Department of Developmental Neurology and Psychiatry, Centre for Pediatric Sleep Disorders, Sapienza University, Via dei Sabelli 108, Rome, Italy.
Curr Opin Pulm Med. 2010 Nov;16(6):568-73. doi: 10.1097/MCP.0b013e32833ef547.
Although several studies in the last years have evaluated obesity, obstructive sleep apnea (OSAS), and excessive daytime sleepiness (EDS) in patients with Prader-Willi syndrome (PWS), their pathophysiologies and interactions and the role of treatment with growth hormone are not completely understood. The present review analyzes the contributing role of obesity, OSAS, and sleep structure abnormalities in determining the EDS and the role of specific treatment in improving the clinical outcome.
The studies on sleep structure of PWS patients show abnormalities of rapid eye movement (REM) sleep and a decrease in non-REM sleep instability, corroborating the hypothesis of the presence of a primary disorder of vigilance and the similarities with narcolepsy. These sleep alterations might also be linked to the action of mediators of inflammation (i.e. adiponectin or cytokines) determined by obesity. Obesity and hypothalamic dysfunction could be responsible for the primary abnormalities of ventilation during sleep that, in turn, might contribute to EDS. Although EDS seems to resemble narcolepsy, PWS patients do not present the other typical symptoms of narcolepsy.
The most consistent hypothesis for linking the three different symptoms of PWS is a primary central hypothalamic dysfunction. Further research is needed to evaluate the contribution of the upper airway resistance syndrome in the pathogenesis of EDS, the role of the alterations of sleep microstructure, the relationships between PWS and narcoleptic phenotype, the involvement of orexin/hypocretin, and the effects of drugs acting on REM sleep and/or wakefulness.
尽管近年来有几项研究评估了肥胖症、阻塞性睡眠呼吸暂停（OSAS）和 Prader-Willi 综合征（PWS）患者的日间嗜睡（EDS），但其病理生理学及其相互作用以及生长激素治疗的作用尚不完全清楚。本综述分析了肥胖症、OSAS 和睡眠结构异常在确定 EDS 中的作用，以及特定治疗改善临床结局的作用。
对 PWS 患者睡眠结构的研究表明，快速眼动（REM）睡眠异常和非快速眼动睡眠不稳定性下降，这与警觉存在原发性障碍的假说以及与嗜睡症的相似性相吻合。这些睡眠改变也可能与肥胖症引起的炎症介质（如脂联素或细胞因子）有关。肥胖症和下丘脑功能障碍可能是导致睡眠期间通气原发性异常的原因，而通气异常反过来可能导致 EDS。尽管 EDS 似乎类似于嗜睡症，但 PWS 患者不表现出嗜睡症的其他典型症状。
将 PWS 的三种不同症状联系起来的最一致假设是原发性中枢下丘脑功能障碍。需要进一步研究来评估上气道阻力综合征在 EDS 发病机制中的作用、睡眠微结构改变的作用、PWS 与嗜睡表型的关系、食欲素/下丘脑分泌素的参与，以及作用于 REM 睡眠和/或觉醒的药物的影响。
