Multiple sclerosis and thermoregulatory dysfunction.

Multiple sclerosis is a demyelinating disease of the central nervous system, characterized by a relapsing and remitting or, alternatively, by a steady and continuous course of dysfunction. The hallmark of the disease is heterogeneity. How the disease presents itself depends on the exact location and total accumulation of lesions and on the impact of demyelination on nerve conduction. Conduction maybe be enhanced, producing positive symptoms like tic douloureux, paresthesiae, or tingling, or conduction may be diminished, producing negative symptoms like blindness and paralysis (7, 8). Diminished conduction may be total or partial, with decreases in the maximum of frequency or velocity of conduction. During remission, which may last months or years, symptoms improve as inflammation subsides, sodium channels migrate into the bare axon, remyelination of the denuded site occurs, and, ultimately, conduction resumes through the lesion sites. The deficit may also become permanent as axons degenerate (9). During shorter periods lasting hours or days, symptoms may also worsen, as conduction through old lesions fluctuates; conduction is “highly insecure” and subject to inflammatory factors like nitric oxide and temperature changes (5, 8). Heat worsens and cooling improves negative symptoms of multiple sclerosis, sometimes dramatically so. The underlying mechanism relates to the influence of temperature on sodium channels and on current necessary for depolarization of the axon. Increases in temperature diminish the depolarizing current, whereas decreases in temperature have the opposite effect (8). Sensitivity can be extreme, and very small changes can have profound effects. Heating, for example by radiation from the sun, can turn a limping gait into no gait at all. Alternatively, hot air from a hair dryer can turn a hopeful morning into an exhausting one. Cooling, on the other hand, by sitting in a cool bath or shower, can turn the “disease off” (at least for a little while) and give an individual back the freedom for exercise or work. As you might expect, the impact of the disease on the thermoregulatory system takes a myriad of forms, depending on lesion location and severity. With any location and lesion load, however, the impact of the disease depends on body temperature, worsening as activity is diminished in more and more demyelinated axons. In addition, thermoregulatory impact is worsened by lack of physical fitness and lowered blood volume. The individual may be suddenly overcome. Getting into a hot bath may seem a great way to relax, but then suddenly the individual with multiple sclerosis is too weak to get out. Triggering such a collapse of the thermoregulatory system explains sudden deaths associated with sun exposure (1). This editorial has been prepared to provide insight gained from living with multiple sclerosis and its heatrelated symptoms and from working many years as a research physiologist. Discussions focus on three areas where further research may have important implications to those living and coping with the disease: thermoregulatory failure, the cranial radiator, and exercise-induced heat. Thermoregulatory system. Recently, one study has assessed the thermoregulatory center and its impact on multiple sclerosis (3). In this study of a single subject with a history of multiple sclerosis and thermoregulatory dysfunction, temperature thresholds were calculated as the core temperature was slowly warmed to sweating and again as the core temperature was gradually cooled to vasoconstriction and shivering. It was found that the sweating threshold was a full 1°C higher than normal and the vasoconstriction threshold was 2°C below normal, making the calculated sweating-to-vasoconstriction range four times the normal amount. The shivering threshold was also lower than normal (31.8°C), making the vasoconstriction-to-shivering range more than twice the normal amount. Providing such information may sound academic and simplistic; however, this may be an important point to those with multiple sclerosis, altering them to the extent of dysfunction, and to others like caretakers and insurance companies, alerting them to the hazards of increased body temperature and the need for cooling devices. Address for reprint requests and other correspondence: D. G. Baker, 144 Richardson Drive, Mill Valley, CA 94941 (E-mail: [email protected]). J Appl Physiol 92: 1779–1780, 2002; 10.1152/japplphysiol.01251.2001.