The progression of pathology in longitudinally followed patients with Parkinson's disease
The progression of pathology in longitudinally followed patients with Parkinson's disease
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DOI：
10.1007/s00401-008-0344-8
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发表时间：
2008-04-01
影响因子：
12.7
通讯作者：
Morris, John
中科院分区：
文献类型：
--
作者：
Halliday, Glenda;Hely, Mariese;Morris, John
本研究描述了左旋多巴反应性帕金森病纵向随访病例的病理进展，这些病例在悉尼帕金森病多中心研究期间进行了尸检。标准化的临床和神经病理评估在五个时期验证了三个不同的临床病理组。一组发病较年轻的帕金森病患者，具有典型的长期临床病程。这组病例的路易体分布与疾病的布拉克分期一致。在这一组中，活到5岁的以脑干路易体为主；到13岁时，50%的病例出现路易体边缘分布；到18岁时，所有人至少都会有这种病理表型。大约25%的病例有早期恶性、痴呆显性综合征和与路易体痴呆一致的严重新皮质疾病。最后一组患者发病年龄更大，生存期更短，病程更复杂，路易体负荷更高，伴有额外神经病变的比例更高。这些路易体负荷较高而存活时间较短的病例表明，广泛的路易体病理要么发生在临床发病时，要么迅速浸润到大脑。在这些存活时间较短的病例中，有更多的斑块病理，支持更具侵略性和相关性的表型。我们的数据表明，仅通过病理学选择相似的研究队列将无法区分所确定的三种不同的表型。这些数据也不符合路易体病发病机制的单一概念。
The present study describes the pathological progression of longitudinally followed cases with levodopa-responsive Parkinson's disease who came to autopsy during the Sydney Multicenter Study of Parkinson's disease. Standardised clinical and neuropathological assessments over five epochs of time verified three different clinicopathological groups. A group of younger onset patients with a typical long duration clinical course of Parkinson's disease. This group of cases had Lewy body distributions consistent with the Braak staging of disease. In this group, brainstem Lewy bodies dominate in those surviving to 5 years; by 13 years, 50% of cases have a limbic distribution of Lewy bodies; and by 18 years, all will have at least this pathological phenotype. Approximately 25% of cases had an early malignant, dementia-dominant syndrome and severe neocortical disease consistent with dementia with Lewy bodies. The last group had an older onset, shorter survival, and a more complex disease course with higher Lewy body loads and a higher proportion with additional neuropathologies. These cases with higher loads of Lewy bodies and shorter survivals suggest that widespread Lewy body pathology either occurs at the onset of clinical disease or rapidly infiltrates the brain. In these cases with shorter survivals, there was more plaque pathology, supporting a more aggressive and linked phenotype. Our data suggest that the selection of similar study cohorts by pathology alone would not be able to differentiate the three different phenotypes identified. The data are also not consistent with a unitary concept of the pathogenesis of Lewy body disease.