PROMINENT WHITE-MATTER CAVITATION IN AN INFANT WITH ALEXANDERS-DISEASE

The clinical history and autopsy findings are reported on a case of in fantile Alexander's disease (AD). The patient, a white baby girl, deve loped seizures at age 4 months accompanied by internal hydrocephalus. She died at age 11 months following a progressive, downhill course of profound psychomotor retardation, recurrent seizures and cachexia. The general autopsy was remarkable for cachexia. The formalin fixed brain and spinal cord were studied by light and electron microscopy (EM). T he brain was normal in weight for age but showed diffuse pallor of whi te matter and marked cavitation involving the cerebral and cerebellar subcortical white matter, most profound in the frontal lobes. Microsco pically the CNS showed classic features of AD with diffuse paucity of myelin and mas sive proliferation of astrocytes bearing Rosenthal fibe rs (RF). The latter appeared as granular osmiophilic deposits associat ed with 8-10 nm filaments within astrocytic processes and cell bodies by EM. This case of AD is remarkable for the extreme degree of cavitat ion. Cavitary changes affect up to one third of typical cases of AD an d are invariably present in the frontal white matter. Affected patient s are generally much younger and have a shorter clinical course than A D patients without brain cavitation. The dysmyelination of AD inversel y parallels the temporal sequence of normal myelination and suggests a relative resistance of early myelinated structures to the presumed as trocytic defect causing AD. Adults with de novo formation of RF's in t he CNS have a varied clinical and pathological appearance, rarely show brain cavitation and should probably be distinguished from classic AD in children.