Acute effects of riluzole and retigabine on axonal excitability in patients with ALS: A randomized, double-blind, placebo-controlled, cross-over trial.

Increased excitability of motor neurons in patients with amyotrophic lateral sclerosis (ALS) may be a relevant factor leading to motor neuron damage. This randomized, double-blind, three-way crossover, placebo-controlled study evaluated peripheral motor nerve excitability testing as a biomarker of hyperexcitability and assessed the effects of riluzole and retigabine in 18 patients with ALS. We performed excitability testing at baseline, and twice after participants had received a single dose of either 100 mg riluzole, 300 mg retigabine, or placebo. Between- and within-day repeatability was at least acceptable for 14 out of 18 recorded excitability variables. No effects of riluzole on excitability testing were observed, but retigabine significantly decreased strength-duration time-constant (9.2%) and refractoriness at 2 ms (10.2) compared to placebo. Excitability testing was shown to be a reliable biomarker in patients with ALS, and the acute reversal of previously abnormal variables by retigabine justifies long-term studies evaluating the impact on disease progression and survival.