Fatigue and activity-dependent conduction block in neuromuscular disorders

•Demyelination and increased axonal branching reduce the safety factor for impulse transmission.•Axonal hyperpolarization induced by voluntary contraction result in conduction block, and thereby fatigue in CIDP/SBMA patients.•Activity-dependent conduction block causes peripheral fatigue in neuromuscular diseases. 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. 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. Patients with CIDP/SBMA had prominent fatigue with higher FSMC motor scores (P