Dendritic and axonal spherules in the neocortex of a patient with Creutzfeldt-Jakob disease (CJD): Golgi and electron-microscopical investigation--neurobiological significance.

Vacuolization is a pathognomonic change occurring in Creutzfeldt-Jakob disease (CJD) and in other spongiform encephalopathies. The spongiform status takes place within nerve and glial cells. Its mechanism of formation is unknown. This paper concentrates on a possible sequence of morphological changes that culminate with empty and dilated neurites. A biopsy was taken from the right frontal cortex of a 44-year-old man, who had a brief history of dementia and myoclonus. An EEG showed periodical discharges and the routine histological stains showed changes compatible with CJD, including prominent vacuolization. Some fragments of tissue were impregnated with the rapid-Golgi method, and some others were processed for transmission electron microscopy (TEM). In the Golgi stained material, many of the impregnated neurons showed fewer dendrites and loss of spines, and the dendritic processes appeared smaller in diameter. Frequently the silhouette of nerve-cell bodies was distorted; irregular surfaces and lumpinesses had replaced the otherwise smooth contour of many granule and pyramidal cells. In addition, spherical axonal and dendritic dilations were found. These globular dilations were seen in primary and secondary dendrites, mainly from pyramidal cells. They were not present in all the impregnated cells, showed a stochastic distribution, and appeared to proportionally reach a larger diameter in axons. The light-microscopic changes are correlated with those obtained with the TEM, and a morphological classification of affected neurites is used to postulate a hypothetical centrifugal emptying process, which is proposed as the putative mechanism for the production of these spherules. The possible neurobiological significance of these spherules is discussed.