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Prominent white matter cavitation in an infant with Alexander's disease
Insights
This case study details infantile Alexander's disease (AD), a rare neurological disorder. It highlights extreme brain cavitation as a key feature in this severe form of AD.
Area of Science:
- Neuropathology
- Pediatric Neurology
- Neurodegenerative Diseases
Background:
- Alexander's disease (AD) is a rare, progressive, often fatal, white matter disorder of the central nervous system.
- Infantile AD is characterized by early onset, severe neurological deficits, and distinctive neuropathological findings.
- Rosenthal fibers (RFs) are hallmarkPathognomonic inclusions in astrocytes.
Abstract:
The clinical history and autopsy findings are reported on a case of infantile Alexander's disease (AD). The patient, a white baby girl, developed 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). The brain was normal in weight for age but showed diffuse pallor of white matter and marked cavitation involving the cerebral and cerebellar subcortical white matter, most profound in the frontal lobes. Microscopically the CNS showed classic features of AD with diffuse paucity of myelin and massive proliferation of astrocytes bearing Rosenthal fibers (RF). The latter appeared as granular osmiophilic deposits associated with 8-10 nm filaments within astrocytic processes and cell bodies by EM. This case of AD is remarkable for the extreme degree of cavitation. Cavitary changes affect up to one third of typical cases of AD and are invariably present in the frontal white matter. Affected patients are generally much younger and have a shorter clinical course than AD patients without brain cavitation. The dysmyelination of AD inversely parallels the temporal sequence of normal myelination and suggests a relative resistance of early myelinated structures to the presumed astrocytic defect causing AD. Adults with de novo formation of RF's in the CNS have a varied clinical and pathological appearance, rarely show brain cavitation and should probably be distinguished from classic AD in children.