Oral 4-aminopyridine in multiple sclerosis: Results of a six months randomised, double-blind, placebo-controlled, crossover trial

Forty-nine patients (20 males, 29 females, age min 23, max 60) suffering from a chronic progressive form of MS (mean illness duration 13. SD 9 years) were enrolled in the study, with a mean EDSS of 6.2 (SD 0.8). Treatment was carried out via oral administration of capsules of Placebo or containing 4 or 8 mgs of 4-AP up to a daily dosage of 32 mgs. Patients took 6 months of placebo and of 4-AP in a double blind, randomized, cross-over design. Peak serum levels showed patients grouping into three categories : poor, moderate and good absorbers (five patients had undeterminable value). Electrophysiological evaluation of visual, somatosensory and motor pathways and a comprehensive battery of neuropsychological tests were performed at Times 0, 6 and 12 months. Side effects were observed in five patients (11%), all of them were moderate or good absorbers. As general result, none of the examined parameters improved significantly after 4-AP administration vs. Placebo. However, 4-AP pure effect (measured as difference between 4-AP and Placebo effects) has been also evaluated by means of analysis of variance with Peak serum level (three levels, poor, medium, good) and order of treatment (two-levels : Placebo as first, 4-AP as first) as between factors Improvements in VEPs P100 latency and N75-N145 temporal dispersion were slightly dependent (respectively, p=0.06 and p=0.09) on Peak serum level as well as Fatigue scale (p=0.08); good 4-AP absorbers took more advantage of 4-AP than other groups which showed scanty changes.