Abstract
Background: To collect preliminary data on the effects of mexiletine on cortical and axonal hyperexcitability in sporadic amyotrophic lateral sclerosis (ALS) in a phase 2 double-blind randomized controlled trial. Methods: Twenty ALS subjects were randomized to placebo and mexiletine 300 or 600 mg daily for 4 wk and assessed by transcranial magnetic stimulation and axonal excitability studies. The primary endpoint was change in resting motor threshold (RMT). Results: RMT was unchanged with 4 wk of mexiletine (combined active therapies) as compared to placebo, which showed a significant increase (P =.039). Reductions of motor evoked potential (MEP) amplitude (P =.013) and accommodation half-time (P =.002), secondary outcome measures of cortical and axonal excitability, respectively, were also evident at 4 wk on mexiletine. Conclusions: The relative stabilization of RMT in the treated subjects was unexpected and could be attributed to unaccounted sources of error or chance. However, a possible alternative cause is neuromodulation preventing an increase. The change in MEP amplitude and accommodation half-time supports the reduction of cortical and axonal hyperexcitability with mexiletine.
Original language | English (US) |
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Pages (from-to) | 371-383 |
Number of pages | 13 |
Journal | Muscle and Nerve |
Volume | 63 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2021 |
Keywords
- amyotrophic lateral sclerosis
- axonal excitability
- outcome research
- randomized controlled clinical trial
- transcranial magnetic stimulation
ASJC Scopus subject areas
- Physiology
- Clinical Neurology
- Cellular and Molecular Neuroscience
- Physiology (medical)