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July 2007

Salt-Wasting and Hyponatremia in Neuroleptic Malignant Syndrome—Reply

Arch Neurol. 2007;64(7):1058-1059. doi:10.1001/archneur.64.7.1058-b

In reply

We thank Dr Ronald Gurrera for his inspiring comments regarding our observation on cerebral salt-wasting syndrome (CSWS) in NMS.1 But we also would like to emphasize that extrapolations from a single case to the pathophysiology of a complex disorder should be taken with necessary care. Many questions have to be addressed in the future to give us a more comprehensive understanding of the pathophysiology of CSWS as well as NMS. For example, the definitive origin of BNP in CSWS has to be resolved in detail, whether it arises from peripheral nervous tissue (most likely adrenal medulla) or central or both. Are there other natriuretic peptides or natriuretic active molecules involved? What are the mechanisms in other pathological states, such as subarachnoid hemorrhage (SAH)? Does CSWS in SAH2,3 underlie also a dopamine deprivation and as a consequence a sympathoadrenal dysregulation as it suggests itself in NMS? If this should be the case, dopaminergic deprivation in patients with SAH could contribute to a poor outcome for such patients not only via salt-wasting but also via aggravation of cerebral vasospasms. The latter appears plausible because brain arteries are innervated intimately with sympathetic nerve terminals whose preganglionic neurons arise from the cervical spinal sympathetic cell columns. These neurons are surrounded by BNP-positive cell clusters, as Dr Gurrera pointed out in his correspondence, and are also innervated via hypothalamic dopaminergic projections.4 It remains unclear whether the known BNP expression pattern in intimate association with central sympathetic nervous system can be applied to humans because results are derived from animal studies. Recording levels of natriuretic peptides with aminergic neurotransmitter levels in the cerebrospinal fluid of patients with SAH, NMS, or other pathological states with CSWS may contribute to resolving some of these questions.