WorldWideScience

Sample records for optic atrophy

  1. Optic nerve atrophy

    Science.gov (United States)

    Optic atrophy; Optic neuropathy ... There are many causes of optic atrophy. The most common is poor blood flow. This is called ischemic optic neuropathy. The problem most often affects older adults. The optic ...

  2. Dominant optic atrophy

    DEFF Research Database (Denmark)

    Lenaers, Guy; Hamel, Christian; Delettre, Cécile

    2012-01-01

    DEFINITION OF THE DISEASE: Dominant Optic Atrophy (DOA) is a neuro-ophthalmic condition characterized by a bilateral degeneration of the optic nerves, causing insidious visual loss, typically starting during the first decade of life. The disease affects primary the retinal ganglion cells (RGC...

  3. Dominant optic atrophy

    Directory of Open Access Journals (Sweden)

    Lenaers Guy

    2012-07-01

    Full Text Available Abstract Definition of the disease Dominant Optic Atrophy (DOA is a neuro-ophthalmic condition characterized by a bilateral degeneration of the optic nerves, causing insidious visual loss, typically starting during the first decade of life. The disease affects primary the retinal ganglion cells (RGC and their axons forming the optic nerve, which transfer the visual information from the photoreceptors to the lateral geniculus in the brain. Epidemiology The prevalence of the disease varies from 1/10000 in Denmark due to a founder effect, to 1/30000 in the rest of the world. Clinical description DOA patients usually suffer of moderate visual loss, associated with central or paracentral visual field deficits and color vision defects. The severity of the disease is highly variable, the visual acuity ranging from normal to legal blindness. The ophthalmic examination discloses on fundoscopy isolated optic disc pallor or atrophy, related to the RGC death. About 20% of DOA patients harbour extraocular multi-systemic features, including neurosensory hearing loss, or less commonly chronic progressive external ophthalmoplegia, myopathy, peripheral neuropathy, multiple sclerosis-like illness, spastic paraplegia or cataracts. Aetiology Two genes (OPA1, OPA3 encoding inner mitochondrial membrane proteins and three loci (OPA4, OPA5, OPA8 are currently known for DOA. Additional loci and genes (OPA2, OPA6 and OPA7 are responsible for X-linked or recessive optic atrophy. All OPA genes yet identified encode mitochondrial proteins embedded in the inner membrane and ubiquitously expressed, as are the proteins mutated in the Leber Hereditary Optic Neuropathy. OPA1 mutations affect mitochondrial fusion, energy metabolism, control of apoptosis, calcium clearance and maintenance of mitochondrial genome integrity. OPA3 mutations only affect the energy metabolism and the control of apoptosis. Diagnosis Patients are usually diagnosed during their early childhood, because of

  4. Optic atrophy and glaucomatous cupping.

    Science.gov (United States)

    Radius, R L; Maumenee, A E

    1978-02-01

    We reviewed 170 eyes of 112 patients with optic atrophy from various causes. Special attention was directed towards measured cup:disk ratios as well as presence of glaucomatous-like cupping of the optic nerve head. We observed a small but significant increase in nerve head cupping in eyes with optic atrophy when compared to contralateral eyes, as well as to eyes of 50 diabetic patients. No characteristic glaucomatous disk changes were documented. We evaluated these findings with respect to possible causes of glaucomatous disk and field changes.

  5. An unusual cause of optic atrophy in a child

    Directory of Open Access Journals (Sweden)

    Nishant Kumar

    2014-01-01

    Full Text Available A 13-year-old child presenting with gross visual impairment was diagnosed as a case of optic atrophy. However, radiological investigations revealed osteopetrosis, which, though rare, can result in optic atrophy. The aim of this case report is to highlight this possibility while evaluating cases of optic atrophy in young patients.

  6. Optic atrophy and cerebral infarcts caused by methanol intoxication: MRI

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, H.H. [Dept. of Diagnostic Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei (Taiwan, Province of China); Chen, C.Y. [Dept. of Diagnostic Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei (Taiwan, Province of China); Chen, F.H. [Dept. of Diagnostic Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei (Taiwan, Province of China); Lee, C.C. [Dept. of Diagnostic Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei (Taiwan, Province of China); Chou, T.Y. [Dept. of Diagnostic Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei (Taiwan, Province of China); Zimmerman, R.A. [Children`s Hospital of Philadelphia, PA (United States). Dept. of Radiology

    1997-03-01

    We present the MRI findings of cerebral and optic pathway damage in the acute and subacute stages of methanol intoxication. In the acute stage, CT and MRI showed bilateral haemorrhagic necrosis of the corpus striatum and infarcts in the anterior and middle cerebral arterial territories. MRI in the subacute stage demonstrated atrophy of the optic chiasm and prechiasmatic optic nerves in addition to the cerebral infarcts. The patient survived, with total blindness. (orig.)

  7. Axonal loss occurs early in dominant optic atrophy

    DEFF Research Database (Denmark)

    Milea, Dan; Sander, Birgit; Wegener, Marianne

    2010-01-01

    Purpose: This study set out to investigate retinal nerve fibre layer (RNFL) thickness and best corrected visual acuity (BCVA) in relation to age in healthy subjects and patients with OPA1 autosomal dominant optic atrophy (DOA). Methods: We carried out a cross-sectional investigation of RNFL...... thickness and ganglion cell layer density in 30 healthy subjects and 10 patients with OPA1 DOA using optical coherence tomography (OCT). We then performed a regression analysis of RNFL thickness and BCVA versus age. Results: Both healthy subjects and DOA patients demonstrated a gradual reduction in RNFL...

  8. LHON and other optic nerve atrophies: the mitochondrial connection.

    Science.gov (United States)

    Howell, Neil

    2003-01-01

    The clinical, biochemical and genetic features of Leber's hereditary optic neuropathy (LHON) are reviewed. The etiology of LHON is complex, but the primary risk factor is a mutation in one of the seven mitochondrial genes that encode subunits of respiratory chain complex I. The pathogenesis of LHON is not yet understood, but one plausible model is that increased or altered mitochondrial ROS production renders the retinal ganglion cells vulnerable to apoptotic cell death. In addition to LHON, there are a large number of other optic nerve degenerative disorders including autosomal dominant optic atrophy, the toxic/nutritional optic neuropathies and glaucoma. A review of the recent scientific literature suggests that these disorders also involve mitochondrial dysfunction or altered mitochondrial signaling pathways in their pathogenesis. This mitochondrial link provides new avenues of experimental investigation to these major causes of loss of vision.

  9. Imaging of the Macula Indicates Early Completion of Structural Deficit in Autosomal-Dominant Optic Atrophy

    DEFF Research Database (Denmark)

    Rönnbäck, Cecilia; Milea, Dan; Larsen, Michael

    2013-01-01

    Optical coherence tomography (OCT) enables 3-dimensional imaging of the retina, including the layer of ganglion cells that supplies the optic nerve with its axons. We tested OCT as means of diagnosing and phenotyping autosomal-dominant optic atrophy (ADOA).......Optical coherence tomography (OCT) enables 3-dimensional imaging of the retina, including the layer of ganglion cells that supplies the optic nerve with its axons. We tested OCT as means of diagnosing and phenotyping autosomal-dominant optic atrophy (ADOA)....

  10. Optic nerve atrophy and retinal nerve fibre layer thinning following optic neuritis: evidence that axonal loss is a substrate of MRI-detected atrophy.

    Science.gov (United States)

    Trip, S Anand; Schlottmann, Patricio G; Jones, Stephen J; Li, Wai-Yung; Garway-Heath, David F; Thompson, Alan J; Plant, Gordon T; Miller, David H

    2006-05-15

    Magnetic resonance imaging (MRI) measures of brain atrophy are often considered to be a marker of axonal loss in multiple sclerosis (MS) but evidence is limited. Optic neuritis is a common manifestation of MS and results in optic nerve atrophy. Retinal nerve fibre layer (RNFL) imaging is a non-invasive way of detecting axonal loss following optic neuritis. We hypothesise that if the optic nerve atrophy that develops following optic neuritis is contributed to by axonal loss, it will correlate with thinning of the RNFL. Twenty-five patients were studied at least 1 year after a single unilateral attack of optic neuritis without recurrence, with a selection bias towards incomplete recovery. They had MR quantification of optic nerve cross-sectional area and optic nerve lesion length, as well as optical coherence tomography (OCT) measurement of mean RNFL thickness and macular volume, quantitative visual testing, and visual evoked potentials (VEPs). Fifteen controls were also studied. Significant optic nerve atrophy (mean decrease 30% versus controls), RNFL thinning (mean decrease 33% versus controls), and macular volume loss occurred in patients' affected eyes when compared with patients' unaffected eyes and healthy controls. The optic nerve atrophy was correlated with the RNFL thinning, macular volume loss, visual acuity, visual field mean deviation, and whole field VEP amplitude but not latency. These findings suggest that axonal loss contributes to optic nerve atrophy following a single attack of optic neuritis. By inference, axonal loss due to other post-inflammatory brain lesions is likely to contribute to the global MRI measure of brain atrophy in multiple sclerosis.

  11. Parapapillary atrophy and optic disc region assessment (PANDORA): retinal imaging tool for assessment of the optic disc and parapapillary atrophy

    Science.gov (United States)

    Lu, Cheng-Kai; Tang, Tong Boon; Laude, Augustinus; Dhillon, Baljean; Murray, Alan F.

    2012-10-01

    We describe a computer-aided measuring tool, named parapapillary atrophy and optic disc region assessment (PANDORA), for automated detection and quantification of both the parapapillary atrophy (PPA) and the optic disc (OD) regions in two-dimensional color retinal fundus images. The OD region is segmented using a combination of edge detection and ellipse fitting methods. The PPA region is identified by the presence of bright pixels in the temporal zone of the OD, and it is segmented using a sequence of techniques, including a modified Chan-Vese approach, thresholding, scanning filter, and multiseed region growing. PANDORA has been tested with 133 color retinal images (82 with PPA; 51 without PPA) drawn randomly from the Lothian Birth Cohort (LBC) database, together with a "ground truth" estimate from an ophthalmologist. The PPA detection rate is 89.47% with a sensitivity of 0.83 and a specificity of 1. The mean accuracy in defining the OD region is 81.31% (SD=10.45) when PPA is present and 95.32% (SD=4.36) when PPA is absent. The mean accuracy in defining the PPA region is 73.57% (SD=11.62). PANDORA demonstrates for the first time how to quantify the OD and PPA regions using two-dimensional fundus images, enabling ophthalmologists to study ocular diseases related to PPA using a standard fundus camera.

  12. Optic atrophy differentially diagnosed as spinocerebellar ataxia from Leber hereditary optic neuropathy by gene mutation analysis.

    Science.gov (United States)

    Song, Y P; Chen, Z S; Mo, G Y; Ding, Q; Zhu, L; Yan, M

    2012-01-01

    Optic atrophy describes a group of diseases of retinal ganglion cells and axons that eventually lead to loss of vision. Optic atrophy has both congenital and acquired causes, and its diagnosis (or differential diagnosis) is complicated. This case report describes a 20-year-old man who presented with a 1-year history of progressive vision loss in both eyes and no obvious systemic symptoms. Fundus examination revealed bilateral optic atrophy. Based on clinical characteristics, visual field analysis and pattern visual evoked potential examination, the presumptive diagnosis was Leber hereditary optic neuropathy (LHON). Analysis of mitochondrial DNA indicated the absence of all of three common mutations associated with LHON (m.3460G>A, m.11778G>A, m.14484T>C). Detailed questioning of the patient revealed a history of prolonged language development and poor balance. Neurological examination indicated abnormal co-ordination, suggesting the presence of inherited spinocerebellar ataxia (SCA). Analysis of the SCA7 gene revealed a high number of trinucleotide repeats [(CAG)(n), n > 64], confirming the diagnosis of SCA. The aetiology of optic atrophies is complicated and the molecular genetic detection approach provides the best information for diagnosing these diseases.

  13. Optic atrophy 1-dependent mitochondrial remodeling controls steroidogenesis in trophoblasts.

    Science.gov (United States)

    Wasilewski, Michał; Semenzato, Martina; Rafelski, Susanne M; Robbins, Jennifer; Bakardjiev, Anna I; Scorrano, Luca

    2012-07-10

    During human pregnancy, placental trophoblasts differentiate and syncytialize into syncytiotrophoblasts that sustain progesterone production [1]. This process is accompanied by mitochondrial fragmentation and cristae remodeling [2], two facets of mitochondrial apoptosis, whose molecular mechanisms and functional consequences on steroidogenesis are unclear. Here we show that the mitochondria-shaping protein Optic atrophy 1 (Opa1) controls efficiency of steroidogenesis. During syncytialization of trophoblast BeWo cells, levels of the profission mitochondria-shaping protein Drp1 increase, and those of Opa1 and mitofusin (Mfn) decrease, leading to mitochondrial fragmentation and cristae remodeling. Manipulation of the levels of Opa1 reveal an inverse relationship with the efficiency of steroidogenesis in trophoblasts and in mouse embryonic fibroblasts where the mitochondrial steroidogenetic pathway has been engineered. In an in vitro assay, accumulation of cholesterol is facilitated in the inner membrane of isolated mitochondria lacking Opa1. Thus, Opa1-dependent inner membrane remodeling controls efficiency of steroidogenesis.

  14. Diabetes mellitus, diabetes insipidus, optic atrophy, and deafness: A case of Wolfram (DIDMOAD) syndrome.

    Science.gov (United States)

    Maleki, Nasrollah; Bashardoust, Bahman; Zakeri, Anahita; Salehifar, Azita; Tavosi, Zahra

    2015-01-01

    To report a case of Wolfram syndrome (WS) characterized by diabetes mellitus, diabetes insipidus, progressive optic atrophy, and deafness. A 19-year-old female patient, a known case of diabetes mellitus type I from six years before, presented with progressive vision loss since four years earlier. On fundoscopic examination, she had bilateral optic atrophy without diabetic retinopathy. The patient also had diabetes insipidus, neurosensory deafness, and neurogenic bladder. WS should be considered a differential diagnosis in patients with diabetes mellitus who present with optic atrophy, and it is necessary to perform a hearing test as well as collecting 24-h urine output.

  15. Neurocysticercosis (NCC) with Hydrocephalus, Optic Atrophy and Vision Loss: A Rare Presentation.

    Science.gov (United States)

    Chaudhary, Nagendra; Mahato, Shyam Kumar; Khan, Salamat; Pathak, Santosh; Bhatia, B D

    2015-02-01

    Neurocysticercosis (NCC) is one of the most common parasitic infestations (Taenia solium) of central nervous system (CNS) in children. Seizures are the common presenting symptoms. Hydrocephalus and optic atrophy are rare complications which may require neurosurgical interventions. We report a case of NCC with hydrocephalus and bilateral optic atrophy associated with vision loss in a Nepalese patient who improved with anti-parasitic therapy followed by ventriculo-peritoneal (VP) shunting.

  16. NR2F1 Mutations Cause Optic Atrophy with Intellectual Disability

    NARCIS (Netherlands)

    Bosch, D.G.M.; Boonstra, F.N.; Gonzaga-Jauregui, C.; Xu, M.; Ligt, J. de; Jhangiani, S.; Wiszniewski, W.; Muzny, D.M.; Yntema, H.G.; Pfundt, R.P.; Vissers, L.E.L.M.; Spruijt, L.; Blokland, E.A.W.; Chen, C.A.; Lewis, R.A.; Tsai, S.Y.; Gibbs, R.A.; Tsai, M.J.; Lupski, J.R.; Zoghbi, H.Y.; Cremers, F.P.M.; Vries, B. de; Schaaf, C.P.

    2014-01-01

    Optic nerve atrophy and hypoplasia can be primary disorders or can result from trans-synaptic degeneration arising from cerebral visual impairment (CVI). Here we report six individuals with CVI and/or optic nerve abnormalities, born after an uneventful pregnancy and delivery, who have either de novo

  17. Genomic deletions in OPA1 in Danish patients with autosomal dominant optic atrophy

    DEFF Research Database (Denmark)

    Almind, Gitte J; Grønskov, Karen; Milea, Dan;

    2011-01-01

    Autosomal dominant optic atrophy (ADOA, Kjer disease, MIM #165500) is the most common form of hereditary optic neuropathy. Mutations in OPA1 located at chromosome 3q28 are the predominant cause for ADOA explaining between 32 and 89% of cases. Although deletions of OPA1 were recently reported...

  18. Clinical variability in hereditary optic neuropathies: Two novel mutations in two patients with dominant optic atrophy and Wolfram syndrome.

    Science.gov (United States)

    Galvez-Ruiz, Alberto

    2015-01-01

    Dominant optic atrophy (DOA) and Wolfram syndrome share a great deal of clinical variability, including an association with hearing loss and the presence of optic atrophy at similar ages. The objective of this paper was to discuss the phenotypic variability of these syndromes with respect to the presentation of two clinical cases. We present two patients, each with either DOA or Wolfram syndrome, and contribute to the research literature through our findings of two novel mutations. The overlapping of several clinical characteristics in hereditary optic neuropathies can complicate the differential diagnosis. Future studies are needed to better determine the genotype-phenotype correlation for these diseases.

  19. Optic atrophy, cataracts, lipodystrophy/lipoatrophy, and peripheral neuropathy caused by a de novo OPA3 mutation

    Science.gov (United States)

    Bourne, Stephanie C.; Townsend, Katelin N.; Shyr, Casper; Matthews, Allison; Lear, Scott A.; Attariwala, Raj; Lehman, Anna; Wasserman, Wyeth W.; van Karnebeek, Clara; Sinclair, Graham; Vallance, Hilary; Gibson, William T.

    2017-01-01

    We describe a woman who presented with cataracts, optic atrophy, lipodystrophy/lipoatrophy, and peripheral neuropathy. Exome sequencing identified a c.235C > G p.(Leu79Val) variant in the optic atrophy 3 (OPA3) gene that was confirmed to be de novo. This report expands the severity of the phenotypic spectrum of autosomal dominant OPA3 mutations. PMID:28050599

  20. Relationship Between Peripapillary Atrophy and Optic Disc Parameters in Eyes with Primary Open-Angle Glaucoma

    Directory of Open Access Journals (Sweden)

    Tamer Takmaz

    2011-10-01

    Full Text Available Pur po se: To evaluate the relationship between peripapillary atrophy and optic disc parameters measured by Heidelberg Retina Tomography (HRT and visual field findings in eyes with primary open-angle glaucoma. Methods: Thirty eyes of 30 patients with primary open-angle glaucoma were included in this study. In addition to routine ophthalmic examination, optic disc parameters were evaluated with HRT and visual field was evaluated with Humphrey Visual Field Analyzer. Peripapillary atrophy area was measured by drawing contour of the border of the peripapillary atrophy (Beta zone: chorioretinal atrophy area in which sclera and big choroid blood vessels were seen in HRT. The relationship between this atrophy area and both visual field findings and optic disc parameters was evaluated. Pearson’s correlation coefficient and statistical significance were calculated. Results: The mean age of the patients was 61.4±8.9 years. Measured beta zone area was 0.65±0.40 mm2. Mean deviation measured with Humphrey Visual Field Analyzer was -8.6±8.2 dB and pattern standard deviation was 6.4±4.6. Statistically significant correlation between peripapillary atrophy area and age (PC=0.495, p=0.005, mean deviation (PC=-0.554, p=0.001, cup area (PC=0.382, p=0.037, cup/disc area ratio (PC=0.562, p=0.001, linear cup/disc area ratio (PC=0.422, p=0.020 and mean retinal nerve fiber layer thickness (PC=-0.360, p=0.047 was found. There was not a significant relationship between other optic disc parameters and peripapillary atrophy area (p>0.05. Conclusion: Significant correlation was seen between peripapillary beta zone atrophy area and some important optic disk parameters in primary open-angle glaucoma patients. More meaningful information would have been obtained if sectoral investigation of the optic disc was performed. (Turk J Ophthalmol 2011; 41: 291-4

  1. Macular sensitivity and fixation patterns in patients with autosomal dominant optic atrophy

    DEFF Research Database (Denmark)

    Rönnbäck, Cecilia; Larsen, Michael

    2014-01-01

    INTRODUCTION: The objective of this study was to test macular sensitivity, fixation stability and fixation location using microperimetry in patients with autosomal dominant optic atrophy (ADOA) and mutation-free relatives. MATERIAL AND METHODS: This was a cross-sectional study of 43 patients...

  2. Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2

    NARCIS (Netherlands)

    S. Zuchner; P. de Jonghe; A. Jordanova; K.G. Claeys; V. Guergueltcheva; S. Cherninkova; S.R. Hamilton; G. van Stavern; K.M. Krajewski; J. Stajich; I. Tournev; K. Verhoeven; C.T. Langerhorst; M. de Visser; F. Baas; T. Bird; V. Timmerman; M. Shy; J.M. Vance

    2006-01-01

    Objective: Charcot-Marie-Tooth (CMT) neuropathy with visual impairment due to optic atrophy has been designated as hereditary motor and sensory neuropathy type VI (HMSN VI). Reports of affected families have indicated autosomal dominant and recessive forms, but the genetic cause of this disease has

  3. A longitudinal comparison of spectral-domain optical coherence tomography and fundus autofluorescence in geographic atrophy.

    Science.gov (United States)

    Simader, Christian; Sayegh, Ramzi G; Montuoro, Alessio; Azhary, Malek; Koth, Anna Lucia; Baratsits, Magdalena; Sacu, Stefan; Prünte, Christian; Kreil, David P; Schmidt-Erfurth, Ursula

    2014-09-01

    To identify reliable criteria based on spectral-domain optical coherence tomography (SD OCT) to monitor disease progression in geographic atrophy attributable to age-related macular degeneration (AMD) compared with lesion size determination based on fundus autofluorescence (FAF). Prospective longitudinal observational study. setting: Institutional. study population: A total of 48 eyes in 24 patients with geographic atrophy. observation procedures: Eyes with geographic atrophy were included and examined at baseline and at months 3, 6, 9, and 12. At each study visit best-corrected visual acuity (BCVA), FAF, and SD OCT imaging were performed. FAF images were analyzed using the region overlay device. Planimetric measurements in SD OCT, including alterations or loss of outer retinal layers and the RPE, as well as choroidal signal enhancement, were performed with the OCT Toolkit. main outcome measures: Areas of interest in patients with geographic atrophy measured from baseline to month 12 by SD OCT compared with the area of atrophy measured by FAF. Geographic atrophy lesion size increased from 8.88 mm² to 11.22 mm² based on quantitative FAF evaluation. Linear regression analysis demonstrated that results similar to FAF planimetry for determining lesion progression can be obtained by measuring the areas of outer plexiform layer thinning (adjusted R(2) = 0.93), external limiting membrane loss (adjusted R(2) = 0.89), or choroidal signal enhancement (R(2) = 0.93) by SD OCT. SD OCT allows morphologic markers of disease progression to be identified in geographic atrophy and may improve understanding of the pathophysiology of atrophic AMD. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Optical coherence tomography of macular atrophy associated with microcephaly and presumed intrauterine Zika virus infection

    Directory of Open Access Journals (Sweden)

    Adriana Gondim de Moura Campos

    Full Text Available ABSTRACT This case report describes the retinal optical coherence tomography (OCT findings in a microcephalic infant with macular atrophy presumably caused by intrauterine Zika virus infection. OCT demonstrated atrophy of the outer retinal layers and choriocapillaris, including the outer nuclear layer and ellipsoid zone, associated with retinal pigment epithelium hyper-reflectivity and increased OCT penetration into deeper layers of the choroid and sclera. A major concern associated with this infection is the apparent increased incidence of microcephaly in fetuses born to mothers infected with the Zika virus. It is becoming increasingly difficult to ignore the upsurge in congenital microcephaly observed in Brazil. Recently, ocular findings in infants with microcephaly associated with intrauterine Zika virus infection have been described. This is the first report of OCT imaging of macular atrophy in a child with presumed Zika virus infection-associated microcephaly.

  5. A recurrent deletion mutation in OPA1 causes autosomal dominant optic atrophy in a Chinese family

    Science.gov (United States)

    Zhang, Liping; Shi, Wei; Song, Liming; Zhang, Xiao; Cheng, Lulu; Wang, Yanfang; Ge, Xianglian; Li, Wei; Zhang, Wei; Min, Qingjie; Jin, Zi-Bing; Qu, Jia; Gu, Feng

    2014-11-01

    Autosomal dominant optic atrophy (ADOA) is the most frequent form of hereditary optic neuropathy and occurs due to the degeneration of the retinal ganglion cells. To identify the genetic defect in a family with putative ADOA, we performed capture next generation sequencing (CNGS) to screen known retinal disease genes. However, six exons failed to be sequenced by CNGS in optic atrophy 1 gene (OPA1). Sequencing of those exons identified a 4 bp deletion mutation (c.2983-1_2985del) in OPA1. Furthermore, we sequenced the transcripts of OPA1 from the patient skin fibroblasts and found there is six-nucleotide deletion (c.2984-c.2989, AGAAAG). Quantitative-PCR and Western blotting showed that OPA1 mRNA and its protein expression have no obvious difference between patient skin fibroblast and control. The analysis of protein structure by molecular modeling suggests that the mutation may change the structure of OPA1 by formation of an alpha helix protruding into an existing pocket. Taken together, we identified an OPA1 mutation in a family with ADOA by filling the missing CNGS data. We also showed that this mutation affects the structural intactness of OPA1. It provides molecular insights for clinical genetic diagnosis and treatment of optic atrophy.

  6. Detecting Optic Atrophy in Multiple Sclerosis Patients Using New Colorimetric Analysis Software: From Idea to Application.

    Science.gov (United States)

    Bambo, Maria Pilar; Garcia-Martin, Elena; Perez-Olivan, Susana; Larrosa-Povés, José Manuel; Polo-Llorens, Vicente; Gonzalez-De la Rosa, Manuel

    2016-01-01

    Neuro-ophthalmologists typically observe a temporal pallor of the optic disc in patients with multiple sclerosis. Here, we describe the emergence of an idea to quantify these optic disc color changes in multiple sclerosis patients. We recruited 12 multiple sclerosis patients with previous optic neuritis attack and obtained photographs of their optic discs. The Laguna ONhE, a new colorimetric software using hemoglobin as the reference pigment in the papilla, was used for the analysis. The papilla of these multiple sclerosis patients showed greater pallor, especially in the temporal sector. The software detected the pallor and assigned hemoglobin percentages below normal reference values. Measurements of optic disc hemoglobin levels obtained with the Laguna ONhE software program had good ability to detect optic atrophy and, consequently, axonal loss in multiple sclerosis patients. This new technology is easy to implement in routine clinical practice.

  7. [STUDY EFFECT OF ASSOSIATED PATHOLOGY ON THE DEVELOPMENT OF OPTIC NERVE ATROPHY].

    Science.gov (United States)

    Vasyuta, V A

    2015-01-01

    Studied effect of assosiated pathology on the development of optic nerve atrophy (ONA). The basis of population study was comparison some factors in the groups with ONA and without ONA (analysis case-control) and evaluation of relative risk. Analysis showed that the risk of development of ONA increased in coronary heart disease, hypertension, diabetes, atherosclerosis. A functional-organizational model of care for patients with ONA was proposed.

  8. Marinesco-Sjogren Syndrome With Sensori Neural Deafness And Primary Optic Atrophy

    Directory of Open Access Journals (Sweden)

    Aleem M A

    1999-01-01

    Full Text Available Marinesco-Sjogren syndrome (MSS is a rare genetically determined disorder characterised by bilateral cataract, cerebellar ataxia and mental deficiency. The pattern of inheritance is autosomal recessive but it may be variable. In MSS association of hyperlactacidaemia and hypopyruvicaemia, a defective oxidative phosphorylation in mitochondria, is supposed. We are reporting three patients of MSS along with sensorineural deafness and optic atrophy from a single Indian family.

  9. Novel OPA1 missense mutation in a family with optic atrophy and severe widespread neurological disorder.

    Science.gov (United States)

    Liskova, Petra; Ulmanova, Olga; Tesina, Petr; Melsova, Hana; Diblik, Pavel; Hansikova, Hana; Tesarova, Marketa; Votruba, Marcela

    2013-05-01

    To identify the underlying molecular genetic cause in a Czech family with optic atrophy, deafness, ptosis, ophthalmoplegia, polyneuropathy and ataxia transmitted as an autosomal dominant trait. Ophthalmological and neurological examination followed by molecular genetic analyses. Seven family members were clinically affected. There was a variable but progressive visual, hearing and neurological disability across the family as a whole. The majority of subjects presented with impairment of visual function and a variable degree of ptosis and/or ophthalmoplegia from the first to the third decade of life. Deafness, neuropathy and ataxia appeared later, in the third and fourth decade. Migraine, tachycardia, intention tremor, nystagmus and cervical dystonia were observed in isolated individuals. A significant overall feature was the high level of neurological disability leading to 3 of 4 members being unable to walk or stand unaided before the age of 60 years. A novel missense mutation c.1345A>C (p.Thr449Pro) in OPA1 segregating with the disease phenotype over three generations was detected. In silico analysis supported pathogenicity of the identified sequence variant. Our work expands the spectrum of mutation in OPA1, which may lead to severe multisystem neurological disorder. The molecular genetic cause of dominant optic atrophy in the Czech population is reported for the first time. We propose that regular cardiac follow-up in patients diagnosed with dominant optic atrophy and widespread neurological disease should be considered. © 2013 The Authors. Acta Ophthalmologica © 2013 Acta Ophthalmologica Scandinavica Foundation.

  10. Etiology and clinical profile of childhood optic nerve atrophy at a tertiary eye care center in South India

    Directory of Open Access Journals (Sweden)

    Supriya Chinta

    2014-01-01

    Full Text Available Background: Optic nerve atrophy is an important ophthalmological sign that may be associated with serious systemic conditions having a significant bearing on the overall morbidity of the child. Studies specific to etiology of childhood optic atrophy are scarce, this being the first such study from India to the best of our knowledge. Aim: The aim was to analyze the clinical features and etiology of diagnosed cases of optic nerve atrophy in children <16 years of age. Materials and Methods: Retrospective review of records of children diagnosed with optic nerve atrophy between the ages of 0 and 16 years from 2006 to 2011. Results: A total of 324 children (583 eyes were identified. Among these 160 (49% presented with defective vision, 71 (22% with strabismus, 18 (6% with only nystagmus. Rest had a combination of two or three of the above symptoms. Sixty-five patients (20% had a unilateral affection. Hypoxic ischemic encephalopathy seen in 133 patients (41% was the most frequent cause of childhood optic atrophy, followed by idiopathic in 98 (30%, hydrocephalus in 24 (7%, compressive etiology in 18 (5%, infective in 19 (6%, congenital in 6 (2%, inflammatory in 5 (2% patients, respectively. Conclusion: Hypoxic ischemic encephalopathy appears to be the most common cause of optic atrophy in children in this series. The most common presenting complaint was defective vision.

  11. The mechanism of disc pallor in experimental optic atrophy. A fluorescein angiographic study.

    Science.gov (United States)

    Radius, R L; Anderson, D R

    1979-03-01

    Ascending optic atrophy was produced in 13 eyes of owl monkeys (Aotestrivirgatus) by retinal photocoagulation. Color fundus photography and fluorescein angiography were used to study and document the evolution of nerve head abnormalities. The optic nerve heads were also studied histopathologically. Except in certain instances of early transient (relative) filling defects, normal disc fluorescent patterns were preserved, despite clinically apparent optic nerve head pallor. Sectorial defects did not persist into the later phases of the angiogram. These findings may suggest a reduced blood flow, but neither angiographic nor histopathologic studies detected a reduced vascularity in the atrophic optic nerve. Pallor of the optic nerve head seems to result from alterations in the tissue reflectance and translucency following axonal loss and glial reorganization rather than from a decreased microvascular bed.

  12. OPA1-related dominant optic atrophy is not strongly influenced by mitochondrial DNA background

    Directory of Open Access Journals (Sweden)

    Amati-Bonneau Patrizia

    2009-07-01

    Full Text Available Abstract Background Leber's hereditary optic neuropathy (LHON and autosomal dominant optic atrophy (ADOA are the most frequent forms of hereditary optic neuropathies. LHON is associated with mitochondrial DNA (mtDNA mutations whereas ADOA is mainly due to mutations in the OPA1 gene that encodes a mitochondrial protein involved in the mitochondrial inner membrane remodeling. A striking influence of mtDNA haplogroup J on LHON expression has been demonstrated and it has been recently suggested that this haplogroup could also influence ADOA expression. In this study, we have tested the influence of mtDNA backgrounds on OPA1 mutations. Methods To define the relationships between OPA1 mutations and mtDNA backgrounds, we determined the haplogroup affiliation of 41 French patients affected by OPA1-related ADOA by control-region sequencing and RFLP survey of their mtDNAs. Results The comparison between patient and reference populations did not revealed any significant difference. Conclusion Our results argue against a strong influence of mtDNA background on ADOA expression. These data allow to conclude that OPA1 could be considered as a "severe mutation", directly responsible of the optic atrophy, whereas OPA1-negative ADOA and LHON mutations need an external factor(s to express the pathology (i.e. synergistic interaction with mitochondrial background.

  13. A novel OPA1 mutation in a Chinese family with autosomal dominant optic atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Juanjuan; Yuan, Yimin; Lin, Bing; Feng, Hao; Li, Yan [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou 325027, Zhejiang (China); Dai, Xianning; Zhou, Huihui [Attardi Institute of Mitochondrial Biomedicine and Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou 325035, Zhejiang (China); Dong, Xujie [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou 325027, Zhejiang (China); Liu, Xiao-Ling, E-mail: lxl@mail.eye.ac.cn [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou 325027, Zhejiang (China); Guan, Min-Xin, E-mail: min-xin.guan@cchmc.org [Attardi Institute of Mitochondrial Biomedicine and Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou 325035, Zhejiang (China); Institute of Genetics, Zhejiang University, Hangzhou, Zhejiang 310012 (China); Division of Human Genetics, Cincinnati Children' s Hospital Medical Center, OH 45229 (United States)

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer We report the characterization of a four-generation large Chinese family with ADOA. Black-Right-Pointing-Pointer We find a new heterozygous mutation c.C1198G in OPA1 gene which may be a novel pathogenic mutation in this pedigree. Black-Right-Pointing-Pointer We do not find any mitochondrial DNA mutations associated with optic atrophy. Black-Right-Pointing-Pointer Other factors may also contribute to the phenotypic variability of ADOA in this pedigree. -- Abstract: A large four-generation Chinese family with autosomal dominant optic atrophy (ADOA) was investigated in the present study. Eight of the family members were affected in this pedigree. The affected family members exhibited early-onset and progressive visual impairment, resulting in mild to profound loss of visual acuity. The average age-at-onset was 15.9 years. A new heterozygous mutation c.C1198G was identified by sequence analysis of the 12th exon of the OPA1 gene. This mutation resulted in a proline to alanine substitution at codon 400, which was located in an evolutionarily conserved region. This missense mutation in the GTPase domain was supposed to result in a loss of function for the encoded protein and act through a dominant negative effect. No other mutations associated with optic atrophy were found in our present study. The c.C1198G heterozygous mutation in the OPA1 gene may be a novel key pathogenic mutation in this pedigree with ADOA. Furthermore, additional nuclear modifier genes, environmental factors, and psychological factors may also contribute to the phenotypic variability of ADOA in this pedigree.

  14. Direct optical activation of skeletal muscle fibres efficiently controls muscle contraction and attenuates denervation atrophy.

    Science.gov (United States)

    Magown, Philippe; Shettar, Basavaraj; Zhang, Ying; Rafuse, Victor F

    2015-10-13

    Neural prostheses can restore meaningful function to paralysed muscles by electrically stimulating innervating motor axons, but fail when muscles are completely denervated, as seen in amyotrophic lateral sclerosis, or after a peripheral nerve or spinal cord injury. Here we show that channelrhodopsin-2 is expressed within the sarcolemma and T-tubules of skeletal muscle fibres in transgenic mice. This expression pattern allows for optical control of muscle contraction with comparable forces to nerve stimulation. Force can be controlled by varying light pulse intensity, duration or frequency. Light-stimulated muscle fibres depolarize proportionally to light intensity and duration. Denervated triceps surae muscles transcutaneously stimulated optically on a daily basis for 10 days show a significant attenuation in atrophy resulting in significantly greater contractile forces compared with chronically denervated muscles. Together, this study shows that channelrhodopsin-2/H134R can be used to restore function to permanently denervated muscles and reduce pathophysiological changes associated with denervation pathologies.

  15. Retinal vessel diameters decrease with macular ganglion cell layer thickness in autosomal dominant optic atrophy and in healthy subjects

    DEFF Research Database (Denmark)

    Rönnbäck, Cecilia; Grønskov, Karen; Larsen, Michael

    2014-01-01

    PURPOSE: To investigate retinal trunk vessel diameters in subjects with autosomal dominant optic atrophy (ADOA) and mutation-free healthy relatives. METHODS: This cross-sectional study included 52 ADOA patients with the optic atrophy 1 (OPA1) exon 28 (c.2826_2836delinsGGATGCTCCA) mutation (age 8...... ganglion cell-inner plexiform layer (GC-IPL) thickness (p = 0.0017 and p = 0.0057, respectively). CONCLUSION: Narrow retinal arteries and veins were associated not only with the severity of ADOA but with ganglion cell volume in patients with ADOA and in healthy subjects. This suggests that narrow vessels...

  16. Neither retinal nor brain atrophy can be shown in patients with isolated unilateral optic neuritis at the time of presentation

    DEFF Research Database (Denmark)

    Kallenbach, Klaus; Sander, Birgit; Tsakiri, Anna;

    2011-01-01

    BACKGROUND: Acute monosymptomatic optic neuritis (ON) may be the earliest manifestation of multiple sclerosis (MS). Atrophy has been shown to be a prominent feature of MS with great impact on disability. OBJECTIVES: The objectives of this study were to evaluate retinal and brain atrophy and possi......BACKGROUND: Acute monosymptomatic optic neuritis (ON) may be the earliest manifestation of multiple sclerosis (MS). Atrophy has been shown to be a prominent feature of MS with great impact on disability. OBJECTIVES: The objectives of this study were to evaluate retinal and brain atrophy...... and possible associations at the earliest possible stages of MS. METHODS: In a prospective observational cohort study we included 60 untreated patients with monosymptomatic ON and 19 healthy volunteers. Unaffected fellow eyes were examined with optical coherence tomography (OCT) and normalized brain volumes...... were calculated based on MRI. Additionally, visual evoked potentials (VEPs) were recorded. RESULTS: Neither OCT measurements nor brain volume measures revealed signs of localized or generalized atrophy in patients compared with healthy volunteers. Stratification of patients into high risk based...

  17. Microcystic Changes in the Retinal Internal Nuclear Layer Associated with Optic Atrophy: A Prospective Study

    Directory of Open Access Journals (Sweden)

    Benjamin Wolff

    2014-01-01

    Full Text Available Purpose. This study aimed at assessing the prevalence of pathologies presenting retinal inner nuclear layer (RINL microcystic perimacular changes associated with optic nerve atrophy (OA. The charts of patients presenting a significant defect of the Retinal Nerve Fiber Layer (RNFL were included prospectively in this study. Patients were classified according to the etiology of the RNFL defect. Two hundred and one eyes of 138 patients were enrolled in this analysis. Retinal images obtained showed the typical hyporeflective perifoveal crescent-shaped lesion composed of small round hyporeflective microcysts confined to the RINL in 35.3% of the eyes. Those findings were found in 75% of eyes presenting hereditary OA, 50% of eyes presenting ischemic optic neuritis, 50% of eyes with drusen of the optic nerve (ON, 44.4% of eyes presenting a compressive OA, 32% of eyes presenting inflammatory optic neuropathy from multiple sclerosis, 18.5% of eyes presenting OA from undetermined origin, and 17.6% of eyes having primary open-angle glaucoma. This study demonstrates that microcystic changes in RINL are not specific to a disease but are found in OA of various etiologies. Moreover, their incidence was found to be dependent upon the cause of OA, with the highest incidence occurring in genetic OA.

  18. Application effect of hyperbaric oxygen in the patients with optic atrophy and influence for the hemodynamic parameters

    Directory of Open Access Journals (Sweden)

    Kun Zhang

    2015-01-01

    Full Text Available AIM: To observe the application effect of hyperbaric oxygen in the patients with optic atrophy and influence degree for the hemodynamic parameters.METHODS: Fifty patients with optic atrophy in our hospital from January 2012 to January 2014 were objected, they were randomly divided into control group(conventional optic atrophy treatment groupand observation group(conventional treatment and hyperbaric oxygen treatment group, each group was 25 cases. Statistical analysis of two group before and after treatment eyesight, vision acuity, visual field defect and ophthalmic artery, central retinal artery blood flow parameters were undergone.RESULTS: The sight, visual field sensitivity and field vision defect of observation group were all better than those of control group at first, second and third course after the treatment, arteriae ophthalmica and arteriae centralis retinae EDV and PSV were all higher than those of control group, PI and RI were all lower than those of control group were all significant differences(PCONCLUSION: The application effect of hyperbaric oxygen in the patients with optic atrophy is better, and the influence of treatment method for the ocular hemodynamic parameters are more active.

  19. Correlation between Retinal Nerve Fiber Layer Thickness by Optical Coherence Tomography and Perimetric Parameters in Optic Atrophy

    Directory of Open Access Journals (Sweden)

    Mostafa Soltan-Sanjari

    2008-12-01

    Full Text Available

    PURPOSE: To investigate the correlation between retinal nerve fiber layer (RNFL thickness determined by optical coherence tomography (OCT and visual field (VF parameters in patients with optic atrophy. METHODS: This study was performed on 35 eyes of 28 patients with optic atrophy. RNFL thickness was measured by OCT (Carl Zeiss, Jena, Germany and automated perimetry was performed using the Humphrey Field Analyzer (Carl Zeiss, Jena, Germany. The correlation between RNFL thickness and VF parameters was evaluated. RESULTS: Mean global RNFL thickness was 44.9±27.5 µm which was significantly correlated with mean deviation score on automated perimetry (r=0.493, P=0.003; however, no significant correlation was observed between visual field pattern standard deviation and the corresponding quadrantic RNFL thickness. In a similar manner, no significant association was found between visual acuity and RNLF thickness. CONCLUSION: Mean global RNFL thickness as determined by OCT seems to be correlated with VF defect depth as represented by the mean deviation score on Humphrey VF testing. OCT may be used as an objective diagnostic tool in the evaluation of patients with optic atrophy.

  20. Charles Bonnet Syndrome Following Trans-Sphenoidal Adenomectomy without Optic Nerve Atrophy

    Science.gov (United States)

    Park, Jang-Ho; Ahn, Joon-Ho; Park, Jun-Bum

    2016-01-01

    Charles Bonnet syndrome (CBS) can develop after trans-sphenoidal adenomectomy (TSA); however, the neural mechanisms remain unknown. Sensory deprivation and releasing phenomenon are both hypothetical explanations for this condition; however, there is no definite evidence that strongly supports either supposition. We report the first case of CBS after TSA without optic nerve atrophy. Postoperatively, the patient's vision seemed to be relatively well preserved, apart from the left-side hemianopsia in the right eye. Distinctive visual hallucinations only appeared when his eyes were closed, and these responded to quetiapine in a dose-dependent manner. Dose dependent change in colors and formation of hallucination was reported. Two weeks after quetiapine initiation, the patient's CBS was completely resolved. This unique case suggests that blocking sensory input from the periphery is more critical than neural damage of the bottom-up connection to the visual association cortex. In addition, quetiapine should be considered as a specific treatment for CBS. PMID:27757139

  1. Genomic deletions in OPA1 in Danish patients with autosomal dominant optic atrophy

    Directory of Open Access Journals (Sweden)

    Larsen Michael

    2011-04-01

    Full Text Available Abstract Background Autosomal dominant optic atrophy (ADOA, Kjer disease, MIM #165500 is the most common form of hereditary optic neuropathy. Mutations in OPA1 located at chromosome 3q28 are the predominant cause for ADOA explaining between 32 and 89% of cases. Although deletions of OPA1 were recently reported in ADOA, the frequency of OPA1 genomic rearrangements in Denmark, where ADOA has a high prevalence, is unknown. The aim of the study was to identify copy number variations in OPA1 in Danish ADOA patients. Methods Forty unrelated ADOA patients, selected from a group of 100 ADOA patients as being negative for OPA1 point mutations, were tested for genomic rearrangements in OPA1 by multiplex ligation probe amplification (MLPA. When only one probe was abnormal results were confirmed by additional manually added probes. Segregation analysis was performed in families with detected mutations when possible. Results Ten families had OPA1 deletions, including two with deletions of the entire coding region and eight with intragenic deletions. Segregation analysis was possible in five families, and showed that the deletions segregated with the disease. Conclusion Deletions in the OPA1 gene were found in 10 patients presenting with phenotypic autosomal dominant optic neuropathy. Genetic testing for deletions in OPA1 should be offered for patients with clinically diagnosed ADOA and no OPA1 mutations detected by DNA sequencing analysis.

  2. Dysregulated mitophagy and mitochondrial organization in optic atrophy due to OPA1 mutations

    Science.gov (United States)

    Liao, Chunyan; Ashley, Neil; Diot, Alan; Morten, Karl; Phadwal, Kanchan; Williams, Andrew; Fearnley, Ian; Rosser, Lyndon; Lowndes, Jo; Fratter, Carl; Ferguson, David J.P.; Vay, Laura; Quaghebeur, Gerardine; Moroni, Isabella; Bianchi, Stefania; Lamperti, Costanza; Downes, Susan M.; Sitarz, Kamil S.; Flannery, Padraig J.; Carver, Janet; Dombi, Eszter; East, Daniel; Laura, Matilde; Reilly, Mary M.; Mortiboys, Heather; Prevo, Remko; Campanella, Michelangelo; Daniels, Matthew J.; Zeviani, Massimo; Yu-Wai-Man, Patrick; Simon, Anna Katharina; Votruba, Marcela

    2017-01-01

    Objective: To investigate mitophagy in 5 patients with severe dominantly inherited optic atrophy (DOA), caused by depletion of OPA1 (a protein that is essential for mitochondrial fusion), compared with healthy controls. Methods: Patients with severe DOA (DOA plus) had peripheral neuropathy, cognitive regression, and epilepsy in addition to loss of vision. We quantified mitophagy in dermal fibroblasts, using 2 high throughput imaging systems, by visualizing colocalization of mitochondrial fragments with engulfing autophagosomes. Results: Fibroblasts from 3 biallelic OPA1(−/−) patients with severe DOA had increased mitochondrial fragmentation and mitochondrial DNA (mtDNA)–depleted cells due to decreased levels of OPA1 protein. Similarly, in siRNA-treated control fibroblasts, profound OPA1 knockdown caused mitochondrial fragmentation, loss of mtDNA, impaired mitochondrial function, and mitochondrial mislocalization. Compared to controls, basal mitophagy (abundance of autophagosomes colocalizing with mitochondria) was increased in (1) biallelic patients, (2) monoallelic patients with DOA plus, and (3) OPA1 siRNA–treated control cultures. Mitophagic flux was also increased. Genetic knockdown of the mitophagy protein ATG7 confirmed this by eliminating differences between patient and control fibroblasts. Conclusions: We demonstrated increased mitophagy and excessive mitochondrial fragmentation in primary human cultures associated with DOA plus due to biallelic OPA1 mutations. We previously found that increased mitophagy (mitochondrial recycling) was associated with visual loss in another mitochondrial optic neuropathy, Leber hereditary optic neuropathy (LHON). Combined with our LHON findings, this implicates excessive mitochondrial fragmentation, dysregulated mitophagy, and impaired response to energetic stress in the pathogenesis of mitochondrial optic neuropathies, potentially linked with mitochondrial mislocalization and mtDNA depletion. PMID:27974645

  3. Vaginal Atrophy

    Science.gov (United States)

    ... Body in Balance › Vaginal Atrophy Fact Sheet Vaginal Atrophy November, 2011 Download PDFs English Espanol Editors JoAnn ... MD Richard J. Santen, MD What is vaginal atrophy? Vaginal atrophy is a condition in which the ...

  4. Optic atrophy, necrotizing anterior scleritis and keratitis presenting in association with Streptococcal Toxic Shock Syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Papageorgiou Konstantinos I

    2008-02-01

    Full Text Available Abstract Introduction We report a case of optic atrophy, necrotizing anterior scleritis and keratitis presenting in a patient with Streptococcal Toxic Shock Syndrome. Case presentation A 43-year-old woman developed streptococcal toxic shock syndrome secondary to septic arthritis of her right ankle. Streptococcus pyogenes (b-haemolyticus Group A was isolated from blood cultures and joint aspirate. She was referred for ophthalmology review as her right eye became injected and the pupil had become unresponsive to light whilst she was in the Intensive Therapy Unit (ITU. The iris appeared atrophic and was mid-dilated with no direct or consensual response to light. Three zones of sub-epithelial opacification where noted in the cornea. There where extensive posterior synechiae. Indirect ophthalmoscopy showed a pale right disc. The vision was reduced to hand movements (HM. A diagnosis of optic atrophy was made secondary to post-streptococcal uveitis. She subsequently developed a necrotizing anterior scleritis. Conclusion This case illustrates a previously unreported association of optic atrophy, necrotizing anterior scleritis and keratitis in a patient with post-streptococcal uveitis. This patient had developed Streptococcal Toxic Shock Syndrome secondary to septic arthritis. We recommend increased awareness of the potential risks of these patients developing severe ocular involvement.

  5. A novel mutation of AFG3L2 might cause dominant optic atrophy in patients with mild intellectual disability

    Directory of Open Access Journals (Sweden)

    Majida eCharif

    2015-10-01

    Full Text Available Dominant optic neuropathies causing fiber loss in the optic nerve are among the most frequent inherited mitochondrial diseases. In most genetically resolved cases, the disease is associated to a mutation in OPA1, which encodes an inner mitochondrial dynamin involved in network fusion, cristae structure and mitochondrial genome maintenance. OPA1 cleavage is regulated by two m-AAA proteases, SPG7 and AFG3L2, which are respectively involved in Spastic Paraplegia 7 and Spino-Cerebellar Ataxia 28. Here, we identified a novel mutation c.1402C>T in AFG3L2, modifying the arginine 468 in cysteine in an evolutionary highly conserved arginine-finger motif, in a family with optic atrophy and mild intellectual disability. Ophthalmic examinations disclosed a loss of retinal nerve fibers on the temporal and nasal sides of the optic disk and a red-green dyschromatopsia. Thus, our results suggest that neuro-ophthalmological symptom as optic atrophy might be associated with AFG3L2 mutations, and should prompt the screening of this gene in patients with isolated and syndromic inherited optic neuropathies.

  6. Genotype-phenotype heterogeneity of ganglion cell and inner plexiform layer deficit in autosomal-dominant optic atrophy

    DEFF Research Database (Denmark)

    Rönnbäck, Cecilia; Nissen, Claus; Almind, Gitte J;

    2015-01-01

    PURPOSE: To describe the thickness of the combined ganglion cell and inner plexiform layers (GC-IPL) and the peripapillary retinal nerve fibre layer (RNFL) in patients with OPA1 c.983A>G or c.2708_2711delTTAG autosomal-dominant optic atrophy (ADOA). METHODS: The study included 20 individuals with c...... measurement and high-definition optical coherence tomography. RESULTS: There was overlap in GC-IPL thickness in subjects younger than 20-30 years between the two new groups of ADOA patients and controls. Numerical decreases in GC-IPL thickness with age did not reach statistical significance in individuals...

  7. Detection of optic nerve atrophy following a single episode of unilateral optic neuritis by MRI using a fat-saturated short-echo fast FLAIR sequence

    Energy Technology Data Exchange (ETDEWEB)

    Hickman, S.J. [Inst. of Neurology, Univ. College London (United Kingdom); Dept. of Neuro-Ophthalmology, Moorfields Eye Hospital, London (United Kingdom); Brex, P.A.; Silver, N.C.; Barker, G.J.; Miller, D.H. [Inst. of Neurology, Univ. College London (United Kingdom); Brierley, C.M.H.; Compston, D.A.S. [Cambridge Centre for Brain Repair, Cambridge (United Kingdom); Scolding, N.J. [Inst. of Clinical Neurosciences, Frenchay Hospital, Bristol (United Kingdom); Moseley, I.F. [Lysholm Radiological Dept., National Hospital for Neurology and Neurosurgery, London (United Kingdom); Plant, G.T. [Dept. of Neuro-Ophthalmology, Moorfields Eye Hospital, London (United Kingdom)

    2001-02-01

    We describe an MRI technique for quantifying optic nerve atrophy resulting from a single episode of unilateral optic neuritis. We imaged 17 patients, with a median time since onset of optic neuritis of 21 months (range 3-81 months), using a coronal-oblique fat-saturated short-echo fast fluid-attenuated inversion-recovery (sTE fFLAIR) sequence. The mean cross-sectional area of the intraorbital portion of the optic nerves was calculated by a blinded observer from five consecutive 3 mm slices from the orbital apex forwards using a semiautomated contouring technique and compared with data from 16 controls. The mean optic nerve area was 11.2mm{sup 2} in the affected eye of the patients, 12.9mm{sup 2} in the contralateral eye (P = 0.006 compared to the affected eye) and 12.8mm{sup 2} in controls (P = 0.03 compared to the affected eyes). There was a significant negative correlation between disease duration and the size of the affected optic nerve (r = -0.59, P = 0.012). The measurement coefficient of variation was 4.8 %. The sTE fFLAIR sequence enables measurement of optic nerve area with sufficient reproducibility to show optic nerve atrophy following a single episode of unilateral optic neuritis. The correlation of increasing optic nerve atrophy with disease duration would be consistent with ongoing axonal loss in a persistently demyelinated lesion, or Wallerian degeneration following axonal damage during the acute inflammatory phase. (orig.)

  8. [Diffusion tensor imaging of the visual pathway in glaucomatous optic nerve atrophy].

    Science.gov (United States)

    Engelhorn, T; A Schmidt, M; Dörfler, A; Michelson, G

    2017-03-01

    In Germany more than one million inhabitants suffer from glaucoma, more than 100,000 are threatened with blindness because glaucoma is often diagnosed too late or not at all. Diagnosis and monitoring is usually carried out "only" by examination of the retina and not the whole visual pathway. However, the eye is just "the tip of the iceberg" of the actual visual pathway, which extends through the brain to the visual cortex. The interdisciplinary holistic assessment of the whole visual pathway in glaucoma is of crucial importance because glaucoma is a complex neurodegenerative disease. Subtypes, such as normal tension glaucoma (NTG), seem to originate from primary damage to the intracranial visual pathway with secondary retrograde retinal degeneration. Recent studies including glaucoma patients and healthy controls could show that diffusion tensor imaging with calculation of diffusion coefficients, i.e. fractional anisotropy (FA), mean and radial diffusivity (MD and RD) as markers of axonal integrity, provide the potential to assess the intracranial visual pathway with a high correlation to established ophthalmological examinations. In particular, calculation of FA maps of the visual pathway and accompanying voxel-based approaches, can be integrated into clinical routine. Thus, detection of glaucoma-related intracranial alterations, even in early stages of the disease, as well as differentiation of different glaucoma subtypes, is made possible. Furthermore, the diagnosis of normal tension glaucoma seems to be possible much earlier with these new imaging techniques compared to established ophthalmological work-up. Moreover, holistic imaging provides new insights into the pathophysiology of this form of glaucoma. This review article gives an overview of these novel magnetic resonance imaging techniques for assessment of the visual pathway in glaucomatous optic nerve atrophy and reveals the potential of an interdisciplinary approach.

  9. Scattered depressions with temporal preponderance in visual field test coexisting with optic disc temporal atrophy in cerebral arteriovenous malformation

    Directory of Open Access Journals (Sweden)

    Gokce G

    2013-10-01

    Full Text Available Gokcen Gokce,1 Nisa Cem Oren,2 Osman Melih Ceylan,3 Tarkan Mumcuoglu,3 Volkan Hurmeric3 1Sarikamis Military Hospital, Department of Ophthalmology, 2Department of Radiology, Kars, 3Gulhane Military Medical Academy, Department of Ophthalmology, Ankara, Turkey Abstract: In this article, the unusual association of optic disc temporal atrophy associated with scattered depressions with temporal preponderance in visual field test resembling incomplete bitemporal hemianopsia is reported. A 22-year-old man with cerebral arteriovenous malformation (AVM, which was located adjacent to the inferomedial portion of the posterior limb of the right internal capsule at the level of lateral ventricle, revealed interesting and unexpected ophthalmological findings. Possible mechanisms including anatomical variant, previously larger AVM, and retrograde optic neuropathy were mentioned. This case also highlighted that the usual complaint of visual disturbance might associate with unusual visual field defect in cerebral AVMs. Keywords: arteriovenous malformation, bitemporal hemianopsia, optic chiasm, optic nerve, vascular steal

  10. Mitochondrial oxidative phosphorylation compensation may preserve vision in patients with OPA1-linked autosomal dominant optic atrophy.

    Science.gov (United States)

    Van Bergen, Nicole J; Crowston, Jonathan G; Kearns, Lisa S; Staffieri, Sandra E; Hewitt, Alex W; Cohn, Amy C; Mackey, David A; Trounce, Ian A

    2011-01-01

    Autosomal Dominant Optic Atrophy (ADOA) is the most common inherited optic atrophy where vision impairment results from specific loss of retinal ganglion cells of the optic nerve. Around 60% of ADOA cases are linked to mutations in the OPA1 gene. OPA1 is a fission-fusion protein involved in mitochondrial inner membrane remodelling. ADOA presents with marked variation in clinical phenotype and varying degrees of vision loss, even among siblings carrying identical mutations in OPA1. To determine whether the degree of vision loss is associated with the level of mitochondrial impairment, we examined mitochondrial function in lymphoblast cell lines obtained from six large Australian OPA1-linked ADOA pedigrees. Comparing patients with severe vision loss (visual acuity [VA]vision (VA>6/9) a clear defect in mitochondrial ATP synthesis and reduced respiration rates were observed in patients with poor vision. In addition, oxidative phosphorylation (OXPHOS) enzymology in ADOA patients with normal vision revealed increased complex II+III activity and levels of complex IV protein. These data suggest that OPA1 deficiency impairs OXPHOS efficiency, but compensation through increases in the distal complexes of the respiratory chain may preserve mitochondrial ATP production in patients who maintain normal vision. Identification of genetic variants that enable this response may provide novel therapeutic insights into OXPHOS compensation for preventing vision loss in optic neuropathies.

  11. Vaginal Atrophy

    Science.gov (United States)

    Vaginal atrophy Overview Vaginal atrophy (atrophic vaginitis) is thinning, drying and inflammation of the vaginal walls due to your body having less estrogen. Vaginal atrophy occurs most often after ...

  12. Improve the understanding and diagnostic skill of optic atrophy%进一步提高视神经萎缩的诊断水平

    Institute of Scientific and Technical Information of China (English)

    张晓君

    2011-01-01

    Optic atrophy is clinically common and usually accompanied with different severity of visual function impairment. The key point is that the clinical manifestation and visual outcomes are different among the patients with optic atrophies caused by different conditions. Special attention should be paid to distinguishing optic atrophy and congenital optic disc anomaly, isolated inherited optic neuropathy and optic atrophy as part of the systemic neurological diseases, and some conditions mimicking optic atrophy. Precise understanding of optic atrophy is very important for finding the causes, starting good treatment strategy and eventually protecting the patients' visual function.%视神经萎缩在眼科临床较为常见,患者通常有不同程度视功能损害.导致视神经萎缩的原因不同其临床表现和视功能预后也有所不同,应区分病因分别对待.在临床工作中可根据视盘形态的差异鉴别视神经萎缩,应注重区分视神经萎缩与先天性视盘形态异常、孤立性遗传性视神经病变与系统性神经系统疾病所致视神经改变以及视神经的生理性变异等.正确认识视神经萎缩,对于判断其病因,并采取适当的干预措施、保护患者视功能非常重要.(眼科,2011,20:364-366)

  13. Non-image-forming light driven functions are preserved in a mouse model of autosomal dominant optic atrophy.

    Science.gov (United States)

    Perganta, Georgia; Barnard, Alun R; Katti, Christiana; Vachtsevanos, Athanasios; Douglas, Ron H; MacLaren, Robert E; Votruba, Marcela; Sekaran, Sumathi

    2013-01-01

    Autosomal dominant optic atrophy (ADOA) is a slowly progressive optic neuropathy that has been associated with mutations of the OPA1 gene. In patients, the disease primarily affects the retinal ganglion cells (RGCs) and causes optic nerve atrophy and visual loss. A subset of RGCs are intrinsically photosensitive, express the photopigment melanopsin and drive non-image-forming (NIF) visual functions including light driven circadian and sleep behaviours and the pupil light reflex. Given the RGC pathology in ADOA, disruption of NIF functions might be predicted. Interestingly in ADOA patients the pupil light reflex was preserved, although NIF behavioural outputs were not examined. The B6; C3-Opa1(Q285STOP) mouse model of ADOA displays optic nerve abnormalities, RGC dendropathy and functional visual disruption. We performed a comprehensive assessment of light driven NIF functions in this mouse model using wheel running activity monitoring, videotracking and pupillometry. Opa1 mutant mice entrained their activity rhythm to the external light/dark cycle, suppressed their activity in response to acute light exposure at night, generated circadian phase shift responses to 480 nm and 525 nm pulses, demonstrated immobility-defined sleep induction following exposure to a brief light pulse at night and exhibited an intensity dependent pupil light reflex. There were no significant differences in any parameter tested relative to wildtype littermate controls. Furthermore, there was no significant difference in the number of melanopsin-expressing RGCs, cell morphology or melanopsin transcript levels between genotypes. Taken together, these findings suggest the preservation of NIF functions in Opa1 mutants. The results provide support to growing evidence that the melanopsin-expressing RGCs are protected in mitochondrial optic neuropathies.

  14. Non-image-forming light driven functions are preserved in a mouse model of autosomal dominant optic atrophy.

    Directory of Open Access Journals (Sweden)

    Georgia Perganta

    Full Text Available Autosomal dominant optic atrophy (ADOA is a slowly progressive optic neuropathy that has been associated with mutations of the OPA1 gene. In patients, the disease primarily affects the retinal ganglion cells (RGCs and causes optic nerve atrophy and visual loss. A subset of RGCs are intrinsically photosensitive, express the photopigment melanopsin and drive non-image-forming (NIF visual functions including light driven circadian and sleep behaviours and the pupil light reflex. Given the RGC pathology in ADOA, disruption of NIF functions might be predicted. Interestingly in ADOA patients the pupil light reflex was preserved, although NIF behavioural outputs were not examined. The B6; C3-Opa1(Q285STOP mouse model of ADOA displays optic nerve abnormalities, RGC dendropathy and functional visual disruption. We performed a comprehensive assessment of light driven NIF functions in this mouse model using wheel running activity monitoring, videotracking and pupillometry. Opa1 mutant mice entrained their activity rhythm to the external light/dark cycle, suppressed their activity in response to acute light exposure at night, generated circadian phase shift responses to 480 nm and 525 nm pulses, demonstrated immobility-defined sleep induction following exposure to a brief light pulse at night and exhibited an intensity dependent pupil light reflex. There were no significant differences in any parameter tested relative to wildtype littermate controls. Furthermore, there was no significant difference in the number of melanopsin-expressing RGCs, cell morphology or melanopsin transcript levels between genotypes. Taken together, these findings suggest the preservation of NIF functions in Opa1 mutants. The results provide support to growing evidence that the melanopsin-expressing RGCs are protected in mitochondrial optic neuropathies.

  15. Reevaluation of the linkage of an optic atrophy susceptibility gene to X-chromosomal markers in Finnish families with Leber hereditary optic neuroretinopathy (LHON)

    Energy Technology Data Exchange (ETDEWEB)

    Juvonen, V.; Aula, P.; Vilkki, J.; Nikoskelainen, E.; Savontaus, M.-L.

    1993-07-01

    One of the commonest reasons for sudden-onset optic nerve degeneration in young men can be attributed to maternally inherited Leber hereditary optic neuroretinopathy (LHON) (Nikoskelainen et al. 1987). Specific point mutations at either np 11778 (Wallace et al. 1988) or np 3460 (Howell et al. 1991; Huoponen et al. 1991) in mitochondrial DNA (mtDNA) encoding for respiratory enzyme complex I subunits (i.e., ND4 or ND1) can be found in 70% of families. These mutations exist as being either homoplasmic or heteroplasmic, but the correlation between the degree of heteroplasmy and the risk of developing optic atrophy is far from clear (Holt et al. 1989; Vilkki et al. 1990). Neither does heteroplasmy explain the strong male bias seen in LHON families, when the sex ratio of patients with visual impairment is observed. Earlier results indicated that susceptibility to optic atrophy in Finnish families with LHON was probably determined by an X-chromosomal gene closely linked to DXS7. Contradictory results prompted reevaluation of the existence of an X-chromosomal visual loss susceptibility gene in Finnish LHON families. The results of this present study clearly demonstrate that the earlier close linkage to DXS7 is implausible. The altered Z is due to revised pedigrees, the use of liability classes, and separation of the families according to the associated mtDNA mutation. 16 refs., 1 fig., 1 tab.

  16. Muscle atrophy

    Science.gov (United States)

    ... atrophy. Exercises may include ones done in a swimming pool to reduce the muscle workload, and other types ... a physical examination and ask about your medical history and symptoms, including: When did the muscle atrophy ...

  17. Retinal atrophy correlates with fMRI response in patients with recovered optic neuritis

    DEFF Research Database (Denmark)

    Fuglø, D; Kallenbach, K; Tsakiri, A;

    2011-01-01

    We wanted to investigate if retinal nerve fiber layer thickness (RNFLT) measured by optical coherence tomography (OCT) might be a good marker of acute and chronic changes in the afferent visual pathway following acute optic neuritis (ON).......We wanted to investigate if retinal nerve fiber layer thickness (RNFLT) measured by optical coherence tomography (OCT) might be a good marker of acute and chronic changes in the afferent visual pathway following acute optic neuritis (ON)....

  18. [A case or Leber hereditary optic neuropathy (LHON): differential diagnosis with post inflammatory atrophy of nerve II using the mtDNA analysis].

    Science.gov (United States)

    Lubos, Leszek; Wajgt, Andrzej; Maciejowski, Maciej; Mroczek-Tońska, Katarzyna; Bartnik, Ewa; Dziekanowska, Danuta

    2003-01-01

    The Leber hereditary optic neuropathy (LHON) is a disease due to a mtDNA mutation. The disorder results from enzymatic perturbations in the mitochondrial respiratory chain. Clinically the LHON may present as a progressive axonal atrophy of the optic nerves with or without other neurological symptoms. The process of reaching the diagnosis of the LHON by means of the molecular analysis of mtDNA is discussed.

  19. High-Resolution En Face Images of Microcystic Macular Edema in Patients with Autosomal Dominant Optic Atrophy

    Directory of Open Access Journals (Sweden)

    Kiyoko Gocho

    2013-01-01

    Full Text Available The purpose of this study was to investigate the characteristics of microcystic macular edema (MME determined from the en face images obtained by an adaptive optics (AO fundus camera in patients with autosomal dominant optic atrophy (ADOA and to try to determine the mechanisms underlying the degeneration of the inner retinal cells and RNFL by using the advantage of AO. Six patients from 4 families with ADOA underwent detailed ophthalmic examinations including spectral domain optical coherence tomography (SD-OCT. Mutational screening of all coding and flanking intron sequences of the OPA1 gene was performed by DNA sequencing. SD-OCT showed a severe reduction in the retinal nerve fiber layer (RNFL thickness in all patients. A new splicing defect and two new frameshift mutations with premature termination of the Opa1 protein were identified in three families. A reported nonsense mutation was identified in one family. SD-OCT of one patient showed MME in the inner nuclear layer (INL of the retina. AO images showed microcysts in the en face images of the INL. Our data indicate that AO is a useful method to identify MME in neurodegenerative diseases and may also help determine the mechanisms underlying the degeneration of the inner retinal cells and RNFL.

  20. SDOCT Thickness Measurements of Various Retinal Layers in Patients with Autosomal Dominant Optic Atrophy due to OPA1 Mutations

    Directory of Open Access Journals (Sweden)

    Andrea M. Schild

    2013-01-01

    Full Text Available Purpose. To specify thickness values of various retinal layers on macular spectral domain Optical Coherence Tomography (SDOCT scans in patients with autosomal dominant optic atrophy (ADOA compared to healthy controls. Methods. SDOCT volume scans of 7 patients with ADOA (OPA-1 mutation and 14 healthy controls were quantitatively analyzed using manual grading software. Mean thickness values for the ETDRS grid subfields 5–8 were calculated for the spaces neurosensory retina, retinal nerve fiber layer (RNFL, ganglion cell layer (GCL, a combined space of inner plexiform layer/outer plexiform layer/inner nuclear layer (IPL+INL+OPL, and a combined space of outer nuclear layer/photoreceptor layers (ONL+PL. Results. ADOA patients showed statistically significant lower retinal thickness values than controls (. RNFL ( and GCL thicknesses ( were significantly lower in ADOA patients. There was no difference in IPL+INL+OPL and in ONL+PL thickness. Conclusion. Manual subanalysis of macular SDOCT volume scans allowed detailed subanalysis of various retinal layers. Not only RNFL but also GCL thicknesses are reduced in the macular area of ADOA patients whereas subjacent layers are not involved. Together with clinical findings, macular SDOCT helps to identify patients with suspicion for hereditary optic neuropathy before genetic analysis confirms the diagnosis.

  1. Identification of copy number variation in the gene for autosomal dominant optic atrophy, OPA1, in a Chinese pedigree.

    Science.gov (United States)

    Jin, X; Chen, Y H; Liu, Z; Deng, Y; Li, N N; Huang, H; Qi, M; Yi, X; Zhu, J

    2015-09-21

    Autosomal dominant optic atrophy (ADOA) is an optic neuropathy characterized by bilateral optic nerve pallor and decreased visual acuity. It has been reported to be associated with two genes, OPA1, OPA3, and the OPA4, OPA5, and OPA8 loci. However, mutations in OPA1 constitute the most prevalent cause of ADOA. The purpose of this study was to identify the underlying genetic defect in a Chinese pedigree with ADOA. DNA from six members of a Chinese pedigree was collected for testing genomic and copy number variation (CNV) by targeted region capture and next generation sequencing (targeted NGS). A new developmental CNV detection method was applied to analyze the sequence data. Further verification of CNV was performed by real-time polymerase chain reaction (PCR). Three members of the pedigree with clinically diagnosed ADOA were screened for pathogenic genes related to ophthalmic genetic disease. No eligible pathogenic point mutations associated with ADOA disease-causing genes were found in pedigree members with ADOA. Upon further analysis for CNVs, we found a heterozygous deletion in exons 1-9 of OPA1, which was confirmed by real-time PCR. In this study we used a new developmental method to detect CNVs associated with ADOA in a Chinese pedigree. To our knowledge, this is the first case of ADOA caused by a CNV of the OPA1 gene in Chinese patients. The findings suggest that CNVs might be an important mutation type in Chinese patients with ADOA, and that CNV screening should be performed when point mutation screens are negative in these patients.

  2. Identification of p.A684V missense mutation in the WFS1 gene as a frequent cause of autosomal dominant optic atrophy and hearing impairment

    DEFF Research Database (Denmark)

    Rendtorff, Nanna D; Lodahl, Marianne; Boulahbel, Houda

    2011-01-01

    Optic atrophy (OA) and sensorineural hearing loss (SNHL) are key abnormalities in several syndromes, including the recessively inherited Wolfram syndrome, caused by mutations in WFS1. In contrast, the association of autosomal dominant OA and SNHL without other phenotypic abnormalities is rare......, and almost exclusively attributed to mutations in the Optic Atrophy-1 gene (OPA1), most commonly the p.R445H mutation. We present eight probands and their families from the US, Sweden, and UK with OA and SNHL, whom we analyzed for mutations in OPA1 and WFS1. Among these families, we found three heterozygous...... DNA deletions were detected in muscle from one p.A684V patient analyzed. Finally, wolframin p.A684V mutant ectopically expressed in HEK cells showed reduced protein levels compared to wild-type wolframin, strongly indicating that the mutation is disease-causing. Our data support OA and SNHL...

  3. Optic atrophy 1 mediates coenzyme Q-responsive regulation of respiratory complex IV activity in brain mitochondria.

    Science.gov (United States)

    Takahashi, Kazuhide; Ohsawa, Ikuroh; Shirasawa, Takuji; Takahashi, Mayumi

    2017-11-01

    The oxygen consumption rate (OCR) in brain mitochondria is significantly lower in aged mice than in young mice, and the reduced OCR is rescued by administration of water-solubilized CoQ10 to aged mice via drinking water. However, the mechanism behind this remains unclear. Here, we show that the activity of respiratory complex IV (CIV) in brain mitochondria declined in aged mice than in young mice, with no significant change in individual respiratory complex levels and their supercomplex assembly. Reduced CIV activity in the aged mice coincided with reduced binding of optic atrophy 1 (OPA1) to CIV. Both reduced activity and OPA1 binding of CIV were rescued by water-solubilized CoQ10 administration to aged mice via drinking water. OCR and the activity and OPA1 binding of CIV in isolated brain mitochondria from aged mice were restored by incubation with CoQ10, but not in the presence of 15-deoxy-prostaglandin J2, an inhibitor of a GTPase effector domain-containing GTPase such as OPA1 and DRP1. By contrast, the CoQ10-responsive restoration of OCR in the isolated mitochondria was not inhibited by Mdivi-1, a selective inhibitor of DRP1. Thus, we propose a novel function of OPA1 in regulating the CIV activity in brain mitochondria in response to CoQ10. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Assessment of β-zone peripapillary atrophy by optical coherence tomography and scanning laser ophthalmoscopy imaging in glaucoma patients

    Directory of Open Access Journals (Sweden)

    Seidensticker F

    2014-06-01

    Full Text Available Florian Seidensticker,1,* Lukas Reznicek,2,* Thomas Mann,2 Irene Hübert,2 Anselm Kampik,2 Michael Ulbig,2 Christoph Hirneiss,2 Aljoscha S Neubauer,2 Marcus Kernt2 1Department of Ophthalmology, Hannover Medical School, Hannover, Germany; 2Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany  *These authors have contributed equally to this work Purpose: To assess β-zone peripapillary atrophy (β-PPA using spectral domain optical coherence tomography (SD-OCT, scanning laser ophthalmoscopy (SLO, and fundus autofluorescence (FAF imaging in patients with primary open-angle glaucoma with advanced glaucomatous visual field defects. Methods: A consecutive, prospective series of 82 study eyes with primary open-angle glaucoma were included in this study. All study participants underwent a full ophthalmic examination followed by SD-OCT, wide-field SLO, and FAF imaging of the optic nerve head and the peripapillary region. Results: Eighty-four glaucomatous eyes were included in our prospective study. Correlation analyses for horizontally and vertically obtained β-PPA for all three imaging modalities (color SLO, FAF, and SD-OCT revealed highest correlations between FAF and color SLO (Pearson correlation coefficient: 0.904 [P<0.001] for horizontal β-PPA and 0.786 [P<0.001] for vertical β-PPA. Bland–Altman plotting revealed highest agreements between color SLO and FAF, with −2.1 pixels ±1.96 standard deviation (SD for horizontal β-PPA, SD: 10.5 pixels and 2.4 pixels ±1.96 SD for vertical β-PPA. Conclusion: β-PPA can be assessed using en-face SLO and cross-sectional SD-OCT imaging. Correlation analyses revealed highest correlations between color SLO and FAF imaging, while correlations between SLO and SD-OCT were weak. A more precise structural definition of β-PPA is needed. Keywords: fundus autofluorescence, FAF, OCT, SD-OCT, SLO, glaucomatous optic neuropathy

  5. Neuroblastoma amplified sequence gene is associated with a novel short stature syndrome characterised by optic nerve atrophy and Pelger-Huët anomaly.

    Science.gov (United States)

    Maksimova, Nadezda; Hara, Kenju; Nikolaeva, Irina; Chun-Feng, Tan; Usui, Tomoaki; Takagi, Mineo; Nishihira, Yasushi; Miyashita, Akinori; Fujiwara, Hiroshi; Oyama, Tokuhide; Nogovicina, Anna; Sukhomyasova, Aitalina; Potapova, Svetlana; Kuwano, Ryozo; Takahashi, Hitoshi; Nishizawa, Masatoyo; Onodera, Osamu

    2010-08-01

    Hereditary short stature syndromes are clinically and genetically heterogeneous disorders and the cause have not been fully identified. Yakuts are a population isolated in Asia; they live in the far east of the Russian Federation and have a high prevalence of hereditary short stature syndrome including 3-M syndrome. A novel short stature syndrome in Yakuts is reported here, which is characterised by autosomal recessive inheritance, severe postnatal growth retardation, facial dysmorphism with senile face, small hands and feet, normal intelligence, Pelger-Huët anomaly of leucocytes, and optic atrophy with loss of visual acuity and colour vision. This new syndrome is designated as short stature with optic atrophy and Pelger-Huët anomaly (SOPH) syndrome. To identify a causative gene for SOPH syndrome. Genomewide homozygosity mapping was conducted in 33 patients in 30 families. The disease locus was mapped to the 1.1 Mb region on chromosome 2p24.3, including the neuroblastoma amplified sequence (NBAS) gene. Subsequently, 33 of 34 patients were identified with SOPH syndrome and had a 5741G/A nucleotide substitution (resulting in the amino acid substitution R1914H) in the NBAS gene in the homozygous state. None of the 203 normal Yakuts individuals had this substitution in the homozygous state. Immunohistochemical analysis revealed that the NBAS protein is well expressed in retinal ganglion cells, epidermal skin cells, and leucocyte cytoplasm in controls as well as a patient with SOPH syndrome. These findings suggest that function of NBAS may associate with the pathogenesis of short stature syndrome as well as optic atrophy and Pelger-Huët anomaly.

  6. Refinement of the OPA1 gene locus on chromosome 3q28-q29 to a region of 2-8 cM, in one Cuban pedigree with autosomal dominant optic atrophy type Kjer

    Energy Technology Data Exchange (ETDEWEB)

    Lunkes, A.; Hartung, U.; Auburger, G. [Univ. Hospital Duesseldorf (Germany)] [and others

    1995-10-01

    Kjer type autosomal dominant optic atrophy was reported to have a prevalence of 1:50,000 and is therefore the most common form of familial optic atrophy. Age at onset and chronic progressive course were used as subclassification criteria by Kjer, Jaeger, and Smith, stating that almost all cases manifested subacutely before 8 years of age. Typically, tritan color defects and small paracentral scotomas are found together with both variable reduction of visual acuity, of approximately 0.3/0.1, and a temporal pallor on fundoscopy. Pathologically the retinal ganglion cells are affected, resulting in a progressive degeneration of the optic nerve. 12 refs., 1 fig., 1 tab.

  7. Effect observation of Zengshisan on optic atrophy%增视散对视神经萎缩的疗效观察

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@1 Subject and methods 1.1 Subject On the basis of diagnosis criterion of optic atrophy from the bock Pratical Ophthalonlogy,we selecte 82 inpatients of outpatients from January 1997 to December 2000,total 116 eyes. Except for any frontoptomein agents that influence reversion of VA for example transparent interstitial turbid of refraction,there were 49 males and 33 femals aging from 10 to 62 years old with an average of 37 years and the course from 15 days to 6 years with the mean of 4.5 months.According to etiological factor,40 eyes trauma caused by trauma,25 eyes caused by optic neuritis,14 eyes caused by hyperpyrexia,10 eyes caused by avascular disease of optic disc,16 eyes caused by glaucoma,11 eyes caused by pigmentary retinopathy.

  8. Optic Nerve Atrophy

    Science.gov (United States)

    ... Corneal Abrasions Dilating Eye Drops Lazy eye (defined) Pink eye (defined) Retinopathy of Prematurity Strabismus Stye (defined) Vision ... Corneal Abrasions Dilating Eye Drops Lazy eye (defined) Pink eye (defined) Retinopathy of Prematurity Strabismus Stye (defined) Vision ...

  9. Solving a 50 year mystery of a missing OPA1 mutation: more insights from the first family diagnosed with autosomal dominant optic atrophy

    Directory of Open Access Journals (Sweden)

    Zrenner Eberhart

    2010-06-01

    Full Text Available Abstract Background Up to the 1950s, there was an ongoing debate about the diversity of hereditary optic neuropathies, in particular as to whether all inherited optic atrophies can be ascribed to Leber's hereditary optic neuropathy (LHON or represent different disease entities. In 1954 W. Jaeger published a detailed clinical and genealogical investigation of a large family with explicit autosomal dominant segregation of optic atrophy thus proving the existence of a discrete disease different from LHON, which is nowadays known as autosomal dominant optic atrophy (ADOA. Since the year 2000 ADOA is associated with genomic mutations in the OPA1 gene, which codes for a protein that is imported into mitochondria where it is required for mitochondrial fusion. Interestingly enough, the underlying mutation in this family has not been identified since then. Results We have reinvestigated this family with the aim to identify the mutation and to further clarify the underlying pathomechanism. Patients showed a classical non-syndromic ADOA. The long term deterioration in vision in the two teenagers examined 50 years later is of particular note 5/20 to 6/120. Multiplex ligation probe amplification revealed a duplication of the OPA1 exons 7-9 which was confirmed by long distance PCR and cDNA analysis, resulting in an in-frame duplication of 102 amino acids. Segregation was verified in 53 available members of the updated pedigree and a penetrance of 88% was calculated. Fibroblast cultures from skin biopsies were established to assess the mitochondrial network integrity and to qualitatively and quantitatively study the consequences of the mutation on transcript and protein level. Fibroblast cultures demonstrated a fragmented mitochondrial network. Processing of the OPA1 protein was altered. There was no correlation of the OPA1 transcript levels and the OPA1 protein levels in the fibroblasts. Intriguingly an overall decrease of mitochondrial proteins was observed

  10. Learning about Spinal Muscular Atrophy

    Science.gov (United States)

    ... News Release Fischbeck Group Learning About Spinal Muscular Atrophy What is spinal muscular atrophy? What are the ... for Spinal Muscular Atrophy What is spinal muscular atrophy? Spinal muscular atrophy is a group of inherited ...

  11. A new autosomal recessive non-progressive congenital cerebellar ataxia associated with mental retardation, optic atrophy, and skin abnormalities (CAMOS) maps to chromosome 15q24-q26 in a large consanguineous Lebanese Druze Family.

    Science.gov (United States)

    Delague, Valérie; Bareil, Corinne; Bouvagnet, Patrice; Salem, Nabiha; Chouery, Eliane; Loiselet, Jacques; Mégarbané, André; Claustres, Mireille

    2002-03-01

    Congenital cerebellar ataxias are a heterogeneous group of non-progressive disorders characterized by hypotonia and developmental delay followed by the appearance of ataxia, and often associated with dysarthria, mental retardation, and atrophy of the cerebellum. We report the mapping of a disease gene in a large inbred Lebanese Druze family, with five cases of a new form of non-progressive autosomal recessive congenital ataxia associated with optic atrophy, severe mental retardation, and structural skin abnormalities, to a 3.6-cM interval on chromosome 15q24-15q26.

  12. Heterogeneidade genética em atrofia óptica autossômica dominante Genetic heterogeneity in autosomal dominant optic atrophy

    Directory of Open Access Journals (Sweden)

    Juliana Maria Ferraz Sallum

    2002-08-01

    locus para esta doença.Purpose: Autosomal dominant optic atrophy is a hereditary optic neuropathy characterized by progressive visual loss in childhood, color vision anomalies, visual field defects and temporal pallor of the optic disc. This disease has been mapped to a 1.4 cM interval in chromosome 3q28-29 between markers D3S3669 and D3S3562. One family was mapped to chromosome 18q12.2-12.3. Linkage analysis in three families with autosomal dominant optic atrophy with polymorphic DNA markers for chromosome 3q28-29 and 18q12.2-12.3. Methods: 57 individuals from three families underwent ophthalmological examination. Genomic DNA was extracted from blood samples. Linkage analysis was performed between the disease and 11 polymorphic markers around 3q28-qter and 18q12.2-12.3. Polymerase chain reaction (PCR fragments sizes were identified in a scanner gel using a 373 DNA sequencer. These numbers were used as alleles for pedigree analysis. The lod scores were calculated using the MLINK program. Results: All three families presented optic atrophy with autosomal dominant pattern of inheritance, variable expression and high penetrance. Two families were linked to 3q28-29 markers. A maximal lod score of 3.56, at a recombination fraction of zero, was obtained using the marker D3S3669 in one family. The linkage area was defined in a 2 cM interval by haplotype analysis between markers D3S2418 and D3S1305, because patients III.4 and III.14 showed crossing-overs. The third family was not linked to 3q28-29 neither to 18q12.2-12.3. Conclusions: There is genetic heterogeneity in autosomal dominant optic atrophy, because the third family did not map to any known locus. And a third locus for this disease may exist.

  13. Correlation of central corneal thickness and axial length to the optic disc and peripapillary atrophy among healthy individuals, glaucoma and ocular hypertension patients

    Directory of Open Access Journals (Sweden)

    Michalis Moschos

    2008-10-01

    Full Text Available George Tomais1, Gerasimos Georgopoulos2, Chryssanthi Koutsandrea2, Michalis Moschos21University of Athens, Department of Ophthalmology, Athens, Greece; 2Athens University Medical School, Department of Ophthalmology, Athens, GreecePurpose: Clinical observational study for the correlation between the central corneal thickness (CCT, axial length (AXL, optic disc area (D, cupping area (C and peripapillary atrophy (PPA, in healthy eyes (group A, eyes with primary open angle glaucoma (POAG (group B and eyes with ocular hypertension (OH (group C, in order to assess the possible contribution of this correlation to the diagnosis or prognosis of glaucoma.Methods: Ninety eyes of 90 persons participated in the study (30 eyes of 30 persons in each group. All eyes underwent intraocular pressure measurement, visual field testing, endothelial cell count (ECC, measurement of the CCT and AXL, and gonioscopy. After dilation of the pupil, a digital photograph of each optic disc was performed, followed by PPA, D area and C area measurements.Results: We found a statistically significant difference in the C/D area ratio between healthy and POAG eyes and a moderate negative relationship between AXL and D in healthy eyes. We also found a moderate negative relationship between CCT and C/D area ratio in POAG eyes and a strong negative relationship between PPA and D in OH eyes.Conclusions: CCT was not correlated with PPA and AXL in any one of the three groups. OH eyes seem to have more tolerant and stable disc and peripapillary area compared to healthy and POAG eyes.Keywords: glaucoma, peripapillary, cupping, corneal thickness, axial length, optic disc

  14. Clinical profile and aetiology of optic atrophy in Malaysia%马来西亚视神经萎缩的临床特点及病因

    Institute of Scientific and Technical Information of China (English)

    Evelyn Tai Li Min; Jessica Mani Penny Tevaraj; Zunaina Embong; Raja Azmi Mohd Noor; Wan-Hazabbah Wan Hitam

    2014-01-01

    AIM:To describe the aetiology and clinical profile of non-glaucomatous optic atrophy in a tertiary hospital in M alaysia. METHODS: A retrospective case series was conducted on patients diagnosed with non -glaucomatous optic atroph y who presented to the Eye Clinic of Hospital Universiti Sains Malaysia from 2007 until 2011 with a minimum of one year follo w-up.Medical records of these patients were reviewed and the findings compiled. RESULT S: Of the 100 patients who met th e selection criteria, 56% had bilateral involvement. The chief presentingsymptom was visual blurring (61%), followed by v isual blurring with neurological symptoms (18%) and visual field constriciton (9%).Most patients (63%) had a presenting vi sual acuity worse than 3/60 in the affected eye. The main aetiologies were space -occupying intracranial lesions (26%), con genital/hereditary diseases ( 13%) , hydrocephalus ( 12%) , trauma ( 12%) , and vascular causes ( 12%) . The majority of c ases ( 67%) were managed conservatively.Regardless of aetiology, optic atrophy was associated with variable degrees of visual dysfunction.At the end of one year, 50% of the patients had some degree of visual impairment. CONCLUSION:The main aetiology of optic atrophy was space -occupying intracranial lesions, followed by congenital/hereditary, trauma and vascular problems. Visual or neurological symptoms usually preceded the diagnosis, and visual acuity was significantly affected by the disease.A high level of suspicion is required in order to make an early diagnosis of optic atrophy, as the main complaint of visual blurring is usually non-specific.%目的:研究在马来西亚非青光眼视神经萎缩的病因及临床特点。  方法:一系列回顾性的研究分析马来西亚理科大学校医院眼诊所在2007/2011年间被诊断为非青光眼视神经萎缩的患者。至少随访1a。评估这些患者的医疗记录及汇编调查结果。  结果:100例患者符合选择标准,56%

  15. Analysis of the thickness and vascular layers of the choroid in eyes with geographic atrophy using spectral-domain optical coherence tomography.

    Science.gov (United States)

    Adhi, Mehreen; Lau, Marisa; Liang, Michelle C; Waheed, Nadia K; Duker, Jay S

    2014-02-01

    To analyze the total choroidal thickness and thickness of the individual vascular layers of the choroid in eyes with geographic atrophy (GA), using spectral-domain optical coherence tomography. A cross-sectional retrospective review identified 17 patients with GA (17 eyes) and 14 age-matched healthy subjects (14 eyes), who underwent high-definition raster scanning at New England Eye Center, Boston, MA. Patients were diagnosed with GA based on clinical examination and investigations. Two independent raters evaluated the thickness and vascular layers of the choroid. Mean choroidal thickness was significantly lower in eyes with GA when compared with age-matched healthy eyes (P choroidal thickness in eyes with GA was significantly less when compared with healthy eyes (158.1 ± 23.65 μm versus 267.5 ± 19.27 μm, P = 0.001). Subfoveal large choroidal vessel layer thickness and medium choroidal vessel layer/choriocapillaris layer thickness were significantly reduced in eyes with GA when compared with healthy eyes (P = 0.001 and P choroid is significantly thinner in eyes with GA involving the fovea when compared with healthy eyes. Choroidal thinning in GA involves all its vascular layers. Further studies involving prospective correlation of choroidal vascular changes to the quantitative progression of GA is expected to provide further insight on the choroidal angiopathy associated with GA.

  16. Dan Zhi Xiao Yao Yin Combined With Auricular-Point-Pressing for Treatment of Optic Atrophy - A Clinical Observation of 51 Cases

    Institute of Scientific and Technical Information of China (English)

    杨海燕

    2004-01-01

    To evaluate the therapeutic effect of Dan Zhi Xiao Yao Yin (丹栀消遥饮 Decoction of Moutan Bark and Capejasmine) combined with auricular-point- pressing therapy for treatment of optic atrophy. The visual acuity and visual field was observed in the 51 cases (58 eyes) from the treatment group that were treated with Dan Zhi Xiao Yao Yin combined with auricular-point-pressing therapy and the 43 cases (49 eyes)from the control group that were treated with routine western drugs at the end of the trial (60 days). The effective rates of increase in visual acuity obtained in the treatment and the control groups were 79.3% and 44.89% respectively and enlargement in visual field were 61.9% and 22.6% respectively. Statistical analysis showed that there were significant differences between two groups (P<0.05). The therapeutic effect of Dan Zhi Xiao Yao Yin combined with auricular-point -pressing therapy in increasing the visual acuity and enlarging the visual field was superior to that of the routine western drugs.

  17. Spinal Muscular Atrophy (SMA)

    Science.gov (United States)

    ... Habits for TV, Video Games, and the Internet Spinal Muscular Atrophy (SMA) KidsHealth > For Parents > Spinal Muscular Atrophy (SMA) Print ... treatment for the disease's most troubling symptoms. About SMA Normally, healthy nerve cells in the brain called ...

  18. Multiple System Atrophy (MSA)

    Science.gov (United States)

    Diseases and Conditions Multiple system atrophy (MSA) By Mayo Clinic Staff Multiple system atrophy (MSA) is a rare neurological disorder that impairs your body's involuntary (autonomic) functions, including blood ...

  19. Spinal Muscular Atrophy (SMA)

    Science.gov (United States)

    ... Your 1- to 2-Year-Old Spinal Muscular Atrophy (SMA) KidsHealth > For Parents > Spinal Muscular Atrophy (SMA) A A A What's in this article? ... Outlook en español Atrofia muscular espinal Spinal muscular atrophy, or SMA, is an inherited condition that causes ...

  20. Clinical observation of acupuncturing "Qiaoming" on optic atrophy%针刺“窍明穴”(枕视皮质对应区)治疗视神经萎缩的疗效观察

    Institute of Scientific and Technical Information of China (English)

    孙河; 赵爽

    2012-01-01

    OBJECTIVE To observe the clinical efficacy of needling Qiaoming (corresponding area of occipital and visual cortex) on optic atrophy. METHODS Sixty-one (94 eyes) optic atrophy patients were randomly divided into the treatment group (31 cases,48 eyes) and control group (30 cases ,46 eyes). In addition to the common acupoints for optic atrophy, Qiaoming was used in the treatment group while in the control group only the common acupoints for optic atrophy were applied. Then, the curative effect was compared between the two groups after 4 weeks' needling treatment. RESULTS The effective rates of the treatment group and control group were 66.67% and 52.17% respectively. CONCLUSIONS Adding Qiaoming to the common acupoints in treating optic atrophy could improve the curative effect.%目的 观察针刺治疗“窍明穴”治疗视神经萎缩的临床疗效.方法 将视神经萎缩患者61例94只眼随机分为治疗组和对照组,均予针刺治疗.治疗组31例48只眼选用治疗视神经萎缩的常规穴位配合“窍明穴”,对照组30例46只眼只选用治疗视神经萎缩的常规穴位,4周后对比2组疗效.结果 治疗组和对照组的总有效率分别为66.67%和52.17%,差异有统计学意义(x2=4.2363,P<0.05).结论 针刺枕叶视中枢对应头皮部穴位治疗视神经萎缩的效果优于针刺常规穴位治疗视神经萎缩的疗效.

  1. Dissociation of Pupillary Post-Illumination Responses from Visual Function in Confirmed OPA1 c.983A > G and c.2708_2711delTTAG Autosomal Dominant Optic Atrophy

    DEFF Research Database (Denmark)

    Nissen, Claus; Rönnbäck, Cecilia; Sander, Birgit;

    2015-01-01

    the c.983A > G (n = 14) or the c.2708_ 2711delTTAG mutation (n = 15) were examined with monochromatic pupillometry, using isoluminant (300 cd/m(2)), red (660 nm) or blue (470 nm) light, optical coherence tomography, automated visual field analysis, and with determination of best corrected visual acuity......)) was preserved in both c.983A > G and c.2708_2711delTTAG ADOA despite severe visual loss and optic nerve atrophy. The study confirms, in a large sample of two genetically homogenous groups, that the ipRGCs are spared in ADOA....

  2. Disturbed mitochondrial and peroxisomal dynamics due to loss of MFF causes Leigh-like encephalopathy, optic atrophy and peripheral neuropathy.

    Science.gov (United States)

    Koch, Johannes; Feichtinger, René G; Freisinger, Peter; Pies, Mechthild; Schrödl, Falk; Iuso, Arcangela; Sperl, Wolfgang; Mayr, Johannes A; Prokisch, Holger; Haack, Tobias B

    2016-04-01

    Mitochondria are dynamic organelles which undergo continuous fission and fusion to maintain their diverse cellular functions. Components of the fission machinery are partly shared between mitochondria and peroxisomes, and inherited defects in two such components (dynamin-related protein (DRP1) and ganglioside-induced differentiation-associated protein 1 (GDAP1)) have been associated with human disease. Deficiency of a third component (mitochondrial fission factor, MFF) was recently reported in one index patient, rendering MFF another candidate disease gene within the expanding field of mitochondrial and peroxisomal dynamics. Here we investigated three new patients from two families with pathogenic mutations in MFF. The patients underwent clinical examination, brain MRI, and biochemical, cytological and molecular analyses, including exome sequencing. The patients became symptomatic within the first year of life, exhibiting seizures, developmental delay and acquired microcephaly. Dysphagia, spasticity and optic and peripheral neuropathy developed subsequently. Brain MRI showed Leigh-like patterns with bilateral changes of the basal ganglia and subthalamic nucleus, suggestive of impaired mitochondrial energy metabolism. However, activities of mitochondrial respiratory chain complexes were found to be normal in skeletal muscle. Exome sequencing revealed three different biallelic loss-of-function variants in MFF in both index cases. Western blot studies of patient-derived fibroblasts indicated normal content of mitochondria and peroxisomes, whereas immunofluorescence staining revealed elongated mitochondria and peroxisomes. Furthermore, increased mitochondrial branching and an abnormal distribution of fission-mediating DRP1 were observed. Our findings establish MFF loss of function as a cause of disturbed mitochondrial and peroxisomal dynamics associated with early-onset Leigh-like basal ganglia disease. We suggest that, even if laboratory findings are not indicative of

  3. Dominant optic atrophy in Denmark – report of 15 novel mutations in OPA1, using a strategy with a detection rate of 90%

    Directory of Open Access Journals (Sweden)

    Almind Gitte J

    2012-08-01

    Full Text Available Abstract Background Investigation of the OPA1 mutation spectrum in autosomal dominant optic atrophy (ADOA in Denmark. Methods Index patients from 93 unrelated ADOA families were assessed for a common Danish founder mutation (c.2826_2836delinsGGATGCTCCA inOPA1. If negative, direct DNA sequencing of the coding sequence and multiplex ligation-dependent probe amplification (MLPA were performed. Results from MLPA analysis have been previously reported. Haplotype analysis was carried out analysing single nucleotide polymorphisms (SNP. Retrospective clinical data were retrieved from medical files. Results Probably causative mutations were identified in 84 out of 93 families (90% including 15 novel mutations. Three mutations c.983A > G, c.2708_2711delTTAG and c.2826_2836delinsGGATGCTCCA, were responsible for ADOA in10, 11 and 28 families, respectively, corresponding to 11%, 12% and 30%. A common haplotype in nine of ten c.983A > G families suggests that they descend from a single founder. The c.2708_2711delTTAG mutation was present on at least two haplotypes and has been repeatedly reported in various ethnic groups,thus represents a mutational hotspot. Clinical examinations of index patients with the two latter mutations demonstrated large inter- and intra-familial variations apparently. Conclusions Genetic testing for OPA1mutations assist in the diagnosis. We have identified mutations in OPA1 in 90% of families including 15 novel mutations. Both DNA sequencing and MLPA analysis are necessary to achieve a high detection rate. More than half of the affected families in Denmark are represented by three common mutations, at least two of which are due to a founder effect, which may account for the high prevalence of ADOA in Denmark.

  4. Posterior cortical atrophy: a brief review.

    Science.gov (United States)

    Kirshner, Howard S; Lavin, Patrick J M

    2006-11-01

    Posterior cortical atrophy is a striking clinical syndrome in which a dementing illness begins with visual symptoms. Initially, the problem may seem to be loss of elementary vision, but over time the patient develops features of visual agnosia, topographical difficulty, optic ataxia, simultanagnosia, ocular apraxia (Balint's syndrome), alexia, acalculia, right-left confusion, and agraphia (Gerstmann's syndrome), and later a more generalized dementia. Occasional patients have visual hallucinations and signs of Parkinson's disease or Lewy body dementia. A number of different neuropathologic disorders are associated with posterior cortical atrophy.

  5. Progressive hemifacial atrophy

    Directory of Open Access Journals (Sweden)

    Abhijeet Sande

    2013-01-01

    Full Text Available Progressive hemifacial atrophy, also known as Parry-Romberg Syndrome, is an uncommon degenerative and poorly understood condition. It is characterized by a slow and progressive but self-limited atrophy affecting one side of the face. The incidence and the cause of this alteration are unknown. A cerebral disturbance of fat metabolism has been proposed as a primary cause. Possible factors that are involved in the pathogenesis include trauma, viral infections, heredity, endocrine disturbances and auto-immunity. The most common complications that appear in association to this disorder are: trigeminal neuralgia, facial paresthesia, severe headache and epilepsy. Characteristically, the atrophy progresses slowly for several years and, it becomes stable. The objective of this work is, through the presentation of a clinical case, to accomplish a literature review concerning general characteristics, etiology, physiopathology and treatment of progressive hemifacial atrophy.

  6. Spinal muscular atrophy

    National Research Council Canada - National Science Library

    D'Amico, Adele; Mercuri, Eugenio; Tiziano, Francesco D; Bertini, Enrico

    2011-01-01

    Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by degeneration of alpha motor neurons in the spinal cord, resulting in progressive proximal muscle weakness and paralysis...

  7. Spinal Muscular Atrophy

    Science.gov (United States)

    Spinal muscular atrophy (SMA) is a genetic disease that attacks nerve cells, called motor neurons, in the spinal cord. These cells communicate with your voluntary muscles - the ones you can control, like in your ...

  8. Bed Rest Muscular Atrophy

    Science.gov (United States)

    Greenleaf, John E.

    2000-01-01

    A major debilitating response from prolonged bed rest (BR) is muscle atrophy, defined as a "decrease in size of a part of tissue after full development has been attained: a wasting away of tissue as from disuse, old age, injury or disease". Part of the complicated mechanism for the dizziness, increased body instability, and exaggerated gait in patients who arise immediately after BR may be a result of not only foot pain, but also of muscular atrophy and associated reduction in lower limb strength. Also, there seems to be a close association between muscle atrophy and bone atrophy. A discussion of many facets of the total BR homeostatic syndrome has been published. The old adage that use determines form which promotes function of bone (Wolff's law) also applies to those people exposed to prolonged BR (without exercise training) in whom muscle atrophy is a consistent finding. An extreme case involved a 16-year-old boy who was ordered to bed by his mother in 1932: after 50 years in bed he had "a lily-white frame with limbs as thin as the legs of a ladder-back chair". These findings emphasize the close relationship between muscle atrophy and bone atrophy. In addition to loss of muscle mass during deconditioning, there is a significant loss of muscle strength and a decrease in protein synthesis. Because the decreases in force (strength) are proportionately greater than those in fiber size or muscle cross-sectional area, other contributory factors must be involved; muscle fiber dehydration may be important.

  9. Bed Rest Muscular Atrophy

    Science.gov (United States)

    Greenleaf, John E.

    2000-01-01

    A major debilitating response from prolonged bed rest (BR) is muscle atrophy, defined as a "decrease in size of a part of tissue after full development has been attained: a wasting away of tissue as from disuse, old age, injury or disease". Part of the complicated mechanism for the dizziness, increased body instability, and exaggerated gait in patients who arise immediately after BR may be a result of not only foot pain, but also of muscular atrophy and associated reduction in lower limb strength. Also, there seems to be a close association between muscle atrophy and bone atrophy. A discussion of many facets of the total BR homeostatic syndrome has been published. The old adage that use determines form which promotes function of bone (Wolff's law) also applies to those people exposed to prolonged BR (without exercise training) in whom muscle atrophy is a consistent finding. An extreme case involved a 16-year-old boy who was ordered to bed by his mother in 1932: after 50 years in bed he had "a lily-white frame with limbs as thin as the legs of a ladder-back chair". These findings emphasize the close relationship between muscle atrophy and bone atrophy. In addition to loss of muscle mass during deconditioning, there is a significant loss of muscle strength and a decrease in protein synthesis. Because the decreases in force (strength) are proportionately greater than those in fiber size or muscle cross-sectional area, other contributory factors must be involved; muscle fiber dehydration may be important.

  10. Research opportunities in muscle atrophy

    Science.gov (United States)

    Herbison, G. J. (Editor); Talbot, J. M. (Editor)

    1984-01-01

    Muscle atrophy in a weightless environment is studied. Topics of investigation include physiological factors of muscle atrophy in space flight, biochemistry, countermeasures, modelling of atrophied muscle tissue, and various methods of measurement of muscle strength and endurance. A review of the current literature and suggestions for future research are included.

  11. 针刺眶内穴位结合头针治疗视神经萎缩的疗效观察%Therapeutic effect of intraorbital acupuncture combined with scalp acupuncture treating optic atrophy

    Institute of Scientific and Technical Information of China (English)

    蔡萧君; 王丽媛; 赵晓龙

    2015-01-01

    OBJECTIVE To observe the therapeutic effect of intraorbital acupuncture combined with scalp acupuncture to treat optic atrophy. METHODS Ninety optic atrophy patients (111 eyes) were randomized divided into 3 groups. The treatment group (30 cases, 36 eyes) was treated by intraorbital acupuncture and scalp acupunc-ture, the intraorbital acupuncture control group (30 cases, 38 eyes) was treated only by intraorbital acupuncture, and the scalp acupuncture control group (30 cases, 37 eyes) was treated only by scalp acupuncture. All groups treated 2 weeks (14 days) as a course, continuous observation of 2 courses. RESULTS The total effective rate was 83.33%in the treatment group, 60.53%in the intraorbital acupuncture control group and 64.86%in the scalp acupuncture con-trol group, and the total effective rate of treatment group was significantly superior to that of the other 2 groups (P<0.05). Of treatment group,the improvement of vision, average light sensitivity and defects of visual field, amplitude and peak latencies of visual evoked potential (VEP) P100 wave after treatment were significantly better than the other 2 groups (P<0.05). CONCLUSIONS Intraorbital acupuncture combined with scalp acupuncture had better efficacy for optic atrophy, and was effective in improving the vision, average light sensitivity and defects of visual field, en-hancing the optic nerve fiber conduction velocity and the strength of the excitement of visual impulse.%目的:观察针刺眶内穴位结合头针治疗视神经萎缩的疗效。方法将90例视神经萎缩患者(111只眼)随机分为2组,治疗组30例(36只眼)采用针刺眶内穴位结合头针治疗;眶内对照组30例(38只眼)单用针刺眶内穴位治疗;头针对照组30例(37只眼)单用针刺头部穴位治疗。各组均以2周(14 d)为1个疗程,连续观察2个疗程。结果治疗组总有效率83.33%,眼针对照组总有效率60.53%,头针对照组总有效率64.86%,治疗

  12. [Posterior cortical atrophy].

    Science.gov (United States)

    Solyga, Volker Moræus; Western, Elin; Solheim, Hanne; Hassel, Bjørnar; Kerty, Emilia

    2015-06-02

    Posterior cortical atrophy is a neurodegenerative condition with atrophy of posterior parts of the cerebral cortex, including the visual cortex and parts of the parietal and temporal cortices. It presents early, in the 50s or 60s, with nonspecific visual disturbances that are often misinterpreted as ophthalmological, which can delay the diagnosis. The purpose of this article is to present current knowledge about symptoms, diagnostics and treatment of this condition. The review is based on a selection of relevant articles in PubMed and on the authors' own experience with the patient group. Posterior cortical atrophy causes gradually increasing impairment in reading, distance judgement, and the ability to perceive complex images. Examination of higher visual functions, neuropsychological testing, and neuroimaging contribute to diagnosis. In the early stages, patients do not have problems with memory or insight, but cognitive impairment and dementia can develop. It is unclear whether the condition is a variant of Alzheimer's disease, or whether it is a separate disease entity. There is no established treatment, but practical measures such as the aid of social care workers, telephones with large keypads, computers with voice recognition software and audiobooks can be useful. Currently available treatment has very limited effect on the disease itself. Nevertheless it is important to identify and diagnose the condition in its early stages in order to be able to offer patients practical assistance in their daily lives.

  13. Progressive hemifacial atrophy with ciliary body atrophy and ocular hypotony

    Directory of Open Access Journals (Sweden)

    T Ashwini Kini

    2015-01-01

    Full Text Available Progressive hemifacial atrophy (PHA is a disease of unknown etiology affecting one-half of the face. Ocular involvement is uncommon. Atrophy of iris is rare, with only a few cases of partial atrophy being reported in the literature. We report a case of total atrophy of iris and ciliary body with associated ocular hypotony in a 16-year-old girl with PHA. We believe this is the first reported case of complete atrophy of iris and ciliary body in PHA. Ocular hypotony in PHA was thought to be due to intra-ocular inflammation. However in our case it appears to be secondary to severe atrophy of the ciliary body.

  14. [Biomechanical properties of the cribriform lamina in glaucoma-induced atrophy of the optic nerve and after decompression operations on the scleral canal].

    Science.gov (United States)

    Mostovoĭ, E N; Shmyreva, V F; Kaĭdalov, A B

    2008-01-01

    The authors made a mathematical and clinical analysis of the cribriform lamina (CL) of the optic nerve and nerve fiber bundles passing through its foramens in glaucoma-induced optic neuropathy. It was shown that in elevated intraocular pressure, there was a significant CL deformity leading to the compression and deformity of nerve fibers. The important biomechanical characteristic of CL deformity is the tangent of the angle between the longitudinal axis of the scleral canal and the perpendicular to the CL surface. An increase in the inner radius of the scleral canal of the optic nerve due to its dissection at decompression surgery is one of the ways of diminishing CL flexure and nerve fiber deformity. A small increase in the scleral canal radius (by approximately 10%) was demonstrated to eliminate significant CL flexure.

  15. [Hereditary optic neuropathies].

    Science.gov (United States)

    Milea, D; Verny, C

    2012-10-01

    Hereditary optic neuropathies are a group of heterogeneous conditions affecting both optic nerves, with an autosomal dominant, autosomal recessive, X-related or mitochondrial transmission. The two most common non-syndromic hereditary optic neuropathies (Leber's hereditary optic neuropathy and autosomal dominant optic atrophy) are very different in their clinical presentation and their genetic transmission, leading however to a common, non-specific optic nerve atrophy. Beyond the optic atrophy-related visual loss, which is the clinical hallmark of this group of diseases, other associated neurological signs are increasingly recognized.

  16. The Molecular Pathogenesis of Autosomal Dominant Optic Atrophy%常染色体显性视神经萎缩的分子遗传学研究进展

    Institute of Scientific and Technical Information of China (English)

    张娟娟; 周翔天; 瞿佳; 管敏鑫

    2008-01-01

    Autosomal dominant optic atrophy (ADOA), also called Kjer optic neuropathy, is the most common form of inherited optic neuropathy with a prevalence between 1: 10 000 and 1 : 50 000. The optic atrophy often occurs in the childhood (the average age-of-onset: 7 years old) and with an insidious onset of variable visual loss, temperal optic nerve pallor, central or caecocentral visual field scotoma and dyschromatopsia (often appears tetartanopia). Histopathological studies suggest that the underlying defect is retinal ganglion cell degeneration. Mutations in OPA1 encoding a conserved mitochondrial dynamin-related GTPase are the major cause of ADOA. 117 OPA1 ADOA-associated mutations consisted of 31.6% of deletions/insertions, 16.2% of nonsense, 25.6% of missense and 28. 8% of splicing mutations. The majority of mutations reside at the ceding sequence of this gene, especially in the GTPase domain. Other ADOA-associated genes were OPA3 (19q13. 2-q13.3), OPA4 (18q12.2-q12.3) and OPA5 (22q12.1-q13.1). The variable phenotypes of vision loss suggest the involvement of other genetic factors, personal factors and environmental factors in the pathogcnesis of ADOA.%常染色体显性视神经萎缩常在儿童期发病,发病率约1:10 000~1:50 000,表现为隐匿性渐进性视力减退,双颞侧视盘苍白,中心或旁中心暗点,色觉障碍(常表现为蓝黄色盲).组织病理学表现为:视网膜神经节细胞退行性变.OPA1编码一种保守的动力相关GTPase,OPA1突变是ADOA发病的主要原因,目前已发现117个ADOA相关OPA1突变,包括:31.6%缺失和插人突变,16.2%无义突变,25.6%错义突变和28.8%剪接突变.这些突变分布于OPA1基因编码区,但多数位于GTPase区.另外,本病还与OPA3(19q13.2-q13.3)、OPA4(18q12.2-q12.3)及OPA5(22q12.1-q13.1)基因突变有关.个体间的表型差异表明:其他遗传因素、个人因素以及环境因素可能与ADOA发病有关.

  17. Muscular atrophy in diabetic neuropathy

    DEFF Research Database (Denmark)

    Andersen, H; Gadeberg, P C; Brock, B

    1997-01-01

    Diabetic patients with polyneuropathy develop motor dysfunction. To establish whether motor dysfunction is associated with muscular atrophy the ankle dorsal and plantar flexors of the non-dominant leg were evaluated with magnetic resonance imaging in 8 patients with symptomatic neuropathy, in 8 non...... confirmed that the atrophy predominated distally. We conclude that muscular atrophy underlies motor weakness at the ankle in diabetic patients with polyneuropathy and that the atrophy is most pronounced in distal muscles of the lower leg indicating that a length dependent neuropathic process explains...

  18. OPA1基因G401D突变导致常染色体视神经萎缩和听力受损%The G401D mutation of OPA1 causes autosomal dominant optic atrophy and hearing loss in a Chinese family

    Institute of Scientific and Technical Information of China (English)

    柯铁; 聂尚武; 杨琴波; 刘剑萍; 周琳娜; 任翔; 刘静宇; 王擎; 刘木根

    2006-01-01

    Objective To describe the clinical and genetic characteristics of a Chinese family affected with optic atrophy 1 (OPA1). Methods Linkage analysis and DNA sequencing as well as PCR/restriction fragment length polymorphism (RFLP) analysis were performed to identify the disease-causing mutation. Results A missense mutation, G401D in the OPA1 gene was identified, and the patients demonstrate inherited syndrome of optic atrophy and hearing loss. Conclusion The present study demonstrates that a mutation in the OPA1 gene can cause optic atrophy in Chinese patients, and supports the notion that OPA1 mutation may lead to OPA1 combined with hearing loss.%目的 对一个中国视神经萎缩1(optic atrophy 1, OPA1)家系进行临床和基因分析. 方法 对家系进行连锁分析,通过测序和限制性片段长度多态鉴定致病基因突变. 结果 在家系患者中均发现OPA1基因的一个错义突变1202(G→A),即G401D, 而且患者呈现出视神经萎缩以及听力受损的综合征症状.结论 在中国OPA1患者中鉴定了OPA1基因突变,并支持OPA1基因突变可导致伴随有听力受损的视神经萎缩.

  19. Comparação entre o polarímetro de varredura a laser, a tomografia de coerência óptica 1 e o Stratus-oct na detecção da perda axonal da atrofia em banda do nervo óptico Comparison of scanning laser polarimetry, optical coherence tomography 1 and Stratus optical coherence tomography for the detection of axonal loss in band atrophy of the optic nerve

    Directory of Open Access Journals (Sweden)

    Bruno Campelo Leal

    2006-08-01

    Full Text Available OBJETIVO: Comparar a capacidade do polarímetro de varredura a laser (GDx, do tomógrafo de coerência óptica (OCT 1 e do Stratus-OCT em diferenciar olhos normais de olhos com atrofia em banda do nervo óptico e hemianopsia temporal. MÉTODOS: Vinte e três olhos de pacientes com atrofia em banda do nervo óptico e 23 olhos de indivíduos normais foram incluídos em estudo prospectivo observacional caso-controle. Todos foram submetidos à análise da camada de fibras nervosas retiniana (CFNR utilizando GDx, OCT-1 e Stratus-OCT. As médias dos valores obtidos em cada aparelho foram comparadas entre olhos com atrofia em banda e controles normais. Curvas ROC (receiver operating characteristic e sensibilidade para especificidades fixas (80% e 95% foram calculadas para cada parâmetro produzido pelos três instrumentos e comparadas entre si. RESULTADOS: Quando comparados aos indivíduos normais, os resultados dos pacientes referentes à camada de fibras nervosas retiniana (média global e quatro quadrantes estudados foram significativamente menores (pPURPOSE: To compare the abilitiy of scanning laser polarimetry (GDx, optical coherence tomography (OCT 1 and Stratus- optical coherence tomography to discriminate between healthy eyes and eyes with band atrophy of the optic nerve and temporal hemianopsia. METHODS: Twenty-three eyes with band atrophy of the optic nerve and 23 eyes from healthy subjects were included in this observational prospective case-control study. All eyes underwent retinal nerve fiber layer (RNFL thickness analysis using GDx, optical coherence tomography-1 and Stratus-optical coherence tomography. Mean values obtained with each equipment were compared between band atrophy and normal eyes. Receiver operating characteristic (ROC curves and sensitivities at fixed specificities (80% e 95% were calculated for each parameter calculated with each equipment and compared. RESULTS: When compared with healthy subjects, the parameters

  20. Genetics Home Reference: multiple system atrophy

    Science.gov (United States)

    ... Home Health Conditions multiple system atrophy multiple system atrophy Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Multiple system atrophy is a progressive brain disorder that affects movement ...

  1. The inheritance of peripapillary atrophy

    NARCIS (Netherlands)

    Healey, Paul R.; Mitchell, Paul; Gilbert, Clare E.; Lee, Anne J.; Ge, Dongliang; Snieder, Harold; Spector, Timothy D.; Hammond, Christopher J.

    2007-01-01

    PURPOSE. To estimate the relative importance of genes and environment in peripapillary atrophy type beta (beta-PPA) in a classic twin study. METHODS. Female twin pairs (n = 506) aged 49 to 79 years were recruited from the St. Thomas' UK Adult Twin Registry. Peripapillary atrophy was identified from

  2. CAOS-Episodic Cerebellar Ataxia, Areflexia, Optic Atrophy, and Sensorineural Hearing Loss: A Third Allelic Disorder of the ATP1A3 Gene.

    Science.gov (United States)

    Heimer, Gali; Sadaka, Yair; Israelian, Lori; Feiglin, Ariel; Ruggieri, Alessandra; Marshall, Christian R; Scherer, Stephen W; Ganelin-Cohen, Esther; Marek-Yagel, Dina; Tzadok, Michal; Nissenkorn, Andreea; Anikster, Yair; Minassian, Berge A; Zeev, Bruria Ben

    2015-11-01

    We describe the molecular basis of a distinctive syndrome characterized by infantile stress-induced episodic weakness, ataxia, and sensorineural hearing loss, with permanent areflexia and optic nerve pallor. Whole exome sequencing identified a deleterious heterozygous c.2452 G>A, p.(E818K) variant in the ATP1A3 gene and structural analysis predicted its protein-destabilizing effect. This variant has not been reported in context with rapid-onset dystonia parkinsonism and alternating hemiplegia of childhood, the 2 main diseases associated with ATP1A3. The clinical presentation in the family described here differs categorically from these diseases in age of onset, clinical course, cerebellar over extrapyramidal movement disorder predominance, and peripheral nervous system involvement. While this paper was in review, a highly resembling phenotype was reported in additional patients carrying the same c.2452 G>A variant. Our findings substantiate this variant as the cause of a unique inherited autosomal dominant neurologic syndrome that constitutes a third allelic disease of the ATP1A3 gene. © The Author(s) 2015.

  3. Bilaterally impaired hand dexterity with posterior cortical atrophy

    Directory of Open Access Journals (Sweden)

    Nages Nagaratnam, MD, FRACP, FRCPA, FACC

    2015-12-01

    Full Text Available A 79-year- old man presented with bilaterally impaired hand movements pertaining to handling of objects although hand movements without the use of objects were preserved, findings consistent with tactile apraxia. His hand and finger movements were slow and clumsy. He had an isolated optic ataxia, a component of Balint's syndrome. The computed tomography scan showed enlargement of the posterior horns of the lateral ventricles. He had recurrent falls probably owing to visual attentional deficits, which may be present in patients with posterior cortical atrophy. The findings can be deemed to fall within the posterior cortical atrophy spectrum. The underlying mechanisms are discussed.

  4. Optic neuropathy in familial dysautonomia.

    Science.gov (United States)

    Groom, M; Kay, M D; Corrent, G F

    1997-06-01

    Optic atrophy, which is indicative of a CNS disorder, is a rarely described manifestation of familial dysautonomia (Riley-Day syndrome). As these patients are now living longer, the prevalence of optic neuropathy also may be increasing. We present a man with familial dysautonomia and visual loss resulting from optic atrophy and visual field defect suggestive of chiasmal pathology.

  5. Multiple system atrophy.

    Science.gov (United States)

    Peeraully, Tasneem

    2014-04-01

    Multiple system atrophy (MSA) is a rare adult-onset synucleinopathy associated with dysautonomia and the variable presence of poorly levodopa-responsive parkinsonism and/or cerebellar ataxia. Other clinical symptoms that can be associated with MSA include hyperreflexia, stridor, sleep apnea, and rapid eye movement sleep behavior disorder (RBD). Mean survival from time of diagnosis ranges between 6 to 10 years, and definitive diagnosis is made on autopsy with demonstration of oligodendroglial cytoplasmic inclusions consisting of fibrillar α-synuclein. Magnetic resonance imaging (MRI) may be positive for cruciform T2 hyperintensity within the pons (the "hot cross bun sign"), volume loss in the pons and cerebellum, and T2 signal loss in the dorsolateral putamen with hyperintense rim on fluid attenuated inversion recovery (FLAIR) sequencing. Although most cases are sporadic, genetic polymorphisms have been identified both in familial and sporadic cases of MSA, and influence observed phenotypes. Treatment is symptomatic, with both pharmacological and nonpharmacological strategies. There are currently no consensus guidelines on management. Current and future research is aimed at identifying biomarkers and developing disease-modifying therapies.

  6. Genetics Home Reference: optic atrophy type 1

    Science.gov (United States)

    ... organization of the shape and structure of the mitochondria and in controlled cell death ( apoptosis ). The OPA1 protein is also involved ... energy production. Cells that contain these poorly functioning mitochondria are ... In particular, cells that have high energy demands, such as retinal ...

  7. Idiopathic atrophie blanche.

    Science.gov (United States)

    Amato, Lauretta; Chiarini, Caterina; Berti, Samantha; Massi, Daniela; Fabbri, Paolo

    2006-01-01

    clinical, serologic, histopathologic, and immunopathologic findings, a diagnosis of idiopathic atrophie blanche was made. The patient was treated with dapsone (50 mg p.o. q.d.) and pentoxifylline (400 mg p.o. t.i.d.) with pain relief and complete resolution of the ulcerations after 6 weeks of therapy.

  8. [Atrophy of the bone marrow].

    Science.gov (United States)

    Dziecioł, J; Kemona, A; Sulik, M; Sulkowski, S; Brykalska, A; Sobaniec-Lotowska, M; Ostapiuk, H

    1990-01-01

    The authors made a quantitative analysis of the active hematopoietic tissue of the bone marrow with particular consideration of its atrophy in the course of various diseases. The material consisted of 407 non-selected autopsy cases. For a morphometric analysis the bone marrow was sampled from the sternum, ala ossis illi and spine. In the quantitative analysis of the active hematopoietic tissue we took into account age groups as quantitative changes appear with age. Atrophy of the bone marrow was in 19.4% of the studied cases. The presence of bone marrow atrophy was found in the course of various diseases, most frequently neoplastic, particularly in patients aged from 50 to 59 years.

  9. 利用频域光学相干断层扫描测量青光眼视盘旁萎缩区%Application of Spectral-domain Optical Coherence Tomography for Measuring Peripapillary Atrophy in Glaucoma

    Institute of Scientific and Technical Information of China (English)

    马小力; 刘贤洁; 陈禹橦; 李丹丹; 张宏伟; 华瑞

    2015-01-01

    目的:利用频域光学相干断层扫描(SD-OCt)和眼底彩色照相方法测量青光眼视盘旁萎缩区,并比较二者结果的一致性。方法连续收集就诊于中国医科大学附属第一医院眼科的青光眼患者30例(54只眼),进行视盘SD-OCt检查和眼底彩色立体照相。分别测量以视盘为中心6条子午线上视盘旁萎缩区β区宽度并计算平均值,比较2种检查结果的相关性,并进行一致性评价。结果使用眼底彩色照相法和 SD-OCt 检查法测量青光眼患者眼底视盘旁萎缩区β区平均宽度分别为(229.89±99.82)μm和(224.14±97.10)μm,二者比较无统计学差异(P =0.280)。2种检查方法结果具有高度相关性(r =0.825,P <0.001),二者间具有良好的一致性(ICC=0.923,95% CI 0.870~0.954)。结论利用SD-OCt法与眼底彩色照相法测量青光眼视盘旁萎缩区β区结果具有良好的一致性,可以利用SD-OCt方法测量青光眼视盘旁萎缩区β区。%Objective to measure peripapillary atrophy(PPA)in glaucoma with high-resolution spectral domain-optical coherence tomography (SD-OCt)and conventional color fundus photograph,and compare the consistency of the results between the two imaging methods. Methods A to-tal of 30 patients(54 eyes)with glaucoma from Department of Opthalmology,the First Hospital,China Medical University were prospectively includ-ed for the study. SD-OCt images and color fundus photographs taken through the region of PPA were qualitatively analyzed. the average width of β-PPA area in 6 reference lines centered optic nerve were measured using SD-OCt and color fundus photograph. Correlation and agreement between the two measuring methods were analyzed. Results the average width of β-PPA was 229.89±99.82 μm using color fundus photographs and 224.14±97.10 μm using SD-OCt,respectively. there was no significant difference(P = 0.280). the correlation coefficient was 0.825 between re

  10. Types of SMA (Spinal Muscular Atrophy)

    Science.gov (United States)

    ... genes other than the SMN1 gene. Spinal Muscular Atrophy Respiratory Distress (SMARD) SMARD is a very rare ... and 50. It causes muscle weakness and wasting (atrophy) throughout the body, which is most noticeable in ...

  11. Genetics Home Reference: dentatorubral-pallidoluysian atrophy

    Science.gov (United States)

    ... Understand Genetics Home Health Conditions DRPLA dentatorubral-pallidoluysian atrophy Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Dentatorubral-pallidoluysian atrophy , commonly known as DRPLA , is a progressive brain ...

  12. Hereditary optic neuropathies share a common mitochondrial coupling defect.

    Science.gov (United States)

    Chevrollier, Arnaud; Guillet, Virginie; Loiseau, Dominique; Gueguen, Naïg; de Crescenzo, Marie-Anne Pou; Verny, Christophe; Ferre, Marc; Dollfus, Hélène; Odent, Sylvie; Milea, Dan; Goizet, Cyril; Amati-Bonneau, Patrizia; Procaccio, Vincent; Bonneau, Dominique; Reynier, Pascal

    2008-06-01

    Hereditary optic neuropathies are heterogeneous diseases characterized by the degeneration of retinal ganglion cells leading to optic nerve atrophy and impairment of central vision. We found a common coupling defect of oxidative phosphorylation in fibroblasts of patients affected by autosomal dominant optic atrophy (mutations of OPA1), autosomal dominant optic atrophy associated with cataract (mutations of OPA3), and Leber's hereditary optic neuropathy, a disorder associated with point mutations of mitochondrial DNA complex I genes. Interestingly, the energetic defect was significantly more pronounced in Leber's hereditary optic neuropathy and autosomal dominant optic atrophy patients with a more complex phenotype, the so-called plus phenotype.

  13. Mitochondrial signaling contributes to disuse muscle atrophy

    Science.gov (United States)

    Wiggs, Michael P.; Duarte, Jose A.; Zergeroglu, A. Murat; Demirel, Haydar A.

    2012-01-01

    It is well established that long durations of bed rest, limb immobilization, or reduced activity in respiratory muscles during mechanical ventilation results in skeletal muscle atrophy in humans and other animals. The idea that mitochondrial damage/dysfunction contributes to disuse muscle atrophy originated over 40 years ago. These early studies were largely descriptive and did not provide unequivocal evidence that mitochondria play a primary role in disuse muscle atrophy. However, recent experiments have provided direct evidence connecting mitochondrial dysfunction to muscle atrophy. Numerous studies have described changes in mitochondria shape, number, and function in skeletal muscles exposed to prolonged periods of inactivity. Furthermore, recent evidence indicates that increased mitochondrial ROS production plays a key signaling role in both immobilization-induced limb muscle atrophy and diaphragmatic atrophy occurring during prolonged mechanical ventilation. Moreover, new evidence reveals that, during denervation-induced muscle atrophy, increased mitochondrial fragmentation due to fission is a required signaling event that activates the AMPK-FoxO3 signaling axis, which induces the expression of atrophy genes, protein breakdown, and ultimately muscle atrophy. Collectively, these findings highlight the importance of future research to better understand the mitochondrial signaling mechanisms that contribute to disuse muscle atrophy and to develop novel therapeutic interventions for prevention of inactivity-induced skeletal muscle atrophy. PMID:22395111

  14. Gastric atrophy, diagnosing and staging

    Institute of Scientific and Technical Information of China (English)

    Hala MT El-Zimaity

    2006-01-01

    H pylori is now accepted as the cause of gastritis and gastritis-associated diseases, such as duodenal ulcer,gastric ulcer, gastric carcinoma, and gastric MALT lymphoma. The natural history of H pylori gastritis includes inflammation progressing from the antrum into the adjacent corpus resulting in an atrophic front of advancing injury leading to a reduction in acid secretion and eventual loss of parietal cells and development of atrophy. Sub-typing intestinal metaplasia has no clinical value to the patient, the pathologist, or the endoscopist.The pattern, extent, and severity of atrophy, with or without intestinal metaplasia, is a far more important predictor than is intestinal metaplasia subtype. The challenge remains to identify a reliable marker that relates to pre-malignant potential.

  15. Neuronal involvement in muscular atrophy

    Directory of Open Access Journals (Sweden)

    Bruno Alejandro Cisterna

    2014-12-01

    Full Text Available The innervation of skeletal myofibers exerts a crucial influence on the maintenance of muscle tone and normal operation. Consequently, denervated myofibers manifest atrophy, which is preceded by an increase in sarcolemma permeability. Recently, de novo expression of hemichannels formed by connexins and other none selective channels, including P2X7 receptors, TRPV2 channels were demonstrated in denervated fast skeletal muscles. The denervation-induced atrophy was drastically prevented in denervated muscles deficient in connexins 43 and 45. Nonetheless, the transduction mechanism by which the nerve represses the expression of the above mentioned none selective channels remains unknown. The paracrine action of extracellular signaling molecules including ATP, neurotrophic factors (i.e., BDNF, agrin/Lrp4/MuSK and acetylcholine are among the possible perpetrators of repression for connexin expression. This review discusses the possible role of relevant factors in maintaining the normal functioning of fast skeletal muscles and suppression of connexin hemichannel expression.

  16. Ultrawide-field fundus photography of the first reported case of gyrate atrophy from Australia.

    Science.gov (United States)

    Moloney, Thomas P; O'Hagan, Stephen; Lee, Lawrence

    2014-01-01

    Gyrate atrophy of the choroid and retina is a rare chorioretinal dystrophy inherited in an autosomal recessive pattern. We describe the first documented case of gyrate atrophy from Australia in a 56-year-old woman with a history of previous diagnosis of retinitis pigmentosa and worsening night vision in her right eye over several years. She was myopic and bilaterally pseudophakic, and fundus examination revealed pale optic discs and extensive peripheral chorioretinal atrophy exposing bare sclera bilaterally with only small islands of normal-appearing retina at each posterior pole. Visual field testing showed grossly constricted fields, blood testing showed hyperornithinemia, and further questioning revealed consanguinity between the patient's parents. We then used the patient's typical retinal findings of gyrate atrophy to demonstrate the potential use of ultrawide-field fundus photography and angiography in diagnosis and monitoring response in future treatment.

  17. Mitochondrial signaling contributes to disuse muscle atrophy

    OpenAIRE

    Powers, Scott K.; Wiggs, Michael P.; Duarte, Jose A.; Zergeroglu, A. Murat; Demirel, Haydar A.

    2012-01-01

    It is well established that long durations of bed rest, limb immobilization, or reduced activity in respiratory muscles during mechanical ventilation results in skeletal muscle atrophy in humans and other animals. The idea that mitochondrial damage/dysfunction contributes to disuse muscle atrophy originated over 40 years ago. These early studies were largely descriptive and did not provide unequivocal evidence that mitochondria play a primary role in disuse muscle atrophy. However, recent exp...

  18. Cube propagation for focal brain atrophy estimation

    DEFF Research Database (Denmark)

    Pai, Akshay Sadananda Uppinakudru; Sørensen, Lauge; Darkner, Sune

    2013-01-01

    or localization of atrophy and subsequent summing to an ROI measure of atrophy. ST and SF only offer whole ROI atrophy measures. JI and SF suffer from a lack of precision originating from respectively approximating a space and a time integral by a finite sum. VM suffers from a high computational burden and the ST......Precise and robust whole brain, ventricle, and hippocampal atrophy measurements are important as they serve as biomarkers for Alzheimer’s disease. They are used as secondary outcomes in drug trials, and they correlate with the cognitive scores. When two successive scans are non-linearly aligned...

  19. Genetics Home Reference: spinal and bulbar muscular atrophy

    Science.gov (United States)

    ... Kennedy spinal and bulbar muscular atrophy Kennedy's disease SBMA X-linked spinal and bulbar muscular atrophy Related ... Natural history of spinal and bulbar muscular atrophy (SBMA): a study of 223 Japanese patients. Brain. 2006 ...

  20. Seronegative Intestinal Villous Atrophy: A Diagnostic Challenge

    Directory of Open Access Journals (Sweden)

    Cláudio Martins

    2016-01-01

    Full Text Available Celiac disease is the most important cause of intestinal villous atrophy. Seronegative intestinal villous atrophy, including those that are nonresponsive to a gluten-free diet, is a diagnostic challenge. In these cases, before establishing the diagnosis of seronegative celiac disease, alternative etiologies of atrophic enteropathy should be considered. Recently, a new clinical entity responsible for seronegative villous atrophy was described—olmesartan-induced sprue-like enteropathy. Herein, we report two uncommon cases of atrophic enteropathy in patients with arterial hypertension under olmesartan, who presented with severe chronic diarrhea and significant involuntary weight loss. Further investigation revealed intestinal villous atrophy and intraepithelial lymphocytosis. Celiac disease and other causes of villous atrophy were ruled out. Drug-induced enteropathy was suspected and clinical improvement and histologic recovery were verified after olmesartan withdrawal. These cases highlight the importance for clinicians to maintain a high index of suspicion for olmesartan as a precipitant of sprue-like enteropathy.

  1. Imaging geographic atrophy in age-related macular degeneration.

    Science.gov (United States)

    Göbel, Arno P; Fleckenstein, Monika; Schmitz-Valckenberg, Steffen; Brinkmann, Christian K; Holz, Frank G

    2011-01-01

    Advances in retinal imaging technology have largely contributed to the understanding of the natural history, prognostic markers and disease mechanisms of geographic atrophy (GA) due to age-related macular degeneration. There is still no therapy available to halt or slow the disease process. In order to evaluate potential therapeutic effects in interventional trials, there is a need for precise quantification of the GA progression rate. Fundus autofluorescence imaging allows for accurate identification and segmentation of atrophic areas and currently represents the gold standard for evaluating progressive GA enlargement. By means of high-resolution spectral-domain optical coherence tomography, distinct microstructural alterations related to GA can be visualized.

  2. Quantitative MRI study of progressive cerebral atrophy in multiple system atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Konagaya, Masaaki; Matsuoka, Yukihiko [Suzuka National Hospital, Suzuka, Mie (Japan); Konagaya, Yoko [JR Tokai General Hospital, Nagoya (Japan)

    2002-02-01

    We investigated cerebral atrophy in multiple system atrophy (MSA) by quantitative analysis of MRI. The subjects were 28 patients with MSA (14 striato-nigral degeneration; SND, 14 olivo-ponto-cerebellar atrophy; OPCA. 106 MRI examinations were performed totally) and 85 normal persons for control. The ratios of the ventral pons to the infratentorial space in the sagittal section, the putamen, cerebrum, frontal lobe and parietal and occipital lobes to the intracranial space in the horizontal section, and the temporal lobe to the intracranial space in the coronal section were measured. In the early stage of the disease, OPCA showed significant atrophy of the ventral pons compared with SND, and conversely, SND demonstrated significantly smaller putamen than that in OPCA. According to the progression of the disease, the atrophy of these neural tissues progressed, which resulted in so significant differences between SND and OPCA. The cerebral atrophy was observed in 17 MSA patients. The atrophy of the frontal lobe was much frequent and prominent to that in the temporal lobe and parietal and occipital lobes. SND showed higher incidence of the cerebral atrophy than OPCA in the early stage of the disease. In long period follow-up cases, one case showed cerebral atrophy in earlier stage, and another case in late stage. We indicated the involvement of the cerebral hemispheres in MSA, especially the frontal lobe. (author)

  3. Infraspinatus muscle atrophy from suprascapular nerve compression.

    Science.gov (United States)

    Cordova, Christopher B; Owens, Brett D

    2014-02-01

    Muscle weakness without pain may signal a nerve compression injury. Because these injuries should be identified and treated early to prevent permanent muscle weakness and atrophy, providers should consider suprascapular nerve compression in patients with shoulder muscle weakness.

  4. Mitochondrial signaling contributes to disuse muscle atrophy

    National Research Council Canada - National Science Library

    Powers, Scott K; Wiggs, Michael P; Duarte, Jose A; Zergeroglu, A Murat; Demirel, Haydar A

    2012-01-01

    It is well established that long durations of bed rest, limb immobilization, or reduced activity in respiratory muscles during mechanical ventilation results in skeletal muscle atrophy in humans and other animals...

  5. Hippocampal atrophy rates in Alzheimer disease

    Science.gov (United States)

    Henneman, W J.P.; Sluimer, J D.; Barnes, J; van der Flier, W M.; Sluimer, I C.; Fox, N C.; Scheltens, P; Vrenken, H; Barkhof, F

    2009-01-01

    Objective: To investigate the added value of hippocampal atrophy rates over whole brain volume measurements on MRI in patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI), and controls. Methods: We included 64 patients with AD (67 ± 9 years; F/M 38/26), 44 patients with MCI (71 ± 6 years; 21/23), and 34 controls (67 ± 9 years; 16/18). Two MR scans were performed (scan interval: 1.8 ± 0.7 years; 1.0 T), using a coronal three-dimensional T1-weighted gradient echo sequence. At follow-up, 3 controls and 23 patients with MCI had progressed to AD. Hippocampi were manually delineated at baseline. Hippocampal atrophy rates were calculated using regional, nonlinear fluid registration. Whole brain baseline volumes and atrophy rates were determined using automated segmentation and registration tools. Results: All MRI measures differed between groups (p < 0.005). For the distinction of MCI from controls, larger effect sizes of hippocampal measures were found compared to whole brain measures. Between MCI and AD, only whole brain atrophy rate differed significantly. Cox proportional hazards models (variables dichotomized by median) showed that within all patients without dementia, hippocampal baseline volume (hazard ratio [HR]: 5.7 [95% confidence interval: 1.5–22.2]), hippocampal atrophy rate (5.2 [1.9–14.3]), and whole brain atrophy rate (2.8 [1.1–7.2]) independently predicted progression to AD; the combination of low hippocampal volume and high atrophy rate yielded a HR of 61.1 (6.1–606.8). Within patients with MCI, only hippocampal baseline volume and atrophy rate predicted progression. Conclusion: Hippocampal measures, especially hippocampal atrophy rate, best discriminate mild cognitive impairment (MCI) from controls. Whole brain atrophy rate discriminates Alzheimer disease (AD) from MCI. Regional measures of hippocampal atrophy are the strongest predictors of progression to AD. GLOSSARY AD = Alzheimer disease; BET = brain

  6. Optics

    CERN Document Server

    Fincham, W H A

    2013-01-01

    Optics: Ninth Edition Optics: Ninth Edition covers the work necessary for the specialization in such subjects as ophthalmic optics, optical instruments and lens design. The text includes topics such as the propagation and behavior of light; reflection and refraction - their laws and how different media affect them; lenses - thick and thin, cylindrical and subcylindrical; photometry; dispersion and color; interference; and polarization. Also included are topics such as diffraction and holography; the limitation of beams in optical systems and its effects; and lens systems. The book is recommen

  7. Zika virus causes testicular atrophy

    Science.gov (United States)

    Uraki, Ryuta; Hwang, Jesse; Jurado, Kellie Ann; Householder, Sarah; Yockey, Laura J.; Hastings, Andrew K.; Homer, Robert J.; Iwasaki, Akiko; Fikrig, Erol

    2017-01-01

    Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that has recently been found to cause fetal infection and neonatal abnormalities, including microcephaly and neurological dysfunction. ZIKV persists in the semen months after the acute viremic phase in humans. To further understand the consequences of ZIKV persistence in males, we infected Ifnar1−/− mice via subcutaneous injection of a pathogenic but nonlethal ZIKV strain. ZIKV replication persists within the testes even after clearance from the blood, with interstitial, testosterone-producing Leydig cells supporting virus replication. We found high levels of viral RNA and antigen within the epididymal lumen, where sperm is stored, and within surrounding epithelial cells. Unexpectedly, at 21 days post-infection, the testes of the ZIKV-infected mice were significantly smaller compared to those of mock-infected mice, indicating progressive testicular atrophy. ZIKV infection caused a reduction in serum testosterone, suggesting that male fertility can be affected. Our findings have important implications for nonvector-borne vertical transmission, as well as long-term potential reproductive deficiencies, in ZIKV-infected males. PMID:28261663

  8. Can antioxidants protect against disuse muscle atrophy?

    Science.gov (United States)

    Powers, Scott K

    2014-11-01

    Long periods of skeletal muscle inactivity (e.g. prolonged bed rest or limb immobilization) results in a loss of muscle protein and fibre atrophy. This disuse-induced muscle atrophy is due to both a decrease in protein synthesis and increased protein breakdown. Although numerous factors contribute to the regulation of the rates of protein breakdown and synthesis in skeletal muscle, it has been established that prolonged muscle inactivity results in increased radical production in the inactive muscle fibres. Further, this increase in radical production plays an important role in the regulation of redox-sensitive signalling pathways that regulate both protein synthesis and proteolysis in skeletal muscle. Indeed, it was suggested over 20 years ago that antioxidant supplementation has the potential to protect skeletal muscles against inactivity-induced fibre atrophy. Since this original proposal, experimental evidence has implied that a few compounds with antioxidant properties are capable of delaying inactivity-induced muscle atrophy. The objective of this review is to discuss the role that radicals play in the regulation of inactivity-induced skeletal muscle atrophy and to provide an analysis of the recent literature indicating that specific antioxidants have the potential to defer disuse muscle atrophy.

  9. Ultrawide-field fundus photography of the first reported case of gyrate atrophy from Australia

    Directory of Open Access Journals (Sweden)

    Moloney TP

    2014-08-01

    Full Text Available Thomas P Moloney,1 Stephen O’Hagan,1 Lawrence Lee2,3 1Department of Ophthalmology, Cairns Hospital, Cairns, QLD, Australia; 2City Eye Centre, Brisbane, QLD, Australia; 3Associate Professor of Ophthalmology, School of Medicine, University of Queensland, Brisbane, QLD, Australia Abstract: Gyrate atrophy of the choroid and retina is a rare chorioretinal dystrophy inherited in an autosomal recessive pattern. We describe the first documented case of gyrate atrophy from Australia in a 56-year-old woman with a history of previous diagnosis of retinitis pigmentosa and worsening night vision in her right eye over several years. She was myopic and bilaterally pseudophakic, and fundus examination revealed pale optic discs and extensive peripheral chorioretinal atrophy exposing bare sclera bilaterally with only small islands of normal-appearing retina at each posterior pole. Visual field testing showed grossly constricted fields, blood testing showed hyperornithinemia, and further questioning revealed consanguinity between the patient’s parents. We then used the patient’s typical retinal findings of gyrate atrophy to demonstrate the potential use of ultrawide-field fundus photography and angiography in diagnosis and monitoring response in future treatment. Keywords: gyrate atrophy, ultrawide-field retinal photography, angiography, retinal photography, hyperornithinemia

  10. [Familial posterior cortical atrophy with visual agnosia and Bálint's syndrome].

    Science.gov (United States)

    Otsuki, M; Soma, Y; Tanaka, M; Tanaka, K; Tanno, Y; Uesugi, Y; Tsuji, S

    1995-12-01

    We report a patient of posterior cortical atrophy with progressive visual agnosia, Bálint's syndrome and dementia in which posterior cortical atrophy with similar characteristics on CT and progressive dementia were found in a sister. The patient was a 75-year-old woman who noted the onset of a progressive visual disorder at the age of 70, and whose family first noticed disoriented behavior at around the same period. Ophthalmologic examinations revealed mild cataract but no evidence of peripheral optic nerve or retinal lesions. Neuropsychological examination showed right homonymous hemianopia, visual agnosia, Bálint's syndrome, mild transcortical sensory aphasia, Gerstmann's syndrome, constructional apraxia, mild ideomotor apraxia and memory disorder. MRI showed marked dilatation of both lateral ventricles, especially the posterior horns, and severe atrophy of the occipital lobes, hippocampus, and the parahippocampal gyrus. Assessment of regional cerebral blood flow by IMP-SPECT revealed a generalized decrease in the temporo-parieto-occipital region bilaterally. The patient's sister began to show evidence of progressive dementia at 80 years of age and CT of the brain revealed marked atrophy, predominantly in the occipital lobes, similar to that of the patient. We believe this to be the first report of posterior cortical atrophy with a positive family history, suggesting the possibility of a hereditary syndrome.

  11. Optic nerve oxygenation

    DEFF Research Database (Denmark)

    Stefánsson, Einar; Pedersen, Daniella Bach; Jensen, Peter Koch

    2005-01-01

    at similar levels of perfusion pressure. The levels of perfusion pressure that lead to optic nerve hypoxia in the laboratory correspond remarkably well to the levels that increase the risk of glaucomatous optic nerve atrophy in human glaucoma patients. The risk for progressive optic nerve atrophy in human...... glaucoma patients is six times higher at a perfusion pressure of 30 mmHg, which corresponds to a level where the optic nerve is hypoxic in experimental animals, as compared to perfusion pressure levels above 50 mmHg where the optic nerve is normoxic. Medical intervention can affect optic nerve oxygen......-oxygenase inhibitor, indomethacin, which indicates that prostaglandin metabolism plays a role. Laboratory studies suggest that carbonic anhydrase inhibitors might be useful for medical treatment of optic nerve and retinal ischemia, potentially in diseases such as glaucoma and diabetic retinopathy. However, clinical...

  12. Optic nerve oxygenation

    DEFF Research Database (Denmark)

    Stefánsson, Einar; Pedersen, Daniella Bach; Jensen, Peter Koch;

    2005-01-01

    at similar levels of perfusion pressure. The levels of perfusion pressure that lead to optic nerve hypoxia in the laboratory correspond remarkably well to the levels that increase the risk of glaucomatous optic nerve atrophy in human glaucoma patients. The risk for progressive optic nerve atrophy in human...... glaucoma patients is six times higher at a perfusion pressure of 30 mmHg, which corresponds to a level where the optic nerve is hypoxic in experimental animals, as compared to perfusion pressure levels above 50 mmHg where the optic nerve is normoxic. Medical intervention can affect optic nerve oxygen......-oxygenase inhibitor, indomethacin, which indicates that prostaglandin metabolism plays a role. Laboratory studies suggest that carbonic anhydrase inhibitors might be useful for medical treatment of optic nerve and retinal ischemia, potentially in diseases such as glaucoma and diabetic retinopathy. However, clinical...

  13. Global brain atrophy but not hippocampal atrophy is related to type 2 diabetes

    NARCIS (Netherlands)

    Wisse, L.E.; Bresser, J. de; Geerlings, M.I.; Reijmer, Y.D.; Portegies, M.L.; Brundel, M.; Kappelle, L.J.; Graaf, Y. van der; Biessels, G.J.; Kessels, R.P.C.

    2014-01-01

    AIMS: It has been suggested that in patients with type 2 diabetes mellitus (T2DM), brain atrophy is most pronounced in the hippocampus, but this has not been investigated systematically. The present pooled analysis of three studies examined if hippocampal atrophy is more prominent than global brain

  14. Can endoscopic atrophy predict histological atrophy? Historical study in United Kingdom and Japan.

    Science.gov (United States)

    Kono, Shin; Gotoda, Takuji; Yoshida, Shigeaki; Oda, Ichiro; Kondo, Hitoshi; Gatta, Luigi; Naylor, Greg; Dixon, Michael; Moriyasu, Fuminori; Axon, Anthony

    2015-12-14

    To assess the diagnostic concordance between endoscopic and histological atrophy in the United Kingdom and Japan. Using published data, a total of 252 patients, 126 in the United Kingdom and 126 in Japan, aged 20 to 80 years, were evaluated. The extent of endoscopic atrophy was classified into five subgroups according to a modified Kimura-Takemoto classification system and was compared with histological findings of atrophy at five biopsy sites according to the updated Sydney system. The strength of agreement of the extent of atrophy between histology and visual endoscopic inspection showed good reproducibility, with a weighted kappa value of 0.76 (P atrophy (OR = 0.10, 95%CI: 0.03-0.36). The strength of agreement between endoscopic and histological atrophy, assessed by cancer risk-oriented grading, was reproducible, with a kappa value of 0.81 (95%CI: 0.75-0.87). Only nine patients (3.6%) were endoscopically underdiagnosed with antral predominant rather than extensive atrophy and were considered false negatives. Endoscopic grading can predict histological atrophy with few false negatives, indicating that precancerous conditions can be identified during screening endoscopy, particularly in patients in western countries.

  15. Correlation of Brain Atrophy, Disability, and Spinal Cord Atrophy in a Murine Model of Multiple Sclerosis.

    Science.gov (United States)

    Paz Soldán, M Mateo; Raman, Mekala R; Gamez, Jeffrey D; Lohrey, Anne K; Chen, Yi; Pirko, Istvan; Johnson, Aaron J

    2015-01-01

    Disability progression in multiple sclerosis (MS) remains incompletely understood. Unlike lesional measures, central nervous system atrophy has a strong correlation with disability. Theiler's murine encephalomyelitis virus infection in SJL/J mice is an established model of progressive MS. We utilized in vivo MRI to quantify brain and spinal cord atrophy in this model and analyzed the temporal relationship between atrophy and disability. Infected and control mice were followed for 12 months. Disability was assessed periodically using rotarod assay. Volumetric MRI datasets were acquired at 7 Tesla. Ventricular volume and C4-5 spinal cord cross-sectional area measurements were performed using Analyze 10. At 3 months, brain atrophy reached statistical significance (P = .005). In contrast, disability did not differ until 4 months post-infection (P = .0005). Cord atrophy reached significance by 9 months (P = 0.009). By 12 months, brain atrophy resulted in 111.8% increased ventricular volume (P = .00003), while spinal cord cross-sectional area was 25.6% reduced (P = .001) among cases. Our results suggest that significant brain atrophy precedes and predicts the development of disability, while spinal cord atrophy occurs late and correlates with severe disability. The observed temporal relationship establishes a framework for mechanisms of disability progression and enables further investigations of their underlying substrate. Copyright © 2015 by the American Society of Neuroimaging.

  16. Optics

    CERN Document Server

    Fincham, W H A

    2013-01-01

    Optics: Eighth Edition covers the work necessary for the specialization in such subjects as ophthalmic optics, optical instruments and lens design. The text includes topics such as the propagation and behavior of light; reflection and refraction - their laws and how different media affect them; lenses - thick and thin, cylindrical and subcylindrical; photometry; dispersion and color; interference; and polarization. Also included are topics such as diffraction and holography; the limitation of beams in optical systems and its effects; and lens systems. The book is recommended for engineering st

  17. No relevant midbrain atrophy in Parkinson's disease.

    Science.gov (United States)

    Mäkinen, E; Joutsa, J; Isotalo, J; Kaasinen, V

    2016-11-01

    To investigate whether significant midbrain atrophy is present in Parkinson's disease (PD), and if so, whether it can be used as a marker of striatal dopaminergic degeneration. In total, 150 PD patients and 155 controls were scanned with both brain dopamine transporter (DAT) [(123) I]FP-CIT SPECT and 1.5T MRI. Midbrain atrophy was measured from sagittal MRIs using the midbrain-to-pons ratios. Both striatal region-of-interest-based (Brass) and striatal and extrastriatal voxel-by-voxel-based DAT binding (SPM8) were investigated in relation to midbrain atrophy. The midbrain-to-pons ratios in PD patients were slightly lower than those in the controls (mean 0.59 vs 0.61, P atrophy is present in PD and can be detected with MRI. However, the midbrain atrophy in PD is not associated with the level of striatal dopaminergic dysfunction, and midbrain measurements therefore cannot be used as a clinically useful predictor of dopamine function. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Newly developed vaginal atrophy symptoms II and vaginal pH: a better correlation in vaginal atrophy?

    Science.gov (United States)

    Tuntiviriyapun, P; Panyakhamlerd, K; Triratanachat, S; Chatsuwan, T; Chaikittisilpa, S; Jaisamrarn, U; Taechakraichana, N

    2015-04-01

    The primary objective of this study was to evaluate the correlation among symptoms, signs, and the number of lactobacilli in postmenopausal vaginal atrophy. The secondary objective was to develop a new parameter to improve the correlation. A cross-sectional descriptive study. Naturally postmenopausal women aged 45-70 years with at least one clinical symptom of vaginal atrophy of moderate to severe intensity were included in this study. All of the objective parameters (vaginal atrophy score, vaginal pH, the number of lactobacilli, vaginal maturation index, and vaginal maturation value) were evaluated and correlated with vaginal atrophy symptoms. A new parameter of vaginal atrophy, vaginal atrophy symptoms II, was developed and consists of the two most bothersome symptoms (vaginal dryness and dyspareunia). Vaginal atrophy symptoms II was analyzed for correlation with the objective parameters. A total of 132 naturally postmenopausal women were recruited for analysis. Vaginal pH was the only objective parameter found to have a weak correlation with vaginal atrophy symptoms (r = 0.273, p = 0.002). The newly developed vaginal atrophy symptoms II parameter showed moderate correlation with vaginal pH (r = 0.356, p atrophy score (r = 0.230, p atrophy symptoms and the objective parameters. Vaginal pH was significantly correlated with vaginal atrophy symptoms. The newly developed vaginal atrophy symptoms II was associated with a better correlation. The vaginal atrophy symptoms II and vaginal pH may be better tools for clinical evaluation and future study of the vaginal ecosystem.

  19. [Hereditary optic neuropathies: clinical and molecular genetic characteristics].

    Science.gov (United States)

    Khanakova, N A; Sheremet, N L; Loginova, A N; Chukhrova, A L; Poliakov, A V

    2013-01-01

    The article presents a review of literature on hereditary optic neuropathies: Leber mitochondrial hereditary optic neuropathy, autosomal dominant and autosomal recessive optic neuropathies, X-linked optic atrophy. Clinical and molecular genetic characteristics are covered. Isolated optic neuropathies, as well as hereditary optic disorders, being a part of a complex syndromic disease are described.

  20. Cardiac Atrophy and Heart Failure In Cancer.

    Science.gov (United States)

    Sweeney, Mark; Yiu, Angela; Lyon, Alexander R

    2017-04-01

    Functional changes in the heart in patients with cancer can be a result of both the disease itself and various cancer therapies, and limiting cardiac damage has become an increasingly important issue as survival rates in patients with cancer have improved. Processes involved in cancer-induced cardiac atrophy may include cardiomyocyte atrophy and apoptosis, decreased protein synthesis, increased autophagy and proteolysis via the ubiquitin-proteosome system. Further to direct effects of malignancy on the heart, several chemotherapeutic agents are known to affect the myocardium, in particular the anthracyclines. The aim of this report is to review the effects of cancer and cancer treatment on the heart and what is known about the underlying mechanisms. Furthermore, clinical strategies to limit and treat cancer-associated cardiac atrophy are discussed, emphasising the benefit of a multidisciplinary approach by cardiologists and oncologists to optimise models of care to improve outcomes for patients with cancer.

  1. Does gastric atrophy exist in children?

    Institute of Scientific and Technical Information of China (English)

    Georges Dimitrov; Frédéric Gottrand

    2006-01-01

    Several clinical reports confirmed that gastric atrophy is a pathology not only limited to adult patients. In pediatrics, it is most often described in association with a Hpylori infection but this bacteria does not seem to be the only etiological factor of this preneoplastic state in children. The frequency of gastric atrophy and intestinal metaplasia in children are unknown because they are not systematically sought during upper gastrointestinal endoscopy. The lack of specific histological classification of children's gastropathies makes their diagnosis difficult for pathologists. Based on our knowledge to date, we think that it is necessary to describe, in detail, the natural course of this lesion during childhood. A close and prolonged clinical and endoscopic follow-up is important for children with gastric atrophy.

  2. Differential induction of muscle atrophy pathways in two mouse models of spinal muscular atrophy

    Science.gov (United States)

    Deguise, Marc-Olivier; Boyer, Justin G.; McFall, Emily R.; Yazdani, Armin; De Repentigny, Yves; Kothary, Rashmi

    2016-01-01

    Motor neuron loss and neurogenic atrophy are hallmarks of spinal muscular atrophy (SMA), a leading genetic cause of infant deaths. Previous studies have focused on deciphering disease pathogenesis in motor neurons. However, a systematic evaluation of atrophy pathways in muscles is lacking. Here, we show that these pathways are differentially activated depending on severity of disease in two different SMA model mice. Although proteasomal degradation is induced in skeletal muscle of both models, autophagosomal degradation is present only in Smn2B/− mice but not in the more severe Smn−/−; SMN2 mice. Expression of FoxO transcription factors, which regulate both proteasomal and autophagosomal degradation, is elevated in Smn2B/− muscle. Remarkably, administration of trichostatin A reversed all molecular changes associated with atrophy. Cardiac muscle also exhibits differential induction of atrophy between Smn2B/− and Smn−/−; SMN2 mice, albeit in the opposite direction to that of skeletal muscle. Altogether, our work highlights the importance of cautious analysis of different mouse models of SMA as distinct patterns of atrophy induction are at play depending on disease severity. We also revealed that one of the beneficial impacts of trichostatin A on SMA model mice is via attenuation of muscle atrophy through reduction of FoxO expression to normal levels. PMID:27349908

  3. Geographic atrophy phenotype identification by cluster analysis.

    Science.gov (United States)

    Monés, Jordi; Biarnés, Marc

    2017-07-20

    To identify ocular phenotypes in patients with geographic atrophy secondary to age-related macular degeneration (GA) using a data-driven cluster analysis. This was a retrospective analysis of data from a prospective, natural history study of patients with GA who were followed for ≥6 months. Cluster analysis was used to identify subgroups within the population based on the presence of several phenotypic features: soft drusen, reticular pseudodrusen (RPD), primary foveal atrophy, increased fundus autofluorescence (FAF), greyish FAF appearance and subfoveal choroidal thickness (SFCT). A comparison of features between the subgroups was conducted, and a qualitative description of the new phenotypes was proposed. The atrophy growth rate between phenotypes was then compared. Data were analysed from 77 eyes of 77 patients with GA. Cluster analysis identified three groups: phenotype 1 was characterised by high soft drusen load, foveal atrophy and slow growth; phenotype 3 showed high RPD load, extrafoveal and greyish FAF appearance and thin SFCT; the characteristics of phenotype 2 were midway between phenotypes 1 and 3. Phenotypes differed in all measured features (p≤0.013), with decreases in the presence of soft drusen, foveal atrophy and SFCT seen from phenotypes 1 to 3 and corresponding increases in high RPD load, high FAF and greyish FAF appearance. Atrophy growth rate differed between phenotypes 1, 2 and 3 (0.63, 1.91 and 1.73 mm(2)/year, respectively, p=0.0005). Cluster analysis identified three distinct phenotypes in GA. One of them showed a particularly slow growth pattern. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. Restless legs syndrome in multiple system atrophy.

    Science.gov (United States)

    Ghorayeb, Imad; Dupouy, Sandrine; Tison, François; Meissner, Wassilios G

    2014-12-01

    The purpose of the study was to evaluate the frequency of restless legs syndrome in 30 patients with multiple system atrophy. Eight patients complained from restless legs syndrome, their severity score was 19.4 ± 4.1. Pittsburgh Sleep Quality Index scores were significantly higher in patients with restless legs syndrome than those without (9.3 ± 3.7 vs. 4.8 ± 2.9, p = 0.00165). Periodic limb movements were found in 75% of patients with restless legs syndrome. Restless legs syndrome is more prevalent in multiple system atrophy as compared to the acknowledged prevalence in the general population.

  5. Progressive cerebral atrophy in neuromyelitis optica.

    Science.gov (United States)

    Warabi, Yoko; Takahashi, Toshiyuki; Isozaki, Eiji

    2015-12-01

    We report two cases of neuromyelitis optica patients with progressive cerebral atrophy. The patients exhibited characteristic clinical features, including elderly onset, secondary progressive tetraparesis and cognitive impairment, abnormally elevated CSF protein and myelin basic protein levels, and extremely highly elevated serum anti-AQP-4 antibody titer. Because neuromyelitis optica pathology cannot switch from an inflammatory phase to the degenerative phase until the terminal phase, neuromyelitis optica rarely appears as a secondary progressive clinical course caused by axonal degeneration. However, severe intrathecal inflammation and massive destruction of neuroglia could cause a secondary progressive clinical course associated with cerebral atrophy in neuromyelitis optica patients.

  6. Mirror movements in progressive hemifacial atrophy

    Science.gov (United States)

    Verma, Rajesh; Dixit, Puneet Kumar; Lalla, Rakesh; Singh, Babita

    2015-01-01

    Mirror movements are simultaneous, involuntary, identical movements occurring during contralateral voluntary movements. These movements are considered as soft neurologic signs seen uncommonly in clinical practice. The mirror movements are described in various neurological disorders which include parkinsonism, cranio veretebral junction anamolies, and hemiplegic cerebral palsy. These movements are intriguing and can pose significant disability. However, no such observation regarding mirror movements in progressive hemifacial atrophy have been reported previously. We are reporting a teenage girl suffering from progressive hemifacial atrophy and epilepsy with demonstrable mirror movements in hand. PMID:26019431

  7. Mirror movements in progressive hemifacial atrophy

    Directory of Open Access Journals (Sweden)

    Rajesh Verma

    2015-01-01

    Full Text Available Mirror movements are simultaneous, involuntary, identical movements occurring during contralateral voluntary movements. These movements are considered as soft neurologic signs seen uncommonly in clinical practice. The mirror movements are described in various neurological disorders which include parkinsonism, cranio veretebral junction anamolies, and hemiplegic cerebral palsy. These movements are intriguing and can pose significant disability. However, no such observation regarding mirror movements in progressive hemifacial atrophy have been reported previously. We are reporting a teenage girl suffering from progressive hemifacial atrophy and epilepsy with demonstrable mirror movements in hand.

  8. Genetics Home Reference: spinal muscular atrophy with progressive myoclonic epilepsy

    Science.gov (United States)

    ... Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) is a neurological condition that causes muscle weakness ... muscle jerks (myoclonic epilepsy). In individuals with SMA-PME, spinal muscular atrophy results from a loss of ...

  9. Grey matter atrophy in patients suffering from multiple sclerosis.

    Science.gov (United States)

    Kincses, Zsigmond Tamás; Tóth, Eszter; Bankó, Nóra; Veréb, Dániel; Szabó, Nikoletta; Csete, Gergő; Faragó, Péter; Király, András; Bencsik, Krisztina; Vécsei, László

    2014-09-30

    White matter lesions are defining characteristics of multiple sclerosis (MS), whereas grey matter involvement is a less recognised attribute. Recent investigations using dedicated imaging approaches have made it possible to depict cortical lesions. Additionally, grey matter atrophy may be estimated using various methods. Several studies have suggested that grey matter atrophy closely correlates to clinical disability. In this review we have collected information on grey matter atrophy in MS and the effect of disease modifying therapies upon brain atrophy.

  10. Redox control of skeletal muscle atrophy.

    Science.gov (United States)

    Powers, Scott K; Morton, Aaron B; Ahn, Bumsoo; Smuder, Ashley J

    2016-09-01

    Skeletal muscles comprise the largest organ system in the body and play an essential role in body movement, breathing, and glucose homeostasis. Skeletal muscle is also an important endocrine organ that contributes to the health of numerous body organs. Therefore, maintaining healthy skeletal muscles is important to support overall health of the body. Prolonged periods of muscle inactivity (e.g., bed rest or limb immobilization) or chronic inflammatory diseases (i.e., cancer, kidney failure, etc.) result in skeletal muscle atrophy. An excessive loss of muscle mass is associated with a poor prognosis in several diseases and significant muscle weakness impairs the quality of life. The skeletal muscle atrophy that occurs in response to inflammatory diseases or prolonged inactivity is often associated with both oxidative and nitrosative stress. In this report, we critically review the experimental evidence that provides support for a causative link between oxidants and muscle atrophy. More specifically, this review will debate the sources of oxidant production in skeletal muscle undergoing atrophy as well as provide a detailed discussion on how reactive oxygen species and reactive nitrogen species modulate the signaling pathways that regulate both protein synthesis and protein breakdown.

  11. Matrix metalloproteinase imbalance in muscle disuse atrophy.

    Science.gov (United States)

    Giannelli, G; De Marzo, A; Marinosci, F; Antonaci, S

    2005-01-01

    Muscle atrophy commonly occurs as a consequence of prolonged muscle inactivity, as observed after cast immobilization, bed rest or space flights. The molecular mechanisms responsible for muscle atrophy are still unknown, but a role has been proposed for altered permeability of the sarcolemma and of the surrounding connective tissue. Matrix metallo-proteinases (MMPs) are a family of enzymes with proteolytic activity toward a number of extracellular matrix (ECM) components; they are inhibited by tissue inhibitors of MMPs (TIMPs). In a rat tail-suspension experimental model, we show that after fourteen days of non-weight bearing there is increased expression of MMP-2 in the atrophic soleus and gastrocnemius and decreased expression of TIMP-2. In the same experimental model the expression of Collagen I and Collagen IV, two main ECM components present in the muscles, was reduced and unevenly distributed in unloaded animals. The difference was more evident in the soleus than in the gastrocnemius muscle. This suggests that muscle disuse induces a proteolytic imbalance, which could be responsible for the breakdown of basal lamina structures such as Collagen I and Collagen IV, and that this leads to an altered permeability with consequent atrophy. In conclusion, an MMP-2/TIMP-2 imbalance could have a role in the mechanism underlying muscle disuse atrophy; more studies are needed to expand our molecular knowledge on this issue and to explore the possibility of targeting the proteolytic imbalance with MMP inhibitors.

  12. Genetics Home Reference: spinal muscular atrophy

    Science.gov (United States)

    ... and abdomen, weakness in the leg muscles, involuntary muscle contractions, tremors, and a protrusion of the abdomen thought to be related to muscle weakness. Some affected individuals experience difficulty swallowing and problems with bladder and ... Frequency Spinal muscular atrophy affects 1 in 6,000 to 1 ...

  13. White matter atrophy and cognitive dysfunctions in neuromyelitis optica.

    Directory of Open Access Journals (Sweden)

    Frederic Blanc

    Full Text Available Neuromyelitis optica (NMO is an inflammatory disease of central nervous system characterized by optic neuritis and longitudinally extensive acute transverse myelitis. NMO patients have cognitive dysfunctions but other clinical symptoms of brain origin are rare. In the present study, we aimed to investigate cognitive functions and brain volume in NMO. The study population consisted of 28 patients with NMO and 28 healthy control subjects matched for age, sex and educational level. We applied a French translation of the Brief Repeatable Battery (BRB-N to the NMO patients. Using SIENAx for global brain volume (Grey Matter, GM; White Matter, WM; and whole brain and VBM for focal brain volume (GM and WM, NMO patients and controls were compared. Voxel-level correlations between diminished brain concentration and cognitive performance for each tests were performed. Focal and global brain volume of NMO patients with and without cognitive impairment were also compared. Fifteen NMO patients (54% had cognitive impairment with memory, executive function, attention and speed of information processing deficits. Global and focal brain atrophy of WM but not Grey Matter (GM was found in the NMO patients group. The focal WM atrophy included the optic chiasm, pons, cerebellum, the corpus callosum and parts of the frontal, temporal and parietal lobes, including superior longitudinal fascicle. Visual memory, verbal memory, speed of information processing, short-term memory and executive functions were correlated to focal WM volumes. The comparison of patients with, to patients without cognitive impairment showed a clear decrease of global and focal WM, including brainstem, corticospinal tracts, corpus callosum but also superior and inferior longitudinal fascicles. Cognitive impairment in NMO patients is correlated to the decreased of global and focal WM volume of the brain. Further studies are needed to better understand the precise origin of cognitive impairment in

  14. Clinical observation of Dengzhanxixin Mistura combined with citicoline in treatment of glaucoma optic atrophy%灯盏细辛合剂联合胞二磷胆碱治疗青光眼视神经萎缩的疗效观察

    Institute of Scientific and Technical Information of China (English)

    董洁玉

    2016-01-01

    Objective To explore the clinical effect of Dengzhanxixin Mistura combined with citicoline in treatment of glaucoma optic atrophy.Methods Patients (84 cases) with glaucoma optic atrophy in the First Clinical Medical College of Three Gorges University from August 2014 to August 2015 were enrolled in this study. According to the different treatment plans, patients were divided into treatment group (42 cases) and control group (42 cases). The patients in the control group were iv administered with Citicoline Injection by postocular tissue proper, 2 mL/time, once every other day, and 20 times were as one course of treatment. The patients in the treatment group werepoadministered with Dengzhanxixin Mistura on the basis of control group, 10 mL/time, three times daily, and 40 d was as one course of treatment. Patients in two groups were treated for two courses. After treatment, the clinical efficacy was evaluated, and the changes of visual field defect, P100wave incubation period, and the lines number of eyesight improvement in two groups were compared.Results After treatment, the clinical efficacies in the control and treatment groups were 73.81% and 90.48%, respectively, and there were differences between two groups (P < 0.05). Compared with those before treatment, after treatment, visual field defect and P100wave incubation period in two groups were significantly decreased, and the difference was statistically significant in the same group (P < 0.05). The decreased extent in the treatment group was more significantly, and there were differences between two groups (P < 0.05). The line numbers of eyesight improvement in treatment group was better than that of control group, with significant difference between two groups (P < 0.05).Conclusion Dengzhanxixin Mistura combined with citicoline has distinct clinical effect in treatment of glaucoma optic atrophy, and can promote the visual acuity, also can improve visual field defect, which has a certain clinical application

  15. [Mechanism of cardiac atrophy under weightlessness/simulated weightlessness].

    Science.gov (United States)

    Zhong, Guo-Hui; Ling, Shu-Kuan; Li, Ying-Xian

    2016-04-25

    Cardiac remodeling is the heart's response to external or internal stimuli. Weightlessness/simulated weightlessness leads to cardiac atrophy and heart function declining. Understanding the mechanism of cardiac atrophy under weightlessness is important to help astronaut recover from unloading-induced cardiovascular changes after spaceflight. Unloading-induced changes of hemodynamics, metabolic demands and neurohumoral regulation contribute to cardiac atrophy and function declining. During this process, Ca(2+)-related signaling, NF-κB signaling, ERK signaling, ubiquitin-proteasome pathway and autophagy are involved in weightlessness-induced cardiac atrophy. This article reviews the underlying mechanism of cardiac atrophy under weightlessness/simulated weightlessness.

  16. Arginine-Restricted Therapy Resistant Bilateral Macular Edema Associated with Gyrate Atrophy

    Directory of Open Access Journals (Sweden)

    Sibel Doguizi

    2015-01-01

    Full Text Available Introduction. Gyrate atrophy is a rare genetical metabolic disorder affecting vision. Here, we report a 9-year-old boy with gyrate atrophy associated with bilateral macular edema at the time of diagnosis and the effect of long term metabolic control on macular edema. Case Presentation. A 9-year-old boy presented with a complaint of low visual acuity (best corrected visual acuity: 20/80 in both eyes, refractive error: −12.00 D. Dilated fundus examination revealed multiple bilateral, sharply defined, and scalloped chorioretinal atrophy areas in the midperipheral and peripheral zone. Spectral-domain optical coherence tomography revealed bilateral cystoid macular edema in both eyes. Serum ornithine level was high (622 μmol/L. An arginine-restricted diet reduced serum ornithine level (55 μmol/L. However, visual findings including macular edema remained unchanged in 2 years of follow-up. Conclusion. Arginine-restricted diet did not improve macular edema in our patient with gyrate atrophy. A more comprehensive understanding of the underlying factors for macular edema will lead to the development of effective therapies.

  17. Update on alternative therapies for vulvovaginal atrophy

    Directory of Open Access Journals (Sweden)

    Chollet J

    2011-10-01

    Full Text Available Janet A Chollet1,2 1Beth Israel Deaconess Medical Center, Boston, 2Pear Tree Pharmaceuticals, Waltham, MA, USA Abstract: Although systemic absorption of estrogen with local treatment for vulvovaginal atrophy (VVA is most likely to be negligible, it is unknown whether this minimal absorption will affect outcomes in women with breast cancer. Use of adjuvant therapy with aromatase inhibitors for breast cancer is associated with high incidence of VVA symptoms. Because of the impact of moderate to severe VVA symptoms on the quality of life in breast cancer survivors, there has been an intense search for alternative therapies. Further, the publicity that followed the publication of data from the Women’s Health Initiative Study has led to the suggestion by the medical community to use the lowest dose therapy possible for minimal time duration in order to avoid risks. This article will highlight the progress in alternative therapies for VVA. Keywords: vulvovaginal atrophy, hormone therapy, alternative therapy

  18. Research progress of posterior cortical atrophy

    Directory of Open Access Journals (Sweden)

    Li-jun PENG

    2016-06-01

    Full Text Available Posterior cotical atrophy (PCA is a kind of progressive dementia with main clinical manifestations of visual dysfunction as the starting symptom and associated with progressive cognitive disorder. The histopathology and imaging of PCA show visual dysfunction, neuritic plaques (NPs and neurofibrillary tangles (NFTs, which are the same as those in Alzheimer's disease (AD. Researches also showed that mutation of presenilin-1 (PS-1 gene and apolipoprotein E (ApoE genotype may participate in the occurrence and development of PCA. Parieto-occipital lobe atrophy, hypoperfusion and/or glucose metabolism reduction in the right posterior cerebrum can be seen in PCA. Cholinesterase inhibitors (ChEIs may improve the symptoms and postpone the progression of illness. No unified diagnostic criteria will reduce the comparability between different studies. Reasonable usage of the diagnostic criteria of PCA will be helpful in classifying and differentiating this disease. DOI: 10.3969/j.issn.1672-6731.2016.06.011

  19. Very severe spinal muscular atrophy (Type 0).

    Science.gov (United States)

    Al Dakhoul, Suleiman

    2017-01-01

    This case report describes a rare phenotype of very severe spinal muscular atrophy (SMA) in a newborn who presented with reduced fetal movements in utero and significant respiratory distress at birth. The patient was homozygously deleted for exon 7 and exon 8 of the survival motor neuron gene 1. Very severe SMA should be considered in the differential diagnosis of respiratory distress at birth, and more research should be dedicated to investigate the genetic determinants of its widely variable phenotypes.

  20. Multiple system atrophy and cognitive dysfunction

    Directory of Open Access Journals (Sweden)

    Sen-yang LANG

    2016-06-01

    Full Text Available As the survival of patients with multiple system atrophy (MSA is prolonged, patients may present cognitive dysfunction or even dementia in addition to autonomic dysfunction, damage of extrapyramidal system and cerebellar ataxia. This article made a brief summary on the research progress of MSA combined with cognitive dysfunction reported at home and abroad. DOI: 10.3969/j.issn.1672-6731.2016.06.003

  1. Cerebellar and cerebral atrophy in trichothiodystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Hye-Kyung; Sargent, Michael A.; Poskitt, Kenneth J. [British Columbia Children' s Hospital, Department of Radiology, Vancouver, BC (Canada); Prendiville, Julie S. [British Columbia Children' s Hospital, Division of Paediatric Dermatology, Department of Paediatrics, Vancouver, BC (Canada)

    2005-10-01

    Trichothiodystrophy is a rare neuroectodermal disorder of autosomal recessive inheritance that is characterized by brittle hair, nail dysplasia, ichthyosis, mental retardation, and gonadal failure. We describe a female patient whose cranial MRI revealed almost total lack of myelination in the supratentorial white matter, which is similar to the previously described cases. In addition, there was progressive cerebellar and cerebral atrophy, which has not been well documented in association with trichothiodystrophy. (orig.)

  2. Sensorimotor gating deficits in multiple system atrophy

    DEFF Research Database (Denmark)

    Zoetmulder, Marielle; Biernat, Heidi Bryde; Nikolic, Miki

    2014-01-01

    Prepulse inhibition (PPI) of the auditory blink reflex is a measure of sensorimotor gating, which reflects an organism's ability to filter out irrelevant sensory information. PPI has never been studied in patients with multiple system atrophy (MSA), although sensorimotor deficits are frequently...... associated with synucleinopathies. We investigated whether alterations in PPI were more pronounced in MSA compared with Parkinson's disease (PD), idiopathic rapid eye movement sleep behavior disorder (iRBD) and healthy controls....

  3. Coeliac disease: more than villous atrophy.

    Science.gov (United States)

    Wahab, Peter J; Meijer, Jos W R; Dumitra, Daniela; Goerres, Marije S; Mulder, Chris J J

    2002-06-01

    A continuing flow of new scientific developments concerning coeliac disease in the last decade asks for the formulation of a new concept of pathophysiology and clinical approach of the coeliac condition. Immunogenetic studies have shown a correlation of the disease to the HLA region on the short arm of chromosome 6. Immunological research has led to the concept of a T-cell driven immunologic response of the small intestine, with the identification of highly sensitive and specific antibodies, and in addition the understanding of the histopathology of coeliac disease has changed dramatically, initiated by the proposition of a spectrum of gluten sensitive enteropathy by Marsh in 1992. Clinical studies report a significant change in patient characteristics and epidemiology. The incidence of the disease has shifted to a majority of adult coeliacs and the disease may present with less severe symptoms of malabsorption while screening studies suggest an overall prevalence of up to 1 in 200-300. In the present paper (an update on histopathology) we specifically describe the work of our group in Arnhem, concerning the identification and validation of the spectrum of intestinal histopathology in gluten sensitive enteropathy, i.e. lymphocytic enteritis (Marsh I lesion), lymphocytic enteritis with crypthyperplasia (Marsh II lesion), and villous atrophy, subdivided in partial villous atrophy (Marsh IIIA), subtotal villous atrophy (Marsh IIIB) and total villous atrophy (Marsh IIIC). Special attention is given to a subgroup of "refractory coeliacs", including the identification of (pre-) malignant aberrant T-cells in the intestinal mucosa of these patients. The new data on immunogenetics, epidemiology, histo-pathology and patient characteristics point to a significant change of views on coeliac disease.

  4. Proximal spinal muscular atrophy: current orthopedic perspective

    Directory of Open Access Journals (Sweden)

    Haaker G

    2013-11-01

    Full Text Available Gerrit Haaker, Albert Fujak Department of Orthopaedic Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany Abstract: Spinal muscular atrophy (SMA is a hereditary neuromuscular disease of lower motor neurons that is caused by a defective "survival motor neuron" (SMN protein that is mainly associated with proximal progressive muscle weakness and atrophy. Although SMA involves a wide range of disease severity and a high mortality and morbidity rate, recent advances in multidisciplinary supportive care have enhanced quality of life and life expectancy. Active research for possible treatment options has become possible since the disease-causing gene defect was identified in 1995. Nevertheless, a causal therapy is not available at present, and therapeutic management of SMA remains challenging; the prolonged survival is increasing, especially orthopedic, respiratory and nutritive problems. This review focuses on orthopedic management of the disease, with discussion of key aspects that include scoliosis, muscular contractures, hip joint disorders, fractures, technical devices, and a comparative approach of conservative and surgical treatment. Also emphasized are associated complications including respiratory involvement, perioperative care and anesthesia, nutrition problems, and rehabilitation. The SMA disease course can be greatly improved with adequate therapy with established orthopedic procedures in a multidisciplinary therapeutic approach. Keywords: spinal muscular atrophy, scoliosis, contractures, fractures, lung function, treatment, rehabilitation, surgery, ventilation, nutrition, perioperative management

  5. Space travel directly induces skeletal muscle atrophy

    Science.gov (United States)

    Vandenburgh, H.; Chromiak, J.; Shansky, J.; Del Tatto, M.; Lemaire, J.

    1999-01-01

    Space travel causes rapid and pronounced skeletal muscle wasting in humans that reduces their long-term flight capabilities. To develop effective countermeasures, the basis of this atrophy needs to be better understood. Space travel may cause muscle atrophy indirectly by altering circulating levels of factors such as growth hormone, glucocorticoids, and anabolic steroids and/or by a direct effect on the muscle fibers themselves. To determine whether skeletal muscle cells are directly affected by space travel, tissue-cultured avian skeletal muscle cells were tissue engineered into bioartificial muscles and flown in perfusion bioreactors for 9 to 10 days aboard the Space Transportation System (STS, i.e., Space Shuttle). Significant muscle fiber atrophy occurred due to a decrease in protein synthesis rates without alterations in protein degradation. Return of the muscle cells to Earth stimulated protein synthesis rates of both muscle-specific and extracellular matrix proteins relative to ground controls. These results show for the first time that skeletal muscle fibers are directly responsive to space travel and should be a target for countermeasure development.

  6. Cellular and molecular mechanisms of muscle atrophy

    Science.gov (United States)

    Bonaldo, Paolo; Sandri, Marco

    2013-01-01

    Skeletal muscle is a plastic organ that is maintained by multiple pathways regulating cell and protein turnover. During muscle atrophy, proteolytic systems are activated, and contractile proteins and organelles are removed, resulting in the shrinkage of muscle fibers. Excessive loss of muscle mass is associated with poor prognosis in several diseases, including myopathies and muscular dystrophies, as well as in systemic disorders such as cancer, diabetes, sepsis and heart failure. Muscle loss also occurs during aging. In this paper, we review the key mechanisms that regulate the turnover of contractile proteins and organelles in muscle tissue, and discuss how impairments in these mechanisms can contribute to muscle atrophy. We also discuss how protein synthesis and degradation are coordinately regulated by signaling pathways that are influenced by mechanical stress, physical activity, and the availability of nutrients and growth factors. Understanding how these pathways regulate muscle mass will provide new therapeutic targets for the prevention and treatment of muscle atrophy in metabolic and neuromuscular diseases. PMID:23268536

  7. Space travel directly induces skeletal muscle atrophy

    Science.gov (United States)

    Vandenburgh, H.; Chromiak, J.; Shansky, J.; Del Tatto, M.; Lemaire, J.

    1999-01-01

    Space travel causes rapid and pronounced skeletal muscle wasting in humans that reduces their long-term flight capabilities. To develop effective countermeasures, the basis of this atrophy needs to be better understood. Space travel may cause muscle atrophy indirectly by altering circulating levels of factors such as growth hormone, glucocorticoids, and anabolic steroids and/or by a direct effect on the muscle fibers themselves. To determine whether skeletal muscle cells are directly affected by space travel, tissue-cultured avian skeletal muscle cells were tissue engineered into bioartificial muscles and flown in perfusion bioreactors for 9 to 10 days aboard the Space Transportation System (STS, i.e., Space Shuttle). Significant muscle fiber atrophy occurred due to a decrease in protein synthesis rates without alterations in protein degradation. Return of the muscle cells to Earth stimulated protein synthesis rates of both muscle-specific and extracellular matrix proteins relative to ground controls. These results show for the first time that skeletal muscle fibers are directly responsive to space travel and should be a target for countermeasure development.

  8. Cellular and molecular mechanisms of muscle atrophy

    Directory of Open Access Journals (Sweden)

    Paolo Bonaldo

    2013-01-01

    Full Text Available Skeletal muscle is a plastic organ that is maintained by multiple pathways regulating cell and protein turnover. During muscle atrophy, proteolytic systems are activated, and contractile proteins and organelles are removed, resulting in the shrinkage of muscle fibers. Excessive loss of muscle mass is associated with poor prognosis in several diseases, including myopathies and muscular dystrophies, as well as in systemic disorders such as cancer, diabetes, sepsis and heart failure. Muscle loss also occurs during aging. In this paper, we review the key mechanisms that regulate the turnover of contractile proteins and organelles in muscle tissue, and discuss how impairments in these mechanisms can contribute to muscle atrophy. We also discuss how protein synthesis and degradation are coordinately regulated by signaling pathways that are influenced by mechanical stress, physical activity, and the availability of nutrients and growth factors. Understanding how these pathways regulate muscle mass will provide new therapeutic targets for the prevention and treatment of muscle atrophy in metabolic and neuromuscular diseases.

  9. OCT Minimum Intensity as a Predictor of Geographic Atrophy Enlargement

    Science.gov (United States)

    Stetson, Paul F.; Yehoshua, Zohar; Garcia Filho, Carlos Alexandre A.; Portella Nunes, Renata; Gregori, Giovanni; Rosenfeld, Philip J.

    2014-01-01

    Purpose. We determined whether the minimum intensity (MI) of the optical coherence tomography (OCT) A-scans within the retina can predict locations of growth at the margin of geographic atrophy (GA) and the growth rate outside the margin. Methods. The OCT scans were analyzed at baseline and 52 weeks. Expert graders manually segmented OCT images of GA. The 52-week follow-up scans were registered to the baseline scan coordinates for comparison. The OCT MI values were studied within a 180-μm margin around the boundary of GA at baseline. Baseline MI values were compared in areas of progression and nonprogression of the GA, and sensitivity and specificity were assessed for prediction of growth at the margin. Average MI values in the margins were compared to overall growth rates to evaluate the prediction of growth outside the margins. Results. A statistically significant increase in MI (P < 0.05) was seen in areas of growth in 21/24 cases (88%), and 22/24 cases (92%) when the foveal subfield was excluded. Locations of growth within the margins at 52 weeks were predicted with 61% sensitivity and 61% specificity. The MI values correlated significantly with overall growth rate, and high and low growth rate subjects were identified with 80% sensitivity and 64% specificity. Conclusions. The MI may be increased at the margins of GA lesions before enlargement, which may indicate disruption or atrophy of the photoreceptors in these areas before GA becomes apparent. Increased MI may help predict areas of enlargement of GA, and may relate to overall growth rate and be a useful screening tool for GA. (ClinicalTrials.gov number, NCT00935883.) PMID:24408973

  10. Severe spinal muscular atrophy variant associated with congenital bone fractures.

    Science.gov (United States)

    Felderhoff-Mueser, Ursula; Grohmann, Katja; Harder, Anja; Stadelmann, Christine; Zerres, Klaus; Bührer, Christoph; Obladen, Michael

    2002-09-01

    Infantile autosomal recessive spinal muscular atrophy (type I) represents a lethal disorder leading to progressive symmetric muscular atrophy of limb and trunk muscles. Ninety-six percent cases of spinal muscular atrophy type I are caused by deletions or mutations in the survival motoneuron gene (SMNI) on chromosome 5q11.2-13.3. However, a number of chromosome 5q-negative patients with additional clinical features (respiratory distress, cerebellar hypoplasia) have been designated in the literature as infantile spinal muscular atrophy plus forms. In addition, the combination of severe spinal muscular atrophy and neurogenic arthrogryposis has been described. We present clinical, molecular, and autopsy findings of a newborn boy presenting with generalized muscular atrophy in combination with congenital bone fractures and extremely thin ribs but without contractures.

  11. Network structure of brain atrophy in de novo Parkinson's disease.

    Science.gov (United States)

    Zeighami, Yashar; Ulla, Miguel; Iturria-Medina, Yasser; Dadar, Mahsa; Zhang, Yu; Larcher, Kevin Michel-Herve; Fonov, Vladimir; Evans, Alan C; Collins, D Louis; Dagher, Alain

    2015-09-07

    We mapped the distribution of atrophy in Parkinson's disease (PD) using magnetic resonance imaging (MRI) and clinical data from 232 PD patients and 117 controls from the Parkinson's Progression Markers Initiative. Deformation-based morphometry and independent component analysis identified PD-specific atrophy in the midbrain, basal ganglia, basal forebrain, medial temporal lobe, and discrete cortical regions. The degree of atrophy reflected clinical measures of disease severity. The spatial pattern of atrophy demonstrated overlap with intrinsic networks present in healthy brain, as derived from functional MRI. Moreover, the degree of atrophy in each brain region reflected its functional and anatomical proximity to a presumed disease epicenter in the substantia nigra, compatible with a trans-neuronal spread of the disease. These results support a network-spread mechanism in PD. Finally, the atrophy pattern in PD was also seen in healthy aging, where it also correlated with the loss of striatal dopaminergic innervation.

  12. Circulating micrornas as potential biomarkers of muscle atrophy

    Science.gov (United States)

    Wang, Fei

    2016-07-01

    Noninvasive biomarkers with diagnostic value and prognostic applications have long been desired to replace muscle biopsy for muscle atrophy patients. Growing evidence indicates that circulating microRNAs are biomarkers to assess pathophysiological status. Here, we show that the medium levels of six muscle-specific miRNAs (miR-1/23a/206/133/499/208b, also known as myomiRs) were all elevated in the medium of starved C2C12 cell (P atrophy patients, indicating that they might represent the degree of muscle atrophy. Collectively, our data indicated that circulating myomiRs could serve as promising biomarkers for muscle atrophy.

  13. Acceleration of hippocampal atrophy rates in asymptomatic amyloidosis.

    Science.gov (United States)

    Andrews, K Abigail; Frost, Chris; Modat, Marc; Cardoso, M Jorge; Rowe, Chris C; Villemagne, Victor; Fox, Nick C; Ourselin, Sebastien; Schott, Jonathan M

    2016-03-01

    Increased rates of brain atrophy measured from serial magnetic resonance imaging precede symptom onset in Alzheimer's disease and may be useful outcome measures for prodromal clinical trials. Appropriate trial design requires a detailed understanding of the relationships between β-amyloid load and accumulation, and rate of brain change at this stage of the disease. Fifty-two healthy individuals (72.3 ± 6.9 years) from Australian Imaging, Biomarkers and Lifestyle Study of Aging had serial (0, 18 m, 36 m) magnetic resonance imaging, (0, 18 m) Pittsburgh compound B positron emission tomography, and clinical assessments. We calculated rates of whole brain and hippocampal atrophy, ventricular enlargement, amyloid accumulation, and cognitive decline. Over 3 years, rates of whole brain atrophy (p atrophy (p = 0.001, p = 0.023), and ventricular expansion (p atrophy rates were also independently associated with β-amyloid accumulation over the first 18 months (p = 0.003). Acceleration of left hippocampal atrophy rate was associated with baseline β-amyloid load across the cohort (p atrophy are associated with both baseline β-amyloid load and accumulation, and that there is presymptomatic, amyloid-mediated acceleration of hippocampal atrophy. Clinical trials using rate of hippocampal atrophy as an outcome measure should not assume linear decline in the presymptomatic phase.

  14. The Impact of Gastric Atrophy on the Incidence of Diabetes

    Science.gov (United States)

    Yu, Tse-Ya; Wei, Jung-Nan; Kuo, Chun-Heng; Liou, Jyh-Ming; Lin, Mao-Shin; Shih, Shyang-Rong; Hua, Cyue-Huei; Hsein, Yenh-Chen; Hsu, Ya-Wen; Chuang, Lee-Ming; Lee, Mei-Kuei; Hsiao, Ching-Hsiang; Wu, Ming-Shiang; Li, Hung-Yuan

    2017-01-01

    Gastric atrophy results in lower plasma ghrelin, higher gastrin secretion, a change in gut microbiota, and altered dietary nutrient absorption, which may be associated with the incidence of diabetes. Helicobacter pylori (H. pylori) infection is a major cause of gastric atrophy and is associated with diabetes in some reports. Since there is no study which investigates the impact of gastric atrophy on diabetes, we conduct a prospective cohort study to examine the relationship between H. pylori infection, gastric atrophy, and incident diabetes. In this study, subjects with gastric atrophy had a lower risk of incident diabetes, compared to those without gastric atrophy. The extent of gastric atrophy, measured by serum pepsinogen (PG) I/II ratio, was correlated with age, H. pylori IgG titer, HOMA2-IR, and HOMA2%B. When gastric atrophy is more extensive, presented as a lower serum PG I/II ratio, the risk of incident diabetes is lower. On the other hand, there was no significant association between H. pylori infection and the incidence of diabetes. In conclusion, the presence and the extent of gastric atrophy, but not H. pylori infection, are associated with incident diabetes. Further studies are needed to investigate the detailed mechanisms and the potential applications of the findings to guide diabetes screening and treatment strategies. PMID:28045079

  15. CLADA: cortical longitudinal atrophy detection algorithm.

    Science.gov (United States)

    Nakamura, Kunio; Fox, Robert; Fisher, Elizabeth

    2011-01-01

    Measurement of changes in brain cortical thickness is useful for the assessment of regional gray matter atrophy in neurodegenerative conditions. A new longitudinal method, called CLADA (cortical longitudinal atrophy detection algorithm), has been developed for the measurement of changes in cortical thickness in magnetic resonance images (MRI) acquired over time. CLADA creates a subject-specific cortical model which is longitudinally deformed to match images from individual time points. The algorithm was designed to work reliably for lower resolution images, such as the MRIs with 1×1×5 mm(3) voxels previously acquired for many clinical trials in multiple sclerosis (MS). CLADA was evaluated to determine reproducibility, accuracy, and sensitivity. Scan-rescan variability was 0.45% for images with 1mm(3) isotropic voxels and 0.77% for images with 1×1×5 mm(3) voxels. The mean absolute accuracy error was 0.43 mm, as determined by comparison of CLADA measurements to cortical thickness measured directly in post-mortem tissue. CLADA's sensitivity for correctly detecting at least 0.1mm change was 86% in a simulation study. A comparison to FreeSurfer showed good agreement (Pearson correlation=0.73 for global mean thickness). CLADA was also applied to MRIs acquired over 18 months in secondary progressive MS patients who were imaged at two different resolutions. Cortical thinning was detected in this group in both the lower and higher resolution images. CLADA detected a higher rate of cortical thinning in MS patients compared to healthy controls over 2 years. These results show that CLADA can be used for reliable measurement of cortical atrophy in longitudinal studies, even in lower resolution images.

  16. Cardiac atrophy after bed rest and spaceflight

    Science.gov (United States)

    Perhonen, M. A.; Franco, F.; Lane, L. D.; Buckey, J. C.; Blomqvist, C. G.; Zerwekh, J. E.; Peshock, R. M.; Weatherall, P. T.; Levine, B. D.

    2001-01-01

    Cardiac muscle adapts well to changes in loading conditions. For example, left ventricular (LV) hypertrophy may be induced physiologically (via exercise training) or pathologically (via hypertension or valvular heart disease). If hypertension is treated, LV hypertrophy regresses, suggesting a sensitivity to LV work. However, whether physical inactivity in nonathletic populations causes adaptive changes in LV mass or even frank atrophy is not clear. We exposed previously sedentary men to 6 (n = 5) and 12 (n = 3) wk of horizontal bed rest. LV and right ventricular (RV) mass and end-diastolic volume were measured using cine magnetic resonance imaging (MRI) at 2, 6, and 12 wk of bed rest; five healthy men were also studied before and after at least 6 wk of routine daily activities as controls. In addition, four astronauts were exposed to the complete elimination of hydrostatic gradients during a spaceflight of 10 days. During bed rest, LV mass decreased by 8.0 +/- 2.2% (P = 0.005) after 6 wk with an additional atrophy of 7.6 +/- 2.3% in the subjects who remained in bed for 12 wk; there was no change in LV mass for the control subjects (153.0 +/- 12.2 vs. 153.4 +/- 12.1 g, P = 0.81). Mean wall thickness decreased (4 +/- 2.5%, P = 0.01) after 6 wk of bed rest associated with the decrease in LV mass, suggesting a physiological remodeling with respect to altered load. LV end-diastolic volume decreased by 14 +/- 1.7% (P = 0.002) after 2 wk of bed rest and changed minimally thereafter. After 6 wk of bed rest, RV free wall mass decreased by 10 +/- 2.7% (P = 0.06) and RV end-diastolic volume by 16 +/- 7.9% (P = 0.06). After spaceflight, LV mass decreased by 12 +/- 6.9% (P = 0.07). In conclusion, cardiac atrophy occurs during prolonged (6 wk) horizontal bed rest and may also occur after short-term spaceflight. We suggest that cardiac atrophy is due to a physiological adaptation to reduced myocardial load and work in real or simulated microgravity and demonstrates the plasticity

  17. Cardiac atrophy after bed rest and spaceflight

    Science.gov (United States)

    Perhonen, M. A.; Franco, F.; Lane, L. D.; Buckey, J. C.; Blomqvist, C. G.; Zerwekh, J. E.; Peshock, R. M.; Weatherall, P. T.; Levine, B. D.

    2001-01-01

    Cardiac muscle adapts well to changes in loading conditions. For example, left ventricular (LV) hypertrophy may be induced physiologically (via exercise training) or pathologically (via hypertension or valvular heart disease). If hypertension is treated, LV hypertrophy regresses, suggesting a sensitivity to LV work. However, whether physical inactivity in nonathletic populations causes adaptive changes in LV mass or even frank atrophy is not clear. We exposed previously sedentary men to 6 (n = 5) and 12 (n = 3) wk of horizontal bed rest. LV and right ventricular (RV) mass and end-diastolic volume were measured using cine magnetic resonance imaging (MRI) at 2, 6, and 12 wk of bed rest; five healthy men were also studied before and after at least 6 wk of routine daily activities as controls. In addition, four astronauts were exposed to the complete elimination of hydrostatic gradients during a spaceflight of 10 days. During bed rest, LV mass decreased by 8.0 +/- 2.2% (P = 0.005) after 6 wk with an additional atrophy of 7.6 +/- 2.3% in the subjects who remained in bed for 12 wk; there was no change in LV mass for the control subjects (153.0 +/- 12.2 vs. 153.4 +/- 12.1 g, P = 0.81). Mean wall thickness decreased (4 +/- 2.5%, P = 0.01) after 6 wk of bed rest associated with the decrease in LV mass, suggesting a physiological remodeling with respect to altered load. LV end-diastolic volume decreased by 14 +/- 1.7% (P = 0.002) after 2 wk of bed rest and changed minimally thereafter. After 6 wk of bed rest, RV free wall mass decreased by 10 +/- 2.7% (P = 0.06) and RV end-diastolic volume by 16 +/- 7.9% (P = 0.06). After spaceflight, LV mass decreased by 12 +/- 6.9% (P = 0.07). In conclusion, cardiac atrophy occurs during prolonged (6 wk) horizontal bed rest and may also occur after short-term spaceflight. We suggest that cardiac atrophy is due to a physiological adaptation to reduced myocardial load and work in real or simulated microgravity and demonstrates the plasticity

  18. [Susceptibility gene in multiple system atrophy (MSA)].

    Science.gov (United States)

    Tsuji, Shoji

    2014-01-01

    To elucidate molecular bases of multiple system atrophy (MSA), we first focused on recently identified MSA multiplex families. Though linkage analyses followed by whole genome resequencing, we have identified a causative gene, COQ2, for MSA. We then conducted comprehensive nucleotide sequence analysis of COQ2 of sporadic MSA cases and controls, and found that functionally deleterious COQ2 variants confer a strong risk for developing MSA. COQ2 encodes an enzyme in the biosynthetic pathway of coenzyme Q10. Decreased synthesis of coenzyme Q10 is considered to be involved in the pathogenesis of MSA through decreased electron transport in mitochondria and increased vulnerability to oxidative stress.

  19. Oats induced villous atrophy in coeliac disease

    Science.gov (United States)

    Lundin, K E A; Nilsen, E M; Scott, H G; Løberg, E M; Gjøen, A; Bratlie, J; Skar, V; Mendez, E; Løvik, A; Kett, K

    2003-01-01

    The current trend is to allow coeliac disease (CD) patients to introduce oats to their gluten free diet. We sought further data from the clinical setting with regards to oats consumption by coeliac patients. Several oat products were tested for wheat contamination using a commercial enzyme linked immunoassay (ELISA) kit, and six samples were examined by an ELISA using a cocktail of monoclonal antibodies, mass spectrometry, and western blot analysis. Nineteen adult CD patients on a gluten free diet were challenged with 50 g of oats per day for 12 weeks. Serological testing and gastroduodenoscopy was performed before and after the challenge. Biopsies were scored histologically and levels of mRNA specific for interferon γ were determined by reverse transcription-polymerase chain reaction analysis. Oats were well tolerated by most patients but several reported initial abdominal discomfort and bloating. One of the patients developed partial villous atrophy and a rash during the first oats challenge. She subsequently improved on an oats free diet but developed subtotal villous atrophy and dramatic dermatitis during a second challenge. Five of the patients showed positive levels of interferon γ mRNA after challenge. Some concerns therefore remain with respect to the safety of oats for coeliacs. PMID:14570737

  20. Geographic atrophy: Etiopathogenesis and current therapies.

    Science.gov (United States)

    Sastre-Ibáñez, M; Barreiro-González, A; Gallego-Pinazo, R; Dolz-Marco, R; García-Armendariz, B

    2017-09-05

    Geographic atrophy is characterized by severe visual deficit whose etiology and pathophysiology are yet to be elucidated. As a working hypothesis, oxidative damage could trigger a chronic inflammation in Bruch's membrane-RPE-choriocapillaris complex, mostly due to complement pathway overactivation. Some individuals with mutations in the complement system and other factors have diminished capacity in the modulation of the inflammatory response, which results in cell damage and waste accumulation. This accumulation of intracellular and extracellular waste products manifests as drusen and pigmentary changes that precede the atrophy of photoreceptors, RPE, choriocapillaris with an ischemic process with decreased choroid flow. All these processes can be detected as tomographic findings and autofluorescence signals that are useful in the evaluation of patients with atrophic AMD, which helps to establish an individualized prognosis. Anti-inflammatory, antioxidant and therapies that decrease the accumulation of toxins for the preservation of the RPE cells and photoreceptors are being investigated in order to slow down the progression of this disease. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Effects of muscle atrophy on motor control

    Science.gov (United States)

    Stuart, D. G.

    1985-01-01

    As a biological tissue, muscle adapts to the demands of usage. One traditional way of assessing the extent of this adaptation has been to examine the effects of an altered-activity protocol on the physiological properties of muscles. However, in order to accurately interpret the changes associated with an activity pattern, it is necessary to employ an appropriate control model. A substantial literature exists which reports altered-use effects by comparing experimental observations with those from animals raised in small laboratory cages. Some evidence suggests that small-cage-reared animals actually represent a model of reduced use. For example, laboratory animals subjected to limited physical activity have shown resistance to insulin-induced glucose uptake which can be altered by exercise training. This project concerned itself with the basic mechanisms underlying muscle atrophy. Specifically, the project addressed the issue of the appropriateness of rats raised in conventional-sized cages as experimental models to examine this phenomenon. The project hypothesis was that rats raised in small cages are inappropriate models for the study of muscle atrophy. The experimental protocol involved: 1) raising two populations of rats, one group in conventional (small)-sized cages and the other group in a much larger (133x) cage, from weanling age (21 days) through to young adulthood (125 days); 2) comparison of size- and force-related characteristics of selected test muscles in an acute terminal paradigm.

  2. Corpus callosum atrophy in patients with mild Alzheimer's disease

    DEFF Research Database (Denmark)

    Frederiksen, Kristian Steen; Garde, Ellen; Skimminge, Arnold

    2011-01-01

    Several studies have found atrophy of the corpus callosum (CC) in patients with Alzheimer's disease (AD). However, it remains unclear whether callosal atrophy is already present in the early stages of AD, and to what extent it may be associated with other structural changes in the brain......, such as age-related white matter changes (ARWMC) and progression of the disease....

  3. Cerebral atrophy after acute traumatic subdural orextradural hematomas in adults

    Institute of Scientific and Technical Information of China (English)

    冯海龙; 谭海斌; 黄光富; 廖晓灵

    2002-01-01

    @@ Cerebral atrophy is one of the serious sequelae ofsevere head injury. 1 Neuropathologicalinvestigation has revealed that cerebral atrophy iscaused by either diffuse axonal injury or cerebralhypoxia and ischemia. Secondary ipsilateral cerebralatrophy caused by acute subdural hematomas in infantshas been reported recently, but this unilateral cerebralatrophy after head injury in adult patients has rarelybeen reported.

  4. A case of spinocerebellar ataxia type 6 mimicking olivopontocerebellar atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Nakagawa, N.; Katayama, T.; Makita, Y.; Kuroda, K.; Aizawa, H.; Kikuchi, K. [First Dept. of Internal Medicine, Asahikawa Medical Coll. (Japan)

    1999-07-01

    Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant, slowly progressive cerebellar ataxia without multisystem involvement. We report a 57-year-old woman with genetically confirmed SCA6 who showed clinical features of olivopontocerebellar atrophy. Conventional T2-weighted and FLAIR MRI demonstrated high signal in the middle cerebellar peduncles, in addition to mild atrophy of the pons and cerebellum. (orig.)

  5. Multifocal motor neuropathy and progressive atrophy : Pathophysiological similarities and differences

    NARCIS (Netherlands)

    Vlam, L.

    2015-01-01

    Progressive muscular atrophy (PMA) and multifocal motor neuropathy (MMN) share many clinical similarities. They are both characterized by progressive asymmetric muscle weakness with atrophy and fasciculations. Tendon reflexes are normally low or absent, although in some patients with MMN normal or e

  6. Bone and muscle atrophy with suspension of the rat

    Science.gov (United States)

    Leblanc, A.; Marsh, C.; Evans, H.; Johnson, P.; Schneider, V.; Jhingran, S.

    1985-01-01

    In order to identify a suitable model for the study of muscle atrophy due to suspension in space, a modified version of the Morey tail suspension model was used to measure the atrophic responses of rat bone and muscle to 14-30 days of unloading of the hindlimbs. The progress of atrophy was measured by increases in methylene diphosphonate (MDP) uptake. It is found that bone uptake of methylene diphosphonate followed a phasic pattern similar to changes in the bone formation rate of immobilized dogs and cats. Increased MDP uptake after a period of 60 days indicated an accelerated bone metabolism. Maximum muscle atrophy in the suspended rats was distinctly different from immobilization atrophy. On the basis of the experimental results, it is concluded that the tail suspension model is an adequate simulation of bone atrophy due to suspension.

  7. Centrifugal intensity and duration as countermeasures to soleus muscle atrophy

    Science.gov (United States)

    D'Aunno, Dominick S.; Thomason, Donald B.; Booth, Frank W.

    1990-01-01

    The effects of artificially induced gravity on the atrophy process of slow-twitch soleus muscle are studied in order to determine whether centrifugation could be an effective countermeasure to nonweight bearing at 1 G. It is observed that the soleus muscle atrophied 32 percent during seven days of nonweight bearing without countermeasures, and centrifugation treatment did not completely prevent atrophy relative to precontrol wet weight of the soleus muscle. Nonweight-bearing groups receiving treatments of 1, 1.5, or 2.6 G had 48, 56, and 65 percent, respectively, of the atrophy observed in a nonweight-bearing-only group compared with the precontrol group. It is concluded that, as a countermeasure to nonweight-bearing-induced atrophy of the soleus muscle, centrifugation at 2.6 G is no more effective than exposure to 1 or 1.5 G.

  8. Bone and muscle atrophy with suspension of the rat

    Science.gov (United States)

    Leblanc, A.; Marsh, C.; Evans, H.; Johnson, P.; Schneider, V.; Jhingran, S.

    1985-01-01

    In order to identify a suitable model for the study of muscle atrophy due to suspension in space, a modified version of the Morey tail suspension model was used to measure the atrophic responses of rat bone and muscle to 14-30 days of unloading of the hindlimbs. The progress of atrophy was measured by increases in methylene diphosphonate (MDP) uptake. It is found that bone uptake of methylene diphosphonate followed a phasic pattern similar to changes in the bone formation rate of immobilized dogs and cats. Increased MDP uptake after a period of 60 days indicated an accelerated bone metabolism. Maximum muscle atrophy in the suspended rats was distinctly different from immobilization atrophy. On the basis of the experimental results, it is concluded that the tail suspension model is an adequate simulation of bone atrophy due to suspension.

  9. Indices of Regional Brain Atrophy: Formulae and Nomenclature

    Science.gov (United States)

    Arias-Carrión, Oscar

    2015-01-01

    The pattern of brain atrophy helps to discriminate normal age-related changes from neurodegenerative diseases. Albeit indices of regional brain atrophy have proven to be a parameter useful in the early diagnosis and differential diagnosis of some neurodegenerative diseases, indices of absolute regional atrophy still have some important limitations. We propose using indices of relative atrophy for representing how the volume of a given region of interest (ROI) changes over time in comparison to changes in global brain measures over the same time. A second problem in morphometric studies is terminology. There is a lack of systematization naming indices and the same measure can be named with different terms by different research groups or imaging softwares. This limits the understanding and discussion of studies. In this technological report, we provide a general description on how to compute indices of absolute and relative regional brain atrophy and propose a standardized nomenclature. PMID:26261753

  10. [Hereditary optic neuropathies: from clinical signs to diagnosis].

    Science.gov (United States)

    Meunier, I; Lenaers, G; Hamel, C; Defoort-Dhellemmes, S

    2013-12-01

    Inherited optic atrophy must be considered when working up any optic nerve involvement and any systemic disease with signs of optic atrophy, even with a negative family history. There are two classical forms: dominant optic atrophy, characterized by insidious, bilateral, slowly progressive visual loss and temporal disc pallor, and Leber's optic atrophy, characterized by acute loss of central vision followed by the same event in the fellow eye within a few weeks to months, with disc hyperemia in the acute phase. Family history is critical for diagnosis. In the absence of family history, the clinician must rule out an identifiable acquired cause, i.e. toxic, inflammatory, perinatal injury, traumatic or tumoral, with orbital and brain imaging (MRI). Recessive optic atrophies are more rare and more severe and occur as part of multisystemic disorders, particularly Wolfram syndrome (diabetes mellitus, diabetes insipidus, and hearing loss). Effective treatments are limited; alcohol and smoking should be avoided. A cyclosporine trial (taken immediately upon visual loss in the first eye) is in progress in Leber's optic atrophy to prevent involvement of the fellow eye.

  11. Retinal thinning correlates with clinical severity in multiple system atrophy.

    Science.gov (United States)

    Ahn, Jeeyun; Lee, Jee-Young; Kim, Tae Wan

    2016-10-01

    To analyze retinal thickness changes in multiple system atrophy (MSA) and correlate changes with disease severity and subtypes of MSA. A total of 36 MSA (27 MSA-P and 9 MSA-C) patients and 71 healthy control subjects underwent general ophthalmologic examination and optical coherence tomography (OCT) scans. Peripapillary retinal nerve fiber layer (RNFL) thickness and perifoveal retinal thickness were analyzed separately. The generalized estimating equation model was used with age as a covariate to adjust for within-patient inter-eye correlations and the effect of age on retinal or RNFL thickness. Correlation analysis between RNFL, perifoveal thickness, and clinical parameters, the Unified MSA Rating Scale (UMSARS) and Global Disability Score (GDS), was also done. MSA patients showed significantly decreased peripapillary RNFL thickness in the inferior (P = 0.047) and inferotemporal (P = 0.017) sectors and significant perifoveal thinning in the superior outer sector (P = 0.042) compared to healthy controls. Both RNFL and perifoveal thinning were more marked and widespread in MSA-P than MSA-C patients. The UMSARS and GDS showed significant negative correlation with center and total macular perifoveal thickness and also the inferior and nasal outer sectors. Peripapillary RNFL and perifoveal retinal thinning were observed in MSA patients and retinal thinning correlated with the clinical severity of MSA. Structural changes in the retina may reflect the degree and pattern of neurodegeneration occurring in MSA.

  12. Cardiac atrophy in women following bed rest.

    Science.gov (United States)

    Dorfman, Todd A; Levine, Benjamin D; Tillery, Tommy; Peshock, Ronald M; Hastings, Jeff L; Schneider, Suzanne M; Macias, Brandon R; Biolo, Gianni; Hargens, Alan R

    2007-07-01

    Both chronic microgravity exposure and long-duration bed rest induce cardiac atrophy, which leads to reduced standing stroke volume and orthostatic intolerance. However, despite the fact that women appear to be more susceptible to postspaceflight presyncope and orthostatic hypotension than male astronauts, most previous high-resolution studies of cardiac morphology following microgravity have been performed only in men. Because female athletes have less physiological hypertrophy than male athletes, we reasoned that they also might have altered physiological cardiac atrophy after bed rest. Magnetic resonance imaging was performed in 24 healthy young women (32.1 +/- 4 yr) to measure left ventricular (LV) and right ventricular (RV) mass, volumes, and morphology accurately before and after 60 days of 6 degrees head-down tilt (HDT) bed rest. Subjects were matched and then randomly assigned to sedentary bed rest (controls, n = 8) or two treatment groups consisting of 1) exercise training using supine treadmill running within lower body negative pressure plus resistive training (n = 8), or 2) protein (0.45 g x kg(-1) x day(-1) increase) plus branched-chain amino acid (BCAA) (7.2 g/day) supplementation (n = 8). After sedentary bed rest without nutritional supplementation, there were significant reductions in LV (96 +/- 26 to 77 +/- 25 ml; P = 0.03) and RV volumes (104 +/- 33 to 86 +/- 25 ml; P = 0.02), LV (2.2 +/- 0.2 to 2.0 +/- 0.2 g/kg; P = 0.003) and RV masses (0.8 +/- 0.1 to 0.6 +/- 0.1 g/kg; P men (8.0%; Perhonen MA, Franco F, Lane LD, Buckey JC, Blomqvist Zerwekh JE, Peshock RM, Weatherall PT, Levine BD. J Appl Physiol 91: 645-653, 2001). In contrast, there were no significant reductions in LV or RV volumes in the exercise-trained group, and the length of the major axis was preserved. Moreover, there were significant increases in LV (1.9 +/- 0.4 to 2.3 +/- 0.3 g/kg; P women similar to men following sedentary 60 days HDT bed rest. However, exercise training and, to a

  13. Assessing atrophy measurement techniques in dementia: Results from the MIRIAD atrophy challenge

    Science.gov (United States)

    Cash, David M.; Frost, Chris; Iheme, Leonardo O.; Ünay, Devrim; Kandemir, Melek; Fripp, Jurgen; Salvado, Olivier; Bourgeat, Pierrick; Reuter, Martin; Fischl, Bruce; Lorenzi, Marco; Frisoni, Giovanni B.; Pennec, Xavier; Pierson, Ronald K.; Gunter, Jeffrey L.; Senjem, Matthew L.; Jack, Clifford R.; Guizard, Nicolas; Fonov, Vladimir S.; Collins, D. Louis; Modat, Marc; Cardoso, M. Jorge; Leung, Kelvin K.; Wang, Hongzhi; Das, Sandhitsu R.; Yushkevich, Paul A.; Malone, Ian B.; Fox, Nick C.; Schott, Jonathan M.; Ourselin, Sebastien

    2015-01-01

    Structural MRI is widely used for investigating brain atrophy in many neurodegenerative disorders, with several research groups developing and publishing techniques to provide quantitative assessments of this longitudinal change. Often techniques are compared through computation of required sample size estimates for future clinical trials. However interpretation of such comparisons is rendered complex because, despite using the same publicly available cohorts, the various techniques have been assessed with different data exclusions and different statistical analysis models. We created the MIRIAD atrophy challenge in order to test various capabilities of atrophy measurement techniques. The data consisted of 69 subjects (46 Alzheimer's disease, 23 control) who were scanned multiple (up to twelve) times at nine visits over a follow-up period of one to two years, resulting in 708 total image sets. Nine participating groups from 6 countries completed the challenge by providing volumetric measurements of key structures (whole brain, lateral ventricle, left and right hippocampi) for each dataset and atrophy measurements of these structures for each time point pair (both forward and backward) of a given subject. From these results, we formally compared techniques using exactly the same dataset. First, we assessed the repeatability of each technique using rates obtained from short intervals where no measurable atrophy is expected. For those measures that provided direct measures of atrophy between pairs of images, we also assessed symmetry and transitivity. Then, we performed a statistical analysis in a consistent manner using linear mixed effect models. The models, one for repeated measures of volume made at multiple time-points and a second for repeated “direct” measures of change in brain volume, appropriately allowed for the correlation between measures made on the same subject and were shown to fit the data well. From these models, we obtained estimates of the

  14. Assessing atrophy measurement techniques in dementia: Results from the MIRIAD atrophy challenge.

    Science.gov (United States)

    Cash, David M; Frost, Chris; Iheme, Leonardo O; Ünay, Devrim; Kandemir, Melek; Fripp, Jurgen; Salvado, Olivier; Bourgeat, Pierrick; Reuter, Martin; Fischl, Bruce; Lorenzi, Marco; Frisoni, Giovanni B; Pennec, Xavier; Pierson, Ronald K; Gunter, Jeffrey L; Senjem, Matthew L; Jack, Clifford R; Guizard, Nicolas; Fonov, Vladimir S; Collins, D Louis; Modat, Marc; Cardoso, M Jorge; Leung, Kelvin K; Wang, Hongzhi; Das, Sandhitsu R; Yushkevich, Paul A; Malone, Ian B; Fox, Nick C; Schott, Jonathan M; Ourselin, Sebastien

    2015-12-01

    Structural MRI is widely used for investigating brain atrophy in many neurodegenerative disorders, with several research groups developing and publishing techniques to provide quantitative assessments of this longitudinal change. Often techniques are compared through computation of required sample size estimates for future clinical trials. However interpretation of such comparisons is rendered complex because, despite using the same publicly available cohorts, the various techniques have been assessed with different data exclusions and different statistical analysis models. We created the MIRIAD atrophy challenge in order to test various capabilities of atrophy measurement techniques. The data consisted of 69 subjects (46 Alzheimer's disease, 23 control) who were scanned multiple (up to twelve) times at nine visits over a follow-up period of one to two years, resulting in 708 total image sets. Nine participating groups from 6 countries completed the challenge by providing volumetric measurements of key structures (whole brain, lateral ventricle, left and right hippocampi) for each dataset and atrophy measurements of these structures for each time point pair (both forward and backward) of a given subject. From these results, we formally compared techniques using exactly the same dataset. First, we assessed the repeatability of each technique using rates obtained from short intervals where no measurable atrophy is expected. For those measures that provided direct measures of atrophy between pairs of images, we also assessed symmetry and transitivity. Then, we performed a statistical analysis in a consistent manner using linear mixed effect models. The models, one for repeated measures of volume made at multiple time-points and a second for repeated "direct" measures of change in brain volume, appropriately allowed for the correlation between measures made on the same subject and were shown to fit the data well. From these models, we obtained estimates of the

  15. Muscle Atrophy Reversed by Growth Factor Activation of Satellite Cells in a Mouse Muscle Atrophy Model

    DEFF Research Database (Denmark)

    Hauerslev, Simon; Vissing, John; Krag, Thomas O

    2014-01-01

    Muscular dystrophies comprise a large group of inherited disorders that lead to progressive muscle wasting. We wanted to investigate if targeting satellite cells can enhance muscle regeneration and thus increase muscle mass. We treated mice with hepatocyte growth factor and leukemia inhibitory...... factor under three conditions: normoxia, hypoxia and during myostatin deficiency. We found that hepatocyte growth factor treatment led to activation of the Akt/mTOR/p70S6K protein synthesis pathway, up-regulation of the myognic transcription factors MyoD and myogenin, and subsequently the negative growth...... control factor, myostatin and atrophy markers MAFbx and MuRF1. Hypoxia-induced atrophy was partially restored by hepatocyte growth factor combined with leukemia inhibitory factor treatment. Dividing satellite cells were three-fold increased in the treatment group compared to control. Finally, we...

  16. Different atrophy-hypertrophy transcription pathways in muscles affected by severe and mild spinal muscular atrophy

    Directory of Open Access Journals (Sweden)

    Millino Caterina

    2009-04-01

    Full Text Available Abstract Background Spinal muscular atrophy (SMA is a neurodegenerative disorder associated with mutations of the survival motor neuron gene SMN and is characterized by muscle weakness and atrophy caused by degeneration of spinal motor neurons. SMN has a role in neurons but its deficiency may have a direct effect on muscle tissue. Methods We applied microarray and quantitative real-time PCR to study at transcriptional level the effects of a defective SMN gene in skeletal muscles affected by the two forms of SMA: the most severe type I and the mild type III. Results The two forms of SMA generated distinct expression signatures: the SMA III muscle transcriptome is close to that found under normal conditions, whereas in SMA I there is strong alteration of gene expression. Genes implicated in signal transduction were up-regulated in SMA III whereas those of energy metabolism and muscle contraction were consistently down-regulated in SMA I. The expression pattern of gene networks involved in atrophy signaling was completed by qRT-PCR, showing that specific pathways are involved, namely IGF/PI3K/Akt, TNF-α/p38 MAPK and Ras/ERK pathways. Conclusion Our study suggests a different picture of atrophy pathways in each of the two forms of SMA. In particular, p38 may be the regulator of protein synthesis in SMA I. The SMA III profile appears as the result of the concurrent presence of atrophic and hypertrophic fibers. This more favorable condition might be due to the over-expression of MTOR that, given its role in the activation of protein synthesis, could lead to compensatory hypertrophy in SMA III muscle fibers.

  17. Nutritional optic neuropathy.

    Science.gov (United States)

    Sawicka-Pierko, Anna; Obuchowska, Iwona; Mariak, Zofia

    2014-01-01

    Nutritional optic neuropathy (aka deficiency optic neuropathy) is a dysfunction of the optic nerve resulting from improper dietary content of certain nutrients essential for normal functioning of the nerve fibers. Most commonly, it results from folic acid and vitamin B complex deficiency associated with malnutrition or poor dietary habits, incorrectly applied vegetarian diet, or chronic alcohol abuse. Obese patients after bariatric surgery constitute another risk group of optic neuropathy. Nutritional optic neuropathy is characterized by painless, gradually progressing, bilateral and symmetrical decrease in visual acuity, which can be accompanied by the color vision dysfunction. Progression of the neuropathy is associated with optic nerve atrophy, manifesting as complete disc pallor. Treatment of nutritional neuropathy includes dietary supplementation, aimed at compensating for the deficient nutrients. The treatment is mostly based on folic acid, vitamin B complex, and protein replacement, as well as eliminating risk factors of neuropathy. Early treatment commencement, prior to irreversible optic nerve atrophy, is a prerequisite of effective treatment. We would like to highlight this problem by presenting the case of a young woman in whom chronic use "water-based" diet resulted in anemia and bilateral nutritional optic neuropathy.

  18. Visual Dysfunction in Posterior Cortical Atrophy

    Directory of Open Access Journals (Sweden)

    Mari N. Maia da Silva

    2017-08-01

    Full Text Available Posterior cortical atrophy (PCA is a syndromic diagnosis. It is characterized by progressive impairment of higher (cortical visual function with imaging evidence of degeneration affecting the occipital, parietal, and posterior temporal lobes bilaterally. Most cases will prove to have Alzheimer pathology. The aim of this review is to summarize the development of the concept of this disorder since it was first introduced. A critical discussion of the evolving diagnostic criteria is presented and the differential diagnosis with regard to the underlying pathology is reviewed. Emphasis is given to the visual dysfunction that defines the disorder, and the classical deficits, such as simultanagnosia and visual agnosia, as well as the more recently recognized visual field defects, are reviewed, along with the evidence on their neural correlates. The latest developments on the imaging of PCA are summarized, with special attention to its role on the differential diagnosis with related conditions.

  19. Visual Dysfunction in Posterior Cortical Atrophy

    Science.gov (United States)

    da Silva, Mari N. Maia; Millington, Rebecca S.; Bridge, Holly; James-Galton, Merle; Plant, Gordon T.

    2017-01-01

    Posterior cortical atrophy (PCA) is a syndromic diagnosis. It is characterized by progressive impairment of higher (cortical) visual function with imaging evidence of degeneration affecting the occipital, parietal, and posterior temporal lobes bilaterally. Most cases will prove to have Alzheimer pathology. The aim of this review is to summarize the development of the concept of this disorder since it was first introduced. A critical discussion of the evolving diagnostic criteria is presented and the differential diagnosis with regard to the underlying pathology is reviewed. Emphasis is given to the visual dysfunction that defines the disorder, and the classical deficits, such as simultanagnosia and visual agnosia, as well as the more recently recognized visual field defects, are reviewed, along with the evidence on their neural correlates. The latest developments on the imaging of PCA are summarized, with special attention to its role on the differential diagnosis with related conditions. PMID:28861031

  20. Fluid biomarkers in multiple system atrophy

    DEFF Research Database (Denmark)

    Laurens, Brice; Constantinescu, Radu; Freeman, Roy

    2015-01-01

    Despite growing research efforts, no reliable biomarker currently exists for the diagnosis and prognosis of multiple system atrophy (MSA). Such biomarkers are urgently needed to improve diagnostic accuracy, prognostic guidance and also to serve as efficacy measures or surrogates of target...... engagement for future clinical trials. We here review candidate fluid biomarkers for MSA and provide considerations for further developments and harmonization of standard operating procedures. A PubMed search was performed until April 24, 2015 to review the literature with regard to candidate blood...... and cerebrospinal fluid (CSF) biomarkers for MSA. Abstracts of 1760 studies were retrieved and screened for eligibility. The final list included 60 studies assessing fluid biomarkers in patients with MSA. Most studies have focused on alpha-synuclein, markers of axonal degeneration or catecholamines. Their results...

  1. Diagnosis and therapy of multiple system atrophy

    Directory of Open Access Journals (Sweden)

    GU Wei-hong

    2012-06-01

    Full Text Available Multiple system atrophy (MSA is a sporadic and rapidly progressive neurodegenerative disorder characterised clinically by any combination of autonomic, cerebellar ataxia, parkinsonian, and pyramidal signs. Over the past 10 years, substantial progress has been achieved to establish MSA as an α-synucleinopathy along with other neurodegenerative diseases. Although the diagnosis of this disorder is largely based on clinical expertise, some investigations have been proposed to assist in early differential diagnosis, especially neuroimaging examination, which have resulted in revised diagnostic criteria. The UMSARS is a reliable and valid scale for semiquantitative clinical assessments of MSA patients. An outline of the rationale for managing symptomatic deterioration in MSA is provided including novel neuroprotective therapeutic approaches, together with the treatment of traditional Chinese medicine.

  2. Reviewing the options for local estrogen treatment of vaginal atrophy

    Directory of Open Access Journals (Sweden)

    Lindahl SH

    2014-03-01

    Full Text Available Sarah H Lindahl Sutter East Bay Medical Foundation, SEBMF – Diablo Division, Castro Valley, CA, USA Background: Vaginal atrophy is a chronic condition with symptoms that include vaginal dryness, pain during sex, itching, irritation, burning, and discharge, as well as various urinary problems. Up to 45% of postmenopausal women may be affected, but it often remains underreported and undertreated. This article aims to review the current recommendations for treatment of vaginal atrophy, and current data on the effectiveness and safety of local vaginal estrogen therapies. Methods: Literature regarding vaginal atrophy (2007–2012 was retrieved from PubMed and summarized, with emphasis on data related to the treatment of vaginal atrophy with local vaginal estrogen therapy. Results: Published data support the effectiveness and endometrial safety of low-dose local estrogen therapies. These results further support the general recommendation by the North American Menopause Society that a progestogen is not needed for endometrial protection in patients using low-dose local vaginal estrogen. Benefits of long-term therapy for vaginal atrophy include sustained relief of symptoms as well as physiological improvements (eg, decreased vaginal pH and increased blood flow, epithelial thickness, secretions. Conclusion: Currently available local vaginal estrogen therapies are well tolerated and effective in relieving symptoms of vaginal atrophy. Recent data support the endometrial safety of low-dose regimens for up to 1 year. Keywords: menopause, estrogen, local estrogen therapy, vaginal atrophy

  3. Transcriptional profile of a myotube starvation model of atrophy

    Science.gov (United States)

    Stevenson, Eric J.; Koncarevic, Alan; Giresi, Paul G.; Jackman, Robert W.; Kandarian, Susan C.

    2005-01-01

    Skeletal muscle wasting is a pervasive phenomenon that can result from a wide range of pathological conditions as well as from habitual muscular inactivity. The present work describes a cell-culture condition that induces significant atrophy in skeletal muscle C2C12 myotubes. The failure to replenish differentiation media in mature myotubes leads to rapid atrophy (53% in diameter), which is referred to here as starvation. Affymetrix microarrays were used to develop a transcriptional profile of control (fed) vs. atrophied (nonfed) myotubes. Myotube starvation was characterized by an upregulation of genes involved in translational inhibition, amino acid biosynthesis and transport, and cell cycle arrest/apoptosis, among others. Downregulated genes included several structural and regulatory elements of the extracellular matrix as well as several elements of Wnt/frizzled and TGF-beta signaling pathways. Interestingly, the characteristic transcriptional upregulation of the ubiquitin-proteasome system, calpains, and cathepsins known to occur in multiple in vivo models of atrophy were not seen during myotube starvation. With the exception of the downregulation of extracellular matrix genes, serine protease inhibitor genes, and the upregulation of the translation initiation factor PHAS-I, this model of atrophy in cell culture has a transcriptional profile quite distinct from any study published to date with atrophy in whole muscle. These data show that, although the gross morphology of atrophied muscle fibers may be similar in whole muscle vs. myotube culture, the processes by which this phenotype is achieved differ markedly.

  4. White matter hyperintensities are associated with disproportionate progressive hippocampal atrophy

    Science.gov (United States)

    Manning, Emily N.; Bartlett, Jonathan W.; Cash, David M.; Malone, Ian B.; Ridgway, Gerard R.; Lehmann, Manja; Leung, Kelvin K.; Sudre, Carole H.; Ourselin, Sebastien; Biessels, Geert Jan; Carmichael, Owen T.; Fox, Nick C.; Cardoso, M. Jorge; Barnes, Josephine

    2017-01-01

    ABSTRACT This study investigates relationships between white matter hyperintensity (WMH) volume, cerebrospinal fluid (CSF) Alzheimer's disease (AD) pathology markers, and brain and hippocampal volume loss. Subjects included 198 controls, 345 mild cognitive impairment (MCI), and 154 AD subjects with serial volumetric 1.5‐T MRI. CSF Aβ42 and total tau were measured (n = 353). Brain and hippocampal loss were quantified from serial MRI using the boundary shift integral (BSI). Multiple linear regression models assessed the relationships between WMHs and hippocampal and brain atrophy rates. Models were refitted adjusting for (a) concurrent brain/hippocampal atrophy rates and (b) CSF Aβ42 and tau in subjects with CSF data. WMH burden was positively associated with hippocampal atrophy rate in controls (P = 0.002) and MCI subjects (P = 0.03), and with brain atrophy rate in controls (P = 0.03). The associations with hippocampal atrophy rate remained following adjustment for concurrent brain atrophy rate in controls and MCIs, and for CSF biomarkers in controls (P = 0.007). These novel results suggest that vascular damage alongside AD pathology is associated with disproportionately greater hippocampal atrophy in nondemented older adults. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc. PMID:27933676

  5. White matter hyperintensities are associated with disproportionate progressive hippocampal atrophy.

    Science.gov (United States)

    Fiford, Cassidy M; Manning, Emily N; Bartlett, Jonathan W; Cash, David M; Malone, Ian B; Ridgway, Gerard R; Lehmann, Manja; Leung, Kelvin K; Sudre, Carole H; Ourselin, Sebastien; Biessels, Geert Jan; Carmichael, Owen T; Fox, Nick C; Cardoso, M Jorge; Barnes, Josephine

    2017-03-01

    This study investigates relationships between white matter hyperintensity (WMH) volume, cerebrospinal fluid (CSF) Alzheimer's disease (AD) pathology markers, and brain and hippocampal volume loss. Subjects included 198 controls, 345 mild cognitive impairment (MCI), and 154 AD subjects with serial volumetric 1.5-T MRI. CSF Aβ42 and total tau were measured (n = 353). Brain and hippocampal loss were quantified from serial MRI using the boundary shift integral (BSI). Multiple linear regression models assessed the relationships between WMHs and hippocampal and brain atrophy rates. Models were refitted adjusting for (a) concurrent brain/hippocampal atrophy rates and (b) CSF Aβ42 and tau in subjects with CSF data. WMH burden was positively associated with hippocampal atrophy rate in controls (P = 0.002) and MCI subjects (P = 0.03), and with brain atrophy rate in controls (P = 0.03). The associations with hippocampal atrophy rate remained following adjustment for concurrent brain atrophy rate in controls and MCIs, and for CSF biomarkers in controls (P = 0.007). These novel results suggest that vascular damage alongside AD pathology is associated with disproportionately greater hippocampal atrophy in nondemented older adults. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.

  6. Pattern of inner retinal layers involvement in pigmented paravenous retinochoroidal atrophy as determined by SD-OCT: case report.

    Science.gov (United States)

    Junqueira, Daniela Laura Melo; Lopes, Flavio Siqueira Santos; Biteli, Luís Gustavo; Prata, Tiago Santos

    2013-01-01

    Pigmented paravenous retinochoroidal atrophy is an ocular disease characterized by outer retina and choroidal atrophy often with overlying intraretinal bone spicule pigment deposition along the retinal veins. As a rare condition, there is scant information in the literature regarding the pattern of inner retinal layers involvement. We present a case of a 41-year-old white man initially referred for a glaucoma evaluation. Fundoscopy revealed patches of retinochoroidal atrophy and light pigmentation extending from the optic nerve head along the inferior-temporal retinal veins in both eyes. Using different spectral-domain optical coherence tomography (SD-OCT) protocols we identified a significant thinning of the inner retinal layers along the inferior-temporal veins, but with a lucid interval surrounding the optic nerve head. Standard automated perimetry revealed a superior absolute arcuate scotoma sparing the central fixation (good structure-functional correlation). This pattern of inner retinal layers involvement was not previously described. We believe SD-OCT added significantly to the anatomical description of this case. Physicians should consider these new anatomical findings and correlate them with functional status while assessing these patients.

  7. Pattern of inner retinal layers involvement in pigmented paravenous retinochoroidal atrophy as determined by SD-OCT: case report

    Directory of Open Access Journals (Sweden)

    Daniela Laura Melo Junqueira

    2013-12-01

    Full Text Available Pigmented paravenous retinochoroidal atrophy is an ocular disease characterized by outer retina and choroidal atrophy often with overlying intraretinal bone spicule pigment deposition along the retinal veins. As a rare condition, there is scant information in the literature regarding the pattern of inner retinal layers involvement. We present a case of a 41-year-old white man initially referred for a glaucoma evaluation. Fundoscopy revealed patches of retinochoroidal atrophy and light pigmentation extending from the optic nerve head along the inferior-temporal retinal veins in both eyes. Using different spectral-domain optical coherence tomography (SD-OCT protocols we identified a significant thinning of the inner retinal layers along the inferior-temporal veins, but with a lucid interval surrounding the optic nerve head. Standard automated perimetry revealed a superior absolute arcuate scotoma sparing the central fixation (good structure-functional correlation. This pattern of inner retinal layers involvement was not previously described. We believe SD-OCT added significantly to the anatomical description of this case. Physicians should consider these new anatomical findings and correlate them with functional status while assessing these patients.

  8. Retinal atrophy in relation to visual functioning and vision-related quality of life in patients with multiple sclerosis.

    Science.gov (United States)

    Balk, Lisanne J; Coric, Danko; Nij Bijvank, Jenny A; Killestein, Joep; Uitdehaag, Bernard Mj; Petzold, Axel

    2017-05-01

    Inner retinal layer atrophy in patients with multiple sclerosis (MS) has been validated as a structural imaging biomarker for neurodegeneration. To determine how retinal layer thickness relates to high-contrast visual acuity (HCVA), low-contrast visual acuity (LCVA) and vision-related quality of life (QoL) and to investigate the effect of previous episodes on MS-associated optic neuritis (MSON). Spectral-domain optical coherence tomography (SD-OCT) was performed in 267 patients with MS. Images were segmented for the peripapillary retinal nerve fiber layer (pRNFL) and the macular ganglion cell inner plexiform layer (GCIPL). Ophthalmological evaluations included history of MSON, HCVA, LCVA, and vision-related QoL. Independent of MSON, HCVA and LCVA were significantly associated with pRNFL and GCIPL thicknesses. Vision-related QoL was positively associated with pRNFL (β = 0.92, p = 0.06) and GCIPL (β = 0.93, p = 0.02) thicknesses. These associations were independent of MSON. Not only binocular but also monocular atrophy of the inner retinal layers was associated with lower vision-related QoL. This study showed that retinal atrophy has a significant impact on visual functioning in patients with MS. OCT may therefore provide useful insight to patients with visual dysfunction, and our findings support including OCT and vision-related QoL measures into optic neuritis treatment trials.

  9. Cerebellar Atrophy in Adult Survivors of Childhood Cerebellar Tumor.

    Science.gov (United States)

    Ailion, Alyssa S; King, Tricia Z; Wang, Liya; Fox, Michelle E; Mao, Hui; Morris, Robin M; Crosson, Bruce

    2016-05-01

    The cerebellum (CB) is known for its role in supporting processing speed (PS) and cognitive efficiencies. The CB often sustains damage from treatment and resection in pediatric patients with posterior fossa tumors. Limited research suggests that CB atrophy may be associated with the radiation treatment experienced during childhood. The purpose of the study was to measure cerebellar atrophy to determine its neurobehavioral correlates. Brain magnetic resonance images were collected from 25 adult survivors of CB tumors and age- and gender-matched controls (M age= 24 years (SD=5), 52% female). Average age at diagnosis was 9 years (SD=5) and average time since diagnosis was 15 years (SD=5). PS was measured by the Symbol Digit Modality Test. To quantify atrophy, an objective formula was developed based on prior literature, in which Atrophy=[(CB White+CB Gray Volume)/Intracranial Vault (ICV)]controls-[(CB White+CB Gray+Lesion Size Volume)/ICV]survivors. Regression analyses found that the interaction term (age at diagnosis*radiation) predicts CB atrophy; regression equations included the Neurological Predictor Scale, lesion size, atrophy, and the interaction term and accounted for 33% of the variance in oral PS and 48% of the variance in written PS. Both interactions suggest that individuals with smaller CB lesion size but a greater degree of CB atrophy had slower PS, whereas individuals with a larger CB lesion size and less CB atrophy were less affected. The results of the current study suggest that young age at diagnosis and radiation is associated with CB atrophy, which interacts with lesion size to impact both written and oral PS.

  10. Botulinum Toxin and Muscle Atrophy: A Wanted or Unwanted Effect.

    Science.gov (United States)

    Durand, Paul D; Couto, Rafael A; Isakov, Raymond; Yoo, Donald B; Azizzadeh, Babak; Guyuron, Bahman; Zins, James E

    2016-04-01

    While the facial rejuvenating effect of botulinum toxin type A is well known and widespread, its use in body and facial contouring is less common. We first describe its use for deliberate muscle volume reduction, and then document instances of unanticipated and undesirable muscle atrophy. Finally, we investigate the potential long-term adverse effects of botulinum toxin-induced muscle atrophy. Although the use of botulinum toxin type A in the cosmetic patient has been extensively studied, there are several questions yet to be addressed. Does prolonged botulinum toxin treatment increase its duration of action? What is the mechanism of muscle atrophy and what is the cause of its reversibility once treatment has stopped? We proceed to examine how prolonged chemodenervation with botulinum toxin can increase its duration of effect and potentially contribute to muscle atrophy. Instances of inadvertent botulinum toxin-induced atrophy are also described. These include the "hourglass deformity" secondary to botulinum toxin type A treatment for migraine headaches, and a patient with atrophy of multiple facial muscles from injections for hemifacial spasm. Numerous reports demonstrate that muscle atrophy after botulinum toxin type A treatment occurs and is both reversible and temporary, with current literature supporting the notion that repeated chemodenervation with botulinum toxin likely responsible for both therapeutic and incidental temporary muscle atrophy. Furthermore, duration of response may be increased with subsequent treatments, thus minimizing frequency of reinjection. Practitioners should be aware of the temporary and reversible effect of botulinum toxin-induced muscle atrophy and be prepared to reassure patients on this matter.

  11. Brain atrophy in multiple sclerosis: therapeutic, cognitive and clinical impact

    Directory of Open Access Journals (Sweden)

    Juan Ignacio Rojas

    2016-03-01

    Full Text Available ABSTRACT Multiple sclerosis (MS was always considered as a white matter inflammatory disease. Today, there is an important body of evidence that supports the hypothesis that gray matter involvement and the neurodegenerative mechanism are at least partially independent from inflammation. Gray matter atrophy develops faster than white matter atrophy, and predominates in the initial stages of the disease. The neurodegenerative mechanism creates permanent damage and correlates with physical and cognitive disability. In this review we describe the current available evidence regarding brain atrophy and its consequence in MS patients.

  12. Posterior cortical atrophy: an atypical variant of Alzheimer disease.

    Science.gov (United States)

    Suárez-González, Aida; Henley, Susie M; Walton, Jill; Crutch, Sebastian J

    2015-06-01

    Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by striking progressive visual impairment and a pattern of atrophy mainly involving posterior cortices. PCA is the most frequent atypical presentation of Alzheimer disease. The purpose of this article is to provide a summary of PCA's neuropsychiatric manifestations. Emotional and psychotic symptoms are discussed in the context of signal characteristic features of the PCA syndrome (the early onset, focal loss of visual perception, focal posterior brain atrophy) and the underlying cause of the disease. The authors' experience with psychotherapeutic intervention and PCA support groups is shared in detail.

  13. Deformation-Based Atrophy Estimation for Alzheimer’s Disease

    DEFF Research Database (Denmark)

    Pai, Akshay Sadananda Uppinakudru

    Alzheimer’s disease (AD) - the most common form of dementia, is a term used for accelerated memory loss and cognitive abilities enough to severely hamper day-to-day activities. One of the most globally accepted markers for AD is atrophy, in mainly the brain parenchyma. The goal of the PhD project...... and a new way to estimate atrophy from a deformation field. We demonstrate the performance of the proposed solution but applying it on the publicly available Alzheimer’s disease neuroimaging data (ADNI) initiative and compare to existing state-of-art atrophy estimation methods....

  14. Deformation-Based Atrophy Estimation for Alzheimer’s Disease

    DEFF Research Database (Denmark)

    Pai, Akshay Sadananda Uppinakudru

    Alzheimer’s disease (AD) - the most common form of dementia, is a term used for accelerated memory loss and cognitive abilities enough to severely hamper day-to-day activities. One of the most globally accepted markers for AD is atrophy, in mainly the brain parenchyma. The goal of the PhD project...... and a new way to estimate atrophy from a deformation field. We demonstrate the performance of the proposed solution but applying it on the publicly available Alzheimer’s disease neuroimaging data (ADNI) initiative and compare to existing state-of-art atrophy estimation methods....

  15. Deletion of atrophy enhancing genes fails to ameliorate the phenotype in a mouse model of spinal muscular atrophy.

    Science.gov (United States)

    Iyer, Chitra C; McGovern, Vicki L; Wise, Dawnne O; Glass, David J; Burghes, Arthur H M

    2014-05-01

    Spinal muscular atrophy (SMA) is an autosomal recessive disease causing degeneration of lower motor neurons and muscle atrophy. One therapeutic avenue for SMA is targeting signaling pathways in muscle to ameliorate atrophy. Muscle Atrophy F-box, MAFbx, and Muscle RING Finger 1, MuRF1, are muscle-specific ubiquitin ligases upregulated in skeletal and cardiac muscle during atrophy. Homozygous knock-out of MAFbx or MuRF1 causes muscle sparing in adult mice subjected to atrophy by denervation. We wished to determine whether blockage of the major muscle atrophy pathways by deletion of MAFbx or MuRF1 in a mouse model of SMA would improve the phenotype. Deletion of MAFbx in the Δ7 SMA mouse model had no effect on the weight and the survival of the mice while deletion of MuRF1 was deleterious. MAFbx(-/-)-SMA mice showed a significant alteration in fiber size distribution tending towards larger fibers. In skeletal and cardiac tissue MAFbx and MuRF1 transcripts were upregulated whereas MuRF2 and MuRF3 levels were unchanged in Δ7 SMA mice. We conclude that deletion of the muscle ubiquitin ligases does not improve the phenotype of a Δ7 SMA mouse. Furthermore, it seems unlikely that the beneficial effect of HDAC inhibitors is mediated through inhibition of MAFbx and MuRF1. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Mechanisms of cisplatin-induced muscle atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Hiroyasu, E-mail: sakai@hoshi.ac.jp [Department of Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Division of Pharmacy Professional Development and Research, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Sagara, Atsunobu; Arakawa, Kazuhiko; Sugiyama, Ryoto; Hirosaki, Akiko; Takase, Kazuhide; Jo, Ara [Department of Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Sato, Ken [Department of Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Division of Pharmacy Professional Development and Research, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Chiba, Yoshihiko [Department of Biology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Yamazaki, Mitsuaki [Department of Anesthesiology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 9300194 (Japan); Matoba, Motohiro [Department of Palliative Medicine and Psychooncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 1040045 (Japan); Narita, Minoru, E-mail: narita@hoshi.ac.jp [Department of Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan)

    2014-07-15

    Fatigue is the most common side effect of chemotherapy. However, the mechanisms of “muscle fatigue” induced by anti-cancer drugs are not fully understood. We therefore investigated the muscle-atrophic effect of cisplatin, a platinum-based anti-cancer drug, in mice. C57BL/6J mice were treated with cisplatin (3 mg/kg, i.p.) or saline for 4 consecutive days. On Day 5, hindlimb and quadriceps muscles were isolated from mice. The loss of body weight and food intake under the administration of cisplatin was the same as those in a dietary restriction (DR) group. Under the present conditions, the administration of cisplatin significantly decreased not only the muscle mass of the hindlimb and quadriceps but also the myofiber diameter, compared to those in the DR group. The mRNA expression levels of muscle atrophy F-box (MAFbx), muscle RING finger-1 (MuRF1) and forkhead box O3 (FOXO3) were significantly and further increased by cisplatin treated group, compared to DR. Furthermore, the mRNA levels of myostatin and p21 were significantly upregulated by the administration of cisplatin, compared to DR. On the other hand, the phosphorylation of Akt and FOXO3a, which leads to the blockade of the upregulation of MuRF1 and MAFbx, was significantly and dramatically decreased by cisplatin. These findings suggest that the administration of cisplatin increases atrophic gene expression, and may lead to an imbalance between protein synthesis and protein degradation pathways, which would lead to muscle atrophy. This phenomenon could, at least in part, explain the mechanism of cisplatin-induced muscle fatigue. - Highlights: • Cisplatin decreased mass and myofiber diameter in quadriceps muscle. • The mRNA of MAFbx, MuRF1 and FOXO3 were increased by the cisplatin. • The mRNA of myostatin and p21 were upregulated by cisplatin. • The phosphorylation of Akt and FOXO3a was decreased by cisplatin.

  17. Muscle ring finger 1 mediates cardiac atrophy in vivo

    National Research Council Canada - National Science Library

    Monte S. Willis; Mauricio Rojas; Luge Li; Craig H. Selzman; Ru-Hang Tang; William E. Stansfield; Jessica E. Rodriguez; David J. Glass; Cam Patterson

    2009-01-01

    ...; cardiac hypertrophy. We now demonstrate that therapeutic cardiac atrophy induced in patients after left ventricular assist device placement is associated with an increase in cardiac MuRF1 expression...

  18. The pathogenesis and treatment of cardiac atrophy in cancer cachexia

    National Research Council Canada - National Science Library

    Murphy, Kate T

    2016-01-01

    .... In addition to a loss of skeletal muscle mass and function, many patients with cancer cachexia also experience cardiac atrophy, remodeling, and dysfunction, which in the field of cancer cachexia...

  19. Genetics Home Reference: gyrate atrophy of the choroid and retina

    Science.gov (United States)

    ... atrophy may also cause disturbances in the nerves connecting the brain and spinal cord to muscles and ... Criteria for Links Data Files & API Site Map Customer Support USA.gov Copyright Privacy Accessibility FOIA Viewers & ...

  20. Biochemical adaptations of antigravity muscle fibers to disuse atrophy

    Science.gov (United States)

    Booth, F. W.

    1978-01-01

    Studies are presented in four parts of this report. The four parts include; (1) studies to gain information on the molecular basis of atrophy by antigravity muscle; (2) studies on the work capacity of antigravity muscles during atrophy and during recovery from atrophy; (3) studies on recovery of degenerated antigravity fibers after removal of hind-limb casts; and (4) studies on the atrophy and recovery of bone. The philosophy of these studies was to identify the time sequence of events in the soleus muscle of the rat following immobilization of the hind limbs, so that the length of the soleus muscle within the fixed limb is less than its resting length. In two separate studies, no decline in the weight of the soleus muscle could be detected during the first 72 hours of limb immobilization.

  1. Disease-Induced Skeletal Muscle Atrophy and Fatigue

    NARCIS (Netherlands)

    Powers, Scott K.; Lynch, Gordon S.; Murphy, Kate T.; Reid, Michael B.; Zijdewind, Inge

    2016-01-01

    Numerous health problems including acute critical illness, cancer, diseases associated with chronic inflammation, and neurological disorders often result in skeletal muscle weakness and fatigue. Disease-related muscle atrophy and fatigue is an important clinical problem because acquired skeletal mus

  2. Mechanisms of muscle growth and atrophy in mammals and Drosophila

    National Research Council Canada - National Science Library

    Piccirillo, Rosanna; Demontis, Fabio; Perrimon, Norbert; Goldberg, Alfred L

    2014-01-01

    .... Although the pathogenesis of this condition has been primarily studied in mammals, Drosophila is emerging as an attractive system to investigate some of the mechanisms involved in muscle growth and atrophy. Results...

  3. Abnormalities of fixation, saccade and pursuit in posterior cortical atrophy.

    Science.gov (United States)

    Shakespeare, Timothy J; Kaski, Diego; Yong, Keir X X; Paterson, Ross W; Slattery, Catherine F; Ryan, Natalie S; Schott, Jonathan M; Crutch, Sebastian J

    2015-07-01

    The clinico-neuroradiological syndrome posterior cortical atrophy is the cardinal 'visual dementia' and most common atypical Alzheimer's disease phenotype, offering insights into mechanisms underlying clinical heterogeneity, pathological propagation and basic visual phenomena (e.g. visual crowding). Given the extensive attention paid to patients' (higher order) perceptual function, it is surprising that there have been no systematic analyses of basic oculomotor function in this population. Here 20 patients with posterior cortical atrophy, 17 patients with typical Alzheimer's disease and 22 healthy controls completed tests of fixation, saccade (including fixation/target gap and overlap conditions) and smooth pursuit eye movements using an infrared pupil-tracking system. Participants underwent detailed neuropsychological and neurological examinations, with a proportion also undertaking brain imaging and analysis of molecular pathology. In contrast to informal clinical evaluations of oculomotor dysfunction frequency (previous studies: 38%, current clinical examination: 33%), detailed eyetracking investigations revealed eye movement abnormalities in 80% of patients with posterior cortical atrophy (compared to 17% typical Alzheimer's disease, 5% controls). The greatest differences between posterior cortical atrophy and typical Alzheimer's disease were seen in saccadic performance. Patients with posterior cortical atrophy made significantly shorter saccades especially for distant targets. They also exhibited a significant exacerbation of the normal gap/overlap effect, consistent with 'sticky fixation'. Time to reach saccadic targets was significantly associated with parietal and occipital cortical thickness measures. On fixation stability tasks, patients with typical Alzheimer's disease showed more square wave jerks whose frequency was associated with lower cerebellar grey matter volume, while patients with posterior cortical atrophy showed large saccadic intrusions

  4. Reversible "brain atrophy" in patients with Cushing's disease

    OpenAIRE

    Gnjidić, Živko; Sajko, Tomislav; Kudelić, Nenad; Malenica, Maša; Vizner, Branka; Vrkljan, Milan; Hat, Josip; Rumboldt, Zoran

    2008-01-01

    During the past 25 years, we came across 60 patients with corticotroph pituitary adenomas and Cushing’s disease. Neuroradiological examination showed prominent volume loss of the brain parenchyma, unexpected for the patient’s age. This »brain atrophy« appeared to regress after surgical removal of pituitary adenoma and normalization of cortisol level. Observed difference between degree of »brain atrophy« in the Cushing’s disease group and in the control group was statistically sign...

  5. Steroid-induced Kager's fat pad atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Taneja, Atul K. [Hospital Israelita Albert Einstein, Musculoskeletal Radiology Division, Imaging Department, Sao Paulo (Brazil); Musculoskeletal Imaging, Diagnostic Center, Hospital do Coracao (HCor) and Teleimagem, Sao Paulo, SP (Brazil); Santos, Durval C.B. [Hospital Israelita Albert Einstein, Musculoskeletal Radiology Division, Imaging Department, Sao Paulo (Brazil)

    2014-08-15

    We report a rare case of Kager's fat pad atrophy and fibrosis in a 60-year-old woman 1 year after a steroid injection for Achilles tendinopathy. There are few published reports of steroid-induced atrophy affecting deeper layers of fat tissue. To our knowledge, this case report is the first to illustrate its features using magnetic resonance imaging. A review of the scientific literature is also presented. (orig.)

  6. Early and Degressive Putamen Atrophy in Multiple Sclerosis

    OpenAIRE

    Julia Krämer; Meuth, Sven G.; Jan-Gerd Tenberge; Patrick Schiffler; Heinz Wiendl; Michael Deppe

    2015-01-01

    Putamen atrophy and its long-term progress during disease course were recently shown in patients with multiple sclerosis (MS). Here we investigated retrospectively the time point of atrophy onset in patients with relapsing-remitting MS (RRMS). 68 patients with RRMS and 26 healthy controls (HC) were admitted to 3T MRI in a cross-sectional study. We quantitatively analyzed the putamen volume of individual patients in relation to disease duration by correcting for age and intracranial volume (IC...

  7. The Relationship between Osteogenesis Imperfecta and Spinal Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Babak Soltani

    2011-09-01

    Full Text Available ObjectiveA 4-month-old female with osteogenesis imperfecta (OI type II was admitted in PICU of our center due to severe respiratory distress and fever with a diagnosis of severe pneumonia, and mechanical ventilation was initiated. Due to severe hypotonia, NCV and EMG were performed, and spinal muscular atrophy (SMA type I was diagnosed.Keywords: Osteogenesis imperfecta; spinal muscular atrophy; hypotonia

  8. Crossed cerebro-cerebellar atrophy with Dyke Davidoff Masson syndrome.

    Science.gov (United States)

    Algahtani, Hussein A; Aldarmahi, Ahmed A; Al-Rabia, Mohammed W; Young, G Bryan

    2014-01-01

    Dyke Davidoff Masson syndrome (DDMS) refers to atrophy or hypoplasia of one cerebral hemisphere following a prior fetal or childhood insult. It has characteristics of clinical and radiological changes. These changes include hemiparesis, seizures, facial-asymmetry, and mental retardation. We present a 25-year-old man with crossed cerebrocerebellar atrophy and DDMS. His seizures were well controlled using a combination of antiepileptic drugs.

  9. "Apperceptive" alexia in posterior cortical atrophy.

    Science.gov (United States)

    Mendez, Mario F; Shapira, Jill S; Clark, David G

    2007-02-01

    The most common presenting complaint in posterior cortical atrophy (PCA) is reading difficulty. Although often described as an alexia without agraphia, alexia in PCA may have multiple causes, including a primary visuoperceptual etiology, attentional alexia, and central reading difficulty. This study evaluated 14 patients with early PCA and disturbances in reading ability in comparison to 14 normal controls. All 14 patients had a progressive disorder of complex visual functions and neuroimaging evidence of occipitoparietal dysfunction. They underwent a task requiring identification of single letters with and without flanking distractors. They also read single words consisting of regular English spelling or irregular grapheme-phoneme correspondence (irregular words) and pronounceable nonsense words (pseudowords). The PCA patients made errors in letter identification when letters were flanked by visually similar letters or numbers. They could read most single regular and irregular words but made visual errors and had particular trouble with pseudowords. They could not use a letter-by-letter reading strategy effectively. The PCA patients had similar difficulties on other visuoperceptual tests. These findings are consistent with an alexia manifested by perceptual and attentional difficulty on attempting serial visual processing of letters in the context of other letters. This "apperceptive alexia" results when the configuration of letters into words is impaired during letter-by-letter reading. Disproportionate difficulty reading pseudowords suggests an additional impairment in phonological processing. PCA patients have variable neuropathology and individual patients may have other contributions to their reading impairment.

  10. Spinal Muscular Atrophy: Current Therapeutic Strategies

    Science.gov (United States)

    Kiselyov, Alex S.; Gurney, Mark E.

    Proximal spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by death of motor neurons in the spinal cord. SMA is caused by deletion and/or mutation of the survival motor neuron gene (SMN1) on chromosome 5q13. There are variable numbers of copies of a second, related gene named SMN2 located in the proximity to SMN1. Both genes encode the same protein (Smn). Loss of SMN1 and incorrect splicing of SMN2 affect cellular levels of Smn triggering death of motor neurons. The severity of SMA is directly related to the normal number of copies of SMN2 carried by the patient. A considerable effort has been dedicated to identifying modalities including both biological and small molecule agents that increase SMN2 promoter activity to upregulate gene transcription and produce increased quantities of full-length Smn protein. This review summarizes recent progress in the area and suggests potential target product profile for an SMA therapeutic.

  11. Forced oscillation technique in spinal muscular atrophy.

    Science.gov (United States)

    Gauld, Leanne M; Keeling, Lucy A; Shackleton, Claire E; Sly, Peter D

    2014-09-01

    Spinal muscular atrophy (SMA) causes respiratory compromise that is difficult to assess in young children. The forced oscillation technique (FOT) is commercially available for children as young as 2 years of age and is nonvolitional. The aim of this study was to assess the usefulness of FOT in young children with SMA. Children with SMA aged resistance at 8 Hz (Rrs8) (mean z score, +0.66; SD, 1.34; P = .12) were abnormal. Four children performed spirometry. Linear relationships to Xrs8 exist: FVC (R2, 0.54), unassisted PCF (R2, 0.33), assisted PCF (R2, 0.43), and AHI (R2, 0.32). Over 12 months, Xrs8z score worsened (rate of change of +1.08, P change +0.51, P .05) was found between clinical characteristics and FOT values. FOT is feasible in young children with SMA, with abnormal values of reactance and resistance on grouped data, worsening over 12 months. Xrs8 is related to respiratory tests used to monitor progress in SMA (FVC, PCF, AHI). Further research on the value of FOT in managing individuals is warranted.

  12. Evaluation of the progression rate of atrophy lesions in punctate inner choroidopathy (PIC) based on autofluorescence analysis.

    Science.gov (United States)

    Hua, Rui; Liu, Limin; Chen, Lei

    2014-12-01

    To investigate the autofluorescence (AF) characteristics of punctate inner choroidopathy (PIC) and to evaluate the progression rate of retinal pigment epithelium (RPE) atrophy lesions in PIC using confocal scanning laser ophthalmoscopy. Twenty-two eyes of 14 PIC cases and 21 eyes of 21 non-proliferative diabetic retinopathy (NPDR) cases which received retinal coagulation as a control group were enrolled in this study. Enhanced depth imaging optical coherence tomography (EDI-OCT) and AF were recorded from all patients at 18 months follow-up. The RPE atrophy areas of PIC and laser scars in NPDR were analyzed using the Region Finder software of the Heidelberg Eye Explorer. This software allows direct export of AF images from the database and semi-automated detection of atrophic areas by shadow correction, vessel detection, and selection of seed points. At baseline, both hyperfluorescence and hypofluorescence were observed in the lesions of PIC eyes with a focal elevation of RPE and corresponding disruption of the ellipsoid region of the inner segment ellipsoid zone (EZ). In contrast, hypo-AF was detected when there was a lack of RPE. The mean progression rate of RPE atrophy in PIC and NPDR were 3.735 mm(2)/year (0.056-0.545) and 0.127 mm(2)/year (0.015-0.466), respectively. Compared with the atrophy area in the last visit, the progression rate in PIC was significantly greater than that in NPDR (Z=5.615, P<0.0001). The results of AF reflect the status of PIC and the progression rate of RPE atrophy in PIC, which can be used to predict the progress of PIC noninvasively. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Change of retinal pigment epithelial atrophy after anti-vascular endothelial growth factor treatment in exudative age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Moosang Kim

    2016-01-01

    Full Text Available Purpose: The study aimed to investigate the quantitative changes of retinal pigment epithelial (RPE atrophy during a 24-month follow-up period of anti-vascular endothelial growth factor (VEGF for exudative age-related macular degeneration (AMD. Materials and Methods: This is a retrospective study. Sixty-five eyes of 62 consecutive patients with naοve exudative AMD who had received treatment with anti-VEGF therapy and followed for more 24 months were enrolled. All patients received three initial monthly injections of anti-VEGF (ranibizumab or bevacizumab, followed by pro re nata or treat-and-extend protocol. Color fundus image, optical coherence tomography, and fundus autofluorescence were evaluated for RPE atrophy. Multiple regression analysis was performed to investigate the predictive factors found during univariate analysis to identify an association with increased RPE atrophic areas. Results: The mean number of anti-VEGF treatments was 9.18. RPE atrophic area was 1.293 ± 1.298 mm 2 at baseline and enlarged to 2.394 ± 1.940 mm 2 after 24 months, which differed significantly (P = 0.001. Multiple regression analysis revealed that larger areas of RPE atrophy at month 4 and larger numbers of anti-VEGF treatments were associated with increased RPE atrophic areas. Conclusions: RPE atrophy progresses in eyes with exudative AMD during anti-VEGF treatment. Larger areas of RPE atrophy at month 4 and larger numbers of anti-VEGF injections were associated with an increased risk of progression of RPE atrophy the following treatment. These findings may be useful to clinicians using intravitreal anti-VEGF for the treatment of exudative AMD, both for selecting an appropriate treatment plan and for predicting the progression of RPE atrophy.

  14. Calculation of brain atrophy using computed tomography and a new atrophy measurement tool

    Science.gov (United States)

    Bin Zahid, Abdullah; Mikheev, Artem; Yang, Andrew Il; Samadani, Uzma; Rusinek, Henry

    2015-03-01

    Purpose: To determine if brain atrophy can be calculated by performing volumetric analysis on conventional computed tomography (CT) scans in spite of relatively low contrast for this modality. Materials & Method: CTs for 73 patients from the local Veteran Affairs database were selected. Exclusion criteria: AD, NPH, tumor, and alcohol abuse. Protocol: conventional clinical acquisition (Toshiba; helical, 120 kVp, X-ray tube current 300mA, slice thickness 3-5mm). Locally developed, automatic algorithm was used to segment intracranial cavity (ICC) using (a) white matter seed (b) constrained growth, limited by inner skull layer and (c) topological connectivity. ICC was further segmented into CSF and brain parenchyma using a threshold of 16 Hu. Results: Age distribution: 25-95yrs; (Mean 67+/-17.5yrs.). Significant correlation was found between age and CSF/ICC(r=0.695, patrophy among elderly VA patients is attributable to the presence of other comorbidities. Conclusion: Brain atrophy can be reliably calculated using automated software and conventional CT. Compared to MRI, CT is more widely available, cheaper, and less affected by head motion due to ~100 times shorter scan time. Work is in progress to improve the precision of the measurements, possibly leading to assessment of longitudinal changes within the patient.

  15. Muscle atrophy reversed by growth factor activation of satellite cells in a mouse muscle atrophy model.

    Directory of Open Access Journals (Sweden)

    Simon Hauerslev

    Full Text Available Muscular dystrophies comprise a large group of inherited disorders that lead to progressive muscle wasting. We wanted to investigate if targeting satellite cells can enhance muscle regeneration and thus increase muscle mass. We treated mice with hepatocyte growth factor and leukemia inhibitory factor under three conditions: normoxia, hypoxia and during myostatin deficiency. We found that hepatocyte growth factor treatment led to activation of the Akt/mTOR/p70S6K protein synthesis pathway, up-regulation of the myognic transcription factors MyoD and myogenin, and subsequently the negative growth control factor, myostatin and atrophy markers MAFbx and MuRF1. Hypoxia-induced atrophy was partially restored by hepatocyte growth factor combined with leukemia inhibitory factor treatment. Dividing satellite cells were three-fold increased in the treatment group compared to control. Finally, we demonstrated that myostatin regulates satellite cell activation and myogenesis in vivo following treatment, consistent with previous findings in vitro. Our results suggest, not only a novel in vivo pharmacological treatment directed specifically at activating the satellite cells, but also a myostatin dependent mechanism that may contribute to the progressive muscle wasting seen in severely affected patients with muscular dystrophy and significant on-going regeneration. This treatment could potentially be applied to many conditions that feature muscle wasting to increase muscle bulk and strength.

  16. Visual neglect in posterior cortical atrophy

    Directory of Open Access Journals (Sweden)

    Andrade Katia

    2010-08-01

    Full Text Available Abstract Background In posterior cortical atrophy (PCA, there is a progressive impairment of high-level visual functions and parietal damage, which might predict the occurrence of visual neglect. However, neglect may pass undetected if not assessed with specific tests, and might therefore be underestimated in PCA. In this prospective study, we aimed at establishing the side, the frequency and the severity of visual neglect, visual extinction, and primary visual field defects in an unselected sample of PCA patients. Methods Twenty-four right-handed PCA patients underwent a standardized battery of neglect tests. Visual fields were examined clinically by the confrontation method. Results Sixteen of the 24 patients (66% had signs of visual neglect on at least one test, and fourteen (58% also had visual extinction or hemianopia. Five patients (21% had neither neglect nor visual field defects. As expected, left-sided neglect was more severe than right-sided neglect. However, right-sided neglect resulted more frequently in this population (29% than in previous studies on focal brain lesions. Conclusion When assessed with specific visuospatial tests, visual neglect is frequent in patients with PCA. Diagnosis of neglect is important because of its negative impact on daily activities. Clinicians should consider the routine use of neglect tests to screen patients with high-level visual deficits. The relatively high frequency of right-sided neglect in neurodegenerative patients supports the hypothesis that bilateral brain damage is necessary for right-sided neglect signs to occur, perhaps because of the presence in the right hemisphere of crucial structures whose damage contributes to neglect.

  17. In vivo models of multiple system atrophy.

    Science.gov (United States)

    Fernagut, Pierre-Olivier; Ghorayeb, Imad; Diguet, Elsa; Tison, François

    2005-08-01

    Multiple system atrophy (MSA) is a sporadic adult-onset neurodegenerative disorder of unknown etiology clinically characterized by a combination of parkinsonian, pyramidal, and cerebellar signs. Levodopa-unresponsive parkinsonism is present in 80% of MSA cases, and this dominant clinical presentation (MSA-P) is associated with a combined degeneration of the substantia nigra pars compacta and the striatum in anatomically related areas. The limited knowledge of the pathophysiology of MSA and the lack of therapeutic strategies prompted the development of lesion models reproducing striatonigral degeneration, the substrate of levodopa-unresponsive parkinsonism in MSA-P. This method was carried out first in rats with two different stereotaxic strategies using either two neurotoxins ("double toxin-double lesion") or a single neurotoxin ("single toxin-double lesion"). Double-lesioned rat models showed severe motor impairment compared to those with a single nigral or striatal lesion and helped to mimic different stages of the disease. Systemic models were also developed in mice and primates using the nigral toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and the striatal toxin 3-nitropropionic (3-NP). In mice, although MPTP reduced the subsequent sensitivity to 3-NP in a sequential lesion, simultaneous nigral and striatal insults were shown to exacerbate striatal damage. MPTP-treated monkeys displayed a significant worsening of parkinsonism and a loss of levodopa-responsiveness after the appearance of hindlimb dystonia and striatal lesion formation induced by subsequent 3-NP intoxication. The different species and intoxication paradigms used will be useful to investigate functional changes in substantia nigra and striatum and to define neuroprotective, neurorestorative, or symptomatic therapeutic strategies.

  18. Possible role of polyamines in gyrate atrophy.

    Directory of Open Access Journals (Sweden)

    Sulochana Konerirajapuram

    2000-01-01

    Full Text Available PURPOSE: Gyrate atrophy (GA is marked by hyperornithinemia and lowered ornithine amino transferase (OAT. However there are patients of GA without hyperornithinemia and those with hyperornithinemia without GA. Some cases of GA have been reported to have low lysine. The purpose of the study was to determine if polyamines, the metabolites of ornithine, and lysine have any diagnostic role in GA. METHODS: Ornithine in plasma was estimated by two-dimensional paper chromatography, with elution of the coloured spot, and the absorbance measured using a spectrophotometer at 560 nm. OAT assay in lymphocytes was done spectrophotometrically using ornithine as substrate. Blood and urinary polyamines were extracted with n-butanol, benzoylated and analysed with HPLC; putrescine, spermine, spermidine, and cadaverine were assayed individually at 254 nm with the UV detector using ODS, G18 column with 63% methanol as solvent. RESULTS: Of the 7 patients investigated, 6 had features typical of GA. One was diagnosed to have atypical retinitis pigmentosa (case 3. The first five cases had elevated ornithine and diminished OAT, but cases 6 and 7 had near-normal ornithine and case 7 had near-normal OAT. However, all 7 patients had increased levels of total polyamines in urine compared to normals. Five had increased putrescine and three had increased spermine. All the 7 had decreased cadaverine in urine. Thus, though there were inconsistencies with ornithine and OAT, all the 7 patients had elevated polyamines from ornithine and decreased cadaverine. CONCLUSION: In addition to estimating ornithine and OAT in GA, it is suggested that urinary polyamines may be analysed as the latter appears to correlate better with the clinical condition and help in the diagnosis to a greater extent. Moreover, while ornithine is an innocuous amino acid, polyamines are known to damage DNA and proteins.

  19. Neural correlates of cognitive impairment in posterior cortical atrophy.

    Science.gov (United States)

    Kas, Aurélie; de Souza, Leonardo Cruz; Samri, Dalila; Bartolomeo, Paolo; Lacomblez, Lucette; Kalafat, Michel; Migliaccio, Raffaella; Thiebaut de Schotten, Michel; Cohen, Laurent; Dubois, Bruno; Habert, Marie-Odile; Sarazin, Marie

    2011-05-01

    With the prospect of disease-modifying drugs that will target the physiopathological process of Alzheimer's disease, it is now crucial to increase the understanding of the atypical focal presentations of Alzheimer's disease, such as posterior cortical atrophy. This study aimed to (i) characterize the brain perfusion profile in posterior cortical atrophy using regions of interest and a voxel-based approach; (ii) study the influence of the disease duration on the clinical and imaging profiles; and (iii) explore the correlations between brain perfusion and cognitive deficits. Thirty-nine patients with posterior cortical atrophy underwent a specific battery of neuropsychological tests, mainly targeting visuospatial functions, and a brain perfusion scintigraphy with 99mTc-ethyl cysteinate dimer. The imaging analysis included a comparison with a group of 24 patients with Alzheimer's disease, matched for age, disease duration and Mini-Mental State Examination, and 24 healthy controls. The single-photon emission computed tomography profile in patients with posterior cortical atrophy was characterized by extensive and severe hypoperfusion in the occipital, parietal, posterior temporal cortices and in a smaller cortical area corresponding to the frontal eye fields (Brodmann areas 6/8). Compared with patients with Alzheimer's disease, the group with posterior cortical atrophy showed more severe occipitoparietal hypoperfusion and higher perfusion in the frontal, anterior cingulate and mesiotemporal regions. When considering the disease duration, the functional changes began and remained centred on the posterior lobes, even in the late stage. Correlation analyses of brain perfusion and neuropsychological scores in posterior cortical atrophy highlighted the prominent role of left inferior parietal damage in acalculia, Gerstmann's syndrome, left-right indistinction and limb apraxia, whereas damage to the bilateral dorsal occipitoparietal regions appeared to be involved in B

  20. Expression of atrophy-related transcription factors in the process of intrinsic laryngeal muscle atrophy after denervation.

    Science.gov (United States)

    Sei, Hirofumi; Taguchi, Aki; Nishida, Naoya; Hato, Naohito; Gyo, Kiyofumi

    2015-01-01

    We examined changes in the expressions of three atrophy-related transcription factors (FOXO3a, P-FOXO3a, and PGC-1α) in the process of intrinsic laryngeal muscle atrophy after denervation. In total, 51 Wistar rats were used. After transection of the unilateral recurrent laryngeal nerve, the thyroarytenoid (TA) muscle and the posterior cricoarytenoid (PCA) muscle were excised and subjected to histological and Western blot studies. Relationships between the expressions of transcription factors during atrophy of the intrinsic laryngeal muscles were investigated by comparing the results of the treated side (T) with those of the untreated side (U), and sequential changes in the T/U ratio after denervation were assessed. Loss of wet muscle weight, together with a decrease in muscle fiber cross-sectional area and increase in the number of muscle fibers/mm(2), occurred more quickly in TA muscle than in PCA muscle. Muscle atrophy progressed rapidly between 7 and 28 days after denervation, while expression of FOXO3a was maximal on day 7, in both TA and PCA muscles. By contrast, P-FOXO3a expression decreased gradually after denervation. Expression of PGC-1α increased slowly until day 7, and then it declined. Denervation-induced atrophy of the intrinsic laryngeal muscles was closely linked with the expression of FOXO3a and PGC-1α, suggesting that atrophy of these muscles may involve the actions of these transcription factors. In addition, muscle atrophy progressed faster in TA muscle than in PCA muscle, due mainly to differences in muscle fiber composition.

  1. Early and Degressive Putamen Atrophy in Multiple Sclerosis.

    Science.gov (United States)

    Krämer, Julia; Meuth, Sven G; Tenberge, Jan-Gerd; Schiffler, Patrick; Wiendl, Heinz; Deppe, Michael

    2015-09-25

    Putamen atrophy and its long-term progress during disease course were recently shown in patients with multiple sclerosis (MS). Here we investigated retrospectively the time point of atrophy onset in patients with relapsing-remitting MS (RRMS). 68 patients with RRMS and 26 healthy controls (HC) were admitted to 3T MRI in a cross-sectional study. We quantitatively analyzed the putamen volume of individual patients in relation to disease duration by correcting for age and intracranial volume (ICV). Patient's relative putamen volume (RPV), expressed in percent of ICV, was significantly reduced compared to HC. Based on the correlation between RPV and age, we computed the age-corrected RPV deviation (ΔRPV) from HC. Patients showed significantly negative ΔRPV. Interestingly, the age-corrected ΔRPV depended logarithmically on disease duration: Directly after first symptom manifestation, patients already showed a reduced RPV followed by a further degressive volumetric decline. This means that atrophy progression was stronger in the first than in later years of disease. Putamen atrophy starts directly after initial symptom manifestation or even years before, and progresses in a degressive manner. Due to its important role in neurological functions, early detection of putamen atrophy seems necessary. High-resolution structural MRI allows monitoring of disease course.

  2. Congenital segmental spinal muscular atrophy: a case report.

    Science.gov (United States)

    Savaş, Tülin; Erol, Ilknur; Özkale, Yasemin; Saygi, Semra

    2015-03-01

    Spinal muscular atrophies are genetic disorders in which anterior horn cells in the spinal cord and motor nuclei of the brainstem are progressively lost. We present a patient with arthrogryposis due to congenital spinal muscular atrophy predominantly affecting the upper limbs. Spinal muscular atrophies with onset at birth may be a cause of arthrogryposis. Localized forms of neurogenic arthrogryposis have been divided into cervical and caudal forms. Our case is similar to the cases described by Hageman et al (J Neurol Neurosurg Psychiatry 1993;56:365-368): severe symmetric lower motor neuron deficit in the upper extremities at the time of birth, no history of injury to the cervical spinal cord or the brachial plexus during delivery, and severe muscle wasting suggesting chronic denervation in utero. Because there was improvement of our patient's situation, her disease was also possibly nonprogressive and sporadic. To our knowledge, this is the first reported case of a Turkish patient with congenital cervical spinal muscular atrophy. Congenital cervical spinal muscular atrophy affecting predominantly the upper limbs is a relatively rare form of motor neuron disease and should be considered in the differential diagnosis of infants with congenital contractures and severe muscle weakness by wasting mainly confined to the upper limbs.

  3. Early and Degressive Putamen Atrophy in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Julia Krämer

    2015-09-01

    Full Text Available Putamen atrophy and its long-term progress during disease course were recently shown in patients with multiple sclerosis (MS. Here we investigated retrospectively the time point of atrophy onset in patients with relapsing-remitting MS (RRMS. 68 patients with RRMS and 26 healthy controls (HC were admitted to 3T MRI in a cross-sectional study. We quantitatively analyzed the putamen volume of individual patients in relation to disease duration by correcting for age and intracranial volume (ICV. Patient’s relative putamen volume (RPV, expressed in percent of ICV, was significantly reduced compared to HC. Based on the correlation between RPV and age, we computed the age-corrected RPV deviation (ΔRPV from HC. Patients showed significantly negative ΔRPV. Interestingly, the age-corrected ΔRPV depended logarithmically on disease duration: Directly after first symptom manifestation, patients already showed a reduced RPV followed by a further degressive volumetric decline. This means that atrophy progression was stronger in the first than in later years of disease. Putamen atrophy starts directly after initial symptom manifestation or even years before, and progresses in a degressive manner. Due to its important role in neurological functions, early detection of putamen atrophy seems necessary. High-resolution structural MRI allows monitoring of disease course.

  4. Astaxanthin intake attenuates muscle atrophy caused by immobilization in rats.

    Science.gov (United States)

    Shibaguchi, Tsubasa; Yamaguchi, Yusuke; Miyaji, Nobuyuki; Yoshihara, Toshinori; Naito, Hisashi; Goto, Katsumasa; Ohmori, Daijiro; Yoshioka, Toshitada; Sugiura, Takao

    2016-08-01

    Astaxanthin is a carotenoid pigment and has been shown to be an effective inhibitor of oxidative damage. We tested the hypothesis that astaxanthin intake would attenuate immobilization-induced muscle atrophy in rats. Male Wistar rats (14-week old) were fed for 24 days with either astaxanthin or placebo diet. After 14 days of each experimental diet intake, the hindlimb muscles of one leg were immobilized in plantar flexion position using a plaster cast. Following 10 days of immobilization, both the atrophic and the contralateral plantaris muscles were removed and analyzed to determine the level of muscle atrophy along with measurement of the protein levels of CuZn-superoxide dismutase (CuZn-SOD) and selected proteases. Compared with placebo diet animals, the degree of muscle atrophy in response to immobilization was significantly reduced in astaxanthin diet animals. Further, astaxanthin supplementation significantly prevented the immobilization-induced increase in the expression of CuZn-SOD, cathepsin L, calpain, and ubiquitin in the atrophied muscle. These results support the postulate that dietary astaxanthin intake attenuates the rate of disuse muscle atrophy by inhibiting oxidative stress and proteolysis via three major proteolytic pathways. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  5. Muscle atrophy, ubiquitin-proteasome, and autophagic pathways in dysferlinopathy.

    Science.gov (United States)

    Fanin, Marina; Nascimbeni, Anna C; Angelini, Corrado

    2014-09-01

    Muscle fiber atrophy and the molecular pathways underlying this process have not been investigated in dysferlinopathy patients. In 22 muscles from dysferlinopathy patients we investigated fiber atrophy by morphometry and ubiquitin-proteasome and autophagic pathways using protein and/or transcriptional analysis of atrophy- and autophagy-related genes (MuRF1, atrogin1, LC3, p62, Bnip3). Dysferlinopathy showed significant fiber atrophy and higher MuRF-1 protein and mRNA levels, which correlated with fiber size, suggesting activation of the atrophy program by proteasome induction. Some of the MuRF-1 upregulation and proteasome induction may be attributed to the prominent regeneration found. A potential role of impaired autophagy was suggested by p62-positive protein aggregates in atrophic fibers and significantly higher levels of LC3-II and p62 proteins and overexpression of p62 and Bnip3 mRNA. Damaged muscle fibers and prominent inflammatory changes may also enhance autophagy due to the insufficient level of proteasomal degradation of mutant dysferlin. Copyright © 2014 Wiley Periodicals, Inc.

  6. Apoptosis in skeletal muscle and its relevance to atrophy

    Institute of Scientific and Technical Information of China (English)

    Esther E Dupont-Versteegden

    2006-01-01

    Apoptosis is necessary for maintaining the integrity of proliferative tissues, such as epithelial cells of the gastrointestinal system. The role of apoptosis in post mitotic tissues, such as skeletal muscle, is less well defined. Apoptosis during muscle atrophy occurs in both myonuclei and other muscle cell types. Apoptosis of myonuclei likely contributes to the loss of muscle mass, but the mechanisms underlying this process are largely unknown. Caspase-dependent as well as -independent pathways have been implicated and the mode by which atrophy is induced likely determines the apoptotic mechanisms that are utilized. It remains to be determined whether a decrease in apoptosis will alleviate atrophy and distinct research strategies may be required for different causes of skeletal muscle loss.

  7. Can endurance exercise preconditioning prevention disuse muscle atrophy?

    Directory of Open Access Journals (Sweden)

    Michael P Wiggs

    2015-03-01

    Full Text Available Emerging evidence suggests that exercise training can provide a level of protection against disuse muscle atrophy. Endurance exercise training imposes oxidative, metabolic, and heat stress on skeletal muscle which activates a variety of cellular signaling pathways that ultimately leads to the increased expression of proteins that have been demonstrated to protect muscle from inactivity –induced atrophy. This review will highlight the effect of exercise-induced oxidative stress on endogenous enzymatic antioxidant capacity (i.e., superoxide dismutase, glutathione peroxidase, and catalase, the role of oxidative and metabolic stress on PGC1-α, and finally highlight the effect heat stress and HSP70 induction. Finally, this review will discuss the supporting scientific evidence that these proteins can attenuate muscle atrophy through exercise preconditioning.

  8. Small bowel villous atrophy: celiac disease and beyond.

    Science.gov (United States)

    Elli, Luca; Branchi, Federica; Sidhu, Reena; Guandalini, Stefano; Assiri, Asaad; Rinawi, Firas; Shamir, Raanan; Das, Prasenjit; Makharia, Govind K

    2017-02-01

    Small bowel villous atrophy can represent a diagnostic challenge for gastroenterologists and pathologists. In Western countries small bowel atrophy and mild non-atrophic alterations are frequently caused by celiac disease. However, other pathology can mimic celiac disease microscopically, widening the differential diagnosis. The several novelties on this topic and the introduction of the device-assisted enteroscopy in the diagnostic flowchart make an update of the literature necessary. Areas covered: In this review, a description of the different clinical scenarios when facing with small bowel mucosal damage, particularly small bowel atrophy, is described. The published literature on this subject has been summarized and reviewed. Expert commentary: When an intestinal mucosal alteration is histologically demonstrated, the pathology report forms part of a more complex workup including serological data, clinical presentation and clinical history. A multidisciplinary team, including pathologists and enteroscopy-devoted endoscopists, is frequently required to manage patients with small bowel alterations, especially in cases of severe malabsorption syndrome.

  9. Atrophy of the corpus callosum correlates with white matter lesions in patients with cerebral ischaemia

    Energy Technology Data Exchange (ETDEWEB)

    Meguro, K.; Yamadori, A. [Section of Neuropsychology, Division of Disability Science, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku, 980-8575 Sendai (Japan); Constans, J.M.; Courtheoux, P.; Theron, J. [MR Unit, University of Caen School of Medicine, Caen (France); Viader, F. [Department of Neuroradiology, University of Caen School of Medicine, Caen (France)

    2000-06-01

    Many studies of white matter high signal (WMHS) on T2-weighted MRI have disclosed that it is related to cerebral ischaemia and to brain atrophy. Atrophy of the corpus callosum (CC) has also been studied in relation to ischaemia. Our objective was to test the hypothesis that CC atrophy could be due to ischaemia. We therefore assessed CC, WMHS and brain atrophy in patients with risk factors without strokes (the risk factor group) and in those with infarcts (the infarct group), to investigate the relationships between these factors. We studied 30 patients in the infarct group, 14 in the risk factor group, and 29 normal subjects. Using axial T1-weighted MRI, cortical atrophy and ventricular enlargement (brain atrophy) were visually rated. Using axial T2-weighted MRI, WMHS was assessed in three categories: periventricular symmetrical, periventricular asymmetrical and subcortical. Using the mid-sagittal T1-weighted image, the CC was measured in its anterior, posterior, midanterior and midposterior portions. In the normal group, no correlations were noted between parameters. In the infarct group, there were significant correlations between CC and brain atrophy, and between CC atrophy and WMHS. After removing the effects of age, gender and brain atrophy, significant correlations were noted between some CC measures and subcortical WMHS. In the risk factor group, there were significant correlations between CC and brain atrophy and between CC atrophy and WMHS. After allowance for age, gender and brain atrophy, significant correlations between some CC measures and periventricular WMHS remained. The hypothesis that CC atrophy could be due to cerebral ischaemia was supported by other analyses. Namely, for correlations between the extent of infarcts and partial CC atrophy in patients with anterior middle cerebral artery (MCA) and with posterior MCA infarcts, there were significant correlations between the extent of infarct and midanterior CC atrophy in the former, and posterior

  10. Parapapillary Diffuse Choroidal Atrophy in Children Is Associated With Extreme Thinning of Parapapillary Choroid.

    Science.gov (United States)

    Yokoi, Tae; Zhu, Dan; Bi, Hong Sheng; Jonas, Jost B; Jonas, Rahul A; Nagaoka, Natsuko; Moriyama, Muka; Yoshida, Takeshi; Ohno-Matsui, Kyoko

    2017-02-01

    To analyze morphologic features of segmental parapapillary diffuse choroidal atrophy (PDCA) in children. The study group included children (age ≤15 years) with high myopia who attended the Tokyo High Myopia Clinic. Control groups comprised participants of the population-based Gobi Desert Children Eye Study (GobiDCES). Fundus photographs were examined for presence of PDCA and choroidal thickness (CT) was measured by optical coherence tomography. The study group included 41 eyes of 21 children with PDCA (mean age: 9.4 ± 3.7 years; mean refractive error: -11.5 ± 3.1 diopters) and the GobiDCES included 1463 children (age: 11.8 ± 3.5 years). In the study group, all eyes showed an extreme and abrupt thinning of the temporal parapapillary choroid. At 2500 μm nasal to the foveola, CT was choroidal atrophy in children is associated with abrupt segmental thinning of the choroid in the temporal parapapillary region, in addition to the thinning of the subfoveal choroid after adjusting for refractive error and age.

  11. Accelerating regional atrophy rates in the progression from normal aging to Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Sluimer, Jasper D. [VU University Medical Centre, Department of Diagnostic Radiology, Amsterdam (Netherlands); VU University Medical Centre, Alzheimer Centre, Amsterdam (Netherlands); VU University Medical Centre, Image Analysis Centre, Amsterdam (Netherlands); VU University Medical Centre, Department of Diagnostic Radiology and Alzheimer Centre, PO Box 7057, Amsterdam (Netherlands); Flier, Wiesje M. van der; Scheltens, Philip [VU University Medical Centre, Alzheimer Centre, Amsterdam (Netherlands); VU University Medical Centre, Department of Neurology, Amsterdam (Netherlands); Karas, Giorgos B.; Barkhof, Frederik [VU University Medical Centre, Department of Diagnostic Radiology, Amsterdam (Netherlands); VU University Medical Centre, Alzheimer Centre, Amsterdam (Netherlands); VU University Medical Centre, Image Analysis Centre, Amsterdam (Netherlands); Schijndel, Ronald van [VU University Medical Centre, Image Analysis Centre, Amsterdam (Netherlands); VU University Medical Centre, Department of Informatics, Amsterdam (Netherlands); Barnes, Josephine; Boyes, Richard G. [UCL, Institute of Neurology, Dementia Research Centre, London (United Kingdom); Cover, Keith S. [VU University Medical Centre, Department of Physics and Medical Technology, Amsterdam (Netherlands); Olabarriaga, Silvia D. [University of Amsterdam, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, Amsterdam (Netherlands); Fox, Nick C. [VU University Medical Centre, Department of Neurology, Amsterdam (Netherlands); UCL, Institute of Neurology, Dementia Research Centre, London (United Kingdom); Vrenken, Hugo [VU University Medical Centre, Alzheimer Centre, Amsterdam (Netherlands); VU University Medical Centre, Image Analysis Centre, Amsterdam (Netherlands); VU University Medical Centre, Department of Physics and Medical Technology, Amsterdam (Netherlands)

    2009-12-15

    We investigated progression of atrophy in vivo, in Alzheimer's disease (AD), and mild cognitive impairment (MCI). We included 64 patients with AD, 44 with MCI and 34 controls with serial MRI examinations (interval 1.8 {+-} 0.7 years). A nonlinear registration algorithm (fluid) was used to calculate atrophy rates in six regions: frontal, medial temporal, temporal (extramedial), parietal, occipital lobes and insular cortex. In MCI, the highest atrophy rate was observed in the medial temporal lobe, comparable with AD. AD patients showed even higher atrophy rates in the extramedial temporal lobe. Additionally, atrophy rates in frontal, parietal and occipital lobes were increased. Cox proportional hazard models showed that all regional atrophy rates predicted conversion to AD. Hazard ratios varied between 2.6 (95% confidence interval (CI) = 1.1-6.2) for occipital atrophy and 15.8 (95% CI = 3.5-71.8) for medial temporal lobe atrophy. In conclusion, atrophy spreads through the brain with development of AD. MCI is marked by temporal lobe atrophy. In AD, atrophy rate in the extramedial temporal lobe was even higher. Moreover, atrophy rates also accelerated in parietal, frontal, insular and occipital lobes. Finally, in nondemented elderly, medial temporal lobe atrophy was most predictive of progression to AD, demonstrating the involvement of this region in the development of AD. (orig.)

  12. Muscle ring finger 1 mediates cardiac atrophy in vivo.

    Science.gov (United States)

    Willis, Monte S; Rojas, Mauricio; Li, Luge; Selzman, Craig H; Tang, Ru-Hang; Stansfield, William E; Rodriguez, Jessica E; Glass, David J; Patterson, Cam

    2009-04-01

    Pathological cardiac hypertrophy, induced by various etiologies such as high blood pressure and aortic stenosis, develops in response to increased afterload and represents a common intermediary in the development of heart failure. Understandably then, the reversal of pathological cardiac hypertrophy is associated with a significant reduction in cardiovascular event risk and represents an important, yet underdeveloped, target of therapeutic research. Recently, we determined that muscle ring finger-1 (MuRF1), a muscle-specific protein, inhibits the development of experimentally induced pathological; cardiac hypertrophy. We now demonstrate that therapeutic cardiac atrophy induced in patients after left ventricular assist device placement is associated with an increase in cardiac MuRF1 expression. This prompted us to investigate the role of MuRF1 in two independent mouse models of cardiac atrophy: 1) cardiac hypertrophy regression after reversal of transaortic constriction (TAC) reversal and 2) dexamethasone-induced atrophy. Using echocardiographic, histological, and gene expression analyses, we found that upon TAC release, cardiac mass and cardiomyocyte cross-sectional areas in MuRF1(-/-) mice decreased approximately 70% less than in wild type mice in the 4 wk after release. This was in striking contrast to wild-type mice, who returned to baseline cardiac mass and cardiomyocyte size within 4 days of TAC release. Despite these differences in atrophic remodeling, the transcriptional activation of cardiac hypertrophy measured by beta-myosin heavy chain, smooth muscle actin, and brain natriuretic peptide was attenuated similarly in both MuRF1(-/-) and wild-type hearts after TAC release. In the second model, MuRF1(-/-) mice also displayed resistance to dexamethasone-induced cardiac atrophy, as determined by echocardiographic analysis. This study demonstrates, for the first time, that MuRF1 is essential for cardiac atrophy in vivo, both in the setting of therapeutic

  13. Recommendations for the management of postmenopausal vaginal atrophy

    DEFF Research Database (Denmark)

    Sturdee, D W; Panay, N; Ulrich, Lian

    2010-01-01

    for hormone replacement therapy (HRT) over recent years that has suggested an increased risk of breast cancer, heart disease and stroke. But, regardless of whether these scares are justified, local treatment of vaginal atrophy is not associated with these possible risks of systemic HRT. Other reasons...... dryness can be helped by simple lubricants but the best and most logical treatment for urogenital atrophy is to use local estrogen. This is safe, effective and with few contraindications. It is hoped that these guidelines and recommendations, produced to coincide with World Menopause Day 2010, will help...

  14. From alveolar diffuse atrophy to aggressive periodontitis: a brief history.

    Science.gov (United States)

    Guzeldemir, Esra; Toygar, Hilal Uslu

    2006-01-01

    Technologic advances in mechanics, electronics, physics, chemistry, and computer science have contributed to advances in dental medicine. Periodontology is not only a clinical science but is also directly related to the basic sciences. Research is conducted in laboratories rather than in clinics now. During the last century, aggressive periodontitis has received attention from numerous researchers because of its multifactorial features. This paper explores the long scientific journey of aggressive periodontitis, beginning with its first definition as alveolar diffuse atrophy. Perhaps in the future, "alveolar diffuse atrophy" will be referred to by another name or term. However, this journey will never end.

  15. Vulvar and Vaginal Atrophy: Physiology, Clinical Presentation, and Treatment Considerations.

    Science.gov (United States)

    Lev-Sagie, Ahinoam

    2015-09-01

    Vulvovaginal atrophy is a common condition associated with decreased estrogenization of the vaginal tissue. Symptoms include vaginal dryness, irritation, itching, soreness, burning, dyspareunia, discharge, urinary frequency, and urgency. It can occur at any time in a woman's life cycle, although more commonly in the postmenopausal phase, during which the prevalence is approximately 50%. Despite the high prevalence and the substantial effect on quality of life, vulvovaginal atrophy often remains underreported and undertreated. This article aims to review the physiology, clinical presentation, assessment, and current recommendations for treatment, including aspects of effectiveness and safety of local vaginal estrogen therapies.

  16. Mechanisms of Muscle Growth and Atrophy in Mammals and Drosophila

    Science.gov (United States)

    Piccirillo, Rosanna; Demontis, Fabio; Perrimon, Norbert; Goldberg, Alfred L.

    2014-01-01

    The loss of skeletal muscle mass (atrophy) that accompanies disuse and systemic diseases is highly debilitating. Although the pathogenesis of this condition has been primarily studied in mammals, Drosophila is emerging as an attractive system to investigate some of the mechanisms involved in muscle growth and atrophy. In this review, we highlight the outstanding unsolved questions that may benefit from a combination of studies in both flies and mammals. In particular, we discuss how different environmental stimuli and signaling pathways influence muscle mass and strength and how a variety of disease states can cause muscle wasting. PMID:24038488

  17. Homocysteine, Liver Function Derangement and Brain Atrophy in Alcoholics.

    Science.gov (United States)

    Fernández-Rodríguez, Camino; González-Reimers, Emilio; Quintero-Platt, Geraldine; de la Vega-Prieto, María José; Pérez-Hernández, Onán; Martín-González, Candelaria; Espelosín-Ortega, Elisa; Romero-Acevedo, Lucía; Santolaria-Fernández, Francisco

    2016-11-01

    Hyperhomocysteinemia may be involved in the development of brain atrophy in alcoholics. Its pathogenesis is multifactorial. In the present study, we analyse the relationship between homocysteine levels and brain atrophy, and the relative weight of co-existing factors such as liver function impairment, the amount of ethanol consumed, serum vitamin B12, B6, and folic acid levels on homocysteine levels and brain alterations in alcoholic patients. We included 59 patients admitted to this hospital for major withdrawal symptoms and 24 controls. The mini-mental state examination test and a brain computed tomography (CT) scan were performed and several indices were calculated. Serum levels of homocysteine, folic acid, vitamin B6 and vitamin B12 were determined. Liver function was assessed by Child-Pugh score. The daily consumption of ethanol in grams per day and years of addiction were recorded. A total of 83.6% and 80% of the patients showed cerebellar or frontal atrophy, respectively. Patients showed altered values of brain indices, higher levels of homocysteine and vitamin B12, but lower levels of folic acid, compared with controls. Homocysteine, B12 and liver function variables showed significant correlations with brain CT indices. Multivariate analyses disclosed that Pugh's score, albumin and bilirubin were independently related to cerebellar atrophy, frontal atrophy, cella index or ventricular index. Serum vitamin B12 was the only factor independently related to Evans index. It was also related to cella index, but after bilirubin. Homocysteine levels were independently related to ventricular index, but after bilirubin. Vitamin B12 and homocysteine levels are higher among alcoholics. Liver function derangement, vitamin B12 and homocysteine are all independently related to brain atrophy, although not to cognitive alterations. Hyperhomocysteinemia has been described in alcoholics and may be related to brain atrophy, a reversible condition with an obscure pathogenesis

  18. Brain atrophy and lesion load predict long term disability in multiple sclerosis

    DEFF Research Database (Denmark)

    Popescu, Veronica; Agosta, Federica; Hulst, Hanneke E

    2013-01-01

    To determine whether brain atrophy and lesion volumes predict subsequent 10 year clinical evolution in multiple sclerosis (MS).......To determine whether brain atrophy and lesion volumes predict subsequent 10 year clinical evolution in multiple sclerosis (MS)....

  19. Genetics Home Reference: spinal muscular atrophy with respiratory distress type 1

    Science.gov (United States)

    ... Home Health Conditions SMARD1 spinal muscular atrophy with respiratory distress type 1 Enable Javascript to view the expand/ ... All Close All Description Spinal muscular atrophy with respiratory distress type 1 ( SMARD1 ) is an inherited condition that ...

  20. A rare case of bilateral optic nerve sheath meningioma

    Directory of Open Access Journals (Sweden)

    Somen Misra

    2014-01-01

    Full Text Available A 60-year-old female presented with gradual, painless, progressive diminution of vision, and progressive proptosis of left eye since 7 years. Ophthalmological examination revealed mild proptosis and total optic atrophy in the left eye. Magnetic resonance imaging (MRI and computed tomography (CT brain with orbit showed bilateral optic nerve sheath meningioma (ONSM involving the intracranial, intracanalicular, intraorbital part of the optic nerve extending up to optic chiasma and left cavernous sinus.

  1. Longitudinal assessment of global and regional atrophy rates in Alzheimer's disease and dementia with Lewy bodies

    Directory of Open Access Journals (Sweden)

    Elijah Mak

    2015-01-01

    Conclusions: AD showed a faster rate of global brain atrophy compared to DLB, which had similar rates of atrophy to HC. Among dementia subjects, younger age was associated with accelerated atrophy, reflecting more aggressive disease in younger people. PBVC could aid in differentiating between DLB and AD, however its utility as an outcome marker in DLB is limited.

  2. [Liver Atrophy and Failure Associated with Paclitaxel and Bevacizumab Combination Therapy for Metastatic Breast Cancer].

    Science.gov (United States)

    Yamamoto, Mari; Ikeda, Masahiko; Kubo, Shinichiro; Tsukioki, Takahiro; Nakamoto, Shougo

    2016-07-01

    We managed 6 cases of severe liver atrophy and failure associated with paclitaxel and bevacizumab combination therapy (PB therapy)for HER2-negative metastatic breast cancer. In this case-controlstudy, we examined the records of these 6 patients to investigate past treatment, medication history, and degree of atrophy, and compared their data with that of 67 patients without liver atrophy. The degree of the liver atrophy used SYNAPSE VINCENT®of the image analysis software. The results showed that patients with liver atrophy had a longer pretreatment period than those without liver atrophy(33.5 months vs 15.5 months), and they also experienced a longer median time to treatment failure with PB therapy than other patients(11 months vs 6 months). The ratio of individuals presenting with diffuse liver metastasis among patients with liver metastasis was 80% with liver atrophy, compared to 8% without liver atrophy. The degree of liver atrophy was an average of 67%in terms of volume ratio before/after PB therapy(57-82%). The individualwith the greatest extent of liver atrophy died of liver failure, not as a result of breast cancer progression. The direct causal link between bevacizumab and liver atrophy and failure is unclear, but the individuals in this study had a long previous history of treatment, and diffuse liver metastases may develop in patients undergoing long periods of PB therapy, which may also cause liver atrophy; therefore, the possibility of liver failure should be considered in such cases.

  3. Is the Supraspinatus Muscle Atrophy Truly Irreversible after Surgical Repair of Rotator Cuff Tears?

    Science.gov (United States)

    Chung, Seok Won; Kim, Sae Hoon; Tae, Suk-Kee; Yoon, Jong Pil; Choi, Jung-Ah

    2013-01-01

    Background Atrophy of rotator cuff muscles has been considered an irreversible phenomenon. The purpose of this study is to evaluate whether atrophy is truly irreversible after rotator cuff repair. Methods We measured supraspinatus muscle atrophy of 191 patients with full-thickness rotator cuff tears on preoperative magnetic resonance imaging and postoperative multidetector computed tomography images, taken at least 1 year after operation. The occupation ratio was calculated using Photoshop CS3 software. We compared the change between pre- and postoperative occupation ratios after modifying the preoperative occupation ratio. In addition, possible relationship between various clinical factors and the change of atrophy, and between the change of atrophy and cuff integrity after surgical repair were evaluated. Results The mean occupation ratio was significantly increased postoperatively from 0.44 ± 0.17 to 0.52 ± 0.17 (p atrophy (more than a 10% increase in occupation ratio) and 33 (17.3%) worsening (more than a 10% decrease). Various clinical factors such as age tear size, or initial degree of atrophy did not affect the change of atrophy. However, the change of atrophy was related to repair integrity: cuff healing failure rate of 48.5% (16 of 33) in worsened atrophy; and 22.2% (18 of 81) in improved atrophy (p = 0.007). Conclusions The supraspinatus muscle atrophy as measured by occupation ratio could be improved postoperatively in case of successful cuff repair. PMID:23467404

  4. Stress-induced Skeletal Muscle Gadd45a Expression Reprograms Myonuclei and Causes Muscle Atrophy*

    Science.gov (United States)

    Ebert, Scott M.; Dyle, Michael C.; Kunkel, Steven D.; Bullard, Steven A.; Bongers, Kale S.; Fox, Daniel K.; Dierdorff, Jason M.; Foster, Eric D.; Adams, Christopher M.

    2012-01-01

    Diverse stresses including starvation and muscle disuse cause skeletal muscle atrophy. However, the molecular mechanisms of muscle atrophy are complex and not well understood. Here, we demonstrate that growth arrest and DNA damage-inducible 45a protein (Gadd45a) is a critical mediator of muscle atrophy. We identified Gadd45a through an unbiased search for potential downstream mediators of the stress-inducible, pro-atrophy transcription factor ATF4. We show that Gadd45a is required for skeletal muscle atrophy induced by three distinct skeletal muscle stresses: fasting, muscle immobilization, and muscle denervation. Conversely, forced expression of Gadd45a in muscle or cultured myotubes induces atrophy in the absence of upstream stress. We show that muscle-specific ATF4 knock-out mice have a reduced capacity to induce Gadd45a mRNA in response to stress, and as a result, they undergo less atrophy in response to fasting or muscle immobilization. Interestingly, Gadd45a is a myonuclear protein that induces myonuclear remodeling and a comprehensive program for muscle atrophy. Gadd45a represses genes involved in anabolic signaling and energy production, and it induces pro-atrophy genes. As a result, Gadd45a reduces multiple barriers to muscle atrophy (including PGC-1α, Akt activity, and protein synthesis) and stimulates pro-atrophy mechanisms (including autophagy and caspase-mediated proteolysis). These results elucidate a critical stress-induced pathway that reprograms muscle gene expression to cause atrophy. PMID:22692209

  5. Characterization of disuse skeletal muscle atrophy and the efficacy of a novel muscle atrophy countermeasure during spaceflight and simulated microgravity

    Science.gov (United States)

    Hanson, Andrea Marie

    Humans are an integral part of the engineered systems that will enable return to the Moon and eventually travel to Mars. Major advancements in countermeasure development addressing deleterious effects of microgravity and reduced gravity on the musculoskeletal system need to be made to ensure mission safety and success. The primary objectives of this dissertation are to advance the knowledge and understanding of skeletal muscle atrophy, and support development of novel countermeasures for disuse atrophy to enable healthy long-duration human spaceflight. Models simulating microgravity and actual spaceflight were used to examine the musculoskeletal adaptations during periods of unloading. Myostatin inhibition, a novel anti-atrophy drug therapy, and exercise were examined as a means of preventing and recovering from disuse atrophy. A combination of assays was used to quantify adaptation responses to unloading and examine efficacy of the countermeasures. Body and muscle masses were collected to analyze systemic changes due to treatments. Hindlimb strength and individual muscle forces were measured to demonstrate functional adaptations to treatments. Muscle fiber morphology and myosin heavy chain (MHC) expression was examined to identify adaptations at the cellular level. Protein synthesis signals insulin-like growth factor-1 (IGF-1), Akt, and p70s6 kinase; and the degradation signals Atrogin-1 and MuRF-1 were examined to identify adaptations at the molecular level that ultimately lead to muscle hypertrophy and atrophy. A time course study provided a thorough characterization of the adaptation of skeletal muscle during unloading in C57BL/6 mice, and baseline data for comparison to and evaluation of subsequent studies. Time points defining the on-set and endpoints of disuse muscle atrophy were identified to enable characterization of rapid vs. long-term responses of skeletal muscle to hindlimb suspension. Unloading-induced atrophy primarily resulted from increased protein

  6. Skeletal muscle training for spinal muscular atrophy type 3 (Protocol).

    NARCIS (Netherlands)

    Bartels, B.; Montes, J.; Pol, W.L. van der; Groot, J.F. de

    2016-01-01

    Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease caused by a genetic mutation in the survival motor neuron 1 (SMN1) gene (5q11.2-q13.3) (Lefebvre 1995). With an incidence of one in 10,000 live births, it is the leading genetic cause of infant death (Lunn 2008; Mercur

  7. Pigmented paravenous chorioretinal atrophy with Coat′s like response

    Directory of Open Access Journals (Sweden)

    Manish Tandon

    2013-01-01

    Full Text Available Pigmented paravenous chorioretinal atrophy (PPCRA is an uncommon retinal disorder of unknown etiology that is neither well understood nor classified. We report an atypical case of PPCRA, associated with Coat′s like response (CLR in a 64-year-old man of Asian origin. Both the eyes were involved, though asymmetrically.

  8. Best practice guidelines for molecular analysis in spinal muscular atrophy

    NARCIS (Netherlands)

    Scheffer, H; Cobben, JM; Matthijs, G; Wirth, B

    With a prevalence of approximately 1/10 000, and a carrier frequency of 1/40-1/60 the proximal spinal muscular atrophies (SMAs) are among the most frequent autosomal recessive hereditary disorders. Patients can be classified clinically into four groups: acute, intermediate, mild, and adult (SMA

  9. Tubular atrophy in the pathogenesis of chronic kidney disease progression.

    Science.gov (United States)

    Schelling, Jeffrey R

    2016-05-01

    The longstanding focus in chronic kidney disease (CKD) research has been on the glomerulus, which is sensible because this is where glomerular filtration occurs, and a large proportion of progressive CKD is associated with significant glomerular pathology. However, it has been known for decades that tubular atrophy is also a hallmark of CKD and that it is superior to glomerular pathology as a predictor of glomerular filtration rate decline in CKD. Nevertheless, there are vastly fewer studies that investigate the causes of tubular atrophy, and fewer still that identify potential therapeutic targets. The purpose of this review is to discuss plausible mechanisms of tubular atrophy, including tubular epithelial cell apoptosis, cell senescence, peritubular capillary rarefaction and downstream tubule ischemia, oxidative stress, atubular glomeruli, epithelial-to-mesenchymal transition, interstitial inflammation, lipotoxicity and Na(+)/H(+) exchanger-1 inactivation. Once a a better understanding of tubular atrophy (and interstitial fibrosis) pathophysiology has been obtained, it might then be possible to consider tandem glomerular and tubular therapeutic strategies, in a manner similar to cancer chemotherapy regimens, which employ multiple drugs to simultaneously target different mechanistic pathways.

  10. Brain atrophy at onset and physical disability in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Juan Ignacio Rojas

    2012-10-01

    Full Text Available The aim of this study was to investigate if brain atrophy in multiple sclerosis (MS patients during the disease onset predicts long term disability. METHODS: MS patients with follow-up time of at least 7 years from disease onset and with baseline and second magnetic resonance 12 months later were included to measure brain atrophy. Expanded Disability Status Scale (EDSS was categorized in three groups, EDSS=0, EDSS=1 and 2.5 and EDSS>2.5, and used as disability measure. RESULTS: Twenty-six patients were included. Mean atrophy during the first year in patients that reached an EDSS≥3 was -0.76±0.45 %, in patients with an EDSS between 1 and 2.5 was -0.59±0.56, while in patients with an EDSS of 0 it was -0.38±0.42 (p=0.003. DISCUSSION: Brain atrophy rates during the first year of disease were predictive of disease progression in our population.

  11. Skeletal muscle training for spinal muscular atrophy type 3 (Protocol).

    NARCIS (Netherlands)

    Bartels, B.; Montes, J.; Pol, W.L. van der; Groot, J.F. de

    2016-01-01

    Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease caused by a genetic mutation in the survival motor neuron 1 (SMN1) gene (5q11.2-q13.3) (Lefebvre 1995). With an incidence of one in 10,000 live births, it is the leading genetic cause of infant death (Lunn 2008;

  12. Excessive daytime sleepiness in multiple system atrophy (SLEEMSA study)

    NARCIS (Netherlands)

    Moreno-Lopez, C.; Santamaria, J.; Salamero, M.; Del Sorbo, F.; Albanese, A.; Pellecchia, M.T.; Barone, P.; Overeem, S.; Bloem, B.R.; Aarden, W.C.C.A.; Canesi, M.; Antonini, A.; Duerr, S.; Wenning, G.K.; Poewe, W.; Rubino, A.; Meco, G.; Schneider, S.A.; Bhatia, K.P.; Djaldetti, R.; Coelho, M.; Sampaio, C.; Cochen, V.; Hellriegel, H.; Deuschl, G.; Colosimo, C.; Marsili, L.; Gasser, T.; Tolosa, E.

    2011-01-01

    BACKGROUND: Sleep disorders are common in multiple system atrophy (MSA), but the prevalence of excessive daytime sleepiness (EDS) is not well known. OBJECTIVE: To assess the frequency and associations of EDS in MSA. DESIGN: Survey of EDS in consecutive patients with MSA and comparison with patients

  13. Atrophy of the Parietal Lobe in Preclinical Dementia

    Science.gov (United States)

    Jacobs, Heidi I. L.; Van Boxtel, Martin P. J.; Uylings, Harry B. M.; Gronenschild, Ed H. B. M.; Verhey, Frans R.; Jolles, Jelle

    2011-01-01

    Cortical grey matter atrophy patterns have been reported in healthy ageing and Alzheimer disease (AD), but less consistently in the parietal regions of the brain. We investigated cortical grey matter volume patterns in parietal areas. The grey matter of the somatosensory cortex, superior and inferior parietal lobule was measured in 75 older adults…

  14. Reversible Altered Consciousness and Brain Atrophy Induced by Valproic Acid

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2003-08-01

    Full Text Available A 5-year-old female child with valproic acid (VPA-related alteration of consciousness and brain atrophy that progressed over a 3 day period and resolved within 12 hours of discontinuing VPA is reported from Dokkyo University School of Medicine and Shimotsuga General Hospital, Tochigi, Japan.

  15. The Relationship between Osteogenesis Imperfecta and Spinal Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Babak Soltani

    2011-06-01

    Full Text Available ObjectiveA 4-month-old female with osteogenesis imperfecta (OI type II was admitted in PICU of our center due to severe respiratory distress and fever with a diagnosis of severe pneumonia, and mechanical ventilation was initiated. Due to severe hypotonia, NCV and EMG were performed, and spinal muscular atrophy (SMA type I was diagnosed.

  16. Acylated and unacylated ghrelin impair skeletal muscle atrophy in mice

    Science.gov (United States)

    Cachexia is a wasting syndrome associated with cancer, AIDS, multiple sclerosis, and several other disease states. It is characterized by weight loss, fatigue, loss of appetite, and skeletal muscle atrophy and is associated with poor patient prognosis, making it an important treatment target. Ghreli...

  17. CT findings of hereditary dentatorubral-pallidoluysian atrophy (DRPLA)

    Energy Technology Data Exchange (ETDEWEB)

    Tokiguchi, Susumu; Kurashima, Akihiko; Tsuchiya, Toshiaki; Ito, Jusuke; Naito, Haruhiko; Nagai, Hiroko; Wakabayashi, Masatoshi; Morita, Masahiro

    1987-12-01

    Hereditary dentatorubral-pallidoluysian atrophy (DRPLA) has recently been recognized as a clinicopathological entity. It may be defined as a multisystem degenerative disease of dominant inheritance, and characterized clinically by a combination of epilepsy, myoclonus, ataxia, dementia, and choreo-athetosis. This paper reports on the CT findings of ten patients (in four families) with DRPLA. In two families, the diagnosis was established on the basis of the clinicopathological findings, while in the other two, the diagnosis was made clinically. Although the CT findings were not identical in all patients, some degree of atrophic change was always observed in the cerebellum, brainstem, and cerebral cortex. Cerebellar atrophy was always accompanied by a dilatation of the fourth ventricle. Midbrain atrophy was characterized by a prominent tegmental atrophy and aqueductal dilatation, such as is seen in progressive supranuclear palsy. Of the four patients over 40 years of age, three had a diffuse hypodensity of the cerebral white matter on CT. To our knowledge, there have been no previous reports on this hypodensity in patients with spino-cerebellar degeneration or Huntington's chorea. CT may be helpful in the differential diagnosis of progressive neuro-degenerative disorders.

  18. Epidural anaesthesia in a child with possible spinal muscular atrophy

    NARCIS (Netherlands)

    Veen, A; Molenbuur, B; Richardson, FJ

    2002-01-01

    Spinal muscular atrophy (SMA) is a rare lower motor neurone disease in which anaesthetic management is often difficult as a result of muscle weakness and hypersensitivity to neuromuscular blocking agents. Neuraxial anaesthesia is controversial in these patients; however, some cases have been reporte

  19. Prefrontal involvement related to cognitive impairment in progressive muscular atrophy

    NARCIS (Netherlands)

    Raaphorst, Joost; van Tol, Marie-José; Groot, Paul F C; Altena, Ellemarije; van der Werf, Ysbrand D; Majoie, Charles B; van der Kooi, Anneke J; van den Berg, Leonard H; Schmand, Ben; de Visser, Marianne; Veltman, Dick J

    2014-01-01

    OBJECTIVE: To examine brain activation patterns during verbal fluency performance in patients with progressive muscular atrophy (PMA) and amyotrophic lateral sclerosis (ALS). METHODS: fMRI was used to examine the blood oxygen level-dependent response during letter and category fluency performance in

  20. Prefrontal involvement related to cognitive impairment in progressive muscular atrophy

    NARCIS (Netherlands)

    J. Raaphorst; M.J. van Tol; P.F.C. Groot; E. Altena; Y.D. van der Werf; C.B. Majoie; A.J. van der Kooi; L.H. van den Berg; B. Schmand; M. de Visser; D.J. Veltman

    2014-01-01

    Objective: To examine brain activation patterns during verbal fluency performance in patients with progressive muscular atrophy (PMA) and amyotrophic lateral sclerosis (ALS). Methods: fMRI was used to examine the blood oxygen level-dependent response during letter and category fluency performance in

  1. Cardiac pathology in spinal muscular atrophy : a systematic review

    NARCIS (Netherlands)

    Wijngaarde, C A; Blank, A C; Stam, M; Wadman, R I; van den Berg, L H; van der Pol, W L

    2017-01-01

    BACKGROUND: Hereditary proximal spinal muscular atrophy (SMA) is a severe neuromuscular disease of childhood caused by homozygous loss of function of the survival motor neuron (SMN) 1 gene. The presence of a second, nearly identical SMN gene (SMN2) in the human genome ensures production of residual

  2. Impact of diaphragm muscle fiber atrophy on neuromotor control.

    Science.gov (United States)

    Mantilla, Carlos B; Sieck, Gary C

    2013-11-01

    In skeletal muscles, motor units comprise a motoneuron and the group of muscle fibers innervated by it, which are usually classified based on myosin heavy chain isoform expression. Motor units displaying diverse contractile and fatigue properties are important in determining the range of motor behaviors that can be accomplished by a muscle. Muscle fiber atrophy and weakness may disproportionately affect specific fiber types across a variety of diseases or clinical conditions, thus impacting neuromotor control. In this regard, fiber atrophy that affects a specific fiber type will alter the relative contribution of different motor units to overall muscle structure and function. For example, in various diseases there is fairly selective atrophy of type IIx and/or IIb fibers comprising the strongest yet most fatigable motor units. As a result, there is muscle weakness (i.e., reductions in force per cross-sectional area) associated with an apparent improvement in resistance to fatiguing contractions. This review will examine neuromotor control of respiratory muscles such as the diaphragm muscle and the impact of muscle fiber atrophy on motor performance. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Epidural anaesthesia in a child with possible spinal muscular atrophy

    NARCIS (Netherlands)

    Veen, A; Molenbuur, B; Richardson, FJ

    2002-01-01

    Spinal muscular atrophy (SMA) is a rare lower motor neurone disease in which anaesthetic management is often difficult as a result of muscle weakness and hypersensitivity to neuromuscular blocking agents. Neuraxial anaesthesia is controversial in these patients; however, some cases have been reporte

  4. Excessive daytime sleepiness in multiple system atrophy (SLEEMSA study)

    NARCIS (Netherlands)

    Moreno-Lopez, C.; Santamaria, J.; Salamero, M.; Del Sorbo, F.; Albanese, A.; Pellecchia, M.T.; Barone, P.; Overeem, S.; Bloem, B.R.; Aarden, W.C.C.A.; Canesi, M.; Antonini, A.; Duerr, S.; Wenning, G.K.; Poewe, W.; Rubino, A.; Meco, G.; Schneider, S.A.; Bhatia, K.P.; Djaldetti, R.; Coelho, M.; Sampaio, C.; Cochen, V.; Hellriegel, H.; Deuschl, G.; Colosimo, C.; Marsili, L.; Gasser, T.; Tolosa, E.

    2011-01-01

    BACKGROUND: Sleep disorders are common in multiple system atrophy (MSA), but the prevalence of excessive daytime sleepiness (EDS) is not well known. OBJECTIVE: To assess the frequency and associations of EDS in MSA. DESIGN: Survey of EDS in consecutive patients with MSA and comparison with patients

  5. Posterior Cortical Atrophy Presenting with Superior Arcuate Field Defect

    Directory of Open Access Journals (Sweden)

    Sue Ling Wan

    2015-01-01

    Full Text Available An 80-year-old female with reading difficulty presented with progressive arcuate field defect despite low intraocular pressure. Over a 5-year period, the field defect evolved into an incongruous homonymous hemianopia and the repeated neuroimaging revealed progressive posterior cortical atrophy. Further neuropsychiatric assessment demonstrated symptoms and signs consistent with Benson’s syndrome.

  6. Benefits of Laser Therapy in Postmenopausal Vaginal Atrophy

    Science.gov (United States)

    Brînzan, Daniela; Pǎiuşan, Lucian; Daşcǎu, Voicu; Furǎu, Gheorghe

    2011-08-01

    Maybe the worst aspect of menopause is the decline of the quality of the sexual life. The aim of the study is to demonstrate the beneficial effects of laser therapy in comparison with topical application of estrogen preparations, for the treatment of vaginal atrophy and sexual dysfunctions induced by menopause. A total of 50 menopausal patients were examined during a one year period. The methods used for objectifying vaginal atrophy and sexual dysfunctions were history taking, local clinical exam and PAP smear. From this group, 40 patients had vaginal atrophy with sexual dysfunctions. They have been treated differently, being included in four groups: patients treated with local estrogens, patients treated with intravaginal laser therapy, patients treated with both laser therapy and estrogens, patients treated with estrogens and placebo laser therapy. Therapeutic benefit, improvement of vaginal atrophy and quality of sexual life, were objectified by anamnesis (questionnaire), local and general clinical examination and PAP smear. The best results have been obtained, by far, in the 3rd group, followed by the women treated only with laser. In conclusion, we can say that laser therapy is the best way for solving the sexual inconveniences of menopause.

  7. Skeletal muscle training for spinal muscular atrophy type 3

    NARCIS (Netherlands)

    Bartels, Bart; Montes, Jacqueline; van der Pol, W. Ludo; de Groot, Janke F.

    2016-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects of skeletal muscle training on functional performance in people with spinal muscular atrophy (SMA) type 3 and to identify any adverse effects.

  8. Intravaginally applied oxytocin improves post-menopausal vaginal atrophy.

    Science.gov (United States)

    Al-Saqi, Shahla H; Uvnäs-Moberg, Kerstin; Jonasson, Aino F

    2015-09-01

    To explore the efficacy of local oxytocin for the treatment of post-menopausal vaginal atrophy. Double-blinded randomised controlled trial. Healthy post-menopausal women in Stockholm, Sweden. Sixty four post-menopausal women between February and June 2012 at the Karolinska University Hospital Huddinge/Sweden. The efficacy of oxytocin for treatment of vaginal atrophy after seven weeks and cytological evaluation. The percentage of superficial cells in the vaginal smears and the maturation values were significantly increased after seven weeks of treatment with vagitocin 400 IU (p = 0.0288 and p = 0.0002, respectively). The vaginal pH decreased significantly after seven weeks of treatment with vagitocin 100 IU (p = 0.02). The scores of vaginal atrophy, according to the histological evaluation, were significantly reduced after administration of vagitocin 100 IU (p = 0.03). The thickness of the endometrium did not differ between the treatment and placebo groups after seven weeks of treatment. The symptom experienced as the most bothersome was significantly reduced after seven weeks of treatment in the women receiving vagitocin 400 IU compared to women in the placebo group (p = 0.0089). Treatment with intravaginally applied oxytocin could be an alternative to local estrogen treatment in women with post-menopausal vaginal atrophy. © The Author(s) 2015.

  9. Atrophy of the Parietal Lobe in Preclinical Dementia

    Science.gov (United States)

    Jacobs, Heidi I. L.; Van Boxtel, Martin P. J.; Uylings, Harry B. M.; Gronenschild, Ed H. B. M.; Verhey, Frans R.; Jolles, Jelle

    2011-01-01

    Cortical grey matter atrophy patterns have been reported in healthy ageing and Alzheimer disease (AD), but less consistently in the parietal regions of the brain. We investigated cortical grey matter volume patterns in parietal areas. The grey matter of the somatosensory cortex, superior and inferior parietal lobule was measured in 75 older adults…

  10. The Retina in Multiple System Atrophy: Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Carlos E. Mendoza-Santiesteban

    2017-05-01

    Full Text Available BackgroundMultiple system atrophy (MSA is a rare, adult-onset, rapidly progressive fatal synucleinopathy that primarily affects oligodendroglial cells in the brain. Patients with MSA only rarely have visual complaints, but recent studies of the retina using optical coherence tomography (OCT showed atrophy of the peripapillary retinal nerve fiber layer (RNFL and to a lesser extent the macular ganglion cell layer (GCL complex.MethodsWe performed a literature review and meta-analysis according to the preferred reporting items for systematic reviews and meta-analyses guidelines for studies published before January 2017, identified through PubMed and Google Scholar databases, which reported OCT-related outcomes in patients with MSA and controls. A random-effects model was constructed.ResultsThe meta-analysis search strategy yielded 15 articles of which 7 met the inclusion criteria. The pooled difference in the average thickness of the RNFL was −5.48 μm (95% CI, −6.23 to −4.73; p < 0.0001, indicating significant thinning in patients with MSA. The pooled results showed significant thinning in all the specific RNFL quadrants, except in the temporal RNFL quadrant, where the thickness in MSA and controls was similar [pooled difference of 1.11 µm (95% CI, −4.03 to 6.26; p = 0.67]. This pattern of retinal damage suggests that MSA patients have preferential loss of retinal ganglion cells projecting to the magnocellular pathway (M-cells, which are mainly located in the peripheral retina and are not essential for visual acuity. Visual acuity, on the other hand, relies mostly on macular ganglion cells projecting to the parvocellular pathway (P-cells through the temporal portion of the RNFL, which are relatively spared in MSA patients.ConclusionThe retinal damage in patients with MSA differs from that observed in patients with Parkinson disease (PD. Patients with MSA have more relative preservation of temporal sector of the RNFL and less

  11. Medical management of hereditary optic neuropathies

    Directory of Open Access Journals (Sweden)

    Chiara eLa Morgia

    2014-07-01

    Full Text Available Hereditary optic neuropathies are diseases of the optic nerve. The most common are mitochondrial hereditary optic neuropathies, i.e. the maternally inherited Leber’s Hereditary Optic Neuropathy (LHON and Dominant Optic Atrophy (DOA. They both share a mitochondrial pathogenesis that leads to the selective loss of retinal ganglion cells and axons, in particular of the papillo-macular bundle. Typically, LHON is an acute/subacute loss of central vision associated with impairment of color vision and swelling of retinal nerve fibers followed by optic atrophy. DOA, instead, is characterized by a childhood-onset and slowly progressive loss of central vision, worsening over the years, leading to optic atrophy. The diagnostic workup includes neuro-ophthalmologic evaluation and genetic testing of the three most common mitochondrial DNA mutations affecting complex I (11778/ND4, 3460/ND1 and 14484/ND6 for LHON and sequencing of the nuclear gene OPA1 for DOA. Therapeutic strategies are limited including agents that bypass the complex I defect and exert an antioxidant effect (idebenone. Further strategies are aimed at stimulating compensatory mitochondrial biogenesis. Gene therapy is also a promising venue that still needs to be validated.

  12. Medical Management of Hereditary Optic Neuropathies

    Science.gov (United States)

    La Morgia, Chiara; Carbonelli, Michele; Barboni, Piero; Sadun, Alfredo Arrigo; Carelli, Valerio

    2014-01-01

    Hereditary optic neuropathies are diseases affecting the optic nerve. The most common are mitochondrial hereditary optic neuropathies, i.e., the maternally inherited Leber’s hereditary optic neuropathy (LHON) and dominant optic atrophy (DOA). They both share a mitochondrial pathogenesis that leads to the selective loss of retinal ganglion cells and axons, in particular of the papillo-macular bundle. Typically, LHON is characterized by an acute/subacute loss of central vision associated with impairment of color vision and swelling of retinal nerve fibers followed by optic atrophy. DOA, instead, is characterized by a childhood-onset and slowly progressive loss of central vision, worsening over the years, leading to optic atrophy. The diagnostic workup includes neuro-ophthalmologic evaluation and genetic testing of the three most common mitochondrial DNA mutations affecting complex I (11778/ND4, 3460/ND1, and 14484/ND6) for LHON and sequencing of the nuclear gene OPA1 for DOA. Therapeutic strategies are still limited including agents that bypass the complex I defect and exert an antioxidant effect (idebenone). Further strategies are aimed at stimulating compensatory mitochondrial biogenesis. Gene therapy is also a promising avenue that still needs to be validated. PMID:25132831

  13. Medical management of hereditary optic neuropathies.

    Science.gov (United States)

    La Morgia, Chiara; Carbonelli, Michele; Barboni, Piero; Sadun, Alfredo Arrigo; Carelli, Valerio

    2014-01-01

    Hereditary optic neuropathies are diseases affecting the optic nerve. The most common are mitochondrial hereditary optic neuropathies, i.e., the maternally inherited Leber's hereditary optic neuropathy (LHON) and dominant optic atrophy (DOA). They both share a mitochondrial pathogenesis that leads to the selective loss of retinal ganglion cells and axons, in particular of the papillo-macular bundle. Typically, LHON is characterized by an acute/subacute loss of central vision associated with impairment of color vision and swelling of retinal nerve fibers followed by optic atrophy. DOA, instead, is characterized by a childhood-onset and slowly progressive loss of central vision, worsening over the years, leading to optic atrophy. The diagnostic workup includes neuro-ophthalmologic evaluation and genetic testing of the three most common mitochondrial DNA mutations affecting complex I (11778/ND4, 3460/ND1, and 14484/ND6) for LHON and sequencing of the nuclear gene OPA1 for DOA. Therapeutic strategies are still limited including agents that bypass the complex I defect and exert an antioxidant effect (idebenone). Further strategies are aimed at stimulating compensatory mitochondrial biogenesis. Gene therapy is also a promising avenue that still needs to be validated.

  14. Renal atrophy after stereotactic body radiotherapy for renal cell carcinoma.

    Science.gov (United States)

    Yamamoto, Takaya; Kadoya, Noriyuki; Takeda, Ken; Matsushita, Haruo; Umezawa, Rei; Sato, Kiyokazu; Kubozono, Masaki; Ito, Kengo; Ishikawa, Yojiro; Kozumi, Maiko; Takahashi, Noriyoshi; Katagiri, Yu; Onishi, Hiroshi; Jingu, Keiichi

    2016-05-26

    Renal atrophy is observed in an irradiated kidney. The aim of this study was to determine dose-volume histogram parameters and other factors that predict renal atrophy after 10-fraction stereotactic body radiotherapy (SBRT) for primary renal cell carcinoma (RCC). A total of 14 patients (11 males, 3 females) who received SBRT for RCC at Tohoku University Hospital between April 2010 and February 2014 were analyzed. The median serum creatinine level was 1.1 mg/dl and two patients had a single kidney. Nine patients were implanted with fiducial markers. The median tumor diameter was 30 mm. SBRT was delivered at 70 Gy in 10 fractions for 7 tumors, at 60 Gy in 10 fractions for 2 tumors, and at 50 Gy in 10 fractions for 5 tumors with 6 and/or 15 MV X-ray using 5 to 8 multi-static beams. Renal atrophy was assessed using post-SBRT CT images after 12-24 months intervals. Correlations were examined by Spearman rank correlation analysis. Differences between two groups were evaluated by the Mann-Whitney test, and pairwise comparisons were made by the Wilcoxon signed-rank test. The median tumor volume shrunk from 14.8 cc to 10.6 cc (p = 0.12), and the median irradiated kidney volume changed from 160.4 cc to 137.1 cc (p atrophy (p = 0.02). Significant renal atrophic change was observed. Dose distribution of SBRT at 20-30 Gy had a strong correlation with renal atrophy when irradiation was performed in 10 fractions.

  15. Factors Associated with Changes in Brain Atrophy during a Three-Year Observation in Elderly Diabetic Patients: Effect of Renal Impairment on Hippocampal Atrophy

    Directory of Open Access Journals (Sweden)

    Takahiko Kawamura

    2016-02-01

    Full Text Available Background/Aims: We conducted a 3-year longitudinal study concerning factors associated with changes in brain atrophy in elderly diabetic patients. Methods: We evaluated hippocampal and global brain atrophy using automatic voxel-based morphometry of structural magnetic resonance images, 4 cognitive function tests, and cerebral small vessel disease (SVD in 66 diabetic patients. Results: During the 3-year follow-up, hippocampal and global brain atrophy advanced, and cognitive functions worsened. For changes in hippocampal atrophy, changes in estimated glomerular filtration rate (eGFR, albuminuria, and being an ApoE ε4 carrier were independent factors; change in the number of silent brain infarctions was an independent factor for changes in global brain atrophy. A significant association of changes in eGFR and albuminuria with hippocampal atrophy remained after adjusting for confounders including SVD. Both types of brain atrophy at baseline were significantly correlated with cognitive impairment at baseline and especially associated with changes in delayed word recall during the follow-up after adjusting for confounders. Conclusion: Changes in eGFR and albuminuria during follow-up were independent risk factors for hippocampal atrophy, which was associated with decline in delayed word recall, suggesting that management of chronic kidney disease may prevent the progression of hippocampal atrophy.

  16. Inherited mitochondrial optic neuropathies

    Science.gov (United States)

    Yu-Wai-Man, P; Griffiths, P G; Hudson, G; Chinnery, P F

    2009-01-01

    Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (DOA) are the two most common inherited optic neuropathies and they result in significant visual morbidity among young adults. Both disorders are the result of mitochondrial dysfunction: LHON from primary mitochondrial DNA (mtDNA) mutations affecting the respiratory chain complexes; and the majority of DOA families have mutations in the OPA1 gene, which codes for an inner mitochondrial membrane protein critical for mtDNA maintenance and oxidative phosphorylation. Additional genetic and environmental factors modulate the penetrance of LHON, and the same is likely to be the case for DOA which has a markedly variable clinical phenotype. The selective vulnerability of retinal ganglion cells (RGCs) is a key pathological feature and understanding the fundamental mechanisms that underlie RGC loss in these disorders is a prerequisite for the development of effective therapeutic strategies which are currently limited. PMID:19001017

  17. Dynamic Foot Pressure as a Countermeasure to Muscle Atrophy

    Science.gov (United States)

    Kyparos, A.; Layne, C. S.; Martinez, D. A.; Clarke, M. S. F.; Feeback, D. L.

    2002-01-01

    Mechanical unloading of skeletal muscle (SKM) as a consequence of space flight or ground-based analogues, such as human bedrest and rodent hindlimb suspension (HLS) models, induces SKM atrophy particularly affecting the anti-gravity musculature of the lower limbs. In the context of manned space flight, the subsequent loss of muscle strength and functionality will pose operational implications jeopardizing mission success. Exercise, currently the primary muscle degradation countermeasure, has not proven completely effective in preventing muscle atrophy. It is therefore imperative that some other forms of in- flight countermeasure be also developed to supplement the prescribed exercise regimen the astronauts follow during spaceflight. Previous work in both humans and rats has shown that mechanical stimulation of the soles of the feet increases neuromuscular activation in the lower limb musculature and that such stimulation results in the limited prevention of atrophy in the soleus muscle of unloaded rats. This study was designed to investigate the effect of cutaneous mechanoreceptor stimulation on hindlimb unloading- induced SKM atrophy in rats. It was hypothesized that mechanical stimulation of the plantar surface of the rat foot during hindlimb suspension (HLS), utilizing a novel stimulation paradigm known as Dynamic Foot Pressure (DFP), would attenuate unloading-induced SKM atrophy. Mature adult male Wistar rats were randomly assigned to four groups of 10 rats each as follows: sedentary controls (Ctrl), hindlimb suspended only (HLS), hindlimb suspended wearing an inflatable boot (HLS-IFL) and hindlimb suspended rats wearing a non-inflatable boot (HLS-NIFL). The stimulation of mechanoreceptors was achieved by applying pressure to the plantar surface of the foot during the 10-day period of HLS using a custom-built boot. The anti-atrophic effects of DFP application was quantified directly by morphological (muscle wet weight, myofiber cross-sectional area

  18. Progressive Brain Atrophy in Super-refractory Status Epilepticus.

    Science.gov (United States)

    Hocker, Sara; Nagarajan, Elanagan; Rabinstein, Alejandro A; Hanson, Dennis; Britton, Jeffrey W

    2016-10-01

    Prolonged seizures in super-refractory status epilepticus (SRSE) have been shown to cause neuronal death and reorganization, and visual inspection in individual case studies has demonstrated progressive cortical and subcortical atrophy. At present, magnetic resonance imaging (MRI) studies that evaluate brain atrophy in SRSE are lacking. To document and quantify the development of atrophy over time in SRSE. This retrospective medical record review included all patients with SRSE who were admitted to a tertiary referral campus of the Mayo Clinic Hospital with SRSE from January 1, 2001, to December 31, 2013. Patients with (1) an initial MRI scan performed within 2 weeks of SRSE onset, (2) a second MRI scan within 6 months of SRSE resolution, and (3) a minimum duration of 1 week between MRI scans were included. The ventricular brain ratio (VBR) was measured on T2-weighted fluid-attenuated inversion recovery (FLAIR) images at disease onset and during follow-up. Measurements were performed on axial FLAIR images with section thickness of less than 5 mm. The plane immediately superior to the caudate head was chosen for analysis. The hypothesis that atrophy develops during SRSE despite seizure control (electroencephalogram background suppression with anesthetic drugs) was tested. Data were analyzed from June 1 to December 31, 2015. Change in VBR (ΔVBR) as a percentage of the starting measure. Nineteen patients met the inclusion criteria; these included 10 men (53%) and 9 women (47%) with a median age of 41 (interquartile range [IQR], 25-68) years. Anesthetic agents were required for a median of 13 (IQR, 5-37) days. Initial MRI was performed a median of 2 (IQR, 1-7.5) days from the onset of SRSE, and the second MRI was performed a median of 11 (IQR, 5-15.5) days from the resolution of SRSE, with a median of 40 (IQR, 15-65) days between MRI scans. Median ΔVBR was 23.3% (IQR, 10.5%-70.3%). A significant correlation between the duration of anesthetic agent use and ΔVBR was

  19. Neuro-Behcet's disease showing severe atrophy of the cerebrum.

    Science.gov (United States)

    Miyakawa, T; Murayama, E; Deshimaru, M; Shikai, I; Kozuma, S

    1976-03-15

    A 38-year-old female died 6 years after the onset of what was, clinically and histopathologically, consistent with neuro-Behcet's disease. Pathologically the cerebrum showed severe atrophy. The main changes were observed in the grey and white matter, the diencephalon and the basal ganglia by light microscopy. All these changes originated in softenings around blood vessels, especially small vessels or capillaries. These foci fused together to form large regions of softening. Glial or mesenchymal reactions were minimal. In the white matter there was slight perivascular-infiltration, mainly consisting of lymphocytes. In view of these findings, it is suggested that these changes were caused by an allergic vasculitis. The present case of Neuro-Behcet's disease is the first one showing general atrophy of the cerebrum. It is very important in relation to demyelinating encephalitis.

  20. Spinal muscular atrophy: development and implementation of potential treatments.

    Science.gov (United States)

    Arnold, W David; Burghes, Arthur H M

    2013-09-01

    In neurodegenerative disorders, effective treatments are urgently needed, along with methods to determine whether treatment worked. In this review, we discuss the rapid progress in the understanding of recessive proximal spinal muscular atrophy and how this is leading to exciting potential treatments of the disease. Spinal muscular atrophy is caused by loss of the survival motor neuron 1 (SMN1) gene and reduced levels of SMN protein. The critical downstream targets of SMN deficiency that result in motor neuron loss are not known. However, increasing SMN levels has a marked impact in mouse models, and these therapeutics are rapidly moving toward clinical trials. Promising preclinical therapies, the varying degree of impact on the mouse models, and potential measures of treatment effect are reviewed. One key issue discussed is the variable outcome of increasing SMN at different stages of disease progression.

  1. Crustaceans as a model for microgravity-induced muscle atrophy

    Science.gov (United States)

    Mykles, D. L.

    1996-01-01

    Atrophy of skeletal muscles is a serious problem in a microgravity environment. It is hypothesized that the unloading of postural muscles, which no longer must resist gravity force, causes an accelerated breakdown of contractile proteins, resulting in reduction in muscle mass and strength. A crustacean model using the land crab, Gecarcinus lateralis, to assess the effects of spaceflight on protein meatabolism is presented. The model is compared to a developmentally-regulated atrophy in which a premolt reduction in muscle mass allows the withdrawal of the large claws at molt. The biochemical mechanisms underlying protein breakdown involves both Ca2(+) -dependent and multicatalytic proteolytic enzymes. Crustacean claw muscle can be used to determine the interactions between shortening and unloading at the molecular level.

  2. Cortical atrophy in presymptomatic Alzheimer's disease presenilin 1 mutation carriers.

    Science.gov (United States)

    Quiroz, Yakeel T; Stern, Chantal E; Reiman, Eric M; Brickhouse, Michael; Ruiz, Adriana; Sperling, Reisa A; Lopera, Francisco; Dickerson, Bradford C

    2013-05-01

    Sporadic late-onset Alzheimer's disease (AD) dementia has been associated with a 'signature' of cortical atrophy in paralimbic and heteromodal association regions measured with MRI. To investigate whether a similar pattern of cortical atrophy is present in presymptomatic presenilin 1 E280A mutation carriers an average of 6 years before clinical symptom onset. 40 cognitively normal volunteers from a Colombian population with familial AD were included; 18 were positive for the AD-associated presenilin 1 mutation (carriers, mean age=38) whereas 22 were non-carriers. T1-weighted volumetric MRI images were acquired and cortical thickness was measured. A priori regions of interest from our previous work were used to obtain thickness from AD-signature regions. Compared to non-carriers, presymptomatic presenilin 1 mutation carriers exhibited thinner cortex within the AD-signature summary measure (p<0.008). Analyses of individual regions demonstrated thinner angular gyrus, precuneus and superior parietal lobule in carriers compared to non-carriers, with trend-level effects in the medial temporal lobe. Results demonstrate that cognitively normal individuals genetically determined to develop AD have a thinner cerebral cortex than non-carriers in regions known to be affected by typical late-onset sporadic AD. These findings provide further support for the hypothesis that cortical atrophy is present in preclinical AD more than 5 years prior to symptom onset. Further research is needed to determine whether this method could be used to characterise the age-dependent trajectory of cortical atrophy in presymptomatic stages of AD.

  3. Patterns of regional cerebellar atrophy in genetic frontotemporal dementia

    Directory of Open Access Journals (Sweden)

    Martina Bocchetta

    2016-01-01

    Conclusion: There appears to be a differential pattern of cerebellar atrophy in the major genetic forms of FTD, being relatively spared in GRN, localized to the lobule VIIa-Crus I in the superior-posterior region of the cerebellum in C9orf72, the area connected via the thalamus to the prefrontal cortex and involved in cognitive function, and localized to the vermis in MAPT, the ‘limbic cerebellum’ involved in emotional processing.

  4. [Association of post-radiation focal muscular atrophy and hypertrophy].

    Science.gov (United States)

    Serratrice, G; Sangla, I; Pouget, J; Azulay, J P

    1993-01-01

    We report a 48 year old woman who had radiotherapy for uterine carcinoma and who developed amyotrophy and muscle hypertrophy in one lower limb. Very few cases of post-radiation monomelic amyotrophy have been reported. On the other hand denervation hypertrophy was presumed to be well known. The seat of the lesions was presumed to be radicular and spinal. The mechanism of atrophy and hypertrophy is discussed.

  5. MR imaging of psychosurgery: rostral atrophy following stereotacic subcaudate tractotomy.

    Science.gov (United States)

    Cauley, K A; Waheed, W; Salmela, M; Filippi, C G

    2010-11-01

    There are few reports of MR imaging findings following psychosurgery. Here, we report the findings of 3T MR imaging of the sequelae of stereotactic subcaudate tractotomy (SST). Rostral atrophy is noted on conventional imaging. Diffusion tensor (DT) tractography demonstrated no communicating white matter tracts between the inferior frontal lobes, which appeared normally as thick fibre bundles in age-matched controls. DT tractography provides a unique tool for the evaluation of sequelae of ablative psychosurgical procedures.

  6. Serological assessment of gastric mucosal atrophy in gastric cancer

    Directory of Open Access Journals (Sweden)

    Bornschein Jan

    2012-01-01

    Full Text Available Abstract Background Non-invasive tools for gastric cancer screening and diagnosis are lacking. Serological testing with the detection of pepsinogen 1 (PG1, pepsinogen 2 (PG2 and gastrin 17 (G17 offers the possibility to detect preneoplastic gastric mucosal conditions. Aim of this study was to assess the performance of these serological tests in the presence of gastric neoplasia. Methods Histological and serological samples of 118 patients with gastric cancer have been assessed for tumor specific characteristics (Laurén type, localisation, degree of mucosal abnormalities (intestinal metaplasia, atrophy and serological parameters (PG1, PG2, PG1/2-ratio, G17, H. pylori IgG, CagA status. Association of the general factors to the different serological values have been statistically analyzed. Results Patients with intestinal type gastric cancer had lower PG1 levels and a lower PG1/2-ratio compared to those with diffuse type cancer (p = 0.003. The serum levels of PG2 itself and G17 were not significantly altered. H. pylori infection in general had no influence on the levels of PG1, PG2 and G17 in the serum of gastric cancer patients. There was a trend towards lower PG1 levels in case of positive CagA-status (p = 0.058. The degree of both intestinal metaplasia and atrophy correlated inversely with serum levels for PG1 and the PG1/2-ratio (p Conclusions Glandular atrophy and a positive CagA status are determinant factors for decreased pepsinogen 1 levels in the serum of patients with gastric cancer. The serological assessment of gastric atrophy by analysis of serum pepsinogen is only adequate for patients with intestinal type cancer.

  7. Phenytoin-induced cerebellar atrophy in an epileptic boy

    Directory of Open Access Journals (Sweden)

    Nithin Kumar

    2013-01-01

    Full Text Available Epilepsy is an important health problem due to its high prevalence and potential for causing long-term morbidity. It is commonly treated in children with phenytoin sodium. It has wide pharmacokinetic variability and a narrow therapeutic range that leads to toxicity. Here, we report a case of phenytoin-induced cerebellar atrophy in a 16-year-old epileptic boy who presented to the hospital with a viral infection.

  8. The treatment of postmenopausal vaginal atrophy with ovestin

    NARCIS (Netherlands)

    Kicovic, P.M.; Cortesprieto, J.; Milojevic, S.; Haspels, A.A.; Aljinovic, A.

    1980-01-01

    Seventy-four postmenopausal women presenting with vaginal atrophy were treated with either Ovestin® vaginal cream (Group A, 23 women: 1 mg/day E3; Group B, 30 women: 0.5 mg/day E3) or vaginal suppositories (Group C, 21 women: 0.5 mg/day E3), applied daily for 3 wk (A and B) or 2 wk (C) before

  9. Intermittent acceleration as a countermeasure to soleus muscle atrophy

    Science.gov (United States)

    D'Aunno, Dominick S.; Robinson, Ronald R.; Smith, Gregory S.; Thomason, Donald B.; Booth, Frank W.

    1992-01-01

    The effectiveness of using intermittent acceleration as a countermeasure to muscle atrophy was investigated in rats subjected to 7 days of hindlimb suspension interrupted by daily periods of 1.2 g acceleration, for 15-min periods evenly spaced over 12-hr interval. It was found that this regimen, when repeated for 7 days, failed to completely maintain the mass of soleus muscle, which was 84 percent of control.

  10. Olmesartan-Induced Enteropathy: An Unusual Cause of Villous Atrophy

    Directory of Open Access Journals (Sweden)

    Marta Eusébio

    2016-03-01

    Olmesartan is an angiotensin receptor blocker commonly prescribed for the management of hypertension. Spruelike enteropathy associated with this drug is a recently described entity with few cases reported. It presents with chronic diarrhea and intestinal villous atrophy and should be included in its differential diagnosis. This case intends to alert clinicians for the possibility of this event in a patient on treatment with this drug.

  11. Interactive segmentation for geographic atrophy in retinal fundus images

    OpenAIRE

    Lee, Noah; SMITH, R. THEODORE; Laine, Andrew F.

    2008-01-01

    Fundus auto-fluorescence (FAF) imaging is a non-invasive technique for in vivo ophthalmoscopic inspection of age-related macular degeneration (AMD), the most common cause of blindness in developed countries. Geographic atrophy (GA) is an advanced form of AMD and accounts for 12–21% of severe visual loss in this disorder [3]. Automatic quantification of GA is important for determining disease progression and facilitating clinical diagnosis of AMD. The problem of automatic segmentation of patho...

  12. Regulation of muscle atrophy in aging and disease.

    Science.gov (United States)

    Vinciguerra, Manlio; Musaro, Antonio; Rosenthal, Nadia

    2010-01-01

    Muscle aging is characterized by a decline in functional performance and restriction of adaptability, due to progressive loss of muscle tissue coupled with a decrease in strength and force output. Together with selective activation ofapoptotic pathways, a hallmark of age-related muscle loss or sarcopenia is the progressive incapacity of regeneration machinery to replace damaged muscle. These characteristics are shared by pathologies involving muscle wasting, such as muscular dystrophies or amyotrophic lateral sclerosis, cancer and AIDS, all characterized by alterations in metabolic and physiological parameters, progressive weakness in specific muscle groups. Modulation ofextracellular agonists, receptors, protein kinases, intermediate molecules, transcription factors and tissue-specific gene expression collectively compromise the functionality of skeletal muscle tissue, leading to muscle degeneration and persistent protein degradation through activation ofproteolytic systems, such as calpain, ubiquitin-proteasome and caspase. Additional decrements in muscle growth factors compromise skeletal muscle growth, differentiation, survival and regeneration. A better understanding of the mechanisms underlying the pathogenesis of muscle atrophy and wasting associated with different diseases has been the objective of numerous studies and represents an important first step for the development of therapeutic approaches. Among these, insulin-like growth factor-1 (IGF-1) has emerged as a growth factor with a remarkably wide range of actions and a tremendous potential as a therapeutic in attenuating the atrophy and frailty associated with muscle aging and diseases. In this chapter we provide an overview of current concepts in muscle atrophy, focusing specifically on the molecular basis of IGF-1 action and survey current gene and cell therapeutic approaches to rescue muscle atrophy in aging and disease.

  13. The pathogenesis and treatment of cardiac atrophy in cancer cachexia.

    Science.gov (United States)

    Murphy, Kate T

    2016-02-15

    Cancer cachexia is a multifactorial syndrome characterized by a progressive loss of skeletal muscle mass associated with significant functional impairment. In addition to a loss of skeletal muscle mass and function, many patients with cancer cachexia also experience cardiac atrophy, remodeling, and dysfunction, which in the field of cancer cachexia is described as cardiac cachexia. The cardiac alterations may be due to underlying heart disease, the cancer itself, or problems initiated by the cancer treatment and, unfortunately, remains largely underappreciated by clinicians and basic scientists. Despite recent major advances in the treatment of cancer, little progress has been made in the treatment of cardiac cachexia in cancer, and much of this is due to lack of information regarding the mechanisms. This review focuses on the cardiac atrophy associated with cancer cachexia, describing some of the known mechanisms and discussing the current and future therapeutic strategies to treat this condition. Above all else, improved awareness of the condition and an increased focus on identification of mechanisms and therapeutic targets will facilitate the eventual development of an effective treatment for cardiac atrophy in cancer cachexia. Copyright © 2016 the American Physiological Society.

  14. Counteracting Muscle Atrophy using Galvanic Stimulation of the Vestibular System

    Science.gov (United States)

    Fox, Robert A.; Polyakov, Igor

    1999-01-01

    The unloading of weight bearing from antigravity muscles during space flight produces significant muscle atrophy and is one of the most serious health problems facing the space program. Various exercise regimens have been developed and used either alone or in combination with pharmacological techniques to ameliorate this atrophy, but no effective countermeasure exists for this problem. The research in this project was conducted to evaluate the potential use of vestibular galvanic stimulation (VGS) to prevent muscle atrophy resulting from unloading of weight bearing from antigravity muscles. This approach was developed based on two concepts related to the process of maintaining the status of the anti-gravity neuromuscular system. These two premises are: (1) The "tone," or bias on spinal motorneurons is affected by vestibular projections that contribute importantly to maintaining muscle health and status. (2) VGS can be used to modify the excitability, or 'tone' of motorneuron of antigravity muscles. Thus, the strategy is to use VGS to modify the gain of vestibular projections to antigravity muscles and thereby change the general status of these muscles.

  15. Masticatory muscles of mouse do not undergo atrophy in space.

    Science.gov (United States)

    Philippou, Anastassios; Minozzo, Fabio C; Spinazzola, Janelle M; Smith, Lucas R; Lei, Hanqin; Rassier, Dilson E; Barton, Elisabeth R

    2015-07-01

    Muscle loading is important for maintaining muscle mass; when load is removed, atrophy is inevitable. However, in clinical situations such as critical care myopathy, masticatory muscles do not lose mass. Thus, their properties may be harnessed to preserve mass. We compared masticatory and appendicular muscles responses to microgravity, using mice aboard the space shuttle Space Transportation System-135. Age- and sex-matched controls remained on the ground. After 13 days of space flight, 1 masseter (MA) and tibialis anterior (TA) were frozen rapidly for biochemical and functional measurements, and the contralateral MA was processed for morphologic measurements. Flight TA muscles exhibited 20 ± 3% decreased muscle mass, 2-fold decreased phosphorylated (P)-Akt, and 4- to 12-fold increased atrogene expression. In contrast, MAs had no significant change in mass but a 3-fold increase in P-focal adhesion kinase, 1.5-fold increase in P-Akt, and 50-90% lower atrogene expression compared with limb muscles, which were unaltered in microgravity. Myofibril force measurements revealed that microgravity caused a 3-fold decrease in specific force and maximal shortening velocity in TA muscles. It is surprising that myofibril-specific force from both control and flight MAs were similar to flight TA muscles, yet power was compromised by 40% following flight. Continued loading in microgravity prevents atrophy, but masticatory muscles have a different set point that mimics disuse atrophy in the appendicular muscle.

  16. Hippocampal complex atrophy in poststroke and mild cognitive impairment.

    Science.gov (United States)

    Selnes, Per; Grambaite, Ramune; Rincon, Mariano; Bjørnerud, Atle; Gjerstad, Leif; Hessen, Erik; Auning, Eirik; Johansen, Krisztina; Almdahl, Ina S; Due-Tønnessen, Paulina; Vegge, Kjetil; Bjelke, Börje; Fladby, Tormod

    2015-11-01

    To investigate putative interacting or distinct pathways for hippocampal complex substructure (HCS) atrophy and cognitive affection in early-stage Alzheimer's disease (AD) and cerebrovascular disease (CVD), we recruited healthy controls, patients with mild cognitive impairment (MCI) and poststroke patients. HCSs were segmented, and quantitative white-matter hyperintensity (WMH) load and cerebrospinal fluid (CSF) amyloid-β concentrations were determined. The WMH load was higher poststroke. All examined HCSs were smaller in amyloid-positive MCI than in controls, and the subicular regions were smaller poststroke. Memory was reduced in amyloid-positive MCI, and psychomotor speed and executive function were reduced in poststroke and amyloid-positive MCI. Size of several HCS correlated with WMH load poststroke and with CSF amyloid-β concentrations in MCI. In poststroke and amyloid-positive MCI, neuropsychological function correlated with WMH load and hippocampal volume. There are similar patterns of HCS atrophy in CVD and early-stage AD, but different HCS associations with WMH and CSF biomarkers. WMHs add to hippocampal atrophy and the archetypal AD deficit delayed recall. In line with mounting evidence of a mechanistic link between primary AD pathology and CVD, these additive effects suggest interacting pathologic processes.

  17. Counteracting Muscle Atrophy using Galvanic Stimulation of the Vestibular System

    Science.gov (United States)

    Fox, Robert A.; Polyakov, Igor

    1999-01-01

    The unloading of weight bearing from antigravity muscles during space flight produces significant muscle atrophy and is one of the most serious health problems facing the space program. Various exercise regimens have been developed and used either alone or in combination with pharmacological techniques to ameliorate this atrophy, but no effective countermeasure exists for this problem. The research in this project was conducted to evaluate the potential use of vestibular galvanic stimulation (VGS) to prevent muscle atrophy resulting from unloading of weight bearing from antigravity muscles. This approach was developed based on two concepts related to the process of maintaining the status of the anti-gravity neuromuscular system. These two premises are: (1) The "tone," or bias on spinal motorneurons is affected by vestibular projections that contribute importantly to maintaining muscle health and status. (2) VGS can be used to modify the excitability, or 'tone' of motorneuron of antigravity muscles. Thus, the strategy is to use VGS to modify the gain of vestibular projections to antigravity muscles and thereby change the general status of these muscles.

  18. Thymus atrophy and regeneration following dexamethasone administration to beef cattle.

    Science.gov (United States)

    Cannizzo, F T; Spada, F; Benevelli, R; Nebbia, C; Giorgi, P; Brina, N; Bollo, E; Biolatti, B

    2010-08-28

    Thymus atrophy and regeneration were studied in 13- to 22-month-old beef calves treated with dexamethasone (DMT), using anabolic dosages and implementing different withdrawal times. Two trials were conducted. In trial 1, group A (n=6) received 0.7 mg/day DMT orally for 40 days, group B (n=6) received 1.4 mg/day orally for 40 days and group C (n=6) was the control. In trial 2, group D (n=6) received 0.7 mg/day DMT orally for 40 days, group E (n=6) received 1.4 mg/day orally for 40 days and group K (n=6) was the control. DMT withdrawal times before slaughter were six days (groups A and B) and 26 days (groups D and E). At slaughter, thymus atrophy was severe and progressive in animals from groups A and B. In contrast, thymus weight and volume of the animals from groups D and E were almost normal. Slight atrophy was also detected in the calves in these groups. Histological changes and Ki67 immunostaining revealed a large number of positive lymphoid cells, mostly in the cortical area, associated with higher expression of apoptosis in the medulla compared with controls. This demonstrated that the thymus of beef cattle is still able to regenerate following DMT administration.

  19. Preprosthetic and implantological surgery in patients with severe maxillary atrophy.

    Science.gov (United States)

    González-García, Raúl; Naval-Gías, Luís; Muñoz-Guerra, Mario Fernando; Sastre-Pérez, Jesús; Rodríguez-Campo, Francisco José; Gil-Díez-Usandizaga, José Luís

    2005-01-01

    To evaluate the success of the osseointegration of dental implants in patients with severe maxillary atrophy after sinus lift augmentation and onlay graft surgery with autologous bone grafts. A descriptive and analytic study of 27 patients with severe maxillary atrophy and partial or total edentulism, after 4 years follow-up. All cases underwent to autologous bone graft sinus lift augmentation with or without onlay grafts in the anterior maxillae. After this, reconstruction with osseointegrated implants was performed. After the follow-up period, 89.1% of implants were osseointegrated and loaded. Anterior iliac crest bone graft provides good results with respect to implant osseointegration. The achievement of two surgical procedures for bone grafts surgery and implants surgery, separated 2 or more months, provides better results for osseointegration in comparison to a sole surgical procedure (p<0.01). Implants survival predictability is greater when a second surgical procedure is performed, once bone grafts have experimented an appropriate consolidation. The use of onlay graft and sinus lift augmentation techniques is useful in the resolution of complex problems such as the severe maxillary atrophy.

  20. Choroidal atrophy in a patient with paraneoplastic retinopathy and anti-TRPM1 antibody

    Directory of Open Access Journals (Sweden)

    Ueno S

    2014-02-01

    Full Text Available Shinji Ueno,1 Yasuki Ito,1 Ruka Maruko,1 Mineo Kondo,2 Hiroko Terasaki1 1Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, 2Department of Ophthalmology, Mie University Graduate School of Medicine, Tsu, Japan Abstract: The purpose of this paper is to report choroidal atrophy in a patient with cancer-associated retinopathy who had autoantibodies against the transient receptor potential cation channel, subfamily M, member 1 (TRPM1. A 69-year-old man visited our clinic in July 2010 with complaints of blurred vision and night blindness in both eyes. The full-field electroretinograms were negative type, indicating ON bipolar cell dysfunction. General physical examination revealed small cell carcinoma of the lung, and Western blot of the patient's serum showed autoantibodies against TRPM1. We diagnosed this patient with cancer-associated retinopathy and retinal ON bipolar dysfunction due to anti-TRPM1 autoantibody. We followed him for more than 2 years from the initial visit and his symptoms have not changed. However, consistent with the choroidal hypopigmentation of the fundus, spectral domain optical coherence tomography showed a decrease in choroidal thickness of about one third over a 2-year follow-up period. We suggest that this case of gradually progressive choroidal atrophy was caused by the autoantibody against TRPM1 directly, because TRPM1 is expressed not only on ON bipolar cells but also on melanocytes. These findings indicate that we should be aware of choroidal thickness in patients with paraneoplastic retinopathy who have retinal ON bipolar dysfunction with the anti-TRPM1 antibody. Keywords: choroidal thickness, melanocyte, TRPM1, cancer-associated retinopathy, paraneoplastic retinopathy

  1. Optics/Optical Diagnostics Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Optics/Optical Diagnostics Laboratory supports graduate instruction in optics, optical and laser diagnostics and electro-optics. The optics laboratory provides...

  2. The role of clinical parapapillary atrophy evaluation in the diagnosis of open angle glaucoma

    Directory of Open Access Journals (Sweden)

    Joshua R Ehrlich

    2010-08-01

    Full Text Available Joshua R Ehrlich, Nathan M RadcliffeDepartment of Ophthalmology, Weill Cornell Medical College, New York, NY, USAPurpose: To determine if clinical evaluation of parapapillary atrophy (PPA significantly improves the ability to distinguish open-angle glaucoma (OAG patients from glaucoma suspects.Methods: Patients in this study were under evaluation for glaucoma and had open angles, at least one reliable 24-2 SITA-standard automatic perimetry, and digital stereophotographs of the optic disc. PPA was identified clinically as a parapapillary region of absent (βPPA or hyper/hypopigmented (αPPA retinal pigment epithelium. A single masked observer evaluated photos for: vertical cup-to-disc ratio (CDR, clock hours of total and βPPA, βPPA as percentage width of the optic disc, presence or absence of βPPA at each disc quadrant, and ordinal rating of total PPA. Generalized linear models were used to determine odds of an abnormal or borderline glaucoma hemifield test (GHT as a function of PPA variables and covariates; model fit was assessed using the log-likelihood ratio test.Results: Of 410 consecutive patients, 540 eyes (of 294 patients met inclusion criteria. Mean age was greater among patients with abnormal compared with normal GHT (P < 0.001, but sex and race/ethnicity did not differ between groups (P ≥ 0.22. Age, central corneal thickness (CCT and CDR (P ≤ 0.006, but not intraocular pressure (IOP (P = 0.71, were significant univariable predictors of the odds of an abnormal GHT. All PPA parameters significantly ­predicted GHT (P ≤ 0.03, except presence of temporal βPPA (P = 0.25. Adjustment for age, CCT, IOP, and CDR reduced the association between PPA and GHT, and model fit was not greatly improved by addition of PPA variables.Conclusions: Addition of most PPA parameters to a model already containing commonly assessed variables including age, CCT, IOP, and CDR does not significantly improve the ability to distinguish OAG patients from

  3. Feasibility of the Medial Temporal lobe Atrophy index (MTAi and derived methods for measuring atrophy of the medial temporal lobe

    Directory of Open Access Journals (Sweden)

    Francisco eConejo Bayón

    2014-11-01

    Full Text Available Introduction: the Medial Temporal-lobe Atrophy index (MTAi, 2D-Medial Temporal Atrophy (2D-MTA, yearly rate of MTA (yrRMTA and yearly rate of relative MTA (yrRMTA are simple protocols for measuring the relative extent of atrophy in the MTL in relation to the global brain atrophy. Albeit preliminary studies showed interest of these methods in the diagnosis of AD, FTLD and correlation with cognitive impairment in PD, formal feasibility and validity studies remained pending. As a first step, we aimed to assess the feasibility. Mainly, we aimed to assess the reproducibility of measuring the areas needed to compute these indices. We also aimed to assess the efforts needed to start using these methods correctly. Methods: a series of 290 1.5T-MRI studies from 230 subjects ranging 65-85 years old who had been studied for cognitive impairment were used in this study. Six inexperienced tracers (IT plus one experienced tracer (ET traced the three areas needed to compute the indices. Finally, tracers underwent a short survey on their experience learning to compute the MTAi and experience of usage, including items relative to training time needed to understand and apply the MTAi, time to perform a study after training and overall satisfaction. Results: learning to trace the areas needed to compute the MTAi and derived methods is quick and easy. Results indicate very good intrarater ICC for the MTAi, good intrarater ICC for the 2D-MTA, yrMTA and yrRMTA and also good interrater ICC for the MTAi, 2D-MTA, yrMTA and yrRMTA.Conclusion: our data support that MTAi and derived methods (2D-MTA, yrMTA and yrRTMA have good to very good intrarater and interrater reproducibility and may be easily implemented in clinical practice even if new users have no experience tracing the area of regions of interest.

  4. Analysis of voxel-based rCBF in patients with olivopontocerebellar atrophy of multiple system atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Young Jin; Kang, Do Young; Park, Kyung Won; Kim, Sang Ho; Kim, Jae Woo [School of Medicine, Dong-A University, Busan (Korea, Republic of)

    2004-07-01

    Olivopontocerebellar Atrophy (OPCA) is one phenotype of multiple system atrophy (MSA) and is characterized neuropathologically by neuronal degeneration in the inferior olives, pons and cerebellar cortex. The diagnosis of OPCA requires clinical evaluation to exclude other diseases. And it's usually supported by atrophy of the cerebellum and brainstem visualized on CT or MRI. But there are some reports that the disease can occur without demonstrable atrophy in these anatomic studies. There are only a few reports about perfusion SPECT imaging in patients with OPCA. The aim of this study was to describe voxel-based rCBF of OPCA in comparison of healthy volunteers. We studied 5 patients with OPCA (1 men, 4 women: age 50.4{+-}9.6y) and age matched 13 healthy volunteers (4 men, 9 women: age 54.9{+-}6.6y). All subjects injected 20mCi of Tc-99m HMPAO and scanning was initiated 20 min after injection. Images were analyzed using SPM (SPM99) with Matlab 5.3. On visual analysis, in 3 patients with OPCA, SPECT image showed significant hypoperfusion in the cerebellum. In another 2 patients, diffuse hypoperfusion was found in the both cerebro-cerebellar hemispheres, untypical perfusion pattern in OPCA. So there is existed limitation to diagnosis by only visual analysis. On SPM analysis, in OPCA patients significantly decreased perfusion was present in culmen, tonsil, tuber in Lt. cerebellum and declive, tonsil, pyramid and inf. Semi-lunar lobule in Rt. cerebellum, Rt. inf. frontal gyrus and Rt. temporal lobe (p<0.001, uncorrected). We also performed individual analysis with SPM. Two of 5 patients have additional hypoperfusion brain lesions. In one patient, decreased perfusion found in Lt. temporal, both occipital lobe, Lt. parahippocampal gyrus. In another patient, decreased perfusion found in both frontal and parietal lobe. This study is one of a few trials analysis with SPM for OPCA. We defined the specific location of decreased perfusion in patients with OPCA.

  5. Testicular atrophy following paediatric primary orchidopexy: A prospective study.

    Science.gov (United States)

    Durell, J; Johal, N; Burge, D; Wheeler, R; Griffiths, M; Kitteringham, L; Stanton, M; Manoharan, S; Steinbrecher, H; Malone, P; Griffin, S J

    2016-08-01

    With the Nordic consensus statement advocating orchidopexy at an earlier age, the present study sought to investigate the outcomes of primary paediatric orchidopexy at a tertiary UK centre. To prospectively assess testicular atrophy following primary orchidopexy for undescended testes in a paediatric population. Secondary outcomes were complication rates and whether outcomes were dependent on grade of operating surgeon. Prospective data regarding age at operation, classification of the undescended testis, length of follow-up, and subjective comparison of intraoperative and postoperative testicular volumes compared with the contralateral testis were collected. Testicular atrophy was defined as >50% loss of testicular volume or a postoperative testicular volume atrophy occurred in 2.6% of cases. There was no reported testicular re-ascent. All secondary acquired cases underwent a previous ipsilateral hernia repair. There was no significant difference in outcomes comparing the grade of surgeon (consultant n = 8, trainee/staff-grade surgeon n = 7-8). There was a trend towards postoperative catch-up growth in approximately one fifth of cases. Previous studies have reported a testicular atrophy rate of 5%. The present study reported a similar rate of 2.6%. In agreement with a previous publication, it was also found that testicular atrophy was not dependent on the grade of operating surgeon. The mechanism for testicular catch-up growth is not well understood. Animal studies have supported the hypothesis that increased temperature has a detrimental effect on testicular volume. However, follow-up in the present cohort was short (median 6.9 months), making interpretation of this finding difficult. It is acknowledged that clinical palpation alone to determine testicular volume potentially introduces intra-observer and inter-observer error. However, prospective studies using ultrasound to determine testicular volumes following orchidopexy have reported catch-up growth. This

  6. Significance and usefulness of heart rate variability in patients with multiple system atrophy.

    Science.gov (United States)

    Furushima, Hiroshi; Shimohata, Takayoshi; Nakayama, Hideaki; Ozawa, Tetsutaro; Chinushi, Masaomi; Aizawa, Yoshifusa; Nishizawa, Masatoyo

    2012-04-01

    The purpose of this study was to investigate whether heart rate variability parameters can be useful for evaluating cardiac autonomic dysfunction in multiple system atrophy patients. Both the time and frequency domains of heart rate variability were investigated among 17 multiple system atrophy patients and 27 normal control subjects. All time- and frequency-domain measures, except the low- to high-frequency ratio, were significantly lower in multiple system atrophy patients than in controls. In multiple system atrophy patients, there were significant inverse correlations between heart rate variability parameters and disease duration, as well as disease severity, but heart rate variability parameters were not affected by other autonomic dysfunctions. The cardiac autonomic state of multiple system atrophy was characterized by decreases in both sympathetic and parasympathetic tones. Because heart rate variability parameters were not affected by other autonomic dysfunctions, this may be a useful method for evaluating cardiac autonomic dysfunction in multiple system atrophy. Copyright © 2012 Movement Disorder Society.

  7. β-amyloid, hippocampal atrophy and their relation to longitudinal brain change in cognitively normal individuals.

    Science.gov (United States)

    Fletcher, Evan; Villeneuve, Sylvia; Maillard, Pauline; Harvey, Danielle; Reed, Bruce; Jagust, William; DeCarli, Charles

    2016-04-01

    Recent literature has examined baseline hippocampal volume and extent of brain amyloidosis to test potential synergistic effects on worsening cognition and extent of brain atrophy. Use of hippocampal volume in prior studies was based on the notion that limbic circuit degeneration is an early manifestation of the Alzheimer's Disease (AD) pathophysiology. To clarify these interactions early in the AD process, we tested the effects of amyloid and baseline normalized hippocampal volume on longitudinal brain atrophy rates in a group of cognitively normal individuals. Results showed that the combination of elevated β-amyloid and baseline hippocampal atrophy is associated with increased rates specific to the limbic circuit and splenium. Importantly, this atrophy pattern emerged from a voxelwise analysis, corroborated by regression models over region of interests in native space. The results are broadly consistent with previous studies of the effects of amyloid and baseline hippocampal atrophy in normals, while pointing to accelerated atrophy of AD-vulnerable regions detectable at the preclinical stage.

  8. Systems-based Discovery of Tomatidine as a Natural Small Molecule Inhibitor of Skeletal Muscle Atrophy*

    Science.gov (United States)

    Dyle, Michael C.; Ebert, Scott M.; Cook, Daniel P.; Kunkel, Steven D.; Fox, Daniel K.; Bongers, Kale S.; Bullard, Steven A.; Dierdorff, Jason M.; Adams, Christopher M.

    2014-01-01

    Skeletal muscle atrophy is a common and debilitating condition that lacks an effective therapy. To address this problem, we used a systems-based discovery strategy to search for a small molecule whose mRNA expression signature negatively correlates to mRNA expression signatures of human skeletal muscle atrophy. This strategy identified a natural small molecule from tomato plants, tomatidine. Using cultured skeletal myotubes from both humans and mice, we found that tomatidine stimulated mTORC1 signaling and anabolism, leading to accumulation of protein and mitochondria, and ultimately, cell growth. Furthermore, in mice, tomatidine increased skeletal muscle mTORC1 signaling, reduced skeletal muscle atrophy, enhanced recovery from skeletal muscle atrophy, stimulated skeletal muscle hypertrophy, and increased strength and exercise capacity. Collectively, these results identify tomatidine as a novel small molecule inhibitor of muscle atrophy. Tomatidine may have utility as a therapeutic agent or lead compound for skeletal muscle atrophy. PMID:24719321

  9. Biomechanical implications of skeletal muscle hypertrophy and atrophy: a musculoskeletal model

    OpenAIRE

    Andrew D. Vigotsky; Bret Contreras; Chris Beardsley

    2015-01-01

    Muscle hypertrophy and atrophy occur frequently as a result of mechanical loading or unloading, with implications for clinical, general, and athletic populations. The effects of muscle hypertrophy and atrophy on force production and joint moments have been previously described. However, there is a paucity of research showing how hypertrophy and atrophy may affect moment arm (MA) lengths. The purpose of this model was to describe the mathematical relationship between the anatomical cross-secti...

  10. Associations of Cerebrovascular and Alzheimer’s Disease Pathology with Brain Atrophy

    Science.gov (United States)

    Crystal, Howard A.; Schneider, Julie A.; Bennett, David A.; Leurgans, Sue; Levine, Steven R.

    2015-01-01

    Cortical atrophy and brain vascular disease are both associated with dementia, but there are only limited pathological data on the association of brain vascular disease with cortical atrophy. We studied pathological material from the Rush Memory and Aging Project (MAP, N = 445). Cortical and hippocampal atrophy, and atherosclerosis at the circle of Willis (large vessel disease, LVD) and arteriolosclerosis (small vessel disease, SVD) were rated by neuropathologists unaware of this study’s hypothesis. Quantitative measures of Alzheimer’s disease (AD) pathology, specifically neuronal neurofibrillary tangles (NFT) and amyloid–beta (Aβ) burden, were also obtained. Chronic micro and macroscopic infarcts were noted. In ordinal logistic regression models that included age at death, sex, apoE genotype, statin-use, Aβ and NFT, more severe LVD was significantly associated with more severe cortical and hippocampal atrophy. The odds ratio for the association of the most severe LVD (compared to the least) with cortical atrophy was 2.7 (CI: 1.5–4.7) p = 0.001; for hippocampal atrophy the odds ratio was 2.8 (CI: 1.5–5.2), p = 0.001. The association of SVD with atrophy did not follow a consistent pattern. Neither macroscopic infarcts nor microscopic infarcts were associated with cortical or hippocampal atrophy (p’s > 0.15). Tangle density was associated with cortical (p = 0.014) and hippocampal atrophy (p atrophy. In this large autopsy study LVD was associated with cortical and hippocampal atrophy. The relationship between SVD and atrophy requires further study. PMID:24597507

  11. Presymptomatic atrophy in autosomal dominant Alzheimer's disease: A serial MRI study.

    Science.gov (United States)

    Kinnunen, Kirsi M; Cash, David M; Poole, Teresa; Frost, Chris; Benzinger, Tammie L S; Ahsan, R Laila; Leung, Kelvin K; Cardoso, M Jorge; Modat, Marc; Malone, Ian B; Morris, John C; Bateman, Randall J; Marcus, Daniel S; Goate, Alison; Salloway, Stephen P; Correia, Stephen; Sperling, Reisa A; Chhatwal, Jasmeer P; Mayeux, Richard P; Brickman, Adam M; Martins, Ralph N; Farlow, Martin R; Ghetti, Bernardino; Saykin, Andrew J; Jack, Clifford R; Schofield, Peter R; McDade, Eric; Weiner, Michael W; Ringman, John M; Thompson, Paul M; Masters, Colin L; Rowe, Christopher C; Rossor, Martin N; Ourselin, Sebastien; Fox, Nick C

    2017-07-22

    Identifying at what point atrophy rates first change in Alzheimer's disease is important for informing design of presymptomatic trials. Serial T1-weighed magnetic resonance imaging scans of 94 participants (28 noncarriers, 66 carriers) from the Dominantly Inherited Alzheimer Network were used to measure brain, ventricular, and hippocampal atrophy rates. For each structure, nonlinear mixed-effects models estimated the change-points when atrophy rates deviate from normal and the rates of change before and after this point. Atrophy increased after the change-point, which occurred 1-1.5 years (assuming a single step change in atrophy rate) or 3-8 years (assuming gradual acceleration of atrophy) before expected symptom onset. At expected symptom onset, estimated atrophy rates were at least 3.6 times than those before the change-point. Atrophy rates are pathologically increased up to seven years before "expected onset". During this period, atrophy rates may be useful for inclusion and tracking of disease progression. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  12. Testicular atrophy secondary to a large long standing incarcerated inguinal hernia

    Directory of Open Access Journals (Sweden)

    Nikolaos S Salemis

    2011-09-01

    Full Text Available Testicular atrophy is a rare but distressing complication of inguinal hernia repair. Apart from the postsurgical etiology, ischemic orchitis and subsequent testicular atrophy may occur secondary to compression of the testicular vessels by chronically incarcerated hernias. We present a rare case of testicular atrophy secondary to a large long standing incarcerated inguinal hernia of 2-decade duration in a 79-year-old man. Testicular atrophy should be always considered in long standing incarcerated inguinal hernias and patients should be adequately informed of this possibility during the preoperative work-up. Preoperative scrotal ultrasonography can be used to determine testicular status in this specific group of patients.

  13. Smad2/3 Proteins Are Required for Immobilization-induced Skeletal Muscle Atrophy.

    Science.gov (United States)

    Tando, Toshimi; Hirayama, Akiyoshi; Furukawa, Mitsuru; Sato, Yuiko; Kobayashi, Tami; Funayama, Atsushi; Kanaji, Arihiko; Hao, Wu; Watanabe, Ryuichi; Morita, Mayu; Oike, Takatsugu; Miyamoto, Kana; Soga, Tomoyoshi; Nomura, Masatoshi; Yoshimura, Akihiko; Tomita, Masaru; Matsumoto, Morio; Nakamura, Masaya; Toyama, Yoshiaki; Miyamoto, Takeshi

    2016-06-03

    Skeletal muscle atrophy promotes muscle weakness, limiting activities of daily living. However, mechanisms underlying atrophy remain unclear. Here, we show that skeletal muscle immobilization elevates Smad2/3 protein but not mRNA levels in muscle, promoting atrophy. Furthermore, we demonstrate that myostatin, which negatively regulates muscle hypertrophy, is dispensable for denervation-induced muscle atrophy and Smad2/3 protein accumulation. Moreover, muscle-specific Smad2/3-deficient mice exhibited significant resistance to denervation-induced muscle atrophy. In addition, expression of the atrogenes Atrogin-1 and MuRF1, which underlie muscle atrophy, did not increase in muscles of Smad2/3-deficient mice following denervation. We also demonstrate that serum starvation promotes Smad2/3 protein accumulation in C2C12 myogenic cells, an in vitro muscle atrophy model, an effect inhibited by IGF1 treatment. In vivo, we observed IGF1 receptor deactivation in immobilized muscle, even in the presence of normal levels of circulating IGF1. Denervation-induced muscle atrophy was accompanied by reduced glucose intake and elevated levels of branched-chain amino acids, effects that were Smad2/3-dependent. Thus, muscle immobilization attenuates IGF1 signals at the receptor rather than the ligand level, leading to Smad2/3 protein accumulation, muscle atrophy, and accompanying metabolic changes. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Smad2/3 Proteins Are Required for Immobilization-induced Skeletal Muscle Atrophy*

    Science.gov (United States)

    Tando, Toshimi; Hirayama, Akiyoshi; Furukawa, Mitsuru; Sato, Yuiko; Kobayashi, Tami; Funayama, Atsushi; Kanaji, Arihiko; Hao, Wu; Watanabe, Ryuichi; Morita, Mayu; Oike, Takatsugu; Miyamoto, Kana; Soga, Tomoyoshi; Nomura, Masatoshi; Yoshimura, Akihiko; Tomita, Masaru; Matsumoto, Morio; Nakamura, Masaya; Toyama, Yoshiaki; Miyamoto, Takeshi

    2016-01-01

    Skeletal muscle atrophy promotes muscle weakness, limiting activities of daily living. However, mechanisms underlying atrophy remain unclear. Here, we show that skeletal muscle immobilization elevates Smad2/3 protein but not mRNA levels in muscle, promoting atrophy. Furthermore, we demonstrate that myostatin, which negatively regulates muscle hypertrophy, is dispensable for denervation-induced muscle atrophy and Smad2/3 protein accumulation. Moreover, muscle-specific Smad2/3-deficient mice exhibited significant resistance to denervation-induced muscle atrophy. In addition, expression of the atrogenes Atrogin-1 and MuRF1, which underlie muscle atrophy, did not increase in muscles of Smad2/3-deficient mice following denervation. We also demonstrate that serum starvation promotes Smad2/3 protein accumulation in C2C12 myogenic cells, an in vitro muscle atrophy model, an effect inhibited by IGF1 treatment. In vivo, we observed IGF1 receptor deactivation in immobilized muscle, even in the presence of normal levels of circulating IGF1. Denervation-induced muscle atrophy was accompanied by reduced glucose intake and elevated levels of branched-chain amino acids, effects that were Smad2/3-dependent. Thus, muscle immobilization attenuates IGF1 signals at the receptor rather than the ligand level, leading to Smad2/3 protein accumulation, muscle atrophy, and accompanying metabolic changes. PMID:27129272

  15. miR-29b contributes to multiple types of muscle atrophy

    Science.gov (United States)

    Li, Jin; Chan, Mun Chun; Yu, Yan; Bei, Yihua; Chen, Ping; Zhou, Qiulian; Cheng, Liming; Chen, Lei; Ziegler, Olivia; Rowe, Glenn C.; Das, Saumya; Xiao, Junjie

    2017-01-01

    A number of microRNAs (miRNAs, miRs) have been shown to play a role in skeletal muscle atrophy, but their role is not completely understood. Here we show that miR-29b promotes skeletal muscle atrophy in response to different atrophic stimuli in cells and in mouse models. miR-29b promotes atrophy of myotubes differentiated from C2C12 or primary myoblasts, and conversely, its inhibition attenuates atrophy induced by dexamethasone (Dex), TNF-α and H2O2 treatment. Targeting of IGF-1 and PI3K(p85α) by miR-29b is required for induction of muscle atrophy. In vivo, miR-29b overexpression is sufficient to promote muscle atrophy while inhibition of miR-29b attenuates atrophy induced by denervation and immobilization. These data suggest that miR-29b contributes to multiple types of muscle atrophy via targeting of IGF-1 and PI3K(p85α), and that suppression of miR-29b may represent a therapeutic approach for muscle atrophy induced by different stimuli. PMID:28541289

  16. APOE ε4 is associated with disproportionate progressive hippocampal atrophy in AD.

    Directory of Open Access Journals (Sweden)

    Emily N Manning

    Full Text Available OBJECTIVES: To investigate whether APOE ε4 carriers have higher hippocampal atrophy rates than non-carriers in Alzheimer's disease (AD, mild cognitive impairment (MCI and controls, and if so, whether higher hippocampal atrophy rates are still observed after adjusting for concurrent whole-brain atrophy rates. METHODS: MRI scans from all available visits in ADNI (148 AD, 307 MCI, 167 controls were used. MCI subjects were divided into "progressors" (MCI-P if diagnosed with AD within 36 months or "stable" (MCI-S if a diagnosis of MCI was maintained. A joint multi-level mixed-effect linear regression model was used to analyse the effect of ε4 carrier-status on hippocampal and whole-brain atrophy rates, adjusting for age, gender, MMSE and brain-to-intracranial volume ratio. The difference in hippocampal rates between ε4 carriers and non-carriers after adjustment for concurrent whole-brain atrophy rate was then calculated. RESULTS: Mean adjusted hippocampal atrophy rates in ε4 carriers were significantly higher in AD, MCI-P and MCI-S (p≤0.011, all tests compared with ε4 non-carriers. After adjustment for whole-brain atrophy rate, the difference in mean adjusted hippocampal atrophy rate between ε4 carriers and non-carriers was reduced but remained statistically significant in AD and MCI-P. CONCLUSIONS: These results suggest that the APOE ε4 allele drives atrophy to the medial-temporal lobe region in AD.

  17. Fronto-striatal atrophy correlates of neuropsychiatric dysfunction in frontotemporal dementia (FTD and Alzheimer's disease (AD

    Directory of Open Access Journals (Sweden)

    Dong Seok Yi

    Full Text Available ABSTRACT Behavioural disturbances in frontotemporal dementia (FTD are thought to reflect mainly atrophy of cortical regions. Recent studies suggest that subcortical brain regions, in particular the striatum, are also significantly affected and this pathology might play a role in the generation of behavioural symptoms. Objective: To investigate prefrontal cortical and striatal atrophy contributions to behavioural symptoms in FTD. Methods: One hundred and eighty-two participants (87 FTD patients, 39 AD patients and 56 controls were included. Behavioural profiles were established using the Cambridge Behavioural Inventory Revised (CBI-R and Frontal System Behaviour Scale (FrSBe. Atrophy in prefrontal (VMPFC, DLPFC and striatal (caudate, putamen regions was established via a 5-point visual rating scale of the MRI scans. Behavioural scores were correlated with atrophy rating scores. Results: Behavioural and atrophy ratings demonstrated that patients were significantly impaired compared to controls, with bvFTD being most severely affected. Behavioural-anatomical correlations revealed that VMPFC atrophy was closely related to abnormal behaviour and motivation disturbances. Stereotypical behaviours were associated with both VMPFC and striatal atrophy. By contrast, disturbance of eating was found to be related to striatal atrophy only. Conclusion: Frontal and striatal atrophy contributed to the behavioural disturbances seen in FTD, with some behaviours related to frontal, striatal or combined fronto-striatal pathology. Consideration of striatal contributions to the generation of behavioural disturbances should be taken into account when assessing patients with potential FTD.

  18. Repurposing an orally available drug for the treatment of geographic atrophy.

    Science.gov (United States)

    Ahmed, Chulbul M; Biswal, Manas R; Li, Hong; Han, Pingyang; Ildefonso, Cristhian J; Lewin, Alfred S

    2016-01-01

    Chronic oxidative stress and subacute inflammation have been implicated as causes of age-related macular degeneration (AMD). In this study, we tested whether an orally available 5-OH-tryptamine (5HT) 1a receptor agonist, xaliproden, could protect against retinal pigment epithelium (RPE) cell damage in culture and in a mouse model of geographic atrophy. Paraquat was used to create mitochondrial oxidative stress in ARPE-19 cells, and tumor necrosis factor-α (TNF-α) was used to stimulate the production of inflammatory cytokines in these cells. The production of antioxidant proteins, metallothionein, and inflammatory cytokines was assayed with quantitative real-time PCR. Cell survival was analyzed with microscopy and a cell titer assay. Integrity of the RPE monolayer was determined by measuring the transepithelial electrical resistance (TEER) and with immunocytochemistry with zona occludens protein 1 (ZO-1) antibody. RPE atrophy was studied in mice deleted for Sod2 (the gene for mitochondrial superoxide dismutase) specifically in the RPE. The mice were treated orally with daily doses of xaliproden at 0.5 and 3 mg/kg for 4 months. The retinal structure was analyzed with spectral domain optical coherence tomography (SD-OCT) and with light and electron microscopy. Retinal function was assessed with full-field electroretinography (ERG) and with optokinetic measurements. Xaliproden led to a dose-dependent increase in cell survival following treatment with paraquat. Synthesis of the antioxidant response genes NqO1, GSTM1, CAT, HO-1, and Nrf2 was increased in response to the drug, as was the zinc chaperone metallothionein. Treatment of cells with TNF-α led to increased production of IL-1β, IL-6, chemokine (C-C motif) ligand 20 (CCL20), and vascular endothelial growth factor (VEGF) by ARPE-19 cells, and this response was attenuated by treatment with xaliproden. TNF-α also led to a decrease in the TEER that was prevented by treatment with the 5HT1a agonist. Daily gavage

  19. Muscle wasting in collagen-induced arthritis and disuse atrophy.

    Science.gov (United States)

    de Oliveira Nunes Teixeira, Vivian; Filippin, Lidiane Isabel; Viacava, Paula Ramos; de Oliveira, Patrícia Gnieslaw; Xavier, Ricardo Machado

    2013-12-01

    The mechanisms of muscle wasting and decreased mobility have a major functional effect in rheumatoid arthritis, but they have been poorly studied. The objective of our study is to describe muscular involvement and the pathways in an experimental model of arthritis compared to the pathways in disuse atrophy. Female Wistar rats were separated into three groups: control (CO), collagen-induced arthritis (CIA), and immobilized (IM). Spontaneous locomotion and weight were evaluated weekly. The gastrocnemius muscle was evaluated by histology and immunoblotting to measure the expression of myostatin (a negative regulator), LC3 (autophagy), MuRF-1 (proteasome-mediated proteolysis), MyoD, and myogenin (satellite-cell activation). The significance level was set at P muscle weight, and relative muscle weight decreased 20%, 30%, and 20%, respectively, in the CIA rats. Inflammatory infiltration and swelling were present in the gastrocnemius muscles of the CIA rats. The mean cross-sectional area was reduced by 30% in the CIA group and by 60% in the IM group. The expressions of myostatin and LC3 between the groups were similar. There was increased expression of MuRF-1 in the IM (1.9-fold) and CIA (3.1-fold) groups and of myogenin in the muscles of the CIA animals (1.7-fold), while MyoD expression was decreased in the IM (20%) rats. This study demonstrated that the development of experimental arthritis is associated with decreased mobility, body weight, and muscle loss. Both IM and CIA animal models presented muscle atrophy, but while proteolysis and the regeneration pathways were activated in the CIA model, there was no activation of regeneration in the IM model. We can assume that muscle atrophy in experimental arthritis is associated with the disease itself and not simply with decreased mobility.

  20. Fibrosis, adipogenesis, and muscle atrophy in congenital muscular torticollis.

    Science.gov (United States)

    Chen, Huan-Xiong; Tang, Sheng-Ping; Gao, Fu-Tang; Xu, Jiang-Long; Jiang, Xian-Ping; Cao, Juan; Fu, Gui-Bing; Sun, Ke; Liu, Shi-Zhe; Shi, Wei

    2014-11-01

    In the traditional view, muscle atrophy and interstitial fibrosis were regarded as the basic pathological features of congenital muscular torticollis (CMT). But in the ultrastructure study, the mesenchyme-like cells, myoblasts, myofibroblasts, and fibroblasts were found in the proliferation of interstitium of CMT. To investigate the characteristics of pathological features and the mechanisms of muscle atrophy in CMT, we retrospectively reviewed the medical records of 185 CMT patients from July 2009 to July 2011 in Shenzhen Children's Hospital in China and performed pathological studies. According to age, the 185 CMT patients were divided into 4 groups. All resected surgical specimens were processed for hematoxylin and eosin staining and Masson trichromic staining. Sudan III staining was used for frozen sections, whereas immunohistochemical staining for S-100, calpain-1, ubiquitin, and 20S proteasome was carried out on 40 CMT specimens. Eight adductor muscle specimens from 8 patients with development dysplasia of the hip were taken as control group in the immunohistochemical staining. By Masson trichromic staining, the differences in the percent area of fibrous tissue in each CMT groups were significant. In Sudan III staining and immunostaining for S-100, adipocyte hyperplasia was the pathological feature of CMT. Moreover, compared with controls, most atrophic muscle fibers in CMT specimens were found to show strong immunoreactivity for calpain-1, ubiquitin, and 20S proteasome. With increasing age, fibrosis peaked at both sides and it was low in middle age group. Adipocytes increased with age. The characteristics of pathological features in CMT are changeable with age. The calpain and the ubiquitin-proteasome system may play a role in muscle atrophy of CMT. In the CMT, adipogenesis, fibrogenesis, and myogenesis may be the results of mesenchyme-like cells in SCM (sternocleidomastoid muscle). In conclusion, the present study furthermore supports maldevelopment of the

  1. Evaluation of the endogenous glucocorticoid hypothesis of denervation atrophy

    Science.gov (United States)

    Konagaya, Masaaki; Konagaya, Yoko; Max, Stephen R.

    1988-01-01

    The effects are studied of the oral administration of RU38486, a potent selective glucocorticoid antagonist, on muscle weight, non-collagen protein content, and selected enzyme activities (choline acetyltransferase, glucose 6-phosphate dehydrogenase, and glutamine synthetase) following denervation of rat skeletal muscle. Neither decreases in muscle weight, protein content, and choline acetyltransferase activity, nor increases in the activities of glucose 6-phosphate dehydrogernase and glutamine synthetase were affected by RU38486. These data do not support the hypothesis that denervation atrophy results from enhanced sensitivity of muscle to endogenous glucocorticoids.

  2. Atrophy rates in asymptomatic amyloidosis: implications for Alzheimer prevention trials.

    Directory of Open Access Journals (Sweden)

    K Abigail Andrews

    Full Text Available There is considerable interest in designing therapeutic studies of individuals at risk of Alzheimer disease (AD to prevent the onset of symptoms. Cortical β-amyloid plaques, the first stage of AD pathology, can be detected in vivo using positron emission tomography (PET, and several studies have shown that ~1/3 of healthy elderly have significant β-amyloid deposition. Here we assessed whether asymptomatic amyloid-PET-positive controls have increased rates of brain atrophy, which could be harnessed as an outcome measure for AD prevention trials. We assessed 66 control subjects (age = 73.5±7.3 yrs; MMSE = 29±1.3 from the Australian Imaging Biomarkers & Lifestyle study who had a baseline Pittsburgh Compound B (PiB PET scan and two 3T MRI scans ~18-months apart. We calculated PET standard uptake value ratios (SUVR, and classified individuals as amyloid-positive/negative. Baseline and 18-month MRI scans were registered, and brain, hippocampal, and ventricular volumes and annualized volume changes calculated. Increasing baseline PiB-PET measures of β-amyloid load correlated with hippocampal atrophy rate independent of age (p = 0.014. Twenty-two (1/3 were PiB-positive (SUVR>1.40, the remaining 44 PiB-negative (SUVR≤1.31. Compared to PiB-negatives, PiB-positive individuals were older (76.8±7.5 vs. 71.7±7.5, p<0.05 and more were APOE4 positive (63.6% vs. 19.2%, p<0.01 but there were no differences in baseline brain, ventricle or hippocampal volumes, either with or without correction for total intracranial volume, once age and gender were accounted for. The PiB-positive group had greater total hippocampal loss (0.06±0.08 vs. 0.02±0.05 ml/yr, p = 0.02, independent of age and gender, with non-significantly higher rates of whole brain (7.1±9.4 vs. 4.7±5.5 ml/yr and ventricular (2.0±3.0 vs. 1.1±1.0 ml/yr change. Based on the observed effect size, recruiting 384 (95%CI 195-1080 amyloid-positive subjects/arm will provide 80% power to detect 25

  3. Neuropathology and Therapeutic Intervention in Spinal and Bulbar Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Haruhiko Banno

    2009-03-01

    Full Text Available Spinal and bulbar muscular atrophy (SBMA is a hereditary motor neuron disease caused by the expansion of a polyglutamine tract in the androgen receptor (AR. The histopathological finding in SBMA is loss of lower motor neurons in the anterior horn of the spinal cord as well as in the brainstem motor nuclei. Animal studies have revealed that the pathogenesis of SBMA depends on the level of serum testosterone, and that androgen deprivation mitigates neurodegeneration through inhibition of nuclear accumulation of the pathogenic AR. Heat shock proteins, ubiquitin-proteasome system and transcriptional regulation are also potential targets of therapy development for SBMA.

  4. Chorioretinal Atrophy after Spontaneous Resolution of Myopic Foveoschisis

    Directory of Open Access Journals (Sweden)

    Antonio García-Ben

    2014-01-01

    Full Text Available Myopic foveoschisis is one of the major complications of pathologic myopia, and it was most recently identified by new imaging modalities. During the natural evolution of this complication, anatomical and visual improvement without surgical intervention is an unusual course, and most of these eyes remain stable or progressively worsen. The authors report a case of a highly myopic eye that developed patchy chorioretinal atrophy after spontaneous resolution of myopic foveoschisis, which to the best of our knowledge has not been reported previously in the medical literature.

  5. Agent-based computational model investigates muscle-specific responses to disuse-induced atrophy

    Science.gov (United States)

    Martin, Kyle S.; Peirce, Shayn M.

    2015-01-01

    Skeletal muscle is highly responsive to use. In particular, muscle atrophy attributable to decreased activity is a common problem among the elderly and injured/immobile. However, each muscle does not respond the same way. We developed an agent-based model that generates a tissue-level skeletal muscle response to disuse/immobilization. The model incorporates tissue-specific muscle fiber architecture parameters and simulates changes in muscle fiber size as a result of disuse-induced atrophy that are consistent with published experiments. We created simulations of 49 forelimb and hindlimb muscles of the rat by incorporating eight fiber-type and size parameters to explore how these parameters, which vary widely across muscles, influence sensitivity to disuse-induced atrophy. Of the 49 muscles modeled, the soleus exhibited the greatest atrophy after 14 days of simulated immobilization (51% decrease in fiber size), whereas the extensor digitorum communis atrophied the least (32%). Analysis of these simulations revealed that both fiber-type distribution and fiber-size distribution influence the sensitivity to disuse atrophy even though no single tissue architecture parameter correlated with atrophy rate. Additionally, software agents representing fibroblasts were incorporated into the model to investigate cellular interactions during atrophy. Sensitivity analyses revealed that fibroblast agents have the potential to affect disuse-induced atrophy, albeit with a lesser effect than fiber type and size. In particular, muscle atrophy elevated slightly with increased initial fibroblast population and increased production of TNF-α. Overall, the agent-based model provides a novel framework for investigating both tissue adaptations and cellular interactions in skeletal muscle during atrophy. PMID:25722379

  6. Muscular hypertrophy and atrophy in normal rats provoked by the administration of normal and denervated muscle extracts.

    Science.gov (United States)

    Agüera, Eduardo; Castilla, Salvador; Luque, Evelio; Jimena, Ignacio; Leiva-Cepas, Fernando; Ruz-Caracuel, Ignacio; Peña, José

    2016-12-01

    This study was conducted to determine the effects of extracts obtained from both normal and denervated muscles on different muscle types. Wistar rats were used and were divided into a control group and four experimental groups. Each experimental group was treated intraperitoneally during 10 consecutive days with a different extract. These extracts were obtained from normal soleus muscle, denervated soleus, normal extensor digitorum longus, and denervated extensor digitorum longus. Following treatment, the soleus and extensor digitorum longus muscles were obtained for study under optic and transmission electron microscope; morphometric parameters and myogenic responses were also analyzed. The results demonstrated that the treatment with normal soleus muscle and denervated soleus muscle extracts provoked hypertrophy and increased myogenic activity. In contrast, treatment with extracts from the normal and denervated EDL had a different effect depending on the muscle analyzed. In the soleus muscle it provoked hypertrophy of type I fibers and increased myogenic activity, while in the extensor digitorum longus atrophy of the type II fibers was observed without changes in myogenic activity. This suggests that the muscular responses of atrophy and hypertrophy may depend on different factors related to the muscle type which could be related to innervation.

  7. Development and Translation of Therapies for Spinal Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Hannah K. Shorrock

    2016-07-01

    Full Text Available Spinal muscular atrophy (SMA is an autosomal recessive neuromuscular disorder characterised by widespread loss of lower motor neurons from the spinal cord, leading to progressive weakness and muscle atrophy. SMA is largely caused by homozygous loss of the survival motor neuron (SMN 1 gene, resulting in reduced levels of full-length SMN protein. Although no approved treatment is currently available for SMA, several clinical trials investigating different approaches to increase SMN levels are showing promising early results. Trials investigating the use of therapies targeting muscle strength and neuroprotective pathways are also in progress, generating the possibility of delivering combination therapies utilising both SMN-dependent and SMN-independent targets. Due to an increased understanding of the cellular and molecular consequences of SMN depletion, a second wave of therapies targeted at pathways downstream of SMN are currently undergoing preclinical development. As these therapies move forward towards the clinic, new treatment options are likely to become available, raising the potential to generate an effective ‘cure’ for SMA.

  8. Carbocalcitonin treatment in Sudeck's atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Nuti, R.; Vattimo, A.; Martini, G.; Turchetti, V.; Righi, G.A.

    1987-02-01

    The efficacy of new calcitonin, the amino analog of eel calcitonin (carboCT) on Sudeck's atrophy of the foot was investigated in 14 patients. CarboCT was administered at the dose of 40 Medical Research Council (MRC) units per day, and the duration of treatment was two to ten months. No adverse effects were noted. Bone pain and local edema decreased associated with improvement of motility. CarboCT induced a slight decrease in plasma calcium, plasma phosphate, and 24-hour urinary calcium excretion. An increase in cAMP/Cr ratio, an index of parathyroid function, was also observed (probably a manifestation of the hypocalcemic effect of calcitonin and secondary parathyroid stimulation). The whole body retention of 99mTc-MDP represents a valuable index of bone turnover, it decreased progressively and significantly on treatment. A dynamic study of local bone uptake of 99mTC-MDP was performed in eight patients. After carboCT therapy, statistically significant decreases in local blood flow, early uptake, and delayed uptake were appreciated in the involved foot. These findings lead to the conclusion that carboCT is effective in the treatment of Sudeck's atrophy.

  9. Impaired cognitive performance and hippocampal atrophy in Parkinson disease.

    Science.gov (United States)

    Yildiz, Demet; Erer, Sevda; Zarifoğlu, Mehmet; Hakyemez, Bahattin; Bakar, Mustafa; Karli, Necdet; Varlibaş, Zeynep Nigar; Tufan, Fatih

    2015-01-01

    Dementia is common in Parkinson disease (PD). Since magnetic resonance imaging has been used, hippocampal atrophy has been shown in PD patients with or without dementia. In this study we sought the correlation of cognitive decline with bilateral hippocampal volume in PD patients. Thirty-three patients with diagnosis of idiopathic PD and 16 healthy subjects were included in this study. PD patients were divided into two groups as normal cognitive function and mild cognitive impairment (MCI). The Mini-Mental State Examination and detailed cognitive assessment tests were performed for all patients for cognitive analyses. Depression was excluded by the Geriatric Depression Scale. The mean onset age of disease was 55 years for PD patients without dementia and 59 for PD patients with MCI. According to the Hoehn-Yahr scales, 24% of patients had grade 1, 58% had grade 2, and 18% had grade 3 disease. Right and left hippocampal volumes decreased along with cognitive test scores in PD patients. Increased right hippocampal volume was correlated with forward number test in the MCI-PD group. These findings suggest that memory deficit is associated with hippocampal atrophy in PD patients.

  10. Periorbital muscle atrophy associated with topical bimatoprost therapy

    Directory of Open Access Journals (Sweden)

    Wang PX

    2014-01-01

    Full Text Available Priscilla Xinhui Wang, Victor Teck Chang Koh, Jin Fong ChengDepartment of Ophthalmology, National University Health System, SingaporeAbstract: Topical Bimatoprost is a common and popular prostaglandin analog used as an ocular hypotensive agent in the treatment of glaucoma. Side effects include ocular hyperaemia, ocular pruritus, and periocular and iris pigmentary changes. Perioribital lipodystrophy is another well-documented outcome associated with chronic use of topical bimatoprost, which results in periorbital hallowing, upper eyelid sulcus deepening, eyelid retraction and enophthalmos. We report an unusual case of periocular muscle atrophy and weakness from unilateral topical bimatoprost use. Our patient had primary angle closure and experienced a right upper eyelid ptosis 2 months after she started to use topical bimatoprost in that eye. Clinical measurements of her eyelids clearly showed reduction in the function of her right levator muscle, suggesting that effects of topical bimatoprost may not be limited to periorbital fat. She was advised to stop topical bimatoprost and right ptosis correction surgery with levator muscle advancement was performed successfully. Ophthalmologists and patients should be aware of this potential rare side effect of topical bimatoprost, as it may be potentially disfiguring, especially with monocular use. However, its exact mechanism of action needs to be clarified further.Keywords: prostaglandin analog, levator, muscle atrophy, muscle weakness, ptosis, side effects

  11. Memory Impairment at Initial Clinical Presentation in Posterior Cortical Atrophy.

    Science.gov (United States)

    Ahmed, Samrah; Baker, Ian; Husain, Masud; Thompson, Sian; Kipps, Christopher; Hornberger, Michael; Hodges, John R; Butler, Christopher R

    2016-04-23

    Posterior cortical atrophy (PCA) is characterized by core visuospatial and visuoperceptual deficits, and predominant atrophy in the parieto-occipital cortex. The most common underlying pathology is Alzheimer's disease (AD). Existing diagnostic criteria suggest that episodic memory is relatively preserved. The aim of this study was to examine memory performance at initial clinical presentation in PCA, compared to early-onset AD patients (EOAD). 15 PCA patients and 32 EOAD patients, and 34 healthy controls were entered into the study. Patients were tested on the Addenbrooke's Cognitive Examination (ACE-R), consisting of subscales in memory and visuospatial skills. PCA and EOAD patients were significantly impaired compared to controls on the ACE total score (p skills (p skills compared to EOAD patients (p presentation. The findings suggest that memory impairment must be considered in assessment and management of PCA. Further study into memory in PCA is warranted, since the ACE-R is a brief screening tool and is likely to underestimate the presence of memory impairment.

  12. Picture agnosia as a characteristic of posterior cortical atrophy.

    Science.gov (United States)

    Sugimoto, Azusa; Midorikawa, Akira; Koyama, Shinichi; Futamura, Akinori; Hieda, Sotaro; Kawamura, Mitsuru

    2012-01-01

    Posterior cortical atrophy (PCA) is a degenerative disease characterized by progressive visual agnosia with posterior cerebral atrophy. We examine the role of the picture naming test and make a number of suggestions with regard to diagnosing PCA as atypical dementia. We investigated 3 cases of early-stage PCA with 7 control cases of Alzheimer disease (AD). The patients and controls underwent a naming test with real objects and colored photographs of familiar objects. We then compared rates of correct answers. Patients with early-stage PCA showed significant inability to recognize photographs compared to real objects (F = 196.284, p = 0.0000) as measured by analysis of variants. This difficulty was also significant to AD controls (F = 58.717, p = 0.0000). Picture agnosia is a characteristic symptom of early-stage PCA, and the picture naming test is useful for the diagnosis of PCA as atypical dementia at an early stage. Copyright © 2012 S. Karger AG, Basel.

  13. Connectivity network measures predict volumetric atrophy in mild cognitive impairment.

    Science.gov (United States)

    Nir, Talia M; Jahanshad, Neda; Toga, Arthur W; Bernstein, Matt A; Jack, Clifford R; Weiner, Michael W; Thompson, Paul M

    2015-01-01

    Alzheimer's disease (AD) is characterized by cortical atrophy and disrupted anatomic connectivity, and leads to abnormal interactions between neural systems. Diffusion-weighted imaging (DWI) and graph theory can be used to evaluate major brain networks and detect signs of a breakdown in network connectivity. In a longitudinal study using both DWI and standard magnetic resonance imaging (MRI), we assessed baseline white-matter connectivity patterns in 30 subjects with mild cognitive impairment (MCI, mean age 71.8 ± 7.5 years, 18 males and 12 females) from the Alzheimer's Disease Neuroimaging Initiative. Using both standard MRI-based cortical parcellations and whole-brain tractography, we computed baseline connectivity maps from which we calculated global "small-world" architecture measures, including mean clustering coefficient and characteristic path length. We evaluated whether these baseline network measures predicted future volumetric brain atrophy in MCI subjects, who are at risk for developing AD, as determined by 3-dimensional Jacobian "expansion factor maps" between baseline and 6-month follow-up anatomic scans. This study suggests that DWI-based network measures may be a novel predictor of AD progression.

  14. Progressive cerebellar atrophy: hereditary ataxias and disorders with spinocerebellar degeneration.

    Science.gov (United States)

    Wolf, Nicole I; Koenig, Michel

    2013-01-01

    The hereditary ataxias with onset in childhood are a group of heterogeneous disorders, usually with autosomal recessive inheritance. In many of them, magnetic resonance imaging (MRI) shows cerebellar atrophy. The most prominent exception to this is Friedreich's ataxia, where MRI shows normal cerebellar volume, but sometimes spinal cord atrophy. In several of the hereditary ataxias, the causative gene plays an important role in DNA repair: ataxia telangiectasia and ataxia telangiectasia-like disorder, and ataxia with oculomotor apraxia type I and II. Mitochondrial metabolism is impaired in another group of inherited ataxias including the emergent group of defects in coenzyme Q10 synthesis. Few of these disorders are amenable to effective treatment, the most important of these being vitamin E-responsive ataxia. The autosomal dominant spinocerebellar ataxias are rare in childhood. Some of them, especially SCA7 and SCA2, may begin in childhood or even infancy, family history being positive in these cases. Additional clinical clues such as presence or absence of neuropathy or oculomotor apraxia still help in making a definitive diagnosis albeit there are still many unsolved cases. In pontocerebellar hypoplasia, a neurodegenerative disease with prenatal onset, the genetic basis of the different subtypes has recently been elucidated and involves genes with different functions.

  15. Interactive segmentation for geographic atrophy in retinal fundus images.

    Science.gov (United States)

    Lee, Noah; Smith, R Theodore; Laine, Andrew F

    2008-10-01

    Fundus auto-fluorescence (FAF) imaging is a non-invasive technique for in vivo ophthalmoscopic inspection of age-related macular degeneration (AMD), the most common cause of blindness in developed countries. Geographic atrophy (GA) is an advanced form of AMD and accounts for 12-21% of severe visual loss in this disorder [3]. Automatic quantification of GA is important for determining disease progression and facilitating clinical diagnosis of AMD. The problem of automatic segmentation of pathological images still remains an unsolved problem. In this paper we leverage the watershed transform and generalized non-linear gradient operators for interactive segmentation and present an intuitive and simple approach for geographic atrophy segmentation. We compare our approach with the state of the art random walker [5] algorithm for interactive segmentation using ROC statistics. Quantitative evaluation experiments on 100 FAF images show a mean sensitivity/specificity of 98.3/97.7% for our approach and a mean sensitivity/specificity of 88.2/96.6% for the random walker algorithm.

  16. Current Status of Treatment of Spinal and Bulbar Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Fumiaki Tanaka

    2012-01-01

    Full Text Available Spinal and bulbar muscular atrophy (SBMA is the first member identified among polyglutamine diseases characterized by slowly progressive muscle weakness and atrophy of the bulbar, facial, and limb muscles pathologically associated with motor neuron loss in the spinal cord and brainstem. Androgen receptor (AR, a disease-causing protein of SBMA, is a well-characterized ligand-activated transcription factor, and androgen binding induces nuclear translocation, conformational change and recruitment of coregulators for transactivation of AR target genes. Some therapeutic strategies for SBMA are based on these native functions of AR. Since ligand-induced nuclear translocation of mutant AR has been shown to be a critical step in motor neuron degeneration in SBMA, androgen deprivation therapies using leuprorelin and dutasteride have been developed and translated into clinical trials. Although the results of these trials are inconclusive, renewed clinical trials with more sophisticated design might prove the effectiveness of hormonal intervention in the near future. Furthermore, based on the normal function of AR, therapies targeted for conformational changes of AR including amino-terminal (N and carboxy-terminal (C (N/C interaction and transcriptional coregulators might be promising. Other treatments targeted for mitochondrial function, ubiquitin-proteasome system (UPS, and autophagy could be applicable for all types of polyglutamine diseases.

  17. Transgenic mouse models of spinal and bulbar muscular atrophy (SBMA).

    Science.gov (United States)

    Katsuno, M; Adachi, H; Inukai, A; Sobue, G

    2003-01-01

    Spinal and bulbar muscular atrophy (SBMA) is a late-onset motor neuron disease characterized by proximal muscle atrophy, weakness, contraction fasciculations, and bulbar involvement. Only males develop symptoms, while female carriers usually are asymptomatic. A specific treatment for SBMA has not been established. The molecular basis of SBMA is the expansion of a trinucleotide CAG repeat, which encodes the polyglutamine (polyQ) tract, in the first exon of the androgen receptor (AR) gene. The pathologic hallmark is nuclear inclusions (NIs) containing the mutant and truncated AR with expanded polyQ in the residual motor neurons in the brainstem and spinal cord as well as in some other visceral organs. Several transgenic (Tg) mouse models have been created for studying the pathogenesis of SBMA. The Tg mouse model carrying pure 239 CAGs under human AR promoter and another model carrying truncated AR with expanded CAGs show motor impairment and nuclear NIs in spinal motor neurons. Interestingly, Tg mice carrying full-length human AR with expanded polyQ demonstrate progressive motor impairment and neurogenic pathology as well as sexual difference of phenotypes. These models recapitulate the phenotypic expression observed in SBMA. The ligand-dependent nuclear localization of the mutant AR is found to be involved in the disease mechanism, and hormonal therapy is suggested to be a therapeutic approach applicable to SBMA.

  18. Pathogenesis and therapy of spinal and bulbar muscular atrophy (SBMA).

    Science.gov (United States)

    Katsuno, Masahisa; Tanaka, Fumiaki; Adachi, Hiroaki; Banno, Haruhiko; Suzuki, Keisuke; Watanabe, Hirohisa; Sobue, Gen

    2012-12-01

    Spinal and bulbar muscular atrophy (SBMA) is a late-onset motor neuron disease characterized by slowly progressive muscle weakness and atrophy. During the last two decades, basic and clinical research has provided important insights into the disease phenotype and pathophysiology. The cause of SBMA is the expansion of a trinucleotide CAG repeat encoding a polyglutamine tract within the first exon of the androgen receptor (AR) gene. SBMA exclusively affects adult males, whereas females homozygous for the AR mutation do not manifest neurological symptoms. The ligand-dependent nuclear accumulation of the polyglutamine-expanded AR protein is central to the gender-specific pathogenesis of SBMA, although additional steps, e.g., DNA binding, inter-domain interactions, and post-translational modification of AR, modify toxicity. The interactions with co-regulators are another requisite for the toxic properties of the polyglutamine-expanded AR. It is also shown that the polyglutamine-expanded AR induces diverse molecular events, such as transcriptional dysregulation, axonal transport disruption, and mitochondrial dysfunction, which play causative roles in the neurodegeneration in SBMA. The pathogenic AR-induced myopathy also contributes to the non-cell autonomous degeneration of motor neurons. Pre-clinical studies using animal models show that the pathogenic AR-mediated neurodegeneration is suppressed by androgen inactivation, the efficacy of which has been tested in clinical trials. Pharmacological activation of cellular defense machineries, such as molecular chaperones, ubiquitin-proteasome system, and autophagy, also exerts neuroprotective effects in experimental models of SBMA.

  19. Normalized regional brain atrophy measurements in multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Zivadinov, Robert; Locatelli, Laura; Stival, Barbara; Bratina, Alessio; Nasuelli, Davide; Zorzon, Marino [Department of Clinical Medicine and Neurology, Cattinara Hospital, University of Trieste, Strada di Fiume, 447-34149, Trieste (Italy); Grop, Attilio [Department of Electrical, Electronics and Computer Science, University of Trieste, Trieste (Italy); Brnabic-Razmilic, Ozana [Statistical Analysis Centre, Heilbronn (Germany)

    2003-11-01

    There is still a controversy regarding the best regional brain atrophy measurements in multiple sclerosis (MS) studies. The aim of this study was to establish whether, in a cross-sectional study, the normalized measurements of regional brain atrophy correlate better with the MRI-defined regional brain lesions than the absolute measurements of regional brain atrophy. We assessed 45 patients with clinically definite relapsing-remitting (RR) MS (median disease duration 12 years), and measured T1-lesion load (LL) and T2-LL of frontal lobes and pons, using a reproducible semi-automated technique. The regional brain parenchymal volume (RBPV) of frontal lobes and pons was obtained by use of a computerized interactive program, which incorporates semi-automated and automated segmentation processes. A normalized measurement, the regional brain parenchymal fraction (RBPF), was calculated as the ratio of RBPV to the total volume of the parenchyma and the cerebrospinal fluid (CSF) in the frontal lobes and in the region of the pons. The total regional brain volume fraction (TRBVF) was obtained after we had corrected for the total volume of the parenchyma and the CSF in the frontal lobes and in the region of the pons for the total intracranial volume. The mean coefficient of variation (CV) for RBPF of the pons was 1% for intra-observer reproducibility and 1.4% for inter-observer reproducibility. Generally, the normalized measurements of regional brain atrophy correlated with regional brain volumes and disability better than did the absolute measurements. RBPF and TRBVF correlated with T2-LL of the pons (r=-0.37, P=0.011, and r= -0.40, P=0.0005 respectively) and with T1-LL of the pons (r=-0.27, P=0.046, and r=-0.31, P=0.04, respectively), whereas RBPV did not (r=-0.18, P = NS). T1-LL of the frontal lobes was related to RBPF (r=-0.32, P=0.033) and TRBVF (r=-0.29, P=0.05), but not to RBPV (R=-0.27, P= NS). There was only a trend of correlation between T2-LL of the frontal lobes and

  20. Treatment of hereditary optic neuropathies.

    Science.gov (United States)

    Newman, Nancy J

    2012-10-01

    The hereditary optic neuropathies are inherited disorders in which optic nerve dysfunction is a prominent feature in the phenotypic expression of disease. Optic neuropathy may be primarily an isolated finding, such as in Leber hereditary optic neuropathy and dominant optic atrophy, or part of a multisystem disorder. The pathophysiological mechanisms underlying the hereditary optic neuropathies involve mitochondrial dysfunction owing to mutations in mitochondrial or nuclear DNA that encodes proteins essential to mitochondrial function. Effective treatments are limited, and current management includes therapies directed at enhancing mitochondrial function and preventing oxidative damage, as well as genetic counselling, and supportive and symptomatic measures. New therapies, including gene therapy, are emerging via animal models and human clinical trials. Leber hereditary optic neuropathy, in particular, provides a unique model for testing promising treatments owing to its characteristic sequential bilateral involvement and the accessibility of target tissue within the eye. Lessons learned from treatment of the hereditary optic neuropathies may have therapeutic implications for other disorders of presumed mitochondrial dysfunction. In this Review, the natural history of the common inherited optic neuropathies, the presumed pathogenesis of several of these disorders, and the literature to date regarding potential therapies are summarized.

  1. Association between blood pressure levels over time and brain atrophy in the elderly.

    NARCIS (Netherlands)

    Heijer, T.; Skoog, I.; Oudkerk, M.; Leeuw, H.F. de; Groot, J.C. de; Hofman, A.W.I.M.; Breteler, M.H.M.

    2003-01-01

    The relation between blood pressure level and degree of global brain atrophy is equivocal. We evaluated past and present blood pressure levels and change in blood pressure over 20 years in relation to the degree of cortical atrophy on magnetic resonance imaging (MRI). In 1995-1996, we measured blood

  2. Dissociated small hand muscle atrophy in aging: the 'senile hand' is a split hand.

    NARCIS (Netherlands)

    Voermans, N.C.; Schelhaas, H.J.; Munneke, M.; Zwarts, M.J.

    2006-01-01

    The term 'split hand' refers to a pattern of dissociated atrophy of hand muscles and was first described in ALS. We hypothesize that this phenomenon also occurs in 'normal' aging. We investigated healthy subjects of different ages and found a progressive dissociation in atrophy of the hand muscles,

  3. Diabetes mellitus, hypertension and medial temporal lobe atrophy: the LADIS study.

    NARCIS (Netherlands)

    Korf, E.S.; Straaten, E.C. van; Leeuw, F.E. de; Flier, W.M.; Barkhof, F.; Pantoni, L.; Basile, A.M.; Inzitari, D.; Erkinjuntti, T.; Wahlund, L.O.; Rostrup, E.; Schmidt, R.; Fazekas, F.; Scheltens, P.

    2007-01-01

    HYPOTHESIS: Based on recent findings on the association between vascular risk factors and hippocampal atrophy, we hypothesized that hypertension and diabetes mellitus (DM) are associated with medial temporal lobe atrophy (MTA) in subjects without disability, independent of the severity of white

  4. Inhibition of autophagy recovers cardiac dysfunction and atrophy in response to tail-suspension.

    Science.gov (United States)

    Liu, Hong; Xie, Qiong; Xin, Bing-Mu; Liu, Jun-Lian; Liu, Yu; Li, Yong-Zhi; Wang, Jia-Ping

    2015-01-15

    Physical inactivity during space flight or prolonged bed rest may cause cardiac dysfunction and atrophy, but the exact mechanism that governs the regulation of myocardial dysfunction and cardiac atrophy remains poorly understood. Autophagy, a protein degradation pathway, has recently been shown to be involved in the regulation of cardiac dysfunction and atrophy. In this study, we investigated the relationships between dysfunction and inactivity-induced atrophy and autophagy in rat cardiac tissue. Physical inactivity was simulated by a tail suspension model, and cardiac function was examined by echocardiography. Cardiac atrophy was measured by wheat germ agglutinin staining and autophagic activity was detected by Western blot analysis and immunofluorescence staining. We demonstrated that cardiac function, especially contractility, declined and the area of cardiac atrophy increased in the tail-suspended cardiac tissue. Additionally, the cross-sectional area of myocardial cells decreased; however, apoptosis did not increase with tail suspension. Similarly, the expression of autophagy-related proteins and the number of autophagosomes were elevated in the tail-suspended cardiac tissue. Moreover, the administration of chloroquine, an autophagy inhibitor, reversed cardiac dysfunction and atrophy via the suppression of autophagic activity during suspension. Our results indicate that autophagy facilitates the development and progression of cardiac dysfunction and atrophy induced by tail suspension. Our studies hint that the components of the autophagy-related signaling pathway are potential therapeutic targets for the treatment of cardiac diseases induced by physical inactivity. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Association between blood pressure levels over time and brain atrophy in the elderly

    NARCIS (Netherlands)

    den Heijer, T; Skoog, [No Value; Oudkerk, M; de Leeuw, FE; de Groot, JC; Hofman, A; Breteler, MMB

    2003-01-01

    The relation between blood pressure level and degree of global brain atrophy is equivocal. We evaluated past and present blood pressure levels and change in blood pressure over 20 years in relation to the degree of cortical atrophy on magnetic resonance imaging (MRI). In 1995-1996, we measured blood

  6. Association between blood pressure levels over time and brain atrophy in the elderly.

    NARCIS (Netherlands)

    Heijer, T.; Skoog, I.; Oudkerk, M.; Leeuw, H.F. de; Groot, J.C. de; Hofman, A.W.I.M.; Breteler, M.H.M.

    2003-01-01

    The relation between blood pressure level and degree of global brain atrophy is equivocal. We evaluated past and present blood pressure levels and change in blood pressure over 20 years in relation to the degree of cortical atrophy on magnetic resonance imaging (MRI). In 1995-1996, we measured blood

  7. Brain atrophy in patients with arterial disease. The SMART-MR study

    NARCIS (Netherlands)

    Appelman, A.P.A.

    2008-01-01

    Brain atrophy is often observed on magnetic resonance imaging (MRI) in the elderly. This is of clinical importance since the extent and rate of progression of brain atrophy are associated with future cognitive deterioration and conversion to Alzheimer’s dementia. The overall aim of this thesis was t

  8. Dominant inherited distal spinal muscular atrophy with atrophic and hypertrophic calves

    NARCIS (Netherlands)

    Groen, R J; Sie, O G; van Weerden, T W

    1993-01-01

    The clinical, electrophysiological, radiological and morphological data of 3 members of a family with autosomal dominant distal spinal muscular atrophy (DSMA) are reported. One patient has the clinical picture of peroneal muscular atrophy with atrophic calves. His father and sister suffer from cramp

  9. Toll-like Receptor 4 Signaling in Ventilator-induced Diaphragm Atrophy.

    NARCIS (Netherlands)

    Schellekens, W.J.M.; Hees, H.W.H. van; Vaneker, M.; Linkels, M.; Dekhuijzen, P.N.R.; Scheffer, G.J.; Hoeven, J.G. van der; Heunks, L.M.A.

    2012-01-01

    BACKGROUND:: Mechanical ventilation induces diaphragm muscle atrophy, which plays a key role in difficult weaning from mechanical ventilation. The signaling pathways involved in ventilator-induced diaphragm atrophy are poorly understood. The current study investigated the role of Toll-like receptor

  10. Relating Cortical Atrophy in Temporal Lobe Epilepsy with Graph Diffusion-Based Network Models

    Science.gov (United States)

    Abdelnour, Farras; Mueller, Susanne; Raj, Ashish

    2015-01-01

    Mesial temporal lobe epilepsy (TLE) is characterized by stereotyped origination and spread pattern of epileptogenic activity, which is reflected in stereotyped topographic distribution of neuronal atrophy on magnetic resonance imaging (MRI). Both epileptogenic activity and atrophy spread appear to follow white matter connections. We model the networked spread of activity and atrophy in TLE from first principles via two simple first order network diffusion models. Atrophy distribution is modeled as a simple consequence of the propagation of epileptogenic activity in one model, and as a progressive degenerative process in the other. We show that the network models closely reproduce the regional volumetric gray matter atrophy distribution of two epilepsy cohorts: 29 TLE subjects with medial temporal sclerosis (TLE-MTS), and 50 TLE subjects with normal appearance on MRI (TLE-no). Statistical validation at the group level suggests high correlation with measured atrophy (R = 0.586 for TLE-MTS, R = 0.283 for TLE-no). We conclude that atrophy spread model out-performs the hyperactivity spread model. These results pave the way for future clinical application of the proposed model on individual patients, including estimating future spread of atrophy, identification of seizure onset zones and surgical planning. PMID:26513579

  11. Correlation of hippocampal atrophy with hyperhomocysteinemia in hemodialysis patients: An exploratory pilot study.

    Science.gov (United States)

    Maesato, Kyoko; Ohtake, Takayasu; Mochida, Yasuhiro; Ishioka, Kunihiro; Oka, Machiko; Moriya, Hidekazu; Hidaka, Sumi; Kobayashi, Shuzo

    2017-01-01

    Cognitive impairment is one of the important critical issues in hemodialysis (HD) patients. However, the associating factors of brain atrophy in HD patients have not been fully elucidated. Brain magnetic resonance imaging (MRI) was performed in 34 of total 72 HD outpatients in our dialysis center. These MRI images were analyzed by an application software; Voxel-based Specific Regional Analysis System for Alzheimer's Disease (VSRAD). VSRAD quantitatively calculates the extent of brain atrophy (percent of volume reduction) comparing with a MRI imaging database of 80 age-matched healthy controls. The extent of both hippocampal and whole-brain atrophy was evaluated with possible contributing factors. In all patients, the mean extent of hippocampal atrophy was 27.3%, and the mean extent of whole-brain atrophy was 11.2%. The extent of hippocampal atrophy was significantly correlated with low body mass index (BMI), total serum homocysteine (tHcy) levels, and brachial-ankle pulse wave velocity (baPWV). The extent of whole-brain atrophy showed significant correlations with age, hypoalbuminemia, and baPWV. Based on the multiple regression analysis, tHcy was an independent determinant of hippocampal atrophy (β = 0.460, R2 = 0.189, Patrophy (β = 0.594, R2 = 0.333, Patrophy was significantly correlated with hyperhomocysteinemia in HD patients.

  12. Evaluating Alzheimer’s Disease Progression Using Rate of Regional Hippocampal Atrophy

    Science.gov (United States)

    Frankó, Edit; Joly, Olivier

    2013-01-01

    Alzheimer’s disease (AD) is characterized by neurofibrillary tangle and neuropil thread deposition, which ultimately results in neuronal loss. A large number of magnetic resonance imaging studies have reported a smaller hippocampus in AD patients as compared to healthy elderlies. Even though this difference is often interpreted as atrophy, it is only an indirect measurement. A more direct way of measuring the atrophy is to use repeated MRIs within the same individual. Even though several groups have used this appropriate approach, the pattern of hippocampal atrophy still remains unclear and difficult to relate to underlying pathophysiology. Here, in this longitudinal study, we aimed to map hippocampal atrophy rates in patients with AD, mild cognitive impairment (MCI) and elderly controls. Data consisted of two MRI scans for each subject. The symmetric deformation field between the first and the second MRI was computed and mapped onto the three-dimensional hippocampal surface. The pattern of atrophy rate was similar in all three groups, but the rate was significantly higher in patients with AD than in control subjects. We also found higher atrophy rates in progressive MCI patients as compared to stable MCI, particularly in the antero-lateral portion of the right hippocampus. Importantly, the regions showing the highest atrophy rate correspond to those that were described to have the highest burden of tau deposition. Our results show that local hippocampal atrophy rate is a reliable biomarker of disease stage and progression and could also be considered as a method to objectively evaluate treatment effects. PMID:23951142

  13. Endometrial safety of ultra-low-dose Vagifem 10 microg in postmenopausal women with vaginal atrophy

    DEFF Research Database (Denmark)

    Ulrich, L S G; Naessen, T; Elia, D

    2010-01-01

    The objective of the study was to evaluate the endometrial safety of a 10 microg estradiol vaginal tablet in the treatment of vaginal atrophy in postmenopausal women.......The objective of the study was to evaluate the endometrial safety of a 10 microg estradiol vaginal tablet in the treatment of vaginal atrophy in postmenopausal women....

  14. Dominant inherited distal spinal muscular atrophy with atrophic and hypertrophic calves

    NARCIS (Netherlands)

    Groen, R J; Sie, O G; van Weerden, T W

    1993-01-01

    The clinical, electrophysiological, radiological and morphological data of 3 members of a family with autosomal dominant distal spinal muscular atrophy (DSMA) are reported. One patient has the clinical picture of peroneal muscular atrophy with atrophic calves. His father and sister suffer from cramp

  15. Cerebrospinal fluid volumetric MRI mapping as a simple measurement for evaluating brain atrophy

    NARCIS (Netherlands)

    De Vis, J B; Zwanenburg, J J|info:eu-repo/dai/nl/290473683; van der Kleij, L A; Spijkerman, J M; Biessels, G J|info:eu-repo/dai/nl/165576367; Hendrikse, J|info:eu-repo/dai/nl/266590268; Petersen, E T

    2016-01-01

    OBJECTIVES: To assess whether volumetric cerebrospinal fluid (CSF) MRI can be used as a surrogate for brain atrophy assessment and to evaluate how the T2 of the CSF relates to brain atrophy. METHODS: Twenty-eight subjects [mean age 64 (sd 2) years] were included; T1-weighted and CSF MRI were perform

  16. Association between blood pressure levels over time and brain atrophy in the elderly

    NARCIS (Netherlands)

    den Heijer, T; Skoog, [No Value; Oudkerk, M; de Leeuw, FE; de Groot, JC; Hofman, A; Breteler, MMB

    2003-01-01

    The relation between blood pressure level and degree of global brain atrophy is equivocal. We evaluated past and present blood pressure levels and change in blood pressure over 20 years in relation to the degree of cortical atrophy on magnetic resonance imaging (MRI). In 1995-1996, we measured blood

  17. Relating Cortical Atrophy in Temporal Lobe Epilepsy with Graph Diffusion-Based Network Models.

    Science.gov (United States)

    Abdelnour, Farras; Mueller, Susanne; Raj, Ashish

    2015-10-01

    Mesial temporal lobe epilepsy (TLE) is characterized by stereotyped origination and spread pattern of epileptogenic activity, which is reflected in stereotyped topographic distribution of neuronal atrophy on magnetic resonance imaging (MRI). Both epileptogenic activity and atrophy spread appear to follow white matter connections. We model the networked spread of activity and atrophy in TLE from first principles via two simple first order network diffusion models. Atrophy distribution is modeled as a simple consequence of the propagation of epileptogenic activity in one model, and as a progressive degenerative process in the other. We show that the network models closely reproduce the regional volumetric gray matter atrophy distribution of two epilepsy cohorts: 29 TLE subjects with medial temporal sclerosis (TLE-MTS), and 50 TLE subjects with normal appearance on MRI (TLE-no). Statistical validation at the group level suggests high correlation with measured atrophy (R = 0.586 for TLE-MTS, R = 0.283 for TLE-no). We conclude that atrophy spread model out-performs the hyperactivity spread model. These results pave the way for future clinical application of the proposed model on individual patients, including estimating future spread of atrophy, identification of seizure onset zones and surgical planning.

  18. Quantitative analysis of the muscle atrophy in osteoarthritis of the hip by computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Tajiri, Masahiro; Hieda, Hiroshi (Kurume Univ., Fukuoka (Japan). School of Medicine)

    1984-06-01

    Twenty normal hips and 30 cases of the unilateral osteoarthritic hips were examined by computed tomography in order to measure the atrophy of the muscles around the hip. We discussed the relationship among the muscle atrophy, stages of the osteoarthritic hip, and the clinical score of the JOA's criteria. The results were as follows: 1. There is no difference between the muscle volume of both sides in normal hips. 2. Atrophy of the gluteus maximus and the gluteus medius were already observed at the preosteoarthritic stage and the gluteus minimus, the tensor fasciae latae, iliopsoas revealed atrophy at the late stage. 3. There was a negative correlation between the percentage of atrophy of the gluteus maximus and the clinical score of the JOA's criteria. 4. In cases of normal position of the greater trochanter, artophy of the gluteus medius was more distinguished in cases of abductors of grade 4 by MMT than in those of normal grade.

  19. Large deletions within the spinal muscular atrophy gene region in a patient with spinal muscular atrophy type 3

    Institute of Scientific and Technical Information of China (English)

    Wei Wei; Chunyue Chen; Wenting Liu; Zhenfang Du; Xiaoling Chen; Xianning Zhang

    2011-01-01

    Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration and loss of anterior horn cells in the spinal cord and brain stem nuclei, leading to progressive limb and trunk paralysis and muscular atrophy. Depending on the age of onset and maximum muscular function achieved, SMA is recognized as SMA1, SMA2, SMA3 or SMA4, and most patients have a deletion or truncation of the survival motor neuron 1 (SMN1) gene. In this report, we present a patient with a mild SMA phenotype, SMA3, and define his genetic abnormality. Tetra-primer amplification refractory mutation system PCR combined with restriction fragment length polymorphism analysis and array comparative genomic hybridization were used to determine the genetic variations in this patient. A 500 kb deletion in chromosome 5q13.2, including homozygous deletion of neuronal apoptosis inhibitory protein, and heterozygous deletion of occludin and B-double prime 1 was identified. This SMA region deletion did not involve SMN, indicating that SMN was likely to function normally. The phenotype was dependent of the large deletion and neuronal apoptosis inhibitory protein, occludin and B-double prime 1 may be candidate genes for SMA3.

  20. Semi-automatic geographic atrophy segmentation for SD-OCT images.

    Science.gov (United States)

    Chen, Qiang; de Sisternes, Luis; Leng, Theodore; Zheng, Luoluo; Kutzscher, Lauren; Rubin, Daniel L

    2013-01-01

    Geographic atrophy (GA) is a condition that is associated with retinal thinning and loss of the retinal pigment epithelium (RPE) layer. It appears in advanced stages of non-exudative age-related macular degeneration (AMD) and can lead to vision loss. We present a semi-automated GA segmentation algorithm for spectral-domain optical coherence tomography (SD-OCT) images. The method first identifies and segments a surface between the RPE and the choroid to generate retinal projection images in which the projection region is restricted to a sub-volume of the retina where the presence of GA can be identified. Subsequently, a geometric active contour model is employed to automatically detect and segment the extent of GA in the projection images. Two image data sets, consisting on 55 SD-OCT scans from twelve eyes in eight patients with GA and 56 SD-OCT scans from 56 eyes in 56 patients with GA, respectively, were utilized to qualitatively and quantitatively evaluate the proposed GA segmentation method. Experimental results suggest that the proposed algorithm can achieve high segmentation accuracy. The mean GA overlap ratios between our proposed method and outlines drawn in the SD-OCT scans, our method and outlines drawn in the fundus auto-fluorescence (FAF) images, and the commercial software (Carl Zeiss Meditec proprietary software, Cirrus version 6.0) and outlines drawn in FAF images were 72.60%, 65.88% and 59.83%, respectively.

  1. HDAC1 activates FoxO and is both sufficient and required for skeletal muscle atrophy

    Science.gov (United States)

    Beharry, Adam W.; Sandesara, Pooja B.; Roberts, Brandon M.; Ferreira, Leonardo F.; Senf, Sarah M.; Judge, Andrew R.

    2014-01-01

    ABSTRACT The Forkhead box O (FoxO) transcription factors are activated, and necessary for the muscle atrophy, in several pathophysiological conditions, including muscle disuse and cancer cachexia. However, the mechanisms that lead to FoxO activation are not well defined. Recent data from our laboratory and others indicate that the activity of FoxO is repressed under basal conditions via reversible lysine acetylation, which becomes compromised during catabolic conditions. Therefore, we aimed to determine how histone deacetylase (HDAC) proteins contribute to activation of FoxO and induction of the muscle atrophy program. Through the use of various pharmacological inhibitors to block HDAC activity, we demonstrate that class I HDACs are key regulators of FoxO and the muscle-atrophy program during both nutrient deprivation and skeletal muscle disuse. Furthermore, we demonstrate, through the use of wild-type and dominant-negative HDAC1 expression plasmids, that HDAC1 is sufficient to activate FoxO and induce muscle fiber atrophy in vivo and is necessary for the atrophy of muscle fibers that is associated with muscle disuse. The ability of HDAC1 to cause muscle atrophy required its deacetylase activity and was linked to the induction of several atrophy genes by HDAC1, including atrogin-1, which required deacetylation of FoxO3a. Moreover, pharmacological inhibition of class I HDACs during muscle disuse, using MS-275, significantly attenuated both disuse muscle fiber atrophy and contractile dysfunction. Together, these data solidify the importance of class I HDACs in the muscle atrophy program and indicate that class I HDAC inhibitors are feasible countermeasures to impede muscle atrophy and weakness. PMID:24463822

  2. Cerebrospinal fluid volumetric MRI mapping as a simple measurement for evaluating brain atrophy.

    Science.gov (United States)

    De Vis, J B; Zwanenburg, J J; van der Kleij, L A; Spijkerman, J M; Biessels, G J; Hendrikse, J; Petersen, E T

    2016-05-01

    To assess whether volumetric cerebrospinal fluid (CSF) MRI can be used as a surrogate for brain atrophy assessment and to evaluate how the T2 of the CSF relates to brain atrophy. Twenty-eight subjects [mean age 64 (sd 2) years] were included; T1-weighted and CSF MRI were performed. The first echo data of the CSF MRI sequence was used to obtain intracranial volume, CSF partial volume was measured voxel-wise to obtain CSF volume (VCSF) and the T2 of CSF (T2,CSF) was calculated. The correlation between VCSF/T2,CSF and brain atrophy scores [global cortical atrophy (GCA) and medial temporal lobe atrophy (MTA)] was evaluated. Relative total, peripheral subarachnoidal, and ventricular VCSF increased significantly with increased scores on the GCA and MTA (R = 0.83, 0.78 and 0.78 and R = 0.72, 0.62 and 0.86). Total, peripheral subarachnoidal, and ventricular T2 of the CSF increased significantly with higher scores on the GCA and MTA (R = 0.72, 0.70 and 0.49 and R = 0.60, 0.57 and 0.41). A fast, fully automated CSF MRI volumetric sequence is an alternative for qualitative atrophy scales. The T2 of the CSF is related to brain atrophy and could thus be a marker of neurodegenerative disease. • A 1:11 min CSF MRI volumetric sequence can evaluate brain atrophy. • CSF MRI provides accurate atrophy assessment without partial volume effects. • CSF MRI data can be processed quickly without user interaction. • The measured T 2 of the CSF is related to brain atrophy.

  3. Optic glioma

    Science.gov (United States)

    Glioma - optic; Optic nerve glioma; Juvenile pilocytic astrocytoma; Brain cancer - optic glioma ... Optic gliomas are rare. The cause of optic gliomas is unknown. Most optic gliomas are slow-growing ...

  4. Association of retinal and macular damage with brain atrophy in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Jan Dörr

    Full Text Available Neuroaxonal degeneration in the central nervous system contributes substantially to the long term disability in multiple sclerosis (MS patients. However, in vivo determination and monitoring of neurodegeneration remain difficult. As the widely used MRI-based approaches, including the brain parenchymal fraction (BPF have some limitations, complementary in vivo measures for neurodegeneration are necessary. Optical coherence tomography (OCT is a potent tool for the detection of MS-related retinal neurodegeneration. However, crucial aspects including the association between OCT- and MRI-based atrophy measures or the impact of MS-related parameters on OCT parameters are still unclear. In this large prospective cross-sectional study on 104 relapsing remitting multiple sclerosis (RRMS patients we evaluated the associations of retinal nerve fiber layer thickness (RNFLT and total macular volume (TMV with BPF and addressed the impact of disease-determining parameters on RNFLT, TMV or BPF. BPF, normalized for subject head size, was estimated with SIENAX. Relations were analyzed primarily by Generalized Estimating Equation (GEE models considering within-patient inter-eye relations. We found that both RNFLT (p = 0.019, GEE and TMV (p = 0.004, GEE associate with BPF. RNFLT was furthermore linked to the disease duration (p<0.001, GEE but neither to disease severity nor patients' age. Contrarily, BPF was rather associated with severity (p<0.001, GEE than disease duration and was confounded by age (p<0.001, GEE. TMV was not associated with any of these parameters. Thus, we conclude that in RRMS patients with relatively short disease duration and rather mild disability RNFLT and TMV reflect brain atrophy and are thus promising parameters to evaluate neurodegeneration in MS. Furthermore, our data suggest that RNFLT and BPF reflect different aspects of MS. Whereas BPF best reflects disease severity, RNFLT might be the better parameter for monitoring axonal

  5. Longitudinal patterns of leukoaraiosis and brain atrophy in symptomatic small vessel disease.

    Science.gov (United States)

    Lambert, Christian; Benjamin, Philip; Zeestraten, Eva; Lawrence, Andrew J; Barrick, Thomas R; Markus, Hugh S

    2016-04-01

    Cerebral small vessel disease is a common condition associated with lacunar stroke, cognitive impairment and significant functional morbidity. White matter hyperintensities and brain atrophy, seen on magnetic resonance imaging, are correlated with increasing disease severity. However, how the two are related remains an open question. To better define the relationship between white matter hyperintensity growth and brain atrophy, we applied a semi-automated magnetic resonance imaging segmentation analysis pipeline to a 3-year longitudinal cohort of 99 subjects with symptomatic small vessel disease, who were followed-up for ≥1 years. Using a novel two-stage warping pipeline with tissue repair step, voxel-by-voxel rate of change maps were calculated for each tissue class (grey matter, white matter, white matter hyperintensities and lacunes) for each individual. These maps capture both the distribution of disease and spatial information showing local rates of growth and atrophy. These were analysed to answer three primary questions: first, is there a relationship between whole brain atrophy and magnetic resonance imaging markers of small vessel disease (white matter hyperintensities or lacune volume)? Second, is there regional variation within the cerebral white matter in the rate of white matter hyperintensity progression? Finally, are there regionally specific relationships between the rates of white matter hyperintensity progression and cortical grey matter atrophy? We demonstrate that the rates of white matter hyperintensity expansion and grey matter atrophy are strongly correlated (Pearson's R = -0.69, P atrophy occurs annually (P atrophy rates, in the medial-frontal, orbito-frontal, parietal and occipital regions. Conversely, increased rates of global grey matter atrophy are significantly associated with faster white matter hyperintensity growth in the frontal and parietal regions. Together, these results link the progression of white matter hyperintensities

  6. A Patient With PHACE Syndrome With Marked Ipsilateral Cerebral Atrophy

    Directory of Open Access Journals (Sweden)

    Nan-Koong Wang

    2010-04-01

    Full Text Available The association of posterior fossa malformation, facial cavernous hemangioma, arterial anomalies, coarctation of the aorta/cardiac defects and eye abnormalities (PHACE syndrome represents a rare congenital anomaly with a broad spectrum of clinical manifestations and female predominance. We herein report on a girl who manifested the typical clinical features of PHACE syndrome, unusually associated with severe ipsilateral cerebral atrophy and hemiplegia. She received surgical aortoplasty, local steroid injection and laser therapy for the hemangioma, and intense physical therapy soon after diagnosis. The etiology of PHACE syndrome remains unclear, and its clinical spectrum is broad. The current case suggests that the spectrum of PHACE syndrome should be further expanded to include other forms of cerebral disorder.

  7. Unusual association of sporadic olivopontocerebellar atrophy and motor neuron disease.

    Science.gov (United States)

    Testa, D; Tiranti, V; Girotti, F

    2002-12-01

    Sporadic olivopontocerebellar atrophy (OPCA) is a neurodegenerative disorder that presents a wide clinical spectrum. Motor neuron disease (MND) is characterized by a selective degeneration of motor neurons. A 60-year-old man developed slurred speech and unsteadiness of gait. He had also noticed difficulty in holding his head upright and shoulder weakness. The disease had a rapid progression. At the age of 63 years, magnetic resonance imaging supported a diagnosis of OPCA, and a diagnosis of MND was suggested by clinical and electrophysiological findings. He also had upward gaze palsy. A muscular biopsy showed sporadic ragged red and Cox deficient fibers. The present case could define a unique disorder, as the occasional occurrence of two degenerative disorders appears unlikely.

  8. Spinal muscular atrophy: Factors that modulate motor neurone vulnerability.

    Science.gov (United States)

    Tu, Wen-Yo; Simpson, Julie E; Highley, J Robin; Heath, Paul R

    2017-02-02

    Spinal muscular atrophy (SMA), a leading genetic cause of infant death, is a neurodegenerative disease characterised by the selective loss of particular groups of motor neurones in the anterior horn of the spinal cord with concomitant muscle weakness. To date, no effective treatment is available, however, there are ongoing clinical trials are in place which promise much for the future. However, there remains an ongoing problem in trying to link a single gene loss to motor neurone degeneration. Fortunately, given successful disease models that have been established and intensive studies on SMN functions in the past ten years, we are fast approaching the stage of identifying the underlying mechanisms of SMA pathogenesis Here we discuss potential disease modifying factors on motor neurone vulnerability, in the belief that these factors give insight into the pathological mechanisms of SMA and therefore possible therapeutic targets.

  9. The nature of the autonomic dysfunction in multiple system atrophy

    Science.gov (United States)

    Parikh, Samir M.; Diedrich, Andre; Biaggioni, Italo; Robertson, David

    2002-01-01

    The concept that multiple system atrophy (MSA, Shy-Drager syndrome) is a disorder of the autonomic nervous system is several decades old. While there has been renewed interest in the movement disorder associated with MSA, two recent consensus statements confirm the centrality of the autonomic disorder to the diagnosis. Here, we reexamine the autonomic pathophysiology in MSA. Whereas MSA is often thought of as "autonomic failure", new evidence indicates substantial persistence of functioning sympathetic and parasympathetic nerves even in clinically advanced disease. These findings help explain some of the previously poorly understood features of MSA. Recognition that MSA entails persistent, constitutive autonomic tone requires a significant revision of our concepts of its diagnosis and therapy. We will review recent evidence bearing on autonomic tone in MSA and discuss their therapeutic implications, particularly in terms of the possible development of a bionic baroreflex for better control of blood pressure.

  10. Exercise Therapy in Spinobulbar Muscular Atrophy and Other Neuromuscular Disorders

    DEFF Research Database (Denmark)

    Dahlqvist, Julia Rebecka; Vissing, John

    2016-01-01

    There is no curative treatment for most neuromuscular disorders. Exercise, as a treatment for these diseases, has therefore received growing attention. When executed properly, exercise can maintain and improve health and reduce the risk of cardiovascular disease, obesity, and diabetes. In persons...... in patients with neuromuscular diseases associated with weakness and wasting. We review studies that have investigated different types of exercise in both myopathies and motor neuron diseases, with particular emphasis on training of persons affected by spinobulbar muscular atrophy (SBMA). Finally, we provide...... with muscle wasting due to neuromuscular conditions, however, a common belief has been that physical activity could accelerate degeneration of the diseased muscle and a careful approach to training has therefore been suggested. In this review, we describe the current knowledge about physical training...

  11. Alexander disease with mild dorsal brainstem atrophy and infantile spasms.

    Science.gov (United States)

    Torisu, Hiroyuki; Yoshikawa, Yoko; Yamaguchi-Takada, Yui; Yano, Tamami; Sanefuji, Masafumi; Ishizaki, Yoshito; Sawaishi, Yukio; Hara, Toshiro

    2013-05-01

    We present the case of a Japanese male infant with Alexander disease who developed infantile spasms at 8 months of age. The patient had a cluster of partial seizures at 4 months of age. He presented with mild general hypotonia and developmental delay. Macrocephaly was not observed. Brain magnetic resonance imaging (MRI) findings fulfilled all MRI-based criteria for the diagnosis of Alexander disease and revealed mild atrophy of the dorsal pons and medulla oblongata with abnormal intensities. DNA analysis disclosed a novel heterozygous missense mutation (c.1154 C>T, p.S385F) in the glial fibrillary acidic protein gene. At 8 months of age, tonic spasms occurred, and electroencephalography (EEG) revealed hypsarrhythmia. Lamotrigine effectively controlled the infantile spasms and improved the abnormal EEG findings. Although most patients with infantile Alexander disease have epilepsy, infantile spasms are rare. This comorbid condition may be associated with the distribution of the brain lesions and the age at onset of Alexander disease.

  12. Strategies for treating scoliosis in children with spinal muscular atrophy.

    Science.gov (United States)

    Tobert, Daniel G; Vitale, Michael G

    2013-11-01

    Progressive pulmonary dysfunction is a major complication of spinal muscular atrophy (SMA). Growing constructs are a well-established alternative to spinal arthrodesis to maximize pulmonary growth. We describe patients who demonstrated sustained pulmonary function and improved quality of life following hybrid growing construct implantation. The purpose of this article is to demonstrate a range of approaches for managing scoliosis in children with SMA by utilizing vertical expandable prosthetic titanium rib implantation or growing rods with lateral rib fixation to improve clinical and patient-reported outcomes. Pulmonary compromise and quality of life decline are leading concerns in the SMA population. This case series highlights important surgical strategies that can be utilized to treat scoliosis in patients with SMA.

  13. Recommendations for the management of postmenopausal vaginal atrophy

    DEFF Research Database (Denmark)

    Sturdee, D W; Panay, N; Ulrich, Lian

    2010-01-01

    for hormone replacement therapy (HRT) over recent years that has suggested an increased risk of breast cancer, heart disease and stroke. But, regardless of whether these scares are justified, local treatment of vaginal atrophy is not associated with these possible risks of systemic HRT. Other reasons......Unlike hot flushes and night sweats which resolve spontaneously in time, atrophic symptoms affecting the vagina and lower urinary tract are often progressive and frequently require treatment. The prevalence of vaginal dryness increases as a woman advances through the postmenopausal years, causing...... for the continued suffering in silence may be cultural and an understandable reluctance to discuss such matters, particularly with a male doctor, but the medical profession must also take much of the blame for failing to enquire of all postmenopausal women about the possibility of vaginal atrophic symptoms. Vaginal...

  14. [Development of therapeutics for spinal and bulbar muscular atrophy (SBMA)].

    Science.gov (United States)

    Sobue, Gen

    2003-11-01

    Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's disease, is a hereditary motor neuron disease that affects males, caused by the expansion of a polyglutamine (polyQ) tract in androgen receptor (AR). Female carriers are usually asymptomatic. The transgenic mouse (Tg) model carrying a full-length human AR with expanded polyQ has significant gender-related motor impairment. This phenotype is inhibited by castration, which prevents nuclear translocation of mutant AR. Leuprorelin, an LHRH agonist that reduces testosterone release from the testis, also rescues motor dysfunction and nuclear accumulation of mutant AR in the male Tg. Over-expression of a molecular chaperone HSP70, which renatures misfolded mutant AR, ameliorates neuromuscular phenotypes of the Tg by reducing nuclear-localized mutant AR. HSP70 appears to enhance the degradation of mutant AR via ubiquitin-proteasome pathway. These experimental approaches indicate the possibility of clinical application of drugs, such as leuprorelin, for SBMA patients.

  15. Neocortical Neuronal Loss in Patients with Multiple System Atrophy

    DEFF Research Database (Denmark)

    Salvesen, Lisette; Winge, Kristian; Brudek, Tomasz

    2016-01-01

    To determine the extent of neocortical involvement in multiple system atrophy (MSA), we used design-based stereological methods to estimate the total numbers of neurons, oligodendrocytes, astrocytes, and microglia in the frontal, parietal, temporal, and occipital cortex of brains from 11 patients...... with MSA and 11 age- and gender-matched control subjects. The stereological data were supported by cell marker expression analyses in tissue samples from the prefrontal cortex. We found significantly fewer neurons in the frontal and parietal cortex of MSA brains compared with control brains. Significantly...... more astrocytes and microglia were observed in the frontal, parietal, and temporal cortex of MSA brains, whereas no change in the total number of oligodendrocytes was seen in any of the neocortical regions. There were significantly fewer neurons in the frontal cortex of MSA patients with impaired...

  16. Optic pathway degeneration in Japanese black cattle.

    Science.gov (United States)

    Chiba, Shiori; Funato, Shingo; Horiuchi, Noriyuki; Matsumoto, Kotaro; Inokuma, Hisashi; Furuoka, Hidefumi; Kobayashi, Yoshiyasu

    2015-02-01

    Degeneration of the optic pathway has been reported in various animal species including cattle. We experienced a case of bilateral optic tract degeneration characterized by severe gliosis in a Japanese black cattle without any obvious visual defects. To evaluate the significance, pathological nature and pathogenesis of the lesions, we examined the optic pathway in 60 cattle (41 Japanese black, 13 Holstein and 6 crossbreed) with or without ocular abnormalities. None of these animals had optic canal stenosis. Degenerative changes with severe gliosis in the optic pathway, which includes the optic nerve, optic chiasm and optic tract, were only observed in 8 Japanese black cattle with or without ocular abnormalities. Furthermore, strong immunoreactivity of glial fibrillary acidic protein was observed in the retinal stratum opticum and ganglion cell layer in all 5 cattle in which the optic pathway lesions could be examined. As etiological research, we also examined whether the concentrations of vitamin A and vitamin B12 or bovine viral diarrhea virus (BVDV) infection was associated with optic pathway degeneration. However, our results suggested that the observed optic pathway degeneration was probably not caused by these factors. These facts indicate the presence of optic pathway degeneration characterized by severe gliosis that has never been reported in cattle without bilateral compressive lesions in the optic pathway or bilateral severe retinal atrophy.

  17. Clinical significance of proliferative inflammatory atrophy in prostate biopsy.

    Science.gov (United States)

    Celma, A; Servián, P; Planas, J; Placer, J; Quilez, M T; Arbós, M A; de Torres, I; Morote, J

    2014-03-01

    Proliferative inflammatory atrophy (PIA) is a frequently observed lesion in prostate biopsies and some authors have postulated its involvement in prostate carcinogenesis. However, the mechanisms that would permit its neoplastic transformation and the clinical significance of its finding in a prostate biopsy is currently not well known. To analyze the characteristics of the PIA lesion, its possible role in prostate carcinogenesis and its relation with the tumor aggressiveness. A systematic review was made of the literature in PubMed with the terms «proliferative inflammatory atrophy» or «PIA» and «prostate.» The most important findings are summarized in accordance with the study objective. PIA seems to be involved in prostate carcinogenesis. This hypothesis is based on its frequent association to cancer lesions (CaP) and on some genetic alterations that are common to the high grade prostatic intraepithelial neoplasia (HGPIN) and to the CaP, fundamentally deficit in GSTP1 expression and overexpression of AGR2. Currently, there are no epidemiological studies that evaluate the incidence of PIA or its association with HGPIN and CaP. Only one study, carried out by our group, has determined the global incidence of PIA in 30% of the prostate biopsies, a lower association to CaP than the HGPIN lesion and an association between PIA and tumors of lower and insignificant grade. PIA shares genetic alterations with HGPIN and CaP. Currently, there is no epidemiologic evidence to consider that the PIA is associated to a greater incidence of CaP and the genetic and epidemiological data available suggest its association to not very aggressive tumors. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

  18. [Infantile spinal atrophy: our experience in the last 25 years].

    Science.gov (United States)

    Madrid Rodríguez, A; Martínez Martínez, P L; Ramos Fernández, J M; Urda Cardona, A; Martínez Antón, J

    2015-03-01

    To determine the incidence of spinal muscular atrophy (SMA) in our study population and genetic distribution and epidemiological and clinical characteristics and to analyze the level of care and development. Retrospective descriptive study of patients treated in our hospital in the past 25 years (from 1987 to early 2013), with a clinical and neurophysiological diagnosis of SMA. A total of 37 patients were found, representing an incidence for our reference population and year of 1 case per 10,000 live births. Males predominated (male/female ratio: 1.6/1). The type of SMA diagnosed more frequently was, type i (26 cases), followed by type ii (9 cases), one case with SMA type iii, and one case of spinal muscular atrophy with respiratory distress type 1 (SMARD1). The most frequent genetic alteration was homozygous deletion of exons 7 and 8 of SMN1 gene in 31 cases, while five patients had atypical genetics. The median survival for type i was 8.0 months and 15.8 years for type ii. The incidence in our population remains stable at around 1/10.000. Most cases presented with, predominantly male, typical genetics. In approximately 1/10 patients the genetic alteration was different from the classical one to the SMN gene. The prevalence of AME unrelated SMN gene was 1/37. The level of care has increased in line with social and welfare demands in recent years. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  19. Ventricular assist devices in heart failure: how to support the heart but prevent atrophy?

    Science.gov (United States)

    Pokorný, M; Cervenka, L; Netuka, I; Pirk, J; Koňařík, M; Malý, J

    2014-01-01

    Ventricular assist devices (VAD) have recently established themselves as an irreplaceable therapeutic modality of terminal heart failure. Because of the worldwide shortage of donors, ventricular assist devices play a key role in modern heart failure therapy. Some clinical data have revealed the possibility of cardiac recovery during VAD application. On the other hand, both clinical and experimental studies indicate the risk of the cardiac atrophy development, especially after prolonged mechanical unloading. Little is known about the specific mechanisms governing the unloading-induced cardiac atrophy and about the exact ultrastructural changes in cardiomyocytes, and even less is known about the ways in which possible therapeutical interventions may affect heart atrophy. One aim of this review was to present important aspects of the development of VAD-related cardiac atrophy in humans and we also review the most significant observations linking clinical data and those derived from studies using experimental models. The focus of this article was to review current methods applied to alleviate cardiac atrophy which follows mechanical unloading of the heart. Out of many pharmacological agents studied, only the selective beta2 agonist clenbuterol has been proved to have a significantly beneficial effect on unloading-induced atrophy. Mechanical means of atrophy alleviation also seem to be effective and promising.

  20. Mapping the Progression of Atrophy in Early- and Late-Onset Alzheimer's Disease.

    Science.gov (United States)

    Migliaccio, Raffaella; Agosta, Federica; Possin, Katherine L; Canu, Elisa; Filippi, Massimo; Rabinovici, Gil D; Rosen, Howard J; Miller, Bruce L; Gorno-Tempini, Maria Luisa

    2015-01-01

    The term early-onset Alzheimer's disease (EOAD) identifies patients who meet criteria for AD, but show onset of symptoms before the age of 65. We map progression of gray matter atrophy in EOAD patients compared to late-onset AD (LOAD). T1-weighted MRI scans were obtained at diagnosis and one-year follow-up from 15 EOAD, 10 LOAD, and 38 age-matched controls. Voxel-based and tensor-based morphometry were used, respectively, to assess the baseline and progression of atrophy. At baseline, EOAD patients already showed a widespread atrophy in temporal, parietal, occipital, and frontal cortices. After one year, EOAD had atrophy progression in medial temporal and medial parietal cortices. At baseline, LOAD patients showed atrophy in the medial temporal regions only, and, after one year, an extensive pattern of atrophy progression in the same neocortical cortices of EOAD. Although atrophy mainly involved different lateral neocortical or medial temporal hubs at baseline, it eventually progressed along the same brain default-network regions in both groups. The cortical region showing a significant progression in both groups was the medial precuneus/posterior cingulate.

  1. Congenital Bone Fractures in Spinal Muscular Atrophy: Functional Role for SMN Protein in Bone Remodeling

    Science.gov (United States)

    Shanmugarajan, Srinivasan; Swoboda, Kathryn J.; Iannaccone, Susan T.; Ries, William L.; Maria, Bernard L.; Reddy, Sakamuri V.

    2009-01-01

    Spinal muscular atrophy is the second most common fatal childhood disorder. Core clinical features include muscle weakness caused by degenerating lower motor neurons and a high incidence of bone fractures and hypercalcemia. Fractures further compromise quality of life by progression of joint contractures or additional loss of motor function. Recent observations suggest that bone disease in spinal muscular atrophy may not be attributed entirely to lower motor neuron degeneration. The presence of the spinal muscular atrophy disease-determining survival motor neuron gene (SMN), SMN expression, and differential splicing in bone-resorbing osteoclasts was recently discovered. Its ubiquitous expression and the differential expression of splice variants suggest that SMN has specific roles in bone cell function. SMN protein also interacts with osteoclast stimulatory factor. Mouse models of human spinal muscular atrophy disease suggest a potential role of SMN protein in skeletal development. Dual energy x-ray absorptiometry analysis demonstrated a substantial decrease in total bone area and poorly developed caudal vertebra in the mouse model. These mice also had pelvic bone fractures. Studies delineating SMN signaling mechanisms and gene transcription in a cell-specific manner will provide important molecular insights into the pathogenesis of bone disease in children with spinal muscular atrophy. Moreover, understanding bone remodeling in spinal muscular atrophy may lead to novel therapeutic approaches to enhance skeletal health and quality of life. This article reviews the skeletal complications associated with spinal muscular atrophy and describes a functional role for SMN protein in osteoclast development and bone resorption activity. PMID:17761651

  2. The relationship between tear severity, fatty infiltration, and muscle atrophy in the supraspinatus.

    Science.gov (United States)

    Barry, Jeffrey J; Lansdown, Drew A; Cheung, Sunny; Feeley, Brian T; Ma, C Benjamin

    2013-01-01

    Fatty infiltration and muscle atrophy have been described as interrelated characteristic changes that occur within the muscles of the rotator cuff after cuff tears, and both are independently associated with poor outcomes after surgical repair. We hypothesize that fatty infiltration and muscle atrophy are two distinct processes independently associated with supraspinatus tears. A retrospective review of 377 patients who underwent shoulder magnetic resonance imaging at one institution was performed. Multivariate analysis was performed based on parameters including age, sex, rotator cuff tear severity, fatty infiltration grade, and muscle atrophy. A total of 116 patients (30.8%) had full-thickness tears of the supraspinatus, 153 (40.6%) had partial thickness tears, and 108 (28.7%) had no evidence of tear. With increasing tear severity, the prevalence of substantial fatty infiltration (grade ≥2) increased: 6.5% of patients with no tears vs 41.4% for complete tears (P tear severity: 36.1% of no tears vs 77.6% of complete tears (P muscle atrophy when taking into account sex, age, and tear severity. Fatty infiltration and muscle atrophy are independently associated processes. Fatty infiltration is also related to increasing age, muscle tear severity, and sex, whereas muscle atrophy is related to increasing age but not tear severity. In patients without rotator cuff tears, fatty infiltration and atrophy prevalence increased independently with increasing age. Copyright © 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

  3. Cerebrospinal fluid volumetric MRI mapping as a simple measurement for evaluating brain atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Vis, J.B. de; Zwanenburg, J.J.; Kleij, L.A. van der; Spijkerman, J.M.; Hendrikse, J. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Biessels, G.J. [University Medical Center Utrecht, Department of Neurology, Brain Center Rudolf Magnus, Utrecht (Netherlands); Petersen, E.T. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Hvidovre Hospital, Danish Research Centre for Magnetic Resonance, Hvidovre (Denmark)

    2016-05-15

    To assess whether volumetric cerebrospinal fluid (CSF) MRI can be used as a surrogate for brain atrophy assessment and to evaluate how the T{sub 2} of the CSF relates to brain atrophy. Twenty-eight subjects [mean age 64 (sd 2) years] were included; T{sub 1}-weighted and CSF MRI were performed. The first echo data of the CSF MRI sequence was used to obtain intracranial volume, CSF partial volume was measured voxel-wise to obtain CSF volume (V{sub CSF}) and the T{sub 2} of CSF (T{sub 2,CSF}) was calculated. The correlation between V{sub CSF} / T{sub 2,CSF} and brain atrophy scores [global cortical atrophy (GCA) and medial temporal lobe atrophy (MTA)] was evaluated. Relative total, peripheral subarachnoidal, and ventricular V{sub CSF} increased significantly with increased scores on the GCA and MTA (R = 0.83, 0.78 and 0.78 and R = 0.72, 0.62 and 0.86). Total, peripheral subarachnoidal, and ventricular T{sub 2} of the CSF increased significantly with higher scores on the GCA and MTA (R = 0.72, 0.70 and 0.49 and R = 0.60, 0.57 and 0.41). A fast, fully automated CSF MRI volumetric sequence is an alternative for qualitative atrophy scales. The T{sub 2} of the CSF is related to brain atrophy and could thus be a marker of neurodegenerative disease. (orig.)

  4. Calpain and caspase-3 play required roles in immobilization-induced limb muscle atrophy.

    Science.gov (United States)

    Talbert, Erin E; Smuder, Ashley J; Min, Kisuk; Kwon, Oh Sung; Powers, Scott K

    2013-05-15

    Prolonged skeletal muscle inactivity results in a rapid decrease in fiber size, primarily due to accelerated proteolysis. Although several proteases are known to contribute to disuse muscle atrophy, the ubiquitin proteasome system is often considered the most important proteolytic system during many conditions that promote muscle wasting. Emerging evidence suggests that calpain and caspase-3 may also play key roles in inactivity-induced atrophy of respiratory muscles, but it remains unknown if these proteases are essential for disuse atrophy in limb skeletal muscles. Therefore, we tested the hypothesis that activation of both calpain and caspase-3 is required for locomotor muscle atrophy induced by hindlimb immobilization. Seven days of immobilization (i.e., limb casting) promoted significant atrophy in type I muscle fibers of the rat soleus muscle. Independent pharmacological inhibition of calpain or caspase-3 prevented this casting-induced atrophy. Interestingly, inhibition of calpain activity also prevented caspase-3 activation, and, conversely, inhibition of caspase-3 prevented calpain activation. These findings indicate that a regulatory cross talk exists between these proteases and provide the first evidence that the activation of calpain and caspase-3 is required for inactivity-induced limb muscle atrophy.

  5. Influence of muscle length on muscle atrophy in the mouse tibialis anterior and soleus muscles.

    Science.gov (United States)

    Fujita, Naoto; Fujimoto, Taro; Tasaki, Hiromitsu; Arakawa, Takamitsu; Matsubara, Takako; Miki, Akinori

    2009-02-01

    The tibialis anterior and soleus muscles were fixed at the stretched or shortened positions to examine the influence of muscle length on muscle atrophy. Mice were divided into control (C), hindlimb suspension (HS), hindlimb suspension with ankle joint fixation at the maximum dorsiflexion (HSD), and hindlimb suspension with ankle joint fixation at the maximum plantarflexion (HSP). During the hindlimb suspension, the length of these muscles in the HS and HSP groups was very similar. Fourteen days after the hindlimb suspension, the atrophy of the tibialis anterior muscle in the HS and HSP groups was evidently milder than that in the HSD group, and that in the HS and HSP groups was very similar, suggesting that atrophy of the tibialis anterior muscle might largely depend on muscle length. Atrophy of the soleus muscle in the HSD group was milder than that in the HS and HSP groups, indicating that atrophy of the soleus muscle might also depend on muscle length. But atrophy of this muscle in the HSP group was milder than that in the HS group. These results demonstrate that some factors induced by the joint immobilization might be effective in preventing atrophy of the soleus muscle.

  6. Brain MRI atrophy quantification in MS: From methods to clinical application.

    Science.gov (United States)

    Rocca, Maria A; Battaglini, Marco; Benedict, Ralph H B; De Stefano, Nicola; Geurts, Jeroen J G; Henry, Roland G; Horsfield, Mark A; Jenkinson, Mark; Pagani, Elisabetta; Filippi, Massimo

    2017-01-24

    Patients with the main clinical phenotypes of multiple sclerosis (MS) manifest varying degrees of brain atrophy beyond that of normal aging. Assessment of atrophy helps to distinguish clinically and cognitively deteriorating patients and predicts those who will have a less-favorable clinical outcome over the long term. Atrophy can be measured from brain MRI scans, and many technological improvements have been made over the last few years. Several software tools, with differing requirements on technical ability and levels of operator intervention, are currently available and have already been applied in research or clinical trial settings. Despite this, the measurement of atrophy in routine clinical practice remains an unmet need. After a short summary of the pathologic substrates of brain atrophy in MS, this review attempts to guide the clinician towards a better understanding of the methods currently used for quantifying brain atrophy in this condition. Important physiologic factors that affect brain volume measures are also considered. Finally, the most recent research on brain atrophy in MS is summarized, including whole brain and various compartments thereof (i.e., white matter, gray matter, selected CNS structures). Current methods provide sufficient precision for cohort studies, but are not adequate for confidently assessing changes in individual patients over the scale of months or a few years. © 2016 American Academy of Neurology.

  7. Inflammation and focal atrophy in prostate needle biopsy cores and association to prostatic adenocarcinoma.

    Science.gov (United States)

    Benedetti, Ines; Bettin, Alfonso; Reyes, Niradiz

    2016-10-01

    The possible origin of proliferative inflammatory atrophy in the regenerative proliferation of prostate epithelial cells in response to injury caused by inflammation, and their relation to prostate adenocarcinoma have not been defined. Inflammation and focal atrophy are common pathological findings in prostate biopsies, currently not routinely included in surgical pathology reports. The objective of the study was to determine the correlation between inflammation and focal atrophy with prostate adenocarcinoma. Prostate needle biopsies from 203 patients with clinical parameters suspicious for malignancy were evaluated for the presence and extent of chronic inflammation, type and grade of focal atrophy, high-grade intraepithelial neoplasia, and adenocarcinoma. Relations among them and with age were also analyzed. χ(2) tests and binary logistic regression were used to estimate associations. Chronic inflammation was observed in 77.3% of the biopsies, significantly associated to adenocarcinoma (P = .031). Moderate/severe inflammation in at least 1 biopsy core increased the risk of prostate adenocarcinoma (odds ratio, 2.94; 95% confidence interval, 1.27-6.8), whereas glandular localization of inflammation decreased the risk. Focal atrophy was present in 72.9% of the biopsies, proliferative inflammatory atrophy was the most common type, and its grade was significantly associated to inflammation (P atrophy were associated to high levels of inflammation, supporting its previously proposed inflammatory nature. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. The Association Between Neurocysticercosis and Hippocampal Atrophy is Related to Age.

    Science.gov (United States)

    Del Brutto, Oscar H; Issa, Naoum P; Salgado, Perla; Del Brutto, Victor J; Zambrano, Mauricio; Lama, Julio; García, Héctor H

    2017-01-11

    Neurocysticercosis (NCC) has been associated with hippocampal atrophy, but the prevalence and pathogenic mechanisms implicated in this relationship are unknown. Using a population-based, case-control study design, residents in a rural village (Atahualpa) aged ≥ 40 years with calcified NCC were identified as cases and paired to NCC-free individuals (control subjects) matched by age, sex, and level of education. Cases and control subjects underwent magnetic resonance imaging for hippocampal rating according to the Scheltens' scale for medial temporal atrophy and were interviewed to identify those with a clinical seizure disorder. The prevalence of hippocampal atrophy was compared between cases and control subjects by the use of the McNemar's test for correlated proportions. Seventy-five individuals with calcified NCC and their matched control subjects were included in the analysis. Hippocampal atrophy was noted in 26 (34.7%) cases and nine (12%) control subjects (odds ratio: 4.4; 95% confidence interval: 1.6-14.9, P atrophy, and the single control subject had normal hippocampi. This study confirms an association between NCC and hippocampal atrophy, and shows that this association is stronger in older age groups. This suggests that NCC-related hippocampal atrophy takes a long time to develop. © The American Society of Tropical Medicine and Hygiene.

  9. The combined influence of stretch, mobility and electrical stimulation in the prevention of muscle fiber atrophy caused hypokinesia and hypodynamia

    Science.gov (United States)

    Goldspink, G.; Goldspink, D.; Loughna, P.

    1984-01-01

    The morphological and biochemical changes which occur in the hind limb muscles of the rat in response to hypokinesia and hypodynamia were investigated. Hind limb cast fixation and suspension techniques were employed to study the musclar atrophy after five days of hypokinesia and hypodynamia induced by suspension, appreciable muscular atrophy was apparent, particularly in the anti-gravity muscles. The effect of passive stretching and electrical stimulation on muscle atrophy was studied. Changes in muscle protein mass were assessed with spectrophotometric and radioactive techniques. Passive stretch is shown to counteract muscle disuse atrophy. The change in the numbers of specific muscle fibers in atrophied muscles is discussed.

  10. Bilateral optic neuropathy in acute cryptococcal meningitis

    Institute of Scientific and Technical Information of China (English)

    Qi Zhe Ngoo; Li Min Evelyn Tai; Wan Hazabbah Wan Hitam; John Tharakan

    2016-01-01

    We reported a case of cryptococcal meningitis presenting with bilateral optic neuropathy in an immunocompetent patient. A 64-year-old Malay gentleman with no medical comorbidities presented with acute bilateral blurring of vision for a week, which was associated with generalised throbbing headache and low grade fever. He also had som-nolence and altered consciousness. Visual acuity in both eyes was no perception of light with poor pupillary reflexes. Extraocular muscle movements were normal. Anterior segments were unremarkable bilaterally. Fundoscopy revealed bilateral optic disc swelling. CT scan of the brain showed multifocal infarct, but no meningeal enhancement or mass. Cerebrospinal fluid opening pressure was normal, while its culture grew Cryptococcus neoformans. A diagnosis of cryptococcal meningitis with bilateral optic neuropathy was made. Patient was treated with a six-week course of intravenous flu-conazole and started concomitantly on a fortnight's course of intravenous amphotericin B. After that, his general condition improved, but there was still no improvement in his visual acuity. On reviewing at two months post-initiation of treatment, fundi showed bilateral optic atrophy. Bilateral optic neuropathy secondary to cryptococcal meningitis was rare. The prognosis was guarded due to the sequelae of optic atrophy. Anti-fungal medication alone may not be sufficient to manage this condition. However, evidence for other treatment modalities is still lacking and further clinical studies are required.

  11. Severe brain atrophy in the elderly as a risk factor for lower respiratory tract infection

    Directory of Open Access Journals (Sweden)

    Okada R

    2012-11-01

    Full Text Available Rieko Okada,1 Takashi Okada,2 Akira Okada,2 Hideyuki Muramoto,3 Masahisa Katsuno,4 Gen Sobue,4 Nobuyuki Hamajima11Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 2Okada Medical Clinic, 3Muramoto Clinic, 4Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, JapanBackground: The purpose of this study is to determine whether elderly subjects with severe brain atrophy, which is associated with neurodegeneration and difficulty swallowing (dysphagia, are more susceptible to lower respiratory tract infections (LRTI, including pneumonia.Methods: The severity of brain atrophy was assessed by computed tomography in 51 nursing home residents aged 60–96 years. The incidence of LRTI, defined by body temperature ≥ 38.0°C, presence of two or more respiratory symptoms, and use of antibiotics, was determined over 4 years. The incidence of LRTI was compared according to the severity and type of brain atrophy.Results: The incidence rate ratio of LRTI was significantly higher (odds ratio 4.60, 95% confidence interval 1.18–17.93, fully adjusted P = 0.028 and the time to the first episode of LRTI was significantly shorter (log-rank test, P = 0.019 in subjects with severe brain atrophy in any lobe. Frontal and parietal lobe atrophy was associated with a significantly increased risk of LRTI, while temporal lobe atrophy, ventricular dilatation, and diffuse white matter lesions did not influence the risk of LRTI.Conclusion: Elderly subjects with severe brain atrophy are more susceptible to LRTI, possibly as a result of neurodegeneration causing dysphagia and silent aspiration. Assessing the severity of brain atrophy might be useful to identify subjects at increased risk of respiratory infections in a prospective manner.Keywords: brain atrophy, dysphagia, elderly, pneumonia, respiratory infection, white matter lesions

  12. Heterogeneous atrophy occurs within individual lower limb muscles during 60 days of bed rest.

    Science.gov (United States)

    Miokovic, Tanja; Armbrecht, Gabriele; Felsenberg, Dieter; Belavý, Daniel L

    2012-11-01

    To better understand disuse muscle atrophy, via magnetic resonance imaging, we sequentially measured muscle cross-sectional area along the entire length of all individual muscles from the hip to ankle in nine male subjects participating in 60-day head-down tilt bed rest (2nd Berlin BedRest Study; BBR2-2). We hypothesized that individual muscles would not atrophy uniformly along their length such that different regions of an individual muscle would atrophy to different extents. This hypothesis was confirmed for the adductor magnus, vasti, lateral hamstrings, medial hamstrings, rectus femoris, medial gastrocnemius, lateral gastrocnemius, tibialis posterior, flexor hallucis longus, flexor digitorum longus, peroneals, and tibialis anterior muscles (P ≤ 0.004). In contrast, the hypothesis was not confirmed in the soleus, adductor brevis, gracilis, pectineus, and extensor digitorum longus muscles (P ≥ 0.20). The extent of atrophy only weakly correlated (r = -0.30, P atrophy during bed rest also differed between muscles (P muscles recovered to their baseline size between 14 and 90 days after bed rest, but flexor hallucis longus, flexor digitorum longus, and lateral gastrocnemius required longer than 90 days before recovery occurred. On the basis of findings of differential atrophy between muscles and evidence in the literature, we interpret our findings of intramuscular atrophy to reflect differential disuse of functionally different muscle regions. The current work represents the first lower-limb wide survey of intramuscular differences in disuse atrophy. We conclude that intramuscular differential atrophy occurs in most, but not all, of the muscles of the lower limb during prolonged bed rest.

  13. APOE ε4 Is Associated with Disproportionate Progressive Hippocampal Atrophy in AD

    Science.gov (United States)

    Manning, Emily N.; Barnes, Josephine; Cash, David M.; Bartlett, Jonathan W.; Leung, Kelvin K.; Ourselin, Sebastien; Fox, Nick C.

    2014-01-01

    Objectives To investigate whether APOE ε4 carriers have higher hippocampal atrophy rates than non-carriers in Alzheimer's disease (AD), mild cognitive impairment (MCI) and controls, and if so, whether higher hippocampal atrophy rates are still observed after adjusting for concurrent whole-brain atrophy rates. Methods MRI scans from all available visits in ADNI (148 AD, 307 MCI, 167 controls) were used. MCI subjects were divided into “progressors” (MCI-P) if diagnosed with AD within 36 months or “stable” (MCI-S) if a diagnosis of MCI was maintained. A joint multi-level mixed-effect linear regression model was used to analyse the effect of ε4 carrier-status on hippocampal and whole-brain atrophy rates, adjusting for age, gender, MMSE and brain-to-intracranial volume ratio. The difference in hippocampal rates between ε4 carriers and non-carriers after adjustment for concurrent whole-brain atrophy rate was then calculated. Results Mean adjusted hippocampal atrophy rates in ε4 carriers were significantly higher in AD, MCI-P and MCI-S (p≤0.011, all tests) compared with ε4 non-carriers. After adjustment for whole-brain atrophy rate, the difference in mean adjusted hippocampal atrophy rate between ε4 carriers and non-carriers was reduced but remained statistically significant in AD and MCI-P. Conclusions These results suggest that the APOE ε4 allele drives atrophy to the medial-temporal lobe region in AD. PMID:24878738

  14. Prevalence and cognitive impact of medial temporal atrophy in a hospital stroke service: retrospective cohort study.

    Science.gov (United States)

    Kebets, Valeria; Gregoire, Simone M; Charidimou, Andreas; Barnes, Josephine; Rantell, Khadija; Brown, Martin M; Jäger, Hans R; Cipolotti, Lisa; Werring, David J

    2015-08-01

    Cerebrovascular disease and neurodegeneration cause cognitive impairment and frequently coexist. Our objectives were to investigate the prevalence and cognitive impact of medial temporal lobe atrophy - a radiological marker often associated with Alzheimer's disease - in a hospital stroke service. Retrospective cohort study of patients from a hospital stroke service. Patients assessed for suspected ischemic stroke or transient ischemic attack, irrespective of final diagnosis, underwent neuropsychological testing and magnetic resonance imaging. medial temporal lobe atrophy, white matter hyperintensities, lacunes, and cerebral microbleeds were rated using established criteria and validated scales. The associations between medial temporal lobe atrophy and cognition were tested using multivariable logistic regression analyses, adjusted for age and imaging markers of cerebrovascular disease. Three hundred and ninety-three patients were included, of whom 169 (43%; 95% confidence interval: 38·1-48·1%) had medial temporal lobe atrophy; in 38 patients (9·7%), medial temporal lobe atrophy was severe (mean score ≥2). In unadjusted logistic regression analyses in the whole cohort, mean medial temporal lobe atrophy score was associated with verbal memory, nominal and perceptual skills, executive function, and speed and attention. After adjustment for age, white matter hyperintensities, number of lacunes, presence of cerebral microbleeds, previous ischemic stroke or transient ischemic attack, and premorbid intelligence quotient, mean medial temporal lobe atrophy score remained associated with impairment in verbal memory (odds ratio: 1·64; 95% confidence interval 1·04-2·58) and nominal skills (odds ratio: 1·61; 95% confidence interval 1·04-2·48). Medial temporal lobe atrophy is common and has an independent impact on cognitive function in a stroke service population, independent of confounding factors including age and magnetic resonance imaging markers of

  15. MRI phenotypes based on cerebral lesions and atrophy in patients with multiple sclerosis.

    Science.gov (United States)

    Tauhid, Shahamat; Neema, Mohit; Healy, Brian C; Weiner, Howard L; Bakshi, Rohit

    2014-11-15

    While disease categories (i.e. clinical phenotypes) of multiple sclerosis (MS) are established, there remains MRI heterogeneity among patients within those definitions. MRI-defined lesions and atrophy show only moderate inter-correlations, suggesting that they represent partly different processes in MS. We assessed the ability of MRI-based categorization of cerebral lesions and atrophy in individual patients to identify distinct phenotypes. We studied 175 patients with MS [age (mean ± SD) 42.7 ± 9.1 years, 124 (71%) women, Expanded Disability Status (EDSS) score 2.5 ± 2.3, n = 18 (10%) clinically isolated demyelinating syndrome (CIS), n=115 (66%) relapsing-remitting (RR), and n = 42 (24%) secondary progressive (SP)]. Brain MRI measures included T2 hyperintense lesion volume (T2LV) and brain parenchymal fraction (to assess whole brain atrophy). Medians were used to create bins for each parameter, with patients assigned a low or high severity score. Four MRI phenotype categories emerged: Type I = low T2LV/mild atrophy [n = 67 (38%); CIS = 14, RR = 47, SP = 6]; Type II = high T2LV/mild atrophy [n = 21 (12%); RR = 19, SP = 2]; Type III = low T2LV/high atrophy [n = 21 (12%); CIS = 4, RR = 16, SP = 1]; and Type IV = high T2LV/high atrophy [n = 66 (38%); RR = 33, S P = 33]. Type IV was the most disabled and was the only group showing a correlation between T2LV vs. BPF and MRI vs. EDSS score (all p atrophy in individual patients to identify four phenotypes in MS. Most patients have congruent extremes related to the degree of lesions and atrophy. However, many have a dissociation. Longitudinal studies will help define the stability of these patterns and their role in risk stratification. Copyright © 2014. Published by Elsevier B.V.

  16. Tract-specific atrophy in focal epilepsy: Disease, genetics, or seizures?

    Science.gov (United States)

    Vaughan, David N; Raffelt, David; Curwood, Evan; Tsai, Meng-Han; Tournier, Jacques-Donald; Connelly, Alan; Jackson, Graeme D

    2017-02-01

    To investigate whether genetics, underlying pathology, or repeated seizures contribute to atrophy in specific white matter tracts. Medically refractory unilateral temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS-TLE, n = 26) was studied as an archetype of focal epilepsy, using fixel-based analysis of diffusion-weighted imaging. A genetic effect was assessed in first-degree relatives of HS-TLE subjects who did not have epilepsy themselves (HS-1°Rel; n = 26). The role of disease process was uncovered by comparing HS-TLE to unilateral TLE with normal clinical magnetic resonance imaging (MRI-neg TLE; n = 26, matched for seizure severity). The effect of focal seizures was inferred from lateralized atrophy common to both HS-TLE and MRI-neg TLE, in comparison to healthy controls (n = 76). HS-1 °Rel had bilaterally small hippocampi, but no focal white matter atrophy was detected, indicating a limited effect of genetics. HS-TLE subjects had lateralized atrophy of most temporal lobe tracts, and hippocampal volumes in HS-TLE correlated with parahippocampal cingulum and anterior commissure atrophy, indicating an effect of the underlying pathology. Ipsilateral atrophy of the tapetum, uncinate, and inferior fronto-occipital fasciculus was found in both HS-TLE and MRI-neg TLE, suggesting a common lateralized effect of focal seizures. Both epilepsy groups had bilateral atrophy of the dorsal cingulum and corpus callosum fibers, which we interpret as a consequence of bilateral insults (potentially generalized seizures and/or medications). Underlying pathology, repeated focal seizures, and global insults each contribute to atrophy in specific tracts. Genetic factors make less of a contribution in this cohort. A multifactorial model of white matter atrophy in focal epilepsy is proposed. Ann Neurol 2017;81:240-250. © 2016 American Neurological Association.

  17. The transitional association between β-amyloid pathology and regional brain atrophy.

    Science.gov (United States)

    Insel, Philip S; Mattsson, Niklas; Donohue, Michael C; Mackin, R Scott; Aisen, Paul S; Jack, Clifford R; Shaw, Leslie M; Trojanowski, John Q; Weiner, Michael W

    2015-10-01

    Alzheimer's disease (AD) is characterized by the accumulation of β-amyloid (Aβ) associated with brain atrophy and cognitive decline. The functional form to model the association between Aβ and regional brain atrophy has not been well defined. To determine the relationship between Aβ and atrophy, we compared the performance of the usual dichotomization of cerebrospinal fluid (CSF) Aβ to identify subjects as Aβ+ and Aβ- with a trilinear spline model of CSF Aβ. One hundred and eighty-three subjects with mild cognitive impairment and 108 cognitively normal controls with baseline CSF Aβ and up to 4 years of longitudinal magnetic resonance imaging data from the Alzheimer's Disease Neuroimaging Initiative were analyzed using mixed-effects regression. Piecewise-linear splines were used to evaluate the nonlinear nature of the association between CSF Aβ and regional atrophy and to identify points of acceleration of atrophy with respect to Aβ. Several parameterizations of CSF Aβ were compared using likelihood ratio tests and the Akaike information criterion. Periods of acceleration of atrophy in which subjects transition from CSF Aβ negativity to CSF Aβ positivity were estimated from the spline models and tested for significance. Spline models resulted in better fits for many temporal and parietal regions compared with the dichotomous models. The trilinear model showed that periods of acceleration of atrophy varied greatly by region with early changes seen in the insula, amygdala, precuneus, hippocampus, and other temporal regions, occurring before the clinical threshold for CSF Aβ positivity. The use of piecewise-linear splines provides an improved model of the nonlinear association between CSF Aβ and regional atrophy in regions implicated in the progression of AD. The important biological finding of this work is that some brain regions show periods of accelerated volume loss well before the CSF Aβ42 threshold. This implies that signs of brain atrophy

  18. Little effects of Insulin-like Growth Factor-I on testicular atrophy induced by hypoxia

    OpenAIRE

    Casares Amelia; Diaz-Sanchez Matias; Puche Juan; Garcia-Fernandez Maria; Castilla-Cortázar Inma; Diez-Caballero Fernando; Aliaga-Montilla M Aurelia; Rodriguez-Borrajo Coronación; Gonzalez-Barón Salvador

    2006-01-01

    Abstract Background Insulin-like Growth Factor-I (IGF-I) supplementation restores testicular atrophy associated with advanced liver cirrhosis that is a condition of IGF-I deficiency. The aim of this work was to evaluate the effect of IGF-I in rats with ischemia-induced testicular atrophy (AT) without liver disease and consequently with normal serum level of IGF-I. Methods Testicular atrophy was induced by epinephrine (1, 2 mg/Kg intra-scrotal injection five times per week) during 11 weeks. Th...

  19. Combining the boundary shift integral and tensor-based morphometry for brain atrophy estimation

    Science.gov (United States)

    Michalkiewicz, Mateusz; Pai, Akshay; Leung, Kelvin K.; Sommer, Stefan; Darkner, Sune; Sørensen, Lauge; Sporring, Jon; Nielsen, Mads

    2016-03-01

    Brain atrophy from structural magnetic resonance images (MRIs) is widely used as an imaging surrogate marker for Alzheimers disease. Their utility has been limited due to the large degree of variance and subsequently high sample size estimates. The only consistent and reasonably powerful atrophy estimation methods has been the boundary shift integral (BSI). In this paper, we first propose a tensor-based morphometry (TBM) method to measure voxel-wise atrophy that we combine with BSI. The combined model decreases the sample size estimates significantly when compared to BSI and TBM alone.

  20. Parry-Romberg syndrome (progressive hemifacial atrophy) with spasmodic dysphonia--a rare association.

    Science.gov (United States)

    Mugundhan, K; Selvakumar, C J; Gunasekaran, K; Thiruvarutchelvan, K; Sivakumar, S; Anguraj, M; Arun, S

    2014-04-01

    Parry-Romberg syndrome is a rare clinical entity characterised by progressive hemifacial atrophy with appearance of 'saber'. Various neurological and otorhinolaryngological disorders are associated with this syndrome. The association of Parry -Romberg syndrome with Spasmodic dysphonia has rarely been reported. A 37 year old female presented with progressive atrophy of tissues of left side of face for 10 years and change in voice for 1 year. On examination, wasting and atrophy of tissues including tongue was noted on left side of the face. ENT examination revealed adductor spasmodic dysphonia. We report the rare association of Parry -Romberg syndrome with spasmodic dysphonia.

  1. Clinical significance of corpus callosum atrophy in a mixed elderly population

    DEFF Research Database (Denmark)

    Ryberg, C; Rostrup, E; Stegmann, M B;

    2007-01-01

    Corpus callosum (CC) is the main tract connecting the hemispheres, but the clinical significance of CC atrophy is poorly understood. The aim of this work was to investigate clinical and functional correlates of CC atrophy in subjects with age-related white matter changes (ARWMC). In 569 elderly......) score, history of depression, geriatric depression scale (GDS) score, subjective gait difficulty, history of falls, walking speed, and total score on the short physical performance battery (SPPB) were analyzed. Significant correlations between CC atrophy and MMSE, SPPB, and walking speed were identified...

  2. Diffusion tensor imaging detects rarefaction of optic radiation in glaucoma patients.

    Science.gov (United States)

    Engelhorn, Tobias; Michelson, Georg; Waerntges, Simone; Struffert, Tobias; Haider, Sultan; Doerfler, Arnd

    2011-06-01

    Diffusion tensor imaging (DTI) can depict rarefaction of the optical fibres. Hence, we applied DTI to assess pathological changes of the optic radiation in glaucoma patients. Fifty glaucoma patients and 50 healthy age-matched controls were examined by a 3T high-field magnetic resonance scanner. Fiber tracts were volume rendered using a semiquantitative approach to assess rarefaction and results were correlated with the extent of optic nerve atrophy and reduced spatial-temporal contrast sensitivity of the retina using established ophthalmological examinations. Twenty-two glaucoma patients (44%) showed significant rarefaction of the optic radiation: the volume was reduced to 67 ± 16% compared with controls. Hereby, the glaucomatous optic nerve atrophy stage correlated with the presence of DTI-derived rarefied optic radiation (Kendall tau-b 0.272, P = .016). Aside, cerebral microangiopathy affecting the optic radiation was significantly higher among glaucoma patients compared to controls (10 patients compared with 2 patients, P < .05). In patients with glaucomatous optic nerve atrophy, there is anterograde and-most likely because of microangiopathic lesions within the optic radiation-retrograde transneuronal rarefaction of the optic radiation that can be assessed in vivo using DTI with good correlation to established ophthalmological examinations. Copyright © 2011 AUR. Published by Elsevier Inc. All rights reserved.

  3. Optical coherence tomography in late solar retinopathy

    Directory of Open Access Journals (Sweden)

    Janković Aleksandar

    2011-01-01

    Full Text Available Introduction. Solar retinopathy refers to retinal injury induced by direct or indirect solar viewing. Case report. We presented a patient who had observed partial solar eclipse 51 year before. He had bilaterally decreased vision and scar of the macular region at the time of presentation. The basic diagnostic tool applied in the presented patient, optical coherence tomography, showed hyporeflexivity of the outer retina in the segment of retinal pigment epithelialphotoreceptors complex with atrophy and thinning of the foveolar region. Conclusion. Optical coherence tomography is a powerful, non-invasive diagnostic tool which can ease the diagnosis and estimate the level and nature of the macular region damage.

  4. [Applications of optical coherence tomography (OCT) in neuro-ophthalmology].

    Science.gov (United States)

    Kernstock, C; Friebe, K; Tonagel, F

    2013-11-01

    Optical coherence tomography (OCT) has revolutionised ophthalmology. Due to modern instruments with extremely high resolution there are more and more applications also in neuro-ophthalmological disorders. This review gives an overview on typical changes in OCT for the following diseases: autosomal dominant optic atrophy, Leber hereditary optic neuropathy, toxic, traumatic and compressive optic neuropathy, optic nerve drusen, anterior ischaemic optic neuropathy, optic disc pit, papilledema, optic neuritis (isolated or associated with multiple sclerosis or neuromyelitis optica), neurodegenerative diseases and hereditary retinal diseases. A diagnosis exclusively based on an OCT examination is not always possible, but in several diseases there are pathognomonic changes that directly lead to the correct diagnosis. Particularly with the often complex settings in neuro-ophtalmology the OCT should be seen as a supplementary modality and not as a replacement for other techniques.

  5. Diffusion tensor imaging in the characterization of multiple system atrophy

    Directory of Open Access Journals (Sweden)

    Rulseh AM

    2016-08-01

    Full Text Available Aaron Michael Rulseh,1–3 Jiri Keller,1,4 Jan Rusz,5,6 Michael Syka,1 Hana Brozova,6 Robert Rusina,6,7 Petra Havrankova,6 Katerina Zarubova,8 Hana Malikova,1 Robert Jech,6 Josef Vymazal1 1Department of Radiology, Na Homolce Hospital, Prague, Czech Republic; 2Department of Radiology, 1st Faculty of Medicine, General University Hospital, Charles University in Prague, Prague, Czech Republic; 3National Institute of Mental Health, Klecany, Czech Republic; 43rd Faculty of Medicine, Charles University in Prague, Prague, Czech Republic; 5Department of Circuit Theory, Faculty of Electrical Engineering, Czech Technical University in Prague, Prague, Czech Republic; 6Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic; 7Thomayer Hospital, Prague, Czech Republic; 8Department of Neurology, 2nd Faculty of Medicine, Charles University in Prague, Prague, Czech Republic Purpose: Multiple system atrophy (MSA is a rare neurodegenerative disease that remains poorly understood, and the diagnosis of MSA continues to be challenging. We endeavored to improve the diagnostic process and understanding of in vivo characteristics of MSA by diffusion tensor imaging (DTI.Materials and methods: Twenty MSA subjects, ten parkinsonian dominant (MSA-P, ten cerebellar dominant (MSA-C, and 20 healthy volunteer subjects were recruited. Fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity maps were processed using tract-based spatial statistics. Diffusion data were additionally evaluated in the basal ganglia. A support vector machine was used to assess diagnostic utility, leave-one-out cross-validation in the evaluation of classification schemes, and receiver operating characteristic analyses to determine cutoff values.Results: We detected widespread changes in the brain white matter of MSA subjects; however, no group-wise differences were found between MSA-C and MSA

  6. Aging affects the transcriptional regulation of human skeletal muscle disuse atrophy

    DEFF Research Database (Denmark)

    Suetta, Charlotte; Frandsen, Ulrik; Nielsen, Line;

    2012-01-01

    Important insights concerning the molecular basis of skeletal muscle disuse-atrophy and aging related muscle loss have been obtained in cell culture and animal models, but these regulatory signaling pathways have not previously been studied in aging human muscle. In the present study, muscle...... atrophy was induced by immobilization in healthy old and young individuals to study the time-course and transcriptional factors underlying human skeletal muscle atrophy. The results reveal that irrespectively of age, mRNA expression levels of MuRF-1 and Atrogin-1 increased in the very initial phase (2......-4 days) of human disuse-muscle atrophy along with a marked reduction in PGC-1a and PGC-1ß (1-4 days) and a ~10% decrease in myofiber size (4 days). Further, an age-specific decrease in Akt and S6 phosphorylation was observed in young muscle within the first days (1-4 days) of immobilization. In contrast...

  7. Intermittent blood flow restriction does not reduce atrophy following anterior cruciate ligament reconstruction

    Directory of Open Access Journals (Sweden)

    Erik Iversen

    2016-03-01

    Conclusion: In conflict with other studies using a similar protocol, application of blood flow restriction the first 14 days after ACL reconstruction did not reduce quadriceps ACSA muscle atrophy measured by MR in a population of athletes.

  8. Effects of ventricular unloading on apoptosis and atrophy of cardiac myocytes.

    Science.gov (United States)

    Schena, Stefano; Kurimoto, Yoshihiko; Fukada, Johji; Tack, Ivan; Ruiz, Phillip; Pang, Manhui; Striker, Liliane J; Aitouche, Abdelouahab; Pham, Si M

    2004-07-01

    Ventricular unloading decreases cardiac ventricular mass. This loss of ventricular mass can be due to either atrophy (a reversible process) or apoptosis (an irreversible process) of the cardiac myocytes. We investigated the effect of ventricular unloading on atrophy and apoptosis of cardiac myocytes, using working and nonworking transplant heart models in rats. ACI rats underwent heterotopic heart transplantation with two different techniques to create working and nonworking cardiac grafts. Cardiac grafts were harvested at different time points after transplantation. TUNEL, caspase-3 assay, and electron microscopy were used to assess the degree of apoptosis while cellular atrophy was estimated by calculation of the cytoplasmic index (CI = mean sectional cytoplasmic area/nucleus). Ventricular mass reduction was more pronounced in nonworking than in working hearts (P atrophy is the primary mechanism that accounts for myocardial weight reduction following ventricular unloading. The inference is that ventricular unloading by ventricular assist devices may not cause permanent loss of cardiac myocytes, thus allowing for functional recovery.

  9. Immunosuppressive regimen and interstitial fibrosis and tubules atrophy at 12 months postrenal transplant.

    NARCIS (Netherlands)

    Gelens, M.A.; Steegh, F.M.; Hooff, J.P. van; Suylen, R.J. van; Nieman, F.H.; Heurn, L.W.E. van; Peutz-Kootstra, C.J.; Christiaans, M.H.

    2012-01-01

    BACKGROUND AND OBJECTIVES: Chronic renal transplant dysfunction is histopathologically characterized by interstitial fibrosis and tubular atrophy. This study investigated the relative contribution of baseline donor, recipient, and transplant characteristics to interstitial fibrosis and tubular atrop

  10. Robust Identification of Alzheimer’s Disease subtypes based on cortical atrophy patterns

    Science.gov (United States)

    Park, Jong-Yun; Na, Han Kyu; Kim, Sungsoo; Kim, Hyunwook; Kim, Hee Jin; Seo, Sang Won; Na, Duk L.; Han, Cheol E.; Seong, Joon-Kyung; Weiner, Michael; Aisen, Paul; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowki, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Shaw, Leslie M.; Liu, Enchi; Montine, Tom; Thomas, Ronald G.; Donohue, Michael; Walter, Sarah; Gessert, Devon; Sather, Tamie; Jiminez, Gus; Harvey, Danielle; Bernstein, Matthew; Fox, Nick; Thompson, Paul; Schuff, Norbert; DeCarli, Charles; Borowski, Bret; Gunter, Jeff; Senjem, Matt; Vemuri, Prashanthi; Jones, David; Kantarci, Kejal; Ward, Chad; Koeppe, Robert A.; Foster, Norm; Reiman, Eric M.; Chen, Kewei; Mathis, Chet; Landau, Susan; Cairns, Nigel J.; Householder, Erin; Taylor Reinwald, Lisa; Lee, Virginia; Korecka, Magdalena; Figurski, Michal; Crawford, Karen; Neu, Scott; Foroud, Tatiana M.; Potkin, Steven G.; Shen, Li; Kelley, Faber; Kim, Sungeun; Nho, Kwangsik; Kachaturian, Zaven; Frank, Richard; Snyder, Peter J.; Molchan, Susan; Kaye, Jeffrey; Quinn, Joseph; Lind, Betty; Carter, Raina; Dolen, Sara; Schneider, Lon S.; Pawluczyk, Sonia; Beccera, Mauricio; Teodoro, Liberty; Spann, Bryan M.; Brewer, James; Vanderswag, Helen; Fleisher, Adam; Heidebrink, Judith L.; Lord, Joanne L.; Mason, Sara S.; Albers, Colleen S.; Knopman, David; Johnson, Kris; Doody, Rachelle S.; Villanueva Meyer, Javier; Chowdhury, Munir; Rountree, Susan; Dang, Mimi; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Ances, Beau; Carroll, Maria; Leon, Sue; Mintun, Mark A.; Schneider, Stacy; Oliver, Angela; Marson, Daniel; Griffith, Randall; Clark, David; Geldmacher, David; Brockington, John; Roberson, Erik; Grossman, Hillel; Mitsis, Effie; de Toledo-Morrell, Leyla; Shah, Raj C.; Duara, Ranjan; Varon, Daniel; Greig, Maria T.; Roberts, Peggy; Albert, Marilyn; Onyike, Chiadi; D’Agostino II, Daniel; Kielb, Stephanie; Galvin, James E.; Pogorelec, Dana M.; Cerbone, Brittany; Michel, Christina A.; Rusinek, Henry; de Leon, Mony J.; Glodzik, Lidia; De Santi, Susan; Doraiswamy, P. Murali; Petrella, Jeffrey R.; Wong, Terence Z.; Arnold, Steven E.; Karlawish, Jason H.; Wolk, David; Smith, Charles D.; Jicha, Greg; Hardy, Peter; Sinha, Partha; Oates, Elizabeth; Conrad, Gary; Lopez, Oscar L.; Oakley, MaryAnn; Simpson, Donna M.; Porsteinsson, Anton P.; Goldstein, Bonnie S.; Martin, Kim; Makino, Kelly M.; Ismail, M. Saleem; Brand, Connie; Mulnard, Ruth A.; Thai, Gaby; Mc Adams Ortiz, Catherine; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Diaz Arrastia, Ramon; King, Richard; Weiner, Myron; Martin Cook, Kristen; DeVous, Michael; Levey, Allan I.; Lah, James J.; Cellar, Janet S.; Burns, Jeffrey M.; Anderson, Heather S.; Swerdlow, Russell H.; Apostolova, Liana; Tingus, Kathleen; Woo, Ellen; Silverman, Daniel H. S.; Lu, Po H.; Bartzokis, George; Graff Radford, Neill R.; Parfitt, Francine; Kendall, Tracy; Johnson, Heather; Farlow, Martin R.; Marie Hake, Ann; Matthews, Brandy R.; Herring, Scott; Hunt, Cynthia; van Dyck, Christopher H.; Carson, Richard E.; MacAvoy, Martha G.; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Robin Hsiung, Ging Yuek; Feldman, Howard; Mudge, Benita; Assaly, Michele; Trost, Dick; Bernick, Charles; Munic, Donna; Kerwin, Diana; Marsel Mesulam, Marek; Lipowski, Kristine; Kuo Wu, Chuang; Johnson, Nancy; Sadowsky, Carl; Martinez, Walter; Villena, Teresa; Scott Turner, Raymond; Johnson, Kathleen; Reynolds, Brigid; Sperling, Reisa A.; Johnson, Keith A.; Marshall, Gad; Frey, Meghan; Yesavage, Jerome; Taylor, Joy L.; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Sabbagh, Marwan N.; Belden, Christine M.; Jacobson, Sandra A.; Sirrel, Sherye A.; Kowall, Neil; Killiany, Ronald; Budson, Andrew E.; Norbash, Alexander; Lynn Johnson, Patricia; Obisesan, Thomas O.; Wolday, Saba; Allard, Joanne; Lerner, Alan; Ogrocki, Paula; Hudson, Leon; Fletcher, Evan; Carmichael, Owen; Olichney, John; Kittur, Smita; Borrie, Michael; Lee, T. Y.; Bartha, Rob; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Preda, Adrian; Nguyen, Dana; Tariot, Pierre; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Scharre, Douglas W.; Kataki, Maria; Adeli, Anahita; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Pearlson, Godfrey D.; Blank, Karen; Anderson, Karen; Santulli, Robert B.; Kitzmiller, Tamar J.; Schwartz, Eben S.; Sink, Kaycee M.; Williamson, Jeff D.; Garg, Pradeep; Watkins, Franklin; Ott, Brian R.; Querfurth, Henry; Tremont, Geoffrey; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Rosen, Howard J.; Miller, Bruce L.; Mintzer, Jacobo; Spicer, Kenneth; Bachman, David; Finger, Elizabether; Pasternak, Stephen; Rachinsky, Irina; Rogers, John; Kertesz, Andrew; Pomara, Nunzio; Hernando, Raymundo; Sarrael, Antero; Schultz, Susan K.; Boles Ponto, Laura L.; Shim, Hyungsub; Smith, Karen Elizabeth; Relkin, Norman; Chaing, Gloria; Raudin, Lisa; Smith, Amanda; Fargher, Kristin; Raj, Balebail Ashok

    2017-01-01

    Accumulating evidence suggests that Alzheimer’s disease (AD) is heterogenous and can be classified into several subtypes. Here, we propose a robust subtyping method for AD based on cortical atrophy patterns and graph theory. We calculated similarities between subjects in their atrophy patterns throughout the whole brain, and clustered subjects with similar atrophy patterns using the Louvain method for modular organization extraction. We applied our method to AD patients recruited at Samsung Medical Center and externally validated our method by using the AD Neuroimaging Initiative (ADNI) dataset. Our method categorized very mild AD into three clinically distinct subtypes with high reproducibility (>90%); the parietal-predominant (P), medial temporal-predominant (MT), and diffuse (D) atrophy subtype. The P subtype showed the worst clinical presentation throughout the cognitive domains, while the MT and D subtypes exhibited relatively mild presentation. The MT subtype revealed more impaired language and executive function compared to the D subtype. PMID:28276464

  11. Robust Identification of Alzheimer's Disease subtypes based on cortical atrophy patterns.

    Science.gov (United States)

    Park, Jong-Yun; Na, Han Kyu; Kim, Sungsoo; Kim, Hyunwook; Kim, Hee Jin; Seo, Sang Won; Na, Duk L; Han, Cheol E; Seong, Joon-Kyung

    2017-03-09

    Accumulating evidence suggests that Alzheimer's disease (AD) is heterogenous and can be classified into several subtypes. Here, we propose a robust subtyping method for AD based on cortical atrophy patterns and graph theory. We calculated similarities between subjects in their atrophy patterns throughout the whole brain, and clustered subjects with similar atrophy patterns using the Louvain method for modular organization extraction. We applied our method to AD patients recruited at Samsung Medical Center and externally validated our method by using the AD Neuroimaging Initiative (ADNI) dataset. Our method categorized very mild AD into three clinically distinct subtypes with high reproducibility (>90%); the parietal-predominant (P), medial temporal-predominant (MT), and diffuse (D) atrophy subtype. The P subtype showed the worst clinical presentation throughout the cognitive domains, while the MT and D subtypes exhibited relatively mild presentation. The MT subtype revealed more impaired language and executive function compared to the D subtype.

  12. Assessment atrophy jawbone after tooth extraction in connection with dental implantation

    Directory of Open Access Journals (Sweden)

    Maksyutov A.E.

    2011-03-01

    Full Text Available This article provides a clinically grounded classification of degrees of atrophy of the bone the alveolar processes of jaws in accordance with specific strategies for dental implantation

  13. Atrophying pityriasis versicolor: is this a new variant of pityriasis versicolor?

    Science.gov (United States)

    Yang, Yun-Seok; Shin, Min-Kyung; Haw, Choong-Rim

    2010-11-01

    An atypical clinical form of pityriasis versicolor has been infrequently reported, in which cutaneous atrophy is associated with individual pityriasis versicolor lesions. The pathogenesis of this atrophy remains unclear, but is believed to be a delayed-type hypersensitivity reaction to antigens derived from the Malassezia species. A 60-year-old man presented with multiple, slightly scaly, and depressed maculopatches or plaques on the trunk and extremities. Our microscopic examination of the skin scrapings on a KOH preparation revealed numerous short hyphae and spores. The patient was treated daily with 200 mg of itraconazole in combination with topical antifungals, achieving clinical improvement and mycological recovery, which was confirmed upon follow-up 1 month later. This is the first case report of atrophying pityriasis versicolor in Korea. It needs to be differentiated from other atrophying disorders of the skin.

  14. Training at non-damaging intensities facilitates recovery from muscle atrophy.

    Science.gov (United States)

    Itoh, Yuta; Murakami, Taro; Mori, Tomohiro; Agata, Nobuhide; Kimura, Nahoko; Inoue-Miyazu, Masumi; Hayakawa, Kimihide; Hirano, Takayuki; Sokabe, Masahiro; Kawakami, Keisuke

    2017-02-01

    Resistance training promotes recovery from muscle atrophy, but optimum training programs have not been established. We aimed to determine the optimum training intensity for muscle atrophy. Mice recovering from atrophied muscles after 2 weeks of tail suspension underwent repeated isometric training with varying joint torques 50 times per day. Muscle recovery assessed by maximal isometric contraction and myofiber cross-sectional areas (CSAs) were facilitated at 40% and 60% maximum contraction strength (MC), but at not at 10% and 90% MC. At 60% and 90% MC, damaged and contained smaller diameter fibers were observed. Activation of myogenic satellite cells and a marked increase in myonuclei were observed at 40%, 60%, and 90% MC. The increases in myofiber CSAs were likely caused by increased myonuclei formed through fusion of resistance-induced myofibers with myogenic satellite cells. These data indicate that resistance training without muscle damage facilitates efficient recovery from atrophy. Muscle Nerve 55: 243-253, 2017. © 2016 Wiley Periodicals, Inc.

  15. Robust Identification of Alzheimer’s Disease subtypes based on cortical atrophy patterns

    Science.gov (United States)

    Park, Jong-Yun; Na, Han Kyu; Kim, Sungsoo; Kim, Hyunwook; Kim, Hee Jin; Seo, Sang Won; Na, Duk L.; Han, Cheol E.; Seong, Joon-Kyung; Weiner, Michael; Aisen, Paul; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowki, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Shaw, Leslie M.; Liu, Enchi; Montine, Tom; Thomas, Ronald G.; Donohue, Michael; Walter, Sarah; Gessert, Devon; Sather, Tamie; Jiminez, Gus; Harvey, Danielle; Bernstein, Matthew; Fox, Nick; Thompson, Paul; Schuff, Norbert; Decarli, Charles; Borowski, Bret; Gunter, Jeff; Senjem, Matt; Vemuri, Prashanthi; Jones, David; Kantarci, Kejal; Ward, Chad; Koeppe, Robert A.; Foster, Norm; Reiman, Eric M.; Chen, Kewei; Mathis, Chet; Landau, Susan; Cairns, Nigel J.; Householder, Erin; Taylor Reinwald, Lisa; Lee, Virginia; Korecka, Magdalena; Figurski, Michal; Crawford, Karen; Neu, Scott; Foroud, Tatiana M.; Potkin, Steven G.; Shen, Li; Kelley, Faber; Kim, Sungeun; Nho, Kwangsik; Kachaturian, Zaven; Frank, Richard; Snyder, Peter J.; Molchan, Susan; Kaye, Jeffrey; Quinn, Joseph; Lind, Betty; Carter, Raina; Dolen, Sara; Schneider, Lon S.; Pawluczyk, Sonia; Beccera, Mauricio; Teodoro, Liberty; Spann, Bryan M.; Brewer, James; Vanderswag, Helen; Fleisher, Adam; Heidebrink, Judith L.; Lord, Joanne L.; Mason, Sara S.; Albers, Colleen S.; Knopman, David; Johnson, Kris; Doody, Rachelle S.; Villanueva Meyer, Javier; Chowdhury, Munir; Rountree, Susan; Dang, Mimi; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Ances, Beau; Carroll, Maria; Leon, Sue; Mintun, Mark A.; Schneider, Stacy; Oliver, Angela; Marson, Daniel; Griffith, Randall; Clark, David; Geldmacher, David; Brockington, John; Roberson, Erik; Grossman, Hillel; Mitsis, Effie; de Toledo-Morrell, Leyla; Shah, Raj C.; Duara, Ranjan; Varon, Daniel; Greig, Maria T.; Roberts, Peggy; Albert, Marilyn; Onyike, Chiadi; D'Agostino, Daniel, II; Kielb, Stephanie; Galvin, James E.; Pogorelec, Dana M.; Cerbone, Brittany; Michel, Christina A.; Rusinek, Henry; de Leon, Mony J.; Glodzik, Lidia; de Santi, Susan; Doraiswamy, P. Murali; Petrella, Jeffrey R.; Wong, Terence Z.; Arnold, Steven E.; Karlawish, Jason H.; Wolk, David; Smith, Charles D.; Jicha, Greg; Hardy, Peter; Sinha, Partha; Oates, Elizabeth; Conrad, Gary; Lopez, Oscar L.; Oakley, Maryann; Simpson, Donna M.; Porsteinsson, Anton P.; Goldstein, Bonnie S.; Martin, Kim; Makino, Kelly M.; Ismail, M. Saleem; Brand, Connie; Mulnard, Ruth A.; Thai, Gaby; Mc Adams Ortiz, Catherine; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Diaz Arrastia, Ramon; King, Richard; Weiner, Myron; Martin Cook, Kristen; Devous, Michael; Levey, Allan I.; Lah, James J.; Cellar, Janet S.; Burns, Jeffrey M.; Anderson, Heather S.; Swerdlow, Russell H.; Apostolova, Liana; Tingus, Kathleen; Woo, Ellen; Silverman, Daniel H. S.; Lu, Po H.; Bartzokis, George; Graff Radford, Neill R.; Parfitt, Francine; Kendall, Tracy; Johnson, Heather; Farlow, Martin R.; Marie Hake, Ann; Matthews, Brandy R.; Herring, Scott; Hunt, Cynthia; van Dyck, Christopher H.; Carson, Richard E.; Macavoy, Martha G.; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Robin Hsiung, Ging Yuek; Feldman, Howard; Mudge, Benita; Assaly, Michele; Trost, Dick; Bernick, Charles; Munic, Donna; Kerwin, Diana; Marsel Mesulam, Marek; Lipowski, Kristine; Kuo Wu, Chuang; Johnson, Nancy; Sadowsky, Carl; Martinez, Walter; Villena, Teresa; Scott Turner, Raymond; Johnson, Kathleen; Reynolds, Brigid; Sperling, Reisa A.; Johnson, Keith A.; Marshall, Gad; Frey, Meghan; Yesavage, Jerome; Taylor, Joy L.; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Sabbagh, Marwan N.; Belden, Christine M.; Jacobson, Sandra A.; Sirrel, Sherye A.; Kowall, Neil; Killiany, Ronald; Budson, Andrew E.; Norbash, Alexander; Lynn Johnson, Patricia; Obisesan, Thomas O.; Wolday, Saba; Allard, Joanne; Lerner, Alan; Ogrocki, Paula; Hudson, Leon; Fletcher, Evan; Carmichael, Owen; Olichney, John; Kittur, Smita; Borrie, Michael; Lee, T. Y.; Bartha, Rob; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Preda, Adrian; Nguyen, Dana; Tariot, Pierre; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Scharre, Douglas W.; Kataki, Maria; Adeli, Anahita; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Pearlson, Godfrey D.; Blank, Karen; Anderson, Karen; Santulli, Robert B.; Kitzmiller, Tamar J.; Schwartz, Eben S.; Sink, Kaycee M.; Williamson, Jeff D.; Garg, Pradeep; Watkins, Franklin; Ott, Brian R.; Querfurth, Henry; Tremont, Geoffrey; Salloway, Stephen; Malloy, Paul; Correia, Stephen; Rosen, Howard J.; Miller, Bruce L.; Mintzer, Jacobo; Spicer, Kenneth; Bachman, David; Finger, Elizabether; Pasternak, Stephen; Rachinsky, Irina; Rogers, John; Kertesz, Andrew; Pomara, Nunzio; Hernando, Raymundo; Sarrael, Antero; Schultz, Susan K.; Boles Ponto, Laura L.; Shim, Hyungsub; Smith, Karen Elizabeth; Relkin, Norman; Chaing, Gloria; Raudin, Lisa; Smith, Amanda; Fargher, Kristin; Raj, Balebail Ashok

    2017-03-01

    Accumulating evidence suggests that Alzheimer’s disease (AD) is heterogenous and can be classified into several subtypes. Here, we propose a robust subtyping method for AD based on cortical atrophy patterns and graph theory. We calculated similarities between subjects in their atrophy patterns throughout the whole brain, and clustered subjects with similar atrophy patterns using the Louvain method for modular organization extraction. We applied our method to AD patients recruited at Samsung Medical Center and externally validated our method by using the AD Neuroimaging Initiative (ADNI) dataset. Our method categorized very mild AD into three clinically distinct subtypes with high reproducibility (>90%) the parietal-predominant (P), medial temporal-predominant (MT), and diffuse (D) atrophy subtype. The P subtype showed the worst clinical presentation throughout the cognitive domains, while the MT and D subtypes exhibited relatively mild presentation. The MT subtype revealed more impaired language and executive function compared to the D subtype.

  16. Atrophy of sacrospinal muscle groups in patients with chronic, diffusely radiating lumbar back pain

    Energy Technology Data Exchange (ETDEWEB)

    Laasonen, E.M.

    1984-01-01

    After surgery necessitated by lumbar back pain syndromes, radiolucency verified by CT may appear in the sacrospinal muscle group on the operate side. This radiolucency represents muscular atrophy and is in its most severe form a result of the replacement of muscle tissue with adipose tissue. Such muscular atrophy appeared in the present series in 31 out of all 156 patients (19.9%) and in 29 out of 94 patients operated on because of radiating lumbar back pain (30.9%). The radiological appearance, extent, and HU values of this muscular atrophy are presented in detail. Only weak correlations with the multitude of clinical symptoms and signs were found in this retrospective study. The effects of irreversible muscular atrophy on the indications for surgery and physiotherapy are discussed.

  17. Medial temporal lobe atrophy relates to executive dysfunction in Alzheimer's disease

    NARCIS (Netherlands)

    Oosterman, J.M.; Oosterveld, S.M.; Olde Rikkert, M.G.M.; Claassen, J.A.H.R.; Kessels, R.P.C.

    2012-01-01

    Background: White matter hyperintensities (WMH) have frequently been associated with lower executive function performance. Little is known, however, about the effects of hippocampal atrophy on executive control in Alzheimer's disease (AD). The present study focused on the association of hippocampal

  18. Medial temporal lobe atrophy relates to executive dysfunction in Alzheimer's disease.

    NARCIS (Netherlands)

    Oosterman, J.M.; Oosterveld, S.M.; Olde Rikkert, M.G.; Claassen, J.A.H.R.; Kessels, R.P.C.

    2012-01-01

    ABSTRACT Background: White matter hyperintensities (WMH) have frequently been associated with lower executive function performance. Little is known, however, about the effects of hippocampal atrophy on executive control in Alzheimer's disease (AD). The present study focused on the association of

  19. Pattern Differences of Small Hand Muscle Atrophy in Amyotrophic Lateral Sclerosis and Mimic Disorders

    Directory of Open Access Journals (Sweden)

    Jia Fang

    2016-01-01

    Conclusions: The different patterns of small hand muscle atrophy between the ALS patients and the patients with mimic disorders presumably reflect distinct pathophysiological mechanisms underlying different disorders, and may aid in distinguishing between ALS and mimic disorders.

  20. The significance of type 1 fiber atrophy (hypotrophy) in childhood neuromuscular disorders.

    Science.gov (United States)

    Imoto, C; Nonaka, I

    2001-08-01

    To determine the incidence of selective type 1 fiber atrophy (hypotrophy) and its possible significance in various muscle diseases of childhood, we reviewed 2212 muscle biopsies from children which we had examined in the past 20 years histochemically with ATPase staining. Type 1 fiber atrophy was seen in a variety of neuromuscular disorders, but predominantly in congenital myopathies, including all patients with congenital fiber type disproportion myopathy (20 patients), central core disease (12 patients) and multicore disease (four patients). Although type 1 fiber atrophy was not a constant feature in nemaline myopathy and myotubular myopathy, all patients with these diseases had abnormal fiber type distribution which included type 1 fiber predominance both with and without type 2B fiber deficiency. Together with abnormal fiber type distribution, type 1 fiber atrophy was a common finding in childhood neuromuscular disorders, especially congenital myopathies.

  1. The yearly rate of Relative Thalamic Atrophy (yrRTA: a simple 2D/3D method for estimating deep gray matter atrophy in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Manuel eMenéndez-González

    2014-08-01

    Full Text Available Despite a strong correlation to outcome, the measurement of gray matter (GM atrophy is not being used in daily clinical practice as a prognostic factor and monitor the effect of treatments in Multiple Sclerosis (MS. This is mainly because the volumetric methods available to date are sophisticated and difficult to implement for routine use in most hospitals. In addition, the meaning of raw results from volumetric studies on regions of interest are not always easy to understand. Thus, there is a huge need of a methodology suitable to be applied in daily clinical practice in order to estimate GM atrophy in a convenient and comprehensive way. Given the thalamus is the brain structure found to be more consistently implied in MS both in terms of extent of atrophy and in terms of prognostic value, we propose a solution based in this structure. In particular, we propose to compare the extent of thalamus atrophy (TA with the extent of unspecific, global brain atrophy, represented by ventricular enlargement. We name this ratio the yearly rate of Relative Thalamic Atrophy (yrRTA. In this report we aim to describe the concept of yrRTA and the guidelines for computing it under 2D and 3D approaches and explain the rationale behind this method. We have also conducted a very short crossectional retrospective study to proof the concept of yrRTA. However, we do not seek to describe here the validity of this parameter since these researches are being conducted currently and results will be addressed in future publications.

  2. Measurement of hippocampal atrophy using 4D graph-cut segmentation: application to ADNI.

    Science.gov (United States)

    Wolz, Robin; Heckemann, Rolf A; Aljabar, Paul; Hajnal, Joseph V; Hammers, Alexander; Lötjönen, Jyrki; Rueckert, Daniel

    2010-08-01

    We propose a new method of measuring atrophy of brain structures by simultaneously segmenting longitudinal magnetic resonance (MR) images. In this approach a 4D graph is used to represent the longitudinal data: edges are weighted based on spatial and intensity priors and connect spatially and temporally neighboring voxels represented by vertices in the graph. Solving the min-cut/max-flow problem on this graph yields the segmentation for all timepoints in a single step. By segmenting all timepoints simultaneously, a consistent and atrophy-sensitive segmentation is obtained. The application to hippocampal atrophy measurement in 568 image pairs (Baseline and Month 12 follow-up) as well as 362 image triplets (Baseline, Month 12, and Month 24) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) confirms previous findings for atrophy in Alzheimer's disease (AD) and healthy aging. Highly significant correlations between hippocampal atrophy and clinical variables (Mini Mental State Examination, MMSE and Clinical Dementia Rating, CDR) were found and atrophy rates differ significantly according to subjects' ApoE genotype. Based on one year atrophy rates, a correct classification rate of 82% between AD and control subjects is achieved. Subjects that converted from Mild Cognitive Impairment (MCI) to AD after the period for which atrophy was measured (i.e., after the first 12 months) and subjects for whom conversion is yet to be identified were discriminated with a rate of 64%, a promising result with a view to clinical application. Power analysis shows that 67 and 206 subjects are needed for the AD and MCI groups respectively to detect a 25% change in volume loss with 80% power and 5% significance.

  3. Denervation causes fiber atrophy and myosin heavy chain co-expression in senescent skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Sharon L Rowan

    Full Text Available Although denervation has long been implicated in aging muscle, the degree to which it is causes the fiber atrophy seen in aging muscle is unknown. To address this question, we quantified motoneuron soma counts in the lumbar spinal cord using choline acetyl transferase immunhistochemistry and quantified the size of denervated versus innervated muscle fibers in the gastrocnemius muscle using the in situ expression of the denervation-specific sodium channel, Nav₁.₅, in young adult (YA and senescent (SEN rats. To gain insights into the mechanisms driving myofiber atrophy, we also examined the myofiber expression of the two primary ubiquitin ligases necessary for muscle atrophy (MAFbx, MuRF1. MN soma number in lumbar spinal cord declined 27% between YA (638±34 MNs×mm⁻¹ and SEN (469±13 MNs×mm⁻¹. Nav₁.₅ positive fibers (1548±70 μm² were 35% smaller than Nav₁.₅ negative fibers (2367±78 μm²; P<0.05 in SEN muscle, whereas Nav₁.₅ negative fibers in SEN were only 7% smaller than fibers in YA (2553±33 μm²; P<0.05 where no Nav₁.₅ labeling was seen, suggesting denervation is the primary cause of aging myofiber atrophy. Nav₁.₅ positive fibers had higher levels of MAFbx and MuRF1 (P<0.05, consistent with involvement of the proteasome proteolytic pathway in the atrophy of denervated muscle fibers in aging muscle. In summary, our study provides the first quantitative assessment of the contribution of denervation to myofiber atrophy in aging muscle, suggesting it explains the majority of the atrophy we observed. This striking result suggests a renewed focus should be placed on denervation in seeking understanding of the causes of and treatments for aging muscle atrophy.

  4. Cerebral atrophy as outcome measure in short-term phase 2 clinical trials in multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Elskamp, I.J. van den; Boden, B.; Barkhof, F. [VU University Medical Center, Department of Radiology, MS Center Amsterdam, Amsterdam (Netherlands); Dattola, V. [VU University Medical Center, Department of Radiology, MS Center Amsterdam, Amsterdam (Netherlands); University of Messina, Department of Neurosciences, Psychiatric and Anaesthesiological Sciences, Messina (Italy); Knol, D.L. [VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam (Netherlands); Filippi, M. [Scientific Institute and University Ospedale San Raffaele, Neuroimaging Research Unit, Milan (Italy); Kappos, L. [University Hospital, University of Basel, Department of Neurology, Basel (Switzerland); Fazekas, F. [Medical University of Graz, Department of Neurology, Graz (Austria); Wagner, K. [Bayer-Schering Pharma, Berlin (Germany); Pohl, C. [Bayer-Schering Pharma, Berlin (Germany); University Hospital Bonn, Department of Neurology, Bonn (Germany); Sandbrink, R. [Bayer-Schering Pharma, Berlin (Germany); Heinrich-Heine-University Dusseldorf, Department of Neurology, Dusseldorf (Germany); Polman, C.H. [VU University Medical Center, Department of Neurology, MS Center Amsterdam, Amsterdam (Netherlands); Uitdehaag, B.M.J. [VU University Medical Center, Department of Epidemiology and Biostatistics, Amsterdam (Netherlands); VU University Medical Center, Department of Neurology, MS Center Amsterdam, Amsterdam (Netherlands)

    2010-10-15

    Cerebral atrophy is a compound measure of the neurodegenerative component of multiple sclerosis (MS) and a conceivable outcome measure for clinical trials monitoring the effect of neuroprotective agents. In this study, we evaluate the rate of cerebral atrophy in a 6-month period, investigate the predictive and explanatory value of other magnetic resonance imaging (MRI) measures in relation to cerebral atrophy, and determine sample sizes for future short-term clinical trials using cerebral atrophy as primary outcome measure. One hundred thirty-five relapsing-remitting multiple sclerosis patients underwent six monthly MRI scans from which the percentage brain volume change (PBVC) and the number and volume of gadolinium (Gd)-enhancing lesions, T2 lesions, and persistent black holes (PBH) were determined. By means of multiple linear regression analysis, the relationship between focal MRI variables and PBVC was assessed. Sample size calculations were performed for all patients and subgroups selected for enhancement or a high T2 lesion load at baseline. A significant atrophy occurred over 6 months (PBVC = -0.33%, SE = 0.061, p < 0.0001). The number of baseline T2 lesions (p = 0.024), the on-study Gd-enhancing lesion volume (p = 0.044), and the number of on-study PBHs (p = 0.003) were associated with an increased rate of atrophy. For a 50% decrease in rate of atrophy, the sample size calculations showed that approximately 283 patients per arm are required in an unselected sampled population and 185 patients per arm are required in a selected population. Within a 6-month period, significant atrophy can be detected and on-study associations of PBVC and PBHs emphasizes axonal loss to be a driving mechanism. Application as primary outcome measure in short-term clinical trials with feasible sample size requires a potent drug to obtain sufficient power. (orig.)

  5. Pronounced Impairment of Everyday Skills and Self-Care in Posterior Cortical Atrophy.

    OpenAIRE

    Shakespeare, T. J.; Yong, K. X.; Foxe, D.; Hodges, J.; Crutch, S. J.

    2014-01-01

    Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by progressive visual dysfunction and parietal, occipital, and occipitotemporal atrophy. The aim of this study was to compare the impact of PCA and typical Alzheimer's disease (tAD) on everyday functional abilities and neuropsychiatric status. The Cambridge Behavioural Inventory-Revised was given to carers of 32 PCA and 71 tAD patients. PCA patients showed significantly greater impairment in everyday skills and sel...

  6. The Finnish lapphund retinal atrophy locus maps to the centromeric region of CFA9

    OpenAIRE

    Sargan David R; Wickström Kaisa; Aguirre-Hernández Jesús

    2007-01-01

    Abstract Background Dogs have the second largest number of genetic diseases, after humans. Among the diseases present in dogs, progressive retinal atrophy has been reported in more than a hundred breeds. In some of them, the mutation has been identified and genetic tests have allowed the identification of carriers, thus enabling a drastic reduction in the incidence of the disease. The Finnish lapphund is a dog breed presenting late-onset progressive retinal atrophy for which the disease locus...

  7. IgM MGUS anti-MAG neuropathy with predominant muscle weakness and extensive muscle atrophy.

    Science.gov (United States)

    Kawagashira, Yuichi; Kondo, Naohide; Atsuta, Naoki; Iijima, Masahiro; Koike, Haruki; Katsuno, Masahisa; Tanaka, Fumiaki; Kusunoki, Susumu; Sobue, Gen

    2010-09-01

    We report a patient with anti-myelin-associated glycoprotein (MAG) neuropathy, predominantly exhibiting severe motor symptoms, accompanied by extensive muscle atrophy mimicking Charcot-Marie-Tooth disease. Nerve conduction studies revealed mild retardation of motor conduction velocities and significant prolongation of distal latency. Sural nerve biopsy revealed widely spaced myelin and positive staining of myelinated fibers with an IgM antibody. Predominant motor symptoms with muscle atrophy can be one of the clinical manifestations of anti-MAG neuropathy.

  8. Bilateral spontaneous dislocation of posterior chamber intraocular lens in a patient with gyrate atrophy

    Directory of Open Access Journals (Sweden)

    Michael Kinori

    2012-01-01

    Full Text Available We report a patient with gyrate atrophy, a rare metabolic disease, who had bilateral late spontaneous posterior dislocation of in-the-bag posterior chamber intraocular lens (PCIOL. He underwent pars plana vitrectomy, PCIOL retrieval and anterior chamber intraocular lens implantation in both eyes. This report may imply that patients with gyrate atrophy are at risk for spontaneous dislocation of intraocular lenses.

  9. [Psychosocial intellectual development of children with infantile cystinosis and cerebral atrophy (author's transl)].

    Science.gov (United States)

    Ehrich, J H; Wolff, G; Stoeppler, L; Heyer, R; Offner, G; Brodehl, J

    1979-09-01

    The psychosocial and intellectual development of 4 boys with nephropathic cystinosis and brain atrophy documented by cranial computerized tomography was investigated by use of biographical data and psychological tests (HAWIK, Deutscher Rechtschreibtest). Inspite of the brain atrophy the patients showed low-normal intellectual capacities and mainly average school performance. There were no psychosocial abnormalities correlated to the primary metabolic disease. However, renal dwarfism led to mascotism requiring psychotherapy.

  10. In Vitro Modeling of Microgravity-Induced Muscle Atrophy and Spaceflight Radiation

    OpenAIRE

    Harding, Charles; Takemoto, Jon; Vargis, Elizabeth

    2016-01-01

    Muscular atrophy, defined as the loss of muscle tissue, is a serious issue for immobilized patients on Earth and in human spaceflight, where microgravity prevents normal muscle loading. A major factor in muscular atrophy is oxidative stress, which is amplified not only by muscle disuse, but also by the increased levels of ionizing radiation in spaceflight. Additionally, elevated radiation exposure can damage DNA, increasing cancer risk. To model oxidative stress and DNA damage generated by...

  11. Vaginal atrophy in breast cancer survivors: role of vaginal estrogen therapy.

    Science.gov (United States)

    Mariani, Luciano; Gadducci, Angiolo; Vizza, Enrico; Tomao, Silverio; Vici, Patrizia

    2013-01-01

    Early menopause and related vaginal atrophy is a well known side-effect of hormone adjuvant treatment in breast cancer patients, particularly during aromatase-inhibitors therapy. Due to estrogens contra-indication, proper therapy for such symptom remains often an inadequately addressed clinical problem. After an accurate assessment of the risk/benefit ratio, vaginal low-dose estrogen treatment (better with estriol) [corrected] may have a role in controlling vaginal atrophy in selected and informed breast cancer women.

  12. Relationship between the degree of endoscopic atrophy of the gastric mucosa and carcinogenic risk.

    Science.gov (United States)

    Masuyama, Hironori; Yoshitake, Naoto; Sasai, Takako; Nakamura, Tetsuya; Masuyama, Atsushi; Zuiki, Toru; Kurashina, Kentaro; Mieda, Mitsuyo; Sunada, Keijiro; Yamamoto, Hironori; Togashi, Kazutomo; Terano, Akira; Hiraishi, Hideyuki

    2015-01-01

    The relationship between Helicobacter pylori infection and gastric cancer has been demonstrated, and the risk of gastric cancer occurrence is known to increase with the progression of atrophic changes associated with chronic gastritis. Endoscopic evaluation of the degree and extent of atrophy of the gastric mucosa is a simple and very important means of identifying a group at high risk for gastric cancer. This study aimed to clarify the carcinogenic risk in relation to the degree of atrophy. A total of 27,777 patients (272 with early gastric cancer and 135 with advanced gastric cancer) were included in this study. Endoscopically evaluated atrophy of the gastric mucosa was classified as C-0 to O-3 according to the Kimura and Takemoto classification system. The cancer detection rate in relation to the degree of gastric mucosal atrophy was 0.04% (2/4,183 patients) for C-0, 0% (0/4,506) for C-1, 0.25% (9/3,660) for C-2, 0.71% (21/2,960) for C-3, 1.32% (75/5,684) for O-1, 3.70% (140/3,780) for O-2 and 5.33% (160/3,004) for O-3. As to the proportions of differentiated and undifferentiated cancers, the latter were relatively frequent in the C-0 to C-2 groups, but differentiated cancers became predominant as atrophy progressed. On the other hand, the number of both differentiated and undifferentiated cancers detected increased as gastric mucosal atrophy progressed. In addition, open-type atrophy was found in 29 (96.7%) of 30 patients with synchronous multiple gastric cancers and in all 20 patients with metachronous multiple gastric cancers. Endoscopic evaluation of gastric mucosal atrophy can provide a simple and reliable predictive index for both current and future carcinogenic risk. © 2015 S. Karger AG, Basel.

  13. Atrophy patterns in early clinical stages across distinct phenotypes of Alzheimer's disease.

    Science.gov (United States)

    Ossenkoppele, Rik; Cohn-Sheehy, Brendan I; La Joie, Renaud; Vogel, Jacob W; Möller, Christiane; Lehmann, Manja; van Berckel, Bart N M; Seeley, William W; Pijnenburg, Yolande A; Gorno-Tempini, Maria L; Kramer, Joel H; Barkhof, Frederik; Rosen, Howard J; van der Flier, Wiesje M; Jagust, William J; Miller, Bruce L; Scheltens, Philip; Rabinovici, Gil D

    2015-11-01

    Alzheimer's disease (AD) can present with distinct clinical variants. Identifying the earliest neurodegenerative changes associated with each variant has implications for early diagnosis, and for understanding the mechanisms that underlie regional vulnerability and disease progression in AD. We performed voxel-based morphometry to detect atrophy patterns in early clinical stages of four AD phenotypes: Posterior cortical atrophy (PCA, "visual variant," n=93), logopenic variant primary progressive aphasia (lvPPA, "language variant," n=74), and memory-predominant AD categorized as early age-of-onset (EOAD, 65 years, n=114). Patients with each syndrome were stratified based on: (1) degree of functional impairment, as measured by the clinical dementia rating (CDR) scale, and (2) overall extent of brain atrophy, as measured by a neuroimaging approach that sums the number of brain voxels showing significantly lower gray matter volume than cognitively normal controls (n=80). Even at the earliest clinical stage (CDR=0.5 or bottom quartile of overall atrophy), patients with each syndrome showed both common and variant-specific atrophy. Common atrophy across variants was found in temporoparietal regions that comprise the posterior default mode network (DMN). Early syndrome-specific atrophy mirrored functional brain networks underlying functions that are uniquely affected in each variant: Language network in lvPPA, posterior cingulate cortex-hippocampal circuit in amnestic EOAD and LOAD, and visual networks in PCA. At more advanced stages, atrophy patterns largely converged across AD variants. These findings support a model in which neurodegeneration selectively targets both the DMN and syndrome-specific vulnerable networks at the earliest clinical stages of AD.

  14. Differential effects of ischemic vascular disease and Alzheimer's disease on brain atrophy and cognition.

    Science.gov (United States)

    Zheng, Ling; Vinters, Harry V; Mack, Wendy J; Weiner, Michael W; Chui, Helena C

    2016-01-01

    We previously reported that pathologic measures of arteriosclerosis (AS), cerebral infarction, and Alzheimer’s disease (AD) are independently correlated with cortical gray matter (CGM) atrophy measured by in vivo magnetic resonance imaging (MRI). Here, we use path analyses to model the associations between these three pathology measures and cognitive impairment, as mediated by CGM atrophy, after controlling for age and education. In this sample of 116 elderly persons followed longitudinally to autopsy (ischemic vascular disease (IVD) program project), differential patterns were observed between AS and atrophy/cognition versus AD and atrophy/cognition. The total effect of AD pathology on global cognition (β = -0.61, s.e. = 0.06) was four times stronger than that of AS (β = -0.15, s.e. = 0.08). The effect of AS on cognition appears to occur through cerebral infarction and CGM atrophy (β = -0.13, s.e. = 0.04). In contrast, the effects of AD pathology on global cognition (β = -0.50, s.e. = 0.07) occur through a direct pathway that is five times stronger than the indirect pathway acting through CGM atrophy (β = -0.09, s.e. = 0.03). The strength of this direct AD pathway was not significantly mitigated by adding hippocampal volume to the model. AD pathology affects cognition not only through brain atrophy, but also via an unmeasured pathway that could be related to synaptic dysfunction before the development of cortical atrophy.

  15. Macular sensitivity and fixation patterns in patients with autosomal dominant optic atrophy

    DEFF Research Database (Denmark)

    Rönnbäck, Cecilia; Larsen, Michael

    2014-01-01

    of fixation stability and fixation location. RESULTS: The average (± standard deviation) sensitivity was significantly reduced in ADOA patients compared with controls, 14.9 (± 4.4) dB versus 19.7 (± 0.4) dB (p projection, the largest relative sensitivity deficits in ADOA were seen...

  16. Macular atrophy in patients with long-term anti-VEGF treatment for neovascular age-related macular degeneration.

    Science.gov (United States)

    Munk, Marion R; Ceklic, Lala; Ebneter, Andreas; Huf, Wolfgang; Wolf, Sebastian; Zinkernagel, Martin S

    2016-12-01

    To identify the prevalence and progression of macular atrophy (MA) in neovascular age-related macular degeneration (AMD) patients under long-term anti-vascular endothelial growth factor (VEGF) therapy and to determine risk factors. This retrospective study included patients with neovascular AMD and ≥30 anti-VEGF injections. Macular atrophy (MA) was measured using near infrared and spectral-domain optical coherence tomography (SD-OCT). Yearly growth rate was estimated using square-root transformation to adjust for baseline area and allow for linearization of growth rate. Multiple regression with Akaike information criterion (AIC) as model selection criterion was used to estimate the influence of various parameters on MA area. Forty-nine eyes (47 patients, mean age 77 ± 14) were included with a mean of 48 ± 13 intravitreal anti-VEGF injections (ranibizumab:37 ± 11, aflibercept:11 ± 6, mean number of injections/year 8 ± 2.1) over a mean treatment period of 6.2 ± 1.3 years (range 4-8.5). Mean best-corrected visual acuity improved from 57 ± 17 letters at baseline (= treatment start) to 60 ± 16 letters at last follow-up. The MA prevalence within and outside the choroidal neovascularization (CNV) border at initial measurement was 45% and increased to 74%. Mean MA area increased from 1.8 ± 2.7 mm(2) within and 0.5 ± 0.98 mm(2) outside the CNV boundary to 2.7 ± 3.4 mm(2) and 1.7 ± 1.8 mm(2) , respectively. Multivariate regression determined posterior vitreous detachment (PVD) and presence/development of intraretinal cysts (IRCs) as significant factors for total MA size (R(2) = 0.16, p = 0.02). Macular atrophy (MA) area outside the CNV border was best explained by the presence of reticular pseudodrusen (RPD) and IRC (R(2) = 0.24, p = 0.02). A majority of patients show MA after long-term anti-VEGF treatment. Reticular pseudodrusen (RPD), IRC and PVD but not number of injections or treatment duration seem to be associated with the

  17. Resistance strength training exercise in children with spinal muscular atrophy.

    Science.gov (United States)

    Lewelt, Aga; Krosschell, Kristin J; Stoddard, Gregory J; Weng, Cindy; Xue, Mei; Marcus, Robin L; Gappmaier, Eduard; Viollet, Louis; Johnson, Barbara A; White, Andrea T; Viazzo-Trussell, Donata; Lopes, Philippe; Lane, Robert H; Carey, John C; Swoboda, Kathryn J

    2015-10-01

    Preliminary evidence in adults with spinal muscular atrophy (SMA) and in SMA animal models suggests exercise has potential benefits in improving or stabilizing muscle strength and motor function. We evaluated feasibility, safety, and effects on strength and motor function of a home-based, supervised progressive resistance strength training exercise program in children with SMA types II and III. Up to 14 bilateral proximal muscles were exercised 3 times weekly for 12 weeks. Nine children with SMA, aged 10.4 ± 3.8 years, completed the resistance training exercise program. Ninety percent of visits occurred per protocol. Training sessions were pain-free (99.8%), and no study-related adverse events occurred. Trends in improved strength and motor function were observed. A 12-week supervised, home-based, 3-day/week progressive resistance training exercise program is feasible, safe, and well tolerated in children with SMA. These findings can inform future studies of exercise in SMA. © 2015 Wiley Periodicals, Inc.

  18. [A case of spinal muscular atrophy type 0 in Japan].

    Science.gov (United States)

    Okamoto, Kentaro; Saito, Kayoko; Sato, Takatoshi; Ishigaki, Keiko; Funatsuka, Makoto; Osawa, Makiko

    2012-09-01

    The patient was a 2-month-old female infant born at 41 weeks and 2 days of gestation presenting multiple arthrogryposis, severe muscle hypotonia and respiratory distress with difficulty in feeding. She suffered from repeated complications with aspiration pneumonia. On admission to our hospital, she exhibited fasciculation and absence of deep tendon reflexes. Examination of the motor nerve conduction velocity (MCV) revealed no muscle contraction. Deletions of the SMN and NAIP genes were noted. Based on severe clinical course and disease development in utero, she was given a diagnosis of spinal muscular atrophy (SMA) type 0 (very severe type). Arthrogryposis and disappearance of MCV are exclusion criteria for SMA. However, the clinical course of the infant was very severe and included such exclusion items. Consequently, when an infant presents muscle hypotonia and respiratory distress, SMA must be considered as one of the differential diagnoses, even though arthrogryposis is an exclusion criterion for SMA. We discuss this case in relation to the few extant reports on SMA type 0 in Japanese infants in the literature.

  19. Transmission of multiple system atrophy prions to transgenic mice.

    Science.gov (United States)

    Watts, Joel C; Giles, Kurt; Oehler, Abby; Middleton, Lefkos; Dexter, David T; Gentleman, Steve M; DeArmond, Stephen J; Prusiner, Stanley B

    2013-11-26

    Prions are proteins that adopt alternative conformations, which become self-propagating. Increasing evidence argues that prions feature in the synucleinopathies that include Parkinson's disease, Lewy body dementia, and multiple system atrophy (MSA). Although TgM83(+/+) mice homozygous for a mutant A53T α-synuclein transgene begin developing CNS dysfunction spontaneously at ∼10 mo of age, uninoculated TgM83(+/-) mice (hemizygous for the transgene) remain healthy. To determine whether MSA brains contain α-synuclein prions, we inoculated the TgM83(+/-) mice with brain homogenates from two pathologically confirmed MSA cases. Inoculated TgM83(+/-) mice developed progressive signs of neurologic disease with an incubation period of ∼100 d, whereas the same mice inoculated with brain homogenates from spontaneously ill TgM83(+/+) mice developed neurologic dysfunction in ∼210 d. Brains of MSA-inoculated mice exhibited prominent astrocytic gliosis and microglial activation as well as widespread deposits of phosphorylated α-synuclein that were proteinase K sensitive, detergent insoluble, and formic acid extractable. Our results provide compelling evidence that α-synuclein aggregates formed in the brains of MSA patients are transmissible and, as such, are prions. The MSA prion represents a unique human pathogen that is lethal upon transmission to Tg mice and as such, is reminiscent of the prion causing kuru, which was transmitted to chimpanzees nearly 5 decades ago.

  20. Reducing RBM20 activity improves diastolic dysfunction and cardiac atrophy.

    Science.gov (United States)

    Hinze, Florian; Dieterich, Christoph; Radke, Michael H; Granzier, Henk; Gotthardt, Michael

    2016-12-01

    Impaired diastolic filling is a main contributor to heart failure with preserved ejection fraction (HFpEF), a syndrome with increasing prevalence and no treatment. Both collagen and the giant sarcomeric protein titin determine diastolic function. Since titin's elastic properties can be adjusted physiologically, we evaluated titin-based stiffness as a therapeutic target. We adjusted RBM20-dependent cardiac isoform expression in the titin N2B knockout mouse with increased ventricular stiffness. A ~50 % reduction of RBM20 activity does not only maintain cardiac filling in diastole but also ameliorates cardiac atrophy and thus improves cardiac function in the N2B-deficient heart. Reduced RBM20 activity partially normalized gene expression related to muscle development and fatty acid metabolism. The adaptation of cardiac growth was related to hypertrophy signaling via four-and-a-half lim-domain proteins (FHLs) that translate mechanical input into hypertrophy signals. We provide a novel link between cardiac isoform expression and trophic signaling via FHLs and suggest cardiac splicing as a therapeutic target in diastolic dysfunction. Increasing the length of titin isoforms improves ventricular filling in heart disease. FHL proteins are regulated via RBM20 and adapt cardiac growth. RBM20 is a therapeutic target in diastolic dysfunction.

  1. Biomarkers in Rare Disorders: The Experience with Spinal Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Christina Brahe

    2010-12-01

    Full Text Available Spinal muscular atrophy (SMA is an autosomal recessive neuromuscular disorder caused by homozygous mutations of the SMN1 gene. Based on clinical severity, three forms of SMA are recognized (type I–III. All patients have at least one (usually 2–4 copies of a highly homologous gene (SMN2 which produces insufficient levels of functional SMN protein, due to alternative splicing of exon7. Recently, evidence has been provided that SMN2 expression can be enhanced by different strategies. The availability of potential candidates to treat SMA has raised a number of issues, including the availability of data on the natural history of the disease, the reliability and sensitivity of outcome measures, the duration of the studies, and the number and clinical homogeneity of participating patients. Equally critical is the availability of reliable biomarkers. So far, different tools have been proposed as biomarkers in SMA, classifiable into two groups: instrumental (the Compound Motor Action Potential, the Motor Unit Number Estimation, and the Dual-energy X-ray absorptiometry and molecular (SMN gene products dosage, either transcripts or protein. However, none of the biomarkers available so far can be considered the gold standard. Preclinical studies on SMA animal models and double-blind, placebo-controlled studies are crucial to evaluate the appropriateness of biomarkers, on the basis of correlations with clinical outcome.

  2. Clinical Characteristics of Cases with Spinal Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Mehmet Canpolat

    2016-04-01

    Full Text Available Introduction: The aim of this study is was to evaluate the clinical features of cases with diagnosis of spinal muscular atrophy (SMA. Materials and Methods: Thirty-eight pediatric patients were evaluated retrospectively. All patients were followed in the Pediatric Neurology Department of Erciyes University Faculty of Medicine. The diagnosis of patients had been confirmed by genetic analysis of homozygous deletions of survival motor neuron 1 gene. Detailed history, newborn symptoms, nutritional characteristics, initial complaints, physical examination, concomitant pathologies, genetic characteristics, and treatment modalities were investigated in all patients. Results: The study population consisted of 19 boys (50% and 19 girls (50%. The mean age of patients was 26.9±25.7 months (range: 3-96 months. The mean follow-up period was 12.2±13.3 months (range: 2-48 months. According to SMA classification, 22 patients (57.8% were type 1, 8 patients (21.1% were type 2, and 8 patients were (21.1% type 3. Neonatal respiratory distress, age at early diagnosis, nutritional problems, and recurrent lung diseases were detected as poor prognostic factors. Conclusions: SMA is a neuromuscular disease that requires multidisciplinary approach to medical care. There is a wide range of clinical severity. Identification of poor prognostic factors will help in terms of guiding close monitoring and timely treatments of children with SMA.

  3. Multiple System Atrophy. Using Clinical Pharmacology to Reveal Pathophysiology

    Science.gov (United States)

    Jordan, Jens; Shibao, Cyndya; Biaggioni, Italo

    2015-01-01

    Despite similarities in their clinical presentation, patients with multiple system atrophy (MSA) have residual sympathetic tone and intact post-ganglionic noradrenergic fibers, whereas patients with pure autonomic failure (PAF) and Parkinson’s disease (PD) have efferent post-ganglionic autonomic denervation. These differences are apparent biochemically, with near normal plasma norepinephrine in MSA but very low levels in PAF, and in neurophysiological testing. These differences are also reflected in the response patients have to drugs that interact with the autonomic nervous system. E.g., the ganglionic blocker trimethaphan reduce residual sympathetic tone and lower blood pressure in MSA but less so in PAF. Conversely, the α2-antagonist yohimbine produces a greater increase in blood pressure in MSA compared to PAF, although significant overlap exists. In normal subjects the norepinephrine reuptake (NET) inhibitor atomoxetine has little effect on blood pressure because the peripheral effects of NET inhibition that result in noradrenergic vasoconstriction, are counteracted by the increase in brain norepinephrine which reduces sympathetic outflow (a clonidine-like effect). In patients with autonomic failure and intact peripheral noradrenergic fibers only the peripheral vasoconstriction is apparent. This translates to a significant pressor effect of atomoxetine in MSA, but not in PAF patients. Thus, pharmacological probes can be used to understand the pathophysiology of the different forms of autonomic failure, assist in the diagnosis, and aid in the management of orthostatic hypotension. PMID:25757803

  4. [Postoperative seizure in an epileptic patient with dentatorubral pallidoluysian atrophy].

    Science.gov (United States)

    Yanagidate, Fumi; Dohi, Shuji; Hamaya, Yoshihiro; Ueda, Norio

    2002-05-01

    A 28-year-old male with dentatorubral pallidoluysian atrophy (DRPLA) was scheduled for evulsion of bone marrow nail after tibia fracture. He was diagnosed as having DRPLA at the age of 12. Although he was receiving anticonvulsants, regular seizures had occurred occasionally and his symptoms were exacerbating. General anesthesia was induced and maintained with intravenous propofol supplemented with fentanyl, nitrous oxide, and oxygen. The operation was performed uneventfully. After the surgery, his breathing was depressed and naloxone was administered to reverse the depression. Thereafter, generalized tonic seizure associated with involuntary movement of the left arm occurred. These symptoms ceased soon after rapid injection of diazepam. Inhaled and intravenous anesthetics have been alleged to have both proconvulsant and anticonvulsant activities in humans. In the present patient with DRPLA, propofol, fentanyl, nitrous oxide, naloxone, and neostigmine administered might be factors, which could have lowered the threshold for seizure activity. Further, patients with DRPLA might have decreased GABA in the basal ganglia, and anesthetics would affect GABA receptors. Thus we should be aware of occurrence of convulsion in DRPLA patients during and after anesthesia.

  5. Clinical features of adult spinal muscular atrophy:46 cases

    Institute of Scientific and Technical Information of China (English)

    Xiaojun He; Ping Zhang; Guanghui Chen

    2006-01-01

    BACKGROUND: Spinal muscular atrophy (SMA) is a kind of degenerative disease of nervous system. There are 4 types in clinic, especially types Ⅰ, Ⅱ and Ⅲ are common, and the researches on those 3 types are relative mature. Type Ⅳ is a kind of adult spinal muscular atrophy (ASMA), which has low incidence rate and is often misdiagnosed as amyotrophic lateral sclerosis, muscular dystrophy, cervical syndrome, or others.OBJECTIVE: To observe the clinical features of 46 ASMA patients and analyze the relationship between course and activity of daily living.DESIGN: Case analysis.SETTING: Departments of Neurology of the 81 Hospital of Chinese PLA, the Second Affiliated Hospital of Nanjing Medical College and General Hospital of Nanjing Military Area Command of Chinese PLA.PARTICIPANTS: A total of 46 ASMA patients were selected from the Departments of Neurology of the 81Hospital of Chinese PLA, the Second Affiliated Hospital of Nanjing Medical College and General Hospital of Nanjing Military Area Command of Chinese PLA between April 1998 and January 2002. All patients were consentient. Among 46 cases, there were 37 males and 9 females with the mean age of 42 years. The patients' courses in all ranged from 6 months to 23 years, concretely, courses of 37 cases were less than or equal to 5 years, and those of 9 cases were more than or equal to 6 years.METHODS : ① All the 46 ASMA patients were asked to check blood sedimentation, anti O, serum creatinine,creatine, blood creatine phosphokinase (CPK) and muscular biopsy as early as possible. ② X-ray was used to measure plain film of cervical vertebra borderline film of cranium and neck at proximal end of upper limb of 25 cases and plain film of abdominal vertebra at proximal end of lower limb of 17 cases.③ Cerebrospinal fluid of lumbar puncture was checked on 42 cases, for routine examination, biochemical examination, and immunoglobulin examination. Electromyogram (EMG) was also examined to 42 cases. ④ Barthel index

  6. On the atrophy of the internal carotid artery in capybara.

    Science.gov (United States)

    Steele, Caroline; Fioretto, Emerson T; Sasahara, Tais H C; Guidi, Wanderley L; de Lima, Ana R; Ribeiro, Antonio A C M; Loesch, Andrzej

    2006-12-01

    Capybara might be a useful model for studying changes in cerebral circulation as the natural atrophy of the internal carotid artery (ICA) occurs in this animal at maturation. In this study, confocal and electron microscopy combined with immunohistochemical techniques were applied in order to reveal the changes in morphology and innervation to the proximal part of ICA in young (6-month-old) and mature (12-month-old) capybaras. Some features of the basilar artery (BA) were also revealed. The ICA of young animals degenerated to a ligamentous cord in mature animals. Immunolabelling positive for pan-neuronal marker protein gene product 9.5 but negative for tyrosine hydroxylase was observed in the proximal part of ICA at both ages examined. Axon varicosities positive for synaptophysin were present in the adventitia of ICA of young animals but were absent in the ligamentous cord of mature animals. In the ICA of young animals, adventitial connective tissue invaded the media suggesting that the process of regression of this artery began within the first 6 months of life. An increase in size of the BA was found in mature animals indicating increased blood flow in the vertebro-basilar system, possibly making capybara susceptible to cerebrovascular pathology (e.g. stroke). Capybara may therefore provide a natural model for studying adaptive responses to ICA regression/occlusion.

  7. Iritis and iris atrophy after eyebrow epilation with alexandrite laser

    Directory of Open Access Journals (Sweden)

    Elkin Z

    2011-12-01

    Full Text Available Zachary Elkin1, Milan P Ranka1, Eleanore T Kim1, Ronit Kahanowicz1, Wayne G Whitmore21Department of Ophthalmology, New York University; 2Department of Ophthalmology, New York Presbyterian Hospital, Weill Cornell Medical College, New York, NY, USAPurpose: To report a case of bilateral iritis and transillumination defects after laser hair removal of the eyebrows with an alexandrite laser.Methods: A 41-year-old male presented with bilateral eye pain and mild photophobia 2 days after receiving alexandrite (755 nm laser epilation of both eyebrows. Examination showed visual acuity of 20/20 in both eyes, 2+ conjunctival injection in both eyes, 1+ cells in the anterior chamber of right eye and trace cells in left eye, poor right pupil dilation, and left pupil without movement. Intraocular pressure and fundus examination were normal. He was diagnosed with iritis and iris atrophy, associated with laser epilation. Topical steroids and cycloplegic drops were prescribed for 1 month.Results: After 1 month of treatment, transillumination defects remained in both eyes, but greater in right. In dim light, the right pupil was 4 mm and oval and the left pupil was 6 mm and round. Visual acuity remained 20/20 in both eyes.Conclusion: Laser hair removal of the eyebrows can lead to permanent ocular damage even with eye protection, and should be avoided.Keywords: laser hair removal, transillumination defects, alexandrite laser

  8. A genome-wide association study in multiple system atrophy

    Science.gov (United States)

    Sailer, Anna; Nalls, Michael A.; Schulte, Claudia; Federoff, Monica; Price, T. Ryan; Lees, Andrew; Ross, Owen A.; Dickson, Dennis W.; Mok, Kin; Mencacci, Niccolo E.; Schottlaender, Lucia; Chelban, Viorica; Ling, Helen; O'Sullivan, Sean S.; Wood, Nicholas W.; Traynor, Bryan J.; Ferrucci, Luigi; Federoff, Howard J.; Mhyre, Timothy R.; Morris, Huw R.; Deuschl, Günther; Quinn, Niall; Widner, Hakan; Albanese, Alberto; Infante, Jon; Bhatia, Kailash P.; Poewe, Werner; Oertel, Wolfgang; Höglinger, Günter U.; Wüllner, Ullrich; Goldwurm, Stefano; Pellecchia, Maria Teresa; Ferreira, Joaquim; Tolosa, Eduardo; Bloem, Bastiaan R.; Rascol, Olivier; Meissner, Wassilios G.; Hardy, John A.; Revesz, Tamas; Holton, Janice L.; Gasser, Thomas; Wenning, Gregor K.; Singleton, Andrew B.

    2016-01-01

    Objective: To identify genetic variants that play a role in the pathogenesis of multiple system atrophy (MSA), we undertook a genome-wide association study (GWAS). Methods: We performed a GWAS with >5 million genotyped and imputed single nucleotide polymorphisms (SNPs) in 918 patients with MSA of European ancestry and 3,864 controls. MSA cases were collected from North American and European centers, one third of which were neuropathologically confirmed. Results: We found no significant loci after stringent multiple testing correction. A number of regions emerged as potentially interesting for follow-up at p < 1 × 10−6, including SNPs in the genes FBXO47, ELOVL7, EDN1, and MAPT. Contrary to previous reports, we found no association of the genes SNCA and COQ2 with MSA. Conclusions: We present a GWAS in MSA. We have identified several potentially interesting gene loci, including the MAPT locus, whose significance will have to be evaluated in a larger sample set. Common genetic variation in SNCA and COQ2 does not seem to be associated with MSA. In the future, additional samples of well-characterized patients with MSA will need to be collected to perform a larger MSA GWAS, but this initial study forms the basis for these next steps. PMID:27629089

  9. Hypospadias as a novel feature in spinal bulbar muscle atrophy.

    Science.gov (United States)

    Nordenvall, Anna Skarin; Paucar, Martin; Almqvist, Catarina; Nordenström, Anna; Frisén, Louise; Nordenskjöld, Agneta

    2016-04-01

    Spinal and bulbar muscle atrophy (SBMA) is an X-linked neuromuscular disorder caused by CAG repeat expansions in the androgen receptor (AR) gene. The SBMA phenotype consists of slowly progressive neuromuscular symptoms and undermasculinization features as the result of malfunction of the AR. The latter mainly includes gynecomastia and infertility. Hypospadias is also a feature of undermasculinization with an underdeveloped urethra and penis; it has not been described as part of the SBMA phenotype but has been suggested to be associated with a prolonged CAG repeat in the AR gene. This study includes the first epidemiologic description of the co-occurrence of hypospadias and SBMA in subjects and their male relatives in Swedish population-based health registers, as well as an additional clinical case. One boy with severe hypospadias was screened for mutations in the AR gene and was found to have 42 CAG repeats in it, which is in the full range of mutations causing SBMA later in life. We also detected a maximum of four cases displaying the combination of SBMA and hypospadias in our national register databases. This is the third case report with hypospadias in association with CAG repeat expansions in the AR gene in the full range known to cause SBMA later in life. Our findings suggest that hypospadias may be an under diagnosed feature of the SBMA phenotype and we propose that neurologists working with SBMA further investigate and report the true prevalence of hypospadias among patients with SBMA.

  10. Founder effect in spinal and bulbar muscular atrophy (SBMA).

    Science.gov (United States)

    Tanaka, F; Doyu, M; Ito, Y; Matsumoto, M; Mitsuma, T; Abe, K; Aoki, M; Itoyama, Y; Fischbeck, K H; Sobue, G

    1996-09-01

    We analyzed the polymorphic (CAG)n and (GGC)n repeats of the androgen receptor gene in 113 unrelated X-linked spinal and bulbar muscular atrophy (SBMA) X chromosomes and 173 control X chromosomes in Japanese males. The control chromosomes had an average CAG repeat number of 21 +/- 3 with a range from 14-32 repeat units, and SBMA chromosomes had a range from 40-55 with a median of 47 +/- 3 copies. The control chromosomes had seven different alleles of the (GGC)n repeat with the range of 11 to 17; the most frequent size of (GGC)n was 16 (79%), while (GGC)17 was very rare (1%). However, in SBMA chromosomes only two alleles were seen; the most frequent size of (GGC)n was 16 (61%) followed by 17 (39%). (GGC)n size distribution was significantly different between SBMA and control chromosomes (P SBMA patients, which suggests that a founder effect makes a more significant contribution to generation of Japanese SBMA chromosomes than new mutations.

  11. Optimization of Spinal Muscular Atrophy subject's muscle activity during gait

    Science.gov (United States)

    Umat, Gazlia; Rambely, Azmin Sham

    2014-06-01

    Spinal Muscular Atrophy (SMA) is a hereditary disease related muscle nerve disorder caused by degeneration of the anterior cells of the spinal cord. SMA is divided into four types according to the degree of seriousness. SMA patients show different gait with normal people. Therefore, this study focused on the effects of SMA patient muscle actions and the difference that exists between SMA subjects and normal subjects. Therefore, the electromyography (EMG) test will be used to track the behavior of muscle during walking and optimization methods are used to get the muscle stress that is capable of doing the work while walking. Involved objective function is non-linear function of the quadratic and cubic functions. The study concludes with a comparison of the objective function using the force that sought to use the moment of previous studies and the objective function using the data obtained from EMG. The results shows that the same muscles, peroneus longus and bisepsfemoris, were used during walking activity by SMA subjects and control subjects. Muscle stress force best solution achieved from part D in simulation carried out.

  12. Urinary and erectile dysfunction in multiple system atrophy (MSA).

    Science.gov (United States)

    Papatsoris, A G; Papapetropoulos, S; Singer, C; Deliveliotis, C

    2008-01-01

    Multiple system atrophy (MSA) is a neurodegenerative disease of undetermined etiology that occurs sporadically and manifests itself as a combination of parkinsonian, autonomic, cerebellar, and pyramidal signs. Despite the lack of effective therapies, some of the symptoms may be, at least temporarily, improved with adequate symptomatic therapies. Urinary and erectile dysfunction (ED) symptoms are prominent early features in male MSA patients. Lower urinary tract infections (UTIs) are a major cause of morbidity and mortality in this disorder. More than 50% of MSA patients suffer from recurrent lower UTIs and a significant number (approximately 25%) die of complications related to them. Urogenital symptoms in MSA are usually due to a complex mixture of central and peripheral nervous abnormalities, sometimes superimposed on previous local pathological conditions such as benign prostatic hyperplasia and perineal laxity. There have been instances were MSA-related urological symptoms were confused with symptoms of benign prostatic hyperplasia, leading to unnecessary urological surgery. In this review, we present the phenotypic range and therapeutic approaches for common storage and voiding urological symptoms and ED, in patients with MSA.

  13. Are antioxidants useful for treating skeletal muscle atrophy?

    Science.gov (United States)

    Bonetto, Andrea; Penna, Fabio; Muscaritoli, Maurizio; Minero, Valerio G; Rossi Fanelli, Filippo; Baccino, Francesco M; Costelli, Paola

    2009-10-01

    Changes in the skeletal muscle protein mass frequently occur in both physiological and pathological states. Muscle hypotrophy, in particular, is commonly observed during aging and is characteristic of several pathological conditions such as neurological diseases, cancer, diabetes, and sepsis. The skeletal muscle protein content depends on the relative rates of synthesis and degradation, which must be coordinately regulated to maintain the equilibrium. Pathological muscle depletion is characterized by a negative nitrogen balance, which results from disruption of this equilibrium due to reduced synthesis, increased breakdown, or both. The current view, mainly based on experimental data, considers hypercatabolism as the major cause of muscle protein depletion. Several signaling pathways that probably contribute to muscle atrophy have been identified, and there is increasing evidence that oxidative stress, due to reactive oxygen species production overwhelming the intracellular antioxidant systems, plays a role in causing muscle depletion both during aging and in chronic pathological states. In particular, oxidative stress has been proposed to enhance protein breakdown, directly or by interacting with other factors. This review focuses on the possibility of using antioxidant treatments to target molecular pathways involved in the pathogenesis of skeletal muscle wasting.

  14. False positives to confusable objects predict medial temporal lobe atrophy.

    Science.gov (United States)

    Kivisaari, Sasa L; Monsch, Andreas U; Taylor, Kirsten I

    2013-09-01

    Animal models agree that the perirhinal cortex plays a critical role in object recognition memory, but qualitative aspects of this mnemonic function are still debated. A recent model claims that the perirhinal cortex is required to recognize the novelty of confusable distractor stimuli, and that damage here results in an increased propensity to judge confusable novel objects as familiar (i.e., false positives). We tested this model in healthy participants and patients with varying degrees of perirhinal cortex damage, i.e., amnestic mild cognitive impairment and very early Alzheimer's disease (AD), with a recognition memory task with confusable and less confusable realistic object pictures, and from whom we acquired high-resolution anatomic MRI scans. Logistic mixed-model behavioral analyses revealed that both patient groups committed more false positives with confusable than less confusable distractors, whereas healthy participants performed comparably in both conditions. A voxel-based morphometry analysis demonstrated that this effect was associated with atrophy of the anteromedial temporal lobe, including the perirhinal cortex. These findings suggest that also the human perirhinal cortex recognizes the novelty of confusable objects, consistent with its border position between the hierarchical visual object processing and medial temporal lobe memory systems, and explains why AD patients exhibit a heightened propensity to commit false positive responses with inherently confusable stimuli.

  15. Dental implants for severely atrophied jaws due to ectodermal dysplasia

    Directory of Open Access Journals (Sweden)

    Preetha Balaji

    2015-01-01

    Full Text Available The aim was to present the successful esthetical and functional rehabilitation of partial anodontia in a case of severe ectodermal dysplasia with complete atrophy of the jaws. A 17-year-old male with Class III malocclusion with partial anodontia sought dental implant treatment. His expectation was that of Class I occlusion. The challenge in the case was to match the expectation, reality, and the clinical possibilities. Ridge augmentation was performed with a combination of rib graft and recombinant human bone morphogenetic protein-2. Simultaneously, 6 implants (Nobel Biocare™ - Tapered Groovy were placed in maxillary arch and 10 in the mandible. Simultaneous placement ensured faster and better osseointegration though a mild compromise of the primary stability was observed initially. After adequate healing, Customized Zirconia Procera™ system was used to build the framework. Zirconia crown was cemented to the framework. Radiological and clinical evidence of osseointegration was observed in all 16 dental implants. Successful conversion of Class III to Class I occlusion was achieved with the combination of preprosthetic alveolar ridge augmentation, Procera™ Implant Bridge system. Abnormal angulations and or placement of dental implants would result in failure of the implant. Hence conversion of Class III to Class I occlusion needs complete and complex treatment planning so that the entire masticatory apparatus is sufficiently remodeled. Planning should consider the resultant vectors that would otherwise result in failure of framework or compromise the secondary stability of the dental implant during function. A successful case of rehabilitation of complex partial anodontia is presented.

  16. Muscle fatigue, nNOS and muscle fiber atrophy in limb girdle muscular dystrophy.

    Science.gov (United States)

    Angelini, Corrado; Tasca, Elisabetta; Nascimbeni, Anna Chiara; Fanin, Marina

    2014-12-01

    Muscle fatigability and atrophy are frequent clinical signs in limb girdle muscular dystrophy (LGMD), but their pathogenetic mechanisms are still poorly understood. We review a series of different factors that may be connected in causing fatigue and atrophy, particularly considering the role of neuronal nitric oxide synthase (nNOS) and additional factors such as gender in different forms of LGMD (both recessive and dominant) underlying different pathogenetic mechanisms. In sarcoglycanopathies, the sarcolemmal nNOS reactivity varied from absent to reduced, depending on the residual level of sarcoglycan complex: in cases with complete sarcoglycan complex deficiency (mostly in beta-sarcoglycanopathy), the sarcolemmal nNOS reaction was absent and it was always associated with early severe clinical phenotype and cardiomyopathy. Calpainopathy, dysferlinopathy, and caveolinopathy present gradual onset of fatigability and had normal sarcolemmal nNOS reactivity. Notably, as compared with caveolinopathy and sarcoglycanopathies, calpainopathy and dysferlinopathy showed a higher degree of muscle fiber atrophy. Males with calpainopathy and dysferlinopathy showed significantly higher fiber atrophy than control males, whereas female patients have similar values than female controls, suggesting a gender difference in muscle fiber atrophy with a relative protection in females. In female patients, the smaller initial muscle fiber size associated to endocrine factors and less physical effort might attenuate gender-specific muscle loss and atrophy.

  17. The gross motor function measure is a valid and sensitive outcome measure for spinal muscular atrophy.

    Science.gov (United States)

    Nelson, Leslie; Owens, Hollis; Hynan, Linda S; Iannaccone, Susan T

    2006-06-01

    Spinal muscular atrophy is a genetic disease of the anterior horn cell with high morbidity rate in childhood. Certain drugs may be of benefit and are in or under consideration for Phase II trials. Outcome measures that are age appropriate and representative of disease activity remain under study. Several have not yet been validated for spinal muscular atrophy. The Gross Motor Function Measure is a measure of motor function. We showed previously that the Gross Motor Function Measure is a reliable outcome measure to assess motor function in children with spinal muscular atrophy. By collating our data from 40 spinal muscular atrophy patients, ages 5 through 17 years, we now show the validity of the Gross Motor Function Measure when compared to Quantitative Muscle Testing and ambulatory status in children with spinal muscular atrophy. The median for Gross Motor Function Measure total scores for walkers was 237 (range: 197-261) and for non-walkers, 64 (range: 4-177; PGross Motor Function Measure is valid and sensitive as an outcome measure for clinical trials in pediatric spinal muscular atrophy.

  18. Calcified neurocysticercosis associates with hippocampal atrophy: a population-based study.

    Science.gov (United States)

    Del Brutto, Oscar H; Salgado, Perla; Lama, Julio; Del Brutto, Victor J; Campos, Xavier; Zambrano, Mauricio; García, Héctor H

    2015-01-01

    Calcified neurocysticercosis has been associated with hippocampal atrophy in patients with refractory epilepsy, but the relevance of this association in the population at large is unknown. We assessed calcified cysticerci and its association with hippocampal atrophy in elderly persons living in Atahualpa, an Ecuadorian village endemic for neurocysticercosis. All Atahualpa residents ≥ 60 years of age were invited to undergo computed tomography/magnetic resonance imaging for neurocysticercosis detection. Twenty-eight (11%) out of 248 enrolled persons had calcified cysticerci (case-patients) and were matched 1:1 by age, sex, and years of education to individuals without neurocysticercosis on computed tomography/magnetic resonance imaging (controls). Four case-patients and none of the controls had epilepsy (P = 0.134). Cognitive performance was similar across both groups. The Scheltens' medial temporal atrophy scale was used for hippocampal rating in case-patients and matched controls without neurocysticercosis. Mean score in the Scheltens' scale was higher in case-patients than in controls (P < 0.001). Atrophic hippocampi were noticed in 19 case-patients and five controls (P = 0.003). Atrophy was bilateral in 11 case-patients and unilateral in eight. All case-patients with unilateral hippocampal atrophy had at least one ipsilateral calcification. This study shows an association between calcified cysticerci and hippocampal atrophy and raises the possibility of an inflammation-mediated hippocampal damage as the responsible mechanism for these findings.

  19. Calcified Neurocysticercosis Associates with Hippocampal Atrophy: A Population-Based Study

    Science.gov (United States)

    Del Brutto, Oscar H.; Salgado, Perla; Lama, Julio; Del Brutto, Victor J.; Campos, Xavier; Zambrano, Mauricio; García, Héctor H.

    2015-01-01

    Calcified neurocysticercosis has been associated with hippocampal atrophy in patients with refractory epilepsy, but the relevance of this association in the population at large is unknown. We assessed calcified cysticerci and its association with hippocampal atrophy in elderly persons living in Atahualpa, an Ecuadorian village endemic for neurocysticercosis. All Atahualpa residents ≥ 60 years of age were invited to undergo computed tomography/magnetic resonance imaging for neurocysticercosis detection. Twenty-eight (11%) out of 248 enrolled persons had calcified cysticerci (case-patients) and were matched 1:1 by age, sex, and years of education to individuals without neurocysticercosis on computed tomography/magnetic resonance imaging (controls). Four case-patients and none of the controls had epilepsy (P = 0.134). Cognitive performance was similar across both groups. The Scheltens' medial temporal atrophy scale was used for hippocampal rating in case-patients and matched controls without neurocysticercosis. Mean score in the Scheltens' scale was higher in case-patients than in controls (P < 0.001). Atrophic hippocampi were noticed in 19 case-patients and five controls (P = 0.003). Atrophy was bilateral in 11 case-patients and unilateral in eight. All case-patients with unilateral hippocampal atrophy had at least one ipsilateral calcification. This study shows an association between calcified cysticerci and hippocampal atrophy and raises the possibility of an inflammation-mediated hippocampal damage as the responsible mechanism for these findings. PMID:25349375

  20. Atrophy of muscles surrounding the shoulder in hemiplegia. Analysis with MRI

    Energy Technology Data Exchange (ETDEWEB)

    Fukuda, Fumio; Kobayashi, Tsunesaburo; Matsumoto, Shinichi [Fukushima Rosai Hospital, Iwaki (Japan)

    1996-01-01

    Decrease of range of motion and subluxation of shoulders are common secondary dysfunctions after the stroke. The purpose of this study is to evaluate the atrophy of muscles surrounding shoulders in hemiplegic patients and to delineate the correlations between those atrophies and shoulder functions. MRI studies were done on bilateral shoulders in 13 hemiplegic patients with shoulder pain. The cross sectional areas of muscles surrounding shoulder, i.e., subscapularis, supraspinatus, infraspinatus, teres minor and deltoid muscle were measured on those images obtained. The degree of atrophies were evaluated by dividing cross-sectional area of the muscle on affected shoulder by that of non-affected shoulder, that is muscle atrophy ratio [MAR], for each muscle in every case. Also, the range of movements [ROM], the degree of subluxation and muscle strength of shoulder flexion were evaluated. All muscle cross-sectional areas on the affected side were significantly smaller than those of muscles on the unaffected side (p<0.01). The means of MARs were 0.68, 0.69, 0.86, 0.72 and 0.69 for subscapularis, supraspinatus, infraspinatus, teres minor and deltoid muscle. The pattern of muscle atrophies, however, varies from case to case. Both correlations of ROM versus supraspinatus MAR and degree of shoulder subluxation versus deltoid MAR were statistically significant (p<0.05). These results indicate the contribution of muscle atrophy to the shoulder dysfunction in hemiplegic patients. (author).

  1. Increased cortical atrophy in patients with Alzheimer's disease and type 2 diabetes mellitus

    Science.gov (United States)

    Biessels, G J; De Leeuw, F‐E; Lindeboom, J; Barkhof, F; Scheltens, P

    2006-01-01

    Background The risk of Alzheimer's disease (AD) is increased in type 2 diabetes (DM2). This increased risk has been attributed to vascular comorbidity, but other mechanisms, such as accelerated ageing of the brain, have also been implicated. Objective To determine whether AD in patients with DM2 is associated with an increased occurrence of vascular lesions in the brain, by increased cerebral atrophy, or a combination of both. Methods In total, 29 patients with AD and DM2 and 58 patients with AD and without DM2 were included in the study. Clinical characteristics were recorded, and a neuropsychological examination and magnetic resonance imaging (MRI) scan were performed. MRI scans were rated for cortical and subcortical atrophy, medial temporal lobe atrophy, white matter lesions, and infarcts. Results The neuropsychological profiles of the two groups were identical. Patients with AD and DM2 had increased cortical atrophy on MRI (p<0.05) compared with the non‐DM2 group. In addition, infarcts were more common (odds ratio 2.4; 95% CI 0.8 to 7.8), but this effect did not account for the increased atrophy. The other MR measures did not differ between the groups. Conclusion The results suggest that non‐vascular mechanisms, leading to increased cortical atrophy, are also involved in the increased risk of AD in DM2. PMID:16484636

  2. Dehydroepiandrosterone intra vaginal administration for the management of postmenopausal vulvovaginal atrophy.

    Science.gov (United States)

    Archer, David F

    2015-01-01

    The effects of intravaginal administration of dehydroepiandrosterone (DHEA) for the management of symptomatic vulvovaginal atrophy are reviewed. A literature search related to vulvovaginal atrophy, vaginal atrophy, atrophic vaginitis, estrogen, dehydroepiandrosterone, vulvar itching, burning, dryness, dyspareunia, and libido was performed. Relevant articles addressing the incidence, management, and outcome of DHEA therapy were identified and used for this Expert Opinion. DHEA compared to a placebo is an effective treatment improving symptoms of vaginal atrophy: dyspareunia, burning, itching, and dryness. Objective parameters of vaginal atrophy, specifically pH, vaginal maturation index (VMI), and investigator-evaluated changes in the vagina: moisture, epithelia integrity and color were improved compared to baseline and placebo. There were significant improvements in libido and dyspareunia with the intravaginal use of DHEA that contribute to improved quality of life for postmenopausal women. Dehydroepiandrosterone administered intravaginally on a daily basis is an effective treatment for symptoms, and signs of vulvovaginal atrophy along with libido in postmenopausal women. This article is part of a Special Issue entitled 'Essential role of DHEA'.

  3. Pattern of brain atrophy rates in autopsy-confirmed dementia with Lewy bodies.

    Science.gov (United States)

    Nedelska, Zuzana; Ferman, Tanis J; Boeve, Bradley F; Przybelski, Scott A; Lesnick, Timothy G; Murray, Melissa E; Gunter, Jeffrey L; Senjem, Matthew L; Vemuri, Prashanti; Smith, Glenn E; Geda, Yonas E; Graff-Radford, Jonathan; Knopman, David S; Petersen, Ronald C; Parisi, Joseph E; Dickson, Dennis W; Jack, Clifford R; Kantarci, Kejal

    2015-01-01

    Dementia with Lewy bodies (DLB) is characterized by preserved whole brain and medial temporal lobe volumes compared with Alzheimer's disease dementia (AD) on magnetic resonance imaging. However, frequently coexistent AD-type pathology may influence the pattern of regional brain atrophy rates in DLB patients. We investigated the pattern and magnitude of the atrophy rates from 2 serial MRIs in autopsy-confirmed DLB patients (n = 20) and mixed DLB/AD patients (n = 22), compared with AD (n = 30) and elderly nondemented control subjects (n = 15), followed antemortem. DLB patients without significant AD-type pathology were characterized by lower global and regional rates of atrophy, similar to control subjects. The mixed DLB/AD patients displayed greater atrophy rates in the whole brain, temporoparietal cortices, hippocampus and amygdala, and ventricle expansion, similar to AD patients. In the DLB and DLB/AD patients, the atrophy rates correlated with Braak neurofibrillary tangle stage, cognitive decline, and progression of motor symptoms. Global and regional atrophy rates are associated with AD-type pathology in DLB, and these rates can be used as biomarkers of AD progression in patients with LB pathology.

  4. Evolution of Cerebral Atrophy in a Patient with Super Refractory Status Epilepticus Treated with Barbiturate Coma

    Science.gov (United States)

    George, Pravin; Nattanmai, Premkumar; Ahrens, Christine; Hantus, Stephen; Sarwal, Aarti

    2017-01-01

    Introduction. Status epilepticus is associated with neuronal breakdown. Radiological sequelae of status epilepticus include diffusion weighted abnormalities and T2/FLAIR cortical hyperintensities corresponding to the epileptogenic cortex. However, progressive generalized cerebral atrophy from status epilepticus is underrecognized and may be related to neuronal death. We present here a case of diffuse cerebral atrophy that developed during the course of super refractory status epilepticus management despite prolonged barbiturate coma. Methods. Case report and review of the literature. Case. A 19-year-old male with a prior history of epilepsy presented with focal clonic seizures. His seizures were refractory to multiple anticonvulsants and eventually required pentobarbital coma for 62 days and midazolam coma for 33 days. Serial brain magnetic resonance imaging (MRI) showed development of cerebral atrophy at 31 days after admission to our facility and progression of the atrophy at 136 days after admission. Conclusion. This case highlights the development and progression of generalized cerebral atrophy in super refractory status epilepticus. The cerebral atrophy was noticeable at 31 days after admission at our facility which emphasizes the urgency of definitive treatment in patients who present with super refractory status epilepticus. Further research into direct effects of therapeutic coma is warranted. PMID:28182114

  5. Evolution of Cerebral Atrophy in a Patient with Super Refractory Status Epilepticus Treated with Barbiturate Coma

    Directory of Open Access Journals (Sweden)

    Christopher R. Newey

    2017-01-01

    Full Text Available Introduction. Status epilepticus is associated with neuronal breakdown. Radiological sequelae of status epilepticus include diffusion weighted abnormalities and T2/FLAIR cortical hyperintensities corresponding to the epileptogenic cortex. However, progressive generalized cerebral atrophy from status epilepticus is underrecognized and may be related to neuronal death. We present here a case of diffuse cerebral atrophy that developed during the course of super refractory status epilepticus management despite prolonged barbiturate coma. Methods. Case report and review of the literature. Case. A 19-year-old male with a prior history of epilepsy presented with focal clonic seizures. His seizures were refractory to multiple anticonvulsants and eventually required pentobarbital coma for 62 days and midazolam coma for 33 days. Serial brain magnetic resonance imaging (MRI showed development of cerebral atrophy at 31 days after admission to our facility and progression of the atrophy at 136 days after admission. Conclusion. This case highlights the development and progression of generalized cerebral atrophy in super refractory status epilepticus. The cerebral atrophy was noticeable at 31 days after admission at our facility which emphasizes the urgency of definitive treatment in patients who present with super refractory status epilepticus. Further research into direct effects of therapeutic coma is warranted.

  6. INFLUENCE OF SHORTENED AND LENGTHENED IMMOBILIZATION ON RAT SOLEUS MUSCLE ATROPHY

    Institute of Scientific and Technical Information of China (English)

    邢国刚; 樊小力; 吴苏娣; 宋新爱; 朱保恭; 唐斌

    2001-01-01

    Objective: To study the possible mechanism and prevention of disuse muscle atrophy. Methods: The shortened immobilization (plaster fixation) of rat' s soleus muscle (SOL) was used as the model of muscle and the lengthened immobilization of rat' s SOL muscle as "passive stretch" method. Types of skeletal muscle fibers were differentiated with m - ATPase staining technique. The changes of rat' s SOL muscle weight (wet weight) as well as the types and the mean cross - sectional area (CSA) of muscle fibers were examined respectively on day 2, 4,7, 14 and 21 under both shortened and lengthened immobilization and then the effect of passive stretch on soleus muscle atrophy in immobilized rats was observed. Results: When shortened immobilization was applied for 4 days, SOL muscle weight (wet weight) became lighter; the fiber crosssectional area (CSA) shrank and type Ⅰ muscle fibers started transforming into type Ⅱ, which all indicated immobilized muscles began to atrophy and as immobilization proceeded, muscle atrophy proceeded toward higher level. In contrast to that, when lengthened immobilization was applied, SOL muscle didn' t show any sign of atrophy until 7th day, and reached its highest level on day 14 and maintained that level even though immobilization continued. Conclusion: From the results, we conclude that passive stretch can either relieve or defer disuse muscle atrophy.

  7. EFFECTS OF PASSIVE STRETCH ON SOLEUS MUSCLE ATROPHY IN IMMOBILIZED RATS

    Institute of Scientific and Technical Information of China (English)

    邢国刚; 樊小力; 吴苏娣; 宋新爱; 朱保恭; 唐斌

    2002-01-01

    Objective To study the possible mechanism and prevention of disused muscle atrophy. Methods The shortened immobilization (plaster fixation) of rat's soleus muscle(SOL) was used as the model of muscle "disuse" and the lengthened immobilization of rat's SOL muscle as "passive stretch" method. Types of skeletal muscle fibers were differentiated with m-ATPase staining technique. The changes of rat's SOL weight (wet weight) as well as the types and the mean cross sectional area (CSA) of muscle fibers were examined respectively on days 2,4,7,14 and 21 under both shortened and lengthened immobilization, and then the effect of passive stretch on soleus muscle atrophy in immobilized rats was observed. Results When shortened immobilization was applied for 4 days, SOL weight (wet weight ) became lighter, the fiber cross-sectional area (CSA) shrank, and type Ⅰ muscle fibers started to transform into type Ⅱ, which all indicated that immobilized muscles began to atrophy, and as immobilization proceeded, muscle atrophy proceeded toward higher level. In contrast to that, when lengthened immobilization was applied, SOL didn't show any signs of atrophy until day 7, the sign reached its highest level on day 14 and maintained that level even though immobilization continued. Conclusion From the results, we conclude that the passive stretch can either relieve or retard the disused muscle atrophy.

  8. Brain atrophy rates in first degree relatives at risk for Alzheimer's.

    Science.gov (United States)

    Lampert, Erika J; Roy Choudhury, Kingshuk; Hostage, Christopher A; Rathakrishnan, Bharath; Weiner, Michael; Petrella, Jeffrey R; Doraiswamy, P Murali

    2014-01-01

    A positive family history (FH) raises the risk for late-onset Alzheimer's disease though, other than the known risk conferred by apolipoprotein ε4 (ApoE4), much of the genetic variance remains unexplained. We examined the effect of family history on longitudinal regional brain atrophy rates in 184 subjects (42% FH+, mean age 79.9) with mild cognitive impairment (MCI) enrolled in a national biomarker study. An automated image analysis method was applied to T1-weighted MR images to measure atrophy rates for 20 cortical and subcortical regions. Mixed-effects linear regression models incorporating repeated-measures to control for within-subject variation over multiple time points tested the effect of FH over a follow-up of up to 48 months. Most of the 20 regions showed significant atrophy over time. Adjusting for age and gender, subjects with a positive FH had greater atrophy of the amygdala (p atrophy rates was numerically greater in ε3 homozygotes than in E4 carriers, but this difference was not significant. FH+ subjects had numerically greater 4-year cognitive decline and conversion rates than FH- subjects but the difference was not statistically significant after adjusting for ApoE and other variables. We conclude that a positive family history of AD may influence cortical and temporal lobe atrophy in subjects with mild cognitive impairment, but it does not have a significant additional effect beyond the known effect of the E4 genotype.

  9. l-Carnitine supplement reduces skeletal muscle atrophy induced by prolonged hindlimb suspension in rats.

    Science.gov (United States)

    Jang, Jiwoong; Park, Jonghoon; Chang, Hyukki; Lim, Kiwon

    2016-12-01

    l-Carnitine was recently found to downregulate the ubiquitin proteasome pathway (UPP) and increase insulin-like growth factor 1 concentrations in animal models. However, the effect of l-carnitine administration on disuse muscle atrophy induced by hindlimb suspension has not yet been studied. Thus, we hypothesized that l-carnitine may have a protective effect on muscle atrophy induced by hindlimb suspension via the Akt1/mTOR and/or UPP. Male Wistar rats were assigned to 3 groups: hindlimb suspension group, hindlimb suspension with l-carnitine administration (1250 mg·kg(-1)·day(-1)) group, and pair-fed group adjusted hindlimb suspension. l-Carnitine administration for 2 weeks of hindlimb suspension alleviated the decrease in weight and fiber size in the soleus muscle. In addition, l-carnitine suppressed atrogin-1 mRNA expression, which has been reported to play a pivotal role in muscle atrophy. The present study shows that l-carnitine has a protective effect against soleus muscle atrophy caused by hindlimb suspension and decreased E3 ligase messenger RNA expression, suggesting the possibility that l-carnitine protects against muscle atrophy, at least in part, through the inhibition of the UPP. These observations suggest that l-carnitine could serve as an effective supplement in the decrease of muscle atrophy caused by weightlessness in the fields of clinical and rehabilitative research.

  10. The analysis of antioxidant expression during muscle atrophy induced by hindlimb suspension in mice.

    Science.gov (United States)

    Nuoc, Tran-Non; Kim, Suhee; Ahn, Sun Hee; Lee, Jin-Sil; Park, Byung-Ju; Lee, Tae-Hoon

    2017-01-01

    Oxidative stress contributes to acceleration of muscle atrophy. However, it is still not completely understood what triggers the production of reactive oxygen species (ROS) during muscle atrophy. The objective of this study was to investigate redox balance during muscle atrophy. ROS generators and antioxidants were analyzed in atrophied soleus muscles after 2 weeks of hindlimb suspension (HLS) in mice. The HLS group showed an increase in lipid peroxidation, upregulated NOX1 and NOXO1, and downregulated mitochondrial complex I subunits NDUFS5 and NDUFV2. Additionally, HLS mice demonstrated a decrease in Prdx5 and MnSOD, but an increase in GPX2 and GPX3 in both mRNA and protein levels. As expected, MnSOD activity declined in the HLS group, while GPX activity was enhanced. These results suggest that redox imbalance occurs during muscle atrophy through NOX1 activation, mitochondrial complex I deficiency, and disturbance of antioxidants. Antioxidants altered by HLS may represent potential therapeutic targets for the protection against muscle atrophy.

  11. Recommendations to quantify villous atrophy in video capsule endoscopy images of celiac disease patients

    Science.gov (United States)

    Ciaccio, Edward J; Bhagat, Govind; Lewis, Suzanne K; Green, Peter H

    2016-01-01

    AIM To quantify the presence of villous atrophy in endoscopic images for improved automation. METHODS There are two main categories of quantitative descriptors helpful to detect villous atrophy: (1) Statistical and (2) Syntactic. Statistical descriptors measure the small intestinal substrate in endoscope-acquired images based on mathematical methods. Texture is the most commonly used statistical descriptor to quantify villous atrophy. Syntactic descriptors comprise a syntax, or set of rules, for analyzing and parsing the substrate into a set of objects with boundaries. The syntax is designed to identify and distinguish three-dimensional structures based on their shape. RESULTS The variance texture statistical descriptor is useful to describe the average variability in image gray level representing villous atrophy, but does not determine the range in variability and the spatial relationships between regions. Improved textural descriptors will incorporate these factors, so that areas with variability gradients and regions that are orientation dependent can be distinguished. The protrusion syntactic descriptor is useful to detect three-dimensional architectural components, but is limited to identifying objects of a certain shape. Improvement in this descriptor will require incorporating flexibility to the prototypical template, so that protrusions of any shape can be detected, measured, and distinguished. CONCLUSION Improved quantitative descriptors of villous atrophy are being developed, which will be useful in detecting subtle, varying patterns of villous atrophy in the small intestinal mucosa of suspected and known celiac disease patients. PMID:27803772

  12. Functional Connectivity of Ventral and Dorsal Visual Streams in Posterior Cortical Atrophy.

    Science.gov (United States)

    Migliaccio, Raffaella; Gallea, Cécile; Kas, Aurélie; Perlbarg, Vincent; Samri, Dalila; Trotta, Laura; Michon, Agnès; Lacomblez, Lucette; Dubois, Bruno; Lehericy, Stéphane; Bartolomeo, Paolo

    2016-01-01

    Posterior cortical atrophy (PCA) induces progressive dysfunction of ventral and dorsal visual networks. Little is known, however, about corresponding changes in functional connectivity (FC). To investigate FC changes in the visual networks, their relationship with cortical atrophy, and the association with Alzheimer's disease (AD) pathology. Ten PCA patients and 28 age-matched controls participated in the study. Using resting state fMRI, we measured FC in ventral and dorsal cortical visual networks, defined on the basis of a priori knowledge of long-range white matter connections. To assess the relationships with AD, we determined AD biomarkers in cerebrospinal fluid and FC in the default mode network (DMN), which is vulnerable to AD pathology. Voxel-based morphometry analysis assessed the pattern of grey matter (GM) atrophy. PCA patients showed GM atrophy in bilateral occipital and inferior parietal regions. PCA patients had lower FC levels in a ventral network than controls, but higher FC in inferior components of the dorsal network. In particular, the increased connectivity correlated with greater GM atrophy in occipital regions. All PCA patients had positive cerebrospinal fluid biomarkers for AD; however, FC in global DMN did not differ from controls. FC in PCA reflects brain structure in a non-univocal way. Hyperconnectivity of dorsal networks may indicate aberrant communication in response to posterior brain atrophy or processes of neural resilience during the initial stage of brain dysfunction. The lack of difference from controls in global DMN FC highlights the atypical nature of PCA with respect to typical AD.

  13. Skeletal muscle atrophy is induced by Fbxw7β via atrogene upregulation.

    Science.gov (United States)

    Shin, Kyungshin; Ko, Young-Gyu; Jeong, Jaemin; Kwon, Heechung

    2017-02-01

    Muscle atrophy decreases skeletal muscle mass and is induced by inherited cachectic symptoms, genetic disorders, and sarcopenia. However, the molecular pathways associated with the onset of muscle atrophy are still unclear. In this study, we evaluated Fbxw7β, a gene associated with the development of muscle atrophy in vitro and in vivo. Among the three Fbxw7 isoforms, ectopically overexpressed Fbxw7β induced the expression of myogenin and major atrogene markers (atrogin-1 and MuRF-1) and reduced myoblast differentiation. In addition, endogenous expression of Fbxw7β was also upregulated by dexamethasone, which mimics muscle atrophy in vitro, accompanied by induction of myogenin and atrogene expression in primary myoblasts. Functional analysis of Fbxw7β using short hairpin RNA (shRNA) and a dominant-negative mutant (ΔFbox) suggested that Fbxw7β regulated muscle atrophy in vitro and in vivo. In particular, ΔFbox did not reduce the sizes of muscle fibers and did not induce myogenin and atrogene expression in vivo. Therefore, our findings demonstrated, for the first time, that Fbxw7β induced muscle atrophic phenotypes via atrogenes in adult muscle precursor cells and myofibers; this mechanism could be a potential therapeutic target for skeletal muscle atrophy. © 2016 International Federation for Cell Biology.

  14. Topical Mineralocorticoid Receptor Blockade Limits Glucocorticoid-Induced Epidermal Atrophy in Human Skin.

    Science.gov (United States)

    Maubec, Eve; Laouénan, Cédric; Deschamps, Lydia; Nguyen, Van Tuan; Scheer-Senyarich, Isabelle; Wackenheim-Jacobs, Anne-Catherine; Steff, Maud; Duhamel, Stéphanie; Tubiana, Sarah; Brahimi, Nesrine; Leclerc-Mercier, Stéphanie; Crickx, Béatrice; Perret, Claudine; Aractingi, Selim; Escoubet, Brigitte; Duval, Xavier; Arnaud, Philippe; Jaisser, Frederic; Mentré, France; Farman, Nicolette

    2015-07-01

    A major deleterious side effect of glucocorticoids is skin atrophy. Glucocorticoids activate the glucocorticoid and the mineralocorticoid (MR) receptor, both present in the epidermis. We hypothesized that glucocorticoid-induced epidermal atrophy may be related to inappropriate occupancy of MR by glucocorticoids. We evaluated whether epidermal atrophy induced by the topical glucocorticoid clobetasol could be limited by coadministration of MR antagonist. In cultured human skin explants, the epidermal atrophy induced by clobetasol was significantly limited by MR antagonism (canrenoate and eplerenone). Blockade of the epithelial sodium channel ENaC by phenamil was also efficient, identifying a role of MR-ENaC cascade in keratinocytes, acting through restoration of clobetasol-induced impairment of keratinocyte proliferation. In the SPIREPI randomized double-blind controlled trial, gels containing clobetasol, the MR antagonist spironolactone, both agents, or placebo were applied on four zones of the forearms of 23 healthy volunteers for 28 days. Primary outcome was histological thickness of the epidermis with clobetasol alone or clobetasol+spironolactone. Spironolactone alone did not affect the epidermal thickness but coapplication of clobetasol and spironolactone significantly limited clobetasol-induced atrophy and was well tolerated. Altogether, these findings identify MR as a factor regulating epidermal homeostasis and suggest that topical MR blockade could limit glucocorticoid-induced epidermal atrophy.

  15. Regional gray matter atrophy and neuropsychologcal problems in relapsing-remitting multiple sclerosis

    Institute of Scientific and Technical Information of China (English)

    Aiyu Lin; Fuyong Chen; Fang Liu; Zhiwen Li; Ying Liu; Shifang Lin; Xiaoyi Wang; Jiting Zhu

    2013-01-01

    In multiple sclerosis, gray matter atrophy is extensive, and cognitive deficits and mood disorders are frequently encountered. It has been conjectured that focal atrophy is associated with emotional de-cline. However, conventional MRI has revealed that the pathological characteristics cannot ful y account for the mood disorders. Moreover, there is no correlation between cognitive disorders and MRI results in clinical y isolated syndromes or in cases of definite multiple sclerosis. In this case-control study, voxel-based morphometric analysis was performed on 11 subjects with relapsing-remitting multiple sclerosis, and the results show that these patients exhibit gray matter atrophy. Moreover, the gray matter atrophy in the superior and middle gyri of the right frontal lobe in patients with multiple sclerosis was correlated with scores from the Hamilton Anxiety Rating Scale. The scores obtained with the Repeatable Battery for the Assessment of Neuropsychological Status were associated with gray matter atrophy in the middle gyrus of the left frontal lobe, the superior and middle gyrus of the right frontal lobe, the middle gyrus of the left cingulate, the superior and middle gyri of the left frontal lobe, and the triangular area of the left frontal lobe. However, there was no statistical significance. These findings suggest that the cingulate and frontal cortices of the nant hemisphere are the most severely atrophic regions of the brain, and this atrophy is correlated with cognitive decline and emotional abnormalities.

  16. Age- and gender-related changes in contractile properties of non-atrophied EDL muscle.

    Directory of Open Access Journals (Sweden)

    Stephen Chan

    Full Text Available BACKGROUND: In humans, ageing causes skeletal muscles to become atrophied, weak, and easily fatigued. In rodent studies, ageing has been associated with significant muscle atrophy and changes in the contractile properties of the muscles. However, it is not entirely clear whether these changes in contractile properties can occur before there is significant atrophy, and whether males and females are affected differently. METHODS AND RESULTS: We investigated various contractile properties of whole isolated fast-twitch EDL muscles from adult (2-6 months-old and aged (12-22 months-old male and female mice. Atrophy was not present in the aged mice. Compared with adult mice, EDL muscles of aged mice had significantly lower specific force, longer tetanus relaxation times, and lower fatiguability. In the properties of absolute force and muscle relaxation times, females were affected by ageing to a greater extent than males. Additionally, EDL muscles from a separate group of male mice were subjected to eccentric contractions of 15% strain, and larger force deficits were found in aged than in adult mice. CONCLUSION: Our findings provide further insight into the muscle atrophy, weakness and fatiguability experienced by the elderly. We have shown that even in the absence of muscle atrophy, there are definite alterations in the physiological properties of whole fast-twitch muscle from ageing mice, and for some of these properties the alterations are more pronounced in female mice than in male mice.

  17. Age- and Gender-Related Changes in Contractile Properties of Non-Atrophied EDL Muscle

    Science.gov (United States)

    Chan, Stephen; Head, Stewart I.

    2010-01-01

    Background In humans, ageing causes skeletal muscles to become atrophied, weak, and easily fatigued. In rodent studies, ageing has been associated with significant muscle atrophy and changes in the contractile properties of the muscles. However, it is not entirely clear whether these changes in contractile properties can occur before there is significant atrophy, and whether males and females are affected differently. Methods and Results We investigated various contractile properties of whole isolated fast-twitch EDL muscles from adult (2–6 months-old) and aged (12–22 months-old) male and female mice. Atrophy was not present in the aged mice. Compared with adult mice, EDL muscles of aged mice had significantly lower specific force, longer tetanus relaxation times, and lower fatiguability. In the properties of absolute force and muscle relaxation times, females were affected by ageing to a greater extent than males. Additionally, EDL muscles from a separate group of male mice were subjected to eccentric contractions of 15% strain, and larger force deficits were found in aged than in adult mice. Conclusion Our findings provide further insight into the muscle atrophy, weakness and fatiguability experienced by the elderly. We have shown that even in the absence of muscle atrophy, there are definite alterations in the physiological properties of whole fast-twitch muscle from ageing mice, and for some of these properties the alterations are more pronounced in female mice than in male mice. PMID:20808812

  18. Early onset cerebellar ataxia with retained tendon reflexes (EOCA and olivopontocerebellar atrophy (OPCA : a computed tomographic study.

    Directory of Open Access Journals (Sweden)

    Pal P

    1999-10-01

    Full Text Available Computed tomographic (CT studies in olivopontocerebellar atrophies (OPCA and ′early onset cerebellar ataxia with retained tendon reflexes (EOCA′ are few and vary widely in methodology and criteria for cerebellar and brainstem atrophy. In this prospective study, CT scan observations on 26 patients (EOCA-11, OPCA-15 were compared with 31 controls using qualitative and quantitative assessment of cisterns, ventricles and atrophy of brain. Vermian and/or cerebellar hemispheric (predominantly anterior atrophy was present in 80.8% and both were equally common. Cerebral cortical atrophy (26.9% and leukoariosis (15.4% were less frequently seen. Statistically significant atrophy of pons, brachium pontis, cerebellum and midbrain was noted in patient group. No significant differences were observed between EOCA and OPCA groups. Evidence of atrophy did not correlate with either the duration of illness or the severity of cerebellar ataxia in both the groups. The severity of brainstem atrophy in 14 patients with and 12 patients without abnormal brainstem auditory evoked response did not differ significantly. This study highlights the methodology of CT evaluation for brainstem and cerebellar atrophy, draws attention to cerebral atrophy and emphasizes the lack of significant differences in CT morphology between OPCA and EOCA patients.

  19. Gadd45a Protein Promotes Skeletal Muscle Atrophy by Forming a Complex with the Protein Kinase MEKK4.

    Science.gov (United States)

    Bullard, Steven A; Seo, Seongjin; Schilling, Birgit; Dyle, Michael C; Dierdorff, Jason M; Ebert, Scott M; DeLau, Austin D; Gibson, Bradford W; Adams, Christopher M

    2016-08-19

    Skeletal muscle atrophy is a serious and highly prevalent condition that remains poorly understood at the molecular level. Previous work found that skeletal muscle atrophy involves an increase in skeletal muscle Gadd45a expression, which is necessary and sufficient for skeletal muscle fiber atrophy. However, the direct mechanism by which Gadd45a promotes skeletal muscle atrophy was unknown. To address this question, we biochemically isolated skeletal muscle proteins that associate with Gadd45a as it induces atrophy in mouse skeletal muscle fibers in vivo We found that Gadd45a interacts with multiple proteins in skeletal muscle fibers, including, most prominently, MEKK4, a mitogen-activated protein kinase kinase kinase that was not previously known to play a role in skeletal muscle atrophy. Furthermore, we found that, by forming a complex with MEKK4 in skeletal muscle fibers, Gadd45a increases MEKK4 protein kinase activity, which is both sufficient to induce skeletal muscle fiber atrophy and required for Gadd45a-mediated skeletal muscle fiber atrophy. Together, these results identify a direct biochemical mechanism by which Gadd45a induces skeletal muscle atrophy and provide new insight into the way that skeletal muscle atrophy occurs at the molecular level. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Photoreceptor atrophy in acute zonal occult outer retinopathy

    DEFF Research Database (Denmark)

    Zibrandtsen, N.; Munch, I.C.; Klemp, K.

    2006-01-01

    Purpose: To assess retinal morphology in acute zonal occult outer retinopathy (AZOOR). Methods: Three patients with a normal ophthalmoscopic fundus appearance, a history of photopsia, and visual field loss compatible with AZOOR were examined using optical coherence tomography, automated perimetry...