Halliday Glenda M, Macdonald Virginia, Henderson Jasmine M
Prince of Wales Medical Research Institute and University of New South Wales, Sydney, Australia.
Brain. 2005 Oct;128(Pt 10):2272-80. doi: 10.1093/brain/awh596. Epub 2005 Jul 13.
Changes in motor cortical activation are associated with the major symptoms observed in both Parkinson's disease and progressive supranuclear palsy (PSP). While research has concentrated on basal ganglia abnormalities as central to these cortical changes, several studies in both disorders have shown pathology in the thalamus and motor cortices. In particular, we recently reported an 88% loss of corticocortical projection neurones in the pre-supplementary motor (pre-SMA) cortex in Parkinson's disease. Further analysis of the degree of neuronal loss and pathology in motor cortices and their thalamocortical relays in Parkinson's disease and PSP is warranted. Six cases with PSP, nine cases with Parkinson's disease and nine controls were selected from a prospectively studied brain donor cohort. alpha-Synuclein, ubiquitin and tau immunohistochemistry were used to identify pathological lesions. Unbiased stereological methods were used to analyse atrophy and neuronal loss in the motor thalamus [ventral anterior, ventrolateral anterior and ventrolateral posterior (VLp) nuclei] and motor cortices (primary motor, dorsolateral premotor and pre-SMA cortices). Analysis of variance and post hoc testing was used to determine differences between groups. In Parkinson's disease, the motor thalamus and motor cortices (apart from the pre-SMA) were preserved containing only rare alpha-synuclein-positive and ubiquitin-positive Lewy bodies. In contrast, patients with PSP had significant atrophy and neuronal loss in VLp (22 and 30%, respectively), pre-SMA (21 and 51%, respectively) and primary motor cortices (33 and 54%, respectively). In the primary motor cortex of PSP cases, neuronal loss was confined to inhibitory interneurones, whereas in the pre-SMA both interneurones (reduced by 26%) and corticocortical projection neurones (reduced by 82%) were affected. Tau-positive neurofibrillary and glial tangles were observed throughout the motor thalamus and motor cortices in PSP. These non-dopaminergic lesions in motor circuits are likely to contribute to the pathogenesis of both PSP and Parkinson's disease. The selective involvement of the VLp and primary motor cortex in PSP implicates these cerebellothalamocortical pathways as differentiating this disease, possibly contributing to the early falls.
运动皮质激活的变化与帕金森病和进行性核上性麻痹（PSP）中观察到的主要症状相关。虽然研究主要集中在基底神经节异常是这些皮质变化的核心，但这两种疾病的多项研究都显示丘脑和运动皮质存在病变。特别是，我们最近报告帕金森病患者的辅助运动前区（pre-SMA）皮质中皮质-皮质投射神经元损失了88%。有必要进一步分析帕金森病和PSP患者运动皮质及其丘脑-皮质投射中的神经元损失程度和病变情况。从一个前瞻性研究的脑捐赠者队列中选取了6例PSP患者、9例帕金森病患者和9例对照。采用α-突触核蛋白、泛素和tau免疫组化来识别病理病变。使用无偏倚的立体学方法分析运动丘脑[腹前核、腹外侧前核和腹外侧后核（VLp）]和运动皮质（初级运动皮质、背外侧运动前皮质和pre-SMA皮质）的萎缩和神经元损失。采用方差分析和事后检验来确定组间差异。在帕金森病中，运动丘脑和运动皮质（除pre-SMA外）得以保留，仅含有罕见的α-突触核蛋白阳性和泛素阳性路易小体。相比之下，PSP患者的VLp（分别为22%和30%）、pre-SMA（分别为21%和51%）和初级运动皮质（分别为33%和54%）出现了明显萎缩和神经元损失。在PSP病例的初级运动皮质中，神经元损失仅限于抑制性中间神经元，而在pre-SMA中，中间神经元（减少26%）和皮质-皮质投射神经元（减少82%）均受到影响。在PSP患者的整个运动丘脑和运动皮质中均观察到tau阳性神经原纤维缠结和胶质缠结。运动回路中的这些非多巴胺能病变可能在PSP和帕金森病的发病机制中起作用。PSP中VLp和初级运动皮质的选择性受累表明这些小脑-丘脑-皮质通路是区分该疾病的关键，可能是导致早期跌倒的原因。
