Thermoregulatory dysfunction in multiple sclerosis

Multiple sclerosis (MS) is a progressive neurologic disorder that disrupts axonal myelin in the central nervous system. Demyelination produces alterations in saltatory conduction, slowed conduction velocity, and a predisposition to conduction block. An estimated 60-80% of MS patients experience temporary worsening of clinical signs and neurologic symptoms with heat exposure (Uhthoff's phenomenon). This heat intolerance in MS is related to the detrimental effects of increased temperature on action potential propagation in demyelinated axons, resulting in conduction slowing and/or block. Additionally, MS may produce impaired neural control of autonomic and endocrine functions. Isolating and interpreting mechanisms responsible for autonomic dysfunction due to MS can be difficult as it may involve sensory impairments, altered neural integration within the central nervous system, impaired effector responses, or combinations of all of these factors. MS lesions occur in areas of the brain responsible for the control and regulation of body temperature and thermoregulatory effector responses, resulting in impaired neural control of sudomotor pathways or neural-induced changes in eccrine sweat glands, as evidenced by observations of reduced sweating responses in MS patients. Although not comprehensive, some evidence exists concerning treatments (cooling, precooling, and pharmacologic) for the MS patient to preserve function and decrease symptom worsening during heat stress. This review focuses on four main themes influencing current understanding of thermoregulatory dysfunction in MS: (1) heat intolerance; (2) central regulation of body temperature; (3) thermoregulatory effector responses; and (4) countermeasures to improve or maintain function during thermal stress.