Riluzole does not have an acute effect on motor thresholds and the intracortical excitability in amyotrophic lateral sclerosis

Intracortical excitability in amyotrophic lateral sclerosis (ALS) is impair ed. The effectiveness of the glutamate antagonist riluzole (Rilutek(R), Rho ne-Poulene Porer) in ALS has been shown in clinical studies. In healthy sub jects it modifies intracortical excitability in a frequently used double-st imulus paradigm of transcranial magnetic stimulation (TMS). Under riluzole intracortical inhibition is enhanced in healthy individuals, although not a lways significantly, whereas intracortical facilitation has been described as reduced [10, 11]. We wanted to find out whether riluzole affects and pot entially rebalances impaired intracortical excitability in ALS. We, therefo re, enrolled 13 patients with clinically and electromyographically confirme d ALS into this study. Five patients had to be excluded because motor thres holds were too high to get reliable motor evoked potentials (MEPs). In the remaining 8 patients, mean age was 59.9 +/- 11.9 years (+/- standard deviat ion) and mean symptom duration 9.6 +/- 2.5 months. Intracortical excitabili ty was assessed before and 1.5 hours after the first intake of a loading do se of 100 mg of riluzole using a conventional paired-pulse TMS paradigm wit h interstimulus intervals (ISI) ranging from 1-30 ms and intensities adjust ed to yield MEPs of 1.0 mV for test pulses and of 90% active motor threshol d for conditioning pulses. Patients' baseline results were compared to thes e of 9 age-matched, healthy control subjects. Before drug intake, motor thr esholds did not differ between groups, but there was significantly less int racortical inhibition in the ALS patient group. Riluzole intake did not sig nificantly alter motor thresholds or intracortical excitability in the ALS patients. We conclude that riluzole does not immediately influence intracor tical excitability in ALS. Our results are in contrast to the findings of S tefan et al (1998) [14] where a partial normalization of intracortical inhi bition in ALS was observed after at least 5 days of drug intake. The differ ence between that study and our result may indicate a delayed onset of rilu zole's influence on intracortical excitability.