Queen Square Brain Bank for Neurological Disorders, University College London (UCL) Institute of Neurology, London, United Kingdom.
The Reta Lila Weston Institute of Neurological Studies, University College London (UCL) Institute of Neurology, London, United Kingdom.
JAMA Neurol. 2018 Aug 1;75(8):1008-1012. doi: 10.1001/jamaneurol.2018.0640.
Circadian dysfunction may be associated with the symptoms and neurodegeneration in Parkinson disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP), although the underlying neuroanatomical site of disruption and pathophysiological mechanisms are not fully understood.
To perform a neuropathological analysis of disease-specific inclusions in the key structures of the circadian system in patients with PD, MSA, and PSP.
DESIGN, SETTING, AND PARTICIPANTS: This investigation was a brain bank case-control study assessing neuropathological inclusions in the suprachiasmatic nucleus (SCN) of the hypothalamus and pineal gland in healthy controls, PD (Lewy pathology), MSA (glial cytoplasmic inclusions), and PSP (tau inclusions). The study analyzed 12 healthy control, 28 PD, 11 MSA, and 21 PSP samples from consecutive brain donations (July 1, 2010, to June 30, 2016) to the Queen Square Brain Bank for Neurological Disorders and the Parkinson's UK Brain Bank, London, United Kingdom. Cases were excluded if neither SCN nor pineal tissue was available.
Disease-specific neuropathological changes were graded using a standard semiquantitative scoring system (absent, mild, moderate, severe, or very severe) and compared between groups.
Because of limited tissue availability, the following total samples were examined in a semiquantitative histologic analysis: 5 SCNs and 7 pineal glands in the control group (6 male; median age at death, 83.8 years; interquartile range [IQR], 78.2-88.0 years), 13 SCNs and 17 pineal glands in the PD group (22 male; median age at death, 78.8 years; IQR, 75.5-83.8 years), 5 SCNs and 6 pineal glands in the MSA group (7 male; median age at death, 69.5 years; IQR, 61.6-77.7 years), and 5 SCNs and 19 pineal glands in the PSP group (13 male; median age at death, 74.3 years; IQR, 69.7-81.1 years). No neuropathological changes were found in either the SCN or pineal gland in healthy controls or MSA cases. Nine PD cases had Lewy pathology in the SCN, and only 2 PD cases had Lewy pathology in the pineal gland. All PSP cases showed inclusions in the SCN, but no PSP cases had pathology in the pineal gland.
Disease-related neuropathological changes were found in the SCN but not in the pineal gland in PD and PSP, while both structures were preserved in MSA, reflecting different pathophysiological mechanisms that may have important therapeutic implications.
昼夜节律功能障碍可能与帕金森病（PD）、多系统萎缩（MSA）和进行性核上性麻痹（PSP）的症状和神经退行性变有关，但破坏的潜在神经解剖部位和病理生理机制尚不完全清楚。
对 PD、MSA 和 PSP 患者昼夜节律系统关键结构中的疾病特异性包涵体进行神经病理学分析。
设计、地点和参与者：这是一项脑库病例对照研究，评估了健康对照者（Lewy 病理学）、MSA（细胞质包涵体）和 PSP（tau 包涵体）的下丘脑视交叉上核（SCN）和松果体的神经病理学包涵体。该研究分析了来自英国伦敦皇后广场神经疾病脑库和帕金森英国脑库的 12 名健康对照者、28 名 PD、11 名 MSA 和 21 名 PSP 连续脑捐献者（2010 年 7 月 1 日至 2016 年 6 月 30 日）的样本。如果 SCN 或松果体组织不可用，则排除病例。
使用标准半定量评分系统（无、轻度、中度、重度或重度）对疾病特异性神经病理学变化进行分级，并在组间进行比较。
由于组织有限，在半定量组织学分析中检查了以下总样本：对照组 5 个 SCN 和 7 个松果体（6 名男性；死亡时的中位年龄为 83.8 岁；四分位距 [IQR]，78.2-88.0 岁），PD 组 13 个 SCN 和 17 个松果体（22 名男性；死亡时的中位年龄为 78.8 岁；IQR，75.5-83.8 岁），MSA 组 5 个 SCN 和 6 个松果体（7 名男性；死亡时的中位年龄为 69.5 岁；IQR，61.6-77.7 岁），PSP 组 5 个 SCN 和 19 个松果体（13 名男性；死亡时的中位年龄为 74.3 岁；IQR，69.7-81.1 岁）。健康对照组或 MSA 病例的 SCN 或松果体均未发现神经病理学变化。9 例 PD 患者的 SCN 有 Lewy 病理学，只有 2 例 PD 患者的松果体有 Lewy 病理学。所有 PSP 病例的 SCN 均有包涵体，但没有 PSP 病例的松果体有病理学改变。
PD 和 PSP 患者的 SCN 中存在与疾病相关的神经病理学变化，但松果体中不存在，而 MSA 中两种结构均保留，反映了不同的病理生理机制，这可能具有重要的治疗意义。
