Although murine X-linked muscular dystrophy (mdx) and Duchenne muscular dystrophy (DMD) are genetically homologous and both characterized by a complete absence of dystrophin, the limb muscles of adult mdx mice suffer neither the detectable weakness nor the progressive degeneration that are features of DMD. Here we show that the mdx mouse diaphragm exhibits a pattern of degeneration, fibrosis and severe functional deficit comparable to that of DMD limb muscle, although adult mice show no overt respiratory impairment. Progressive functional changes include reductions in strength (to 13.5% of control by two years of age), elasticity, twitch speed and fibre length. The collagen density rises to at least seven times that of control diaphragm and ten times that of mdx hind-limb muscle. By 1.5 years of age, similar but less severe histological changes emerge in the accessory muscles of respiration. On the basis of these findings, we propose that dystrophin deficiency alters the threshold for work-induced injury. Our data provide a quantitative framework for studying the pathogenesis of dystrophy and extend the application of the mdx mouse as an animal model.

Abstract-Objective:To provide an evidence-based statement to guide physicians in the management of Guillain-Barré syndrome (GBS). Methods: Literature search and derivation of evidence-based statements concerning the use of immunotherapy were performed. Results: Treatment with plasma exchange (PE) or IV immunoglobulin (IVIg) hastens recovery from GBS. Combining the two treatments is not beneficial. Steroid treatment given alone is not beneficial. Recommendations: 1) PE is recommended for nonambulant adult patients with GBS who seek treatment within 4 weeks of the onset of neuropathic symptoms. PE should also be considered for ambulant patients examined within 2 weeks of the onset of neuropathic symptoms; 2) IVIg is recommended for nonambulant adult patients with GBS within 2 or possibly 4 weeks of the onset of neuropathic symptoms. The effects of PE and IVIg are equivalent; 3) Corticosteroids are not recommended for the management of GBS; 4) Sequential treatment with PE followed by IVIg, or immunoabsorption followed by IVIg is not recommended for patients with GBS; and 5) PE and IVIg are treatment options for children with severe GBS. NEUROLOGY 2003;61:736 -740 Guillain-Barré syndrome (GBS) affects between 1 and 4 per 100,000 of the population annually throughout the world, 1 causing respiratory failure requiring ventilation in approximately 25%, death in 4 to 15%, 2-6 persistent disability in approximately 20%, 7 and persistent fatigue in 67%. 8 The costs in the United States have been estimated as $110,000 for direct health care and $360,000 in lost productivity per patient. 9 This practice parameter classifies the relevant evidence on immunotherapy to provide evidence-based recommendations for the management of GBS. 10Evidence review. A search of MEDLINE from 1966 and of the Cochrane library was performed in March 2002. "Polyradiculoneuritis" was limited by "human" and cross-referenced with "therapy." The search results were reviewed for each question by at least two members of the practice parameter group and supplemented from the reference lists in the articles retrieved and the personal reference lists of the members of the practice parameter group. Those titles representing relevant randomized controlled trials (RCTs) are included in the tables on the Neurology Web site for this article (www.neurology.org). Recommendations were graded according to the levels established by the AAN Quality Standards Subcommittee at the inception of this project (table).

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These data indicate that one third of patients with amyotrophic lateral sclerosis report sensory symptoms and sural sensory response amplitudes are reduced in a similar proportion of subjects. Pathologic evidence of sensory nerve pathology was present in 91% of patients who underwent sural nerve biopsy. The electrophysiologic and pathologic findings indicate a pattern of axonal loss that predominantly affects large-caliber myelinated fibers.

Our previous experience with abnormal fatty acid metabolism in several children with spinal muscular atrophy (SMA) prompted evaluation of fatty acid metabolism in a larger cohort. Thirty‐three infants with severe infantile SMA were shown to have a significantly increased ratio of dodecanoic to tetradecanoic acid in plasma compared with normal infants and 6 infants affected with equally debilitating, non‐SMA denervating disorders. Seventeen children with milder forms of SMA had normal fatty acid profiles. In addition, all 5 infants with severe SMA evaluated in a fasting state developed a distinctive and marked dicarboxylic aciduria, including saturated, unsaturated, and 3‐hydroxy forms, comparable in severity with the dicarboxylic aciduria of children with primary defects of mitochondrial fatty acid β‐oxidation. Nine children with chronic SMA and 23 control patients did not develop an abnormal dicarboxylic aciduria during fasting. No known disorder of fatty acid metabolism explains all of the abnormalities we find in SMA. Our data suggest, however, that the abnormalities are not a consequence of SMA‐related immobility, systemic illness, muscle denervation, or muscle atrophy. These abnormalities in fatty acid metabolism may be caused by changes in cellular physiology related to the molecular defects of the SMA‐pathogenic survival motor neuron gene or neighboring genes. Ann Neurol 1999;45:337–343

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The Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet) is a multisite collaboration to determine the prevalence of childhood-onset Duchenne/Becker muscular dystrophy and to characterize health care and health outcomes in this population. MD STARnet uses medical record abstraction to identify patients with Duchenne/Becker muscular dystrophy born January 1, 1982 or later who resided in one of the participating sites. Critical diagnostic elements of each abstracted record are reviewed independently by ≥4 clinicians and assigned to 1 of 6 case definition categories (definite, probable, possible, asymptomatic, female, not Duchenne/Becker muscular dystrophy) by consensus. As of November 2009, 815 potential cases were reviewed. Of the cases included in analysis, 674 (82%) were either “definite” or “probable” Duchenne/Becker muscular dystrophy. These data reflect a change in diagnostic testing, as case assignment based on genetic testing increased from 67% in the oldest cohort (born 1982–1987) to 94% in the cohort born 2004–2009.