CLINICAL AND PATHOLOGICAL AND BIOCHEMICAL STUDIES OF THE MECHANISM UNDERLYING DYSKINESIA AND FROZEN GAIT - PATHHOPHYSIOLOGICAL STUDY USING AUTOPSIED BRAINS OF PARKINSONIAN PATIENTS IN ADVANCED STAGES

由于帕金森病持续时间长，治疗过程中遇到的问题，如运动反应波动、运动障碍和左旋多巴无反应症状，例如，僵硬的步态，痴呆症的发展虽然这些症状的病理生理学已经在一些动物实验的报告中描述，但帕金森病患者的病理生理学尚未阐明。在这项研究中，我们分析了帕金森病患者尸检大脑中的生化标志物，并将其活动或浓度与其临床症状相关联，以研究人类帕金森综合征的病理生理学。在这项研究中检查的生化标志物是酪氨酸羟化酶（TH）或多巴胺（DA）作为多巴胺能神经末梢的标志物，去甲肾上腺素（NE），GABA和谷氨酸（Glu）和神经肽（强啡肽）。测定上述物质活性或浓度的脑区为尾状核和丘脑底核、壳核、黑质、内苍白球、外苍白球、丘脑底核。所得数据与每个患者的临床数据相关，即运动障碍和磨损现象与纹状体TH活性和氨基酸及强啡肽水平相关，而冻结步态和痴呆与中脑核中DA和NE含量相关。冻结步态、痴呆和丘脑核中儿茶酚胺含量减少之间没有相关性。运动障碍和磨损现象往往与壳核中部和尾部TH活性的显着减少。结果表明，从壳核中部到尾部的多巴胺能神经末梢的显着减少是运动并发症发生的一个重要因素。

With the long duration of Parkinson's disease, and problems encountered during its therapy, such as motor response fluctuations, dyskinesia, and levodopa-unresponsive symptoms, e.g., frozen gait, dementia develops. Although the pathophysiology of these symptoms has been described in reports of several animal experiments, the pathophysiology in parkinsonian patients has not been clarified. In this study, we analyzed biochemical markers in autopsied brains of patients with Parkinson's disease and correlated their activities or concentrations with their clinical symptoms, in order to investigate the pathophysiology of parkinsonism in humans. The biochemical markers examined in this study were tyrosine hydroxylase (TH) or dopamine (DA) as a marker of dopaminergic nerve terminals, norepinephrine (NE), GABA and glutamate (Glu) and neuropeptide (dynorphin). The brain regions in which the activity or concentrations of the above-mentioned substances were measured were the caudate nucleus and nucleus accumbens, putamen, substantia nigra, pallidum interna, pallidum externa, subthalamic nucleus. The obtained data were correlated with the clinical data of each patient ; that is, dyskinesia and wearing-off phenomenon were correlated with TH activity and levels of amino acids and dynorphin in the striatum, and frozen gait and dementia were correlated with DA and NE contents in the nucleus accumbens. There is no correlation between frozen gait, dementia and reduction in catecholamine content in the nucleus accumbens. Dyskinesia and the wearing-off phenomenon tended to correlate with a marked reduction in TH activity in the middle and caudal parts of the putamen. Results indicate that a marked reduction in dopaminaergic nerve terminals from the middle to caudal part of the putamen was a significant factor in the development of motor complications.