group three (58.69, and the best is group 4 (45.69. Group one have the largest dead cell, that are 403.5, and the smallest is group four (124.75. Trypan blue staining showed that group four have better viable cell (91.1 compare than group three (86.4. The study conclude disc degeneration can be created by external axial loading for 14 days in rabbit intervertebral disc. Duration of 28 days unloading gave better result for cells to recover. (Med J Indones 2006; 15:199-207  Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 Keywords: Rabbit model –intervertebral disc degeneration- external compression device-X-ray, MRI, Histology, and Cell viabilty /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso

  14. Ultrashort time-to-echo MRI of the cartilaginous endplate: technique and association with intervertebral disc degeneration

    International Nuclear Information System (INIS)

    Law, Travis; Anthony, Marina-Portia; Kim, Mina; Khong, Pek-Lan; Chan, Queenie; Samartzis, Dino

    2013-01-01

    The purpose of this study was to report the feasibility of the ultrashort time-to-echo (UTE) MRI technique to assess cartilaginous endplate (CEP) defects in humans in vivo and to assess their relationship with intervertebral disc (IVD) degeneration. Nine volunteer subjects (mean age=43.9 years; range=22–61 years) were recruited, representing 54 IVDs and 108 CEPs. The subjects underwent T2-weighted and UTE MRI to assess for the presence and severity of IVD degeneration, and for the presence of CEP defects, respectively, from T12 to S1. IVD degeneration was graded according to the Schneiderman et al. classification on T2-weighted MRI. CEP defects were defined on UTE MRI as discontinuity of high signal over four consecutive images and were independently assessed by two observers. Thirty-seven out of 108 (34.3%) CEPs had defects, which mainly occurred at T12/L1, L1/L2 and L4/L5 (P=0.008). Multivariate logistic regression revealed that lower body mass index (P=0.009) and younger (P=0.034) individuals had a decreased likelihood of having CEP defects. A statistically significant association was found to exist between the presence of CEP defects and IVD degeneration (P=0.036). A higher prevalence of degenerated IVDs with CEP defects was found at L4/5 and L5/S1, while degenerated IVDs with no CEP defects were found throughout the whole lumbar region. Mean IVD degeneration scores of the L4/5 and L5/S1 levels with CEP defects were higher in comparison with those with no CEP defects. Our study demonstrates the feasibility of using UTE MRI in humans in vivo to assess the integrity of the CEP. A statistically significant association was found to exist between the presence of CEP defects and IVD degeneration. In the lower lumbar region, more severe degeneration was found to occur in the IVDs with CEP defects than in those without defects.

  15. Anti-inflammatory Chitosan/Poly-γ-glutamic acid nanoparticles control inflammation while remodeling extracellular matrix in degenerated intervertebral disc.

    Science.gov (United States)

    Teixeira, Graciosa Q; Leite Pereira, Catarina; Castro, Flávia; Ferreira, Joana R; Gomez-Lazaro, Maria; Aguiar, Paulo; Barbosa, Mário A; Neidlinger-Wilke, Cornelia; Goncalves, Raquel M

    2016-09-15

    Intervertebral disc (IVD) degeneration is one of the most common causes of low back pain (LBP), the leading disorder in terms of years lived with disability. Inflammation can play a role in LPB, while impairs IVD regeneration. In spite of this, different inflammatory targets have been purposed in the context of IVD regeneration. Anti-inflammatory nanoparticles (NPs) of Chitosan and Poly-(γ-glutamic acid) with a non-steroidal anti-inflammatory drug, diclofenac (Df), were previously shown to counteract a pro-inflammatory response of human macrophages. Here, the effect of intradiscal injection of Df-NPs in degenerated IVD was evaluated. For that, Df-NPs were injected in a bovine IVD organ culture in pro-inflammatory/degenerative conditions, upon stimulation with needle-puncture and interleukin (IL)-1β. Df-NPs were internalized by IVD cells, down-regulating IL-6, IL-8, MMP1 and MMP3, and decreasing PGE2 production, compared with IL-1β-stimulated IVD punches. Interestingly, at the same time, Df-NPs promoted an up-regulation of extracellular matrix (ECM) proteins, namely collagen type II and aggrecan. Allover, this study suggests that IVD treatment with Df-NPs not only reduces inflammation, but also delays and/or decreases ECM degradation, opening perspectives to new intradiscal therapies for IVD degeneration, based on the modulation of inflammation. Degeneration of the IVD is an age-related progressive process considered to be the major cause of spine disorders. The pro-inflammatory environment and biomechanics of the degenerated IVD is a challenge for regenerative therapies. The novelty of this work is the intradiscal injection of an anti-inflammatory therapy based on Chitosan (Ch)/Poly-(γ-glutamic acid) (γ-PGA) nanoparticles (NPs) with an anti-inflammatory drug (diclofenac, Df), previously developed by us. This drug delivery system was tested in a pro-inflammatory/degenerative intervertebral disc ex vivo model. The main findings support the success of an anti

  16. Effect of Lumbar Disc Degeneration and Low-Back Pain on the Lumbar Lordosis in Supine and Standing

    DEFF Research Database (Denmark)

    Hansen, Bjarke B; Bendix, Tom; Grindsted, Jacob

    2015-01-01

    STUDY DESIGN: Cross-sectional study. OBJECTIVE: To examine the influence of low-back pain (LBP) and lumbar disc degeneration (LDD) on the lumbar lordosis in weight-bearing positional magnetic resonance imaging (pMRI). SUMMARY OF BACKGROUND DATA: The lumbar lordosis increases with a change...... of position from supine to standing and is known as an essential contributor to dynamic changes. However, the lordosis may be affected by disc degeneration and pain. METHODS: Patients with LBP >40 on a 0 to 100 mm Visual Analog Scale (VAS) both during activity and rest and a sex and age-decade matching...... control group without LBP were scanned in the supine and standing position in a 0.25-T open MRI unit. LDD was graded using Pfirrmann's grading-scale. Subsequently, the L2-to-S1 lumbar lordosis angle (LA) was measured. RESULTS: Thirty-eight patients with an average VAS of 58 (±13.8) mm during rest and 75...

  17. Is the transport of a gadolinium-based contrast agent decreased in a degenerated or aged disc? A post contrast MRI study.

    Directory of Open Access Journals (Sweden)

    Marta Tibiletti

    Full Text Available A post contrast magnetic resonance imaging study has been performed in a wide population of low back pain patients to investigate which radiological and phenotypic characteristics influence the penetration of the contrast agent in lumbar discs in vivo. 37 patients affected by different pathologies (disc herniation, spondylolisthesis, foraminal stenosis, central canal stenosis were enrolled in the study. The selected population included 26 male and 11 female subjects, with a mean age of 42.4 ± 9.3 years (range 18-60. Magnetic resonance images of the lumbar spine were obtained with a 1.5 T scanner (Avanto, Siemens, Erlangen, Germany with a phased-array back coil. A paramagnetic non-ionic contrast agent was injected with a dose of 0.4 ml/kg. T1-weighted magnetic resonance images were subsequently acquired at 5 time points, 5 and 10 minutes, 2, 4 and 6 hours after injection. Endplates presented clear enhancement already 5 minutes after injection, and showed an increase in the next 2 hours followed by a decrease. At 5 and 10 minutes, virtually no contrast medium was present inside the intervertebral disc; afterwards, enhancement significantly increased. Highly degenerated discs showed higher enhancement in comparison with low and medium degenerated discs. Discs classified as Pfirrmann 5 showed a statistically significant higher enhancement than Pfirrmann 1, 2 and 3 at all time points but the first one, possibly due to vascularization. Disc height collapse and Modic changes significantly increased enhancement. Presence of endplate defects did not show any significant influence on post contrast enhancement, but the lack of a clear classification of endplate defects as seen on magnetic resonance scans may be shadowing some effects. In conclusion, disc height, high level of degeneration and presence of Modic changes are factors which increase post contrast enhancement in the intervertebral disc. The effect of age could not be demonstrated.

  18. Progression, incidence, and risk factors for intervertebral disc degeneration in a longitudinal population-based cohort: the Wakayama Spine Study.

    Science.gov (United States)

    Teraguchi, M; Yoshimura, N; Hashizume, H; Yamada, H; Oka, H; Minamide, A; Nagata, K; Ishimoto, Y; Kagotani, R; Kawaguchi, H; Tanaka, S; Akune, T; Nakamura, K; Muraki, S; Yoshida, M

    2017-07-01

    The present study examined the progression, incidence, and risk factors for intervertebral disc degeneration (DD) throughout the lumbar spine using magnetic resonance imaging (MRI) in a large population-based cohort. We followed up 617 subjects for more than 4 years as part of the Wakayama Spine Study. 1) "Progression of DD" in each of the entire, upper (L1/2 to L3/4) and lower (L4/5 and L5/S1) lumbar spine was defined as Pfirrmann grade progression at follow-up in at least one disc in the affected region. 2) "Incidence of DD" in each of these regions was defined if all discs were grade 3 or lower (white disc) at baseline, and at least one disc had progressed to grade 4 or higher (black disc) at follow-up. Logistic regression analyses were used to determine the risk factors for progression and incidence of DD. DD progression and incidence in the entire lumbar spine were 52.0% and 31.6% in men, and 60.4% and 44.7% in women, respectively. Women was associated with DD progression in the upper lumbar spine (odds ratio [OR] = 1.68, 95% confidence interval [CI] = 1.18-2.42). Aging was associated with the incidence of DD in each region (entire: OR = 1.14, CI = 1.06-1.14; upper: OR = 1.10, CI = 1.05-1.15; lower: OR = 1.11, CI = 1.05-1.19). Diabetes mellitus (DM) was associated with the incidence of DD in the upper lumbar spine (OR = 6.83, CI = 1.07-133.7). This 4-year longitudinal study is the first to demonstrate DD progression and incidence in the lumbar spine and their risk factors in a large population-based cohort. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  19. Predictive factors associated with neck pain in patients with cervical disc degeneration

    Science.gov (United States)

    Kong, Lingde; Tian, Weifeng; Cao, Peng; Wang, Haonan; Zhang, Bing; Shen, Yong

    2017-01-01

    Abstract The predictive factors associated with neck pain remain unclear. We conducted a cross-sectional study to assess predictive factors, especially Modic changes (MCs), associated with the intensity and duration of neck pain in patients with cervical disc degenerative disease. We retrospectively reviewed patients in our hospital from January 2013 to December 2016. Severe neck pain (SNP) and persistent neck pain (PNP) were the 2 main outcomes, and were assessed based on the numerical rating scale (NRS). Basic data, and also imaging data, were collected and analyzed as potential predictive factors. Univariate analysis and multiple logistic regression analysis were performed to assess the predictive factors for neck pain. In all, 381 patients (193 males and 188 females) with cervical degenerative disease were included in our study. The number of patients with SNP and PNP were 94 (24.67%) and 109 (28.61%), respectively. The NRS of neck pain in patients with type 1 MCs was significantly higher than type 2 MCs (4.8 ± 0.9 vs 3.9 ± 1.1; P = .004). The multivariate logistic analysis showed that kyphosis curvature (odds ratio [OR] 1.082, 95% confidence interval [CI] 1.044–1.112), spondylolisthesis (OR 1.339, 95% CI 1.226–1.462), and annular tear (OR 1.188, 95% CI 1.021–1.382) were factors associated with SNP, whereas kyphosis curvature (OR 1.568, 95% CI 1.022–2.394), spondylolisthesis (OR 1.486, 95% CI 1.082–2.041), and MCs (OR 1.152, 95% CI 1.074–1.234) were associated with PNP. We concluded that kyphosis curvature, spondylolisthesis, and annular tear are associated with SNP, whereas kyphosis curvature, spondylolisthesis, and MCs are associated with PNP. This study supports the view that MCs can lead to a long duration of neck pain. PMID:29069048

  20. Intervertebral disc disease in dogs - Part 2: Comparison of clinical, magnetic resonance imaging, and histological findings in 74 surgically treated dogs

    NARCIS (Netherlands)

    Kranenburg, H.C.; Grinwis, G.C.M.; Bergknut, N.; Gahrmann, Ninke; Voorhout, G.; Hazewinkel, H.A.W.

    The relationship between intervertebral disc (IVD) disease and IVD degeneration remains unclear. The aim of the present study was to compare the clinical severity of IVD herniation (IVDH), determined with a neurological grading system, with findings of magnetic resonance imaging (MRI) and

  1. Inflammatory microRNA-194 and -515 attenuate the biosynthesis of chondroitin sulfate during human intervertebral disc degeneration.

    Science.gov (United States)

    Hu, Bo; Xu, Chen; Tian, Ye; Shi, Changgui; Zhang, Ying; Deng, Lianfu; Zhou, Hongyu; Cao, Peng; Chen, Huajiang; Yuan, Wen

    2017-07-25

    Intervertebral disc degeneration (IDD) is characterized by dehydration and loss of extracellular matrixes in the nucleus pulposus region. Chondroitin sulfate has been found to be the water-binding molecule that played a key role in IDD. Although investigators have reported that inflammatory cytokines are involved in the reduction of chondroitin sulfate in IDD, but the underlying mechanism is unrevealed. Since chondroitin sulfate synthesis is controlled by chondroitin sulfate glycosyltransferases CHSY-1/2/3 and CSGALNACT-1/2, their functional role and regulatory mechanism in IDD is not fully studied. Here, we set out to investigate the function and regulatory roles of these factors during IDD development. We found that among these chondroitin sulfate glycosyltransferases, CHSY-1/2/3 are significantly down-regulated in severe IDD samples than mild IDD samples. In vitro experiments revealed that Interleukin-1β and Tumor Necrosis Factor-α stimulation led to significant reduction of CHSY-1/2/3 at protein level than mRNA level in NP cells, indicating a post-transcriptional regulatory mechanisms are involved. By computational prediction and analysis, we found that inflammatory cytokines stimulated microRNA-194 and -515 target CHSY-1/2/3 mRNA and significantly interrupt their translation and downstream chondroitin sulfate deposition. Inhibition of microRNA-194 and -515 however, significantly rescued CHSY-1/2/3 expressions and chondroitin sulfate deposition. These findings together demonstrated a vital role of inflammatory stimulated microRNAs in promoting intervertebral disc degeneration by interrupt chondroitin sulfate synthesis, which may provide new insights into the mechanism and therapeutic approaches in IDD.

  2. Sirtuin 6 prevents matrix degradation through inhibition of the NF-κB pathway in intervertebral disc degeneration

    International Nuclear Information System (INIS)

    Kang, Liang; Hu, Jia; Weng, Yuxiong; Jia, Jie; Zhang, Yukun

    2017-01-01

    Intervertebral disc degeneration (IDD) is marked by imbalanced metabolism of the extracellular matrix (ECM) in the nucleus pulposus (NP) of intervertebral discs. This study aimed to determine whether sirtuin 6 (SIRT6), a member of the sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylases, protects the NP from ECM degradation in IDD. Our study showed that expression of SIRT6 markedly decreased during IDD progression. Overexpression of wild-type SIRT6, but not a catalytically inactive mutant, prevented IL-1β-induced NP ECM degradation. SIRT6 depletion by RNA interference in NP cells caused ECM degradation. Moreover, SIRT6 physically interacted with nuclear factor-κB (NF-κB) catalytic subunit p65, transcriptional activity of which was significantly suppressed by SIRT6 overexpression. These results suggest that SIRT6 prevented NP ECM degradation in vitro via inhibiting NF-κB-dependent transcriptional activity and that this effect depended on its deacetylase activity. - Highlights: • SIRT6 expression is decreased in degenerative nucleus pulposus (NP) tissues. • SIRT6 overexpression lowers IL-1β-induced matrix degradation of NP. • SIRT6 inhibition induces matrix degradation of NP. • SIRT6 prevents matrix degradation of NP via the NF-κB signaling pathway.

  3. Sirtuin 6 prevents matrix degradation through inhibition of the NF-κB pathway in intervertebral disc degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Liang [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Hu, Jia [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Weng, Yuxiong [Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Jia, Jie [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Zhang, Yukun, E-mail: zhangyukuncom@126.com [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China)

    2017-03-15

    Intervertebral disc degeneration (IDD) is marked by imbalanced metabolism of the extracellular matrix (ECM) in the nucleus pulposus (NP) of intervertebral discs. This study aimed to determine whether sirtuin 6 (SIRT6), a member of the sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylases, protects the NP from ECM degradation in IDD. Our study showed that expression of SIRT6 markedly decreased during IDD progression. Overexpression of wild-type SIRT6, but not a catalytically inactive mutant, prevented IL-1β-induced NP ECM degradation. SIRT6 depletion by RNA interference in NP cells caused ECM degradation. Moreover, SIRT6 physically interacted with nuclear factor-κB (NF-κB) catalytic subunit p65, transcriptional activity of which was significantly suppressed by SIRT6 overexpression. These results suggest that SIRT6 prevented NP ECM degradation in vitro via inhibiting NF-κB-dependent transcriptional activity and that this effect depended on its deacetylase activity. - Highlights: • SIRT6 expression is decreased in degenerative nucleus pulposus (NP) tissues. • SIRT6 overexpression lowers IL-1β-induced matrix degradation of NP. • SIRT6 inhibition induces matrix degradation of NP. • SIRT6 prevents matrix degradation of NP via the NF-κB signaling pathway.

  4. Molecular Therapy for Degenerative Disc Disease: Clues from Secretome Analysis of the Notochordal Cell-Rich Nucleus Pulposus

    Science.gov (United States)

    Matta, Ajay; Karim, M. Zia; Isenman, David E.; Erwin, W. Mark

    2017-01-01

    Degenerative disc disease (DDD) is associated with spinal pain often leading to long-term disability. However, the non-chondrodystrophic canine intervertebral disc is protected from the development of DDD, ostensibly due to its retention of notochordal cells (NC) in the nucleus pulposus (NP). In this study, we hypothesized that secretome analysis of the NC-rich NP will lead to the identification of key proteins that delay the onset of DDD. Using mass-spectrometry, we identified 303 proteins including components of TGFβ- and Wnt-signaling, anti-angiogeneic factors and proteins that inhibit axonal ingrowth in the bioactive fractions of serum free, notochordal cell derived conditioned medium (NCCM). Ingenuity Pathway Analysis revealed TGFβ1 and CTGF as major hubs in protein interaction networks. In vitro treatment with TGFβ1 and CTGF promoted the synthesis of healthy extra-cellular matrix proteins, increased cell proliferation and reduced cell death in human degenerative disc NP cells. A single intra-discal injection of recombinant TGFβ1 and CTGF proteins in a pre-clinical rat-tail disc injury model restored the NC and stem cell rich NP. In conclusion, we demonstrate the potential of TGFβ1 and CTGF to mitigate the progression of disc degeneration and the potential use of these molecules in a molecular therapy to treat the degenerative disc. PMID:28358123

  5. Dysregulated miR-127-5p contributes to type II collagen degradation by targeting matrix metalloproteinase-13 in human intervertebral disc degeneration.

    Science.gov (United States)

    Hua, Wen-Bin; Wu, Xing-Huo; Zhang, Yu-Kun; Song, Yu; Tu, Ji; Kang, Liang; Zhao, Kang-Cheng; Li, Shuai; Wang, Kun; Liu, Wei; Shao, Zeng-Wu; Yang, Shu-Hua; Yang, Cao

    2017-08-01

    Intervertebral disc degeneration (IDD) is a chronic disease associated with the degradation of extracellular matrix (ECM). Matrix metalloproteinase (MMP)-13 is a major enzyme that mediates the degradation of ECM components. MMP-13 has been predicted to be a potential target of miR-127-5p. However, the exact function of miR-127-5p in IDD is still unclear. We designed this study to evaluate the correlation between miR-127-5p level and the degeneration of human intervertebral discs and explore the potential mechanisms. miR-127-5p levels and MMP-13 mRNA levels were detected by quantitative real-time polymerase chain reaction (qPCR). To determine whether MMP-13 is a target of miR-127-5p, dual luciferase reporter assays were performed. miR-127-5p mimic and miR-127-5p inhibitor were used to overexpress or downregulate miR-127-5p expression in human NP cells, respectively. Small interfering RNA (siRNA) was used to knock down MMP-13 expression in human NP cells. Type II collagen expression in human NP cells was detected by qPCR, western blotting, and immunofluorescence staining. We confirmed that miR-127-5p was significantly downregulated in nucleus pulposus (NP) tissue of degenerative discs and its expression was inversely correlated with MMP-13 mRNA levels. We reveal that MMP-13 may act as a target of miR-127-5p. Expression of miR-127-5p was inversely correlated with type II collagen expression in human NP cells. Moreover, suppression of MMP-13 expression by siRNA blocked downstream signaling and increased type II collagen expression. Dysregulated miR-127-5p contributed to the degradation of type II collagen by targeting MMP-13 in human IDD. Our findings highlight that miR-127-5p may serve as a new therapeutic target in IDD. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  6. Cell-Based Therapies Used to Treat Lumbar Degenerative Disc Disease: A Systematic Review of Animal Studies and Human Clinical Trials

    Directory of Open Access Journals (Sweden)

    David Oehme

    2015-01-01

    Full Text Available Low back pain and degenerative disc disease are a significant cause of pain and disability worldwide. Advances in regenerative medicine and cell-based therapies, particularly the transplantation of mesenchymal stem cells and intervertebral disc chondrocytes, have led to the publication of numerous studies and clinical trials utilising these biological therapies to treat degenerative spinal conditions, often reporting favourable outcomes. Stem cell mediated disc regeneration may bridge the gap between the two current alternatives for patients with low back pain, often inadequate pain management at one end and invasive surgery at the other. Through cartilage formation and disc regeneration or via modification of pain pathways stem cells are well suited to enhance spinal surgery practice. This paper will systematically review the current status of basic science studies, preclinical and clinical trials utilising cell-based therapies to repair the degenerate intervertebral disc. The mechanism of action of transplanted cells, as well as the limitations of published studies, will be discussed.

  7. Análise radiológica da degeneração discal experimental em coelhos Radiological analysis of experimental disc degeneration in rabbits

    Directory of Open Access Journals (Sweden)

    Emiliano Vialle

    2009-01-01

    Full Text Available OBJETIVO: Validar a avaliação radiográfica da degeneração discal experimental em coelhos. MÉTODOS: Os discos intervertebrais lombares de coelhos New Zealand foram puncionados três vezes com uma agulha 18G com profundidade limitada de 5mm, através de abordagem lateral. Foram realizadas radiografias seriadas pré e pós-operatórias imediatas, e depois de quatro, oito e 12 semanas do procedimento, com posterior análise da altura discal, formação de osteófito, esclerose da placa vertebral e presença de degeneração discal. A análise estatística dos dados foi validada pelo coeficiente de concordância Kappa, com intervalo de confiança (IC de 95%. RESULTADOS: Observou-se diminuição significativa do espaço discal nas radiografias em AP após 12 semanas de pós-operatório, com Kappa = 0,489 para IC 95% (0,25-0,72 com p OBJECTIVE: To validate radiographic evaluation of a rabbit model for disc degeneration. METHODS: Lumbar intervertebral discs of New Zealand rabbits were stabbed three times with a 18G needle at a limited depth of 5mm, through lateral approach. Serial radiographic images were taken on the early pre-and postoperative periods, and after four, eight and 12 weeks of the procedure, with subsequent analysis of disc height, osteophyte formation, endplate sclerosis, and presence of disc degeneration. The statistical analysis of data was validated by the Kappa coefficient, with a confidence interval (CI of 95%. RESULTS: A significant reduction of disc space was found on AP X-ray images after 12 postoperative weeks, with Kappa = 0.489 for CI 95% (0.25-0.72 with p < 0.001. X-ray signs of disc degeneration also presented Kappa = 0.63 for CI 95% (0.39-0.86 with p < 0.001. The remaining assessed criteria showed positive results, but with a lower Kappa value. CONCLUSION: The disc degeneration model using rabbits as proposed in this study was shown to be feasible, with positive X-ray correlation between pre- and postoperative images

  8. MRI-based relationships between spine pathology, intervertebral disc degeneration, and muscle fatty infiltration in chondrodystrophic and non-chondrodystrophic dogs.

    Science.gov (United States)

    Lerer, Assaf; Nykamp, Stephanie G; Harriss, Alexandra B; Gibson, Thomas W G; Koch, Thomas G; Brown, Stephen H M

    2015-11-01

    Human studies have revealed a link between muscle degeneration and low back pain, although the cause and effect of this relationship is not clear. Dogs provide a naturally developing model of intervertebral disc (IVD)-related low back pain that may provide insight into relationships between IVD and muscle degeneration. This study aimed to quantify, via magnetic resonance imaging (MRI), the magnitude and location of fatty infiltration in spine muscles of chondrodystrophic (CD) and non-chondrodystrophic (NCD) dogs suffering from both intervertebral disc herniation (IVDH) and non-disc-related spinal disorders, and relate this to intervertebral disc degeneration (IVDD). This study used retrospective MRI-based analysis of IVDD and muscle fatty infiltration in CD and NCD dogs. A portion of this study was funded ($1,000) by the Pet Trust Fund, Ontario Veterinary College. Magnetic resonance imaging from 180 dogs were separated into four groups: (1) CD with IVDH; (2) CD with non-IVDH spinal pathology; (3) NCD with IVDH; (4) NCD with non-IVDH spinal pathology. For each dog at intervertebral levels T12-T13 to L6-L7, IVDD was subjectively graded and muscle-fat indices (MFIndices) were quantified for multifidus, erector spinae, and psoas muscle groups. Intervertebral disc degeneration grade was higher (ppathology. Muscle-fat indices of multifidus and psoas were higher (ppathology compared with dogs with IVDH. Erector spinae demonstrated higher (ppathology. Dog groups with higher average IVDD grades demonstrated less fatty infiltration within their multifidus and psoas muscles, compared with groups with lower IVDD grades. This finding was consistent across both CD and NCD breeds as well as across dogs presenting with IVDH and those presenting with a non-IVDH spinal pathology. Thus, the presence or severity of IVDD is not uniquely related to fatty infiltration in these muscles, but rather the presence, or possibly severity or chronicity, of general spine pathology is likely a

  9. The Pfirrmann classification of lumbar intervertebral disc degeneration: an independent inter- and intra-observer agreement assessment.

    Science.gov (United States)

    Urrutia, Julio; Besa, Pablo; Campos, Mauricio; Cikutovic, Pablo; Cabezon, Mario; Molina, Marcelo; Cruz, Juan Pablo

    2016-09-01

    Grading inter-vertebral disc degeneration (IDD) is important in the evaluation of many degenerative conditions, including patients with low back pain. Magnetic resonance imaging (MRI) is considered the best imaging instrument to evaluate IDD. The Pfirrmann classification is commonly used to grade IDD; the authors describing this classification showed an adequate agreement using it; however, there has been a paucity of independent agreement studies using this grading system. The aim of this study was to perform an independent inter- and intra-observer agreement study using the Pfirrmann classification. T2-weighted sagittal images of 79 patients consecutively studied with lumbar spine MRI were classified using the Pfirrmann grading system by six evaluators (three spine surgeons and three radiologists). After a 6-week interval, the 79 cases were presented to the same evaluators in a random sequence for repeat evaluation. The intra-class correlation coefficient (ICC) and the weighted kappa (wκ) were used to determine the inter- and intra-observer agreement. The inter-observer agreement was excellent, with an ICC = 0.94 (0.93-0.95) and wκ = 0.83 (0.74-0.91). There were no differences between spine surgeons and radiologists. Likewise, there were no differences in agreement evaluating the different lumbar discs. Most differences among observers were only of one grade. Intra-observer agreement was also excellent with ICC = 0.86 (0.83-0.89) and wκ = 0.89 (0.85-0.93). In this independent study, the Pfirrmann classification demonstrated an adequate agreement among different observers and by the same observer on separate occasions. Furthermore, it allows communication between radiologists and spine surgeons.

  10. Degree of tendon degeneration and stage of rotator cuff disease.

    Science.gov (United States)

    Jo, Chris Hyunchul; Shin, Won Hyoung; Park, Ji Wan; Shin, Ji Sun; Kim, Ji Eun

    2017-07-01

    While tendon degeneration has been known to be an important cause of rotator cuff disease, few studies have objectively proven the association of tendon degeneration and rotator cuff disease. The purpose of this study was to investigate changes of tendon degeneration with respect to the stage of rotator cuff disease. A total of 48 patients were included in the study: 12 with tendinopathy, 12 with a partial-thickness tear (pRCT), 12 with a full-thickness tear (fRCT), and 12 as the control. A full-thickness supraspinatus tendon sample was harvested en bloc from the middle portion between the lateral edge and the musculotendinous junction of the tendon using a biopsy punch with a diameter of 3 mm. Harvested samples were evaluated using a semi-quantitative grading scale with 7 parameters after haematoxylin and eosin staining. There was no significant difference in age, gender, symptom duration, and Kellgren-Lawrence grade between the groups except for the global fatty degeneration index. All of the seven parameters were significantly different between the groups and could be categorized as follows: early responders (fibre structure and arrangement), gradual responder (rounding of the nuclei), after-tear responders (cellularity, vascularity, and stainability), and late responder (hyalinization). The total degeneration scores were not significantly different between the control (6.08 ± 1.16) and tendinopathy (6.67 ± 1.83) (n.s.). However, the score of pRCT group (10.42 ± 1.31) was greater than that of tendinopathy (P rotator cuff disease progresses from tendinopathy to pRCT, and then to fRCT. The degree of degeneration of tendinopathy was not different from that of normal but aged tendons, and significant tendon degeneration began from the stage of pRCT. The clinical relevance of the study is that strategies and goals of the treatment for rotator cuff disease should be specific to its stage, in order to prevent disease progression for tendinopathy and pRCT, as

  11. Lumbar paraspinal muscle fat infiltration is independently associated with sex, age, and inter-vertebral disc degeneration in symptomatic patients.

    Science.gov (United States)

    Urrutia, Julio; Besa, Pablo; Lobos, Daniel; Campos, Mauricio; Arrieta, Cristobal; Andia, Marcelo; Uribe, Sergio

    2018-01-29

    To determine the association of paraspinal muscles and psoas relative cross-sectional area (RCSA) and fat signal fraction (FSF) with sex, age, and intervertebral disc degeneration (IDD) in symptomatic patients. We retrospectively evaluated 80 adult patients with spinal symptoms using T2-weighted magnetic resonance images. We determined RCSA and FSF of the paraspinal muscles (erector spinae and multifidus) and psoas from L1-L2 to L5-S1; we determined IDD using the Pfirrmann classification. We compared differences in muscle RCSA and FSF based on sex and IDD, and we correlated age and IDD with RCSA and FSF. Using multivariate linear regression analyses, we determined the impact of sex, age, and IDD on RCSA and FSF. Men exhibited larger psoas RCSA but not larger paraspinal muscles RCSA than women. Women had larger FSF in the paraspinal muscles and psoas. Increasing IDD was associated with larger FSF if ≥2 Pfirrmann grades were observed. IDD correlated with FSF of the paraspinal muscles, and age correlated with FSF of the paraspinal muscles and psoas. IDD was less consistently correlated with RCSA, but age correlated negatively with RCSA of all three muscles. Linear regression analyses demonstrated that sex, age, and IDD were each independently associated with FSF of the paraspinal muscles; additionally, sex and age, but not IDD, were associated with psoas FSF. RCSA was less consistently influenced by these three variables. Sex, age, and IDD are independently associated with paraspinal muscles FSF; only sex and age influence psoas FSF.

  12. Effect of Lumbar Disc Degeneration and Low-Back Pain on the Lumbar Lordosis in Supine and Standing: A Cross-Sectional MRI Study.

    Science.gov (United States)

    Hansen, Bjarke B; Bendix, Tom; Grindsted, Jacob; Bliddal, Henning; Christensen, Robin; Hansen, Philip; Riis, Robert G C; Boesen, Mikael

    2015-11-01

    Cross-sectional study. To examine the influence of low-back pain (LBP) and lumbar disc degeneration (LDD) on the lumbar lordosis in weight-bearing positional magnetic resonance imaging (pMRI). The lumbar lordosis increases with a change of position from supine to standing and is known as an essential contributor to dynamic changes. However, the lordosis may be affected by disc degeneration and pain. Patients with LBP >40 on a 0 to 100 mm Visual Analog Scale (VAS) both during activity and rest and a sex and age-decade matching control group without LBP were scanned in the supine and standing position in a 0.25-T open MRI unit. LDD was graded using Pfirrmann's grading-scale. Subsequently, the L2-to-S1 lumbar lordosis angle (LA) was measured. Thirty-eight patients with an average VAS of 58 (±13.8) mm during rest and 75 (±5.0) mm during activities, and 38 healthy controls were included. MRI findings were common in both groups, whereas, the summation of the Pfirrmann's grades (LDD-score) was significantly higher in the patients [(MD 1.44; 95% confidence intervals (CI) 0.80 to 2.10; P lordosis between the positions may be independent of pain. Decreasing lordosis change seems to be associated with age-related increasing disc degeneration in healthy individuals. 2.

  13. Quantitative T2 magnetic resonance imaging compared to morphological grading of the early cervical intervertebral disc degeneration: an evaluation approach in asymptomatic young adults.

    Directory of Open Access Journals (Sweden)

    Chun Chen

    Full Text Available OBJECTIVE: The objective of this study was to evaluate the efficacy of quantitative T2 magnetic resonance imaging (MRI for quantifying early cervical intervertebral disc (IVD degeneration in asymptomatic young adults by correlating the T2 value with Pfirrmann grade, sex, and anatomic level. METHODS: Seventy asymptomatic young subjects (34 men and 36 women; mean age, 22.80±2.11 yr; range, 18-25 years underwent 3.0-T MRI to obtain morphological data (one T1-fast spin echo (FSE and three-plane T2-FSE, used to assign a Pfirrmann grade (I-V and for T2 mapping (multi-echo spin echo. T2 values in the nucleus pulposus (NP, n = 350 and anulus fibrosus (AF, n = 700 were obtained. Differences in T2 values between sexes and anatomic level were evaluated, and linear correlation analysis of T2 values versus degenerative grade was conducted. FINDINGS: Cervical IVDs of healthy young adults were commonly determined to be at Pfirrmann grades I and II. T2 values of NPs were significantly higher than those of AF at all anatomic levels (P0.05. T2 values decreased linearly with degenerative grade. Linear correlation analysis revealed a strong negative association between the Pfirrmann grade and the T2 values of the NP (P = 0.000 but not the T2 values of the AF (P = 0.854. However, non-degenerated discs (Pfirrmann grades I and II showed a wide range of T2 relaxation time. T2 values according to disc degeneration level classification were as follows: grade I (>62.03 ms, grade II (54.60-62.03 ms, grade III (<54.60 ms. CONCLUSIONS: T2 quantitation provides a more sensitive and robust approach for detecting and characterizing the early stage of cervical IVD degeneration and to create a reliable quantitative in healthy young adults.

  14. Quantitative T2 magnetic resonance imaging compared to morphological grading of the early cervical intervertebral disc degeneration: an evaluation approach in asymptomatic young adults.

    Science.gov (United States)

    Chen, Chun; Huang, Minghua; Han, Zhihua; Shao, Lixin; Xie, Yan; Wu, Jianhong; Zhang, Yan; Xin, Hongkui; Ren, Aijun; Guo, Yong; Wang, Deli; He, Qing; Ruan, Dike

    2014-01-01

    The objective of this study was to evaluate the efficacy of quantitative T2 magnetic resonance imaging (MRI) for quantifying early cervical intervertebral disc (IVD) degeneration in asymptomatic young adults by correlating the T2 value with Pfirrmann grade, sex, and anatomic level. Seventy asymptomatic young subjects (34 men and 36 women; mean age, 22.80±2.11 yr; range, 18-25 years) underwent 3.0-T MRI to obtain morphological data (one T1-fast spin echo (FSE) and three-plane T2-FSE, used to assign a Pfirrmann grade (I-V)) and for T2 mapping (multi-echo spin echo). T2 values in the nucleus pulposus (NP, n = 350) and anulus fibrosus (AF, n = 700) were obtained. Differences in T2 values between sexes and anatomic level were evaluated, and linear correlation analysis of T2 values versus degenerative grade was conducted. Cervical IVDs of healthy young adults were commonly determined to be at Pfirrmann grades I and II. T2 values of NPs were significantly higher than those of AF at all anatomic levels (P0.05). T2 values decreased linearly with degenerative grade. Linear correlation analysis revealed a strong negative association between the Pfirrmann grade and the T2 values of the NP (P = 0.000) but not the T2 values of the AF (P = 0.854). However, non-degenerated discs (Pfirrmann grades I and II) showed a wide range of T2 relaxation time. T2 values according to disc degeneration level classification were as follows: grade I (>62.03 ms), grade II (54.60-62.03 ms), grade III (T2 quantitation provides a more sensitive and robust approach for detecting and characterizing the early stage of cervical IVD degeneration and to create a reliable quantitative in healthy young adults.

  15. Association of age-related macular degeneration and reticular macular disease with cardiovascular disease.

    Science.gov (United States)

    Rastogi, Neelesh; Smith, R Theodore

    2016-01-01

    Age-related macular degeneration is the leading cause of adult blindness in the developed world. Thus, major endeavors to understand the risk factors and pathogenesis of this disease have been undertaken. Reticular macular disease is a proposed subtype of age-related macular degeneration correlating histologically with subretinal drusenoid deposits located between the retinal pigment epithelium and the inner segment ellipsoid zone. Reticular lesions are more prevalent in females and in older age groups and are associated with a higher mortality rate. Risk factors for developing age-related macular degeneration include hypertension, smoking, and angina. Several genes related to increased risk for age-related macular degeneration and reticular macular disease are also associated with cardiovascular disease. Better understanding of the clinical and genetic risk factors for age-related macular degeneration and reticular macular disease has led to the hypothesis that these eye diseases are systemic. A systemic origin may help to explain why reticular disease is diagnosed more frequently in females as males suffer cardiovascular mortality at an earlier age, before the age of diagnosis of reticular macular disease and age-related macular degeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Effects of annulus defects and implantation of poly(lactic-co-glycolic acid) (PLGA)/fibrin gel scaffolds on nerves ingrowth in a rabbit model of annular injury disc degeneration.

    Science.gov (United States)

    Xin, Long; Xu, Weixing; Yu, Leijun; Fan, Shunwu; Wang, Wei; Yu, Fang; Wang, Zhenbin

    2017-05-12

    Growth of nerve fibers has been shown to occur in a rabbit model of intravertebral disc degeneration (IVD) induced by needle puncture. As nerve growth may underlie the process of chronic pain in humans affected by disc degeneration, we sought to investigate the factors underlying nerve ingrowth in a minimally invasive annulotomy rabbit model of IVD by comparing the effects of empty disc defects with those of defects filled with poly(lactic-co-glycolic acid)/fibrin gel (PLGA) plugs. New Zealand white rabbits (n = 24) received annular injuries at three lumbar levels (L3/4, L4/5, and L5/6). The discs were randomly assigned to four groups: (a) annular defect (1.8-mm diameter; 4-mm depth) by mini-trephine, (b) annular defect implanted with a PLGA scaffold containing a fibrin gel, (c) annular puncture by a 16G needle (5-mm depth), and (d) uninjured L2/3 disc (control). Disc degeneration was evaluated by radiography, MRI, histology, real-time PCR, and analysis of proteoglycan (PG) content. Nerve ingrowth into the discs was assessed by immunostaining with the nerve marker protein gene product 9.5. Injured discs showed a progressive disc space narrowing with significant disc degeneration and proteoglycan loss, as confirmed by imaging results, molecular and compositional analysis, and histological examinations. In 16G punctured discs, nerve ingrowth was observed on the surface of scar tissue. In annular defects, nerve fibers were found to be distributed along small fissures within the fibrocartilaginous-like tissue that filled the AF. In discs filled with PLGA/ fibrin gel, more nerve fibers were observed growing deeper into the inner AF along the open annular track.  In addition, innervations scores showed significantly higher than those of punctured discs and empty defects. A limited vascular proliferation was found in the injured sites and regenerated tissues. Nerve ingrowth was significantly higher in PLGA/fibrin-filled discs than in empty defects. Possible

  17. Retina image–based optic disc segmentation

    Directory of Open Access Journals (Sweden)

    Ching-Lin Wang

    2016-05-01

    Full Text Available The change of optic disc can be used to diagnose many eye diseases, such as glaucoma, diabetic retinopathy and macular degeneration. Moreover, retinal blood vessel pattern is unique for human beings even for identical twins. It is a highly stable pattern in biometric identification. Since optic disc is the beginning of the optic nerve and main blood vessels in retina, it can be used as a reference point of identification. Therefore, optic disc segmentation is an important technique for developing a human identity recognition system and eye disease diagnostic system. This article hence presents an optic disc segmentation method to extract the optic disc from a retina image. The experimental results show that the optic disc segmentation method can give impressive results in segmenting the optic disc from a retina image.

  18. Progressive neuronal degeneration of childhood with liver disease

    International Nuclear Information System (INIS)

    Kendall, B.E.; Boyd, S.G.; Egger, J.; Harding, B.N.

    1987-01-01

    The clinical, electrophysiological and neuroradiological features of thirteen patients suffering from progressive neuronal degeneration of childhood with liver failure are presented. The disease commonly presents very early in life with progressive mental retardation, followed by intractable epilepsy, and should be suspected clinically especially if there is a family history of similar disorder in a sibling. On computed tomography there are low density regions, particularly in the occipital and posterior temporal lobes, involving both cortex and white matter, combined with or followed by progressive atrophy. Typical EEG findings may be confirmatory. (orig.)

  19. Magnetic resonance imaging of lumbar spine disc diseases. Frequency of false negatives

    International Nuclear Information System (INIS)

    Berthelot, J.M.; Maugars, Y.; Delecrin, Y.; Caillon, F.; Prost, A.

    1995-01-01

    Magnetic resonance imaging (MRI) has had an impressive impact on evaluation of degenerative diseases of the spine. Nevertheless, false negatives can occur on images involving lumbar discs. Degenerative disc diseases documented on discography and/or pathology examination of the discs can go unrecognized. Likewise sensitivity for the detection of protruding disc hernias is not totally satisfactory (20% false negatives). Finally, a magnetic resonance image visualizing displacement of the disc is not specific (10 to 15% false positives); images showing protrusion or hernia can be seen in 30% of asymptomatic patients. Although MRI gives slightly more information than other imaging techniques, false images do exist. Moreover, the usefulness of MRI to demonstrate disc disease in case of a negative CT-scan remains to be demonstrated. (authors). 26 refs

  20. Early onset of disc degeneration in SM/J mice is associated with changes in ion transport systems and fibrotic events.

    Science.gov (United States)

    Zhang, Ying; Xiong, Chi; Kudelko, Mateusz; Li, Yan; Wang, Cheng; Wong, Yuk Lun; Tam, Vivian; Rai, Muhammad Farooq; Cheverud, James; Lawson, Heather A; Sandell, Linda; Chan, Wilson C W; Cheah, Kathryn S E; Sham, Pak C; Chan, Danny

    2018-04-09

    Intervertebral disc degeneration (IDD) causes back pain and sciatica, affecting quality of life and resulting in high economic/social burden. The etiology of IDD is not well understood. Along with aging and environmental factors, genetic factors also influence the onset, progression and severity of IDD. Genetic studies of risk factors for IDD using human cohorts are limited by small sample size and low statistical power. Animal models amenable to genetic and functional studies of IDD provide desirable alternatives. Despite differences in size and cellular content as compared to human intervertebral discs (IVDs), the mouse is a powerful model for genetics and assessment of cellular changes relevant to human biology. Here, we provide evidence for early onset disc degeneration in SM/J relative to LG/J mice with poor and good tissue healing capacity respectively. In the first few months of life, LG/J mice maintain a relatively constant pool of notochordal-like cells in the nucleus pulposus (NP) of the IVD. In contrast, chondrogenic events are observed in SM/J mice beginning as early as one-week-old, with progressive fibrotic changes. Further, the extracellular matrix changes in the NP are consistent with IVD degeneration. Leveraging on the genomic data of two parental and two recombinant inbred lines, we assessed the genetic contribution to the NP changes and identified processes linked to the regulation of ion transport systems. Significantly, "transport" system is also in the top three gene ontology (GO) terms from a comparative proteomic analysis of the mouse NP. These findings support the potential of the SM/J, LG/J and their recombinant inbred lines for future genetic and biological analysis in mice and validation of candidate genes and biological relevance in human cohort studies. The proteomic data has been deposited to the ProteomeXchange Consortium via the PRIDE [1] partner repository with the dataset identifier PXD008784. Copyright © 2017. Published by

  1. Fatores genéticos e ambientais envolvidos na degeneração do disco intervertebral Genetic and environmental factors involved on intervertebral disc degeneration

    Directory of Open Access Journals (Sweden)

    Francine Teresa Brioni Nunes

    2007-01-01

    Full Text Available A etiologia da degeneração do disco intervertebral (DDI ainda não está totalmente esclarecida. O gene do receptor da vitamina D (VDR tem sido apontado como um dos possíveis envolvidos no surgimento das discopatias. Por outro lado, este estudo relaciona pela primeira vez, a participação dos genes das glutatião transferases M1 e T1 (GSTT1 e GSTM1, responsáveis pela inativação dos componentes do cigarro, na DDI. Foi extraído DNA de leucócitos de 66 pacientes e 88 controles, pareados por gênero e idade. O polimorfismo VDR-FokI foi amplificado por reação em cadeia da polimerase (PCR seguido de restrição com a enzima FokI. Os polimorfismos das GSTT1/M1 foram determinados por meio da PCR multiplex. A história familial e a gravidade da doença se destacaram nos pacientes portadores do alelo f do gene VDR-FokI (P=0,000 e 0,0012, respectivamente. A idade de surgimento da doença mostrou-se precoce nos indivíduos com genótipo _/f (média de 26 anos. Foi encontrada associação do polimorfismo FokI com a degeneração precoce e gravidade da DDI, sendo que o hábito de fumar também interferiu nesse processo, independente da presença ou não do genótipo favorável para GSTT1/M1.The etiology of intervertebral disc degeneration (IDD has not been fully clarified yet. Vitamin D receptor’s gene (VDR has been suggested as one of the potential entities involved in disc pathologies onset. On the other hand, this study correlates, for the first time, glutathione transferases M1 and T1 genes (GSTT1 and GSTM1 participation, which are responsible for cigarette components’ inactivation, in IDD. DNA was extracted from leukocytes of 66 patients and 88 controls, paired by gender and age. The VDR-Fokl polymorphism was amplified by polymerase chain reaction (PCR followed by restriction with Fokl enzyme. GSTT1/M1 polymorphisms were determined by means of PCR multiplex. Family history and disease severity were highlighted in patients carrying the f

  2. Intervertebral Disc Degeneration : The Role of the Mitochondrial Pathway in Annulus Fibrosus Cell Apoptosis Induced by Overload

    OpenAIRE

    Rannou, François; Lee, Tzong-Shyuan; Zhou, Rui-Hai; Chin, Jennie; Lotz, Jeffrey C.; Mayoux-Benhamou, Marie-Anne; Barbet, Jacques Patrick; Chevrot, Alain; Shyy, John Y.-J.

    2004-01-01

    Degeneration of the intervertebral disk (IVD) is a major pathological process implicated in low back pain and is a prerequisite to disk herniation. Although mechanical stress is an important modulator of the degeneration, the underlying molecular mechanism remains unclear. The association of human IVD degeneration, assessed by magnetic resonance imaging, with annulus fibrosus cell apoptosis and anti-cytochrome c staining revealed that the activation of the mitochondria-dependent apoptosome wa...

  3. Efficacy and safety of Mobi-C cervical artificial disc versus anterior discectomy and fusion in patients with symptomatic degenerative disc disease: A meta-analysis.

    Science.gov (United States)

    Lu, Hui; Peng, Lihua

    2017-12-01

    Total disc replacement (TDR) using Mobi-C cervical artificial disc might be promising to treat symptomatic degenerative disc disease. However, the results remained controversial. We conducted a systematic review and meta-analysis to compare the efficacy and safety of Mobi-C cervical artificial disc and anterior cervical discectomy and fusion (ACDF) in patients with symptomatic degenerative disc disease. PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of Mobi-C versus ACDF on the treatment of symptomatic degenerative disc disease were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. The primary outcomes were neck disability index (NDI) score, patient satisfaction, and subsequent surgical intervention. Meta-analysis was performed using the random-effect model. Four RCTs were included in the meta-analysis. Overall, compared with ACDF surgery for symptomatic degenerative disc disease, TDR using Mobi-C was associated with a significantly increased NDI score (Std. mean difference = 0.32; 95% CI = 0.10-0.53; P = .004), patient satisfaction (odds risk [OR] = 2.75; 95% confidence interval [CI] = 1.43-5.27; P = .002), and reduced subsequent surgical intervention (OR = 0.20; 95% CI = 0.11-0.37; P degenerative disc disease, TDR using Mobi-C cervical artificial disc resulted in a significantly improved NDI score, patient satisfaction, and reduced subsequent surgical intervention. There was no significant difference of neurological deterioration, radiographic success, and overall success between TDR using Mobi-C cervical artificial disc versus ACDF surgery. TDR using Mobi-C cervical artificial disc should be recommended for the treatment of symptomatic degenerative disc disease.

  4. Expression of receptors for putative anabolic growth factors in human intervertebral disc: implications for repair and regeneration of the disc.

    Science.gov (United States)

    Le Maitre, Christine L; Richardson, Stephen M A; Baird, Pauline; Freemont, Anthony J; Hoyland, Judith A

    2005-12-01

    Low back pain (LBP) is a common, debilitating and economically important disorder. Current evidence implicates loss of intervertebral disc (IVD) matrix consequent upon 'degeneration' as a major cause of LBP. Degeneration of the IVD involves increases in degradative enzymes and decreases in the extracellular matrix (ECM) component in a process that is controlled by a range of cytokines and growth factors. Studies have suggested using anabolic growth factors to regenerate the normal matrix of the IVD, hence restoring disc height and reversing degenerative disc disease. However, for such therapies to be successful it is vital that the target cells (i.e. the disc cells) express the appropriate receptors. This immunohistochemical study has for the first time investigated the expression and localization of four potentially beneficial growth factor receptors (i.e. TGFbetaRII, BMPRII, FGFR3 and IGFRI) in non-degenerate and degenerate human IVDs. Receptor expression was quantified across regions of the normal and degenerate disc and showed that cells of the nucleus pulposus (NP) and inner annulus fibrosus (IAF) expressed significantly higher levels of the four growth factor receptors investigated. There were no significant differences between the four growth factor expression in non-degenerate and degenerate biopsies. However, expression of TGFbetaRII, FGFR3 and IGFRI, but not BMP RII, were observed in the ingrowing blood vessels that characterize part of the disease aetiology. In conclusion, this study has demonstrated the expression of the four growth factor receptors at similar levels in the chondrocyte-like cells of the NP and IAF in both non-degenerate and degenerate discs, implicating a role in normal disc homeostasis and suggesting that the application of these growth factors to the degenerate human IVD would stimulate matrix production. However, the expression of some of the growth factor receptors on ingrowing blood vessels might be problematic in a therapeutic

  5. Concomitant lower thoracic spine disc disease in lumbar spine MR imaging studies.

    Science.gov (United States)

    Arana, Estanislao; Martí-Bonmatí, Luis; Dosdá, Rosa; Mollá, Enrique

    2002-11-01

    Our objective was to study the coexistence of lower thoracic-spine disc changes in patients with low back pain using a large field of view (FOV) in lumbar spine MR imaging. One hundred fifty patients with low back pain were referred to an MR examination. All patients were studied with a large FOV (27 cm), covering from the coccyx to at least the body of T11. Discs were coded as normal, protrusion, and extrusion (either epiphyseal or intervertebral). The relationship between disc disease and level was established with the Pearson chi(2) test. The T11-12 was the most commonly affected level of the lower thoracic spine with 58 disc cases rated as abnormal. Abnormalities of T11-12 and T12-L1 discs were significantly related only to L1-L2 disease ( p=0.001 and p=0.004, respectively) but unrelated to other disc disease, patient's gender, and age. No correlation was found between other discs. Magnetic resonance imaging of the lumbar spine can detect a great amount of lower thoracic disease, although its clinical significance remains unknown. A statistically significant relation was found within the thoracolumbar junctional region (T11-L2), reflecting common pathoanatomical changes. The absence of relation with lower lumbar spine discs is probably due to differences in their pathomechanisms.

  6. Concomitant lower thoracic spine disc disease in lumbar spine MR imaging studies

    International Nuclear Information System (INIS)

    Arana, Estanislao; Marti-Bonmati, Luis; Dosda, Rosa; Molla, Enrique

    2002-01-01

    Our objective was to study the coexistence of lower thoracic-spine disc changes in patients with low back pain using a large field of view (FOV) in lumbar spine MR imaging. One hundred fifty patients with low back pain were referred to an MR examination. All patients were studied with a large FOV (27 cm), covering from the coccyx to at least the body of T11. Discs were coded as normal, protrusion, and extrusion (either epiphyseal or intervertebral). The relationship between disc disease and level was established with the Pearson χ 2 test. The T11-12 was the most commonly affected level of the lower thoracic spine with 58 disc cases rated as abnormal. Abnormalities of T11-12 and T12-L1 discs were significantly related only to L1-L2 disease (p=0.001 and p=0.004, respectively) but unrelated to other disc disease, patient's gender, and age. No correlation was found between other discs. Magnetic resonance imaging of the lumbar spine can detect a great amount of lower thoracic disease, although its clinical significance remains unknown. A statistically significant relation was found within the thoracolumbar junctional region (T11-L2), reflecting common pathoanatomical changes. The absence of relation with lower lumbar spine discs is probably due to differences in their pathomechanisms. (orig.)

  7. Collagen turnover in normal and degenerate human intervertebral discs as determined by the racemization of aspartic acid

    NARCIS (Netherlands)

    Sivan, S.-S.; Wachtel, E.; Tsitron, E.; Sakkee, N.; Ham, F. van der; Groot, J.de; Roberts, S.; Maroudas, A.

    2008-01-01

    Knowledge of rates of protein turnover is important for a quantitative understanding of tissue synthesis and catabolism. In this work, we have used the racemization of aspartic acid as a marker for the turnover of collagen obtained from healthy and pathological human intervertebral disc matrices. We

  8. Influence of degenerative changes of intervertebral disc

    Directory of Open Access Journals (Sweden)

    WANG Yi

    2012-04-01

    Full Text Available 【Abstract】Objective: To investigate the material properties of normal and degenerated intervertebral discs (IVDs and examine the effect of degenerative changes on IVD pathology. Methods: A computer-based online search was under-taken to identify English articles about material properties of IVDs published from January 1950 to 2011 in PubMed database. The retrieved keywords included material properties, intervertebral disc and degeneration. Based on the principles of reliability, advancement and efficiency, the obtained data were primarily examined, and the original source was retrieved to read the full-text. Repetitive articles were excluded. The data of material properties of normal and degenerated IVDs were summarized and analyzed by meta-analysis. Results: The data of Young's modulus, Poisson's ratio, shear modulus, hydraulic permeability and intradiscal pres-sure of normal and degenerated IVDs were obtained. Com-pared with normal IVDs, the Young's modulus and shear modulus of annulus fibrosus and nucleus pulposus were higher in degenerated IVDs, the Poisson's ratio was lower while the hydraulic permeability and intradiscal pressure were higher. Besides, the degeneration-related alterations in IVDs had an influence both on itself and other spinal structures, leading to diseases such as bulging disc, discogenic pain and spinal stenosis. Meanwhile, the heavy mechanical loading and injury indicated important pathways to IVD degeneration. Conclusions: To a certain extent, the degenerative changes of IVD influence its material properties. And the degeneration-related alterations of composition can cause structural failure of IVDs, leading to injuries and diseases. Key words: Intervertebral disc; Mechanical phenomena; Degeneration; Elastic modulus; Permeability; Pathology

  9. Fast localization of optic disc and fovea in retinal images for eye disease screening

    Science.gov (United States)

    Yu, H.; Barriga, S.; Agurto, C.; Echegaray, S.; Pattichis, M.; Zamora, G.; Bauman, W.; Soliz, P.

    2011-03-01

    Optic disc (OD) and fovea locations are two important anatomical landmarks in automated analysis of retinal disease in color fundus photographs. This paper presents a new, fast, fully automatic optic disc and fovea localization algorithm developed for diabetic retinopathy (DR) screening. The optic disc localization methodology comprises of two steps. First, the OD location is identified using template matching and directional matched filter. To reduce false positives due to bright areas of pathology, we exploit vessel characteristics inside the optic disc. The location of the fovea is estimated as the point of lowest matched filter response within a search area determined by the optic disc location. Second, optic disc segmentation is performed. Based on the detected optic disc location, a fast hybrid level-set algorithm which combines the region information and edge gradient to drive the curve evolution is used to segment the optic disc boundary. Extensive evaluation was performed on 1200 images (Messidor) composed of 540 images of healthy retinas, 431 images with DR but no risk of macular edema (ME), and 229 images with DR and risk of ME. The OD location methodology obtained 98.3% success rate, while fovea location achieved 95% success rate. The average mean absolute distance (MAD) between the OD segmentation algorithm and "gold standard" is 10.5% of estimated OD radius. Qualitatively, 97% of the images achieved Excellent to Fair performance for OD segmentation. The segmentation algorithm performs well even on blurred images.

  10. ISSLS PRIZE IN BASIC SCIENCE 2018: Growth differentiation factor-6 attenuated pro-inflammatory molecular changes in the rabbit anular-puncture model and degenerated disc-induced pain generation in the rat xenograft radiculopathy model.

    Science.gov (United States)

    Miyazaki, Shingo; Diwan, Ashish D; Kato, Kenji; Cheng, Kevin; Bae, Won C; Sun, Yang; Yamada, Junichi; Muehleman, Carol; Lenz, Mary E; Inoue, Nozomu; Sah, Robert L; Kawakami, Mamoru; Masuda, Koichi

    2018-04-01

    To elucidate the effects of growth differentiation factor-6 (GDF6) on: (i) gene expression of inflammatory/pain-related molecules and structural integrity in the rabbit intervertebral disc (IVD) degeneration model, and (ii) sensory dysfunction and changes in pain-marker expression in dorsal nerve ganglia (DRGs) in the rat xenograft radiculopathy model. Forty-six adolescent rabbits received anular-puncture in two non-consecutive lumbar IVDs. Four weeks later, phosphate-buffered saline (PBS) or GDF6 (1, 10 or 100 µg) was injected into the nucleus pulposus (NP) of punctured discs and followed for 4 weeks for gene expression analysis and 12 weeks for structural analyses. For pain assessment, eight rabbits were sacrificed at 4 weeks post-injection and NP tissues of injected discs were transplanted onto L5 DRGs of 16 nude rats to examine mechanical allodynia. The rat DRGs were analyzed immunohistochemically. In GDF6-treated rabbit NPs, gene expressions of interleukin-6, tumor necrosis factor-α, vascular endothelial growth factor, prostaglandin-endoperoxide synthase 2, and nerve growth factor were significantly lower than those in the PBS group. GDF6 injections resulted in partial restoration of disc height and improvement of MRI disc degeneration grades with statistical significance in rabbit structural analyses. Allodynia induced by xenograft transplantation of rabbit degenerated NPs onto rat DRGs was significantly reduced by GDF6 injection. Staining intensities for ionized calcium-binding adaptor molecule-1 and calcitonin gene-related peptide in rat DRGs of the GDF6 group were significantly lower than those of the PBS group. GDF6 injection may change the pathological status of degenerative discs and attenuate degenerated IVD-induced pain.

  11. Effects of single injection of local anesthetic agents on intervertebral disc degeneration: ex vivo and long-term in vivo experimental study.

    Directory of Open Access Journals (Sweden)

    Koji Iwasaki

    Full Text Available Analgesic discography (discoblock can be used to diagnose or treat discogenic low back pain by injecting a small amount of local anesthetics. However, recent in vitro studies have revealed cytotoxic effects of local anesthetics on intervertebral disc (IVD cells. Here we aimed to investigate the deteriorative effects of lidocaine and bupivacaine on rabbit IVDs using an organotypic culture model and an in vivo long-term follow-up model.For the organotypic culture model, rabbit IVDs were harvested and cultured for 3 or 7 days after intradiscal injection of local anesthetics (1% lidocaine or 0.5% bupivacaine. Nucleus pulposus (NP cell death was measured using confocal microscopy. Histological and TUNEL assays were performed. For in vivo study, each local anesthetic was injected into rabbit lumbar IVDs under a fluoroscope. Six or 12 months after the injection, each IVD was prepared for magnetic resonance imaging (MRI and histological analysis.In the organotypic culture model, both anesthetic agents induced time-dependent NP cell death; when compared with injected saline solution, significant effects were detected within 7 days. Compared with the saline group, TUNEL-positive NP cells were significantly increased in the bupivacaine group. In the in vivo study, MRI analysis did not show any significant difference. Histological analysis revealed that IVD degeneration occurred to a significantly level in the saline- and local anesthetics-injected groups compared with the untreated control or puncture-only groups. However, there was no significant difference between the saline and anesthetic agents groups.In the in vivo model using healthy IVDs, there was no strong evidence to suggest that discoblock with local anesthetics has the potential of inducing IVD degeneration other than the initial mechanical damage of the pressurized injection. Further studies should be performed to investigate the deteriorative effects of the local injection of analgesic agents

  12. Thoracic spine disc-related abnormalities: longitudinal MR imaging assessment

    Energy Technology Data Exchange (ETDEWEB)

    Girard, Charles J.; Schweitzer, Mark E.; Morrison, William B.; Parellada, Joan A. [TJUH Radiology, Philadelphia, Pennsylvania (United States); Carrino, J.A. [Department of Radiology ASB-1, Harvard Medical School, Brigham and Women' s Hospital, L1, Room 002B, 75 Francis Street, MA 02115, Boston (United States)

    2004-04-01

    To describe and characterize the temporal changes in disc-related disorders of the thoracic spine using MR imaging. A retrospective longitudinal cohort study was carried out of 40 patients with two sequential thoracic spine MR images at variable intervals. The images were assessed for baseline presence of, new incidence of and changes in disc herniation, degenerative disc disease, endplate marrow signal alteration and Schmorl nodes. The range of follow-up was 4-149 weeks. Baseline presence was: disc herniation, 10% (49/480); degenerative disc disease, 14% (66/480); endplate marrow signal alteration, 2.3% (11/480); Schmorl nodes 9.6% (46/480). Most pre-existing lesions tended to remain unchanged. Herniations showed the most change, tending to improve in 27%. New incidence was: disc herniation, 1.5% (7/480), degenerative disc disease, 2% (10/480); endplate marrow signal alteration, 1.6% (8/480); Schmorl nodes, 2.1% (10/480). Disc degeneration was first visible at an 11-week interval and once established almost never changed over many weeks to months. Endplate signal alterations (Modic changes) were uncommon. Schmorl nodes show no change from baseline for up to 2 1/2 years. All findings predominated in the lower intervertebral levels from T6 to T10. The most prevalent thoracic spine disc-related findings are degeneration and herniation. Disc herniations predominate in the lower segments and are a dynamic phenomenon. Disc degeneration can be rapidly evolving but tends to remain unchanged after occurrence. Endplate marrow signal changes were an uncommon manifestation of thoracic disc disease. Schmorl nodes showed the least change over time. (orig.)

  13. Loss of Arf4 causes severe degeneration of the exocrine pancreas but not cystic kidney disease or retinal degeneration.

    Directory of Open Access Journals (Sweden)

    Jillian N Pearring

    2017-04-01

    Full Text Available Arf4 is proposed to be a critical regulator of membrane protein trafficking in early secretory pathway. More recently, Arf4 was also implicated in regulating ciliary trafficking, however, this has not been comprehensively tested in vivo. To directly address Arf4's role in ciliary transport, we deleted Arf4 specifically in either rod photoreceptor cells, kidney, or globally during the early postnatal period. Arf4 deletion in photoreceptors did not cause protein mislocalization or retinal degeneration, as expected if Arf4 played a role in protein transport to the ciliary outer segment. Likewise, Arf4 deletion in kidney did not cause cystic disease, as expected if Arf4 were involved in general ciliary trafficking. In contrast, global Arf4 deletion in the early postnatal period resulted in growth restriction, severe pancreatic degeneration and early death. These findings are consistent with Arf4 playing a critical role in endomembrane trafficking, particularly in the pancreas, but not in ciliary function.

  14. Neuropsychological differences between frontotemporal lobar degeneration and Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Claudia Sellitto Porto

    Full Text Available Abstract Memory impairment is the main clinical feature in Alzheimer disease (AD, whereas in frontotemporal lobar degeneration (FTLD behavioral and language disorders predominate. Objectives: To investigate possible differences between the neuropsychological performance in FTLD and AD. Methods: Fifty-six AD patients (mean age=72.98±7.43; mean schooling=9.62±4.68; 35 women and 21 men, 17 FTLD patients (mean age=67.64±7.93; mean schooling=12.12±4.77; 9 women and 8 men, and 60 controls (mean age=68.90±7.48; mean schooling=10.72±4.74; 42 women and 18 men were submitted to a Dementia Rating Scale (DRS and a comprehensive neuropsychological evaluation composed of tasks assessing attention, visuoperceptual abilities, constructive abilities, executive functions, memory and language. Results: DRS total score and subscales were not able to differentiate FTLD from AD patients. However, FTLD and AD patients showed statistically significant differences in performance in tests of verbal (Logical Memory, Rey Auditory Verbal Learning Test and visual (Visual Reproduction, recall of the Rey Complex Figure episodic memory, verbal immediate memory (Logical Memory, attention with interference (Trail Making Test - Part B, verbal fluency (semantic and phonemic and concept formation (WCST. Conclusion: Contrary to expectations, only a few tasks executive function tasks (Trail Making Test - Part B, F.A.S. and WCST and two memory tests (verbal and visual episodic memory tests were able to differentiate between FTLD and AD patients.

  15. Functional communication ability in frontotemporal lobar degeneration and Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Isabel Albuquerque M. de Carvalho

    Full Text Available Abstract Functional communication is crucial for independent and efficient communicative behavior in response to every day activities. In the course of dementia progression, cognitive losses may impair these abilities. For this reason, functional communication assessment should be part of a formal assessment to quantify and qualify the impact of deficiency on patients' lives. Objective: To compare functional communication abilities in fronto-temporal lobar degeneration (FLTD and Alzheimer's disease (AD. Methods: Six AD patients (mean age: 82.50±2.66 years; mean education: 5.67±3.61 years, and eight FTLD patients (mean age: 57.13±9.63 years; mean education: 10.86±6.91 years had their close relatives answer the Functional Assessment of Communication Skills for Adults (Asha-facs . Statistical analyses correlated the performance on each of the Asha-facs domains (social communication, communication of basic needs; reading, writing, number concept and daily planning between both groups. Results: Analyses showed that functional communication was similar for AD and FTLD patients. Only two items had statistical difference, namely 'Comprehension of inference' (AD 6.7±1.33; FTLD 2.43±2.30, p=0.017 and 'capacity to make basic money transactions' (AD 2.17±2.04; FTLD 4.00±0.90, p=0.044. Comparison among the four domains' mean scores revealed no significant difference. Conclusion: The Asha-facs is a useful instrument to characterize functional communication abilities in both FTLD and AD. Nevertheless, the analysis presented for this sample showed that the Asha-facs could not discriminate which aspects of the FTLD and AD differed.

  16. Role of LncRNA TUG1 in intervertebral disc degeneration and nucleus pulposus cells via regulating Wnt/β-catenin signaling pathway.

    Science.gov (United States)

    Chen, Jiang; Jia, Yu-Song; Liu, Gen-Zhe; Sun, Qi; Zhang, Fan; Ma, Sheng; Wang, Yong-Jun

    2017-09-23

    To investigate the role of TUG1 in intervertebral disc degeneration (IDD) and human nucleus pulposus cells (NPCs) via regulating Wnt/β-catenin pathway. The study collected nucleus pulposus (NP) tissue samples from 30 patients with lumbar disc herniation (LDH) (Case group) and 18 patients with lumbar spine trauma (Control group). NPCs induced by TNF-α in vitro were divided into Blank, Vector, TUG1, TUG1-siRNA, XAV-939, TUG1 + XAV-939 groups. qRT-PCR was used to detect the expression of TUG1 and ECM-related genes, Western blot to determine the expression of Wnt/β-catenin pathway and apoptosis-related proteins, and ELISA to measure the expression of ECM-related proteins. The apoptosis was detected by TUNEL and Annexin V-FITC/PI double-staining. The proliferation and senescence were tested by CCK-8 and SA-β-gal staining respectively. TUG1 was upregulated in patients with IDD, which was positively related to Wnt and β-catenin. Besides, TUG1, Wnt1 and β-catenin were greatly increased in the NPCs after TNF-α induction. Compared with the Blank group, TUG1-siRNA and XAV-939 can appreciably down-regulate the expressions of Wnt1, β-catenin, Caspase-3, Bax, MMP3 and ADAMTS5, up-regulate the expression of Bcl-2, Aggrecan and COL2A1, inhibit the apoptosis and senescence, and promote cell proliferation; however, the TUG1 group had the completely opposite results. Silencing TUG1 may not only protect human NPCs from TNF-α-induced apoptosis and senescence, but also promote cell proliferation by blocking Wnt/β-catenin pathway, which provides a theoretical basis for the clinical treatment of IDD. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Plasma vitamin D and osteo-cartilaginous markers in Italian males affected by intervertebral disc degeneration: Focus on seasonal and pathological trend of type II collagen degradation.

    Science.gov (United States)

    Brayda-Bruno, Marco; Viganò, Marco; Cauci, Sabina; Vitale, Jacopo A; de Girolamo, Laura; De Luca, Paola; Lombardi, Giovanni; Banfi, Giuseppe; Colombini, Alessandra

    2017-08-01

    To evaluate plasma vitamin D and cross-linked C-telopeptides of type I (CTx-I) and type II (CTx-II) collagen concentrations in males with lumbar intervertebral disc degeneration (IVD) compared to healthy controls. Improved knowledge might suggest to optimize the vitamin D status of IVD patients and contribute to clarify mechanisms of cartilage degradation. 79 Italian males with lumbar IVD assessed by Magnetic Resonance Imaging (MRI) and 79 age, sex and BMI-matched healthy controls were enrolled. Plasma 25hydroxyvitamin D (25(OH)D), CTx-I and CTx-II were measured by immunoassays. Circannual seasonality, correlation between biomarkers concentrations and clinical variables were assessed. Overall subjects 25(OH)D and CTx-II showed month rhythmicity with acrophase in August/September and October/November, and nadir in February/March and April/May, respectively. An inverse correlation between 25(OH)D and CTx-I, and a direct correlation between CTx-II and CTx-I were observed. IVD patients, particularly with osteochondrosis, showed higher CTx-II than healthy controls. Month of sampling may affect plasma 25(OH)D and CTx-II concentrations. The correlation between CTx-I and CTx-II suggests an interplay between the osteo-cartilaginous endplate and the fibro-cartilaginous disc. The results of this study highlighted that osteochondrosis associates with increased cartilaginous catabolism. Vitamin D supplementation seems more necessary in winter for lumbar IVD patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. The Clinical Correlations between Diabetes, Cigarette Smoking and Obesity on Intervertebral Degenerative Disc Disease of the Lumbar Spine.

    Science.gov (United States)

    Jakoi, Ande M; Pannu, Gurpal; D'Oro, Anthony; Buser, Zorica; Pham, Martin H; Patel, Neil N; Hsieh, Patrick C; Liu, John C; Acosta, Frank L; Hah, Raymond; Wang, Jeffrey C

    2017-06-01

    Retrospective analysis of a nationwide private insurance database. Chi-square analysis and linear regression models were utilized for outcome measures. The purpose of this study was to investigate any relationship between lumbar degenerative disc disease, diabetes, obesity and smoking tobacco. Diabetes, obesity, and smoking tobacco are comorbid conditions known to individually have effect on degenerative disc disease. Most studies have only been on a small populous scale. No study has yet to investigate the combination of these conditions within a large patient cohort nor have they reviewed the combination of these conditions on degenerative disc disease. A retrospective analysis of insurance billing codes within the nationwide Humana insurance database was performed, using PearlDiver software (PearlDiver, Inc., Fort Wayne, IN, USA), to identify trends among patients diagnosed with lumbar disc degenerative disease with and without the associated comorbidities of obesity, diabetes, and/or smoking tobacco. Patients billed for a comorbidity diagnosis on the same patient record as the lumbar disc degenerative disease diagnosis were compared over time to patients billed for lumbar disc degenerative disease without a comorbidity. There were no sources of funding for this manuscript and no conflicts of interest. The total number and prevalence of patients (per 10,000) within the database diagnosed with lumbar disc degenerative disease increased by 241.4% and 130.3%, respectively. The subsets of patients within this population who were concurrently diagnosed with either obesity, diabetes, tobacco use, or a combination thereof, was significantly higher than patients diagnosed with lumbar disc degenerative disease alone ( p degenerative disease and smoking rose significantly more than patients diagnosed with lumbar disc degenerative disease and either diabetes or obesity ( p degenerative disease, smoking and obesity rose significantly more than the number of patients

  19. Outcome of physiotherapy after surgery for cervical disc disease: a prospective randomised multi-centre trial

    Science.gov (United States)

    2014-01-01

    Background Many patients with cervical disc disease require leave from work, due to long-lasting, complex symptoms, including chronic pain and reduced levels of physical and psychological function. Surgery on a few segmental levels might be expected to resolve disc-specific pain and reduce neurological deficits, but not the non-specific neck pain and the frequent illness. No study has investigated whether post-surgery physiotherapy might improve the outcome of surgery. The main purpose of this study was to evaluate whether a well-structured rehabilitation programme might add benefit to the customary post-surgical treatment for cervical disc disease, with respect to function, disability, work capability, and cost effectiveness. Methods/Design This study was designed as a prospective, randomised, controlled, multi-centre study. An independent, blinded investigator will compare two alternatives of rehabilitation. We will include 200 patients of working age, with cervical disc disease confirmed by clinical findings and symptoms of cervical nerve root compression. After providing informed consent, study participants will be randomised to one of two alternative physiotherapy regimes; (A) customary treatment (information and advice on a specialist clinic); or (B) customary treatment plus active physiotherapy. Physiotherapy will follow a standardised, structured programme of neck-specific exercises combined with a behavioural approach. All patients will be evaluated both clinically and subjectively (with questionnaires) before surgery and at 6 weeks, 3 months, 6 months, 12 months, and 24 months after surgery. The main outcome variable will be neck-specific disability. Cost-effectiveness will also be calculated. Discussion We anticipate that the results of this study will provide evidence to support physiotherapeutic rehabilitation applied after surgery for cervical radiculopathy due to cervical disc disease. Trial registration ClinicalTrials.gov identifier: NCT01547611

  20. MR imaging of degenerative lumbar disc disease emphasizing on signal intensity changes in vertebral body

    International Nuclear Information System (INIS)

    Toyoda, Keiko; Ida, Masahiro; Murakami, Yoshitaka; Harada, Junta; Tada, Shimpei

    1992-01-01

    Magnetic resonance imaging was performed in 400 patients with degenerative disc disease. Signal changes and their sites in the vertebral body were classified and referred to narrowing of the intervertebral disc space. MR findings were compared with those of plain roentgenograms of the lumbar spine. Signal changes in the vertebral body were noted in 83 cases (102 vertebral bodies). Low-intensity abnormality on both T1- and T2-weighted images (WI) was the most common finding, and was most frequently seen at the end plate and/or the angle. These changes were correlated with narrowing of the disc space and osteosclerosis on the plain roentgenogram of the lumbar spine. Signal changes occasionally occurred in the inner region of the vertebral body, and these lesions tended to show a high-intensity abnormality on T1-WI. We conclude that signal changes in degenerative disc disease are not specific, but are sometimes difficult to distinguish from the signal changes in other conditions such as spinal tumor or bone marrow disorder. (author)

  1. [Modern treatments for degenerative disc diseases of the lumbosacral spine. A literature review].

    Science.gov (United States)

    Konovalov, N A; Nazarenko, A G; Asyutin, D S; Zelenkov, P V; Onoprienko, R A; Korolishin, V A; Cherkiev, I U; Martynova, M A; Zakirov, B A; Timonin, S Yu; Kosyr'kova, A V; Pimenova, L F; Pogosyan, A L; Batyrov, A A

    Many researchers consider degenerative diseases of the spine as a pandemic of the XXIst century. Herniated intervertebral discs of the lumbosacral spine occur in 61% of patients with degenerative spine diseases. Of these, 15% of patients have herniated discs at the LII-LIII level, 10% of patients at the LIII-LIV level, and 40% of patients at the LIV-LV and LV-SI levels. A high cost of conservative treatment of degenerative spine disease symptoms and its low efficacy in reducing the intensity and duration of pain necessitate the development of new methods of surgical treatment. In this paper, we analyze the literature data on minimally invasive spine surgery and demonstrate the main advantages of percutaneous endoscopic surgical techniques.

  2. Intervertebral Fusion with Mobile Microendoscopic Discectomy for Lumbar Degenerative Disc Disease.

    Science.gov (United States)

    Xu, Bao-Shan; Liu, Yue; Xu, Hai-Wei; Yang, Qiang; Ma, Xin-Long; Hu, Yong-Cheng

    2016-05-01

    The aim of this article is to introduce a technique for lumbar intervertebral fusion that incorporates mobile microendoscopic discectomy (MMED) for lumbar degenerative disc disease. Minimally invasive transforaminal lumbar interbody fusion is frequently performed to treat degenerative diseases of the lumbar spine; however, the scope of such surgery and vision is limited by what the naked eye can see through the expanding channel system. To expand the visual scope and reduce trauma, we perform lumbar intervertebral fusion with the aid of a MMED system that provides a wide field through freely tilting the surgical instrument and canals. We believe that this technique is a good option for treating lumbar degenerative disc disease that requires lumbar intervertebral fusion. © 2016 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.

  3. Treatment of intervertebral disc degenerative disease using percutaneous nucleotomy–an overview of less invasive procedures

    Directory of Open Access Journals (Sweden)

    Miran Jeromel

    2014-04-01

    Full Text Available Background: Less invasive treatment methods for intervertebral disc disease and decompression of neural structures as a consequence of contained disc herniation represent an alternative to surgical procedure. Percutaneus nucleotomy uses a percutaneous approach to the intervertebral disc. The article presents the evolution of numerous procedureds in clinical practice.Methods: Percutaneous nucleoplasty is a fluoroscopy-guided procedure which enables controlled and safe entrance into the intervertebral disc. The procedure is performed under strict aseptic conditions, using a local anaesthesia with the patient under analgosedation. Based on the principle of therapeutic intradiscal action, the procedures can be divided into three groups: chemical (chemonucleolysis with chimopapain, alcohol, ozone, mechanical (automated percutaneous lumbar discectomy – APLD, arthroscopic discectomy and thermical methods (laser, radiofrequency ablation, intradiscal electrothermal annuloplasty – IDET, Coblation®.Results: Percutaneous nucleotomy by the majority of the mentioned procedures results in a therapeutic effect (reduction of pain and decompression of neural structures. Fast recovery represents a major advantage of less invasive treatment.Conclusions: Less invasive method (nucleotomy using different procedures represents a successful alternative approach to surgical discectomy. Proper patient selection and safe technique are mandatory in order to achieve a good clinical outcome.

  4. Patterns of cortical degeneration in an elderly cohort with cerebral small vessel disease.

    NARCIS (Netherlands)

    Reid, A.T.; Norden, A.G.W. van; Laat, K.F. de; Oudheusden, L.J.B. van; Zwiers, M.P.; Evans, A.C.; Leeuw, F.E. de; Kotter, R.

    2010-01-01

    Emerging noninvasive neuroimaging techniques allow for the morphometric analysis of patterns of gray and white matter degeneration in vivo, which may help explain and predict the occurrence of cognitive impairment and Alzheimer's disease. A single center prospective follow-up study (Radboud

  5. Cells and Biomaterials for Intervertebral Disc Regeneration

    CERN Document Server

    Grad, Sibylle

    2010-01-01

    Disorders related to the intervertebral disc (IVD) are common causes of morbidity and of severe life quality deterioration. IVD degeneration, although in many cases asymptomatic, is often the origin of painful neck and back diseases. In Western societies IVD related pain and disability account for enormous health care costs as a result of work absenteeism and thus lost production, disability benefits, medical and insurance expenses. Although only a small percentage of patients with disc disorders finally will undergo surgery, spinal surgery has been one of the fastest growing disciplines in th

  6. evaluation of a new method for the treatment of degenerative disc disease

    OpenAIRE

    Leidenberger, Tilman Albert Ulrich

    2015-01-01

    Introduction – Purpose: Evaluation of a new treatment option and applicator-system for MR-guided Percutaneous Intradiscal Thermotherapy (MRgPIT), a combinative method of Percutaneous Laser Discus Decompression (PLDD) and annuloplasty for the treatment of degenerative disc disease in open MRI. Materials and Methods: We evaluated the application of a MR-compatible thermoablative applicator-system (Invivo Germany GmbH, Schwerin, D) as well as different laser protocols for annuloplasty in an o...

  7. Spread of neuronal degeneration in a dopaminergic, Lrrk-G2019S model of Parkinson disease

    Science.gov (United States)

    Hindle, Samantha J.; Elliott, Christopher J.H.

    2013-01-01

    Flies expressing the most common Parkinson disease (PD)-related mutation, LRRK2-G2019S, in their dopaminergic neurons show loss of visual function and degeneration of the retina, including mitochondrial abnormalities, apoptosis and autophagy. Since the photoreceptors that degenerate are not dopaminergic, this demonstrates nonautonomous degeneration, and a spread of pathology. This provides a model consistent with Braak’s hypothesis on progressive PD. The loss of visual function is specific for the G2019S mutation, implying the cause is its increased kinase activity, and is enhanced by increased neuronal activity. These data suggest novel explanations for the variability in animal models of PD. The specificity of visual loss to G2019S, coupled with the differences in neural firing rate, provide an explanation for the variability between people with PD in visual tests. PMID:23529190

  8. Glial degeneration with oxidative damage drives neuronal demise in MPSII disease.

    Science.gov (United States)

    Zalfa, Cristina; Verpelli, Chiara; D'Avanzo, Francesca; Tomanin, Rosella; Vicidomini, Cinzia; Cajola, Laura; Manara, Renzo; Sala, Carlo; Scarpa, Maurizio; Vescovi, Angelo Luigi; De Filippis, Lidia

    2016-08-11

    Mucopolysaccharidosis type II (MPSII) is a lysosomal storage disorder due to the deficit of the iduronate 2-sulfatase (IDS) enzyme, causing progressive neurodegeneration in patients. Neural stem cells (NSCs) derived from the IDS-ko mouse can recapitulate MPSII pathogenesis in vitro. In differentiating IDS-ko NSCs and in the aging IDS-ko mouse brain, glial degeneration precedes neuronal degeneration. Here we show that pure IDS-ko NSC-derived astrocytes are selectively able to drive neuronal degeneration when cocultured with healthy neurons. This phenotype suggests concurrent oxidative damage with metabolic dysfunction. Similar patterns were observed in murine IDS-ko animals and in human MPSII brains. Most importantly, the mutant phenotype of IDS-ko astrocytes was reversed by low oxygen conditions and treatment with vitamin E, which also reversed the toxic effect on cocultured neurons. Moreover, at very early stages of disease we detected in vivo the development of a neuroinflammatory background that precedes astroglial degeneration, thus suggesting a novel model of MPSII pathogenesis, with neuroinflammation preceding glial degeneration, which is finally followed by neuronal death. This hypothesis is also consistent with the progression of white matter abnormalities in MPSII patients. Our study represents a novel breakthrough in the elucidation of MPSII brain pathogenesis and suggests the antioxidant molecules as potential therapeutic tools to delay MPSII onset and progression.

  9. Exosomes as potential alternatives to stem cell therapy for intervertebral disc degeneration: in-vitro study on exosomes in interaction of nucleus pulposus cells and bone marrow mesenchymal stem cells.

    Science.gov (United States)

    Lu, Kang; Li, Hai-Yin; Yang, Kuang; Wu, Jun-Long; Cai, Xiao-Wei; Zhou, Yue; Li, Chang-Qing

    2017-05-10

    The stem cell-based therapies for intervertebral disc degeneration have been widely studied. However, the mechanisms of mesenchymal stem cells interacting with intervertebral disc cells, such as nucleus pulposus cells (NPCs), remain unknown. Exosomes as a vital paracrine mechanism in cell-cell communication have been highly focused on. The purpose of this study was to detect the role of exosomes derived from bone marrow mesenchymal stem cells (BM-MSCs) and NPCs in their interaction with corresponding cells. The exosomes secreted by BM-MSCs and NPCs were purified by differential centrifugation and identified by transmission electron microscope and immunoblot analysis of exosomal marker proteins. Fluorescence confocal microscopy was used to examine the uptake of exosomes by recipient cells. The effects of NPC exosomes on the migration and differentiation of BM-MSCs were determined by transwell migration assays and quantitative RT-PCR analysis of NPC phenotypic genes. Western blot analysis was performed to examine proteins such as aggrecan, sox-9, collagen II and hif-1α in the induced BM-MSCs. Proliferation and the gene expression profile of NPCs induced by BM-MSC exosomes were measured by Cell Counting Kit-8 and qRT-PCR analysis, respectively. Both the NPCs and BM-MSCs secreted exosomes, and these exosomes underwent uptake by the corresponding cells. NPC-derived exosomes promoted BM-MSC migration and induced BM-MSC differentiation to a nucleus pulposus-like phenotype. BM-MSC-derived exosomes promoted NPC proliferation and healthier extracellular matrix production in the degenerate NPCs. Our study indicates that the exosomes act as an important vehicle in information exchange between BM-MSCs and NPCs. Given a variety of functions and multiple advantages, exosomes alone or loaded with specific genes and drugs would be an appropriate option in a cell-free therapy strategy for intervertebral disc degeneration.

  10. Qualitative grading of disc degeneration by magnetic resonance in the lumbar and cervical spine: lack of correlation with histology in surgical cases.

    Science.gov (United States)

    Davies, B M; Atkinson, R A; Ludwinski, F; Freemont, A J; Hoyland, J A; Gnanalingham, K K

    2016-08-01

    Clinically, magnetic resonance (MR) imaging is the most effective non-invasive tool for assessing IVD degeneration. Histological examination of the IVD provides a more detailed assessment of the pathological changes at a tissue level. However, very few reports have studied the relationship between these techniques. Identifying a relationship may allow more detailed staging of IVD degeneration, of importance in targeting future regenerative therapies. To investigate the relationship between MR and histological grading of IVD degeneration in the cervical and lumbar spine in patients undergoing discectomy. Lumbar (N = 99) and cervical (N = 106) IVD samples were obtained from adult patients undergoing discectomy surgery for symptomatic IVD herniation and graded to ascertain a histological grade of degeneration. The pre-operative MR images from these patients were graded for the degree of IVD (MR grade) and vertebral end-plate degeneration (Modic Changes, MC). The relationship between histological and MR grades of degeneration were studied. In lumbar and cervical IVD the majority of samples (93%) exhibited moderate levels of degeneration (ie MR grades 3-4) on pre-operative MR scans. Histologically, most specimens displayed moderate to severe grades of degeneration in lumbar (99%) and cervical spine (93%). MR grade was weakly correlated with patient age in lumbar and cervical study groups. MR and histological grades of IVD degeneration did not correlate in lumbar or cervical study groups. MC were more common in the lumbar than cervical spine (e.g. 39 versus 20% grade 2 changes; p < 0.05), but failed to correlate with MR or histological grades for degeneration. In this surgical series, the resected IVD tissue displayed moderate to severe degeneration, but there is no correlation between MR and histological grades using a qualitative classification system. There remains a need for a quantitative, non-invasive, pre-clinical measure of IVD degeneration that

  11. Thermo-sensitive injectable glycol chitosan-based hydrogel for treatment of degenerative disc disease.

    Science.gov (United States)

    Li, Zhengzheng; Shim, Hyeeun; Cho, Myeong Ok; Cho, Ik Sung; Lee, Jin Hyun; Kang, Sun-Woong; Kwon, Bosun; Huh, Kang Moo

    2018-03-15

    The use of injectable hydrogel formulations have been suggested as a promising strategy for the treatment of degenerative disc disease to both restore the biomechanical function and reduce low back pain. In this work, a new thermo-sensitive injectable hydrogels with tunable thermo-sensitivity and enhanced stability were developed with N-hexanoylation of glycol chitosan (GC) for treatment of degenerative disc disease, and their physico-chemical and biological properties were evaluated. The sol-gel transition temperature of the hydrogels was controlled in a range of 23-56 °С, depending on the degree of hexanoylation and the polymer concentration. In vitro and in vivo tests showed no cytotoxicity and no adverse effects in a rat model. The hydrogel filling of the defective IVD site in an ex vivo porcine model maintained its stability for longer than 28 days. These results suggest that the hydrogel can be used as an alternative material for treatment of disc herniation. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Cost-effectiveness of cervical total disc replacement vs fusion for the treatment of 2-level symptomatic degenerative disc disease.

    Science.gov (United States)

    Ament, Jared D; Yang, Zhuo; Nunley, Pierce; Stone, Marcus B; Kim, Kee D

    2014-12-01

    Cervical total disc replacement (CTDR) was developed to treat cervical spondylosis, while preserving motion. While anterior cervical discectomy and fusion (ACDF) has been the standard of care for 2-level disease, a randomized clinical trial (RCT) suggested similar outcomes. Cost-effectiveness of this intervention has never been elucidated. To determine the cost-effectiveness of CTDR compared with ACDF. Data were derived from an RCT that followed up 330 patients over 24 months. The original RCT consisted of multi-institutional data including private and academic institutions. Using linear regression for the current study, health states were constructed based on the stratification of the Neck Disability Index and a visual analog scale. Data from the 12-item Short-Form Health Survey questionnaires were transformed into utilities values using the SF-6D mapping algorithm. Costs were calculated by extracting Diagnosis-Related Group codes from institutional billing data and then applying 2012 Medicare reimbursement rates. The costs of complications and return-to-work data were also calculated. A Markov model was built to evaluate quality-adjusted life-years (QALYs) for both treatment groups. The model adopted a third-party payer perspective and applied a 3% annual discount rate. Patients included in the original RCT had to be diagnosed as having radiculopathy or myeloradiculopathy at 2 contiguous levels from C3-C7 that was unresponsive to conservative treatment for at least 6 weeks or demonstrated progressive symptoms. Incremental cost-effectiveness ratio of CTDR compared with ACDF. A strong correlation (R2 = 0.6864; P sensitivity analysis, the incremental cost-effectiveness ratio value stays below the threshold of $50,000 per QALY in most scenarios (range, -$58,194 to $147,862 per QALY). The incremental cost-effectiveness ratio of CTDR compared with traditional ACDF is lower than the commonly accepted threshold of $50,000 per QALY. This remains true with varying input

  13. Posterior Transpedicular Dynamic Stabilization versus Total Disc Replacement in the Treatment of Lumbar Painful Degenerative Disc Disease: A Comparison of Clinical Results

    Directory of Open Access Journals (Sweden)

    Tunc Oktenoglu

    2013-01-01

    Full Text Available Study Design. Prospective clinical study. Objective. This study compares the clinical results of anterior lumbar total disc replacement and posterior transpedicular dynamic stabilization in the treatment of degenerative disc disease. Summary and Background Data. Over the last two decades, both techniques have emerged as alternative treatment options to fusion surgery. Methods. This study was conducted between 2004 and 2010 with a total of 50 patients (25 in each group. The mean age of the patients in total disc prosthesis group was 37,32 years. The mean age of the patients in posterior dynamic transpedicular stabilization was 43,08. Clinical (VAS and Oswestry and radiological evaluations (lumbar lordosis and segmental lordosis angles of the patients were carried out prior to the operation and 3, 12, and 24 months after the operation. We compared the average duration of surgery, blood loss during the surgery and the length of hospital stay of both groups. Results. Both techniques offered significant improvements in clinical parameters. There was no significant change in radiologic evaluations after the surgery for both techniques. Conclusion. Both dynamic systems provided spine stability. However, the posterior dynamic system had a slight advantage over anterior disc prosthesis because of its convenient application and fewer possible complications.

  14. Oxidative stress participates in age-related changes in rat lumbar intervertebral discs.

    Science.gov (United States)

    Hou, Gang; Lu, Huading; Chen, Mingjuan; Yao, Hui; Zhao, Huiqing

    2014-01-01

    Aging is a major factor associated with lumber intervertebral disc degeneration, and oxidative stress is known to play an essential role in the pathogenesis of many age-related diseases. In this study, we investigated oxidative stress in intervertebral discs of Wistar rats in three different age groups: youth, adult, and geriatric. Age-related intervertebral disc changes were examined by histological analysis. In addition, oxidative stress was evaluated by assessing nitric oxide (NO), superoxide dismutase (SOD), malondialdehyde (MDA), and advanced oxidation protein products (AOPPs). Intervertebral disc, but not serum, NO concentrations significantly differed between the three groups. Serum and intervertebral disc SOD activity gradually decreased with age. Furthermore, both serum and intervertebral disc MDA and AOPP levels gradually increased with age. Our studies suggest that oxidative stress is associated with age-related intervertebral disc changes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Callosal degeneration topographically correlated with cognitive function in amnestic mild cognitive impairment and Alzheimer's disease dementia.

    Science.gov (United States)

    Wang, Pei-Ning; Chou, Kun-Hsien; Chang, Ni-Jung; Lin, Ker-Neng; Chen, Wei-Ta; Lan, Gong-Yau; Lin, Ching-Po; Lirng, Jiing-Feng

    2014-04-01

    Degeneration of the corpus callosum (CC) is evident in the pathogenesis of Alzheimer's disease (AD). However, the correlation of microstructural damage in the CC on the cognitive performance of patients with amnestic mild cognitive impairment (aMCI) and AD dementia is undetermined. We enrolled 26 normal controls, 24 patients with AD dementia, and 40 single-domain aMCI patients with at least grade 1 hippocampal atrophy and isolated memory impairment. Diffusion tensor imaging (DTI) with fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (DA), and radial diffusivity (DR) were measured. The entire CC was parcellated based on fiber trajectories to specific cortical Brodmann areas using a probabilistic tractography method. The relationship between the DTI measures in the subregions of the CC and cognitive performance was examined. Although the callosal degeneration in the patients with aMCI was less extended than in the patients with AD dementia, degeneration was already exhibited in several subregions of the CC at the aMCI stage. Scores of various neuropsychological tests were correlated to the severity of microstructural changes in the subregional CC connecting to functionally corresponding cortical regions. Our results confirm that CC degeneration is noticeable as early as the aMCI stage of AD and the disconnection of the CC subregional fibers to the corresponding Brodmann areas has an apparent impact on the related cognitive performance. Copyright © 2013 Wiley Periodicals, Inc.

  16. Word recognition in Alzheimer's disease: Effects of semantic degeneration.

    Science.gov (United States)

    Cuetos, Fernando; Arce, Noemí; Martínez, Carmen; Ellis, Andrew W

    2017-03-01

    Impairments of word recognition in Alzheimer's disease (AD) have been less widely investigated than impairments affecting word retrieval and production. In particular, we know little about what makes individual words easier or harder for patients with AD to recognize. We used a lexical selection task in which participants were shown sets of four items, each set consisting of one word and three non-words. The task was simply to point to the word on each trial. Forty patients with mild-to-moderate AD were significantly impaired on this task relative to matched controls who made very few errors. The number of patients with AD able to recognize each word correctly was predicted by the frequency, age of acquisition, and imageability of the words, but not by their length or number of orthographic neighbours. Patient Mini-Mental State Examination and phonological fluency scores also predicted the number of words recognized. We propose that progressive degradation of central semantic representations in AD differentially affects the ability to recognize low-imageability, low-frequency, late-acquired words, with the same factors affecting word recognition as affecting word retrieval. © 2015 The British Psychological Society.

  17. Music Recognition in Frontotemporal Lobar Degeneration and Alzheimer Disease

    Science.gov (United States)

    Johnson, Julene K; Chang, Chiung-Chih; Brambati, Simona M; Migliaccio, Raffaella; Gorno-Tempini, Maria Luisa; Miller, Bruce L; Janata, Petr

    2013-01-01

    Objective To compare music recognition in patients with frontotemporal dementia, semantic dementia, Alzheimer disease, and controls and to evaluate the relationship between music recognition and brain volume. Background Recognition of familiar music depends on several levels of processing. There are few studies about how patients with dementia recognize familiar music. Methods Subjects were administered tasks that assess pitch and melody discrimination, detection of pitch errors in familiar melodies, and naming of familiar melodies. Results There were no group differences on pitch and melody discrimination tasks. However, patients with semantic dementia had considerable difficulty naming familiar melodies and also scored the lowest when asked to identify pitch errors in the same melodies. Naming familiar melodies, but not other music tasks, was strongly related to measures of semantic memory. Voxel-based morphometry analysis of brain MRI showed that difficulty in naming songs was associated with the bilateral temporal lobes and inferior frontal gyrus, whereas difficulty in identifying pitch errors in familiar melodies correlated with primarily the right temporal lobe. Conclusions The results support a view that the anterior temporal lobes play a role in familiar melody recognition, and that musical functions are affected differentially across forms of dementia. PMID:21617528

  18. Music recognition in frontotemporal lobar degeneration and Alzheimer disease.

    Science.gov (United States)

    Johnson, Julene K; Chang, Chiung-Chih; Brambati, Simona M; Migliaccio, Raffaella; Gorno-Tempini, Maria Luisa; Miller, Bruce L; Janata, Petr

    2011-06-01

    To compare music recognition in patients with frontotemporal dementia, semantic dementia, Alzheimer disease, and controls and to evaluate the relationship between music recognition and brain volume. Recognition of familiar music depends on several levels of processing. There are few studies about how patients with dementia recognize familiar music. Subjects were administered tasks that assess pitch and melody discrimination, detection of pitch errors in familiar melodies, and naming of familiar melodies. There were no group differences on pitch and melody discrimination tasks. However, patients with semantic dementia had considerable difficulty naming familiar melodies and also scored the lowest when asked to identify pitch errors in the same melodies. Naming familiar melodies, but not other music tasks, was strongly related to measures of semantic memory. Voxel-based morphometry analysis of brain magnetic resonance imaging showed that difficulty in naming songs was associated with the bilateral temporal lobes and inferior frontal gyrus, whereas difficulty in identifying pitch errors in familiar melodies correlated with primarily the right temporal lobe. The results support a view that the anterior temporal lobes play a role in familiar melody recognition, and that musical functions are affected differentially across forms of dementia.

  19. Facet joint orientation and tropism in lumbar degenerative disc disease and spondylolisthesis.

    Science.gov (United States)

    Pichaisak, Witchate; Chotiyarnwong, Chayaporn; Chotiyarnwong, Pojchong

    2015-04-01

    Although degenerative disc disease (DDD) and degenerative spondylolisthesis (DS) are two common causes of back pain in elderly, the association between the lumbarfacet joint angle and tropism in these conditions are still unclear. To evaluate the difference in facet joint angles between normal population and lumbar degenerative disc disease and spondylolisthesis patient. The angle of lumbar facet joints were retrospectively measured with magnetic resonance imaging (MRI) to determine whether there was a difference between degenerative diseases. MRI of patients with DDD, DS, and control group at facet joint between L3-4, L4-5 and L5-S1 level were measured in axial view (60 subjects in each group). There was no difference infacetjoint angle in DDD (44.1 ± 11.9) and control (45.6 ± 8.9), but differed in DS (40.1 ± 10. 7) and control group (p = 0.010) at L4-5 level. Facet tropism showed difference between degenerative groups and control group at L4-5 level. DS group showed difference in facet joints angle and tropism when compared with control population, while DDD showed difference only in facet tropism. In addition, longitudinal studies are needed to understand the clinical significant between facet joint angle and tropism in spinal degenerative diseases.

  20. Relationship between nigrostriatal dopaminergic degeneration, urinary symptoms, and bladder control in Parkinson's disease

    DEFF Research Database (Denmark)

    Winge, K; Friberg, L; Werdelin, L

    2005-01-01

    Patients with Parkinson's disease (PD) often have lower urinary tract symptoms (LUTS). Studies have indicated a correlation between dopaminergic degeneration and LUTS and presence of overactive bladder. We evaluated 18 patients with Parkinson's disease using single-photon emission computerized....... The effects of medication on bladder control, as evaluated by urodynamics are believed to involve structures outside the basal ganglia....... tomography (SPECT) imaging of the dopamine transporter with [(123)I]-FP-CIT, and bladder symptoms were assessed using questionnaires and full urodynamic evaluation both in medicated state and after cessation. Bladder symptoms correlated with age, stage and severity of disease but not with uptake...

  1. Depression, social factors, and pain perception before and after surgery for lumbar and cervical degenerative vertebral disc disease.

    Science.gov (United States)

    Jabłońska, Renata; Ślusarz, Robert; Królikowska, Agnieszka; Haor, Beata; Antczak, Anna; Szewczyk, Maria

    2017-01-01

    The purpose of this study was to evaluate the effects of psychosocial factors on pain levels and depression, before and after surgical treatment, in patients with degenerative lumbar and cervical vertebral disc disease. The study included 188 patients (98 women, 90 men) who were confirmed to have cervical or lumbar degenerative disc disease on magnetic resonance imaging, and who underwent a single microdiscectomy procedure, with no postoperative surgical complications. All patients completed two questionnaires before and after surgery - the Beck Depression Inventory scale (I-IV) and the Visual Analog Scale for pain (0-10). On hospital admission, all patients completed a social and demographic questionnaire. The first pain and depression questionnaire evaluations were performed on the day of hospital admission (n=188); the second on the day of hospital discharge, 7 days after surgery (n=188); and the third was 6 months after surgery (n=140). Patient ages ranged from 22 to 72 years, and 140 patients had lumbar disc disease (mean age, 42.7±10.99 years) and 44 had cervical disc disease (mean age, 48.9±7.85 years). Before surgery, symptoms of depression were present in 47.3% of the patients (11.7% cervical; 35.6% lumbar), at first postoperative evaluation in 25.1% of patients (7% cervical; 18.1% lumbar), and 6 months following surgery in 31.1% of patients (7.5% cervical; 23.6% lumbar). Patients with cervical disc disease who were unemployed had the highest incidence of depression before and after surgery ( p =0.037). Patients with lumbar disc disease who had a primary level of education or work involving standing had the highest incidence of depression before and after surgery ( p =0.368). This study highlighted the association between social and demographic factors, pain perception, and depression that may persist despite surgical treatment for degenerative vertebral disc disease.

  2. Predictive factors associated with neck pain in patients with cervical disc degeneration: A cross-sectional study focusing on Modic changes.

    Science.gov (United States)

    Kong, Lingde; Tian, Weifeng; Cao, Peng; Wang, Haonan; Zhang, Bing; Shen, Yong

    2017-10-01

    The predictive factors associated with neck pain remain unclear. We conducted a cross-sectional study to assess predictive factors, especially Modic changes (MCs), associated with the intensity and duration of neck pain in patients with cervical disc degenerative disease.We retrospectively reviewed patients in our hospital from January 2013 to December 2016. Severe neck pain (SNP) and persistent neck pain (PNP) were the 2 main outcomes, and were assessed based on the numerical rating scale (NRS). Basic data, and also imaging data, were collected and analyzed as potential predictive factors. Univariate analysis and multiple logistic regression analysis were performed to assess the predictive factors for neck pain.In all, 381 patients (193 males and 188 females) with cervical degenerative disease were included in our study. The number of patients with SNP and PNP were 94 (24.67%) and 109 (28.61%), respectively. The NRS of neck pain in patients with type 1 MCs was significantly higher than type 2 MCs (4.8 ± 0.9 vs 3.9 ± 1.1; P = .004). The multivariate logistic analysis showed that kyphosis curvature (odds ratio [OR] 1.082, 95% confidence interval [CI] 1.044-1.112), spondylolisthesis (OR 1.339, 95% CI 1.226-1.462), and annular tear (OR 1.188, 95% CI 1.021-1.382) were factors associated with SNP, whereas kyphosis curvature (OR 1.568, 95% CI 1.022-2.394), spondylolisthesis (OR 1.486, 95% CI 1.082-2.041), and MCs (OR 1.152, 95% CI 1.074-1.234) were associated with PNP.We concluded that kyphosis curvature, spondylolisthesis, and annular tear are associated with SNP, whereas kyphosis curvature, spondylolisthesis, and MCs are associated with PNP. This study supports the view that MCs can lead to a long duration of neck pain.

  3. Clinical outcome of stand-alone ALIF compared to posterior instrumentation for degenerative disc disease

    DEFF Research Database (Denmark)

    Udby, Peter M.; Bech-Azeddine, Rachid

    2015-01-01

    The objective of the article was to: a) present results from a case cohort pilot study comparing stand-alone ALIF and TLIF and, b) review the literature on studies comparing the clinical outcome of stand-alone ALIF with posterior instrumentation including TLIF or PLIF, in patients with disabling...... low back pain resulting from degenerative disc disease. ALIF surgery has previously been linked with certain high risk complications and unfavorable long term fusion results. Newer studies suggest that stand-alone ALIF can possibly be advantageous compared to other types of posterior instrumented...

  4. Wallerian degeneration demonstrated by MRI and functional outcome in patients suffering from supratentorial cerebrovascular disease

    Energy Technology Data Exchange (ETDEWEB)

    Shirotani, Toshiki; Takahara, Takashi; Arimoto, Hirohiko; Inohara, Masashi; Ono, Kenichiro; Shimizu, Akira [Self-Defense Force Central Hospital, Tokyo (Japan)

    2002-07-01

    An early diagnosis of the outcome of patients with cerebrovascular disease is important for selecting the optimal treatment strategy. The purpose of this study was to estimate the prognosis of Wallerian degeneration on MRI in stroke patients with hemiparesis. The subjects consisted of 87 stroke patients, 50 hemorrhagic patients and 37 ischemic patients, who were evaluated by MRI at 1 to 6,275 days after stroke onset. Among the 36 patients who were evaluated by consecutive MRI, 161 films were obtained and analyzed. Wallerian degeneration was diagnosed when a small prolonged T2 lesion was seen in the corticospinal tract of the brainstem on at least two contiguous slices. The atrophic rate of the midbrain was calculated as: (the area of the unaffected side of the midbrain - the area of the affected side of the midbrain)/2 x (the area of the unaffected side of the midbrain). The patients' ability to perform the activities of daily living was scored by the Barthel index (BI). Wallerian degeneration in the ipsilateral brainstem was seen for two to three months in 32 cases (37%) and in 58 films (36%) and disappeared about 3 years after the onset of stroke. Wallerian degeneration correlated with the BI scores from 2 to 6 months after stroke (p<0.05), although no relationship was observed at 7 months or later. From 2 to 6 months after stroke, the shrinkage of the midbrain on MRI correlated with the BI scores (p<0.001), although no relationship was observed at 7 months or later. It was therefore both Wallerian degeneration and a shrunken midbrain observed on MRIs, evaluated from 2 to 6 months after stroke were thus suggested to indicate a poor outcome in such patients. (author)

  5. Cost Utility Analysis of the Cervical Artificial Disc vs Fusion for the Treatment of 2-Level Symptomatic Degenerative Disc Disease: 5-Year Follow-up.

    Science.gov (United States)

    Ament, Jared D; Yang, Zhuo; Nunley, Pierce; Stone, Marcus B; Lee, Darrin; Kim, Kee D

    2016-07-01

    The cervical total disc replacement (cTDR) was developed to treat cervical degenerative disc disease while preserving motion. Cost-effectiveness of this intervention was established by looking at 2-year follow-up, and this update reevaluates our analysis over 5 years. Data were derived from a randomized trial of 330 patients. Data from the 12-Item Short Form Health Survey were transformed into utilities by using the SF-6D algorithm. Costs were calculated by extracting diagnosis-related group codes and then applying 2014 Medicare reimbursement rates. A Markov model evaluated quality-adjusted life years (QALYs) for both treatment groups. Univariate and multivariate sensitivity analyses were conducted to test the stability of the model. The model adopted both societal and health system perspectives and applied a 3% annual discount rate. The cTDR costs $1687 more than anterior cervical discectomy and fusion (ACDF) over 5 years. In contrast, cTDR had $34 377 less productivity loss compared with ACDF. There was a significant difference in the return-to-work rate (81.6% compared with 65.4% for cTDR and ACDF, respectively; P = .029). From a societal perspective, the incremental cost-effective ratio (ICER) for cTDR was -$165 103 per QALY. From a health system perspective, the ICER for cTDR was $8518 per QALY. In the sensitivity analysis, the ICER for cTDR remained below the US willingness-to-pay threshold of $50 000 per QALY in all scenarios (-$225 816 per QALY to $22 071 per QALY). This study is the first to report the comparative cost-effectiveness of cTDR vs ACDF for 2-level degenerative disc disease at 5 years. The authors conclude that, because of the negative ICER, cTDR is the dominant modality. ACDF, anterior cervical discectomy and fusionAWP, average wholesale priceCE, cost-effectivenessCEA, cost-effectiveness analysisCPT, Current Procedural TerminologycTDR, cervical total disc replacementCUA, cost-utility analysisDDD, degenerative disc disease

  6. Correlation of plain radiographic and lumbar myelographic findings with surgical findings in thoracolumbar disc disease

    International Nuclear Information System (INIS)

    Oldby, N.J.; Dyce, J.; Houlton, J.E.F.

    1994-01-01

    The results of a prospective study to compare the plain radiographic and lumbar myelographic findings with the surgical findings in 70 cases of suspected thoracolumbar disc protrusion in the dog are reported. The aim was to assess the relative accuracy of disc lesion localisation using plain and contrast radiography. From the plain radiographs, the affected disc space was correctly identified in 40 cases (57.1 per cent), and incorrectly identified in seven. More than one site was identified in 11; in eight of these dogs, the affected disc space was strongly suspected. It was not possible to identify an affected disc in 12 cases. The site of disc protrusion was accurately identified by myelography in 60 dogs (85.7 per cent). In four dogs, myelography was helpful in identifying an adjacent disc and, in a further two, cord swelling was found at surgery. In one dog, neither disc material nor cord swelling was identified. Three myelograms were non-diagnostic

  7. Pain drawings predict outcome of surgical treatment for degenerative disc disease in the cervical spine.

    Science.gov (United States)

    MacDowall, Anna; Robinson, Yohan; Skeppholm, Martin; Olerud, Claes

    2017-08-01

    Pain drawings have been frequently used in the preoperative evaluation of spine patients. For lumbar conditions comprehensive research has established both the reliability and predictive value, but for the cervical spine most of this knowledge is lacking. The aims of this study were to validate pain drawings for the cervical spine, and to investigate the predictive value for treatment outcome of four different evaluation methods. We carried out a post hoc analysis of a randomized controlled trial, comparing cervical disc replacement to fusion for radiculopathy related to degenerative disc disease. A pain drawing together with Neck Disability Index (NDI) was completed preoperatively, after 2 and 5 years. The inter- and intraobserver reliability of four evaluation methods was tested using κ statistics, and its predictive value investigated by correlation to change in NDI. Included were 151 patients, mean age of 47 years, female/male: 78/73. The interobserver reliability was fair for the modified Ransford and Udén methods, good for the Gatchel method, and very good for the modified Ohnmeiss method. Markings in the shoulder and upper arm region on the pain drawing were positive predictors of outcome after 2 years of follow-up, and markings in the upper arm region remained a positive predictor of outcome even after 5 years of follow-up. Pain drawings were a reliable tool to interpret patients' pain prior to cervical spine surgery and were also to some extent predictive for treatment outcome.

  8. Assessment of socioemotional processes facilitates the distinction between frontotemporal lobar degeneration and Alzheimer's disease.

    Science.gov (United States)

    Narme, Pauline; Mouras, Harold; Roussel, Martine; Devendeville, Agnès; Godefroy, Olivier

    2013-01-01

    We explored the value of a battery of socioemotional tasks for differentiating between frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). Patients with FTLD (n = 13) or AD (n = 13) and healthy controls (n = 26) underwent a neuropsychological assessment and the socioemotional battery (an empathy questionnaire, an emotion recognition task, and theory of mind tasks). Socioemotional processes were markedly impaired in FTLD but relatively unaffected in mild AD. The computed Socioemotional Index discriminated more accurately between FTLD from AD than behavioral and executive assessments did. Furthermore, impairments in socioemotional processes were correlated with indifference to others.

  9. Association between nutritional status and Modic classification in degenerative disc disease.

    Science.gov (United States)

    Seyithanoglu, Hakan; Aydin, Teoman; Taşpınar, Ozgur; Camli, Adil; Kiziltan, Huriye; Eris, Ali Hikmet; Hocaoglu, Ilknur Turk; Ozder, Aclan; Denizli, Ebru; Kepekci, Muge; Keskin, Yasar; Mutluer, Ahmet Serdar

    2016-04-01

    [Purpose] This study was conducted to examine the association between Modic classification and the eating habits in patients with degenerative disc disease (DDD) and to determine the influence of nutrition on disease severity. [Subjects and Methods] Sixty patients with DDD visiting a low back pain outpatient clinic were enrolled. Through face-to-face interviews, they completed questionnaires regarding their demographics, disease activity, smoking and alcohol use, concomitant diseases, disease duration, and nutritional status.Exclusion criteria were age 65 years, other comorbidities, missing MRI data, and inability to speak Turkish. [Results] Forty patients were finally included in the study. The frequency with which they consumed water, salt, fast food, eggs, milk, yogurt, cheese, whole wheat bread, white bread, butter, and margarine was recorded. A weak negative correlation was observed between the Modic types and fish and egg consumption. [Conclusion] Modic changes, which indicate the severity of DDD, seem to be correlated to patients' dietary habits. However, studies with comparison groups and larger samples are needed to confirm our promising results before any cause-and-effect relationship can be proposed.

  10. Magnetic resonance imaging of lumbar spine disc diseases. Frequency of false negatives; Imagerie par resonance magnetique pour pathologie discale lombaire. Frequence des faux-negatifs

    Energy Technology Data Exchange (ETDEWEB)

    Berthelot, J.M.; Maugars, Y.; Delecrin, Y.; Caillon, F.; Prost, A. [Hopital Hotel-Dieu de Nantes, 44 (France)

    1995-10-01

    Magnetic resonance imaging (MRI) has had an impressive impact on evaluation of degenerative diseases of the spine. Nevertheless, false negatives can occur on images involving lumbar discs. Degenerative disc diseases documented on discography and/or pathology examination of the discs can go unrecognized. Likewise sensitivity for the detection of protruding disc hernias is not totally satisfactory (20% false negatives). Finally, a magnetic resonance image visualizing displacement of the disc is not specific (10 to 15% false positives); images showing protrusion or hernia can be seen in 30% of asymptomatic patients. Although MRI gives slightly more information than other imaging techniques, false images do exist. Moreover, the usefulness of MRI to demonstrate disc disease in case of a negative CT-scan remains to be demonstrated. (authors). 26 refs.

  11. Nucleus basalis of Meynert degeneration precedes and predicts cognitive impairment in Parkinson's disease.

    Science.gov (United States)

    Schulz, Jonathan; Pagano, Gennaro; Fernández Bonfante, Juan Alberto; Wilson, Heather; Politis, Marios

    2018-05-01

    Currently, no reliable predictors of cognitive impairment in Parkinson's disease exist. We hypothesized that microstructural changes at grey matter T1-weighted MRI and diffusion tensor imaging in the cholinergic system nuclei and associated limbic pathways underlie cognitive impairment in Parkinson's disease. We performed a cross-sectional comparison between patients with Parkinson's disease with and without cognitive impairment. We also performed a longitudinal 36-month follow-up study of cognitively intact Parkinson's disease patients, comparing patients who remained cognitively intact to those who developed cognitive impairment. Patients with Parkinson's disease with cognitive impairment showed lower grey matter volume and increased mean diffusivity in the nucleus basalis of Meynert, compared to patients with Parkinson's disease without cognitive impairment. These results were confirmed both with region of interest and voxel-based analyses, and after partial volume correction. Lower grey matter volume and increased mean diffusivity in the nucleus basalis of Meynert was predictive for developing cognitive impairment in cognitively intact patients with Parkinson's disease, independent of other clinical and non-clinical markers of the disease. Structural and microstructural alterations in entorhinal cortex, amygdala, hippocampus, insula, and thalamus were not predictive for developing cognitive impairment in Parkinson's disease. Our findings provide evidence that degeneration of the nucleus basalis of Meynert precedes and predicts the onset of cognitive impairment, and might be used in a clinical setting as a reliable biomarker to stratify patients at higher risk of cognitive decline.

  12. Aging Is Not a Disease: Distinguishing Age-Related Macular Degeneration from Aging

    Science.gov (United States)

    Ardeljan, Daniel; Chan, Chi-Chao

    2013-01-01

    Age-related macular degeneration (AMD) is a disease of the outer retina, characterized most significantly by atrophy of photoreceptors and retinal pigment epithelium accompanied with or without choroidal neovascularization. Development of AMD has been recognized as contingent on environmental and genetic risk factors, the strongest being advanced age. In this review, we highlight pathogenic changes that destabilize ocular homeostasis and promote AMD development. With normal aging, photoreceptors are steadily lost, Bruch's membrane thickens, the choroid thins, and hard drusen may form in the periphery. In AMD, many of these changes are exacerbated in addition to the development of disease-specific factors such as soft macular drusen. Para-inflammation, which can be thought of as an intermediate between basal and robust levels of inflammation, develops within the retina in an attempt to maintain ocular homeostasis, reflected by increased expression of the anti-inflammatory cytokine IL-10 coupled with shifts in macrophage plasticity from the pro-inflammatory M1 to the anti-inflammatory M2 polarization. In AMD, imbalances in the M1 and M2 populations together with activation of retinal microglia are observed and potentially contribute to tissue degeneration. Nonetheless, the retina persists in a state of chronic inflammation and increased expression of certain cytokines and inflammasomes is observed. Since not everyone develops AMD, the vital question to ask is how the body establishes a balance between normal age-related changes and the pathological phenotypes in AMD. PMID:23933169

  13. Parametric T2 and T2* mapping techniques to visualize intervertebral disc degeneration in patients with low back pain: initial results on the clinical use of 3.0 Tesla MRI

    International Nuclear Information System (INIS)

    Welsch, Goetz Hannes; Trattnig, Siegfried; Goed, Sabine; Stelzeneder, David; Paternostro-Sluga, Tatjana; Bohndorf, Klaus; Mamisch, Tallal Charles

    2011-01-01

    To assess, compare and correlate quantitative T2 and T2* relaxation time measurements of intervertebral discs (IVDs) in patients suffering from low back pain, with respect to the IVD degeneration as assessed by the morphological Pfirrmann Score. Special focus was on the spatial variation of T2 and T2* between the annulus fibrosus (AF) and the nucleus pulposus (NP). Thirty patients (mean age: 38.1 ± 9.1 years; 20 female, 10 male) suffering from low back pain were included. Morphological (sagittal T1-FSE, sagittal and axial T2-FSE) and biochemical (sagittal T2- and T2* mapping) MRI was performed at 3 Tesla covering IVDs L1-L2 to L5-S1. All IVDs were morphologically classified using the Pfirrmann score. Region-of-interest (ROI) analysis was performed on midsagittal T2 and T2* maps at five ROIs from anterior to posterior to obtain information on spatial variation between the AF and the NP. Statistical analysis-of-variance and Pearson correlation was performed. The spatial variation as an increase in T2 and T2* values from the AF to the NP was highest at Pfirmann grade I and declined at higher Pfirmann grades II-IV (p < 0.05). With increased IVD degeneration, T2 and T2* revealed a clear differences in the NP, whereas T2* was additionally able to depict changes in the posterior AF. Correlation between T2 and T2* showed a medium Pearson's correlation (0.210 to 0.356 [p < 0.001]). The clear differentiation of IVD degeneration and the possible quantification by means of T2 and fast T2* mapping may provide a new tool for follow-up therapy protocols in patients with low back pain. (orig.)

  14. Assessment of axonal degeneration in Alzheimer's disease with diffusion tensor MRI

    International Nuclear Information System (INIS)

    Stahl, R.; Dietrich, O.; Reiser, M.F.; Schoenberg, S.O.; Teipel, S.; Hampel, H.

    2003-01-01

    Alzheimer disease (AD) causes cortical degeneration with subsequent degenerative changes of the white matter. The aim of this study was to investigate the extent of white matter tissue damage of patients with Alzheimer's disease in comparison with healthy subjects using diffusion tensor MRI (DTI). The value of integrated parallel imaging techniques (iPAT) for reduction of image distortion was assessed. We studied 9 patients with mild AD and 10 age and gender matched healthy controls. DTI brain scans were obtained on a 1.5 tesla system (Siemens Magnetom Sonata) using parallel imaging (iPAT) and an EPI diffusion sequence with TE/TR 71 ms/6000 ms. We used an 8-element head coil and a GRAPPA reconstruction algorithm with an acceleration factor of 2. From the tensor, the mean diffusivity (D), the fractional anisotropy (FA), and the relative anisotropy (RA) of several white matter regions were determined. FA was significantly lower (p [de

  15. Genome-Wide Association Study in Dachshund: Identification of a Major Locus Affecting Intervertebral Disc Calcification

    DEFF Research Database (Denmark)

    Mogensen, Mette Sloth; Karlskov-Mortensen, Peter; Proschowsky, Helle Friis

    2011-01-01

    Intervertebral disc calcification and herniation commonly affects Dachshund where the predisposition is caused by an early onset degenerative process resulting in disc calcification. A continuous spectrum of disc degeneration is seen within and among clog breeds, suggesting a multifactorial etiol...

  16. Longevity of elastin in human intervertebral disc as probed by the racemization of aspartic acid

    DEFF Research Database (Denmark)

    Sivan, Sarit-Sara; Van El, Benno; Merkher, Yulia

    2012-01-01

    BACKGROUND: Aging and degeneration of human intervertebral disc (IVD) are associated with biochemical changes, including racemization and glycation. These changes can only be counteracted by protein turnover. Little is known about the longevity of IVD elastin in health or disease. Yet, such knowl...

  17. Acquired hepatocerebral degeneration and hepatic encephalopathy: correlations and variety of clinical presentations in overt and subclinical liver disease

    Directory of Open Access Journals (Sweden)

    Fernando G. Romeiro

    2011-06-01

    Full Text Available Acquired hepatocerebral degeneration (AHD and hepatolenticular degeneration can have similar clinical presentations, but when a chronic liver disease and atypical motor findings coexist, the distinction between AHD and hepatic encephalopathy (HE can be even more complicated. We describe three cases of AHD (two having HE with different neuroimaging findings, distinct hepatic diseases and similar motor presentations, all presenting chronic arterial hypertension and weight loss before the disease manifestations. The diagnosis and physiopathology are commented upon and compared with previous reports. In conclusion, there are many correlations among HE, hepatolenticular degeneration and AHD, but the overlapping of AHD and HE could be more common depending on the clinical knowledge and diagnostic criteria adopted for each condition. Since AHD is not considered a priority that affects the liver transplant list, the prognosis in AHD patients remains poor, and flow interruption in portosystemic shunts must always be taken into account.

  18. Polygalae Radix Extract Prevents Axonal Degeneration and Memory Deficits in a Transgenic Mouse Model of Alzheimer's Disease.

    Science.gov (United States)

    Kuboyama, Tomoharu; Hirotsu, Keisuke; Arai, Tetsuya; Yamasaki, Hiroo; Tohda, Chihiro

    2017-01-01

    Memory impairments in Alzheimer's disease (AD) occur due to degenerated axons and disrupted neural networks. Since only limited recovery is possible after the destruction of neural networks, preventing axonal degeneration during the early stages of disease progression is necessary to prevent AD. Polygalae Radix (roots of Polygala tenuifolia ; PR) is a traditional herbal medicine used for sedation and amnesia. In this study, we aimed to clarify and analyze the preventive effects of PR against memory deficits in a transgenic AD mouse model, 5XFAD. 5XFAD mice demonstrated memory deficits at the age of 5 months. Thus, the water extract of Polygalae Radix (PR extract) was orally administered to 4-month-old 5XFAD mice that did not show signs of memory impairment. After consecutive administrations for 56 days, the PR extract prevented cognitive deficit and axon degeneration associated with the accumulation of amyloid β (Aβ) plaques in the perirhinal cortex of the 5XFAD mice. PR extract did not influence the formation of Aβ plaques in the brain of the 5XFAD mice. In cultured neurons, the PR extract prevented axonal growth cone collapse and axonal atrophy induced by Aβ. Additionally, it prevented Aβ-induced endocytosis at the growth cone of cultured neurons. Our previous study reported that endocytosis inhibition was enough to prevent Aβ-induced growth cone collapse, axonal degeneration, and memory impairments. Therefore, the PR extract possibly prevented axonal degeneration and memory impairment by inhibiting endocytosis. PR is the first preventive drug candidate for AD that inhibits endocytosis in neurons.

  19. Validation of the baseline severity stratification of objective functional impairment in lumbar degenerative disc disease.

    Science.gov (United States)

    Stienen, Martin N; Smoll, Nicolas R; Joswig, Holger; Corniola, Marco V; Schaller, Karl; Hildebrandt, Gerhard; Gautschi, Oliver P

    2017-05-01

    OBJECTIVE The Timed Up and Go (TUG) test is a simple, objective, and standardized method to measure objective functional impairment (OFI) in patients with lumbar degenerative disc disease (DDD). The objective of the current work was to validate the OFI baseline severity stratification (BSS; with levels of "none," "mild," "moderate," and "severe"). METHODS Data were collected in a prospective IRB-approved 2-center study. Patients were assessed with a comprehensive panel of scales for measuring pain (visual analog scale [VAS] for back and leg pain), functional impairment (Roland-Morris Disability Index [RMDI] and Oswestry Disability Index [ODI]), and health-related quality of life (HRQOL; EQ-5D and SF-12). OFI BSS was determined using age- and sex-adjusted cutoff values. RESULTS A total of 375 consecutive patients scheduled for lumbar spine surgery were included. Each 1-step increase on the OFI BSS corresponded to an increase of 0.53 in the back pain VAS score, 0.69 in the leg pain VAS score, 1.81 points in the RMDI, and 5.93 points in the ODI, as well as to a decrease in HRQOL of -0.073 in the EQ-5D, -1.99 in the SF-12 physical component summary (PCS), and -1.62 in the SF-12 mental component summary (MCS; all p measure of functional impairment for use in daily clinical practice. The presence of OFI indicates the presence of significant functional impairment on subjective outcome measures.

  20. Preliminary Experience with Anterior Interbody Titanium Cage Fusion for Treatment of Cervical Disc Disease

    Directory of Open Access Journals (Sweden)

    Chung-Nan Lin

    2003-05-01

    Full Text Available This study evaluated the efficacy and safety of titanium cage implants in cervical reconstruction to treat cervical spondylosis. Surgical data covered a 4-year period from January 1999 to December 2002 and included 34 consecutive patients, 20 men and 14 women, with ages ranging from 27 to 84 years (mean, 57 years. Patients underwent anterior cervical microdiscectomy followed by interbody fusion with a titanium cage implant (rather than an autogenous iliac crest bone graft at a single level ranging from C3 to C7. Twenty-one patients had a herniated intervertebral disc, nine had degenerative disc disease, and four had previous failed autograft fusion surgery that required revision. At clinical presentation, 26 patients had neck pain, 23 had radiculopathy, and nine had myelopathy. Diagnostic imaging studies included spinal dynamic roentgenography, computerized tomography, and magnetic resonance imaging. Lesions were located at C3-4 in seven cases, C4-5 in 14 cases, C5-6 in nine cases, and C6-7 in four cases. The follow-up period ranged from 7 to 48 months (mean, 26 months. Results revealed that the procedure was technically feasible. There were no intra- or postoperative complications. The most commonly used cage was 9 mm high. Imaging studies showed no cage instability, migration, or pseudarthrosis. Although mild subsidence (< 5 mm was observed in three cases, these patients preserved adequate postoperative cervical lordosis and the subsidence did not preclude a good clinical result. The advantages of this procedure over a similar operation using traditional tricorticate bone graft are: no graft morbidity; shorter operation time (mean time saved, 35 minutes; reduced blood loss (average blood loss, 75 mL; and early postoperative ambulation (mean, 4.7 hospital days. Nearly all patients rapidly lost their neck pain (92%, 24/26 and radicular symptoms (87%, 20/23 after surgery. The recovery rate from myelopathy was 44% (4/9. Progressive bony shield

  1. [Non-pharmacologic therapy of age-related macular degeneration, based on the etiopathogenesis of the disease].

    Science.gov (United States)

    Fischer, Tamás

    2015-07-12

    It has a great therapeutic significance that the disorder of the vascular endothelium, which supplies the affected ocular structures, plays a major role in the development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfuncition and age-related macular degeneration is accompanied by a general inflammatory response. The vascular wall including those in chorioids may be activated by several repeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic and genetic factors causing a protracted host defence response with a consequent vascular damage, which leads to age-related macular degeneration. Based on this concept, age-related macular degeneration is a local manifestation of the systemic vascular disease. This recognition should have therapeutic implications because restoration of endothelial dysfunction can stabilize the condition of chronic vascular disease including age-related macular degeneration, as well. Restoration of endothelial dysfunction by non-pharmacological or pharmacological interventions may prevent the development or improve endothelial dysfunction resulting in prevention or improvement of age-related macular degeneration. Non-pharmacological interventions which may have beneficial effect in endothelial dysfunction include (1) smoking cessation; (2) reduction of increased body weight; (3) adequate physical activity; (4) appropriate diet (a) proper dose of flavonoids, polyphenols and kurcumin; (b) omega-3 long-chain polyunsaturated fatty acids: docosahexaenoic acid and eicosapentaenoic acid; (c) carotenoids, lutein and zeaxanthins), (d) management of dietary glycemic index, (e) caloric restriction, and (5) elimination of stressful lifestyle. Non-pharmacological interventions should be preferable even if medicaments are also used for the treatment of endothelial dysfunction.

  2. Dietary compound score and risk of age-related macular degeneration in the Age-Related Eye Disease Study

    Science.gov (United States)

    Purpose: Because foods provide many nutrients, which may interact with each other to modify risk for multifactorial diseases such as age-related macular degeneration (AMD), we sought to develop a composite scoring system to summarize the combined effect of multiple dietary nutrients on AMD risk. Th...

  3. [The age-related macular degeneration as a vascular disease/part of systemic vasculopathy: contributions to its pathogenesis].

    Science.gov (United States)

    Fischer, Tamás

    2015-03-01

    The wall of blood vessels including those in choroids may be harmed by several repeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic, and genetic impacts (risk factors), which may trigger a protracted response, the so-called host defense response. As a consequence, pathological changes resulting in vascular injury (e. g. atherosclerosis, age-related macular degeneration) may be evolved. Risk factors can also act directly on the endothelium through an increased production of reactive oxygen species promoting an endothelial activation, which leads to endothelial dysfunction, the onset of vascular disease. Thus, endothelial dysfunction is a link between the harmful stimulus and vascular injury; any kind of harmful stimuli may trigger the defensive chain that results in inflammation that may lead to vascular injury. It has been shown that even early age-related macular degeneration is associated with the presence of diffuse arterial disease and patients with early age-related macular degeneration demonstrate signs of systemic and retinal vascular alterations. Chronic inflammation, a feature of AMD, is tightly linked to diseases associated with ED: AMD is accompanied by a general inflammatory response, in the form of complement system activation, similar to that observed in degenerative vascular diseases such as atherosclerosis. All these facts indicate that age-related macular degeneration may be a vascular disease (or part of a systemic vasculopathy). This recognition could have therapeutic implications because restoration of endothelial dysfunction may prevent the development or improve vascular disease resulting in prevention or improvement of age-related macular degeneration as well.

  4. Perfusion SPECT studies with mapping of Brodmann areas in differentiating Alzheimer's disease from frontotemporal degeneration syndromes.

    Science.gov (United States)

    Valotassiou, Varvara; Papatriantafyllou, John; Sifakis, Nikolaos; Tzavara, Chara; Tsougos, Ioannis; Kapsalaki, Eftychia; Hadjigeorgiou, George; Georgoulias, Panagiotis

    2012-12-01

    The aim of this study was to evaluate the contribution of brain perfusion single-photon emission computed tomography (SPECT) studies with mapping of Brodmann areas (BAs) in the differential diagnosis between Alzheimer's disease (AD) and frontotemporal degeneration (FTLD) syndromes. Thirty-nine patients with AD and 73 patients with FTLD syndromes [behavioural variant FTLD (bvFTLD); language variant FTLD (lvFTLD), including semantic dementia (SD) and progressive nonfluent aphasia (PNFA); and corticobasal degeneration (CBD)/progressive supranuclear palsy (PSP) syndromes] underwent brain perfusion SPECT. The NeuroGam software was used for the semiquantitative evaluation of perfusion in BAs of the left (L) and right (R) hemispheres. Compared with those in AD patients, BAs with statistically significant hypoperfusion were found in the prefrontal, orbitofrontal and cingulated cortices and Broca's areas of FTLD and bvFTLD patients; in the temporal and prefrontal cortices and Broca's areas of lvFTLD patients; in the left temporal gyrus of SD patients; in premotor and supplementary motor, prefrontal, orbitofrontal, temporal and anterior cingulated cortices and Broca's areas of PNFA patients; and in the prefrontal, temporal, posterior cingulated and primary and secondary visual cortices of CBD/PSP patients. BA 46R could differentiate AD patients from FTLD and bvFTLD patients; 21L and 25L were found to be independent predictors for lvFTLD in comparison with AD, and 25R, 21L and 23R could differentiate AD patients from PNFA, SD and CBD/PSP patients, respectively. Brain perfusion SPECT with BA mapping in AD and FTLD patients could improve the definition of brain areas that are specifically implicated in these disorders, resulting in a more accurate differential diagnosis.

  5. Prediction of coronary artery disease in patients undergoing operations for mitral valve degeneration

    Science.gov (United States)

    Lin, S. S.; Lauer, M. S.; Asher, C. R.; Cosgrove, D. M.; Blackstone, E.; Thomas, J. D.; Garcia, M. J.

    2001-01-01

    OBJECTIVES: We sought to develop and validate a model that estimates the risk of obstructive coronary artery disease in patients undergoing operations for mitral valve degeneration and to demonstrate its potential clinical utility. METHODS: A total of 722 patients (67% men; age, 61 +/- 12 years) without a history of myocardial infarction, ischemic electrocardiographic changes, or angina who underwent routine coronary angiography before mitral valve prolapse operations between 1989 and 1996 were analyzed. A bootstrap-validated logistic regression model on the basis of clinical risk factors was developed to identify low-risk (< or =5%) patients. Obstructive coronary atherosclerosis was defined as 50% or more luminal narrowing in one or more major epicardial vessels, as determined by means of coronary angiography. RESULTS: One hundred thirty-nine (19%) patients had obstructive coronary atherosclerosis. Independent predictors of coronary artery disease include age, male sex, hypertension, diabetes mellitus,and hyperlipidemia. Two hundred twenty patients were designated as low risk according to the logistic model. Of these patients, only 3 (1.3%) had single-vessel disease, and none had multivessel disease. The model showed good discrimination, with an area under the receiver-operating characteristic curve of 0.84. Cost analysis indicated that application of this model could safely eliminate 30% of coronary angiograms, corresponding to cost savings of $430,000 per 1000 patients without missing any case of high-risk coronary artery disease. CONCLUSION: A model with standard clinical predictors can reliably estimate the prevalence of obstructive coronary atherosclerosis in patients undergoing mitral valve prolapse operations. This model can identify low-risk patients in whom routine preoperative angiography may be safely avoided.

  6. Prediction of coronary artery disease in patients undergoing operations for mitral valve degeneration

    Science.gov (United States)

    Lin, S. S.; Lauer, M. S.; Asher, C. R.; Cosgrove, D. M.; Blackstone, E.; Thomas, J. D.; Garcia, M. J.

    2001-01-01

    OBJECTIVES: We sought to develop and validate a model that estimates the risk of obstructive coronary artery disease in patients undergoing operations for mitral valve degeneration and to demonstrate its potential clinical utility. METHODS: A total of 722 patients (67% men; age, 61 +/- 12 years) without a history of myocardial infarction, ischemic electrocardiographic changes, or angina who underwent routine coronary angiography before mitral valve prolapse operations between 1989 and 1996 were analyzed. A bootstrap-validated logistic regression model on the basis of clinical risk factors was developed to identify low-risk (coronary atherosclerosis was defined as 50% or more luminal narrowing in one or more major epicardial vessels, as determined by means of coronary angiography. RESULTS: One hundred thirty-nine (19%) patients had obstructive coronary atherosclerosis. Independent predictors of coronary artery disease include age, male sex, hypertension, diabetes mellitus,and hyperlipidemia. Two hundred twenty patients were designated as low risk according to the logistic model. Of these patients, only 3 (1.3%) had single-vessel disease, and none had multivessel disease. The model showed good discrimination, with an area under the receiver-operating characteristic curve of 0.84. Cost analysis indicated that application of this model could safely eliminate 30% of coronary angiograms, corresponding to cost savings of $430,000 per 1000 patients without missing any case of high-risk coronary artery disease. CONCLUSION: A model with standard clinical predictors can reliably estimate the prevalence of obstructive coronary atherosclerosis in patients undergoing mitral valve prolapse operations. This model can identify low-risk patients in whom routine preoperative angiography may be safely avoided.

  7. Neuroprotective effects of curcumin alleviate lumbar intervertebral disc degeneration through regulating the expression of iNOS, COX‑2, TGF‑β1/2, MMP‑9 and BDNF in a rat model.

    Science.gov (United States)

    Hu, Yuan; Tang, Jin-Shu; Hou, Shu-Xun; Shi, Xiu-Xiu; Qin, Jiang; Zhang, Tie-Song; Wang, Xiao-Jing

    2017-11-01

    Curcumin is a natural product with antimutagenic, antitumor, antioxidant and neuroprotective properties. However, to the best of our knowledge, curcumin has yet to be investigated for the treatment of lumbar intervertebral disc degeneration LIDD). The aim of the present study was to investigate whether curcumin can alleviate LIDD through regulating the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)‑2, transforming growth factor (TGF)‑β1/2, matrix metalloproteinase (MMP)‑9 and brain‑derived neurotrophic factor (BDNF) in a rat model of LIDD. The results of the present study suggest that pretreatment with curcumin can prevent the development of LIDD in rats. It was revealed that treatment with curcumin significantly reduced interleukin (IL)‑1β and IL‑6, iNOS, COX‑2 and MMP‑9 levels in rats with LIDD. In addition, treatment with curcumin reduced the mRNA expression levels of TGF‑β1 and TGF‑β2, whereas it increased the mRNA expression levels of BDNF in rats with LIDD. In conclusion, the present findings indicate that curcumin may exert protective effects on LIDD development, exerting its action through the regulation of iNOS, COX‑2, TGF‑β1/2, MMP‑9 and BDNF.

  8. Laenderyggens degeneration og radiologi

    DEFF Research Database (Denmark)

    Jacobsen, Steffen; Gosvig, Kasper Kjaerulf; Sonne-Holm, Stig

    2006-01-01

    Low back pain (LBP) is one of the most common conditions, and at the same time one of the most complex nosological entities. The lifetime prevalence is approximately 80%, and radiological features of lumbar degeneration are almost universal in adults. The individual risk factors for LBP and signi...... is cyclic: exacerbations relieved by asymptomatic periods. New imaging modalities, including the combination of MR imaging and multiplanar 3-D CT scans, have broadened our awareness of possible pain-generating degenerative processes of the lumbar spine other than disc degeneration....

  9. A Double-Blind, Placebo-Controlled, Parallel-Group Pilot Study of Milnacipran for Chronic Radicular Pain (Sciatica) Associated With Lumbosacral Disc Disease

    OpenAIRE

    Marks, David M.; Pae, Chi-Un; Patkar, Ashwin A.

    2014-01-01

    Objective: The current study investigates whether milnacipran, an equipotent serotonin-norepinephrine reuptake inhibitor, is effective in reducing chronic radicular pain in patients (N = 11) with lumbosacral disc disease.

  10. Chinese herbal medicine for chronic neck pain due to cervical degenerative disc disease.

    Science.gov (United States)

    Trinh, Kien; Cui, Xuejun; Wang, Yong-Jun

    2010-11-15

    Systematic review. To assess the efficacy of Chinese herbal medicines in treating chronic neck pain with radicular signs or symptoms. Chronic neck pain with radicular signs or symptoms is a common condition. Many patients use complementary and alternative medicine, including traditional Chinese medicine, to address their symptoms. We electronically searched CENTRAL, MEDLINE, EMBASE, CINAHL, and AMED (up to 2009), the Chinese Biomedical Database and related herbal medicine databases in Japan and South Korea (up to 2007). We also contacted content experts and hand searched a number of journals published in China.We included randomized controlled trials with adults with a clinical diagnosis of cervical degenerative disc disease, cervical radiculopathy, or myelopathy supported by appropriate radiologic findings. The interventions were Chinese herbal medicines. The primary outcome was pain relief, measured with a visual analogue scale, numerical scale, or other validated tool. All 4 included studies were in Chinese; 2 of which were unpublished. Effect sizes were not clinically relevant and there was low quality evidence for all outcomes due to study limitations and sparse data (single studies). Two trials (680 participants) found that Compound Qishe Tablets relieved pain better in the short-term than either placebo or Jingfukang; one trial (60 participants) found than an oral herbal formula of Huangqi relieved pain better than Mobicox or Methycobal, and another trial (360 participants) showed that a topical herbal medicine, Compound Extractum Nucis Vomicae, relieved pain better than Diclofenac Diethylamine Emulgel. There is low quality evidence that an oral herbal medication, Compound Qishe Tablet, reduced pain more than placebo or Jingfukang and a topical herbal medicine, Compound Extractum Nucis Vomicae, reduced pain more than Diclofenac Diethylamine Emulgel. Further research is very likely to change both the effect size and our confidence in the results.

  11. Laenderyggens degeneration og radiologi

    DEFF Research Database (Denmark)

    Jacobsen, Steffen; Gosvig, Kasper Kjaerulf; Sonne-Holm, Stig

    2006-01-01

    and significant relationships between radiological findings and subjective symptoms have both been notoriously difficult to identify. The lack of consensus on clinical criteria and radiological definitions has hampered the undertaking of properly executed epidemiological studies. The natural history of LBP...... is cyclic: exacerbations relieved by asymptomatic periods. New imaging modalities, including the combination of MR imaging and multiplanar 3-D CT scans, have broadened our awareness of possible pain-generating degenerative processes of the lumbar spine other than disc degeneration....

  12. Brain metabolic correlates of dopaminergic degeneration in de novo idiopathic Parkinson's disease

    International Nuclear Information System (INIS)

    Berti, Valentina; Polito, Cristina; Vanzi, Eleonora; Cristofaro, Maria Teresa de; Pellicano, Giannantonio; Mungai, Francesco; Formiconi, Andreas Robert; Pupi, Alberto; Ramat, Silvia; Marini, Paolo; Sorbi, Sandro

    2010-01-01

    The aim of the present study was to evaluate the reciprocal relationships between motor impairment, dopaminergic dysfunction, and cerebral metabolism (rCMRglc) in de novo Parkinson's disease (PD) patients. Twenty-six de novo untreated PD patients were scanned with 123 I-FP-CIT SPECT and 18 F-FDG PET. The dopaminergic impairment was measured with putaminal 123 I-FP-CIT binding potential (BP), estimated with two different techniques: an iterative reconstruction algorithm (BP OSEM ) and the least-squares (LS) method (BP LS ). Statistical parametric mapping (SPM) multiple regression analyses were performed to determine the specific brain regions in which UPDRS III scores and putaminal BP values correlated with rCMRglc. The SPM results showed a negative correlation between UPDRS III and rCMRglc in premotor cortex, and a positive correlation between BP OSEM and rCMRglc in premotor and dorsolateral prefrontal cortex, not surviving at multiple comparison correction. Instead, there was a positive significant correlation between putaminal BP LS and rCMRglc in premotor, dorsolateral prefrontal, anterior prefrontal, and orbitofrontal cortex (p LS is an efficient parameter for exploring the correlations between PD severity and rCMRglc cortical changes. The correlation between dopaminergic degeneration and rCMRglc in several prefrontal regions likely represents the cortical functional correlate of the dysfunction in the motor basal ganglia-cortical circuit in PD. This finding suggests focusing on the metabolic course of these areas to follow PD progression and to analyze treatment effects. (orig.)

  13. Longitudinal patterns of semantic and episodic memory in frontotemporal lobar degeneration and Alzheimer's disease.

    Science.gov (United States)

    Xie, Sharon X; Libon, David J; Wang, Xingmei; Massimo, Lauren; Moore, Peachie; Vesely, Luisa; Khan, Alea; Chatterjee, Anjan; Coslett, H Branch; Hurtig, Howard I; Liang, Tsao-Wei; Grossman, Murray

    2010-03-01

    The longitudinal assessment of episodic and semantic memory was obtained from 236 patients diagnosed with Alzheimer's disease (AD, n = 128) and with frontotemporal lobar degeneration (FTLD, n = 108), including patients with a social comportment/dysexecutive (SOC/EXEC) disorder, progressive nonfluent aphasia (PNFA), semantic dementia (SemD), and corticobasal syndrome (CBS). At the initial assessment, AD patients obtained a lower score on the delayed free recall test than other patients. Longitudinal analyses for delayed free recall found converging performance, with all patients reaching the same level of impairment as AD patients. On the initial evaluation for delayed recognition, AD patients also obtained lower scores than other groups. Longitudinal analyses for delayed recognition test performance found that AD patients consistently produced lower scores than other groups and no convergence between AD and other dementia groups was seen. For semantic memory, there were no initial between-group differences. However, longitudinal analyses for semantic memory revealed group differences over illness duration, with worse performance for SemD versus AD, PNFA, SOC/EXEC, and CBS patients. These data suggest the presence of specific longitudinal patterns of impairment for episodic and semantic memory in AD and FTLD patients suggesting that all forms of dementia do not necessarily converge into a single phenotype.

  14. Volumetric MRI for evaluation of regional pattern and progression of neocortical degeneration in Alzheimer's disease

    International Nuclear Information System (INIS)

    Leinsinger, G.; Teipel, S.; Pruessner, J.; Hampel, H.; Wismueller, A.; Born, C.; Meindl, T.; Flatz, W.; Schoenberg, S.; Reiser, M.

    2003-01-01

    Volumetric analysis of the corpus callosum and hippocampus using MRI in Alzheimer's disease (AD) to evaluate the regional pattern and progression of neocortical neurodegeneration. In subsequent studies we investigated patients with AD and healthy controls. Volumetry was based on MRI-data from a sagittal 3D T1w-gradient echo sequence. The corpus callosum (CC) was measured in a midsagittal slice, and subdivided into 5 subregions. Volumetry of the hippocampus/amygdala-formation (HAF) was performed by segmentation in coronary reoriented slices. In AD patients we found a significant atrophy in the rostrum und splenium of CC. The atrophy was correlated with the severity of dementia, but no correlation was found with the load of white matter lesions. In comparison with 18 FDG-PET, we found a significant correlation of regional CC-atrophy with the regional decline of cortical glucose metabolism. A ROC-analysis demonstrated no significant differences in the diagostic accuracy of HAF volumetry and regional CC volumetry of the splenium (region C5) even in mild stages of dementia. Regional atrophy of CC can be used as a marker of neocortical degeneration even in early stages of dementia in AD. (orig.) [de

  15. Retinal pigment epithelial detachments and tears, and progressive retinal degeneration in light chain deposition disease.

    Science.gov (United States)

    Spielberg, Leigh H; Heckenlively, John R; Leys, Anita M

    2013-05-01

    Light-chain deposition disease (LCDD) is a rare condition characterised by deposition of monoclonal immunoglobulin light chains (LCs) in tissues, resulting in varying degrees of organ dysfunction. This study reports the characteristic clinical ocular findings seen in advanced LCDD upon development of ocular fundus changes. This is the first report to describe this entity in vivo in a series of patients. A case series of ocular fundus changes in three patients with kidney biopsy-proven LCDD. All patients underwent best corrected visual acuity (BCVA) exam, perimetry, colour fundus photography and fluorescein angiography; two patients underwent indocyanine green angiography, optical coherence tomography, ultrasound and electroretinography; and one patient underwent fundus autofluorescence. Three patients, 53-60 years old at initial presentation, were studied. All three presented with night blindness, poor dark adaptation, metamorphopsia and visual loss. Examination revealed serous and serohaemorrhagic detachments, multiple retinal pigment epithelial (RPE) tears, diffuse RPE degeneration and progressive fibrotic changes. Neither choroidal neovascularisation nor other vascular abnormalities were present. Final best corrected visual acuity (BCVA) ranged from 20/40 to 20/300. Progressive LC deposition in the fundus seems to damage RPE pump function with flow disturbance between choroid and retina. This pathogenesis can explain the evolution to RPE detachments and subsequent rips and progressive retinal malfunction.

  16. Variability of disease activity in patients treated with ranibizumab for neovascular age-related macular degeneration.

    Science.gov (United States)

    Enders, P; Scholz, P; Muether, P S; Fauser, S

    2016-08-01

    PurposeTo analyze choroidal neovasularization (CNV) activity and recurrence patterns in patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab, and the correlation with individual intraocular vascular endothelial growth factor (VEGF) suppression time (VST).MethodsPost-hoc analysis of data from a prospective, non-randomized clinical study. Patients with nAMD treated with ranibizumab on a pro re nata regimen. Disease activity was analyzed monthly by spectral-domain optical coherence tomography and correlated with VSTs.ResultsOverall, 73 eyes of 73 patients were included in the study with a mean follow-up of 717 days (range: 412-1239 days). Overall, the mean CNV-activity-free interval was 76.5 days (range: 0-829 days). The individual range of the length of dry intervals was high. A total of 42% of patients had a range of more than 90 days. Overall, 16% of patients showed persistent activity. And 12% stayed dry after the initial ranibizumab treatment. No significant correlation was found between the CNV-recurrence pattern and VST (P=0.12).ConclusionsCNV activity in nAMD is irregular, which is reflected in the range of the duration of dry intervals and late recurrences. The biomarker VST solely seems not to be sufficient to explain recurrence pattern of CNV in all AMD patients.

  17. Gradient-echo imaging of intervertebral disk degeneration and facet joint disease

    International Nuclear Information System (INIS)

    Berns, D.H.; Kormos, D.; Modic, M.T.; Carter, J.; Masaryk, T.J.; Ross, J.S.

    1988-01-01

    The purpose of this study was to evaluate the accuracy of gradient-echo, partial-flip angle images in the evaluation of components of degenerative spine disease. First, cadaveric spines were studied with plain radiographs, high-resolution CT, T1-weighted spin-echo (SE) MR images (repetition time msec/echo time msec=500/17). T2-weighted SE images (2,000/30-90), and fast low-angle shot (FLASH) images (200/10.50 0 ) before and after intradiskal injection of air (0.1-1cc). Second, lumbar spine MR images were retrospectively evaluated to compare gradient-echo and SE sequences. Results indicate that the signal intensity changes of the intervertebral disk related to degeneration were best appreciated on T2-weighted SE studies in both groups. Vacuum phenomenon and calcification were most accurately assessed with FLASH imaging (based on susceptibility changes) and CT images. SE images appeared more sensitive to adjacent marrow change. In the facet joints, CT was more accurate for changes in the subarticular bone, but FLASH images were more sensitive to change in the articular cartilage

  18. The Age-Related Eye Disease 2 Study: Micronutrients in the Treatment of Macular Degeneration.

    Science.gov (United States)

    Gorusupudi, Aruna; Nelson, Kelly; Bernstein, Paul S

    2017-01-01

    Age-related macular degeneration (AMD) is one of the leading causes of vision loss in the elderly. With an increasingly aged population worldwide, the need for the prevention of AMD is rising. Multiple studies investigating AMD with the use of animal models and cell culture have identified oxidative stress-related retinal damage as an important contributing factor. In general, diet is an excellent source of the antioxidants, vitamins, and minerals necessary for healthy living; moreover, the general public is often receptive to recommendations made by physicians and health care workers regarding diet and supplements as a means of empowering themselves to avoid common and worrisome ailments such as AMD, which has made epidemiologists and clinicians enthusiastic about dietary intervention studies. A wide variety of nutrients, such as minerals, vitamins, ω-3 (n-3) fatty acids, and various carotenoids, have been associated with reducing the risk of AMD. Initial results from the Age-Related Eye Disease Study (AREDS) indicated that supplementation with antioxidants (β-carotene and vitamins C and E) and zinc was associated with a reduced risk of AMD progression. The AREDS2 follow-up study, designed to improve upon the earlier formulation, tested the addition of lutein, zeaxanthin, and ω-3 fatty acids. In this review, we examine the science behind the nutritional factors included in these interventional studies and the reasons for considering their inclusion to lower the rate of AMD progression. © 2017 American Society for Nutrition.

  19. The Age-Related Eye Disease 2 Study: Micronutrients in the Treatment of Macular Degeneration123

    Science.gov (United States)

    Gorusupudi, Aruna; Nelson, Kelly; Bernstein, Paul S

    2017-01-01

    Age-related macular degeneration (AMD) is one of the leading causes of vision loss in the elderly. With an increasingly aged population worldwide, the need for the prevention of AMD is rising. Multiple studies investigating AMD with the use of animal models and cell culture have identified oxidative stress–related retinal damage as an important contributing factor. In general, diet is an excellent source of the antioxidants, vitamins, and minerals necessary for healthy living; moreover, the general public is often receptive to recommendations made by physicians and health care workers regarding diet and supplements as a means of empowering themselves to avoid common and worrisome ailments such as AMD, which has made epidemiologists and clinicians enthusiastic about dietary intervention studies. A wide variety of nutrients, such as minerals, vitamins, ω-3 (n–3) fatty acids, and various carotenoids, have been associated with reducing the risk of AMD. Initial results from the Age-Related Eye Disease Study (AREDS) indicated that supplementation with antioxidants (β-carotene and vitamins C and E) and zinc was associated with a reduced risk of AMD progression. The AREDS2 follow-up study, designed to improve upon the earlier formulation, tested the addition of lutein, zeaxanthin, and ω-3 fatty acids. In this review, we examine the science behind the nutritional factors included in these interventional studies and the reasons for considering their inclusion to lower the rate of AMD progression. PMID:28096126

  20. Sensitization of the nociceptive system in patients with low back pain and sickness absence: Disc degeneration disease or pain syndrome

    DEFF Research Database (Denmark)

    Jensen, Ole Kudsk; Nielsen, Claus Vinther; Stengaard-Pedersen, Kristian

    SENSITIZATION OF THE NOCICEPTIVE SYSTEM IN PATIENTS WITH LOW BACK PAIN AND SICKNESS ABSENCE O.K. Jensen1, C.V. Nielsen2, K. Stengaard-Pedersen3 1The Spine Center, Department of Internal Medicine, Region Hospital Silkeborg, 2Department of Clinical Social Medicine, University of Aarhus, and 3...... characterized by sensitization of the nociceptive system. Purpose: To assess sensitization of the nociceptive system in low back pain (LBP) patients by means of TP examination and measure of Pressure Pain Threshold (PPT) on the thumb nails. To search for associations between the number of TPs and structural...... = 1.35, p = 0.017) and mental distress (anxiety) in men (OR = 1.39, p = 0.003). After adjustment for age and sex, a positive association between LBP score and DDS was found only in patients with less than six TPs (OR = 1.21 (1.0-1.47), p = 0.043). Low PPT on the thumb nails was associated with DDS...

  1. Polygalae Radix Extract Prevents Axonal Degeneration and Memory Deficits in a Transgenic Mouse Model of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Tomoharu Kuboyama

    2017-11-01

    Full Text Available Memory impairments in Alzheimer’s disease (AD occur due to degenerated axons and disrupted neural networks. Since only limited recovery is possible after the destruction of neural networks, preventing axonal degeneration during the early stages of disease progression is necessary to prevent AD. Polygalae Radix (roots of Polygala tenuifolia; PR is a traditional herbal medicine used for sedation and amnesia. In this study, we aimed to clarify and analyze the preventive effects of PR against memory deficits in a transgenic AD mouse model, 5XFAD. 5XFAD mice demonstrated memory deficits at the age of 5 months. Thus, the water extract of Polygalae Radix (PR extract was orally administered to 4-month-old 5XFAD mice that did not show signs of memory impairment. After consecutive administrations for 56 days, the PR extract prevented cognitive deficit and axon degeneration associated with the accumulation of amyloid β (Aβ plaques in the perirhinal cortex of the 5XFAD mice. PR extract did not influence the formation of Aβ plaques in the brain of the 5XFAD mice. In cultured neurons, the PR extract prevented axonal growth cone collapse and axonal atrophy induced by Aβ. Additionally, it prevented Aβ-induced endocytosis at the growth cone of cultured neurons. Our previous study reported that endocytosis inhibition was enough to prevent Aβ-induced growth cone collapse, axonal degeneration, and memory impairments. Therefore, the PR extract possibly prevented axonal degeneration and memory impairment by inhibiting endocytosis. PR is the first preventive drug candidate for AD that inhibits endocytosis in neurons.

  2. Comparing the driving behaviours of individuals with frontotemporal lobar degeneration and those with Alzheimer's disease.

    Science.gov (United States)

    Fujito, Ryoko; Kamimura, Naoto; Ikeda, Manabu; Koyama, Asuka; Shimodera, Shinji; Morinobu, Shigeru; Inoue, Shimpei

    2016-01-01

    Assessing driving aptitude in dementia patients is critically important for both patient and public safety. However, there have been only a few reports on the driving behaviours and accident risk of patients with dementia, especially frontotemporal lobar degeneration (FTLD). Therefore, we compared the characteristics of driving behaviours in patients with FTLD and those with Alzheimer's disease (AD). The subjects were 28 FTLD and 67 AD patients who visited the Department of Psychiatry, Kochi Medical School Hospital. We conducted semi-structured interviews with their families and caregivers about traffic accident history and changes in patient driving behaviours after dementia onset and then compared the findings between the two groups. Overall changes in driving behaviours were reported in 89% (25/28) and 76% (51/67) of the FTLD and AD patients, respectively (P = 0.17). In the FTLD group, difficulty in judging inter-vehicle distances, ignoring road signs and traffic signals, and distraction were reported in 50% (14/28), 61% (17/28), and 50% (14/28) of patients, respectively, and 75% (21/28) patients had caused a traffic accident after dementia onset. The risk of causing an accident was higher in the FTLD group than in the AD group (odds ratio = 10.4, 95% confidence interval = 3.7-29.1). In addition, the mean duration between dementia onset and a traffic accident was 1.35 years in the FTLD group compared with 3.0 years in the AD group (P driving behaviours than those with AD, and the risk of causing a traffic accident may be higher in patients with FTLD from an early disease stage. © 2015 The Authors. Psychogeriatrics © 2015 Japanese Psychogeriatric Society.

  3. Anterior cervical discectomy with fusion in patients with cervical disc degeneration: a prospective outcome study of 258 patients (181 fused with autologous bone graft and 77 fused with a PEEK cage)

    Science.gov (United States)

    2010-01-01

    Background Anterior cervical discectomy with fusion (ACDF) is challenging with respect to both patient selection and choice of surgical procedure. The aim of this study was to evaluate the clinical outcome of ACDF, with respect to both patient selection and choice of surgical procedure: fusion with an autologous iliac crest graft (AICG) versus fusion with an artificial cage made of polyetheretherketone (PEEK). Methods This was a non-randomized prospective single-center outcome study of 258 patients who underwent ACDF for cervical disc degeneration (CDD). Fusion was attained with either tricortical AICG or PEEK cages without additional anterior plating, with treatment selected at surgeon's discretion. Radicular pain, neck-pain, headache and patient satisfaction with the treatment were scored using the visual analogue scale (VAS). Results The median age was 47.5 (28.3-82.8) years, and 44% of patients were female. 59% had single-level ACDF, 40% had two level ACDF and 1% had three-level ACDF. Of the patients, 181 were fused with AICG and 77 with a PEEK-cage. After surgery, the patients showed a significant reduction in radicular pain (ΔVAS = 3.05), neck pain (ΔVAS = 2.30) and headache (ΔVAS = 0.55). Six months after surgery, 48% of patients had returned to work: however 24% were still receiving workers' compensation. Using univariate and multivariate analyses we found that high preoperative pain intensity was significantly associated with a decrease in pain intensity after surgery, for all three pain categories. There were no significant correlations between pain relief and the following patient characteristics: fusion method (AICG or PEEK-cage), sex, age, number of levels fused, disc level fused, previous neck surgery (except for neck pain), previous neck trauma, or preoperative symptom duration. Two hundred out of the 256 (78%) patients evaluated the surgical result as successful. Only 27/256 (11%) classified the surgical result as a failure. Patient satisfaction

  4. Anterior cervical discectomy with fusion in patients with cervical disc degeneration: a prospective outcome study of 258 patients (181 fused with autologous bone graft and 77 fused with a PEEK cage

    Directory of Open Access Journals (Sweden)

    Roenning Paal

    2010-03-01

    Full Text Available Abstract Background Anterior cervical discectomy with fusion (ACDF is challenging with respect to both patient selection and choice of surgical procedure. The aim of this study was to evaluate the clinical outcome of ACDF, with respect to both patient selection and choice of surgical procedure: fusion with an autologous iliac crest graft (AICG versus fusion with an artificial cage made of polyetheretherketone (PEEK. Methods This was a non-randomized prospective single-center outcome study of 258 patients who underwent ACDF for cervical disc degeneration (CDD. Fusion was attained with either tricortical AICG or PEEK cages without additional anterior plating, with treatment selected at surgeon's discretion. Radicular pain, neck-pain, headache and patient satisfaction with the treatment were scored using the visual analogue scale (VAS. Results The median age was 47.5 (28.3-82.8 years, and 44% of patients were female. 59% had single-level ACDF, 40% had two level ACDF and 1% had three-level ACDF. Of the patients, 181 were fused with AICG and 77 with a PEEK-cage. After surgery, the patients showed a significant reduction in radicular pain (ΔVAS = 3.05, neck pain (ΔVAS = 2.30 and headache (ΔVAS = 0.55. Six months after surgery, 48% of patients had returned to work: however 24% were still receiving workers' compensation. Using univariate and multivariate analyses we found that high preoperative pain intensity was significantly associated with a decrease in pain intensity after surgery, for all three pain categories. There were no significant correlations between pain relief and the following patient characteristics: fusion method (AICG or PEEK-cage, sex, age, number of levels fused, disc level fused, previous neck surgery (except for neck pain, previous neck trauma, or preoperative symptom duration. Two hundred out of the 256 (78% patients evaluated the surgical result as successful. Only 27/256 (11% classified the surgical result as a failure

  5. DIAM device for low back pain in degenerative disc disease : 24 months follow-up.

    Science.gov (United States)

    Buric, Josip; Pulidori, Massimiliano; Sinan, Tariq; Mehraj, Sheikh

    2011-01-01

    To evaluate the usefulness of the DIAM device in patients affected by low back pain due to degenerative disc disease. Recently a number of interspinous devices for dynamic interspinous distraction-stabilization have entered the clinical practice in Europe. All of these devices have a common property of acting on the posterior part of the functional spinal unit by distracting the spinous processes and avoiding extension of the treated segment. Consequently, these systems seem to improve the cross-sectional area of the thecal sac and enlarge the diameter of the intervertebral foramina. What was found as a collateral observation after implantation of these devices was that those patients affected by low back pain, improved significantly in their pain level. Fifty-two consecutive patients were included in the study. There were 29 females and 23 males, aged between 29 and 77 years (mean 49.4 ± s.d. 12.4). The pre-operative symptom duration ranged from 6 to 84 months (mean 31.8 ± s.d. 20.2, median 24 months).The following diagnostic measures were performed in each patient: MRI, dynamic X-rays and provocative discography positive for pain reproduction.The patients were followed for pain by VAS and for functional status by self-reported Roland-Morris Disability Questionnaire. The minimum follow-up was 24 months (24-36). The intermediate follow-up at 6, 12 and 18 months was tested for, too. To determine the number of improved patients we have arbitrarily selected a cut-off criteria based on a ≥30% of improvement as calculated on the Roland Morris Disability Questionnaire scale comparing the 24 months values to the baseline values. Forty-six patients (88%) were considered as success and 2 (4%) were considered as failure. No long-term complications were observed. This preliminary report indicates that the DIAM device could possibly be useful in the treatment of LBP due to DDD. Further research with RCT is necessary to confirm these preliminary results.

  6. Transforaminal Percutaneous Endoscopic Discectomy for Lumbar Disc Herniation in Parkinson's Disease: A Case-Control Study.

    Science.gov (United States)

    Kapetanakis, Stylianos; Giovannopoulou, Eirini; Charitoudis, George; Kazakos, Konstantinos

    2016-08-01

    A case-control study. To investigate the effectiveness of transforaminal percutaneous endoscopic discectomy (TPED) in Parkinson's disease (PD). Patients with PD frequently suffer from radiculopathy and low back pain. Additionally, they demonstrate higher complication rates after open spine surgery. However, the clinical outcome of minimally invasive techniques for lumbar discectomy, such as TPED, have not been established for this population. Patients diagnosed with lumbar disc hernia were divided into Group A (11 patients diagnosed with PD), and Group B (10 patients as the control, non-PD group). All patients underwent TPED. Indexes of visual analogue scale (VAS) for leg pain and Oswestry disability index (ODI) were assessed right before surgery and at six weeks, three months, six months and one year post-surgery. At the baseline visit, groups did not differ significantly with age (p=0.724), gender (p=0.835), level of operation (p=0.407), ODI (p=0.497) and VAS (p=0.772). Parkinson's patients had higher scores in ODI at every visit, but the outcome was statistically significant only at 3 months (p=0.004) and one year (p=0.007). Similarly, VAS measurements were higher at each time point, with the difference being significant at 3 (p<0.001), 6 (0.021), and 12 (p<0.001) months after surgery. At the end of a year of follow up, ODI was reduced by 49.6% (±16.7) in Group A and 59.2% (±8.0) in Group B (p=0.111), translating to a 79.5% (±13.0) and 91.5% (±4.1) average improvement in daily functionality (p=0.024). VAS was reduced by 59.1 mm (±11.8) in Group A and 62.2 mm (±7.4) in Group B (p=0.485), leading to an 85.3 % (±4.0) and 91.9% (±2.6) general improvement in leg pain (p<0.001). Our data indicate that TPED led to satisfactory improvement in leg pain and daily living in PD patients a year after surgery.

  7. Dual pathology of corticobasal degeneration and Parkinson's disease in a patient with clinical features of progressive supranuclear palsy.

    Science.gov (United States)

    Mooney, Tomin; Tampiyappa, Anthony; Robertson, Thomas; Grimley, Rohan; Burke, Chris; Ng, Kenneth; Patrikios, Peter

    2011-01-01

    Corticobasal degeneration and Parkinson's disease are pathologically distinct disorders with unique histological and biochemical features of a tauopathy and a-synucleinopathy respectively. We report the first case of co-occurrence of these pathologies in the same patient. Convergence of such distinctly separate neuropathology in the same brain highlights the need for extensive brain banking and further research in supporting the hypothesis that tauopathies and a-synucleinopathies might share common pathogenic mechanisms.

  8. Genome-wide analysis of disease progression in age-related macular degeneration.

    Science.gov (United States)

    Yan, Qi; Ding, Ying; Liu, Yi; Sun, Tao; Fritsche, Lars G; Clemons, Traci; Ratnapriya, Rinki; Klein, Michael L; Cook, Richard J; Liu, Yu; Fan, Ruzong; Wei, Lai; Abecasis, Gonçalo R; Swaroop, Anand; Chew, Emily Y; Weeks, Daniel E; Chen, Wei

    2018-03-01

    Family- and population-based genetic studies have successfully identified multiple disease-susceptibility loci for Age-related macular degeneration (AMD), one of the first batch and most successful examples of genome-wide association study. However, most genetic studies to date have focused on case-control studies of late AMD (choroidal neovascularization or geographic atrophy). The genetic influences on disease progression are largely unexplored. We assembled unique resources to perform a genome-wide bivariate time-to-event analysis to test for association of time-to-late-AMD with ∼9 million variants on 2721 Caucasians from a large multi-center randomized clinical trial, the Age-Related Eye Disease Study. To our knowledge, this is the first genome-wide association study of disease progression (bivariate survival outcome) in AMD genetic studies, thus providing novel insights to AMD genetics. We used a robust Cox proportional hazards model to appropriately account for between-eye correlation when analyzing the progression time in the two eyes of each participant. We identified four previously reported susceptibility loci showing genome-wide significant association with AMD progression: ARMS2-HTRA1 (P = 8.1 × 10-43), CFH (P = 3.5 × 10-37), C2-CFB-SKIV2L (P = 8.1 × 10-10) and C3 (P = 1.2 × 10-9). Furthermore, we detected association of rs58978565 near TNR (P = 2.3 × 10-8), rs28368872 near ATF7IP2 (P = 2.9 × 10-8) and rs142450006 near MMP9 (P = 0.0006) with progression to choroidal neovascularization but not geographic atrophy. Secondary analysis limited to 34 reported risk variants revealed that LIPC and CTRB2-CTRB1 were also associated with AMD progression (P < 0.0015). Our genome-wide analysis thus expands the genetics in both development and progression of AMD and should assist in early identification of high risk individuals.

  9. Differential Disease Progression in Atrophic Age-Related Macular Degeneration and Late-Onset Stargardt Disease.

    Science.gov (United States)

    Lindner, Moritz; Lambertus, Stanley; Mauschitz, Matthias M; Bax, Nathalie M; Kersten, Eveline; Lüning, Anna; Nadal, Jennifer; Schmitz-Valckenberg, Steffen; Schmid, Matthias; Holz, Frank G; Hoyng, Carel B; Fleckenstein, Monika

    2017-02-01

    To compare the disease course of retinal pigment epithelium (RPE) atrophy secondary to age-related macula degeneratio (AMD) and late-onset Stargardt disease (STGD1). Patients were examined longitudinally by fundus autofluorescence, near-infrared reflectance imaging, and best-corrected visual acuity (BCVA). Areas of RPE atrophy were quantified using semi-automated software, and the status of the fovea was evaluated based on autofluorescence and near-infrared reflectance images. Mixed-effects models were used to compare atrophy progression rates. BCVA loss and loss of foveal integrity were analyzed using Turnbull's estimator. A total of 151 patients (226 eyes) with RPE atrophy secondary to AMD and 38 patients (66 eyes) with RPE atrophy secondary to late-onset STGD1 were examined for a median time of 2.3 years (interquartile range, 2.7). Mean baseline age was 74.2 years (SD, 7.6) in AMD and 63.4 (SD, 9.9) in late-onset STGD1 (P = 1.1 × 10-7). Square root atrophy progression was significantly faster in AMD when compared with late-onset STGD1 (0.28 mm/year [SE, 0.01] vs. 0.23 [SE, 0.03]; P = 0.030). In late-onset STGD1, the median survival of the fovea was significantly longer when compared with eyes with AMD (8.60 vs. 3.35 years; P = 0.005) with a trend to a later BCVA loss of ≥3 lines (5.97 vs. 4.37 years; P = 0.382). These natural history data indicate differential disease progression in AMD versus late-onset STGD1. The results underline the relevance of refined phenotyping in elderly patients presenting with RPE atrophy in regard to prognosis and design of interventional trials.

  10. High sensitive C-reactive protein-Effective tool in determining postoperative recovery in lumbar disc disease

    Directory of Open Access Journals (Sweden)

    Tushar Narayan Rathod

    2014-01-01

    Full Text Available Background: It is common in medical practice to see patients having persistent pain and radiculopathy even after undergoing discectomy surgery. Inflammatory cytokines, such as interleukins are produced at the site of disc herniation and are now considered responsible for the pain perceived by the patient. This study has used high sensitive C-reactive protein (HSCRP assay for predicting inflammation around the nerve roots on very same principle, which has used HSCRP for predicting coronary artery diseases in current clinical practice. Thus, purpose of this study is to test whether HSCRP can stand as an objective tool to predict postoperative recovery in patients undergoing lumbar discectomy. That is, to study association between preoperative HSCRP blood level and postoperative recovery with the help of modified Oswestry Back Disability Score. Materials and Methods: A study group consisting of 50 cases of established lumbar disc disease and control group of 50 normal subjects, matched with the study group. Both the study and control groups were subjected to detailed evaluation with the help of modified Oswestry Low Back Pain Scale both pre and postoperatively at 3 months, 6 months and 1-year. The preoperative blood samples were analyzed to assess the HSCRP concentration. All the cases underwent surgery over a period of 1-year by the same surgeon. Results: The level of HSCRP in the study group was between 0.050- and 0.710 mg/dL and in the control group, 0.005-0.020 mg/dL. There was highly significant positive correlation between preoperative HSCRP level and postoperative score at P 10 points, while those with HSCRP level in the range of 0.470 ± 0.163 mg/dL, showed poor recovery (score improved < 10 points. Conclusion: HSCRP will serve as a good supplementary prognostic marker for operative decision making in borderline and troublesome cases of lumbar disc disease.

  11. Assessment of axonal degeneration in Alzheimer's disease with diffusion tensor MRI; Diffusion tensor imaging zur Erfassung axonaler Degeneration bei Morbus Alzheimer

    Energy Technology Data Exchange (ETDEWEB)

    Stahl, R. [Institut fuer Klinische Radiologie - Grosshadern, Klinikum der Universitaet Muenchen (Germany); Institut fuer Klinische Radiologie - Grosshadern, Klinikum der Universitaet Muenchen, Marchioninistr. 15, 81377, Muenchen (Germany); Dietrich, O.; Reiser, M.F.; Schoenberg, S.O. [Institut fuer Klinische Radiologie - Grosshadern, Klinikum der Universitaet Muenchen (Germany); Teipel, S.; Hampel, H. [Klinik fuer Psychiatrie und Psychotherapie, Klinikum der Universitaet Muenchen (Germany)

    2003-07-01

    Alzheimer disease (AD) causes cortical degeneration with subsequent degenerative changes of the white matter. The aim of this study was to investigate the extent of white matter tissue damage of patients with Alzheimer's disease in comparison with healthy subjects using diffusion tensor MRI (DTI). The value of integrated parallel imaging techniques (iPAT) for reduction of image distortion was assessed. We studied 9 patients with mild AD and 10 age and gender matched healthy controls. DTI brain scans were obtained on a 1.5 tesla system (Siemens Magnetom Sonata) using parallel imaging (iPAT) and an EPI diffusion sequence with TE/TR 71 ms/6000 ms. We used an 8-element head coil and a GRAPPA reconstruction algorithm with an acceleration factor of 2. From the tensor, the mean diffusivity (D), the fractional anisotropy (FA), and the relative anisotropy (RA) of several white matter regions were determined. FA was significantly lower (p <0,05) in the white matter of the genu of corpus callosum from patients with AD than in the corresponding regions from healthy controls. There was a trend observed for slightly higher ADC values in the AD group (p=0,06). No significant changes were observed in the regions of the splenium, internal capsule, pericallosal areas, frontal, temporal, parietal, and occipital lobe. The images obtained with iPAT contained substantially less susceptibility artefacts and were less distorted than images acquired with non-parallel imaging technique. DTI is a method with potential to assess early stages of white matter damage in vivo. The altered FA and ADC values in the genu of corpus callosum of patients with AD presumably reflect the microscopic white matter degeneration. Acquisition time can be reduced by iPAT methods with less image distortion from susceptibility artefacts resulting in a more accurate calculation of the diffusion tensor. (orig.) [German] Bei der Alzheimer-Erkrankung (AD) kommt es zur kortikalen Degeneration und sekundaer zu

  12. Heterogeneity of cerebral blood flow in frontotemporal lobar degeneration and Alzheimer's disease

    International Nuclear Information System (INIS)

    Nagao, Michinobu; Sugawara, Yoshifumi; Mochizuki, Teruhito; Miki, Hitoshi; Kikuchi, Takanori; Ikeda, Manabu; Fukuhara, Ryuji; Hokoishi, Kazuhiko; Murase, Kenya

    2004-01-01

    This study was designed to quantify the heterogeneity on cerebral blood flow single-photon emission tomography (SPET) images in frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD) using a three-dimensional fractal analysis. Twenty-one FTLD patients, 21 AD patients and 11 healthy controls underwent technetium-99m hexamethylpropylene amine oxime SPET scanning. Patients with FTLD and AD matched for sex, age and the severity of dementia as estimated with the Clinical Dementia Rating and were determined to be in the early stage of illness. We delineated the SPET images using a 35% cut-off and a 50% cut-off of the maximal voxel radioactivity and measured the number of voxels included in the contours of two different cut-offs. The fractal dimension (FD) was calculated by relating the logarithms of the cut-offs and the numbers of voxels, and it was defined as the heterogeneity of the cerebral perfusion. We divided the SPET images into two sets, anterior and posterior, with equal numbers of coronal SPET slices. We calculated total FD, anterior FD and posterior FD for total, anterior and posterior SPET images. Anterior FDs for FTLD and AD were 1.55±0.34 and 1.24±0.19 (P=0.0002). The ratios of anterior to posterior FD for FTLD and AD were 1.81±0.41 and 1.32±0.14 (P<0.0001). Use of the anterior FD and the ratio of anterior to posterior FD separated FTLD patients from AD patients and controls with a sensitivity of 85.7% and a specificity of 93.8%. Anterior FD and the ratio of anterior to posterior FD may be useful in distinguishing FTLD from AD. (orig.)

  13. Amygdala TDP-43 Pathology in Frontotemporal Lobar Degeneration and Motor Neuron Disease.

    Science.gov (United States)

    Takeda, Takahiro; Seilhean, Danielle; Le Ber, Isabelle; Millecamps, Stéphanie; Sazdovitch, Véronique; Kitagawa, Kazuo; Uchihara, Toshiki; Duyckaerts, Charles

    2017-09-01

    TDP-43-positive inclusions are present in the amygdala in frontotemporal lobar degeneration (FTLD) and motor neuron disease (MND) including amyotrophic lateral sclerosis. Behavioral abnormalities, one of the chief symptoms of FTLD, could be, at least partly, related to amygdala pathology. We examined TDP-43 inclusions in the amygdala of patients with sporadic FTLD/MND (sFTLD/MND), FTLD/MND with mutation of the C9ORF72 (FTLD/MND-C9) and FTLD with mutation of the progranulin (FTLD-GRN). TDP-43 inclusions were common in each one of these subtypes, which can otherwise be distinguished on topographical and genetic grounds. Conventional and immunological stainings were performed and we quantified the numerical density of inclusions on a regional basis. TDP-43 inclusions in amygdala could be seen in 10 out of 26 sFTLD/MND cases, 5 out of 9 FTLD/MND-C9 cases, and all 4 FTLD-GRN cases. Their numerical density was lower in FTLD/MND-C9 than in sFTLD/MND and FTLD-GRN. TDP-43 inclusions were more numerous in the ventral region of the basolateral nucleus group in all subtypes. This contrast was apparent in sporadic and C9-mutated FTLD/MND, while it was less evident in FTLD-GRN. Such differences in subregional involvement of amygdala may be related to the region-specific neuronal connections that are differentially affected in FTLD/MND and FTLD-GRN. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

  14. Brain metabolic correlates of dopaminergic degeneration in de novo idiopathic Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Berti, Valentina; Polito, Cristina; Vanzi, Eleonora; Cristofaro, Maria Teresa de; Pellicano, Giannantonio; Mungai, Francesco; Formiconi, Andreas Robert; Pupi, Alberto [University of Florence, Department of Clinical Pathophysiology, Florence (Italy); Ramat, Silvia; Marini, Paolo; Sorbi, Sandro [University of Florence, Department of Psychiatric and Neurological Sciences, Florence (Italy)

    2010-03-15

    The aim of the present study was to evaluate the reciprocal relationships between motor impairment, dopaminergic dysfunction, and cerebral metabolism (rCMRglc) in de novo Parkinson's disease (PD) patients. Twenty-six de novo untreated PD patients were scanned with {sup 123}I-FP-CIT SPECT and {sup 18}F-FDG PET. The dopaminergic impairment was measured with putaminal {sup 123}I-FP-CIT binding potential (BP), estimated with two different techniques: an iterative reconstruction algorithm (BP{sub OSEM}) and the least-squares (LS) method (BP{sub LS}). Statistical parametric mapping (SPM) multiple regression analyses were performed to determine the specific brain regions in which UPDRS III scores and putaminal BP values correlated with rCMRglc. The SPM results showed a negative correlation between UPDRS III and rCMRglc in premotor cortex, and a positive correlation between BP{sub OSEM} and rCMRglc in premotor and dorsolateral prefrontal cortex, not surviving at multiple comparison correction. Instead, there was a positive significant correlation between putaminal BP{sub LS} and rCMRglc in premotor, dorsolateral prefrontal, anterior prefrontal, and orbitofrontal cortex (p < 0.05, corrected for multiple comparison). Putaminal BP{sub LS} is an efficient parameter for exploring the correlations between PD severity and rCMRglc cortical changes. The correlation between dopaminergic degeneration and rCMRglc in several prefrontal regions likely represents the cortical functional correlate of the dysfunction in the motor basal ganglia-cortical circuit in PD. This finding suggests focusing on the metabolic course of these areas to follow PD progression and to analyze treatment effects. (orig.)

  15. Artificial Disc Replacement

    Science.gov (United States)

    ... Spondylolisthesis BLOG FIND A SPECIALIST Treatments Artificial Disc Replacement (ADR) Patient Education Committee Jamie Baisden The disc ... Disc An artificial disc (also called a disc replacement, disc prosthesis or spine arthroplasty device) is a ...

  16. Continuous lumbar hemilaminectomy for intervertebral disc disease in an Amur tiger (Panthera tigris altaica).

    Science.gov (United States)

    Flegel, Thomas; Böttcher, Peter; Alef, Michaele; Kiefer, Ingmar; Ludewig, Eberhard; Thielebein, Jens; Grevel, Vera

    2008-09-01

    A 13-yr-old Amur tiger (Panthera tigris altaica) was presented for an acute onset of paraplegia. Spinal imaging that included plain radiographs, myelography, and computed tomography performed under general anesthesia revealed lateralized spinal cord compression at the intervertebral disc space L4-5 caused by intervertebral disc extrusion. This extrusion was accompanied by an extensive epidural hemorrhage from L3 to L6. Therefore, a continuous hemilaminectomy from L3 to L6 was performed, resulting in complete decompression of the spinal cord. The tiger was ambulatory again 10 days after the surgery. This case suggests that the potential benefit of complete spinal cord decompression may outweigh the risk of causing clinically significant spinal instability after extensive decompression.

  17. Molecular regulation of CCN2 in the intervertebral disc: lessons learned from other connective tissues.

    Science.gov (United States)

    Tran, Cassie M; Shapiro, Irving M; Risbud, Makarand V

    2013-08-08

    Connective tissue growth factor (CCN2/CTGF) plays an important role in extracellular matrix synthesis, especially in skeletal tissues such as cartilage, bone, and the intervertebral disc. As a result there is a growing interest in examining the function and regulation of this important molecule in the disc. This review discusses the regulation of CCN2 by TGF-β and hypoxia, two critical determinants that characterize the disc microenvironment, and discusses known functions of CCN2 in the disc. The almost ubiquitous regulation of CCN2 by TGF-β, including that seen in the disc, emphasizes the importance of the TGF-β-CCN2 relationship, especially in terms of extracellular matrix synthesis. Likewise, the unique cross-talk between CCN2 and HIF-1 in the disc highlights the tissue and niche specific mode of regulation. Taken together the current literature supports an anabolic role for CCN2 in the disc and its involvement in the maintenance of tissue homeostasis during both health and disease. Further studies of CCN2 in this tissue may reveal valuable targets for the biological therapy of disc degeneration. © 2013 Elsevier B.V. All rights reserved.

  18. MR findings of degenerative changes of nucleus pulposus in lumbar spine: sequential changes after disc herniation

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    Kim, Sang Joon [Choong-Ang Gil Hospital, Seoul (Korea, Republic of); Cha, Yoo Mi; Hwang, Hee Young [College of Medicine, Dankook University, Chenoan (Korea, Republic of)

    1994-04-15

    To evaluate the relationship between MR changes of the nucleus pulposus and the time interval after traumatic disc herniation. T2-weighted MR images of 132 patients with back pain and/or sciatica were reviewed. The changes of signal intensity, central cleft and height of the nucleus pulposus were used as criteria of disc degeneration and they were graded as normal, mild, moderate and severe degree of degeneration. Putting these criteria together we provided integrated grade of degeneration of the nucleus pulposus(grade 0-3). To get the preliminary data for normal and age-related disc degeneration, we measured the disc height by age groups and disc levels and analyzed the relationship between the age of the patients and the signal intensity, cleft and height in normal disc levels of the 132 patients. In 68 patients of 88 levels disc herniation, we analyzed the relationship between symptom duration and the degree of degeneration. Among these 68 patients we selected 14 patients(16 levels) who were under 30 years of age and had history of recent trauma to minimize data distortion from age related degeneration and ambiguity of initiation point of degeneration. In this group we analyzed the relationship between the time period after traumatic disc herniation and the degree of degeneration. The age of the patient had close relationship with the grade of signal intensity, central cleft, and disc height and grade of degeneration of the nucleus pulposus in normal discs. In 88 levels of herniated discs, the duration of symptom and degree of degeneration showed moderate correlation. In 14 patients of disc herniation who were under 30 years old and had trauma history in recent 2 years, grade 1 disc degeneration occurred in average 3.7 months after trauma. Although it was difficult to proceed statistical analysis in the last group because of small patients number, the degree of degeneration of nucleus pulposus had close relationship with the duration after traumas or duration of

  19. MR findings of degenerative changes of nucleus pulposus in lumbar spine: sequential changes after disc herniation

    International Nuclear Information System (INIS)

    Kim, Sang Joon; Cha, Yoo Mi; Hwang, Hee Young

    1994-01-01

    To evaluate the relationship between MR changes of the nucleus pulposus and the time interval after traumatic disc herniation. T2-weighted MR images of 132 patients with back pain and/or sciatica were reviewed. The changes of signal intensity, central cleft and height of the nucleus pulposus were used as criteria of disc degeneration and they were graded as normal, mild, moderate and severe degree of degeneration. Putting these criteria together we provided integrated grade of degeneration of the nucleus pulposus(grade 0-3). To get the preliminary data for normal and age-related disc degeneration, we measured the disc height by age groups and disc levels and analyzed the relationship between the age of the patients and the signal intensity, cleft and height in normal disc levels of the 132 patients. In 68 patients of 88 levels disc herniation, we analyzed the relationship between symptom duration and the degree of degeneration. Among these 68 patients we selected 14 patients(16 levels) who were under 30 years of age and had history of recent trauma to minimize data distortion from age related degeneration and ambiguity of initiation point of degeneration. In this group we analyzed the relationship between the time period after traumatic disc herniation and the degree of degeneration. The age of the patient had close relationship with the grade of signal intensity, central cleft, and disc height and grade of degeneration of the nucleus pulposus in normal discs. In 88 levels of herniated discs, the duration of symptom and degree of degeneration showed moderate correlation. In 14 patients of disc herniation who were under 30 years old and had trauma history in recent 2 years, grade 1 disc degeneration occurred in average 3.7 months after trauma. Although it was difficult to proceed statistical analysis in the last group because of small patients number, the degree of degeneration of nucleus pulposus had close relationship with the duration after traumas or duration of

  20. An ex vivo study on immunohistochemical localization of MMP-7 and MMP-9 in temporomandibular joint discs with internal derangement

    Directory of Open Access Journals (Sweden)

    C. Loreto

    2013-04-01

    Full Text Available Internal derangement (ID is among the most common disorders of the temporomandibular joint (TMJ. Previous research by our group highlighted a correlation between apoptosis and TMJ ID. Metalloproteinases (MMP-7 and -9 have been shown to play an important role in extracellular matrix ECM homeostasis and, through it, in joint disc remodelling. The immunohistochemical expression of MMP-7 and -9 was investigated in discs from patients with TMJ ID and from healthy donors and compared with the degree of histological tissue degeneration. The collagen fibre arrangement in pathological discs exhibited varying degrees of disruption. New vessels were consistently detected; endothelial cells from these vessels were immunolabelled with both MMP-7 and MMP-9. More or less intense MMP-7 and MMP-9 immunolabelling was detected in the cytoplasm of disc cells from all patients. MMP-7 and MMP-9 immunostaining was significantly different between pathological and normal discs and correlated with the extent of histopathological degeneration. MMP-7 and MMP-9 upregulation in discs from patients with TMJ ID demonstrates their involvement in disc damage in this disorder. A greater understanding of these processes could help identify ways to curb MMP overproduction without affecting their tissue remodelling action. The design of specific inhibitors for these MMPs would not only help to gain insights into the biological roles of MMPs, but would also aid in developing therapeutic interventions for diseases associated with abnormal ECM degradation.

  1. Assessment of trunk muscle density using CT and its association with degenerative disc and facet joint disease of the lumbar spine.

    Science.gov (United States)

    Sebro, Ronnie; O'Brien, Liam; Torriani, Martin; Bredella, Miriam A

    2016-09-01

    The purpose of this study was (1) to evaluate the association of trunk muscle density assessed by computed tomography (CT) with age, gender, and BMI and (2) to evaluate the association between trunk muscle CT density and degenerative disc and facet joint disease of the lumbar spine. The study was IRB approved and HIPAA compliant. The study group comprised 100 subjects (mean age 44.4 ± 22.2 years, 51 % male) who underwent CT of the abdomen and pelvis without intravenous contrast. Exclusion criteria included prior abdominal or spine surgery, active malignancy and scoliosis. CTs were reviewed and the attenuation of the rectus abdominis, transverse abdominis, internal and external obliques, psoas, multifidus, longissimus and gluteus maximus were measured bilaterally at consistent levels. Degenerative disc and bilateral facet joint disease were scored using established methods. Univariate analyses were performed using linear regression. Multivariate linear regression was performed to adjust for age, gender and BMI. CT density of each trunk muscle correlated inversely with age (p degenerative disc and facet joint disease in the univariate analyses (p degenerative disc and facet joint disease respectively in the multivariate analysis. Fatty infiltration of trunk musculature increases with age and BMI. Fatty infiltration of the gluteus maximus and transverse abdominis are associated with degenerative disc and facet joint disease, independent of age, gender and BMI.

  2. Cumulative occupational lumbar load and lumbar disc disease – results of a German multi-center case-control study (EPILIFT

    Directory of Open Access Journals (Sweden)

    Michaelis Martina

    2009-05-01

    Full Text Available Abstract Background The to date evidence for a dose-response relationship between physical workload and the development of lumbar disc diseases is limited. We therefore investigated the possible etiologic relevance of cumulative occupational lumbar load to lumbar disc diseases in a multi-center case-control study. Methods In four study regions in Germany (Frankfurt/Main, Freiburg, Halle/Saale, Regensburg, patients seeking medical care for pain associated with clinically and radiologically verified lumbar disc herniation (286 males, 278 females or symptomatic lumbar disc narrowing (145 males, 206 females were prospectively recruited. Population control subjects (453 males and 448 females were drawn from the regional population registers. Cases and control subjects were between 25 and 70 years of age. In a structured personal interview, a complete occupational history was elicited to identify subjects with certain minimum workloads. On the basis of job task-specific supplementary surveys performed by technical experts, the situational lumbar load represented by the compressive force at the lumbosacral disc was determined via biomechanical model calculations for any working situation with object handling and load-intensive postures during the total working life. For this analysis, all manual handling of objects of about 5 kilograms or more and postures with trunk inclination of 20 degrees or more are included in the calculation of cumulative lumbar load. Confounder selection was based on biologic plausibility and on the change-in-estimate criterion. Odds ratios (OR and 95% confidence intervals (CI were calculated separately for men and women using unconditional logistic regression analysis, adjusted for age, region, and unemployment as major life event (in males or psychosocial strain at work (in females, respectively. To further elucidate the contribution of past physical workload to the development of lumbar disc diseases, we performed lag

  3. The activL® Artificial Disc: a next-generation motion-preserving implant for chronic lumbar discogenic pain

    Directory of Open Access Journals (Sweden)

    Yue JJ

    2016-05-01

    Full Text Available James J Yue,1 Rolando Garcia Jr,2 Larry E Miller3 1Department of Orthopaedic Surgery, Yale School of Medicine, New Haven, CT, 2Orthopedic Care Center, Miami, FL, 3Miller Scientific Consulting, Inc., Asheville, NC, USA Abstract: Degeneration of the lumbar intervertebral discs is a leading cause of chronic low back pain in adults. Treatment options for patients with chronic lumbar discogenic pain unresponsive to conservative management include total disc replacement (TDR or lumbar fusion. Until recently, only two lumbar TDRs had been approved by the US Food and Drug Administration - the Charité Artificial Disc in 2004 and the ProDisc-L Total Disc Replacement in 2006. In June 2015, a next-generation lumbar TDR received Food and Drug Administration approval - the activL® Artificial Disc (Aesculap Implant Systems. Compared to previous-generation lumbar TDRs, the activL® Artificial Disc incorporates specific design enhancements that result in a more precise anatomical match and allow a range of motion that better mimics the healthy spine. The results of mechanical and clinical studies demonstrate that the activL® Artificial Disc results in improved mechanical and clinical outcomes versus earlier-generation artificial discs and compares favorably to lumbar fusion. The purpose of this report is to describe the activL® Artificial Disc including implant characteristics, intended use, surgical technique, postoperative care, mechanical testing, and clinical experience to date. Keywords: activL® Artificial Disc, artificial disc, degenerative disc disease, discogenic, implant, lumbar, motion preservation, pain

  4. Treatments for dry age-related macular degeneration and Stargardt disease: a systematic review.

    Science.gov (United States)

    Waugh, Norman; Loveman, Emma; Colquitt, Jill; Royle, Pamela; Yeong, Jian Lee; Hoad, Geraldine; Lois, Noemi

    2018-05-01

    Age-related macular degeneration (AMD) is the leading cause of visual loss in older people. Advanced AMD takes two forms, neovascular (wet) and atrophic (dry). Stargardt disease (STGD) is the commonest form of inherited macular dystrophy. To carry out a systematic review of treatments for dry AMD and STGD, and to identify emerging treatments where future NIHR research might be commissioned. Systematic review. We searched MEDLINE, EMBASE, Web of Science and The Cochrane Library from 2005 to 13 July 2017 for reviews, journal articles and meeting abstracts. We looked for studies of interventions that aim to preserve or restore vision in people with dry AMD or STGD. The most important outcomes are those that matter to patients: visual acuity (VA), contrast sensitivity, reading speed, ability to drive, adverse effects of treatment, quality of life, progression of disease and patient preference. However, visual loss is a late event and intermediate predictors of future decline were accepted if there was good evidence that they are strong predictors of subsequent visual outcomes. These include changes detectable by investigation, but not necessarily noticed by people with AMD or STGD. ClinicalTrials.gov, the World Health Organization search portal and the UK Clinical Trials gateway were searched for ongoing and recently completed clinical trials. The titles and abstracts of 7948 articles were screened for inclusion. The full text of 398 articles were obtained for further screening and checking of references and 112 articles were included in the final report. Overall, there were disappointingly few good-quality studies (including of sufficient size and duration) reporting useful outcomes, particularly in STGD. However we did identify a number of promising research topics, including drug treatments, stem cells, new forms of laser treatment, and implantable intraocular lens telescopes. In many cases, research is already under way, funded by industry or governments. In AMD

  5. Effect of intervertebral disc disease on scoliosis in the lumbar spine

    Directory of Open Access Journals (Sweden)

    Wojcik Gustaw

    2014-09-01

    Full Text Available Lumbar intervertebral discopathy is a common clinical problem and a significant cause of low back pain. Usually it is associated with overload and damage to the intervertebral disc, which directly relates to the instability of the motion segment. Renal normal anatomy between tissues within the spinal canal is a cause of the reflex curvature of the spine, the goal is to increase the volume of the spinal channel and reduce the compression of the nerve tissue. Knee-jerk reaction to pain is an non physiological change of the setting of the spine in the frontal plane.

  6. MRI comparative study of the progressive supranuclear palsy, striatonigral degeneration and Parkinson disease

    International Nuclear Information System (INIS)

    Wu Wulin; Lou Mingwu; Wang Xiaoyi; Liao Weihua

    2009-01-01

    Objective: To provide a reliable differential diagnosis among the progressive supranuclear palsy (PSP), striatonigral degeneration (SND) and Parkinson disease (PD). Methods: Conventional MRI data in clinically proved PSP (8 cases), SND (9 cases), PD (12 cases) and 12 normal controls were retrospectively analyzed. Midbrain area, pons area, pons diameter and middle cerebellar peduncles width were measured. The ratio of pons area over midbrain area (pons area / midbrain area) was calculated in all patients and normal controls. Then one way ANOVA and a Kruskal-Wallis H test were used for statistical analysis. Results: Midbrain area of the PSP group [(85.8 ± 12.0 mm 2 ] was the smallest, and there was statistically significant difference (P 2 ], PD group [(133.5 ± 10.8)mm 2 ] and the control group [(135.9 ± 7.5) mm 2 ]. There was no overlapping in the distribution of midbrain area between the PSP group (66.0-98.2 mm 2 ) and SND, PD and normal groups (116.2-142.1, 110.8-146.2 and 121.7-145.8 mm 2 ). The pons area-midbrain area ratio (P/M) of the PSP group (5.9 ± 0.8) was the largest in four groups, and there was statistically significant difference (P 2 , (18.6 ± 2.0) mm and (12.9 ± 2.4) mm] in all groups, and significant difference (P 2 , (22.7 ± 1.7) mm and (16.3 ± 1.1) mm], PD group [3.8 ± 0.3, (500.2 ± 25.8) mm 2 , (23.7 ± 1.0) mm and (16.8 ± 1.1) mm] and the control group [3.8 ± 0.3, (508.8 ± 20.6) mm 2 , (23.2 ± 1.2) mm and (16.4 ± 0.9) mm]. But the PD group and control group had no statistically significant difference in the midbrain area, pons area, pons diameter, P/M and middle cerebellar peduncles width (P > 0.05). Conclusion: MRI measurements helps in the differential diagnosis among PSP, SND and PD. (authors)

  7. The atrophy pattern in the subtypes of frontotemporal lobar degeneration and Alzheimer disease by structural MRI

    International Nuclear Information System (INIS)

    Zhang Bing; Zhang Xin; Li Ming; Chen Fei; Xu Jun; Wang Huiting; Qian Lai; Zhao Hui; Xu Yun; Zhu Bin

    2012-01-01

    Objective: To analyze the patterns of cortical atrophy of the two subtypes of frontotemporal lobar degeneration (FTLD), behavioural-variant frontotemporal dementia (bvFTD) and primary progressive aphasia (PPA). And to compare them with that of Alzheimer disease (AD) to provide an objective basis for early diagnosis and differential diagnosis. Methods: A total of 83 patients were enrolled in this study and there were 30 patients with cognitively normal controls (CN), 30 with AD and 23 with FTLD (10 with bvFTD, 13 with PPA). Philips 3.0 T TX scanner and 8 channel head coil was employed. Three dimensional turbo fast echo (3D-TFE) T 1 WI sequence with high resolution was used to collect the volume data of gray matter. 3D-TFE T 1 WI images were normalized and segmented into gray matter map for statistical analysis by SPM 8 and VBM 8. The false discovery rate (FDR) was adopted in P value adjustment, P<0.001, and the cluster size was set at 5. The full width at half maximum (FWHM) was set at 4 mm for the smoothing. Paired t test was used for statistics. Results: In bvFTD, PPA and AD groups,there were diffuse regions with reduced volume in cerebral cortex and subcortical structures (such as the hippocampus, the amygdala, the caudate nuclei, et al). The most obvious atrophic region in bvFTD and PPA group was found in the frontotemporal. Compared with AD, gray matter atrophy in bvFTD was found in brain regions including bilateral temporal lobes, bilateral superior temporal pole gyri, bilateral middle temporal pole gyri, right fusiform gyrus and bilateral frontal lobes. Among them, temporal and frontal lobes atrophy had obvious right partial lateralizing, with 14 301 voxels in right temporal lobe and 5105 in left (t=-5.03, P<0.05). The number of atrophy voxels in right and left frontal lobe were 1344 and 125 (t=3.45, P<0.05). The left temporooccipital lobe atrophy was more obvious than the right in PPA,with 15 637 voxels in left and 10 723 in right (t=-2.65, P<0

  8. Physical Limitations to Tissue Engineering of Intervertabral Disc Cells

    OpenAIRE

    Kobayashi, Shigeru; Baba, Hisatoshi; Takeno, Kenichi; Miyazaki, Tsuyoshi; Meir, Adam; Urban, Jill

    2010-01-01

    There is increasing interest in the using biological methods to repair degenerate discs. Biological repair depends on the disc maintaining a population of viable and active cells. Adequate nutrition of the disc influences the outcome of such therapies and, hence, must be considered to be a crucial parameter. Therefore, it is very important to maintain an appropriate physicochemical environment to achieve successful disc repair by biological methods and tissue engineering procedures.

  9. Association between promoter -1607 polymorphism of MMP1 and Lumbar Disc Disease in Southern Chinese

    Directory of Open Access Journals (Sweden)

    Leong John CY

    2008-04-01

    Full Text Available Abstract Background Matrix metalloproteinases (MMPs are involved in the degradation of the extracellular matrix of the intervertebral disc. A SNP for guanine insertion/deletion (G/D, the -1607 promoter polymorphism, of the MMP1 gene was found significantly affecting promoter activity and corresponding transcription level. Hence it is a good candidate for genetic studies in DDD. Methods Southern Chinese volunteers between 18 and 55 years were recruited from the population. DDD in the lumbar spine was defined by MRI using Schneiderman's classification. Genomic DNA was isolated from the leukocytes and genotyping was performed using the Sequenom® platform. Association and Hardy-Weinberg equilibrium checking were assessed by Chi-square test and Mann-Whitney U test. Results Our results showed substantial evidence of association between -1607 promoter polymorphism of MMP1 and DDD in the Southern Chinese subjects. D allelic was significantly associated with DDD (p value = 0.027, odds ratio = 1.41 with 95% CI = 1.04–1.90 while Genotypic association on the presence of D allele was also significantly associated with DDD (p value = 0.046, odds ratio = 1.50 with 95% CI = 1.01–2.24. Further age stratification showed significant genotypic as well as allelic association in the group of over 40 years (genotypic: p value = 0.035, odds ratio = 1.617 with 95% CI = 1.033–2.529; allelic: p value = 0.033, odds ratio = 1.445 with 95% CI = 1.029–2.029. Disc bulge, annular tears and the Schmorl's nodes were not associated with the D allele. Conclusion We demonstrated that individuals with the presence of D allele for the -1607 promoter polymorphism of MMP1 are about 1.5 times more susceptible to develop DDD when compared with those having G allele only. Further association was identified in individuals over 40 years of age. Disc bulge, annular tear as well as Schmorl's nodes were not associated with this polymorphism.

  10. Feasibility of minimally-invasive fiber-based evaluation of chondrodystrophoid canine intervertebral discs by light absorption and scattering spectroscopy

    Science.gov (United States)

    Jiang, Yuanyuan; McKeirnan, Kelci; Piao, Daqing; Bartels, Kenneth E.

    2011-03-01

    Extrusion or protrusion of an intervertebral disc is a common, frequently debilitating, painful, and sometimes fatal neurologic disease in the chondrodystrophic dog (dachshund, Pekingese, etc.). A similar condition of intervertebral disc degeneration with extrusion/protrusion is also a relatively common neurologic condition in human patients. Degeneration of the relatively avascular chondrodystrophoid intervertebral disc is associated with loss of water content, increased collagen, and deposits of calcified mineral in the nucleus pulposus. Current diagnostic methods have many limitations for providing accurate information regarding disc composition in situ prior to surgical intervention. Disc composition (i.e., mineralization), can influence the type of treatment regime and potentially prognosis and recurrence rates. The objective of this study is to investigate the feasibility of using a fiber-needle spectroscopy sensor to analyze the changes of tissue compositions involved in the chondrodystrophoid condition of the canine intervertebral disc. The nucleous pulposus, in which the metaplastic process / degeneration develops, is approximately 2mm thick and 5mm in diameter in the dachshund-sized dog. It lies in the center of the disc, surrounded by the annulus fibrosis and is enclosed by cartilaginous vertebral endplates cranially and caudally. This "shallow-and-small-slab" geometry limits the configuration of a fiber probe to sense the disc tissue volume without interference from the vertebrae. A single-fiber sensor is inserted into a 20 gauge myelographic spinal needle for insertion into the disc in situ and connected via a bifurcated fiber to the light source and a spectrometer. A tungsten light source and a 940nm light-emitting-diode are combined for spectral illumination covering VIS/NIR with expected improved sensitivity to water. Analysis of the reflectance spectra is expected to provide information of scattering and absorption compositions of tissue in

  11. Biomechanical analysis of the camelid cervical intervertebral disc

    Directory of Open Access Journals (Sweden)

    Dean K. Stolworthy

    2015-01-01

    Full Text Available Chronic low back pain (LBP is a prevalent global problem, which is often correlated with degenerative disc disease. The development and use of good, relevant animal models of the spine may improve treatment options for this condition. While no animal model is capable of reproducing the exact biology, anatomy, and biomechanics of the human spine, the quality of a particular animal model increases with the number of shared characteristics that are relevant to the human condition. The purpose of this study was to investigate the camelid (specifically, alpaca and llama cervical spine as a model of the human lumbar spine. Cervical spines were obtained from four alpacas and four llamas and individual segments were used for segmental flexibility/biomechanics and/or morphology/anatomy studies. Qualitative and quantitative data were compared for the alpaca and llama cervical spines, and human lumbar specimens in addition to other published large animal data. Results indicate that a camelid cervical intervertebral disc (IVD closely approximates the human lumbar disc with regard to size, spinal posture, and biomechanical flexibility. Specifically, compared with the human lumbar disc, the alpaca and llama cervical disc size are approximately 62%, 83%, and 75% with regard to area, depth, and width, respectively, and the disc flexibility is approximately 133%, 173%, and 254%, with regard to range of motion (ROM in axial-rotation, flexion-extension, and lateral-bending, respectively. These results, combined with the clinical report of disc degeneration in the llama lower cervical spine, suggest that the camelid cervical spine is potentially well suited for use as an animal model in biomechanical studies of the human lumbar spine.

  12. Technique and results of the spinal computed tomography in the diagnosis of cervical disc disease

    International Nuclear Information System (INIS)

    Artmann, H.; Salbeck, R.; Grau, H.

    1985-01-01

    We give a description of a technique of the patient's positioning with traction of the arms during the cervical spinal computed tomography which allows to draw the shoulders downwards by about one to three cervical segments. By this method the quality of the images can be improved in 96% in the cervical segment 6/7 and in 81% in the cervical/thoracal segment 7/1 to such a degree that a reliable judgement of the soft parts in the spinal canal becomes possible. The diagnostic reliability of the computed tomography of the cervical disc herniation is thus improved so that the necessity of a myelography is decreasing. The results of 396 cervical spinal computed tomographies are presented. (orig.) [de

  13. [Research progress of intervertebral disc endogenous stem cells for intervertebral disc regeneration].

    Science.gov (United States)

    Liang, Hang; Deng, Xiangyu; Shao, Zengwu

    2017-10-01

    To summarize the research progress of intervertebral disc endogenous stem cells for intervertebral disc regeneration and deduce the therapeutic potential of endogenous repair for intervertebral disc degeneration. The original articles about intervertebral disc endogenous stem cells for intervertebral disc regeneration were extensively reviewed; the reparative potential in vivo and the extraction and identification in vitro of intervertebral disc endogenous stem cells were analyzed; the prospect of endogenous stem cells for intervertebral disc regeneration was predicted. Stem cell niche present in the intervertebral discs, from which stem cells migrate to injured tissues and contribute to tissues regeneration under certain specific microenvironment. Moreover, the migration of stem cells is regulated by chemokines system. Tissue specific progenitor cells have been identified and successfully extracted and isolated. The findings provide the basis for biological therapy of intervertebral disc endogenous stem cells. Intervertebral disc endogenous stem cells play a crucial role in intervertebral disc regeneration. Therapeutic strategy of intervertebral disc endogenous stem cells is proven to be a promising biological approach for intervertebral disc regeneration.

  14. Helicoid peripapillary chorioretinal degeneration complicated by choroidal neovascularization.

    Science.gov (United States)

    Triantafylla, Magdalini; Panos, Georgios D; Dardabounis, Doukas; Nanos, Panagiotis; Konstantinidis, Aristeidis

    2016-02-15

    Helicoid peripapillary chorioretinal degeneration (HPCD) is a hereditary disease of the fundus that is characterized by atrophic chorioretinal areas that appear early in life and expand gradually from the optic disc towards the macula and the periphery. We describe the case of an elderly man with a known diagnosis of HPCD who developed choroidal neovascular membrane (CNV) in both eyes during the course of the disease. The patient was treated with intravitreal injection of ranibizumab, to which he had excellent response. The CNV subsided with 2 injections in the right eye and 1 in the left. Two years after the initial diagnosis of CNV in the right eye, visual acuity was 5/10 OD and 9/10 OS. Helicoid peripapillary chorioretinal degeneration is rarely complicated by CNV as the fundus lacks the trigger factors that would sustain this process. Although rare, HPCD complicated by CNV can be seen bilaterally, but responds well to few ranibizumab injections.

  15. GPR84 deficiency reduces microgliosis, but accelerates dendritic degeneration and cognitive decline in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Audoy-Rémus, Julie; Bozoyan, Lusine; Dumas, Aline; Filali, Mohammed; Lecours, Cynthia; Lacroix, Steve; Rivest, Serge; Tremblay, Marie-Eve; Vallières, Luc

    2015-05-01

    Microglia surrounds the amyloid plaques that form in the brains of patients with Alzheimer's disease (AD), but their role is controversial. Under inflammatory conditions, these cells can express GPR84, an orphan receptor whose pathophysiological role is unknown. Here, we report that GPR84 is upregulated in microglia of APP/PS1 transgenic mice, a model of AD. Without GPR84, these mice display both accelerated cognitive decline and a reduced number of microglia, especially in areas surrounding plaques. The lack of GPR84 affects neither plaque formation nor hippocampal neurogenesis, but promotes dendritic degeneration. Furthermore, GPR84 does not influence the clinical progression of other diseases in which its expression has been reported, i.e., experimental autoimmune encephalomyelitis (EAE) and endotoxic shock. We conclude that GPR84 plays a beneficial role in amyloid pathology by acting as a sensor for a yet unknown ligand that promotes microglia recruitment, a response affecting dendritic degeneration and required to prevent further cognitive decline. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Rheumatic Heart Disease and Myxomatous Degeneration: Differences and Similarities of Valve Damage Resulting from Autoimmune Reactions and Matrix Disorganization.

    Science.gov (United States)

    Martins, Carlo de Oliveira; Demarchi, Lea; Ferreira, Frederico Moraes; Pomerantzeff, Pablo Maria Alberto; Brandao, Carlos; Sampaio, Roney Orismar; Spina, Guilherme Sobreira; Kalil, Jorge; Cunha-Neto, Edecio; Guilherme, Luiza

    2017-01-01

    Autoimmune inflammatory reactions leading to rheumatic fever (RF) and rheumatic heart disease (RHD) result from untreated Streptococcus pyogenes throat infections in individuals who exhibit genetic susceptibility. Immune effector mechanisms have been described that lead to heart tissue damage culminating in mitral and aortic valve dysfunctions. In myxomatous valve degeneration (MXD), the mitral valve is also damaged due to non-inflammatory mechanisms. Both diseases are characterized by structural valve disarray and a previous proteomic analysis of them has disclosed a distinct profile of matrix/structural proteins differentially expressed. Given their relevance in organizing valve tissue, we quantitatively evaluated the expression of vimentin, collagen VI, lumican, and vitronectin as well as performed immunohistochemical analysis of their distribution in valve tissue lesions of patients in both diseases. We identified abundant expression of two isoforms of vimentin (45 kDa, 42 kDa) with reduced expression of the full-size protein (54 kDa) in RHD valves. We also found increased vitronectin expression, reduced collagen VI expression and similar lumican expression between RHD and MXD valves. Immunohistochemical analysis indicated disrupted patterns of these proteins in myxomatous degeneration valves and disorganized distribution in rheumatic heart disease valves that correlated with clinical manifestations such as valve regurgitation or stenosis. Confocal microscopy analysis revealed a diverse pattern of distribution of collagen VI and lumican into RHD and MXD valves. Altogether, these results demonstrated distinct patterns of altered valve expression and tissue distribution/organization of structural/matrix proteins that play important pathophysiological roles in both valve diseases.

  17. Striatonigral Degeneration

    Science.gov (United States)

    ... See More About Research The NINDS supports and conducts research on disorders of the brain and nervous system such as striatonigral degeneration. This research ... Publications Definition Striatonigral ...

  18. Association of rs731236 polymorphism in the vitamin D receptor gene with degenerative disc disease: evidence from a meta-analysis.

    Science.gov (United States)

    Zong, Qiang; Ni, Dongkui; Li, Lijun; Shi, Yubo

    2015-01-01

    The purpose of this study was to investigate the association between the rs731236 polymorphism in the vitamin D receptor gene and degenerative disc disease, especially in Chinese. We elaborately searched the relevant studies through China National Knowledge Infrastructure (CNKI), PubMed and EMBASE databases. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the association. A total of 10 studies involving 1,220 cases and 1,225 controls were included in the present study. Overall, no evidence of significant risk between rs731236 polymorphism and degenerative disc disease was found in any genetic models. In addition, stratified analyses by ethnicity revealed similar results. However, stratified analyses by sample size in Chinese population show that sample size may be the primary source of heterogeneity. This meta-analysis suggested that the rs731236 polymorphism may not be associated with degenerative disc disease. However, for Asians, there existed some diversities, especially in Chinese population. Therefore, a large number of well-designed studies are still required to assess this polymorphism and degenerative disc disease.

  19. The Role of the Innate Immune System in Alzheimer’s Disease and Frontotemporal Lobar Degeneration: An Eye on Microglia

    Directory of Open Access Journals (Sweden)

    Elisa Ridolfi

    2013-01-01

    Full Text Available In the last few years, genetic and biomolecular mechanisms at the basis of Alzheimer’s disease (AD and frontotemporal lobar degeneration (FTLD have been unraveled. A key role is played by microglia, which represent the immune effector cells in the central nervous system (CNS. They are extremely sensitive to the environmental changes in the brain and are activated in response to several pathologic events within the CNS, including altered neuronal function, infection, injury, and inflammation. While short-term microglial activity has generally a neuroprotective role, chronic activation has been implicated in the pathogenesis of neurodegenerative disorders, including AD and FTLD. In this framework, the purpose of this review is to give an overview of clinical features, genetics, and novel discoveries on biomolecular pathogenic mechanisms at the basis of these two neurodegenerative diseases and to outline current evidence regarding the role played by activated microglia in their pathogenesis.

  20. The role of the innate immune system in Alzheimer's disease and frontotemporal lobar degeneration: an eye on microglia.

    Science.gov (United States)

    Ridolfi, Elisa; Barone, Cinzia; Scarpini, Elio; Galimberti, Daniela

    2013-01-01

    In the last few years, genetic and biomolecular mechanisms at the basis of Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) have been unraveled. A key role is played by microglia, which represent the immune effector cells in the central nervous system (CNS). They are extremely sensitive to the environmental changes in the brain and are activated in response to several pathologic events within the CNS, including altered neuronal function, infection, injury, and inflammation. While short-term microglial activity has generally a neuroprotective role, chronic activation has been implicated in the pathogenesis of neurodegenerative disorders, including AD and FTLD. In this framework, the purpose of this review is to give an overview of clinical features, genetics, and novel discoveries on biomolecular pathogenic mechanisms at the basis of these two neurodegenerative diseases and to outline current evidence regarding the role played by activated microglia in their pathogenesis.

  1. Assessment of trunk muscle density using CT and its association with degenerative disc and facet joint disease of the lumbar spine

    International Nuclear Information System (INIS)

    Sebro, Ronnie; O'Brien, Liam; Torriani, Martin; Bredella, Miriam A.

    2016-01-01

    The purpose of this study was (1) to evaluate the association of trunk muscle density assessed by computed tomography (CT) with age, gender, and BMI and (2) to evaluate the association between trunk muscle CT density and degenerative disc and facet joint disease of the lumbar spine. The study was IRB approved and HIPAA compliant. The study group comprised 100 subjects (mean age 44.4 ± 22.2 years, 51 % male) who underwent CT of the abdomen and pelvis without intravenous contrast. Exclusion criteria included prior abdominal or spine surgery, active malignancy and scoliosis. CTs were reviewed and the attenuation of the rectus abdominis, transverse abdominis, internal and external obliques, psoas, multifidus, longissimus and gluteus maximus were measured bilaterally at consistent levels. Degenerative disc and bilateral facet joint disease were scored using established methods. Univariate analyses were performed using linear regression. Multivariate linear regression was performed to adjust for age, gender and BMI. CT density of each trunk muscle correlated inversely with age (p < 0.001) and BMI (p < 0.001). CT density of each trunk muscle correlated inversely with degenerative disc and facet joint disease in the univariate analyses (p < 0.001); however, only the gluteus maximus and the transverse abdominis remained significant predictors of degenerative disc and facet joint disease respectively in the multivariate analysis. Fatty infiltration of trunk musculature increases with age and BMI. Fatty infiltration of the gluteus maximus and transverse abdominis are associated with degenerative disc and facet joint disease, independent of age, gender and BMI. (orig.)

  2. Prevalence of spheroidal degeneration of cornea and its association with other eye diseases in tribes of Western Rajasthan

    Directory of Open Access Journals (Sweden)

    Amit Mohan

    2017-01-01

    Full Text Available Purpose: To determine the prevalence of spheroidal degeneration of cornea (SDC and its association with other eye diseases in the tribes of South-West Rajasthan. Methods: A total of 5012 patients were examined on slit lamp for the diagnosis of SDC. Diagnosis of SDC was made based on presence of amber granules in the superficial stroma of peripheral interpalpebral cornea with increasing opacification, coalescence and central spread or nodular and hazy surrounding stroma and divided in three stages. Results: The prevalence of SDC was 10.7%. Around 55% of the total of 535 cases examined were found to have Stage I followed by Stage II (32% and Stage III (13%. The prevalence is greatest in both men and women over 70 years of age. The severity of SDC is greater in men. SDC was significantly associated with pterygium and pseudocapsular exfoliation. Conclusion: Extreme temperature, low humidity, dust, high wind, and microtrauma caused by sand particles are the probable etiologies for higher prevalence of this kind of degeneration in this region.

  3. Metabolic bone disease and central retinal degeneration in a kitten due to nutritional inadequacy of an all-meat raw diet

    Directory of Open Access Journals (Sweden)

    Catherine Lenox

    2015-05-01

    Full Text Available A 5-month-old castrated male Sphynx kitten presented with left hindlimb lameness shortly after adoption. Prior to adoption, the breeder had fed the kitten an exclusively raw chicken diet. Radiographs revealed generalized osteopenia and a left tibia–fibula fracture. Ophthalmic examination revealed corneal vascularization and opacity in the right eye, and lesions suggestive of feline central retinal degeneration in the left eye. The patient’s diagnoses included metabolic bone disease and feline central retinal degeneration, which can result from taurine deficiency. The kitten’s nutritional diseases were managed with a complete and balanced canned diet designed for kitten growth and with taurine supplementation.

  4. The 'Lumbar Fusion Outcome Score' (LUFOS): a new practical and surgically oriented grading system for preoperative prediction of surgical outcomes after lumbar spinal fusion in patients with degenerative disc disease and refractory chronic axial low back pain.

    Science.gov (United States)

    Mattei, Tobias A; Rehman, Azeem A; Teles, Alisson R; Aldag, Jean C; Dinh, Dzung H; McCall, Todd D

    2017-01-01

    In order to evaluate the predictive effect of non-invasive preoperative imaging methods on surgical outcomes of lumbar fusion for patients with degenerative disc disease (DDD) and refractory chronic axial low back pain (LBP), the authors conducted a retrospective review of 45 patients with DDD and refractory LBP submitted to anterior lumbar interbody fusion (ALIF) at a single center from 2007 to 2010. Surgical outcomes - as measured by Visual Analog Scale (VAS/back pain) and Oswestry Disability Index (ODI) - were evaluated pre-operatively and at 6 weeks, 3 months, 6 months, and 1 year post-operatively. Linear mixed-effects models were generated in order to identify possible preoperative imaging characteristics (including bone scan/99mTc scintigraphy increased endplate uptake, Modic endplate changes, and disc degeneration graded according to Pfirrmann classification) which may be predictive of long-term surgical outcomes . After controlling for confounders, a combined score, the Lumbar Fusion Outcome Score (LUFOS), was developed. The LUFOS grading system was able to stratify patients in two general groups (Non-surgical: LUFOS 0 and 1; Surgical: LUFOS 2 and 3) that presented significantly different surgical outcomes in terms of estimated marginal means of VAS/back pain (p = 0.001) and ODI (p = 0.006) beginning at 3 months and continuing up to 1 year of follow-up. In conclusion,  LUFOS has been devised as a new practical and surgically oriented grading system based on simple key parameters from non-invasive preoperative imaging exams (magnetic resonance imaging/MRI and bone scan/99mTc scintigraphy) which has been shown to be highly predictive of surgical outcomes of patients undergoing lumbar fusion for treatment for refractory chronic axial LBP.

  5. Two cases of cervical disc disease with intramedullary pathological changes, which are responsible for their neurological syndromes, on delayed CT myelography

    International Nuclear Information System (INIS)

    Isu, Toyohiko; Iwasaki, Yoshinobu; Abe, Hiroshi; Tashiro, Kunio; Murai, Hiroshi; Miyasaka, Kazuo

    1987-01-01

    We report two cases of cervical disc disease with myelopathy classified as of motor system syndrome type showing small contrast accumulation within the spinal cord on delayed CT myelography. In our two cases, high density spots on delayed CT myelography were bilaterally localized within the spinal cord, and believed represent pathological changes of the spinal cord, such as collection of microcavities or cystic necrosis. In case 1, the high density areas seemed to be localized in the anterior horn and corticospinal tract, and in case 2, they seemed to be localized in the corticospinal tract. The patient in case 1 produced signs and symptoms resembling motor neurone disease and lesion could not be differentiated from the latter. Delayed CT myelography showed that the cause of the upper limb amyotrophy was attributed to an anterior horn disorder and that of pyramidal tract sign to a corticospinal tract disorder. Therefore, we could differentiate the lesion from motor neurone disease on delayed CT myelography in case 1. In conclusion, we emphasize that delayed CT myelography can demonstrate the intramedullary pathological changes in the cervical disc disease and is useful in distinguishing between cervical disc disease simulating motor neurone disease and the latter. (author)

  6. Effects of age, replicative lifespan and growth rate of human nucleus pulposus cells on selecting age range for cell-based biological therapies for degenerative disc diseases.

    Science.gov (United States)

    Lee, J S; Lee, S M; Jeong, S W; Sung, Y G; Lee, J H; Kim, K W

    2016-07-01

    Autologous disc cell implantation, growth factors and gene therapy appear to be promising therapies for disc regeneration. Unfortunately, the replicative lifespan and growth kinetics of human nucleus pulposus (NP) cells related to host age are unclear. We investigated the potential relations among age, replicative lifespan and growth rate of NP cells, and determined the age range that is suitable for cell-based biological therapies for degenerative disc diseases. We used NP tissues classified by decade into five age groups: 30s, 40s, 50s, 60s and 70s. The mean cumulative population doubling level (PDL) and population doubling rate (PDR) of NP cells were assessed by decade. We also investigated correlations between cumulative PDL and age, and between PDR and age. The mean cumulative PDL and PDR decreased significantly in patients in their 60s. The mean cumulative PDL and PDR in the younger groups (30s, 40s and 50s) were significantly higher than those in the older groups (60s and 70s). There also were significant negative correlations between cumulative PDL and age, and between PDR and age. We found that the replicative lifespan and growth rate of human NP cells decreased with age. The replicative potential of NP cells decreased significantly in patients 60 years old and older. Young individuals less than 60 years old may be suitable candidates for NP cell-based biological therapies for treating degenerative disc diseases.

  7. Dissociating Memory Networks in Early Alzheimer’s Disease and Frontotemporal Lobar Degeneration - A Combined Study of Hypometabolism and Atrophy

    Science.gov (United States)

    Frisch, Stefan; Dukart, Juergen; Vogt, Barbara; Horstmann, Annette; Becker, Georg; Villringer, Arno; Barthel, Henryk; Sabri, Osama; Müller, Karsten; Schroeter, Matthias L.

    2013-01-01

    Introduction We aimed at dissociating the neural correlates of memory disorders in Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD). Methods We included patients with AD (n = 19, 11 female, mean age 61 years) and FTLD (n = 11, 5 female, mean age 61 years) in early stages of their diseases. Memory performance was assessed by means of verbal and visual memory subtests from the Wechsler Memory Scale (WMS-R), including forgetting rates. Brain glucose utilization was measured by [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) and brain atrophy by voxel-based morphometry (VBM) of T1-weighted magnetic resonance imaging (MRI) scans. Using a whole brain approach, correlations between test performance and imaging data were computed separately in each dementia group, including a group of control subjects (n = 13, 6 female, mean age 54 years) in both analyses. The three groups did not differ with respect to education and gender. Results Patients in both dementia groups generally performed worse than controls, but AD and FTLD patients did not differ from each other in any of the test parameters. However, memory performance was associated with different brain regions in the patient groups, with respect to both hypometabolism and atrophy: Whereas in AD patients test performance was mainly correlated with changes in the parieto-mesial cortex, performance in FTLD patients was correlated with changes in frontal cortical as well as subcortical regions. There were practically no overlapping regions associated with memory disorders in AD and FTLD as revealed by a conjunction analysis. Conclusion Memory test performance may not distinguish between both dementia syndromes. In clinical practice, this may lead to misdiagnosis of FTLD patients with poor memory performance. Nevertheless, memory problems are associated with almost completely different neural correlates in both dementia syndromes. Obviously, memory functions are carried out by

  8. Stem-cell treatment in disc degeneration: What is the evidence? Células madre en el tratamiento de degeneración de disco: ¿Cual es la evidencia? Células tronco no tratamento de doença degenerativa discal: Qual é a evidência?

    Directory of Open Access Journals (Sweden)

    Manuela Peletti-Figueiró

    2013-01-01

    Full Text Available To review the potential role of stem cells in treating degenerative disc disease of the intervertebral disc (IVD. A review was performed of articles from the Medline database concerning stem cells and degenerative disc disease (DDD. To discuss the data, the papers were classified as: review, in vitro, experimental, and clinical. The currently available treatments were basically for symptom reduction, not to revert the IVD degenerative process. The use of mesenchymal stem cells (MSC is being proposed as an option of treatment for DDD. In vitro studies have shown that the MSC are able to differentiate into NP cells and that the MSC also reduce the inflammatory levels of the degenerated IVD. Besides, experimental studies demonstrated that the MSC remained viable when injected into the IVD, and that they were able to regenerate partially from the degenerated IVD and its structure. The few clinical studies found in the literature presented diverging results. The use of MSC is being widely studied and shows promising results for the treatment of DDD. Although many advances are being achieved in studies in vitro and experimental, there is a lack of clinical studies to prove the role of MSC in DDD management.Revisar el papel potencial de las células madre en el tratamiento de la enfermedad degenerativa del disco intervertebral (IVD. Se realizó una revisión de los artículos de la base de datos Medline sobre células madre y la enfermedad degenerativa del disco (DDD. Para fines de discusión de los datos, los trabajos se dividieron en: revisión, in vitro, experimentales y clínicos. Los tratamientos disponibles actualmente enfocan básicamente la reducción de los síntomas, y no la reversión del proceso degenerativo del IVD. El uso de células madre mesenquimales (MSC se propone como una opción de tratamiento para DDD. Estudios in vitro demostraron que las MSC son capaces de diferenciarse en células NP y que las MSC también reducen los niveles

  9. Estudo comparativo dos mecanorreceptores dos discos intervertebrais normais e degenerados da coluna lombar de humanos pela radiografia, ressonância magnética e estudo anatomopatológico Comparative study of normal and degenerated intervertebral discs' mechanoreceptors of human lumar spine X-ray, magnetic resonance and anatomopathologic study

    Directory of Open Access Journals (Sweden)

    Valdeci Manoel de Oliveira

    2007-01-01

    Full Text Available Os autores fizeram um estudo da coluna lombar de humanos, objetivando avaliar e determinar os diferentes tipos de fibras nervosas no disco intervertebral normal e no degenerado. Foram usadas dez colunas lombares de cadáveres com aproximadamente 48 a 72 horas de óbito. As peças foram submetidas a exames de radiografia simples e ressonância magnética. Após os exames, os discos foram classificados em normais e degenerados. Em seguida, foram dissecados, divididos em regiões anterior e posterior, incluídos em parafina e realizado estudo de imuno-histoquímica com a proteína S100. Com o auxílio de um programa de computador Image-Pro Plus (media cybernetics®, as fibras nervosas tiveram seu diâmetro medidos em micrômetros e classificadas em quatro tipos de fibras. Foram encontrados quatro tipos de fibras nervosas nas diferentes regiões discais. O número e o tipo de fibras variaram de acordo com a região e grau de degeneração do disco intervertebral. Concluíram que as fibras do tipo III são mais freqüentes na região anterior; as fibras dos tipos II e IV são mais freqüentes na região posterior, e as fibras do tipo I não apresentaram diferenças entre a região anterior e a posterior; além disso, o disco degenerado tem mais fibras nervosas que o disco normal.The authors conducted a study on human lumbar spine, aiming to assess and determine the different kinds of nervous fibers in normal and degenerated intervertebral discs. Ten cadaver’s lumbar spines with approximately 48 - 72 of death have been used. The pieces were submitted to simple X-ray and magnetic resonance tests. Subsequently to the tests, discs were divided into normal and degenerated. Then, they were dissected, divided into anterior and posterior according to the region, included in paraffin and an immunohistochemical study with S100 protein was performed. With the aid of Image-Pro Plus computer software (media cybernetics ®, nervous fibers’ diameters were

  10. Endophenotypes for Age-Related Macular Degeneration: Extending Our Reach into the Preclinical Stages of Disease.

    Science.gov (United States)

    Gorin, Michael B; Weeks, Daniel E; Baron, Robert V; Conley, Yvette P; Ortube, Maria C; Nusinowitz, Steven

    2014-11-28

    The key to reducing the individual and societal burden of age-related macular degeneration (AMD)-related vision loss, is to be able to initiate therapies that slow or halt the progression at a point that will yield the maximum benefit while minimizing personal risk and cost. There is a critical need to find clinical markers that, when combined with the specificity of genetic testing, will identify individuals at the earliest stages of AMD who would benefit from preventive therapies. These clinical markers are endophenotypes for AMD, present in those who are likely to develop AMD, as well as in those who have clinical evidence of AMD. Clinical characteristics associated with AMD may also be possible endophenotypes if they can be detected before or at the earliest stages of the condition, but we and others have shown that this may not always be valid. Several studies have suggested that dynamic changes in rhodopsin regeneration (dark adaptation kinetics and/or critical flicker fusion frequencies) may be more subtle indicators of AMD-associated early retinal dysfunction. One can test for the relevance of these measures using genetic risk profiles based on known genetic risk variants. These functional measures may improve the sensitivity and specificity of predictive models for AMD and may also serve to delineate clinical subtypes of AMD that may differ with respect to prognosis and treatment.

  11. Endophenotypes for Age-Related Macular Degeneration: Extending Our Reach into the Preclinical Stages of Disease

    Directory of Open Access Journals (Sweden)

    Michael B. Gorin

    2014-11-01

    Full Text Available The key to reducing the individual and societal burden of age-related macular degeneration (AMD-related vision loss, is to be able to initiate therapies that slow or halt the progression at a point that will yield the maximum benefit while minimizing personal risk and cost. There is a critical need to find clinical markers that, when combined with the specificity of genetic testing, will identify individuals at the earliest stages of AMD who would benefit from preventive therapies. These clinical markers are endophenotypes for AMD, present in those who are likely to develop AMD, as well as in those who have clinical evidence of AMD. Clinical characteristics associated with AMD may also be possible endophenotypes if they can be detected before or at the earliest stages of the condition, but we and others have shown that this may not always be valid. Several studies have suggested that dynamic changes in rhodopsin regeneration (dark adaptation kinetics and/or critical flicker fusion frequencies may be more subtle indicators of AMD-associated early retinal dysfunction. One can test for the relevance of these measures using genetic risk profiles based on known genetic risk variants. These functional measures may improve the sensitivity and specificity of predictive models for AMD and may also serve to delineate clinical subtypes of AMD that may differ with respect to prognosis and treatment.

  12. [The impact of the spa therapy on reduction of the perception of pain intensity in patients with degenerative joints and disc disease].

    Science.gov (United States)

    Kuciel-Lewandowska, Jadwiga; Paprocka-Borowicz, Małgorzata

    2015-01-01

    Degenerative joints and disc disease is accompanied by chronic pain which is the main symptom of the disease. Medical spa therapy has the task of providing comprehensive treatment embracing diseases of limbs as well as other systems and the essential role of medical treatment, in particular spa therapy, is pain relief. The aim of the study was to evaluate the effect of the spa treatment on the level of pain perception in patients with degenerative joints and disc disease. The observation embraced 120 people with degenerative joints and disc disease treated in the spa. The study included a comprehensive therapy conducted over a 21-day stays at the spa Przerzeczyn-Zdrój with the application of selected physical treatments, physiotherapy and the use of therapeutic natural resources: peloid mud and healing radon-sulphide water. Moreover, there was psychological counseling and health education conducted. The study also included observation of 21 persons from the control group. However, the patients in the control group did not benefit from balneotherapy, psychological care and education. There was a standard VAS scale for pain and non-standard questionnaire of pain assessment constructed for the study purposes. The assessment of pain using the VAS scale and questionnaire of pain assessment both in the study group and the control group were performed before and after the treatment. The results were analyzed statistically, there was Statistica program in Polish version used. In the analysis of the obtained results there were two tests scheduled: the sign test, the Wilcoxon test and descriptive statistics. As a result of the spa therapy and treatments administered on an outpatient basis there was reduction of pain intensity observed. 1. Spa therapy and outpatient treatment reduce the level of pain in patients with degenerative joints and disc disease. 2. The reduction of pain level was more effective in case of therapy conducted in the spa.

  13. Cerebellar Degeneration

    Science.gov (United States)

    ... FARA) National Ataxia Foundation (NAF) National Multiple Sclerosis Society See all related organizations Publications Degeneración cerebelosa Order NINDS Publications Definition Cerebellar degeneration is a process in which neurons ( ...

  14. Macular degeneration

    Science.gov (United States)

    The macula is the part of the retina that distinguishes fine details at the center of the field of vision. Macular degeneration results from a partial breakdown of the insulating layer between the retina and the choroid layer of ...

  15. Correlation of matrix metalloproteinase (MMP)-1, -2, -3, and -9 expressions with demographic and radiological features in primary lumbar intervertebral disc disease.

    Science.gov (United States)

    Basaran, Recep; Senol, Mehmet; Ozkanli, Seyma; Efendioglu, Mustafa; Kaner, Tuncay

    2017-07-01

    Degeneration of IVD is a progressive and irreversible process and can be evaluated with immunohistochemical examination or radiological grading. MMPs are a family of proteolytic enzymes and involved in the degradation of the matrix components of the IVD. We aimed to compare MMP-1, -2, -3, and -9 expressions with demographic features, visual analogue scale (VAS), Oswestry Disability Index (ODI) and radiological (MRI) grades. The study involved 60 participants. We recorded data about age, complaint, radiological imaging, expression levels of MMP-1, -2, -3, and -9, ODI and VAS for back pain retrospectively. Intervertebral disc degeneration was graded on a 0-5 scale according to the Pfirrmann classification. As a result of the study, the median age was 52.09±12.74years. There were statistical significances between age and MMP-1, and MMP-2. There was a close correlation between grade and MMP-9. We found correlation between the VAS and the MMP-9 expression. In addition, there was relationship between expression of MMP-2 and MMP-1, MMP-3, MMP-9. In conclusion, the expressions of MMP-1 and -2 are increased with aging. There was no relationship between radiological evaluation of IVDD and aging. Increased expression of MMPs affected IVDD positively. The relationship with MMPs is not explained. This study adds to our understanding of the interaction between MMPs and IVDD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. [Retinal imaging of the macula and optic disc in neurodegenerative diseases].

    Science.gov (United States)

    Turski, G N; Schmitz-Valckenberg, S; Holz, F G; Finger, R P

    2017-02-01

    Due to current demographic trends, the prevalence of mild cognitive impairment and dementia is expected to increase considerably. For potential new therapies it is important to identify patients at risk as early as possible. Currently, there is no population-based screening. Therefore, identification of biomarkers that will help screen the population at risk is urgently needed. Thus, a literature review on retinal pathology in neurodegenerative diseases was performed. PubMed was searched for studies published up to August 2016 using the following keywords: "mild cognitive impairment", "dementia", "eye", "ocular biomarkers", "OCT" and "OCT angiography". Relevant publications were selected and summarized qualitatively. Multiple studies using noninvasive in vivo optical coherence tomography (OCT) imaging showed nonspecific retinal pathological changes in patients with neurodegenerative diseases such as mild cognitive impairment, Alzheimer's and Parkinson's disease. Pathological changes in macular volume, optic nerve fiber layer thickness and the ganglion cell complex were observed. However, based on available evidence, no ocular biomarkers for neurodegeneration which could be integrated in routine clinical diagnostics have been identified. The potential use of OCT in the early diagnostic workup and monitoring of progression of neurodegenerative diseases needs to be further explored in longitudinal studies with large cohorts.

  17. Primary immune system responders to nucleus pulposus cells: evidence for immune response in disc herniation

    Directory of Open Access Journals (Sweden)

    K Murai

    2010-01-01

    Full Text Available Although intervertebral disc herniation and associated sciatica is a common disease, its molecular pathogenesis is not well understood. Immune responses are thought to be involved. This study provides direct evidence that even non-degenerated nucleus pulposus (NP cells elicit immune responses. An in vitro colony forming inhibition assay demonstrated the suppressive effects of autologous spleen cells on NP cells and an in vitro cytotoxicity assay showed the positive cytotoxic effects of natural killer (NK cells and macrophages on NP cells. Non-degenerated rat NP tissues transplanted into wild type rats and immune-deficient mice demonstrated a significantly higher NP cell survival rate in immune-deficient mice. Immunohistochemical staining showed the presence of macrophages and NK cells in the transplanted NP tissues. These results suggest that even non-degenerated autologous NP cells are recognized by macrophages and NK cells, which may have an immunological function in the early phase of disc herniation. These findings contribute to understanding resorption and the inflammatory reaction to disc herniation.

  18. Does eating particular diets alter risk of age-related macular degeneration in users of the Age-Related Eye Disease Study supplements?

    Science.gov (United States)

    Background: Recent information suggests that the Age-Related Eye Disease Study (AREDS) supplement, enhanced intake of omega-3 fatty acids, and diminishing dietary glycemic index (dGI) are protective against advanced age-related macular degeneration (AMD). Methods: Dietary information was collected a...

  19. Burned-out discs stop hurting: fact or fiction?

    DEFF Research Database (Denmark)

    Bendix, Tom; Kjær, Per; Korsholm, Lars

    2008-01-01

      STUDY DESIGN: Cross-sectional study of a general-population sample. OBJECTIVE: The aim was to test the hypothesis that moderate disc degeneration (DD) is stronger associated with low back pain (LBP) than severe degeneration, and also to identify a possible dose-response relationship between num...

  20. Disc defect classification for optical disc drives

    NARCIS (Netherlands)

    Helvoirt, van J.; Leenknegt, G.A.L.; Steinbuch, M.; Goossens, H.J.

    2005-01-01

    Optical disc drives are subject to various disturbances and faults. A special type of fault is the so-called disc defect. In this paper we present an approach for disc defect classification. It is based on hierarchical clustering of measured signals that are affected by disc defects. The

  1. Association of rs2228570 polymorphism of vitamin D receptor gene with degenerative disc disease: a meta-analysis involving 2947 subjects.

    Science.gov (United States)

    Zong, Qiang; Ni, Dongkui; Li, Lijun; Shi, Yubo

    2015-01-01

    This study aimed to explore the association between the rs2228570 polymorphism in the vitamin D receptor gene and degenerative disc disease (IDD), especially in European. We perform a meta-analysis to analyze the association after searching the relevant studies through China National Knowledge Infrastructure (CNKI), PubMed, Medline and EMBASE databases. And odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. A total of 10 studies involving 1,465 cases and 1,482 controls were included in the meta-analysis. Overall, there was not significant risk between rs2228570 polymorphism and degenerative disc disease in any genetic models. In addition, stratified analyses by ethnicity revealed similar results. However, stratified analyses by others indicates an association between IDD and the FF genotype (OR=0.62, 95% CI=0.43- 0.90, P=0.486) in age =40, and the F allele (OR=0.84, 95% CI=0.73-0.96, P=0.992), FF genotype (OR=0.78, 95% CI=0.65-0.93, P=0.853) in sample size > 300, and ff genotype (OR=0.91, 95% CI=1.11-3.29, P=0.783), FF genotype (OR=0.70, 95% CI=0.51-0.96, P=0.258) in Northern European. This meta-analysis suggested that the rs2228570 polymorphism may not be associated with degenerative disc disease. However, there existed some diversities, especially in age 300, countries in Northern Europe, suggesting that carrying the VDR FokI F allele may be a protective factor against IDD development. But a large number of well-designed studies are still required to assess this polymorphism and degenerative disc disease.

  2. Influence of osmotic pressure changes on the opening of existing cracks in 2 intervertebral disc models

    NARCIS (Netherlands)

    Wognum, Silvia; Huyghe, Jacques M.; Baaijens, Frank P. T.

    2006-01-01

    An experimental hydrogel model and a numerical mixture model were used to investigate why the disc herniates while osmotic pressure is decreasing. To investigate the influence of decreasing osmotic pressure on the opening of cracks in the disc. In the degeneration process, the disc changes structure

  3. Topographical Short-Term Memory Differentiates Alzheimer's Disease From Frontotemporal Lobar Degeneration

    NARCIS (Netherlands)

    Bird, C.M.; Chan, D.; Hartley, T.; Pijnenburg, Y.A.L.; Rossor, M.N.; Burgess, N.

    2010-01-01

    We used a recently developed test of spatial memory-the Four Mountains Test-to investigate the core cognitive processes underpinning topographical disorientation in patients with amnestic mild cognitive impairment (a-MCI) and mild Alzheimer's disease (AD). Performance of these clinical groups was

  4. Influence of the mental health status on a new measure of objective functional impairment in lumbar degenerative disc disease.

    Science.gov (United States)

    Stienen, Martin N; Smoll, Nicolas R; Joswig, Holger; Snagowski, Jan; Corniola, Marco V; Schaller, Karl; Hildebrandt, Gerhard; Gautschi, Oliver P

    2017-06-01

    The Timed Up and Go (TUG) test has recently been proposed as a simple and standardized measure for objective functional impairment (OFI) in patients with lumbar degenerative disc disease (DDD). The study aimed to explore the relationship between a patient's mental health status and both patient-reported outcome measures (PROMs) and TUG test results. This is a prospective institutional review board-approved two-center study. The sample was composed of 375 consecutive patients scheduled for lumbar spine surgery and a healthy cohort of 110 control subjects. Patients and control subjects were assessed with the TUG test and a comprehensive panel of subjective PROMs of pain intensity (visual analog scale [VAS]), functional impairment (Roland-Morris Disability Index [RMDI]), Oswestry Disability Index [ODI]), as well as health-related quality of life (hrQoL; Euro-Qol [EQ]-5D). Standardized age- and sex-adjusted TUG test T-scores were calculated. The dependent variable was the short-form (SF)-12 mental component summary (MCS) quartiles, and the independent variables were the TUG T-scores and PROMs. Direct and adjusted analyses of covariance were performed to estimate the interaction between the SF-12 MCS quartiles and the independent variables. In patients, there was a significant decrease in the subjective PROMs, notably the VAS back pain (p=.001) and VAS leg pain (p=.035), as well as significant increase in the RMDI (pmental hrQoL on subjective measures of pain, functional impairment, and hrQoL that might lead to bias when evaluating patients with lumbar DDD who suffer from reduced mental hrQoL. The TUG test appears to be a stable instrument and especially helpful in the evaluation of patients with lumbar DDD and mental health problems. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Current and future perspectives on lumbar degenerative disc disease: a UK survey exploring specialist multidisciplinary clinical opinion

    Science.gov (United States)

    McGregor, Alison H

    2016-01-01

    Objectives Despite lumbar degenerative disc disease (LDDD) being significantly associated with non-specific low back pain and effective treatment remaining elusive, specialist multidisciplinary clinical stakeholder opinion remains unexplored. The present study examines the views of such experts. Design A reliable and valid electronic survey was designed to establish trends using theoretical constructs relating to current assessment and management practices. Clinicians from the Society of Back Pain Research (SBPR) UK were invited to take part. Quantitative data were collated and coded using Bristol Online Surveys (BOS) software, and content analysis was used to systematically code and categorise qualitative data. Setting Specialist multidisciplinary spinal interest group in the UK. Participants 38/141 clinically active, multidisciplinary SBPR members with specialist spinal interest participated. Among them, 84% had >9 years postgraduate clinical experience. Interventions None. Outcome measures Frequency distributions were used to establish general trends in quantitative data. Qualitative responses were coded and categorised in relation to each theme and percentage responses were calculated. Results LDDD symptom recurrence, in the absence of psychosocial influence, was associated with physical signs of joint stiffness (26%), weakness (17%) and joint hypermobility (6%), while physical factors (21%) and the ability to adapt (11%) were postulated as reasons why some experience pain and others do not. No one management strategy was supported exclusively or with consensus. Regarding effective modalities, there was no significant difference between allied health professional and medic responses (p=0.1–0.8). The future of LDDD care was expressed in terms of improvements in patient communication (35%), patient education (38%) and treatment stratification (24%). Conclusions Results suggest that multidisciplinary expert spinal clinicians appear to follow UK

  6. Regional disc change in segmental hypoplasia of the lumbosacral vertebral bodies: MR findings

    International Nuclear Information System (INIS)

    Kim, Sung Kyu; Lee Seung Ro; Moon, Won Jin; Park, Dong Woo; Hahm, Chang Kok

    2000-01-01

    To classify types of vertebral hypoplasia and to investigate the prevalence and patterns of associated disc degeneration. Defining vertebral hypoplasia as occurring when the AP diameter of a lower vertebral body is smaller than that of an upper ones, we retrospectively reviewed the MR images obtained in 34 cases of this condition involving young adults. Two major types and two subtypes, a total of four different entities were classified as follows; type I: hypoplasia involving a single vertebral body; type II: hypoplasia involving serial lower segmental vertebral bodies; subtype a: hypoplastic body located anteriorly along the anterior spinal line; subtype b: hypoplastic body located posteriorly along the posterior spinal line. We also investigated each type of vertebral hypoplasia and patterns of associated disc changes. Three different types were observed. In type IIa (n=3D29), posterior disc occurred in 8/29 cases, diffuse degeneration in 21/29 patients, and posterior disc herniation in all. All type Ia cases (3/3) showed diffuse disc degeneration at both upper and lower disc levels, with posterior disc herniation, while both type IIb cases (2/2) showed diffuse disc degeneration, with bidirectional disc herniation. By identifying the exact patterns of vertebral hypoplasia, we were able to predict which portion of the disc was likely to degenerate. (author)

  7. Predictors and Neuropsychiatric Profile of Nucleus Basalis of Meynert Degeneration in Parkinson Disease

    Science.gov (United States)

    2017-10-01

    information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and...region with deep brain stimulation as a potential symptomatic and neuroprotective therapy for psychosis in PD. 15. SUBJECT TERMS Parkinson disease...protein tau (MAPT); Deep brain stimulation . 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE

  8. Tau truncation is a productive posttranslational modification of neurofibrillary degeneration in Alzheimer's disease.

    Science.gov (United States)

    Kovacech, B; Novak, M

    2010-12-01

    Deposits of the misfolded neuronal protein tau are major hallmarks of neurodegeneration in Alzheimer's disease (AD) and other tauopathies. The etiology of the transformation process of the intrinsically disordered soluble protein tau into the insoluble misordered aggregate has attracted much attention. Tau undergoes multiple modifications in AD, most notably hyperphosphorylation and truncation. Hyperphosphorylation is widely regarded as the hottest candidate for the inducer of the neurofibrillary pathology. However, the true nature of the impetus that initiates the whole process in the human brains remains unknown. In AD, several site-specific tau cleavages were identified and became connected to the progression of the disease. In addition, western blot analyses of tau species in AD brains reveal multitudes of various truncated forms. In this review we summarize evidence showing that tau truncation alone is sufficient to induce the complete cascade of neurofibrillary pathology, including hyperphosphorylation and accumulation of misfolded insoluble forms of tau. Therefore, proteolytical abnormalities in the stressed neurons and production of aberrant tau cleavage products deserve closer attention and should be considered as early therapeutic targets for Alzheimer's disease.

  9. Phenotypic variability within the inclusion body spectrum of basophilic inclusion body disease and neuronal intermediate filament inclusion disease in frontotemporal lobar degenerations with FUS-positive inclusions.

    Science.gov (United States)

    Gelpi, Ellen; Lladó, Albert; Clarimón, Jordi; Rey, Maria Jesús; Rivera, Rosa Maria; Ezquerra, Mario; Antonell, Anna; Navarro-Otano, Judith; Ribalta, Teresa; Piñol-Ripoll, Gerard; Pérez, Anna; Valldeoriola, Francesc; Ferrer, Isidre

    2012-09-01

    Basophilic inclusion body disease and neuronal intermediate filament inclusion disease (NIFID) are rare diseases included among frontotemporal lobar degenerations with FUS-positive inclusions (FTLD-FUS). We report clinical and pathologic features of 2 new patients and reevaluate neuropathologic characteristics of 2 previously described cases, including an early-onset case of basophilic inclusion body disease (aged 38 years) with a 5-year disease course and abundant FUS-positive inclusion bodies and 3 NIFID cases. One NIFID case (aged 37 years) presented with early-onset psychiatric disturbances and rapidly progressive cognitive decline. Two NIFID cases had later onset (aged 64 years and 70 years) and complex neurologic deficits. Postmortem neuropathologic studies in late-onset NIFID cases disclosed α-internexin-positive "hyaline conglomerate"-type inclusions that were positive with 1 commercial anti-FUS antibody directed to residues 200 and 250, but these were negative to amino acids 90 and 220 of human FUS. Early-onset NIFID had similar inclusions that were positive with both commercial anti-FUS antibodies. Genetic testing performed on all cases revealed no FUS gene mutations. These findings indicate that phenotypic variability in NIFID, including clinical manifestations and particular neuropathologic findings, may be related to the age at onset and individual differences in the evolution of lesions.

  10. Interaction of Aluminum with PHFτ in Alzheimer’s Disease Neurofibrillary Degeneration Evidenced by Desferrioxamine-Assisted Chelating Autoclave Method

    Science.gov (United States)

    Murayama, Harunobu; Shin, Ryong-Woon; Higuchi, Jun; Shibuya, Satoshi; Muramoto, Tamaki; Kitamoto, Tetsuyuki

    1999-01-01

    To demonstrate that aluminum III (Al) interacts with PHFτ in neurofibrillary degeneration (NFD) of Alzheimer’s disease (AD) brain, we developed a “chelating autoclave method” that allows Al chelation by using trivalent-cationic chelator desferrioxamine. Its application to AD brain sections before Morin histochemistry for Al attenuated the positive fluorescence of neurofibrillary tangles, indicating Al removal from them. This method, applied for immunostaining with phosphorylation-dependent anti-τ antibodies, significantly enhanced the PHFτ immunoreactivity of the NFD. These results suggest that each of the phosphorylated epitopes in PHFτ are partially masked by Al binding. Incubation of AD sections with AlCl3 before Morin staining revealed Al accumulation with association to neurofibrillary tangles. Such incubation before immunostaining with the phosphorylation-dependent anti-τ antibodies abolished the immunolabeling of the NFD and this abolition was reversed by the Al chelation. These findings indicate cumulative Al binding to and thereby antigenic masking of the phosphorylated epitopes of PHFτ. Al binding was further documented for electrophoretically-resolved PHFτ on immunoblots, indicating direct Al binding to PHFτ. In vitro aggregation by AlCl3 was observed for PHFτ but was lost on dephosphorylation of PHFτ. Taken together, phosphorylation-dependent and direct PHFτ-Al interaction occurs in the NFD of the AD brain. PMID:10487845

  11. Nucleoplasty as a therapeutic option for lumbar disc degeneration related pain: a retrospective study of 396 cases Nucleoplastia como opção terapêutica para dor relacionada à degeneração do disco lombar: um estudo retrospectivo de 396 casos

    Directory of Open Access Journals (Sweden)

    José Lourenço Kallás

    2013-01-01

    Full Text Available OBJECTIVES: To make a retrospective analysis and evaluate a clinical response to the control of disc degeneration related pain of 396 patients submitted to percutaneous lumbar nucleoplasty; and to make a record of visual analogical scale (VAS up to a three-year follow-up after the surgical procedure. METHODS: Analysis of VAS score in 396 patients with lumbar disc degeneration related pain, according to anamnesis, clinical examination and magnetic resonance imaging (MRI, without improvement of previous clinical treatment, submitted to percutaneous nucleoplasty. RESULTS: A total of 26% of the patients presented 100% remission of pain or paresthesia, of whom 75% showed at least 50% of pain improvement. The median VAS pain improvement was about 67%. CONCLUSIONS: The median VAS improvement in inferior disc levels was higher than four points. The VAS showed improvement of the pain and paresthesia up to a three-year follow up after the surgical procedure.OBJETIVOS: Analisar retrospectivamente a resposta clínica no controle da dor relacionada à degeneração discal em 396 pacientes submetidos à nucleoplastia percutânea lombar; e fazer um registro da escala analógica visual (EAV com seguimento de três anos após a cirurgia. MÉTODOS: Análise da EAV de 396 pacientes com diagnóstico de hérnia de disco, de acordo com anamnese, exame clínico e imagens por meio de ressonância magnética (RM, sendo que nenhum deles apresentou melhora com tratamento clínico prévio. Estes pacientes foram submetidos à nucleoplastia percutânea. O estudo utilizou, para avaliação, o registro de escala analógica visual (EAV durante seguimento de até três anos após o procedimento cirúrgico. RESULTADOS: Um total de 26% apresentou 100% de remissão da dor ou parestesia; 75% apresentaram pelo menos 50% de melhora da dor. A mediana da EAV de melhora da dor foi de aproximadamente 67%. CONCLUSÕES: Houve melhora da EAV, com mediana maior do que quatro pontos nos

  12. Radiological assessment of loss of disc height during acute and chronic degenerative lumbar disc alterations

    International Nuclear Information System (INIS)

    Zoellner, J.; Sancaktaroglu, T.; Nafe, B.; Eysel, P.; Loew, R.

    2001-01-01

    Aim of the study: A loss of disc height with increasing segmental mobility is an important reason for low back pain. The measurement of hyaluronic acid content of the nucleus pulposus prolaps shows a difference between acute (group 1) and chronic (group 2) disc degeneration. The purpose of the present investigation was to determine the decreasing of disc height between these two groups and the no-symptomatic segments of these patients. Methods: 20 human lateral preoperative X-ray measurements according to Frobin et al. were taken; group 1 with 7 patients (mean age 41 years) and group 2 with 13 patients (mean age 44 years). Results: There was a significant tendency (p=0.091) to a reduction of disc height in group 2 between symptomatic and asymptomatic discs. Conclusion: The used method is not suitable to answer the present question conclusively. (orig.) [de

  13. Functional connectivity modeling of consistent cortico-striatal degeneration in Huntington's disease

    Directory of Open Access Journals (Sweden)

    Imis Dogan

    2015-01-01

    Full Text Available Huntington's disease (HD is a progressive neurodegenerative disorder characterized by a complex neuropsychiatric phenotype. In a recent meta-analysis we identified core regions of consistent neurodegeneration in premanifest HD in the striatum and middle occipital gyrus (MOG. For early manifest HD convergent evidence of atrophy was most prominent in the striatum, motor cortex (M1 and inferior frontal junction (IFJ. The aim of the present study was to functionally characterize this topography of brain atrophy and to investigate differential connectivity patterns formed by consistent cortico-striatal atrophy regions in HD. Using areas of striatal and cortical atrophy at different disease stages as seeds, we performed task-free resting-state and task-based meta-analytic connectivity modeling (MACM. MACM utilizes the large data source of the BrainMap database and identifies significant areas of above-chance co-activation with the seed-region via the activation-likelihood-estimation approach. In order to delineate functional networks formed by cortical as well as striatal atrophy regions we computed the conjunction between the co-activation profiles of striatal and cortical seeds in the premanifest and manifest stages of HD, respectively. Functional characterization of the seeds was obtained using the behavioral meta-data of BrainMap. Cortico-striatal atrophy seeds of the premanifest stage of HD showed common co-activation with a rather cognitive network including the striatum, anterior insula, lateral prefrontal, premotor, supplementary motor and parietal regions. A similar but more pronounced co-activation pattern, additionally including the medial prefrontal cortex and thalamic nuclei was found with striatal and IFJ seeds at the manifest HD stage. The striatum and M1 were functionally connected mainly to premotor and sensorimotor areas, posterior insula, putamen and thalamus. Behavioral characterization of the seeds confirmed that experiments

  14. Interactive Image Analysis in Age-related Macular Degeneration (AMD) and Stargardt Disease (STGD).

    Science.gov (United States)

    Smith, R Theodore; Lee, Noah; Chen, Jian; Busuioc, Mihai; Laine, Andrew F

    2008-10-26

    The literature of the last three decades is replete with automatic methods for retinal image analysis. Acceptance has been limited due to post-processing or tuning requirements that may be just as time consuming as the original manual methods. The point of view herein is that by taking advantage of the human visual system and expert knowledge from the outset, the promised efficiencies of digital methods can be achieved in practice as well as in theory. Thus, simple labeling of regions of interest that is accepted and easily performed in a few moments by the human can provide enormous advantage to an already well-developed algorithm. Three examples are provided: drusen segmentation, image registration, and geographic atrophy segmentation, with applications to disease understanding.

  15. Distinction between the extracellular matrix of the nucleus pulposus and hyaline cartilage: a requisite for tissue engineering of intervertebral disc

    OpenAIRE

    Mwale F.; Roughley P.; Antoniou J.

    2004-01-01

    Tissue engineering of intervertebral discs (IVD) using mesenchymal stem cells (MSCs) induced to differentiate into a disc-cell phenotype has been considered as an alternative treatment for disc degeneration. However, since there is no unique marker characteristic of discs and since hyaline cartilage and immature nucleus pulposus (NP) possess similar macromolecules in their extracellular matrix, it is currently difficult to recognize MSC conversion to a disc cell. This study was performed to c...

  16. Functional implications of hippocampal degeneration in early Alzheimer's disease: a combined DTI and PET study

    International Nuclear Information System (INIS)

    Yakushev, Igor; Mueller, Matthias J.; Schermuly, Ingrid; Fellgiebel, Andreas; Schreckenberger, Matthias; Cumming, Paul; Stoeter, Peter; Gerhard, Alex

    2011-01-01

    Hypometabolism of the posterior cingulate cortex (PCC) in early Alzheimer's disease (AD) is thought to arise in part due to AD-specific neuronal damage to the hippocampal formation. Here, we explored the association between microstructural alterations within the hippocampus and whole-brain glucose metabolism in subjects with AD, also in relation to episodic memory impairment. Twenty patients with early AD (Mini-Mental State Examination 25.7 ± 1.7) were studied with [ 18 F]fluorodeoxyglucose (FDG) positron emission tomography and diffusion tensor imaging. Episodic memory performance was assessed using the free delayed verbal recall task (DVR). Voxel-wise relative FDG uptake was correlated to diffusivity indices of the hippocampus, followed by extraction of FDG uptake values from significant clusters. Linear regression analysis was performed to test for unique contributions of diffusivity and metabolic indices in the prediction of memory function. Diffusivity in the left anterior hippocampus negatively correlated with FDG uptake primarily in the left anterior hippocampus, parahippocampal gyrus and the PCC (p< 0.005). The same correlation pattern was found for right hippocampal diffusivity (p< 0.05). In linear regression analysis, left anterior hippocampal diffusivity and FDG uptake from the PCC cluster were the only significant predictors for performance on DVR, together explaining 60.6% of the variance. We found an inverse association between anterior hippocampal diffusivity and PCC glucose metabolism, which was in turn strongly related to episodic memory performance in subjects with early AD. These findings support the diaschisis hypothesis of AD and implicate a dysfunction of structures along the hippocampal output pathways as a significant contributor to the genesis of episodic memory impairment. (orig.)

  17. Loss of the E3 ubiquitin ligase LRSAM1 sensitizes peripheral axons to degeneration in a mouse model of Charcot-Marie-Tooth disease

    OpenAIRE

    Bogdanik, Laurent P.; Sleigh, James N.; Tian, Cong; Samuels, Mark E.; Bedard, Karen; Seburn, Kevin L.; Burgess, Robert W.

    2013-01-01

    SUMMARY Charcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous condition characterized by peripheral axon degeneration with subsequent motor and sensory deficits. Several CMT gene products function in endosomal sorting and trafficking to the lysosome, suggesting that defects in this cellular pathway might present a common pathogenic mechanism for these conditions. LRSAM1 is an E3 ubiquitin ligase that is implicated in this process, and mutations in LRSAM1 have rece...

  18. The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease

    DEFF Research Database (Denmark)

    Lill, Christina M; Rengmark, Aina; Pihlstrøm, Lasse

    2015-01-01

    A rare variant in TREM2 (p.R47H, rs75932628) was recently reported to increase the risk of Alzheimer's disease (AD) and, subsequently, other neurodegenerative diseases, i.e. frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Here we......) and total-tau protein levels in the cerebrospinal fluid (CSF) of 828 individuals with AD or mild cognitive impairment. Our data show that rs75932628 is highly significantly associated with the risk of AD across 24,086 AD cases and 148,993 controls of European descent (odds ratio or OR = 2.71, P = 4.67 × 10......(-25)). No consistent evidence for association was found between this marker and the risk of FTLD (OR = 2.24, P = .0113 across 2673 cases/9283 controls), PD (OR = 1.36, P = .0767 across 8311 cases/79,938 controls) and ALS (OR = 1.41, P = .198 across 5544 cases/7072 controls). Furthermore, carriers of the rs75932628...

  19. Highly sensitive measurements of disease progression in rare disorders: Developing and validating a multimodal model of retinal degeneration in Stargardt disease.

    Science.gov (United States)

    Lambertus, Stanley; Bax, Nathalie M; Fakin, Ana; Groenewoud, Joannes M M; Klevering, B Jeroen; Moore, Anthony T; Michaelides, Michel; Webster, Andrew R; van der Wilt, Gert Jan; Hoyng, Carel B

    2017-01-01

    Each inherited retinal disorder is rare, but together, they affect millions of people worldwide. No treatment is currently available for these blinding diseases, but promising new options-including gene therapy-are emerging. Arguably, the most prevalent retinal dystrophy is Stargardt disease. In each case, the specific combination of ABCA4 variants (> 900 identified to date) and modifying factors is virtually unique. It accounts for the vast phenotypic heterogeneity including variable rates of functional and structural progression, thereby potentially limiting the ability of phase I/II clinical trials to assess efficacy of novel therapies with few patients. To accommodate this problem, we developed and validated a sensitive and reliable composite clinical trial endpoint for disease progression based on structural measurements of retinal degeneration. We used longitudinal data from early-onset Stargardt patients from the Netherlands (development cohort, n = 14) and the United Kingdom (external validation cohort, n = 18). The composite endpoint was derived from best-corrected visual acuity, fundus autofluorescence, and spectral-domain optical coherence tomography. Weighting optimization techniques excluded visual acuity from the composite endpoint. After optimization, the endpoint outperformed each univariable outcome, and showed an average progression of 0.41° retinal eccentricity per year (95% confidence interval, 0.30-0.52). Comparing with actual longitudinal values, the model accurately predicted progression (R2, 0.904). These properties were largely preserved in the validation cohort (0.43°/year [0.33-0.53]; prediction: R2, 0.872). We subsequently ran a two-year trial simulation with the composite endpoint, which detected a 25% decrease in disease progression with 80% statistical power using only 14 patients. These results suggest that a multimodal endpoint, reflecting structural macular changes, provides a sensitive measurement of disease progression in

  20. Highly sensitive measurements of disease progression in rare disorders: Developing and validating a multimodal model of retinal degeneration in Stargardt disease.

    Directory of Open Access Journals (Sweden)

    Stanley Lambertus

    Full Text Available Each inherited retinal disorder is rare, but together, they affect millions of people worldwide. No treatment is currently available for these blinding diseases, but promising new options-including gene therapy-are emerging. Arguably, the most prevalent retinal dystrophy is Stargardt disease. In each case, the specific combination of ABCA4 variants (> 900 identified to date and modifying factors is virtually unique. It accounts for the vast phenotypic heterogeneity including variable rates of functional and structural progression, thereby potentially limiting the ability of phase I/II clinical trials to assess efficacy of novel therapies with few patients. To accommodate this problem, we developed and validated a sensitive and reliable composite clinical trial endpoint for disease progression based on structural measurements of retinal degeneration.We used longitudinal data from early-onset Stargardt patients from the Netherlands (development cohort, n = 14 and the United Kingdom (external validation cohort, n = 18. The composite endpoint was derived from best-corrected visual acuity, fundus autofluorescence, and spectral-domain optical coherence tomography. Weighting optimization techniques excluded visual acuity from the composite endpoint. After optimization, the endpoint outperformed each univariable outcome, and showed an average progression of 0.41° retinal eccentricity per year (95% confidence interval, 0.30-0.52. Comparing with actual longitudinal values, the model accurately predicted progression (R2, 0.904. These properties were largely preserved in the validation cohort (0.43°/year [0.33-0.53]; prediction: R2, 0.872. We subsequently ran a two-year trial simulation with the composite endpoint, which detected a 25% decrease in disease progression with 80% statistical power using only 14 patients.These results suggest that a multimodal endpoint, reflecting structural macular changes, provides a sensitive measurement of disease

  1. Highly sensitive measurements of disease progression in rare disorders: Developing and validating a multimodal model of retinal degeneration in Stargardt disease

    Science.gov (United States)

    Bax, Nathalie M.; Fakin, Ana; Groenewoud, Joannes M. M.; Klevering, B. Jeroen; Moore, Anthony T.; Michaelides, Michel; Webster, Andrew R.; van der Wilt, Gert Jan; Hoyng, Carel B.

    2017-01-01

    Background Each inherited retinal disorder is rare, but together, they affect millions of people worldwide. No treatment is currently available for these blinding diseases, but promising new options—including gene therapy—are emerging. Arguably, the most prevalent retinal dystrophy is Stargardt disease. In each case, the specific combination of ABCA4 variants (> 900 identified to date) and modifying factors is virtually unique. It accounts for the vast phenotypic heterogeneity including variable rates of functional and structural progression, thereby potentially limiting the ability of phase I/II clinical trials to assess efficacy of novel therapies with few patients. To accommodate this problem, we developed and validated a sensitive and reliable composite clinical trial endpoint for disease progression based on structural measurements of retinal degeneration. Methods and findings We used longitudinal data from early-onset Stargardt patients from the Netherlands (development cohort, n = 14) and the United Kingdom (external validation cohort, n = 18). The composite endpoint was derived from best-corrected visual acuity, fundus autofluorescence, and spectral-domain optical coherence tomography. Weighting optimization techniques excluded visual acuity from the composite endpoint. After optimization, the endpoint outperformed each univariable outcome, and showed an average progression of 0.41° retinal eccentricity per year (95% confidence interval, 0.30–0.52). Comparing with actual longitudinal values, the model accurately predicted progression (R2, 0.904). These properties were largely preserved in the validation cohort (0.43°/year [0.33–0.53]; prediction: R2, 0.872). We subsequently ran a two-year trial simulation with the composite endpoint, which detected a 25% decrease in disease progression with 80% statistical power using only 14 patients. Conclusions These results suggest that a multimodal endpoint, reflecting structural macular changes, provides a

  2. Short-Term Therapeutic Efficacy of the Isobar TTL Dynamic Internal Fixation System for the Treatment of Lumbar Degenerative Disc Diseases.

    Science.gov (United States)

    Qian, Jiale; Bao, Zhaohua; Li, Xuefeng; Zou, Jun; Yang, Huilin

    2016-07-01

    At present, posterior interbody fusion surgery with pedicle internal fixation is the gold standard for the treatment of lumbar degenerative disc diseases. However, an increasing number of studies have shown that because fused lumbar vertebrae lose their physiological activity, the compensatory range of motion (ROM) of the adjacent levels increases. To address this issue, dynamic internal fixation systems have been developed. Our goal was to investigate the short-term therapeutic efficacy of the Isobar TTL dynamic internal fixation system for the treatment of lumbar degenerative disc diseases and its effect on the ROM of the surgical segments. Retrospective Evaluation. Tertiary hospital setting in China. Twenty-four lumbar degenerative disc disease patients who underwent posterior lumbar decompression and single-segment Isobar TTL dynamic internal fixation at our hospital between January 2013 and July 2014 were retrospectively analyzed. The preoperative and one month, 3 month, and 12 month postoperative visual analog scale (VAS) pain scores, Japanese Orthopedic Association (JOA) scores, and Oswestry Disability Index (ODI) scores were observed and recorded to assess the clinical therapeutic effect; the lumbar ROM was measured preoperatively and at the last follow-up to evaluate the preservation of functional movement in the dynamically stabilized segment. All patients underwent the operation successfully without complications during hospitalization and were followed for 12 to 27 months, with an average of 18 months. The patients' preoperative and one month, 3 month, and 12 month postoperative VAS scores were 6.42 ± 0.72, 1.71 ± 0.86, 1.38 ± 0.65, and 1.37 ± 0.58, respectively, and their JOA scores were 9.54 ± 1.89, 21.21 ± 1.98, 22.50 ± 1.47, and 23.46 ± 1.32, respectively. The preoperative ODI score was 42.04 ± 2.63; the one month, 3 month, and 12 month postoperative ODI scores were 22.79 ± 1.61, 18.63 ± 1.61, and 15.08 ± 1.21, respectively. These

  3. Influence of HLA Matching on the Efficacy of Allogeneic Mesenchymal Stromal Cell Therapies for Osteoarthritis and Degenerative Disc Disease

    Directory of Open Access Journals (Sweden)

    Javier García-Sancho, MD, PhD

    2017-09-01

    Conclusions. This lack of reactivity is presumably due to the cooperation of 2 factors, (1 downregulation of the host immune responses by the transplanted MSCs and (2 effective insulation of these cells inside the articular cavity or the intervertebral disc, respectively. Interestingly, better HLA matching did not enhance efficacy. These observations have medical relevance as they support the clinical use of allogeneic cells, at least as a single-dose administration. Multiple-dose applications will require further research to exclude possible sensitization.

  4. Lesion of the locus coeruleus aggravates dopaminergic neuron degeneration by modulating microglial function in mouse models of Parkinson׳s disease.

    Science.gov (United States)

    Yao, Ning; Wu, Yanhong; Zhou, Yan; Ju, Lili; Liu, Yujun; Ju, Rongkai; Duan, Deyi; Xu, Qunyuan

    2015-11-02

    The degeneration of noradrenergic neurons in the locus coeruleus (LC) commonly occurs in patients with Parkinson's disease (PD), which is characterized by a selective injury of dopaminergic neurons in the substantia nigra (SN). The pathological impact of the LC on the SN in the disease is unknown. In the present study, we used a noradrenergic toxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4), to deplete noradrenaline (NA) derived from the LC to explore its influence on degeneration or injury of dopaminergic neurons in the SN in mouse model produced by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or lipopolysaccharide (LPS). Our results demonstrated that lesion of the LC could change microglial function in the brain, which led to enhanced or prolonged expression of pro-inflammatory cytokines, diminished neurotrophic factors, and weakened ability of anti-oxidation in the SN. The in vitro experiments further confirmed that NA could reduce the inflammatory reaction of microglia. The selective injury of dopaminergic neurons by inflammation, however, was due to the inflammation in different brain regions rather than the depletion of NA. Our results indicate that the lesion in the LC is an important factor in promoting dopaminergic neuron degeneration by impacting the function of microglia in the midbrain. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Therapy of degeneration diseases

    International Nuclear Information System (INIS)

    Altmannsberger, H.M.

    1978-01-01

    The possibilities of radiotherapy in humeroscapular periarthritis, cervical, syndrome, gonarthrosis and coxarthrosis are described. The degenerative processes themselves can not be improved by the treatment; the main therapeutical goal therefore is alleviation of pain and normalisation of the metabolism. A questionnaire was sent to 303 patients who had been treated at Marburg university hospital between 1969 and 1973. 72% of the patients with humeroscapular periarthritis had been improved by the radiotherapy and 47% of the patients with cervical syndrome. On the other hand, only 38% of the patients with gonarthrosis and 21% of the coxarthrosis patients had been improved. (orig.) [de

  6. [Surgical treatment of thoracic disc herniation].

    Science.gov (United States)

    Hrabálek, L; Kalita, O; Langová, K

    2010-08-01

    The aim of this study was to compare the efficiency of different surgical approaches to thoracic disc herniation, and to show the role of segmental fusion and selection of an appropriate microsurgical decompression technique for the successful outcome of surgery. A group of 27 patients, 10 men and 17 women, between 31 and 70 years (average age, 49.33 years) were included in this prospective study. They underwent surgery for thoracic degeneration disc disease in the period from June 1994 to August 2008. In all patients, the severity of myelopathy was assessed using the grading Frankel system and JOA score, axial and radicular pain intensity was evaluated with VAS and ODI rating systems. The diagnosis was established on the basis of thoracic spine radiography, thoracic spine MRI and a CT scan of the segment. A total of 30 thoracic segments, in the range of Th4/Th5 to Th12/L1, were indicated for surgery. Localisation of the hernia was medial at 19 segments, mediolateral at three and lateral at eight segments. Soft disc herniation was found in 17 cases and hard disc protrusion at the remaining 13 segments. Surgery for significant myelopathy was carried out in 23 patients and for pain in four patients. According to the surgical procedure used, the patients were allocated to two groups: group A comprised 10 patients treated without disc replacement through a laminectomy or a costotransversectomy exposure, and group B consisted of 17 patients undergo- ing intersomatic fusion via a thoracotomy. Clinical and radiographic examinations were made at regular intervals for at least 1 year of follow-up. The results of clinical assessment, including JOA scores, JOA Recovery Rate, VAS scores at rest and after exercise and ODI, were statistically analysed for each group and compared. There was a statistically significant difference in JOA evaluation of myelopathy between the groups in group A, the mean JOA score declined from 7.9 to 7.0, i.e., -0.9 point, while in group B it

  7. Comparison among perfect-C®, zero-P®, and plates with a cage in single-level cervical degenerative disc disease.

    Science.gov (United States)

    Noh, Sung Hyun; Zhang, Ho Yeol

    2018-01-25

    We intended to analyze the efficacy of a new integrated cage and plate device called Perfect-C for anterior cervical discectomy and fusion (ACDF) to cure single-level cervical degenerative disc disease. We enrolled 148 patients who were subjected to single-level ACDF with one of the following three surgical devices: a Perfect-C implant (41 patients), a Zero-P implant (36 patients), or a titanium plate with a polyetheretherketone (PEEK) cage (71 patients). We conducted a retrospective study to compare the clinical and radiological results among the three groups. The length of the operation, intraoperative blood loss, and duration of hospitalization were significantly lower in the Perfect-C group than in the Zero-P and plate-with-cage groups (P Zero-P groups but was noted in 21 cases (30%) in the plate-with-cage group. The cephalad and caudal plate-to-disc distance (PDD) and the cephalad and caudal PDD/anterior body height (ABH) were significantly greater in the Perfect-C and Zero-P groups than in the plate-with-cage group (P Zero-P group, and in 15 cases (21%) in the plate-with-cage group. Fusion occurred in 37 cases (90%) in the Perfect-C group, in 31 cases (86%) in the Zero-P group, and in 68 cases (95%) in the plate-with-cage group. The Perfect-C, Zero-P, and plate-with-cage devices are effective for treating single-level cervical degenerative disc disease. However, the Perfect-C implant has many advantages over both the Zero-P implant and conventional plate-cage treatments. The Perfect-C implant was associated with shorter operation times and hospitalization durations, less blood loss, and lower subsidence rates compared with the Zero-P implant or the titanium plate with a PEEK cage.

  8. CT-guided ozone/steroid therapy for the treatment of degenerative spinal disease - effect of age, gender, disc pathology and multi-segmental changes

    Energy Technology Data Exchange (ETDEWEB)

    Oder, Bernhard; Loewe, Maria; Reisegger, Michael; Thurnher, Siegfried A. [Hospital Brothers of St. John of God, Department of Radiology and Nuclear Medicine, Vienna (Austria); Lang, Wilfried [Hospital Brothers of St. John of God, Department of Neurology, Vienna (Austria); Ilias, Wilfried [Hospital Brothers of St. John of God, Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, Vienna (Austria)

    2008-09-15

    Oxygen-ozone nucleolysis (ONL) is a new, minimally invasive procedure for the treatment of discogenic low back pain with or without radicular symptoms. The aim of the present study was to determine associations between the morphology of the basic disease, patient-specific factors and the outcome of the treatment. Six hundred and twelve patients not responding to conservative therapy were divided into five groups (disc bulging, disc herniation, postoperative patients, osteochondrosis, others) and subjected to nucleolysis with ozone and to periradicular infiltration with steroids and local anaesthesia. The success of treatment was assessed by means of a visual analog pain scale (VAS) and the Oswestry Disability Index (ODI). A significant reduction in the VAS was registered after 2 and 6 months (from 8.6 to 5.4 and 6.0; p<0.001) in all patient groups; an excellent therapy response (VAS below 3.0) was achieved by about a third of the patients. A significant improvement in ODI was registered in all patients (46 to 31; p<0.001), most pronounced in the herniation group (25.5, p=0.015). Patients below 50 years had significantly better values in the VAS and ODI score 6 months after treatment. Final VAS and ODI scores for patients with a single diseased segment were 4.2 and 28.0, in two affected segments 6.5 and 32 and in three segments 6.7 and 38.5 (p<0.001 and p=0.051). ONL with periradicular steroid therapy might exert a functional and sustained analgesic effect in patients with degenerative changes in the lumbar spine not responding to conservative therapy and was most effective below 50 years with disc herniation in one segment. (orig.)

  9. CT-guided ozone/steroid therapy for the treatment of degenerative spinal disease - effect of age, gender, disc pathology and multi-segmental changes

    International Nuclear Information System (INIS)

    Oder, Bernhard; Loewe, Maria; Reisegger, Michael; Thurnher, Siegfried A.; Lang, Wilfried; Ilias, Wilfried

    2008-01-01

    Oxygen-ozone nucleolysis (ONL) is a new, minimally invasive procedure for the treatment of discogenic low back pain with or without radicular symptoms. The aim of the present study was to determine associations between the morphology of the basic disease, patient-specific factors and the outcome of the treatment. Six hundred and twelve patients not responding to conservative therapy were divided into five groups (disc bulging, disc herniation, postoperative patients, osteochondrosis, others) and subjected to nucleolysis with ozone and to periradicular infiltration with steroids and local anaesthesia. The success of treatment was assessed by means of a visual analog pain scale (VAS) and the Oswestry Disability Index (ODI). A significant reduction in the VAS was registered after 2 and 6 months (from 8.6 to 5.4 and 6.0; p<0.001) in all patient groups; an excellent therapy response (VAS below 3.0) was achieved by about a third of the patients. A significant improvement in ODI was registered in all patients (46 to 31; p<0.001), most pronounced in the herniation group (25.5, p=0.015). Patients below 50 years had significantly better values in the VAS and ODI score 6 months after treatment. Final VAS and ODI scores for patients with a single diseased segment were 4.2 and 28.0, in two affected segments 6.5 and 32 and in three segments 6.7 and 38.5 (p<0.001 and p=0.051). ONL with periradicular steroid therapy might exert a functional and sustained analgesic effect in patients with degenerative changes in the lumbar spine not responding to conservative therapy and was most effective below 50 years with disc herniation in one segment. (orig.)

  10. Automatic Detection of Optic Disc in Retinal Image by Using Keypoint Detection, Texture Analysis, and Visual Dictionary Techniques

    Directory of Open Access Journals (Sweden)

    Kemal Akyol

    2016-01-01

    Full Text Available With the advances in the computer field, methods and techniques in automatic image processing and analysis provide the opportunity to detect automatically the change and degeneration in retinal images. Localization of the optic disc is extremely important for determining the hard exudate lesions or neovascularization, which is the later phase of diabetic retinopathy, in computer aided eye disease diagnosis systems. Whereas optic disc detection is fairly an easy process in normal retinal images, detecting this region in the retinal image which is diabetic retinopathy disease may be difficult. Sometimes information related to optic disc and hard exudate information may be the same in terms of machine learning. We presented a novel approach for efficient and accurate localization of optic disc in retinal images having noise and other lesions. This approach is comprised of five main steps which are image processing, keypoint extraction, texture analysis, visual dictionary, and classifier techniques. We tested our proposed technique on 3 public datasets and obtained quantitative results. Experimental results show that an average optic disc detection accuracy of 94.38%, 95.00%, and 90.00% is achieved, respectively, on the following public datasets: DIARETDB1, DRIVE, and ROC.

  11. The comparative study of lumbar disc disruption with MRI and CT discography

    International Nuclear Information System (INIS)

    Chen Xingcan; Liu Naifang; Li Xiaohong; Xu Wengen; Zou Qing; Yang Yonghong

    2005-01-01

    Objective: To compare MRI with CT discography (CTD) for diagnostic assessment of lumbar disc disruption. Methods: Paired comparative examination in 16 patients with chronic lower back pain without radicular pain and no disc herniation was conducted using CT or MRI. The standard of CTD classification and positive disc was formulated and the correlation between the induced lower back pain and dosage used in CTD was observed. Results: For a total of 21 discs in the 16 patients, CTD showed the disc as type 2 in 12 discs and type 5 in 1 disc with 13 positive discs, while MRI only showed the high-intensity zone of posterior annulus in 6 discs as the indirect sign of disc disruption and disc degeneration in 7 discs. Conclusion: CTD was the only method for showing the direct sign of disc disruption. The induced lower back pain was related with the type of disc disruption. MRI can show some of the indirect signs of disc disruption and CTD can show the direct sign of disc disruption. (authors)

  12. Cervical disc arthroplasty: Pros and cons.

    Science.gov (United States)

    Moatz, Bradley; Tortolani, P Justin

    2012-01-01

    Cervical disc arthroplasty has emerged as a promising potential alternative to anterior cervical discectomy and fusion (ACDF) in appropriately selected patients. Despite a history of excellent outcomes after ACDF, the question as to whether a fusion leads to adjacent segment degeneration remains unanswered. Numerous US investigational device exemption trials comparing cervical arthroplasty to fusion have been conducted to answer this question. This study reviews the current research regarding cervical athroplasty, and emphasizes both the pros and cons of arthroplasty as compared with ACDF. Early clinical outcomes show that cervical arthroplasty is as effective as the standard ACDF. However, this new technology is also associated with an expanding list of novel complications. Although there is no definitive evidence that cervical disc replacement reduces the incidence of adjacent segment degeneration, it does show other advantages; for example, faster return to work, and reduced need for postoperative bracing.

  13. Degenerative disease of the spine

    International Nuclear Information System (INIS)

    Czervionke, L.F.; Daniels, D.L.

    1991-01-01

    With few exceptions, magnetic resonance imaging (MRI) is becoming the modality of choice for the evaluation of degenerative disorders of the entire spine. With the implementation of surface coils and continued refinement and development of new pulse sequences, osseous and soft tissue structures of the spine can now be studied in great detail. The introduction of paramagnetic contrast agents has made it possible to differentiate epidural scar from recurrent disc herniation in the postoperative setting and to discern previously undetected degenerative changes within the intervertebral disc itself. This paper discusses the spectrum of degenerative diseases of the spine, including disc degeneration (intervertebral osteochondrosis), disc herniation, spinal stenosis, spondylosis deformans, and osteoarthritis. A brief description of the MR techniques and strategies used to evaluate these disorders is also

  14. Degenerative inter-vertebral disc disease osteochondrosis intervertebralis in Europe: prevalence, geographic variation and radiological correlates in men and women aged 50 and over.

    Science.gov (United States)

    Armbrecht, Gabriele; Felsenberg, Dieter; Ganswindt, Melanie; Lunt, Mark; Kaptoge, Stephen K; Abendroth, Klaus; Aroso Dias, Antonio; Bhalla, Ashok K; Cannata Andia, Jorge; Dequeker, Jan; Eastell, Richard; Hoszowski, Krzysztof; Lyritis, George; Masaryk, Pavol; van Meurs, Joyce; Miazgowski, Tomasz; Nuti, Ranuccio; Poór, Gyula; Redlund-Johnell, Inga; Reid, David M; Schatz, Helmut; Todd, Christopher J; Woolf, Anthony D; Rivadeneira, Fernando; Javaid, Muhammad K; Cooper, Cyrus; Silman, Alan J; O'Neill, Terence W; Reeve, Jonathan

    2017-07-01

    To assess the prevalences across Europe of radiological indices of degenerative inter-vertebral disc disease (DDD); and to quantify their associations with, age, sex, physical anthropometry, areal BMD (aBMD) and change in aBMD with time. In the population-based European Prospective Osteoporosis Study, 27 age-stratified samples of men and women from across the continent aged 50+ years had standardized lateral radiographs of the lumbar and thoracic spine to evaluate the severity of DDD, using the Kellgren-Lawrence (KL) scale. Measurements of anterior, mid-body and posterior vertebral heights on all assessed vertebrae from T4 to L4 were used to generate indices of end-plate curvature. Images from 10 132 participants (56% female, mean age 63.9 years) passed quality checks. Overall, 47% of men and women had DDD grade 3 or more in the lumbar spine and 36% in both thoracic and lumbar spine. Risk ratios for DDD grades 3 and 4, adjusted for age and anthropometric determinants, varied across a three-fold range between centres, yet prevalences were highly correlated in men and women. DDD was associated with flattened, non-ovoid inter-vertebral disc spaces. KL grade 4 and loss of inter-vertebral disc space were associated with higher spine aBMD. KL grades 3 and 4 are often used clinically to categorize radiological DDD. Highly variable European prevalences of radiologically defined DDD grades 3+ along with the large effects of age may have growing and geographically unequal health and economic impacts as the population ages. These data encourage further studies of potential genetic and environmental causes. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  15. Degenerative Inter-Vertebral Disc Disease (Osteochondrosis Intervertebralis) in Europe: Prevalence, Geographic Variation, and Radiological Correlates in Men and Women Aged 50 and Over

    Science.gov (United States)

    Armbrecht, Gabriele; Felsenberg, Dieter; Ganswindt, Melanie; Lunt, Mark; Kaptoge, Stephen K; Abendroth, Klaus; Aroso Dias, Antonio; Bhalla, Ashok K; Cannata Andia, Jorge; Dequeker, Jan; Eastell, Richard; Hoszowski, Krysztoff; Lyritis, George; Masaryk, Pavol; van Meurs, Joyce; Miazgowski, Tomasz; Nuti, Ranuccio; Poór, Gyula; Redlund-Johnell, Inga; Reid, David M; Schatz, Helmut; Todd, Christopher J; Woolf, Anthony D; Rivadeneira, Fernando; Javaid, Muhammad K; Cooper, Cyrus; Silman, Alan J; O’Neill, Terence W; Reeve, Jonathan

    2017-01-01

    Objectives To assess the prevalence across Europe of radiological indices of degenerative inter-vertebral disc disease (DDD); and to quantify their associations with, age, sex, physical anthropometry, areal bone mineral density (aBMD) and change in aBMD with time. Methods In the population-based European Prospective Osteoporosis Study 27 age-stratified samples of men and women from across the continent aged 50+ had standardized lateral radiographs of the lumbar and thoracic spine to evaluate the severity of DDD, using the Kellgren-Lawrence (KL) scale. Measurements of anterior, mid-body and posterior vertebral heights on all assessed vertebrae from T4 to L4 were used to generate indices of end-plate curvature. Results Images from 10,132 participants (56% female, mean age 63.9 years) passed quality checks. Overall, 47% of men and women had DDD grade 3 or more in the lumbar spine and 36% in both thoracic and lumbar spine. Risk ratios for DDD grades 3 and 4, adjusted for age and anthropometric determinants, varied across a three-fold range between centres, yet prevalences were highly correlated in men and women. DDD was associated with flattened, non-ovoid inter-vertebral disc spaces. KL grade 4 and loss of inter-vertebral disc space were associated with higher spine aBMD. Discussion KL Grades 3 and 4 are often used clinically to categorise radiological DDD. Highly variable European prevalences of radiologically-defined DDD Grades 3+ along with the large effects of age may have growing and geographically unequal health and economic impacts as the population ages. These data encourage further studies of potential genetic and environmental causes. PMID:28398504

  16. Can Vitamin A be Improved to Prevent Blindness due to Age-Related Macular Degeneration, Stargardt Disease and Other Retinal Dystrophies?

    Science.gov (United States)

    Saad, Leonide; Washington, Ilyas

    2016-01-01

    We discuss how an imperfect visual cycle results in the formation of vitamin A dimers, thought to be involved in the pathogenesis of various retinal diseases, and summarize how slowing vitamin A dimerization has been a therapeutic target of interest to prevent blindness. To elucidate the molecular mechanism of vitamin A dimerization, an alternative form of vitamin A, one that forms dimers more slowly yet maneuvers effortlessly through the visual cycle, was developed. Such a vitamin A, reinforced with deuterium (C20-D3-vitamin A), can be used as a non-disruptive tool to understand the contribution of vitamin A dimers to vision loss. Eventually, C20-D3-vitamin A could become a disease-modifying therapy to slow or stop vision loss associated with dry age-related macular degeneration (AMD), Stargardt disease and retinal diseases marked by such vitamin A dimers. Human clinical trials of C20-D3-vitamin A (ALK-001) are underway.

  17. Agreement between T2 and haste sequences in the evaluation of thoracolumbar intervertebral disc disease in dogs.

    Science.gov (United States)

    Mankin, Joseph M; Hecht, Silke; Thomas, William B

    2012-01-01

    The purpose of this study was to compare half-Fourier-acquisition single-shot turbo spin-echo (HASTE) and T2-weighted (T2-W) sequences in dogs with thoracolumbar disc extrusion. MRI studies in 60 dogs (767 individual intervertebral disc spaces) were evaluated. Agreement between T2-W and HASTE sequences was assessed for two criteria: presence of an extradural lesion and treatment recommendation. There was moderate agreement between T2-W and HASTE sequences as to presence of an extradural lesion (kappa = 0.575). HASTE was in agreement in 96.1% of the sites where no extradural lesion was identified on T2-W images, but only in 58.1% of the sites where extradural lesions were identified on T2-W images. There was also moderate agreement between T2-W and HASTE sequences as to treatment recommendations (kappa = 0.476). HASTE was in agreement in 98.4% of the sites where a lesion was considered nonsurgical on T2 but only 82.1% of sites a lesion was considered surgical on T2. In 1.0% of sites considered not surgical and in 9.8% of sites considered equivocal based on T2-W images, a surgical lesion was identified on HASTE. Acquisition of a HASTE sequence in addition to conventional sequences may be beneficial in determining the severity of spinal cord compression in some cases when evaluating the canine spine.

  18. Human and bovine spinal disc mechanics subsequent to trypsin injection

    Directory of Open Access Journals (Sweden)

    Jeremy Alsup

    2017-10-01

    The Translational Potential of this Article: Preclinical testing of novel spinal devices is essential to the design validation and regulatory processes, but current testing techniques rely on cadaveric testing of primarily older spines with essentially random amounts of disc degeneration. The present work investigates the viability of using trypsin injections to create a more uniform preclinical model of disc degeneration from a mechanics perspective, for the purpose of testing spinal devices. Such a model would facilitate translation of new spinal technologies to clinical practice.

  19. Senescent intervertebral disc cells exhibit perturbed matrix homeostasis phenotype.

    Science.gov (United States)

    Ngo, Kevin; Patil, Prashanti; McGowan, Sara J; Niedernhofer, Laura J; Robbins, Paul D; Kang, James; Sowa, Gwendolyn; Vo, Nam

    2017-09-01

    Aging greatly increases the risk for intervertebral disc degeneration (IDD) as a result of proteoglycan loss due to reduced synthesis and enhanced degradation of the disc matrix proteoglycan (PG). How disc matrix PG homeostasis becomes perturbed with age is not known. The goal of this study is to determine whether cellular senescence is a source of this perturbation. We demonstrated that disc cellular senescence is dramatically increased in the DNA repair-deficient Ercc1 -/Δ mouse model of human progeria. In these accelerated aging mice, increased disc cellular senescence is closely associated with the rapid loss of disc PG. We also directly examine PG homeostasis in oxidative damage-induced senescent human cells using an in vitro cell culture model system. Senescence of human disc cells treated with hydrogen peroxide was confirmed by growth arrest, senescence-associated β-galactosidase activity, γH2AX foci, and acquisition of senescence-associated secretory phenotype. Senescent human disc cells also exhibited perturbed matrix PG homeostasis as evidenced by their decreased capacity to synthesize new matrix PG and enhanced degradation of aggrecan, a major matrix PG. of the disc. Our in vivo and in vitro findings altogether suggest that disc cellular senescence is an important driver of PG matrix homeostatic perturbation and PG loss. Published by Elsevier B.V.

  20. Spectroscopic Parameters of Lumbar Intervertebral Disc Material

    Science.gov (United States)

    Terbetas, G.; Kozlovskaja, A.; Varanius, D.; Graziene, V.; Vaitkus, J.; Vaitkuviene, A.

    2009-06-01

    needle can give additional information of needle position, assuring the needle tip is directed into intervertebral disc material. Spectroscopic analysis of intervertebral disc removed during open surgery, creates background for further investigation on intervertebral disc degeneration spectral classification.

  1. Vertebral osteomyelitis without disc involvement

    Energy Technology Data Exchange (ETDEWEB)

    Kamani, I.; Syed, I.; Saifuddin, A. E-mail: asaifuddin@aol.com; Green, R.; MacSweeney, F

    2004-10-01

    Vertebral osteomyelitis is most commonly due to pyogenic or granulomatous infection and typically results in the combined involvement of the intervertebral disc and adjacent vertebral bodies. Non-infective causes include the related conditions of chronic recurrent multifocal osteomyelitis (CRMO) and SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome. Occasionally, these conditions may present purely within the vertebral body, resulting in various combinations of vertebral marrow oedema and sclerosis, destructive lesions of the vertebral body and pathological vertebral collapse, thus mimicking neoplastic disease. This review illustrates the imaging features of vertebral osteomyelitis without disc involvement, with emphasis on magnetic resonance imaging (MRI) findings.

  2. Can magnetic resonance imaging accurately predict concordant pain provocation during provocative disc injection?

    International Nuclear Information System (INIS)

    Kang, Chang Ho; Kim, Yun Hwan; Kim, Jung Hyuk; Chung, Kyoo Byung; Sung, Deuk Jae; Lee, Sang-Heon; Derby, Richard

    2009-01-01

    To correlate magnetic resonance (MR) image findings with pain response by provocation discography in patients with discogenic low back pain, with an emphasis on the combination analysis of a high intensity zone (HIZ) and disc contour abnormalities. Sixty-two patients (aged 17-68 years) with axial low back pain that was likely to be disc related underwent lumbar discography (178 discs tested). The MR images were evaluated for disc degeneration, disc contour abnormalities, HIZ, and endplate abnormalities. Based on the combination of an HIZ and disc contour abnormalities, four classes were determined: (1) normal or bulging disc without HIZ; (2) normal or bulging disc with HIZ; (3) disc protrusion without HIZ; (4) disc protrusion with HIZ. These MR image findings and a new combined MR classification were analyzed in the base of concordant pain determined by discography. Disc protrusion with HIZ [sensitivity 45.5%; specificity 97.8%; positive predictive value (PPV), 87.0%] correlated significantly with concordant pain provocation (P < 0.01). A normal or bulging disc with HIZ was not associated with reproduction of pain. Disc degeneration (sensitivity 95.4%; specificity 38.8%; PPV 33.9%), disc protrusion (sensitivity 68.2%; specificity 80.6%; PPV 53.6%), and HIZ (sensitivity 56.8%; specificity 83.6%; PPV 53.2%) were not helpful in the identification of a disc with concordant pain. The proposed MR classification is useful to predict a disc with concordant pain. Disc protrusion with HIZ on MR imaging predicted positive discography in patients with discogenic low back pain. (orig.)

  3. Pedigree with frontotemporal lobar degeneration – motor neuron disease and Tar DNA binding protein-43 positive neuropathology: genetic linkage to chromosome 9

    Directory of Open Access Journals (Sweden)

    Loy Clement T

    2008-08-01

    Full Text Available Abstract Background Frontotemporal lobar degeneration (FTLD represents a clinically, pathologically and genetically heterogenous neurodegenerative disorder, often complicated by neurological signs such as motor neuron-related limb weakness, spasticity and paralysis, parkinsonism and gait disturbances. Linkage to chromosome 9p had been reported for pedigrees with the neurodegenerative disorder, frontotemporal lobar degeneration (FTLD and motor neuron disease (MND. The objective in this study is to identify the genetic locus in a multi-generational Australian family with FTLD-MND. Methods Clinical review and standard neuropathological analysis of brain sections from affected pedigree members. Genome-wide scan using microsatellite markers and single nucleotide polymorphism fine mapping. Examination of candidate genes by direct DNA sequencing. Results Neuropathological examination revealed cytoplasmic deposition of the TDP-43 protein in three affected individuals. Moreover, we identify a family member with clinical Alzheimer's disease, and FTLD-Ubiquitin neuropathology. Genetic linkage and haplotype analyses, defined a critical region between markers D9S169 and D9S1845 on chromosome 9p21. Screening of all candidate genes within this region did not reveal any novel genetic alterations that co-segregate with disease haplotype, suggesting that one individual carrying a meiotic recombination may represent a phenocopy. Re-analysis of linkage data using the new affection status revealed a maximal two-point LOD score of 3.24 and a multipoint LOD score of 3.41 at marker D9S1817. This provides the highest reported LOD scores from a single FTLD-MND pedigree. Conclusion Our reported increase in the minimal disease region should inform other researchers that the chromosome 9 locus may be more telomeric than predicted by published recombination boundaries. Moreover, the existence of a family member with clinical Alzheimer's disease, and who shares the disease

  4. Risk factors for adjacent segment degeneration after surgical correction of degenerative lumbar scoliosis

    Directory of Open Access Journals (Sweden)

    Kee-yong Ha

    2013-01-01

    Full Text Available Background: Degenerative lumbar scoliosis surgery can lead to development of adjacent segment degeneration (ASD after lumbar or thoracolumbar fusion. Its incidence, risk factors, morbidity and correlation between radiological and clinical symptoms of ASD have no consensus. We evaluated the correlation between the occurrence of radiologic adjacent segment disease and certain imperative parameters. Materials and Methods: 98 patients who had undergone surgical correction and lumbar/thoracolumbar fusion with pedicle screw instrumentation for degenerative lumbar scoliosis with a minimum 5 year followup were included in the study. We evaluated the correlation between the occurrence of radiologic adjacent segment disease and imperative patient parameters like age at operation, sex, body mass index (BMI, medical comorbidities and bone mineral density (BMD. The radiological parameters taken into consideration were Cobb′s angle, angle type, lumbar lordosis, pelvic incidence, intercristal line, preoperative existence of an ASD on plain radiograph and magnetic resonance imaging (MRI and surgical parameters were number of the fusion level, decompression level, floating OP (interlumbar fusion excluding L5-S1 level and posterolateral lumbar interbody fusion (PLIF. Clinical outcomes were assessed with the Visual Analogue Score (VAS and Oswestry Disability Index (ODI. Results: ASD was present in 44 (44.9% patients at an average period of 48.0 months (range 6-98 months. Factors related to occurrence of ASD were preoperative existence of disc degeneration (as revealed by MRI and age at operation ( P = 0.0001, 0.0364. There were no statistically significant differences between radiological adjacent segment degeneration and clinical results (VAS, P = 0.446; ODI, P = 0.531. Conclusions: Patients over the age of 65 years and with preoperative disc degeneration (as revealed by plain radiograph and MRI were at a higher risk of developing ASD.

  5. Radially truncated galactic discs

    NARCIS (Netherlands)

    Grijs, R. de; Kregel, M.; Wesson, K H

    2000-01-01

    Abstract: We present the first results of a systematic analysis of radially truncatedexponential discs for four galaxies of a sample of disc-dominated edge-onspiral galaxies. Edge-on galaxies are very useful for the study of truncatedgalactic discs, since we can follow their light distributions out

  6. At the centre of neuronal, synaptic and axonal pathology in murine prion disease: degeneration of neuroanatomically linked thalamic and brainstem nuclei

    Science.gov (United States)

    Reis, Renata; Hennessy, Edel; Murray, Caoimhe; Griffin, Éadaoin W.

    2015-01-01

    Aims The processes by which neurons degenerate in chronic neurodegenerative diseases remain unclear. Synaptic loss and axonal pathology frequently precede neuronal loss and protein aggregation demonstrably spreads along neuroanatomical pathways in many neurodegenerative diseases. The spread of neuronal pathology is less studied. Methods We previously demonstrated severe neurodegeneration in the posterior thalamus of multiple prion disease strains. Here we used the ME7 model of prion disease to examine the nature of this degeneration in the posterior thalamus and the major brainstem projections into this region. Results We objectively quantified neurological decline between 16 and 18 weeks post‐inoculation and observed thalamic subregion‐selective neuronal, synaptic and axonal pathology while demonstrating relatively uniform protease‐resistant prion protein (PrP) aggregation and microgliosis across the posterior thalamus. Novel amyloid precursor protein (APP) pathology was particularly prominent in the thalamic posterior (PO) and ventroposterior lateral (VPL) nuclei. The brainstem nuclei forming the major projections to these thalamic nuclei were examined. Massive neuronal loss in the PO was not matched by significant neuronal loss in the interpolaris (Sp5I), while massive synaptic loss in the ventral posteromedial nucleus (VPM) did correspond with significant neuronal loss in the principal trigeminal nucleus. Likewise, significant VPL synaptic loss was matched by significant neuronal loss in the gracile and cuneate nuclei. Conclusion These findings demonstrate significant spread of neuronal pathology from the thalamus to the brainstem in prion disease. The divergent neuropathological features in adjacent neuronal populations demonstrates that there are discrete pathways to neurodegeneration in different neuronal populations. PMID:25727649

  7. Mechanical design criteria for intervertebral disc tissue engineering.

    Science.gov (United States)

    Nerurkar, Nandan L; Elliott, Dawn M; Mauck, Robert L

    2010-04-19

    Due to the inability of current clinical practices to restore function to degenerated intervertebral discs, the arena of disc tissue engineering has received substantial attention in recent years. Despite tremendous growth and progress in this field, translation to clinical implementation has been hindered by a lack of well-defined functional benchmarks. Because successful replacement of the disc is contingent upon replication of some or all of its complex mechanical behaviors, it is critically important that disc mechanics be well characterized in order to establish discrete functional goals for tissue engineering. In this review, the key functional signatures of the intervertebral disc are discussed and used to propose a series of native tissue benchmarks to guide the development of engineered replacement tissues. These benchmarks include measures of mechanical function under tensile, compressive, and shear deformations for the disc and its substructures. In some cases, important functional measures are identified that have yet to be measured in the native tissue. Ultimately, native tissue benchmark values are compared to measurements that have been made on engineered disc tissues, identifying where functional equivalence was achieved, and where there remain opportunities for advancement. Several excellent reviews exist regarding disc composition and structure, as well as recent tissue engineering strategies; therefore this review will remain focused on the functional aspects of disc tissue engineering. Copyright 2009 Elsevier Ltd. All rights reserved.

  8. The Mobi-C cervical disc for one-level and two-level cervical disc replacement: a review of the literature

    Directory of Open Access Journals (Sweden)

    Alvin MD

    2014-11-01

    Full Text Available Matthew D Alvin,1,2 Thomas E Mroz1,3,41Cleveland Clinic Center for Spine Health, Cleveland Clinic, Cleveland, OH, USA; 2Case Western Reserve University School of Medicine, Cleveland, OH, USA; 3Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA; 4Department of Neurological Surgery, Cleveland Clinic, Cleveland, OH, USABackground: Cervical disc arthroplasty (CDA is a novel motion-preserving procedure that is an alternative to fusion. The Mobi-C disc prosthesis, one of many Food and Drug Administration (FDA-approved devices for CDA, is the only FDA-approved prosthesis for two-level CDA. Hence, it may allow for improved outcomes compared with multilevel fusion procedures.Purpose: To critically assess the available literature on CDA with the Mobi-C prosthesis, with a focus on two-level CDA.Methods: All clinical articles involving the Mobi-C disc prosthesis for CDA through September 1, 2014 were identified on Medline. Any paper that presented Mobi-C CDA clinical results was included. Study design, sample size, length of follow-up, use of statistical analysis, quality of life outcome scores, conflict of interest, and complications were recorded.Results: Fifteen studies were included that investigated Mobi-C CDA, only one of which was a level Ib randomized control trial. All studies included showed non-inferiority of one-level Mobi-C CDA to one-level anterior cervical discectomy and fusion (ACDF. Only one study analyzed outcomes of one-level versus two-level Mobi-C CDA, and only one study analyzed two-level Mobi-C CDA versus two-level ACDF. In comparison with other cervical disc prostheses, the Mobi-C prosthesis is associated with higher rates of heterotopic ossification (HO. Studies with conflicts of interest reported lower rates of HO. Adjacent segment degeneration or disease, along with other complications, were not assessed in most studies.Conclusion: One-level Mobi-C CDA is non-inferior, but not superior, to one-level ACDF for patients

  9. Imaging characteristics of noncontained migrating disc fragment and cyst

    International Nuclear Information System (INIS)

    Eerens, I.; Demaerel, P.; Haven, F.; Wilms, G.; Loon, J. van; Calenbergh, F. van

    2001-01-01

    The purpose of this article is to review less common presentations of degenerative disc disease on MR imaging. The images of eight patients were retrospectively analyzed. Six of them had transligamentous (or noncontained) disc herniations, the fragments of which were located in the posterior epidural space in three of them. One patient had a transdural disc fragment and one patient had a disc cyst. The cyst was located in the ventrolateral epidural space. On T2-weighted images, the migrated disc fragment returned a higher signal than the disc of origin in 6 of 7 patients. The disc cyst returned a signal similar to that of cerebrospinal fluid. The MR appearances of disc fragments can be puzzling, particularly if they are located in the posterior epidural space. It is important to recognize the abnormalities in order to differentiate them from less common lesions such as hematoma, abscess and neurinoma. (orig.)

  10. Imaging characteristics of noncontained migrating disc fragment and cyst

    Energy Technology Data Exchange (ETDEWEB)

    Eerens, I.; Demaerel, P.; Haven, F.; Wilms, G. [Dept. of Radiology, University Hospitals, Leuven (Belgium); Loon, J. van; Calenbergh, F. van [Dept. of Neurosurgery, University Hospitals, Leuven (Belgium)

    2001-05-01

    The purpose of this article is to review less common presentations of degenerative disc disease on MR imaging. The images of eight patients were retrospectively analyzed. Six of them had transligamentous (or noncontained) disc herniations, the fragments of which were located in the posterior epidural space in three of them. One patient had a transdural disc fragment and one patient had a disc cyst. The cyst was located in the ventrolateral epidural space. On T2-weighted images, the migrated disc fragment returned a higher signal than the disc of origin in 6 of 7 patients. The disc cyst returned a signal similar to that of cerebrospinal fluid. The MR appearances of disc fragments can be puzzling, particularly if they are located in the posterior epidural space. It is important to recognize the abnormalities in order to differentiate them from less common lesions such as hematoma, abscess and neurinoma. (orig.)

  11. Abnormal Mitochondrial Dynamics and Synaptic Degeneration as Early Events in Alzheimer’s Disease: Implications to Mitochondria-Targeted Antioxidant Therapeutics

    Science.gov (United States)

    Reddy, P. Hemachandra; Tripathy, Raghav; Troung, Quang; Thirumala, Karuna; Reddy, Tejaswini P.; Anekonda, Vishwanath; Shirendeb, Ulziibat P.; Calkins, Marcus J.; Reddy, Arubala P.; Mao, Peizhong; Manczak, Maria

    2011-01-01

    Synaptic pathology and mitochondrial oxidative damage are early events in Alzheimer’s disease (AD) progression. Loss of synapses and synaptic damage are the best correlate of cognitive deficits found in AD patients. Recent research on amyloid bet (Aβ) and mitochondria in AD revealed that Aβ accumulates in synapses and synaptic mitochondria, leading to abnormal mitochondrial dynamics and synaptic degeneration in AD neurons. Further, recent studies using live-cell imaging and primary neurons from amyloid beta precursor protein (AβPP) transgenic mice revealed that reduced mitochondrial mass, defective axonal transport of mitochondria and synaptic degeneration, indicating that Aβ is responsible for mitochondrial and synaptic deficiencies. Tremendous progress has been made in studying antioxidant approaches in mouse models of AD and clinical trials of AD patients. This article highlights the recent developments made in Aβ-induced abnormal mitochondrial dynamics, defective mitochondrial biogenesis, impaired axonal transport and synaptic deficiencies in AD. This article also focuses on mitochondrial approaches in treating AD, and also discusses latest research on mitochondria-targeted antioxidants in AD. PMID:22037588

  12. Loss of the E3 ubiquitin ligase LRSAM1 sensitizes peripheral axons to degeneration in a mouse model of Charcot-Marie-Tooth disease

    Directory of Open Access Journals (Sweden)

    Laurent P. Bogdanik

    2013-05-01

    Charcot-Marie-Tooth disease (CMT is a clinically and genetically heterogeneous condition characterized by peripheral axon degeneration with subsequent motor and sensory deficits. Several CMT gene products function in endosomal sorting and trafficking to the lysosome, suggesting that defects in this cellular pathway might present a common pathogenic mechanism for these conditions. LRSAM1 is an E3 ubiquitin ligase that is implicated in this process, and mutations in LRSAM1 have recently been shown to cause CMT. We have generated mouse mutations in Lrsam1 to create an animal model of this form of CMT (CMT2P. Mouse Lrsam1 is abundantly expressed in the motor and sensory neurons of the peripheral nervous system. Both homozygous and heterozygous mice have largely normal neuromuscular performance and only a very mild neuropathy phenotype with age. However, Lrsam1 mutant mice are more sensitive to challenge with acrylamide, a neurotoxic agent that causes axon degeneration, indicating that the axons in the mutant mice are indeed compromised. In transfected cells, LRSAM1 primarily localizes in a perinuclear compartment immediately beyond the Golgi and shows little colocalization with components of the endosome to lysosome trafficking pathway, suggesting that other cellular mechanisms also merit consideration.

  13. Loss of the E3 ubiquitin ligase LRSAM1 sensitizes peripheral axons to degeneration in a mouse model of Charcot-Marie-Tooth disease.

    Science.gov (United States)

    Bogdanik, Laurent P; Sleigh, James N; Tian, Cong; Samuels, Mark E; Bedard, Karen; Seburn, Kevin L; Burgess, Robert W

    2013-05-01

    Charcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous condition characterized by peripheral axon degeneration with subsequent motor and sensory deficits. Several CMT gene products function in endosomal sorting and trafficking to the lysosome, suggesting that defects in this cellular pathway might present a common pathogenic mechanism for these conditions. LRSAM1 is an E3 ubiquitin ligase that is implicated in this process, and mutations in LRSAM1 have recently been shown to cause CMT. We have generated mouse mutations in Lrsam1 to create an animal model of this form of CMT (CMT2P). Mouse Lrsam1 is abundantly expressed in the motor and sensory neurons of the peripheral nervous system. Both homozygous and heterozygous mice have largely normal neuromuscular performance and only a very mild neuropathy phenotype with age. However, Lrsam1 mutant mice are more sensitive to challenge with acrylamide, a neurotoxic agent that causes axon degeneration, indicating that the axons in the mutant mice are indeed compromised. In transfected cells, LRSAM1 primarily localizes in a perinuclear compartment immediately beyond the Golgi and shows little colocalization with components of the endosome to lysosome trafficking pathway, suggesting that other cellular mechanisms also merit consideration.

  14. Comparison of the SF6D, the EQ5D, and the oswestry disability index in patients with chronic low back pain and degenerative disc disease.

    Science.gov (United States)

    Johnsen, Lars G; Hellum, Christian; Nygaard, Oystein P; Storheim, Kjersti; Brox, Jens I; Rossvoll, Ivar; Leivseth, Gunnar; Grotle, Margreth

    2013-04-26

    The need for cost effectiveness analyses in randomized controlled trials that compare treatment options is increasing. The selection of the optimal utility measure is important, and a central question is whether the two most commonly used indexes - the EuroQuol 5D (EQ5D) and the Short Form 6D (SF6D) - can be used interchangeably. The aim of the present study was to compare change scores of the EQ5D and SF6D utility indexes in terms of some important measurement properties. The psychometric properties of the two utility indexes were compared to a disease-specific instrument, the Oswestry Disability Index (ODI), in the setting of a randomized controlled trial for degenerative disc disease. In a randomized controlled multicentre trial, 172 patients who had experienced low back pain for an average of 6 years were randomized to either treatment with an intensive back rehabilitation program or surgery to insert disc prostheses. Patients filled out the ODI, EQ5D, and SF-36 at baseline and two-year follow up. The utility indexes was compared with respect to measurement error, structural validity, criterion validity, responsiveness, and interpretability according to the COSMIN taxonomy. At follow up, 113 patients had change score values for all three instruments. The SF6D had better similarity with the disease-specific instrument (ODI) regarding sensitivity, specificity, and responsiveness. Measurement error was lower for the SF6D (0.056) compared to the EQ5D (0.155). The minimal important change score value was 0.031 for SF6D and 0.173 for EQ5D. The minimal detectable change score value at a 95% confidence level were 0.157 for SF6D and 0.429 for EQ5D, and the difference in mean change score values (SD) between them was 0.23 (0.29) and so exceeded the clinical significant change score value for both instruments. Analysis of psychometric properties indicated that the indexes are unidimensional when considered separately, but that they do not exactly measure the same

  15. Temporomandibular joint fibrocartilage degeneration from unilateral dental splints.

    Science.gov (United States)

    Henderson, Sarah E; Lowe, Jesse R; Tudares, Mauro A; Gold, Michael S; Almarza, Alejandro J

    2015-01-01

    The objective of this study was to determine the extent to which altered loading in the temporomandibular joint (TMJ), as might be associated with a malocclusion, drives degeneration of articulating surfaces in the TMJ. We therefore sought to quantify the effects of altered joint loading on the mechanical properties and biochemical content and distribution of TMJ fibrocartilage in the rabbit. Altered TMJ loading was induced with a 1mm splint placed unilaterally over the maxillary and mandibular molars for 6 weeks. At that time, TMJ fibrocartilage was assessed by compression testing, biochemical content (collagen, glycosaminoglycan (GAG), DNA) and distribution (histology), for both the TMJ disc and the condylar fibrocartilage. There were no changes in the TMJ disc for any of the parameters tested. The condylar fibrocartilage from the splinted animals was significantly stiffer and the DNA content was significantly lower than that in control animals. There was significant remodeling in the condylar fibrocartilage layers as manifested by a change in GAG and collagen II distribution and a loss of defined cell layers. A connection between the compressive properties of TMJ condylar fibrocartilage after 6 weeks of splinting and the changes in histology was observed. These results suggest a change in joint loading leads to condylar damage, which may contribute to pain associated with at least some forms of TMJ disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Stem cell therapy for intervertebral disc regeneration: review article

    Directory of Open Access Journals (Sweden)

    Mohsen Sheykhhasan

    2017-02-01

    Full Text Available Intervertebral disks (IVD acts as shock absorber between each of the vertebrae in the spinal column by keeping the vertebrae separated when the shock caused by the action. They also serve to protect the nerves that run down the middle of the spine and intervertebral disks. The disks are made of fibrocartilaginous material. The outside of the disk is made of a strong material called the annulus fibrosus. Inside this protective covering is a jelly-like substance known as mucoprotein gel. This interior is known as the nucleus pulposus. The nucleus pulposus consists of large vacuolated notochord cells, small chondrocyte-like cells, collagen fibrils, and aggrecan, a proteoglycan that aggregates by binding to hyaluronan. Attached to each aggrecan molecule are glycosaminoglycan (GAG chains of chondroitin sulfate and keratan sulfate. Intervertebral disks degeneration is frequently associated with low back and neck pain, which accounts as a disability. Despite the known outcomes of the Intervertebral disks degeneration cascade, the treatment of IVD degeneration is limited in that available conservative and surgical treatments do not reverse the pathology or restore the IVD tissue. Regenerative medicine for IVD degeneration, by injection of Intervertebral disks cells, chondrocytes or stem cells, has been extensively studied in the past decade in various animal models of induced IVD degeneration, and has progressed to clinical trials in the treatment of various spinal disease. Despite preliminary results showing positive effects of cell-injection strategies for IVD regeneration, detailed basic research on Intervertebral disks cells and their niche demonstrates that transplanted cells are unable to survive and adapt in the avascular niche of the IVD. For this therapeutic strategy to succeed, the indications for its use and the patients who would benefit need to be better defined. To surmount these obstacles, the solution will be identified only by focused

  17. Human and bovine spinal disc mechanics subsequent to trypsin injection.

    Science.gov (United States)

    Alsup, Jeremy; Bishop, Timothy; Eggett, Dennis; Bowden, Anton E

    2017-10-01

    To investigate the biomechanical effects of injections of a protease on the characteristics of bovine coccygeal and human lumbar disc motion segments. Mechanics of treated tissues were measured immediately after injection and 3 h after injection. Motion segments underwent axial rotation and flexion-extension loading. Stiffness and neutral zone parameters experienced significant changes over time, with bovine tissues more strongly affected than human cadaver tissues. This was true in both axial rotation and flexion-extension. The treatment type significantly affected the neutral zone measurements in axial rotation. Hysteresis parameters were impacted by control injections. The extrapolation of bovine coccygeal motion testing results to human lumbar disc mechanics is not yet practical. The injected treatment may have a smaller impact on disc mechanics than time in testing. Viscoelasticity of human lumbar discs may be impacted by any damage to the annulus fibrosis induced by needlestick. Preclinical testing of novel spinal devices is essential to the design validation and regulatory processes, but current testing techniques rely on cadaveric testing of primarily older spines with essentially random amounts of disc degeneration. The present work investigates the viability of using trypsin injections to create a more uniform preclinical model of disc degeneration from a mechanics perspective, for the purpose of testing spinal devices. Such a model would facilitate translation of new spinal technologies to clinical practice.

  18. Hippocampal P3-like auditory event-related potentials are disrupted in a rat model of cholinergic degeneration in Alzheimer's disease: reversal by donepezil treatment.

    Science.gov (United States)

    Laursen, Bettina; Mørk, Arne; Kristiansen, Uffe; Bastlund, Jesper Frank

    2014-01-01

    P300 (P3) event-related potentials (ERPs) have been suggested to be an endogenous marker of cognitive function and auditory oddball paradigms are frequently used to evaluate P3 ERPs in clinical settings. Deficits in P3 amplitude and latency reflect some of the neurological dysfunctions related to several psychiatric and neurological diseases, e.g., Alzheimer's disease (AD). However, only a very limited number of rodent studies have addressed the back-translational validity of the P3-like ERPs as suitable markers of cognition. Thus, the potential of rodent P3-like ERPs to predict pro-cognitive effects in humans remains to be fully validated. The current study characterizes P3-like ERPs in the 192-IgG-SAP (SAP) rat model of the cholinergic degeneration associated with AD. Following training in a combined auditory oddball and lever-press setup, rats were subjected to bilateral intracerebroventricular infusion of 1.25 μg SAP or PBS (sham lesion) and recording electrodes were implanted in hippocampal CA1. Relative to sham-lesioned rats, SAP-lesioned rats had significantly reduced amplitude of P3-like ERPs. P3 amplitude was significantly increased in SAP-treated rats following pre-treatment with 1 mg/kg donepezil. Infusion of SAP reduced the hippocampal choline acetyltransferase activity by 75%. Behaviorally defined cognitive performance was comparable between treatment groups. The present study suggests that AD-like deficits in P3-like ERPs may be mimicked by the basal forebrain cholinergic degeneration induced by SAP. SAP-lesioned rats may constitute a suitable model to test the efficacy of pro-cognitive substances in an applied experimental setup.

  19. Superluminous accretion discs

    Energy Technology Data Exchange (ETDEWEB)

    Sikora, M [Cambridge Univ. (UK). Inst. of Astronomy; Polska Akademia Nauk, Warsaw. Centrum Astronomiczne)

    1981-07-01

    Upper limits are computed for the total luminosities and collimation of radiation from thick, radiation supported accretion discs around black holes. Numerical results are obtained for the 'extreme' discs with rsub(out) = 10/sup 3/ GMsub(BH)/c/sup 2/, the angular momentum of the black hole being Jsub(BH) = 0.998 GMsub(BH)/c. The high luminosity (L approximately 8.5 Lsub(Edd)) and substantial collimation of radiation found for these discs indicate that such discs can explain both the high luminosities of quasars and similar objects and may produce some of the observed beams and jets.

  20. Macular degeneration (image)

    Science.gov (United States)

    ... macula in the back of the eye. The macula is important for clear central vision, allowing an individual to see fine details. There are two types of macular degeneration, dry and wet. Dry macular degeneration is more ...

  1. Effect of total lumbar disc replacement on lumbosacral lordosis.

    Science.gov (United States)

    Kasliwal, Manish K; Deutsch, Harel

    2012-10-01

    Original article : To study effect of lumbar disc replacement on lumbosacral lordosis. There has been a growing interest in total disc replacement (TDR) for back pain with the rising concern of adjacent segment degeneration. Lumbar fusion surgery has been shown to lead to decrease in lumbar lordosis, which may account for postfusion pain resulting in less acceptable clinical outcome after successful fusion. TDR has recently emerged as an alternative treatment for back pain. There have been very few studies reporting lumbar sagittal outcome after TDR. Retrospective study of radiographic data of 17 patients who underwent TDR for single level degenerative disc disease at the author's institution was carried out. Study included measurement of preoperative and postoperative segmental and global lumbar lordosis and angle of lordosis. Patients age varied from 19 to 54 (mean, 35) years. Follow-up ranged from 12 to 24 months. TDR was performed at L4-5 level in 3 patients and L5-S1 level in 14 patients. The average values for segmental lordosis, global lordosis, and angle of lordosis at the operated level before and after surgery were 17.3, 49.7, and 8.6 degrees and 21.6, 54, and 9.5 degrees, respectively. There was a trend toward significant (P=0.02) and near significant (P=0.057) increase in segmental and global lordosis, respectively after TDR. Although prosthesis increased angle of lordosis at the level implanted in majority of the patients, the difference in preoperative and postoperative angle of lordosis was not significant (P=0.438). In addition, there was no correlation between the angle of implant of chosen and postoperative angle of lordosis at the operated level. The effect of TDR on sagittal balance appears favorable with an increase in global and segmental lumbar lordosis after single level TDR for degenerative disc disease. The degree of postoperative angle of lordosis was not affected by the angle of implant chosen at the operated level and varied

  2. Degenerative disc disease of the lumbar spine: a prospective comparison of fast T1-weighted fluid-attenuated inversion recovery and T1-weighted turbo spin echo MR imaging

    International Nuclear Information System (INIS)

    Erdem, L. Oktay; Erdem, C. Zuhal; Acikgoz, Bektas; Gundogdu, Sadi

    2005-01-01

    Objective: To compare fast T1-weighted fluid-attenuated inversion recovery (FLAIR) and T1-weighted turbo spin-echo (TSE) imaging of the degenerative disc disease of the lumbar spine. Materials and methods: Thirty-five consecutive patients (19 females, 16 males; mean age 41 years, range 31-67 years) with suspected degenerative disc disease of the lumbar spine were prospectively evaluated. Sagittal images of the lumbar spine were obtained using T1-weighted TSE and fast T1-weighted FLAIR sequences. Two radiologists compared these sequences both qualitatively and quantitatively. Results: On qualitative evaluation, CSF nulling, contrast at the disc-CSF interface, the disc-spinal cord (cauda equina) interface, and the spinal cord (cauda equina)-CSF interface of fast T1-weighted FLAIR images were significantly higher than those for T1-weighted TSE images (P < 0.001). On quantitative evaluation of the first 15 patients, signal-to-noise ratios of cerebrospinal fluid of fast T1-weighted FLAIR imaging were significantly lower than those for T1-weighted TSE images (P < 0.05). Contrast-to-noise ratios of spinal cord/CSF and normal bone marrow/disc for fast T1-weighted FLAIR images were significantly higher than those for T1-weighted TSE images (P < 0.05). Conclusion: Results in our study have shown that fast T1-weighted FLAIR imaging may be a valuable imaging modality in the armamentarium of lumbar spinal T1-weighted MR imaging, because the former technique has definite superior advantages such as CSF nulling, conspicuousness of the normal anatomic structures and changes in the lumbar spinal discogenic disease and image contrast and also almost equally acquisition times

  3. Degenerative disc disease of the lumbar spine: a prospective comparison of fast T1-weighted fluid-attenuated inversion recovery and T1-weighted turbo spin echo MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Erdem, L. Oktay [Department of Radiology, Zonguldak Karaelmas University, School of Medicine, 6700 Kozlu, Zonguldak (Turkey)]. E-mail: sunarerdem@yahoo.com; Erdem, C. Zuhal [Department of Radiology, Zonguldak Karaelmas University, School of Medicine, 6700 Kozlu, Zonguldak (Turkey); Acikgoz, Bektas [Department of Neurosurgery, Zonguldak Karaelmas University, School of Medicine, Zonguldak (Turkey); Gundogdu, Sadi [Department of Radiology, Zonguldak Karaelmas University, School of Medicine, 6700 Kozlu, Zonguldak (Turkey)

    2005-08-01

    Objective: To compare fast T1-weighted fluid-attenuated inversion recovery (FLAIR) and T1-weighted turbo spin-echo (TSE) imaging of the degenerative disc disease of the lumbar spine. Materials and methods: Thirty-five consecutive patients (19 females, 16 males; mean age 41 years, range 31-67 years) with suspected degenerative disc disease of the lumbar spine were prospectively evaluated. Sagittal images of the lumbar spine were obtained using T1-weighted TSE and fast T1-weighted FLAIR sequences. Two radiologists compared these sequences both qualitatively and quantitatively. Results: On qualitative evaluation, CSF nulling, contrast at the disc-CSF interface, the disc-spinal cord (cauda equina) interface, and the spinal cord (cauda equina)-CSF interface of fast T1-weighted FLAIR images were significantly higher than those for T1-weighted TSE images (P < 0.001). On quantitative evaluation of the first 15 patients, signal-to-noise ratios of cerebrospinal fluid of fast T1-weighted FLAIR imaging were significantly lower than those for T1-weighted TSE images (P < 0.05). Contrast-to-noise ratios of spinal cord/CSF and normal bone marrow/disc for fast T1-weighted FLAIR images were significantly higher than those for T1-weighted TSE images (P < 0.05). Conclusion: Results in our study have shown that fast T1-weighted FLAIR imaging may be a valuable imaging modality in the armamentarium of lumbar spinal T1-weighted MR imaging, because the former technique has definite superior advantages such as CSF nulling, conspicuousness of the normal anatomic structures and changes in the lumbar spinal discogenic disease and image contrast and also almost equally acquisition times.

  4. Auto fluorescence of intervertebral disc tissue: a new diagnostic tool.

    Science.gov (United States)

    Hoell, T; Huschak, G; Beier, A; Hüttmann, G; Minkus, Y; Holzhausen, H J; Meisel, H J

    2006-08-01

    The paper reports on auto fluorescence phenomena of inter-vertebral human discs. It systematically investigates the auto fluorescence effects of ex vivo disc specimen and reports on surgical cases to demonstrate the potential value of the new method. The paper offers biologic explanations of the phenomenon and discusses the potential value of the UV auto fluorescence technique as a diagnostic tool. Intra- and postoperative observations are made by a surgical microscope with an integrated UV light source. Quantitative measurements were carried out using a photon counter and a spectrometer ex vivo. The auto fluorescence phenomenon allows the differentiation of traumatized and degenerated disc tissue intraoperatively in some cases, it allows the differentiation of bony and collagen endplate in cervical disc surgery. The source of the auto fluorescent light emission are amino acids of the collagen molecules. The proteoglycan components and the liquid components of the disc do not show relevant auto fluorescence. Emission wavelength of disc material is equivalent to color perception. It differs due to different collagen composition of the intervertebral disc components from yellow-green to blue-green and can be visualized in situ by naked eye.UV-auto fluorescence of inter-vertebral discs is a new clinical tool that has the potential to differentiate disc material from the anatomical surrounding, to distinguish between different fractions of the disc and to give information on the quality and status of the disc material. Since the technology has just emerged, it needs further investigations to quantify the clinical observations reported in this paper.

  5. Dumbbell-shaped Hodgkin's disease with cauda equina compression mimicking a herniated inter-vertebral disc, a case report.

    Science.gov (United States)

    Liao, Jen-Chung; Fu, Tsai-Sheng; Chen, Wen-Jer; Jung, Shih-Ming

    2007-01-01

    Hodgkin's disease may involve the spine as a setting of the advanced disease. An initial manifestation of Hodgkin's disease in spine is extremely rare and the major involved sites usually are the thoracic or cervical spine. The mechanisms of pathogenesis for the formation of an epidural mass during Hodgkin's disease are hematogenous dissemination from nodal sites or local infiltration of lymphomatous tissue. We document here a case of a 16 year-old boy who suffered from incomplete voiding due to dumbbell-shaped retroperitoneal Hodgkin's disease with cauda equina compression. He was successfully managed using surgery and adjuvant chemotherapy. Although lymphadenomatous tissue responds well to radiotherapy and chemotherapy, the role of surgery in this case was to achieve immediate nerve tissue decompression and to obtain an adequate specimen for pathological diagnosis. Magnetic resonance imaging (MRI) is a non-invasive and helpful tool when detecting spinal and paraspinal lesions and we emphasize that spinal MRI should be performed without delay if there is persistent back pain or sciatica.

  6. Instability of warped discs

    Science.gov (United States)

    Doǧan, S.; Nixon, C. J.; King, A. R.; Pringle, J. E.

    2018-05-01

    Accretion discs are generally warped. If a warp in a disc is too large, the disc can `break' apart into two or more distinct planes, with only tenuous connections between them. Further, if an initially planar disc is subject to a strong differential precession, then it can be torn apart into discrete annuli that precess effectively independently. In previous investigations, torque-balance formulae have been used to predict where and when the disc breaks into distinct parts. In this work, focusing on discs with Keplerian rotation and where the shearing motions driving the radial communication of the warp are damped locally by turbulence (the `diffusive' regime), we investigate the stability of warped discs to determine the precise criterion for an isolated warped disc to break. We find and solve the dispersion relation, which, in general, yields three roots. We provide a comprehensive analysis of this viscous-warp instability and the emergent growth rates and their dependence on disc parameters. The physics of the instability can be understood as a combination of (1) a term that would generally encapsulate the classical Lightman-Eardley instability in planar discs (given by ∂(νΣ)/∂Σ < 0) but is here modified by the warp to include ∂(ν1|ψ|)/∂|ψ| < 0, and (2) a similar condition acting on the diffusion of the warp amplitude given in simplified form by ∂(ν2|ψ|)/∂|ψ| < 0. We discuss our findings in the context of discs with an imposed precession, and comment on the implications for different astrophysical systems.

  7. Volumetric MRI for evaluation of regional pattern and progression of neocortical degeneration in Alzheimer's disease; MR-Volumetrie zur Darstellung von Verteilung und zeitlicher Abfolge neokortikaler Degeneration bei Morbus Alzheimer

    Energy Technology Data Exchange (ETDEWEB)

    Leinsinger, G. [Institut fuer Klinische Radiologie, Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Muenchen (Germany); Institut fuer Klinische Radiologie, LMU Muenchen, Ziemssenstrasse 1, 80336, Muenchen (Germany); Teipel, S.; Pruessner, J.; Hampel, H. [Klinik fuer Psychiatrie, Ludwig-Maximilians-Universitaet Muenchen, Muenchen (Germany); Wismueller, A.; Born, C.; Meindl, T.; Flatz, W.; Schoenberg, S.; Reiser, M. [Institut fuer Klinische Radiologie, Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Muenchen (Germany)

    2003-07-01

    Volumetric analysis of the corpus callosum and hippocampus using MRI in Alzheimer's disease (AD) to evaluate the regional pattern and progression of neocortical neurodegeneration. In subsequent studies we investigated patients with AD and healthy controls. Volumetry was based on MRI-data from a sagittal 3D T1w-gradient echo sequence. The corpus callosum (CC) was measured in a midsagittal slice, and subdivided into 5 subregions. Volumetry of the hippocampus/amygdala-formation (HAF) was performed by segmentation in coronary reoriented slices. In AD patients we found a significant atrophy in the rostrum und splenium of CC. The atrophy was correlated with the severity of dementia, but no correlation was found with the load of white matter lesions. In comparison with {sup 18}FDG-PET, we found a significant correlation of regional CC-atrophy with the regional decline of cortical glucose metabolism. A ROC-analysis demonstrated no significant differences in the diagostic accuracy of HAF volumetry and regional CC volumetry of the splenium (region C5) even in mild stages of dementia. Regional atrophy of CC can be used as a marker of neocortical degeneration even in early stages of dementia in AD. (orig.) [German] Volumetrische Analyse des Corpus callosum und Hippokampus mittels MRT bei der Alzheimer-Erkrankung (AD), mit dem Ziel die regionale Verteilung und Progression der neokortikalen relativ zur allokortikalen Neurodegeneration zu erfassen. In mehreren Studienabschnitten wurden Patienten mit AD und gesunde Kontrollen untersucht. Als Grundlage fuer die Volumetrie diente eine sagittale 3D-T1w-Gradientenechosequenz. Die Vermessung des Corpus callosum (CC) erfolgte in der mittsagittalen Schicht, wobei 5 Subregionen definiert wurden. Die Volumetrie des Hippokampus-Amygdala-Komplexes (HAK) wurde durch Segmentierung an koronar reorientierten Schichten durchgefuehrt. Bei Patienten mit AD fand sich eine signifikante Atrophie in Rostrum und Splenium des CC. Dabei zeigte sich

  8. Intervertebral Disc Characteristic on Progressive Neurological Deficit

    Directory of Open Access Journals (Sweden)

    Farid Yudoyono

    2017-09-01

    Full Text Available Objective: To examine the intervertebral disc characteristic on magnetic resonance imaging (MRI in lumbar herniated disc (LHD patients with progressive neurological deficit. Methods: Patients were collected retrospectively from Dr. Hasan Sadikin General Hospital Database from 2011–2013 with LHD, had neurological deficit such as radiculopathy and cauda equine syndrome for less than four weeks with a positive sign confirmed by neurological examination and confirmatory with MRI examination. Results: A total of 14 patients with lumbar herniated disc disease (10 males, 4 females suffered from progressive neurological deficit with an average age of (52.07±10.9 years old. Early disc height was 9.38±0.5 mm and progressive neurological deficit state disc height was 4.03±0.53 mm, which were significantly different statisticaly (p<0.01. Symptoms of radiculopathy were seen in 11 patients and cauda equine syndrome in three patients. Modic changes grade 1 was found in five patients, grade 2 in eight patients,grade 3 in one patient, Pfirmman grade 2 in eleven patients and grade 3 in three patients. Thecal sac compression 1/3 compression was seen in four patients and 2/3 compression in ten patients. Conclusions: Neurosurgeon should raise concerns on the characteristic changes of intervertebral disc in magnetic resonance imaging examination to avoid further neural injury in lumbar herniated disc patients.

  9. Adjacent Lumbar Disc Herniation after Lumbar Short Spinal Fusion

    Directory of Open Access Journals (Sweden)

    Koshi Ninomiya

    2014-01-01

    Full Text Available A 70-year-old outpatient presented with a chief complaint of sudden left leg motor weakness and sensory disturbance. He had undergone L4/5 posterior interbody fusion with L3–5 posterior fusions for spondylolisthesis 3 years prior, and the screws were removed 1 year later. He has been followed up for 3 years, and there had been no adjacent segment problems before this presentation. Lumbar magnetic resonance imaging (MRI showed a large L2/3 disc hernia descending to the L3/4 level. Compared to the initial MRI, this hernia occurred in an “intact” disc among multilevel severely degenerated discs. Right leg paresis and bladder dysfunction appeared a few days after admission. Microscopic lumbar disc herniotomy was performed. The right leg motor weakness improved just after the operation, but the moderate left leg motor weakness and difficulty in urination persisted.

  10. Disc operational system

    International Nuclear Information System (INIS)

    Veretenov, V.Yu.; Volkov, A.I.; Gurevich, M.I.; Kozik, V.S.; Pod'yachev, E.I.; Shapiro, M.L.

    1974-01-01

    A disc operational system is proposed, which is based on the file structure and designed for use in a BESM-6 computer with the software system comprising a dispatcher DD-73 and a monitor 'Dubna'. The main distinguishing feature of the disc operational system is the decentralization of the file system. Each disc package is an independent file unaffected by the state of the other disc packages. The use of several disc packages is allowed. The above feature of the disc operational system makes it possible to simplify the language of communication with the system, to give the user the opportunity of controlling the file quite independently, and to simplify the maintenance of the discs by the computer personnel. One and the same disc can be simultaneously addressed by all problems in the processor (both mathematical and service). A single file, however, may be used in the recording mode by only one problem. The description presented is the instruction for users. It also describes special possibilities open to the system programmers [ru

  11. Intratracheal Seal Disc

    DEFF Research Database (Denmark)

    Christiansen, Karen J; Moeslund, Niels; Lauridsen, Henrik

    2017-01-01

    . The device consisted of an intratracheal silicone seal disc fixated by a cord through the stoma to an external part. At day 14, computed tomography (CT) was performed before the device was extracted. With the pulling of a cord, the disc unraveled into a thin thread and was extracted through the stoma. At day...

  12. Heat Shock Cognate 70 Inhibitor, VER-155008, Reduces Memory Deficits and Axonal Degeneration in a Mouse Model of Alzheimer’s Disease

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    Ximeng Yang

    2018-01-01

    Full Text Available Alzheimer’s disease (AD is a progressive neurodegenerative disorder resulting in structural brain changes and memory impairment. We hypothesized that reconstructing neural networks is essential for memory recovery in AD. Heat shock cognate 70 (HSC70, a member of the heat shock protein family of molecular chaperones, is upregulated in AD patient brains, and recent studies have demonstrated that HSC70 facilitates axonal degeneration and pathological progression in AD. However, the direct effects of HSC70 inhibition on axonal development and memory function have never been investigated. In this study, we examined the effects of a small-molecule HSC70 inhibitor, VER-155008, on axonal morphology and memory function in a mouse model of AD (5XFAD mice. We found that VER-155008 significantly promoted axonal regrowth in amyloid β-treated neurons in vitro and improved object recognition, location, and episodic-like memory in 5XFAD mice. Furthermore, VER-155008 penetrated into the brain after intraperitoneal administration, suggesting that VER-155008 acts in the brain in situ. Immunohistochemistry revealed that VER-155008 reduced bulb-like axonal swelling in the amyloid plaques in the perirhinal cortex and CA1 in 5XFAD mice, indicating that VER-155008 also reverses axonal degeneration in vivo. Moreover, the two main pathological features of AD, amyloid plaques and paired helical filament tau accumulation, were reduced by VER-155008 administration in 5XFAD mice. This is the first report to show that the inhibition of HSC70 function may be critical for axonal regeneration and AD-like symptom reversal. Our study provides evidence that HSC70 can be used as a new therapeutic target for AD treatment.

  13. Spinal cord swelling as a myelographic indicator of prognosis: a retrospective study in dogs with intervertebral disc disease and loss of deep pain perception

    International Nuclear Information System (INIS)

    Duval, J.; Dewey, C.; Roberts, R.; Aron, D.

    1996-01-01

    The association of myelographic spinal cord swelling with neurological outcome was examined in 46 dogs with intervertebral disc disease and absence of deep pain perception (DPP). Spinal cord swelling was measured by calculating a ratio of the length of the loss of the myelographic dye column to the length of the second lumbar vertebra (L2). A positive neurological outcome was defined as return of voluntary motor function. A cut-off value for swelling:L2 of 5.0 was established by the creation of a receiver operator characteristic curve. Using a swelling:L2 ratio of 5.0 as a cutoff for indication of neurological recovery yielded a sensitivity of 74% and a specificity of 61%. Overall neurological recovery rate was 43%. Dogs with spinal cord swelling:L2 ratios less than 5.0 had a recovery rate of 61%, whereas dogs with a ratio greater than or equal to 5.0 had a recovery rate of 26%. Evaluation of these data by chi square analysis confirmed that a ratio less than 5.0 was associated with a positive outcome, and a ratio greater than or equal to 5.0 was associated with a negative outcome, (P < .05). Although other factors, such as duration of neurological signs, affect neurological outcome in dogs with no DPP, evaluation of myelographic spinal cord swelling can assist in establishing a prognosis

  14. Measurement of Intervertebral Motion Using Quantitative Fluoroscopy: Report of an International Forum and Proposal for Use in the Assessment of Degenerative Disc Disease in the Lumbar Spine

    Directory of Open Access Journals (Sweden)

    Alan C. Breen

    2012-01-01

    Full Text Available Quantitative fluoroscopy (QF is an emerging technology for measuring intervertebral motion patterns to investigate problem back pain and degenerative disc disease. This International Forum was a networking event of three research groups (UK, US, Hong Kong, over three days in San Francisco in August 2009. Its aim was to reach a consensus on how best to record, analyse, and communicate QF information for research and clinical purposes. The Forum recommended that images should be acquired during regular trunk motion that is controlled for velocity and range, in order to minimise externally imposed variability as well as to correlate intervertebral motion with trunk motion. This should be done in both the recumbent passive and weight bearing active patient configurations. The main recommended outputs from QF were the true ranges of intervertebral rotation and translation, neutral zone laxity and the consistency of shape of the motion patterns. The main clinical research priority should initially be to investigate the possibility of mechanical subgroups of patients with chronic, nonspecific low back pain by comparing their intervertebral motion patterns with those of matched healthy controls.

  15. Investigation of intervertebral disc degeneration using multivariate FTIR spectroscopic imaging

    NARCIS (Netherlands)

    Mader, Kerstin T.; Peeters, Mirte; Detiger, Suzanne E. L.; Helder, Marco N.; Smit, Theo H.; Le Maitre, Christine L.; Sammon, Chris

    2016-01-01

    Traditionally tissue samples are analysed using protein or enzyme specific stains on serial sections to build up a picture of the distribution of components contained within them. In this study we investigated the potential of multivariate curve resolution-alternating least squares (MCR-ALS) to

  16. Double rupture disc experience

    International Nuclear Information System (INIS)

    1979-01-01

    Result of these observations, comparisons and evaluations can be summarized in the following list of concerns regarding the use of double rupture discs coupled to the liquid space of a steam generator that is subjected to a large leak sodium water reaction event. Single rupture disc show delayed collapse characteristics in LLTR Series I and double disc assemblies are presumed to be more complex with additional delay before opening to give pressure relief. Delayed failure increases pressures in the IHTS and must be adequately covered by design requirements. With CRBR design, the first disc may fail only partially reducing the loading on the second disc with the result that relief performance may not meet requirements

  17. Reduced tissue osmolarity increases TRPV4 expression and pro-inflammatory cytokines in intervertebral disc cells

    Directory of Open Access Journals (Sweden)

    BA Walter

    2016-07-01

    Full Text Available The mechanical behaviour and cellular metabolism of intervertebral discs (IVDs and articular cartilage are strongly influenced by their proteoglycan content and associated osmotic properties. This osmotic environment is a biophysical signal that changes with disease and may contribute to the elevated matrix breakdown and altered biologic response to loading observed in IVD degeneration and osteoarthritis. This study tested the hypothesis that changes in osmo-sensation by the transient receptor potential vallinoid-4 (TRPV4 ion channel occur with disease and contribute to the inflammatory environment found during degeneration. Immunohistochemistry on bovine IVDs from an inflammatory organ culture model were used to investigate if TRPV4 is expressed in the IVD and how expression changes with degeneration. Western blot, live-cell calcium imaging, and qRT-PCR were used to investigate whether osmolarity changes or tumour necrosis factor α (TNFα regulate TRPV4 expression, and how altered TRPV4 expression influences calcium signalling and pro-inflammatory cytokine expression. TRPV4 expression correlated with TNFα expression, and was increased when cultured in reduced medium osmolarity and unaltered with TNFα-stimulation. Increased TRPV4 expression increased the calcium flux following TRPV4 activation and increased interleukin-1β (IL-1β and IL-6 gene expression in IVD cells. TRPV4 expression was qualitatively elevated in regions of aggrecan depletion in degenerated human IVDs. Collectively, results suggest that reduced tissue osmolarity, likely following proteoglycan degradation, can increase TRPV4 signalling and enhance pro-inflammatory cytokine production, suggesting changes in TRPV4 mediated osmo-sensation may contribute to the progressive matrix breakdown in disease.

  18. Neuroinflammation and common mechanism in Alzheimer's disease and prion amyloidosis: amyloid-associated proteins, neuroinflammation and neurofibrillary degeneration

    NARCIS (Netherlands)

    Rozemuller, A.J.M.; Jansen, C.; Carrano, A.; van Haastert, E.S.; Hondius, D.; van der Vies, S.M.; Hoozemans, J.J.M.

    2012-01-01

    Background: In cases with a long (>1 year) clinical duration of prion disease, the prion protein can form amyloid deposits. These cases do not show accumulation of 4-kDa β-amyloid, which is observed in amyloid deposits in Alzheimer's disease (AD). In AD, amyloid is associated with inflammation and

  19. Cell therapy for intervertebral disc repair: advancing cell therapy from bench to clinics

    Directory of Open Access Journals (Sweden)

    LM Benneker

    2014-05-01

    Full Text Available Intervertebral disc (IVD degeneration is a major cause of pain and disability; yet therapeutic options are limited and treatment often remains unsatisfactory. In recent years, research activities have intensified in tissue engineering and regenerative medicine, and pre-clinical studies have demonstrated encouraging results. Nonetheless, the translation of new biological therapies into clinical practice faces substantial barriers. During the symposium "Where Science meets Clinics", sponsored by the AO Foundation and held in Davos, Switzerland, from September 5-7, 2013, hurdles for translation were outlined, and ways to overcome them were discussed. With respect to cell therapy for IVD repair, it is obvious that regenerative treatment is indicated at early stages of disc degeneration, before structural changes have occurred. It is envisaged that in the near future, screening techniques and non-invasive imaging methods will be available to detect early degenerative changes. The promises of cell therapy include a sustained effect on matrix synthesis, inflammation control, and prevention of angio- and neuro-genesis. Discogenic pain, originating from "black discs" or annular injury, prevention of adjacent segment disease, and prevention of post-discectomy syndrome were identified as prospective indications for cell therapy. Before such therapy can safely and effectively be introduced into clinics, the identification of the patient population and proper standardisation of diagnostic parameters and outcome measurements are indispensable. Furthermore, open questions regarding the optimal cell type and delivery method need to be resolved in order to overcome the safety concerns implied with certain procedures. Finally, appropriate large animal models and well-designed clinical studies will be required, particularly addressing safety aspects.

  20. A comprehensive survey of sequence variation in the ABCA4 (ABCR) gene in Stargardt disease and age-related macular degeneration.

    Science.gov (United States)

    Rivera, A; White, K; Stöhr, H; Steiner, K; Hemmrich, N; Grimm, T; Jurklies, B; Lorenz, B; Scholl, H P; Apfelstedt-Sylla, E; Weber, B H

    2000-10-01

    Stargardt disease (STGD) is a common autosomal recessive maculopathy of early and young-adult onset and is caused by alterations in the gene encoding the photoreceptor-specific ATP-binding cassette (ABC) transporter (ABCA4). We have studied 144 patients with STGD and 220 unaffected individuals ascertained from the German population, to complete a comprehensive, population-specific survey of the sequence variation in the ABCA4 gene. In addition, we have assessed the proposed role for ABCA4 in age-related macular degeneration (AMD), a common cause of late-onset blindness, by studying 200 affected individuals with late-stage disease. Using a screening strategy based primarily on denaturing gradient gel electrophoresis, we have identified in the three study groups a total of 127 unique alterations, of which 90 have not been previously reported, and have classified 72 as probable pathogenic mutations. Of the 288 STGD chromosomes studied, mutations were identified in 166, resulting in a detection rate of approximately 58%. Eight different alleles account for 61% of the identified disease alleles, and at least one of these, the L541P-A1038V complex allele, appears to be a founder mutation in the German population. When the group with AMD and the control group were analyzed with the same methodology, 18 patients with AMD and 12 controls were found to harbor possible disease-associated alterations. This represents no significant difference between the two groups; however, for detection of modest effects of rare alleles in complex diseases, the analysis of larger cohorts of patients may be required.

  1. An order in Lewy body disorders: Retrograde degeneration in hyperbranching axons as a fundamental structural template accounting for focal/multifocal Lewy body disease.

    Science.gov (United States)

    Uchihara, Toshiki

    2017-04-01

    Initial clinical recognition of "paralysis agitans" by James Parkinson was expanded by Jean-Martin Charcot, who recognized additional clinical findings of his own, such as slowness (distinct from paralysis), rigidity (distinct from spasticity) and characteristic countenance. Charcot assembled these findings under the umbrella of "Parkinson disease (PD)". This purely clinical concept was so prescient and penetrating that subsequent neuropathological and biochemical evidences were ordered along this axis to establish the nigra-central trinity of PD (dopamine depletion, nigral lesion with Lewy bodies: LBs). Although dramatic efficacy of levodopa boosted an enthusiasm for this nigra-centralism, extranigral lesions were identified, especially after identification of alpha-synuclein (αS) as a major constituent of LBs. Frequent αS lesions in the lower brainstem with their presumed upward spread were coupled with the self-propagating property of αS molecule, as a molecular template, to constitute the prion-Braak hypothesis. This hybrid concept might expectedly explain clinical, structural and biochemical features of PD/dementia with Lewy bodies (DLB) as if they were stereotypic. In spite of this ordered explanation, recent studies have demonstrated unexpectedly that αS lesions in the human brain, as well as their corresponding clinical manifestations, are much more disordered. Even with such a chaos of LB disorders, affected neuronal groups are uniformly characterized by hyperbranching axons, which may facilitate distal-dominant degeneration and retrograde progression of LB-related degeneration along axons as a fundamental structural order to template LB disorders. This "structural template" hypothesis may explain why: (i) some selective groups are prone to develop Lewy pathology; (ii) their clinical manifestations (especially non-motor components) are vague and generalized without somatotopic accentuation; (iii) distal axons and terminals are preferentially affected

  2. A novel PRNP Y218N mutation in Gerstmann-Sträussler-Scheinker disease with neurofibrillary degeneration.

    Science.gov (United States)

    Alzualde, Ainhoa; Indakoetxea, Begoña; Ferrer, Isidre; Moreno, Fermin; Barandiaran, Myriam; Gorostidi, Ana; Estanga, Ainara; Ruiz, Irune; Calero, Miguel; van Leeuwen, Fred W; Atares, Begoña; Juste, Ramón; Rodriguez-Martínez, Ana Belén; López de Munain, Adolfo

    2010-08-01

    Gerstmann-Sträussler-Scheinker (GSS) disease is a prion disease associated with prion protein gene (PRNP) mutations. We report a novel PRNP mutation (Y218N) associated with GSS disease in a pathologically confirmed case and in two other affected family members. The clinical features of these cases met criteria for possible Alzheimer disease and possible frontotemporal dementia. Neuropathologic analysis revealed deposition of proteinase K-resistant prion protein (PrP(res)), widespread hyperphosphorylated tau pathology, abnormal accumulation of mitochondria in the vicinity of PrP deposits, and expression of mutant ubiquitin (UBB(+1)) in neurofibrillary tangles and dystrophic neurites. Prion protein immunoblotting using 3F4 and 1E4 antibodies disclosed multiple bands ranging from approximately 20 kd to 80 kd and lower bands of 15 kd and approximately 10 kd, the latter only seen after a long incubation. These bands were partially resistant to proteinase K pretreatment. This pattern differs from those seen in Creutzfeldt-Jakob disease andresembles those reported in other GSS cases. The approximately 10kd band was recognized with anti-PrP C-terminus antibodies but not with anti-N terminus antibodies, suggesting PrP truncation at the N terminal. This new mutation extends the list of known mutations responsible for GSS disease and reinforces its clinical heterogeneity. Genetic examination of the PRNP gene should be included in the workup of patients with poorly classifiable dementia.

  3. Fas ligand exists on intervertebral disc cells: a potential molecular mechanism for immune privilege of the disc.

    Science.gov (United States)

    Takada, Toru; Nishida, Kotaro; Doita, Minoru; Kurosaka, Masahiro

    2002-07-15

    clinical treatments for disc degenerative diseases, including disc herniation with radicular pain.

  4. Immunogenesity of spesific protein molecular weight 16 KDa (PS16 leaf of siam citrus infected by citrus vein phloem degeneration (CVPD disease

    Directory of Open Access Journals (Sweden)

    Made Sritamin

    2012-02-01

    Full Text Available Citrus Vein Phloem degeneration (CVPD is an important citrus disese, which damaged citrus plantation and causing decrease of citrus production. In Indonesia, the CVPD disease caused by Liberobacter asiaticum bactery and the disease spread out by vectir insect Diaphorina citri and using infected bud in wood grafting. In infected citrus plant, two specific protein molecules with molecular weigt 16 kDa and 66 kDa are found. These protein molecules are not found in healthy citrus plant. The immunogenicity of PS16 accumulated on leaf of citrus plant infected by CVPD is known yet. The research material were leaves of citrus plant infected CVPD, leaves of healthy citrus plant and reagent used these research are for isolation of the total protein leaf of citrus plant, SDS-PAGE electroforesis, electroelution of PS16, ELISA Methods, Dot-Blot Method, anti-PS16 as aprimery antibody and secondary antibody is anti-Rabbit IgG Conjugated AP. The result of the research showed that of PS16 accumulated on leaf of citrus plant infected CVPD has immunogenic character. It is indicated by increase of the titer anti-PS16 after first immunization ang 2nd booster by indirect ELISA method and can be used to induce antibody (anti-PS16 and so showed that positive reaction between PS16 with anti-PS16. It is indicated by purples dark blue on cellulose membrane by Dot Blot method.

  5. Confiabilidade de um método de análise histológica da degeneração discal experimental em coelhos Confiabilidad de un método para el análisis histológico de la degeneración discal experimental en conejos Reliability of a method for histological analysis of experimental disc degeneration in rabbits

    Directory of Open Access Journals (Sweden)

    Emiliano Neves Vialle

    2011-01-01

    Zealand fueron sometidos a procedimiento de inducción de la degeneración discal a través de punción directa de tres discos intervertebrales (DIV consecutivos con aguja 18G bajo anestesia. Al fin de dos meses, se colectó la columna vertebral completa de cada conejo y se procedió a la preparación de las piezas para análisis histológico de los discos intervertebrales (Experimentales y Controles, siendo coloreadas por el método hematoxilina-eosina. Las láminas histológicas fueron evaluadas cuanto a ocurrencia de degeneración a través del análisis de los siguientes criterios: presencia de vasos sanguíneos; presencia de protrusión del núcleo pulposo (NP a través del anillo fibroso (AF; y rotura de las fibras del AF. RESULTADOS: Al final de los procesos de eutanasia, remoción y preparación histológica de la columna, se obtuvieron 60 DIV viables para evaluación de degeneración. De este total, 25 piezas eran de DIV experimentales y 35 piezas de DIV control. La presencia de vaso sanguíneo fue observada en 18 de los 25 DIV degenerados, con concordancia de Kappa = 0,95 entre los observadores. La presencia de la extrusión del NP fue identificada en 19 de los 25 DIV experimentales, con concordancia de Kappa = 0,78 entre los observadores. Con relación a la rotura de las fibras del AF, se puede identificar la positividad en 24 de los 25 DIV degenerados, con concordancia entre los observadores de Kappa = 0,65. CONCLUSIÓN: Este modelo de evaluación histológica de la degeneración experimental del DIV se mostró viable, con alto grado de concordancia entre los observadores en la identificación de la degeneración discal.OBJECTIVE: To validate a method for histological evaluation of disc degeneration in rabbits based on the reliability of interobserver analysis. METHODS: Thirteen New Zealand white rabbits underwent a procedure to induce disc degeneration through direct puncture of three consecutive intervertebral discs (IVD with an 18G needle under anesthesia

  6. Optic disc oedema

    DEFF Research Database (Denmark)

    Nielsen, Marianne Kromann; Hamann, Steffen

    2014-01-01

    Optic disc oedema describes the nonspecific, localized swelling of the optic nerve head regardless of aetiology. Therefore, differentiating among the various aetiologies depends on a thorough history and knowledge of the clinical characteristics of the underlying conditions. Papilloedema strictly...... refers to optic disc oedema as a consequence of elevated intracranial pressure. It is usually a bilateral condition and visual function is preserved until late. Optic disc oedema caused by an anterior optic neuropathy is usually unilateral and accompanied by the loss of visual function....

  7. Herniated Cervical Disc

    Science.gov (United States)

    ... are sometimes prescribed for more severe arm and neck pain because of their very powerful anti-inflammatory effect. ... caused by a herniated cervical disc. However, some neck pain may persist. Most patients respond well to discectomy; ...

  8. Effects of 17-allylamino-17-demethoxygeldanamycin (17-AAG) in transgenic mouse models of frontotemporal lobar degeneration and Alzheimer's disease.

    Science.gov (United States)

    Ho, Shuk Wai; Tsui, Yuk Tung Chanel; Wong, Ting Ting; Cheung, Stanley Kwok-Kuen; Goggins, William B; Yi, Lau Ming; Cheng, Kwok Kin; Baum, Larry

    2013-12-17

    Alzheimer's disease (AD), the most common dementia, is characterized by potentially neurotoxic aggregation of Aβ peptide and tau protein, and their deposition as amyloid plaques and neurofibrillary tangles (NFTs). Tau aggregation also occurs in other common neurodegenerative diseases. Frontotemporal dementia (FTD) can be caused by tau mutations that increase the susceptibility of tau to hyperphosphorylation and aggregation, which may cause neuronal dysfunction and deposition of NFTs. 17-allylamino-17-demethoxygeldanamycin (17-AAG) is a potent inhibitor of heat shock protein 90 (Hsp90), a cytosolic chaperone implicated in the proper folding and functions of a repertoire of client proteins. 17-AAG binds to Hsp90 and enhances degradation of Hsp90 client protein. We sought to determine whether 17-AAG can reduce Aβ and tau pathology in the brains of AD and FTD model mice expressing Aβ or P301L mutant tau, respectively. Mice were randomized to receive 25, 5, or 0 mg/kg 17-AAG thrice weekly from age eight to 11 months. Analysis was performed by rotarod test on motor function, on the area occupied by plaques in hippocampus or NFTs in medulla tissue sections, and on mortality. A high dose of 17-AAG tended to decrease NFTs in male mice (p = 0.08). Further studies are required to confirm the effect of 17-AAG in diseases of tau aggregation.

  9. LUMBOSACRAL TRANSITIONAL ANATOMY TYPES AND DISC DEGENERATIVE CHANGES

    Directory of Open Access Journals (Sweden)

    Chabukovska Radulovska Jasminka

    2014-07-01

    Full Text Available Background and purpose: The relationship between presence of lumbo sacral transitional vertebra (LSTV and disc degenerative changes is unclear. The aim of the study was to examine the relation between different types of LSTV and disc degenerative changes at the transitional and the adjacent cephalad segment. Material and methods: Sixty-three patients (mean age 51.48 ± 13.51 out of 200 adults with low back pain who performed MRI examination of the lumbo sacral spine, classified as positive for LSTV, were included in the study. Annular tears, disc degeneration according to Phirmann classification and disc herniations were evaluated and graded at transitional and adjacent cephalad level. Results: The severity of disc degeneration at the transitional level and the adjacent level correlated with the types of LSTV. Severe disc degenerative changes were most frequent in articulated connection LSTV types and incombined LSTV type at the transitional level and in osseus connection LSTV types at the adjacent cephalad level. These changes were more frequent in unilateral articulated connection LSTV subtype (64% vs 54%; and in unilateral osseus connection LSTV subtype (25% vs no patients at transitional level, and in bilateral osseus connection LSTV subtype (100% vs 50% at the level above. High prevalence of disc herniations was observed in articulated connection LSTV types as well as in unilateral osseus connection LSTV subtype at transitional and the adjacent cephalad level. At the transitional level higher prevalence of disc herniations was characteristic for unilateral articulated connection LSTV sub type (46%vs 41% and for unilateral osseus connection LSTV subtype (50% vs no patients. At the adjacent level higher prevalence of disc herniations was observed in bilateral articulated connection LSTV subtype (38% vs 27% and in bilateral osseus connection LSTV subtype (50% vs 25%. Conclusions: The compact osseus connection (osseus bridging vs articular

  10. Lumbosacral transitional anatomy types and disc degenerative changes

    Directory of Open Access Journals (Sweden)

    Chabukovska-Radulovska Jasminka

    2014-07-01

    Full Text Available Background and purpose: The relationship between presence of lumbosacral transitional vertebra (LSTV and disc degenerative changes is unclear. The aim of the study was to examine the relation between different types of LSTV and disc degenerative changes at the transitional and the adjacent cephalad segment. Material and methods: Sixty-three patients (mean age 51.48 ± 13.51 out of200 adults with low back pain who performed MRI examination of the lumbosacral spine, classified as positive for LSTV, were included in the study. Annular tears, disc degeneration according to Phirmann classification and disc herniations were evaluated and graded at transitional and adjacent cephalad level. Results: The severity of disc degeneration at the transitional level and the adjacent level correlated with the types of LSTV. Severe disc degenerative changes were most frequent in articulated connection LSTV types and in combined LSTV type at the transitional level and in osseus connection LSTV types at the adjacent cephalad level. These changes were more frequent in unilateral articulated connection LSTV subtype (64% vs 54%; and in unilateral osseus connection LSTV subtype (25% vs no patients at transitional level, and in bilateral osseus connection LSTV subtype (100% vs 50% at the level above. High prevalence of disc herniations was observed in articulated connection LSTV types as well as in unilateral osseus connection LSTV subtype at transitional and the adjacent cephalad level. At the transitional level higher prevalence of disc herniations was characteristic for unilateral articulated connection LSTV subtype (46%vs 41% and for unilateral osseus connection LSTV subtype (50% vs no patients. At the adjacent level higher prevalence of disc herniations was observed in bilateral articulated connection LSTV subtype (38% vs 27% and in bilateral osseus connection LSTV subtype (50% vs 25%. Conclusions: The compact osseus connection (osseus bridging vs articular

  11. Light and inherited retinal degeneration

    OpenAIRE

    Paskowitz, D M; LaVail, M M; Duncan, J L

    2006-01-01

    Light deprivation has long been considered a potential treatment for patients with inherited retinal degenerative diseases, but no therapeutic benefit has been demonstrated to date. In the few clinical studies that have addressed this issue, the underlying mutations were unknown. Our rapidly expanding knowledge of the genes and mechanisms involved in retinal degeneration have made it possible to reconsider the potential value of light restriction in specific genetic contexts. This review summ...

  12. Lattice degeneration of the retina.

    Science.gov (United States)

    Byer, N E

    1979-01-01

    Lattice degeneration of the retina is the most important of all clinically distinct entities that effect the peripheral fundus and are related to retinal detachment. The purpose of this review is to survey the extensive literature, to evaluate the many diverse opinions on this subject, and to correlate and summarize all the known facts regarding this disease entity. The disease is fully defined and described, both clinically and histologically. Some aspects of the disease are still poorly understood, and some remain controversial, especially in the area of management. For this reason, the indications for treatment are discussed under eight subsections, with a view toward providing practical guidelines for recommendations in management.

  13. Design, synthesis, and evaluation of nonretinoid retinol binding protein 4 antagonists for the potential treatment of atrophic age-related macular degeneration and Stargardt disease.

    Science.gov (United States)

    Cioffi, Christopher L; Dobri, Nicoleta; Freeman, Emily E; Conlon, Michael P; Chen, Ping; Stafford, Douglas G; Schwarz, Daniel M C; Golden, Kathy C; Zhu, Lei; Kitchen, Douglas B; Barnes, Keith D; Racz, Boglarka; Qin, Qiong; Michelotti, Enrique; Cywin, Charles L; Martin, William H; Pearson, Paul G; Johnson, Graham; Petrukhin, Konstantin

    2014-09-25

    Accumulation of lipofuscin in the retina is associated with pathogenesis of atrophic age-related macular degeneration and Stargardt disease. Lipofuscin bisretinoids (exemplified by N-retinylidene-N-retinylethanolamine) seem to mediate lipofuscin toxicity. Synthesis of lipofuscin bisretinoids depends on the influx of retinol from serum to the retina. Compounds antagonizing the retinol-dependent interaction of retinol-binding protein 4 (RBP4) with transthyretin in the serum would reduce serum RBP4 and retinol and inhibit bisretinoid formation. We recently showed that A1120 (3), a potent carboxylic acid based RBP4 antagonist, can significantly reduce lipofuscin bisretinoid formation in the retinas of Abca4(-/-) mice. As part of the NIH Blueprint Neurotherapeutics Network project we undertook the in vitro exploration to identify novel conformationally flexible and constrained RBP4 antagonists with improved potency and metabolic stability. We also demonstrate that upon acute and chronic dosing in rats, 43, a potent cyclopentyl fused pyrrolidine antagonist, reduced circulating plasma RBP4 protein levels by approximately 60%.

  14. Cosegregation and functional analysis of mutant ABCR (ABCA4) alleles in families that manifest both Stargardt disease and age-related macular degeneration.

    Science.gov (United States)

    Shroyer, N F; Lewis, R A; Yatsenko, A N; Wensel, T G; Lupski, J R

    2001-11-01

    Mutations in ABCR (ABCA4) have been reported to cause a spectrum of autosomal recessively inherited retinopathies, including Stargardt disease (STGD), cone-rod dystrophy and retinitis pigmentosa. Individuals heterozygous for ABCR mutations may be predisposed to develop the multifactorial disorder age-related macular degeneration (AMD). We hypothesized that some carriers of STGD alleles have an increased risk to develop AMD. We tested this hypothesis in a cohort of families that manifest both STGD and AMD. With a direct-sequencing mutation detection strategy, we found that AMD-affected relatives of STGD patients are more likely to be carriers of pathogenic STGD alleles than predicted based on chance alone. We further investigated the role of AMD-associated ABCR mutations by testing for expression and ATP-binding defects in an in vitro biochemical assay. We found that mutations associated with AMD have a range of assayable defects ranging from no detectable defect to apparent null alleles. Of the 21 missense ABCR mutations reported in patients with AMD, 16 (76%) show abnormalities in protein expression, ATP-binding or ATPase activity. We infer that carrier relatives of STGD patients are predisposed to develop AMD.

  15. A rapid method of accurate detection and differentiation of Newcastle disease virus pathotypes by demonstrating multiple bands in degenerate primer based nested RT-PCR.

    Science.gov (United States)

    Desingu, P A; Singh, S D; Dhama, K; Kumar, O R Vinodh; Singh, R; Singh, R K

    2015-02-01

    A rapid and accurate method of detection and differentiation of virulent and avirulent Newcastle disease virus (NDV) pathotypes was developed. The NDV detection was carried out for different domestic avian field isolates and pigeon paramyxo virus-1 (25 field isolates and 9 vaccine strains) by using APMV-I "fusion" (F) gene Class II specific external primer A and B (535bp), internal primer C and D (238bp) based reverses transcriptase PCR (RT-PCR). The internal degenerative reverse primer D is specific for F gene cleavage position of virulent strain of NDV. The nested RT-PCR products of avirulent strains showed two bands (535bp and 424bp) while virulent strains showed four bands (535bp, 424bp, 349bp and 238bp) on agar gel electrophoresis. This is the first report regarding development and use of degenerate primer based nested RT-PCR for accurate detection and differentiation of NDV pathotypes by demonstrating multiple PCR band patterns. Being a rapid, simple, and economical test, the developed method could serve as a valuable alternate diagnostic tool for characterizing NDV isolates and carrying out molecular epidemiological surveillance studies for this important pathogen of poultry. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Subretinal hyper-reflective material seen on optical coherence tomography as a biomarker for disease monitoring in age-related macular degeneration

    Science.gov (United States)

    Lee, H. B.; Ong, B. B.; Katta, M.; Yvon, C.; Lu, L.; Zakri, R.; Patel, N.

    2018-03-01

    Subretinal hyper-reflective material (SHRM) seen on optical coherence tomography (OCT) is thought to be a collection of fibrous tissues and vascular networks that are identified in age-related macular degeneration (ARMD). We have carried out a retrospective analysis of 91 OCT scans of neovascular ARMD subtypes including classic and occult choroidal neovascularization (CNV) and retinal angiomatous proliferation (RAP). All three subtypes received ranibizumab, an anti-vascular endothelial growth factor (Anti-VEGF) intravitreal injections on an as-needed basis following the loading doses. Volumes of SHRM were calculated using caliper measurements of maximal height and length of SHRM seen on OCT. The ellipsoid formula derived from tumour models was used to calculate the volume. It was found that occult CNV and RAP have larger SHRM volumes than those of classic CNV. SHRM volumes reduced overall following loading doses of Anti-VEGF injections at 4 months in all three subtypes. However, a rebound increase in volume was noticed in both occult CNV and RAP cohort at 12 months despite the initial, steeper reductions in the subtypes. These findings were consistent with the data seen in volume measurement using Topcon's automated segmentation algorithm in a smaller cohort of patients. We propose that SHRM should be used as a potential biomarker to quantify both disease progression and prognosis of neovascular ARMD alongside other conventional methods.

  17. Amyloid precursor protein expression is enhanced in human platelets from subjects with Alzheimer's disease and frontotemporal lobar degeneration: a real-time PCR study.

    Science.gov (United States)

    Vignini, Arianna; Morganti, Stefano; Salvolini, Eleonora; Sartini, Davide; Luzzi, Simona; Fiorini, Rosamaria; Provinciali, Leandro; Di Primio, Roberto; Mazzanti, Laura; Emanuelli, Monica

    2013-12-01

    Frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD) represent the most frequent causes of early-onset and late-onset degenerative dementia, respectively. A correct diagnosis entails the choice of appropriate therapies. In this view the present study aimed to identify biomarkers that could improve the differential diagnosis. We recently found an overexpression of platelet amyloid precursor protein (APP) in AD; furthermore, recent studies have suggested the presence of changes in APP processing in FTLD. In this context, we analyzed the mRNA expression level of Total APP (TOT) and APP containing a Kunitz-type serine protease inhibitor domain (KPI) in platelets obtained from AD patients, subjects with FTLD, and healthy subjects. In addition, we evaluated the correlation between platelet APP mRNA expression levels and cognitive impairment.Differential gene expression measurements revealed a significant up-regulation of APP TOT and APP KPI in both AD and FTLD patients compared to the controls (being AD/Controls: 1.67 for APP TOT and 1.47 for APP KPI; FTLD/Controls: 1.62 for APP TOT and 1.51 for APP KPI; p < 0.05), although it is interesting to note that in FTLD patients this expression did not correlate with the severity of cognitive impairment.This could be related to a reduced beta-amyloid (Aβ) formation, caused by an alteration of secretase enzymatic activity, even though a post-transcriptional regulation of APP mRNAs in FTLD cannot be excluded.

  18. Electroacupuncture Promotes Recovery of Motor Function and Reduces Dopaminergic Neuron Degeneration in Rodent Models of Parkinson's Disease.

    Science.gov (United States)

    Lin, Jaung-Geng; Chen, Chao-Jung; Yang, Han-Bin; Chen, Yi-Hung; Hung, Shih-Ya

    2017-08-24

    Parkinson's disease (PD) is a common neurodegenerative disease. The pathological hallmark of PD is a progressive loss of dopaminergic neurons in the substantia nigra (SN) pars compacta in the brain, ultimately resulting in severe striatal dopamine deficiency and the development of primary motor symptoms (e.g., resting tremor, bradykinesia) in PD. Acupuncture has long been used in traditional Chinese medicine to treat PD for the control of tremor and pain. Accumulating evidence has shown that using electroacupuncture (EA) as a complementary therapy ameliorates motor symptoms of PD. However, the most appropriate timing for EA intervention and its effect on dopamine neuronal protection remain unclear. Thus, this study used the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model (systemic-lesioned by intraperitoneal injection) and the 1-methyl-4-phenylpyridinium (MPP⁺)-lesioned rat model (unilateral-lesioned by intra-SN infusion) of PD, to explore the therapeutic effects and mechanisms of EA at the GB34 (Yanglingquan) and LR3 (Taichong) acupoints. We found that EA increased the latency to fall from the accelerating rotarod and improved striatal dopamine levels in the MPTP studies. In the MPP⁺ studies, EA inhibited apomorphine induced rotational behavior and locomotor activity, and demonstrated neuroprotective effects via the activation of survival pathways of Akt and brain-derived neurotrophic factor (BDNF) in the SN region. In conclusion, we observed that EA treatment reduces motor symptoms of PD and dopaminergic neurodegeneration in rodent models, whether EA is given as a pretreatment or after the initiation of disease symptoms. The results indicate that EA treatment may be an effective therapy for patients with PD.

  19. Repressed SIRT1/PGC-1α pathway and mitochondrial disintegration in iPSC-derived RPE disease model of age-related macular degeneration.

    Science.gov (United States)

    Golestaneh, Nady; Chu, Yi; Cheng, Shuk Kei; Cao, Hong; Poliakov, Eugenia; Berinstein, Daniel M

    2016-12-20

    Study of age related macular degeneration (AMD) has been hampered by lack of human models that represent the complexity of the disease. Here we have developed a human in vitro disease model of AMD to investigate the underlying AMD disease mechanisms. Generation of iPSCs from retinal pigment epithelium (RPE) of AMD donors, age-matched normal donors, skin fibroblasts of a dry AMD patient, and differentiation of iPSCs into RPE (AMD RPE-iPSC-RPE, normal RPE-iPSC-RPE and AMD Skin-iPSC-RPE, respectively). Immunostaining, cell viability assay and reactive oxygen species (ROS) production under oxidative stress conditions, electron microscopy (EM) imaging, ATP production and glycogen concentration assays, quantitative real time PCR, western blot, karyotyping. The AMD RPE-iPSC-RPE and AMD Skin-iPSC-RPE present functional impairment and exhibit distinct disease phenotypes compared to RPE-iPSC-RPE generated from normal donors (Normal RPE-iPSC-RPE). The AMD RPE-iPSC-RPE and AMD Skin-iPSC-RPE show increased susceptibility to oxidative stress and produced higher levels of reactive oxygen species (ROS) under stress in accordance with recent reports. The susceptibility to oxidative stress-induced cell death in AMD RPE-iPSC-RPE and Skin-iPSC-RPE was consistent with inability of the AMD RPE-iPSC-RPE and Skin-iPSC-RPE to increase SOD2 expression under oxidative stress. Phenotypic analysis revealed disintegrated mitochondria, accumulation of autophagosomes and lipid droplets in AMD RPE-iPSC-RPE and AMD Skin-iPSC-RPE. Mitochondrial activity was significantly lower in AMD RPE-iPSC-RPE and AMD Skin-iPSC-RPE compared to normal cells and glycogen concentration was significantly increased in the diseased cells. Furthermore, Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a regulator of mitochondrial biogenesis and function was repressed, and lower expression levels of NAD-dependent deacetylase sirtuin1 (SIRT1) were found in AMD RPE-iPSC-RPE and AMD Skin

  20. European survey on the opinion and use of micronutrition in age-related macular degeneration: 10 years on from the Age-Related Eye Disease Study

    Directory of Open Access Journals (Sweden)

    Aslam T

    2014-10-01

    Full Text Available Tariq Aslam,1 Cécile Delcourt,2 Frank Holz,3 Alfredo García-Layana,4 Anita Leys,5 Rufino M Silva,6 Eric Souied7 1Manchester Royal Eye Hospital, Manchester, UK; 2University of Bordeaux, Bordeaux, France; 3University of Bonn, Bonn, Germany; 4Clínica Universidad de Navarra, Pamplona, Spain; 5University Hospitals, Leuven, Belgium; 6University of Coimbra, Coimbra, Portugal; 7Université Paris Est Créteil, Créteil, FrancePurpose: To evaluate ophthalmologists’ opinion of, and use of, micronutritional dietary supplements 10 years after publication of the first Age-Related Eye Disease Study (AREDS study.Methods: Participation was solicited from 4,000 European ophthalmologists. Responding physicians were screened, and those treating at least 40 patients with age-related macular degeneration (AMD per month and prescribing nutrition supplements at least 4 times per month were admitted and completed a 40-item questionnaire.Results: The surveyed sample included 112 general ophthalmologists and 104 retinal specialists. Most nutritional supplements (46% were initiated when early/intermediate AMD was confirmed, although 18% were initiated on confirmation of neovascular AMD. Clinical studies were well known: 90% were aware of AREDS, with 88% aware of AREDS1 and 36% aware of the, as-yet-unpublished, AREDS2 studies. Respondents considered lutein, zeaxanthin, zinc, omega-3, and vitamins to be the most important components of nutritional supplements, with the results of AREDS2 already having been taken into consideration by many. Ophthalmologists anticipate more scientific studies as well as improved product quality but identify cost as a barrier to wider uptake.Conclusion: Micronutrition is now part of the routine management of AMD for many ophthalmologists. Ophthalmologists choosing to use nutritional supplements are well-informed regarding current scientific studies. Keywords: age-related macular degeneration, micronutrition, nutritional

  1. Low virulence bacterial infections in cervical intervertebral discs: a prospective case series.

    Science.gov (United States)

    Chen, Yilei; Wang, Xianjun; Zhang, Xuyang; Ren, Hong; Huang, Bao; Chen, Jian; Liu, Junhui; Shan, Zhi; Zhu, Zhihai; Zhao, Fengdong

    2018-04-19

    A prospective cross-sectional case series study. To investigate the prevalence of low virulence disc infection and its associations with characteristics of patients or discs in the cervical spine. Low virulence bacterial infections could be a possible cause of intervertebral disc degeneration and/or back pain. Controversies are continuing over whether these bacteria, predominantly Propionibacterium acnes (P. acnes), represent infection or contamination. However, the current studies mainly focus on the lumbar spine, with very limited data on the cervical spine. Thirty-two patients (20 men and 12 women) who underwent anterior cervical fusion for degenerative cervical spondylosis or traumatic cervical cord injury were enrolled. Radiological assessments included X-ray, CT, and MRI of the cervical spine. Endplate Modic changes, intervertebral range of motion, and disc herniation type were evaluated. Disc and muscle tissues were collected under strict sterile conditions. Samples were enriched in tryptone soy broth and subcultured under anaerobic conditions, followed by identification of the resulting colonies by the PCR method. Sixty-six intervertebral discs were excised from thirty-two patients. Positive disc cultures were noted in eight patients (25%) and in nine discs (13.6%). The muscle biopsy (control) cultures were negative in 28 patients and positive in 4 patients (12.5%); three of whom had a negative disc culture. Seven discs (10.6%) were positive for coagulase-negative Staphylococci (CNS) and two discs were positive for P. acnes (3.0%). A younger patient age and the extrusion or sequestration type of disc herniation, which represented a complete annulus fibrous failure, were associated with positive disc culture. Our data show that CNS is more prevalent than P. acnes in degenerative cervical discs. The infection route in cervical discs may be predominantly through an annulus fissure. Correlation between these infections and clinical symptoms is uncertain

  2. Neurotrophin Expression in Lymphocytes: a Powerful Indicator of Degeneration in Parkinson's Disease, Amyotrophic Lateral Sclerosis and Ataxia.

    Science.gov (United States)

    Sadanand, Anjana; Janardhanan, Anjali; Vanisree, A J; Pavai, Thamil

    2018-02-01

    Deregulated neurotrophin is an etiological factor in the pathology of neurodegenerative diseases (ND) that are clinically different entities but characterised by similar limb dysfunction. Earlier validation of peripheral biomarkers can provide significant translational benefit to ND patients. We analysed brain-derived neurotrophic factor (BDNF)-tropomyosin possessing tyrosine-related kinase (Trk B) and its key downstream proteins which are implicated in ND such as Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and ataxia. Blood from ND patients with PD, ALS and Ataxia with movement dysfunctions were obtained to analyse mRNA and protein expressions of the above mentioned factors in lymphocytes. The mRNA and protein expression of BDNF-Trk B and its key downstream molecules showed a significant variation when compared to control and among NDs. The study intends to show that on identifying the variation of these key molecules in the blood samples of patients with ND can serve as early diagnostic candidates. Thus by intervening, the neurotrophins and their pathways can help in early diagnosis and optimising levels of diagnostic certainty.

  3. Rat disc torsional mechanics: effect of lumbar and caudal levels and axial compression load.

    Science.gov (United States)

    Espinoza Orías, Alejandro A; Malhotra, Neil R; Elliott, Dawn M

    2009-03-01

    Rat models with altered loading are used to study disc degeneration and mechano-transduction. Given the prominent role of mechanics in disc function and degeneration, it is critical to measure mechanical behavior to evaluate changes after model interventions. Axial compression mechanics of the rat disc are representative of the human disc when normalized by geometry, and differences between the lumbar and caudal disc have been quantified in axial compression. No study has quantified rat disc torsional mechanics. Compare the torsional mechanical behavior of rat lumbar and caudal discs, determine the contribution of combined axial load on torsional mechanics, and compare the torsional properties of rat discs to human lumbar discs. Cadaveric biomechanical study. Cyclic torsion without compressive load followed by cyclic torsion with a fixed compressive load was applied to rat lumbar and caudal disc levels. The apparent torsional modulus was higher in the lumbar region than in the caudal region: 0.081+/-0.026 (MPa/degrees, mean+/-SD) for lumbar axially loaded; 0.066+/-0.028 for caudal axially loaded; 0.091+/-0.033 for lumbar in pure torsion; and 0.056+/-0.035 for caudal in pure torsion. These values were similar to human disc properties reported in the literature ranging from 0.024 to 0.21 MPa/degrees. Use of the caudal disc as a model may be appropriate if the mechanical focus is within the linear region of the loading regime. These results provide support for use of this animal model in basic science studies with respect to torsional mechanics.

  4. Contribution of facet joints, axial compression, and composition to human lumbar disc torsion mechanics.

    Science.gov (United States)

    Bezci, Semih E; Eleswarapu, Ananth; Klineberg, Eric O; O'Connell, Grace D

    2018-02-12

    Stresses applied to the spinal column are distributed between the intervertebral disc and facet joints. Structural and compositional changes alter stress distributions within the disc and between the disc and facet joints. These changes influence the mechanical properties of the disc joint, including its stiffness, range of motion, and energy absorption under quasi-static and dynamic loads. There have been few studies evaluating the role of facet joints in torsion. Furthermore, the relationship between biochemical composition and torsion mechanics is not well understood. Therefore, the first objective of this study was to investigate the role of facet joints in torsion mechanics of healthy and degenerated human lumbar discs under a wide range of compressive preloads. To achieve this, each disc was tested under four different compressive preloads (300-1200 N) with and without facet joints. The second objective was to develop a quantitative structure-function relationship between tissue composition and torsion mechanics. Facet joints have a significant contribution to disc torsional stiffness (∼60%) and viscoelasticity, regardless of the magnitude of axial compression. The findings from this study demonstrate that annulus fibrosus GAG content plays an important role in disc torsion mechanics. A decrease in GAG content with degeneration reduced torsion mechanics by more than an order of magnitude, while collagen content did not significantly influence disc torsion mechanics. The biochemical-mechanical and compression-torsion relationships reported in this study allow for better comparison between studies that use discs of varying levels of degeneration or testing protocols and provide important design criteria for biological repair strategies. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  5. Can Exercise Positively Influence the Intervertebral Disc?

    Science.gov (United States)

    Belavý, Daniel L; Albracht, Kirsten; Bruggemann, Gert-Peter; Vergroesen, Pieter-Paul A; van Dieën, Jaap H

    2016-04-01

    To better understand what kinds of sports and exercise could be beneficial for the intervertebral disc (IVD), we performed a review to synthesise the literature on IVD adaptation with loading and exercise. The state of the literature did not permit a systematic review; therefore, we performed a narrative review. The majority of the available data come from cell or whole-disc loading models and animal exercise models. However, some studies have examined the impact of specific sports on IVD degeneration in humans and acute exercise on disc size. Based on the data available in the literature, loading types that are likely beneficial to the IVD are dynamic, axial, at slow to moderate movement speeds, and of a magnitude experienced in walking and jogging. Static loading, torsional loading, flexion with compression, rapid loading, high-impact loading and explosive tasks are likely detrimental for the IVD. Reduced physical activity and disuse appear to be detrimental for the IVD. We also consider the impact of genetics and the likelihood of a 'critical period' for the effect of exercise in IVD development. The current review summarises the literature to increase awareness amongst exercise, rehabilitation and ergonomic professionals regarding IVD health and provides recommendations on future directions in research.

  6. Optimizing power to track brain degeneration in Alzheimer's disease and mild cognitive impairment with tensor-based morphometry: an ADNI study of 515 subjects.

    Science.gov (United States)

    Hua, Xue; Lee, Suh; Yanovsky, Igor; Leow, Alex D; Chou, Yi-Yu; Ho, April J; Gutman, Boris; Toga, Arthur W; Jack, Clifford R; Bernstein, Matt A; Reiman, Eric M; Harvey, Danielle J; Kornak, John; Schuff, Norbert; Alexander, Gene E; Weiner, Michael W; Thompson, Paul M

    2009-12-01

    Tensor-based morphometry (TBM) is a powerful method to map the 3D profile of brain degeneration in Alzheimer's disease (AD) and mild cognitive impairment (MCI). We optimized a TBM-based image analysis method to determine what methodological factors, and which image-derived measures, maximize statistical power to track brain change. 3D maps, tracking rates of structural atrophy over time, were created from 1030 longitudinal brain MRI scans (1-year follow-up) of 104 AD patients (age: 75.7+/-7.2 years; MMSE: 23.3+/-1.8, at baseline), 254 amnestic MCI subjects (75.0+/-7.2 years; 27.0+/-1.8), and 157 healthy elderly subjects (75.9+/-5.1 years; 29.1+/-1.0), as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI). To determine which TBM designs gave greatest statistical power, we compared different linear and nonlinear registration parameters (including different regularization functions), and different numerical summary measures derived from the maps. Detection power was greatly enhanced by summarizing changes in a statistically-defined region-of-interest (ROI) derived from an independent training sample of 22 AD patients. Effect sizes were compared using cumulative distribution function (CDF) plots and false discovery rate methods. In power analyses, the best method required only 48 AD and 88 MCI subjects to give 80% power to detect a 25% reduction in the mean annual change using a two-sided test (at alpha=0.05). This is a drastic sample size reduction relative to using clinical scores as outcome measures (619 AD/6797 MCI for the ADAS-Cog, and 408 AD/796 MCI for the Clinical Dementia Rating sum-of-boxes scores). TBM offers high statistical power to track brain changes in large, multi-site neuroimaging studies and clinical trials of AD.

  7. Optimizing power to track brain degeneration in Alzheimer’s disease and mild cognitive impairment with tensor-based morphometry: An ADNI study of 515 subjects

    Science.gov (United States)

    Hua, Xue; Lee, Suh; Yanovsky, Igor; Leow, Alex D.; Chou, Yi-Yu; Ho, April J.; Gutman, Boris; Toga, Arthur W.; Jack, Clifford R.; Bernstein, Matt A.; Reiman, Eric M.; Harvey, Danielle J.; Kornak, John; Schuff, Norbert; Alexander, Gene E.; Weiner, Michael W.; Thompson, Paul M.

    2010-01-01

    Tensor-based morphometry (TBM) is a powerful method to map the 3D profile of brain degeneration in Alzheimer’s disease (AD) and mild cognitive impairment (MCI). We optimized a TBM-based image analysis method to determine what methodological factors, and which image-derived measures, maximize statistical power to track brain change. 3D maps, tracking rates of structural atrophy over time, were created from 1030 longitudinal brain MRI scans (1-year follow-up) of 104 AD patients (age: 75.7 ± 7.2 years; MMSE: 23.3 ± 1.8, at baseline), 254 amnestic MCI subjects (75.0 ± 7.2 years; 27.0 ± 1.8), and 157 healthy elderly subjects (75.9 ± 5.1 years; 29.1 ± 1.0), as part of the Alzheimer’s Disease Neuroimaging Initiative (ADNI). To determine which TBM designs gave greatest statistical power, we compared different linear and nonlinear registration parameters (including different regularization functions), and different numerical summary measures derived from the maps. Detection power was greatly enhanced by summarizing changes in a statistically-defined region-of-interest (ROI) derived from an independent training sample of 22 AD patients. Effect sizes were compared using cumulative distribution function (CDF) plots and false discovery rate methods. In power analyses, the best method required only 48 AD and 88 MCI subjects to give 80% power to detect a 25% reduction in the mean annual change using a two-sided test (at α = 0.05). This is a drastic sample size reduction relative to using clinical scores as outcome measures (619 AD/6797 MCI for the ADAS-Cog, and 408 AD/796 MCI for the Clinical Dementia Rating sum-of-boxes scores). TBM offers high statistical power to track brain changes in large, multi-site neuroimaging studies and clinical trials of AD. PMID:19615450

  8. Functional implications of hippocampal degeneration in early Alzheimer's disease: a combined DTI and PET study

    Energy Technology Data Exchange (ETDEWEB)

    Yakushev, Igor; Mueller, Matthias J.; Schermuly, Ingrid; Fellgiebel, Andreas [University Medical Center Mainz, Department of Psychiatry and Psychotherapy, Mainz (Germany); Schreckenberger, Matthias [University Medical Center Mainz, Department of Nuclear Medicine, Mainz (Germany); Cumming, Paul [University of Munich, Department of Nuclear Medicine, Munich (Germany); Stoeter, Peter [University Medical Center Mainz, Institute of Neuroradiology, Mainz (Germany); Gerhard, Alex [University Medical Center Mainz, Department of Psychiatry and Psychotherapy, Mainz (Germany); University of Manchester, Wolfson Molecular Imaging Centre, Manchester (United Kingdom)

    2011-12-15

    Hypometabolism of the posterior cingulate cortex (PCC) in early Alzheimer's disease (AD) is thought to arise in part due to AD-specific neuronal damage to the hippocampal formation. Here, we explored the association between microstructural alterations within the hippocampus and whole-brain glucose metabolism in subjects with AD, also in relation to episodic memory impairment. Twenty patients with early AD (Mini-Mental State Examination 25.7 {+-} 1.7) were studied with [{sup 18}F]fluorodeoxyglucose (FDG) positron emission tomography and diffusion tensor imaging. Episodic memory performance was assessed using the free delayed verbal recall task (DVR). Voxel-wise relative FDG uptake was correlated to diffusivity indices of the hippocampus, followed by extraction of FDG uptake values from significant clusters. Linear regression analysis was performed to test for unique contributions of diffusivity and metabolic indices in the prediction of memory function. Diffusivity in the left anterior hippocampus negatively correlated with FDG uptake primarily in the left anterior hippocampus, parahippocampal gyrus and the PCC (p< 0.005). The same correlation pattern was found for right hippocampal diffusivity (p< 0.05). In linear regression analysis, left anterior hippocampal diffusivity and FDG uptake from the PCC cluster were the only significant predictors for performance on DVR, together explaining 60.6% of the variance. We found an inverse association between anterior hippocampal diffusivity and PCC glucose metabolism, which was in turn strongly related to episodic memory performance in subjects with early AD. These findings support the diaschisis hypothesis of AD and implicate a dysfunction of structures along the hippocampal output pathways as a significant contributor to the genesis of episodic memory impairment. (orig.)

  9. A Deep Learning Algorithm for Prediction of Age-Related Eye Disease Study Severity Scale for Age-Related Macular Degeneration from Color Fundus Photography.

    Science.gov (United States)

    Grassmann, Felix; Mengelkamp, Judith; Brandl, Caroline; Harsch, Sebastian; Zimmermann, Martina E; Linkohr, Birgit; Peters, Annette; Heid, Iris M; Palm, Christoph; Weber, Bernhard H F

    2018-04-10

    Age-related macular degeneration (AMD) is a common threat to vision. While classification of disease stages is critical to understanding disease risk and progression, several systems based on color fundus photographs are known. Most of these require in-depth and time-consuming analysis of fundus images. Herein, we present an automated computer-based classification algorithm. Algorithm development for AMD classification based on a large collection of color fundus images. Validation is performed on a cross-sectional, population-based study. We included 120 656 manually graded color fundus images from 3654 Age-Related Eye Disease Study (AREDS) participants. AREDS participants were >55 years of age, and non-AMD sight-threatening diseases were excluded at recruitment. In addition, performance of our algorithm was evaluated in 5555 fundus images from the population-based Kooperative Gesundheitsforschung in der Region Augsburg (KORA; Cooperative Health Research in the Region of Augsburg) study. We defined 13 classes (9 AREDS steps, 3 late AMD stages, and 1 for ungradable images) and trained several convolution deep learning architectures. An ensemble of network architectures improved prediction accuracy. An independent dataset was used to evaluate the performance of our algorithm in a population-based study. κ Statistics and accuracy to evaluate the concordance between predicted and expert human grader classification. A network ensemble of 6 different neural net architectures predicted the 13 classes in the AREDS test set with a quadratic weighted κ of 92% (95% confidence interval, 89%-92%) and an overall accuracy of 63.3%. In the independent KORA dataset, images wrongly classified as AMD were mainly the result of a macular reflex observed in young individuals. By restricting the KORA analysis to individuals >55 years of age and prior exclusion of other retinopathies, the weighted and unweighted κ increased to 50% and 63%, respectively. Importantly, the algorithm

  10. The Association of Statin Use with Age-Related Macular Degeneration Progression: The Age-Related Eye Disease Study 2 Report Number 9.

    Science.gov (United States)

    Al-Holou, Shaza N; Tucker, William R; Agrón, Elvira; Clemons, Traci E; Cukras, Catherine; Ferris, Frederick L; Chew, Emily Y

    2015-12-01

    To evaluate the association of statin use with progression of age-related macular degeneration (AMD). Preplanned, prospective cohort study within a controlled clinical trial of oral supplementation for age-related eye diseases. Age-Related Eye Disease Study 2 (AREDS2) participants, aged 50 to 85 years. Factors, including age, gender, smoking status, aspirin use, and history of diabetes, hypertension, heart disease, angina, and stroke-all known to be associated with statin use-were included in a logistic regression model to estimate propensity scores for each participant. Age-adjusted proportional hazards regression models, with and without propensity score matching, were performed to evaluate the association of statin use with progression to late AMD. Analyses adjusting for the competing risk of death were also performed. Baseline and annual stereoscopic fundus photographs were assessed centrally by masked graders for the development of late AMD, either neovascular AMD or geographic atrophy (GA). Of the 3791 participants (2462 with bilateral large drusen and 1329 with unilateral late AMD at baseline), 1659 (43.8%) were statin users. The overall analysis, with no matching of propensity scores and no adjustment for death as a competing risk, showed that statin use was not associated with progression to late AMD (hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.83-1.41; P = 0.56). When matched for propensity scores and adjusted for death as a competing risk, the result was not statistically significant (HR, 0.81; 95% CI, 0.55-1.20; P = 0.29). Furthermore, subgroup analyses of persons with or without late AMD at baseline and the various components of late AMD (neovascular AMD, central GA, or any GA) also showed no statistically significant association of statin use with progression to AMD. Statin use was not statistically significantly associated with progression to late AMD in the AREDS2 participants, and these findings are consistent with findings in the

  11. The Association of Statin Use with Age-Related Macular Degeneration Progression The Age-Related Eye Disease Study 2 Report Number 9

    Science.gov (United States)

    Al-Holou, Shaza N.; Tucker, William R.; Agrón, Elvira; Clemons, Traci E.; Cukras, Catherine; Ferris, Frederick L.; Chew, Emily Y.

    2015-01-01

    Objective/purpose To evaluate the association of statin use with progression of age-related macular degeneration (AMD). Design Preplanned, prospective cohort study within a controlled clinical trial of oral supplementation for age-related eye diseases. Subjects Age-Related Eye Disease Study 2 participants, aged 50 to 85 years. Methods Factors, including age, gender, smoking status, aspirin use, and history of diabetes, hypertension, heart disease, angina, and stroke, all known to be associated with statin use, were included in a logistic regression model to estimate propensity scores for each participant. Age-adjusted proportional hazards regression models, with and without propensity score matching, were performed to evaluate the association of statin use with progression to late AMD. Analyses were also performed adjusting for the competing risk of death. Main Outcome Measures Baseline and annual stereoscopic fundus photographs were assessed centrally by masked graders for the development of late AMD, either neovascular AMD or geographic atrophy (GA). Results Of the 3791 participants (2462 with bilateral large drusen and 1329 with unilateral late AMD at baseline), 1659 (43.8%) were statin users. The overall analysis, with no matching of propensity scores and no adjustment for death as a competing risk, showed that statin use was not associated with progression to late AMD (hazard ratios [HR] of 1.08, 95% confidence intervals [CI] of 0.83–1.41, P=0.56). When matched for propensity scores and adjusted for death as a competing risk, the result was not statistically significant with HR: 0.81, 95% CI: 0.55–1.20, P=0.29. Further subgroup analyses of persons with or without late AMD at baseline to the various components of late AMD (neovascular, central geographic atrophy, or any geographic atrophy) also showed no statistically significant association of statin use with progression to AMD. Conclusions Statin use was not statistically significantly associated with the

  12. A potential role for cell-based therapeutics in the treatment of intervertebral disc herniation

    OpenAIRE

    Ganey, Timothy M.; Meisel, Hans

    2002-01-01

    Lower back pain and disc degeneration negatively affect quality of life and impose an enormous financial burden. An extensive body of scientific work has evolved that characterizes the disc, demonstrating spinal anatomy and morphology that contribute to risk and likely promote failure. Ultimately, matrix failure is responsible for mechanical failure, which in turn results in spinal compromise anatomically and subsequent pain. One intervening approach to breaking this sequence has been to repo...

  13. Quantitative evaluation of degenerative lumbar intervertebral disc applying an equivalent cross-relaxation rate using MRI

    International Nuclear Information System (INIS)

    Obata, Hideaki; Inaba, Tadashi; Kato, Takaya; Tokuda, Masataka; Matsushima, Shigeru; Yamada, Michiaki; Kinosada, Yasutomi

    2004-01-01

    The equivalent cross-relaxation rate (ECR) is a measurement method to evaluate a change in organizational structure quantitatively utilizing MRI. The objectives of this study are to understand the characteristics related to water contents in degenerative lumbar intervertebral discs, and to investigate the usefulness of quantitative evaluation using ECR in order to find as early as possible disordered discs. Seven normal volunteers and four asymptomatic volunteers with degeneration in lumbar intervertebral discs, 21 to 26 years of age, were studied using a SIGNA model of GE Medical Systems equipped with a 1.5 T clinical scanner and spine coil. The ECR values were defined as the percentage of signal loss between unsaturated and saturated images. The results showed that the ECR value of annulus fibrosus in an intervertebral disc was higher than nucleus pulposus. Furthermore, it was found that the ECR value of nucleus pulposus (L5-S1) with degeneration was significantly higher than that without degeneration. It was considered that this result reflected an increase of water contents in the degenerative nucleus. This study suggests that the ECR value of a nucleus could be an effective parameter to diagnosis of degenerated discs or grades of disorder. (author)

  14. Nuclear magnetic resonance therapy in lumbar disc herniation with lumbar radicular syndrome: effects of the intervention on pain intensity, health-related quality of life, disease-related disability, consumption of pain medication, duration of sick leave and MRI analysis.

    Science.gov (United States)

    Salfinger, H; Salomonowitz, G; Friedrich, K M; Hahne, J; Holzapfel, J; Friedrich, M

    2015-06-01

    The objective was to assess the effects of therapeutic nuclear magnetic resonance (tNMR) as a conservative treatment for lumbar radicular syndrome (LRS) in patients with lumbar disc herniation. The prospective, randomised, double-blind, placebo-controlled trial included 94 patients, aged 20-60 years (44.79 ± 8.83), with LRS caused by lumbar disc herniation confirmed by MRI scans and with clinical signs of a radicular lesion without indication for surgical intervention. Treatment group (TG) and control group (CG) received standard non-surgical therapy. Additionally, the TG had seven sessions with the tNMR device with a magnetic flux density of 2.3 mT and a frequency of 85 kHz; the CG received 7 sham treatments. Outcome parameters were the treatment effect on pain intensity (Visual Analogue Scale-VAS), health-related quality of life (36-item Short Form Health Survey-SF-36), disease-related disability (Roland Morris Disability Questionnaire-RMDQ), pain medication intake, duration of sick leave and morphological changes assessed by MRI scan analysis. VAS scores improved significantly in both groups (p Patients in the TG recorded significantly fewer days of sick leave in month 3 after treatment (p = 0.026). MRI scan summary scores improved significantly in both groups (L4/5 p treatment of lumbar disc herniation with LRS. The application of tNMR did not meet MCID criteria. It rendered few statistically significant differences between patient groups. The overall results of this trial make a clinical implementation of tNMR in the treatment of lumbar disc herniation with LRS appear premature. Further research is needed to better understand the mode of action of tNMR on compressed neural tissue and to elucidate the issue of the cost/benefit ratio.

  15. Age-related macular degeneration

    DEFF Research Database (Denmark)

    la Cour, Morten; Kiilgaard, Jens Folke; Nissen, Mogens Holst

    2002-01-01

    Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterised by the appearance of drusen in the macula, accompanied by choroidal neovascularisation (CNV) or geographic atrophy. The disease is more common in Caucasian....... Smoking is probably also a risk factor. Preventive strategies using macular laser photocoagulation are under investigation, but their efficacy in preventing visual loss is as yet unproven. There is no treatment with proven efficacy for geographic atrophy. Optimal treatment for exudative AMD requires...

  16. The Galactic stellar disc

    International Nuclear Information System (INIS)

    Feltzing, S; Bensby, T

    2008-01-01

    The study of the Milky Way stellar discs in the context of galaxy formation is discussed. In particular, we explore the properties of the Milky Way disc using a new sample of about 550 dwarf stars for which we have recently obtained elemental abundances and ages based on high-resolution spectroscopy. For all the stars we also have full kinematic information as well as information about their stellar orbits. We confirm results from previous studies that the thin and the thick discs have distinct abundance patterns. But we also explore a larger range of orbital parameters than what has been possible in our previous studies. Several new results are presented. We find that stars that reach high above the Galactic plane and have eccentric orbits show remarkably tight abundance trends. This implies that these stars formed out of well-mixed gas that had been homogenized over large volumes. We find some evidence that suggest that the event that most likely caused the heating of this stellar population happened a few billion years ago. Through a simple, kinematic exploration of stars with super-solar [Fe/H], we show that the solar neighbourhood contains metal-rich, high velocity stars that are very likely associated with the thick disc. Additionally, the HR1614 moving group and the Hercules and Arcturus stellar streams are discussed and it is concluded that, probably, a large fraction of the groups and streams so far identified in the disc are the result of evolution and interactions within the stellar disc rather than being dissolved stellar clusters or engulfed dwarf galaxies.

  17. Validation of the German revised Addenbrooke's cognitive examination for detecting mild cognitive impairment, mild dementia in alzheimer's disease and frontotemporal lobar degeneration.

    Science.gov (United States)

    Alexopoulos, P; Ebert, A; Richter-Schmidinger, T; Schöll, E; Natale, B; Aguilar, C A; Gourzis, P; Weih, M; Perneczky, R; Diehl-Schmid, J; Kneib, T; Förstl, H; Kurz, A; Danek, A; Kornhuber, J

    2010-01-01

    The diagnostic accuracy of the German version of the revised Addenbrooke's Cognitive Examination (ACE-R) in identifying mild cognitive impairment (MCI), mild dementia in Alzheimer's disease (AD) and mild dementia in frontotemporal lobar degeneration (FTLD) in comparison with the conventional Mini Mental State Examination (MMSE) was assessed. The study encompasses 76 cognitively healthy elderly individuals, 75 patients with MCI, 56 with AD and 22 with FTLD. ACE-R and MMSE were validated against an expert diagnosis based on a comprehensive diagnostic procedure. Statistical analysis was performed using the receiver operating characteristic method and regression analyses. The optimal cut-off score for the ACE-R for detecting MCI, AD, and FTLD was 86/87, 82/83 and 83/84, respectively. ACE-R was superior to MMSE only in the detection of patients with FTLD [area under the curve (AUC): 0.97 vs. 0.92], whilst the accuracy of the two instruments did not differ in identifying MCI and AD. The ratio of the scores of the memory ACE-R subtest to verbal fluency subtest contributed significantly to the discrimination between AD and FTLD (optimal cut-off score: 2.30/2.31, AUC: 0.77), whereas the MMSE and ACE-R total scores did not. The German ACE-R is superior to the most commonly employed MMSE in detecting mild dementia in FTLD and in the differential diagnosis between AD and FTLD. Thus it might serve as a valuable instrument as part of a comprehensive diagnostic workup in specialist centres/clinics contributing to the diagnosis and differential diagnosis of the cause of dementia.

  18. Neovascular age-related macular degeneration is not associated with coronary heart disease in a Chinese Population: a population-based study.

    Science.gov (United States)

    Hu, Chao-Chien; Lin, Herng-Ching; Sheu, Jau-Jiuan; Kao, Li-Ting

    2017-11-01

    This case-control study aimed to explore the association between prior coronary heart disease (CHD) and neovascular age-related macular degeneration (AMD) using a population-based data set in Taiwan. We analysed data sourced from the Taiwan Longitudinal Health Insurance Database 2005. The study consisted of 1970 patients with neovascular AMD as cases and 5910 age- and sex-matched controls. We performed a conditional logistic regression to examine the odds ratio (OR) and its corresponding 95% confidence interval (CI) for previously diagnosed CHD between cases and controls. Of the 7880 sampled patients, 24.5% had a prior history of CHD; CHD was found in 25.7% of cases and in 22.7% of controls (p = 0.008). The conditional logistic regression analysis indicated that the OR for prior CHD for cases was 1.17 [95% confidence interval (CI): 1.04-1.32] compared to the controls. However, after adjusting for patient's monthly income, geographic location, urbanization level, age, hyperlipidaemia, diabetes and hypertension, we failed to observe an association between prior CHD and AMD (OR = 1.03, 95% CI = 0.91-1.17). Additionally, the medical comorbidities of hyperlipidaemia (adjusted OR = 1.29, 95% CI = 1.15-1.45), hypertension (adjusted OR = 1.20, 95% CI = 1.05-1.37) and diabetes (adjusted OR = 1.47, 95% CI = 1.32-1.65) were significantly associated with AMD. This study presented no significant difference in the odds of prior CHD between patients with AMD and those without AMD after adjusting for comorbidities and sociodemographic characteristics in a Chinese population. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  19. Isolated Optic Disc Tuberculosis

    Science.gov (United States)

    Mansour, Ahmad M.; Tabbara, Khalid F.; Tabbarah, Zuhair

    2015-01-01

    We present a healthy male subject who developed progressive visual loss in the left eye initially diagnosed as optic neuritis. Upon suspicion of infectious etiology, testing was positive for tuberculosis. There were no signs or symptoms of active systemic tuberculosis infection. The patient responded swiftly to antimycobacterial therapy with return of vision and resolution of disc swelling. Positive purified protein derivative skin test, negative chest radiograph, negative systemic workup, negative workup for other causes of unilateral optic neuritis and quick response to mycobacterial therapy reaffirm the entity of isolated optic disc tuberculosis similar to isolated choroidal tuberculosis without systemic manifestation. PMID:26483675

  20. Isolated Optic Disc Tuberculosis

    Directory of Open Access Journals (Sweden)

    Ahmad M. Mansour

    2015-09-01

    Full Text Available We present a healthy male subject who developed progressive visual loss in the left eye initially diagnosed as optic neuritis. Upon suspicion of infectious etiology, testing was positive for tuberculosis. There were no signs or symptoms of active systemic tuberculosis infection. The patient responded swiftly to antimycobacterial therapy with return of vision and resolution of disc swelling. Positive purified protein derivative skin test, negative chest radiograph, negative systemic workup, negative workup for other causes of unilateral optic neuritis and quick response to mycobacterial therapy reaffirm the entity of isolated optic disc tuberculosis similar to isolated choroidal tuberculosis without systemic manifestation.

  1. Hybrid testing of lumbar CHARITE discs versus fusions.

    Science.gov (United States)

    Panjabi, Manohar; Malcolmson, George; Teng, Edward; Tominaga, Yasuhiro; Henderson, Gweneth; Serhan, Hassan

    2007-04-20

    An in vitro human cadaveric biomechanical study. To quantify effects on operated and other levels, including adjacent levels, due to CHARITE disc implantations versus simulated fusions, using follower load and the new hybrid test method in flexion-extension and bilateral torsion. Spinal fusion has been associated with long-term accelerated degeneration at adjacent levels. As opposed to the fusion, artificial discs are designed to preserve motion and diminish the adjacent-level effects. Five fresh human cadaveric lumbar specimens (T12-S1) underwent multidirectional testing in flexion-extension and bilateral torsion with 400 N follower load. Intact specimen total ranges of motion were determined with +/-10 Nm unconstrained pure moments. The intact range of motion was used as input for the hybrid tests of 5 constructs: 1) CHARITE disc at L5-S1; 2) fusion at L5-S1; 3) CHARITE discs at L4-L5 and L5-S1; 4) CHARITE disc at L4-L5 and fusion at L5-S1; and 5) 2-level fusion at L4-L5-S1. Using repeated-measures single factor analysis of variance and Bonferroni statistical tests (P < 0.05), intervertebral motion redistribution of each construct was compared with the intact. In flexion-extension, 1-level CHARITE disc preserved motion at the operated and other levels, while 2-level CHARITE showed some amount of other-level effects. In contrast, 1- and 2-level fusions increased other-level motions (average, 21.0% and 61.9%, respectively). In torsion, both 1- and 2-level discs preserved motions at all levels. The 2-level simulated fusion increased motions at proximal levels (22.9%), while the 1-level fusion produced no significant changes. In general, CHARITE discs preserved operated- and other-level motions. Fusion simulations affected motion redistribution at other levels, including adjacent levels.

  2. Tracing notochord-derived cells using a Noto-cre mouse: implications for intervertebral disc development.

    Science.gov (United States)

    McCann, Matthew R; Tamplin, Owen J; Rossant, Janet; Séguin, Cheryle A

    2012-01-01

    Back pain related to intervertebral disc degeneration is the most common musculoskeletal problem, with a lifetime prevalence of 82%. The lack of effective treatment for this widespread problem is directly related to our limited understanding of disc development, maintenance and degeneration. The aim of this study was to determine the developmental origins of nucleus pulposus cells within the intervertebral disc using a novel notochord-specific Cre mouse. To trace the fate of notochordal cells within the intervertebral disc, we derived a notochord-specific Cre mouse line by targeting the homeobox gene Noto. Expression of this gene is restricted to the node and the posterior notochord during gastrulation [embryonic day 7.5 (E7.5)-E12.5]. The Noto-cre mice were crossed with a conditional lacZ reporter for visualization of notochord fate in whole-mount embryos. We performed lineage-tracing experiments to examine the contribution of the notochord to spinal development from E12.5 through to skeletally mature mice (9 months). Fate mapping studies demonstrated that, following elongation and formation of the primitive axial skeleton, the notochord gives rise to the nucleus pulposus in fully formed intervertebral discs. Cellular localization of β-galactosidase (encoded by lacZ) and cytokeratin-8 demonstrated that both notochordal cells and chondrocyte-like nucleus pulposus cells are derived from the embryonic notochord. These studies establish conclusively that notochordal cells act as embryonic precursors to all cells found within the nucleus pulposus of the mature intervertebral disc. This suggests that notochordal cells might serve as tissue-specific progenitor cells within the disc and establishes the Noto-cre mouse as a unique tool to interrogate the contribution of notochordal cells to both intervertebral disc development and disc degeneration.

  3. Genome-wide analysis of pain-, nerve- and neurotrophin -related gene expression in the degenerating human annulus

    Science.gov (United States)

    2012-01-01

    Background In spite of its high clinical relevance, the relationship between disc degeneration and low back pain is still not well understood. Recent studies have shown that genome-wide gene expression studies utilizing ontology searches provide an efficient and valuable methodology for identification of clinically relevant genes. Here we use this approach in analysis of pain-, nerve-, and neurotrophin-related gene expression patterns in specimens of human disc tissue. Control, non-herniated clinical, and herniated clinical specimens of human annulus tissue were studied following Institutional Review Board approval. Results Analyses were performed on more generated (Thompson grade IV and V) discs vs. less degenerated discs (grades I-III), on surgically operated discs vs. control discs, and on herniated vs. control discs. Analyses of more degenerated vs. less degenerated discs identified significant upregulation of well-recognized pain-related genes (bradykinin receptor B1, calcitonin gene-related peptide and catechol-0-methyltransferase). Nerve growth factor was significantly upregulated in surgical vs. control and in herniated vs. control discs. All three analyses also found significant changes in numerous proinflammatory cytokine- and chemokine-related genes. Nerve, neurotrophin and pain-ontology searches identified many matrix, signaling and functional genes which have known importance in the disc. Immunohistochemistry was utilized to confirm the presence of calcitonin gene-related peptide, catechol-0-methyltransferase and bradykinin receptor B1 at the protein level in the human annulus. Conclusions Findings point to the utility of microarray analyses in identification of pain-, neurotrophin and nerve-related genes in the disc, and point to the importance of future work exploring functional interactions between nerve and disc cells in vitro and in vivo. Nerve, pain and neurotrophin ontology searches identified numerous changes in proinflammatory cytokines and

  4. Highly sensitive measurements of disease progression in rare disorders: Developing and validating a multimodal model of retinal degeneration in Stargardt disease

    OpenAIRE

    Lambertus, Stanley; Bax, Nathalie M.; Fakin, Ana; Groenewoud, Joannes M. M.; Klevering, B. Jeroen; Moore, Anthony T.; Michaelides, Michel; Webster, Andrew R.; van der Wilt, Gert Jan; Hoyng, Carel B.

    2017-01-01

    BACKGROUND: Each inherited retinal disorder is rare, but together, they affect millions of people worldwide. No treatment is currently available for these blinding diseases, but promising new options-including gene therapy-are emerging. Arguably, the most prevalent retinal dystrophy is Stargardt disease. In each case, the specific combination of ABCA4 variants (> 900 identified to date) and modifying factors is virtually unique. It accounts for the vast phenotypic heterogeneity including vari...

  5. Highly sensitive measurements of disease progression in rare disorders: Developing and validating a multimodal model of retinal degeneration in Stargardt disease

    OpenAIRE

    Lambertus, S.; Bax, N. M.; Fakin, A.; Groenewoud, J. M. M.; Klevering, B. J.; Moore, A. T.; Michaelides, M.; Webster, A. R.; van der Wilt, G. J.; Hoyng, C. B.

    2017-01-01

    BACKGROUND: Each inherited retinal disorder is rare, but together, they affect millions of people worldwide. No treatment is currently available for these blinding diseases, but promising new options—including gene therapy—are emerging. Arguably, the most prevalent retinal dystrophy is Stargardt disease. In each case, the specific combination of ABCA4 variants (> 900 identified to date) and modifying factors is virtually unique. It accounts for the vast phenotypic heterogeneity including ...

  6. Regenerative and immunogenic characteristics of cultured nucleus pulposus cells from human cervical intervertebral discs.

    Directory of Open Access Journals (Sweden)

    Stefan Stich

    Full Text Available Cell-based regenerative approaches have been suggested as primary or adjuvant procedures for the treatment of degenerated intervertebral disc (IVD diseases. Our aim was to evaluate the regenerative and immunogenic properties of mildly and severely degenerated cervical nucleus pulposus (NP cells with regard to cell isolation, proliferation and differentiation, as well as to cell surface markers and co-cultures with autologous or allogeneic peripheral blood mononuclear cells (PBMC including changes in their immunogenic properties after 3-dimensional (3D-culture. Tissue from the NP compartment of 10 patients with mild or severe grades of IVD degeneration was collected. Cells were isolated, expanded with and without basic fibroblast growth factor and cultured in 3D fibrin/poly (lactic-co-glycolic acid transplants for 21 days. Real-time reverse-transcription polymerase chain reaction (RT-PCR showed the expression of characteristic NP markers ACAN, COL1A1 and COL2A1 in 2D- and 3D-culture with degeneration- and culture-dependent differences. In a 5,6-carboxyfluorescein diacetate N-succinimidyl ester-based proliferation assay, NP cells in monolayer, regardless of their grade of degeneration, did not provoke a significant proliferation response in T cells, natural killer (NK cells or B cells, not only with donor PBMC, but also with allogeneic PBMC. In conjunction with low inflammatory cytokine expression, analyzed by Cytometric Bead Array and fluorescence-activated cell sorting (FACS, a low immunogenicity can be assumed, facilitating possible therapeutic approaches. In 3D-culture, however, we found elevated immune cell proliferation levels, and there was a general trend to higher responses for NP cells from severely degenerated IVD tissue. This emphasizes the importance of considering the specific immunological alterations when including biomaterials in a therapeutic concept. The overall expression of Fas receptor, found on cultured NP cells, could have

  7. Potential genetic modifiers of disease risk and age at onset in patients with frontotemporal lobar degeneration and GRN mutations: a genome-wide association study.

    Science.gov (United States)

    Pottier, Cyril; Zhou, Xiaolai; Perkerson, Ralph B; Baker, Matt; Jenkins, Gregory D; Serie, Daniel J; Ghidoni, Roberta; Benussi, Luisa; Binetti, Giuliano; López de Munain, Adolfo; Zulaica, Miren; Moreno, Fermin; Le Ber, Isabelle; Pasquier, Florence; Hannequin, Didier; Sánchez-Valle, Raquel; Antonell, Anna; Lladó, Albert; Parsons, Tammee M; Finch, NiCole A; Finger, Elizabeth C; Lippa, Carol F; Huey, Edward D; Neumann, Manuela; Heutink, Peter; Synofzik, Matthis; Wilke, Carlo; Rissman, Robert A; Slawek, Jaroslaw; Sitek, Emilia; Johannsen, Peter; Nielsen, Jørgen E; Ren, Yingxue; van Blitterswijk, Marka; DeJesus-Hernandez, Mariely; Christopher, Elizabeth; Murray, Melissa E; Bieniek, Kevin F; Evers, Bret M; Ferrari, Camilla; Rollinson, Sara; Richardson, Anna; Scarpini, Elio; Fumagalli, Giorgio G; Padovani, Alessandro; Hardy, John; Momeni, Parastoo; Ferrari, Raffaele; Frangipane, Francesca; Maletta, Raffaele; Anfossi, Maria; Gallo, Maura; Petrucelli, Leonard; Suh, EunRan; Lopez, Oscar L; Wong, Tsz H; van Rooij, Jeroen G J; Seelaar, Harro; Mead, Simon; Caselli, Richard J; Reiman, Eric M; Noel Sabbagh, Marwan; Kjolby, Mads; Nykjaer, Anders; Karydas, Anna M; Boxer, Adam L; Grinberg, Lea T; Grafman, Jordan; Spina, Salvatore; Oblak, Adrian; Mesulam, M-Marsel; Weintraub, Sandra; Geula, Changiz; Hodges, John R; Piguet, Olivier; Brooks, William S; Irwin, David J; Trojanowski, John Q; Lee, Edward B; Josephs, Keith A; Parisi, Joseph E; Ertekin-Taner, Nilüfer; Knopman, David S; Nacmias, Benedetta; Piaceri, Irene; Bagnoli, Silvia; Sorbi, Sandro; Gearing, Marla; Glass, Jonathan; Beach, Thomas G; Black, Sandra E; Masellis, Mario; Rogaeva, Ekaterina; Vonsattel, Jean-Paul; Honig, Lawrence S; Kofler, Julia; Bruni, Amalia C; Snowden, Julie; Mann, David; Pickering-Brown, Stuart; Diehl-Schmid, Janine; Winkelmann, Juliane; Galimberti, Daniela; Graff, Caroline; Öijerstedt, Linn; Troakes, Claire; Al-Sarraj, Safa; Cruchaga, Carlos; Cairns, Nigel J; Rohrer, Jonathan D; Halliday, Glenda M; Kwok, John B; van Swieten, John C; White, Charles L; Ghetti, Bernardino; Murell, Jill R; Mackenzie, Ian R A; Hsiung, Ging-Yuek R; Borroni, Barbara; Rossi, Giacomina; Tagliavini, Fabrizio; Wszolek, Zbigniew K; Petersen, Ronald C; Bigio, Eileen H; Grossman, Murray; Van Deerlin, Vivianna M; Seeley, William W; Miller, Bruce L; Graff-Radford, Neill R; Boeve, Bradley F; Dickson, Dennis W; Biernacka, Joanna M; Rademakers, Rosa

    2018-06-01

    Loss-of-function mutations in GRN cause frontotemporal lobar degeneration (FTLD). Patients with GRN mutations present with a uniform subtype of TAR DNA-binding protein 43 (TDP-43) pathology at autopsy (FTLD-TDP type A); however, age at onset and clinical presentation are variable, even within families. We aimed to identify potential genetic modifiers of disease onset and disease risk in GRN mutation carriers. The study was done in three stages: a discovery stage, a replication stage, and a meta-analysis of the discovery and replication data. In the discovery stage, genome-wide logistic and linear regression analyses were done to test the association of genetic variants with disease risk (case or control status) and age at onset in patients with a GRN mutation and controls free of neurodegenerative disorders. Suggestive loci (p<1 × 10 -5 ) were genotyped in a replication cohort of patients and controls, followed by a meta-analysis. The effect of genome-wide significant variants at the GFRA2 locus on expression of GFRA2 was assessed using mRNA expression studies in cerebellar tissue samples from the Mayo Clinic brain bank. The effect of the GFRA2 locus on progranulin concentrations was studied using previously generated ELISA-based expression data. Co-immunoprecipitation experiments in HEK293T cells were done to test for a direct interaction between GFRA2 and progranulin. Individuals were enrolled in the current study between Sept 16, 2014, and Oct 5, 2017. After quality control measures, statistical analyses in the discovery stage included 382 unrelated symptomatic GRN mutation carriers and 1146 controls free of neurodegenerative disorders collected from 34 research centres located in the USA, Canada, Australia, and Europe. In the replication stage, 210 patients (67 symptomatic GRN mutation carriers and 143 patients with FTLD without GRN mutations pathologically confirmed as FTLD-TDP type A) and 1798 controls free of neurodegenerative diseases were recruited

  8. Calcification of intervertebral discs in children

    International Nuclear Information System (INIS)

    Hoermann, D.

    1984-01-01

    Thirteen children with intervertebral disc calcifications of the cervical, thoracal and lumbar spine have been diagnosed since 1970. Most of them were observed over a period of several years. Ten children fell ill with acute pains, but only 2 of them sufferred from a trauma. In 3 cases the features were discovered accidentally combined with malformations of vertebral bodies and congenital diseases. Our results suggest a primary structural inferiority of the calcified discs. The calcifications arise partially from a birth trauma, partially from an unknown etiology. They can last for a long time without symptoms. An acute event effects the pains due to shifting or herniation of calcified disc-fragments. Secondary findings such as decrease of the height of cervical vertebral bodies or destructions of the endplates of thoracal and lumbar vertebral bodies disappear retarded and often incompletely and demand a control for a long time. (orig.)

  9. Degenerate nonlinear diffusion equations

    CERN Document Server

    Favini, Angelo

    2012-01-01

    The aim of these notes is to include in a uniform presentation style several topics related to the theory of degenerate nonlinear diffusion equations, treated in the mathematical framework of evolution equations with multivalued m-accretive operators in Hilbert spaces. The problems concern nonlinear parabolic equations involving two cases of degeneracy. More precisely, one case is due to the vanishing of the time derivative coefficient and the other is provided by the vanishing of the diffusion coefficient on subsets of positive measure of the domain. From the mathematical point of view the results presented in these notes can be considered as general results in the theory of degenerate nonlinear diffusion equations. However, this work does not seek to present an exhaustive study of degenerate diffusion equations, but rather to emphasize some rigorous and efficient techniques for approaching various problems involving degenerate nonlinear diffusion equations, such as well-posedness, periodic solutions, asympt...

  10. Refsum Disease

    Science.gov (United States)

    ... night blindness due to degeneration of the retina (retinitis pigmentosa). If the disease progresses, other symptoms may include ... night blindness due to degeneration of the retina (retinitis pigmentosa). If the disease progresses, other symptoms may include ...

  11. Tracing Planets in Circumstellar Discs

    Directory of Open Access Journals (Sweden)

    Uribe Ana L.

    2013-04-01

    Full Text Available Planets are assumed to form in circumstellar discs around young stellar objects. The additional gravitational potential of a planet perturbs the disc and leads to characteristic structures, i.e. spiral waves and gaps, in the disc density profile. We perform a large-scale parameter study on the observability of these planet-induced structures in circumstellar discs in the (submm wavelength range for the Atacama Large (SubMillimeter Array (ALMA. On the basis of hydrodynamical and magneto-hydrodynamical simulations of star-disc-planet models we calculate the disc temperature structure and (submm images of these systems. These are used to derive simulated ALMA maps. Because appropriate objects are frequent in the Taurus-Auriga region, we focus on a distance of 140 pc and a declination of ≈ 20°. The explored range of star-disc-planet configurations consists of six hydrodynamical simulations (including magnetic fields and different planet masses, nine disc sizes with outer radii ranging from 9 AU to 225 AU, 15 total disc masses in the range between 2.67·10-7 M⊙ and 4.10·10-2 M⊙, six different central stars and two different grain size distributions, resulting in 10 000 disc models. At almost all scales and in particular down to a scale of a few AU, ALMA is able to trace disc structures induced by planet-disc interaction or the influence of magnetic fields in the wavelength range between 0.4...2.0 mm. In most cases, the optimum angular resolution is limited by the sensitivity of ALMA. However, within the range of typical masses of protoplane tary discs (0.1 M⊙...0.001 M⊙ the disc mass has a minor impact on the observability. At the distance of 140 pc it is possible to resolve discs down to 2.67·10-6 M⊙ and trace gaps in discs with 2.67·10-4 M⊙ with a signal-to-noise ratio greater than three. In general, it is more likely to trace planet-induced gaps in magneto-hydrodynamical disc models, because gaps are wider in the presence of

  12. Highly sensitive measurements of disease progression in rare disorders: Developing and validating a multimodal model of retinal degeneration in Stargardt disease

    NARCIS (Netherlands)

    Lambertus, S.; Bax, N.M.; Fakin, A.; Groenewoud, J.M.M.; Klevering, B.J.; Moore, A.T.; Michaelides, M.; Webster, A.R.; Wilt, G.J. van der; Hoyng, C.B.

    2017-01-01

    BACKGROUND: Each inherited retinal disorder is rare, but together, they affect millions of people worldwide. No treatment is currently available for these blinding diseases, but promising new options-including gene therapy-are emerging. Arguably, the most prevalent retinal dystrophy is Stargardt

  13. Genetics of lattice degeneration of the retina.

    Science.gov (United States)

    Murakami, F; Ohba, N

    1982-01-01

    First-degree relatives of proband patients with lattice degeneration of the retina revealed a significantly higher prevalence of the disease than the prevalence in the general population: the former had the disease about three times as frequently as the latter. The observed data were analyzed in terms of their accordance with recognized genetic models. The inheritance pattern did not fit well to a monogenic mode of inheritance, and it was hypothesized that a polygenic or multifactorial mode of inheritance is the most likely for lattice degeneration of the retina.

  14. Whole-genome sequencing reveals important role for TBK1 and OPTN mutations in frontotemporal lobar degeneration without motor neuron disease

    NARCIS (Netherlands)

    Pottier, C.; Bieniek, K.F.; Finch, N.; Vorst, M. van de; Baker, M.; Perkersen, R.; Brown, P.; Ravenscroft, T.; Blitterswijk, M. van; Nicholson, A.M.; DeTure, M.; Knopman, D.S.; Josephs, K.A.; Parisi, J.E.; Petersen, R.C.; Boylan, K.B.; Boeve, B.F.; Graff-Radford, N.R.; Veltman, J.A.; Gilissen, C.; Murray, M.E.; Dickson, D.W.; Rademakers, R.

    2015-01-01

    Frontotemporal lobar degeneration with TAR DNA-binding protein 43 inclusions (FTLD-TDP) is the most common pathology associated with frontotemporal dementia (FTD). Repeat expansions in chromosome 9 open reading frame 72 (C9ORF72) and mutations in progranulin (GRN) are the major known genetic causes

  15. Pericellular colocalisation and interactive properties of type VI collagen and perlecan in the intervertebral disc

    Directory of Open Access Journals (Sweden)

    AJ Hayes

    2016-07-01

    Full Text Available The aim of this study was to immunolocalise type VI collagen and perlecan and determine their interactive properties in the intervertebral disc (IVD. Confocal laser scanning microscopy co-localised perlecan with type VI collagen as pericellular components of IVD cells and translamellar cross-bridges in ovine and murine IVDs. These cross-bridges were significantly less abundant in the heparin sulphate deficient Hspg2 exon 3 null mouse IVD than in wild type. This association of type VI collagen with elastic components provides clues as to its roles in conveying elastic recoil properties to annular tissues. Perlecan and type VI collagen were highly interactive in plasmon resonance studies. Pericellular colocalisation of perlecan and type VI collagen provides matrix stabilisation and cell-matrix communication which allows IVD cells to perceive and respond to perturbations in their biomechanical microenvironment. Perlecan, at the cell surface, provides an adhesive interface between the cell and its surrounding extracellular matrix. Elastic microfibrillar structures regulate tensional connective tissue development and function. The 2010 Global Burden of Disease study examined 291 disorders and identified disc degeneration and associated low back pain as the leading global musculoskeletal disorder emphasising its massive socioeconomic impact and the need for more effective treatment strategies. A greater understanding of how the IVD achieves its unique biomechanical functional properties is of great importance in the development of such therapeutic measures.

  16. A method for quantifying intervertebral disc signal intensity on T2-weighted imaging

    International Nuclear Information System (INIS)

    Nagashima, Masaki; Abe, Hitoshi; Amaya, Kenji; Matsumoto, Hideo; Yanaihara, Hisashi; Nishiwaki, Yuji; Toyama, Yoshiaki; Matsumoto, Morio

    2012-01-01

    Background Quantification of intervertebral disc degeneration based on intensity of the nucleus pulposus in magnetic resonance imaging (MRI) often uses the mean intensity of the region of interest (ROI) within the nucleus pulposus. However, the location and size of ROI have varied in different reports, and none of the reported methods can be considered fully objective. Purpose To develop a more objective method of establishing ROIs for quantitative evaluation of signal intensity in the nucleus pulposus using T2-weighted MRI. Material and Methods A 1.5-T scanner was used to obtain T2-weighted mid-sagittal images. A total of 288 intervertebral discs from 48 patients (25 men, 23 women) were analyzed. Mean age was 47.4 years (range, 17-69 years). All discs were classified into five grades according to Pfirrmann et al. Discs in grades I and II were defined as bright discs, and discs in grades IV and V were defined as dark discs. Eight candidate methods of ROI determination were devised. The method offering the highest degree of discrimination between bright and dark discs was investigated among these eight methods. Results The method with the greatest degree of discrimination was as follows. The quadrangle formed by anterior and posterior edges of the upper and lower end plates in contact with the intervertebral disc to be measured was defined as the intervertebral area. A shape similar to the intervertebral area but with one-quarter the area was drawn. The geometrical center of the shape was matched to the center of intensity, and this shape was then used as the ROI. Satisfactory validity and reproducibility were obtained using this method. Conclusion The present method offers adequate discrimination and could be useful for longitudinal tracking of intervertebral disc degeneration with sufficient reproducibility

  17. Evaluation of apoptotic cell death in normal and chondrodystrophic canine intervertebral discs

    Directory of Open Access Journals (Sweden)

    Marie Klauser

    2012-02-01

    Full Text Available Disc degeneration occurs commonly in dogs. A variety of factors is thought to contribute an inappropriate disc matrix that isolate cells in the disc and lead to apoptosis. Disc herniation with radiculopathy and discogenic pain are the results of the degenerative process. The objective of this prospective study was to determine the extent of apoptosis in intact and herniated intervertebral discs of chondrodystrophic dogs and non-chondrodystrophic dogs. In addition, the nucleus pulposus (NP was histologically compared between non-chondrodystrophic and chondrodystrophic dogs. Thoracolumbar intervertebral discs and parts of the extruded nucleus pulposus were harvested from 45 dogs. Samples were subsequently stained with haematoxylin-eosin and processed to detect cleaved caspase-3 and poly(ADP-ribose polymerase. A significant greater degree of apoptosis was observed in herniated NPs of chondrodystrophic dogs compared to non- chondrodystrophic dogs with poly (ADP-ribose polymerase and cleaved caspase- 3 detection. Within the group of chondrodystrophic dogs, dogs with an intact disc and younger than 6 years showed a significant lower incidence of apoptosis in the NP compared to the herniated NP of chondrodystrophic dogs. The extent of apoptosis in the annulus fibrosus was not different between the intact disc from chondrodystrophic and non- chondrodystrophic dogs. An age-related increase of apoptotic cells in NP and annulus fibrosus was found in the intact non-herniated intervertebral discs. Histologically, absence of notochordal cells and occurrence of chondroid metaplasia were observed in the nucleus pulposus of chondrodystrophic dogs. As a result, we found that apoptosis plays a role in disc degeneration in chondrodystrophic dogs.

  18. A method for quantifying intervertebral disc signal intensity on T2-weighted imaging

    Energy Technology Data Exchange (ETDEWEB)

    Nagashima, Masaki [Dept. of Orthopaedic Surgery, Keio Univ. School of Medicine, Tokyo (Japan); Dept. of Orthopaedic Surgery, Kitasato Univ. Kitasato Inst. Hospital, Tokyo (Japan); Abe, Hitoshi [Dept. of Orthopaedic Surgery, Kitasato Univ. Kitasato Inst. Hospital, Tokyo (Japan)], E-mail: hit-abe@insti.kitasato-u.ac.jp; Amaya, Kenji [Graduate School of Information Science and Engineering, Tokyo Inst. of Technology, Tokyo (Japan); Matsumoto, Hideo [Inst. for Integrated Sports Medicine, Keio Univ. School of Medicine, Tokyo (Japan); Yanaihara, Hisashi [Dept. of Diagnostic Radiology, Kitasato Univ. Kitasato Inst. Hospital, Tokyo (Japan); Nishiwaki, Yuji [Dept. of Environmental and Occupational Health, Toho Univ. School of Medicine, Tokyo (Japan); Toyama, Yoshiaki; Matsumoto, Morio [Dept. of Orthopaedic Surgery, Keio Univ. School of Medicine, Tokyo (Japan)

    2012-11-15

    Background Quantification of intervertebral disc degeneration based on intensity of the nucleus pulposus in magnetic resonance imaging (MRI) often uses the mean intensity of the region of interest (ROI) within the nucleus pulposus. However, the location and size of ROI have varied in different reports, and none of the reported methods can be considered fully objective. Purpose To develop a more objective method of establishing ROIs for quantitative evaluation of signal intensity in the nucleus pulposus using T2-weighted MRI. Material and Methods A 1.5-T scanner was used to obtain T2-weighted mid-sagittal images. A total of 288 intervertebral discs from 48 patients (25 men, 23 women) were analyzed. Mean age was 47.4 years (range, 17-69 years). All discs were classified into five grades according to Pfirrmann et al. Discs in grades I and II were defined as bright discs, and discs in grades IV and V were defined as dark discs. Eight candidate methods of ROI determination were devised. The method offering the highest degree of discrimination between bright and dark discs was investigated among these eight methods. Results The method with the greatest degree of discrimination was as follows. The quadrangle formed by anterior and posterior edges of the upper and lower end plates in contact with the intervertebral disc to be measured was defined as the intervertebral area. A shape similar to the intervertebral area but with one-quarter the area was drawn. The geometrical center of the shape was matched to the center of intensity, and this shape was then used as the ROI. Satisfactory validity and reproducibility were obtained using this method. Conclusion The present method offers adequate discrimination and could be useful for longitudinal tracking of intervertebral disc degeneration with sufficient reproducibility.

  19. Natural history of drusenoid pigment epithelial detachment in age-related macular degeneration: Age-Related Eye Disease Study Report No. 28.

    Science.gov (United States)

    Cukras, Catherine; Agrón, Elvira; Klein, Michael L; Ferris, Frederick L; Chew, Emily Y; Gensler, Gary; Wong, Wai T

    2010-03-01

    To describe the natural history of eyes with drusenoid pigment epithelial detachments (DPEDs) associated with age-related macular degeneration (AMD). Multicenter, clinic-based, prospective cohort study. Among 4757 participants enrolled in the Age-Related Eye Disease Study (AREDS), 255 were identified as having DPED in at least 1 eye and having 5 or more years of follow-up after the initial detection of the DPED. Baseline and annual fundus photographs were evaluated for the evolution of the fundus features and the development of advanced AMD in the forms of central geographic atrophy (CGA) or neovascular (NV) AMD. Kaplan-Meier analyses of progression to advanced AMD and of moderate vision loss (> or =15 letters compared with baseline) were performed. Rate of progression to advanced AMD and change in visual acuity from baseline (in terms of mean letters lost and proportion losing > or =15 letters). A total of 311 eyes (from 255 participants) with DPED were followed for a median follow-up time of 8 years subsequent to the initial detection of a DPED. Of the 282 eyes that did not have advanced AMD at baseline, advanced AMD developed within 5 years in 119 eyes (42%) (19% progressing to CGA and 23% progressing to NV-AMD). In the remaining eyes that did not develop advanced AMD (n=163), progressive fundus changes, typified by the development of calcified drusen and pigmentary changes, were detected. Visual decline was prominent among study eyes, with approximately 40% of all eyes decreasing in visual acuity by > or =15 letters at 5 years follow-up. Mean visual acuity decreased from 76 letters ( approximately 20/30) at baseline to 61 letters ( approximately 20/60) at 5 years. Five-year decreases in mean visual acuity averaged 26 letters for eyes progressing to advanced AMD and 8 letters for non-progressing eyes. The natural history of eyes containing DPED is characterized by a high rate of progression to both CGA and NV-AMD. Among eyes not progressing to advanced AMD

  20. Lumbar internal disc derangement in patients with chronic low back pain: diagnostic value of the MR imaging findings as compared with provoked discography as the standard

    International Nuclear Information System (INIS)

    Park, Hyeon Seon; Park, Jee Young; Lee, Sang Ho; Ahn, Yong; Lee, Sang Yeun

    2006-01-01

    The aim of this study was to evaluate the diagnostic value of the MR imaging findings with provoked discography used as the standard for painful lumbar disc derangement. Two hundred patients (412 discs), (age rang: 21-77 year), with chronic low back pain underwent MRI and provoked discography. We evaluated the MRI T2-WI findings such as disc degeneration, high-Intensity zones and endplate abnormalities. Subsequently, provocative discography was independently performed with using MR imaging, and a painful disc was defined when moderate to severe and concordant pain was provoked. We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the MRI findings with using provoked discography as the standard. 400 discs showed abnormal findings such as disc degeneration, HIZ and endplate abnormalities on the T2-WI images. 12 discs showed normal finding. HIZ or endplate abnormalities were always combined with disc degeneration. The prevalence of each findings were disc degeneration (400 discs: 97.1%), HIZ (111 discs: 26.9%), type I endplate abnormalities (34 discs: 8.3%), type II endplate abnormalities (75 discs: 18.2%), the combined findings of HIZ and type I endplate abnormalities (2 discs: 0.5%) and the combined findings of HIZ and type II endplate abnormalities (7 discs: 1.7%). The disc degeneration showed high sensitivity (99.5%) and low specificity (5.0%), so only the NPV (91.7%) was significant, and not the PPV (47.8%). Each findings of HIZ (sensitivity, 36.5%, specificity, 81.4%; PPV, 63.18%; NPV, 59.5%), type I endplate abnormalities (11.0%, 94.1%, 61.8% and 54.8%, respectively), type II endplate abnormalities (19.8%, 83.2%, 50.7% and 54.3%, respectively), the combined findings of HIZ and type I endplate abnormalities (0.5%, 99.6%, 50.0% and 53.4%, respectively) and the combined findings of HIZ and type II endplate abnormalities (26.0%, 99.1%, 71.4% and 53.8%, respectively) show high specificity, but low

  1. Lumbar internal disc derangement in patients with chronic low back pain: diagnostic value of the MR imaging findings as compared with provoked discography as the standard

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hyeon Seon; Park, Jee Young; Lee, Sang Ho; Ahn, Yong [Wooridul spine Hospital, Seoul (Korea, Republic of); Lee, Sang Yeun [Puchon Daesung Hospital, Puchon (Korea, Republic of)

    2006-04-15

    The aim of this study was to evaluate the diagnostic value of the MR imaging findings with provoked discography used as the standard for painful lumbar disc derangement. Two hundred patients (412 discs), (age rang: 21-77 year), with chronic low back pain underwent MRI and provoked discography. We evaluated the MRI T2-WI findings such as disc degeneration, high-Intensity zones and endplate abnormalities. Subsequently, provocative discography was independently performed with using MR imaging, and a painful disc was defined when moderate to severe and concordant pain was provoked. We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the MRI findings with using provoked discography as the standard. 400 discs showed abnormal findings such as disc degeneration, HIZ and endplate abnormalities on the T2-WI images. 12 discs showed normal finding. HIZ or endplate abnormalities were always combined with disc degeneration. The prevalence of each findings were disc degeneration (400 discs: 97.1%), HIZ (111 discs: 26.9%), type I endplate abnormalities (34 discs: 8.3%), type II endplate abnormalities (75 discs: 18.2%), the combined findings of HIZ and type I endplate abnormalities (2 discs: 0.5%) and the combined findings of HIZ and type II endplate abnormalities (7 discs: 1.7%). The disc degeneration showed high sensitivity (99.5%) and low specificity (5.0%), so only the NPV (91.7%) was significant, and not the PPV (47.8%). Each findings of HIZ (sensitivity, 36.5%, specificity, 81.4%; PPV, 63.18%; NPV, 59.5%), type I endplate abnormalities (11.0%, 94.1%, 61.8% and 54.8%, respectively), type II endplate abnormalities (19.8%, 83.2%, 50.7% and 54.3%, respectively), the combined findings of HIZ and type I endplate abnormalities (0.5%, 99.6%, 50.0% and 53.4%, respectively) and the combined findings of HIZ and type II endplate abnormalities (26.0%, 99.1%, 71.4% and 53.8%, respectively) show high specificity, but low

  2. Concomitance of fibromyalgia syndrome and cervical disc herniation

    OpenAIRE

    G?ler, Mustafa; Ayd?n, Teoman; Akg?l, Erdal; Ta?p?nar, ?zg?r

    2015-01-01

    [Purpose] Fibromyalgia syndrome (FMS) and cervical disc herniation (CDH) are a common diseases commonly encountered in physical therapy clinics. There are also patients who have both of these diseases. In this study we aim to investigated whether FMS is a risk factor for cervical disc herniation and the frequency of their coincident occurrence. [Subjects and Methods] Thirty-five patients having a primary FMS diagnosis according to the American Rheumatism Association criteria are taken into co...

  3. Ozone therapy for t he complex prolapse of lumbar intervertebral disc: a clinical observation

    International Nuclear Information System (INIS)

    Peng Yong; Wei Mengqi; Wu Juan; Zhou Jianshou; Yang Yong; Zhao Hongliang; Shi Mingguo

    2010-01-01

    Objective: To evaluate the therapeutic outcome of ozone injection therapy for the treatment of complex prolapse of lumbar intervertebral disc, which is accompanied with spinal stenosis due to hypertrophy of ligamentum flavum, degeneration of intervertebral facet joints, intervertebral hyperosteogeny and degeneration, lumbar muscle strain and negative pressure in intervertebral discs. Methods: Seventy patients with simple intervertebral disc prolapse (simple group) and 70 patients with complex intervertebral disc prolapse (complex group) were selected for the study. The complex intervertebral disc prolapse included negative pressure in intervertebral disc (n=11), recurrence after resection of nucleus polposus of intervertebral disc (n=5), spinal stenosis (n=10), degeneration of intervertebral facet joints and interver-tebral hyperosteogeny (n=30), stenosis of lateral recess (n=4) and lumbar muscle strain (n=10). All patients were treated with ozone injection under the CT guidance. A total of 2-3 ml ozone with the concentration of 40-50 μg / ml was injected into the intervertebral disk and a total of 5-8 ml ozone with the concentration of 30-40 μg / ml was injected into the paraspinal space. Infiltration injection into the pain spots with 20 ml ozone was carried out in patients with lumbar muscle strain. Results: A comparison of the therapeutic outcomes between simple group and complex group was made. Immediate relief from clinical symptoms was obtained in 80% of all treated patients. The effective rate one week after the procedure was 95%, which became 96% at 3-6 months after the treatment. Conclusion: Correct clinical diagnosis, skilled and accurate manipulation during the surgery and reasonable use of ozone injection in the treatment of soft tissue injury, etc. can markedly improve the therapeutic effect for complex lumbar intervertebral disc prolase. (authors)

  4. Retinal Nerve Fiber Layer Protrusion Associated with Tilted Optic Discs.

    Science.gov (United States)

    Chiang, Jaclyn; Yapp, Michael; Ly, Angelica; Hennessy, Michael P; Kalloniatis, Michael; Zangerl, Barbara

    2018-03-01

    This study resulted in the identification of an optic nerve head (ONH) feature associated with tilted optic discs, which might potentially contribute to ONH pathologies. Knowledge of such findings will enhance clinical insights and drive future opportunities to understand disease processes related to tilted optic discs. The aim of this study was to identify novel retinal nerve fiber layer (RNFL) anomalies by evaluating tilted optic discs using optical coherence tomography. An observed retinal nerve fiber protrusion was further investigated for association with other morphological or functional parameters. A retrospective review of 400 randomly selected adult patients with ONH examinations was conducted in a referral-only, diagnostic imaging center. After excluding other ONH pathologies, 215 patients were enrolled and evaluated for optic disc tilt and/or torsion. Gross anatomical ONH features, including size and rim or parapapillary region elevation, were assessed with stereoscopic fundus photography. Optical coherence tomography provided detailed morphological information of individual retinal layers. Statistical analysis was applied to identify significant changes between individual patient cohorts. A dome-shaped hyperreflective RNFL bulge, protruding into the neurosensory retina at the optic disc margins, was identified in 17 eyes with tilted optic discs. Available follow-up data were inconclusive regarding natural changes with this ONH feature. This RNFL herniation was significantly correlated with smaller than average optic disc size (P = .005), congenital disc tilt (P optic discs, which has not previously been assessed as an independent ONH structure. The feature is predominantly related to congenital crowded, small optic discs and variable between patients. This study is an important first step to elucidate diagnostic capabilities of tilted disc morphological changes and understanding associated functional deficits.

  5. Nearby stars of the Galactic disc and halo - IV

    Science.gov (United States)

    Fuhrmann, Klaus

    2008-02-01

    The Milky Way Galaxy has an age of about 13 billion years. Solar-type stars evolve all the long way to the realm of degenerate objects on essentially this time-scale. This, as well as the particular advantage that the Sun offers through reliable differential spectroscopic analyses, render these stars the ideal tracers for the fossil record of our parent spiral. Astrophysics is a science that is known to be notoriously plagued by selection effects. The present work - with a major focus in this fourth contribution on model atmosphere analyses of spectroscopic binaries and multiple star systems - aims at a volume-complete sample of about 300 nearby F-, G-, and K-type stars that particularly avoids any kinematical or chemical pre-selection from the outset. It thereby provides an unbiased record of the local stellar populations - the ancient thick disc and the much younger thin disc. On this base, the detailed individual scrutiny of the long-lived stars of both populations unveils the thick disc as a single-burst component with a local normalization of no less than 20 per cent. This enormous fraction, combined with its much larger scaleheight, implies a mass for the thick disc that is comparable to that of the thin disc. On account of its completely different mass-to-light ratio the thick disc thereby becomes the dark side of the Milky Way, an ideal major source for baryonic dark matter. This massive, ancient population consequently challenges any gradual build-up scenario for our parent spiral. Even more, on the supposition that the Galaxy is not unusual, the thick disc - as it emerges from this unbiased spectroscopic work - particularly challenges the hierarchical cold-dark-matter-dominated formation picture for spiral galaxies in general.

  6. Wave disc engine apparatus

    Energy Technology Data Exchange (ETDEWEB)

    Muller, Norbert; Piechna, Janusz; Sun, Guangwei; Parraga, Pablo-Francisco

    2018-01-02

    A wave disc engine apparatus is provided. A further aspect employs a constricted nozzle in a wave rotor channel. A further aspect provides a sharp bend between an inlet and an outlet in a fluid pathway of a wave rotor, with the bend being spaced away from a peripheral edge of the wave rotor. A radial wave rotor for generating electricity in an automotive vehicle is disclosed in yet another aspect.

  7. Spheroidal degeneration in H626R TGFBI variant lattice dystrophy: a multimodality analysis.

    Science.gov (United States)

    Lai, Kevin; Reidy, Jason; Bert, Benjamin; Milman, Tatyana

    2014-07-01

    The aim of this study was to describe clinical, imaging, molecular genetic, histopathologic, immunohistochemical, and ultrastructural characteristics of coexistent amyloid and spheroidal degeneration-type deposits in a family with histidine-626-arginine transforming growth factor beta-induced (H626R TGFBI) variant lattice dystrophy. This is a retrospective clinical-pathological and genetic analysis of one family with H626R variant lattice dystrophy. Pedigree analysis showed an autosomal dominant inheritance pattern of the disease. Examination of 3 affected family members revealed asymmetric, thick, branching lattice-like deposits associated with corneal haze. Sequencing of the TGFBI gene revealed a high-penetrance disease-causing sequence variation (H626R CAT>CGT heterozygous). Optical coherence tomography demonstrated fusiform, poorly demarcated hyperechoic stromal deposits with focal hypoechoic central regions. Histology of the corneal discs from 2 affected family members showed stromal deposits consistent with TGFBI amyloid. Some amyloid deposits contained a central nidus of spheroidal degeneration-type material that demonstrated autofluorescence, stained with elastic and Masson trichrome stains, did not stain with periodic acid-Schiff or Congo red stains, was nonbirefringent, and did not immunoreact with keratoepithelin antibodies. Transmission electron microscopy confirmed the presence of amyloid fibrils with central, electrodense, homogeneous, discrete, spheroidal degeneration-type deposits. The presence of spheroidal deposits in a subset of affected patients, variability in presentation within an individual and between family members, predominant anterior corneal stromal location and nonimmunoreactivity of deposits for keratoepithelin suggest that these deposits are degenerative in nature. The deposits may arise from ultraviolet light-altered proteins diffused from the limbus, which form a nidus for keratoepithelin deposition.

  8. Long-Term Creep Behavior of the Intervertebral Disc: Comparison between Bioreactor Data and Numerical Results

    Directory of Open Access Journals (Sweden)

    APG eCastro

    2014-11-01

    Full Text Available The Loaded Disc Culture System (LDCS is an Intervertebral Disc (IVD-oriented bioreactor developed by the VU Medical Center (VUmc, Amsterdam, The Netherlands, which has the capacity of maintaining up to 12 IVDs in culture, for approximately 3 weeks after extraction. Using this system, 8 goat IVDs were provided with the essential nutrients and submitted to compression tests without losing their biomechanical and physiological properties, for 22 days. Based on previous reports (Detiger et al., 2013; Paul et al., 2013, 2012, 4 of these IVDs were kept in physiological condition (control and the other 4 were previously injected with chondroitinase ABC (CABC, in order to promote Degenerative Disc Disease (DDD. The loading profile intercalated 16h of activity loading with 8h of loading recovery to express the standard circadian variations.The displacement behavior of these 8 IVDs along the first 2 days of the experiment was numerically reproduced, using an IVD osmo-poro-hyper-viscoelastic and fiber-reinforced Finite Element (FE model. The simulations were run on a custom FE solver (Castro et al., 2014.The analysis of the experimental results allowed concluding that the effect of the CABC injection was only significant in 2 of the 4 IVDs. The 4 control IVDs showed no signs of degeneration, as expected. In what concerns to the numerical simulations, the IVD FE model was able to reproduce the generic behavior of the two groups of goat IVDs (control and injected. However, some discrepancies were still noticed on the comparison between the injected IVDs and the numerical simulations, namely on the recovery periods. This may be justified by the complexity of the pathways for DDD, associated with the multiplicity of physiological responses to each direct or indirect stimulus. Nevertheless, one could conclude that ligaments, muscles and IVD covering membranes could be added to the FE model, in order to improve its accuracy and properly describe the recovery

  9. Changes seen on magnetic resonance imaging in the intervertebral disc space after chemonucleosis: a hypothesis concerning regeneration of the disc after chemonucleosis

    International Nuclear Information System (INIS)

    Kato, F.; Mimatsu, K.; Kawakami, N.; Miura, T.

    1992-01-01

    Measurements of the intervertebral disc space were made by magnetic resonance imaging and plain film examinations over a period of 2 years in 26 patients who had undergone chemonucleolysis. The height of the posterior portion of the disc decreased after 3 months and never recovered; the height of the anterior portion also decreased but recovered slightly over the same period. The angle of lordosis and the range of motion in the treated segment were decreased, but recovered. Marked decrease in signal from the disc was observed after 2 weeks which did not recover till 2 years after chemonucleolysis. We suspect that the disc degenerated markedly after chemonucleolysis and changed into a type of scar tissue, maturation of which could stabilize the affected segment. (orig.)

  10. Changes seen on magnetic resonance imaging in the intervertebral disc space after chemonucleosis: a hypothesis concerning regeneration of the disc after chemonucleosis

    Energy Technology Data Exchange (ETDEWEB)

    Kato, F; Mimatsu, K; Kawakami, N; Miura, T [Dept. of Orthopaedic Surgery, School of Medicine, Nagoya Univ. (Japan)

    1992-08-01

    Measurements of the intervertebral disc space were made by magnetic resonance imaging and plain film examinations over a period of 2 years in 26 patients who had undergone chemonucleolysis. The height of the posterior portion of the disc decreased after 3 months and never recovered; the height of the anterior portion also decreased but recovered slightly over the same period. The angle of lordosis and the range of motion in the treated segment were decreased, but recovered. Marked decrease in signal from the disc was observed after 2 weeks which did not recover till 2 years after chemonucleolysis. We suspect that the disc degenerated markedly after chemonucleolysis and changed into a type of scar tissue, maturation of which could stabilize the affected segment. (orig.).

  11. Adipose stem cells for intervertebral disc regeneration: Current status and concepts for the future: Tissue Engineering Review Series

    NARCIS (Netherlands)

    Hoogendoorn, R.J.W.; Lu, Z.F.; Kroeze, R.J.; Bank, R.A.; Wuisman, P.I.; Helder, M.N.

    2008-01-01

    Introduction Degenerative disc disease and emerging biological treatment approaches Stem cell sources Integration of ASC-based regenerative medicine and surgery In vitro studies Animal models Cells in disc regeneration in vivo In vivo studies Perspective Conclusions Abstract New regenerative

  12. Accretion discs around neutron stars

    International Nuclear Information System (INIS)

    Pringle, J.E.

    1982-01-01

    If the central object in the disc is a neutron star, then we do not need the disc itself to produce the X-rays. In other words, the disc structure itself is not important as long as it plays the role of depositing matter on the neutron star at a sufficient rate to produce the X-ray flux. Similarly, in the outer disc regions, the main disc luminosity comes from absorption and reradiation of X-ray photons and not from the intrinsic, viscously-produced, local energy production rate. These two points indicate why in the compact binary X-ray sources confrontation between disc theory and observations is not generally practicable. For this reason I will divide my talk into two parts: one on observational discs in which I discuss what observational evidence there is for discs in the compact X-ray sources and what the evidence can tell the theorist about disc behaviour, and the other on theoretical discs where I consider in what ways theoretical arguments can put limits or cast doubt on some of the empirical models put forward to explain the observations. (orig.)

  13. Hippocampal P3-Like Auditory Event-Related Potentials are Disrupted in a Rat Model of Cholinergic Degeneration in Alzheimer's Disease: Reversal by Donepezil Treatment

    DEFF Research Database (Denmark)

    Laursen, Bettina; Mørk, Arne; Kristiansen, Uffe

    2014-01-01

    P300 (P3) event-related potentials (ERPs) have been suggested to be an endogenous marker of cognitive function and auditory oddball paradigms are frequently used to evaluate P3 ERPs in clinical settings. Deficits in P3 amplitude and latency reflect some of the neurological dysfunctions related...... cholinergic degeneration induced by SAP. SAP-lesioned rats may constitute a suitable model to test the efficacy of pro-cognitive substances in an applied experimental setup....

  14. Total disc replacement using tissue-engineered intervertebral discs in the canine cervical spine.

    Directory of Open Access Journals (Sweden)

    Yu Moriguchi

    Full Text Available The most common reason that adults in the United States see their physician is lower back or neck pain secondary to degenerative disc disease. To date, approaches to treat degenerative disc disease are confined to purely mechanical devices designed to either eliminate or enable flexibility of the diseased motion segment. Tissue engineered intervertebral discs (TE-IVDs have been proposed as an alternative approach and have shown promise in replacing native IVD in the rodent tail spine. Here we demonstrate the efficacy of our TE-IVDs in the canine cervical spine. TE-IVD components were constructed using adult canine annulus fibrosis and nucleus pulposus cells seeded into collagen and alginate hydrogels, respectively. Seeded gels were formed into a single disc unit using molds designed from the geometry of the canine spine. Skeletally mature beagles underwent discectomy with whole IVD resection at levels between C3/4 and C6/7, and were then divided into two groups that received only discectomy or discectomy followed by implantation of TE-IVD. Stably implanted TE-IVDs demonstrated significant retention of disc height and physiological hydration compared to discectomy control. Both 4-week and 16-week histological assessments demonstrated chondrocytic cells