Treatment of internuclear ophthalmoparesis in multiple sclerosis with fampridine: A randomized double-blind, placebo-controlled cross-over trial

Kawita M. S. Kanhai, Jenny A. Nij Bijvank, Yorick L. Wagenaar, Erica S. Klaassen, KyoungSoo Lim, Sandrin C. Bergheanu, Axel Petzold, Ajay Verma, Jacob Hesterman, Mike P. Wattjes, Bernard M. J. Uitdehaag, Laurentius J. van Rijn, Geert Jan Groeneveld

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Abstract

Aim: To examine whether the velocity of saccadic eye movements in internuclear ophthalmoparesis (INO) improves with fampridine treatment in patients with multiple sclerosis (MS). Methods: Randomized, double-blind, placebo-controlled, cross-over trial with fampridine in patients with MS and INO. Horizontal saccades were recorded at baseline and at multiple time points post-dose. Main outcome measures were the change of peak velocity versional dysconjugacy index (PV-VDI) and first-pass amplitude VDI (FPA-VDI). Both parameters were compared between fampridine and placebo using a mixed model analysis of variance taking patients as their own control. Pharmacokinetics was determined by serial blood sampling. Results: Thirteen patients had a bilateral and 10 had a unilateral INO. One patient had an INO of abduction (posterior INO of Lutz) and was excluded. Fampridine significantly reduced both PV-VDI (−17.4%, 95% CI: −22.4%, −12.1%; P < 0.0001) and FPA-VDI (−12.5%, 95% CI: −18.9%, −5.5%; P < 0.01). Pharmacokinetics demonstrated that testing coincided with the average tmax at 2.08 hours (SD 45 minutes). The main adverse event reported after administration of fampridine was dizziness (61%). Conclusion: Fampridine improves saccadic eye movements due to INO in MS. Treatment response to fampridine may gauge patient selection for inclusion to remyelination strategies in MS using saccadic eye movements as primary outcome measure.
Original languageEnglish
Pages (from-to)697-703
JournalCNS Neuroscience and Therapeutics
Volume25
Issue number6
DOIs
Publication statusPublished - 1 Jun 2019
Externally publishedYes

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