EARLY LOSS OF NEOSTRIATAL STRIOSOME NEURONS IN HUNTINGTONS-DISEASE

During the first years of symptomatic Huntington's disease (HD), no re adily apparent pathology is seen in the neostriatum at autopsy. To inv estigate the pathological correlates of chorea and other early clinica l signs, we examined the evolution of neuronal loss and accompanying a strocytosis in neostriatal tissue from autopsy cases of early HD. We f ound scattered islands of astrocytosis and neuronal loss that were pre sent before the previously described ventrally progressive wave of gen eralized neuronal loss. Histological demonstration of these islands, w hich are apparently specific to HD, is very helpful in the pathologica l differential diagnosis of this disease. Immunocytochemical stains fo r glial fibrillary acidic protein and for markers of the neostriatal s triosome-matrix system showed that these islands correspond to the str iosome compartment. Striosomal neuronal loss was present throughout th e dorsoventral extent of the caudate nucleus and putamen during the ea rly phase of symptomatic disease, and this loss extended to the most v entral region of the nucleus accumbens in later stages. Analysis of th e functional circuitry of the basal ganglia suggests that early degene ration of striosomal neurons may produce hyperactivity of the nigrostr iatal dopaminergic pathway, causing chorea and other early clinical ma nifestations of HD.