School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
Forefront Parkinson's Disease Research Clinic, Brain and Mind Centre, University of Sydney, Sydney, Australia.
Neurotherapeutics. 2021 Jan;18(1):107-123. doi: 10.1007/s13311-020-00983-7. Epub 2021 Jan 6.
Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by dream enactment and the loss of muscle atonia during REM sleep, known as REM sleep without atonia (RSWA). RBD can result in significant injuries, prompting patients to seek medical attention. However, in others, it may present only as non-violent behaviors noted as an incidental finding during polysomnography (PSG). RBD typically occurs in the context of synuclein-based neurodegenerative disorders but can also be seen accompanying brain lesions and be exacerbated by medications, particularly antidepressants. There is also an increasing appreciation regarding isolated or idiopathic RBD (iRBD). Symptomatic treatment of RBD is a priority to prevent injurious complications, with usual choices being melatonin or clonazepam. The discovery that iRBD represents a prodromal stage of incurable synucleinopathies has galvanized the research community into delineating the pathophysiology of RBD and defining biomarkers of neurodegeneration that will facilitate future disease-modifying trials in iRBD. Despite many advances, there has been no progress in available symptomatic or neuroprotective therapies for RBD, with recent negative trials highlighting several challenges that need to be addressed to prepare for definitive therapeutic trials for patients with this disorder. These challenges relate to i) the diagnostic and screening strategies applied to RBD, ii) the limited evidence base for symptomatic therapies, (iii) the existence of possible subtypes of RBD, (iv) the relevance of triggering medications, (v) the absence of objective markers of severity, (vi) the optimal design of disease-modifying trials, and vii) the implications around disclosing the risk of future neurodegeneration in otherwise healthy individuals. Here, we review the current concepts in the therapeutics of RBD as it relates to the above challenges and identify pertinent research questions to be addressed by future work.
快速眼动（REM）睡眠行为障碍（RBD）的特征是在 REM 睡眠期间出现梦境行为和肌肉弛缓丧失，称为 REM 睡眠无弛缓（RSWA）。RBD 可导致严重损伤，促使患者寻求医疗关注。然而，在其他情况下，它可能仅表现为非暴力行为，在多导睡眠图（PSG）检查中被偶然发现。RBD 通常发生在基于突触核蛋白的神经退行性疾病的背景下，但也可能伴随脑损伤，并因药物，特别是抗抑郁药而加重。对于孤立或特发性 RBD（iRBD）也有越来越多的认识。RBD 的症状治疗是预防损伤性并发症的首要任务，通常的选择是褪黑素或氯硝西泮。发现 iRBD 代表不可治愈的突触核蛋白病的前驱阶段，这激发了研究界阐明 RBD 的病理生理学，并定义神经退行性变的生物标志物，这将有助于未来在 iRBD 中进行疾病修饰试验。尽管取得了许多进展，但 RBD 的现有症状或神经保护治疗仍没有进展，最近的阴性试验强调了需要解决的几个挑战，以为该疾病患者的确定性治疗试验做好准备。这些挑战涉及：i）应用于 RBD 的诊断和筛选策略，ii）症状治疗的有限证据基础，iii）RBD 可能存在亚型，iv）触发药物的相关性，v）缺乏严重程度的客观标志物，vi）疾病修饰试验的最佳设计，以及 vii）在其他健康个体中揭示未来神经退行性变风险的含义。在这里，我们回顾了与上述挑战相关的 RBD 治疗的当前概念，并确定了未来工作需要解决的相关研究问题。
