Effects of mexiletine on hyperexcitability in sporadic amyotrophic lateral sclerosis: Preliminary findings from a small phase II randomized controlled trial

for the Mexiletine-2 ALS Study Group

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)371-383
Number of pages13
JournalMuscle and Nerve
Volume63
Issue number3
DOIs
StatePublished - 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)

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