Pathology of the cerebellar dentate and interpositus nuclei in Joseph disease: a morphometric investigation.

Cerebellar dentate and interpositus nuclei pathology was studied morphometrically in 3 patients with Joseph disease compared to 3 control subjects. Size of neurons, number of small neurons (cell body area: 50-199 microns 2) and large neurons (cell body area: 200 microns 2 or greater) at the rostral, medial and caudal levels, neuronal cell density, total volume of the gray bands, and total neuronal cell number were evaluated in the dentate, emboliform, and globose nuclei, using an image analyzer, after making horizontal serial 20-microns thick sections of a unilateral cerebellar hemisphere embedded in celloidin. The number of large neurons in Joseph disease was around 20% of that in the controls at each level in the individual nucleus (P less than 0.05 or P less than 0.01). In contrast, the number of small neurons was significantly reduced only at the caudal level of the dentate nucleus (P less than 0.05). The neuronal cell density was decreased within the nuclei. The total volume of the gray bands was reduced to about 70% within the nuclei (P less than 0.05 or P less than 0.01). The total number of neurons was decreased to about a third, a half, and a third within the dentate (P less than 0.001), emboliform (P less than 0.01), and globose nuclei (P less than 0.001), respectively. The principal pathologic change of the dentate and interpositus nuclei in Joseph disease was severe loss of neurons, with significant loss of the large neurons, indicating that Joseph disease is a type of cerebellar efferent system disorder.