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From the Institute for Exercise & Environmental Medicine (S.L.D., C.G.C., M.J.B.), Presbyterian Hospital of Dallas, TX; Departments of Internal Medicine (S.L.D., C.G.C.), Neurology (S.L.D., T.C.F., D.A.M., O.S., E.M.F.), and Ophthalmology (E.M.F.), University of Texas Southwestern Medical Center at Dallas; New Jersey Neuroscience Institute (P.D.K.), Seton Hall University, Edison; and Neurology Section (O.S.), Medical Service, Veterans Affairs North Texas Health Care Service.
Address correspondence and reprint requests to Dr. Elliot M. Frohman, Department of Neurology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390 Elliot.Frohman{at}UTSouthwestern.edu
Objective: The goal of this investigation was to demonstrate that internuclear ophthalmoparesis (INO) can be utilized to model the effects of body temperature-induced changes on the fidelity of axonal conduction in multiple sclerosis (Uhthoff's phenomenon).
Methods: Ocular motor function was measured using infrared oculography at 10-minute intervals in patients with multiple sclerosis (MS) with INO (MS-INO; n = 8), patients with MS without INO (MS-CON; n = 8), and matched healthy controls (CON; n = 8) at normothermic baseline, during whole-body heating (increase in core temperature 0.8°C as measured by an ingestible temperature probe and transabdominal telemetry), and after whole-body cooling. The versional disconjugacy index (velocity-VDI), the ratio of abducting/adducting eye movements for velocity, was calculated to assess changes in interocular disconjugacy. The first pass amplitude (FPA), the position of the adducting eye when the abducting eye achieves a centrifugal fixation target, was also computed.
Results: Velocity-VDI and FPA in MS-INO patients was elevated (p < 0.001) following whole body heating with respect to baseline measures, confirming a compromise in axonal electrical impulse transmission properties. Velocity-VDI and FPA in MS-INO patients was then restored to baseline values following whole-body cooling, confirming the reversible and stereotyped nature of this characteristic feature of demyelination.
Conclusions: We have developed a neurophysiologic model for objectively understanding temperature-related reversible changes in axonal conduction in multiple sclerosis. Our observations corroborate the hypothesis that changes in core body temperature (heating and cooling) are associated with stereotypic decay and restoration in axonal conduction mechanisms.
GLOSSARY: CON = controls; COV = coefficient of variation; FPA = first pass amplitude; INO = internuclear ophthalmoparesis; LED = light emitting diode; MLF = medial longitudinal fasciculus; MS = multiple sclerosis; NC = normal control; VDI = versional disconjugacy index.
e-Pub ahead of print on February 20, 2008, at www.neurology.org.
Supported by a National Multiple Sclerosis Society pilot grant PP-1040 (C.G. Crandall), the Once Upon A Time Foundation (E.M. Frohman), the Cain/Denius Comprehensive Center for Mobility Research (E.M. Frohman), the Irene Wadel and Robert Atha fund (E.M. Frohman), the Kenney Marie Dixon Pickens fund (E.M. Frohman), the Jean Ann and Steve Brock Fund for Medical Sciences (E.M. Frohman), and the Hawn Foundation (E.M. Frohman).
Disclosure: Dr. Frohman has received speaking honoraria from Biogen Idec, TEVA, and Serono. The other authors report no conflicts of interest.
Received June 14, 2007. Accepted in final form September 10, 2007.
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  R. J. Leigh and A. Serra Taking the temperature of MS with INO Neurology, March 25, 2008; 70(13_Part_2): 1063 - 1064. [Full Text] [PDF]
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