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Osmotic Demyelination Syndrome
Osmotic demyelination syndrome (ODS) refers to demyelination of white matter tracts traversing the pons (central pontine myelinolysis (CPM)) or in the extrapontine regions (extrapontine myelinolysis (EPM)).
CPM is a noninflammatory, symmetric, demyelinating condition involving the central pons. EPM refers to demyelination, which occurs in the region outside the pons including midbrain, thalamus, basal ganglia, internal capsule, lateral geniculate bodies, cerebellum, and spinal cord. It is seen in approximately 10% of patients with CPM.
CPM was first described in 1959 by Adams et al. in chronic alcoholics and malnourished individuals. They observed that patients who were chronic alcoholics or undernourished developed spastic quadriplegia, pseudobulbar palsy, encephalopathy, or coma as a result of an acute, noninflammatory demyelinating lesion within the basis pontis. It was later recognized that lesions can occur even outside the pons, i.e., EPM. Though originally described in chronic alcoholics and malnourished patients, the condition is typically seen in the setting of rapid correction of hyponatremia.
Chronic alcoholism is the most common underlying condition seen in approximately 40% of patients who develop CPM. Singh et al. reported the incidence of CPM to be 29% during autopsy examination of liver transplant recipients. CPM is more commonly seen in females than males.
Pathophysiology
The exact mechanism is still not well understood. According to one hypothesis, the central pons and other areas of EPM are the region of maximum admixture and apposition of gray and white matter. In these regions of rich gray–white matter interface, a rapid change in osmotic forces (such as rapid correction of sodium following prolonged hyponatremia) causes osmotic endothelial damage, vasogenic edema, and release of myelinotoxic factors inducing demyelination of the adjacent white matter tracts. Histologically, demyelination in CPM is characterized by intramyelinitic splitting, vacuolization, and rupture of myelin sheaths presumably due to osmotic effects. The lesion exhibits degeneration and loss of oligodendrocytes with relative sparing of neural cell bodies and axons. Therefore, the distribution of myelinolysis parallels the distribution of oligodendrocytes.
During hyponatremia, fall in serum osmolality leads to entry of water into the brain cells and causes edema. Various protective mechanisms prevent this from happening, which include a shift in interstitial sodium-rich fluid to CSF (within minutes), loss of inorganic ion (K + , Cl − ) over a few hours, and loss of organic osmoles (myoinisotol, taurine, aspartate, glutamate, and glycine) from one to a few days, rendering the cell isotonic to extracellular fluid and maintaining cell volume. During correction of hyponatremia, the reverse happens and lost electrolytes are restored. Once the shift of inorganic ions has exhausted, the rate of rise in serum tonicity more than the rate of synthesis and/or transport of organic osmoles into the cell will cause the brain cell to shrink. Oligodendrocytes are particularly susceptible to volume loss. In malnourished patients, impaired ability to regenerate organic osmoles makes them vulnerable to this condition.
Etiology
After the first description of CPM in alcoholics, a number of other illnesses have been recognized where this condition is reported. It is most commonly seen in the setting of osmotic changes, typically during rapid correction of hyponatremia. Risk factors for the development of CPM in hyponatremic patients include serum sodium <120 mEq/L for more than 48 h, aggressive IV fluid therapy with hypertonic saline solutions, and development of hypernatremia during treatment. CPM can also occur in patients with hypophosphatemia.
Various conditions associated with CPM and EPM are given in Table 1 . Myelinolysis has also been reported in patients with inadequate secretion of antidiuretic hormone, adrenal insufficiency, Wilson’s disease, patients undergoing renal dialysis, eating disorders like anorexia and bulimia, severe liver disease and liver transplant, pancreatic encephalopathy, AIDS, lymphoma, systemic lupus erythematous, hematopoietic stem cell transplant patients, hyperemesis gravidarum, Marchiafava–Bignami disease, and hyperosmolar hyperglycemic state.
Table 1
Common Conditions Associated with CPM and/or EPM
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