Liewluck, T

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.

ABSTRACTIntroduction: Valosin‐containing protein (VCP) is a ubiquitously expressed, multifunctional AAA‐ATPase protein. Its dominant mutations cause hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia (IBMPFD) or amyotrophic lateral sclerosis. The pattern of muscle weakness in IBMPFD patients is variable and includes limb‐girdle, scapuloperoneal, distal, or axial distributions. Case Report: We report a 63‐year‐old man with progressive scapuloperoneal weakness, head drop, and hyperCKemia since age 40 years. Electromyography showed myopathic changes and rare myotonic discharges. Muscle biopsy revealed numerous lobulated fibers, few fibers with glycogen accumulation, and rare fibers with polyglucosan bodies. Rimmed vacuoles and congophilic inclusions, often seen in IBMPFD, were absent. VCP sequencing identified a novel heterozygous c. 1160G>A mutation resulting in p.Asn387Ser substitution. Conclusions: Our patient broadens the pathological spectrum of VCP‐myopathy and emphasizes the importance of VCP analysis in patients with scapuloperoneal muscular dystrophy despite the absence of Paget disease, dementia, rimmed vacuoles, or intracellular amyloid deposition. Muscle Nerve 50:295–299, 2014

ABSTRACTIntroduction: Mitochondrial trifunctional protein deficiency is a rare autosomal recessive disorder of mitochondrial fatty acid β‐oxidation that may be due to mutations in 2 different nuclear genes, HADHA and HADHB. Perturbation of this multienzyme complex compromises the oxidation of long‐chain fatty acids, which leads to multiorgan dysfunction. Childhood‐ or adolescent‐onset recurrent rhabdomyolysis is a common muscular manifestation and is preceded frequently by clinically overt peripheral neuropathy. Methods: In this report we describe a patient with late adult‐onset recurrent rhabdomyolysis. Results: Despite normal sensory examination, nerve conduction studies showed a mild axonal peripheral neuropathy. The acylcarnitine profile showed elevated long‐chain and 3‐hydroxy long‐chain acylcarnitine species. HADHA sequencing revealed known compound heterozygous mutations c.180+3A>G (p.Thr37SerfsX6) and c.1528G>C (p.Glu510Gln). During a 10‐month follow‐up period, he had no further episodes of rhabdomyolysis after appropriate dietary modifications. Conclusions: Mitochondrial trifunctional protein deficiency should be considered in patients with adult‐onset recurrent rhabdomyolysis, especially in those with either clinically overt or subclinical peripheral neuropathy. Muscle Nerve 48: 989–991, 2013

ABSTRACTIntroduction: We investigated the clinical, electrophysiological and neural autoantibody characteristics in cramp‐fasciculation syndrome (CFS) patients. Methods: We reviewed Mayo Clinic records from 2000 to 2011 to identify clinically defined CFS patients who underwent neural autoantibody testing. Stored sera of patients who tested positive for antibodies to voltage‐gated potassium channel complex (VGKC complex) were analyzed further for leucine‐rich glioma‐inactivated 1 (LGI1) or contactin‐associated protein‐2 immunoglobulin G (CASPR2‐IgG) antibodies. Results: Thirty‐seven patients were identified. Twelve were seropositive for neural autoantibodies. Clinical manifestations were similar in seropositive and seronegative patients, although central and autonomic neuronal hyperexcitability symptoms were more common in seropositive cases. No patients had a malignancy. Repetitive tibial nerve stimulation at 10 Hz revealed longer afterdischarges in seropositive patients. Two of 7 patients with VGKC‐complex autoimmunity demonstrated LGI1 or CASPR2‐IgG antibodies. Only 2 of 12 seropositive patients required immunotherapy. Conclusions: VGKC‐complex autoimmunity occurs in a minority of CFS patients. Antibody positivity was associated with extramuscular manifestations, typically without malignancy. Target antigens within the VGKC complex remain unknown in most patients. Muscle Nerve 49:351–356, 2014