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J. Neurol. Neurosurg. Psychiatr. · Aug 2022
Relationship between motor cortical and peripheral axonal hyperexcitability in amyotrophic lateral sclerosis.
- Yo-Ichi Suzuki, Kazumoto Shibuya, Sonoko Misawa, Tomoki Suichi, Atsuko Tsuneyama, Yuta Kojima, Keigo Nakamura, Hiroki Kano, Mario Prado, Yuya Aotsuka, Ryo Otani, Marie Morooka, and Satoshi Kuwabara.
- Neurology, Chiba University, Graduate School of Medicine, Chiba, Japan.
- J. Neurol. Neurosurg. Psychiatr. 2022 Aug 22.
BackgroundPrevious studies have shown that patients with amyotrophic lateral sclerosis (ALS) have hyperexcitability in both the motor cortex and peripheral motor axons, but the relationship between central and peripheral excitability has not been fully disclosed.MethodsThreshold tracking transcranial magnetic stimulation (TMS) and motor nerve excitability testing were prospectively performed in 53 patients with ALS and 50 healthy subjects, and their relations to compound muscle action potential (CMAP) amplitude and revised ALS Functional Rating Scale were cross-sectionally analysed.ResultsCompared with controls, patients with ALS showed both cortical and peripheral hyperexcitability; TMS showed reduced short-interval intracortical inhibition (interstimulus interval 1-7 ms) (p<0.001) and shortened silent period (p<0.05), and median nerve excitability testing revealed greater changes in depolarising threshold electrotonus (TEd) and greater superexcitability (p<0.0001, both), suggesting reduced axonal potassium currents. Significant correlations between cortical and peripheral excitability indices were not found. Greater changes in TEd (90-100 ms) (R=-0.33, p=0.03) and superexcitability (R=0.36, p=0.01) were associated with smaller amplitude of CMAP, whereas cortical excitability indices had no correlation with CMAP amplitude. More rapid motor functional decline was associated with only greater TEd (90-100 ms) (β=0.46, p=0.001).ConclusionsOur results suggest that in ALS, cortical excitability is continuously high regardless of the extent of the peripheral burden, but peripheral hyperexcitability is associated with the extent of the peripheral burden and disease evolution speed. Alterations of ion channel function may play an important role in ALS pathophysiology.© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.
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