Thermoregulation in multiple sclerosis

Abstract

Multiple sclerosis (MS) is a progressive neurological 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 neurological symptoms with heat exposure. Additionally, MS may produce impaired neural control of autonomic and endocrine functions. This review focuses on five main themes regarding the current understanding of thermoregulatory dysfunction in MS: 1) heat sensitivity; 2) central regulation of body temperature; 3) thermoregulatory effector responses; 4) heat-induced fatigue; and 5) countermeasures to improve or maintain function during thermal stress. Heat sensitivity 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, which can be quantitatively characterized using precise measurements of ocular movements. MS lesions can also 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. Fatigue during thermal stress is common in MS and results in decreased motor function and increased symptomatology likely due to impairments in central conduction. Although not comprehensive, some evidence exists concerning treatments (cooling, precooling, and pharmacological) for the MS patient to preserve function and decrease symptom worsening during heat stress.

Fig. 1.

Clinical courses of multiple sclerosis (MS). Adapted from Confavreux and Vukusic (11) with permission from Lippincott Williams and Wilkins/Wolters Kluwer Health.

Fig. 2.

Data from healthy controls (Control; n = 8), MS patients without internuclear opthalmoparesis (MS-Control; n = 8), and MS patients diagnosed with internuclear ophthalmoparesis (MS-INO; n = 8) showing ocular function responses [velocity-versional dysconjugacy index (VDI)] during whole body heat stress (increase internal temperature ∼0.8°C) and subsequent whole body cooling (return to normothermic baseline). A significant slowing (P < 0.001) of horizontal eye movements (increasing velocity-VDI) was observed in MS patients with INO during whole body heating. However, ocular function was restored to preheating baseline with subsequent whole body cooling. Data are expressed as means ± SD. Reproduced from Davis et al. (15) with permission from Lippincott Williams and Wilkins/Wolters Kluwer Health.

Fig. 3.

Data from control and MS patients showing decreased sweat gland output per gland (P < 0.05) compared with matched, healthy controls following iontophoresis of pilocarpine, a cholinergic agent (A). No differences were observed in the number of sweat glands recruited between healthy controls and MS patients (B). Data are expressed as means ± SD. Modified from Davis et al. (17).

Fig. 4.

Core body temperatures responses during 30 min of aerobic exercise and subsequent recovery following a noncooled trial (open circles) and a precooled trial (closed circles). Core body temperature during the precooled trial remained below baseline values during exercise and recovery whereas core temperature during the noncooled trial exceeded a critical threshold (0.5°C) for potential increases in symptom worsening. Data are expressed as means ± SD. Modified from White et al. (86) with permission from Sage Publication Ltd., UK.