Hedreen J C, Folstein S E
Department of Psychiatry, New England Medical Center, Boston, MA 02111.
J Neuropathol Exp Neurol. 1995 Jan;54(1):105-20. doi: 10.1097/00005072-199501000-00013.
During the first years of symptomatic Huntington's disease (HD), no readily apparent pathology is seen in the neostriatum at autopsy. To investigate the pathological correlates of chorea and other early clinical signs, we examined the evolution of neuronal loss and accompanying astrocytosis in neostriatal tissue from autopsy cases of early HD. We found scattered islands of astrocytosis and neuronal loss that were present before the previously described ventrally progressive wave of generalized neuronal loss. Histological demonstration of these islands, which are apparently specific to HD, is very helpful in the pathological differential diagnosis of this disease. Immunocytochemical stains for glial fibrillary acidic protein and for markers of the neostriatal striosome-matrix system showed that these islands correspond to the striosome compartment. Striosomal neuronal loss was present throughout the dorsoventral extent of the caudate nucleus and putamen during the early phase of symptomatic disease, and this loss extended to the most ventral region of the nucleus accumbens in later stages. Analysis of the functional circuitry of the basal ganglia suggests that early degeneration of striosomal neurons may produce hyperactivity of the nigrostriatal dopaminergic pathway, causing chorea and other early clinical manifestations of HD.
在症状性亨廷顿舞蹈病（HD）的最初几年里，尸检时在新纹状体中未发现明显的病理学改变。为了研究舞蹈症及其他早期临床症状的病理相关性，我们检查了早期HD尸检病例新纹状体组织中神经元丢失及伴随的星形胶质细胞增生的演变情况。我们发现，在先前描述的全身性神经元丢失的腹侧进展波之前，就已存在散在的星形胶质细胞增生岛和神经元丢失区域。这些明显为HD所特有的岛状区域的组织学证明，对该疾病的病理鉴别诊断非常有帮助。对胶质纤维酸性蛋白以及新纹状体纹状体小体-基质系统标志物的免疫细胞化学染色显示，这些岛状区域对应于纹状体小体部分。在症状性疾病的早期阶段，整个尾状核和壳核的背腹范围内均存在纹状体小体神经元丢失，且在后期这种丢失扩展到伏隔核的最腹侧区域。对基底神经节功能回路的分析表明，纹状体小体神经元的早期变性可能导致黑质纹状体多巴胺能通路的活动亢进，从而引起HD的舞蹈症及其他早期临床表现。
