Sleep Research & Clinical Chronobiology, Institute of Physiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
Clinic for Sleep- & Chronomedicine, St. Hedwig-Krankenhaus, Berlin, Germany.
J Neurol Neurosurg Psychiatry. 2023 Jul;94(7):532-540. doi: 10.1136/jnnp-2022-330048. Epub 2023 Feb 1.
Isolated rapid eye movement (REM) sleep behaviour disorder (iRBD) is a prodromal state of clinical α-synucleinopathies such as Parkinson's disease and Lewy body dementia. The lead-time until conversion is unknown. The most reliable marker of progression is reduced striatal dopamine transporter (DAT) binding, but low availability of imaging facilities limits general use. Our prospective observational study aimed to relate metrics of REM sleep without atonia (RWA)-a hallmark of RBD-to DAT-binding ratios in a large, homogeneous sample of patients with RBD to explore the utility of RWA as a marker of progression in prodromal α-synucleinopathies.
DAT single-photon emission CT (SPECT) and video polysomnography (vPSG) were performed in 221 consecutive patients with clinically suspected RBD.
vPSG confirmed RBD in 176 patients (162 iRBD, 14 phenoconverted, 45 non-synucleinopathies). Specific DAT-binding ratios differed significantly between groups, but showed considerable overlap. Most RWA metrics correlated significantly with DAT-SPECT ratios (eg, Montreal tonic vs most-affected-region: r=-0.525; p<0.001). In patients taking serotonergic/noradrenergic antidepressants or dopaminergic substances or with recent alcohol abuse, correlations were weaker, suggesting a confounding influence, unlike other possible confounders such as beta-blocker use or comorbid sleep apnoea.
In this large single-centre prospective observational study, we found evidence that DAT-binding ratios in patients with iRBD can be used to describe a continuum in the neurodegenerative process. Overlap with non-synucleinopathies and clinical α-synucleinopathies, however, precludes the use of DAT-binding ratios as a precise diagnostic marker. The parallel course of RWA metrics and DAT-binding ratios suggests in addition to existing data that RWA, part of the routine diagnostic workup in these patients, may represent a marker of progression. Based on our findings, we suggest ranges of RWA values to estimate whether patients are in an early, medium or advanced state within the prodromal phase of α-synucleinopathies, providing them with important information about time until possible conversion.
孤立性快速眼动（REM）睡眠行为障碍（iRBD）是临床 α-突触核蛋白病（如帕金森病和路易体痴呆）的前驱状态。向临床疾病的转变时间尚不清楚。进展最可靠的标志物是纹状体多巴胺转运体（DAT）结合减少，但成像设备的可用性低限制了其广泛应用。我们的前瞻性观察性研究旨在将 REM 睡眠无张力（RWA）——RBD 的一个标志——与大量同质性 RBD 患者的 DAT 结合率相关联，以探索 RWA 作为前驱 α-突触核蛋白病进展标志物的效用。
对 221 例临床疑似 RBD 患者进行 DAT 单光子发射计算机断层扫描（SPECT）和视频多导睡眠图（vPSG）检查。
vPSG 证实 176 例患者存在 RBD（162 例 iRBD、14 例表型转化、45 例非突触核蛋白病）。各组间 DAT 结合率差异有统计学意义，但重叠较大。大多数 RWA 指标与 DAT-SPECT 比值有显著相关性（例如，蒙特利尔强直与最受影响区域：r=-0.525；p<0.001）。在服用 5-羟色胺能/去甲肾上腺素能抗抑郁药或多巴胺能物质或近期酗酒的患者中，相关性较弱，提示存在混杂影响，与其他可能的混杂因素（如β受体阻滞剂的使用或合并睡眠呼吸暂停）不同。
在这项大型单中心前瞻性观察性研究中，我们发现证据表明，iRBD 患者的 DAT 结合率可用于描述神经退行性过程中的连续变化。然而，与非突触核蛋白病和临床 α-突触核蛋白病的重叠，排除了 DAT 结合率作为精确诊断标志物的可能性。RWA 指标与 DAT 结合率的平行过程表明，除了现有数据外，RWA 可能代表进展的标志物，RWA 是这些患者常规诊断工作的一部分。基于我们的发现，我们建议 RWA 值的范围，以估计患者是否处于 α-突触核蛋白病前驱期的早期、中期或晚期，为患者提供有关可能转化时间的重要信息。
