Central and Extrapontine Myelinolysis: Then…and Now :

Myelinolysis is a neurologic disorder that can occur after rapid correction of hyponatremia. Initially named "central pontine myelinolysis," this disease is now known to also affect extrapontine brain areas. Manifestations of myelinolysis usually evolve several days after correction of hyponatremia. Typical features are disorders of upper motor neurons, spastic quadriparesis and pseudobulbar palsy, and mental disorders ranging from mild confusion to coma. Death may occur. The motor and localizing signs of myelinolysis differ from the generalized encephalopathy that is caused by untreated hyponatremia. Experiments have duplicated the clinical and pathologic features of myelinolysis by rapidly reversing hyponatremia in animals. Myelinolysis is more likely to occur after the treatment of chronic rather than acute hyponatremia and is more likely to occur with a rapid rate of correction. The exact pathogenesis of myelinolysis has not been determined. Optimal management of hyponatremic patients involves weighing the risk for illness and death from untreated hyponatremia against the risk for myelinolysis due to correction of hyponatremia. Experiments in animals and clinical experience suggest that correction of chronic hyponatremia should be kept at a rate less than 10 mmol/L in any 24-hour period.

Focal symmetric demyelination in the central nervous system may be precipitated by aggressive correction of a hyper- or hypo-osmolar state and until recently has been associated with a high rate of morbidity and mortality. Specific anatomical locations are more susceptible to demyelination than others, although the mechanism of injury is unknown. Classic clinical and anatomical descriptions associated with a central pontine location have been supplemented by descriptions of patients with unusual symptoms associated with demyelinating lesions in extrapontine locations. The separation of patients with myelinolysis in central pontine and extrapontine locations is possible on the basis of clinical symptoms, and may direct specific pharmacological treatment. Patients at risk of central myelinolysis who are subjected to aggressive osmolar correction may be rescued with appropriate fluid management before brain injury has occurred; once injury is suspected on the basis of neurological symptoms, additional forms of intervention may still improve the outcome. Recent investigation of the molecular basis of the demyelinating process and the adaptive responses of the brain to dysosmolar challenge has allowed for the refinement of standard treatments and has made the osmotic demyelination syndrome a treatable condition with a better than expected prognosis.