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Objective: Fatigue is a major disabling problem in patients with neuromuscular disorders. Both nerve demyelination and increased axonal branching associated with collateral sprouting reduce the safety factor for impulse transmission and could cause activity-dependent hyperpolarization and conduction block during voluntary contraction, and thus fatigue. This study aimed to investigate whether activity-dependent conduction block is associated with fatigue in demyelinating neuropathies and lower motor neuron disorders., Methods: This study included 31 patients (17 with chronic inflammatory demyelinating polyneuropathy [CIDP] and 14 with spinal and bulbar muscular atrophy [SBMA]). Sixteen healthy subjects served as normal controls. Fatigue was assessed using the Fatigue Scale for Motor and Cognitive Functions (FSMC). Compound muscle action potential (CMAP) recording and nerve excitability testing after median nerve stimulation in the wrist were performed before and after maximal voluntary contraction of the abductor pollicis brevis for 1 min., Results: Patients with CIDP/SBMA had prominent fatigue with higher FSMC motor scores (P < 0.0001) than normal controls. After voluntary contractions, CMAP amplitudes decreased significantly in four of the 17 patients with CIDP and one of the 14 patients with SBMA. The reduction in CMAP amplitude was associated with the fatigue score in the motor but not in the cognitive domain. After voluntary contraction, excitability testing showed axonal hyperpolarization in the normal and CIDP/SBMA groups., Conclusions: In CIDP or SBMA, fatigue is caused by voluntary contraction-induced membrane hyperpolarization and conduction block, presumably due to the critically lowered safety factor due to demyelination or increased axonal branching., Significance: Peripheral fatigue can be objectively assessed using CMAP amplitudes and nerve excitability testing., Competing Interests: The authors declare that they have no conflict of interest., (© 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V.)

POEMS (polyneuropathy, organomegaly, endocrinopathy monoclonal gammopathy, and skin changes) syndrome is occasionally associated with Castleman disease (CD) and their prognosis is considered as poorer than that in POEMS alone patients. To elucidate recent prognosis of POEMS syndrome coexisting with CD, we reviewed clinical data of 102 patients with POEMS syndrome treated at our institution between 2000 and 2018 and compared clinical characteristics, response to treatment, and prognosis between POEMS patients with biopsy-proven CD (POEMS-CD) and those without it. Fourteen POEMS-CD patients and 56 POEMS alone patients were identified, and the remaining 32 patients with unbiopsied lymphadenopathy were excluded. POEMS-CD patients significantly showed earlier onset and less severe neuropathic symptoms. Most of the POEMS-CD patients were treated with thalidomide and dexamethasone (n = 10, 71%), and subsequently received autologous stem cell transplantation (n = 6, 43%). Response to thalidomide was better in patients with POEMS-CD than those with POEMS alone (90% vs 43% clinical response, [p = .012]; 80% vs 45% normalization of serum VEGF levels, [p = .079]). The 10-year overall survival (95% confidence interval) was 89% (50-98%) in POEMS-CD patients and 61% (42-77%) in those with POEMS alone. POEMS syndrome associated with CD constitutes a subgroup of POEMS syndromes characterized by earlier onset, mild polyneuropathy, and favorable response to treatment. Recognition of this subgroup is significant for determination of therapeutic strategy., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Central polydactyly, syndactyly, and cleft hand are categorized separately in the International Federation of Societies for Surgery of the Hand classification. However, some investigators have proposed that these malformations should be classified into a single category: abnormal induction of finger rays. In this article, we report 5 hands with central polydactyly, syndactyly, and cleft hand in 3 patients from the same family and discuss the phenotypes in each hand.

Alpha-dystroglycan is a component of the dystrophin-glycoprotein-complex, which is the major mechanism of attachment between the cytoskeleton and the extracellular matrix. Muscle-eye-brain disease (MEB) is an autosomal recessive disorder characterized by congenital muscular dystrophy, ocular abnormalities and lissencephaly. We recently found that MEB is caused by mutations in the protein O-linked mannose beta1,2-N-acetylglucosaminyltransferase (POMGnT1) gene. POMGnT1 is a glycosylation enzyme that participates in the synthesis of O-mannosyl glycan, a modification that is rare in mammals but is known to be a laminin-binding ligand of alpha-dystroglycan. Here we report a selective deficiency of alpha-dystroglycan in MEB patients. This finding suggests that alpha-dystroglycan is a potential target of POMGnT1 and that altered glycosylation of alpha-dystroglycan may play a critical role in the pathomechanism of MEB and some forms of muscular dystrophy., ((C)2002 Elsevier Science (USA).)