Liewluck, Teerin

ABSTRACTIntroduction: Decremental responses in repetitive nerve stimulation have been reported in a few hereditary myopathies. We examined the frequency of decrement in a cohort of myopathy patients. Methods: We reviewed all patients referred for myopathy who underwent repetitive nerve stimulation between January 2007 and May 2017. We included patients with decrement (>10%) and either a pathological or molecular diagnosis of myopathy. Results: Among 157 patients with myopathies, 4 patients had decrement (2 hydroxychloroquine‐associated vacuolar myopathy, 1 centronuclear myopathy, and 1 distal myopathy). One hydroxychloroquine‐associated vacuolar myopathy patient also had inflammatory myopathy. Pyridostigmine improved weakness in the centronuclear myopathy patient, but not in the distal myopathy patient. No patient with an acquired myopathy received pyridostigmine. Conclusions: Despite the rare occurrence of decrement in myopathy, its presence may urge consideration of pharmacological intervention. Muscle Nerve 59:475–478, 2019

ABSTRACT Introduction: Recessive mutations in the anoctamin‐5‐encoding gene (ANO5) cause muscular dystrophy of various phenotypes. Intramuscular interstitial amyloid deposits were detected in a few patients with anoctaminopathy‐5, some with cardiac involvement. The frequency of amyloid deposition in anoctaminopathy‐5 and its impact on phenotype are unknown. Methods: We retrospectively identified patients with genetically proven anoctaminopathy‐5 who had undergone muscle biopsy and reviewed their clinical and laboratory data. Results: Eight of 15 patients with anoctaminopathy‐5 had intramuscular interstitial amyloid deposits. The median age at onset of weakness was 40 and 45 years in the amyloidosis and nonamyloidosis groups, respectively. Mutations occurred throughout the entire gene in the amyloidosis group. Atrial arrhythmia was noted in 4 patients with amyloidosis and in 4 patients without amyloidosis. The latter group also had premature ventricular contractions. One nonamyloidosis patient had septal hypokinesia. Discussion: Intramuscular amyloidosis occurred in 53% of patients with anoctaminopathy‐5 who underwent muscle biopsy and had no impact on the phenotype. Muscle Nerve 59:133–137, 2019

ABSTRACTDistal myopathies are a group of rare muscle diseases characterized by distal weakness at onset. Although acquired myopathies can occasionally present with distal weakness, the majority of distal myopathies have a genetic etiology. Their age of onset varies from early‐childhood to late‐adulthood while the predominant muscle weakness can affect calf, ankle dorsiflexor, or distal upper limb muscles. A spectrum of muscle pathological changes, varying from nonspecific myopathic changes to rimmed vacuoles to myofibrillar pathology to nuclei centralization, have been noted. Likewise, the underlying molecular defect is heterogeneous. In addition, there is emerging evidence that distal myopathies can result from defective proteins encoded by genes causative of neurogenic disorders, be manifestation of multisystem proteinopathies or the result of the altered interplay between different genes. In this review, we provide an overview on the clinical, electrophysiological, pathological, and molecular aspects of distal myopathies, focusing on the most recent developments in the field. Muscle Nerve 59:283–294, 2019

ABSTRACTThe limb‐girdle muscular dystrophies (LGMDs) are a group of genetically heterogeneous, autosomal inherited muscular dystrophies with a childhood to adult onset, manifesting with hip‐ and shoulder‐girdle muscle weakness. When the term LGMD was first conceptualized in 1954, it was thought to be a single entity. Currently, there are 8 autosomal dominant (LGMD1A–1H) and 26 autosomal recessive (LGMD2A–2Z) variants according to the Online Mendelian Inheritance in Man database. In addition, there are other genetically identified muscular dystrophies with an LGMD phenotype not yet classified as LGMD. This highlights the entanglement of LGMDs, which represents an area in continuous expansion. Herein we aim to simplify the complexity of LGMDs by subgrouping them on the basis of the underlying defective protein and impaired function. Muscle Nerve 58: 167–177, 2018

Background and purpose Amyloid myopathy frequently occurs in the setting of systemic amyloidosis and less commonly in isolation (isolated amyloid myopathy). Anoctaminopathy‐5 and dysferlinopathy were recently recognized as causes of isolated amyloid myopathy. The present study aimed to characterize the isolated amyloid myopathy and to compare it with amyloid myopathy associated with systemic amyloidosis. Methods We searched the Muscle Laboratory database to identify patients with pathologically confirmed amyloid myopathy seen in neurology clinics between January 1998 and September 2016. Patients with monoclonal gammopathy, peripheral neuropathy, organomegaly or symptoms or pathologic evidence of amyloid deposition outside skeletal muscle were classified as having systemic amyloidosis‐associated myopathy. Results Fifty‐two patients were identified, including 14 with isolated amyloid myopathy (eight anoctaminopathy‐5, two dysferlinopathy and four genetically unknown) and 38 with systemic amyloidosis (32 immunoglobulin light‐chain amyloidosis, four familial amyloid polyneuropathy and two senile systemic amyloidosis). Compared with patients with systemic amyloidosis, patients with isolated amyloid myopathy had a younger age of onset (median, 41.5 vs. 65 years), no dysphagia (0% vs. 26%) or weight loss (0% vs. 26%), but more frequent calf atrophy (57% vs. 0%), small collections of inflammatory cells on muscle biopsy (43% vs. 0%) and asymptomatic hyper CK emia at onset (21% vs. 0%). All patients with isolated amyloid myopathy had creatine kinase (CK) values >2.5 times the upper limit of normal. Conclusions Isolated amyloid myopathy accounts for 27% of patients with amyloid myopathy, mostly due to anoctaminopathy‐5. There are various clinical and laboratory parameters that can help to differentiate isolated amyloid myopathy from systemic amyloidosis.