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特发性帕金森病患者纹状体中多巴胺丧失的不均匀模式。病理生理学及临床意义。

Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson's disease. Pathophysiologic and clinical implications.

作者信息

Kish S J, Shannak K, Hornykiewicz O

机构信息

Human Brain Laboratory, Clarke Institute of Psychiatry, Toronto, Ontario, Canada.

出版信息

N Engl J Med. 1988 Apr 7;318(14):876-80. doi: 10.1056/NEJM198804073181402.

DOI:10.1056/NEJM198804073181402
PMID:3352672
Abstract

Autografting of dopamine-producing adrenal medullary tissue to the striatal region of the brain is now being attempted in patients with Parkinson's disease. Since the success of this neurosurgical approach to dopamine-replacement therapy may depend on the selection of the most appropriate subregion of the striatum for implantation, we examined the pattern and degree of dopamine loss in striatum obtained at autopsy from eight patients with idiopathic Parkinson's disease. We found that in the putamen there was a nearly complete depletion of dopamine in all subdivisions, with the greatest reduction in the caudal portions (less than 1 percent of the dopamine remaining). In the caudate nucleus, the only subdivision with severe dopamine reduction was the most dorsal rostral part (4 percent of the dopamine remaining); the other subdivisions still had substantial levels of dopamine (up to approximately 40 percent of control levels). We propose that the motor deficits that are a constant and characteristic feature of idiopathic Parkinson's disease are for the most part a consequence of dopamine loss in the putamen, and that the dopamine-related caudate deficits (in "higher" cognitive functions) are, if present, less marked or restricted to discrete functions only. We conclude that the putamen--particularly its caudal portions--may be the most appropriate site for intrastriatal application of dopamine-producing autografts in patients with idiopathic Parkinson's disease.

摘要

目前正在对帕金森病患者尝试将产生多巴胺的肾上腺髓质组织自体移植到脑的纹状体区域。由于这种多巴胺替代疗法的神经外科手术方法的成功可能取决于选择最合适的纹状体亚区域进行植入,我们检查了8例特发性帕金森病患者尸检获得的纹状体中多巴胺丧失的模式和程度。我们发现,壳核的所有亚区域中多巴胺几乎完全耗竭,尾部部分减少最为明显(剩余多巴胺不到1%)。在尾状核中,多巴胺严重减少的唯一亚区域是最背侧的嘴侧部分(剩余多巴胺4%);其他亚区域仍有大量多巴胺(高达对照水平的约40%)。我们提出,特发性帕金森病持续且特征性的运动缺陷在很大程度上是壳核中多巴胺丧失的结果,而与多巴胺相关的尾状核缺陷(在“更高”认知功能方面)如果存在,则不太明显或仅局限于离散功能。我们得出结论,壳核——尤其是其尾部部分——可能是特发性帕金森病患者纹状体内应用产生多巴胺的自体移植物的最合适部位。

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