From Harvard Medical School (J.H., J.D.S.); Harvard T.H. Chan School of Public Health (J.H.), Boston, MA; Department of Neurology (A.M.B.), Columbia University Medical Center, New York, NY; Laboratory for Cognitive Neurobiology, Department of Anatomy and Neurobiology (F.M.), Boston University School of Medicine, MA; and Departments of Pathology (D.H.O., M.P.F.) and Ataxia Unit, Cognitive Behavioral Neurology Unit, Laboratory for Neuroanatomy and Cerebellar Neurobiology, Department of Neurology (J.D.H.), Massachusetts General Hospital, Boston.
Neurology. 2019 Aug 13;93(7):302-309. doi: 10.1212/WNL.0000000000007949.
To test the hypothesis that myoclonus in patients with multiple system atrophy with predominant cerebellar ataxia (MSA-C) is associated with a heavier burden of α-synuclein deposition in the motor regions of the spinal cord, we compared the degree of α-synuclein deposition in spinal cords of 3 patients with MSA-C with myoclonus and 3 without myoclonus.
All human tissue was obtained by the Massachusetts General Hospital Department of Pathology with support from and according to neuropathology guidelines of the Massachusetts Alzheimer's Disease Research Center. Tissue was stained with Luxol fast blue and hematoxylin & eosin for morphologic evaluation, and with a mouse monoclonal antibody to α-synuclein and Vectastain DAB kit. Images of the spinal cord sections were digitized using a 10× objective lens. Grayscale versions of these images were transferred to ImageJ software for quantitative analysis of 8 different regions of interest (ROIs) in the spinal cord: dorsal column, anterior white column, left and right dorsal horns, left and right anterior horns, and left and right lateral corticospinal tracts. A mixed-effect, multiple linear regression model was constructed to determine if patients with and without myoclonus had significantly different distributions of α-synuclein deposition across the various ROIs.
Patients with myoclonus had more α-synuclein in the anterior horns ( < 0.001) and lateral corticospinal tracts ( = 0.02) than those without myoclonus.
In MSA-C, myoclonus appears to be associated with a higher burden of α-synuclein deposition within spinal cord motor regions. Future studies with more patients will be needed to confirm these findings.
为了验证“多系统萎缩伴小脑性共济失调（MSA-C）患者的肌阵挛与脊髓运动区α-突触核蛋白沉积负担加重有关”这一假设，我们比较了 3 例有肌阵挛和 3 例无肌阵挛的 MSA-C 患者脊髓中α-突触核蛋白沉积程度。
所有人体组织均由马萨诸塞州综合医院病理学系获得，并得到马萨诸塞州阿尔茨海默病研究中心神经病理学指南的支持。组织用卢索快速蓝和苏木精和曙红进行形态学评估，并使用抗α-突触核蛋白的小鼠单克隆抗体和 Vectorstain DAB 试剂盒进行染色。使用 10×物镜对脊髓切片的图像进行数字化。将这些图像的灰度版本传输到 ImageJ 软件中，用于对脊髓的 8 个不同感兴趣区域（ROI）进行定量分析：背柱、前白柱、左右背角、左右前角以及左右外侧皮质脊髓束。构建混合效应、多元线性回归模型，以确定有无肌阵挛的患者在各 ROI 之间α-突触核蛋白沉积的分布是否存在显著差异。
有肌阵挛的患者在前角（<0.001）和外侧皮质脊髓束（=0.02）中α-突触核蛋白沉积较多。
在 MSA-C 中，肌阵挛似乎与脊髓运动区α-突触核蛋白沉积负担增加有关。需要更多患者的未来研究来证实这些发现。
