7. Effects of fampridine PR on axonal function in multiple sclerosis

Abstract

Fampridine PR (prolonged-release 4-aminopyridine tablets) is a treatment for walking disability in multiple sclerosis (MS). While 4-aminopyridine is known to block kV 1.1 potassium channels in vitro, the mechanisms underlying its beneficial effects in the clinical setting have not been investigated. The aim of the present study was to investigate the effects of fampridine on axonal function in an MS cohort. Studies were conducted on 13 MS patients and 29 aged-matched controls. Studies were conducted at baseline and 6 weeks following the commencement of fampridine PR 10 mg b.d. Axonal function was assessed using nerve excitability techniques, which provide information on axonal ion channel function and membrane potential. Neurophysiological parameters were correlated with clinical measures of functional ability, namely hand grip dynamometry, 9-hole peg test, timed 25 foot walk and through questionnaires assessing aspects of upper and lower limb function. There were prominent alterations in nerve excitability parameters noted in baseline recordings in MS patients compared to age-matched controls. Specifically there were reductions in depolarizing threshold electrotonus at 40–60 ms and 90–100 ms ( p = 0.007 and p < 0.001 respectively). These changes were accompanied by reduced superexcitability ( p = 0.002). Following fampridine treatment these abnormalities became less prominent, with mean values approaching the normal range. Significant correlations were also noted between changes in nerve excitability parameters following fampridine treatment and measures of functional performance. Of note, changes in hyperpolarizing threshold electrotonus at the 90–100 ms correlated with changes in hand grip strength ( r = −0.615) and in subjective assessments of lower limb function using the ABILOCO questionnaire ( r = 0.587). The study has demonstrated baseline alterations in nerve excitability parameters in MS patients, which improve following fampridine PR treatment. Furthermore, the study has demonstrated that there are significant correlations between changes in excitability and measures of functional performance and that these are detectable in measures of both upper and lower limb function.