Previous studies suggest that
aminopyridine may play a role in the symptomatic treatment of
fatigue in
multiple sclerosis. Although the mechanism underlying the beneficial effect on
fatigue remains unclear, it has been proposed that
aminopyridines may help to improve conduction in demyelinated central pathways, implicating both axonal and synaptic mechanisms. The objective of the present study is to determine whether 4-AP decreases daily-living
fatigue in progressive
multiple sclerosis. The effect of 4-AP on other neurophysiological and neuropsychological parameters was also considered. A 'double-blind', randomized, 'placebo-controlled', crossover trial was conducted on 54 patients with progressive
multiple sclerosis. All patients received treatment with placebo and 32 mg per day of 4-AP, each for 6 months. The main outcome measure was the
Fatigue Severity Scale. Secondary measures were EDSS, cognitive functions and neurophysiological parameters. Forty-nine patients (91%) completed the study. Changes in
fatigue scores, EDSS and cognitive functions were not significantly different between 4-AP and placebo. However, when patients treated with 4-AP were divided into two groups according to the serum level of 4-AP, a significant effect on
fatigue compared with placebo was observed in the 'high level' (>30 ng/ml) group (P=0.05). Synchronization of motor evoked potentials improved during 4-AP with respect to placebo (P=0.019) and this correlated positively with
fatigue reduction (P=0.010). No relevant side effects were observed.