Ocular-motor conduction dynamics and variability in multiple sclerosis-related internuclear ophthalmoparesis: A...

Internuclear ophthalmoparesis (INO) in multiple sclerosis (MS) reflects impaired signal transmission within the medial longitudinal fasciculus (MLF). Increased pulse size ratio (PSR) and prolonged pulse time delay (PTD) quantify interocular velocity asymmetry and transmission timing.

To characterize PSR and PTD during ocular-motor fatigue in MS-related INO and the effects of dalfampridine.

In a randomized, double-blind, placebo-controlled crossover trial, 19 participants with MS-related INO underwent eye-movement recordings during a 10-min saccadic task. PSR and PTD were analyzed at saccade, INO, and participant levels.

23,904 INO and 2408 control paired saccades were analyzed. In INO, PTD was prolonged and PSR elevated, with a positive correlation. Dalfampridine did not significantly improve prespecified ocular-motor outcomes, including mean PSR, mean PTD, or early-late fatigue measures. Responses were heterogeneous. Exploratory analyses showed dynamic PSR and PTD fluctuations, with a trend toward reduced PSR variability during dalfampridine. Greater trough PTD variability was associated with larger PTD shortening during dalfampridine, but not placebo.

Dalfampridine did not significantly improve prespecified ocular-motor outcomes. PSR and PTD capture complementary aspects of internuclear signal transmission, with ocular-motor fatigue reflecting dynamic instability. PTD variability is associated with variation in response to dalfampridine, supporting further study as a tract-specific biomarker.