NeuroQAM Centre, Université du Québec à Montréal (UQAM), Canada; McConnell Brain Imaging Centre, Montreal Neurological Institute, Canada.
Centre for Advanced Research in Sleep Medicine, Hôpital du Sacré-Coeur de Montréal, Canada; Department of Neurology and Neurosurgery, McGill University, Canada.
Sleep Med. 2019 Jun;58:35-41. doi: 10.1016/j.sleep.2018.12.020. Epub 2019 Jan 6.
REM sleep behaviour disorder (RBD) occurs frequently in patients with synucleinopathies such as Parkinson's disease, dementia with Lewy body, or multiple system atrophy, but may also occur as a prodromal stage of those diseases; and is termed idiopathic RBD (iRBD) when not accompanied by other symptoms. Cholinergic degeneration of the mesopontine nuclei have been described in synucleinopathies with or without RBD, but this has not yet been explored in iRBD. We sought to assess cholinergic neuronal integrity in iRBD using PET neuroimaging with the F-fluoroethoxybenzovesamicol (FEOBV).
The sample included 10 participants evenly divided between healthy subjects and patients with iRBD. Polysomnography and PET imaging with FEOBV were performed in all participants. Standardized uptake value ratios (SUVRs) were compared between the two groups using voxel wise t-tests. Non-parametric correlations were also computed in patients with iRBD between FEOBV uptake and muscle tonic and phasic activity during REM sleep.
Compared with healthy participants, significantly higher FEOBV uptakes were observed in patients with iRBD. The largest differences were observed in specific brainstem areas corresponding to the bulbar reticular formation, pontine coeruleus/subcoeruleus complex, tegmental periacqueductal grey, and mesopontine cholinergic nuclei. FEOBV uptake in iRBD was also higher than in controls in the ventromedial area of the thalamus, deep cerebellar nuclei, and some cortical territories (including the paracentral lobule, anterior cingulate, and orbitofrontal cortex). Significant correlation was found between muscle activity during REM sleep, and SUVR increases in both the mesopontine area and paracentral cortex.
We showed here for the first time the brain cholinergic alterations in patients with iRBD. As opposed to the cholinergic depletion described previously in RBD associated with clinical Parkinson's disease, increased cholinergic innervation was found in multiple areas in iRBD. The most significant changes were observed in brainstem areas containing structures involved in the promotion of REM sleep and muscle atonia. This suggests that iRBD might be a clinical condition in which compensatory cholinergic upregulation in those areas occurs in association with the initial phases of a neurodegenerative process leading to a clinically observable synucleinopathy.
快速眼动睡眠行为障碍（RBD）常发生于帕金森病、路易体痴呆或多系统萎缩等突触核蛋白病患者中，但也可能作为这些疾病的前驱期出现；当不伴有其他症状时，被称为特发性 RBD（iRBD）。突触核蛋白病患者的中脑导水管周围灰质胆碱能变性已被描述，无论是否伴有 RBD，但在 iRBD 中尚未得到探索。我们试图使用 F-氟乙氧基苯并昔维莫尔（FEOBV）正电子发射断层扫描（PET）神经影像学评估 iRBD 中的胆碱能神经元完整性。
该样本包括 10 名参与者，平均分为健康对照组和 iRBD 患者组。所有参与者均进行了多导睡眠图和 FEOBV PET 成像。使用体素-wise t 检验比较两组之间的标准化摄取值比值（SUVR）。还对 iRBD 患者进行了非参数相关性分析，分析 FEOBV 摄取与 REM 睡眠期间肌肉紧张和相位活动之间的相关性。
与健康参与者相比，iRBD 患者的 FEOBV 摄取明显更高。最大的差异出现在与延髓网状结构、脑桥蓝斑/蓝斑下复合体、中脑导水管周围灰质和中脑胆碱能核相对应的特定脑干区域。iRBD 患者的 FEOBV 摄取也高于对照组的丘脑腹内侧区、小脑深部核团和一些皮质区域（包括旁中央小叶、前扣带回和眶额皮质）。在 REM 睡眠期间肌肉活动与中脑区域和旁中央皮质 SUVR 增加之间发现了显著相关性。
我们首次在 iRBD 患者中显示了脑内胆碱能改变。与先前在与临床帕金森病相关的 RBD 中描述的胆碱能耗竭相反，在 iRBD 中发现了多个区域的胆碱能传入增加。最显著的变化发生在包含与 REM 睡眠和肌肉弛缓相关的结构的脑干区域。这表明 iRBD 可能是一种临床情况，其中这些区域的胆碱能代偿性上调与导致临床可观察到的突触核蛋白病的神经退行性过程的初始阶段相关。
