The role of edema in diffuse sclerosis and other leukoencephalopathies

The pathologic changes associated with broad zones of demyelination of the cerebral white matter, the diffuse sclerosis group, are analyzed with respect to the contribution of cerebral edema to their pathogenesis. The characteristics of cerebral edema in general are reviewed, and the interpretation offered that only one type of cerebral edema, that characterized by an extracellular accumulation of fluid, occurs in man. In the diffuse sclerosis group, edema is most readily recognized by the tendency for the arcuate zone of the white matter to be spared when the deeper white matter is severely degenerated. Edema is demonstrated in metachromatic leukodystrophy, globoid cell leukodystrophy, adrenoleukodystrophy, disorders of amino acid metabolism, trauma, hypertensive disease, radiation effect, diffuse hypoxia with acidosis, and other conditions, i.e., both in disorders of myelin metabolism and in conditions in which normal myelin is injured by extrinsic influences. These groups cannot be consistently distinguished morphologically, in part because the injury by edema often obscures any primary morphologic change which may have been present. A familial tendency does not necessarily denote a metabolic abnormality specifically related to the chemistry of a myelin constituent, since the lesions might result from edema induced by some other type of familial process. Such familial processes might be metabolic, but are not specifically related to myelin formation or catabolism, as might be true of diseases like phenylketonuria or maple syrup urine disease. Edema may also occur in instances in which a familial disease induces diffuse hypoxia and acidosis, as exemplified by two instances of severe white matter degeneration in subacute necrotizing encephalomyelopathy; one of these is an additional instance of apparent "crib death" by this cause.