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With their report1 of cerebral salt-wasting syndrome in a patient with neuroleptic malignant syndrome (NMS), Dr Lenhard and colleagues have taken a potentially important step toward explicating the pathophysiology of NMS. Previous work2 suggested that salt-wasting caused by profound diaphoresis might explain electrolyte and fluid imbalances in NMS and the frequent co-occurrence of severe diaphoresis, hyponatremia, and polydipsia in that disorder. However, Lenhard et al propose that elevated levels of adrenomedullary brain natriuretic peptide (BNP) caused the severe hyponatremia observed in their patient. This alternative mechanism is intriguing because it represents a more direct consequence of the dysregulated hyperautonomic state that is central to NMS.
Although BNP is synthesized and secreted primarily by heart tissue, particularly in response to volume overload,3 comprehensive clinical evaluation excluded relevant cardiac pathology in their patient.1 Within the porcine nervous system, BNP concentrations are highest in spinal cord, followed by medulla-pons and striatum; only modest levels are found in the hypothalamus.4 This pattern is even more pronounced in the rat central nervous system, where initial studies5 - 6 found significant BNP levels only in spinal cord, and subsequent work7 demonstrated BNP-staining cell bodies that were more widely distributed but dispersed in clusters throughout sympathetic preganglionic cell columns. These data imply a functional linkage between sympathetic nervous system activation and BNP levels and support the hypothesis that elevated BNP associated with sympathoadrenal hyperactivity may cause hyponatremia in NMS. Obviously, extreme diaphoresis may also contribute to salt-wasting in some cases of NMS.
Correspondence: Dr Gurrera, Psychiatry Service, VA Boston Healthcare System and Department of Psychiatry, Harvard Medical School, 940 Belmont St (116A), Brockton, MA 02301 (ronald.gurrera@va.gov).
Financial Disclosure: None reported.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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