The effect of 4‐aminopyridine on clinical signs in multiple sclerosis: A randomized, placebo‐controlled, double‐blind, cross‐over study

Abstract

To find out whether treatment with 4‐aminopyridine is beneficial in multiple sclerosis (MS), 70 patients with definite MS entered into a randomized, double‐blind, placebo‐controlled, cross‐over trial in which they were treated with 4‐aminopyridine and placebo for 12 weeks each (maximum dose, 0.5 mg/kg of body weight). The estimated effect of the treatment as measured with the Kurtzke expanded disability status scale, which was the main evaluation parameter, was 0.28 point (p = 0.001). A significant decrease in the scale score (1.0 point or more) was encountered in 10 patients (16.4%) during oral treatment with 4‐aminopyridine whereas it was not seen during placebo treatment (p < 0.05). A significant subjective improvement (defined as an improvement that significantly affected the activities of normal daily life) was indicated by 18 patients (29.5%) during 4‐aminopyridine treatment and by 1 patient (1.6%) during placebo treatment (p < 0.05). Significant improvements related to 4‐aminopyridine occurred in a number of neurophysiological parameters. No serious side effects were encountered. However, subjective side effects such as paresthesias, dizziness, and light‐headedness were frequently reported during 4‐aminopyridine treatment. Analysis of subgroups revealed that there was no difference in efficacy between those patients randomized to receive 4‐aminopyridine and then placebo and those randomized to receive placebo and then 4‐aminopyridine or between patients with and those without subjective side effects. Especially patients with temperature‐sensitive symptoms and patients characterized by having a longer duration of the disease and being in a progressive phase of the disease were likely to show clear clinical benefit.