Joseph Disease with Severe Atrophy of the Brain Stem Tegmentum: Report of an Autopsied Case

Abstract

An autopsied case of Joseph disease with severe atrophy of the brain stem tegmentum is reported. A Japanese male noticed unsteady gait at age 30 and showed cerebellar ataxia, pyramidal signs, progressive external ophthalmoplegia, peripheral amyotrophy, sensory disturbance, and bradykinesia. He also developed mild dementia and nocturnal delirium at the terminal stage of his illness. His mother, older and younger brothers and daughter also presented progressive ataxia. The mode of inheritance is considered to be autosomal deminant. He died of cardiac failure at age 57. The autopsy revealed significant atrophy of the brain stem and spinal cord. Microscopic examination showed severe degeneration of the dentato‐rubral and subthalamo‐pallidal systems, pontine nuclei, spinal anterior horn, Clarke's column, accessory cuneate nucleus and spinocerebellar tract, moderate degeneration of the brain stem motor nuclei including the oculomotor nuclei and substantia nigra, and mild degeneration of the spinal posterior and intermediolateral column, and cerebellar cortex. An additional finding, which has received little attention in this disease, was severe atrophy of the brain stem tegmentum associated with degeneration of the reticular formation, raphe nuclei and locus ceruleus. The significance of brain stem tegmental atrophy in Joseph disease is discussed.