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

Journal: CNS neuroscience & therapeutics 2020;25(6):697-703

PMID: 30756475

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 t 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.

© 2019 The Authors CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.

Address: Centre for Human Drug Research, Leiden, the Netherlands.; Department of Ophthalmology, Neuro-ophthalmology Expertise Center, Amsterdam UMC, Amsterdam, the Netherlands.; Department of Neurology, MS Center and Neuro-ophthalmology Expertise Center, Amsterdam UMC, Amsterdam, the Netherlands.; Centre for Human Drug Research, Leiden, the Netherlands.; KCRN Research, Germantown, Maryland.; Department of Ophthalmology, Neuro-ophthalmology Expertise Center, Amsterdam UMC, Amsterdam, the Netherlands.; Department of Neurology, MS Center and Neuro-ophthalmology Expertise Center, Amsterdam UMC, Amsterdam, the Netherlands.; The National Hospital for Neurology and Neurosurgery, Queen Square and Moorfields Eye Hospital, London, UK.; Experimental Medicine, Biogen, Cambridge, Massachusetts.; inviCRO, Boston, Massachusetts.; Department of Radiology and Nuclear Medicine, Amsterdam University Medical Center, Amsterdam, the Netherlands.; Department of Neurology, MS Center and Neuro-ophthalmology Expertise Center, Amsterdam UMC, Amsterdam, the Netherlands.; Department of Ophthalmology, Neuro-ophthalmology Expertise Center, Amsterdam UMC, Amsterdam, the Netherlands.; Department of Ophthalmology, Onze Lieve Vrouwe Gasthuis, Amsterdam, the Netherlands.; Centre for Human Drug Research, Leiden, the Netherlands.; Department of Neurology, MS Center and Neuro-ophthalmology Expertise Center, Amsterdam UMC, Amsterdam, the Netherlands.
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