Cardinali Daniel P, Garay Arturo
CENECON, Faculty of Medical Sciences, University of Buenos Aires, Buenos Aires C1431FWO, Argentina.
Unidad de Medicina del Sueño-Sección Neurología, Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno" (CEMIC), Buenos Aires C1431FWO, Argentina.
Brain Sci. 2023 May 13;13(5):797. doi: 10.3390/brainsci13050797.
Dream-enactment behavior that emerges during episodes of rapid eye movement (REM) sleep without muscle atonia is a parasomnia known as REM sleep behavior disorder (RBD). RBD constitutes a prodromal marker of α-synucleinopathies and serves as one of the best biomarkers available to predict diseases such as Parkinson disease, multiple system atrophy and dementia with Lewy bodies. Most patients showing RBD will convert to an α-synucleinopathy about 10 years after diagnosis. The diagnostic advantage of RBD relies on the prolonged prodromal time, its predictive power and the absence of disease-related treatments that could act as confounders. Therefore, patients with RBD are candidates for neuroprotection trials that delay or prevent conversion to a pathology with abnormal α-synuclein metabolism. The administration of melatonin in doses exhibiting a chronobiotic/hypnotic effect (less than 10 mg daily) is commonly used as a first line treatment (together with clonazepam) of RBD. At a higher dose, melatonin may also be an effective cytoprotector to halt α-synucleinopathy progression. However, allometric conversion doses derived from animal studies (in the 100 mg/day range) are rarely employed clinically regardless of the demonstrated absence of toxicity of melatonin in phase 1 pharmacological studies with doses up to 100 mg in normal volunteers. This review discusses the application of melatonin in RBD: (a) as a symptomatic treatment in RBD; (b) as a possible disease-modifying treatment in α-synucleinopathies. To what degree melatonin has therapeutic efficacy in the prevention of α-synucleinopathies awaits further investigation, in particular multicenter double-blind trials.
在快速眼动（REM）睡眠期间出现的、无肌肉张力缺失的梦呓行为是一种被称为快速眼动睡眠行为障碍（RBD）的异态睡眠。RBD是α-突触核蛋白病的前驱标志物，也是预测帕金森病、多系统萎缩和路易体痴呆等疾病的最佳生物标志物之一。大多数表现出RBD的患者在诊断后约10年将转变为α-突触核蛋白病。RBD的诊断优势在于其前驱期较长、具有预测能力，且不存在可能成为混杂因素的疾病相关治疗。因此，RBD患者是神经保护试验的候选对象，这些试验旨在延缓或预防转变为具有异常α-突触核蛋白代谢的病理状态。给予具有生物钟调节/催眠作用剂量的褪黑素（每日小于10毫克）通常被用作RBD的一线治疗（与氯硝西泮联合使用）。在更高剂量下，褪黑素也可能是一种有效的细胞保护剂，可阻止α-突触核蛋白病的进展。然而，尽管在正常志愿者中进行的1期药理学研究表明，剂量高达100毫克的褪黑素无毒性，但源自动物研究的剂量换算剂量（在100毫克/天范围内）在临床上很少使用。这篇综述讨论了褪黑素在RBD中的应用：（a）作为RBD的对症治疗；（b）作为α-突触核蛋白病可能的疾病修饰治疗。褪黑素在预防α-突触核蛋白病方面具有多大的治疗效果有待进一步研究，特别是多中心双盲试验。
