BACKGROUND: Internuclear ophthalmoplegia (INO) is a common cause of visual symptoms in patients with multiple sclerosis (MS). It is characterized by slowing eye adduction during horizontal saccades. Recent studies suggest fampridine may improve nerve conduction in MS patients. We performed a study in MS patients with INO to determine effects of fampridine on eye movement speed. METHODS: This was a randomized, double-blind, placebo-controlled, crossover study with fampridine in 24 MS patients with INO. The patients had 2 visits, and received either 20 mg fampridine or placebo. We analyzed eye movements recorded by the EyeLink1000 at baseline and 5 times post-dose. The primary outcome measure was velocity Versional Dysconjugacy Index (VDI). Higher VDI values indicate a delay in eye adduction relative to abduction, associated with INO. Eye movements at baseline and tmax (1.5 hours after drug administration) were compared with a mixed model analysis of variance; patients served as their own control-group. RESULTS: All patients completed the study. A significant decrease (p5.0005) in VDI was observed after fampridine administration compared with placebo (216.0% (95% CI: 223.2% to 28.2%)), which indicates a significant improvement in eye adduction at tmax. The main adverse events reported after administration of fampridine were dizziness and fatigue. CONCLUSION: Fampridine was associated with a significant decrease in VDI, corresponding with an improvement in INO severity in comparison with placebo. It remains to be determined whether this also translates into clinical improvement of visual symptoms of MS patients with INO. This study shows that the method that we employed can be used to show pharmacological effects of compounds that influence nerve conduction of demyelinated nerve fibers.
Kanhai, K., Wagenaar, Y., Nij-Bijvank, J., Klaassen, E., Lim, K., Ber-Gheanu, S., … Groeneveld, G. (2017). The effects of fampridine on eye movements in multiple sclerosis patients with internuclear ophthalmoplegia. Clinical Pharmacology & Therapeutics, 101, S32–S33.