One is compelled to define this disease in terms of its pathologic anatomy because this stands as its most characteristic feature, but it has been appreciated that the pons is not the only structure that may be affected. Transverse sectioning of the fixed brainstem discloses a grayish discoloration and fine granularity in the center of the base of the pons. The lesion may be only a few millimeters in diameter, or it may occupy almost the entire ventral pons. There is always a rim of intact myelin between the lesion and the surface of the pons. Posteriorly, it may reach and involve the medial lemnisci and, in the most advanced cases, other tegmental structures as well. Rarely, the lesion encroaches on the midbrain but it does not extend as far as the medulla. Identical extrapontine myelinolytic foci in the internal capsule, deep cerebral white matter and corpus callosum may occur independently (“extrapontine myelinolysis”). Exceptionally, symmetrically distributed lesions are found in the thalamus, subthalamic nucleus, striatum, amygdaloid nuclei, lateral geniculate body, white matter of the cerebellar folia (Wright et al).
Microscopically, the fundamental abnormality consists of destruction of the myelinated sheaths throughout the lesion, with relative sparing of the axons and intactness of the nerve cells of the pontine nuclei. These changes always begin and are most severe in the geometric center of the pons, where they may proceed to frank necrosis of tissue. Reactive phagocytes and glia cells are in evidence throughout the demyelinative focus, but oligodendrocytes are depleted. Signs of inflammation are conspicuously absent.
This constellation of pathologic findings provides easy differentiation of the lesion from infarction and the inflammatory demyelination of multiple sclerosis and postinfectious encephalomyelitis. Microscopically, the lesion resembles that of Marchiafava-Bignami disease (Chap. 40), with which CPM is rarely associated. In the chronic alcoholic, Wernicke disease is often associated with osmotic demyelination, but the lesions bear no resemblance to one another in terms of topography and histology.
More than half the cases have appeared in the late stages of chronic alcoholism, often in association with Wernicke disease and polyneuropathy. Most cases occur in the context of other serious medical conditions, and diseases with which osmotic demyelination has been conjoined are chronic renal failure being treated with dialysis, hepatic failure, advanced lymphoma, cancer, cachexia from a variety of other causes, severe bacterial infections, dehydration and electrolyte disturbances, acute hemorrhagic pancreatitis, and pellagra. The changes in serum sodium concentration, with which the process is closely aligned, are discussed below. The 2 sexes are affected equally, and the patients do not fall into any one age period. Whereas the cases first reported had occurred in adults, there are now many reports of the disease in children, particularly in those with severe burns (McKee et al).