Central Pontine Myelinolysis

Central pontine myelinolysis (CPM), now more broadly termed osmotic demyelination syndrome (ODS), is a devastating neurological condition caused by the non-inflammatory destruction of myelin sheaths in the central pons and, in many cases, extrapontine structures (basal ganglia, thalamus, cerebellum, lateral geniculate body, and cerebral white matter). The condition is most commonly iatrogenic, occurring when chronic hyponatremia (serum sodium less than 130 mEq/L present for more than 48 hours) is corrected too rapidly, though it can also occur in other clinical contexts involving rapid osmolar shifts. Understanding the pathogenesis requires detailed knowledge of brain volume regulation, organic osmolyte physiology, oligodendrocyte biology, and the unique vulnerability of pontine white matter to osmotic stress. Under normal conditions, brain cells maintain osmotic equilibrium with the extracellular fluid (ECF) through regulated transport of electrolytes and organic osmolytes. When hyponatremia develops acutely (over hours), the hypotonic ECF causes water to shift into brain cells by osmosis, producing cerebral edema. However, when hyponatremia is chronic (present for more than 48 hours), the brain activates powerful volume regulatory mechanisms to prevent fatal cerebral edema. Brain cells extrude electrolytes...