Modeling Uhthoff's phenomenon in MS patients with internuclear ophthalmoparesis

S. L. Davis, T. C. Frohman, Craig G Crandall, M. J. Brown, D. A. Mills, P. D. Kramer, Olaf Stuve, Elliot Frohman

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1098-1106
Number of pages9
JournalNeurology
Volume70
Issue number13 PART 2
DOIs
StatePublished - Mar 2008

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Ophthalmoplegia
Multiple Sclerosis
Heating
Temperature
Body Temperature Changes
Telemetry
Demyelinating Diseases
Eye Movements
Body Temperature

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Modeling Uhthoff's phenomenon in MS patients with internuclear ophthalmoparesis. / Davis, S. L.; Frohman, T. C.; Crandall, Craig G; Brown, M. J.; Mills, D. A.; Kramer, P. D.; Stuve, Olaf; Frohman, Elliot.

In: Neurology, Vol. 70, No. 13 PART 2, 03.2008, p. 1098-1106.

Research output: Contribution to journalArticle

Davis, S. L. ; Frohman, T. C. ; Crandall, Craig G ; Brown, M. J. ; Mills, D. A. ; Kramer, P. D. ; Stuve, Olaf ; Frohman, Elliot. / Modeling Uhthoff's phenomenon in MS patients with internuclear ophthalmoparesis. In: Neurology. 2008 ; Vol. 70, No. 13 PART 2. pp. 1098-1106.
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abstract = "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.",
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