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NEUROLOGY 2009;73:798-804
© 2009 American Academy of Neurology

Using fast eye movements to study fatigue in multiple sclerosis

M. Matta, MD, PhD, R. J. Leigh, MD, M. Pugliatti, MD, PhD, I. Aiello, MD and A. Serra, MD, PhD

From Clinical Neurology (M.M., M.P., I.A., A.S.), Department of Neuroscience, University of Sassari, Italy; and The Daroff-Dell’Osso Laboratory (R.J.L., A.S.), Veterans Affairs Medical Center and University Hospitals, Case Western Reserve University, Cleveland, OH.

Address correspondence and reprint requests to Dr. Alessandro Serra, Department of Neurology, 11100 Euclid Avenue, Cleveland, OH 44106-5040 alessandro.serra{at}Uhhospitals.org

Objective: To investigate whether internuclear ophthalmoparesis (INO) due to demyelination of the medial longitudinal fasciculus (MLF) provides a model for studying the poorly understood symptom of fatigue in multiple sclerosis (MS). We asked whether repetitive horizontal saccades increased eye movement disconjugacy in patients with MS with INO, but not in healthy subjects.

Methods: We compared conjugacy of horizontal saccades in 9 patients with INO (4 bilateral, total 13) and 8 controls during minute 1 and minute 10 of a fatigue test; we measured the ratio of abducting/adducting peak velocity (versional disconjugacy index [VDI]).

Results: VDI values were greater in patients than controls. During the fatigue test, controls showed no changes of VDI, but patients did (p < 0.005) for 10/13 INOs, with increased ratios in 5 cases and a decrease in the other 5.

Conclusion: Fatigue-induced worsening of conjugacy was observed in milder internuclear ophthalmoparesis (INO), and may reflect deteriorated fidelity of saccadic pulse transmission along demyelinated medial longitudinal fasciculus. Improved conjugacy was observed in the more severe INOs, and may be due to adaptive mechanisms, such as recruitment of vergence to aid gaze shifts. INO may provide an accessible, reductionist model to study how decreased neural transmission influences fatigue in multiple sclerosis, how the brain adapts to it, and whether drugs may prove therapeutic.

Abbreviations: AR = amplitude ratio; INO = internuclear ophthalmoparesis; IVD = interocular velocity difference; MLF = medial longitudinal fasciculus; MS = multiple sclerosis; PI = prediction interval; VDI = versional disconjugacy index.

Supplemental data at www.neurology.org

Supported by NIH R01EY06717, Department of Veterans Affairs, the Evenor Armington Fund, and Regione Autonoma della Sardegna (Assessorato dell’Igiene e Sanità e dell’Assistenza Sociale), Fondazione Italiana Sclerosi Multipla (Cod. 2002/R/43 e Cod. 97/R/69).

Disclosure: Author disclosures are provided at the end of the article.

Received March 2, 2009. Accepted in final form June 15, 2009.






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