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Central pontine myelinolysis: historical and mechanistic considerations

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Abstract

Central pontine myelinolysis (CPM) is a demyelinating condition affecting not only the pontine base, but also involving other brain areas. It usually occurs on a background of chronic systemic illness, and is commonly observed in individuals with alcoholism, malnutrition and liver disease. Studies carried out 25–30 years ago established that the principal etiological factor was the rapid correction of hyponatremia resulting in osmotic stress. This article reviews progress achieved since that time on its pathogenesis, focusing on the role of organic osmolytes, the blood–brain, barrier, endothelial cells, myelinotoxic factors triggered by osmotic stress, and the role of various factors that predispose to the development of CPM. These advances show great promise in providing novel therapeutic options for the management of patients afflicted with CPM.

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Acknowledgments

This article is dedicated to Bette Kleinschmidt-DeMasters, Kevin O. Leslie, Roger E. Riepe, Scott R. VandenBerg and Andrew S. Robertson, all terrific residents who spent uncountable hours analyzing human clinical and pathological data, performing animal experiments and providing ideas that ultimately led to the concept of CPM resulting as the consequence of a rapid rise in serum osmolarity—most commonly following the rapid correction of hyponatremia. All have gone on to achieve outstanding careers as neuropathologists, pathologists, and neurologists. I also would like to especially thank Professor Karin Weissenborn, Hannover Medical School, Germany, for encouraging me to write this article. This work was supported by a Merit Review from the Department of Veterans Affairs and NIH Grant No. DK063311.

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  1. Departments of Pathology, University of Miami School of Medicine, PO Box 016960, Miami, FL, 33101, USA

    Michael D. Norenberg

  2. Veterans Affairs Medical Center, Miami, FL, USA

    Michael D. Norenberg

  3. Departments of Biochemistry & Molecular Biology, University of Miami Miller School of Medicine, Miami, FL, USA

    Michael D. Norenberg

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Norenberg, M.D. Central pontine myelinolysis: historical and mechanistic considerations. Metab Brain Dis 25, 97–106 (2010). https://doi.org/10.1007/s11011-010-9175-0

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