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Neuroleptic Malignant Syndrome

Reuven Sandyk, MD, MSc; Robert P. Iacono, MD
JAMA. 1986;255(17):2291. doi:10.1001/jama.1986.03370170055016.
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To the Editor.—  We read with interest the recent article by Friedman et al entitled "A Neuroleptic Malignantlike Syndrome due to Levodopa Therapy Withdrawal."1 The authors speculate that the dysfunction underlying the neuroleptic malignant syndrome (NMS) occurs at more than one level of the neuraxis, on the ground that the multiple symptoms and signs cannot be reconciled to the pathophysiology of one anatomic area. We would like to suggest, however, that the key factor to the pathophysiology of the NMS is a dysregulation in the activity of endorphins at the diencephalic level. Our hypothesis is based on the following evidence and rationale.First, it is understood that the hypothalamus regulates temperature,2 level of consciousness,3 and motor activity.4 The hypothalamus is rich in endorphins and dopamine, the former being implicated in both hypothermia and hyperthermia. Dopaminergic pathways link the hypothalamus with the substantia nigra.5Recent studies


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