Thermoregulatory dysfunction in neuroleptic malignant syndrome

Hyperthermia is the central feature of neuroleptic malignant syndrome (NMS), but its etiology remains elusive. Two competing hypotheses implicate either hypothalamic dysfunction (inappropriate ''set point'') or direct myotoxicity (excessive peripheral heat production). These two models have distinct implications for thermoregulatory activity in NMS. The first predicts that the individual should respond as to a hypothermic threat or infection (the hypothalamus signals the body to raise its temperature). The second implies that an excessive heat load is perceived by the hypothalamus, which responds to this hyperthermic threat (it signals the body to lower its temperature). To assess the validity of these two hypotheses the thermoregulatory responses of a series of NMS patients (36 patients, 46 episodes) were examined using standard statistical methods. In contrast to normal mammalian thermoregulatory behavior, thermoeffector responses were not organized into either mode, but appeared to function somewhat independently and paradoxically. We conclude that neither hypothesis is sufficient to explain altered thermoregulation in NMS, and that the loss of integrated thermoeffector activity may be unique to this disorder.