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Sample records for recessive spinal muscular

  1. Clinico-epidemiologic characteristics of spinal muscular atrophy ...

    African Journals Online (AJOL)

    Rabah M. Shawky

    Deletion;. Chromosome 5;. Mutations. Abstract Spinal muscular atrophy (SMA) is characterized by progressive hypotonia and muscular weakness because of progressive degeneration of alpha motor neuron from anterior horn cells in the spinal cord. It is inherited by an autosomal recessive pattern. The precise frequency of ...

  2. Genetics Home Reference: spinal muscular atrophy

    Science.gov (United States)

    ... difficulty breathing. Children with this type often have joint deformities (contractures) that impair movement. In severe cases, ... Proximal spinal muscular atrophy Washington University, St. Louis: Neuromuscular Disease Center: Spinal Muscular Atrophy Patient Support and ...

  3. Spinal Muscular Atrophy FAQ

    Science.gov (United States)

    ... as ALS (Lou Gehrig’s Disease), cystic fibrosis and Duchenne muscular dystrophy. Approximately 1 in 50 Americans, or about 6 ... Pediatric Neuromuscular Clinical Research Network ( PNCR ) and the Muscular ... is the SMN2 gene? Muscle weakness and atrophy in SMA results from the ...

  4. 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;

  5. Spinal and bulbar muscular atrophy.

    Science.gov (United States)

    Lieberman, Andrew P

    2018-01-01

    Spinal and bulbar muscular atrophy (SBMA) is an adult-onset degenerative disorder of the neuromuscular system resulting in slowly progressive weakness and atrophy of the proximal limb and bulbar muscles. The disease is caused by the expansion of a CAG/glutamine tract in the amino-terminus of the androgen receptor. That SBMA exclusively affects males reflects the fact that critical pathogenic events are hormone-dependent. These include translocation of the polyglutamine androgen receptor from the cytoplasm to the nucleus and unfolding of the mutant protein. Studies of the pathology of SBMA subjects have revealed nuclear aggregates of the mutant androgen receptor, loss of lower motor neurons in the brainstem and spinal cord, and both neurogenic and myopathic changes in skeletal muscle. Mechanisms underlying disease pathogenesis include toxicity in both lower motor neurons and skeletal muscle, where effects on transcription, intracellular transport, and mitochondrial function have been documented. Therapies to treat SBMA patients remain largely supportive, although experimental approaches targeting androgen action or promoting degradation of the mutant androgen receptor protein or the encoding RNA are under active study. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Preimplantation genetic diagnosis of spinal muscular atrophy

    NARCIS (Netherlands)

    Dreesen, JCFM; Bras, M; de Die-Smulders, C; Dumoulin, JCM; Cobben, JM; Evers, JLH; Smeets, HJM; Geraedts, JPM

    After Duchenne muscular dystrophy, spinal muscular atrophy (SMA) is the most common severe neuromuscular disease in childhood. Since 1995, homozygous deletions in exon 7 of the survival motor neuron (SMN) gene have been described in >90-95% of SMA patients. However, the presence of a highly

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

    Science.gov (United States)

    ... myoclonic epilepsy Spinal muscular atrophy with progressive myoclonic epilepsy Printable PDF Open All Close All Enable Javascript ... boxes. Description Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) is a neurological condition that causes ...

  8. New Frontiers in the Treatment of Spinal Muscular Atrophy

    LENUS (Irish Health Repository)

    Power, CL

    2018-03-01

    Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder, with a current estimated incidence of 1 in 11,000 live births. Although there is a variable phenotype, 60% of patients with SMA have type 1 disease. Typically diagnosed by the age of six months, this severe form of the condition is characterised by progressive weakness and the failure to meet motor milestones. There is an early need for permanent assisted ventilation, without which the median life expectancy is less than two years.\\r\

  9. 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

  10. Atrofia muscular espinal en el niño Spinal muscular atrophy present in children

    Directory of Open Access Journals (Sweden)

    Nicolás Garófalo Gómez

    2009-09-01

    Full Text Available INTRODUCCIÓN. Las atrofias musculares espinales en la infancia (AME son trastornos genéticos autosómicos recesivos, caracterizados por degeneración de las motoneuronas espinales y bulbares. El presente estudio tuvo el objetivo principal de describir las principales características clínicas en una serie de niños con AME. MÉTODOS. Se realizó un estudio retrospectivo de los pacientes con AME atendidos en el Instituto de Neurología y Neurocirugía de Cuba, entre enero de 1997 y diciembre de 2001. Se recopilaron los datos de 35 pacientes, 4 de ellos, fetos con confirmación prenatal de AME. Se precisaron las principales características clínicas, electromiográficas, de la biopsia muscular y de los estudios genéticos moleculares realizados en cada caso. RESULTADOS. La AME de tipo II resultó la forma clínica más frecuente (58 %, seguida por la AME de tipo I (42 %. Las principales manifestaciones clínicas resultaron la debilidad muscular generalizada con predominio proximal en extremidades, asociada a hipotonía y arreflexia osteotendinosa. La deleción de los exones 7 y 8 del gen SMN1 se detectó en 20 de 23 casos estudiados (87 %.INTRODUCTION: Spinal muscular atrophies (SMA in childhood are autosomal recessive genetic disorders, characterized by spinal and bulbar motoneurons degenerations. Aim of present paper was to describe the main clinical features in a series of children presenting SMA. METHODS: A retrospective study of patients with SMA seen in the Neurology and Neurosurgery Institute of Cuba from January, 2997 and December, 2001 was made. Data from 35 patients were available; four of them were fetus with prenatal confirmation of SMA. Main clinical, electromyography, muscular biopsy, and of molecular genetic studies performed in each case were determined. RESULTS: Type II SMA was the more frequent clinical presentation (58%, followed by type I SMA (42,%. Main clinical manifestations were a systemic muscular weakness with

  11. Spinal muscular atrophy associated with progressive myoclonus epilepsy.

    Science.gov (United States)

    Topaloglu, Haluk; Melki, Judith

    2016-09-01

    A rare syndrome characterized by lower motor neuron disease associated with progressive myoclonic epilepsy, referred to as "spinal muscular atrophy associated with progressive myoclonic epilepsy" (SMA-PME), has been described in childhood and is inherited as an autosomal recessive trait. SMA-PME is caused by mutation in the ASAH1 gene encoding acid ceramidase. Ceramide and the metabolites participate in various cellular events as lipid mediators. The catabolism of ceramide in mammals occurs in lysosomes through the activity of ceramidase. Three different ceramidases (acid, neutral and alkaline) have been identified and appear to play distinct roles in sphingolipid metabolism. The enzymatic activity of acid ceramidase is deficient in two rare inherited disorders; Farber disease and SMA-PME. Farber disease is a very rare and severe autosomal recessive condition with a distinct clinical phenotype. The marked difference in disease manifestations may explain why Farber and SMA-PME diseases were not previously suspected to be allelic conditions. The precise molecular mechanism underlying the phenotypic differences remains to be clarified. Recently, a condition with mutation in CERS1, the gene encoding ceramide synthase 1, has been identified as a novel form of PME. This finding underlies the essential role of enzymes regulating either the synthesis (CERS1) or degradation (ASAH1) of ceramide, and the link between defects in ceramide metabolism and PME.

  12. Molecular Mechanisms of Neurodegeneration in Spinal Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Saif Ahmad

    2016-01-01

    Full Text Available Spinal muscular atrophy (SMA is an autosomal recessive motor neuron disease with a high incidence and is the most common genetic cause of infant mortality. SMA is primarily characterized by degeneration of the spinal motor neurons that leads to skeletal muscle atrophy followed by symmetric limb paralysis, respiratory failure, and death. In humans, mutation of the Survival Motor Neuron 1 (SMN1 gene shifts the load of expression of SMN protein to the SMN2 gene that produces low levels of full-length SMN protein because of alternative splicing, which are sufficient for embryonic development and survival but result in SMA. The molecular mechanisms of the (a regulation of SMN gene expression and (b degeneration of motor neurons caused by low levels of SMN are unclear. However, some progress has been made in recent years that have provided new insights into understanding of the cellular and molecular basis of SMA pathogenesis. In this review, we have briefly summarized recent advances toward understanding of the molecular mechanisms of regulation of SMN levels and signaling mechanisms that mediate neurodegeneration in SMA.

  13. 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.

  14. Carrier screening for spinal muscular atrophy in Italian population

    Indian Academy of Sciences (India)

    SMA is necessary for effective clinical/prenatal diagnosis ... of SMA critical region in the group of 450 normal controls. ... izing and quality test are as described in Calì et al. .... nosis for spinal muscular atrophy: clinical laboratory analysis of.

  15. Physical complaints in ageing persons with spinal muscular atrophy.

    NARCIS (Netherlands)

    Groot, I.J.M. de; Witte, L.P de

    2005-01-01

    OBJECTIVE: While life expectancy is improving for persons with spinal muscular atrophy, new physical complaints may arise. To investigate this, we studied persons with a long duration and severe course (high functional limitations) of the disease. DESIGN: Cross-sectional descriptive study.

  16. Common recessive limb girdle muscular dystrophies differential diagnosis: why and how?

    Directory of Open Access Journals (Sweden)

    Ana Cotta

    2014-09-01

    Full Text Available Limb girdle muscular dystrophies are heterogeneous autosomal hereditary neuromuscular disorders. They produce dystrophic changes on muscle biopsy and they are associated with mutations in several genes involved in muscular structure and function. Detailed clinical, laboratorial, imaging, diagnostic flowchart, photographs, tables, and illustrated diagrams are presented for the differential diagnosis of common autosomal recessive limb girdle muscular dystrophy subtypes diagnosed nowadays at one reference center in Brazil. Preoperative image studies guide muscle biopsy site selection. Muscle involvement image pattern differs depending on the limb girdle muscular dystrophy subtype. Muscle involvement is conspicuous at the posterior thigh in calpainopathy and fukutin-related proteinopathy; anterior thigh in sarcoglycanopathy; whole thigh in dysferlinopathy, and telethoninopathy. The precise differential diagnosis of limb girdle muscular dystrophies is important for genetic counseling, prognostic orientation, cardiac and respiratory management. Besides that, it may probably, in the future, provide specific genetic therapies for each subtype.

  17. Prenatal diagnosis of spinal muscular atrophy in Chinese by genetic analysis of fetal cells

    Institute of Scientific and Technical Information of China (English)

    WU Ting; DING Xin-sheng; LI Wen-lei; YAO Juan; DENG Xiao-xuan

    2005-01-01

    Background Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by degeneration of anterior horn cells of the spinal cord.The survival motor neuron gene is SMA-determining gene deleted in approximately 95% of SMA patients.This study was undertaken to predict prenatal SMA efficiently and rapidly in families with previously affected child.Methods Prenatal diagnosis was made in 8 fetuses with a family history of SMA.Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used for the detection of the survival motor neuron gene.Results The survival motor neuron gene was not found in 6 fetuses, ruling out the diagnosis of SMA.Two fetuses were detected positive and the pregnancies were terminated.Conclusion Our method is effective and convenient in prenatal diagnosis of SMA.

  18. 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.

  19. Spinal muscular atrophy present in children

    OpenAIRE

    Garófalo Gómez, Nicolás; Zaldívar Vaillant, Tatiana; Vargas Díaz, José; Rojas Massipe, Edelsia; Novoa López, Lucía

    2009-01-01

    INTRODUCCIÓN. Las atrofias musculares espinales en la infancia (AME) son trastornos genéticos autosómicos recesivos, caracterizados por degeneración de las motoneuronas espinales y bulbares. El presente estudio tuvo el objetivo principal de describir las principales características clínicas en una serie de niños con AME. MÉTODOS. Se realizó un estudio retrospectivo de los pacientes con AME atendidos en el Instituto de Neurología y Neurocirugía de Cuba, entre enero de 1997 y diciembre de 2001....

  20. Recent developments in the treatment of Duchenne muscular dystrophy and spinal muscular atrophy

    Science.gov (United States)

    Liew, Wendy K. M.

    2013-01-01

    Pediatric neuromuscular disorders comprise a large variety of disorders that can be classified based on their neuroanatomical localization, patterns of weakness, and laboratory test results. Over the last decade, the field of translational research has been active with many ongoing clinical trials. This is particularly so in two common pediatric neuromuscular disorders: Duchenne muscular dystrophy and spinal muscular atrophy. Although no definitive therapy has yet been found, numerous active areas of research raise the potential for novel therapies in these two disorders, offering hope for improved quality of life and life expectancy for affected individuals. PMID:23634188

  1. Parental attitudes toward newborn screening for Duchenne/Becker muscular dystrophy and spinal muscular atrophy.

    Science.gov (United States)

    Wood, Molly F; Hughes, Sarah C; Hache, Lauren P; Naylor, Edwin W; Abdel-Hamid, Hoda Z; Barmada, M Michael; Dobrowolski, Steven F; Stickler, David E; Clemens, Paula R

    2014-06-01

    Disease inclusion in the newborn screening (NBS) panel should consider the opinions of those most affected by the outcome of screening. We assessed the level and factors that affect parent attitudes regarding NBS panel inclusion of Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and spinal muscular atrophy (SMA). The attitudes toward NBS for DMD, BMD, and SMA were surveyed and compared for 2 categories of parents, those with children affected with DMD, BMD, or SMA and expectant parents unselected for known family medical history. The level of support for NBS for DMD, BMD, and SMA was 95.9% among parents of children with DMD, BMD, or SMA and 92.6% among expectant parents. There was strong support for NBS for DMD, BMD, and SMA in both groups of parents. Given advances in diagnostics and promising therapeutic approaches, discussion of inclusion in NBS should continue. Copyright © 2013 Wiley Periodicals, Inc.

  2. Pain in adolescents with spinal muscular atrophy and Duchenne and Becker muscular dystrophy.

    Science.gov (United States)

    Lager, Christina; Kroksmark, Anna-Karin

    2015-09-01

    The purpose of this study was to explore the prevalence, nature and scope of pain in adolescents with spinal muscular atrophy and Duchenne and Becker muscular dystrophy and whether the pain differs between diagnostic groups or between adolescents with different ambulation status. Furthermore to study the consequences of pain and to identify pain-exacerbating and pain-relieving factors. In a national survey, fifty-five adolescents with spinal muscular atrophy and dystrophinopathy completed a questionnaire assessing pain frequency, duration, location using a body map, intensity and discomfort using visual analogue scales, pain interference using a modified version of Brief Pain Inventory and factors exacerbating and relieving pain. Sixty-nine per cent of the adolescents reported pain during the past three months and 50% reported chronic pain. The pain prevalence did not differ significantly between diagnostic groups or between ambulators and non-ambulators. The average pain intensity was graded as mild and the worst pain as moderate. The pain typically occurred weekly, most frequently in the neck/back or legs. General activity and mood were the areas that were most affected by pain. Common pain-exacerbating factors were sitting, too much movement/activity and being lifted or transferred. Pain is a frequent problem in adolescents with spinal muscular atrophy and dystrophinopathy. The assessments used enable an understanding both of the nature and scope of pain and of the impact of pain in everyday life. The study highlights the importance of assessing pain in a systematic manner and offering an individual approach to interventions designed to reduce pain in this population. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  3. X-linked lethal infantile spinal muscular atrophy: From clinical description to molecular mapping

    Energy Technology Data Exchange (ETDEWEB)

    Baumbach, L.; Schiavi, A. [Univ. of Miami, FL (United States)] [and others

    1994-09-01

    The proximal spinal muscular atrophies (PSMA), one of the most common forms of lower motor neuron disease in children, are characterized by progressive muscle weakness due to loss of anterior horn cells. All three autosomal recessive forms have been mapped to chromosome 5q11.2-11.3, implying an allelic association between these disorders. Recent evidence from our laboratories, as well as others, suggests that a distinct form of lethal neonatal spinal muscular atrophy, associated with early onset contractures, is determined by a gene on the X chromosome. We report our efforts in mapping this disease locus. Our original studies have focused on two unrelated multigenerational families with similar clinical presentations of severe hypotonia, muscle weakness, and a disease course similar to Werdnig Hoffman except for the additional finding of congenital or early onset contractures. Muscle biopsy and/or autopsy were indicative of anterior horn cell loss in affected males. Disease occurrence in each of the families was consistent with an X-linked recessive mode of inheritance. Subsequently, two additional families have been identified, as well as several sporadic male cases. Linkage analysis has been completed in one of these families using highly polymorphic repeats dispersed 10 cM on the X chromosome. Interpretation of results was achieved using an automated data acquisition program. Analysis of over 300 haplotypes generated using PCR-based DNA markers have identified two 16 cM regions on Xp with complete concordance to the disease phenotype. Our currents efforts are focused on the region surrounding the Kallman gene, in attempts to better define a candidate region, as well as analyze possible candidate genes within this region.

  4. Synaptic defects in the spinal and neuromuscular circuitry in a mouse model of spinal muscular atrophy.

    Directory of Open Access Journals (Sweden)

    Karen K Y Ling

    2010-11-01

    Full Text Available Spinal muscular atrophy (SMA is a major genetic cause of death in childhood characterized by marked muscle weakness. To investigate mechanisms underlying motor impairment in SMA, we examined the spinal and neuromuscular circuitry governing hindlimb ambulatory behavior in SMA model mice (SMNΔ7. In the neuromuscular circuitry, we found that nearly all neuromuscular junctions (NMJs in hindlimb muscles of SMNΔ7 mice remained fully innervated at the disease end stage and were capable of eliciting muscle contraction, despite a modest reduction in quantal content. In the spinal circuitry, we observed a ∼28% loss of synapses onto spinal motoneurons in the lateral column of lumbar segments 3-5, and a significant reduction in proprioceptive sensory neurons, which may contribute to the 50% reduction in vesicular glutamate transporter 1(VGLUT1-positive synapses onto SMNΔ7 motoneurons. In addition, there was an increase in the association of activated microglia with SMNΔ7 motoneurons. Together, our results present a novel concept that synaptic defects occur at multiple levels of the spinal and neuromuscular circuitry in SMNΔ7 mice, and that proprioceptive spinal synapses could be a potential target for SMA therapy.

  5. Splice-Switching Therapy for Spinal Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Katharina E. Meijboom

    2017-06-01

    Full Text Available Spinal muscular atrophy (SMA is a genetic disorder with severity ranging from premature death in infants to restricted motor function in adult life. Despite the genetic cause of this disease being known for over twenty years, only recently has a therapy been approved to treat the most severe form of this disease. Here we discuss the genetic basis of SMA and the subsequent studies that led to the utilization of splice switching oligonucleotides to enhance production of SMN protein, which is absent in patients, through a mechanism of exon inclusion into the mature mRNA. Whilst approval of oligonucleotide-based therapies for SMA should be celebrated, we also discuss some of the limitations of this approach and alternate genetic strategies that are currently underway in clinical trials.

  6. Prominent fatigue in spinal muscular atrophy and spinal and bulbar muscular atrophy: evidence of activity-dependent conduction block.

    Science.gov (United States)

    Noto, Yu-ichi; Misawa, Sonoko; Mori, Masahiro; Kawaguchi, Naoki; Kanai, Kazuaki; Shibuya, Kazumoto; Isose, Sagiri; Nasu, Saiko; Sekiguchi, Yukari; Beppu, Minako; Ohmori, Shigeki; Nakagawa, Masanori; Kuwabara, Satoshi

    2013-09-01

    To clarify whether patients with spinal muscular atrophy (SMA) or spinal and bulbar muscular atrophy (SBMA) suffer disabling muscle fatigue, and whether activity-dependent conduction block (ADCB) contributes to their fatigue. ADCB is usually caused by reduced safety factor for impulse transmission in demyelinating diseases, whereas markedly increased axonal branching associated with collateral sprouting may reduce the safety factor in chronic lower motor neuron disorders. We assessed the fatigue severity scale (FSS) in 22 patients with SMA/SBMA, and in 100 disease controls (multiple sclerosis, myasthenia gravis, chronic inflammatory demyelinating polyneuropathy (CIDP), and axonal neuropathy). We then performed stimulated-single fibre electromyography (s-SFEMG) in the extensor digitorum communis (EDC) muscle of 21 SMA/SBMA patients, 6 CIDP patients, and 10 normal subjects. The FSS score was the highest in SMA/SBMA patients [4.9 ± 1.1 (mean ± SD)], with 81% of them complaining of disabling fatigue, compared with normal controls (3.5 ± 1.0), whereas patients with multiple sclerosis (4.3 ± 1.6), myasthenia gravis (4.0 ± 1.6) or CIDP (4.3 ± 1.4) also showed higher FSS score. When 2000 stimuli were delivered at 20 Hz in s-SFEMG, conduction block of single motor axons developed in 46% of patients with SMA/SBMA, and 40% of CIDP patients, but in none of the normal controls. SMA/SBMA patients frequently suffer from disabling fatigue presumably caused by ADCB induced by voluntary activity. ADCB could be the mechanism for muscle fatigue in chronic lower motor neuron diseases. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  7. Prevention of pectus excavatum for children with spinal muscular atrophy type 1.

    Science.gov (United States)

    Bach, John R; Bianchi, Carlo

    2003-10-01

    To demonstrate the elimination of pectus excavatum and promotion of more normal lung growth and chest wall development by the use of high-span positive inspiratory pressure plus positive end-expiratory pressure (PIP+PEEP), patients with spinal muscular atrophy type 1 with paradoxical breathing were placed on high-span PIP+PEEP when sleeping from the point of diagnosis of spinal muscular atrophy. Although the appearance of pectus excavatum is ubiquitous in untreated infants with spinal muscular atrophy type 1, after institution of high-span PIP+PEEP, pectus resolves and lungs and chest walls grow more normally. High-span PIP+PEEP is indicated for all infants diagnosed with spinal muscular atrophy who demonstrate paradoxical breathing for the purpose of promoting more normal lung and chest development.

  8. Dominant inherited distal spinal muscular atrophy with atrophic and hypertrophic calves

    NARCIS (Netherlands)

    Groen, R J; Sie, O G; van Weerden, T W

    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

  9. Distribution of skeletal muscle involvement in autosomal recessive distal muscular dystrophy

    International Nuclear Information System (INIS)

    Mizusawa, Hidehiro; Nakanishi, Takao; Kobayashi, Fumie.

    1987-01-01

    Distribution of skeletal muscle involvement in 5 cases with autosomal recessive distal muscular dystrophy was studied clinically and by computed tomography (CT). Manual muscle test showed muscle involvement with a predilection for flexors in the lower leg and adductors in the thigh. Flexion and extension of the thigh and the lower leg was impaired to similar degree. In progressed cases, neck flexors and trunk muscles were also affected mildly. CT disclosed more clearly the preferential involvement of flexors in the lower leg, and involvement of both hamstrings · adductors group and extensors group of the thigh to similar degree. However, m. popliteus was curiously well preserved. In addition, there was a stage showing high density and hypertrophy of m. sartorius, m. gracilis, m. adductor, m. biceps femoris, m. semimenbranosus, m. semitendinosus or m. rectus femoris, which in thought to be compensatory hypertrophy. M. gluteus minimus in the pelvic girdle and m. dorsi proprii in the trunk were also liable to be affected. The CT findings are regarded as characteristic features noted clearly before muscle weakness and atrophy become apparent clinically. CT is very useful for distinguishing distal muscular dystrophy from rimmed vacuolar distal myopathy in which m. quadriceps femoris and flexors of the lower leg are usually well preserved without compensatory hypertrophy on CT. (author)

  10. Abnormal motoneuron migration, differentiation, and axon outgrowth in spinal muscular atrophy

    NARCIS (Netherlands)

    Simic, G.; Mladinov, M.; Seso Simic, D.; Jovanov Milosevic, N.; Islam, A.; Pajtak, A.; Barisic, N.; Sertic, J.; Lucassen, P.J.; Hof, P.R.; Kruslin, B.

    2008-01-01

    The role of heterotopic (migratory) motoneurons (HMN) in the pathogenesis of spinal muscular atrophy (SMA) is still controversial. We examined the occurrence and amount of HMN in spinal cord tissue from eight children with SMA (six with SMA-I and two with SMA-II). All affected subjects were carrying

  11. Serum cholinesterase activity in infantile and juvenile spinal muscular atrophy.

    Science.gov (United States)

    Niebroj-Dobosz, I; Hausmanowa-Petrusewicz, I

    1989-09-01

    Serum acetylcholinesterase (AChE) and pseudocholinesterase (ChE) activity in infantile and juvenile spinal muscular atrophy (SMA) was determined. The total AChE activity was either normal or decreased in the childhood SMA (Type 1), the other SMA groups and disease controls (ALS, X-linked SMA). In the majority of SMA Type 1 cases (6/7 tested) an absence of the asymmetric A12 form was found. This was accompanied by changes in the other asymmetric and globular forms. The latter was, however, not specific for SMA Type 1 cases. The ChE activity was increased in the majority of SMA cases as well as disease controls. The asymmetric A12 ChE form was increased in all SMA Type 3 cases, the values of this form in SMA Type 1 was variable. A change in the ChE globular forms in SMA Type 1 and SMA Type 2 was a frequent finding. It is suggested that the absence of the asymmetric A12 AChE form in SMA Type 1 arises because of muscle cell immaturity and undeveloped muscle-nerve interactions. The reason of ChE changes is obscure.

  12. Spinal Muscular Atrophy: More than a Disease of Motor Neurons?

    Science.gov (United States)

    Nash, L A; Burns, J K; Chardon, J Warman; Kothary, R; Parks, R J

    2016-01-01

    Spinal muscular atrophy (SMA) is the most common genetically inherited neurodegenerative disease resulting in infant mortality. SMA is caused by genetic deletion or mutation in the survival of motor neuron 1 (SMN1) gene, which results in reduced levels of the survival of motor neuron (SMN) protein. SMN protein deficiency preferentially affects α- motor neurons, leading to their degeneration and subsequent atrophy of limb and trunk muscles, progressing to death in severe forms of the disease. More recent studies have shown that SMN protein depletion is detrimental to the functioning of other tissues including skeletal muscle, heart, autonomic and enteric nervous systems, metabolic/endocrine (e.g. pancreas), lymphatic, bone and reproductive system. In this review, we summarize studies discussing SMN protein's function in various cell and tissue types and their involvement in the context of SMA disease etiology. Taken together, these studies indicate that SMA is a multi-organ disease, which suggests that truly effective disease intervention may require body-wide correction of SMN protein levels. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. The Smn-independent beneficial effects of trichostatin A on an intermediate mouse model of spinal muscular atrophy.

    Directory of Open Access Journals (Sweden)

    Hong Liu

    Full Text Available Spinal muscular atrophy is an autosomal recessive neuromuscular disease characterized by the progressive loss of alpha motor neurons in the spinal cord. Trichostatin A (TSA is a histone deacetylase inhibitor with beneficial effects in spinal muscular atrophy mouse models that carry the human SMN2 transgene. It is currently unclear whether TSA specifically targets the SMN2 gene or whether other genes respond to TSA and in turn provide neuroprotection in SMA mice. We have taken advantage of the Smn2B/- mouse model that does not harbor the human SMN2 transgene, to test the hypothesis that TSA has its beneficial effects through a non-SMN mediated pathway. TSA increased the median lifespan of Smn2B/- mice from twenty days to eight weeks. As well, there was a significant attenuation of weight loss and improved motor behavior. Pen test and righting reflex both showed significant improvement, and motor neurons in the spinal cord of Smn2B/- mice were protected from degeneration. Both the size and maturity of neuromuscular junctions were significantly improved in TSA treated Smn2B/- mice. Of interest, TSA treatment did not increase the levels of Smn protein in mouse embryonic fibroblasts or myoblasts obtained from the Smn2B/- mice. In addition, no change in the level of Smn transcripts or protein in the brain or spinal cord of TSA-treated SMA model mice was observed. Furthermore, TSA did not increase Smn protein levels in the hind limb muscle, heart, or liver of Smn2B/- mice. We therefore conclude that TSA likely exerts its effects independent of the endogenous mouse Smn gene. As such, identification of the pathways regulated by TSA in the Smn2B/- mice could lead to the development of novel therapeutics for treating SMA.

  14. [Upper limb functional assessment scale for children with Duchenne muscular dystrophy and Spinal muscular atrophy].

    Science.gov (United States)

    Escobar, Raúl G; Lucero, Nayadet; Solares, Carmen; Espinoza, Victoria; Moscoso, Odalie; Olguín, Polín; Muñoz, Karin T; Rosas, Ricardo

    2016-08-16

    Duchenne muscular dystrophy (DMD) and Spinal muscular atrophy (SMA) causes significant disability and progressive functional impairment. Readily available instruments that assess functionality, especially in advanced stages of the disease, are required to monitor the progress of the disease and the impact of therapeutic interventions. To describe the development of a scale to evaluate upper limb function (UL) in patients with DMD and SMA, and describe its validation process, which includes self-training for evaluators. The development of the scale included a review of published scales, an exploratory application of a pilot scale in healthy children and those with DMD, self-training of evaluators in applying the scale using a handbook and video tutorial, and assessment of a group of children with DMD and SMA using the final scale. Reliability was assessed using Cronbach and Kendall concordance and with intra and inter-rater test-retest, and validity with concordance and factorial analysis. A high level of reliability was observed, with high internal consistency (Cronbach α=0.97), and inter-rater (Kendall W=0.96) and intra-rater concordance (r=0.97 to 0.99). The validity was demonstrated by the absence of significant differences between results by different evaluators with an expert evaluator (F=0.023, P>.5), and by the factor analysis that showed that four factors account for 85.44% of total variance. This scale is a reliable and valid tool for assessing UL functionality in children with DMD and SMA. It is also easily implementable due to the possibility of self-training and the use of simple and inexpensive materials. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Computed tomography of skeletal muscles in childhood spinal progressive muscular atrophies

    International Nuclear Information System (INIS)

    Arai, Yumi; Osawa, Makiko; Sumida, Sawako; Shishikura, Keiko; Suzuki, Haruko; Fukuyama, Yukio; Kohno, Atsushi

    1992-01-01

    Computed tomographic (CT) scanning of skeletal muscles was performed in patients with type 1 and type 2 spinal progressive muscular atrophy (SPMA) and Kugelberg-Welander disease (K-W) to delineate the characteristic CT features of each category. Marked muscular atrophy was observed in type 1 SPMA, and both muscular atrophy and intramuscular low density areas in type 2 SPMA, changes being more pronounced in older patients. In contrast, in K-W, muscular atrophy was slight, and intramuscular low density areas constituted the most prominent findings. These observations indicate that SPMA and K-W are each characterized by distinct CT findings. (author)

  16. Investigation of New Morpholino Oligomers to Increase Survival Motor Neuron Protein Levels in Spinal Muscular Atrophy.

    Science.gov (United States)

    Ramirez, Agnese; Crisafulli, Sebastiano G; Rizzuti, Mafalda; Bresolin, Nereo; Comi, Giacomo P; Corti, Stefania; Nizzardo, Monica

    2018-01-06

    Spinal muscular atrophy (SMA) is an autosomal-recessive childhood motor neuron disease and the main genetic cause of infant mortality. SMA is caused by deletions or mutations in the survival motor neuron 1 ( SMN1 ) gene, which results in SMN protein deficiency. Only one approved drug has recently become available and allows for the correction of aberrant splicing of the paralogous SMN2 gene by antisense oligonucleotides (ASOs), leading to production of full-length SMN protein. We have already demonstrated that a sequence of an ASO variant, Morpholino (MO), is particularly suitable because of its safety and efficacy profile and is both able to increase SMN levels and rescue the murine SMA phenotype. Here, we optimized this strategy by testing the efficacy of four new MO sequences targeting SMN2 . Two out of the four new MO sequences showed better efficacy in terms of SMN protein production both in SMA induced pluripotent stem cells (iPSCs) and SMAΔ7 mice. Further, the effect was enhanced when different MO sequences were administered in combination. Our data provide an important insight for MO-based treatment for SMA. Optimization of the target sequence and validation of a treatment based on a combination of different MO sequences could support further pre-clinical studies and the progression toward future clinical trials.

  17. Mapping of the bovine spinal muscular atrophy locus to Chromosome 24.

    Science.gov (United States)

    Medugorac, Ivica; Kemter, Juliane; Russ, Ingolf; Pietrowski, Detlef; Nüske, Stefan; Reichenbach, Horst-Dieter; Schmahl, Wolfgang; Förster, Martin

    2003-06-01

    A hereditary form of spinal muscular atrophy (SMA) caused by an autosomal recessive gene has been reported for American Brown-Swiss cattle and in advanced backcrosses between American Brown-Swiss and many European brown cattle breeds. Bovine SMA (bovSMA) bears remarkable resemblance to the human SMA (SMA1). Affected homozygous calves also show progressive symmetric weakness and neurogenic atrophy of proximal muscles. The condition is characterized by severe muscle atrophy, quadriparesis, and sternal recumbency as result of neurogenic atrophy. We report on the localization of the gene causing bovSMA within a genomic interval between the microsatellite marker URB031 and the telomeric end of bovine Chromosome (Chr) 24 (BTA24). Linkage analysis of a complex pedigree of German Braunvieh cattle revealed a recombination fraction of 0.06 and a three-point lod score of 11.82. The results of linkage and haplotyping analysis enable a marker-assisted selection against bovSMA based on four microsatellite markers most telomeric on BTA24 to a moderate accuracy of 89-94%. So far, this region is not orthologous to any human chromosome segments responsible for twelve distinct disease phenotypes of autosomal neuropathies. Our results indicate the apoptosis-inhibiting protein BCL2 as the most promising positional candidate gene causing bovSMA. Our findings offer an attractive animal model for a better understanding of human forms of SMA and for a probable anti-apoptotic synergy of SMN-BCL2 aggregates in mammals.

  18. Therapeutic strategies for spinal muscular atrophy: SMN and beyond

    Directory of Open Access Journals (Sweden)

    Melissa Bowerman

    2017-08-01

    Full Text Available Spinal muscular atrophy (SMA is a devastating neuromuscular disorder characterized by loss of motor neurons and muscle atrophy, generally presenting in childhood. SMA is caused by low levels of the survival motor neuron protein (SMN due to inactivating mutations in the encoding gene SMN1. A second duplicated gene, SMN2, produces very little but sufficient functional protein for survival. Therapeutic strategies to increase SMN are in clinical trials, and the first SMN2-directed antisense oligonucleotide (ASO therapy has recently been licensed. However, several factors suggest that complementary strategies may be needed for the long-term maintenance of neuromuscular and other functions in SMA patients. Pre-clinical SMA models demonstrate that the requirement for SMN protein is highest when the structural connections of the neuromuscular system are being established, from late fetal life throughout infancy. Augmenting SMN may not address the slow neurodegenerative process underlying progressive functional decline beyond childhood in less severe types of SMA. Furthermore, individuals receiving SMN-based treatments may be vulnerable to delayed symptoms if rescue of the neuromuscular system is incomplete. Finally, a large number of older patients living with SMA do not fulfill the present criteria for inclusion in gene therapy and ASO clinical trials, and may not benefit from SMN-inducing treatments. Therefore, a comprehensive whole-lifespan approach to SMA therapy is required that includes both SMN-dependent and SMN-independent strategies that treat the CNS and periphery. Here, we review the range of non-SMN pathways implicated in SMA pathophysiology and discuss how various model systems can serve as valuable tools for SMA drug discovery.

  19. Machine learning algorithms to classify spinal muscular atrophy subtypes.

    Science.gov (United States)

    Srivastava, Tuhin; Darras, Basil T; Wu, Jim S; Rutkove, Seward B

    2012-07-24

    The development of better biomarkers for disease assessment remains an ongoing effort across the spectrum of neurologic illnesses. One approach for refining biomarkers is based on the concept of machine learning, in which individual, unrelated biomarkers are simultaneously evaluated. In this cross-sectional study, we assess the possibility of using machine learning, incorporating both quantitative muscle ultrasound (QMU) and electrical impedance myography (EIM) data, for classification of muscles affected by spinal muscular atrophy (SMA). Twenty-one normal subjects, 15 subjects with SMA type 2, and 10 subjects with SMA type 3 underwent EIM and QMU measurements of unilateral biceps, wrist extensors, quadriceps, and tibialis anterior. EIM and QMU parameters were then applied in combination using a support vector machine (SVM), a type of machine learning, in an attempt to accurately categorize 165 individual muscles. For all 3 classification problems, normal vs SMA, normal vs SMA 3, and SMA 2 vs SMA 3, use of SVM provided the greatest accuracy in discrimination, surpassing both EIM and QMU individually. For example, the accuracy, as measured by the receiver operating characteristic area under the curve (ROC-AUC) for the SVM discriminating SMA 2 muscles from SMA 3 muscles was 0.928; in comparison, the ROC-AUCs for EIM and QMU parameters alone were only 0.877 (p < 0.05) and 0.627 (p < 0.05), respectively. Combining EIM and QMU data categorizes individual SMA-affected muscles with very high accuracy. Further investigation of this approach for classifying and for following the progression of neuromuscular illness is warranted.

  20. Living with illness and self-transcendence: the lived experience of patients with spinal muscular atrophy.

    Science.gov (United States)

    Ho, Hsin-Mei; Tseng, Ying-Hua; Hsin, Yu-Mei; Chou, Fan-Hao; Lin, Wei-Ting

    2016-11-01

    The aim of this study was to explore the lived experiences of patients afflicted with spinal muscular atrophy. Existing research studies on spinal muscular atrophy address the physical and psychological effects and complications of the disease; they also provide suggestions for how to improve the current management of this disease. However, information is limited on the disease process and the lived experience of spinal muscular atrophy patients. A phenomenological approach was conducted. Through 18 in-depth interviews recorded by a pen voice recorder, this study collected data obtained from a purposive sample of nine patients from the, 'Taiwan spinal muscular atrophy Families,' between November 2010-August 2011. The audio recordings were transcribed verbatim and data were analysed using Colaizzi's steps. Four themes and eight subthemes were identified: a loss of control (loss of muscular strength and independence), breaking limitations (assistive device use and mobility design), transcending limitations (independence/autonomy and social development) and living with hope (cherishing life and self-control). The results showed that the lived experiences of the spinal muscular atrophy patients involved living with illness, transcending the self and pursuing the meaning of life. Facing a life-threatening illness, these patients made self-adjustments in their lifestyles and exerted themselves to positively cope with hardships and maintain dignity and self-control. These findings could serve as evidence-based practice resources for healthcare professionals in helping individuals and their family members gain an in-depth understanding of spinal muscular atrophy's progression and life course and assist individuals in improving self-integrity to with hope. © 2016 John Wiley & Sons Ltd.

  1. Compensatory axon sprouting for very slow axonal die-back in a transgenic model of spinal muscular atrophy type III.

    Science.gov (United States)

    Udina, Esther; Putman, Charles T; Harris, Luke R; Tyreman, Neil; Cook, Victoria E; Gordon, Tessa

    2017-03-01

    Smn +/- transgenic mouse is a model of the mildest form of spinal muscular atrophy. Although there is a loss of spinal motoneurons in 11-month-old animals, muscular force is maintained. This maintained muscular force is mediated by reinnervation of the denervated fibres by surviving motoneurons. The spinal motoneurons in these animals do not show an increased susceptibility to death after nerve injury and they retain their regenerative capacity. We conclude that the hypothesized immaturity of the neuromuscular system in this model cannot explain the loss of motoneurons by systematic die-back. Spinal muscular atrophy (SMA) is a common autosomal recessive disorder in humans and is the leading genetic cause of infantile death. Patients lack the SMN1 gene with the severity of the disease depending on the number of copies of the highly homologous SMN2 gene. Although motoneuron death in the Smn +/- transgenic mouse model of the mildest form of SMA, SMA type III, has been reported, we have used retrograde tracing of sciatic and femoral motoneurons in the hindlimb with recording of muscle and motor unit isometric forces to count the number of motoneurons with intact neuromuscular connections. Thereby, we investigated whether incomplete maturation of the neuromuscular system induced by survival motoneuron protein (SMN) defects is responsible for die-back of axons relative to survival of motoneurons. First, a reduction of ∼30% of backlabelled motoneurons began relatively late, at 11 months of age, with a significant loss of 19% at 7 months. Motor axon die-back was affirmed by motor unit number estimation. Loss of functional motor units was fully compensated by axonal sprouting to retain normal contractile force in four hindlimb muscles (three fast-twitch and one slow-twitch) innervated by branches of the sciatic nerve. Second, our evaluation of whether axotomy of motoneurons in the adult Smn +/- transgenic mouse increases their susceptibility to cell death demonstrated

  2. Defective Ca2+ channel clustering in axon terminals disturbs excitability in motoneurons in spinal muscular atrophy

    OpenAIRE

    Jablonka, Sibylle; Beck, Marcus; Lechner, Barbara Dorothea; Mayer, Christine; Sendtner, Michael

    2007-01-01

    Proximal spinal muscular atrophy (SMA) is a motoneuron disease for which there is currently no effective treatment. In animal models of SMA, spinal motoneurons exhibit reduced axon elongation and growth cone size. These defects correlate with reduced β-actin messenger RNA and protein levels in distal axons. We show that survival motoneuron gene (Smn)–deficient motoneurons exhibit severe defects in clustering Cav2.2 channels in axonal growth cones. These defects also correlate with a reduced f...

  3. Clinical applications of MARSALA for preimplantation genetic diagnosis of spinal muscular atrophy.

    Science.gov (United States)

    Ren, Yixin; Zhi, Xu; Zhu, Xiaohui; Huang, Jin; Lian, Ying; Li, Rong; Jin, Hongyan; Zhang, Yan; Zhang, Wenxin; Nie, Yanli; Wei, Yuan; Liu, Zhaohui; Song, Donghong; Liu, Ping; Qiao, Jie; Yan, Liying

    2016-09-20

    Conventional PCR methods combined with linkage analysis based on short tandem repeats (STRs) or Karyomapping with single nucleotide polymorphism (SNP) arrays, have been applied to preimplantation genetic diagnosis (PGD) for spinal muscular atrophy (SMA), an autosome recessive disorder. However, it has limitations in SMA diagnosis by Karyomapping, and these methods are unable to distinguish wild-type embryos with carriers effectively. Mutated allele revealed by sequencing with aneuploidy and linkage analyses (MARSALA) is a new method allowing embryo selection by a one-step next-generation sequencing (NGS) procedure, which has been applied in PGD for both autosome dominant and X-linked diseases in our group previously. In this study, we carried out PGD based on MARSALA for two carrier families with SMA affected children. As a result, one of the couples has given birth to a healthy baby free of mutations in SMA-causing gene. It is the first time that MARSALA was applied to PGD for SMA, and we can distinguish the embryos with heterozygous deletion (carriers) from the wild-type (normal) ones accurately through this NGS-based method. In addition, direct mutation detection allows us to identify the affected embryos (homozygous deletion), which can be regarded as probands for linkage analysis, in case that the affected family member is absent. In the future, the NGS-based MARSALA method is expected to be used in PGD for all monogenetic disorders with known pathogenic gene mutation. Copyright © 2016 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

  4. Novel mutations expand the clinical spectrum of DYNC1H1-associated spinal muscular atrophy

    NARCIS (Netherlands)

    Scoto, Mariacristina; Rossor, Alexander M.; Harms, Matthew B.; Cirak, Sebahattin; Calissano, Mattia; Robb, Stephanie; Manzur, Adnan Y.; Martínez Arroyo, Amaia; Rodriguez Sanz, Aida; Mansour, Sahar; Fallon, Penny; Hadjikoumi, Irene; Klein, Andrea; Yang, Michele; de Visser, Marianne; Overweg-Plandsoen, W. C. G. Truus; Baas, Frank; Taylor, J. Paul; Benatar, Michael; Connolly, Anne M.; Al-Lozi, Muhammad T.; Nixon, John; de Goede, Christian G. E. L.; Foley, A. Reghan; Mcwilliam, Catherine; Pitt, Matthew; Sewry, Caroline; Phadke, Rahul; Hafezparast, Majid; Chong, W. K. Kling; Mercuri, Eugenio; Baloh, Robert H.; Reilly, Mary M.; Muntoni, Francesco

    2015-01-01

    To expand the clinical phenotype of autosomal dominant congenital spinal muscular atrophy with lower extremity predominance (SMA-LED) due to mutations in the dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene. Patients with a phenotype suggestive of a motor, non-length-dependent neuronopathy

  5. Fatigue in patients with spinal muscular atrophy type II and congenital myopathies

    DEFF Research Database (Denmark)

    Werlauff, Ulla; Højberg, A; Firla-Holme, R

    2014-01-01

    PURPOSE: The aim of this study was to evaluate whether the fatigue severity scale (FSS) is an appropriate instrument to assess fatigue in patients with spinal muscular atrophy type II (SMA II) and congenital myopathies (CM). METHODS: FSS and visual analog scale (VAS) were administered to 33 SMA II...

  6. Electromyographic and computed tomographic findings in five patients with monomelic spinal muscular atrophy

    NARCIS (Netherlands)

    de Visser, M.; Ongerboer de Visser, B. W.; Verbeeten, B.

    1988-01-01

    Five patients with monomelic spinal muscular atrophy are described. Clinical features included insidious onset of wasting and weakness of one limb, lack of involvement of the cranial nerves, brain stem, pyramidal tracts and sensory system, and a stable condition over a period of 4-20 years. Clinical

  7. Aquatic Therapy for a Child with Type III Spinal Muscular Atrophy: A Case Report

    Science.gov (United States)

    Salem, Yasser; Gropack, Stacy Jaffee

    2010-01-01

    Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by degeneration of alpha motor neurons. This case report describes an aquatic therapy program and the outcomes for a 3-year-old girl with type III SMA. Motor skills were examined using the 88-item Gross Motor Function Measure (GMFM), the Peabody Developmental Motor Scales…

  8. Prenatal molecular diagnosis of inherited neuromuscular diseases: Duchenne/Becker muscular dystrophy, myotonic dystrophy type 1 and spinal muscular atrophy.

    Science.gov (United States)

    Esposito, Gabriella; Ruggiero, Raffaella; Savarese, Maria; Savarese, Giovanni; Tremolaterra, Maria Roberta; Salvatore, Francesco; Carsana, Antonella

    2013-12-01

    Neuromuscular disease is a broad term that encompasses many diseases that either directly, via an intrinsic muscle disorder, or indirectly, via a nerve disorder, impairs muscle function. Here we report the experience of our group in the counselling and molecular prenatal diagnosis of three inherited neuromuscular diseases, i.e., Duchenne/Becker muscular dystrophy (DMD/BMD), myotonic dystrophy type 1 (DM1), spinal muscular atrophy (SMA). We performed a total of 83 DMD/BMD, 15 DM1 and 54 SMA prenatal diagnoses using a combination of technologies for either direct or linkage diagnosis. We identified 16, 5 and 10 affected foetuses, respectively. The improvement of analytical procedures in recent years has increased the mutation detection rate and reduced the analytical time. Due to the complexity of the experimental procedures and the high, specific professional expertise required for both laboratory activities and the related counselling, these types of analyses should be preferentially performed in reference molecular diagnostic centres.

  9. Modeling the phenotype of spinal muscular atrophy by the direct conversion of human fibroblasts to motor neurons.

    Science.gov (United States)

    Zhang, Qi-Jie; Li, Jin-Jing; Lin, Xiang; Lu, Ying-Qian; Guo, Xin-Xin; Dong, En-Lin; Zhao, Miao; He, Jin; Wang, Ning; Chen, Wan-Jin

    2017-02-14

    Spinal muscular atrophy (SMA) is a lethal autosomal recessive neurological disease characterized by selective degeneration of motor neurons in the spinal cord. In recent years, the development of cellular reprogramming technology has provided an alternative and effective method for obtaining patient-specific neurons in vitro. In the present study, we applied this technology to the field of SMA to acquire patient-specific induced motor neurons that were directly converted from fibroblasts via the forced expression of 8 defined transcription factors. The infected fibroblasts began to grow in a dipolar manner, and the nuclei gradually enlarged. Typical Tuj1-positive neurons were generated at day 23. After day 35, induced neurons with multiple neurites were observed, and these neurons also expressed the hallmarks of Tuj1, HB9, ISL1 and CHAT. The conversion efficiencies were approximately 5.8% and 5.5% in the SMA and control groups, respectively. Additionally, the SMA-induced neurons exhibited a significantly reduced neurite outgrowth rate compared with the control neurons. After day 60, the SMA-induced neurons also exhibited a liability of neuronal degeneration and remarkable fracturing of the neurites was observed. By directly reprogramming fibroblasts, we established a feeder-free conversion system to acquire SMA patient-specific induced motor neurons that partially modeled the phenotype of SMA in vitro.

  10. Air stacking: effects on pulmonary function in patients with spinal muscular atrophy and in patients with congenital muscular dystrophy,

    Directory of Open Access Journals (Sweden)

    Tanyse Bahia Carvalho Marques

    2014-10-01

    Full Text Available OBJECTIVE: Respiratory complications are the main causes of morbidity and mortality in patients with neuromuscular disease (NMD. The objectives of this study were to determine the effects that routine daily home air-stacking maneuvers have on pulmonary function in patients with spinal muscular atrophy (SMA and in patients with congenital muscular dystrophy (CMD, as well as to identify associations between spinal deformities and the effects of the maneuvers. METHODS: Eighteen NMD patients (ten with CMD and eight with SMA were submitted to routine daily air-stacking maneuvers at home with manual resuscitators for four to six months, undergoing pulmonary function tests before and after that period. The pulmonary function tests included measurements of FVC; PEF; maximum insufflation capacity (MIC; and assisted and unassisted peak cough flow (APCF and UPCF, respectively with insufflations. RESULTS: After the use of home air-stacking maneuvers, there were improvements in the APCF and UPCF. In the patients without scoliosis, there was also a significant increase in FVC. When comparing patients with and without scoliosis, the increases in APCF and UPCF were more pronounced in those without scoliosis. CONCLUSIONS: Routine daily air-stacking maneuvers with a manual resuscitator appear to increase UPCF and APCF in patients with NMD, especially in those without scoliosis.

  11. Effect of aerobic training in patients with spinal and bulbar muscular atrophy (Kennedy disease)

    DEFF Research Database (Denmark)

    Preisler, N; Andersen, G; Thøgersen, F

    2009-01-01

    ) or any of the other variables examined before and after training, and the patients with SBMA did not feel improvements in ADL. CONCLUSIONS: Frequent, moderate-intensity aerobic conditioning is of little beneficial effect in patients with spinal and bulbar muscular atrophy (SBMA). High levels of plasma......OBJECTIVE: We examined the effect of aerobic exercise in patients with spinal and bulbar muscular atrophy (SBMA). SBMA is caused by a defect androgen receptor. This defect causes motor neuron death, but considering the important function of androgens in muscle, it is possible that muscle damage...... measurements, lung function, plasma proteins, and hormones were evaluated before and after training. Evaluation of improvements in activities of daily living (ADL) was conducted after training. RESULTS: W(max) increased by 18%, and CS activity increased by 35%. There was no significant change in Vo(2max...

  12. Abnormal mitochondrial transport and morphology as early pathological changes in human models of spinal muscular atrophy

    Directory of Open Access Journals (Sweden)

    Chong-Chong Xu

    2016-01-01

    Full Text Available Spinal muscular atrophy (SMA, characterized by specific degeneration of spinal motor neurons, is caused by mutations in the survival of motor neuron 1, telomeric (SMN1 gene and subsequent decreased levels of functional SMN. How the deficiency of SMN, a ubiquitously expressed protein, leads to spinal motor neuron-specific degeneration in individuals affected by SMA remains unknown. In this study, we examined the role of SMN in mitochondrial axonal transport and morphology in human motor neurons by generating SMA type 1 patient-specific induced pluripotent stem cells (iPSCs and differentiating these cells into spinal motor neurons. The initial specification of spinal motor neurons was not affected, but these SMA spinal motor neurons specifically degenerated following long-term culture. Moreover, at an early stage in SMA spinal motor neurons, but not in SMA forebrain neurons, the number of mitochondria, mitochondrial area and mitochondrial transport were significantly reduced in axons. Knocking down of SMN expression led to similar mitochondrial defects in spinal motor neurons derived from human embryonic stem cells, confirming that SMN deficiency results in impaired mitochondrial dynamics. Finally, the application of N-acetylcysteine (NAC mitigated the impairment in mitochondrial transport and morphology and rescued motor neuron degeneration in SMA long-term cultures. Furthermore, NAC ameliorated the reduction in mitochondrial membrane potential in SMA spinal motor neurons, suggesting that NAC might rescue apoptosis and motor neuron degeneration by improving mitochondrial health. Overall, our data demonstrate that SMN deficiency results in abnormal mitochondrial transport and morphology and a subsequent reduction in mitochondrial health, which are implicated in the specific degeneration of spinal motor neurons in SMA.

  13. Early functional impairment of sensory-motor connectivity in a mouse model of spinal muscular atrophy

    Science.gov (United States)

    Mentis, George Z.; Blivis, Dvir; Liu, Wenfang; Drobac, Estelle; Crowder, Melissa E.; Kong, Lingling; Alvarez, Francisco J.; Sumner, Charlotte J.; O'Donovan, Michael J.

    2011-01-01

    SUMMARY To define alterations of neuronal connectivity that occur during motor neuron degeneration, we characterized the function and structure of spinal circuitry in spinal muscular atrophy (SMA) model mice. SMA motor neurons show reduced proprioceptive reflexes that correlate with decreased number and function of synapses on motor neuron somata and proximal dendrites. These abnormalities occur at an early stage of disease in motor neurons innervating proximal hindlimb muscles and medial motor neurons innervating axial muscles, but only at end-stage disease in motor neurons innervating distal hindlimb muscles. Motor neuron loss follows afferent synapse loss with the same temporal and topographical pattern. Trichostatin A, which improves motor behavior and survival of SMA mice, partially restores spinal reflexes illustrating the reversibility of these synaptic defects. De-afferentation of motor neurons is an early event in SMA and may be a primary cause of motor dysfunction that is amenable to therapeutic intervention. PMID:21315257

  14. Sensory neurons do not induce motor neuron loss in a human stem cell model of spinal muscular atrophy.

    Science.gov (United States)

    Schwab, Andrew J; Ebert, Allison D

    2014-01-01

    Spinal muscular atrophy (SMA) is an autosomal recessive disorder leading to paralysis and early death due to reduced SMN protein. It is unclear why there is such a profound motor neuron loss, but recent evidence from fly and mouse studies indicate that cells comprising the whole sensory-motor circuit may contribute to motor neuron dysfunction and loss. Here, we used induced pluripotent stem cells derived from SMA patients to test whether sensory neurons directly contribute to motor neuron loss. We generated sensory neurons from SMA induced pluripotent stem cells and found no difference in neuron generation or survival, although there was a reduced calcium response to depolarizing stimuli. Using co-culture of SMA induced pluripotent stem cell derived sensory neurons with control induced pluripotent stem cell derived motor neurons, we found no significant reduction in motor neuron number or glutamate transporter boutons on motor neuron cell bodies or neurites. We conclude that SMA sensory neurons do not overtly contribute to motor neuron loss in this human stem cell system.

  15. A two-site ELISA can quantify upregulation of SMN protein by drugs for spinal muscular atrophy.

    Science.gov (United States)

    Nguyen thi Man; Humphrey, E; Lam, L T; Fuller, H R; Lynch, T A; Sewry, C A; Goodwin, P R; Mackenzie, A E; Morris, G E

    2008-11-25

    Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by loss of lower motor neurons during early or postnatal development. Severity is variable and is inversely related to the levels of survival of motor neurons (SMN) protein. The aim of this study was to produce a two-site ELISA capable of measuring both the low, basal levels of SMN protein in cell cultures from patients with severe SMA and small increases in these levels after treatment of cells with drugs. A monoclonal antibody against recombinant SMN, MANSMA1, was selected for capture of SMN onto microtiter plates. A selected rabbit antiserum against refolded recombinant SMN was used for detection of the captured SMN. The ratio of SMN levels in control fibroblasts to levels in SMA fibroblasts was greater than 3.0, consistent with Western blot data. The limit of detection was 0.13 ng/mL and SMN could be measured in human NT-2 neuronal precursor cells grown in 96-well culture plates (3 x 10(4) cells per well). Increases in SMN levels of 50% were demonstrable by ELISA after 24 hours treatment of 10(5) SMA fibroblasts with valproate or phenylbutyrate. A rapid and specific two-site, 96-well ELISA assay, available in kit format, can now quantify the effects of drugs on survival of motor neurons protein levels in cell cultures.

  16. Young adults' experiences of living with recessive limb-girdle muscular dystrophy from a salutogenic orientation: an interview study.

    Science.gov (United States)

    Aho, Anna Carin; Hultsjö, Sally; Hjelm, Katarina

    2015-01-01

    To describe young adults' experiences of living with recessive limb-girdle muscular dystrophy (LGMD2) from a salutogenic orientation. A qualitative explorative interview study, including 14 participants aged 20-30 years, was performed focusing on comprehensibility, manageability and meaningfulness in daily life. Content analysis was used for data analysis. Living with LGMD2 not only implies learning to live with the disease and the variations between good and bad periods but also means trying to make sense of a progressive disease that brings uncertainty about future health, by striving to make the best of the situation. Disease progression involves practical and mental struggle, trying to maintain control over one's life despite vanished physical functions that require continual adjustments to the body. Restrictions in a double sense were described, not only due to the disease but also due to poor comprehension of the disease in society. Lack of knowledge about LGMD2 among professionals often results in having to fight for the support needed. In order to manage daily life, it is important to be seen and understood as an individual in contacts with professionals and in society in general, to have informal social support and meaningful activities as well as access to personal assistance if necessary. Recessive limb-girdle muscular dystrophy (LGMD2) is a group of progressive disorders, which manifest in physical and psychological consequences for the individual. According to the salutogenic orientation, people need to find life comprehensible, manageable and meaningful, i.e. to achieve a sense of coherence (SOC), but living with LGMD2 may recurrently challenge the individual's SOC. Through the holistic view of the individual's situation that the salutogenic orientation provides, professionals may support the individual to strengthen SOC and thereby facilitate the movement towards health.

  17. Distribution of skeletal muscle involvement in autosomal recessive distal muscular dystrophy. A clinical and computed tomographic study

    Energy Technology Data Exchange (ETDEWEB)

    Mizusawa, Hidehiro; Nakanishi, Takao; Kobayashi, Fumie

    1987-02-01

    Distribution of skeletal muscle involvement in 5 cases with autosomal recessive distal muscular dystrophy was studied clinically and by computed tomography (CT). Manual muscle test showed muscle involvement with a predilection for flexors in the lower leg and adductors in the thigh. Flexion and extension of the thigh and the lower leg was impaired to similar degree. In progressed cases, neck flexors and trunk muscles were also affected mildly. CT disclosed more clearly the preferential involvement of flexors in the lower leg, and involvement of both hamstrings center dot adductors group and extensors group of the thigh to similar degree. However, m. popliteus was curiously well preserved. In addition, there was a stage showing high density and hypertrophy of m. sartorius, m. gracilis, m. adductor, m. biceps femoris, m. semimenbranosus, m. semitendinosus or m. rectus femoris, which in thought to be compensatory hypertrophy. M. gluteus minimus in the pelvic girdle and m. dorsi proprii in the trunk were also liable to be affected. The CT findings are regarded as characteristic features noted clearly before muscle weakness and atrophy become apparent clinically. CT is very useful for distinguishing distal muscular dystrophy from rimmed vacuolar distal myopathy in which m. quadriceps femoris and flexors of the lower leg are usually well preserved without compensatory hypertrophy on CT.

  18. Recapitulation of spinal motor neuron-specific disease phenotypes in a human cell model of spinal muscular atrophy

    Institute of Scientific and Technical Information of China (English)

    Zhi-Bo Wang; Xiaoqing Zhang; Xue-Jun Li

    2013-01-01

    Establishing human cell models of spinal muscular atrophy (SMA) to mimic motor neuron-specific phenotypes holds the key to understanding the pathogenesis of this devastating disease.Here,we developed a closely representative cell model of SMA by knocking down the disease-determining gene,survival motor neuron (SMN),in human embryonic stem cells (hESCs).Our study with this cell model demonstrated that knocking down of SMN does not interfere with neural induction or the initial specification of spinal motor neurons.Notably,the axonal outgrowth of spinal motor neurons was significantly impaired and these disease-mimicking neurons subsequently degenerated.Furthermore,these disease phenotypes were caused by SMN-full length (SMN-FL) but not SMN-A7 (lacking exon 7)knockdown,and were specific to spinal motor neurons.Restoring the expression of SMN-FL completely ameliorated all of the disease phenotypes,including specific axonal defects and motor neuron loss.Finally,knockdown of SMNFL led to excessive mitochondrial oxidative stress in human motor neuron progenitors.The involvement of oxidative stress in the degeneration of spinal motor neurons in the SMA cell model was further confirmed by the administration of N-acetylcysteine,a potent antioxidant,which prevented disease-related apoptosis and subsequent motor neuron death.Thus,we report here the successful establishment of an hESC-based SMA model,which exhibits disease gene isoform specificity,cell type specificity,and phenotype reversibility.Our model provides a unique paradigm for studying how motor neurons specifically degenerate and highlights the potential importance of antioxidants for the treatment of SMA.

  19. Possible influences on the expression of X chromosome-linked dystrophin abnormalities by heterozygosity for autosomal recessive Fukuyama congenital muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Beggs, A.H.; Neumann, P.E.; Anderson, M.S.; Kunkel, L.M. (Harvard Medical School, Boston, MA (United States)); Arahata, Kiichi; Arikawa, Eri; Nonaka, Ikuya (National Inst. of Neuroscience, Tokyo (Japan))

    1992-01-15

    Abnormalities of dystrophin, a cytoskeletal protein of muscle and nerve, are generally considered specific for Duchenne and Becker muscular dystrophy. However, several patients have recently been identified with dystrophin deficiency who, before dystrophin testing, were considered to have Fukuyama congenital muscular dystrophy (FCMD) on the basis of clinical findings. Epidemiologic data suggest that only 1/3,500 males with autosomal recessive FCMD should have abnormal dystrophin. To explain the observation of 3/23 FCMD males with abnormal dystrophin, the authors propose that dystrophin and the FCMD gene product interact and that the earlier onset and greater severity of these patients' phenotype (relative to Duchenne muscular dystrophy) are due to their being heterozygous for the FCMD mutation in addition to being hemizygous for Duchenne muscular dystrophy, a genotype that is predicted to occur in 1/175,000 Japanese males. This model may help explain the genetic basis for some of the clinical and pathological variability seen among patients with FCMD, and it has potential implications for understanding the inheritance of other autosomal recessive disorders in general. For example, sex ratios for rare autosomal recessive disorders caused by mutations in proteins that interact with X chromosome-linked gene products may display predictable deviation from 1:1.

  20. Imaging Flow Cytometry Analysis to Identify Differences of Survival Motor Neuron Protein Expression in Patients With Spinal Muscular Atrophy.

    Science.gov (United States)

    Arakawa, Reiko; Arakawa, Masayuki; Kaneko, Kaori; Otsuki, Noriko; Aoki, Ryoko; Saito, Kayoko

    2016-08-01

    Spinal muscular atrophy is a neurodegenerative disorder caused by the deficient expression of survival motor neuron protein in motor neurons. A major goal of disease-modifying therapy is to increase survival motor neuron expression. Changes in survival motor neuron protein expression can be monitored via peripheral blood cells in patients; therefore we tested the sensitivity and utility of imaging flow cytometry for this purpose. After the immortalization of peripheral blood lymphocytes from a human healthy control subject and two patients with spinal muscular atrophy type 1 with two and three copies of SMN2 gene, respectively, we used imaging flow cytometry analysis to identify significant differences in survival motor neuron expression. A bright detail intensity analysis was used to investigate differences in the cellular localization of survival motor neuron protein. Survival motor neuron expression was significantly decreased in cells derived from patients with spinal muscular atrophy relative to those derived from a healthy control subject. Moreover, survival motor neuron expression correlated with the clinical severity of spinal muscular atrophy according to SMN2 copy number. The cellular accumulation of survival motor neuron protein was also significantly decreased in cells derived from patients with spinal muscular atrophy relative to those derived from a healthy control subject. The benefits of imaging flow cytometry for peripheral blood analysis include its capacities for analyzing heterogeneous cell populations; visualizing cell morphology; and evaluating the accumulation, localization, and expression of a target protein. Imaging flow cytometry analysis should be implemented in future studies to optimize its application as a tool for spinal muscular atrophy clinical trials. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Stem cell-derived neurotrophic support for the neuromuscular junction in spinal muscular atrophy.

    Science.gov (United States)

    Wyatt, Tanya J; Keirstead, Hans S

    2010-11-01

    Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by specific degeneration of α-motor neurons in the spinal cord. The use of cell transplantation to restore lost function through cell replacement or prevent further degeneration of motor neurons and synapses through neurotrophic support heralds tremendous hope in the SMA field. Much research has been carried out in the last decade on the use of embryonic stem cells in cell replacement strategies for various neurodegenerative diseases. Cell replacement is contingent on the ability of transplanted cells to integrate and form new functional connections with host cells. In the case of SMA, cell replacement is a tall order in that axons of transplanted cells would be required to grow over long distances from the spinal cord through growth-averse terrain to synapse with muscles in the periphery. The efficacy of neurotrophic support is contingent on the ability of transplanted cells to secrete neurotrophins appropriate for degenerating motor neurons in the spinal cord or development/stability of the neuromuscular junction (NMJ) in the periphery. The reader will gain an understanding of the potential of neurotrophins to promote development of the NMJ in a diseased or injured environment. Neurotrophins play a major role in NMJ development and thus may be a key factor in the pathogenesis of NMJs in SMA. Further research into the signaling mechanisms involved in NMJ maturation may identify additional mechanisms by which transplanted cells may be of therapeutic benefit.

  2. Head and Arm Tremor in X-linked Spinal and Bulbar Muscular Atrophy

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    Irene Aicua

    2014-10-01

    Full Text Available Background: X‐linked spinal and bulbar muscular atrophy (SBMA is a rare adult‐onset neuronopathy. Although tremor is known to occur in this disease, the number of reported cases of SBMA with tremor is rare, and the number with videotaped documentation is exceedingly rare. Our aim was to describe/document the characteristic signs of tremor in spinal and bulbar muscular atrophy.Case Report: We report a case of a 58‐year‐old male with a positive family history of tremor. On examination, the patient had jaw and hand tremors but he also exhibited gynecomastia, progressive bulbar paresis, and wasting and weakness primarily in the proximal limb muscles. The laboratory tests revealed an elevated creatine phosphokinase. Genetic testing was positive for X‐SBMA, with 42 CAG repeats.Discussion: Essential tremor is one of the most common movement disorders, yet it is important for clinicians to be aware of the presence of other distinguishing features that point to alternative diagnoses. The presence of action tremor associated with muscle atrophy and gynecomastia should lead to a suspicion of SBMA.

  3. Palliative care in children with spinal muscular atrophy type I: What do they need?

    Science.gov (United States)

    García-Salido, Alberto; de Paso-Mora, María García; Monleón-Luque, Manuel; Martino-Alba, Ricardo

    2015-04-01

    Our aim was to describe the clinical evolution and needs of children with spinal muscular atrophy type I treated in a domiciliary palliative care program. We undertook a retrospective chart review of nine consecutive patients. Descriptions of the clinical and demographic profile of children with spinal muscular atrophy (SMA) type I were referred to a pediatric palliative care team (PPCT). Six males and three females were admitted to the PPCT, all before six months of age, except for one afflicted with SMA type I with respiratory distress. The median time of attention was 57 days (range 1-150). The domiciliary attention mainly consisted of respiratory care. The patient with SMA type I with respiratory distress required domiciliary mechanical ventilation by tracheotomy. In all cases, a nasogastric tube (NT) was indicated. As end-of-life care, eight required morphine to manage the dyspnea, four received it only by enteral (oral or NT) administration, and four received it first by enteral administration with continuous subcutaneous infusion (CSI) later. Three of the four patients with CSI also received benzodiazepines. While they were attended by the PPCT, none required hospital admission. All the patients died at home except for the one attended to for just one day. Domiciliary care for these patients is possible. The respiratory morbidity and its management are the main issues. Application of an NT is useful to maintain nutritional balance. Morphine administration is necessary to manage the dyspnea. Palliative sedation is not always necessary.

  4. Silencing neuronal mutant androgen receptor in a mouse model of spinal and bulbar muscular atrophy.

    Science.gov (United States)

    Sahashi, Kentaro; Katsuno, Masahisa; Hung, Gene; Adachi, Hiroaki; Kondo, Naohide; Nakatsuji, Hideaki; Tohnai, Genki; Iida, Madoka; Bennett, C Frank; Sobue, Gen

    2015-11-01

    Spinal and bulbar muscular atrophy (SBMA), an adult-onset neurodegenerative disease that affects males, results from a CAG triplet repeat/polyglutamine expansions in the androgen receptor (AR) gene. Patients develop progressive muscular weakness and atrophy, and no effective therapy is currently available. The tissue-specific pathogenesis, especially relative pathological contributions between degenerative motor neurons and muscles, remains inconclusive. Though peripheral pathology in skeletal muscle caused by toxic AR protein has been recently reported to play a pivotal role in the pathogenesis of SBMA using mouse models, the role of motor neuron degeneration in SBMA has not been rigorously investigated. Here, we exploited synthetic antisense oligonucleotides to inhibit the RNA levels of mutant AR in the central nervous system (CNS) and explore its therapeutic effects in our SBMA mouse model that harbors a mutant AR gene with 97 CAG expansions and characteristic SBMA-like neurogenic phenotypes. A single intracerebroventricular administration of the antisense oligonucleotides in the presymptomatic phase efficiently suppressed the mutant gene expression in the CNS, and delayed the onset and progression of motor dysfunction, improved body weight gain and survival with the amelioration of neuronal histopathology in motor units such as spinal motor neurons, neuromuscular junctions and skeletal muscle. These findings highlight the importance of the neurotoxicity of mutant AR protein in motor neurons as a therapeutic target. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Established Stem Cell Model of Spinal Muscular Atrophy Is Applicable in the Evaluation of the Efficacy of Thyrotropin-Releasing Hormone Analog.

    Science.gov (United States)

    Ohuchi, Kazuki; Funato, Michinori; Kato, Zenichiro; Seki, Junko; Kawase, Chizuru; Tamai, Yuya; Ono, Yoko; Nagahara, Yuki; Noda, Yasuhiro; Kameyama, Tsubasa; Ando, Shiori; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Hara, Hideaki; Kaneko, Hideo

    2016-02-01

    Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by the degeneration of spinal motor neurons. This disease is mainly caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. Currently, no effective treatment is available, and only symptomatic treatment can be provided. Our purpose in the present study was to establish a human SMA-derived induced pluripotent stem cell (SMA-iPSC) disease model and assay a therapeutic drug in preparation for the development of a novel treatment of SMA. We generated iPSCs from the skin fibroblasts of a patient with SMA and confirmed that they were pluripotent and undifferentiated. The neural differentiation of SMA-iPSCs shortened the dendrite and axon length and increased the apoptosis of the spinal motor neurons. In addition, we found activated astrocytes in differentiated SMA-iPSCs. Using this model, we confirmed that treatment with the thyrotropin-releasing hormone (TRH) analog, 5-oxo-l-prolyl-l-histidyl-l-prolinamide, which had marginal effects in clinical trials, increases the SMN protein level. This increase was mediated through the transcriptional activation of the SMN2 gene and inhibition of glycogen synthase kinase-3β activity. Finally, the TRH analog treatment resulted in dendrite and axon development of spinal motor neurons in differentiated SMA-iPSCs. These results suggest that this human in vitro disease model stimulates SMA pathology and reveal the potential efficacy of TRH analog treatment for SMA. Therefore, we can screen novel therapeutic drugs such as TRH for SMA easily and effectively using the human SMA-iPSC model. Significance: Platelet-derived growth factor (PDGF) has recently been reported to produce the greatest increase in survival motor neuron protein levels by inhibiting glycogen synthase kinase (GSK)-3β; however, motor neurons lack PDGF receptors. A human in vitro spinal muscular atrophy-derived induced pluripotent stem cell model was

  6. Converging Mechanisms of p53 Activation Drive Motor Neuron Degeneration in Spinal Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Christian M. Simon

    2017-12-01

    Full Text Available The hallmark of spinal muscular atrophy (SMA, an inherited disease caused by ubiquitous deficiency in the SMN protein, is the selective degeneration of subsets of spinal motor neurons. Here, we show that cell-autonomous activation of p53 occurs in vulnerable but not resistant motor neurons of SMA mice at pre-symptomatic stages. Moreover, pharmacological or genetic inhibition of p53 prevents motor neuron death, demonstrating that induction of p53 signaling drives neurodegeneration. At late disease stages, however, nuclear accumulation of p53 extends to resistant motor neurons and spinal interneurons but is not associated with cell death. Importantly, we identify phosphorylation of serine 18 as a specific post-translational modification of p53 that exclusively marks vulnerable SMA motor neurons and provide evidence that amino-terminal phosphorylation of p53 is required for the neurodegenerative process. Our findings indicate that distinct events induced by SMN deficiency converge on p53 to trigger selective death of vulnerable SMA motor neurons.

  7. Notch Signaling Pathway Is Activated in Motoneurons of Spinal Muscular Atrophy

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    Gabriel Olmos

    2013-05-01

    Full Text Available Spinal muscular atrophy (SMA is a neurodegenerative disease produced by low levels of Survival Motor Neuron (SMN protein that affects alpha motoneurons in the spinal cord. Notch signaling is a cell-cell communication system well known as a master regulator of neural development, but also with important roles in the adult central nervous system. Aberrant Notch function is associated with several developmental neurological disorders; however, the potential implication of the Notch pathway in SMA pathogenesis has not been studied yet. We report here that SMN deficiency, induced in the astroglioma cell line U87MG after lentiviral transduction with a shSMN construct, was associated with an increase in the expression of the main components of Notch signaling pathway, namely its ligands, Jagged1 and Delta1, the Notch receptor and its active intracellular form (NICD. In the SMNΔ7 mouse model of SMA we also found increased astrocyte processes positive for Jagged1 and Delta1 in intimate contact with lumbar spinal cord motoneurons. In these motoneurons an increased Notch signaling was found, as denoted by increased NICD levels and reduced expression of the proneural gene neurogenin 3, whose transcription is negatively regulated by Notch. Together, these findings may be relevant to understand some pathologic attributes of SMA motoneurons.

  8. Genetic and expression studies of SMN2 gene in Russian patients with spinal muscular atrophy type II and III

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    Schiöth Helgi B

    2011-07-01

    Full Text Available Abstract Background Spinal muscular atrophy (SMA type I, II and III is an autosomal recessive neuromuscular disorder caused by mutations in the survival motor neuron gene (SMN1. SMN2 is a centromeric copy gene that has been characterized as a major modifier of SMA severity. SMA type I patients have one or two SMN2 copies while most SMA type II patients carry three SMN2 copies and SMA III patients have three or four SMN2 copies. The SMN1 gene produces a full-length transcript (FL-SMN while SMN2 is only able to produce a small portion of the FL-SMN because of a splice mutation which results in the production of abnormal SMNΔ7 mRNA. Methods In this study we performed quantification of the SMN2 gene copy number in Russian patients affected by SMA type II and III (42 and 19 patients, respectively by means of real-time PCR. Moreover, we present two families consisting of asymptomatic carriers of a homozygous absence of the SMN1 gene. We also developed a novel RT-qPCR-based assay to determine the FL-SMN/SMNΔ7 mRNA ratio as SMA biomarker. Results Comparison of the SMN2 copy number and clinical features revealed a significant correlation between mild clinical phenotype (SMA type III and presence of four copies of the SMN2 gene. In both asymptomatic cases we found an increased number of SMN2 copies in the healthy carriers and a biallelic SMN1 absence. Furthermore, the novel assay revealed a difference between SMA patients and healthy controls. Conclusions We suggest that the SMN2 gene copy quantification in SMA patients could be used as a prognostic tool for discrimination between the SMA type II and SMA type III diagnoses, whereas the FL-SMN/SMNΔ7 mRNA ratio could be a useful biomarker for detecting changes during SMA pharmacotherapy.

  9. Novel BICD2 mutation in a Japanese family with autosomal dominant lower extremity-predominant spinal muscular atrophy-2.

    Science.gov (United States)

    Yoshioka, Mieko; Morisada, Naoya; Toyoshima, Daisaku; Yoshimura, Hajime; Nishio, Hisahide; Iijima, Kazumoto; Takeshima, Yasuhiro; Uehara, Tomoko; Kosaki, Kenjiro

    2018-04-01

    The most common form of spinal muscular atrophy (SMA) is a recessive disorder caused by SMN1 mutations in 5q13, whereas the genetic etiologies of non-5q SMA are very heterogenous and largely remain to be elucidated. We present a father and son with atrophy and weakness of the lower leg muscles since infancy. Genetic studies in this family revealed a novel BICD2 mutation causing autosomal dominant lower extremity-predominant SMA type 2. The proband was the father, aged 30, and the son was aged 3. Both of them were born uneventfully to nonconsanguineous parents. While the father first walked at the age of 19 months, the son was unable to walk at age 3 years. In both, knee and ankle reflexes were absent and sensation was intact. Serum creatine kinase levels were normal. The son showed congenital arthrogryposis and underwent orthopedic corrections for talipes calcaneovalgus. Investigation of the father at the age of 5 years revealed normal results on nerve conduction studies and sural nerve biopsy. Electromyography showed chronic neurogenic change, and muscle biopsy showed features suggestive of denervation. The father was diagnosed clinically with a sporadic distal SMA. Follow-up studies showed very slow progression. Next-generation and Sanger sequencing revealed a deleterious mutation in BICD2: c.1667A>G, p.Tyr556Cys, in this family. BICD2 is a cytoplasmic conserved motor-adaptor protein involved in anterograde and retrograde transport along the microtubules. Next-generation sequencing will further clarify the genetic basis of non-5q SMA. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  10. Synergic prodegradative activity of Bicalutamide and trehalose on the mutant androgen receptor responsible for spinal and bulbar muscular atrophy

    NARCIS (Netherlands)

    Giorgetti, Elise; Rusmini, Paola; Crippa, Valeria; Cristofani, Riccardo; Boncoraglio, Alessandra; Cicardi, Maria E.; Galbiati, Mariarita; Poletti, Angelo

    2015-01-01

    Spinal and bulbar muscular atrophy (SBMA) is an X-linked motoneuron disease due to a CAG triplet-repeat expansion in the androgen receptor (AR) gene, which is translated into an elongated polyglutamine (polyQ) tract in AR protein (ARpolyQ). ARpolyQ toxicity is activated by the AR ligand testosterone

  11. Quantification of SMN protein in leucocytes from spinal muscular atrophy patients: effects of treatment with valproic acid

    NARCIS (Netherlands)

    Piepers, Sanne; Cobben, Jan-Maarten; Sodaar, Peter; Jansen, Marc D.; Wadman, Renske I.; Meester-Delver, Ann; Poll-The, Bwee Tien; Lemmink, Henny H.; Wokke, John H. J.; van der Pol, W.-Ludo; van den Berg, Leonard H.

    2011-01-01

    Spinal muscular atrophy (SMA) is caused by the homozygous deletion of the survival motor neuron (SMN)1 gene. The nearly identical SMN2 gene produces small amounts of full-length mRNA and functional SMN protein, due to a point mutation in a critical splicing site. Increasing SMN protein production by

  12. Protective Effects of Butyrate-based Compounds on a Mouse Model for Spinal Muscular Atrophy

    Science.gov (United States)

    Butchbach, Matthew E. R.; Lumpkin, Casey J.; Harris, Ashlee W.; Saieva, Luciano; Edwards, Jonathan D.; Workman, Eileen; Simard, Louise R.; Pellizzoni, Livio; Burghes, Arthur H. M.

    2016-01-01

    Proximal spinal muscular atrophy (SMA) is a childhood-onset degenerative disease resulting from the selective loss of motor neurons in the spinal cord. SMA is caused by the loss of SMN1 (survival motor neuron 1) but retention of SMN2. The number of copies of SMN2 modifies disease severity in SMA patients as well as in mouse models, making SMN2 a target for therapeutics development. Sodium butyrate (BA) and its analogue (4PBA) have been shown to increase SMN2 expression in SMA cultured cells. In this study, we examined the effects of BA, 4PBA as well as two BA prodrugs—glyceryl tributyrate (BA3G) and VX563—on the phenotype of SMNΔ7 SMA mice. Treatment with 4PBA, BA3G and VX563 but not BA beginning at PND04 significantly improved the lifespan and delayed disease end stage, with administration of VX563 also improving the growth rate of these mice. 4PBA and VX563 improved the motor phenotype of SMNΔ7 SMA mice and prevented spinal motor neuron loss. Interestingly, neither 4PBA nor VX563 had an effect on SMN expression in the spinal cords of treated SMNΔ7 SMA mice; however, they inhibited histone deacetylase (HDAC) activity and restored the normal phosphorylation states of Akt and glycogen synthase kinase 3β, both of which are altered by SMN deficiency in vivo. These observations show that BA-based compounds with favourable pharmacokinetics ameliorate SMA pathology possibly by modulating HDAC and Akt signaling. PMID:26892876

  13. Spinal muscular atrophy: Selective motor neuron loss and global defect in the assembly of ribonucleoproteins.

    Science.gov (United States)

    Beattie, Christine E; Kolb, Stephen J

    2018-08-15

    Spinal muscular atrophy is caused by deletions or mutations in the SMN1 gene that result in reduced expression of the SMN protein. The SMN protein is an essential molecular chaperone that is required for the biogenesis of multiple ribonucleoprotein (RNP) complexes including spliceosomal small nuclear RNPs (snRNPs). Reductions in SMN expression result in a reduced abundance of snRNPs and to downstream RNA splicing alterations. SMN is also present in axons and dendrites and appears to have important roles in the formation of neuronal mRNA-protein complexes during development or neuronal repair. Thus, SMA is an exemplar, selective motor neuron disorder that is caused by defects in fundamental RNA processing events. A detailed molecular understanding of how motor neurons fail, and why other neurons do not, in SMA will yield important principals about motor neuron maintenance and neuronal specificity in neurodegenerative diseases. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Familial adult spinal muscular atrophy associated with the VAPB gene: report of 42 cases in Brazil

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    Victor Kosac

    2013-10-01

    Full Text Available Familial spinal muscular atrophy (FSMA associated with the vesicle-associated membrane protein-associated protein B (VAPB gene is a rare autosomal dominant disease with late onset and slow progression. We studied 10 of 42 patients from 5 families by taking clinical histories and performing physical exams, electrophysiological studies, and genetic tests. All patients presented late onset disease with slow progression characterized by fasciculations, proximal weakness, amyotrophy, and hypoactive deep tendon reflex, except two who exhibited brisk reflex. Two patients showed tongue fasciculations and respiratory insufficiency. Electrophysiological studies revealed patterns of lower motor neuron disease, and genetic testing identified a P56S mutation of the VAPB gene. Although it is a rare motor neuron disease, FSMA with this mutation might be much more prevalent in Brazil than expected, and many cases may be undiagnosed. Genetic exams should be performed whenever it is suspected in Brazil.

  15. Revised upper limb module for spinal muscular atrophy: Development of a new module.

    Science.gov (United States)

    Mazzone, Elena S; Mayhew, Anna; Montes, Jacqueline; Ramsey, Danielle; Fanelli, Lavinia; Young, Sally Dunaway; Salazar, Rachel; De Sanctis, Roberto; Pasternak, Amy; Glanzman, Allan; Coratti, Giorgia; Civitello, Matthew; Forcina, Nicola; Gee, Richard; Duong, Tina; Pane, Marika; Scoto, Mariacristina; Pera, Maria Carmela; Messina, Sonia; Tennekoon, Gihan; Day, John W; Darras, Basil T; De Vivo, Darryl C; Finkel, Richard; Muntoni, Francesco; Mercuri, Eugenio

    2017-06-01

    There is a growing need for a robust clinical measure to assess upper limb motor function in spinal muscular atrophy (SMA), as the available scales lack sensitivity at the extremes of the clinical spectrum. We report the development of the Revised Upper Limb Module (RULM), an assessment specifically designed for upper limb function in SMA patients. An international panel with specific neuromuscular expertise performed a thorough review of scales currently available to assess upper limb function in SMA. This review facilitated a revision of the existing upper limb function scales to make a more robust clinical scale. Multiple revisions of the scale included statistical analysis and captured clinically relevant changes to fulfill requirements by regulators and advocacy groups. The resulting RULM scale shows good reliability and validity, making it a suitable tool to assess upper extremity function in the SMA population for multi-center clinical research. Muscle Nerve 55: 869-874, 2017. © 2016 Wiley Periodicals, Inc.

  16. Construction of a yeast artifical chromosome contig spanning the spinal muscular atrophy disease gene region

    Energy Technology Data Exchange (ETDEWEB)

    Kleyn, P.W.; Wang, C.H.; Vitale, E.; Pan, J.; Ross, B.M.; Grunn, A.; Palmer, D.A.; Warburton, D.; Brzustowicz, L.M.; Gilliam, T.G. (New York State Psychiatric Institute, NY (United States)); Lien, L.L.; Kunkel, L.M. (Howard Hughes Medical Institute, Boston, MA (United States))

    1993-07-15

    The childhood spinal muscular atrophies (SMAs) are the most common, serious neuromuscular disorders of childhood second to Duchenne muscular dystrophy. A single locus for these disorders has been mapped by recombination events to a region of 0.7 centimorgan (range, 0.1-2.1 centimorgans) between loci D5S435 and MAP1B on chromosome 5q11.2-13.3. By using PCR amplification to screen yeast artificial chromosome (YAC) DNA pools and the PCR-vectorette method to amplify YAC ends, a YAC contig was constructed across the disease gene region. Nine walk steps identified 32 YACs, including a minimum of seven overlapping YAC clones (average size, 460 kb) that span the SMA region. The contig is characterized by a collection of 30 YAC-end sequence tag sites together with seven genetic markers. The entire YAC contig spans a minimum of 3.2 Mb; the SMA locus is confined to roughly half of this region. Microsatellite markers generated along the YAC contig segregate with the SMA locus in all families where the flanking markers (D5S435 and MAP1B) recombine. Construction of a YAC contig across the disease gene region is an essential step in isolation of the SMA-encoding gene. 26 refs., 3 figs., 1 tab.

  17. Deletion analysis of SMN1 and NAIP genes in southern Chinese children with spinal muscular atrophy

    Institute of Scientific and Technical Information of China (English)

    Yu-hua LIANG; Xiao-ling CHEN; Zhong-sheng YU; Chun-yue CHEN; Sheng BI; Lian-gen MAO; Bo-lin ZHOU; Xian-ning ZHANG

    2009-01-01

    Spinal muscular atrophy (SMA) is a disorder characterized by degeneration of lower motor neurons and occasionally bulbar motor neurons leading to progressive limb and trunk paralysis as well as muscular atrophy. Three types of SMA are rec-ognized depending on the age of onset, the maximum muscular activity achieved, and survivorship: SMA1, SMA2, and SMA3. The survival of motor neuron (SMN) gene has been identified as an SMA determining gene, whereas the neuronal apoptosis inhibitory protein (NAIP) gene is considered to be a modifying factor of the severity of SMA. The main objective of this study was to analyze the deletion of SMN1 and NAIP genes in southern Chinese children with SMA. Here, polymerase chain reaction (PCR) combined with restriction fragment length polymorphism (RFLP) was performed to detect the deletion of both exon 7 and exon 8 of SMNI and exon 5 of NAIP in 62 southern Chinese children with strongly suspected clinical symptoms of SMA. All the 32 SMAI patients and 76% (13/17) of SMA2 patients showed homozygous deletions for exon 7 and exon 8, and all the 13 SMA3 patients showed single deletion of SMN1 exon 7 along with 24% (4/17) of SMA2 patients. Eleven out of 32 (34%) SMA1 patients showed NAIP deletion, and none of SMA2 and SMA3 patients was found to have NAIP deletion. The findings of homozygous deletions of exon 7 and/or exon 8 of SMN1 gene confirmed the diagnosis of SMA, and suggested that the deletion of SMN1 exon 7 is a major cause of SMA in southern Chinese children, and that the NA1P gene may be a modifying factor for disease severity of SMA 1. The molecular diagnosis system based on PCR-RFLP analysis can conveniently be applied in the clinical testing, genetic counseling, prenatal diagnosis and preimplantation genetic diagnosis of SMA.

  18. New, Improved Version of the mCOP-PCR Screening System for Detection of Spinal Muscular Atrophy Gene (SMN1) Deletion.

    Science.gov (United States)

    Shinohara, Masakazu; Ar Rochmah, Mawaddah; Nakanishi, Kenta; Harahap, Nur Imma Fatimah; Niba, Emma Tabe Eko; Saito, Toshio; Saito, Kayoko; Takeuchi, Atsuko; Bouike, Yoshihiro; Nishio, Hisahide

    2017-09-07

    Spinal muscular atrophy (SMA) is a frequent autosomal recessive disorder, characterized by lower motor neuron loss in the spinal cord. More than 95% of SMA patients show homozygous survival motor neuron 1 (SMN1) deletion. We previously developed a screening system for SMN1 deletion based on a modified competitive oligonucleotide priming-PCR (mCOP-PCR) technique. However, non-specific amplification products were observed with mCOP-PCR, which might lead to erroneous interpretation of the screening results. To establish an improved version of the mCOP-PCR screening system without non-specific amplification. DNA samples were assayed using a new version of the mCOP-PCR screening system. DNA samples had already been genotyped by PCR-restriction fragment length polymorphism (PCR-RFLP), showing the presence or absence of SMN1 exon 7. The new mCOP-PCR method contained a targeted pre-amplification step of the region, including an SMN1-specific nucleotide, prior to the mCOP-PCR step. mCOP-PCR products were electrophoresed on agarose gels. No non-specific amplification products were detected in electrophoresis gels with the new mCOP-PCR screening system. An additional targeted pre-amplification step eliminated non-specific amplification from mCOP-PCR screening.

  19. Spinal muscular atrophy pathogenic mutations impair the axonogenic properties of axonal-survival of motor neuron.

    Science.gov (United States)

    Locatelli, Denise; d'Errico, Paolo; Capra, Silvia; Finardi, Adele; Colciaghi, Francesca; Setola, Veronica; Terao, Mineko; Garattini, Enrico; Battaglia, Giorgio

    2012-05-01

    The axonal survival of motor neuron (a-SMN) protein is a truncated isoform of SMN1, the spinal muscular atrophy (SMA) disease gene. a-SMN is selectively localized in axons and endowed with remarkable axonogenic properties. At present, the role of a-SMN in SMA is unknown. As a first step to verify a link between a-SMN and SMA, we investigated by means of over-expression experiments in neuroblastoma-spinal cord hybrid cell line (NSC34) whether SMA pathogenic mutations located in the N-terminal part of the protein affected a-SMN function. We demonstrated here that either SMN1 missense mutations or small intragenic re-arrangements located in the Tudor domain consistently altered the a-SMN capability of inducing axonal elongation in vitro. Mutated human a-SMN proteins determined in almost all NSC34 motor neurons the growth of short axons with prominent morphologic abnormalities. Our data indicate that the Tudor domain is critical in dictating a-SMN function possibly because it is an association domain for proteins involved in axon growth. They also indicate that Tudor domain mutations are functionally relevant not only for FL-SMN but also for a-SMN, raising the possibility that also a-SMN loss of function may contribute to the pathogenic steps leading to SMA. © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

  20. Pathogenesis-targeting therapeutics for spinal and bulbar muscular atrophy (SBMA).

    Science.gov (United States)

    Suzuki, Keisuke; Kastuno, Masahisa; Banno, Haruhiko; Sobue, Gen

    2009-08-01

    Spinal and bulbar muscular atrophy (SBMA) is an hereditary, adult-onset, lower motor neuron disease caused by an aberrant elongation of a trinucleotide CAG repeat, which encodes the polyglutamine tract, in the first exon of the androgen receptor (AR) gene. The main symptoms are slowly progressive muscle weakness and atrophy of bulbar, facial and limb muscles. The cardinal histopathological findings of SBMA are an extensive loss of lower motor neurons in the anterior horn of the spinal cord as well as in brainstem motor nuclei and intranuclear accumulations of mutant AR protein in the residual motor neurons. Androgen deprivation therapy rescues neuronal dysfunction in animal models of SBMA, suggesting that the molecular basis for motor neuron degeneration in this disorder is testosterone-dependent nuclear accumulation of the mutant AR. Suppression of disease progression by leuprorelin acetate has also been demonstrated in a phase 2 clinical trial. In addition, the clarification of pathophysiology leads to appearance of candidate drugs to treat this devastating disease: heat shock protein (HSP) inducer, Hsp90 inhibitor, and histone deacetylase inhibitor. Advances in basic and clinical research on SBMA are now paving the way for clinical application of pathogenesis-targeting therapeutics.

  1. Immune dysregulation may contribute to disease pathogenesis in spinal muscular atrophy mice.

    Science.gov (United States)

    Deguise, Marc-Olivier; De Repentigny, Yves; McFall, Emily; Auclair, Nicole; Sad, Subash; Kothary, Rashmi

    2017-02-15

    Spinal muscular atrophy (SMA) has long been solely considered a neurodegenerative disorder. However, recent work has highlighted defects in many other cell types that could contribute to disease aetiology. Interestingly, the immune system has never been extensively studied in SMA. Defects in lymphoid organs could exacerbate disease progression by neuroinflammation or immunodeficiency. Smn depletion led to severe alterations in the thymus and spleen of two different mouse models of SMA. The spleen from Smn depleted mice was dramatically smaller at a very young age and its histological architecture was marked by mislocalization of immune cells in the Smn2B/- model mice. In comparison, the thymus was relatively spared in gross morphology but showed many histological alterations including cortex thinning in both mouse models at symptomatic ages. Thymocyte development was also impaired as evidenced by abnormal population frequencies in the Smn2B/- thymus. Cytokine profiling revealed major changes in different tissues of both mouse models. Consistent with our observations, we found that survival motor neuron (Smn) protein levels were relatively high in lymphoid organs compared to skeletal muscle and spinal cord during postnatal development in wild type mice. Genetic introduction of one copy of the human SMN2 transgene was enough to rescue splenic and thymic defects in Smn2B/- mice. Thus, Smn is required for the normal development of lymphoid organs, and altered immune function may contribute to SMA disease pathogenesis. © The Author 2017. Published by Oxford University Press.

  2. Mitochondrial oxodicarboxylate carrier deficiency is associated with mitochondrial DNA depletion and spinal muscular atrophy-like disease.

    Science.gov (United States)

    Boczonadi, Veronika; King, Martin S; Smith, Anthony C; Olahova, Monika; Bansagi, Boglarka; Roos, Andreas; Eyassu, Filmon; Borchers, Christoph; Ramesh, Venkateswaran; Lochmüller, Hanns; Polvikoski, Tuomo; Whittaker, Roger G; Pyle, Angela; Griffin, Helen; Taylor, Robert W; Chinnery, Patrick F; Robinson, Alan J; Kunji, Edmund R S; Horvath, Rita

    2018-03-08

    PurposeTo understand the role of the mitochondrial oxodicarboxylate carrier (SLC25A21) in the development of spinal muscular atrophy-like disease.MethodsWe identified a novel pathogenic variant in a patient by whole-exome sequencing. The pathogenicity of the mutation was studied by transport assays, computer modeling, followed by targeted metabolic testing and in vitro studies in human fibroblasts and neurons.ResultsThe patient carries a homozygous pathogenic variant c.695A>G; p.(Lys232Arg) in the SLC25A21 gene, encoding the mitochondrial oxodicarboxylate carrier, and developed spinal muscular atrophy and mitochondrial myopathy. Transport assays show that the mutation renders SLC25A21 dysfunctional and 2-oxoadipate cannot be imported into the mitochondrial matrix. Computer models of central metabolism predicted that impaired transport of oxodicarboxylate disrupts the pathways of lysine and tryptophan degradation, and causes accumulation of 2-oxoadipate, pipecolic acid, and quinolinic acid, which was confirmed in the patient's urine by targeted metabolomics. Exposure to 2-oxoadipate and quinolinic acid decreased the level of mitochondrial complexes in neuronal cells (SH-SY5Y) and induced apoptosis.ConclusionMitochondrial oxodicarboxylate carrier deficiency leads to mitochondrial dysfunction and the accumulation of oxoadipate and quinolinic acid, which in turn cause toxicity in spinal motor neurons leading to spinal muscular atrophy-like disease.GENETICS in MEDICINE advance online publication, 8 March 2018; doi:10.1038/gim.2017.251.

  3. Myotonic Muscular Dystrophy

    Science.gov (United States)

    ... Marie-Tooth Disease (CMT) Congenital Muscular Dystrophy (CMD) Duchenne Muscular Dystrophy (DMD) Emery-Dreifuss Muscular Dystrophy Endocrine Myopathies Metabolic Diseases of Muscle Mitochondrial Myopathies (MM) Myotonic Dystrophy (DM) Spinal-Bulbar ...

  4. Association between the SMN2 gene copy number and clinical characteristics of patients with spinal muscular atrophy with homozygous deletion of exon 7 of the SMN1 gene

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    Žarkov Marija

    2015-01-01

    Full Text Available Background/Aim. Spinal muscular atrophy (SMA is an autosomal recessive disease characterized by degeneration of alpha motor neurons in the spinal cord and the medulla oblongata, causing progressive muscle weakness and atrophy. The aim of this study was to determine association between the SMN2 gene copy number and disease phenotype in Serbian patients with SMA with homozygous deletion of exon 7 of the SMN1 gene. Methods. The patients were identified using regional Serbian hospital databases. Investigated clinical characteristics of the disease were: patients’ gender, age at disease onset, achieved and current developmental milestones, disease duration, current age, and the presence of the spinal deformities and joint contractures. The number of SMN1 and SMN2 gene copies was determined using real-time polymerase chain reaction (PCR. Results. Among 43 identified patients, 37 (86.0% showed homozygous deletion of SMN1 exon 7. One (2.7% of 37 patients had SMA type I with 3 SMN2 copies, 11 (29.7% patients had SMA type II with 3.1 ± 0.7 copies, 17 (45.9% patients had SMA type III with 3.7 ± 0.9 copies, while 8 (21.6% patients had SMA type IV with 4.2 ± 0.9 copies. There was a progressive increase in the SMN2 gene copy number from type II towards type IV (p < 0.05. A higher SMN2 gene copy number was associated with better current motor performance (p < 0.05. Conclusion. In the Serbian patients with SMA, a higher SMN2 gene copy number correlated with less severe disease phenotype. A possible effect of other phenotype modifiers should not be neglected.

  5. Mutations in Subunits of the Activating Signal Cointegrator 1 Complex Are Associated with Prenatal Spinal Muscular Atrophy and Congenital Bone Fractures

    Science.gov (United States)

    Knierim, Ellen; Hirata, Hiromi; Wolf, Nicole I.; Morales-Gonzalez, Susanne; Schottmann, Gudrun; Tanaka, Yu; Rudnik-Schöneborn, Sabine; Orgeur, Mickael; Zerres, Klaus; Vogt, Stefanie; van Riesen, Anne; Gill, Esther; Seifert, Franziska; Zwirner, Angelika; Kirschner, Janbernd; Goebel, Hans Hilmar; Hübner, Christoph; Stricker, Sigmar; Meierhofer, David; Stenzel, Werner; Schuelke, Markus

    2016-01-01

    Transcriptional signal cointegrators associate with transcription factors or nuclear receptors and coregulate tissue-specific gene transcription. We report on recessive loss-of-function mutations in two genes (TRIP4 and ASCC1) that encode subunits of the nuclear activating signal cointegrator 1 (ASC-1) complex. We used autozygosity mapping and whole-exome sequencing to search for pathogenic mutations in four families. Affected individuals presented with prenatal-onset spinal muscular atrophy (SMA), multiple congenital contractures (arthrogryposis multiplex congenita), respiratory distress, and congenital bone fractures. We identified homozygous and compound-heterozygous nonsense and frameshift TRIP4 and ASCC1 mutations that led to a truncation or the entire absence of the respective proteins and cosegregated with the disease phenotype. Trip4 and Ascc1 have identical expression patterns in 17.5-day-old mouse embryos with high expression levels in the spinal cord, brain, paraspinal ganglia, thyroid, and submandibular glands. Antisense morpholino-mediated knockdown of either trip4 or ascc1 in zebrafish disrupted the highly patterned and coordinated process of α-motoneuron outgrowth and formation of myotomes and neuromuscular junctions and led to a swimming defect in the larvae. Immunoprecipitation of the ASC-1 complex consistently copurified cysteine and glycine rich protein 1 (CSRP1), a transcriptional cofactor, which is known to be involved in spinal cord regeneration upon injury in adult zebrafish. ASCC1 mutant fibroblasts downregulated genes associated with neurogenesis, neuronal migration, and pathfinding (SERPINF1, DAB1, SEMA3D, SEMA3A), as well as with bone development (TNFRSF11B, RASSF2, STC1). Our findings indicate that the dysfunction of a transcriptional coactivator complex can result in a clinical syndrome affecting the neuromuscular system. PMID:26924529

  6. ROCK inhibition as a therapy for spinal muscular atrophy: understanding the repercussions on multiple cellular targets

    Science.gov (United States)

    Coque, Emmanuelle; Raoul, Cédric; Bowerman, Mélissa

    2014-01-01

    Spinal muscular atrophy (SMA) is the most common genetic disease causing infant death, due to an extended loss of motoneurons. This neuromuscular disorder results from deletions and/or mutations within the Survival Motor Neuron 1 (SMN1) gene, leading to a pathological decreased expression of functional full-length SMN protein. Emerging studies suggest that the small GTPase RhoA and its major downstream effector Rho kinase (ROCK), which both play an instrumental role in cytoskeleton organization, contribute to the pathology of motoneuron diseases. Indeed, an enhanced activation of RhoA and ROCK has been reported in the spinal cord of an SMA mouse model. Moreover, the treatment of SMA mice with ROCK inhibitors leads to an increased lifespan as well as improved skeletal muscle and neuromuscular junction pathology, without preventing motoneuron degeneration. Although motoneurons are the primary target in SMA, an increasing number of reports show that other cell types inside and outside the central nervous system contribute to SMA pathogenesis. As administration of ROCK inhibitors to SMA mice was systemic, the improvement in survival and phenotype could therefore be attributed to specific effects on motoneurons and/or on other non-neuronal cell types. In the present review, we will present the various roles of the RhoA/ROCK pathway in several SMA cellular targets including neurons, myoblasts, glial cells, cardiomyocytes and pancreatic cells as well as discuss how ROCK inhibition may ameliorate their health and function. It is most likely a concerted influence of ROCK modulation on all these cell types that ultimately lead to the observed benefits of pharmacological ROCK inhibition in SMA mice. PMID:25221469

  7. ROCK inhibition as a therapy for spinal muscular atrophy: understanding the repercussions on multiple cellular targets

    Directory of Open Access Journals (Sweden)

    Emmanuelle eCoque

    2014-08-01

    Full Text Available Spinal muscular atrophy (SMA is the most common genetic disease causing infant death, due to an extended loss of motoneurons. This neuromuscular disorder results from deletions and/or mutations within the surviving motor neuron 1 (SMN1 gene, leading to a pathological decreased expression of functional full-length SMN protein. Emerging studies suggest that the small GTPase RhoA and its major downstream effector Rho kinase (ROCK, which both play an instrumental role in cytoskeleton organization, contribute to the pathology of motoneuron diseases. Indeed, an enhanced activation of RhoA and ROCK has been reported in the spinal cord of an SMA mouse model. Moreover, the treatment of SMA mice with ROCK inhibitors leads to an increased lifespan as well as improved skeletal muscle and neuromuscular junction pathology, without preventing motoneuron degeneration. Although motoneurons are the primary target in SMA, an increasing number of reports show that other cell types inside and outside the central nervous system contribute to SMA pathogenesis. As administration of ROCK inhibitors to SMA mice was systemic, the improvement in survival and phenotype could therefore be attributed to specific effects on motoneurons and/or on other non-neuronal cell types. In the present review, we will present the various roles of the RhoA/ROCK pathway in several SMA cellular targets including neurons, myocytes, glial cells, cardiomyocytes and pancreatic cells as well as discuss how ROCK inhibition may ameliorate their health and function. It is most likely a concerted influence of ROCK modulation on all these cell types that ultimately lead to the observed benefits of pharmacological ROCK inhibition in SMA mice.

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

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    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.

  9. Peripheral Androgen Receptor Gene Suppression Rescues Disease in Mouse Models of Spinal and Bulbar Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Andrew P. Lieberman

    2014-05-01

    Full Text Available Spinal and bulbar muscular atrophy (SBMA is caused by the polyglutamine androgen receptor (polyQ-AR, a protein expressed by both lower motor neurons and skeletal muscle. Although viewed as a motor neuronopathy, data from patients and mouse models suggest that muscle contributes to disease pathogenesis. Here, we tested this hypothesis using AR113Q knockin and human bacterial artificial chromosome/clone (BAC transgenic mice that express the full-length polyQ-AR and display androgen-dependent weakness, muscle atrophy, and early death. We developed antisense oligonucleotides that suppressed AR gene expression in the periphery but not the CNS after subcutaneous administration. Suppression of polyQ-AR in the periphery rescued deficits in muscle weight, fiber size, and grip strength, reversed changes in muscle gene expression, and extended the lifespan of mutant males. We conclude that polyQ-AR expression in the periphery is an important contributor to pathology in SBMA mice and that peripheral administration of therapeutics should be explored for SBMA patients.

  10. Is Spinal Muscular Atrophy a disease of the motor neurons only: pathogenesis and therapeutic implications?

    Science.gov (United States)

    Simone, Chiara; Ramirez, Agnese; Bucchia, Monica; Rinchetti, Paola; Rideout, Hardy; Papadimitriou, Dimitra; Re, Diane B.; Corti, Stefania

    2016-01-01

    Spinal Muscular Atrophy (SMA) is a genetic neurological disease that causes infant mortality; no effective therapies are currently available. SMA is due to homozygous mutations and/or deletions in the Survival Motor Neuron 1 (SMN1) gene and subsequent reduction of the SMN protein, leading to the death of motor neurons. However, there is increasing evidence that in addition to motor neurons, other cell types are contributing to SMA pathology. In this review, we will discuss the involvement of non-motor neuronal cells, located both inside and outside the central nervous system, in disease onset and progression. These contribution of non-motor neuronal cells to disease pathogenesis has important therapeutic implications: in fact, even if SMN restoration in motor neurons is needed, it has been shown that optimal phenotypic amelioration in animal models of SMA requires a more widespread SMN correction. It will be crucial to take this evidence into account before clinical translation of the novel therapeutic approaches that are currently under development. PMID:26681261

  11. Management of neuromuscular diseases and spinal muscular atrophy in Latin America.

    Science.gov (United States)

    Monges, S; Rosa, A L

    2017-09-01

    Latin America (LA) has a population of ~645 million people distributed over 33 countries with marked political, cultural and economic differences. In LA, patients with inherited neuromuscular diseases (NMDs) often do not have access to specialized medical centers and many of them go undiagnosed. General management and care of spinal muscular dystrophy (SMA) patients in the region varies due to heterogeneous health care. An active generation of young clinical neurologists is being trained for the specialized care of SMA and other neuromuscular (NM) patients, both in the private and public sectors. The Euro-Latin-American Summer School of Myology (EVELAM) as well as efforts of professionals at large public centers in the major cities of LA have a leading role in this development. Different regional academic-scientific organizations as well as the expanding number of telethon centers and the creation of parent organizations, mostly concerning SMA, all together are contributing to the increased quality of the management of NMD patients. Over the past years, academic and clinical research, as well as the establishment of qualified centers for the molecular testing of NMD are pushing forward the creation of patient registries and the development of specific clinical trials, with Argentina and Brazil having a major role in this field. Nevertheless, increased awareness and further training of specialized health professionals are necessary to reach patients that are currently lacking care throughout the region.

  12. Survival motor neuron protein in motor neurons determines synaptic integrity in spinal muscular atrophy.

    Science.gov (United States)

    Martinez, Tara L; Kong, Lingling; Wang, Xueyong; Osborne, Melissa A; Crowder, Melissa E; Van Meerbeke, James P; Xu, Xixi; Davis, Crystal; Wooley, Joe; Goldhamer, David J; Lutz, Cathleen M; Rich, Mark M; Sumner, Charlotte J

    2012-06-20

    The inherited motor neuron disease spinal muscular atrophy (SMA) is caused by deficient expression of survival motor neuron (SMN) protein and results in severe muscle weakness. In SMA mice, synaptic dysfunction of both neuromuscular junctions (NMJs) and central sensorimotor synapses precedes motor neuron cell death. To address whether this synaptic dysfunction is due to SMN deficiency in motor neurons, muscle, or both, we generated three lines of conditional SMA mice with tissue-specific increases in SMN expression. All three lines of mice showed increased survival, weights, and improved motor behavior. While increased SMN expression in motor neurons prevented synaptic dysfunction at the NMJ and restored motor neuron somal synapses, increased SMN expression in muscle did not affect synaptic function although it did improve myofiber size. Together these data indicate that both peripheral and central synaptic integrity are dependent on motor neurons in SMA, but SMN may have variable roles in the maintenance of these different synapses. At the NMJ, it functions at the presynaptic terminal in a cell-autonomous fashion, but may be necessary for retrograde trophic signaling to presynaptic inputs onto motor neurons. Importantly, SMN also appears to function in muscle growth and/or maintenance independent of motor neurons. Our data suggest that SMN plays distinct roles in muscle, NMJs, and motor neuron somal synapses and that restored function of SMN at all three sites will be necessary for full recovery of muscle power.

  13. Dysfunction of the neuromuscular junction in spinal muscular atrophy types 2 and 3.

    Science.gov (United States)

    Wadman, Renske I; Vrancken, Alexander F J E; van den Berg, Leonard H; van der Pol, W Ludo

    2012-11-13

    Spinal muscular atrophy (SMA) is pathologically characterized by degeneration of anterior horn cells. Recent observations in animal models of SMA and muscle tissue from patients with SMA suggest additional abnormalities in the development and maturation of the neuromuscular junction. We therefore evaluated neuromuscular junction function in SMA with repetitive nerve stimulation. In this case-control study, repetitive nerve stimulation was performed in 35 patients with SMA types 2, 3, and 4, 20 healthy controls, and 5 controls with motor neuron disease. Pathologic decremental responses (>10%) during 3-Hz repetitive nerve stimulation were observed in 17 of 35 patients (49%) with SMA types 2 and 3, but not in healthy controls or controls with motor neuron disease. None of the patients or controls had an abnormal incremental response of >60%. The presence of an abnormal decremental response was not specific for the type of SMA, nor was it associated with compound muscle action potential amplitude, clinical scores, or disease duration. Two of 4 patients with SMA type 3 who tried pyridostigmine reported increased stamina. These data suggest dysfunction of the neuromuscular junction in patients with SMA types 2 and 3. Therefore, drugs that facilitate neuromuscular transmission are candidate drugs for evaluation in carefully designed, placebo-controlled, clinical trials.

  14. Dependence on care experienced by people living with Duchenne muscular dystrophy and spinal cord injury.

    Science.gov (United States)

    Martinsen, Bente; Dreyer, Pia

    2012-04-01

    Being dependent on care in a hospital or in a traditional homecare setting may generate an experience of inferiority in patients. In a private home, dependence is easier to bear if the dependent person has the possibility to influence the planning of care. Little is known about the experience of being dependent on care in a private home, where the dependent person employs his or her own helpers. The aim of this study was to describe the meaning of dependence on care in a private home setting among people living with help requirements for all aspects of daily life. The article draws on two interview studies of people with high cervical spinal cord injury and men with Duschenne muscular dystrophy. Transcriptions of the interviews were analyzed according to a phenomenological hermeneutic approach influenced by Paul Ricoeur's philosophy of interpretation. The meaning of all the interview texts is presented as four short stories. Four themes were identified: the helper as liberating, the paramount verbalization of own needs, the creative engagement in life, and accessibility as an issue in everyday life. Dependence on care was identified to be a movement between freedom and restriction, where the helpers played a crucial role, because it was key that they were sensitive to the signals they got and were able to transform words into meticulous actions.

  15. [Ethical attitudes of intensive care paediatricians as regards patients with spinal muscular atrophy type 1].

    Science.gov (United States)

    Agra Tuñas, María Carmen; Hernández Rastrollo, Ramón; Hernández González, Arturo; Ramil Fraga, Carmen; Cambra Lasaosa, Francisco José; Quintero Otero, Sebastián; Ruiz Extremera, Angela; Rodríguez Núñez, Antonio

    2017-03-01

    Spinal muscular atrophy type 1 (SMA-1) is a progressive and fatal disease that leads to ethical problems for Paediatric professionals. Our objective was to determine the ethical options of Paediatric Intensive Care Unit (PICU) paediatricians as regards a child with SMA-1 and respiratory failure. A cross-sectional descriptive study was conducted using an anonymous questionnaire sent to PICUs in Spain (which can be accessed through the Spanish Society of Paediatric Critical Care web page). Of the 124 responses analysed, 70% were from women, 51% younger than 40 years, 54% from a PICU with more than 10 beds, 69% with prior experience in such cases, and 53% with religious beliefs. In the last patient cared for, most paediatricians opted for non-invasive mechanical ventilation (NIV) and limitation of therapeutic effort (LET) in case of NIV failure. Confronted with a future hypothetical case, half of paediatricians would opt for the same plan (NIV+LET), and 74% would support the family's decision, even in case of disagreement. Age, prior experience and sex were not related to the preferred options. Paediatricians with religious beliefs were less in favour of initial LET. Less than two-thirds (63%) scored the quality of life of a child with SMA-1 and invasive mechanical ventilation as very poor. Faced with child with SMA-1 and respiratory failure, most paediatricians are in favour of initiating NIV and LET when such support is insufficient, but they would accept the family's decision, even in case of disagreement. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. [Spinal muscular atrophy and respiratory failure. How do primary care pediatricians act in a simulated scenario?].

    Science.gov (United States)

    Agra Tuñas, M C; Sánchez Santos, L; Busto Cuiñas, M; Rodríguez Núñez, A

    2015-11-01

    Spinal muscular atrophy type 1 (SMA-1) tends to be fatal in the first year of life if there is no ventilatory support. The decision whether to start such support is an ethical conflict for healthcare professionals. A scenario of acute respiratory failure in an infant with SMA-1 has been included in a training program using advanced simulation for Primary Care pediatricians (PCP). The performances of 34 groups of 4 pediatricians, who participated in 17 courses, were systematically analyzed. Clinical, ethical and communication aspects with parents were evaluated. The initial technical assistance (Administration of oxygen and immediate ventilatory support) was correctly performed by 94% of the teams. However, the PCP had problems in dealing with the ethical aspects of the case. Of the 85% of the teams that raised the ethical conflict with parents, 29% did so on their own initiative, 23% actively excluded them, and only 6% involved them and took their opinion into account in making decisions. Only 11.7% asked about the quality of life of children and 12% for their knowledge of the prognosis of the disease. None explained treatment alternatives, nor tried to contact the pediatrician responsible for the child. When faced with a simulated SMA-1 infant with respiratory failure, PCP have difficulties in interacting with the family, and to involve it in the decision making process. Practical training of all pediatricians should include case scenarios with an ethical clinical problem. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  17. Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy.

    Science.gov (United States)

    Mercuri, Eugenio; Darras, Basil T; Chiriboga, Claudia A; Day, John W; Campbell, Craig; Connolly, Anne M; Iannaccone, Susan T; Kirschner, Janbernd; Kuntz, Nancy L; Saito, Kayoko; Shieh, Perry B; Tulinius, Már; Mazzone, Elena S; Montes, Jacqueline; Bishop, Kathie M; Yang, Qingqing; Foster, Richard; Gheuens, Sarah; Bennett, C Frank; Farwell, Wildon; Schneider, Eugene; De Vivo, Darryl C; Finkel, Richard S

    2018-02-15

    Nusinersen is an antisense oligonucleotide drug that modulates pre-messenger RNA splicing of the survival motor neuron 2 ( SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA). We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of nusinersen in 126 children with SMA who had symptom onset after 6 months of age. The children were randomly assigned, in a 2:1 ratio, to undergo intrathecal administration of nusinersen at a dose of 12 mg (nusinersen group) or a sham procedure (control group) on days 1, 29, 85, and 274. The primary end point was the least-squares mean change from baseline in the Hammersmith Functional Motor Scale-Expanded (HFMSE) score at 15 months of treatment; HFMSE scores range from 0 to 66, with higher scores indicating better motor function. Secondary end points included the percentage of children with a clinically meaningful increase from baseline in the HFMSE score (≥3 points), an outcome that indicates improvement in at least two motor skills. In the prespecified interim analysis, there was a least-squares mean increase from baseline to month 15 in the HFMSE score in the nusinersen group (by 4.0 points) and a least-squares mean decrease in the control group (by -1.9 points), with a significant between-group difference favoring nusinersen (least-squares mean difference in change, 5.9 points; 95% confidence interval, 3.7 to 8.1; PCHERISH ClinicalTrials.gov number, NCT02292537 .).

  18. Respiratory muscle function in infants with spinal muscular atrophy type I.

    Science.gov (United States)

    Finkel, Richard S; Weiner, Daniel J; Mayer, Oscar H; McDonough, Joseph M; Panitch, Howard B

    2014-12-01

    To determine the feasibility and safety of respiratory muscle function testing in weak infants with a progressive neuromuscular disorder. Respiratory insufficiency is the major cause of morbidity and mortality in infants with spinal muscular atrophy type I (SMA-I). Tests of respiratory muscle strength, endurance, and breathing patterns can be performed safely in SMA-I infants. Useful data can be collected which parallels the clinical course of pulmonary function in SMA-I. An exploratory study of respiratory muscle function testing and breathing patterns in seven infants with SMA-I seen in our neuromuscular clinic. Measurements were made at initial study visit and, where possible, longitudinally over time. We measured maximal inspiratory (MIP) and transdiaphragmatic pressures, mean transdiaphragmatic pressure, airway occlusion pressure at 100 msec of inspiration, inspiratory and total respiratory cycle time, and aspects of relative thoracoabdominal motion using respiratory inductive plethysmography (RIP). The tension time index of the diaphragm and of the respiratory muscles, phase angle (Φ), phase relation during the total breath, and labored breathing index were calculated. Age at baseline study was 54-237 (median 131) days. Reliable data were obtained safely for MIP, phase angle, labored breathing index, and the invasive and non-invasive tension time indices, even in very weak infants. Data obtained corresponded to the clinical estimate of severity and predicted the need for respiratory support. The testing employed was both safe and feasible. Measurements of MIP and RIP are easily performed tests that are well tolerated and provide clinically useful information for infants with SMA-I. © 2014 Wiley Periodicals, Inc.

  19. Spinal Muscular Atrophy: From Defective Chaperoning of snRNP Assembly to Neuromuscular Dysfunction

    Directory of Open Access Journals (Sweden)

    Maia Lanfranco

    2017-06-01

    Full Text Available Spinal Muscular Atrophy (SMA is a neuromuscular disorder that results from decreased levels of the survival motor neuron (SMN protein. SMN is part of a multiprotein complex that also includes Gemins 2–8 and Unrip. The SMN-Gemins complex cooperates with the protein arginine methyltransferase 5 (PRMT5 complex, whose constituents include WD45, PRMT5 and pICln. Both complexes function as molecular chaperones, interacting with and assisting in the assembly of an Sm protein core onto small nuclear RNAs (snRNAs to generate small nuclear ribonucleoproteins (snRNPs, which are the operating components of the spliceosome. Molecular and structural studies have refined our knowledge of the key events taking place within the crowded environment of cells and the numerous precautions undertaken to ensure the faithful assembly of snRNPs. Nonetheless, it remains unclear whether a loss of chaperoning in snRNP assembly, considered as a “housekeeping” activity, is responsible for the selective neuromuscular phenotype in SMA. This review thus shines light on in vivo studies that point toward disturbances in snRNP assembly and the consequential transcriptome abnormalities as the primary drivers of the progressive neuromuscular degeneration underpinning the disease. Disruption of U1 snRNP or snRNP assembly factors other than SMN induces phenotypes that mirror aspects of SMN deficiency, and splicing defects, described in numerous SMA models, can lead to a DNA damage and stress response that compromises the survival of the motor system. Restoring the correct chaperoning of snRNP assembly is therefore predicted to enhance the benefit of SMA therapeutic modalities based on augmenting SMN expression.

  20. Phase II open label study of valproic acid in spinal muscular atrophy.

    Directory of Open Access Journals (Sweden)

    Kathryn J Swoboda

    Full Text Available Preliminary in vitro and in vivo studies with valproic acid (VPA in cell lines and patients with spinal muscular atrophy (SMA demonstrate increased expression of SMN, supporting the possibility of therapeutic benefit. We performed an open label trial of VPA in 42 subjects with SMA to assess safety and explore potential outcome measures to help guide design of future controlled clinical trials. Subjects included 2 SMA type I ages 2-3 years, 29 SMA type II ages 2-14 years and 11 type III ages 2-31 years, recruited from a natural history study. VPA was well-tolerated and without evident hepatotoxicity. Carnitine depletion was frequent and temporally associated with increased weakness in two subjects. Exploratory outcome measures included assessment of gross motor function via the modified Hammersmith Functional Motor Scale (MHFMS, electrophysiologic measures of innervation including maximum ulnar compound muscle action potential (CMAP amplitudes and motor unit number estimation (MUNE, body composition and bone density via dual-energy X-ray absorptiometry (DEXA, and quantitative blood SMN mRNA levels. Clear decline in motor function occurred in several subjects in association with weight gain; mean fat mass increased without a corresponding increase in lean mass. We observed an increased mean score on the MHFMS scale in 27 subjects with SMA type II (p

  1. Analysis of the fibroblast growth factor system reveals alterations in a mouse model of spinal muscular atrophy.

    Science.gov (United States)

    Hensel, Niko; Ratzka, Andreas; Brinkmann, Hella; Klimaschewski, Lars; Grothe, Claudia; Claus, Peter

    2012-01-01

    The monogenetic disease Spinal Muscular Atrophy (SMA) is characterized by a progressive loss of motoneurons leading to muscle weakness and atrophy due to severe reduction of the Survival of Motoneuron (SMN) protein. Several models of SMA show deficits in neurite outgrowth and maintenance of neuromuscular junction (NMJ) structure. Survival of motoneurons, axonal outgrowth and formation of NMJ is controlled by neurotrophic factors such as the Fibroblast Growth Factor (FGF) system. Besides their classical role as extracellular ligands, some FGFs exert also intracellular functions controlling neuronal differentiation. We have previously shown that intracellular FGF-2 binds to SMN and regulates the number of a subtype of nuclear bodies which are reduced in SMA patients. In the light of these findings, we systematically analyzed the FGF-system comprising five canonical receptors and 22 ligands in a severe mouse model of SMA. In this study, we demonstrate widespread alterations of the FGF-system in both muscle and spinal cord. Importantly, FGF-receptor 1 is upregulated in spinal cord at a pre-symptomatic stage as well as in a mouse motoneuron-like cell-line NSC34 based model of SMA. Consistent with that, phosphorylations of FGFR-downstream targets Akt and ERK are increased. Moreover, ERK hyper-phosphorylation is functionally linked to FGFR-1 as revealed by receptor inhibition experiments. Our study shows that the FGF system is dysregulated at an early stage in SMA and may contribute to the SMA pathogenesis.

  2. Tissue-specific models of spinal muscular atrophy confirm a critical role of SMN in motor neurons from embryonic to adult stages.

    Science.gov (United States)

    Laird, Angela S; Mackovski, Nikolce; Rinkwitz, Silke; Becker, Thomas S; Giacomotto, Jean

    2016-05-01

    Spinal muscular atrophy (SMA) is an autosomal recessive disease linked to survival motor neuron (SMN) protein deficiency. While SMN protein is expressed ubiquitously, its deficiency triggers tissue-specific hallmarks, including motor neuron death and muscle atrophy, leading to impaired motor functions and premature death. Here, using stable miR-mediated knockdown technology in zebrafish, we developed the first vertebrate system allowing transgenic spatio-temporal control of the smn1 gene. Using this new model it is now possible to investigate normal and pathogenic SMN function(s) in specific cell types, independently or in synergy with other cell populations. We took advantage of this new system to first test the effect of motor neuron or muscle-specific smn1 silencing. Anti-smn1 miRNA expression in motor neurons, but not in muscles, reproduced SMA hallmarks, including abnormal motor neuron development, poor motor function and premature death. Interestingly, smn1 knockdown in motor neurons also induced severe late-onset phenotypes including scoliosis-like body deformities, weight loss, muscle atrophy and, seen for the first time in zebrafish, reduction in the number of motor neurons, indicating motor neuron degeneration. Taken together, we have developed a new transgenic system allowing spatio-temporal control of smn1 expression in zebrafish, and using this model, we have demonstrated that smn1 silencing in motor neurons alone is sufficient to reproduce SMA hallmarks in zebrafish. It is noteworthy that this research is going beyond SMA as this versatile gene-silencing transgenic system can be used to knockdown any genes of interest, filling the gap in the zebrafish genetic toolbox and opening new avenues to study gene functions in this organism. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Molecular chaperones enhance the degradation of expanded polyglutamine repeat androgen receptor in a cellular model of spinal and bulbar muscular atrophy

    NARCIS (Netherlands)

    Bailey, CK; Andriola, IFM; Kampinga, HH; Merry, DE

    2002-01-01

    Spinal and bulbar muscular atrophy (SBMA) is one of a growing number of neurodegenerative diseases caused by a polyglutamine-encoding CAG trinucleotide repeat expansion, and is caused by an expansion within exon 1 of the androgen receptor (AR) gene. The family of polyglutamine diseases is

  4. Isolation of mineralizing Nestin+ Nkx6.1+ vascular muscular cells from the adult human spinal cord

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    Guillon Hélène

    2011-10-01

    Full Text Available Abstract Background The adult central nervous system (CNS contains different populations of immature cells that could possibly be used to repair brain and spinal cord lesions. The diversity and the properties of these cells in the human adult CNS remain to be fully explored. We previously isolated Nestin+ Sox2+ neural multipotential cells from the adult human spinal cord using the neurosphere method (i.e. non adherent conditions and defined medium. Results Here we report the isolation and long term propagation of another population of Nestin+ cells from this tissue using adherent culture conditions and serum. QPCR and immunofluorescence indicated that these cells had mesenchymal features as evidenced by the expression of Snai2 and Twist1 and lack of expression of neural markers such as Sox2, Olig2 or GFAP. Indeed, these cells expressed markers typical of smooth muscle vascular cells such as Calponin, Caldesmone and Acta2 (Smooth muscle actin. These cells could not differentiate into chondrocytes, adipocytes, neuronal and glial cells, however they readily mineralized when placed in osteogenic conditions. Further characterization allowed us to identify the Nkx6.1 transcription factor as a marker for these cells. Nkx6.1 was expressed in vivo by CNS vascular muscular cells located in the parenchyma and the meninges. Conclusion Smooth muscle cells expressing Nestin and Nkx6.1 is the main cell population derived from culturing human spinal cord cells in adherent conditions with serum. Mineralization of these cells in vitro could represent a valuable model for studying calcifications of CNS vessels which are observed in pathological situations or as part of the normal aging. In addition, long term propagation of these cells will allow the study of their interaction with other CNS cells and their implication in scar formation during spinal cord injury.

  5. Feasibility of Using Microsoft Kinect to Assess Upper Limb Movement in Type III Spinal Muscular Atrophy Patients.

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    Xing Chen

    Full Text Available Although functional rating scales are being used increasingly as primary outcome measures in spinal muscular atrophy (SMA, sensitive and objective assessment of early-stage disease progression and drug efficacy remains challenging. We have developed a game based on the Microsoft Kinect sensor, specifically designed to measure active upper limb movement. An explorative study was conducted to determine the feasibility of this new tool in 18 ambulant SMA type III patients and 19 age- and gender-matched healthy controls. Upper limb movement was analysed elaborately through derived features such as elbow flexion and extension angles, arm lifting angle, velocity and acceleration. No significant differences were found in the active range of motion between ambulant SMA type III patients and controls. Hand velocity was found to be different but further validation is necessary. This study presents an important step in the process of designing and handling digital biomarkers as complementary outcome measures for clinical trials.

  6. Inhibition of apoptosis blocks human motor neuron cell death in a stem cell model of spinal muscular atrophy.

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    Dhruv Sareen

    Full Text Available Spinal muscular atrophy (SMA is a genetic disorder caused by a deletion of the survival motor neuron 1 gene leading to motor neuron loss, muscle atrophy, paralysis, and death. We show here that induced pluripotent stem cell (iPSC lines generated from two Type I SMA subjects-one produced with lentiviral constructs and the second using a virus-free plasmid-based approach-recapitulate the disease phenotype and generate significantly fewer motor neurons at later developmental time periods in culture compared to two separate control subject iPSC lines. During motor neuron development, both SMA lines showed an increase in Fas ligand-mediated apoptosis and increased caspase-8 and-3 activation. Importantly, this could be mitigated by addition of either a Fas blocking antibody or a caspase-3 inhibitor. Together, these data further validate this human stem cell model of SMA, suggesting that specific inhibitors of apoptotic pathways may be beneficial for patients.

  7. Histopathological Defects in Intestine in Severe Spinal Muscular Atrophy Mice Are Improved by Systemic Antisense Oligonucleotide Treatment.

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    Palittiya Sintusek

    Full Text Available Gastrointestinal (GI defects, including gastroesophageal reflux, constipation and delayed gastric emptying, are common in patients with spinal muscular atrophy (SMA. Similar GI dysmotility has been identified in mouse models with survival of motor neuron (SMN protein deficiency. We previously described vascular defects in skeletal muscle and spinal cord of SMA mice and we hypothesized that similar defects could be involved in the GI pathology observed in these mice. We therefore investigated the gross anatomical structure, enteric vasculature and neurons in the small intestine in a severe mouse model of SMA. We also assessed the therapeutic response of GI histopathology to systemic administration of morpholino antisense oligonucleotide (AON designed to increase SMN protein expression. Significant anatomical and histopathological abnormalities, with striking reduction of vascular density, overabundance of enteric neurons and increased macrophage infiltration, were detected in the small intestine in SMA mice. After systemic AON treatment in neonatal mice, all the abnormalities observed were significantly restored to near-normal levels. We conclude that the observed GI histopathological phenotypes and functional defects observed in these SMA mice are strongly linked to SMN deficiency which can be rescued by systemic administration of AON. This study on the histopathological changes in the gastrointestinal system in severe SMA mice provides further indication of the complex role that SMN plays in multiple tissues and suggests that at least in SMA mice restoration of SMN production in peripheral tissues is essential for optimal outcome.

  8. Histopathological Defects in Intestine in Severe Spinal Muscular Atrophy Mice Are Improved by Systemic Antisense Oligonucleotide Treatment

    Science.gov (United States)

    Sintusek, Palittiya; Catapano, Francesco; Angkathunkayul, Napat; Marrosu, Elena; Parson, Simon H.; Morgan, Jennifer E.; Muntoni, Francesco; Zhou, Haiyan

    2016-01-01

    Gastrointestinal (GI) defects, including gastroesophageal reflux, constipation and delayed gastric emptying, are common in patients with spinal muscular atrophy (SMA). Similar GI dysmotility has been identified in mouse models with survival of motor neuron (SMN) protein deficiency. We previously described vascular defects in skeletal muscle and spinal cord of SMA mice and we hypothesized that similar defects could be involved in the GI pathology observed in these mice. We therefore investigated the gross anatomical structure, enteric vasculature and neurons in the small intestine in a severe mouse model of SMA. We also assessed the therapeutic response of GI histopathology to systemic administration of morpholino antisense oligonucleotide (AON) designed to increase SMN protein expression. Significant anatomical and histopathological abnormalities, with striking reduction of vascular density, overabundance of enteric neurons and increased macrophage infiltration, were detected in the small intestine in SMA mice. After systemic AON treatment in neonatal mice, all the abnormalities observed were significantly restored to near-normal levels. We conclude that the observed GI histopathological phenotypes and functional defects observed in these SMA mice are strongly linked to SMN deficiency which can be rescued by systemic administration of AON. This study on the histopathological changes in the gastrointestinal system in severe SMA mice provides further indication of the complex role that SMN plays in multiple tissues and suggests that at least in SMA mice restoration of SMN production in peripheral tissues is essential for optimal outcome. PMID:27163330

  9. Analysis of the modifying influence of Plastin 3 (PLS3) on Spinal Muscular Atrophy (SMA) by generation of transgenic mouse models

    OpenAIRE

    Ackermann, Bastian

    2011-01-01

    Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by the loss of α-motor neurons in the ventral horn of the spinal cord. Depending on the severity, the clinical spectrum of SMA ranges from early infant death to normal adult life with only mild muscle weakness. To date, no cure is available. SMA is caused by the homozygous loss of the survival motor neuron gene 1 (SMN1). Besides SMN1, another nearly identical copy of the gene is present in the human genome, thus called...

  10. Diagnosis and management of spinal muscular atrophy: Part 2: Pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics.

    Science.gov (United States)

    Finkel, Richard S; Mercuri, Eugenio; Meyer, Oscar H; Simonds, Anita K; Schroth, Mary K; Graham, Robert J; Kirschner, Janbernd; Iannaccone, Susan T; Crawford, Thomas O; Woods, Simon; Muntoni, Francesco; Wirth, Brunhilde; Montes, Jacqueline; Main, Marion; Mazzone, Elena S; Vitale, Michael; Snyder, Brian; Quijano-Roy, Susana; Bertini, Enrico; Davis, Rebecca Hurst; Qian, Ying; Sejersen, Thomas

    2018-03-01

    This is the second half of a two-part document updating the standard of care recommendations for spinal muscular atrophy published in 2007. This part includes updated recommendations on pulmonary management and acute care issues, and topics that have emerged in the last few years such as other organ involvement in the severe forms of spinal muscular atrophy and the role of medications. Ethical issues and the choice of palliative versus supportive care are also addressed. These recommendations are becoming increasingly relevant given recent clinical trials and the prospect that commercially available therapies will likely change the survival and natural history of this disease. Copyright © 2017. Published by Elsevier B.V.

  11. Identification of a Peptide for Systemic Brain Delivery of a Morpholino Oligonucleotide in Mouse Models of Spinal Muscular Atrophy

    Science.gov (United States)

    Shabanpoor, Fazel; Hammond, Suzan M; Abendroth, Frank; Hazell, Gareth; Wood, Matthew J.A.

    2017-01-01

    Splice-switching antisense oligonucleotides are emerging treatments for neuromuscular diseases, with several splice-switching oligonucleotides (SSOs) currently undergoing clinical trials such as for Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA). However, the development of systemically delivered antisense therapeutics has been hampered by poor tissue penetration and cellular uptake, including crossing of the blood–brain barrier (BBB) to reach targets in the central nervous system (CNS). For SMA application, we have investigated the ability of various BBB-crossing peptides for CNS delivery of a splice-switching phosphorodiamidate morpholino oligonucleotide (PMO) targeting survival motor neuron 2 (SMN2) exon 7 inclusion. We identified a branched derivative of the well-known ApoE (141–150) peptide, which as a PMO conjugate was capable of exon inclusion in the CNS following systemic administration, leading to an increase in the level of full-length SMN2 transcript. Treatment of newborn SMA mice with this peptide-PMO (P-PMO) conjugate resulted in a significant increase in the average lifespan and gains in weight, muscle strength, and righting reflexes. Systemic treatment of adult SMA mice with this newly identified P-PMO also resulted in small but significant increases in the levels of SMN2 pre-messenger RNA (mRNA) exon inclusion in the CNS and peripheral tissues. This work provides proof of principle for the ability to select new peptide paradigms to enhance CNS delivery and activity of a PMO SSO through use of a peptide-based delivery platform for the treatment of SMA potentially extending to other neuromuscular and neurodegenerative diseases. PMID:28118087

  12. Computed tomographic myelography characteristics of spinal cord atrophy in juvenile muscular atrophy of the upper extremity

    International Nuclear Information System (INIS)

    Hirabuki, Norio; Mitomo, Masanori; Miura, Takashi; Hashimoto, Tsutomu; Kawai, Ryuji; Kozuka, Takahiro

    1991-01-01

    Although atrophy of the lower cervical and upper thoracic cord in juvenile muscular atrophy of distal upper extremity has been reported, the atrophic patterns of the cord, especially in the transverse section, have not been studied extensively. The aim of this study is to clarify the atrophic patterns of the cord by CT myelography (CTM) and to discuss the pathogenesis of cord atrophy. Sixteen patients with juvenile muscular atrophy of distal upper extremity were examined by CTM. Atrophy of the lower cervical and upper thoracic cord, consistent with the segmental weakness, was seen in all patients. Flattening of the ventral convexity was a characteristic atrophic pattern of the cord. Bilateral cord atrophy was commonly observed; 8/12 patients with unilateral clinical form and all 4 patients with bilateral form showed bilateral cord atrophy with dominance on the clinical side. There was no correlation between the degree of cord atrophy and duration of symptoms. Flattening of the ventral convexity, associated with purely motor disturbances, reflects selective atrophy of the anterior horns in the cord, which is attributable to chronic ischemia. Cord atrophy proved to precede clinical manifestations. The characteristic atrophy of the cord provides useful information to confirm the diagnosis without long-term observation. (author). 21 refs.; 3 figs.; 2 tabs

  13. Columbia SMA Project: A Randomized, Control Trial of the Effects of Exercise on Motor Function and Strength in Patients with Spinal Muscular Atrophy (SMA)

    Science.gov (United States)

    2012-06-01

    management of the disease. Manual muscle testing (MMT) is performed as part of a routine neurological exam. Manual muscle testing (MMT) was found to be...dynamometry in spinal muscular atrophy. Muscle Nerve. 2002;26(1):64-70. Mostert & Kesselring. Effects of a short-term exercise training program on aerobic...dictated by the diseased motor neuron. The surviving muscles have more viable hypertrophied type 1 motor units possibly resulting in a lower MPF. Our

  14. Edaravone is a candidate agent for spinal muscular atrophy: In vitro analysis using a human induced pluripotent stem cells-derived disease model.

    Science.gov (United States)

    Ando, Shiori; Funato, Michinori; Ohuchi, Kazuki; Kameyama, Tsubasa; Inagaki, Satoshi; Seki, Junko; Kawase, Chizuru; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Kaneko, Hideo; Hara, Hideaki

    2017-11-05

    Spinal muscular atrophy (SMA) is an intractable disease characterized by a progressive loss of spinal motor neurons, which leads to skeletal muscle weakness and atrophy. Currently, there are no curative agents for SMA, although it is understood to be caused by reduced levels of survival motor neuron (SMN) protein. Additionally, why reduced SMN protein level results in selective apoptosis in spinal motor neurons is still not understood. Our purpose in this study was to evaluate the therapeutic potential of edaravone, a free radical scavenger, by using induced pluripotent stem cells from an SMA patient (SMA-iPSCs) and to address oxidative stress-induced apoptosis in spinal motor neurons. We first found that edaravone could improve impaired neural development of SMA-iPSCs-derived spinal motor neurons with limited effect on nuclear SMN protein expression. Furthermore, edaravone inhibited the generation of reactive oxygen species and mitochondrial reactive oxygen species upregulated in SMA-iPSCs-derived spinal motor neurons, and reversed oxidative-stress induced apoptosis. In this study, we suggest that oxidative stress might be partly the reason for selective apoptosis in spinal motor neurons in SMA pathology, and that oxidative stress-induced apoptosis might be the therapeutic target of SMA. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Limb-Girdle Muscular Dystrophy (LGMD)

    Science.gov (United States)

    ... Marie-Tooth Disease (CMT) Congenital Muscular Dystrophy (CMD) Duchenne Muscular Dystrophy (DMD) Emery-Dreifuss Muscular Dystrophy Endocrine Myopathies Metabolic Diseases of Muscle Mitochondrial Myopathies (MM) Myotonic Dystrophy (DM) Spinal-Bulbar ...

  16. Lysine-Less Variants of Spinal Muscular Atrophy SMN and SMNΔ7 Proteins Are Degraded by the Proteasome Pathway

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    Raúl Sánchez-Lanzas

    2017-12-01

    Full Text Available Spinal muscular atrophy is due to mutations affecting the SMN1 gene coding for the full-length protein (survival motor neuron; SMN and the SMN2 gene that preferentially generates an exon 7-deleted protein (SMNΔ7 by alternative splicing. To study SMN and SMNΔ7 degradation in the cell, we have used tagged versions at the N- (Flag or C-terminus (V5 of both proteins. Transfection of those constructs into HeLa cells and treatment with cycloheximide showed that those protein constructs were degraded. Proteasomal degradation usually requires prior lysine ubiquitylation. Surprisingly, lysine-less variants of both proteins tagged either at N- (Flag or C-terminus (V5 were also degraded. The degradation of the endogenous SMN protein, and the protein constructs mentioned above, was mediated by the proteasome, as it was blocked by lactacystin, a specific and irreversible proteasomal inhibitor. The results obtained allowed us to conclude that SMN and SMNΔ7 proteasomal degradation did not absolutely require internal ubiquitylation nor N-terminal ubiquitylation (prevented by N-terminal tagging. While the above conclusions are firmly supported by the experimental data presented, we discuss and justify the need of deep proteomic techniques for the study of SMN complex components (orphan and bound turn-over to understand the physiological relevant mechanisms of degradation of SMN and SMNΔ7 in the cell.

  17. Reduced sensory synaptic excitation impairs motor neuron function via Kv2.1 in spinal muscular atrophy.

    Science.gov (United States)

    Fletcher, Emily V; Simon, Christian M; Pagiazitis, John G; Chalif, Joshua I; Vukojicic, Aleksandra; Drobac, Estelle; Wang, Xiaojian; Mentis, George Z

    2017-07-01

    Behavioral deficits in neurodegenerative diseases are often attributed to the selective dysfunction of vulnerable neurons via cell-autonomous mechanisms. Although vulnerable neurons are embedded in neuronal circuits, the contributions of their synaptic partners to disease process are largely unknown. Here we show that, in a mouse model of spinal muscular atrophy (SMA), a reduction in proprioceptive synaptic drive leads to motor neuron dysfunction and motor behavior impairments. In SMA mice or after the blockade of proprioceptive synaptic transmission, we observed a decrease in the motor neuron firing that could be explained by the reduction in the expression of the potassium channel Kv2.1 at the surface of motor neurons. Chronically increasing neuronal activity pharmacologically in vivo led to a normalization of Kv2.1 expression and an improvement in motor function. Our results demonstrate a key role of excitatory synaptic drive in shaping the function of motor neurons during development and the contribution of its disruption to a neurodegenerative disease.

  18. An Evaluation of a Continuing Education Program for Family Caregivers of Ventilator-Dependent Children with Spinal Muscular Atrophy (SMA

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    Deborah S. Boroughs

    2017-04-01

    Full Text Available Until 25 years ago, there were limited options for long-term mechanical ventilation of children, and the majority of children were cared for in hospitals. However, with improving technology, the pediatric intensive care unit has moved from the hospital to a home setting, as children with increasingly complex healthcare needs are now often cared for by family members. One of the most complex care conditions involves ventilator and tracheostomy support. Advanced respiratory technologies that augment natural respiratory function prolong the lives of children with respiratory compromise; however, this care often comes with serious risks, including respiratory muscle impairment, respiratory failure, and chronic pulmonary disease. Both non-invasive assisted ventilation and assisted ventilation via tracheostomy can prolong survival into adulthood in many cases; however, mechanical ventilation in the home is a high-stakes, high risk intervention. Increasing complexity of care over time requires perpetual skill training of family caregivers that is delivered and supported by professional caregivers; yet, opportunities for additional training outside of the hospital rarely exist. Recent data has confirmed that repetitive caregiver education is essential for retention of memory and skills in adult learners. This study analyzes the use of continued education and training in the community for family caregivers of ventilator-dependent children diagnosed with spinal muscular atrophy (SMA.

  19. 17-AAG increases autophagic removal of mutant androgen receptor in spinal and bulbar muscular atrophy.

    Science.gov (United States)

    Rusmini, Paola; Simonini, Francesca; Crippa, Valeria; Bolzoni, Elena; Onesto, Elisa; Cagnin, Monica; Sau, Daniela; Ferri, Nicola; Poletti, Angelo

    2011-01-01

    Several types of motorneuron diseases are linked to neurotoxic mutant proteins. These acquire aberrant conformations (misfolding) that trigger deleterious downstream events responsible for neuronal dysfunction and degeneration. The pharmacological removal of misfolded proteins might thus be useful in these diseases. We utilized a peculiar motorneuronal disease model, spinobulbar muscular atrophy (SBMA), in which the neurotoxicity of the protein involved, the mutant androgen receptor (ARpolyQ), can be modulated by its ligand testosterone (T). 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) has already been proven to exert beneficial action in SBMA. Here we demonstrated that 17-AAG exerts its pro-degradative activity on mutant ARpolyQ without impacting on proteasome functions. 17-AAG removes ARpolyQ misfolded species and aggregates by activating the autophagic system. We next analyzed the 17-AAG effects on two proteins (SOD1 and TDP-43) involved in related motorneuronal diseases, such as amyotrophic lateral sclerosis (ALS). In these models 17-AAG was unable to counteract protein aggregation. Copyright © 2010 Elsevier Inc. All rights reserved.

  20. Neuroprotective effect of non-viral gene therapy treatment based on tetanus toxin C-fragment in a severe mouse model of Spinal Muscular Atrophy.

    Directory of Open Access Journals (Sweden)

    Sara Olivan Garcia

    2016-08-01

    Full Text Available Spinal muscular atrophy (SMA is a hereditary childhood disease that causes paralysis and progressive degeneration of skeletal muscles and spinal motor neurons. SMA is associated with reduced levels of full-length Survival of Motor Neuron (SMN protein, due to mutations in the Survival of Motor Neuron 1 gene. Nowadays there are no effective therapies available to treat patients with SMA, so our aim was to test whether the non-toxic carboxy-terminal fragment of tetanus toxin heavy chain (TTC, which exhibits neurotrophic properties, might have a therapeutic role or benefit in SMA. In this manuscript, we have demonstrated that TTC enhance the SMN expression in motor neurons in vitro and evaluated the effect of intramuscular injection of TTC-encoding plasmid in the spinal cord and the skeletal muscle of SMNdelta7 mice. For this purpose, we studied the weight and the survival time, as well as, the survival and cell death pathways and muscular atrophy. Our results showed that TTC treatment reduced the expression of autophagy markers (Becn1, Atg5, Lc3 and p62 and pro-apoptotic genes such as Bax and Casp3 in spinal cord. In skeletal muscle, TTC was able to downregulate the expression of the main marker of autophagy, Lc3, to wild type levels and the expression of the apoptosis effector protein, Casp3. Regarding the genes related to muscular atrophy (Ankrd1, Calm1, Col19a1, Fbox32, Mt2, Myod1, NogoA, Pax7, Rrad, and Sln, TTC suggest a compensatory effect for muscle damage response, diminished oxidative stress and modulated calcium homeostasis. These preliminary findings suggest the need for further experiments to depth study the effect of TTC in SMA disease.

  1. Atrofia muscular bulbo espinhal recessiva ligada ao cromossomo X (doença de Kennedy: estudo de uma família X-linked recessive bulbospinal muscular atrophy (Kennedy's disease: study of a family

    Directory of Open Access Journals (Sweden)

    DAMACIO RAMÓN KAIMEN-MACIEL

    1998-09-01

    Full Text Available A doença de Kennedy (DK é forma rara de doença do neurônio motor caracterizada por mutação na região codificadora do gene do receptor androgênico localizado no braço longo do cromossoma X (Xq 11-12. Há expansão das sequências de trinucleotídeos CAG que nos pacientes deve atingir número maior do que 347 repetições de pares de bases. Apresentamos quatro gerações de uma família com dez indivíduos acometidos. Avaliamos três pacientes do sexo masculino com idade variando entre 50 e 60 anos que desenvolveram sintomatologia por volta de 30 anos de idade caracterizada por fraqueza muscular progressiva associada a disfagia e disartria. O exame demonstrou ginecomastia, atrofia testicular, amiotrofia, fasciculações, paresia, abolição de reflexos e tremor postural. A análise do DNA pela técnica do PCR demonstrou número de repetições CAG aumentado no locus Xq 11-12 nos três pacientes e em uma mulher assintomática da família. Demonstramos a primeira família brasileira com diagnóstico de DK através de genética molecular. A DK deve fazer parte do diagnóstico diferencial das doenças do neurônio motor e a identificação destes pacientes é importante para o prognóstico e para o aconselhamento genético.Kennedy's disease is a rare type of motor neuron disease with a sex-linked recessive trait. DNA studies show a mutation at the androgen receptor gene on the long arm of X cromossome (Xq 11-12 with expanded CAG triplets (more than 347 repeats. We present three patients and one carrier among ten patients of a four generation family with clinical phenotype of the disease. The patients' ages ranged from 50 to 60 years with symptomatology usually beginning around 30 years of age. Patients had gynecomastia, testicular atrophy, muscular weakness, fasciculation, amyotrophy, absent deep tendon reflexes and postural tremor. PCR techniques of DNA analysis showed expanded size of CAG repeats on Xq 11-12 in all the three patients and in

  2. B3GALNT2 mutations associated with non-syndromic autosomal recessive intellectual disability reveal a lack of genotype-phenotype associations in the muscular dystrophy-dystroglycanopathies

    NARCIS (Netherlands)

    Maroofian, R.; Riemersma, M.; Jae, L.T.; Zhianabed, N.; Willemsen, M.H.; Wissink-Lindhout, W.M.; Willemsen, M.A.A.P.; Brouwer, A.P.M. de; Mehrjardi, M.Y.V.; Ashrafi, M.R.; Kusters, B.; Kleefstra, T.; Jamshidi, Y.; Nasseri, M.; Pfundt, R.; Brummelkamp, T.R.; Abbaszadegan, M.R.; Lefeber, D.J.; Bokhoven, H. van

    2017-01-01

    BACKGROUND: The phenotypic severity of congenital muscular dystrophy-dystroglycanopathy (MDDG) syndromes associated with aberrant glycosylation of alpha-dystroglycan ranges from the severe Walker-Warburg syndrome or muscle-eye-brain disease to mild, late-onset, isolated limb-girdle muscular

  3. Functional characterizations of rare UBA1 variants in X-linked Spinal Muscular Atrophy [version 1; referees: 2 approved

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    Chris D. Balak

    2017-09-01

    Full Text Available Background: X-linked spinal muscular atrophy (XL-SMA results from mutations in the Ubiquitin-Like Modifier Activating Enzyme 1 (UBA1. Previously, four novel closely clustered mutations have been shown to cause this fatal infantile disorder affecting only males. These mutations, three missense and one synonymous, all lie within Exon15 of the UBA1 gene, which contains the active adenylation domain (AAD. Methods: In this study, our group characterized the three known missense variants in vitro. Using a novel Uba1 assay and other methods, we investigated Uba1 adenylation, thioester, and transthioesterification reactions in vitro to determine possible biochemical effects of the missense variants. Results: Our data revealed that only one of the three XL-SMA missense variants impairs the Ubiquitin-adenylating ability of Uba1. Additionally, these missense variants retained Ubiquitin thioester bond formation and transthioesterification rates equal to that found in the wild type. Conclusions: Our results demonstrate a surprising shift from the likelihood of these XL-SMA mutations playing a damaging role in Uba1’s enzymatic activity with Ubiquitin, to other roles such as altering UBA1 mRNA splicing via the disruption of splicing factor binding sites, similar to a mechanism in traditional SMA, or disrupting binding to other important in vivo binding partners.  These findings help to narrow the search for the areas of possible dysfunction in the Ubiquitin-proteasome pathway that ultimately result in XL-SMA. Moreover, this investigation provides additional critical understanding of the mutations’ biochemical mechanisms, vital for the development of future effective diagnostic assays and therapeutics.

  4. Microarray analysis of gene expression by skeletal muscle of three mouse models of Kennedy disease/spinal bulbar muscular atrophy.

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    Kaiguo Mo

    2010-09-01

    Full Text Available Emerging evidence implicates altered gene expression within skeletal muscle in the pathogenesis of Kennedy disease/spinal bulbar muscular atrophy (KD/SBMA. We therefore broadly characterized gene expression in skeletal muscle of three independently generated mouse models of this disease. The mouse models included a polyglutamine expanded (polyQ AR knock-in model (AR113Q, a polyQ AR transgenic model (AR97Q, and a transgenic mouse that overexpresses wild type AR solely in skeletal muscle (HSA-AR. HSA-AR mice were included because they substantially reproduce the KD/SBMA phenotype despite the absence of polyQ AR.We performed microarray analysis of lower hindlimb muscles taken from these three models relative to wild type controls using high density oligonucleotide arrays. All microarray comparisons were made with at least 3 animals in each condition, and only those genes having at least 2-fold difference and whose coefficient of variance was less than 100% were considered to be differentially expressed. When considered globally, there was a similar overlap in gene changes between the 3 models: 19% between HSA-AR and AR97Q, 21% between AR97Q and AR113Q, and 17% between HSA-AR and AR113Q, with 8% shared by all models. Several patterns of gene expression relevant to the disease process were observed. Notably, patterns of gene expression typical of loss of AR function were observed in all three models, as were alterations in genes involved in cell adhesion, energy balance, muscle atrophy and myogenesis. We additionally measured changes similar to those observed in skeletal muscle of a mouse model of Huntington's Disease, and to those common to muscle atrophy from diverse causes.By comparing patterns of gene expression in three independent models of KD/SBMA, we have been able to identify candidate genes that might mediate the core myogenic features of KD/SBMA.

  5. Non-neural phenotype of spinal and bulbar muscular atrophy: results from a large cohort of Italian patients.

    Science.gov (United States)

    Querin, Giorgia; Bertolin, Cinzia; Da Re, Elisa; Volpe, Marco; Zara, Gabriella; Pegoraro, Elena; Caretta, Nicola; Foresta, Carlo; Silvano, Maria; Corrado, Domenico; Iafrate, Massimo; Angelini, Lorenzo; Sartori, Leonardo; Pennuto, Maria; Gaiani, Alessandra; Bello, Luca; Semplicini, Claudio; Pareyson, Davide; Silani, Vincenzo; Ermani, Mario; Ferlin, Alberto; Sorarù, Gianni

    2016-08-01

    To carry out a deep characterisation of the main androgen-responsive tissues involved in spinal and bulbar muscular atrophy (SBMA). 73 consecutive Italian patients underwent a full clinical protocol including biochemical and hormonal analyses, genitourinary examination, bone metabolism and densitometry, cardiological evaluation and muscle pathology. Creatine kinase levels were slightly to markedly elevated in almost all cases (68 of the 73; 94%). 30 (41%) patients had fasting glucose above the reference limit, and many patients had total cholesterol (40; 54.7%), low-density lipoproteins cholesterol (29; 39.7%) and triglyceride (35; 48%) levels above the recommended values. Although testosterone, luteinising hormone and follicle-stimulating hormone values were generally normal, in one-third of cases we calculated an increased Androgen Sensitivity Index reflecting the presence of androgen resistance in these patients. According to the International Prostate Symptom Score (IPSS), 7/70 (10%) patients reported severe lower urinal tract symptoms (IPSS score >19), and 21/73 (30%) patients were moderately symptomatic (IPSS score from 8 to 19). In addition, 3 patients were carriers of an indwelling bladder catheter. Videourodynamic evaluation indicated that 4 of the 7 patients reporting severe urinary symptoms had an overt prostate-unrelated bladder outlet obstruction. Dual-energy X-ray absorptiometry scan data were consistent with low bone mass in 25/61 (41%) patients. Low bone mass was more frequent at the femoral than at the lumbar level. Skeletal muscle biopsy was carried out in 20 patients and myogenic changes in addition to the neurogenic atrophy were mostly observed. Our study provides evidence of a wide non-neural clinical phenotype in SBMA, suggesting the need for comprehensive multidisciplinary protocols for these patients. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  6. Candidate proteins, metabolites and transcripts in the Biomarkers for Spinal Muscular Atrophy (BforSMA clinical study.

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    Richard S Finkel

    Full Text Available Spinal Muscular Atrophy (SMA is a neurodegenerative motor neuron disorder resulting from a homozygous mutation of the survival of motor neuron 1 (SMN1 gene. The gene product, SMN protein, functions in RNA biosynthesis in all tissues. In humans, a nearly identical gene, SMN2, rescues an otherwise lethal phenotype by producing a small amount of full-length SMN protein. SMN2 copy number inversely correlates with disease severity. Identifying other novel biomarkers could inform clinical trial design and identify novel therapeutic targets.To identify novel candidate biomarkers associated with disease severity in SMA using unbiased proteomic, metabolomic and transcriptomic approaches.A cross-sectional single evaluation was performed in 108 children with genetically confirmed SMA, aged 2-12 years, manifesting a broad range of disease severity and selected to distinguish factors associated with SMA type and present functional ability independent of age. Blood and urine specimens from these and 22 age-matched healthy controls were interrogated using proteomic, metabolomic and transcriptomic discovery platforms. Analyte associations were evaluated against a primary measure of disease severity, the Modified Hammersmith Functional Motor Scale (MHFMS and to a number of secondary clinical measures.A total of 200 candidate biomarkers correlate with MHFMS scores: 97 plasma proteins, 59 plasma metabolites (9 amino acids, 10 free fatty acids, 12 lipids and 28 GC/MS metabolites and 44 urine metabolites. No transcripts correlated with MHFMS.In this cross-sectional study, "BforSMA" (Biomarkers for SMA, candidate protein and metabolite markers were identified. No transcript biomarker candidates were identified. Additional mining of this rich dataset may yield important insights into relevant SMA-related pathophysiology and biological network associations. Additional prospective studies are needed to confirm these findings, demonstrate sensitivity to change with

  7. Evaluation of SMN protein, transcript, and copy number in the biomarkers for spinal muscular atrophy (BforSMA clinical study.

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    Thomas O Crawford

    Full Text Available The universal presence of a gene (SMN2 nearly identical to the mutated SMN1 gene responsible for Spinal Muscular Atrophy (SMA has proved an enticing incentive to therapeutics development. Early disappointments from putative SMN-enhancing agent clinical trials have increased interest in improving the assessment of SMN expression in blood as an early "biomarker" of treatment effect.A cross-sectional, single visit, multi-center design assessed SMN transcript and protein in 108 SMA and 22 age and gender-matched healthy control subjects, while motor function was assessed by the Modified Hammersmith Functional Motor Scale (MHFMS. Enrollment selectively targeted a broad range of SMA subjects that would permit maximum power to distinguish the relative influence of SMN2 copy number, SMA type, present motor function, and age.SMN2 copy number and levels of full-length SMN2 transcripts correlated with SMA type, and like SMN protein levels, were lower in SMA subjects compared to controls. No measure of SMN expression correlated strongly with MHFMS. A key finding is that SMN2 copy number, levels of transcript and protein showed no correlation with each other.This is a prospective study that uses the most advanced techniques of SMN transcript and protein measurement in a large selectively-recruited cohort of individuals with SMA. There is a relationship between measures of SMN expression in blood and SMA type, but not a strong correlation to motor function as measured by the MHFMS. Low SMN transcript and protein levels in the SMA subjects relative to controls suggest that these measures of SMN in accessible tissues may be amenable to an "early look" for target engagement in clinical trials of putative SMN-enhancing agents. Full length SMN transcript abundance may provide insight into the molecular mechanism of phenotypic variation as a function of SMN2 copy number.Clinicaltrials.gov NCT00756821.

  8. Social/economic costs and health-related quality of life in patients with spinal muscular atrophy (SMA) in Spain.

    Science.gov (United States)

    López-Bastida, Julio; Peña-Longobardo, Luz María; Aranda-Reneo, Isaac; Tizzano, Eduardo; Sefton, Mark; Oliva-Moreno, Juan

    2017-08-18

    The aim of this study was to determine the economic burden and health-related quality of life (HRQOL) of patients with Spinal Muscular Atrophy (SMA) and their caregivers in Spain. This was a cross-sectional and retrospective study of patients diagnosed with SMA in Spain. We adopted a bottom up, prevalence approach design to study patients with SMA. The patient's caregivers completed an anonymous questionnaire regarding their socio-demographic characteristics, use of healthcare services and non-healthcare services. Costs were estimated from a societal perspective (including healthcare costs and non-healthcare costs), and health-related quality of life (HRQOL) was assessed using the EQ-5D questionnaire. The main caregivers also answered a questionnaire on their characteristics and on their HRQOL. A total of 81 caregivers of patients with different subtypes of SMA completed the questionnaire. Based on the reference unitary prices for 2014, the average annual costs per patient were € 33,721. Direct healthcare costs were € 10,882 (representing around 32.3% of the total cost) and the direct non-healthcare costs were € 22,839 (67.7% of the total cost). The mean EQ-5D social tariff score for patients was 0.16, and the mean score of the EQ-5D visual analogue scale was 54. The mean EQ-5D social tariff score for caregivers was 0.49 and their mean score on the EQ-5D visual analogue scale was 69. The results highlight the burden that SMA has in terms of costs and decreased HRQOL, not only for patients but also for their caregivers. In particular, the substantial social/economic burden is mostly attributable to the high direct non-healthcare costs.

  9. Human adipose-derived mesenchymal stem cells as a new model of spinal and bulbar muscular atrophy.

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    Marta Dossena

    Full Text Available Spinal and bulbar muscular atrophy (SBMA or Kennedy's disease is an X-linked CAG/polyglutamine expansion motoneuron disease, in which an elongated polyglutamine tract (polyQ in the N-terminal androgen receptor (ARpolyQ confers toxicity to this protein. Typical markers of SBMA disease are ARpolyQ intranuclear inclusions. These are generated after the ARpolyQ binds to its endogenous ligands, which promotes AR release from chaperones, activation and nuclear translocation, but also cell toxicity. The SBMA mouse models developed so far, and used in preclinical studies, all contain an expanded CAG repeat significantly longer than that of SBMA patients. Here, we propose the use of SBMA patients adipose-derived mesenchymal stem cells (MSCs as a new human in vitro model to study ARpolyQ toxicity. These cells have the advantage to express only ARpolyQ, and not the wild type AR allele. Therefore, we isolated and characterized adipose-derived MSCs from three SBMA patients (ADSC from Kennedy's patients, ADSCK and three control volunteers (ADSCs. We found that both ADSCs and ADSCKs express mesenchymal antigens, even if only ADSCs can differentiate into the three typical cell lineages (adipocytes, chondrocytes and osteocytes, whereas ADSCKs, from SBMA patients, showed a lower growth potential and differentiated only into adipocyte. Moreover, analysing AR expression on our mesenchymal cultures we found lower levels in all ADSCKs than ADSCs, possibly related to negative pressures exerted by toxic ARpolyQ in ADSCKs. In addition, with proteasome inhibition the ARpolyQ levels increased specifically in ADSCKs, inducing the formation of HSP70 and ubiquitin positive nuclear ARpolyQ inclusions. Considering all of this evidence, SBMA patients adipose-derived MSCs cultures should be considered an innovative in vitro human model to understand the molecular mechanisms of ARpolyQ toxicity and to test novel therapeutic approaches in SBMA.

  10. The experiences of families living with the anticipatory loss of a school-age child with spinal muscular atrophy - the parents' perspectives.

    Science.gov (United States)

    Yang, Bao-Huan; Mu, Pei-Fan; Wang, Wen-Sheng

    2016-09-01

    To probe into parents' anticipatory loss of school-age children with Type I or II spinal muscular atrophy. Spinal muscular atrophy is a rare disorder that causes death. Children die early due to either gradual atrophy or an infection of the lungs. Therefore, family members experience anticipatory loss, which causes grief before the actual loss. Family members feel physically and mentally exhausted, which results in a family crisis. Therefore, it is important to explore their experiences related to anticipatory loss to assist with the adjustment of the families to their circumstances. This study applied a phenomenology method and purposive sampling. The 19 parents who participated in this study were referred to us by two medical centers in Taiwan. Their average age was 32-49 years. Using in-depth interviews, this study explored parents' anticipatory loss. The interviews were recorded and transcribed. Meanings were extracted using Giorgi analysis, and precision was assessed according to Guba and Lincoln, which was treated as the evaluation standard. Four themes were identified from the parents' interviews. The themes included enduring the helplessness and pressure of care, suffering due to the child's rare and unknown condition, loss of hope and a reinforcement of the parent-child attachment, and avoiding the pressure of death and enriching the child's life. The research findings help nurses identify anticipatory loss among parents of school-age children with type I or II spinal muscular atrophy. They enhance health professionals' understanding of the panic that occurs in the society surrounding the families, family members' dynamic relationships, and the families' demands for care. In an attempt to providing intersubjective empathy and support with family having a child with type I and II SMA, nurses may recognize relevant family reactions and enhancing their hope and parent-child attachment. Encourage family members and child go beyond the pressure of death and

  11. B3GALNT2 mutations associated with non-syndromic autosomal recessive intellectual disability reveal a lack of genotype-phenotype associations in the muscular dystrophy-dystroglycanopathies.

    Science.gov (United States)

    Maroofian, Reza; Riemersma, Moniek; Jae, Lucas T; Zhianabed, Narges; Willemsen, Marjolein H; Wissink-Lindhout, Willemijn M; Willemsen, Michèl A; de Brouwer, Arjan P M; Mehrjardi, Mohammad Yahya Vahidi; Ashrafi, Mahmoud Reza; Kusters, Benno; Kleefstra, Tjitske; Jamshidi, Yalda; Nasseri, Mojila; Pfundt, Rolph; Brummelkamp, Thijn R; Abbaszadegan, Mohammad Reza; Lefeber, Dirk J; van Bokhoven, Hans

    2017-12-22

    The phenotypic severity of congenital muscular dystrophy-dystroglycanopathy (MDDG) syndromes associated with aberrant glycosylation of α-dystroglycan ranges from the severe Walker-Warburg syndrome or muscle-eye-brain disease to mild, late-onset, isolated limb-girdle muscular dystrophy without neural involvement. However, muscular dystrophy is invariably found across the spectrum of MDDG patients. Using linkage mapping and whole-exome sequencing in two families with an unexplained neurodevelopmental disorder, we have identified homozygous and compound heterozygous mutations in B3GALNT2. The first family comprises two brothers of Dutch non-consanguineous parents presenting with mild ID and behavioral problems. Immunohistochemical analysis of muscle biopsy revealed no significant aberrations, in line with the absence of a muscular phenotype in the affected siblings. The second family includes five affected individuals from an Iranian consanguineous kindred with mild-to-moderate intellectual disability (ID) and epilepsy without any notable neuroimaging, muscle, or eye abnormalities. Complementation assays of the compound heterozygous mutations identified in the two brothers had a comparable effect on the O-glycosylation of α-dystroglycan as previously reported mutations that are associated with severe muscular phenotypes. In conclusion, we show that mutations in B3GALNT2 can give rise to a novel MDDG syndrome presentation, characterized by ID associated variably with seizure, but without any apparent muscular involvement. Importantly, B3GALNT2 activity does not fully correlate with the severity of the phenotype as assessed by the complementation assay.

  12. The SMN1 common variant c.22 dupA in Chinese patients causes spinal muscular atrophy by nonsense-mediated mRNA decay in humans.

    Science.gov (United States)

    Bai, JinLi; Qu, YuJin; Cao, YanYan; Yang, Lan; Ge, Lin; Jin, YuWei; Wang, Hong; Song, Fang

    2018-02-20

    Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder that is mostly caused by homozygous deletion of the SMN1 gene. Approximately 5%-10% of SMA patients are believed to have SMN1 variants. c.22 dupA (p.Ser8lysfs*23) has been identified as the most frequent variant in the Chinese SMA population and to be associated with a severe phenotype. However, the exact molecular mechanism of the variant on the pathogenesis of SMA is unclear. We observed that SMN1 mRNA and the SMN protein in the peripheral blood cells of a patient with c.22 dupA were lower than those of controls. The aim of this study is to investigate whether nonsense-mediated mRNA decay (NMD) plays a role in the mechanism of the c.22 dupA variant of the SMN1 gene as it causes SMA. Two lymphoblasts cell lines from two patients (patient 1 and 2) with the c.22 dupA, and one dermal fibroblasts cell line from patient 2 were included in our study. Two-stage validation of the NMD mechanism was supplied. We first measured the changes in the transcript levels of the SMN1 gene by real-time quantitative PCR after immortalized B-lymphoblasts and dermal fibroblasts cells of the SMA patients were treated with inhibitors of the NMD pathway, including puromycin and cyclohemide. Next, lentivirus-mediated knockdown of the key NMD factor-Up-frameshift protein 1 (UPF1)-was performed in the fibroblasts cell line to further clarify whether the variant led to NMD, as UPF1 recognizes abnormally terminated transcripts as NMD substrates during translation. SC35 1.7-kb transcripts, a physiological NMD substrate was determined to be a NMD positive gene in our experiments. The two inhibitors resulted in a dramatic escalation of the levels of the full-length SMN1 (fl-SMN1) transcripts. Additionally, the SC35 1.7-kb mRNA levels were also increased, suggesting that NMD pathway is suppressed by the two inhibitors. For the 3 cell lines, the fold increase of the SMN1 transcript levels of cycloheximide ranged

  13. High-resolution melting (HRM) analysis as a feasible method for detecting spinal muscular atrophy via dried blood spots.

    Science.gov (United States)

    Er, Tze-Kiong; Kan, Tzu-Min; Su, Yu-Fa; Liu, Ta-Chih; Chang, Jan-Gowth; Hung, Shih-Ya; Jong, Yuh-Jyh

    2012-11-12

    Spinal muscular atrophy (SMA) is a neurodegenerative disease with the leading genetic cause of infant mortality. More than 95% of patients with SMA have a homozygous disruption in the survival motor neuron1 (SMN1) gene, caused by mutation, deletion, or rearrangement. Recently, treatment in humans in the immediate postnatal period, prior to the development of weakness or very early in the course of the disease, may be effective. Therefore, our objective was to establish a feasible method for SMA screening. High-resolution melting (HRM) analysis is rapidly becoming the most important mutation-scanning methodology that allows mutation scanning and genotyping without the need for costly labeled oligonucleotides. In the current study, we aim to develop a method for identifying the substitution of single nucleotide in SMN1 exon 7 (c.840C>T) by HRM analysis. Genomic DNA was extracted from peripheral blood samples and dried blood spots obtained from 30 patients with SMA and 30 normal individuals. All results were previously confirmed by denaturing high-performance liquid chromatography (DHPLC). In order to identify the substitution of single nucleotide in SMN1 exon 7 (c.840C>T) by HRM analysis, a primer set was used in HRM analysis. At first, we failed to identify the substitution of single nucleotide in SMN1 exon 7 (c.840C>T) by HRM analysis because the homozygous CC and homozygous TT cannot be distinguished by HRM analysis. Therefore, all samples were mixed with a known SMN1/SMN2 copy number (SMN1/SMN2=0:3), which we may call driver. This strategy is used to differentiate between homozygous CC and homozygous TT. After mixing with driver, the melting profile of homozygous CC becomes heteroduplex; however, the homozygous TT remains the same in the normalized and temperature-shifted difference plots. HRM analysis can be successfully applied to screen SMA via DNA obtained from whole blood and dried blood spots. We strongly believe that HRM analysis, a high-throughput method

  14. Interventions Targeting Glucocorticoid-Krüppel-like Factor 15-Branched-Chain Amino Acid Signaling Improve Disease Phenotypes in Spinal Muscular Atrophy Mice

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    Lisa M. Walter

    2018-05-01

    Full Text Available The circadian glucocorticoid-Krüppel-like factor 15-branched-chain amino acid (GC-KLF15-BCAA signaling pathway is a key regulatory axis in muscle, whose imbalance has wide-reaching effects on metabolic homeostasis. Spinal muscular atrophy (SMA is a neuromuscular disorder also characterized by intrinsic muscle pathologies, metabolic abnormalities and disrupted sleep patterns, which can influence or be influenced by circadian regulatory networks that control behavioral and metabolic rhythms. We therefore set out to investigate the contribution of the GC-KLF15-BCAA pathway in SMA pathophysiology of Taiwanese Smn−/−;SMN2 and Smn2B/− mouse models. We thus uncover substantial dysregulation of GC-KLF15-BCAA diurnal rhythmicity in serum, skeletal muscle and metabolic tissues of SMA mice. Importantly, modulating the components of the GC-KLF15-BCAA pathway via pharmacological (prednisolone, genetic (muscle-specific Klf15 overexpression and dietary (BCAA supplementation interventions significantly improves disease phenotypes in SMA mice. Our study highlights the GC-KLF15-BCAA pathway as a contributor to SMA pathogenesis and provides several treatment avenues to alleviate peripheral manifestations of the disease. The therapeutic potential of targeting metabolic perturbations by diet and commercially available drugs could have a broader implementation across other neuromuscular and metabolic disorders characterized by altered GC-KLF15-BCAA signaling. Keywords: Spinal muscular atrophy, KLF15, Glucocorticoids, Branched-chain amino acids, Metabolism, Therapy

  15. Spinal Muscular Atrophy (SMA)

    Science.gov (United States)

    ... age 3 or so, depending on the child’s maturity and general outlook. Many professionals have observed that ... mak- ing it hard to smile or convey emotion through facial expressions. SBMA is like other forms ...

  16. Spinal Muscular Atrophy

    Science.gov (United States)

    ... most often affected. Complications include scoliosis and joint contractures—chronic shortening of muscles or tendons around joints, ... of SMA include: Congenital SMA with arthrogryposis (persistent contracture of joints with fixed abnormal posture of the ...

  17. Spinal Muscular Atrophy

    Science.gov (United States)

    ... and how it led to collaboration with several pharmaceutical and biotechnology companies. Information from the National Library of Medicine’s ... and how it led to collaboration with several pharmaceutical and biotechnology companies. Information from the National Library of Medicine’s ...

  18. Progression of spinal deformity in wheelchair-dependent patients with Duchenne muscular dystrophy who are not treated with steroids: coronal plane (scoliosis) and sagittal plane (kyphosis, lordosis) deformity.

    Science.gov (United States)

    Shapiro, F; Zurakowski, D; Bui, T; Darras, B T

    2014-01-01

    We determined the frequency, rate and extent of development of scoliosis (coronal plane deformity) in wheelchair-dependent patients with Duchenne muscular dystrophy (DMD) who were not receiving steroid treatment. We also assessed kyphosis and lordosis (sagittal plane deformity). The extent of scoliosis was assessed on sitting anteroposterior (AP) spinal radiographs in 88 consecutive non-ambulatory patients with DMD. Radiographs were studied from the time the patients became wheelchair-dependent until the time of spinal fusion, or the latest assessment if surgery was not undertaken. Progression was estimated using a longitudinal mixed-model regression analysis to handle repeated measurements. Scoliosis ≥ 10° occurred in 85 of 88 patients (97%), ≥ 20° in 78 of 88 (89%) and ≥ 30° in 66 of 88 patients (75%). The fitted longitudinal model revealed that time in a wheelchair was a highly significant predictor of the magnitude of the curve, independent of the age of the patient (p lordosis (16 (27%) abnormal and seven (11%) normal). This study provides a baseline to assess the effects of steroids and other forms of treatment on the natural history of scoliosis in patients with DMD, and an approach to assessing spinal deformity in the coronal and sagittal planes in wheelchair-dependent patients with other neuromuscular disorders.

  19. A Perturbed MicroRNA Expression Pattern Characterizes Embryonic Neural Stem Cells Derived from a Severe Mouse Model of Spinal Muscular Atrophy (SMA

    Directory of Open Access Journals (Sweden)

    Andrea Luchetti

    2015-08-01

    Full Text Available Spinal muscular atrophy (SMA is an inherited neuromuscular disorder and the leading genetic cause of death in infants. Despite the disease-causing gene, survival motor neuron (SMN1, encodes a ubiquitous protein, SMN1 deficiency preferentially affects spinal motor neurons (MNs, leaving the basis of this selective cell damage still unexplained. As neural stem cells (NSCs are multipotent self-renewing cells that can differentiate into neurons, they represent an in vitro model for elucidating the pathogenetic mechanism of neurodegenerative diseases such as SMA. Here we characterize for the first time neural stem cells (NSCs derived from embryonic spinal cords of a severe SMNΔ7 SMA mouse model. SMNΔ7 NSCs behave as their wild type (WT counterparts, when we consider neurosphere formation ability and the expression levels of specific regional and self-renewal markers. However, they show a perturbed cell cycle phase distribution and an increased proliferation rate compared to wild type cells. Moreover, SMNΔ7 NSCs are characterized by the differential expression of a limited number of miRNAs, among which miR-335-5p and miR-100-5p, reduced in SMNΔ7 NSCs compared to WT cells. We suggest that such miRNAs may be related to the proliferation differences characterizing SMNΔ7 NSCs, and may be potentially involved in the molecular mechanisms of SMA.

  20. A Perturbed MicroRNA Expression Pattern Characterizes Embryonic Neural Stem Cells Derived from a Severe Mouse Model of Spinal Muscular Atrophy (SMA).

    Science.gov (United States)

    Luchetti, Andrea; Ciafrè, Silvia Anna; Murdocca, Michela; Malgieri, Arianna; Masotti, Andrea; Sanchez, Massimo; Farace, Maria Giulia; Novelli, Giuseppe; Sangiuolo, Federica

    2015-08-06

    Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder and the leading genetic cause of death in infants. Despite the disease-causing gene, survival motor neuron (SMN1), encodes a ubiquitous protein, SMN1 deficiency preferentially affects spinal motor neurons (MNs), leaving the basis of this selective cell damage still unexplained. As neural stem cells (NSCs) are multipotent self-renewing cells that can differentiate into neurons, they represent an in vitro model for elucidating the pathogenetic mechanism of neurodegenerative diseases such as SMA. Here we characterize for the first time neural stem cells (NSCs) derived from embryonic spinal cords of a severe SMNΔ7 SMA mouse model. SMNΔ7 NSCs behave as their wild type (WT) counterparts, when we consider neurosphere formation ability and the expression levels of specific regional and self-renewal markers. However, they show a perturbed cell cycle phase distribution and an increased proliferation rate compared to wild type cells. Moreover, SMNΔ7 NSCs are characterized by the differential expression of a limited number of miRNAs, among which miR-335-5p and miR-100-5p, reduced in SMNΔ7 NSCs compared to WT cells. We suggest that such miRNAs may be related to the proliferation differences characterizing SMNΔ7 NSCs, and may be potentially involved in the molecular mechanisms of SMA.

  1. Spinal Muscular Atrophy, types I and II: What are the differences in body composition and resting energy expenditure?

    Science.gov (United States)

    Bertoli, Simona; De Amicis, Ramona; Mastella, Chiara; Pieri, Giulia; Giaquinto, Ester; Battezzati, Alberto; Leone, Alessandro; Baranello, Giovanni

    2017-12-01

    Different neuromuscular functional domains in types I and II Spinal Muscular Atrophy (SMAI and SMAII) could lead to differences in body composition (BC) and resting energy expenditure (REE). Their identification could provide the key to defining appropriate strategies in clinical dietary management, but data comparing SMAI and SMAII in terms of BC and REE are not yet available. We measured total and regional fat (FM), lean (LBM), mineral (BMC) masses, body water (total, intra- and extra-cellular, TBW, ICW, ECW) and REE in a sample of SMAI and II children, matched for age and sex, and also adjusting for body size to compare these features of the two SMA phenotypes. 15 SMAI and 15 SMAII children, (M/F = 9/6 vs 9/6, age 3.6 ± 1.9 vs 3.5 ± 1.8 years, p = 0.99), confirmed genetically, were measured as follows: Anthropometric measurements [Body Weight (BW), Supine Length (SL), Arm Length (AL), Femur Length (FL), Tibia Length (TL)], Dual x-ray Energy Absorptiometry (DEXA) [total and segmental FM, LBM, FFM, and BMC], Bioelectrical impedance (BIA) [TBW, ICW, ECW] and Indirect Calorimetry (REE, respiratory quotients) were collected by the same trained dietician. BW, SL and Body Mass Index (BMI) Z-scores were calculated according to CDC Growth Charts (2000). SMA children had high percentages of FM and a lower percentage of TBW and ECW compared to the respective reference values for sex and age, whereas the BMC percentages did not differ, even splitting the two phenotypes. SMA I children had a lower BW and BMI-Z score compared to children with SMA II, but similar total and segmental FM. On the contrary, total FFM and LBM were significantly lower in SMAI (7290.0 ± 1729.1 g vs 8410.1 ± 1508.4 g; 6971.8 ± 1637.1 g vs 8041.7 ± 1427.7 g, p = 0.039, p = 0.037, respectively), particularly at the trunk level. Arm BMC also resulted significantly lower in SMAI. The measured REE values were similar (684 ± 143 kcal/day vs 703 ± 122 Kcal/day p = 0

  2. Motor neuronal repletion of the NMJ organizer, Agrin, modulates the severity of the spinal muscular atrophy disease phenotype in model mice.

    Science.gov (United States)

    Kim, Jeong-Ki; Caine, Charlotte; Awano, Tomoyuki; Herbst, Ruth; Monani, Umrao R

    2017-07-01

    Spinal muscular atrophy (SMA) is a common and often fatal neuromuscular disorder caused by low levels of the Survival Motor Neuron (SMN) protein. Amongst the earliest detectable consequences of SMN deficiency are profound defects of the neuromuscular junctions (NMJs). In model mice these synapses appear disorganized, fail to mature and are characterized by poorly arborized nerve terminals. Given one role of the SMN protein in orchestrating the assembly of spliceosomal snRNP particles and subsequently regulating the alternative splicing of pre-mRNAs, a plausible link between SMN function and the distal neuromuscular SMA phenotype is an incorrectly spliced transcript or transcripts involved in establishing or maintaining NMJ structure. In this study, we explore the effects of one such transcript-Z+Agrin-known to be a critical organizer of the NMJ. We confirm that low SMN protein reduces motor neuronal levels of Z+Agrin. Repletion of this isoform of Agrin in the motor neurons of SMA model mice increases muscle fiber size, enhances the post-synaptic NMJ area, reduces the abnormal accumulation of intermediate filaments in nerve terminals of the neuromuscular synapse and improves the innervation of muscles. While these effects are independent of changes in SMN levels or increases in motor neuron numbers they nevertheless have a significant effect on the overall disease phenotype, enhancing mean survival in severely affected SMA model mice by ∼40%. We conclude that Agrin is an important target of the SMN protein and that mitigating NMJ defects may be one strategy in treating human spinal muscular atrophy. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Muscles in a mouse model of spinal muscular atrophy show profound defects in neuromuscular development even in the absence of failure in neuromuscular transmission or loss of motor neurons

    OpenAIRE

    Lee, Young il; Mikesh, Michelle; Smith, Ian; Rimer, Mendell; Thompson, Wesley

    2011-01-01

    A mouse model of the devastating human disease "spinal muscular atrophy" (SMA) was used to investigate the severe muscle weakness and spasticity that precedes the death of these animals near the end of the 2nd postnatal week. Counts of motor units to the soleus muscle as well as of axons in the soleus muscle nerve showed no loss of motor neurons. Similarly, neither immunostaining of neuromuscular junctions nor the measurement of the tension generated by nerve stimulation gave evidence of any ...

  4. Treatment with Creatine Monohydrate in Spinal and Bulbar Muscular Atrophy: Protocol for a Randomized, Double-Blind, Placebo-Controlled Trial.

    Science.gov (United States)

    Hijikata, Yasuhiro; Katsuno, Masahisa; Suzuki, Keisuke; Hashizume, Atsushi; Araki, Amane; Yamada, Shinichiro; Inagaki, Tomonori; Ito, Daisuke; Hirakawa, Akihiro; Kinoshita, Fumie; Gosho, Masahiko; Sobue, Gen

    2018-03-05

    Although spinal and bulbar muscular atrophy (SBMA) has been classified as a motor neuron disease, several reports have indicated the primary involvement of skeletal muscle in the pathogenesis of this devastating disease. Recent studies reported decreased intramuscular creatine levels in skeletal muscles in both patients with SBMA and transgenic mouse models of SBMA, which appears to contribute to muscle weakness. The present study aimed to examine the efficacy and safety of oral creatine supplementation to improve motor function in patients with SBMA. A randomized, double-blind, placebo-controlled, three-armed clinical trial was conducted to assess the safety and efficacy of creatine therapy in patients with SBMA. Patients with SBMA eligible for this study were assigned randomly in a 1:1:1 ratio to each group of placebo, 10 g, or 15 g daily dose of creatine monohydrate in a double-blind fashion. Participants took creatine or placebo orally 3 times a day for 8 weeks. Outcome measurements were results of neurological assessments, examinations, and questionnaires collected at baseline and at weeks 4, 8, and 16 after a washout period. The primary endpoint was the change in handgrip strength values from baseline to week 8. The secondary endpoints included the following: results of maximum voluntary isometric contraction tests of extremities; tongue pressure; results of the 15-foot timed walk test and the rise from bed test; modified quantitative myasthenia gravis score; respiratory function test results; activities of daily living assessed with the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale and the Spinal and Bulbar Muscular Atrophy Functional Rating Scale; skeletal muscle mass measured with dual-energy X-ray absorptiometry; urinary 8-hydroxydeoxyguanosine levels; and questionnaires examining the quality of life, swallowing function, and fatigue. Participant enrollment in the trial started from June 2014 and follow-up was completed in July 2015. The

  5. Improvement of neuromuscular synaptic phenotypes without enhanced survival and motor function in severe spinal muscular atrophy mice selectively rescued in motor neurons.

    Directory of Open Access Journals (Sweden)

    Ximena Paez-Colasante

    Full Text Available In the inherited childhood neuromuscular disease spinal muscular atrophy (SMA, lower motor neuron death and severe muscle weakness result from the reduction of the ubiquitously expressed protein survival of motor neuron (SMN. Although SMA mice recapitulate many features of the human disease, it has remained unclear if their short lifespan and motor weakness are primarily due to cell-autonomous defects in motor neurons. Using Hb9(Cre as a driver, we selectively raised SMN expression in motor neurons in conditional SMAΔ7 mice. Unlike a previous study that used choline acetyltransferase (ChAT(Cre+ as a driver on the same mice, and another report that used Hb9(Cre as a driver on a different line of conditional SMA mice, we found no improvement in survival, weight, motor behavior and presynaptic neurofilament accumulation. However, like in ChAT(Cre+ mice, we detected rescue of endplate size and mitigation of neuromuscular junction (NMJ denervation status. The rescue of endplate size occurred in the absence of an increase in myofiber size, suggesting endplate size is determined by the motor neuron in these animals. Real time-PCR showed that the expression of spinal cord SMN transcript was sharply reduced in Hb9(Cre+ SMA mice relative to ChAT(Cre+ SMA mice. This suggests that our lack of overall phenotypic improvement is most likely due to an unexpectedly poor recombination efficiency driven by Hb9(Cre . Nonetheless, the low levels of SMN were sufficient to rescue two NMJ structural parameters indicating that these motor neuron cell autonomous phenotypes are very sensitive to changes in motoneuronal SMN levels. Our results directly suggest that even those therapeutic interventions with very modest effects in raising SMN in motor neurons may provide mitigation of neuromuscular phenotypes in SMA patients.

  6. Shoulder muscular activity in individuals with low back pain and spinal cord injury during seated manual load transfer tasks.

    Science.gov (United States)

    Dickerson, Clark R; Alenabi, Talia; Martin, Bernard J; Chaffin, Don B

    2018-03-08

    This study aimed to compare the activity of four shoulder muscles in individuals with low back pain (LBP), spinal cord injuries (SCI) and a control group, during one-handed load transfer trials. Nine individuals with minimum one-year of LBP, eleven with thoracic/lumbar SCI and nine healthy controls participated in this study. The activations of anterior deltoid, upper trapezius, infraspinatus and pectoralis major were recorded by surface EMG during one-handed transferring of a cylinder from a home shelve to six spatially distributed target shelves. The integrated EMG values were compared using repeated measure ANOVA. Both LBPs and SCIs had higher anterior deltoid activation and LBPs required more upper trapezius activation than controls (p demands for these two muscles. The anterior deltoid and upper trapezius in LBP and SCI individuals are under higher demand during occupational load transfer tasks. Practitioner Summary: This study aimed to compare the activation of four shoulder muscles in individuals with low back pain, spinal cord injuries and healthy condition. EMG analysis showed that the injured groups required more upper trapezius and anterior deltoid activation during load transfer tasks, which may predispose them to muscle overexertion.

  7. Theory of mind, empathy and neuropsychological functioning in X-linked spinal and bulbar muscular atrophy: a controlled study of 20 patients.

    Science.gov (United States)

    Di Rosa, Elisa; Sorarù, Gianni; Kleinbub, Johann Roland; Calvo, Vincenzo; Vallesi, Antonino; Querin, Giorgia; Marcato, Sonia; Grasso, Irene; Palmieri, Arianna

    2015-02-01

    Recent studies have described brain involvement, mainly at frontal level, in patients with spinal and bulbar muscular atrophy (SBMA), a rare adult-onset motor neuron disease caused by a CAG repeat in the androgen receptor (AR) gene. The aim of our research was to investigate the poorly characterized neuropsychological and psychological profile of these patients, on the basis of previous literature. We administered a neuropsychological screening and tests relating to cognitive and affective empathy, attributed to the theory of mind (ToM) framework, to 20 males with SBMA, and to age- and education-matched controls. Although patients' neuropsychological performance was unimpaired, a clear dissociation emerged between their cognitive and affective empathy. Patients had distinctive deficits in mentalizing, as assessed with the Faux Pas Test, whilst affective empathy (i.e., sharing experience), assessed with the Reading the Mind in the Eyes test, appeared to be preserved. The likely implications of subtle frontal lobe impairments on the one hand, and a protective influence of androgen insensitivity in these patients on the other, are discussed in the light of our results.

  8. SMA CARNIVAL TRIAL PART II: a prospective, single-armed trial of L-carnitine and valproic acid in ambulatory children with spinal muscular atrophy.

    Directory of Open Access Journals (Sweden)

    John T Kissel

    Full Text Available BACKGROUND: Multiple lines of evidence have suggested that valproic acid (VPA might benefit patients with spinal muscular atrophy (SMA. The SMA CARNIVAL TRIAL was a two part prospective trial to evaluate oral VPA and L-carnitine in SMA children. Part 1 targeted non-ambulatory children ages 2-8 in a 12 month cross over design. We report here Part 2, a twelve month prospective, open-label trial of VPA and L-carnitine in ambulatory SMA children. METHODS: This study involved 33 genetically proven type 3 SMA subjects ages 3-17 years. Subjects underwent two baseline assessments over 4-6 weeks and then were placed on VPA and L-carnitine for 12 months. Assessments were performed at baseline, 3, 6 and 12 months. Primary outcomes included safety, adverse events and the change at 6 and 12 months in motor function assessed using the Modified Hammersmith Functional Motor Scale Extend (MHFMS-Extend, timed motor tests and fine motor modules. Secondary outcomes included changes in ulnar compound muscle action potential amplitudes (CMAP, handheld dynamometry, pulmonary function, and Pediatric Quality of Life Inventory scores. RESULTS: Twenty-eight subjects completed the study. VPA and carnitine were generally well tolerated. Although adverse events occurred in 85% of subjects, they were usually mild and transient. Weight gain of 20% above body weight occurred in 17% of subjects. There was no significant change in any primary outcome at six or 12 months. Some pulmonary function measures showed improvement at one year as expected with normal growth. CMAP significantly improved suggesting a modest biologic effect not clinically meaningful. CONCLUSIONS: This study, coupled with the CARNIVAL Part 1 study, indicate that VPA is not effective in improving strength or function in SMA children. The outcomes used in this study are feasible and reliable, and can be employed in future trials in SMA. TRIAL REGSITRATION: Clinicaltrials.gov NCT00227266.

  9. Genetic screening of spinal muscular atrophy using a real-time modified COP-PCR technique with dried blood-spot DNA.

    Science.gov (United States)

    Ar Rochmah, Mawaddah; Harahap, Nur Imma Fatimah; Niba, Emma Tabe Eko; Nakanishi, Kenta; Awano, Hiroyuki; Morioka, Ichiro; Iijima, Kazumoto; Saito, Toshio; Saito, Kayoko; Lai, Poh San; Takeshima, Yasuhiro; Takeuchi, Atsuko; Bouike, Yoshihiro; Okamoto, Maya; Nishio, Hisahide; Shinohara, Masakazu

    2017-10-01

    Spinal muscular atrophy (SMA) is a common neuromuscular disorder caused by mutations in SMN1. More than 95% of SMA patients carry homozygous SMN1 deletion. SMA is the leading genetic cause of infant death, and has been considered an incurable disease. However, a recent clinical trial with an antisense oligonucleotide drug has shown encouraging clinical efficacy. Thus, early and accurate detection of SMN1 deletion may improve prognosis of many infantile SMA patients. A total of 88 DNA samples (37 SMA patients, 12 carriers and 39 controls) from dried blood spots (DBS) on filter paper were analyzed. All participants had previously been screened for SMN genes by PCR restriction fragment length polymorphism (PCR-RFLP) using DNA extracted from freshly collected blood. DNA was extracted from DBS that had been stored at room temperature (20-25°C) for 1week to 5years. To ensure sufficient quality and quantity of DNA samples, target sequences were pre-amplified by conventional PCR. Real-time modified competitive oligonucleotide priming-PCR (mCOP-PCR) with the pre-amplified PCR products was performed for the gene-specific amplification of SMN1 and SMN2 exon 7. Compared with PCR-RFLP using DNA from freshly collected blood, results from real-time mCOP-PCR using DBS-DNA for detection of SMN1 exon 7 deletion showed a sensitivity of 1.00 (CI [0.87, 1.00])] and specificity of 1.00 (CI [0.90, 1.00]), respectively. We combined DNA extraction from DBS on filter paper, pre-amplification of target DNA, and real-time mCOP-PCR to specifically detect SMN1 and SMN2 genes, thereby establishing a rapid, accurate, and high-throughput system for detecting SMN1-deletion with practical applications for newborn screening. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  10. The spinal muscular atrophy with pontocerebellar hypoplasia gene VRK1 regulates neuronal migration through an amyloid-β precursor protein-dependent mechanism.

    Science.gov (United States)

    Vinograd-Byk, Hadar; Sapir, Tamar; Cantarero, Lara; Lazo, Pedro A; Zeligson, Sharon; Lev, Dorit; Lerman-Sagie, Tally; Renbaum, Paul; Reiner, Orly; Levy-Lahad, Ephrat

    2015-01-21

    Spinal muscular atrophy with pontocerebellar hypoplasia (SMA-PCH) is an infantile SMA variant with additional manifestations, particularly severe microcephaly. We previously identified a nonsense mutation in Vaccinia-related kinase 1 (VRK1), R358X, as a cause of SMA-PCH. VRK1-R358X is a rare founder mutation in Ashkenazi Jews, and additional mutations in patients of different origins have recently been identified. VRK1 is a nuclear serine/threonine protein kinase known to play multiple roles in cellular proliferation, cell cycle regulation, and carcinogenesis. However, VRK1 was not known to have neuronal functions before its identification as a gene mutated in SMA-PCH. Here we show that VRK1-R358X homozygosity results in lack of VRK1 protein, and demonstrate a role for VRK1 in neuronal migration and neuronal stem cell proliferation. Using shRNA in utero electroporation in mice, we show that Vrk1 knockdown significantly impairs cortical neuronal migration, and affects the cell cycle of neuronal progenitors. Expression of wild-type human VRK1 rescues both proliferation and migration phenotypes. However, kinase-dead human VRK1 rescues only the migration impairment, suggesting the role of VRK1 in neuronal migration is partly noncatalytic. Furthermore, we found that VRK1 deficiency in human and mouse leads to downregulation of amyloid-β precursor protein (APP), a known neuronal migration gene. APP overexpression rescues the phenotype caused by Vrk1 knockdown, suggesting that VRK1 affects neuronal migration through an APP-dependent mechanism. Copyright © 2015 the authors 0270-6474/15/350936-08$15.00/0.

  11. Spinal muscular atrophy type I and the dual role of viruses: An interview with Professor Basil T. Darras, Professor of Neurology (Pediatrics) at Harvard Medical School.

    Science.gov (United States)

    Mammas, Ioannis N; Spandidos, Demetrios A

    2018-04-01

    According to Professor Basil T. Darras, Professor of Neurology (Pediatrics) at Harvard Medical School and Director of the Spinal Muscular Atrophy (SMA) Program at Boston Children's Hospital in Boston (MA, USA), the diagnosis of SMA type I is clinical and is based on detailed general physical and neurological examinations. SMA type I remains the most common genetic disease resulting in death in infancy and is really devastating for the child, the parents, as well as the medical professionals with the privilege of caring for patients with SMA and their parents. The proposed management options include: i) no respiratory support; ii) non-invasive ventilation; and iii) tracheotomy with mechanical ventilation. Deciding, which option is the best, is indeed a very personal decision. The optimal clinical care should be extremely mindful of parents' wishes and management goals with regard to the quality of life. Since the end of 2016 in the USA, and recently in Europe, there exists the possibility of accessing a novel treatment drug for SMA, namely Nusinersen. This antisense oligonucleotide is administered intrathecally and increases the production of the fully functional SMN protein, thus improving motor function, the quality of life and survival. Among the ongoing clinical trials, oral treatment with RG7916, a small molecule SMN2 splicing modifier, appears to be really promising. Gene therapy using viral vectors is expected to offer an 'one and done' therapy and possibly a cure, if administered early in life, before any symptoms appear. It is really interesting that viruses, which at the moment are the cause of death of children with SMA, if genetically modified, may be used for their treatment.

  12. Cross‐disease comparison of amyotrophic lateral sclerosis and spinal muscular atrophy reveals conservation of selective vulnerability but differential neuromuscular junction pathology

    Science.gov (United States)

    Nijssen, Jik; Frost‐Nylen, Johanna

    2015-01-01

    Neuromuscular junctions are primary pathological targets in the lethal motor neuron diseases spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). Synaptic pathology and denervation of target muscle fibers has been reported prior to the appearance of clinical symptoms in mouse models of both diseases, suggesting that neuromuscular junctions are highly vulnerable from the very early stages, and are a key target for therapeutic intervention. Here we examined neuromuscular pathology longitudinally in three clinically relevant muscle groups in mouse models of ALS and SMA in order to assess their relative vulnerabilities. We show for the first time that neuromuscular junctions of the extraocular muscles (responsible for the control of eye movement) were resistant to degeneration in endstage SMA mice, as well as in late symptomatic ALS mice. Tongue muscle neuromuscular junctions were also spared in both animal models. Conversely, neuromuscular junctions of the lumbrical muscles of the hind‐paw were vulnerable in both SMA and ALS, with a loss of neuronal innervation and shrinkage of motor endplates in both diseases. Thus, the pattern of selective vulnerability was conserved across these two models of motor neuron disease. However, the first evidence of neuromuscular pathology occurred at different timepoints of disease progression, with much earlier evidence of presynaptic involvement in ALS, progressing to changes on the postsynaptic side. Conversely, in SMA changes appeared concomitantly at the neuromuscular junction, suggesting that mechanisms of neuromuscular disruption are distinct in these diseases. J. Comp. Neurol. 524:1424–1442, 2016. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:26502195

  13. Optimizing Bone Health in Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Jason L. Buckner

    2015-01-01

    Full Text Available Duchenne muscular dystrophy (DMD is an X-linked recessive disorder characterized by progressive muscle weakness, with eventual loss of ambulation and premature death. The approved therapy with corticosteroids improves muscle strength, prolongs ambulation, and maintains pulmonary function. However, the osteoporotic impact of chronic corticosteroid use further impairs the underlying reduced bone mass seen in DMD, leading to increased fragility fractures of long bones and vertebrae. These serious sequelae adversely affect quality of life and can impact survival. The current clinical issues relating to bone health and bone health screening methods in DMD are presented in this review. Diagnostic studies, including biochemical markers of bone turnover and bone mineral density by dual energy X-ray absorptiometry (DXA, as well as spinal imaging using densitometric lateral spinal imaging, and treatment to optimize bone health in patients with DMD are discussed. Treatment with bisphosphonates offers a method to increase bone mass in these children; oral and intravenous bisphosphonates have been used successfully although treatment is typically reserved for children with fractures and/or bone pain with low bone mass by DXA.

  14. SMA CARNI-VAL trial part I: double-blind, randomized, placebo-controlled trial of L-carnitine and valproic acid in spinal muscular atrophy.

    Directory of Open Access Journals (Sweden)

    Kathryn J Swoboda

    2010-08-01

    Full Text Available Valproic acid (VPA has demonstrated potential as a therapeutic candidate for spinal muscular atrophy (SMA in vitro and in vivo.Two cohorts of subjects were enrolled in the SMA CARNIVAL TRIAL, a non-ambulatory group of "sitters" (cohort 1 and an ambulatory group of "walkers" (cohort 2. Here, we present results for cohort 1: a multicenter phase II randomized double-blind intention-to-treat protocol in non-ambulatory SMA subjects 2-8 years of age. Sixty-one subjects were randomized 1:1 to placebo or treatment for the first six months; all received active treatment the subsequent six months. The primary outcome was change in the modified Hammersmith Functional Motor Scale (MHFMS score following six months of treatment. Secondary outcomes included safety and adverse event data, and change in MHFMS score for twelve versus six months of active treatment, body composition, quantitative SMN mRNA levels, maximum ulnar CMAP amplitudes, myometry and PFT measures.At 6 months, there was no difference in change from the baseline MHFMS score between treatment and placebo groups (difference = 0.643, 95% CI = -1.22-2.51. Adverse events occurred in >80% of subjects and were more common in the treatment group. Excessive weight gain was the most frequent drug-related adverse event, and increased fat mass was negatively related to change in MHFMS values (p = 0.0409. Post-hoc analysis found that children ages two to three years that received 12 months treatment, when adjusted for baseline weight, had significantly improved MHFMS scores (p = 0.03 compared to those who received placebo the first six months. A linear regression analysis limited to the influence of age demonstrates young age as a significant factor in improved MHFMS scores (p = 0.007.This study demonstrated no benefit from six months treatment with VPA and L-carnitine in a young non-ambulatory cohort of subjects with SMA. Weight gain, age and treatment duration were significant confounding variables that

  15. Epidemiological survey of X-linked bulbar and spinal muscular atrophy, or Kennedy disease, in the province of Reggio Emilia, Italy.

    Science.gov (United States)

    Guidetti, D; Sabadini, R; Ferlini, A; Torrente, I

    2001-01-01

    Commencing with the work carried out during the epidemiological survey of amyotrophic lateral sclerosis in the period 1980-1992 and the pathology follow-up, we carried out a perspective incidence, prevalence and mortality survey of X-linked bulbar and spinal muscular atrophy (X-BSMA) in the province of Reggio Emilia in Northern Italy. Based on 11 patients (eight familial and three sporadic cases), the mean incidence per year for the period 1980 through 1997, as evaluated at the onset of symptoms, was 0.09 cases/100,000 for the total population and 0.19 cases/100,000 for the male population. On December 31, 1997, the prevalence rate was 1.6/100,000 for the total population and 3.3/100,000 for the male population. In the 18-year period of 1980-1997, the average yearly mortality rate was: 0.03 cases/100,000 per year for the total population and 0.06 cases/ 100,000 for the male population. The average age at onset was 44.8 +/- 10.1, and the average survival period was 27.3 +/- 2.3 years. The average age of the prevalence day was 58.9 +/- 14.9, and the average age at death was 71.3 +/- 4.7 years. Whereas the incidence rate of X-BSMA in the province of Reggio Emilia is 16 times lower that of amyotrophic lateral sclerosis (ALS), the incidence rate of progressive bulbar palsy in the male population is only slightly higher than X-BSMA; and the prevalence rate of ALS for males is two times the prevalence rate for X-BSMA, with overlapping of confidence intervals. X-BSMA is a rare disease, which is probably under-diagnosed, but due to the long survival period of this disease its frequency is not negligible. Because of the presence of sporadic cases or non-evident familial cases, it is appropriate to consider this diagnostic possibility in making a diagnosis of ALS in patients in whom lower motor neuron dysfunction or bulbar onset predominates.

  16. Cardiac involvement in patients with limb-girdle muscular dystrophy type 2 and Becker muscular dystrophy

    DEFF Research Database (Denmark)

    Sveen, Marie-Louise; Thune, Jens Jakob; Køber, Lars

    2008-01-01

    OBJECTIVE: To investigate the extent of cardiac involvement in patients with 1 of the 12 groups of recessively inherited limb-girdle muscular dystrophy type 2 (LGMD2A-L) and Becker muscular dystrophy (BMD). DESIGN: Prospective screening. SETTING: Neuromuscular Clinic and Department of Cardiology...

  17. Learning about Spinal Muscular Atrophy

    Science.gov (United States)

    ... Care Genomic Medicine Working Group New Horizons and Research Patient Management Policy and Ethics Issues Quick Links for Patient Care Education All About the Human Genome Project Fact Sheets Genetic Education Resources for ...

  18. Muscular Dystrophy

    Science.gov (United States)

    ... sets of muscles and cause different degrees of muscle weakness. Duchenne muscular dystrophy is the most common and the most severe ... can walk independently. Prednisone If a child has Duchenne muscular ... to help slow the rate of muscle deterioration. By doing so, the child may be ...

  19. Spinal muscular atrophy type II (intermediary and III (Kugelberg-Welander: evolution of 50 patients with physiotherapy and hydrotherapy in a swimming pool Atrofia muscular espinhal tipo II (intermediária e III (Kugelberg-Welander: evolução de 50 pacientes com fisioterapia e hidroterapia em piscina

    Directory of Open Access Journals (Sweden)

    Márcia C. B. Cunha

    1996-09-01

    Full Text Available We added hydrotherapy to 50 patients with spinal muscular atrophy (SMA who were being treated with individual conventional physiotherapy. Hydrotherapy was performed at an approximate temperature of 30 degrees Celsius, twice a week, for thirty minutes in children and for forty-five minutes in adults during a 2-year period. The outcome derived from this combined modality of treatment was rated according to physiotherapeutic evaluations, the MMT (Manual Muscular Test, and the Barthel Ladder. Patients were reevaluated at 2-month intervals. After two years of ongoing treatment, we were able to observe that the deformities in hip, knee and foot were progressive in all SMA Type II patients, and in some Type III. Muscle strength stabilized in most SMA Type III patients, and improved in some. MMT was not done in SMA Type II. In all patients we were able to detect an improvement in the Barthel Ladder scale. This study suggests that a measurable improvement in the quality of daily living may be obtained in patients with SMA Types II and III subjected to conventional physiotherapy when associated with hydrotherapy.A hidroterapia foi realizada em SO pacientes com atrofia muscular espinhal, os quais foram também tratados com fisioterapia individual convencional. O tratamento hidroterápico foi realizado em piscina aquecida numa temperatura de aproximadamente 30° Celsius, duas vezes por semana, durante 30 minutos em crianças e 45 minutos em adultos num período de dois anos. Os benefícios deste tipo de tratamento foram avaliados de acordo com a evolução clínica, o MMT(Teste de Força Muscular e a Escala de Barthel. Os pacientes foram reavaliados a cada dois meses. Após dois anos de tratamento nós observamos que as deformidades nos quadris, joelhos e pés foram progressivas em todos os pacientes do Tipo II e em alguns do Tipo III. Houve estabilização da força muscular na maioria dos pacientes com SMA Tipo III, e melhora da força em alguns; nos

  20. Seamless Genetic Conversion of SMN2 to SMN1 via CRISPR/Cpf1 and Single-Stranded Oligodeoxynucleotides in Spinal Muscular Atrophy Patient-Specific Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Zhou, Miaojin; Hu, Zhiqing; Qiu, Liyan; Zhou, Tao; Feng, Mai; Hu, Qian; Zeng, Baitao; Li, Zhuo; Sun, Qianru; Wu, Yong; Liu, Xionghao; Wu, Lingqian; Liang, Desheng

    2018-05-09

    Spinal muscular atrophy (SMA) is a kind of neuromuscular disease characterized by progressive motor neuron loss in the spinal cord. It is caused by mutations in the survival motor neuron 1 (SMN1) gene. SMN1 has a paralogous gene, survival motor neuron 2 (SMN2), in humans that is present in almost all SMA patients. The generation and genetic correction of SMA patient-specific induced pluripotent stem cells (iPSCs) is a viable, autologous therapeutic strategy for the disease. Here, c-Myc-free and non-integrating iPSCs were generated from the urine cells of an SMA patient using an episomal iPSC reprogramming vector, and a unique crRNA was designed that does not have similar sequences (≤3 mismatches) anywhere in the human reference genome. In situ gene conversion of the SMN2 gene to an SMN1-like gene in SMA-iPSCs was achieved using CRISPR/Cpf1 and single-stranded oligodeoxynucleotide with a high efficiency of 4/36. Seamlessly gene-converted iPSC lines contained no exogenous sequences and retained a normal karyotype. Significantly, the SMN expression and gems localization were rescued in the gene-converted iPSCs and their derived motor neurons. This is the first report of an efficient gene conversion mediated by Cpf1 homology-directed repair in human cells and may provide a universal gene therapeutic approach for most SMA patients.

  1. Muscular Dystrophy

    Science.gov (United States)

    ... Surveillance Tracking and Research Network , known as MD STAR net . Learn more about CDC’s other muscular dystrophy ... for Disease Control and Prevention Email Recommend Tweet YouTube Instagram Listen Watch RSS ABOUT About CDC Jobs ...

  2. Muscular dystrophy

    Science.gov (United States)

    ... are no known cures for the various muscular dystrophies. The goal of treatment is to control symptoms. Physical therapy may help maintain muscle strength and function. Leg braces and a wheelchair ...

  3. Avaliação dos resultados do tratamento cirúrgico da escoliose na atrofia muscular espinhal tipo 2 Evaluación de los resultados del tratamiento quirúrgico de la escoliosis en la atrofia muscular espinal tipo 2 Results evaluation of surgical treatment of scoliosis in spinal muscular atrophy type 2

    Directory of Open Access Journals (Sweden)

    Luiz Eduardo Munhoz da Rocha

    2011-01-01

    evaluaron el grado y el porcentaje de corrección de la deformidad y la oblicuidad pélvica después de la operación y la pérdida, además de las complicaciones y el impacto del tratamiento sobre la función respiratoria. RESULTADOS: El promedio de seguimiento fue 77,5 meses (6,4 años ± 58,9 meses (4,9 años, el ángulo de Cobb antes de la cirugía en promedio 76,1° ± 31,7° (35° a 144° y el postoperatorio fue 29,5° ± 23,2° (5° a 90°, con un promedio de corrección de 46,6° (61,29%. La oblicuidad pélvica promedio en el preoperatorio fue 15,1 ° ± 13,3° (variación de 0 ° a 37 ° y después de la operación 8,5° ± 9,9° (variación de 0° a 30°, con una corrección promedio de 6,5 ° (43,37%. Cinco pacientes presentaron complicaciones (41,6%. La Capacidad Ventilatoria Forzada (CVF preoperatoria promedio fue 62,9% ± 38,6% (variación de 23,3% a 89%, y 45,9% ± 25,0% (variación de 15% a 86,2% en la última evaluación. La disminución fue de 17% de la capacidad vital, con una reducción de 2,4% por año de seguimiento. CONCLUSIONES: El tratamiento quirúrgico de la escoliosis, en pacientes con AME, permite la corrección de la oblicuidad pélvica y restaurar el equilibrio sagital y coronal, liberando las manos para las actividades de la vida diaria. La función pulmonar se vio afectada positivamente por el tratamiento.OBJECTIVE: To evaluate the outcome of surgical treatment of scoliosis in patients with spinal muscular atrophy (SMA type 2. METHODS: A retrospective study with 12 patients with SMA type 2 who underwent arthrodesis and instrumentation for scoliosis correction with more than two years of follow-up. The degree and rate of correction of deformity and pelvic obliquity postoperatively and loss in the last evaluation were evaluated, in addition to the complications and the impact of treatment on respiratory function. RESULTS: Mean follow-up was 77.5 months (6.4 years ± 58.9 months (4.9 years, Cobb angle before surgery averaged 76.1° ± 31.7

  4. Cardiomyopathy in becker muscular dystrophy: Overview.

    Science.gov (United States)

    Ho, Rady; Nguyen, My-Le; Mather, Paul

    2016-06-26

    Becker muscular dystrophy (BMD) is an X-linked recessive disorder involving mutations of the dystrophin gene. Cardiac involvement in BMD has been described and cardiomyopathy represents the number one cause of death in these patients. In this paper, the pathophysiology, clinical evaluations and management of cardiomyopathy in patients with BMD will be discussed.

  5. Spinal stenosis

    International Nuclear Information System (INIS)

    Beale, S.; Pathria, M.N.; Ross, J.S.; Masaryk, T.J.; Modic, M.T.

    1988-01-01

    The authors studied 50 patients who had spinal stenosis by means of MR imaging. All patients had undergone myelography and CT. Thirty patients underwent surgery. MR imaging included T1-weighted spin echo sequences with repetition time = 600 msec, echo time = 20 (600/20) sagittal and axial sections 4 mm thick with 2 mm gap. T2-weighted 2,000/60 axial images were obtained on 14 patients. Examinations were retrospectively evaluated for central stenosis, lateral recess narrowing, and foraminal encroachment. Measurements of sagittal, interpedicular, interfacet, and recess dimensions were made at L3-5. On MR images, 20 patients had single-level and 30 had multiple-level stenosis. There was excellent agreement between modalities with central canal stenosis, but a discrepancy in six patients with bony foraminal stenosis. MR imaging was an accurate method for assessment of lumbar stenosis, but CT appears marginally better for detection of bony foraminal stenosis in certain cases

  6. Identification of a gene expression core signature for Duchenne Muscular Dystrophy (DMD) via integrative analysis reveals novel potential compounds for treatment

    KAUST Repository

    Ichim-Moreno, Norú ; Aranda, Manuel; Voolstra, Christian R.

    2010-01-01

    Duchenne muscular dystrophy (DMD) is a recessive X-linked form of muscular dystrophy and one of the most prevalent genetic disorders of childhood. DMD is characterized by rapid progression of muscle degeneration, and ultimately death. Currently

  7. Forecasting US Recessions

    DEFF Research Database (Denmark)

    Christiansen, Charlotte; Eriksen, Jonas Nygaard; Møller, Stig Vinther

    2014-01-01

    We study the role of sentiment variables as predictors for US recessions. We combine sentiment variables with either classical recession predictors or common factors based on a large panel of macroeconomic and financial variables. Sentiment variables hold vast predictive power for US recessions...

  8. Muscles in a mouse model of spinal muscular atrophy show profound defects in neuromuscular development even in the absence of failure in neuromuscular transmission or loss of motor neurons.

    Science.gov (United States)

    Lee, Young Il; Mikesh, Michelle; Smith, Ian; Rimer, Mendell; Thompson, Wesley

    2011-08-15

    A mouse model of the devastating human disease "spinal muscular atrophy" (SMA) was used to investigate the severe muscle weakness and spasticity that precede the death of these animals near the end of the 2nd postnatal week. Counts of motor units to the soleus muscle as well as of axons in the soleus muscle nerve showed no loss of motor neurons. Similarly, neither immunostaining of neuromuscular junctions nor the measurement of the tension generated by nerve stimulation gave evidence of any significant impairment in neuromuscular transmission, even when animals were maintained up to 5days longer via a supplementary diet. However, the muscles were clearly weaker, generating less than half their normal tension. Weakness in 3 muscles examined in the study appears due to a severe but uniform reduction in muscle fiber size. The size reduction results from a failure of muscle fibers to grow during early postnatal development and, in soleus, to a reduction in number of fibers generated. Neuromuscular development is severely delayed in these mutant animals: expression of myosin heavy chain isoforms, the elimination of polyneuronal innervation, the maturation in the shape of the AChR plaque, the arrival of SCs at the junctions and their coverage of the nerve terminal, the development of junctional folds. Thus, if SMA in this particular mouse is a disease of motor neurons, it can act in a manner that does not result in their death or disconnection from their targets but nonetheless alters many aspects of neuromuscular development. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. CABLES MUSCULARES

    Directory of Open Access Journals (Sweden)

    Alejandro Gómez

    Full Text Available Los cables musculares o fibras de nitinol presentan una excelente alternativa a los actuadores convencionales, con una fuerza de actuación muy alta, equivalente a la de los actuadores hidráulicos, proporcionalmente a su peso, además de su acción silenciosa. Este material, inventado en 1963, aún no es muy conocido y de ahí que se haya realizado una recopilación de sus propiedades. Entre ellas, la temperatura de transición es la más importante, por ser la que activa la aleación. Muchos sistemas se han creado para alcanzar adecuadamente la temperatura de transición, y también se continúa en la investigación de métodos que ayuden a lograr un control preciso del movimiento de la aleación con memoria de forma (SMA.

  10. X-linked spinal and bulbar muscular atrophy (Kennedy's disease with long-term electrophysiological evaluation: case report Atrofia muscular bulbo-espinal ligada ao cromossomo X (doença de Kennedy com seguimento eletrofisiológico de longo prazo: relato de caso

    Directory of Open Access Journals (Sweden)

    João Aris Kouyoumdjian

    2005-03-01

    Full Text Available X-linked spinal and bulbar muscular atrophy or Kennedy's disease is an adult-onset motor neuronopathy caused by a CAG repeat expansion within the first exon of an androgen receptor gene. We report the case of a 66-year-old man, previously diagnosed with motor neuron disease (MND, who presented acute and reversible left vocal fold (dysphonia and pharyngeal paresis, followed by a slowly progressive weakness and also bouts of weakness, wasting and fasciculation on tongue, masseter, face, pharyngeal, and some proximal more than distal upper limb muscles, associated to bilateral hand tremor and mild gynecomastia. There were 5 electroneuromyography exams between 1989 and 2003 that revealed chronic reinnervation, some fasciculations (less than clinically observed and rare fibrillation potentials, and slowly progressive sensory nerve action potentials (SNAP abnormality, leading to absent/low amplitude potentials. PCR techniques of DNA analysis showed an abnormal number of CAG repeats, found to be 44 (normal 11-34. Our case revealed an acute and asymmetric clinical presentation related to bulbar motoneurons; low amplitude/absent SNAP with mild asymmetry; a sub-clinical or subtle involvement of proximal/distal muscles of both upper and lower limbs; and a probable evolution with bouts of acute dennervation, followed by an efficient reinnervation.Atrofia muscular bulbo-espinal ligada ao cromossomo X (doença de Kennedy é uma neuronopatia motora em adultos causada por expansões na repetição CAG no gene do receptor andrógeno. Neste relato, descreve-se o caso de homem de 66 anos, com diagnóstico prévio de doença do neurônio motor (DNM que apresentou quadro agudo e reversível de paresia de prega vocal (disfonia e de músculos faríngeos à esquerda; posteriormente seguiram-se surtos de fraqueza lentamente progressiva, atrofia e fasciculações em língua, masseter, face, faringe e membros superiores predominantemente proximal, associada a tremor

  11. FUNCTIONAL PATHOLOGY OF LUMBAR SPINAL STENOSIS

    NARCIS (Netherlands)

    PENNING, L

    This paper deals with the effect of motion upon the stenotic lumbar spinal canal and its contents. A review is presented of personal investigations and relevant data from the literature. The normal spinal canal and its lateral recesses are naturally narrowed by retroflexion and/or axial loading, as

  12. The Recession Squeezes Training.

    Science.gov (United States)

    Geber, Beverly

    1991-01-01

    Recession is having an impact on training departments. Besides a slowdown, it provides managers with a chance to reevaluate programs to ensure they are attuned to the specific goals of the company. (JOW)

  13. Distrofia muscular progressiva: alguns aspectos do diagnõstico diferencial

    Directory of Open Access Journals (Sweden)

    Sylvio Saraiva

    1960-09-01

    Full Text Available The authors call attention to some clinical entities which are less known and more difficult to recognize and with which differential diagnosis of progressive muscular dystrophy should be made (infantile spinal muscular atrophy, amyotonia congenita, congenital acute anterior poliomyelitis, anthro-griposis multiplex, von Gierke's disease, central core disease, chronical polymyositis and dermatomyositis, thyrotoxic myopathy and menopausal dys- trophy. The importance of muscle biopsy in the differential diagnosis is emphasized.

  14. Para-muscular and trans-muscular approaches to the lumbar inter-vertebral foramen: an anatomical comparison.

    Science.gov (United States)

    Poetscher, Arthur Werner; Ribas, Guilherme Carvalhal; Yasuda, Alexandre; Nishikuni, Koshiro

    2005-03-01

    Foraminal and extra-foraminal disc herniations comprise up to 11.7% of all lumbar disc herniations. Facetectomy, which had been the classic approach, is now recognized as cause of pain and instability after surgery. Otherwise, posterior lateral approaches through a trans-muscular or a para-muscular technique offer no significant damage to key structures for spinal stability. The surgical anatomy of these approaches has already been described, but they were not compared. In order to quantify the angle of vision towards the intervertebral foramen offered by each technique, 12 fresh cadavers were dissected and studied regarding these approaches. The angle presented by trans-muscular approach was wider in all studied lumbar levels. Surgery through the trans-muscular approach is performed with a better working angle, requiring a smaller resection of surrounding tissues. Therefore, minor surgical trauma can be expected. Our measurements support previously published data that point the trans-muscular approach as the best surgical option.

  15. Gingival Recessions and Biomechanics

    DEFF Research Database (Denmark)

    Laursen, Morten Godtfredsen

    Gingival recessions and biomechanics “Tissue is the issue, but bone sets the tone.“ A tooth outside the cortical plate can result in loss of bone and development of a gingival recession. The presentation aims to show biomechanical considerations in relation to movement of teeth with gingival...... by moving the root back in the alveolus. The tooth movement is accompanied by bone gain and thus increase the success rate for soft tissue augmentation. The choice of biomechanical system influences the treatment outcome. If a standard straight wire appliance is used, a biomechanical dilemma can arise...

  16. Spinal pain

    International Nuclear Information System (INIS)

    Izzo, R.; Popolizio, T.; D’Aprile, P.; Muto, M.

    2015-01-01

    Highlights: • Purpose of this review is to address the current concepts on the pathophysiology of discogenic, radicular, facet and dysfunctional spinal pain, focusing on the role of the imaging in the diagnostic setting, to potentially address a correct approach also to minimally invasive interventional techniques. • Special attention will be given to the discogenic pain, actually considered as the most frequent cause of chronic low back pain. • The correct distinction between referred pain and radicular pain contributes to give a more correct approach to spinal pain. • The pathogenesis of chronic pain renders this pain a true pathology requiring a specific management. - Abstract: The spinal pain, and expecially the low back pain (LBP), represents the second cause for a medical consultation in primary care setting and a leading cause of disability worldwide [1]. LBP is more often idiopathic. It has as most frequent cause the internal disc disruption (IDD) and is referred to as discogenic pain. IDD refers to annular fissures, disc collapse and mechanical failure, with no significant modification of external disc shape, with or without endplates changes. IDD is described as a separate clinical entity in respect to disc herniation, segmental instability and degenerative disc desease (DDD). The radicular pain has as most frequent causes a disc herniation and a canal stenosis. Both discogenic and radicular pain also have either a mechanical and an inflammatory genesis. For to be richly innervated, facet joints can be a direct source of pain, while for their degenerative changes cause compression of nerve roots in lateral recesses and in the neural foramina. Degenerative instability is a common and often misdiagnosed cause of axial and radicular pain, being also a frequent indication for surgery. Acute pain tends to extinguish along with its cause, but the setting of complex processes of peripheral and central sensitization may influence its evolution in chronic

  17. Spinal pain

    Energy Technology Data Exchange (ETDEWEB)

    Izzo, R., E-mail: roberto1766@interfree.it [Neuroradiology Department, A. Cardarelli Hospital, Naples (Italy); Popolizio, T., E-mail: t.popolizio1@gmail.com [Radiology Department, Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo (Fg) (Italy); D’Aprile, P., E-mail: paoladaprile@yahoo.it [Neuroradiology Department, San Paolo Hospital, Bari (Italy); Muto, M., E-mail: mutomar@tiscali.it [Neuroradiology Department, A. Cardarelli Hospital, Napoli (Italy)

    2015-05-15

    Highlights: • Purpose of this review is to address the current concepts on the pathophysiology of discogenic, radicular, facet and dysfunctional spinal pain, focusing on the role of the imaging in the diagnostic setting, to potentially address a correct approach also to minimally invasive interventional techniques. • Special attention will be given to the discogenic pain, actually considered as the most frequent cause of chronic low back pain. • The correct distinction between referred pain and radicular pain contributes to give a more correct approach to spinal pain. • The pathogenesis of chronic pain renders this pain a true pathology requiring a specific management. - Abstract: The spinal pain, and expecially the low back pain (LBP), represents the second cause for a medical consultation in primary care setting and a leading cause of disability worldwide [1]. LBP is more often idiopathic. It has as most frequent cause the internal disc disruption (IDD) and is referred to as discogenic pain. IDD refers to annular fissures, disc collapse and mechanical failure, with no significant modification of external disc shape, with or without endplates changes. IDD is described as a separate clinical entity in respect to disc herniation, segmental instability and degenerative disc desease (DDD). The radicular pain has as most frequent causes a disc herniation and a canal stenosis. Both discogenic and radicular pain also have either a mechanical and an inflammatory genesis. For to be richly innervated, facet joints can be a direct source of pain, while for their degenerative changes cause compression of nerve roots in lateral recesses and in the neural foramina. Degenerative instability is a common and often misdiagnosed cause of axial and radicular pain, being also a frequent indication for surgery. Acute pain tends to extinguish along with its cause, but the setting of complex processes of peripheral and central sensitization may influence its evolution in chronic

  18. Estudio clínico, genético y molecular en un paciente con atrofia muscular espinal

    Directory of Open Access Journals (Sweden)

    Ibis Menéndez Alejo

    1998-03-01

    Full Text Available Las atrofias musculares espinales (AME infantiles son enfermedades neuromusculares hereditarias caracterizadas por la degeneración de las motoneuronas alfa del asta anterior de la médula espinal. La enfermedad de Werdnig-Hoffmann, AME tipo I, es la forma más grave, se transmite como un carácter autosómico recesivo y los afectados suelen fallecer durante el primer año de vida por fallo respiratorio. En este trabajo se presenta una familia cubana con 2 hijos con AME tipo I, en la cual el estudio molecular en uno de ellos permitió identificar los 2 cromosomas parentales asociados con ésta. Se encontró además en el paciente una deleción de ambas copias del gen SMN (exón 8 y del gen NAIP (exón 5. Los hallazgos ilustran la utilidad de estos estudios, con vistas a posibilitar el diagnóstico prenatal de la enfermedad.The infantile spinal muscular atrophies (SMA are hereditary neuromuscular diseases characterized by degenerated Alfa-motoneurons of the anterior spinal marrow horn. Werdning-Hoffman disease, Type 1 SMA, is the most serious affection being transmitted as an autosomal recessive character, so those affected may die from respiratory failures in the first year of life. This paper presents a Cuban family with two kids who suffer from Type-1 SMA; the molecular analysis carried out in one of them identified two parental chromosomes responsible for the disease. Also, a deletion of both copies of SMN gene (exon 8 and NAIP gene (exon 5 were discovered in this patient. These findings showed the usefulness of this kind of studies with a view to making a prenatal diagnosis of Werdning-Hoffman disease.

  19. Muscle-Eye-Brain Disease; a Rare Form of Syndromic Congenital Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Gosal Gurinder S

    2011-03-01

    Full Text Available Congenital muscular dystrophy (CMD is a heterogeneous group of disorders characterized by muscular hypotonia since birth and the histologic features of muscular dystrophy. Syndromic congenital muscular dystrophies are clinically similar autosomal recessive disorders characterized by congenital muscular dystrophy, lissencephaly, and eye anomalies. We present a case of a rare form of syndromic congenital muscular dystrophy in an eight year old girl, born of first- degree consanguinity. She had: global developmental delay; a seizure disorder; hypotonia; progressive muscle contractures including bilateral symmetrical flexion contractures of hips, knees, equinus contracture and thoracolumbar scoliosis; diminished deep tendon reflexes: bilateral premature cataract; pseudophakia; and nystagmus. The patient was also highly myopic. Based on clinical features, muscle biopsy and MRI of the brain, a diagnosis of muscle- eye- brain disease was made. Identification of these patients may help to prevent this crippling disorder in the future siblings of probands by utilizing genetic counselling and mutation analysis.

  20. Co-incidence of Turner syndrome and Duchenne muscular dystrophy - an important problem for the clinician.

    Science.gov (United States)

    Kaczorowska, Ewa; Zimowski, Janusz; Cichoń-Kotek, Monika; Mrozińska, Agnieszka; Purzycka, Joanna; Wierzba, Jolanta; Limon, Janusz; Lipska-Ziętkiewicz, Beata S

    Turner syndrome is a relatively common chromosomal disorder which affects about one in 2000 live born females. Duchenne muscular dystrophy is an X-linked recessive disorder affecting 1:3600 live born males. Considering the above, the coexistence of these two diseases may occur only anecdotally. Here, we report a 4 ½ year-old female with classical 45,X Turner syndrome who also had Duchenne muscular dystrophy caused by a point mutation in the dystrophin gene (c.9055delG). The patient showed the typical phenotype of Turner syndrome including distinctive dysmorphic features (short neck, low posterior hairline, wide position of nipples), aortic coarctation and feet lymphedema. Besides, she presented with an unusually early beginning of muscular dystrophy symptoms with infantile-onset motor developmental delay, intellectual disability and early calf muscular hypertrophy. The coexistence of an X-linked recessive disorder should be considered in women affected by Turner syndrome presenting with additional atypical clinical features.

  1. Barriers for recess physical activity

    DEFF Research Database (Denmark)

    Pawlowski, Charlotte Skau; Tjørnhøj-Thomsen, Tine; Schipperijn, Jasper

    2014-01-01

    BACKGROUND: Many children, in particular girls, do not reach the recommended amount of daily physical activity. School recess provides an opportunity for both boys and girls to be physically active, but barriers to recess physical activity are not well understood. This study explores gender...... differences in children's perceptions of barriers to recess physical activity. Based on the socio-ecological model four types of environmental barriers were distinguished: natural, social, physical and organizational environment. METHODS: Data were collected through 17 focus groups (at 17 different schools...... this study, we recommend promoting recess physical activity through a combination of actions, addressing barriers within the natural, social, physical and organizational environment....

  2. Influência da adequação postural em cadeira de rodas na função respiratória de pacientes com amiotrofia espinhal tipo II Influence of wheelchair positioning aids on the respiratory function of patients with type II spinal muscular atrophy

    Directory of Open Access Journals (Sweden)

    Luanda André Collange

    2009-09-01

    Full Text Available Este estudo visou determinar a influência da adequação postural em cadeira de rodas na função respiratória de pacientes com amiotrofia espinhal tipo II (AME. Doze pacientes (idades entre 7 e 24 anos com diagnóstico de AME II, confirmado por achados clínicos e análise genética, participaram do estudo. Os parâmetros respiratórios - volume minuto (VM, volume corrente (VC, capacidade vital forçada (CVF, pressões inspiratória (PImáx e expiratória (PEmáx máximas e pico de fluxo expiratório (PFE - na cadeira de rodas individual, com adaptações, e em uma cadeira de rodas padrão, isto é, sem reclinação ou inclinação. Os resultados mostram valores melhores estatisticamente significativos de todos os parâmetros respiratórios (VM, p=0,002; VC, p=0,003; CVF, p=0,017; PImáx, p=0,002; PEmáx, p=0,006; e PFE, p=0,007 nas medidas tomadas na cadeira adaptada para a postura adequada. Os resultados permitem concluir que a adequação postural em cadeira de rodas influencia positivamente a função respiratória de pacientes com AME tipo II.This study aimed at determining the influence of adequate wheelchair positioning aids on the respiratory function in spinal muscular atrophy (SMA type II patients. Twelve patients (aged 7 to 24 with SMA diagnosed by clinical findings and confirmed by genetic analysis, who owned wheelchairs with positioning aids, underwent spirometric assessment - as to minute volume (MV, tidal volume (TV, forced vital capacity (FVC, maximum inspiratory (IPmax and expiratory (EPmax pressures, and peak expiratory flow (PEF - both on their own wheelchair and on a standard wheelchair with no recline or tilt. Results show significantly better values in all assessed parameters (MV, p=0.002; TV, p=0.003; FVC, p=0.017; IPmax, p=0.002, EPmax, p=0.006; and PEF, p=0.007 of measures taken at the patient's own chair, with positioning aids. These results allow for concluding that wheelchair positioning aids may positively

  3. Muscular Dystrophy (MD)

    Science.gov (United States)

    ... patients may need assisted ventilation to treat respiratory muscle weakness and a pacemaker for cardiac abnormalities. View Full Treatment Information Definition The muscular dystrophies (MD) are a group of more than 30 ...

  4. Facioscapulohumeral muscular dystrophy

    Science.gov (United States)

    ... There is no known cure for facioscapulohumeral muscular dystrophy. Treatments are given to control symptoms and improve quality of life. Activity is encouraged. Inactivity such as bedrest can make the muscle disease worse. Physical therapy may help maintain muscle ...

  5. Congenital contractural arachnodactyly with neurogenic muscular atrophy: case report

    Directory of Open Access Journals (Sweden)

    Scola Rosana Herminia

    2001-01-01

    Full Text Available We report the case of a 3-1/2-year-old girl with hypotonia, multiple joint contractures, hip luxation, arachnodactyly, adducted thumbs, dolichostenomelia, and abnormal external ears suggesting the diagnosis of congenital contractural arachnodactyly (CCA. The serum muscle enzimes were normal and the needle electromyography showed active and chronic denervation. The muscle biopsy demonstrated active and chronic denervation compatible with spinal muscular atrophy. Analysis of exons 7 and 8 of survival motor neuron gene through polymerase chain reaction did not show deletions. Neurogenic muscular atrophy is a new abnormality associated with CCA, suggesting that CCA is clinically heterogeneous.

  6. Rhabdomyolysis featuring muscular dystrophies.

    Science.gov (United States)

    Lahoria, Rajat; Milone, Margherita

    2016-02-15

    Rhabdomyolysis is a potentially life threatening condition of various etiology. The association between rhabdomyolysis and muscular dystrophies is under-recognized in clinical practice. To identify muscular dystrophies presenting with rhabdomyolysis at onset or as predominant feature. We retrospectively reviewed clinical and laboratory data of patients with a genetically confirmed muscular dystrophy in whom rhabdomyolysis was the presenting or main clinical manifestation. Thirteen unrelated patients (males=6; females=7) were identified. Median age at time of rhabdomyolysis was 18 years (range, 2-47) and median duration between the first episode of rhabdomyolysis and molecular diagnosis was 2 years. Fukutin-related protein (FKRP) muscular dystrophy (n=6) was the most common diagnosis, followed by anoctaminopathy-5 (n=3), calpainopathy-3 (n=2) and dystrophinopathy (n=2). Four patients experienced recurrent rhabdomyolysis. Eight patients were asymptomatic and 3 reported myalgia and exercise intolerance prior to the rhabdomyolysis. Exercise (n=6) and fever (n=4) were common triggers; rhabdomyolysis was unprovoked in 3 patients. Twelve patients required hospitalization. Baseline CK levels were elevated in all patients (median 1200 IU/L; range, 600-3600). Muscular dystrophies can present with rhabdomyolysis; FKRP mutations are particularly frequent in causing such complication. A persistently elevated CK level in patients with rhabdomyolysis warrants consideration for underlying muscular dystrophy. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Genetics Home Reference: Fukuyama congenital muscular dystrophy

    Science.gov (United States)

    ... with mental retardation Muscular dystrophy, congenital, Fukuyama type Muscular dystrophy, congenital, with central nervous system involvement Polymicrogyria with muscular dystrophy Related Information How ...

  8. Next Generation Sequencing approach to molecular diagnosis of Duchenne muscular dystrophy; identification of a novel mutation.

    Science.gov (United States)

    Ebrahimzadeh-Vesal, Reza; Teymoori, Atieh; Azimi-Nezhad, Mohsen; Hosseini, Forough Sadat

    2018-02-20

    Duchenne Muscular Dystrophy (DMD; MIM 310200) is one of the most common and severe type of hereditary muscular dystrophies. The disease is caused by mutations in the dystrophin gene. The dystrophin gene is associated with X-linked recessive Duchenne and Becker muscular dystrophy. This disease occurs almost exclusively in males. The clinical symptoms of muscle weakness usually begin at childhood. The main symptoms of this disorder are gradually muscular weakness. The affected patients have inability to standing up and walking. Death is usually due to respiratory infection or cardiomyopathy. In this article, we have reported the discovery of a new nonsense mutation that creates abnormal stop codon in the dystrophin gene. This mutation was detected using Next Generation Sequencing (NGS) technique. The subject was a 17-year-old male with muscular dystrophy that who was suspected of having DMD. He was referred to Hakim medical genetics center of Neyshabur, IRAN. Copyright © 2017. Published by Elsevier B.V.

  9. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Spinal Cord Injury Facts and Figures Care and Treatment After SCI Spinal Cord Injury Rehabilitation Pediatric Spinal ... Spinal Cord Injury Facts and Figures Care and Treatment After SCI Spinal Cord Injury Rehabilitation Pediatric Spinal ...

  10. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Animated Spinal Cord Injury Chart Spinal Cord Injury Facts and Figures Care and Treatment After SCI Spinal ... Animated Spinal Cord Injury Chart Spinal Cord Injury Facts and Figures Care and Treatment After SCI Spinal ...

  11. Dismorfia muscular Muscle dysmorphia

    Directory of Open Access Journals (Sweden)

    Sheila Seleri Marques Assunção

    2002-12-01

    Full Text Available Preocupações mórbidas com a imagem corporal eram tidas até recentemente como problemas eminentemente femininos. Atualmente estas preocupações também têm sido encontradas no sexo masculino. A dismorfia muscular é um subtipo do transtorno dismórfico corporal que ocorre principalmente em homens que, apesar da grande hipertrofia muscular, consideram-se pequenos e fracos. Além de estar associada a prejuízos sociais, ocupacionais, recreativos e em outras áreas do funcionamento do indivíduo, a dismorfia muscular é também um fator de risco para o abuso de esteróides anabolizantes. Este artigo aborda aspectos epidemiológicos, etiológicos e padrões clínicos da dismorfia muscular, além de tecer comentários sobre estratégias de tratamento para este transtorno.Morbid concern over body image was considered, until recently, a female issue. Nowadays, it has been viewed as a common male disorder. Muscle dysmorphia, a subtype of a body dysmorphic disorder, affects men who, despite having clear muscular hypertroph,y see themselves as frail and small. Besides being associated to major social, leisure and occupational dysfunction, muscle dysmorphia is also a risk factor for the abuse of steroids. This article describes epidemiological, etiological and clinical characteristics of muscle dysmorphia and comments on its treatment strategy.

  12. Evaluation of Narrative Abilities in Patients Suffering from Duchenne Muscular Dystrophy

    Science.gov (United States)

    Marini, A.; Lorusso, M. L.; D'Angelo, M. G.; Civati, F.; Turconi, A. C.; Fabbro, F.; Bresolin, N.

    2007-01-01

    The present work investigated cognitive, linguistic and narrative abilities in a group of children suffering from Duchenne Muscular Dystrophy, an allelic X-linked recessive disorder caused by mutations in the gene encoding dystrophin. The patients showed mildly reduced IQ with lower Verbal than Performance Intelligence Quotient and were mildly…

  13. Copper : recession and recovery

    International Nuclear Information System (INIS)

    Warwick-Ching, T.

    2002-01-01

    In 2002, the world output for copper will fall for the first time in nearly a decade because of financial pressure and voluntary constraints. Cutbacks at copper mines amount to 760,000 tonnes per year. These cutbacks have occurred mostly in the United States which holds the largest share of high cost mines. This paper discussed recent developments in both copper supply and demand. The United States is unique as both a large consumer and producer of copper. At 1.35 million tonnes, US mine output in 2001 was at its lowest since 1987. The cutbacks in mining in general were described in this paper with particular reference to the huge loss of mining and metallurgical activity in the United States during a prolonged period of low prices in the mid 1980s. The author noted that this period was followed by an exceptional decade when much of the industry rebounded. Only 8 mines closed outright in the United States and a handful in Canada since the recession of the 1980s, but that is partly because mines got bigger and there are fewer small mines in North America. There are only 4 electrolytic refineries and 3 smelters still active in the entire United States, of which 2 are operating at a fraction of capacity. It was noted that only the buoyancy of China prevented a much bigger decline in copper demand on a global scale

  14. Evaluation of Limb-Girdle Muscular Dystrophy

    Science.gov (United States)

    2014-03-06

    Becker Muscular Dystrophy; Limb-Girdle Muscular Dystrophy, Type 2A (Calpain-3 Deficiency); Limb-Girdle Muscular Dystrophy, Type 2B (Miyoshi Myopathy, Dysferlin Deficiency); Limb-Girdle Muscular Dystrophy, Type 2I (FKRP-deficiency)

  15. Learning about Duchenne Muscular Dystrophy

    Science.gov (United States)

    ... protein. Often these boys are classified as having Becker muscular dystrophy. Genetic testing (looking at the body's genetic instructions) ... National Library of Medicine Web site Duchenne and Becker muscular dystrophy [ghr.nlm.nih.gov] From Genetics Home Reference ...

  16. Natural history of Duchenne muscular dystrophy

    Directory of Open Access Journals (Sweden)

    Qing KE

    2015-05-01

    Full Text Available Duchenne muscular dystrophy (DMD is X-linked recessive hereditary disease. DMD gene mutations result in dystrophin deficiency, which causes not only muscle movement disorders but also scoliosis, cognitive dysfunction, urinary tract diseases, respiratory diseases and heart diseases. Most patients die in early adult for respiratory and circulatory failure. Early multidisciplinary therapies will significantly delay disease progression and improve patients' quality of life. However, DMD diagnosis and treatment exist significantly time delay now. In this study, we review the natural history of DMD, including motor, cognitive, respiratory and heart function, for improving DMD early recognition, diagnosis and treatment, so as to benefit DMD patients. DOI: 10.3969/j.issn.1672-6731.2015.05.004

  17. What Caused the Great Recession?

    OpenAIRE

    Homburg, Stefan

    2014-01-01

    This paper examines five possible explanations for the Great Recession of 2008 and 2009, using data for the United States and the eurozone. Of these five hypotheses, four are not supported by the data, while the fifth appears reasonable.

  18. Meaning of Muscular Dystrophy

    Science.gov (United States)

    ... is very similar to Duchenne, except kids with Becker MD may not have problems until much later, when they're teenagers or adults. It takes a long time for their muscles to become weak. How Does a Kid Get Muscular Dystrophy? MD is not contagious (say: con-TAY-juss), ...

  19. The Great Recession was not so Great

    NARCIS (Netherlands)

    van Ours, J.C.

    2015-01-01

    The Great Recession is characterized by a GDP-decline that was unprecedented in the past decades. This paper discusses the implications of the Great Recession analyzing labor market data from 20 OECD countries. Comparing the Great Recession with the 1980s recession it is concluded that there is a

  20. Spinal Cord Injury 101

    Medline Plus

    Full Text Available menu Understanding Spinal Cord Injury What is a Spinal Cord Injury Levels of Injury and What They Mean Animated Spinal Cord Injury Chart Spinal Cord Injury Facts and Figures Care and Treatment After SCI Spinal ...

  1. Duchenne muscular dystrophy carriers

    International Nuclear Information System (INIS)

    Matsumura, K.; Nakano, I.

    1989-01-01

    By means of magnetic resonance imaging (MRI), the proton spin-lattice relaxation times (T1 values) of the skeletal muscles were measured in Duchenne muscular dystrophy (DMD) carriers and normal controls. The bound water fraction (BWF) was calculated from the T1 values obtained, according to the fast proton diffusion model. In the DMD carriers, T1 values of the gluteus maximus and quadriceps femoris muscles were significantly higher, and BWFs of these muscles were significantly lower than in normal control. Degenerative muscular changes accompanied by interstitial edema were presumed responsible for this abnormality. No correlation was observed between the muscle T1 and serum creatine kinase values. The present study showed that MRI could be a useful method for studying the dynamic state of water in both normal and pathological skeletal muscles. Its possible utility for DMD carrier detection was discussed briefly. (orig.)

  2. Spinal stenosis

    Science.gov (United States)

    ... in the spine that was present from birth Narrow spinal canal that the person was born with Herniated or slipped disk, which ... when you sit down or lean forward. Most people with spinal stenosis cannot walk for a long ... During a physical exam, your health care provider will try to ...

  3. Emery-Dreifuss muscular dystrophy: the most recognizable laminopathy

    Directory of Open Access Journals (Sweden)

    Agnieszka Madej-Pilarczyk

    2016-03-01

    Full Text Available Emery-Dreifuss muscular dystrophy (EDMD, a rare inherited disease, is characterized clinically by humero-peroneal muscle atrophy and weakness, multijoint contractures, spine rigidity and cardiac insufficiency with conduction defects. There are at least six types of EDMD known so far, of which five have been associated with mutations in genes encoding nuclear proteins. The majority of the EDMD cases described so far are of the emerinopathy (EDMD1 kind, with a recessive X-linked mode of inheritance, or else laminopathy (EDMD2, with an autosomal dominant mode of inheritance. In the work described here, the authors have sought to describe the history by which EDMD came to be distinguished as a separate entity, as well as the clinical and genetic characteristics of the disease, the pathophysiology of lamin-related muscular diseases and, finally, therapeutic issues, prevention and ethical aspects.

  4. The Great Recession: a comparison of recession magnitudes in Europe, USA and Japan

    OpenAIRE

    Mazurek, Jiří

    2013-01-01

    In this article recession magnitudes in Europe, the USA and Japan during the Great Recession are compared. The strongest recessions (of severe category) occurred in Latvia, Lithuania and Estonia, while recessions in Japan and the USA were significantly weaker. Even the strongest recession (in Latvia) was found smaller in its magnitude than the Great Depression 1929-1933 in the USA. Hence, comparisons of the Great Recession to the Great Depression in the literature are somewhat exaggerated.

  5. Repair of an inguinoscrotal hernia in a patient with Becker muscular dystrophy.

    Science.gov (United States)

    Tatulli, F; Caraglia, A; Delcuratolo, A; Cassano, S; Chetta, G S

    2017-01-01

    Inguinal hernia repairs are routinely performed as outpatient procedures in most patients, whereas a few require admission due to clinical or social peculiarities. Muscular dystrophies are inherited disorders characterized by progressive muscle wasting and weakness. In case of surgery there is no definite recommendation for either general or regional anesthesia. This contribution regards a 48 y. o. male patient diagnosed with Becker Muscular Dystrophy by muscle biopsy 10 years earlier. He had a left-sided sizable inguinoscrotal hernia with repeat episodes of incarceration. An elective mesh repair with suction drainage was accomplished under selective spinal anesthesia. The post-operative course was uneventful. A few inguinal hernia repairs require admission due to peculiarities such as extensive scrotal hernias requiring suction drainage. Muscular dystrophies are inherited disorders with no cure and no two dystrophy patients are exactly alike, therefore the health issues will be different for each individual. In case of surgery there is no definite recommendation for either general or regional anesthesia. This contribution regards the successful elective mesh repair with suction drainage of a large left-sided inguino-scrotal hernia in a 48 y. o. male patient affected by Becker muscular dystrophy by selective spinal anesthesia obtained by 10 milligrams of hyperbaric bupivacaine. Effective mesh repair with suction drainage of large inguinal hernias under spinal anesthesia can be achieved in patients affected by muscular dystrophy.

  6. [Muscular disorders associated with ankylosing spondylitis and their correction with the help of whole body cryotherapy].

    Science.gov (United States)

    Kulikov, A G; Tabiev, V I; Rassulova, M A

    2015-01-01

    The objective of the present study was to evaluate the possibilities for the correction of muscular disorders associated with ankylosing spondylitis and their correction with the help of whole body cryotherapy. The study included 55 patients randomly allocated to two groups. Group 1 was comprised of the patients treated with the use of the common mineral baths, physiotherapy, therapeutic physical exercises, spinal massage, and whole body air-cryotherapy. Group 2 contained the patients who were treated in a similar way with the exception of whole body cryotherapy; they served as controls. Muscular disorders were diagnosed by means of functional muscular testing. The study has demonstrated the high prevalence of muscular disorders in the patients suffering from ankylosing spondylitis. Moreover, it revealed the profile of such disorders associated with ankylosing spondylitis and showed significant correlation between the results of functional muscular testing, BASMI and BASFI indices as well as characteristics of chest excursions (pcryotherapy in comparison with the alternative therapeutic modalities employed in the present study. This therapeutic modality ensured the statistically more pronounced improvement of functional muscular testing parameters (pcryotherapy accounting for its corrective influence on the muscular disorders in the patients presenting with ankylosing spondylitis. It is concluded that the proposed approach can be recommended for the introduction in the combined therapeutic and rehabilitative treatment of muscular disorders associated with ankylosing spondylitis.

  7. Algebra, Home Mortgages, and Recessions

    Science.gov (United States)

    Mariner, Jean A. Miller; Miller, Richard A.

    2009-01-01

    The current financial crisis and recession in the United States present an opportunity to discuss relevant applications of some topics in typical first-and second-year algebra and precalculus courses. Real-world applications of percent change, exponential functions, and sums of finite geometric sequences can help students understand the problems…

  8. Measurement of the lateral recess angle as a possible alternative for evaluation of the lateral recess stenosis on a CT scan

    International Nuclear Information System (INIS)

    Strojnik, T.

    2001-01-01

    Stenosis of the lateral recess in the lumbar spinal canal is a clinical problem, especially in terms of surgical management. Criteria for the diagnosis and surgical treatment of lateral recess stenosis (LRS) are not clearly defined. Several authors have suggested measurement of the lateral recess height (LRH) on computed tomography (CT) scans as a helpful tool for making decisions in regard of management. The present study is based an the assumption that measurement of the lateral recess angle (LRA) may be useful in the clinical management of lateral recess stenosis. The reliability and significance of the results have been analyzed. In 35 patients, the stenosis was confirmed by intraoperative measurement of the lateral recess height. Fifty-three affected lateral recesses were analyzed. Before surgery, the heights on CT scans were measured. The mean value was 3.3 mm (SD = 0.9 mm), while 41 of them were 3.6 mm or less. Furthermore, the angles on CT scans were evaluated. The mean value was 25.9 degrees (SD = 4.9 degrees), 48 of them were 30 degrees or less and only 5 of them achieved more than 30 degrees. Results reveal that the best quantitative determination of a lateral recess stenosis is a CT scan angle measurement with a critical value of 30 degrees. A CT scan height of 3.6 mm or less is also indicative of stenosis. Statistical evaluation of the data by multiple regression analysis revealed agreement between intraoperative findings and measured heights (p = 0.02), while even better results were noted for angles (p < 0.01). Interfacet distance (IF) was found to be least predictive (p = 0.04). (author)

  9. Recessed floating pier caps for highway bridges.

    Science.gov (United States)

    1973-01-01

    Presented are alternate designs for two existing bridges in Virginia - one with steel beams and the other with prestressed concrete beams - whereby the pier caps are recessed within the depth of the longitudinal beams. The purpose of this recession i...

  10. Cardio-Muscular Conditioner

    Science.gov (United States)

    1993-01-01

    In the mid-sixties, Gary Graham, a Boeing designer, developed a cardiovascular conditioner for a planned Air Force orbiting laboratory. After the project was cancelled, Graham participated in space station conditioning studies for the Skylab program. Twenty years later, he used this expertise to develop the Shuttle 2000-1, a physical therapy and athletic development conditioner, available through Contemporary Designs. The machine is used by football teams, sports clinics and medical rehabilitation centers. Cardiovascular fitness and muscular strength development are promoted through both kinetic and plyometric exercises.

  11. Evidence for linkage disequilibrium in chromosome 13-linked Duchenne-like muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Othmane, K.B.; Speer, M.C.; Stauffer, J. [Duke Univ. Medical Center, Durham, NC (United States)] [and others

    1995-09-01

    Duchenne-like muscular dystrophy (DLMD) is an autosomal recessive Limb Girdle muscular dystrophy (LGMD2C) characterized by late age of onset, proximal muscle weakness leading to disability, high creatine kinase values, normal intelligence and normal dystrophin in muscle biopsy. We have shown previously that three DLMD families from Tunisia are linked to chromosome 13q12. To further localize the LGMD2C gene, we have investigated seven additional families (119 individuals). Both genotyping and two-point linkage analysis were performed as described elsewhere. 7 refs., 1 fig., 1 tab.

  12. Advances in gene therapy for muscular dystrophies [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Hayder Abdul-Razak

    2016-08-01

    Full Text Available Duchenne muscular dystrophy (DMD is a recessive lethal inherited muscular dystrophy caused by mutations in the gene encoding dystrophin, a protein required for muscle fibre integrity. So far, many approaches have been tested from the traditional gene addition to newer advanced approaches based on manipulation of the cellular machinery either at the gene transcription, mRNA processing or translation levels. Unfortunately, despite all these efforts, no efficient treatments for DMD are currently available. In this review, we highlight the most advanced therapeutic strategies under investigation as potential DMD treatments.

  13. Spinal injury

    Science.gov (United States)

    ... Dallas, TX: American Red Cross; 2016. Kaji AH, Newton EJ, Hockberger RS. Spinal injuries. In: Marx JA, ... member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www. ...

  14. Spinal infections

    International Nuclear Information System (INIS)

    Tali, E. Turgut; Gueltekin, Serap

    2005-01-01

    Spinal infections have an increasing prevalence among the general population. Definitive diagnosis based solely on clinical grounds is usually not possible and radiological imaging is used in almost all patients. The primary aim of the authors is to present an overview of spinal infections located in epidural, intradural and intramedullary compartments and to provide diagnostic clues regarding different imaging modalities, particularly MRI, to the practicing physicians and radiologists. (orig.)

  15. Spinal cysticercosis

    International Nuclear Information System (INIS)

    Goedert, A.V.; Silva, S.H.F.

    1990-01-01

    Spinal cysticercosis is an extremely uncommon condition. We have examined four patients with complaints that resembled nervous root compression by disk herniation. Myelography was shown to be an efficient method to evaluate spinal involvement, that was characterized by findings of multiple filling defect images (cysts) plus signs of adhesive arachnoiditis. One cyst was found to be mobile. Because of the recent development of medical treatment, a quick and precise diagnosis is of high importance to determine the prognosis of this condition. (author)

  16. Differences in Physical Activity during School Recess

    Science.gov (United States)

    Ridgers, Nicola D.; Saint-Maurice, Pedro F.; Welk, Gregory J.; Siahpush, Mohammad; Huberty, Jennifer

    2011-01-01

    Background: School recess provides a daily opportunity for physical activity engagement. The purpose of this study was to examine physical activity levels during recess by gender, ethnicity, and grade, and establish the contribution of recess to daily school physical activity levels. Methods: Two hundred and ten children (45% boys) from grades 3…

  17. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Cord Injury What is a Spinal Cord Injury Levels of Injury and What They Mean Animated Spinal ... Cord Injury What is a Spinal Cord Injury Levels of Injury and What They Mean Animated Spinal ...

  18. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Injury Chart Spinal Cord Injury Facts and Figures Care and Treatment After SCI Spinal Cord Injury Rehabilitation ... Injury Chart Spinal Cord Injury Facts and Figures Care and Treatment After SCI Spinal Cord Injury Rehabilitation ...

  19. Genetics of recessive cognitive disorders

    OpenAIRE

    Musante, Luciana; Ropers, H. Hilger

    2014-01-01

    Most severe forms of intellectual disability (ID) have specific genetic causes. Numerous X chromosome gene defects and disease-causing copy-number variants have been linked to ID and related disorders, and recent studies have revealed that sporadic cases are often due to dominant de novo mutations with low recurrence risk. For autosomal recessive ID (ARID) the recurrence risk is high and, in populations with frequent parental consanguinity, ARID is the most common form of ID. Even so, its elu...

  20. Importância do camundongo mdx na fisiopatologia da distrofia muscular de Duchenne The importance of mdx mouse in the pathophysiology of Duchenne's muscular distrophy

    Directory of Open Access Journals (Sweden)

    Sandra Lopes Seixas

    1997-09-01

    Full Text Available O camundongo mdx desenvolve distrofia muscular recessiva ligada ao cromossoma X (locus Xp21.1 e não expressa distrofina. Embora não apresente intensa fibrose do tecido muscular e acúmulo de tecido adiposo, é considerado o modelo animal mais adequado da distrofia muscular de Duchenne. As alterações estruturais no tecido muscular associadas à mionecrose e presença do infiltrado inflamatório com predomínio de linfócitos e monócitos/macrófagos sugerem uma participação do sistema imunológico nesta miopatia. Além disso a modulação na expressão dos componentes da matriz extracelular no microambiente muscular nas várias fases da doença (início, mionecrose, regeneração indicam um papel importante do conjuntivo no direcionamento das células inflamatórias para o foco da lesão muscular. O camundongo mdx coloca-se como um excelente modelo para o estudo dos mecanismos patogenéticos da mionecrose e regeneração na distrofia muscular de Duchenne, possibilitando inclusive o desenvolvimento de estratégias terapêuticas mais adequadas.The mdx mouse develop an X-linked recessive muscular dystrophy (locus Xp21.1 and lack dystrophin expression. Despite showing less intense myofibrosis and scarce deposition of fatty tissue, mdx mice are considered an adequate animal model for studies on the pathogenesis of Duchenne-type muscular dystrophy. Marked histological alterations in the muscular tissues associated to myonecrosis and inflammatory mononuclear cell infiltrate (lymphocytes, monocytes/macrophages suggest a participation of the immune system in this myopathy. Modulation of the extracellular matrix (ECM components in the muscular tissue during all phases (onset, myonecrosis and regeneration of disease, indicate an important role for the ECM driving inflammatory cells to the foci of lesion. Therefore mdx mice should be regarded as an important tool for studies on pathogenetic mechanisms of Duchenne-type muscular dystrophy. Such

  1. Congenital muscular dystrophies--problems of classification.

    Science.gov (United States)

    Lenard, H G

    1991-04-01

    The classification of congenital muscular dystrophies (CMD), based on perceived clinical and morphological similarities or differences, is controversial. CMD without cerebral involvement has sometimes been divided into a mild and a severe form. This distinction is, however, arbitrary and not uncontested. Whether Ullrich's disease, formerly called atonic-sclerotic dystrophy, is a disease entity and if so, whether it is a primary muscle disorder, is uncertain. CMD without cerebral involvement is inherited in an autosomal recessive fashion in the great majority of cases. CMDs with cerebral involvement are usually classified into at least three forms: the Fukuyama type of CMD, occurring almost exclusively in Japanese patients; CMD with hypomyelination, sometimes also called the occidental type of cerebromuscular dystrophy; and Walker-Warburg syndrome. Muscle-eye-brain disease, described in a number of Finnish patients, may or may not belong in this last category. In CMD with cerebral involvement inheritance is also autosomal recessive. It is possible that single sporadic cases are phenocopies due to infectious or other exogenous causes. Reports of clinical and morphological findings from an increasing number of patients show a high degree of variability within and, on the other hand, certain similarities between the forms of CMD with cerebral involvement. In addition, neuroradiological changes are also found with increasing frequency in CMD patients without clinical neuropsychological abnormalities. It is not unreasonable to speculate that molecular genetic techniques will reveal in the near future a variable defect in one gene locus or defects in a few gene loci as the cause of the various clinical forms of CMDs.

  2. Limb girdle muscular dystrophies

    DEFF Research Database (Denmark)

    Vissing, John

    2016-01-01

    PURPOSE OF REVIEW: The aim of the study was to describe the clinical spectrum of limb girdle muscular dystrophies (LGMDs), the pitfalls of the current classification system for LGMDs, and emerging therapies for these conditions. RECENT FINDINGS: Close to half of all LGMD subtypes have been...... or are registered in other classification systems for muscle disease. On the contrary, diseases that fulfill classical criteria for LGMD have found no place in the LGMD classification system. These shortcomings call for revision/creation of a new classification system for LGMD. The rapidly expanding gene sequencing...... capabilities have helped to speed up new LGMD discoveries, and unveiled pheno-/genotype relations. Parallel to this progress in identifying new LGMD subtypes, emerging therapies for LGMDs are under way, but no disease-specific treatment is yet available for nonexperimental use. SUMMARY: The field of LGMD...

  3. NDST1 missense mutations in autosomal recessive intellectual disability.

    Science.gov (United States)

    Reuter, Miriam S; Musante, Luciana; Hu, Hao; Diederich, Stefan; Sticht, Heinrich; Ekici, Arif B; Uebe, Steffen; Wienker, Thomas F; Bartsch, Oliver; Zechner, Ulrich; Oppitz, Cornelia; Keleman, Krystyna; Jamra, Rami Abou; Najmabadi, Hossein; Schweiger, Susann; Reis, André; Kahrizi, Kimia

    2014-11-01

    NDST1 was recently proposed as a candidate gene for autosomal recessive intellectual disability in two families. It encodes a bifunctional GlcNAc N-deacetylase/N-sulfotransferase with important functions in heparan sulfate biosynthesis. In mice, Ndst1 is crucial for embryonic development and homozygous null mutations are perinatally lethal. We now report on two additional unrelated families with homozygous missense NDST1 mutations. All mutations described to date predict the substitution of conserved amino acids in the sulfotransferase domain, and mutation modeling predicts drastic alterations in the local protein conformation. Comparing the four families, we noticed significant overlap in the clinical features, including both demonstrated and apparent intellectual disability, muscular hypotonia, epilepsy, and postnatal growth deficiency. Furthermore, in Drosophila, knockdown of sulfateless, the NDST ortholog, impairs long-term memory, highlighting its function in cognition. Our data confirm NDST1 mutations as a cause of autosomal recessive intellectual disability with a distinctive phenotype, and support an important function of NDST1 in human development. © 2014 Wiley Periodicals, Inc.

  4. Spinal tumors

    International Nuclear Information System (INIS)

    Goethem, J.W.M. van; Hauwe, L. van den; Oezsarlak, Oe.; Schepper, A.M.A. de; Parizel, P.M.

    2004-01-01

    Spinal tumors are uncommon lesions but may cause significant morbidity in terms of limb dysfunction. In establishing the differential diagnosis for a spinal lesion, location is the most important feature, but the clinical presentation and the patient's age and gender are also important. Magnetic resonance (MR) imaging plays a central role in the imaging of spinal tumors, easily allowing tumors to be classified as extradural, intradural-extramedullary or intramedullary, which is very useful in tumor characterization. In the evaluation of lesions of the osseous spine both computed tomography (CT) and MR are important. We describe the most common spinal tumors in detail. In general, extradural lesions are the most common with metastasis being the most frequent. Intradural tumors are rare, and the majority is extramedullary, with meningiomas and nerve sheath tumors being the most frequent. Intramedullary tumors are uncommon spinal tumors. Astrocytomas and ependymomas comprise the majority of the intramedullary tumors. The most important tumors are documented with appropriate high quality CT or MR images and the characteristics of these tumors are also summarized in a comprehensive table. Finally we illustrate the use of the new World Health Organization (WHO) classification of neoplasms affecting the central nervous system

  5. Isolated spinal accessory neuropathy and intracisternal schwannomas of the spinal accessory nerve

    Directory of Open Access Journals (Sweden)

    Abdullah M. Al-Ajmi

    2015-03-01

    Full Text Available We report a 40-year-old female patient presenting with isolated left spinal accessory neuropathy that developed insidiously over 6 years. She complained of ill-defined deep neck and shoulder pain. On examination, prominent sternocleidomastoid and trapezoid muscle weakness and atrophy, shoulder instability, and lateral scapular winging were observed. MRI identified a small mass of the cisternal portion of the spinal accessory nerve. Its appearance was typical of schwannoma. Surgical treatment was not offered because of the small tumor size, lack of mass effect and the questionable functional recovery in the presence of muscular atrophy.

  6. Orocaecal transit time in Duchenne muscular dystrophy.

    OpenAIRE

    Korman, S H; Bar-Oz, B; Granot, E; Meyer, S

    1991-01-01

    Smooth muscle degeneration may occur in Duchenne muscular dystrophy. We measured fasting orocaecal transit time in patients with advanced Duchenne muscular dystrophy and other muscular dystrophies and in healthy controls. No significant differences were found. In contrast to reports of gastric hypomotility in Duchenne muscular dystrophy, we found no evidence of impaired small intestinal motility.

  7. Spinal tuberculosis.

    Science.gov (United States)

    Dunn, R N; Ben Husien, M

    2018-04-01

    Tuberculosis (TB) remains endemic in many parts of the developing world and is increasingly seen in the developed world due to migration. A total of 1.3 million people die annually from the disease. Spinal TB is the most common musculoskeletal manifestation, affecting about 1 to 2% of all cases of TB. The coexistence of HIV, which is endemic in some regions, adds to the burden and the complexity of management. This review discusses the epidemiology, clinical presentation, diagnosis, impact of HIV and both the medical and surgical options in the management of spinal TB. Cite this article: Bone Joint J 2018;100-B:425-31.

  8. Clinico-epidemiologic characteristics of spinal muscular atrophy ...

    African Journals Online (AJOL)

    Type I was the commonest type (60.6%), followed by type II (26.79%), and type III (8.8%). Consanguinity was reported in 45.5 and family history in 47.8% of patients. Molecular study was done and 54.5% of patients (types I and II) have homozygous deletion of exon 7, 36.3% of whom had also homozygous deletion of exon 8 ...

  9. The trauma of a recession.

    LENUS (Irish Health Repository)

    Murphy, S M

    2011-09-01

    Employment in construction in Ireland fell by 10% from nearly 282,000 in the second quarter of 2007 to 255,000 in the same period of 2008. Our study looks at the differences in soft tissue upper limb trauma dynamics of a pre- and post-recession Ireland. Construction accounted for 330 patients (27%) of all hand injuries in 2006, but only 18 (3%) in 2009. Our data shows a significant drop in hand injuries related to the construction industry, and more home\\/DIY cases and deliberate self-harm presenting in their stead.

  10. The trauma of a recession.

    Science.gov (United States)

    Murphy, S M; Kieran, I; Shaughnessy, M O

    2011-09-01

    Employment in construction in Ireland fell by 10% from nearly 282,000 in the second quarter of 2007 to 255,000 in the same period of 2008. Our study looks at the differences in soft tissue upper limb trauma dynamics of a pre- and post-recession Ireland. Construction accounted for 330 patients (27%) of all hand injuries in 2006, but only 18 (3%) in 2009. Our data shows a significant drop in hand injuries related to the construction industry, and more home/DIY cases and deliberate self-harm presenting in their stead.

  11. Muscular Dystrophy: Hope Through Research

    Science.gov (United States)

    ... of muscular dystrophy appeared in 1830, when Sir Charles Bell wrote an essay about an illness that ... linked disorder to their sons but their daughters will be carriers of that disorder. Carrier females occasionally ...

  12. Rapidly worsening bulbar symptoms in a patient with spinobulbar muscular atrophy

    Directory of Open Access Journals (Sweden)

    Montserrat Diaz-Abad

    2013-12-01

    Full Text Available X-linked spinobulbar muscular atrophy (Kennedy’s disease affects muscles and motor neurons, manifesting as weakness and wasting of bulbar, facial, and proximal limb muscles due to loss of anterior horn cells in the brain and spinal cord. We present the case of a patient with X-linked spinobulbar muscular atrophy with rapidly worsening bulbar symptoms caused by laryngopharyngeal irritation associated with a viral upper respiratory tract infection, seasonal allergies and laryngopharyngeal reflux, who dramatically improved with multimodality therapy.

  13. Congenital bovine spinal dysmyelination is caused by a missense mutation in the SPAST gene

    DEFF Research Database (Denmark)

    Thomsen, Bo; Nissen, Peter H.; Agerholm, Jørgen S

    2010-01-01

     Bovine spinal dysmyelination (BSD) is a recessive congenital neurodegenerative disease in cattle (Bos taurus) characterized by pathological changes of the myelin sheaths in the spinal cord. The occurrence of BSD is a longstanding problem in the American Brown Swiss (ABS) breed and in several...

  14. Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation is associated with cell-type-dependent splicing of mtAspRS mRNA

    NARCIS (Netherlands)

    van Berge, Laura; Dooves, Stephanie; van Berkel, Carola G. M.; Polder, Emiel; van der Knaap, Marjo S.; Scheper, Gert C.

    2012-01-01

    LBSL (leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation) is an autosomal recessive white matter disorder with slowly progressive cerebellar ataxia, spasticity and dorsal column dysfunction. Magnetic resonance imaging shows characteristic abnormalities in the

  15. [Genetic study of the autosomal recessive form of Charcot-Marie-Tooth in an Algerian family].

    Science.gov (United States)

    Hamadouche, T; Tazir-Melboucy, M; Benhassine, T

    1998-01-01

    Charcot-Marie-Tooth disease (CMT) is a hereditary neuropathy characterized by muscular atrophy and progressive sensitive alterations that affect limbs. The CMT is one of the most heterogenous diseases, clinically as well as genetically. At least twelve loci are responsible for the CMT phenotype, four of them for the autosomal recessive form. The aim of our work was to determinate the implication/exclusion of these four loci in an Algerian family by linkage analysis using microsatellites markers. We have tested the four loci on 8q13-21.1 (CMT4A), 11q23 (CMT4B), 5q23-33 (CMT4C) 8q24 (CMTAR). The haplotype reconstruction allowed us to exclude all the loci in this family, suggesting that the locus (gene) responsible for this form of CMT is localized elsewhere in the genome, thus providing an other observation of the great heterogeneity of the CMT, particularly autosomal recessive.

  16. Muscular dystrophy in a dog resembling human becker muscular dystrophy.

    Science.gov (United States)

    Baroncelli, A B; Abellonio, F; Pagano, T B; Esposito, I; Peirone, B; Papparella, S; Paciello, O

    2014-05-01

    A 3-year-old, male Labrador retriever dog was presented with clinical signs of progressive exercise intolerance, bilateral elbow extension, rigidity of the forelimbs, hindlimb flexion and kyphosis. Microscopical examination of muscle tissue showed marked variability in myofibre size, replacement of muscle with mature adipose tissue and degeneration/regeneration of muscle fibres, consistent with muscular dystrophy. Immunohistochemical examination for dystrophin showed markedly reduced labelling with monoclonal antibodies specific for the rod domain and the carboxy-terminal of dystrophin, while expression of β-sarcoglycan, γ-sarcoglycan and β-dystroglycan was normal. Immunoblotting revealed a truncated dystrophin protein of approximately 135 kDa. These findings supported a diagnosis of congenital canine muscular dystrophy resembling Becker muscular dystrophy in man. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Genetics of recessive cognitive disorders.

    Science.gov (United States)

    Musante, Luciana; Ropers, H Hilger

    2014-01-01

    Most severe forms of intellectual disability (ID) have specific genetic causes. Numerous X chromosome gene defects and disease-causing copy-number variants have been linked to ID and related disorders, and recent studies have revealed that sporadic cases are often due to dominant de novo mutations with low recurrence risk. For autosomal recessive ID (ARID) the recurrence risk is high and, in populations with frequent parental consanguinity, ARID is the most common form of ID. Even so, its elucidation has lagged behind. Here we review recent progress in this field, show that ARID is not rare even in outbred Western populations, and discuss the prospects for improving its diagnosis and prevention. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Spinal Cord Injury 101

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    Full Text Available ... spinal cord injury? play_arrow What kind of surgery is common after a spinal cord injury? play_ ... How soon after a spinal cord injury should surgery be performed? play_arrow Is it common to ...

  19. Spinal Cord Injury 101

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    Full Text Available ... L Sarah Harrison, OT Anne Bryden, OT The Role of the Social Worker after Spinal Cord Injury ... a spinal cord injury important? play_arrow What role does “compression” play in a spinal cord injury? ...

  20. Spinal Cord Injury 101

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    Full Text Available ... Cord Injury Diane M. Rowles, MS, NP How Family Life Changes After Spinal Cord Injury Nancy Rosenberg, ... Children with Spinal Cord Injury Patricia Mucia, RN Family Life After Pediatric Spinal Injury Dawn Sheaffer, MSW ...

  1. Spinal Cord Injury 101

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    Full Text Available ... Counseling Blog About Media Donate Spinal Cord Injury Medical Expert Videos Topics menu Topics Spinal Cord Injury ... Jennifer Piatt, PhD David Chen, MD Read Bio Medical Director, Spinal Cord Injury Rehabilitation Program, Rehabilitation Institute ...

  2. Spinal Cord Injury 101

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    Full Text Available ... Blog About Media Donate Spinal Cord Injury Medical Expert Videos Topics menu Topics Spinal Cord Injury 101 ... arrow What is the “Spinal Cord Injury Model Systems” program? play_arrow What are the most promising ...

  3. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Topic Resources Peer Counseling Blog About Media Donate Spinal Cord Injury Medical Expert Videos Topics menu Topics Spinal Cord Injury 101 Adult Injuries Spinal Cord Injury 101 David ...

  4. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Topic Resources Peer Counseling Blog About Media Donate Spinal Cord Injury Medical Expert Videos Topics menu Topics Spinal Cord Injury 101 Adult Injuries Spinal Cord Injury 101 ...

  5. Spinal Cord Diseases

    Science.gov (United States)

    Your spinal cord is a bundle of nerves that runs down the middle of your back. It carries signals back ... of the spine, this can also injure the spinal cord. Other spinal cord problems include Tumors Infections such ...

  6. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Spinal Cord Injury 101 Lawrence Vogel, MD The Basics of Pediatric SCI Rehabilitation Sara Klaas, MSW Transitions for Children with Spinal Cord Injury Patricia Mucia, RN Family Life After Pediatric Spinal Injury Dawn Sheaffer, MSW Rehabilitation ...

  7. The Effect of Recessions on Firms’ Boundaries

    DEFF Research Database (Denmark)

    Knudsen, Eirik Sjåholm; Foss, Kirsten

    2014-01-01

    The economic theory of the firm offers conflicting predictions of how the two major effects of recessions, changes in demand and access to credit, affect firm boundaries. Using data on Norwegian firms in the recent recession, we find support for both increased and reduced vertical integration...... explanation for the conflicting theoretical predictions regarding vertical integration in response to demand and credit shocks....

  8. Life-long course and molecular characterization of the original Dutch family with epidermolysis bullosa simplex with muscular dystrophy due to a homozygous novel plectin point mutation

    NARCIS (Netherlands)

    Koss-Harnes, D; Hoyheim, B; Jonkman, MF; De Groot, WP; De Weerdt, CJ; Nikolic, B; Wiche, G; Gedde-Dahl, T

    Plectin is one of the largest and most versatile cytolinker proteins known. Cloned and sequenced in 1991, it was later shown to have nonsense mutations in recessive epidermolysis bullosa with muscular dystrophy. A dominant mutation in the gene was found to cause epidermolysis bullosa simplex Ogna

  9. Spinal cord contusion.

    Science.gov (United States)

    Ju, Gong; Wang, Jian; Wang, Yazhou; Zhao, Xianghui

    2014-04-15

    Spinal cord injury is a major cause of disability with devastating neurological outcomes and limited therapeutic opportunities, even though there are thousands of publications on spinal cord injury annually. There are two major types of spinal cord injury, transaction of the spinal cord and spinal cord contusion. Both can theoretically be treated, but there is no well documented treatment in human being. As for spinal cord contusion, we have developed an operation with fabulous result.

  10. Vibration therapy tolerated in children with Duchenne muscular dystrophy: a pilot study.

    Science.gov (United States)

    Myers, Kenneth A; Ramage, Barbara; Khan, Aneal; Mah, Jean K

    2014-07-01

    Duchenne muscular dystrophy is an X-linked recessive muscular dystrophy. Clinical management primarily involves rehabilitation strategies aimed at preserving functional mobility as long as possible. Side-alternating vibration therapy is a rehabilitation intervention that has shown promise in a number of different neuromuscular disorders, and has the potential to preserve strength, functional mobility, and bone mass. There has been little research regarding the tolerance to side-alternating vibration therapy in muscle diseases such as Duchenne muscular dystrophy. Four patients were recruited for a pilot study assessing the safety and tolerance of side-alternating vibration therapy in individuals with Duchenne muscular dystrophy. All patients participated in a 4-week training period involving side-alternating vibration therapy sessions three times per week. Serum creatine kinase was measured, and adverse effects reviewed at each session with functional mobility assessed before and after the training period. All patients tolerated the training protocol well, and there were no major changes in functional mobility. One patient had a transient increase in creatine kinase during the study; however, levels of this enzyme were stable overall when comparing the pretraining and posttraining values. Some patients reported subjective improvement during the training period. Side-alternating vibration therapy is well tolerated in children with Duchenne muscular dystrophy and may have potential to improve or maintain functional mobility and strength in these patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Klinefelter′s syndrome associated with progressive muscular atrophy simulating Kennedy′s disease

    OpenAIRE

    Pedro Enrique Jiménez Caballero

    2012-01-01

    Kennedy's disease, an X-linked spinal and bulbar muscular atrophy, is characterized by loss of lower motor neurons. Mild sensory deficits, gynecomastia and infertility may be observed. Klinefelter's syndrome is a variation of sex chromosome disorder characterized by hypogonadism, gynecomastia and azoospermia, and the most frequent karyotype is XXY. A 55-year-old man who presented with slowly progressive and diffuse neurogenic muscle atrophy without bulbar or sensory symptoms. He also had Klin...

  12. 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...

  13. Metabolismo muscular en el ejercicio

    OpenAIRE

    Martín Martín, Laura

    2017-01-01

    Fundamentos: Cada vez son más las personas que realizan algún tipo de actividad física, pero pocas son las que poseen un verdadero conocimiento de los procesos que se desencadenan a nivel muscular y la influencia de la alimentación en la misma. El objetivo de este trabajo es ofrecer información de manera general sobre el metabolismo muscular. Métodos: Revisión bibliográfica de artículos y documentos consultando bases de datos y libros. La mayor parte del análisis ha sido ext...

  14. Respiratory function in facioscapulohumeral muscular dystrophy 1

    NARCIS (Netherlands)

    Wohlgemuth, M.; Horlings, G.C.; Kooi, E.L. van der; Gilhuis, H.J.; Hendriks, J.C.M.; Maarel, S.M. van der; Engelen, B.G.M. van; Heijdra, Y.F.; Padberg, G.W.A.M.

    2017-01-01

    To test the hypothesis that wheelchair dependency and (kypho-)scoliosis are risk factors for developing respiratory insufficiency in facioscapulohumeral muscular dystrophy, we examined 81 patients with facioscapulohumeral muscular dystrophy 1 of varying degrees of severity ranging from ambulatory

  15. What Are the Types of Muscular Dystrophy?

    Science.gov (United States)

    ... muscular dystrophy? There are more than 30 forms of muscular dystrophy (MD), with information on the primary types included in the table below. 1 Duchenne (DMD) What It Is Common Symptoms How It ...

  16. CT evaluation of the anterior epitympanic recess

    International Nuclear Information System (INIS)

    Yamasoba, Tatsuya; Kikuchi, Shigeru; Takeuchi, Naonobu; Harada, Takehiko; Nomura, Yasuya

    1991-01-01

    The structures of the anterior epitympanic recess and its surrounding tissues were examined among non-inflammatory ear, chronic otitis media with central perforation and cholesteatoma, using axial scans of high resolution computed tomography. The length and width of the recess, as well as the number of the slices where the cog was determined, had no significant differences among them. Thus, the bony structure of the recess was considered to be seldom influenced by inflammatory processes. In the non-inflammatory ear, the degree of pneumatization around the recess was similar to that of the petrous apex cells and lower than that of the mastoid cells. In the chronic otitis media with central perforation and cholesteatoma, the pneumatization of the whole temporal bones was suppressed and the tendency was also found that the cells around the recess were less pneumatized than the mastoid cells. When cholesteatoma invaded into the anterior epitympanic recess, the destruction of the bony protrusion of the lateral wall between the recess and the epitympanum was recognized, as well as the disappearance of the cog. The bony protrusion was considered to be an inferior extention of the cog toward the anterior tympanic spine. (author)

  17. Dysphagia in facioscapulohumeral muscular dystrophy.

    NARCIS (Netherlands)

    Wohlgemuth, M.; Swart, B.J.M. de; Kalf, J.G.; Joosten, F.B.M.; Vliet, A.M. van der; Padberg, G.W.A.M.

    2006-01-01

    Dysphagia is not considered a symptom of facioscapulohumeral muscular dystrophy (FSHD). In this study, the authors found that dysphagia does occur in patients with advanced FSHD showing mild involvement of the jaw and lingual muscles. Dysphagia is seldom life threatening in these patients. The

  18. Glucocorticoids for Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2013-07-01

    Full Text Available Investigators at the Dubowitz Neuromuscular Centre, Great Ormond Street Hospital, and other centers in the UK, conducted a prospective longitudinal study across 17 neuromuscular centers in the UK of 360 boys aged 3-15 years with Duchenne muscular dystrophy who were treated with daily or intermittent (10 days on/10 days off prednisolone for a mean duration of 4 years.

  19. BEEF CATTLE MUSCULARITY CANDIDATE GENES

    Directory of Open Access Journals (Sweden)

    Irida Novianti

    2010-04-01

    Full Text Available Muscularity is a potential indicator for the selection of more productive cattle. Mapping quantitative trait loci (QTL for traits related to muscularity is useful to identify the genomic regions where the genes affecting muscularity reside. QTL analysis from a Limousin-Jersey double backcross herd was conducted using QTL Express software with cohort and breed as the fixed effects. Nine QTL suggested to have an association with muscularity were identified on cattle chromosomes BTA 1, 2, 3, 4, 5, 8, 12, 14 and 17. The myostatin gene is located at the centromeric end of chromosome 2 and not surprisingly, the Limousin myostatin F94L variant accounted for the QTL on BTA2. However, when the myostatin F94L genotype was included as an additional fixed effect, the QTL on BTA17 was also no longer significant. This result suggests that there may be gene(s that have epistatic effects with myostatin located on cattle chromosome 17. Based on the position of the QTL in base pairs, all the genes that reside in the region were determined using the Ensembl data base (www.ensembl.org. There were two potential candidate genes residing within these QTL regions were selected. They were Smad nuclear interacting protein 1 (SNIP1 and similar to follistatin-like 5 (FSTL5. (JIIPB 2010 Vol 20 No 1: 1-10

  20. Inherited myopathies and muscular dystrophies

    NARCIS (Netherlands)

    Cardamone, Michael; Darras, Basil T.; Ryan, Monique M.

    The inherited myopathies and muscular dystrophies are a diverse group of muscle diseases presenting with common complaints and physical signs: weakness, motor delay, and respiratory and bulbar dysfunction. The myopathies are caused by genetic defects in the contractile apparatus of muscle, and

  1. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Abuse and Spinal Cord Injury Allen Heinemann, PhD How Peer Counseling Works Julie Gassaway, MS, RN Pediatric Injuries Pediatric Spinal ... What is a spinal cord injury? play_arrow How does the spinal cord work? play_arrow Why is the level of a ...

  2. Spinal deformity in patients with Sotos syndrome (cerebral gigantism).

    Science.gov (United States)

    Tsirikos, Athanasios I; Demosthenous, Nestor; McMaster, Michael J

    2009-04-01

    Retrospective review of a case series. To present the clinical characteristics and progression of spinal deformity in patients with Sotos syndrome. There is limited information on the development of spinal deformity and the need for treatment in this condition. The medical records and spinal radiographs of 5 consecutive patients were reviewed. All patients were followed to skeletal maturity (mean follow-up: 6.6 y). The mean age at diagnosis of spinal deformity was 11.9 years (range: 5.8 to 14.5) with 4 patients presenting in adolescence. The type of deformity was not uniform. Two patients presented in adolescence with relatively small and nonprogressive thoracolumbar and lumbar scoliosis, which required observation but no treatment until the end of spinal growth. Three patients underwent spinal deformity correction at a mean age of 11.7 years (range: 6 to 15.4). The first patient developed a double structural thoracic and lumbar scoliosis and underwent a posterior spinal arthrodesis extending from T3 to L4. Five years later, she developed marked degenerative changes at the L4/L5 level causing symptomatic bilateral lateral recess stenosis and affecting the L5 nerve roots. She underwent spinal decompression at L4/L5 and L5/S1 levels followed by extension of the fusion to the sacrum. The second patient developed a severe thoracic kyphosis and underwent a posterior spinal arthrodesis. The remaining patient presented at the age of 5.9 years with a severe thoracic kyphoscoliosis and underwent a 2-stage antero-posterior spinal arthrodesis. The development of spinal deformity is a common finding in children with Sotos syndrome and in our series it occurred in adolescence in 4 out of 5 patients. There is significant variability on the pattern of spine deformity, ranging from a scoliosis through kyphoscoliosis to a pure kyphosis, and also the age at presentation and need for treatment.

  3. [Central Nervous Involvement in Patients with Fukuyama Congenital Muscular Dystrophy].

    Science.gov (United States)

    Ishigaki, Keiko

    2016-02-01

    Fukuyama congenital muscular dystrophy (FCMD), the second most common muscular dystrophy in the Japanese population, is an autosomal recessive disorder caused by mutations in the fukutin (FKTN) gene. The main features of FCMD are a combination of infantile-onset hypotonia, generalized muscle weakness, eye abnormalities and central nervous system involvement with mental retardation and seizures associated with cortical migration defects. The FKTN gene product is thought to be necessary for maintaining migrating neurons in an immature state during migration, and for supporting migration via α-dystroglycan in the central nervous system. Typical magnetic resonance imaging findings in FCMD patients are cobblestone lissencephaly and cerebellar cystic lesions. White matter abnormalities with hyperintensity on T(2)-weighted images are seen especially in younger patients and those with severe phenotypes. Most FCMD patients are mentally retarded and the level is moderate to severe, with IQs ranging from 30 to 50. In our recent study, 62% of patients developed seizures. Among them, 71% had only febrile seizures, 6% had afebrile seizures from the onset, and 22% developed afebrile seizures following febrile seizures. Most patients had seizures that were controllable with just 1 type of antiepileptic drug, but 18% had intractable seizures that must be treated with 3 medications.

  4. Hospital Capital Investment During the Great Recession.

    Science.gov (United States)

    Choi, Sung

    2017-01-01

    Hospital capital investment is important for acquiring and maintaining technology and equipment needed to provide health care. Reduction in capital investment by a hospital has negative implications for patient outcomes. Most hospitals rely on debt and internal cash flow to fund capital investment. The great recession may have made it difficult for hospitals to borrow, thus reducing their capital investment. I investigated the impact of the great recession on capital investment made by California hospitals. Modeling how hospital capital investment may have been liquidity constrained during the recession is a novel contribution to the literature. I estimated the model with California Office of Statewide Health Planning and Development data and system generalized method of moments. Findings suggest that not-for-profit and public hospitals were liquidity constrained during the recession. Comparing the changes in hospital capital investment between 2006 and 2009 showed that hospitals used cash flow to increase capital investment by $2.45 million, other things equal.

  5. Andhidrotic ectodermal dysplasia-autosomal recessive form

    Directory of Open Access Journals (Sweden)

    Inamadar Arun

    1994-01-01

    Full Text Available Anhidrotic ectodermal dysplasia with classical features in 2 sisters is reported. The mode of inheritance in these seems to be autosomal recessive; which is a very rare occurrence.

  6. The Great Recession and confidence in homeownership

    OpenAIRE

    Anat Bracha; Julian Jamison

    2013-01-01

    Confidence in homeownership shifts for those who personally experienced real estate loss during the Great Recession. Older Americans are confident in the value of homeownership. Younger Americans are less confident.

  7. Bond return predictability in expansions and recessions

    DEFF Research Database (Denmark)

    Engsted, Tom; Møller, Stig Vinther; Jensen, Magnus David Sander

    We document that over the period 1953-2011 US bond returns are predictable in expansionary periods but unpredictable during recessions. This result holds in both in-sample and out-of-sample analyses and using both univariate regressions and combination forecasting techniques. A simulation study...... but negative in recessions. The results are also consistent with tests showing that the expectations hypothesis of the term structure holds in recessions but not in expansions. However, the results for bonds are in sharp contrast to results for stocks showing that stock returns are predictable in recessions...... but not in expansions. Thus, our results indicate that there is not a common predictive pattern of stock and bond returns associated with the state of the economy....

  8. The Great Recession and Workers' Health Benefits.

    Science.gov (United States)

    Koh, Kanghyock

    2018-03-01

    During a recession, cost-sharing of employer-sponsored health benefits could increase to reduce labor costs in the U.S. Using a variation in the severity of recession shocks across industries, I find evidence that the enrollment rate of high deductible health plans (HDHPs) among workers covered by employer-sponsored health benefits increased more among firms in industries that experienced severe recession shocks. As potential mechanisms, I study employer-side and worker-side mechanisms. I find that employers changed health benefit offerings to force or incentivize workers to enroll in HDHPs. But I find little evidence of an increase in workers' demand for HDHPs due to a reduction in income. These results suggest that the HDHP enrollment rate increased during the Great Recession, as employers tried to save costs of offering health benefits. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Recessive Dystrophic Epidermolysis Bullosa and Pregnancy.

    Science.gov (United States)

    Boria, F; Maseda, R; Martín-Cameán, M; De la Calle, M; de Lucas, R

    2017-12-01

    Dystrophic epidermolysis bullosa is a rare inherited disease caused by mutations in the COL7A1 gene. Its recessive variant (recessive dystrophic epidermolysis bullosa) is characterized by the absence or considerably reduced expression of type VII collagen, which leads to marked fragility of the skin and mucous membranes and subsequent blister formation, whether spontaneously or following minimal injury. There have been very few reports of this disease in pregnant women. We present 2 cases of pregnant women with recessive dystrophic epidermolysis bullosa managed in our High-Risk Pregnancy Unit at Hospital Universitario La Paz, Madrid, Spain. Both patients underwent full-term cesarean delivery, with no further complications for mother or child. Although recessive dystrophic epidermolysis bullosa increases the risk of maternal complications, a patient is not advised against pregnancy. With adequate monitoring, these patients can fulfil their desire to become mothers. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Hospital Capital Investment During the Great Recession

    Science.gov (United States)

    Choi, Sung

    2017-01-01

    Hospital capital investment is important for acquiring and maintaining technology and equipment needed to provide health care. Reduction in capital investment by a hospital has negative implications for patient outcomes. Most hospitals rely on debt and internal cash flow to fund capital investment. The great recession may have made it difficult for hospitals to borrow, thus reducing their capital investment. I investigated the impact of the great recession on capital investment made by California hospitals. Modeling how hospital capital investment may have been liquidity constrained during the recession is a novel contribution to the literature. I estimated the model with California Office of Statewide Health Planning and Development data and system generalized method of moments. Findings suggest that not-for-profit and public hospitals were liquidity constrained during the recession. Comparing the changes in hospital capital investment between 2006 and 2009 showed that hospitals used cash flow to increase capital investment by $2.45 million, other things equal. PMID:28617202

  11. The diverse impacts of the great recession

    OpenAIRE

    Makoto Nakajima

    2013-01-01

    The Great Recession had a large negative impact on the U.S. economy. Asset prices, most notably stock and house prices, declined substantially, resulting in a loss in wealth for many American households. In this article, Makoto Nakajima documents how diverse households were affected in a variety of dimensions during the Great Recession, in particular between 2007 and 2009, using newly available data from the 2007-2009 Survey of Consumer Finances. He discusses why it is important to look at th...

  12. Academic Performance and the Great Recession

    OpenAIRE

    Adamopoulou, Effrosyni; Tanzi, Giulia M.

    2014-01-01

    In this paper we study how the Great Recession affected university students in terms of performance, with a special focus on the dropout probability. To do so, we use individual-level data on a representative sample of university students in Italy in 2007 and 2011. We measure the severity of the recession in terms of increases in adult and youth unemployment rate and we exploit geographical variation to achieve identification. On the one hand, an increase in adult male unemployment rate deter...

  13. HYDRORECESSION: A toolbox for streamflow recession analysis

    Science.gov (United States)

    Arciniega, S.

    2015-12-01

    Streamflow recession curves are hydrological signatures allowing to study the relationship between groundwater storage and baseflow and/or low flows at the catchment scale. Recent studies have showed that streamflow recession analysis can be quite sensitive to the combination of different models, extraction techniques and parameter estimation methods. In order to better characterize streamflow recession curves, new methodologies combining multiple approaches have been recommended. The HYDRORECESSION toolbox, presented here, is a Matlab graphical user interface developed to analyse streamflow recession time series with the support of different tools allowing to parameterize linear and nonlinear storage-outflow relationships through four of the most useful recession models (Maillet, Boussinesq, Coutagne and Wittenberg). The toolbox includes four parameter-fitting techniques (linear regression, lower envelope, data binning and mean squared error) and three different methods to extract hydrograph recessions segments (Vogel, Brutsaert and Aksoy). In addition, the toolbox has a module that separates the baseflow component from the observed hydrograph using the inverse reservoir algorithm. Potential applications provided by HYDRORECESSION include model parameter analysis, hydrological regionalization and classification, baseflow index estimates, catchment-scale recharge and low-flows modelling, among others. HYDRORECESSION is freely available for non-commercial and academic purposes.

  14. CT findings of muscular dystrophy

    International Nuclear Information System (INIS)

    Saitoh, Hiroshi

    1991-01-01

    CT scans of muscles in patients with limb girdle type (LG), myotonic type (MYD) and Duchenne type (DMD) dystrophies were obtained at five different body levels: the neck, L3 vertebral body, pelvic girdle, thigh and lower leg. CT numbers, cross sectional areas (CSA) and %CSA of muscle or fat were evaluated in each muscle. The characteristic CT patterns for each type of muscular dystrophy were obtained. Compared with DMD, the gracilis and soleus were more severely damaged in LG and the biceps femoris remained relatively preserved among the hamstrings. In addition, the multifidus of the neck and sternocleidomastoid also were more severely damaged in MYD. This study suggests that CT scan will be useful in the differential diagnosis of these types of muscular dystrophy as well as in planning appropriate rehabilitation and detecting damaged muscles. (author)

  15. A Study of CAP-1002 in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy

    Science.gov (United States)

    2018-04-17

    Muscular Dystrophies; Muscular Dystrophy, Duchenne; Muscular Disorders, Atrophic; Muscular Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn

  16. Duchenne and Becker Muscular Dystrophy: Contribution of a Molecular and Immunohistochemical Analysis in Diagnosis in Morocco

    Directory of Open Access Journals (Sweden)

    Hanane Bellayou

    2009-01-01

    Full Text Available Duchenne muscular dystrophy (DMD and Becker muscular dystrophy (BMD are X-linked recessive disorders caused by mutations of the DMD gene located at Xp21. In DMD patients, dystrophin is virtually absent; whereas BMD patients have 10% to 40% of the normal amount. Deletions in the dystrophin gene represent 65% of mutations in DMD/BMD patients. To explain the contribution of immunohistochemical and genetic analysis in the diagnosis of these dystrophies, we present 10 cases of DMD/BMD with particular features. We have analyzed the patients with immunohistochemical staining and PCR multiplex to screen for exons deletions. Determination of the quantity and distribution of dystrophin by immunohistochemical staining can confirm the presence of dystrophinopathy and allows differentiation between DMD and BMD, but dystrophin staining is not always conclusive in BMD. Therefore, only identification involved mutation by genetic analysis can establish a correct diagnosis.

  17. A case of Fukuyama type congenital muscular dystrophy with progressive changes of brain CT scanning

    International Nuclear Information System (INIS)

    Mori, Kenzi; Saijo, Takahiko; Hamaguchi, Hiroshi; Tayama, Masanobu; Kawano, Noboru; Hashimoto, Toshiaki; Miyao, Masuhide

    1988-01-01

    The Fukuyama type congenital muscular dystrophy (F-CMD) has been generally recognized as a well delineated subgroup of progressive muscular dystrophy with uniform clinical and pathological features. But the pathogenesis is not yet clear. Two theories have been proposed ; autosomal recessive inheritance and intrauterine infection. We experienced a female case of F-CMD, and tried serial brain CT scanning from the birth to one year of age. Low density changes of white matter were not found at the first day of her life. But marked brain atrophy and low density changes of white matter were found after three months. We propose that CT examination should be repeated from early stage to clarify the pathogenesis of F-CMD. (AUTHOR)

  18. Mild and severe muscular dystrophy caused by a single {gamma}-sarcoglycan mutation

    Energy Technology Data Exchange (ETDEWEB)

    McNally, E.M.; Boennemann, C.G.; Lidov, H.G.W. [Brigham and Women`s Hospital, Boston, MA (United States)] [and others

    1996-11-01

    Autosomal recessive muscular dystrophy is genetically heterogeneous. One form of this disorder, limb-girdle muscular dystrophy type 2C (LGMD 2C), is prevalent in northern Africa and has been shown to be associated with a single mutation in the gene encoding the dystrophin-associated protein {gamma}-sarcoglycan. The previous mutation analysis of {gamma}-sarcoglycan required the availability of muscle biopsies. To establish a mutation assay for genomic DNA, the intron-exon structure of the {gamma}-sarcoglycan gene was determined, and primers were designed to amplify each of the exons encoding {gamma}-sarcoglycan. We studied a group of Brazilian muscular dystrophy patients for mutations in the {gamma}-sarcoglycan gene. These patients were selected on the basis of autosomal inheritance and/or the presence of normal dystrophin and/or deficiency of {alpha}-sarcoglycan immunostaining. Four of 19 patients surveyed had a single, homozygous mutation in the {gamma}-sarcoglycan gene. The mutation identified in these patients, all of African-Brazilian descent, is identical to that seen in the North African population, suggesting that even patients of remote African descent may carry this mutation. The phenotype in these patients varied considerably. Of four families with an identical mutation, three have a severe Duchenne-like muscular dystrophy. However, one family has much milder symptoms, suggesting that other loci may be present that modify the severity of the clinical course resulting from {gamma}-sarcoglycan gene mutations. 19 refs., 5 figs., 3 tabs.

  19. Aeroacoustical Study of the Tgv Pantograph Recess

    Science.gov (United States)

    NOGER, C.; PATRAT, J. C.; PEUBE, J.; PEUBE, J. L.

    2000-03-01

    The general focus of this aerodynamic noise research, induced by turbulent incompressible flow, is to improve our knowledge of acoustic production mechanisms in the TGV pantograph recess in order to be able to reduce the radiated noise. This work is performed under contract with SNCF as a part of the German-French Cooperation DEUFRAKO K2, and is supported by French Ministries for Transport and Research. Previous studies on TGV noise source locations (DEUFRAKO K) have identified the pantograph recess as one of the important aerodynamic noise sources, for speeds higher than 300 km/h, due to flow separation. The pantograph recess is a very complex rectangular cavity, located both on the power car and the first coach roofs of the TGV, and has not been studied before due to the complex shapes. Its aeroacoustic features are investigated experimentally in a low-subsonic wind tunnel, on a realistic 1/7th scale mock-up both with and without pantographs. Flow velocities, estimated with hot-wire anemometry, and parietal visualizations show the flow to reattach on the recess bottom wall and to separate again at the downstream face. Wall pressure fluctuations and “acoustic” measurements using 14 and 12 in microphones respectively are also measured to qualify the flow: no aerodynamic or acoustic oscillations are observed. The study indicates that the pantograph recess has a different behaviour compared to the usual cavity grazing flows.

  20. Tratamento cirúrgico da escoliose em pacientes com amiotrofia espinhal com parafusos pediculares (instrumental de 3ª geração e complicações precoces Tratamiento quirúrgico de la escoliosis en pacientes con amiotrofia espinal con tornillos pediculares (instrumental de 3ª generación y complicaciones precoces Surgical treatment of scoliosis in spinal muscular atrophy with pedicle screws (third generation instrumentation and early complications

    Directory of Open Access Journals (Sweden)

    Daniel Cantarelli dos Santos

    2010-06-01

    pacientes tuvieron complicaciones precoces (31.2% con buena resolución. CONCLUSIÓN: el tratamiento quirúrgico de la escoliosis en pacientes con amiotrofia espinal, con artrodesis vía posterior utilizando tornillos pediculares, tiene gran potencial de corrección de la deformidad coronal y de la oblicuidad pélvica, sin grandes complicaciones en el postoperatorio precoz.OBJECTIVES: to report the results on the treatment of scoliosis in spinal muscular atrophy, using posterior arthrodesis with pedicle screws. METHODS: a retrospective study was carried out with 16 patients who underwent posterior spinal fusion with pedicle screws. The general status of the patients, correction of the Cobb angle, correction of pelvic obliquity and early complications were analyzed. RESULTS: the initial Cobb angle mean was 94.6º (65 to 132º turning into 40,4º (2 to 20º after the surgery, correction of 57.2%. The initial pelvic obliquity mean was 34.7º(25 to 56º turning into 11.3º (0 to 20º, correction of 67.4%. CONCLUSIONS: the treatment of scoliosis in spinal muscular atrophy using posterior arthrodesis with pedicle screws presents a great potential of correction for the coronal deformity and pelvic obliquity, without serious early complications.

  1. Lesiones musculares en el deporte. Muscular injuries in sport.

    Directory of Open Access Journals (Sweden)

    Jiménez Díaz, José Fernando

    2006-04-01

    Full Text Available ResumenDurante la práctica de la actividad física hay una gran incidencia de lesiones musculares, si bien se han llevado a cabo pocos estudios clínicos sobre el tratamiento y la resolución de las mismas. Desde el punto de vista etiopatogénico, hay que señalar que la incidencia de lesión es mayor en aquellos músculos poliarticulares en condiciones de acumulación de fatiga y con condiciones ambientales desfavorables. La clasificación de las lesiones musculares permite distinguir entre aquellas que no afectan a la fascia produciéndose un sangrado dentro del mismo (intramuscular o bien si la fascia también se rompe, el sangrado se sitúa entre los diferentes músculos (intermuscular. El tratamiento de estas lesiones se realizará combinando reposo, compresión, aplicación de frío y elevación del área lesionada así como el desarrollo de un adecuado programa de readaptación funcional que permita al jugador incorporarse lo antes posible a la dinámica del equipo. En la actualidad se está llevando a cabo opciones terapéuticas con factores de crecimiento, terapia génica y células madre, si bien todavía no están lo suficientemente desarrolladas.AbstractDuring the practice of the physical activity there is a great effect of muscular injuries, though few clinical studies have been carried out on the treatment and the resolution of the same ones. Inside the reasons it is necessary to indicate that the effect of injury is major in those muscles you will polyarticulate in situation of fatigue and with environmental unfavorable conditions.The classification of the muscular injuries allows to distinguish between those that do not affect the fascia producing the bled intramuscular or if the fascia also breaks, the bled one places between the different muscles (intermuscular.The treatment will be realized combining rest, compression, application of cold and elevation of these injuries as well as the development of a program of functional

  2. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... About Media Donate Spinal Cord Injury Medical Expert Videos ... Home Kim Eberhardt Muir, MS Coping with a New Injury Robin Dorman, PsyD Sex and Fertility After Spinal Cord Injury Diane M. ...

  3. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... of Spinal Cord Injury Rehabilitation Kristine Cichowski, MS Occupational Therapy after Spinal Cord Injury Katie Powell, OT ... does not provide medical advice, recommend or endorse health care products or services, or control the information ...

  4. Spinal Cord Dysfunction (SCD)

    Data.gov (United States)

    Department of Veterans Affairs — The Spinal Cord Dysfunction (SCD) module supports the maintenance of local and national registries for the tracking of patients with spinal cord injury and disease...

  5. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... OT Anne Bryden, OT The Role of the Social Worker after Spinal Cord Injury Patti Rogers, SW Marguerite ... play_arrow What are the latest developments in the use of electrical stimulation for spinal ...

  6. Spinal Cord Injury 101

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    Full Text Available ... with SCI Personal Experiences by Topic Resources Peer Counseling Blog About Media Donate close search Understanding Spinal ... with SCI Personal Experiences by Topic Resources Peer Counseling Blog About Media Donate Spinal Cord Injury Medical ...

  7. Spinal Cord Injury 101

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    Full Text Available ... Injury Facts and Figures Care and Treatment After SCI Spinal Cord Injury Rehabilitation Pediatric Spinal Cord Injuries Video Library SCI Medical Experts People Living with SCI Personal Experiences ...

  8. Spinal Cord Injury 101

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    Full Text Available ... Cord Injury Rehabilitation Pediatric Spinal Cord Injuries Video Library SCI Medical Experts People Living with SCI Personal ... Cord Injury Rehabilitation Pediatric Spinal Cord Injuries Video Library SCI Medical Experts People Living with SCI Personal ...

  9. Spinal Cord Injury 101

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    Full Text Available ... of spinal cord injuries? play_arrow What does stem-cell research on animals tell us? play_arrow When can we expect stem-cell treatments to become available for spinal cord injuries? ...

  10. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... spinal cord injuries? play_arrow What does stem-cell research on animals tell us? play_arrow When can we expect stem-cell treatments to become available for spinal cord injuries? ...

  11. Spinal Cord Injury 101

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    Full Text Available ... Resources Peer Counseling Blog About Media Donate close search Understanding Spinal Cord Injury What is a Spinal ... health care products or services, or control the information found on external websites. The Hill Foundation is ...

  12. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Spinal Cord Injuries Video Library SCI Medical Experts People Living with SCI Personal Experiences by Topic Resources ... Spinal Cord Injuries Video Library SCI Medical Experts People Living with SCI Personal Experiences by Topic Resources ...

  13. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... play_arrow What are the chances of regaining feeling and mobility after a spinal cord injury? play_arrow How long does it usually take for feeling and movement to return after a spinal cord ...

  14. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... RN Pediatric Injuries Pediatric Spinal Cord Injury 101 Lawrence Vogel, MD The Basics of Pediatric SCI Rehabilitation ... Rogers, PT Recreational Therapy after Spinal Cord Injury Jennifer Piatt, PhD David Chen, MD Read Bio Medical ...

  15. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Disabilities Photography by Rona Talcott Website by Mobile Marketing LLC Understanding Spinal Cord Injury About Us Expert Videos Contact Us Personal Experience Videos Blog Videos By Topic Media Resources Donate to support families facing spinal cord ...

  16. Spinal cord stimulation

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/007560.htm Spinal cord stimulation To use the sharing features on this page, please enable JavaScript. Spinal cord stimulation is a treatment for pain that uses ...

  17. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Spinal Cord Injury 101 David Chen, MD Preventing Pressure Sores Mary Zeigler, MS Transition from Hospital to ... a spinal cord injury? play_arrow Why are high-dose steroids often used right after an injury? ...

  18. Spinal segmental dysgenesis

    Directory of Open Access Journals (Sweden)

    N Mahomed

    2009-06-01

    Full Text Available Spinal segmental dysgenesis is a rare congenital spinal abnormality , seen in neonates and infants in which a segment of the spine and spinal cord fails to develop normally . The condition is segmental with normal vertebrae above and below the malformation. This condition is commonly associated with various abnormalities that affect the heart, genitourinary, gastrointestinal tract and skeletal system. We report two cases of spinal segmental dysgenesis and the associated abnormalities.

  19. Evaluation of muscle strength and motor abilities in children with type II and III spinal muscle atrophy treated with valproic acid

    Directory of Open Access Journals (Sweden)

    Zanoteli Edmar

    2011-03-01

    Full Text Available Abstract Background Spinal muscular atrophy (SMA is an autosomal recessive disorder that affects the motoneurons of the spinal anterior horn, resulting in hypotonia and muscle weakness. The disease is caused by deletion or mutation in the telomeric copy of SMN gene (SMN1 and clinical severity is in part determined by the copy number of the centromeric copy of the SMN gene (SMN2. The SMN2 mRNA lacks exon 7, resulting in a production of lower amounts of the full-length SMN protein. Knowledge of the molecular mechanism of diseases has led to the discovery of drugs capable of increasing SMN protein level through activation of SMN2 gene. One of these drugs is the valproic acid (VPA, a histone deacetylase inhibitor. Methods Twenty-two patients with type II and III SMA, aged between 2 and 18 years, were treated with VPA and were evaluated five times during a one-year period using the Manual Muscle Test (Medical Research Council scale-MRC, the Hammersmith Functional Motor Scale (HFMS, and the Barthel Index. Results After 12 months of therapy, the patients did not gain muscle strength. The group of children with SMA type II presented a significant gain in HFMS scores during the treatment. This improvement was not observed in the group of type III patients. The analysis of the HFMS scores during the treatment period in the groups of patients younger and older than 6 years of age did not show any significant result. There was an improvement of the daily activities at the end of the VPA treatment period. Conclusion Treatment of SMA patients with VPA may be a potential alternative to alleviate the progression of the disease. Trial Registration ClinicalTrials.gov: NCT01033331

  20. Recession-An issue for organizations

    Directory of Open Access Journals (Sweden)

    Daniel GEORGESCU

    2009-12-01

    Full Text Available The reality in all organization is that the directors and board are in the position of highest influence and their primary responsibility is leadership. As such, considering the consequences of a recession such as we currently face is not the time for directors to abdicate their responsibilities – it is time for governance leadership. The directors and the board must think and respond strategically. The article shows a matrix for positioning the general manager in recession that is similarly with BCG matrix and in the final a table with a set of essential questions for helping the board in new strategies building.

  1. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... the spinal cord work? play_arrow Why is the level of a spinal cord injury important? play_arrow What role does “compression” play in a spinal cord injury? play_arrow Why are high-dose steroids often used right after an injury? play_arrow What is meant ...

  2. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... arrow What is the “Spinal Cord Injury Model Systems” program? play_arrow What are the most promising new treatments for spinal cord injuries? play_arrow What are the latest developments in the use of electrical stimulation for spinal cord injuries? play_arrow ...

  3. Spinal Cord Injuries

    Science.gov (United States)

    ... forth between your body and your brain. A spinal cord injury disrupts the signals. Spinal cord injuries usually begin with a blow that fractures or ... down on the nerve parts that carry signals. Spinal cord injuries can be complete or incomplete. With a complete ...

  4. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... injury? play_arrow How does the spinal cord work? play_arrow Why is the level of a spinal cord injury important? play_arrow What role does “compression” play in a spinal cord injury? play_arrow Why are high-dose steroids often used right after an injury? play_arrow What is meant ...

  5. Immunohistochemical alterations of dystrophin in congenital muscular dystrophy Alterações imuno-hístoquímicas da distrofina na distrofia muscular congênita

    Directory of Open Access Journals (Sweden)

    Lineu Cesar Werneck

    1995-09-01

    Full Text Available The dystrophin distribution in the plasma muscle membrane using immunohystochemistry was studied in 22 children with congenital muscular dystrophy. The dystrophin was detected by immunofluorescence in muscle biopsy through a polyclonal antibody. All the cases had patchy interruptions of the fluorescence in the plasma membrane. A large patchy interruption of the sarcolemma was found in 17 cases, small interruption in 12, and a combination of large and small patchy discontinuity in 7. Small gaps around the fiber like a rosary were found in 15 cases. The frequency of these abnormalities ranged cases from: all fibers in 5 cases, frequent in 8, occasional in 5, and rare in 4. Five cases had total absence of immunofluorescence. These results suggest that the dystrophin expression is abnormal in this group of children and that this type of abnormalities can not be differentiated from early Becker muscular dystrophy nor childhood autosomal recessive muscular dystrophy through immunohystochemistry alone.Foi estudada a distribuição da distrofina na membrana plasmática das fibras musculares em 22 crianças com distrofia muscular congênita, através de técnicas de imuno-histoquímica. A distrofina foi identificada nas biópsias musculares processadas a fresco, por técnicas de imunofluorescência utilizando anticorpos policlonais. Todos os casos tinham interrupções da imunofluorescência na membrana plasmática. Em 17 elas eram grandes, em 12 eram pequenas e em 7 eram de ambos os tipos. Fibras com interrupções pequenas e constantes, como um rosário, foram vistas em 15 casos. Essas anormalidades estavam presentes em todas as fibras em 5 casos, eram frequentes em 8, ocasionais em 5 e raras em 4. Cinco casos mostraram fibras sem distrofina. Esses dados sugerem que a expressão da distrofina é anormal nesse grupo de crianças. Essas anormalidades podem também ser encontradas em casos precoces de distrofia muscular de Becker e distrofia autoss

  6. Muscular Calf Injuries in Runners.

    Science.gov (United States)

    Fields, Karl B; Rigby, Michael D

    2016-01-01

    Calf pain is a common complaint among runners of all ages but is most frequent in masters athletes. This article focuses on injuries to the triceps surae or true 'calf muscles.' The most common calf injury is a tear of the medial gastrocnemius muscle (Tennis Leg) but other structures including the lateral gastrocnemius, plantaris and soleus also may be the cause of muscular pain. This article looks at the presentation, evaluation, and treatment of these injuries. We also highlight some examples of musculoskeletal ultrasound which is a valuable tool for rapid diagnosis of the cause and extent of injury.

  7. Genetics Home Reference: Duchenne and Becker muscular dystrophy

    Science.gov (United States)

    ... Conditions Duchenne and Becker muscular dystrophy Duchenne and Becker muscular dystrophy Printable PDF Open All Close All Enable Javascript ... dystrophy occur almost exclusively in males. Duchenne and Becker muscular dystrophies have similar signs and symptoms and are caused ...

  8. Anti‐Ma2 associated paraneoplastic neurological syndrome presenting as encephalitis and progressive muscular atrophy

    Science.gov (United States)

    Waragai, M; Chiba, A; Uchibori, A; Fukushima, T; Anno, M; Tanaka, K

    2006-01-01

    A 36 year old man with a history of testicular germ cell tumour presented six months after bilateral orchidectomy with progressive amnesia, irritability, vertical gaze palsy, and generalised seizures. Eight months after initial onset of symptoms, he demonstrated a head drop with muscular atrophy of the upper limbs, shoulder girdle, and posterior neck. He reported no sensory disturbances and his sensory examination was normal. The overall clinical presentation was consistent with motor neurone disease. Cerebrospinal fluid analysis revealed mild pleocytosis and increased protein concentration. Serum and cerebrospinal fluid were positive for the anti‐Ma2 antibody by western blot analysis and immunostaining. Abnormal high signal in the grey matter was noted in the cervical spinal cord and brain by T2 weighted magnetic resonance imaging (MRI). The patient was treated with corticosteroids, intravenous immunoglobulin, and antiepileptic medication. The patient improved clinically and symptom progression ceased after initiation of treatment. There was complete resolution of the abnormal brain MRI lesions; however, the cervical spinal cord MRI lesion and muscular atrophy remained unchanged. It is suggested that the anti‐Ma2 antibody is involved not only in encephalitis, but may also play a role in the cervical spinal cord lesions resulting in a motor neurone disease‐like presentation. PMID:16361608

  9. Anti-Ma2 associated paraneoplastic neurological syndrome presenting as encephalitis and progressive muscular atrophy.

    Science.gov (United States)

    Waragai, M; Chiba, A; Uchibori, A; Fukushima, T; Anno, M; Tanaka, K

    2006-01-01

    A 36 year old man with a history of testicular germ cell tumour presented six months after bilateral orchidectomy with progressive amnesia, irritability, vertical gaze palsy, and generalised seizures. Eight months after initial onset of symptoms, he demonstrated a head drop with muscular atrophy of the upper limbs, shoulder girdle, and posterior neck. He reported no sensory disturbances and his sensory examination was normal. The overall clinical presentation was consistent with motor neurone disease. Cerebrospinal fluid analysis revealed mild pleocytosis and increased protein concentration. Serum and cerebrospinal fluid were positive for the anti-Ma2 antibody by western blot analysis and immunostaining. Abnormal high signal in the grey matter was noted in the cervical spinal cord and brain by T2 weighted magnetic resonance imaging (MRI). The patient was treated with corticosteroids, intravenous immunoglobulin, and antiepileptic medication. The patient improved clinically and symptom progression ceased after initiation of treatment. There was complete resolution of the abnormal brain MRI lesions; however, the cervical spinal cord MRI lesion and muscular atrophy remained unchanged. It is suggested that the anti-Ma2 antibody is involved not only in encephalitis, but may also play a role in the cervical spinal cord lesions resulting in a motor neurone disease-like presentation.

  10. Trauma: Spinal Cord Injury.

    Science.gov (United States)

    Eckert, Matthew J; Martin, Matthew J

    2017-10-01

    Injuries to the spinal column and spinal cord frequently occur after high-energy mechanisms of injury, or with lower-energy mechanisms, in select patient populations like the elderly. A focused yet complete neurologic examination during the initial evaluation will guide subsequent diagnostic procedures and early supportive measures to help prevent further injury. For patients with injury to bone and/or ligaments, the initial focus should be spinal immobilization and prevention of inducing injury to the spinal cord. Spinal cord injury is associated with numerous life-threatening complications during the acute and long-term phases of care that all acute care surgeons must recognize. Published by Elsevier Inc.

  11. Human spinal motor control

    DEFF Research Database (Denmark)

    Nielsen, Jens Bo

    2016-01-01

    Human studies in the past three decades have provided us with an emerging understanding of how cortical and spinal networks collaborate to ensure the vast repertoire of human behaviors. We differ from other animals in having direct cortical connections to spinal motoneurons, which bypass spinal...... the central motor command by opening or closing sensory feedback pathways. In the future, human studies of spinal motor control, in close collaboration with animal studies on the molecular biology of the spinal cord, will continue to document the neural basis for human behavior. Expected final online...

  12. Pattern of Glacier Recession in Indian Himalaya

    Science.gov (United States)

    Singh, Ajay; Patwardhan, Anand

    All currently available climate models predict a near-surface warming trend under the influence of rising levels of greenhouse gases in the atmosphere. In addition to the direct effects on climate — for example, on the frequency of heat waves — this increase in surface temperatures has important consequences for the cryosphere subsequently hydrological cycle, particularly in regions where water supply is currently dominated by melting snow or ice. The Indian Himalayan region occupies a special place in the mountain ecosystems of the world. These geodynamically young mountains are not only important from the standpoint of climate and as a provider of life, giving water to a large part of the Indian subcontinent, but they also harbor a rich variety of flora, fauna, human communities and cultural diversity. Glaciers in this region are changing in area as well as in volume like those in other parts of the world. Studies have been carried out for recession in some of these glaciers using remote sensing as well as field observation techniques. Spatiotemporal pattern in the recession rate of the studied glaciers has been presented in this paper. Plausible causes for the recession have been also discussed. Finally, future scopes for observation and analysis in glaciers recession have been suggested.

  13. Nevada, the Great Recession, and Education

    Science.gov (United States)

    Verstegen, Deborah A.

    2013-01-01

    The impact of the Great Recession and its aftermath has been devastating in Nevada, especially for public education. This article discusses the budget shortfalls and the impact of the economic crisis in Nevada using case study methodology. It provides a review of documents, including Governor Gibbon's proposals for the public K-12 education system…

  14. The Labor Market and the Great Recession

    NARCIS (Netherlands)

    Hobijn, B.; Elsby, M.W.L.; Sahin, A.

    2010-01-01

    From the perspective of a wide range of labor market outcomes, the recession that began in 2007 represents the deepest downturn in the postwar era. Early on, the nature of labor market adjustment displayed a notable resemblance to that observed in past severe downturns. During the latter half of

  15. ECONOMIC RECESSION A CALL FOR COMPETITIVE INTELLIGENCE

    OpenAIRE

    Lucian Marius IVANOV

    2011-01-01

    Global recession brought about a significant growth in competition, stressing the need for relevant and reliable intelligence as a support for making efficient strategic decisions. The recent circumstances draw the attention far more earnestly this time on the need for an intelligence structure within companies to be ready for sustaining business management endeavours in line with increasing competitiveness, protection and promotion of their interests.

  16. Recess for Students with Visual Impairments

    Science.gov (United States)

    Lucas, Matthew D.

    2010-01-01

    During recess, the participation of a student with visual impairments in terms of movement can often be both challenging and rewarding for the student and general education teacher. This paper will address common characteristics of students with visual impairments and present basic solutions to improve the participation of these students in the…

  17. Recessive Epidermolysis Bullosa simplex- A case report

    African Journals Online (AJOL)

    Ademu

    Abstract: Background:Epidermolysis bullosa simplex (EBS) is characterized by intraepidermal blister formation, most commonly appearing in early infancy. Many variants of EBS exist; the four most common variants are inherited in an autosomal dominant fashion. The recessive forms are rare and less reported in our ...

  18. Results after gastrocnemius recession in 73 patients.

    Science.gov (United States)

    Molund, Marius; Paulsrud, Øyvind; Ellingsen Husebye, Elisabeth; Nilsen, Fredrik; Hvaal, Kjetil

    2014-12-01

    Very few studies describe the clinical results and complications following the surgical procedure of gastrocnemius recession. To survey the patient reported outcomes in patients operated with gastrocnemius recession as single procedure for various foot conditions. 93 patients operated with gastrocnemius recession as single procedure between 2006 and 2011 were detected in the database. 73 patients responded to the invitation for study participation. Questionnaires containing patient reported satisfaction, complications, plantar flexion power and visual analog pain score were used for evaluation of the postoperative result. 45/73 (62%) patients reported a good or excellent result. 8/73 (11%) patients reported a significant postoperative complication. 16/73 (22%) patients noted reduced or severely reduced plantar flexion power after surgery. VAS pain score significantly decreased from 7.0 before surgery to 1.8 (p=0.015) after surgery for patients with plantar fasciitis (n=18) and from 5.6 to 2.3 (p<0.01) for patients with metatarsalgia (n=28). Patients treated with gastrocnemius recession for plantar fasciitis demonstrated good clinical results. The complication rate was higher than reported by others. Copyright © 2014 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

  19. Becker muscular dystrophy: an unusual presentation.

    OpenAIRE

    Thakker, P B; Sharma, A

    1993-01-01

    A 15 year old boy who presented with passing painless dark urine was found to have myoglobinuria. His creatine phosphokinase was raised, and a muscle biopsy specimen showed non-specific dystrophic changes. Subsequent DNA analysis led to the diagnosis of Becker muscular dystrophy. Myoglobinuria may be a presenting symptom of Becker muscular dystrophy.

  20. Roentgenological findings in muscular alterations of extremities

    International Nuclear Information System (INIS)

    Palvoelgyi, R.

    1978-01-01

    A survey of roentgenological findings in muscular alterations of extremities based on the author's experiences and on the literature is presented. Following a description of the normal roentgen anatomy, the alterations in different diseases of interstitial lipomatosis are demonstrated. By roentgenological examinations differt muscular lesions of the extremities can be differentiated and the clinical follow-up verified. (orig.) [de

  1. International Spinal Cord Injury

    DEFF Research Database (Denmark)

    Dvorak, M F; Itshayek, E; Fehlings, M G

    2015-01-01

    STUDY DESIGN: Survey of expert opinion, feedback and final consensus. OBJECTIVE: To describe the development and the variables included in the International Spinal Cord Injury (SCI) Spinal Interventions and Surgical Procedures Basic Data set. SETTING: International working group. METHODS......: A committee of experts was established to select and define data elements. The data set was then disseminated to the appropriate committees and organizations for comments. All suggested revisions were considered and both the International Spinal Cord Society and the American Spinal Injury Association endorsed...... spinal intervention and procedure is coded (variables 1 through 7) and the spinal segment level is described (variables 8 and 9). Sample clinical cases were developed to illustrate how to complete it. CONCLUSION: The International SCI Spinal Interventions and Surgical Procedures Basic Data Set...

  2. Postoperative spinal infection mimicking systemic vasculitis with titanium-spinal implants

    Directory of Open Access Journals (Sweden)

    Stathopoulos Konstantinos

    2011-09-01

    Full Text Available Abstract Background Secondary systemic vasculitis after posterior spinal fusion surgery is rare. It is usually related to over-reaction of immune-system, to genetic factors, toxicity, infection or metal allergies. Case Description A 14 year-old girl with a history of extended posterior spinal fusion due to idiopathic scoliosis presented to our department with diffuse erythema and nephritis (macroscopic hemuresis and proteinuria 5 months post surgery. The surgical trauma had no signs of inflammation or infection. The blood markers ESR and CRP were increased. Skin tests were positive for nickel allergy, which is a content of titanium alloy. The patient received corticosteroids systematically (hydrocortisone 10 mg for 6 months, leading to total recess of skin and systemic reaction. However, a palpable mass close to the surgical wound raised the suspicion of a late infection. The patient had a second surgery consisting of surgical debridement and one stage revision of posterior spinal instrumentation. Intraoperative cultures were positive to Staphylococcus aureus. Intravenous antibiotics were administered. The patient is now free of symptoms 24 months post revision surgery without any signs of recurrence of either vasculitis or infection. Literature Review Systemic vasculitis after spinal surgery is exceptionally rare. Causative factors are broad and sometimes controversial. In general, it is associated with allergy to metal ions. This is usually addressed with metal on metal total hip bearings. In spinal surgery, titanium implants are considered to be inert and only few reports have presented cases with systemic vasculitides. Therefore, other etiologies of immune over-reaction should always be considered, such as drug toxicity, infection, or genetic predisposition. Purposes and Clinical Relevance Our purpose was to highlight the difficulties during the diagnostic work-up for systemic vasculitis and management in cases of posterior spinal surgery.

  3. Formulating the spring discharge-function for the recession period ...

    Indian Academy of Sciences (India)

    College of Agricultural Engineering & Post Harvest Technology (CAEPHT),. Central Agricultural ... during the recession period is the key to its proper management. The spring .... In equation (1), Q is the recession flow, t is time, and a, b are ...

  4. Carrier detection of duchenne and becker muscular dystrophy using muscle dystrophin immunohistochemistry

    Directory of Open Access Journals (Sweden)

    Acary S. Bulle Oliveira

    1992-12-01

    Full Text Available To ascertain whether dystrophin immunohistochemistry could improve DMD/ BMD carrier detection, we analyzed 14 muscle biopsies from 13 DMD and one BMD probable and possible carriers. All women were also evaluated using conventional methods, including genetic analysis, clinical and neurological evaluation, serum CK levels, KMG, and muscle biopsy. In 6 cases, there was a mosaic of dystrophin-positive and dystrophin-deficient fibers that allowed to make the diagnosis of a carrier state. Comparing dystrophin immunohistochemistry to the traditional methods, it was noted that this method is less sensitive than serum CK measuremens, but is more sensitive than EMG and muscle biopsy. The use of dystrophin immunohistochemistry in addition to CK, EMG and muscle biopsy improved the accuracy of carrier detection. This method is also helpful to distinguish manifesting DMD carriers from patients with other neuromuscular diseases like limb-girdle muscular dystrophy and spinal muscular atrophy.

  5. Advantage of CT scan in muscular pathology. Personal cases and review of the literature

    International Nuclear Information System (INIS)

    Laroche, M.; Rousseau, H.; Mazieres, B.; Bonafe, A.; Joffre, F.; Arlet, J.

    1989-01-01

    The advantage of CT scans in muscular pathology is studied. The scan, in addition to the diagnosis of tumors and muscular abscesses, permits to differentiate primary myopathies from neurogenic atrophies: in the course of myopathies, the muscle volume is preserved and they appear as a hypodensity; in neurogenic atrophies, the muscle volume is reduced with preserved density. The CT scan permits to determine the extension of these lesions. In the course of polymyositis, certain forms of rheumatid arthritis, the scan discloses a trabecular and 'worm-eaten' aspect of the muscles. This is also observed after long-term steroid therapy and other endocrine diseases (hyperthyroidism, osteomalacia) indicating an infra-clinical myopathy. In vertebral osteoporosis with fractures and patients with chronic lumbalgia, very ofter, an atrophy of the spinal muscle is observed. Finally, in the course of acquired kyphosis of the adult patient (camptocormia), the CT scan suggest an isolated myopathy, with late manifestations, of the paravertebral muscles [fr

  6. Advantage of CT scan in muscular pathology. Personal cases and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Laroche, M.; Rousseau, H.; Mazieres, B.; Bonafe, A.; Joffre, F.; Arlet, J.

    1989-05-01

    The advantage of CT scans in muscular pathology is studied. The scan, in addition to the diagnosis of tumors and muscular abscesses, permits to differentiate primary myopathies from neurogenic atrophies: in the course of myopathies, the muscle volume is preserved and they appear as a hypodensity; in neurogenic atrophies, the muscle volume is reduced with preserved density. The CT scan permits to determine the extension of these lesions. In the course of polymyositis, certain forms of rheumatid arthritis, the scan discloses a trabecular and 'worm-eaten' aspect of the muscles. This is also observed after long-term steroid therapy and other endocrine diseases (hyperthyroidism, osteomalacia) indicating an infra-clinical myopathy. In vertebral osteoporosis with fractures and patients with chronic lumbalgia, very ofter, an atrophy of the spinal muscle is observed. Finally, in the course of acquired kyphosis of the adult patient (camptocormia), the CT scan suggest an isolated myopathy, with late manifestations, of the paravertebral muscles.

  7. Delayed spinal extradural hematoma following thoracic spine surgery and resulting in paraplegia: a case report

    Directory of Open Access Journals (Sweden)

    Parthiban Chandra JKB

    2008-05-01

    Full Text Available Abstract Introduction Postoperative spinal extradural hematomas are rare. Most of the cases that have been reported occured within 3 days of surgery. Their occurrence in a delayed form, that is, more than 72 hours after surgery, is very rare. This case is being reported to enhance awareness of delayed postoperative spinal extradural hematomas. Case presentation We report a case of acute onset dorsal spinal extradural hematoma from a paraspinal muscular arterial bleed, producing paraplegia 72 hours following surgery for excision of a spinal cord tumor at T8 level. The triggering mechanism was an episode of violent twisting movement by the patient. Fresh blood in the postoperative drain tube provided suspicion of this complication. Emergency evacuation of the clot helped in regaining normal motor and sensory function. The need to avoid straining of the paraspinal muscles in the postoperative period is emphasized. Conclusion Most cases of postoperative spinal extradural hematomas occur as a result of venous bleeding. However, an arterial source of bleeding from paraspinal muscular branches causing extradural hematoma and subsequent neurological deficit is underreported. Undue straining of paraspinal muscles in the postoperative period after major spinal surgery should be avoided for at least a few days.

  8. Semiconductor structure and recess formation etch technique

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Bin; Sun, Min; Palacios, Tomas Apostol

    2017-02-14

    A semiconductor structure has a first layer that includes a first semiconductor material and a second layer that includes a second semiconductor material. The first semiconductor material is selectively etchable over the second semiconductor material using a first etching process. The first layer is disposed over the second layer. A recess is disposed at least in the first layer. Also described is a method of forming a semiconductor structure that includes a recess. The method includes etching a region in a first layer using a first etching process. The first layer includes a first semiconductor material. The first etching process stops at a second layer beneath the first layer. The second layer includes a second semiconductor material.

  9. POSSIBLE RECESSION CURVE APPLICATIONS FOR RETENTION EVALUATION

    Directory of Open Access Journals (Sweden)

    Daniel Liberacki

    2015-11-01

    Full Text Available The objective of the article was to present possible applications of recession flow curve in a small lowland watershed retention discharge size evaluation. The examined woodland micro catchment area of 0.52 sq km is located in Puszcza Zielonka in central Wielkopolska. The Hutka catchment is typically woody with high retention abilities. The catchment of the Hutka watercourse is forested in 89%, the other 11% is covered by swamps and wasteland. The predominant sites are fresh mixed coniferous forest (BMśw, fresh coniferous forest (Bśw and alder carr forest (Ol. Landscape in catchment is characterized by a large number of interior depressions, filled partly with rainwater or peatbogs, with poorly developed natural drainage. The watercourses do not exceed 1 km in length, the mean width is approx. 0.5 m, while mean depth ranges from 0.2 to 0.3 m. During hydrological research conducted in 1997/1998–1999/2000, 35 major (characteristic raised water stages were observed in Hutka after substantial precipitation. The recession curve dating from 18–24 September 2000 has the α and n rates nearest to average. Comparing the model curve and the curve created by observing watercourse flow, one can notice their resemblance and that they have similar ordinate values as well as shape. In the case of other recession curves, the maximum differences of ordinate values are also about 0.1–0.2 l/s/km2. The measuured α and n rates do not reveal any regularities. There are no significant statistical Horton model parameter (for recession flow curves dependencies between α and n and e.g. initial flows (Qo or the whole period of high water waves (Qp. Consequently, calculated relation between these parameters is only an approximation for the general evaluation of the retention discharge in the catchment area towards retention with flow function.

  10. Financialisation, oil and the Great Recession

    International Nuclear Information System (INIS)

    Gkanoutas-Leventis, Angelos; Nesvetailova, Anastasia

    2015-01-01

    This article addresses the role of world oil price hike of 2007–08 in serving to transform the financial and banking crisis into what is commonly referred to the Great Recession. Existing literature on the global crisis of 2007–09 tends to view it as a financial or banking phenomenon, with analyses focusing mainly on state policies, governance mechanisms and market dynamics in transforming the banking crisis of 2007–08 into the economic recession of 2008-12/13 Although often attributing the global meltdown to wider phenomenon of financialisation, rarely do existing perspectives delve into the role of the commodity sector in the global credit crunch. In this paper, we aim to fill this gap, by inquiring into the role played by oil as a financial asset class in the political economy of the global crisis. - Highlights: • We study the oil price and its effects on the Great Recession. • We approach oil as a financial asset class. • We observe the transformation of oil through deregulation.

  11. [Post-traumatic reconnection of the cervical spinal cord with skeletal striated muscles. Study in adult rats and marmosets].

    Science.gov (United States)

    Horvat, J C; Affane-Boulaid, F; Baillet-Derbin, C; Davarpanah, Y; Destombes, J; Duchossoy, Y; Emery, E; Kassar-Duchossoy, L; Mira, J C; Moissonnier, P; Pécot-Dechavassine, M; Reviron, T; Rhrich-Haddout, F; Tadié, M; Ye, J H

    1997-01-01

    In an attempt at repairing the injured spinal cord of adult mammals (rat, dog and marmoset) and its damaged muscular connections, we are currently using: 1) peripheral nerve autografts (PNG), containing Schwann cells, to trigger and direct axonal regrowth from host and/or transplanted motoneurons towards denervated muscular targets; 2) foetal spinal cord transplants to replace lost neurons. In adult rats and marmosets, a PNG bridge was used to joint the injured cervical spinal cord to a denervated skeletal muscle (longissimus atlantis [rat] or biceps brachii [rat and marmoset]). The spinal lesion was obtained by the implantation procedure of the PNG. After a post-operative delay ranging from 2 to 22 months, the animals were checked electrophysiologically for functional muscular reconnection and processed for a morphological study including retrograde axonal tracing (HRP, Fast Blue, True Blue), histochemistry (AChE, ATPase), immunocytochemistry (ChAT) and EM. It was thus demonstrated that host motoneurons of the cervical enlargement could extend axons all the way through the PNG bridge as: a) in anaesthetized animals, contraction of the reconnected muscle could be obtained by electrical stimulation of the grafted nerve; b) the retrograde axonal tracing studies indicated that a great number of host cervical neurons extended axons into the PNG bridge up to the muscle; c) many of them were assumed to be motoneurons (double labelling with True Blue and an antibody against ChAT); and even alpha-motoneurons (type C axosomatic synapses in HRP labelled neurons seen in EM in the rat); d) numerous ectopic endplates were seen around the intramuscular tip of the PNG. In larger (cavitation) spinal lesions (rat), foetal motoneurons contained in E14 spinal cord transplants could similarly grow axons through PNG bridges up to the reconnected muscle. Taking all these data into account, it can be concluded that neural transplants are interesting tools for evaluating both the

  12. From proteins to genes: immunoanalysis in the diagnosis of muscular dystrophies

    Directory of Open Access Journals (Sweden)

    Barresi Rita

    2011-06-01

    Full Text Available Abstract Muscular dystrophies are a large heterogeneous group of inherited diseases that cause progressive muscle weakness and permanent muscle damage. Very few muscular dystrophies show sufficient specific clinical features to allow a definite diagnosis. Because of the currently limited capacity to screen for numerous genes simultaneously, muscle biopsy is a time and cost-effective test for many of these disorders. Protein analysis interpreted in correlation with the clinical phenotype is a useful way of directing genetic testing in many types of muscular dystrophies. Immunohistochemistry and western blot are complementary techniques used to gather quantitative and qualitative information on the expression of proteins involved in this group of diseases. Immunoanalysis has a major diagnostic application mostly in recessive conditions where the absence of labelling for a particular protein is likely to indicate a defect in that gene. However, abnormalities in protein expression can vary from absence to very subtle reduction. It is good practice to test muscle biopsies with antibodies for several proteins simultaneously and to interpret the results in context. Indeed, there is a degree of direct or functional association between many of these proteins that is reflected by the presence of specific secondary abnormalities that are of value, especially when the diagnosis is not straightforward.

  13. TRIM32 ubiquitin E3 ligase, one enzyme for several pathologies: From muscular dystrophy to tumours.

    Science.gov (United States)

    Lazzari, Elisa; Meroni, Germana

    2016-10-01

    TRIM32 is a member of the TRIpartite Motif family characterised by the presence of an N-terminal three-domain-module that includes a RING domain, which confers E3 ubiquitin ligase activity, one or two B-box domains and a Coiled-Coil region that mediates oligomerisation. Several TRIM32 substrates were identified including muscular proteins and proteins involved in cell cycle regulation and cell motility. As ubiquitination is a versatile post-translational modification that can affect target turnover, sub-cellular localisation or activity, it is likely that diverse substrates may be differentially affected by TRIM32-mediated ubiquitination, reflecting its multi-faceted roles in muscle physiology, cancer and immunity. With particular relevance for muscle physiology, mutations in TRIM32 are associated with autosomal recessive Limb-Girdle Muscular Dystrophy 2H, a muscle-wasting disease with variable clinical spectrum ranging from almost asymptomatic to wheelchair-bound patients. In this review, we will focus on the ability of TRIM32 to mark specific substrates for proteasomal degradation discussing how the TRIM32-proteasome axis may (i) be important for muscle homeostasis and for the pathogenesis of muscular dystrophy; and (ii) define either an oncogenic or tumour suppressive role for TRIM32 in the context of different types of cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Disabilities Photography by Rona Talcott Website by Mobile Marketing LLC Understanding Spinal Cord Injury About ... Your email address * This iframe contains the logic required to ...

  15. Spinal injury in sport

    Energy Technology Data Exchange (ETDEWEB)

    Barile, Antonio [Department of Radiology, University of L' Aquila, S. Salvatore Hospital, Via Vetoio, Coppito, 67100 L' Aquila (Italy)]. E-mail: antonio.barile@cc.univaq.it; Limbucci, Nicola [Department of Radiology, University of L' Aquila, S. Salvatore Hospital, Via Vetoio, Coppito, 67100 L' Aquila (Italy); Splendiani, Alessandra [Department of Radiology, University of L' Aquila, S. Salvatore Hospital, Via Vetoio, Coppito, 67100 L' Aquila (Italy); Gallucci, Massimo [Department of Radiology, University of L' Aquila, S. Salvatore Hospital, Via Vetoio, Coppito, 67100 L' Aquila (Italy); Masciocchi, Carlo [Department of Radiology, University of L' Aquila, S. Salvatore Hospital, Via Vetoio, Coppito, 67100 L' Aquila (Italy)

    2007-04-15

    Spinal injuries are very common among professional or amateur athletes. Spinal sport lesions can be classified in overuse and acute injuries. Overuse injuries can be found after years of repetitive spinal load during sport activity; however specific overuse injuries can also be found in adolescents. Acute traumas are common in contact sports. Most of the acute injuries are minor and self-healing, but severe and catastrophic events are possible. The aim of this article is to review the wide spectrum of spinal injuries related to sport activity, with special regard to imaging finding.

  16. Spinal CT scan, 1

    International Nuclear Information System (INIS)

    Nakagawa, Hiroshi

    1982-01-01

    Methods of CT of the cervical and thoracic spines were explained, and normal CT pictures of them were described. Spinal CT was evaluated in comparison with other methods in various spinal diseases. Plain CT revealed stenosis due to spondylosis or ossification of posterior longitudinal ligament and hernia of intervertebral disc. CT took an important role in the diagnosis of spinal cord tumors with calcification and destruction of the bone. CT scan in combination with other methods was also useful for the diagnosis of spinal injuries, congenital anomalies and infections. (Ueda, J.)

  17. MULTIPLE SPINAL CANAL MENINGIOMAS

    Directory of Open Access Journals (Sweden)

    Nandigama Pratap Kumar

    2016-10-01

    Full Text Available BACKGROUND Meningiomas of the spinal canal are common tumours with the incidence of 25 percent of all spinal cord tumours. But multiple spinal canal meningiomas are rare in compare to solitary lesions and account for 2 to 3.5% of all spinal meningiomas. Most of the reported cases are both intra cranial and spinal. Exclusive involvement of the spinal canal by multiple meningiomas are very rare. We could find only sixteen cases in the literature to the best of our knowledge. Exclusive multiple spinal canal meningiomas occurring in the first two decades of life are seldom reported in the literature. We are presenting a case of multiple spinal canal meningiomas in a young patient of 17 years, who was earlier operated for single lesion. We analysed the literature, with illustration of our case. MATERIALS AND METHODS In September 2016, we performed a literature search for multiple spinal canal meningiomas involving exclusively the spinal canal with no limitation for language and publication date. The search was conducted through http://pubmed.com, a wellknown worldwide internet medical address. To the best of our knowledge, we could find only sixteen cases of multiple meningiomas exclusively confined to the spinal canal. Exclusive multiple spinal canal meningiomas occurring in the first two decades of life are seldom reported in the literature. We are presenting a case of multiple spinal canal meningiomas in a young patient of 17 years, who was earlier operated for solitary intradural extra medullary spinal canal meningioma at D4-D6 level, again presented with spastic quadriparesis of two years duration and MRI whole spine demonstrated multiple intradural extra medullary lesions, which were excised completely and the histopathological diagnosis was transitional meningioma. RESULTS Patient recovered from his weakness and sensory symptoms gradually and bladder and bowel symptoms improved gradually over a period of two to three weeks. CONCLUSION Multiple

  18. Spinal injury in sport

    International Nuclear Information System (INIS)

    Barile, Antonio; Limbucci, Nicola; Splendiani, Alessandra; Gallucci, Massimo; Masciocchi, Carlo

    2007-01-01

    Spinal injuries are very common among professional or amateur athletes. Spinal sport lesions can be classified in overuse and acute injuries. Overuse injuries can be found after years of repetitive spinal load during sport activity; however specific overuse injuries can also be found in adolescents. Acute traumas are common in contact sports. Most of the acute injuries are minor and self-healing, but severe and catastrophic events are possible. The aim of this article is to review the wide spectrum of spinal injuries related to sport activity, with special regard to imaging finding

  19. Structural Organization of Muscular Elements of a Skin-Muscular Sac of Trematodes: Literature Survey

    OpenAIRE

    Kanat Kambarovich Akhmetov; Irina Yurievna Chidunchi

    2015-01-01

    The issue of structural organization of muscular elements of a trematodes’ skin-muscular sac is considered in the study. Special attention is paid to an analysis of materials of preceding researches, study of foreign authors and also to additional literature reflecting peculiarities of structure of a trematodes’ body muscular system. The stated issue is insufficiently studied and calls for further researches. A comparative analysis of places of trematodes’ localization, taking into considerat...

  20. An unusual variant of Becker muscular dystrophy

    NARCIS (Netherlands)

    de Visser, M.; Bakker, E.; Defesche, J. C.; Bolhuis, P. A.; van Ommen, G. J.

    1990-01-01

    We report on 5 brothers with slowly progressive limbgirdle weakness. Calf hypertrophy was absent. The levels of creatine kinase, electromyography, and findings from a muscle biopsy specimen were compatible with muscular dystrophy. The propositus's biopsy specimen also showed numerous rimmed

  1. Physical Therapy and Facioscapulohumeral Muscular Dystrophy (FSHD)

    Science.gov (United States)

    Physical Therapy & FSHD Facioscapulohumeral Muscular Dystrophy A Guide for Patients & Physical Therapists Authors: Wendy M. King, P.T., Assistant ... Shree Pandya, P.T., M.S., Assistant Professor, Neurology & Physical Medicine and Rehabilitation A publication of the FSH ...

  2. How Do People Cope with Muscular Dystrophy?

    Science.gov (United States)

    ... topic are answered in this section. How do people cope with muscular dystrophy (MD)? Although MD presents ... improve health and quality of life. Almost all people with any form of MD experience a worsening ...

  3. Duchenne muscular dystrophy: the management of scoliosis

    Science.gov (United States)

    Gardner, Adrian C.; Roper, Helen P.; Chikermane, Ashish A.; Tatman, Andrew J.

    2016-01-01

    This study summaries the current management of scoliosis in patients with Duchenne Muscular Dystrophy. A literature review of Medline was performed and the collected articles critically appraised. This literature is discussed to give an overview of the current management of scoliosis within Duchenne Muscular Dystrophy. Importantly, improvements in respiratory care, the use of steroids and improving surgical techniques have allowed patients to maintain quality of life and improved life expectancy in this patient group. PMID:27757431

  4. Muscular Oxygen Uptake Kinetics in Aged Adults.

    Science.gov (United States)

    Koschate, J; Drescher, U; Baum, K; Eichberg, S; Schiffer, T; Latsch, J; Brixius, K; Hoffmann, U

    2016-06-01

    Pulmonary oxygen uptake (V˙O2) kinetics and heart rate kinetics are influenced by age and fitness. Muscular V˙O2 kinetics can be estimated from heart rate and pulmonary V˙O2. In this study the applicability of a test using pseudo-random binary sequences in combination with a model to estimate muscular V˙O2 kinetics was tested. Muscular V˙O2 kinetics were expected to be faster than pulmonary V˙O2 kinetics, slowed in aged subjects and correlated with maximum V˙O2 and heart rate kinetics. 27 elderly subjects (73±3 years; 81.1±8.2 kg; 175±4.7 cm) participated. Cardiorespiratory kinetics were assessed using the maximum of cross-correlation functions, higher maxima implying faster kinetics. Muscular V˙O2 kinetics were faster than pulmonary V˙O2 kinetics (0.31±0.1 vs. 0.29±0.1 s; p=0.004). Heart rate kinetics were not correlated with muscular or pulmonary V˙O2 kinetics or maximum V˙O2. Muscular V˙O2 kinetics correlated with maximum V˙O2 (r=0.35; p=0.033). This suggests, that muscular V˙O2 kinetics are faster than estimates from pulmonary V˙O2 and related to maximum V˙O2 in aged subjects. In the future this experimental approach may help to characterize alterations in muscular V˙O2 under various conditions independent of motivation and maximal effort. © Georg Thieme Verlag KG Stuttgart · New York.

  5. Radiographic features of Golden Retriever muscular dystrophy.

    Science.gov (United States)

    Brumitt, Jason W; Essman, Stephanie C; Kornegay, Joe N; Graham, John P; Weber, William J; Berry, Clifford R

    2006-01-01

    Golden Retriever muscular dystrophy is an inherited, degenerative myopathy due to the absence of dystrophin and is used as a model of Duchenne muscular dystrophy of young boys. This report describes the radiographic abnormalities of Golden Retriever muscular dystrophy in 26 dogs. The thoracic abnormalities included diaphragmatic asymmetry (18/26), diaphragmatic undulation (18/26), and gastro-esophageal hiatal hernia (6/26). Pelvic abnormalities included narrowing of the body of the ilia (14/19), ventral deviation and curvature of the tuber ischii (14/19), elongation of the obturator foramen with a decrease in opacity of the surrounding bone (12/19), and lateral flaring of the wings of the ilia (12/19). Abdominal abnormalities consisted of hepatomegaly (14/22) and poor serosal detail (12/22). The unique thoracic abnormalities were a consistent finding in affected Golden Retriever muscular dystrophy dogs. The diagnosis of muscular dystrophy should be included in the differential list if the combination of diaphragm undulation and asymmetry, and gastro-esophageal hiatal hernia are identified. These diaphragmatic abnormalities are related to hypertrophy and hyperplasia of the diaphragm. Additionally, the skeletal changes of pelvic tilt, elongation of the pelvis, widening of the obturator foramina and thinning of the ischiatic tables appear to be specific to Golden Retriever muscular dystrophy in dogs. These pelvic abnormalities are most likely secondary to bone remodeling associated with the progressive skeletal myopathy and subsequent contracture/fibrosis.

  6. Stretching After Heat But Not After Cold Decreases Contractures After Spinal Cord Injury in Rats.

    Science.gov (United States)

    Iwasawa, Hiroyuki; Nomura, Masato; Sakitani, Naoyoshi; Watanabe, Kosuke; Watanabe, Daichi; Moriyama, Hideki

    2016-12-01

    Contractures are a prevalent and potentially severe complication in patients with neurologic disorders. Although heat, cold, and stretching are commonly used for treatment of contractures and/or spasticity (the cause of many contractures), the sequential effects of these modalities remain unclear. Using an established rat model with spinal cord injury with knee flexion contracture, we sought to determine what combination of heat or cold before stretching is the most effective for treatment of contractures derived from spastic paralyses and investigated which treatment leads to the best (1) improvement in the loss of ROM; (2) restoration of deterioration in the muscular and articular factors responsible for contractures; and (3) amelioration of histopathologic features such as muscular fibrosis in biceps femoris and shortening of the joint capsule. Forty-two adolescent male Wistar rats were used. After spasticity developed at 2 weeks postinjury, each animal with spinal cord injury underwent the treatment protocol daily for 1 week. Knee extension ROM was measured with a goniometer by two examiners blinded to each other's scores. The muscular and articular factors contributing to contractures were calculated by measuring ROM before and after the myotomies. We quantitatively measured the muscular fibrosis and the synovial intima length, and observed the distribution of collagen of skeletal muscle. The results were confirmed by a blinded observer. The ROM of heat alone (34° ± 1°) and cold alone (34° ± 2°) rats were not different with the numbers available from that of rats with spinal cord injury (35° ± 2°) (p = 0.92 and 0.89, respectively). Stretching after heat (24° ± 1°) was more effective than stretching alone (27° ± 3°) at increasing ROM (p contractures. Although quantification of muscular fibrosis in the rats with spinal cord injury (11% ± 1%) was higher than that of controls (9% ± 0.4%) (p = 0.01), no difference was found between spinal cord

  7. Mechanisms underlying chronic whiplash: contributions from an incomplete spinal cord injury?

    Science.gov (United States)

    Elliott, James M; Dewald, Julius P A; Hornby, T George; Walton, David M; Parrish, Todd B

    2014-11-01

    To explore the association between findings on advanced, but available, magnetic resonance imaging (MRI) sequences of the cervical spinal cord and muscular system, in tandem with biomechanical measures of maximum volitional plantar flexion torques as a proxy for a mild incomplete spinal cord injury. Observational case series. University research laboratory. Three patients with chronic whiplash and one patient with history of whiplash injury but no current symptoms. We measured lower extremity muscle fat, morphological changes in descending spinal cord pathways with advanced MRI applications and maximal activation of the plantar flexors. Larger magnitudes of lower extremity muscle fat corresponded to altered spinal cord anatomy and reductions in the ability to maximally activate plantar flexor torques in the three subjects with chronic whiplash. Such findings were not present in the recovered participant. The potential value of MRI to quantify neuromuscular degeneration in chronic whiplash is recognized. Larger scaled prospective studies are warranted before stronger conclusions can be drawn. Wiley Periodicals, Inc.

  8. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Cord Injury Allen Heinemann, PhD How Peer Counseling Works Julie Gassaway, MS, RN Pediatric Injuries Pediatric Spinal ... injury? play_arrow How does the spinal cord work? play_arrow Why is the level of a ...

  9. Glioblastoma with spinal seeding

    International Nuclear Information System (INIS)

    Fakhrai, N.; Fazeny-Doerner, B.; Marosi, C.; Czech, T.; Diekmann, K.; Birner, P.; Hainfellner, J.A.; Prayer, D.

    2004-01-01

    Background: extracranial seeding of glioblastoma multiforme (GBM) is very rare and its development depends on several factors. This case report describes two patients suffering from GBM with spinal seeding. In both cases, the anatomic localization of the primary tumor close to the cerebrospinal fluid (CSF) was the main factor for spinal seeding. Case reports: two patients with GBM and spinal seeding are presented. After diagnosis of spinal seeding, both patients were highly symptomatic from their spinal lesions. Case 1 experienced severe pain requiring opiates, and case 2 had paresis of lower limbs as well as urinary retention/incontinence. Both patients were treated with spinal radiation therapy. Nevertheless, they died 3 months after diagnosis of spinal seeding. Results: in both patients the diagnosis of spinal seeding was made at the time of cranial recurrence. Both tumors showed close contact to the CSF initially. Even though the patients underwent intensive treatment, it was not possible to keep them in a symptom-free state. Conclusion: because of short survival periods, patients deserve optimal pain management and dedicated palliative care. (orig.)

  10. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... arrow What are the latest developments in the use of electrical stimulation for spinal cord injuries? play_arrow What is “Braingate” research? play_arrow How would stem-cell therapies work in the treatment of spinal cord ...

  11. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Spinal Cord Injury Guy W. Fried, MD Substance Abuse and Spinal Cord Injury Allen Heinemann, PhD How ... arrow Why are high-dose steroids often used right after an injury? play_arrow What is meant ...

  12. Lumbar spinal stenosis

    DEFF Research Database (Denmark)

    Lønne, Greger; Fritzell, Peter; Hägg, Olle

    2018-01-01

    BACKGROUND: Decompression surgery for lumbar spinal stenosis (LSS) is the most common spinal procedure in the elderly. To avoid persisting low back pain, adding arthrodesis has been recommended, especially if there is a coexisting degenerative spondylolisthesis. However, this strategy remains con...

  13. Glioblastoma with spinal seeding

    Energy Technology Data Exchange (ETDEWEB)

    Fakhrai, N.; Fazeny-Doerner, B.; Marosi, C. [Clinical Div. of Oncology, Dept. of Medicine I, Univ. of Vienna (Austria); Czech, T. [Dept. of Neurosurgery, Univ. of Vienna (Austria); Diekmann, K. [Dept. of Radiooncology, Univ. of Vienna (Austria); Birner, P.; Hainfellner, J.A. [Clinical Inst. for Neurology, Univ. of Vienna (Austria); Prayer, D. [Dept. of Neuroradiology, Univ. of Vienna (Austria)

    2004-07-01

    Background: extracranial seeding of glioblastoma multiforme (GBM) is very rare and its development depends on several factors. This case report describes two patients suffering from GBM with spinal seeding. In both cases, the anatomic localization of the primary tumor close to the cerebrospinal fluid (CSF) was the main factor for spinal seeding. Case reports: two patients with GBM and spinal seeding are presented. After diagnosis of spinal seeding, both patients were highly symptomatic from their spinal lesions. Case 1 experienced severe pain requiring opiates, and case 2 had paresis of lower limbs as well as urinary retention/incontinence. Both patients were treated with spinal radiation therapy. Nevertheless, they died 3 months after diagnosis of spinal seeding. Results: in both patients the diagnosis of spinal seeding was made at the time of cranial recurrence. Both tumors showed close contact to the CSF initially. Even though the patients underwent intensive treatment, it was not possible to keep them in a symptom-free state. Conclusion: because of short survival periods, patients deserve optimal pain management and dedicated palliative care. (orig.)

  14. A case report: Becker muscular dystrophy presenting with epilepsy and dysgnosia induced by duplication mutation of Dystrophin gene.

    Science.gov (United States)

    Miao, Jing; Feng, Jia-Chun; Zhu, Dan; Yu, Xue-Fan

    2016-12-12

    Becker muscular dystrophy (BMD), a genetic disorder of X-linked recessive inheritance, typically presents with gradually progressive muscle weakness. The condition is caused by mutations of Dystrophin gene located at Xp21.2. Epilepsy is an infrequent manifestation of BMD, while cases of BMD with dysgnosia are extremely rare. We describe a 9-year-old boy with BMD, who presented with epilepsy and dysgnosia. Serum creatine kinase level was markedly elevated (3665 U/L). Wechsler intelligence tests showed a low intelligence quotient (IQ = 65). Electromyogram showed slight myogenic changes and skeletal muscle biopsy revealed muscular dystrophy. Immunohistochemical staining showed partial positivity of sarcolemma for dystrophin-N. Multiplex ligation-dependent probe amplification revealed a duplication mutation in exons 37-44 in the Dystrophin gene. The present case report helps to better understand the clinical and genetic features of BMD.

  15. A major QTL controls susceptibility to spinal curvature in the curveback guppy

    Directory of Open Access Journals (Sweden)

    Dreyer Christine

    2011-01-01

    Full Text Available Abstract Background Understanding the genetic basis of heritable spinal curvature would benefit medicine and aquaculture. Heritable spinal curvature among otherwise healthy children (i.e. Idiopathic Scoliosis and Scheuermann kyphosis accounts for more than 80% of all spinal curvatures and imposes a substantial healthcare cost through bracing, hospitalizations, surgery, and chronic back pain. In aquaculture, the prevalence of heritable spinal curvature can reach as high as 80% of a stock, and thus imposes a substantial cost through production losses. The genetic basis of heritable spinal curvature is unknown and so the objective of this work is to identify quantitative trait loci (QTL affecting heritable spinal curvature in the curveback guppy. Prior work with curveback has demonstrated phenotypic parallels to human idiopathic-type scoliosis, suggesting shared biological pathways for the deformity. Results A major effect QTL that acts in a recessive manner and accounts for curve susceptibility was detected in an initial mapping cross on LG 14. In a second cross, we confirmed this susceptibility locus and fine mapped it to a 5 cM region that explains 82.6% of the total phenotypic variance. Conclusions We identify a major QTL that controls susceptibility to curvature. This locus contains over 100 genes, including MTNR1B, a candidate gene for human idiopathic scoliosis. The identification of genes associated with heritable spinal curvature in the curveback guppy has the potential to elucidate the biological basis of spinal curvature among humans and economically important teleosts.

  16. Chronic spinal subdural hematoma

    International Nuclear Information System (INIS)

    Hagen, T.; Lensch, T.

    2008-01-01

    Compared with spinal epidural hematomas, spinal subdural hematomas are rare; chronic forms are even more uncommon. These hematomas are associated not only with lumbar puncture and spinal trauma, but also with coagulopathies, vascular malformations and tumors. Compression of the spinal cord and the cauda equina means that the patients develop increasing back or radicular pain, followed by paraparesis and bladder and bowel paralysis, so that in most cases surgical decompression is carried out. On magnetic resonance imaging these hematomas present as thoracic or lumbar subdural masses, their signal intensity varying with the age of the hematoma. We report the clinical course and the findings revealed by imaging that led to the diagnosis in three cases of chronic spinal subdural hematoma. (orig.) [de

  17. The Great Recession, unemployment and suicide.

    Science.gov (United States)

    Norström, Thor; Grönqvist, Hans

    2015-02-01

    How have suicide rates responded to the marked increase in unemployment spurred by the Great Recession? Our paper puts this issue into a wider perspective by assessing (1) whether the unemployment-suicide link is modified by the degree of unemployment protection, and (2) whether the effect on suicide of the present crisis differs from the effects of previous economic downturns. We analysed the unemployment-suicide link using time-series data for 30 countries spanning the period 1960-2012. Separate fixed-effects models were estimated for each of five welfare state regimes with different levels of unemployment protection (Eastern, Southern, Anglo-Saxon, Bismarckian and Scandinavian). We included an interaction term to capture the possible excess effect of unemployment during the Great Recession. The largest unemployment increases occurred in the welfare state regimes with the least generous unemployment protection. The unemployment effect on male suicides was statistically significant in all welfare regimes, except the Scandinavian one. The effect on female suicides was significant only in the eastern European country group. There was a significant gradient in the effects, being stronger the less generous the unemployment protection. The interaction term capturing the possible excess effect of unemployment during the financial crisis was not significant. Our findings suggest that the more generous the unemployment protection the weaker the detrimental impact on suicide of the increasing unemployment during the Great Recession. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  18. Application of the International Classification of Functioning, Disability and Health system to symptoms of the Duchenne and Becker muscular dystrophies.

    Science.gov (United States)

    Conway, Kristin M; Ciafaloni, Emma; Matthews, Dennis; Westfield, Chris; James, Kathy; Paramsothy, Pangaja; Romitti, Paul A

    2018-07-01

    Duchenne and Becker muscular dystrophies, collectively referred to as dystrophinopathies, are X-linked recessive diseases that affect dystrophin production resulting in compromised muscle function across multiple systems. The International Classification of Functioning, Disability and Health provides a systematic classification scheme from which body functions affected by a dystrophinopathy can be identified and used to examine functional health. The infrastructure of the Muscular Dystrophy Surveillance, Tracking, and Research Network was used to identify commonly affected body functions and link selected functions to clinical surveillance data collected through medical record abstraction. Seventy-one (24 second-, 41 third- and 7 fourth-level) body function categories were selected via clinician review and consensus. Of these, 15 of 24 retained second-level categories were linked to data elements from the Muscular Dystrophy Surveillance, Tracking, and Research Network surveillance database. Our findings support continued development of a core set of body functions from the International Classification of Functioning, Disability and Health system that are representative of disease progression in dystrophinopathies and the incorporation of these functions in standardized evaluations of functional health and implementation of individualized rehabilitation care plans. Implications for Rehabilitation Duchenne and Becker muscular dystrophies, collectively referred to as dystrophinopathies, are X-linked recessive disorders that affect the production of dystrophin resulting in compromised muscle function across multiple systems. The severity and progressive nature of dystrophinopathies can have considerable impact on a patient's participation in activities across multiple life domains. Our findings support continued development of an International Classification of Functioning, Disability and Health core set for childhood-onset dystrophinopathies. A standardized

  19. Autosomal recessive Charcot-Marie-Tooth neuropathy.

    Science.gov (United States)

    Espinós, Carmen; Calpena, Eduardo; Martínez-Rubio, Dolores; Lupo, Vincenzo

    2012-01-01

    Charcot-Marie-Tooth (CMT) disease, a hereditary motor and sensory neuropathy that comprises a complex group of more than 50 diseases, is the most common inherited neuropathy. CMT is generally divided into demyelinating forms, axonal forms and intermediate forms. CMT is also characterized by a wide genetic heterogeneity with 29 genes and more than 30 loci involved. The most common pattern of inheritance is autosomal dominant (AD), although autosomal recessive (AR) forms are more frequent in Mediterranean countries. In this chapter we give an overview of the associated genes, mechanisms and epidemiology of AR-CMT forms and their associated phenotypes.

  20. Impact of recession on Swiss pension program.

    Science.gov (United States)

    McArdle, F B

    1978-04-01

    Legislation drafted in Switzerland in 1975--77 aims at countering the effects of inflation and recession by bringing increased revenues into the system, reducing expenditures, devising a mechanism to adjust pensions automatically, and improving income maintenance for the unemployed. The proposed legislation to place the social security system on a sound financial basis now needs voter approval in a referendum. Swiss voters meanwhile rejected (in mid-1977) a government-proposed value-added tax designed to finance increasing government contributions during 1978-82. Still to be resolved, therefore, is the problem of how the government will finance higher contributions and still achieve its staged goal of a balanced budget.

  1. Children's Physical Activity Behavior during School Recess

    DEFF Research Database (Denmark)

    Pawlowski, Charlotte Skau; Andersen, Henriette Bondo; Troelsen, Jens

    2016-01-01

    participated in go-along group interviews, and recess behavior was observed using an ethnographical participant observation approach. All data were analyzed separated systematically answering the Five W Questions. Children were categorized into Low, Middle and High physical activity groups and these groups...... quantitative GPS and accelerometer measurements with qualitative go-along group interviews and participant observations. Data were collected during three weekdays in a public school in Denmark. Eighty-one children (47 girls) wore an accelerometer (ActiGraph GT3X) and GPS (QStarz BT-Q1000xt), sixteen children...

  2. Nuclear magnetic imaging for MTRA. Spinal canal and spinal cord

    International Nuclear Information System (INIS)

    Fritzsch, Dominik; Hoffmann, Karl-Titus

    2011-01-01

    The booklet covers the following topics: (1) Clinical indications for NMR imaging of spinal cord and spinal canal; (2) Methodic requirements: magnets and coils, image processing, contrast media: (3) Examination technology: examination conditions, sequences, examination protocols; (4) Disease pattern and indications: diseases of the myelin, the spinal nerves and the spinal canal (infections, tumors, injuries, ischemia and bleedings, malformations); diseases of the spinal cord and the intervertebral disks (degenerative changes, infections, injuries, tumors, malformations).

  3. Muscular cystic hydatidosis: case report

    Directory of Open Access Journals (Sweden)

    Naspetti Riccardo

    2007-03-01

    Full Text Available Abstract Background Hydatidosis is a zoonosis caused by Echinococcus granulosus, and ingesting eggs released through the faeces from infected dogs infects humans. The location of the hydatid cysts is mostly hepatic and/or pulmonary, whereas musculoskeletal hydatidosis is very rare. Case presentation We report an unusual case of primary muscular hydatidosis in proximity of the big adductor in a young Sicilian man. The patient, 34 years old, was admitted to the Department of Infectious and Tropical Diseases for ultrasonographic detection, with successive confirmation by magnetic resonance imaging, of an ovular mass (13 × 8 cm in the big adductor of the left thigh, cyst-like, and containing several small cystic formations. Serological tests for hydatidosis gave negative results. A second drawing of blood was done 10 days after the first one and showed an increase in the antibody titer for hydatidosis. The patient was submitted to surgical excision of the lesion with perioperatory prophylaxis with albendazole. The histopathological examination of the bioptic material was not diriment in the diagnosis, therefore further tests were performed: additional serological tests for hydatidosis for the evaluation of IgE and IgG serotype (Western Blot and REAST, and molecular analysis of the excised material. These more specific serological tests gave positive results for hydatidosis, and the sequencing of the polymerase chain reaction products from the cyst evidenced E. granulosus DNA, genotype G1. Any post-surgery complications was observed during 6 following months. Conclusion Cystic hydatidosis should always be considered in the differential diagnosis of any cystic mass, regardless of its location, also in epidemiological contests less suggestive of the disease. The diagnosis should be achieved by taking into consideration the clinical aspects, the epidemiology of the disease, the imaging and immunological tests but, as demonstrated in this case, without

  4. Duchenne and Becker muscular dystrophy: a molecular and immunohistochemical approach Distrofia muscular de Duchenne e Becker: abordagem molecular e imuno-histoquímica

    Directory of Open Access Journals (Sweden)

    Aline Andrade Freund

    2007-03-01

    Full Text Available Duchenne muscular dystrophy (DMD and Becker muscular dystrophy (BMD are caused by mutations in the dystrophin gene. We studied 106 patients with a diagnosis of probable DMD/BMD by analyzing 20 exons of the dystrophin gene in their blood and, in some of the cases, by immunohistochemical assays for dystrophin in muscle biopsies. In 71.7% of the patients, deletions were found in at least one of the exons; 68% of these deletions were in the hot-spot 3' region. Deletions were found in 81.5% of the DMD cases and in all the BMD cases. The cases without deletions, which included the only woman in the study with DMD, had dystrophin deficiency. The symptomatic female carriers had no deletions but had abnormal dystrophin distribution in the sarcolemma (discontinuous immunostains. The following diagnoses were made for the remaining cases without deletions with the aid of a muscle biopsy: spinal muscular atrophy, congenital myopathy; sarcoglycan deficiency and unclassified limb-girdle muscular dystrophy. Dystrophin analysis by immunohistochemistry continues to be the most specific method for diagnosis of DMD/BMD and should be used when no exon deletions are found in the dystrophin gene in the blood.As distrofias musculares de Duchenne (DMD e de Becker (DMB são doenças causadas por mutação no gene da distrofina. Foram estudados 106 casos com a suspeita diagnóstica de DMD/BMD com a analise de 20 exons do gene da distrofina no sangue e biópsia muscular com imuno-histoquímica para distrofina em alguns casos. Em 71,7% dos casos foi encontrada deleção em pelo menos um dos exons, sendo que 68% das deleções localizam-se na região 3' hot spot. Foram encontradas deleções em 81,5% dos DMD e em todos os BMD, sendo que os sem deleção tinham deficiência de distrofina, incluindo a mulher com DMD. As portadoras sintomáticas não tinham deleções mas anormalidades na distribuição da distrofina no sarcolema. Os outros casos sem deleção, com auxilio da

  5. Exercise recommendations for individuals with spinal cord injury.

    Science.gov (United States)

    Jacobs, Patrick L; Nash, Mark S

    2004-01-01

    within the paralysed tissues. The recommendations for endurance and strength training in persons with SCI do not vary dramatically from the advice offered to the general population. Systems of functional electrical stimulation activate muscular contractions within the paralysed muscles of some persons with SCI. Coordinated patterns of stimulation allows purposeful exercise movements including recumbent cycling, rowing and upright ambulation. Exercise activity in persons with SCI is not without risks, with increased risks related to systemic dysfunction following the spinal injury. These individuals may exhibit an autonomic dysreflexia, significantly reduced bone density below the spinal lesion, joint contractures and/or thermal dysregulation. Persons with SCI can benefit greatly by participation in exercise activities, but those benefits can be enhanced and the relative risks may be reduced with accurate classification of the spinal injury.

  6. Biodegradable chitin conduit tubulation combined with bone marrow mesenchymal stem cell transplantation for treatment of spinal cord injury by reducing glial scar and cavity formation

    Directory of Open Access Journals (Sweden)

    Feng Xue

    2015-01-01

    Full Text Available We examined the restorative effect of modified biodegradable chitin conduits in combination with bone marrow mesenchymal stem cell transplantation after right spinal cord hemisection injury. Immunohistochemical staining revealed that biological conduit sleeve bridging reduced glial scar formation and spinal muscular atrophy after spinal cord hemisection. Bone marrow mesenchymal stem cells survived and proliferated after transplantation in vivo, and differentiated into cells double-positive for S100 (Schwann cell marker and glial fibrillary acidic protein (glial cell marker at 8 weeks. Retrograde tracing showed that more nerve fibers had grown through the injured spinal cord at 14 weeks after combination therapy than either treatment alone. Our findings indicate that a biological conduit combined with bone marrow mesenchymal stem cell transplantation effectively prevented scar formation and provided a favorable local microenvironment for the proliferation, migration and differentiation of bone marrow mesenchymal stem cells in the spinal cord, thus promoting restoration following spinal cord hemisection injury.

  7. Biodegradable chitin conduit tubulation combined with bone marrow mesenchymal stem cell transplantation for treatment of spinal cord injury by reducing glial scar and cavity formation

    Science.gov (United States)

    Xue, Feng; Wu, Er-jun; Zhang, Pei-xun; Li-ya, A; Kou, Yu-hui; Yin, Xiao-feng; Han, Na

    2015-01-01

    We examined the restorative effect of modified biodegradable chitin conduits in combination with bone marrow mesenchymal stem cell transplantation after right spinal cord hemisection injury. Immunohistochemical staining revealed that biological conduit sleeve bridging reduced glial scar formation and spinal muscular atrophy after spinal cord hemisection. Bone marrow mesenchymal stem cells survived and proliferated after transplantation in vivo, and differentiated into cells double-positive for S100 (Schwann cell marker) and glial fibrillary acidic protein (glial cell marker) at 8 weeks. Retrograde tracing showed that more nerve fibers had grown through the injured spinal cord at 14 weeks after combination therapy than either treatment alone. Our findings indicate that a biological conduit combined with bone marrow mesenchymal stem cell transplantation effectively prevented scar formation and provided a favorable local microenvironment for the proliferation, migration and differentiation of bone marrow mesenchymal stem cells in the spinal cord, thus promoting restoration following spinal cord hemisection injury. PMID:25788929

  8. State Government Revenue Recovery from the Great Recession

    OpenAIRE

    James Alm; David L. Sjoquist

    2014-01-01

    The "Great Recession" lasted from December 2007 to June 2009, and it wreaked havoc on the revenues of state (and local) governments. While the U.S. economy has improved since the end of the Great Recession, state government revenues have in most cases still not completely recovered. We use various indicators to measure how different states have -- or have not -- recovered in the aftermath of the Great Recession, and we also attempt to explain why these different patterns of recovery have emer...

  9. CT EVALUATION OF AZYGOESOPHAGEAL RECESS IN ADULTS

    Directory of Open Access Journals (Sweden)

    Kulamani Sahoo

    2015-02-01

    Full Text Available Azygoesophageal recess (AER is right posterior mediastinal recess . Knowledge of normal radiologic appearance and manifestations of disease in AER can facilitate the detection and diagnosis of many intrathoracic diseases ranging from infective processes to tumors involving mediastinum, lung/pleura, lymphatic system, upper gastrointestinal system (esophagus & stomach & cardio - vascular system. Aim of this study was to investigate various intrathoracic pathologies, altering the configuration of AER on CT in adults & to find out any significance with various disease processes. This study was carried out in CT center, Department of Radiodiagnosis, Krishna Institute of medical sciences, Karad from October 2012 - September 2014. CT thorax of 156 patients was studied for configuration of AER irrespective of pathology. In this study , configuration of AER was altered in descending order with pathologies belonging to following systems: Respiratory system (Lung parenchyma pathologies causing volume loss of right lower lobe particularly Koch’s , UIP , Malignancy , Pleural pathologies (Secondary more common than Primary >Lymphatic system(secondary subcarinal lymph node more common than Primary Lymphoma >Cardio - vascular system(Cardiomegaly particularly Left atrial enlargement >Gastrointestinal system ( hiatus herni a & esophageal Cancer > Mediastinum ( Koch’s of dorsal spine with paraspinal abscess.

  10. Child Poverty and the Great Recession in the United States

    OpenAIRE

    Marianne Bitler; Hilary Hoynes; Elira Kuka

    2014-01-01

    In the midst of the Great Recession, median real household income fell from $61,597 in 2007 to $57,025 in 2010 and $51,007 in 2012. Given that the effects of the Great Recession on unemployment were greater for less skilled workers the authors expect the effects of the Great Recession on household incomes to be larger in relative terms for individuals in the lower end of the income distribution. To explore this issue, in this paper, they comprehensively examine the effects of the Great Recess...

  11. Prognostic Indicators of Gingival Recession in Nigeria: Preliminary Findings

    Directory of Open Access Journals (Sweden)

    Michael Adedigba

    2010-06-01

    Full Text Available AIM: Literature is replete with studies on gingival recession, the apical shift of the gingival margin from the cemento-enamel junction. Chronic periodontitis and frequent toothbrushing are among its aetiological factors. Many of these were however prevalence studies. The current study was therefore aimed at separating prognostic indicators from determinants of the number of recessions. METHOD: 650 consecutive adult patients visiting a Nigerian teaching hospital were examined using a checklist including plaque, calculus, Miller’s class of recession and other parameters.. A total of 408 recession sites were identified. RESULTS: The mean age of the patients with recession was 42.3 years; mean number of recession was 4.74 Incisors had the highest number of recessions (35.7%. While a factor such as age was related both to the number and prognosis of recession sites, abrasion and plaque were only related to prognosis. Again, some of the factors previously significantly related to prognosis on univariate analysis like calculus and smoking, lost their significance on regression analysis. CONCLUSION: The three strongest predictors of prognosis (Miller’s class of recession were age, plaque and abrasion. [TAF Prev Med Bull 2010; 9(3.000: 187-194

  12. Gingival recession: a cross-sectional clinical investigation.

    Science.gov (United States)

    Goutoudi, P; Koidis, P T; Konstantinidis, A

    1997-06-01

    In this cross-sectional study, risk and potentially causative factors of gingival recession were examined and their relationship to apical migration of the gingival margin evaluated. Thirty eight patients (18-60 years), displaying one or more sites with gingival recession but without any significant periodontal disease participated. A total of 28 parameters were evaluated in both 'test' teeth (50 teeth with gingival recession) and 'control' teeth (50 contralateral teeth). The results revealed that gingival margin recession was associated with both high inflammatory and plaque scores, with decreased widths of keratinized and attached gingiva and with the subjects' toothbrush bristle hardness.

  13. Disorders of spinal blood circulation

    OpenAIRE

    Hevyak, O.M.; Kuzminskyy, A.P.

    2017-01-01

    Spinal strokes are rare. The most common causes of the haemorrhage are spinal cord trauma, vasculitis with signs of haemorrhagic diathesis, spinal vascular congenital anomalies (malformations) and haemangioma. By localization, haemorrhagic strokes are divided into three groups: haematomyelia, spinal subarachnoid haemorrhage, epidural hematoma. Most cavernous malformations are localized at the cervical level, fewer — at thoracic and lumbar levels of the spinal cord. The clinical case of diagno...

  14. [Human myopathy and animal muscular dystrophy].

    Science.gov (United States)

    Schapira, G; Dreyfus, J C; Schapira, F

    1977-08-01

    Two hereditary muscular dystrophies similar to human progressive muscular dystrophy (P.M.D. Duchenne type) have been isolated in animals, one in mouse, the other in chicken. The decrease in the activity of glycogenolytic enzymes is similar to that observed in denervated muscle. Isozymic fetal types for several muscular enzymes have been observed as well in chicken as in man, but this fetal type may also be found in neurogenic atrophy. The release in circulation of muscle enzymes seems more specific. But the origin of the genetic lesion is still unknown. We describe here the three different theories about this problem: i.e. neurogenic, vascular, or myogenic. This last theory implies a trouble of membrane permeability.

  15. Mitochondrial disorders in progressive muscular dystrophies

    Directory of Open Access Journals (Sweden)

    D. A. Kharlamov

    2014-01-01

    Full Text Available The literature review gives data on the role of mitochondrial disorders in the pathogenesis of different progressive muscular dystrophies. It describes changes in Duchenne, limb-girdle, facial scapulohumeral (Landuzi—Degerina muscular dystrophies. The review is based on both clinical and experimental animal studies. Along with the implication of mitochondria in the pathogenesis of the diseases, it describes muscular dystrophy treatment options compensating for energy disorders and overcoming oxidative stress and mitochondrial dysfunction. Mitochondrial studies in different muscle diseases hand physicians treatment modalities that fail to lead to recovery, but compensate for disorders caused by mutations in the genetic apparatus. 

  16. Muscular pathology: echographic and NMR imaging aspects

    International Nuclear Information System (INIS)

    Pascal-Suisse, P.; Beaurain, P.; Mougniot, C.

    1995-01-01

    A comparison of echographic techniques and NMR imaging has been done for the diagnosis of muscular trauma and tumor pathologies. In traumatic pathology, the echographic analysis allows to determine the complete assessment of recent muscular injuries. NMR imaging can be used in granuloma or fibrous callosity appreciation and for the analysis of deep injury (muscles and muscles-tendon junctions) and of muscular aponeurosis. Echography must be used together with color coding Doppler technique in the diagnosis of tumor pathology and for the study of slow fluxes. The recently available energy Doppler technique seems to be powerful in the study of vascularization of small expansive formations, but their extension to adjacent bone or tissue can only be appreciated using NMR imaging. (J.S.)

  17. Vascular-targeted therapies for Duchenne muscular dystrophy

    Science.gov (United States)

    2013-01-01

    Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy and an X-linked recessive, progressive muscle wasting disease caused by the absence of a functional dystrophin protein. Dystrophin has a structural role as a cytoskeletal stabilization protein and protects cells against contraction-induced damage. Dystrophin also serves a signaling role through mechanotransduction of forces and localization of neuronal nitric oxide synthase (nNOS), which produces nitric oxide (NO) to facilitate vasorelaxation. In DMD, the signaling defects produce inadequate tissue perfusion caused by functional ischemia due to a diminished ability to respond to shear stress induced endothelium-dependent dilation. Additionally, the structural defects seen in DMD render myocytes with an increased susceptibility to mechanical stress. The combination of both defects is necessary to generate myocyte damage, which induces successive rounds of myofiber degeneration and regeneration, loss of calcium homeostasis, chronic inflammatory response, fibrosis, and myonecrosis. In individuals with DMD, these processes inevitably cause loss of ambulation shortly after the first decade and an abbreviated life with death in the third or fourth decade due to cardio-respiratory anomalies. There is no known cure for DMD, and although the culpable gene has been identified for more than twenty years, research on treatments has produced few clinically relevant results. Several recent studies on novel DMD therapeutics are vascular targeted and focused on attenuating the inherent functional ischemia. One approach improves vasorelaxation capacity through pharmaceutical inhibition of either phosphodiesterase 5 (PDE5) or angiotensin-converting enzyme (ACE). Another approach increases the density of the underlying vascular network by inducing angiogenesis, and this has been accomplished through either direct delivery of vascular endothelial growth factor (VEGF) or by downregulating the VEGF decoy

  18. Spinal Cord Injury 101

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    Full Text Available ... Disabilities Photography by Rona Talcott Website by Mobile Marketing LLC Understanding Spinal Cord Injury About Us Expert ... Disabilities Photography by Rona Talcott Website by Mobile Marketing LLC close close

  19. Spinal Cord Injury 101

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    Full Text Available ... Life in a Wheelchair Lisa Rosen, MS Spasticity, Physical Therapy-Lokomat T. George Hornby, PhD, PT Empowering ... Rogers, SW Marguerite David, MSW Kathy Hulse, MSW Physical Therapy after Spinal Cord Injury Laura Wehrli, PT ...

  20. Spinal cord trauma

    Science.gov (United States)

    ... PA: Elsevier Saunders; 2015:chap 32. Kaji AH, Newton EJ, Hockberger RS. Spinal injuries. In: Marx JA, ... member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www. ...

  1. Spinal Cord Injury 101

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    Full Text Available ... How Peer Counseling Works Julie Gassaway, MS, RN Pediatric Injuries Pediatric Spinal Cord Injury 101 Lawrence Vogel, MD The Basics of Pediatric SCI Rehabilitation Sara Klaas, MSW Transitions for Children ...

  2. Spinal Cord Injury 101

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    Full Text Available ... com is an informational and support website for families facing spinal cord injuries. The website does not provide medical advice, recommend or endorse health care products or ...

  3. Spinal Cord Injury 101

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    Full Text Available ... Diane M. Rowles, MS, NP How Family Life Changes After Spinal Cord Injury Nancy Rosenberg, PsyD Understanding SCI Rehabilitation Donald Peck Leslie, MD Adjusting to Social Life in a Wheelchair Lisa Rosen, MS Spasticity, ...

  4. Spinal pain in adolescents

    DEFF Research Database (Denmark)

    Aartun, Ellen; Hartvigsen, Jan; Wedderkopp, Niels

    2014-01-01

    BACKGROUND: The severity and course of spinal pain is poorly understood in adolescents. The study aimed to determine the prevalence and two-year incidence, as well as the course, frequency, and intensity of pain in the neck, mid back, and low back (spinal pain). METHODS: This study was a school......-based prospective cohort study. All 5th and 6th grade students (11-13 years) at 14 schools in the Region of Southern Denmark were invited to participate (N = 1,348). Data were collected in 2010 and again two years later, using an e-survey completed during school time. RESULTS: The lifetime prevalence of spinal pain...... reported their pain as relatively infrequent and of low intensity, whereas the participants with frequent pain also experienced pain of higher intensity. The two-year incidence of spinal pain varied between 40% and 60% across the physical locations. Progression of pain from one to more locations and from...

  5. Spinal Cord Injury 101

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    Full Text Available ... does not provide medical advice, recommend or endorse health care products or services, or control the information ... With Disabilities Photography by Rona Talcott Website by Mobile Marketing LLC Understanding Spinal Cord Injury About Us ...

  6. Spinal Cord Injury 101

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  7. Spinal Cord Injury 101

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  8. Spinal Injury: First Aid

    Science.gov (United States)

    ... EmergencyManual/WhatToDoInMedicalEmergency/Default.aspx?id=258&terms=spinal+injuries. Accessed Jan. 8, 2015. Marx JA, et al. Rosen's Emergency Medicine: Concepts and Clinical Practice. 8th ed. Philadelphia, Pa.: Mosby ...

  9. Spinal Cord Injury 101

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  12. Spinal Cord Injury 101

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  13. Spinal Cord Injury 101

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  14. Spinal Cord Injury 101

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  15. Spinal Cord Injury 101

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    Full Text Available ... SCI Rehabilitation Donald Peck Leslie, MD Adjusting to Social Life in a Wheelchair Lisa Rosen, MS Spasticity, ... OT Anne Bryden, OT The Role of the Social Worker after Spinal Cord Injury Patti Rogers, SW ...

  17. Spinal Cord Injury 101

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  20. Spinal Cord Injury 101

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  1. Occupational health physicians and the impact of the Great Recession on the health of workers: a qualitative study.

    Science.gov (United States)

    Mattei, G; Ferrari, Silvia; Giubbarelli, G; Pingani, L; Urraci, G M; Rigatelli, M; Galeazzi, G M

    2015-11-22

    Italy is one of the Eurozone members where the 2008 "Great Recession" struck worst, with a 9% drop in national GDP between 2008 and 2013. The negative effects of the recession on the health of the Italian population were documented on a nation-wide level. However, few local or regional studies are currently available in the scientific literature. To assess the impact on workers' health of the economic recession in the industrial area of Sassuolo (Modena, Northern Italy), and to provide recommendations for targeted interventions. Two focus groups were conducted, involving 8 occupational health physicians (OHPs) active in the area. Rough descriptions were analyzed using MAXQDA 11, according to the principles of grounded theory. 261 segments were coded, divided into four areas. The first, "changes in contemporary world", pointed out that the recession may have just made pre-existing problems worse, accelerating reductions in staff and workers' benefits. The second, "social area", highlighted a decrease in vertical social capital and the beginning of new trends in emigration. The third, "work area", covered workers' fear of losing their jobs if they were ill and a reduction in horizontal social capital, namely difficult relations between co-workers. The fourth, "medical area", indicated a general worsening of workers' health in the Sassuolo ceramic district compared to previous years. The OHPs reported an increase in muscular-skeletal complaints, gastritis, tension-type headache, irritable bowel syndrome symptoms, back pain, panic attacks, insomnia, tachycardia, and other medically unexplained symptoms. Anxiety problems seemed to prevail over depressive manifestations. An increase was reported for antidepressants and benzodiazepines consumption. The local impact of the economic crisis on health was mainly negative, consistent with available national data. Mental health professionals could work together with OHPs, e.g., through Balint Group-like meetings, to develop

  2. Spinal extradural arachnoid cysts

    Directory of Open Access Journals (Sweden)

    Abolfazl Rahimizadeh

    2013-01-01

    Full Text Available OBJECTIVE: Extradural arachnoid cysts (EACs are rare causes of spinal cord compression and cauda equina. These benign lesions appear in the literature mainly as single case reports. In this article, we present the largest series found in literature, with four new cases of spinal extradural arachnoid cysts. The characteristic imaging features, details of surgical steps and strategies to prevent postoperative kyphosis in this cystic pathology will be discussed.

  3. Emery-Dreifuss muscular dystrophy: anatomical-clinical correlation (case report Distrofia muscular de Emery-Dreifuss: correlação anátomo-clínica (relato de caso

    Directory of Open Access Journals (Sweden)

    ALZIRA ALVES DE SIQUEIRA CARVALHO

    2000-12-01

    Full Text Available We report on a man that had weakness of humeroperoneal distribution associated with limited range of motion of the cervical spine and elbows since he was 5 years old . At age 26 he developed tachycardia episodes. A complex arrhythmia was discovered, and a nodal ablation was done with a cardiac pacemaker implanted. The patient had an arrhythmia and sudden death followed this. Emery-Dreifuss muscular dystrophy is a rare recessive X-linked muscular disorder where mixed patterns in electromyography and muscle histology (neurogenic and/or myopathic have caused nosological confusion. The autopsy findings are here described and correlated to the clinical features in an attempt to better understand the ambiguous findings concerning the process etiology .Relatamos o caso de um paciente com fraqueza muscular de distribuição úmero-peroneal associada a limitação de movimentos da coluna cervical e cotovelos. Aos 26 anos, ele desenvolveu episódios de taquicardia. Uma arritmia complexa foi descoberta sendo feito ablação nodal seguida por implante de marcapasso cardíaco. O paciente evoluiu com arritmia e morte. A distrofia de Emery-Dreifuss é desordem muscular rara, recessiva, ligada ao cromossomo X cujo aspectos mistos (neurogênico e/ou miopático na eletroneuromiografia e biopsia muscular tem provocado dúvidas na nosologia. Os achados de autopsia são descritos e correlacionados aos critérios clínicos na tentativa de melhor compreender os achados ambíguos em relação à etiologia.

  4. Intimate Partner Violence in the Great Recession.

    Science.gov (United States)

    Schneider, Daniel; Harknett, Kristen; McLanahan, Sara

    2016-04-01

    In the United States, the Great Recession was marked by severe negative shocks to labor market conditions. In this study, we combine longitudinal data from the Fragile Families and Child Wellbeing Study with U.S. Bureau of Labor Statistics data on local area unemployment rates to examine the relationship between adverse labor market conditions and mothers' experiences of abusive behavior between 2001 and 2010. Unemployment and economic hardship at the household level were positively related to abusive behavior. Further, rapid increases in the unemployment rate increased men's controlling behavior toward romantic partners even after we adjust for unemployment and economic distress at the household level. We interpret these findings as demonstrating that the uncertainty and anticipatory anxiety that go along with sudden macroeconomic downturns have negative effects on relationship quality, above and beyond the effects of job loss and material hardship.

  5. Did the Great Recession influence retirement plans?

    Science.gov (United States)

    Szinovacz, Maximiliane E; Davey, Adam; Martin, Lauren

    2015-04-01

    The recent recession constitutes one of the macro forces that may have influenced workers' retirement plans. We evaluate a multilevel model that addresses the influence of macro-, meso-, and micro-level factors on retirement plans, changes in these plans, and expected retirement age. Using data from Waves 8 and 9 of the Health and Retirement Study (N=2,618), we find that individuals with defined benefit plans are more prone to change toward plans to stop work before the stock market declined, whereas the opposite trend holds for those without pensions. Debts, ability to reduce work hours, and firm unionization also influenced retirement plans. Findings suggest retirement planning education may be particularly important for workers without defined pensions, especially in times of economic volatility. © The Author(s) 2014.

  6. Dimensions of the lumbar spinal canal: variations and correlations with somatometric parameters using CT

    Energy Technology Data Exchange (ETDEWEB)

    Karantanas, A.H. [Department of CT-MRI, Larissa General Hospital (Greece); Zibis, A.H.; Papaliaga, M.; Georgiou, E.; Rousogiannis, S. [Larissa Medical School, University of Thessaly, Larissa (Greece)

    1998-12-01

    The aim of this study was to investigate the correlation of vertebral dimensions with somatometric parameters in patients without clinical symptoms and radiological signs of central lumbar spinal stenosis. One hundred patients presenting with low back pain or sciatica were studied with CT. In each of the L3, L4 and L5 vertebra three slices were taken with the following measurements: 1. Slice through the intervertebral disc: (a) spinal canal area; (b) interarticular diameter; (c) interligamentous diameter. 2. Slice below the vertebral arcus: (a) dural sac area; (b) vertebral body area. 3. Pediculolaminar level: (a) anteroposterior diameter and interpedicular diameter of the spinal canal; (b) spinal canal area; (c) width of the lateral recesses. The Jones-Thomson index was also estimated. The results of the present study showed that there is a statistically significant correlation of height, weight and age with various vertebral indices. The conventional, widely accepted, anteroposterior diameter of 11.5 mm of the lumbar spinal canal is independent of somatometric parameters, and it is the only constant measurement for the estimation of lumbar spinal stenosis with a single value. The present study suggests that there are variations of the dimensions of the lumbar spinal canal and correlations with height, weight and age of the patient. (orig.) With 1 fig., 6 tabs., 24 refs.

  7. Dimensions of the lumbar spinal canal: variations and correlations with somatometric parameters using CT

    International Nuclear Information System (INIS)

    Karantanas, A.H.; Zibis, A.H.; Papaliaga, M.; Georgiou, E.; Rousogiannis, S.

    1998-01-01

    The aim of this study was to investigate the correlation of vertebral dimensions with somatometric parameters in patients without clinical symptoms and radiological signs of central lumbar spinal stenosis. One hundred patients presenting with low back pain or sciatica were studied with CT. In each of the L3, L4 and L5 vertebra three slices were taken with the following measurements: 1. Slice through the intervertebral disc: (a) spinal canal area; (b) interarticular diameter; (c) interligamentous diameter. 2. Slice below the vertebral arcus: (a) dural sac area; (b) vertebral body area. 3. Pediculolaminar level: (a) anteroposterior diameter and interpedicular diameter of the spinal canal; (b) spinal canal area; (c) width of the lateral recesses. The Jones-Thomson index was also estimated. The results of the present study showed that there is a statistically significant correlation of height, weight and age with various vertebral indices. The conventional, widely accepted, anteroposterior diameter of 11.5 mm of the lumbar spinal canal is independent of somatometric parameters, and it is the only constant measurement for the estimation of lumbar spinal stenosis with a single value. The present study suggests that there are variations of the dimensions of the lumbar spinal canal and correlations with height, weight and age of the patient. (orig.)

  8. Pediatric spinal infections

    Directory of Open Access Journals (Sweden)

    Raj Kumar

    2014-01-01

    Full Text Available The infections of the spinal axis in children are rare when compared with adults. They encompass a large spectrum of diseases ranging from relatively benign diskitis to spinal osteomyleitis and to the rapidly progressive, rare, and potentially devastating spinal epidural, subdural, and intramedullary spinal cord infections. We present a comprehensive review of the literature pertaining to these uncommon entities, in light of our experience from northern India. The most prevalent pediatric spinal infection in Indian scenario is tuberculosis, where an extradural involvement is more common than intradural. The craniovertebral junction is not an uncommon site of involvement in children of our milieu. The majority of pyogenic infections of pediatric spine are associated with congenital neuro-ectodermal defects such as congenital dermal sinus. The clinico-radiological findings of various spinal infections commonly overlap. Hence the endemicity of certain pathogens should be given due consideration, while considering the differential diagnosis. However, early suspicion, rapid diagnosis, and prompt treatment are the key factors in avoiding neurological morbidity and deformity in a growing child.

  9. Duchenne muscular dystrophy diagnosed by dystrophin gene deletion test: A case report

    Directory of Open Access Journals (Sweden)

    Rathod Kishor G, Dawre Rahul M, Kamble Milind B,Tambe Saleem H

    2014-04-01

    Full Text Available Duchenne muscular dystrophy (DMD is an X-linked recessive disease affecting 1 in 3600—6000 live male births. A muscle biopsy is not necessary if a genetic diagnosis is secured first, particularly as some families might view the procedure as traumatic. DMD occurs as a result of mutations (mainly deletions in the dystrophin gene (DMD; locus Xp21.2. Mutations lead to an absence of or defect in the protein dystrophin, which results in progressive muscle degeneration leading to loss of independent ambulation. Ninety percent of out frame mutations result in DMD, while 90% of in-frame mutations result in BMD. Electron microscopy is not required to confirm DMD. Genetic testing is mandatory irrespective of biopsy results. But the muscle biopsy is not required if the diagnosis is secured first by genetic testing.

  10. Limb-girdle muscular dystrophy type 2A in Brazilian children

    Directory of Open Access Journals (Sweden)

    Marco Antônio Veloso de Albuquerque

    2015-12-01

    Full Text Available ABSTRACT Calpainopathy is an autosomal recessive limb girdle muscular dystrophy (LGMD2A caused by mutations in CAPN3 gene. Objective To present clinical and histological findings in six children with a molecular diagnosis of LGMD2A and additionally the MRI findings in two of them. Method We retrospectively assessed medical records of 6 patients with mutation on CAPN3 gene. Results All patients were female (three to 12 years. The mean of age of disease onset was 9 years. All of them showed progressive weakness with predominance in lower limbs. Other findings were scapular winging, joint contractures and calf hypertrophy. One female had a more severe phenotype than her dizygotic twin sister that was confirmed by muscle MRI. Muscle biopsies showed a dystrophic pattern in all patients. Conclusion In this cohort of children with LGMD2A, the clinical aspects were similar to adults with the same disorder.

  11. Unemployment of Non-western Immigrants in the Great Recession

    NARCIS (Netherlands)

    Cervený, J.; van Ours, J.C.

    2013-01-01

    Abstract: This paper examines whether unemployment of non-western immigrant workers in the Netherlands was disproportionally affected by the Great Recession. We analyze unemployment data covering the period November 2007 to February 2013 finding that the Great Recession affected unemployment rates

  12. Who Suffers during Recessions? NBER Working Paper No. 17951

    Science.gov (United States)

    Hoynes, Hilary W.; Miller, Douglas L.; Schaller, Jessamyn

    2012-01-01

    In this paper we examine how business cycles affect labor market outcomes in the United States. We conduct a detailed analysis of how cycles affect outcomes differentially across persons of differing age, education, race, and gender, and we compare the cyclical sensitivity during the Great Recession to that in the early 1980s recession. We present…

  13. American undergraduate students' value development during the Great Recession.

    Science.gov (United States)

    Park, Heejung; Twenge, Jean M; Greenfield, Patricia M

    2017-02-01

    The Great Recession's influence on American undergraduate students' values was examined, testing Greenfield's and Kasser's theories concerning value development during economic downturns. Study 1 utilised aggregate-level data to investigate (a) population-level value changes between the pre-recession (2004-2006: n = 824,603) and recession freshman cohort (2008-2010: n = 662,262) and (b) overall associations of population-level values with national economic climates over long-term periods by correlating unemployment rates and concurrent aggregate-level values across 1966-2015 (n = 10 million). Study 2 examined individual-level longitudinal value development from freshman to senior year, and whether the developmental trajectories differed between those who completed undergraduate education before the Great Recession (freshmen in 2002, n = 12,792) versus those who encountered the Great Recession during undergraduate years (freshmen in 2006, n = 13,358). Results suggest American undergraduate students' increased communitarianism (supporting Greenfield) and materialism (supporting Kasser) during the Great Recession. The recession also appears to have slowed university students' development of positive self-views. Results contribute to the limited literature on the Great Recession's influence on young people's values. They also offer theoretical and practical implications, as values of this privileged group of young adults are important shapers of societal values, decisions, and policies. © 2016 International Union of Psychological Science.

  14. Unemployment of non-western immigrants in the Great Recession

    NARCIS (Netherlands)

    Cervený, J.; van Ours, J.C.

    2013-01-01

    This paper examines whether unemployment of non-western immigrant workers in the Netherlands was disproportionally affected by the Great Recession. We analyze unemployment data covering the period November 2007–February 2013 finding that the Great Recession affected unemployment rates of non-western

  15. Students with Attention Deficit Hyperactivity Disorder Participating in Recess

    Science.gov (United States)

    Lucas, Matthew D.; Justice, Michael J.; Rosko, Kelly M.

    2014-01-01

    The participation of a student with Attention Deficit Hyperactivity Disorder (ADHD) in recess can often be both challenging and rewarding for the student and teacher. This paper will address common characteristics of children with ADHD and present basic solutions to improve the experience of these children in the recess setting. Initially, the…

  16. Students with Sickle Cell Anemia Participating in Recess

    Science.gov (United States)

    Lucas, Matthew D.; Devlin, Katharine M.

    2011-01-01

    The participation of a student with Sickle Cell Anemia in recess can often be both challenging and rewarding for the student and teacher. This paper will address common characteristics of students with Sickle Cell Anemia and present basic solutions to improve the experience of these students in the recess setting. Initially the definition,…

  17. Mining of lethal recessive genetic variation in Danish cattle

    DEFF Research Database (Denmark)

    Das, Ashutosh

    2015-01-01

    in fertility. The primary objective of this PhD projekt was to identify recessive lethal gentic variants in the main Danish dairy cattle breed. Holstein-Friesian utilzing next generation sequencing (NGS) data. This study shows a potential for the use of the NGS-based reverse genetic approach in identifying...... lethal or semi-lethal recessive gentic variation...

  18. Africa and global recessions: Options for reducing vulnerability in ...

    African Journals Online (AJOL)

    Africa and global recessions: Options for reducing vulnerability in future. ... It concludes that traditional or conventional, market-based approaches do not adequately explain the root causes of global recessions and that the dominant counter-cyclical Keynesian-type fiscal and monetary policies that characterised the ...

  19. Business Recovery Strategies in the Economic Crisis of Recession ...

    African Journals Online (AJOL)

    This paper examines Nigeria's theoretical economic foundation, the consequence of recession generally and specifically on the Gross Domestic Product (GDP) growth rate (2008-2010) and on companies together with customers reaction. Business recovery strategies for an upturn over the economic crisis of recession in ...

  20. Muscular Imbalance Correction in the Power Fitness Training

    OpenAIRE

    Olga E. Aftimichuk; Alexander V. Varvarich

    2013-01-01

    Muscular imbalance is one of the manifestations of pathological-biomechanical changes in muscular-skeletal system. It is the result of tonus-power imbalance of short and relaxed muscles. Muscle shortening is the most striking sign of muscular imbalance. Hypodynamia and passive lifestyle can cause such results. The paper justifies the experimental technique of women muscular imbalances correction by means of power training. Selection of exercises, weights and machines was made, taking into acc...

  1. A etiologia multifatorial da recessão periodontal The etiologic factors of periodontal recession

    Directory of Open Access Journals (Sweden)

    Karen Ferreira Gazel Yared

    2006-12-01

    Full Text Available A literatura apresenta vários fatores relacionados na etiologia da recessão periodontal, além do processo inflamatório induzido pelo biofilme bacteriano, os quais incluem fatores externos e anatômicos locais. Por meio deste estudo, revistou-se a literatura sobre tais fatores, cujo conhecimento é de grande importância para o ortodontista, contribuindo durante o diagnóstico, planejamento e tratamento ortodôntico propriamente dito.The literature shows that besides dental plaque, some external and anatomic local factors are still related to gingival recession etiology. This study reviewed the literature about those factors, which knownledge is of great benefit to the orthodontist, contributing during diagnostic, planning and orthodontic treatment.

  2. The diagnosis of a fully flexed neck position MRI diagnosis in juvenile muscular atrophy of the distal upper extremity

    International Nuclear Information System (INIS)

    Liu Huaijun; Li Caiying; He Dan; Chi Chen; Cui Caixia; Huang Boyuan; Wang Guoshi; Zhu Qingfeng

    2006-01-01

    Objective: To investigate the value of the diagnosis of MRI during neck flexion in juvenile muscular atrophy of the distal upper extremity. Methods: Five young male patients (mean age 21 years old) with clinical and electrophysiological alterations were performed MR examination with routine neck position and a fully flexed neck position. Eight age-match young men were examined as control subjects. SE T 1 WI, T 2 WI, Fluid-attenuated inversion recovery (FLAIR) sequences were scanned. Results: A distinctive finding in the disorder was forward displacement of the cervical dural sac, compressive flattening of the lower cervical cord during neck flexion and flow void in the posterior epidural space. The forward displacement was significantly greater in patients than in age-matched control subjects. Conclusion: Flexed neck position MRI is helpful to find radiological abnormalities of the lower cervical dural sac and spinal cord, which were combined with clinical disorder to diagnose juvenile muscular atrophy of the distal upper extremity. (authors)

  3. Health Impacts of the Great Recession: A Critical Review.

    Science.gov (United States)

    Margerison-Zilko, Claire; Goldman-Mellor, Sidra; Falconi, April; Downing, Janelle

    2016-03-01

    The severity, sudden onset, and multipronged nature of the Great Recession (2007-2009) provided a unique opportunity to examine the health impacts of macroeconomic downturn. We comprehensively review empirical literature examining the relationship between the Recession and mental and physical health outcomes in developed nations. Overall, studies reported detrimental impacts of the Recession on health, particularly mental health. Macro- and individual-level employment- and housing-related sequelae of the Recession were associated with declining fertility and self-rated health, and increasing morbidity, psychological distress, and suicide, although traffic fatalities and population-level alcohol consumption declined. Health impacts were stronger among men and racial/ethnic minorities. Importantly, strong social safety nets in some European countries appear to have buffered those populations from negative health effects. This literature, however, still faces multiple methodological challenges, and more time may be needed to observe the Recession's full health impact. We conclude with suggestions for future work in this field.

  4. Congenital spinal malformations; Kongenitale spinale Malformationen

    Energy Technology Data Exchange (ETDEWEB)

    Ertl-Wagner, B.B.; Reiser, M.F. [Klinikum Grosshadern, Ludwig-Maximilians-Univ. Muenchen (Germany). Inst. fuer Klinische Radiologie

    2001-12-01

    Congenital spinal malformations form a complex and heterogeneous group of disorders whose pathogenesis is best explained embryologically. Radiologically, it is important to formulate a diagnosis when the disorder first becomes symptomatic. However, it is also crucial to detect complications of the disorder or of the respective therapeutic interventions in the further course of the disease such as hydromyelia or re-tethering after repair of a meningomyelocele. Moreover, once a congenital spinal malformation is diagnosed, associated malformations should be sought after. A possible syndromal classification such as in OEIS- or VACTERL-syndromes should also be considered. (orig.) [German] Kongenitale spinale Malformationen stellen eine komplexe Gruppe an Stoerungen dar, deren Genese sich am einfachsten aus der Embryologie heraus erklaeren laesst. Bei der klinisch-radiologischen Begutachtung ist zunaechst ihre korrekte Klassifikation im Rahmen der Erstdiagnose wichtig. Im weiteren Verlauf ist es jedoch zudem entscheidend, moegliche Komplikationen wie beispielsweise eine Hydromyelie oder ein Wiederanheften des Myelons nach Operation einer Spina bifida aperta zu erkennen. Zudem sollte bei der Diagnosestellung einer kongenitalen spinalen Malformation immer auch auf assoziierte Fehlbildungen, wie z.B. die Diastematomyelie oder das intraspinale Lipom bei der Spina bifida aperta, sowie auf eine moegliche syndromale Einordnung wie beispielsweise beim OEIS-oder VACTERL-Syndrom geachtet werden. (orig.)

  5. Bimedial faden recession versus augmented medial rectus recession in the treatment of high ac/a ratio partially accommodative esotropia with large distant near disparity

    Directory of Open Access Journals (Sweden)

    Mohammed F Farid

    2016-01-01

    Faden recession achieves marginal superior control of DND and high AC/A ratio in convergence excess partially accommodative ET. Augmented recession also works well with the possible development of consecutive exotropia in cases with extremely high DND. This study recommends Augmented recession for cases with mild to moderate DND and Faden recession for cases with extremely large DND.

  6. Genetic Modifiers of Duchenne Muscular Dystrophy and Dilated Cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Andrea Barp

    Full Text Available Dilated cardiomyopathy (DCM is a major complication and leading cause of death in Duchenne muscular dystrophy (DMD. DCM onset is variable, suggesting modifier effects of genetic or environmental factors. We aimed to determine if polymorphisms previously associated with age at loss of independent ambulation (LoA in DMD (rs28357094 in the SPP1 promoter, rs10880 and the VTTT/IAAM haplotype in LTBP4 also modify DCM onset.A multicentric cohort of 178 DMD patients was genotyped by TaqMan assays. We performed a time-to-event analysis of DCM onset, with age as time variable, and finding of left ventricular ejection fraction 70 mL/m2 as event (confirmed by a previous normal exam < 12 months prior; DCM-free patients were censored at the age of last echocardiographic follow-up.Patients were followed up to an average age of 15.9 ± 6.7 years. Seventy-one/178 patients developed DCM, and median age at onset was 20.0 years. Glucocorticoid corticosteroid treatment (n = 88 untreated; n = 75 treated; n = 15 unknown did not have a significant independent effect on DCM onset. Cardiological medications were not administered before DCM onset in this population. We observed trends towards a protective effect of the dominant G allele at SPP1 rs28357094 and recessive T allele at LTBP4 rs10880, which was statistically significant in steroid-treated patients for LTBP4 rs10880 (< 50% T/T patients developing DCM during follow-up [n = 13]; median DCM onset 17.6 years for C/C-C/T, log-rank p = 0.027.We report a putative protective effect of DMD genetic modifiers on the development of cardiac complications, that might aid in risk stratification if confirmed in independent cohorts.

  7. Limb-girdle muscular dystrophy: an immunohistochemical diagnostic approach Distrofias musculares de cinturas: uma abordagem diagnóstica imuno-histoquímica

    Directory of Open Access Journals (Sweden)

    Enio Alberto Comerlato

    2005-06-01

    Full Text Available The limb-girdle muscle dystrophy (LGMD represents a heterogeneous group of muscular diseases with dominant and recessive inheritance, individualized by gene mutation. A group of 56 patients, 32 males and 24 females, with suggestive LGMD diagnosis were submitted to clinical evaluation, serum muscle enzymes, electromyography, muscle biopsy, and the immunoidentification (ID of sarcoglycans (SG alpha, beta, gamma and delta, dysferlin and western blot for calpain-3. All the patients had normal ID for dystrophin (rod domain, carboxyl and amine terminal. The alpha-SG was normal in 42 patients, beta-SG in 28, beta-SG in 45, delta-SG in 32, dysferlin in 37 and calpain-3 in 9. There was a reduction in the alpha-SG in 7 patients, beta-SG in 4, gamma-SG in 2, and delta-SG in 8. There was deficiency of alpha-SG in 7 patients, beta-SG in 6, gamma-SG in 9, delta-SG in 5, dysferlin in 8, and calpain-3 in 5. The patients were grouped according the ID as sarcoglycans deficiency 18 cases, dysferlin deficiency 8 cases and calpain-3 deficiency 5 cases. Only the sarcoglycans deficiency group showed calf hypertrophy. The dysferlin deficiency group was more frequent in females and the onset was later than sarcoglycan and calpain-3 deficiency groups. The calpain-3 deficiency group occurred only in males and showed an earlier onset and weaker muscular strength.As distrofias musculares de cinturas (DMC representam grupo heterogêneo de doenças musculares com heranças autossômicas dominante ou recessivas, caracterizadas geneticamente por mutações gênicas específicas. Cinqüenta e seis pacientes, 32 masculinos e 24 femininos, com diagnóstico sugestivo de DMC, foram submetidos a avaliação clínica, dosagem séricas das enzimas musculares, eletromiografia, biópsia muscular e imunoidentificação (ID das proteínas sarcoglicanas (SG alfa, beta, gama e delta, disferlina e calpaína-3. A ID da distrofina (domínio rod e terminais carboxila e amino era normal em todos

  8. Economic recession and suicidal behaviour: Possible mechanisms and ameliorating factors.

    Science.gov (United States)

    Haw, Camilla; Hawton, Keith; Gunnell, David; Platt, Stephen

    2015-02-01

    A growing body of research evidence from countries around the world indicates that economic recession is associated with increases in suicide, particularly in males of working age. To explore contributory and ameliorating factors associated with economic recession and suicide and thereby stimulate further research in this area and encourage policy makers to consider how best to reduce the impact of recession on mental health and suicidal behaviour. We conducted a selective review of the worldwide literature focusing on possible risk factors, mechanisms and preventative strategies for suicidal behaviour linked to economic recession. A model of how recession might affect suicide rates is presented. A major and often prolonged effect of recession is on unemployment and job insecurity. Other important effects include those exerted by financial loss, bankruptcy and home repossession. It is proposed these factors may lead directly or indirectly to mental health problems such as depression, anxiety and binge drinking and then to suicidal behaviour. Countries with active labour market programmes and sustained welfare spending during recessions have less marked increases in suicide rates than those that cut spending on welfare and job-search initiatives for the unemployed. Other measures likely to help include targeted interventions for unemployed people, membership of social organisations and responsible media reporting. Good primary care and mental health services are needed to cope with increased demand in times of economic recession but some governments have in fact reduced healthcare spending as an austerity measure. The research evidence linking recession, unemployment and suicide is substantial, but the evidence for the other mechanisms we have investigated is much more tentative. We describe the limitations of the existing body of research as well as make suggestions for future research into the effects of economic recession on suicidal behaviour. © The Author

  9. Management of Penetrating Spinal Cord Injuries in a Non Spinal ...

    African Journals Online (AJOL)

    Management of Penetrating Spinal Cord Injuries in a Non Spinal Centre: Experience at Enugu, Nigeria. ... The thoracic spine{9(41%)}was most often involved. ... Five (23%) patients with injury at cervical level died from respiratory failure.

  10. Respiratory muscle training in Duchenne muscular dystrophy.

    OpenAIRE

    Rodillo, E; Noble-Jamieson, C M; Aber, V; Heckmatt, J Z; Muntoni, F; Dubowitz, V

    1989-01-01

    Twenty two boys with Duchenne muscular dystrophy were entered into a randomised double blind crossover trial to compare respiratory muscle training with a Triflow II inspirometer and 'placebo' training with a mini peak flow meter. Supine posture was associated with significantly impaired lung function, but respiratory muscle training showed no benefit.

  11. A Drosophila model for Duchenne muscular dystrophy

    NARCIS (Netherlands)

    Plas, Mariska Cathelijne van der

    2008-01-01

    Duchenne Muscular Dystrophy (DMD) is a severe X-linked disease characterized by progressive muscle wasting and sometimes mild mental retardation. The disease is caused by mutations in the dystrophin gene. DMD is correlated with the absence of Dp427, which is located along the sarcolemma in skeletal

  12. Duchenne muscular dystrophy models show their age

    OpenAIRE

    Chamberlain, Jeffrey S.

    2010-01-01

    The lack of appropriate animal models has hampered efforts to develop therapies for Duchenne muscular dystrophy (DMD). A new mouse model lacking both dystrophin and telomerase (Sacco et al., 2010) closely mimics the pathological progression of human DMD and shows that muscle stem cell activity is a key determinant of disease severity.

  13. What Are the Treatments for Muscular Dystrophy?

    Science.gov (United States)

    ... Child Neurology Society. (2005). Practice parameter: Corticosteroid treatment of Duchenne dystrophy. Neurology, 64 , 13-20. Retrieved June 22, 2012, ... Statement. (2004). Respiratory care of the patient with Duchenne muscular ... American Journal of Respiratory and Critical Care Medicine, 170, 456-465. ...

  14. Visuospatial Attention Disturbance in Duchenne Muscular Dystrophy

    Science.gov (United States)

    De Moura, Maria Clara Drummond Soares; do Valle, Luiz Eduardo Ribeiro; Resende, Maria Bernadete Dutra; Pinto, Katia Osternack

    2010-01-01

    Aim: The cognitive deficits present in the Duchenne muscular dystrophy (DMD) are not yet well characterized. Attention, considered to be the brain mechanism responsible for the selection of sensory stimuli, could be disturbed in DMD, contributing, at least partially, to the observed global cognitive deficit. The aim of this study was to…

  15. Brain Function in Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    J. Gordon Millichap

    2002-02-01

    Full Text Available The role of dystrophin disorders in the CNS function of boys with Duchenne muscular dystrophy (DMD and the dystrophin-deficient mdx mouse, an animal model of DMD, is reviewed at the University of New South Wales, University of Sydney, Australia.

  16. Duchenne muscular dystrophy - a molecular service

    African Journals Online (AJOL)

    In 1987 a carrier detection and prenatal diagnostic service for. Duchenne muscular dystrophy using molecular technology was instituted at the Department of Human Genetics, Uni- versity of Cape Town, to serve affe.cted families in southern. Africa. DNA samples from 100 affected male subjects and. 350 of their relatives ...

  17. Skull development in the muscular dystrophic mouse

    DEFF Research Database (Denmark)

    Vilmann, H; Kirkeby, S; Moss, M L

    1989-01-01

    Roentgencephalometric tracings of skulls of 7-week-old normal and muscular dystrophic mice were compared. A marked size reduction of the dystrophic skulls relative to the normal ones was observed. However, the visceral parts of the dystrophic skull were more reduced in size than the neural parts....

  18. Hereditary muscular dystrophies and the heart

    NARCIS (Netherlands)

    Hermans, M. C. E.; Pinto, Y. M.; Merkies, I. S. J.; de Die-Smulders, C. E. M.; Crijns, H. J. G. M.; Faber, C. G.

    2010-01-01

    Cardiac disease is a common clinical manifestation of neuromuscular disorders, particularly of muscular dystrophies. Heart muscle cells as well as specialized conducting myocardial fibres may be affected by the dystrophic process. The incidence and nature of cardiac involvement vary with different

  19. Continuous spinal anesthesia.

    Science.gov (United States)

    Moore, James M

    2009-01-01

    Continuous spinal anesthesia (CSA) is an underutilized technique in modern anesthesia practice. Compared with other techniques of neuraxial anesthesia, CSA allows incremental dosing of an intrathecal local anesthetic for an indefinite duration, whereas traditional single-shot spinal anesthesia usually involves larger doses, a finite, unpredictable duration, and greater potential for detrimental hemodynamic effects including hypotension, and epidural anesthesia via a catheter may produce lesser motor block and suboptimal anesthesia in sacral nerve root distributions. This review compares CSA with other anesthetic techniques and also describes the history of CSA, its clinical applications, concerns regarding neurotoxicity, and other pharmacologic implications of its use. CSA has seen a waxing and waning of its popularity in clinical practice since its initial description in 1907. After case reports of cauda equina syndrome were reported with the use of spinal microcatheters for CSA, these microcatheters were withdrawn from clinical practice in the United States but continued to be used in Europe with no further neurologic sequelae. Because only large-bore catheters may be used in the United States, CSA is usually reserved for elderly patients out of concern for the risk of postdural puncture headache in younger patients. However, even in younger patients, sometimes the unique clinical benefits and hemodynamic stability involved in CSA outweigh concerns regarding postdural puncture headache. Clinical scenarios in which CSA may be of particular benefit include patients with severe aortic stenosis undergoing lower extremity surgery and obstetric patients with complex heart disease. CSA is an underutilized technique in modern anesthesia practice. Perhaps more accurately termed fractional spinal anesthesia, CSA involves intermittent dosing of local anesthetic solution via an intrathecal catheter. Where traditional spinal anesthesia involves a single injection with a

  20. Imaging in spinal trauma

    International Nuclear Information System (INIS)

    Goethem, J.W.M. van; Maes, Menno; Oezsarlak, Oezkan; Hauwe, Luc van den; Parizel, Paul M.

    2005-01-01

    Because it may cause paralysis, injury to the spine is one of the most feared traumas, and spinal cord injury is a major cause of disability. In the USA approximately 10,000 traumatic cervical spine fractures and 4000 traumatic thoracolumbar fractures are diagnosed each year. Although the number of individuals sustaining paralysis is far less than those with moderate or severe brain injury, the socioeconomic costs are significant. Since most of the spinal trauma patients survive their injuries, almost one out of 1000 inhabitants in the USA are currently being cared for partial or complete paralysis. Little controversy exists regarding the need for accurate and emergent imaging assessment of the traumatized spine in order to evaluate spinal stability and integrity of neural elements. Because clinicians fear missing occult spine injuries, they obtain radiographs for nearly all patients who present with blunt trauma. We are influenced on one side by fear of litigation and the possible devastating medical, psychologic and financial consequences of cervical spine injury, and on the other side by pressure to reduce health care costs. A set of clinical and/or anamnestic criteria, however, can be very useful in identifying patients who have an extremely low probability of injury and who consequently have no need for imaging studies. Multidetector (or multislice) computed tomography (MDCT) is the preferred primary imaging modality in blunt spinal trauma patients who do need imaging. Not only is CT more accurate in diagnosing spinal injury, it also reduces imaging time and patient manipulation. Evidence-based research has established that MDCT improves patient outcome and saves money in comparison to plain film. This review discusses the use, advantages and disadvantages of the different imaging techniques used in spinal trauma patients and the criteria used in selecting patients who do not need imaging. Finally an overview of different types of spinal injuries is given

  1. Imaging in spinal trauma

    Energy Technology Data Exchange (ETDEWEB)

    Goethem, J.W.M. van [Universitair Ziekenhuis Antwerpen, University of Antwerp, Belgium, Department of Radiology, Edegem (Belgium); Algemeen Ziekenhuis Maria Middelares, Department of Radiology, Sint-Niklaas (Belgium); Maes, Menno; Oezsarlak, Oezkan; Hauwe, Luc van den; Parizel, Paul M. [Universitair Ziekenhuis Antwerpen, University of Antwerp, Belgium, Department of Radiology, Edegem (Belgium)

    2005-03-01

    Because it may cause paralysis, injury to the spine is one of the most feared traumas, and spinal cord injury is a major cause of disability. In the USA approximately 10,000 traumatic cervical spine fractures and 4000 traumatic thoracolumbar fractures are diagnosed each year. Although the number of individuals sustaining paralysis is far less than those with moderate or severe brain injury, the socioeconomic costs are significant. Since most of the spinal trauma patients survive their injuries, almost one out of 1000 inhabitants in the USA are currently being cared for partial or complete paralysis. Little controversy exists regarding the need for accurate and emergent imaging assessment of the traumatized spine in order to evaluate spinal stability and integrity of neural elements. Because clinicians fear missing occult spine injuries, they obtain radiographs for nearly all patients who present with blunt trauma. We are influenced on one side by fear of litigation and the possible devastating medical, psychologic and financial consequences of cervical spine injury, and on the other side by pressure to reduce health care costs. A set of clinical and/or anamnestic criteria, however, can be very useful in identifying patients who have an extremely low probability of injury and who consequently have no need for imaging studies. Multidetector (or multislice) computed tomography (MDCT) is the preferred primary imaging modality in blunt spinal trauma patients who do need imaging. Not only is CT more accurate in diagnosing spinal injury, it also reduces imaging time and patient manipulation. Evidence-based research has established that MDCT improves patient outcome and saves money in comparison to plain film. This review discusses the use, advantages and disadvantages of the different imaging techniques used in spinal trauma patients and the criteria used in selecting patients who do not need imaging. Finally an overview of different types of spinal injuries is given

  2. Relief from Back Pain Through Postural Adjustment: a Controlled Clinical Trial of the Immediate Effects of Muscular Chains Therapy (MCT).

    Science.gov (United States)

    Rosario, Jose L

    2014-09-01

    Back pain can be one of the most common health problems, causing suffering, disabilities, and financial losses. Postural models for pain treatment state that poor posture alters the joint position and causes pain, such as back pain. Muscular Chain Therapy (MCT) is a technique that is used to treat posture pathologies, among others. The aim of the present study was to assess the efficiency of a single session of Muscular Chain Therapy (MCT) on complaints of undiagnosed musculoskeletal spinal pain. Physical therapy clinic of the University of Center-West (Guarapuava, Brazil). 100 subjects, aged between 20 and 39 years, with complaints of spinal musculoskeletal pain. Randomized controlled trial. The participants were randomly assigned by a non-care provider into two groups: The MCT Group that received Muscular Chain Treatment and the Control Group that received a placebo treatment of 15 minutes turned off ultrasound therapy. All volunteers were assessed before and after treatment using an analog pain scale. A score of 0 indicated no pain and 10 was the maximum degree of pain on the scale. Degree of pain measured by analog scale. The chi-square goodness of fit test was used to compare gender distribution among groups displayed a p value = .25. Subject age had differences analyzed using the unpaired t test (p = .44). Pain assessment for treatment and placebo control groups was analyzed using a paired t test and unpaired t test. The paired t test was used for intragroup before/after treatment comparison (MCT p = .00001; Control Group p = .0001). The unpaired t test was used for comparing the difference of the pain level before and after treatment between groups (p = .0001). A priori statistical significance was set a p = .05. It is possible to conclude that one MCT session is an effective treatment of undiagnosed spinal musculoskeletal pain.

  3. Assessing and conceptualizing orgasm after a spinal cord injury.

    Science.gov (United States)

    Courtois, Frédérique; Charvier, Kathleen; Vézina, Jean-Guy; Journel, Nicolas Morel; Carrier, Serge; Jacquemin, Géraldine; Côté, Isabelle

    2011-11-01

    To provide a questionnaire for assessing the sensations characterizing orgasm. To test the hypothesis that orgasm is related to autonomic hyperreflexia (AHR) in individuals with a spinal cord injury (SCI). A total of 97 men with SCI, of whom 50 showed AHR at ejaculation and 39 showed no AHR, were compared. Ejaculation was obtained through natural stimulation, vibrostimulation or vibrostimulation combined with midodrine (5-25 mg). Cardiovascular measures were recorded before, at, and after each test. Responses to the questionnaire were divided into four categories: cardiovascular, muscular, autonomic and dysreflexic sensations. Significantly more sensations were described at ejaculation than with sexual stimulation alone. Men with SCI who experienced AHR at ejaculation reported significantly more cardiovascular, muscular, autonomic and dysreflexic responses than those who did not. There was no difference between men with complete and those with incomplete lesions. The findings show that the questionnaire is a useful tool to assess orgasm and to guide patients in identifying the bodily sensations that accompany or build up to orgasm. The findings also support the hypothesis that orgasm may be related to the presence of AHR in individuals with SCI. Data from able-bodied men also suggest that AHR could be related to orgasm, as increases in blood pressure are observed at ejaculation along with cardiovascular, autonomic and muscular sensations. © 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

  4. Loss of heterozygosity and carrier identification in Duchenne muscular dystrophy: a familiar case with recombination event

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    Fonseca-Mendoza Dora Janeth

    2012-04-01

    Full Text Available Duchenne/Becker Muscular Dystrophy (DMD/BMD is an X-linked recessive disease characterizedby muscular weakness. It is caused by mutations on the dystrophin gen. Loss of heterozygosityallows us to identify female carriers of deletions on the dystrophin gen. Objective: identifyfemale carriers in a family with a patient affected by DMD. Material and methods: nine familymembers and the affected child were analyzed using DNA extraction and posterior amplificationof ten STRs on the dystrophin gen. Haplotypes were constructed and the carrier status determinedin two of the six women analyzed due to loss of heterozygosity in three STRs. Additionally, weobserved a recombination event. Conclusions: loss of heterozygosity allows us to establish witha certainty of 100% the carrier status of females with deletions on the dystrophin gen. By theconstruction of haplotypes we were able to identify the X chromosome with the deletion in twoof the six women analyzed. We also determined a recombination event in one of the sisters of theaffected child. These are described with a high frequency (12%. A possible origin for the mutationis a gonadal mosaicism in the maternal grandfather or in the mother of the affected childin a very early stage in embryogensis. This can be concluded using the analysis of haplotypes.

  5. The Classification, Natural History and Treatment of the Limb Girdle Muscular Dystrophies.

    Science.gov (United States)

    Murphy, Alexander Peter; Straub, Volker

    2015-07-22

    Over sixty years ago John Walton and Frederick Nattrass defined limb girdle muscular dystrophy (LGMD) as a separate entity from the X-linked dystrophinopathies such as Duchenne and Becker muscular dystrophies. LGMD is a highly heterogeneous group of very rare neuromuscular disorders whose common factor is their autosomal inheritance. Sixty years later, with the development of increasingly advanced molecular genetic investigations, a more precise classification and understanding of the pathogenesis is possible.To date, over 30 distinct subtypes of LGMD have been identified, most of them inherited in an autosomal recessive fashion. There are significant differences in the frequency of subtypes of LGMD between different ethnic populations, providing evidence of founder mutations. Clinically there is phenotypic heterogeneity between subtypes of LGMD with varying severity and age of onset of symptoms. The first natural history studies into subtypes of LGMD are in process, but large scale longitudinal data have been lacking due to the rare nature of these diseases. Following natural history data collection, the next challenge is to develop more effective, disease specific treatments. Current management is focussed on symptomatic and supportive treatments. Advances in the application of new omics technologies and the generation of large-scale biomedical data will help to better understand disease mechanisms in LGMD and should ultimately help to accelerate the development of novel and more effective therapeutic approaches.

  6. Preliminary diffusion tensor imaging studies in limb-girdle muscular dystrophies

    Science.gov (United States)

    Hidalgo-Tobon, S.; Hernandez-Salazar, G.; Vargas-Cañas, S.; Marrufo-Melendez, O.; Solis-Najera, S.; Taboada-Barajas, J.; Rodriguez, A. O.; Delgado-Hernandez, R.

    2012-10-01

    Limb-girdle muscular dystrophies (LGMD) are a group of autosomal dominantly or recessively inherited muscular dystrophies that also present with primary proximal (limb-girdle) muscle weakness. This type of dystrophy involves the shoulder and pelvic girdles, distinct phenotypic or clinical characteristics are recognized. Imaging experiments were conducted on a 1.5T GE scanner (General Electric Medical Systems. Milwaukee. USA), using a combination of two eight-channel coil array. Diffusion Tensor Imaging (DTI) data were acquired using a SE-EPI sequence, diffusion weighted gradients were applied along 30 non-collinear directions with a b-value=550 s/mm2. The connective tissue content does not appear to have a significant effect on the directionality of the diffusion, as assessed by fractional anisotropy. The fibers of the Sartorius muscle and gracilis showed decreased number of tracts, secondary to fatty infiltration and replacement of connective tissue and muscle mass loss characteristic of the underlying pathology. Our results demonstrated the utility of non-invasive MRI techniques to characterize the muscle pathology, through quantitative and qualitative methods such as the FA values and tractrography.

  7. Cardiac involvement in children with neuro-muscular disorders

    Directory of Open Access Journals (Sweden)

    E. N. Arkhipova

    2015-01-01

    Full Text Available Many inherited neuromuscular disorders include cardiac involvement as a typical clinical feature. Among the most common of them is the group of muscular dystrophies. Dilated cardiomyopathy, ventricular arrhythmias, atrial fibrillations, atrioventricular and intraventricular conduction abnormalities, and sudden cardiac death are well known pathological findings in Duchenne muscular dystrophies, myotonic dystrophy type I and 2, Emery-Dreifuss muscular dystrophies and different types of limb-girdle muscular dystrophies and other disorders. Detection of cardiac pathology in patients with different muscular dystrophies is possible with ECG, echocardiography and cardiovascular magnetic resonance imaging, which are recommended for screening and early cardioprotective treatment.

  8. Spinal canal stenosis; Spinalkanalstenose

    Energy Technology Data Exchange (ETDEWEB)

    Papanagiotou, P.; Boutchakova, M. [Klinikum Bremen-Mitte/Bremen-Ost, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Bremen (Germany)

    2014-11-15

    Spinal stenosis is a narrowing of the spinal canal by a combination of bone and soft tissues, which can lead to mechanical compression of spinal nerve roots or the dural sac. The lumbal spinal compression of these nerve roots can be symptomatic, resulting in weakness, reflex alterations, gait disturbances, bowel or bladder dysfunction, motor and sensory changes, radicular pain or atypical leg pain and neurogenic claudication. The anatomical presence of spinal canal stenosis is confirmed radiologically with computerized tomography, myelography or magnetic resonance imaging and play a decisive role in optimal patient-oriented therapy decision-making. (orig.) [German] Die Spinalkanalstenose ist eine umschriebene, knoechern-ligamentaer bedingte Einengung des Spinalkanals, die zur Kompression der Nervenwurzeln oder des Duralsacks fuehren kann. Die lumbale Spinalkanalstenose manifestiert sich klinisch als Komplex aus Rueckenschmerzen sowie sensiblen und motorischen neurologischen Ausfaellen, die in der Regel belastungsabhaengig sind (Claudicatio spinalis). Die bildgebende Diagnostik mittels Magnetresonanztomographie, Computertomographie und Myelographie spielt eine entscheidende Rolle bei der optimalen patientenbezogenen Therapieentscheidung. (orig.)

  9. Potentialities of spinal liquor scanography

    International Nuclear Information System (INIS)

    Vlakhov, N.; Vylkanov, P.

    1986-01-01

    It is shown that spinal liquor scanography is a harmless and informative method for the examination of patients, permitting to detect injury foci for spinal cord tumours in 90% cases, for acute injuries of the vertebral column and spinal cord in 89.5% cases, for herniation of nucleus pulposus in 81% cases. The method of spinal liquor scanography can be used in neurology and neurosurgery to select the method of treatment and to evaluate its efficiency

  10. Histopathologic Evolution of Cardiomyopathy in a Canine Model of Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Lygia M.M. Malvestio

    2015-07-01

    Full Text Available Duchenne muscular dystrophy (DMD is a recessive X-linked disorder characterized for mutation in dystrophin gene and manifested by progressive degeneration and necrosis of skeletal and cardiac muscle with replacement leading to generalized muscular weakness and atrophy. The dog Golden Retriever Muscular Dystrophy (GRMD is the best experimental model for DMD, with genotypic and phenotypic manifestations closely of human disease. Similar to patients with DMD, heart failure is a major cause of death in GRMD animals. The objective of this study was to evaluate the pathological progression of myocardial lesions from GRMD dogs in different ages in order to clarify the pathogenesis of Duchenne´s cardiomyopathy. Fragments of left and right ventricle and interventricular septum, from 18 GRMD dogs between 6 to 51 months were collected, fixed, dehydrated, clarified, and finally embedded in paraffin. Five micrometer thick serial sections were obtained and stained with Hematoxylin-Eosin (HE, Picrosirius red, and Von Kossa. Histological analyses were performed at the light microscopy. Myocardial lesions were observed in all GRMD dogs and the sequence of cardiac lesion classified according to according to the age included: abnormal calcium accumulation, myofibrillar necrosis, proliferation of granulation tissue, endomysial and perimysial fibrosis, and finally myocardial fatty infiltration. Interestingly, several Anitschkow cells, the hallmark of rheumatic carditis, were detected in inflammatory infiltrate present at granulation tissue. Our results demonstrate the sequence of cardiac lesions that determine the cardiomyopathy in Golden Retriever dogs affected by DMD and exhibit, for the first time, the Anitschkow cells in the histological findings of this cardiomyopathy. These results are relevant for to clarify the pathogenesis of cardiomyopathy in dogs and humans affected by DMD.

  11. Gene expression profiling in limb-girdle muscular dystrophy 2A.

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    Amets Sáenz

    Full Text Available Limb-girdle muscular dystrophy type 2A (LGMD2A is a recessive genetic disorder caused by mutations in calpain 3 (CAPN3. Calpain 3 plays different roles in muscular cells, but little is known about its functions or in vivo substrates. The aim of this study was to identify the genes showing an altered expression in LGMD2A patients and the possible pathways they are implicated in. Ten muscle samples from LGMD2A patients with in which molecular diagnosis was ascertained were investigated using array technology to analyze gene expression profiling as compared to ten normal muscle samples. Upregulated genes were mostly those related to extracellular matrix (different collagens, cell adhesion (fibronectin, muscle development (myosins and melusin and signal transduction. It is therefore suggested that different proteins located or participating in the costameric region are implicated in processes regulated by calpain 3 during skeletal muscle development. Genes participating in the ubiquitin proteasome degradation pathway were found to be deregulated in LGMD2A patients, suggesting that regulation of this pathway may be under the control of calpain 3 activity. As frizzled-related protein (FRZB is upregulated in LGMD2A muscle samples, it could be hypothesized that beta-catenin regulation is also altered at the Wnt signaling pathway, leading to an incorrect myogenesis. Conversely, expression of most transcription factor genes was downregulated (MYC, FOS and EGR1. Finally, the upregulation of IL-32 and immunoglobulin genes may induce the eosinophil chemoattraction explaining the inflammatory findings observed in presymptomatic stages. The obtained results try to shed some light on identification of novel therapeutic targets for limb-girdle muscular dystrophies.

  12. Muscle function recovery in golden retriever muscular dystrophy after AAV1-U7 exon skipping.

    Science.gov (United States)

    Vulin, Adeline; Barthélémy, Inès; Goyenvalle, Aurélie; Thibaud, Jean-Laurent; Beley, Cyriaque; Griffith, Graziella; Benchaouir, Rachid; le Hir, Maëva; Unterfinger, Yves; Lorain, Stéphanie; Dreyfus, Patrick; Voit, Thomas; Carlier, Pierre; Blot, Stéphane; Garcia, Luis

    2012-11-01

    Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder resulting from lesions of the gene encoding dystrophin. These usually consist of large genomic deletions, the extents of which are not correlated with the severity of the phenotype. Out-of-frame deletions give rise to dystrophin deficiency and severe DMD phenotypes, while internal deletions that produce in-frame mRNAs encoding truncated proteins can lead to a milder myopathy known as Becker muscular dystrophy (BMD). Widespread restoration of dystrophin expression via adeno-associated virus (AAV)-mediated exon skipping has been successfully demonstrated in the mdx mouse model and in cardiac muscle after percutaneous transendocardial delivery in the golden retriever muscular dystrophy dog (GRMD) model. Here, a set of optimized U7snRNAs carrying antisense sequences designed to rescue dystrophin were delivered into GRMD skeletal muscles by AAV1 gene transfer using intramuscular injection or forelimb perfusion. We show sustained correction of the dystrophic phenotype in extended muscle areas and partial recovery of muscle strength. Muscle architecture was improved and fibers displayed the hallmarks of mature and functional units. A 5-year follow-up ruled out immune rejection drawbacks but showed a progressive decline in the number of corrected muscle fibers, likely due to the persistence of a mild dystrophic process such as occurs in BMD phenotypes. Although AAV-mediated exon skipping was shown safe and efficient to rescue a truncated dystrophin, it appears that recurrent treatments would be required to maintain therapeutic benefit ahead of the progression of the disease.

  13. The Great Recession and America's Geography of Unemployment.

    Science.gov (United States)

    Thiede, Brian C; Monnat, Shannon M

    The Great Recession of 2007-2009 was the most severe and lengthy economic crisis in the U.S. since the Great Depression. The impacts on the population were multi-dimensional, but operated largely through local labor markets. To examine differences in recession-related changes in county unemployment rates and assess how population and place characteristics shaped these patterns. We calculate and decompose Theil Indexes to describe recession-related changes in the distribution of unemployment rates between counties and states. We use exploratory spatial statistics to identify geographic clusters of counties that experienced similar changes in unemployment. We use spatial regression to evaluate associations between county-level recession impacts on unemployment and demographic composition, industrial structure, and state context. The recession was associated with increased inequality between county labor markets within states, but declining between-state differences. Counties that experienced disproportionate recession-related increases in unemployment were spatially clustered and characterized by large shares of historically disadvantaged racial and ethnic minority populations, low educational attainment, and heavy reliance on pro-cyclical industries. Associations between these sources of vulnerability were partially explained by unobserved state-level factors. The local consequences of macroeconomic trends are associated with county population characteristics, as well as the structural contexts and policy environments in which they are embedded. The recession placed upward pressure on within-state inequality between local labor market conditions. To present new estimates of the recession's impact on local labor markets, quantify how heterogeneous impacts affected the distribution of unemployment prevalence, and identify county characteristics associated with disproportionately large recession-related increases in unemployment.

  14. Recent declines in cancer incidence: related to the Great Recession?

    Science.gov (United States)

    Gomez, Scarlett Lin; Canchola, Alison J; Nelson, David O; Keegan, Theresa H M; Clarke, Christina A; Cheng, Iona; Shariff-Marco, Salma; DeRouen, Mindy; Catalano, Ralph; Satariano, William A; Davidson-Allen, Kathleen; Glaser, Sally L

    2017-02-01

    In recent years, cancer case counts in the U.S. underwent a large, rapid decline-an unexpected change given population growth for older persons at highest cancer risk. As these declines coincided with the Great Recession, we examined whether they were related to economic conditions. Using California Cancer Registry data from California's 30 most populous counties, we analyzed trends in cancer incidence during pre-recession (1996-2007) and recession/recovery (2008-2012) periods for all cancers combined and the ten most common sites. We evaluated the recession's association with rates using a multifactorial index that measured recession impact, and modeled associations between case counts and county-level unemployment rates using Poisson regression. Yearly cancer incidence rate declines were greater during the recession/recovery (3.3% among males, 1.4% among females) than before (0.7 and 0.5%, respectively), particularly for prostate, lung, and colorectal cancers. Lower case counts, especially for prostate and liver cancer among males and breast cancer, melanoma, and ovarian cancer among females, were associated with higher unemployment rates, irrespective of time period, but independent of secular effects. The associations for melanoma translated up to a 3.6% decrease in cases with each 1% increase in unemployment. Incidence declines were not greater in counties with higher recession impact index. Although recent declines in incidence of certain cancers are not differentially impacted by economic conditions related to the Great Recession relative to pre-recession conditions, the large recent absolute declines in the case counts of some cancer may be attributable to the large declines in unemployment in the recessionary period. This may occur through decreased engagement in preventive health behaviors, particularly for clinically less urgent cancers. Continued monitoring of trends is important to detect any rises in incidence rates as deferred diagnoses come to

  15. The Great Recession and America's geography of unemployment

    Directory of Open Access Journals (Sweden)

    Brian Thiede

    2016-09-01

    Full Text Available Background: The Great Recession of 2007-2009 was the most severe and lengthy economic crisis in the US since the Great Depression of the 1930s. The impacts on the population were multi-dimensional, but operated largely through local labor markets. Objective: To examine differences in recession-related changes in county unemployment rates and assess how population and place characteristics shaped these patterns. Methods: We calculate and decompose Theil Indexes to describe recession-related changes in the distribution of unemployment rates between counties and states. We use exploratory spatial statistics to identify geographic clusters of counties that experienced similar changes in unemployment. We use spatial regression to evaluate associations between county-level recession impacts on unemployment and demographic composition, industrial structure, and state context. Results: The recession was associated with increased inequality between county labor markets within states, but declining between-state differences. Counties that experienced disproportionate recession-related increases in unemployment were spatially clustered and characterized by large shares of historically disadvantaged racial and ethnic minority populations, low educational attainment, and heavy reliance on pro-cyclical industries. Associations between these sources of vulnerability were partially explained by unobserved state-level factors. Conclusions: The local consequences of macroeconomic trends are associated with county population characteristics, and the structural contexts and policy environments in which they are embedded. The recession placed upward pressure on within-state disparities in local labor market conditions. Contribution: To present new estimates of the recession's impact on local labor markets, quantify how heterogeneous impacts affected the distribution of unemployment prevalence, and identify county characteristics associated with disproportionately

  16. Neuroradiology of the spinal canal

    International Nuclear Information System (INIS)

    Lehmann, R.; Molsen, H.P.

    1985-01-01

    Radiodiagnostics of the vertebral column and of the spinal cord under normal conditions and under different pathological alterations are elaborated. Especially cervical and thoracal myelography, lumbosacral myeloradiculography, spinal arteriography and phlebography as well as spinal computerized tomography are discussed in detail

  17. Spinal cord swelling and candidiasis

    International Nuclear Information System (INIS)

    Ho, K.; Gronseth, G.; Aldrich, M.; Williams, A.

    1982-01-01

    Fusiform swelling of the spinal cord was noted myelographically in a patient with Hodgkin's disease. Autopsy revealed that the swelling was cauused by Candida infection of the spinal cord. It is suggested that fungal infection be included in the differential diagnosis of spinal cord swelling in the immunsupporessed cancer patient. (orig.)

  18. Spinal cord swelling and candidiasis

    Energy Technology Data Exchange (ETDEWEB)

    Ho, K.; Gronseth, G.; Aldrich, M.; Williams, A.

    1982-11-01

    Fusiform swelling of the spinal cord was noted myelographically in a patient with Hodgkin's disease. Autopsy revealed that the swelling was caused by Candida infection of the spinal cord. It is suggested that fungal infection be included in the differential diagnosis of spinal cord swelling in the immunosuppressed cancer patient.

  19. Spinal CT scan, 2

    International Nuclear Information System (INIS)

    Nakagawa, Hiroshi

    1982-01-01

    Plain CT described fairly accurately the anatomy and lesions of the lumbar and sacral spines on their transverse sections. Since hernia of the intervertebral disc could be directly diagnosed by CT, indications of myelography could be restricted. Spinal-canal stenosis of the lumbar spine occurs because of various factors, and CT not only demonstrated the accurate size and morphology of bony canals, but also elucidated thickening of the joints and yellow ligament. CT was also useful for the diagnosis of tumors in the lumbar and sacral spines, visualizing the images of bone changes and soft tissues on the trasverse sections. But the diagnosis of intradural tumors required myelography and metrizamide CT. CT has become important for the diagnosis of spinal and spinal-cord diseases and for selection of the route of surgical arrival. (Chiba, N.)

  20. Intramedullary spinal melanocytoma

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    Meic H. Schmidt

    2010-06-01

    Full Text Available Meningeal melanocytoma is a benign lesion arising from leptomeningeal melanocytes that at times can mimic its malignant counterpart, melanoma. Lesions of the spine usually occur in extramedullary locations and present with spinal cord compression symptoms. Because most reported spinal cases occur in the thoracic region, these symptoms usually include lower extremity weakness or numbness. The authors present a case of primary intrame­dullary spinal meningeal melanocytoma presenting with bilateral lower extremity symptoms in which the patient had no known supratentorial primary lesions. Gross total surgical resection allowed for full recovery, but early recurrence of tumor was detected on close follow-up monitoring, allowing for elective local radiation without loss of neurological function. Case reports of such tumors discuss different treatment strategies, but just as important is the close follow-up monitoring in these patients even after gross total surgical resection, since these tumors can recur.

  1. Rescate de colgajo muscular de trapecio con isla cutánea en paciente lesionado medular que precisa rehabilitación inmediata Rescue of a pedicled trapezious muscle flap with skin paddle in a patient with spinal cord injury who needded inmediate rehabilitation

    Directory of Open Access Journals (Sweden)

    J.M. Arévalo Velasco

    2011-12-01

    terapias VAC® y VIA® de absoluta indicación en heridas complejas tanto agudas como crónicas porque ahorran tiempo, no sólo en las curas, sino también en términos de estancia hospitalaria total a la vez que evitan tiempos quirúrgicos innecesarios y con alta morbilidad para los pacientes.Negative pressure therapy (subatmospheric is a noninvasive treatment modality included in the armamentarium of any Service of Plastic Surgery and also in General Surgery, Vascular Surgery and Traumatology Services. It can be applied in the treatment of both chronic and acute wounds to decrease the time and number of priests and also to reduce surgeries with high morbidity for the patient. We present a patient with depressive syndrome secondary to an unfortunate postoperative course of a vertebroplasty that produced an spinal cord injury, classified as ASIA C, level D4. The patient suffered a high dorsal ulcer with 6 months of complicated evolution which finally was covered with a pedicled trapezious flap with skin paddle and, again iatrogenicaly, suffered a partial loss of the paddle and a significant seroma at the donor site. In our opinion, this case is interesting because the use of negative pressure therapy with VAC® system allows: 1 Minimize the loss of flap tissue. 2 To decrease the number of cures. 3 To decrease the time in each healing. 4 Allows the patient to move in his wheelchair with two portable VAC® systems to assist to the gym and follow his rehabilitation program. 5 With this unexpected and fast evolution, the patient had a significant clinical improvement of his depressive-anxious state and 6 The final placement of a latest generation VAC-VIA® systems on autografts allowed the patient to go on with his occupational therapy and physiotherapy for the upper extremities. We think that VAC-VIA® therapy is completely indicated to complex acute and chronic wounds because it can save time in terms of total hospital stance and avoid unnecessary surgeries with high risk

  2. Pregnancy in autosomal recessive polycystic kidney disease.

    Science.gov (United States)

    Banks, Nicole; Bryant, Joy; Fischer, Roxanne; Huizing, Marjan; Gahl, William A; Gunay-Aygun, Meral

    2015-03-01

    Autosomal recessive polycystic kidney disease (ARPKD) is the most common childhood-onset ciliopathy. As treatments improve, more women are reaching reproductive age, but little is known about ARPKD and pregnancy. In our ongoing study on ARPKD and other ciliopathies, 12 females over 18 years of age were identified and systematically evaluated. Six had children; four carried pregnancies and delivered, one used assisted reproductive technology and had a surrogate carry the pregnancy, and one adopted. We report the outcomes of four pregnancies with live birth deliveries and two women who chose alternate family building options. Patient one was diagnosed at 6 months, and at age 21 had a pregnancy complicated by transient worsening of renal function (creatinine increase from 1.15 to 1.78 mg/dL). Patient two was diagnosed with ARPKD at age seven and had an uncomplicated pregnancy at age 23. Patient three was diagnosed incidentally with ARPKD at age 23, 3 months after completion of an uncomplicated pregnancy. Patient four who had an uncomplicated pregnancy at age 33 was diagnosed with ARPKD at age 46. Women with ARPKD face reproductive decisions largely bereft of information about the pregnancies of other ARPKD patients. We report four cases of pregnancy and ARPKD to expand current knowledge and encourage further research.

  3. THE FORCE METAPHOR IN CONCEPTUALIZING ECONOMIC RECESSION

    Directory of Open Access Journals (Sweden)

    Jurga Cibulskienė

    2013-04-01

    Full Text Available Cognitive metaphor analysts comprehend metaphor as a convenient way of not only talking about real life events but also thinking about them: connecting ideas, explaining abstract ideas that are difficult to grasp, conveying messages and emotions, etc. Thus, metaphor in real-world discourse is increasingly becoming the focus of many cognitive studies. In political discourse, metaphor is seen as an ideological tool of deliberate attempts to influence, persuade and manipulate people. As Charteris-Black (2005: 16 put it, politicians try to establish themselves in a positive light or legitimize themselves, i.e., by presenting evidence that they are charismatic leaders who are capable of running their country efficiently. Legitimization goes hand in hand with delegitimization, i.e., negative other-presentation. Metaphor as a cognitive mechanism of ideology may serve both as positive self-representation and as a tool for fault-finding in others. Thus, the study focuses on how three Lithuanian socio-political groups (the leading party, the opposition, and the media legitimize themselves and delegitimize their opponents by using force metaphors to conceptualize the worldwide economic recession. The findings indicate that although the same conceptual metaphor is used for legitimization and delegitimization, its fulfilment scenario appears to be markedly different and it carries different rhetorical implications in the three discourses.

  4. A study of atriphos (ATP) action on muscular circulation in progressive muscular dystrophy by the radioactive xenon clearance technique

    International Nuclear Information System (INIS)

    Chakyrov, B.; Samardzhiev, A.

    1977-01-01

    The effect of intramuscularly and intravenously adminostered atriphos on the muscular circulation was studied with radioactive xenon in 12 children with progressive muscular dystrophy. After combined local intramuscular injection of ATP (atriphos) with the radioactive marker a 12-fold increment of muscular circulation ensues, lasting about 15 minutes. No vasodilatating effect on the muscular flow was oberved after intravenous injection of 20-40 mg of atriphos. It is believed that intramuscular administration of atriphos produced dilatation of capillaries and of the venous part of the muscular circulation. (author)

  5. Autosomal recessive anhidrotic ectodermal dysplasia: A rare entity

    Directory of Open Access Journals (Sweden)

    Sangita Ghosh

    2014-01-01

    Full Text Available We describe a case of anhidrotic ectodermal dysplasia (AED with an autosomal recessive mode of inheritance, a very rare entity, in a 2-year-old female child of two asymptomatic, consanguineous parents. Their previous child also had a similar condition. Autosomal recessive AED (AR-AED can have its full expression both in males and females and it is clinically indistinguishable from the x-linked recessive AED (XL-AED, which is the most common type of ectodermal dysplasia. Unlike the partially symptomatic carriers of XL-AED, the heterozygotes of AR-AED are phenotypically asymptomatic.

  6. Alcohol use during the great recession of 2008-2009.

    Science.gov (United States)

    Bor, Jacob; Basu, Sanjay; Coutts, Adam; McKee, Martin; Stuckler, David

    2013-01-01

    The aim of this study was to assess changes in alcohol use in the USA during the Great Recession. Drinking participation, drinking frequency, drinking intensity, total alcohol consumption and frequency of binge drinking were assessed in a nationally representative sample of 2,050,431 US women and men aged 18 and older, interviewed between 2006 and 2010. The prevalence of any alcohol use significantly declined during the economic recession, from 52.0% in 2006-2007 to 51.6% in 2008-2009 (P Great Recession there was an increase in abstention from alcohol and a rise in frequent binging.

  7. The Role of Credit in Predicting US Recessions

    DEFF Research Database (Denmark)

    Pönkä, Harri

    are useful predictors of US recessions over and above the control variables both in and out of sample. Especially the excess bond premium, capturing the cyclical changes in the relationship between default risk and credit spreads, is found to be a powerful predictor. Overall, models that combine credit......We study the role of credit in forecasting US recession periods with probit models. We employ both classical recession predictors and common factors based on a large panel of financial and macroeconomic variables as control variables. Our findings suggest that a number of credit variables...

  8. Spinal Cord Stimulation

    DEFF Research Database (Denmark)

    Meier, Kaare

    2014-01-01

    Spinal cord stimulation (SCS) is a surgical treatment for chronic neuropathic pain that is refractory to other treatment. Originally described by Shealy et al. in 1967(1), it is used to treat a range of conditions such as complex regional pain syndrome (CRPS I)(2), angina pectoris(3), radicular...... pain after failed back surgery syndrome (FBSS)(4), pain due to peripheral nerve injury, stump pain(5), peripheral vascular disease(6) and diabetic neuropathy(7,8); whereas phantom pain(9), postherpetic neuralgia(10), chronic visceral pain(11), and pain after partial spinal cord injury(12) remain more...

  9. Congenital spinal malformations

    International Nuclear Information System (INIS)

    Ertl-Wagner, B.B.; Reiser, M.F.

    2001-01-01

    Congenital spinal malformations form a complex and heterogeneous group of disorders whose pathogenesis is best explained embryologically. Radiologically, it is important to formulate a diagnosis when the disorder first becomes symptomatic. However, it is also crucial to detect complications of the disorder or of the respective therapeutic interventions in the further course of the disease such as hydromyelia or re-tethering after repair of a meningomyelocele. Moreover, once a congenital spinal malformation is diagnosed, associated malformations should be sought after. A possible syndromal classification such as in OEIS- or VACTERL-syndromes should also be considered. (orig.) [de

  10. Spinal Neurocysticercosis: Case Report

    International Nuclear Information System (INIS)

    Amaya P, Melina; Roa, Jose L

    2011-01-01

    Neurocysticercosis (NCC) is the most frequent parasitic illness of the central nervous system caused by the larval form of Taenia solium and its considered to be endemic in Latin America. Its diagnosis is based on imaging findings and epidemiological data; although its diagnosis can be made through the detection of specific IgG antibodies, these tests have limited availability in our environment. Central nervous system involvement is generally observed in the brain parenchyma, and less commonly in the ventricular system and subarachnoid space; only infrequently is reported to involve the structures within the spinal canal, in this article we review a case of a patient with spinal cysticercal involvement.

  11. Maladaptive spinal plasticity opposes spinal learning and recovery in spinal cord injury

    Directory of Open Access Journals (Sweden)

    Adam R Ferguson

    2012-10-01

    Full Text Available Synaptic plasticity within the spinal cord has great potential to facilitate recovery of function after spinal cord injury (SCI. Spinal plasticity can be induced in an activity-dependent manner even without input from the brain after complete SCI. The mechanistic basis for these effects is provided by research demonstrating that spinal synapses have many of the same plasticity mechanisms that are known to underlie learning and memory in the brain. In addition, the lumbar spinal cord can sustain several forms of learning and memory, including limb-position training. However, not all spinal plasticity promotes recovery of function. Central sensitization of nociceptive (pain pathways in the spinal cord may emerge with certain patterns of activity, demonstrating that plasticity within the spinal cord may contribute to maladaptive pain states. In this review we discuss interactions between adaptive and maladaptive forms of activity-dependent plasticity in the spinal cord. The literature demonstrates that activity-dependent plasticity within the spinal cord must be carefully tuned to promote adaptive spinal training. Stimulation that is delivered in a limb position-dependent manner or on a fixed interval can induce adaptive plasticity that promotes future spinal cord learning and reduces nociceptive hyper-reactivity. On the other hand, stimulation that is delivered in an unsynchronized fashion, such as randomized electrical stimulation or peripheral skin injuries, can generate maladaptive spinal plasticity that undermines future spinal cord learning, reduces recovery of locomotor function, and promotes nociceptive hyper-reactivity after spinal cord injury. We review these basic phenomena, discuss the cellular and molecular mechanisms, and discuss implications of these findings for improved rehabilitative therapies after spinal cord injury.

  12. Anterior spinal cord syndrome of unknown etiology

    OpenAIRE

    Klakeel, Merrine; Thompson, Justin; Srinivasan, Rajashree; McDonald, Frank

    2015-01-01

    A spinal cord injury encompasses a physical insult to the spinal cord. In the case of anterior spinal cord syndrome, the insult is a vascular lesion at the anterior spinal artery. We present the cases of two 13-year-old boys with anterior spinal cord syndrome, along with a review of the anatomy and vasculature of the spinal cord and an explanation of how a lesion in the cord corresponds to anterior spinal cord syndrome.

  13. Genetics Home Reference: autosomal recessive congenital stationary night blindness

    Science.gov (United States)

    ... collapse boxes. Description Autosomal recessive congenital stationary night blindness is a disorder of the retina , which is the specialized tissue at the back of the eye that detects light and color. People with this condition typically have difficulty seeing ...

  14. Recession-Tolerant Sensors for Thermal Protection Systems, Phase II

    Data.gov (United States)

    National Aeronautics and Space Administration — The Phase II project will develop a suite of diagnostic sensors using Direct Write technology to measure temperature, surface recession depth, and heat flux of an...

  15. Ecohealth Approach to Flood Recession Farming in Okavango Delta ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    In the Okavango Delta, Botswana, flood-recession farming (molapu) is a lucrative but ... Moreover, some practices involved in molapu farming may pose a threat to the ... Linking research to urban planning at the ICLEI World Congress 2018.

  16. Quantitative fundus autofluorescence in recessive Stargardt disease.

    Science.gov (United States)

    Burke, Tomas R; Duncker, Tobias; Woods, Russell L; Greenberg, Jonathan P; Zernant, Jana; Tsang, Stephen H; Smith, R Theodore; Allikmets, Rando; Sparrow, Janet R; Delori, François C

    2014-05-01

    To quantify fundus autofluorescence (qAF) in patients with recessive Stargardt disease (STGD1). A total of 42 STGD1 patients (ages: 7-52 years) with at least one confirmed disease-associated ABCA4 mutation were studied. Fundus AF images (488-nm excitation) were acquired with a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference to account for variable laser power and detector sensitivity. The gray levels (GLs) of each image were calibrated to the reference, zero GL, magnification, and normative optical media density to yield qAF. Texture factor (TF) was calculated to characterize inhomogeneities in the AF image and patients were assigned to the phenotypes of Fishman I through III. Quantified fundus autofluorescence in 36 of 42 patients and TF in 27 of 42 patients were above normal limits for age. Young patients exhibited the relatively highest qAF, with levels up to 8-fold higher than healthy eyes. Quantified fundus autofluorescence and TF were higher in Fishman II and III than Fishman I, who had higher qAF and TF than healthy eyes. Patients carrying the G1916E mutation had lower qAF and TF than most other patients, even in the presence of a second allele associated with severe disease. Quantified fundus autofluorescence is an indirect approach to measuring RPE lipofuscin in vivo. We report that ABCA4 mutations cause significantly elevated qAF, consistent with previous reports indicating that increased RPE lipofuscin is a hallmark of STGD1. Even when qualitative differences in fundus AF images are not evident, qAF can elucidate phenotypic variation. Quantified fundus autofluorescence will serve to establish genotype-phenotype correlations and as an outcome measure in clinical trials.

  17. Quantitative Fundus Autofluorescence in Recessive Stargardt Disease

    Science.gov (United States)

    Burke, Tomas R.; Duncker, Tobias; Woods, Russell L.; Greenberg, Jonathan P.; Zernant, Jana; Tsang, Stephen H.; Smith, R. Theodore; Allikmets, Rando; Sparrow, Janet R.; Delori, François C.

    2014-01-01

    Purpose. To quantify fundus autofluorescence (qAF) in patients with recessive Stargardt disease (STGD1). Methods. A total of 42 STGD1 patients (ages: 7–52 years) with at least one confirmed disease-associated ABCA4 mutation were studied. Fundus AF images (488-nm excitation) were acquired with a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference to account for variable laser power and detector sensitivity. The gray levels (GLs) of each image were calibrated to the reference, zero GL, magnification, and normative optical media density to yield qAF. Texture factor (TF) was calculated to characterize inhomogeneities in the AF image and patients were assigned to the phenotypes of Fishman I through III. Results. Quantified fundus autofluorescence in 36 of 42 patients and TF in 27 of 42 patients were above normal limits for age. Young patients exhibited the relatively highest qAF, with levels up to 8-fold higher than healthy eyes. Quantified fundus autofluorescence and TF were higher in Fishman II and III than Fishman I, who had higher qAF and TF than healthy eyes. Patients carrying the G1916E mutation had lower qAF and TF than most other patients, even in the presence of a second allele associated with severe disease. Conclusions. Quantified fundus autofluorescence is an indirect approach to measuring RPE lipofuscin in vivo. We report that ABCA4 mutations cause significantly elevated qAF, consistent with previous reports indicating that increased RPE lipofuscin is a hallmark of STGD1. Even when qualitative differences in fundus AF images are not evident, qAF can elucidate phenotypic variation. Quantified fundus autofluorescence will serve to establish genotype-phenotype correlations and as an outcome measure in clinical trials. PMID:24677105

  18. Muscular cysticercosis: Case report and imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Olmo, Neide Regina Simoes; Fiorio, Ulysses Ferreira; Clemente, Marcel Andreazza, E-mail: neideolmo@yahoo.com.br [Clinica Mult Imagem, Santos, SP (Brazil); Bastos, Eder Amaral [Universidade Metropolitana de Santos (UNIMES), Santos, SP (Brazil); Mendes, Gustavo Gomes [AC Camargo Cancer Center, Sao Paulo, SP (Brazil)

    2016-11-15

    Cysticercosis is a parasitic disease caused by a worm of the Cestoda class. The most prevalent form affects the nervous system. This case report is from a 78-year old female patient evaluated at Clinica Mult Imagem, in the city of Santos, Brazil, who presented a form of the disease that differed from the classic neurocysticercosis, in this case muscular cysticercosis. This and other forms of manifestation justify further studies to ensure adequate recognition, diagnosis and treatment of this parasitic disease. (author)

  19. Defective myoblasts identified in Duchenne muscular dystrophy.

    OpenAIRE

    Blau, H M; Webster, C; Pavlath, G K

    1983-01-01

    A defect in the proliferative capacity of satellite cells, mononucleated precursors of mature muscle fibers, was found in clonal analyses of cells cultured from Duchenne muscular dystrophy (DMD) patients. The total yield of myoblasts per gram of muscle biopsy was decreased to 5% of normal. Of the DMD myoblast clones obtained, a large proportion contained a morphological class of flat distended cells that had an increased generation time and ceased to proliferate beyond 100-1,000 cells but cou...

  20. Intra-muscular hemangioma: A review

    Directory of Open Access Journals (Sweden)

    Shruti Nayak

    2014-01-01

    Full Text Available Intra-muscular hemangiomas (IMH are relatively uncommon benign vascular tumors, which account for less than 1% of all hemangiomas. IMH may be presented as a perceived sporting injury. Diagnosis of this lesion is important not only because of its rarity, but also due to dangers posed by misdiagnosis and mismanagement. They must be considered in the differential diagnosis of unexplained pain and swelling in muscles. IMH occurring in the oral cavity is reviewed below.

  1. Urological manifestations of Duchenne muscular dystrophy.

    Science.gov (United States)

    Askeland, Eric J; Arlen, Angela M; Erickson, Bradley A; Mathews, Katherine D; Cooper, Christopher S

    2013-10-01

    Duchenne muscular dystrophy is a dystrophinopathy affecting males that is associated with multiple organ system complications. To our knowledge urological complications of Duchenne muscular dystrophy have been described only anecdotally to date. We reviewed the medical charts of 135 patients with Duchenne or Duchenne-Becker muscular dystrophy for demographics and disease progression, urological diagnoses, intervention and followup. Of 135 patients 67 (50%) had at least 1 documented urological diagnosis and 38 (28%) had multiple manifestations. Lower urinary tract symptoms were the most common urological diagnosis (32% of patients). Survival analysis revealed a median age at onset of lower urinary tract symptoms of 23 years (95% CI 17.7-23.9). Intervention was required in 12 patients (9%), most commonly due to nephrolithiasis. Urological morbidity increased with Duchenne muscular dystrophy progression when stratified by clinical progression. Lower urinary tract symptoms were more common in nonambulatory patients (40.7% vs 19%, p = 0.007), those with a diagnosis of scoliosis (44% vs 19.7%, p = 0.003) and/or scoliosis spine surgery (60% vs 22%, p <0.001), and those on invasive respiratory support (53% vs 29%, p = 0.046). Likewise, nephrolithiasis was more common in nonambulatory patients (10% vs 0%, p = 0.017), those with scoliosis (12% vs 0%, p = 0.004) and/or scoliosis spine surgery (20% vs 1%, p <0.001), and those on invasive respiratory support (29% vs 3%, p <0.001). Only 28% of patients with a urological manifestation were referred to urology. As these patients transition into adolescence and adulthood, the increased prevalence of urological manifestations warrants increased awareness and referral to urologists. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  2. Disability and Survival in Duchenne Muscular Dystrophy

    OpenAIRE

    Kohler, M; Clarenbach, C F; Bahler, C; Brack, T; Russi, E W; Bloch, K E

    2009-01-01

    BACKGROUND: Duchenne muscular dystrophy (DMD) leads to progressive impairment of muscle function, respiratory failure and premature death. Longitudinal data on the course of physical disability and respiratory function are sparse. OBJECTIVES: To prospectively assess physical impairment and disability, respiratory function and survival in DMD patients over several years in order to describe the course of the disease with current care. METHODS: In 43 patients with DMD, aged 5-35 years, yearly a...

  3. A lesão muscular na miastenia grave: estudo de 17 casos com histoquimica muscular

    Directory of Open Access Journals (Sweden)

    Lineu Cesar Werneck

    1982-03-01

    Full Text Available Estudo de 17 biópsias musculares de pacientes com miastenia grave, utilizando técnicas de coloração a fresco e histoquímica muscular. Foram encontradas 15 biópsias musculares anormais, sendo que as principais alterações foram fibras musculares angulares escuras atróficas, excesso de gotículas de gordura na membrana externa das fibras, variação no diâmetro das fibras e atrofia de fibras do tipo II. Os achados foram interpretados como denervação em 11 biópsias, atrofia de fibras do tipo II em 7, infiltrado linfocitário em 4, necrose de fibras musculares com fagocitose em 1 e em 2 biópsias não foi encontrada qualquer anormalidade. Quanto maior o tempo de doença, mais severa foi a anormalidade encontrada. Dois pacientes apresentavam timoma, um miastenia grave congênita, um artrite reumatoide, um neurite hipertrófica intersticial, um tireoidite de Hashimoto e um com síndrome miastênica concomitante. São discutidos os achados anatomopatológicos e sua possível explicação.

  4. Space, body, time and relationship experiences of recess physical activity

    DEFF Research Database (Denmark)

    Pawlowski, Charlotte Skau; Andersen, Henriette Bondo; Tjørnhøj-Thomsen, Tine

    2016-01-01

    BACKGROUND: Increasing recess physical activity has been the aim of several interventions, as this setting can provide numerous physical activity opportunities. However, it is unclear if these interventions are equally effective for all children, or if they only appeal to children who are already...... the classroom as a space for physical activity, designing schoolyards with smaller secluded spaces and varied facilities, improving children's self-esteem and body image, e.g., during physical education, and creating teacher organised play activities during recess....

  5. The Great Recession and America’s Geography of Unemployment

    Science.gov (United States)

    Thiede, Brian C.; Monnat, Shannon M.

    2017-01-01

    Background The Great Recession of 2007–2009 was the most severe and lengthy economic crisis in the U.S. since the Great Depression. The impacts on the population were multi-dimensional, but operated largely through local labor markets. Objective To examine differences in recession-related changes in county unemployment rates and assess how population and place characteristics shaped these patterns. Methods We calculate and decompose Theil Indexes to describe recession-related changes in the distribution of unemployment rates between counties and states. We use exploratory spatial statistics to identify geographic clusters of counties that experienced similar changes in unemployment. We use spatial regression to evaluate associations between county-level recession impacts on unemployment and demographic composition, industrial structure, and state context. Results The recession was associated with increased inequality between county labor markets within states, but declining between-state differences. Counties that experienced disproportionate recession-related increases in unemployment were spatially clustered and characterized by large shares of historically disadvantaged racial and ethnic minority populations, low educational attainment, and heavy reliance on pro-cyclical industries. Associations between these sources of vulnerability were partially explained by unobserved state-level factors. Conclusions The local consequences of macroeconomic trends are associated with county population characteristics, as well as the structural contexts and policy environments in which they are embedded. The recession placed upward pressure on within-state inequality between local labor market conditions. Contribution To present new estimates of the recession’s impact on local labor markets, quantify how heterogeneous impacts affected the distribution of unemployment prevalence, and identify county characteristics associated with disproportionately large recession

  6. A New Keynesian Perspective on the Great Recession

    OpenAIRE

    Peter N. Ireland

    2010-01-01

    With an estimated New Keynesian model, this paper compares the "Great Recession" of 2007-09 to its two immediate predecessors in 1990-91 and 2001. The model attributes all three downturns to a similar mix of aggregate demand and supply disturbances. The most recent series of adverse shocks lasted longer and became more severe, however, prolonging and deepening the Great Recession. In addition, the zero lower bound on the nominal interest rate prevented monetary policy from stabilizing the US ...

  7. Unemployment of Non-western Immigrants in the Great Recession

    OpenAIRE

    Cerveny, J.; Ours, J.C. van

    2013-01-01

    Abstract: This paper examines whether unemployment of non-western immigrant workers in the Netherlands was disproportionally affected by the Great Recession. We analyze unemployment data covering the period November 2007 to February 2013 finding that the Great Recession affected unemployment rates of non-western immigrant workers in absolute terms more than unemployment rates of native workers. However, in relative terms there is not much of a difference. We also find that the sensitivity of ...

  8. The Indian Stock Market and the Great Recession

    OpenAIRE

    Arindam MANDAL; Prasun BHATTACHARJEE

    2012-01-01

    This study analyzes the impact of the outbreak of the Great Recession of 2007 on the behavior of the Indian stock market. The SENSEX index of the Bombay Stock Exchange is analyzed for the prerecession period of January 2002 – November 2007 and the postrecession outbreak period of December 2007 – July 2010. Substantial increase in SENSEX return volatility observed during the post-recession outbreak period, whereas no substantial difference in returns between two periods is...

  9. SPATACSIN mutations cause autosomal recessive juvenile amyotrophic lateral sclerosis

    OpenAIRE

    Orlacchio, Antonio; Babalini, Carla; Borreca, Antonella; Patrono, Clarice; Massa, Roberto; Basaran, Sarenur; Munhoz, Renato P.; Rogaeva, Ekaterina A.; St George-Hyslop, Peter H.; Bernardi, Giorgio; Kawarai, Toshitaka

    2010-01-01

    The mutation of the spatacsin gene is the single most common cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum. Common clinical, pathological and genetic features between amyotrophic lateral sclerosis and hereditary spastic paraplegia motivated us to investigate 25 families with autosomal recessive juvenile amyotrophic lateral sclerosis and long-term survival for mutations in the spatascin gene. The inclusion criterion was a diagnosis of clinically definite ...

  10. Gingival recession: prevalence and risk indicators among young greek adults.

    Science.gov (United States)

    Chrysanthakopoulos, Nikolaos A

    2014-07-01

    The aim of the current research was to assess the prevalence of gingival recession and to investigate possible associations among this condition, periodontal and epidemiological variables in a sample of young Greek adults in a general dental practice. A total of 1,430 young adults was examined clinically and interviewed regarding several periodontal and epidemiological variables. Collected data included demographic variables, oral hygiene habits and smoking status. Clinical examination included the recording of dental plaque, supragingival calculus presence, gingival status and buccal gingival recession. Multivariate logistic regression analysis model was performed to access the possible association between gingival recession and several periodontal and epidemiological variables as potential risk factors. The overall prevalence of gingival recession was 63.9%. The statistical analysis indicated that higher educational level [OR= 2.12, 95% CI= 0.53-8.51], cigarette smoking [OR= 1.97, 95% CI= 1.48-7.91], frequent tooth brushing [OR= 0.98, 95% CI= 0.56-1.96], presence of oral piercing [OR= 0.92, 95% CI= 0.38-1.58], presence of gingival inflammation [OR= 4.54, 95% CI= 1.68-7.16], presence of dental plaque [OR= 1.67, 95% CI= 0.68-2.83] and presence of supragingival calculus [OR=1.34, 95% CI= 0.59-1.88], were the most important associated factors of gingival recession. The observations of the current research supported the results from previous authors that several periodontal factors, educational level and smoking were significantly associated with the presence of gingival recession, while presence of oral piercing was a new factor that was found to be associated with gingival recession. Key words:Gingival recession, prevalence, risk factors, young adults.

  11. Formal identity of gravitational and weakly interacting recession

    International Nuclear Information System (INIS)

    Muheim, J.T.

    1982-01-01

    The author discusses the construction of models using the five elementary constants esub(s), h/2π, G, c and ksub(B) which can produce a macro or micro world with exacticity. All physical processes in nature determine the gravitational universe recession. A diagram is presented comparing the gravitational and weakly interacting recession. The Big-Bang model is discussed. (A.N.K.)

  12. Lumbar spinal stenosis

    International Nuclear Information System (INIS)

    Anon.

    1985-01-01

    Spinal stenosis, which has attracted increasing attention in recent years, represents an important group of clinical and radiologic entities. Recognition and ultimate surgical management of the many abnormalities found in this group require precise preoperative delineation of the morbid anatomy. Conventional axial tomography provided the first accurate picture of the sagittal dimension, but it was limited by poor contrast resolution. Computerized tomography and ultrasound have finally provided the means for accurate measurement of midsagittal diameter and surface area. It is now possible to provide a preoperative assessment of bony and soft-tissue canal compression and to guide surgical decompression by objective anatomic measurements. True spinal stenosis of the lumbar vertebral canal is a form of compression produced by the walls of the vertebral canal. It involves the whole of the vertebral canal by exerting compression at two of its opposite surfaces. There are two types of stenosis: (1) transport stenosis, wherein the clinical manifestations are due to impeded flow of fluid, which is dependent on the available cross-sectional area of the canal surface of the stenotic structure, and (2) compressive stenosis, which includes abnormal compression of opposing surfaces only. According to these definitions, indentation on the spinal canal by disc protrusion or localized tumor is not considered true spinal stenoses. In this chapter the authors discuss only those conditions that produce true canal stenosis

  13. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... spinal cord injuries? play_arrow What is “Braingate” research? play_arrow How would stem-cell therapies work ... cord injuries? play_arrow What does stem-cell research on animals tell us? play_arrow When can ...

  14. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Home Kim Eberhardt Muir, MS Coping with a New Injury Robin Dorman, PsyD Sex and Fertility After ... program? play_arrow What are the most promising new treatments for spinal cord injuries? play_arrow What ...

  15. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... What is “Braingate” research? play_arrow How would stem-cell therapies work in the treatment of spinal cord injuries? play_arrow What does stem-cell research on animals tell us? play_arrow When ...

  16. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... is “Braingate” research? play_arrow How would stem-cell therapies work in the treatment of spinal cord injuries? play_arrow What does stem-cell research on animals tell us? play_arrow When ...

  17. Occult spinal dysraphism

    African Journals Online (AJOL)

    paediatricians, paediatric neurosurgeons, urologists, orthopaedic surgeons, occupational ... Occult spinal dysraphism refers to a diverse group of congenital abnormalities resulting from varying degrees of disordered neuro- embryogenesis. Several terms have .... can image the whole spine. T1-weighted sagittal and axial ...

  18. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Braingate” research? play_arrow How would stem-cell therapies work in the treatment of spinal cord injuries? play_arrow What does stem-cell research on animals tell us? play_arrow When can we expect ...

  19. Spinal Cord Injury 101

    Medline Plus

    Full Text Available ... Anne Bryden, OT The Role of the Social Worker after Spinal Cord Injury Patti Rogers, SW Marguerite David, ... injuries. The website does not provide medical advice, recommend or endorse health care products or services, or control the information ...

  20. Maladaptive spinal plasticity opposes spinal learning and recovery in spinal cord injury

    Science.gov (United States)

    Ferguson, Adam R.; Huie, J. Russell; Crown, Eric D.; Baumbauer, Kyle M.; Hook, Michelle A.; Garraway, Sandra M.; Lee, Kuan H.; Hoy, Kevin C.; Grau, James W.

    2012-01-01

    Synaptic plasticity within the spinal cord has great potential to facilitate recovery of function after spinal cord injury (SCI). Spinal plasticity can be induced in an activity-dependent manner even without input from the brain after complete SCI. A mechanistic basis for these effects is provided by research demonstrating that spinal synapses have many of the same plasticity mechanisms that are known to underlie learning and memory in the brain. In addition, the lumbar spinal cord can sustain several forms of learning and memory, including limb-position training. However, not all spinal plasticity promotes recovery of function. Central sensitization of nociceptive (pain) pathways in the spinal cord may emerge in response to various noxious inputs, demonstrating that plasticity within the spinal cord may contribute to maladaptive pain states. In this review we discuss interactions between adaptive and maladaptive forms of activity-dependent plasticity in the spinal cord below the level of SCI. The literature demonstrates that activity-dependent plasticity within the spinal cord must be carefully tuned to promote adaptive spinal training. Prior work from our group has shown that stimulation that is delivered in a limb position-dependent manner or on a fixed interval can induce adaptive plasticity that promotes future spinal cord learning and reduces nociceptive hyper-reactivity. On the other hand, stimulation that is delivered in an unsynchronized fashion, such as randomized electrical stimulation or peripheral skin injuries, can generate maladaptive spinal plasticity that undermines future spinal cord learning, reduces recovery of locomotor function, and promotes nociceptive hyper-reactivity after SCI. We review these basic phenomena, how these findings relate to the broader spinal plasticity literature, discuss the cellular and molecular mechanisms, and finally discuss implications of these and other findings for improved rehabilitative therapies after SCI. PMID