Background Modified-release 4-aminopyridine (fampridine-MR) is used in the symptomatic treatment of walking disability in patients with multiple sclerosis (MS). Its potential for use in other MS symptoms remains unproven and its mode of action in this context is uncertain. Interest is growing in the use of upper limb outcome measures in clinical trials in patients with Multiple Sclerosis, particularly in advanced or progressive disease. This study tests the following hypotheses: (1) Fampridine-MR improves upper limb function in patients with MS and upper limb impairment. (2) Treatment with fampridine-MR is associated with measurable alterations in objective electrophysiological parameters (evoked potentials and transcranial magnetic stimulation (TMS)) which may predict response to drug treatment. Methods Study population: patients with MS of any disease subtype, duration and severity who have symptomatic impairment of one or both upper limbs. A healthy control group was included for validation of clinical and electrophysiological measures. Study design: randomised double blind placebo-controlled trial. Treatment details: participants allocated to either fampridine-MR 10 mg bd or placebo of identical appearance for 8 weeks. Primary outcome: performance on 9-hole peg test (9HPT) after 4 weeks. Secondary outcomes: persistence of effect on 9HPT; grip strength; visual acuity and contrast sensitivity; modified fatigue impact scale score; sensory discrimination capacity; visual, somatosensory and motor evoked potentials; resting motor threshold; paired-pulse TMS; peripheral nerve conduction studies. Results 40 patients with MS (60% female, median age 52, median disease duration 13.5 years, median EDSS 6.0) were enrolled. Treatment with fampridine-MR was not associated with any change in upper limb function as measured by the clinical primary or secondary outcomes. Treatment with fampridine-MR was also not associated with any difference in electrophysiological measures of upper limb function. This held true after adjustment for hand dominance, disease duration and severity. Four patients withdrew from the trial because of lack of efficacy or side-effects; all were in the placebo arm. Three patients were admitted to hospital during the study period; one with MS exacerbation (placebo group), one with syncope (drug group) and one with UTI (drug group); otherwise there were no serious adverse events. Conclusion Treatment with fampridine-MR was well-tolerated but did not produce clinical benefit in terms of upper limb function, vision or fatigue, nor was there any measurable effect on objective electrophysiological parameters.
