Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, USA.
Mov Disord. 2018 May;33(5):827-834. doi: 10.1002/mds.27358. Epub 2018 Mar 6.
The etiology of cervical dystonia is unknown. Cholinergic abnormalities have been identified in dystonia animal models and human imaging studies. Some animal models have cholinergic neuronal loss in the striatum and increased acetylcholinesterase activity in the pedunculopontine nucleus.
The objective of this study was to determine the presence of cholinergic abnormalities in the putamen and pedunculopontine nucleus in cervical dystonia human brain donors.
Formalin-fixed brain tissues were obtained from 8 cervical dystonia and 7 age-matched control brains (controls). Pedunculopontine nucleus was available in only 6 cervical dystonia and 5 controls. Neurodegeneration was evaluated pathologically in the putamen, pedunculopontine nucleus, and other regions. Cholinergic neurons were detected using choline acetyltransferase immunohistochemistry in the putamen and pedunculopontine nucleus. Putaminal cholinergic neurons were quantified. A total of 6 cervical dystonia patients and 6 age-matched healthy controls underwent diffusion tensor imaging to determine if there were white matter microstructural abnormalities around the pedunculopontine nucleus.
Decreased or absent choline acetyltransferase staining was identified in all 6 pedunculopontine nucleus samples in cervical dystonia. In contrast, strong choline acetyltransferase staining was present in 4 of 5 pedunculopontine nucleus controls. There were no differences in pedunculopontine nucleus diffusion tensor imaging between cervical dystonia and healthy controls. There was no difference in numbers of putaminal cholinergic neurons between cervical dystonia and controls.
Our findings suggest that pedunculopontine nucleus choline acetyltransferase deficiency represents a functional cholinergic deficit in cervical dystonia. Structural lesions and confounding neurodegenerative processes were excluded by absence of neuronal loss, gliosis, diffusion tensor imaging abnormalities, and beta-amyloid, tau, and alpha-synuclein pathologies. © 2018 International Parkinson and Movement Disorder Society.
颈肌张力障碍的病因尚不清楚。在肌张力障碍动物模型和人类影像学研究中发现了胆碱能异常。一些动物模型的纹状体存在胆碱能神经元丢失，而脚桥核中乙酰胆碱酯酶活性增加。
本研究旨在确定颈肌张力障碍患者脑捐献者纹状体和脚桥核是否存在胆碱能异常。
从 8 例颈肌张力障碍患者和 7 例年龄匹配的对照者（对照组）的福尔马林固定脑组织中获得标本。仅在 6 例颈肌张力障碍患者和 5 例对照组中获得脚桥核标本。对纹状体、脚桥核和其他区域进行病理学评估神经退行性变。纹状体和脚桥核中使用胆碱乙酰转移酶免疫组化检测胆碱能神经元。定量纹状体中的胆碱能神经元。共有 6 例颈肌张力障碍患者和 6 例年龄匹配的健康对照者接受弥散张量成像，以确定脚桥核周围是否存在白质微观结构异常。
在所有 6 例颈肌张力障碍患者的脚桥核样本中均发现胆碱乙酰转移酶染色减少或缺失。相比之下，在 5 例对照组脚桥核中有 4 例显示出强烈的胆碱乙酰转移酶染色。颈肌张力障碍患者与健康对照组之间的脚桥核弥散张量成像无差异。颈肌张力障碍患者与对照组之间的纹状体胆碱能神经元数量无差异。
我们的研究结果表明，脚桥核胆碱乙酰转移酶缺乏代表颈肌张力障碍中的功能性胆碱能缺乏。通过不存在神经元丢失、神经胶质增生、弥散张量成像异常以及β-淀粉样蛋白、tau 和α-突触核蛋白病理学，排除了结构损伤和混杂的神经退行性过程。 © 2018 国际帕金森病和运动障碍协会。
