Citations

Introduction: Nusinersen antisense oligonucleotide infusions have been shown to be effective in the treatment spinal muscular atrophy. The majority of the evidence has been collected in young type 1 and type 2 patients, and evidence of efficacy in adult patients is limited. Case Report: A 48-year-old woman with spinal muscular atrophy type 3 who has received the loading dose and 8 maintenance infusions over an 8-month period. Grip and pinch strength, measured by hand-held dynamometry measured at baseline and in 6 to 12 months interval improved over a 24-month period. She also reported multiple other subjective improvements in function. Conclusions: This is the first published case of nusinersen in a middle-aged adult with spinal muscular atrophy. Sustained clinically meaningful improvement may be possible with nusinersen initiation in mid adulthood.

ABSTRACT Introduction Needle electromyography (EMG) findings help confirm myopathy and may indicate specific pathologic changes on muscle biopsy. Methods We conducted a retrospective chart review of 218 consecutive patients referred for muscle biopsy. Presence of specific needle EMG findings was correlated with pathologic findings of inflammation, necrosis, splitting, and vacuolar changes. Sensitivity, specificity, and positive and negative predictive values of specific EMG findings for pathologic changes were calculated. Results Short‐duration motor unit potentials (MUP) were sensitive (83%–94%) but not specific (34%–49%) for pathologic changes. Fibrillation potentials were 65%–74% sensitive and 58%–81% specific for inflammation, necrosis, splitting, or vacuolar changes. The absence of fibrillation potentials had high negative predictive value (82%–93%) for inflammation, splitting, or vacuolar changes. Discussion Fibrillation potentials and short‐duration MUPs predict pathologic changes of muscle fiber necrosis, splitting, and/or vacuolar changes (as seen with inflammatory myopathies and muscular dystrophies). Absence of fibrillation potentials suggests other myopathologic changes (e.g., congenital myopathy). Muscle Nerve 59 :315–320, 2019

ABSTRACTIntroduction: Routine ulnar nerve conduction studies may be normal in very mild ulnar neuropathies at the elbow (UNE). Short segment ulnar sensory stimulation across the elbow may detect mild abnormalities in these cases. Methods: Short segment ulnar sensory nerve stimulation was performed in 20 controls and 15 patients with clinically suspected mild UNE. Greatest peak latency shift and amplitude drop between 2 adjacent stimulation sites were calculated. Results: The upper limit of normal for peak latency shift and amplitude reduction between sites was 0.7 ms and 15%, respectively. Abnormal latency shift was detected in 12 of 15 patients and focal sensory conduction block in 6 of 15 patients. In 5 of 7 patients in whom all other studies were normal, sensory inching was abnormal. Discussion: Ulnar sensory short segment stimulation may provide diagnostic confirmation and localization of the site of nerve compression in mild UNE, and may improve UNE detection when all other studies are normal. Muscle Nerve 59:125–129, 2019

Abstract Background Pathogenic variants in ryanodine receptor 1 ( RYR 1, MIM # 180901) are the cause of congenital myopathy with fiber‐type disproportion, malignant hyperthermia susceptibility type 1, central core disease of muscle, multiminicore disease and other congenital myopathies. Methods We present a patient with global developmental delay, hypotonia, myopathy, joint hypermobility, and multiple other systemic complaints that were noted early in life. Later she was found to have multiple bone deformities involving her spine, with severe scoliosis that was corrected surgically. She was also diagnosed with ophthalmoplegia, chronic hypercapnic respiratory failure, and hypertension. At 22 years of age she presented to the genetics clinic with a diagnosis of mitochondrial myopathy and underwent whole exome sequencing ( WES ). Results Whole exome sequencing revealed two novel compound heterozygous variants in RYR 1 (c.7060_7062del, p.Val2354del and c.4485_4500del, p.Tyr1495X). Conclusion Review of her clinical, pathologic, and genetic findings pointed to a diagnosis of a congenital myopathy with fiber‐type disproportion.

Abstract Welander distal myopathy is a rare autosomal dominant disorder characterized by muscle weakness in the hands and feet. Exome sequencing of affected families discovered a segregating p.Glu384Lys pathogenic variant in TIA-1 as the main genetic cause of Welander distal myopathy. TIA-1 encodes an RNA-binding protein which serves as a key component of stress granules. This protein also regulates splicing and translation of mRNA. Our patient developed progressive weakness in his hands and feet during his late 40s that was misdiagnosed as a neuropathy that caused muscle atrophy. Follow-up genetic testing revealed a p.Glu384Lys pathogenic variant in TIA-1, and he was then diagnosed with Welander distal myopathy. Our case report underlines the importance of electrodiagnostic and genetic testing of patients.

ABSTRACTIntroductionEosinophilic fasciitis (EF) is a rare disorder that can present with muscle symptoms that mimic other neuromuscular diseases.MethodsWe report the case of a 43‐year‐old woman with chronic muscle aches, tightness, and stiffness with hypertrophied, well‐defined muscles despite physical inactivity, and thickened skin with reduced elasticity and discoloration.ResultsExcept for mild peripheral eosinophilia, laboratory studies, including blood count, electrolytes, paraneoplastic panel, muscle enzymes, thyroid function, and serum protein electrophoresis, were normal. Nerve conduction studies and needle electromyography were normal. Magnetic resonance imaging of the thighs demonstrated superficial and deep fascial thickening with T2 hyperintensity and post‐gadolinium enhancement. Fascial and muscle biopsy demonstrated an inflammatory exudate in the perimysium and endomysium with fragmented perimysial connective tissue and thickened, inflamed fascia. EF was diagnosed. The patient was treated with methotrexate and prednisone followed by improvement of muscle stiffness and tightness.ConclusionEF should be considered when patients present with muscle pain or enlarged muscles. Muscle Nerve 56: 525–529, 2017

Dysferlinopathy is an uncommon, progressive muscular dystrophy that has a wide phenotypic variability and primarily supportive management (Nguyen et al., 2007; Narayanaswami et al., 2014). Amyloid myopathy is a distinct, rare disorder that can present similarly to inflammatory myopathies and requires a high clinical suspicion for early intervention to prolong survival. Amyloid myopathy is typically associated with other systemic manifestations of amyloidosis, but rare cases of isolated amyloid myopathy have been described (Mandl et al., 2000; Hull et al., 2001). Positive Congo red stains on tissue biopsy remain the gold standard for diagnosis (Spuler et al., 1998; Karacostas et al., 2005). A high clinical suspicion and meticulous diagnostic workup that includes novel techniques are necessary for identifying these rare disorders. We report a middle-aged man with progressive leg muscle weakness who was initially treated as having amyloid myopathy but was later diagnosed as having dysferlinopathy by Whole Exome Sequencing (WES) analysis. We also report a novel missense mutation (c.959G>C) to help correlate in any patient with presumed dysferlinopathy and to add to the already known genotype of this disorder.