49.: The fampridine upper limb study (FULS)

Modified-release 4-aminopyridine (fampridine) is licensed in Australia for the symptomatic treatment of walking disability in patients with multiple sclerosis (MS). Its potential for use in other neurological domains, its mode of action, and the reasons for widely variable responses in treated patients remain unknown. This study aims to test the following hypotheses: (1) modified-release fampridine is associated with improvements in upper limb impairment in patients with multiple sclerosis, and (2) objective electrophysiological measures differ between patients on and off treatment, and can potentially be used to differentiate clinical responders and non-responders. We conducted two substudies. Substudy 1 is a randomised, double-blind, placebo-controlled trial in patients with MS and upper limb impairment. Clinical and electrophysiological measurements are made at baseline, conclusion and on three occasions while participants are taking fampridine-modified release or placebo. Substudy 2 is a single-blind study in patients already taking fampridine for walking disability. Clinical and electrophysiological measurements are made in patients while on (twice) and off (once) the drug by a blinded assessor. Clinical measurements are nine-hole peg test, upper limb grip strength, sensory discrimination capacity, visual acuity and contrast sensitivity, and modified fatigue impact scale. Electrophysiological measurements were resting motor threshold, motor evoked potential recruitment curves, short interstimulus intervals paired pulse transcranial magnetic stimulation (TMS), median nerve somatosensory evoked potentials, visual evoked potentials, and median nerve conduction study. The primary outcome measure is clinical response to fampridine as measured by performance on the nine-hole peg test. Secondary outcome measures are correlation between clinical and electrophysiological measures in responders as compared with non-responders, changes in upper limb grip strength, visual acuity and sensory discrimination capacity, and changes in modified fatigue impact scale score. Our hypothesis is that clinical responders to fampridine will show increased motor pathway recruitment and cortical excitability with TMS measures, with improvements in latency and amplitude of evoked potential responses. This novel study seeks to determine whether fampridine can have beneficial effects in domains other than ambulation. By combining clinical and electrophysiological measures, we seek