CLINICAL AND PATHOLOGICAL FEATURES OF AN AUTOSOMAL-DOMINANT, ADULT-ONSET LEUKODYSTROPHY SIMULATING CHRONIC PROGRESSIVE MULTIPLE-SCLEROSIS

Objective: To study the clinical and pathological features of a kindre d with an adult-onset autosomal dominant leukodystrophy. Patients: Fiv e symptomatic and nine asymptomatic at-risk members of the kindred. In terventions: Subjects underwent detailed histories and general and neu rologic examinations. Further evaluation included electroencephalograp hy, evoked potentials, electromyography, autonomic testing, and analys is of serum, urine, and cerebrospinal fluid. One patient underwent sur al nerve biopsy and analysis. Another, previously studied patient, und erwent a limited autopsy. Results: Cerebellar and pyramidal dysfunctio n began in the fourth and fifth decades of life; subtle autonomic symp -toms were often present years earlier. Frontal lobe dysfunction and a bnormalities of the central visual pathways were mild and of late onse t. Sensorineural hearing loss was common. The peripheral nervous syste m was spared. Autopsy results of one patient revealed severe degenerat ion of the white matter at all levels of the neuraxis, but most promin ent in the frontoparietal and cerebellar regions, with sparing of the subcortical U fibers. Histological and ultrastructural examinations fa iled to show evidence of a specific pathogenetic mechanism or etiology . Conclusion: This disorder seems to be a distinct type of hereditary leukodystrophy, but its exact nature remains unknown.