Prominent fatigue in spinal muscular atrophy and spinal and bulbar muscular atrophy: Evidence of activity-dependent conduction block

• Published in: Clinical neurophysiology Vol. 124; no. 9; pp. 1893 - 1898
• Main Authors: Noto, Yu-ichi, Misawa, Sonoko, Mori, Masahiro, Kawaguchi, Naoki, Kanai, Kazuaki, Shibuya, Kazumoto, Isose, Sagiri, Nasu, Saiko, Sekiguchi, Yukari, Beppu, Minako, Ohmori, Shigeki, Nakagawa, Masanori, Kuwabara, Satoshi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ireland Ltd 01.09.2013
• Subjects: Action Potentials; Activity-dependent conduction block; Adult; Aged; Axons - physiology; Chronic inflammatory demyelinating polyneuropathy; Electromyography; Fatigue; Fatigue - diagnosis; Fatigue - etiology; Fatigue - physiopathology; Female; Humans; Male; Middle Aged; Motor Neurons - physiology; Movement - physiology; Muscle Fatigue - physiology; Muscle Weakness - etiology; Muscle Weakness - physiopathology; Muscular Atrophy, Spinal - complications; Muscular Atrophy, Spinal - physiopathology; Muscular Disorders, Atrophic - complications; Muscular Disorders, Atrophic - physiopathology; Neural Conduction - physiology; Neurology; Spinal and bulbar muscular atrophy; Spinal muscular atrophy; Stimulated-single fiber electromyography; Young Adult; Spinal and bulbar muscular atrophy; Fatigue; Stimulated-single fiber electromyography; Chronic inflammatory demyelinating polyneuropathy; Activity-dependent conduction block; Spinal muscular atrophy
• ISSN: 1388-2457; 1872-8952; 1872-8952
• DOI: 10.1016/j.clinph.2012.12.053

•We showed that patients with chronic lower motor neuron disease [spinal muscular atrophy and spinal and bulbar muscular atrophy (SMA/SBMA)] frequently suffer disabling muscle fatigue.•Single fiber electromyography with high-frequency stimulation revealed that SMA/SBMA patients might have activity-dependent conduction block phenomenon in distal motor axons.•Activity-dependent conduction block is presumably produced by the reduced safety factor due to markedly increased axonal branching associated with collateral sprouting. To clarify whether patients with spinal muscular atrophy (SMA) or spinal and bulbar muscular atrophy (SBMA) suffer disabling muscle fatigue, and whether activity-dependent conduction block (ADCB) contributes to their fatigue. ADCB is usually caused by reduced safety factor for impulse transmission in demyelinating diseases, whereas markedly increased axonal branching associated with collateral sprouting may reduce the safety factor in chronic lower motor neuron disorders. We assessed the fatigue severity scale (FSS) in 22 patients with SMA/SBMA, and in 100 disease controls (multiple sclerosis, myasthenia gravis, chronic inflammatory demyelinating polyneuropathy (CIDP), and axonal neuropathy). We then performed stimulated-single fibre electromyography (s-SFEMG) in the extensor digitorum communis (EDC) muscle of 21 SMA/SBMA patients, 6 CIDP patients, and 10 normal subjects. The FSS score was the highest in SMA/SBMA patients [4.9±1.1 (mean±SD)], with 81% of them complaining of disabling fatigue, compared with normal controls (3.5±1.0), whereas patients with multiple sclerosis (4.3±1.6), myasthenia gravis (4.0±1.6) or CIDP (4.3±1.4) also showed higher FSS score. When 2000 stimuli were delivered at 20Hz in s-SFEMG, conduction block of single motor axons developed in 46% of patients with SMA/SBMA, and 40% of CIDP patients, but in none of the normal controls. SMA/SBMA patients frequently suffer from disabling fatigue presumably caused by ADCB induced by voluntary activity. ADCB could be the mechanism for muscle fatigue in chronic lower motor neuron diseases.