Department of Biomedical and Neuromotor Sciences, University of Bologna, Piazza di Porta San Donato 2, 40126, Bologna, Italy.
Clin Auton Res. 2018 Dec;28(6):545-555. doi: 10.1007/s10286-017-0473-z. Epub 2017 Oct 10.
Narcolepsy is a rare disease that entails excessive daytime sleepiness, often associated with sudden episodes of muscle weakness known as cataplexy. Narcolepsy with cataplexy (NC) is due to the loss of hypothalamic neurons that release the neuropeptides orexin A and B. Orexin neuron projections prominently target brain structures involved in wake-sleep state switching and the central autonomic network. This review provides an updated summary of the links between NC and autonomic cardiovascular dysfunction from a translational perspective. The available evidence suggests that, compared with control subjects, the heart rate in patients and animal models with NC is variable during wakefulness and normal to high during sleep. Responses of the heart rate to internal stimuli (arousal from sleep, leg movements during sleep, defense response) are blunted. These alterations result from orexin deficiency and, at least during wakefulness before sleep, involve decreased parasympathetic modulation of the heart rate. On the other hand, NC in patients and animal models is associated with a blunted fall in arterial blood pressure from wakefulness to sleep, and particularly to the REM state, coupled to a variable decrease in arterial blood pressure during wakefulness. The former effect is caused, at least in part, by deranged control of the heart, whereas the latter may be due to decreased vasoconstrictor sympathetic activity. Systematic studies are warranted to help clarify whether and how the links between NC and autonomic dysfunction impact on the cardiovascular risk of patients with narcolepsy.
发作性睡病是一种罕见的疾病,其特征是白天过度嗜睡,常伴有突发性肌肉无力,即猝倒。猝倒型发作性睡病(NC)是由于下丘脑神经元释放神经肽食欲素 A 和 B 的丧失所致。食欲素神经元的投射主要靶向与觉醒-睡眠状态转换和中枢自主神经网络相关的脑结构。从转化医学的角度来看,本综述提供了 NC 与自主心血管功能障碍之间关联的最新综述。现有证据表明,与对照组相比,NC 患者和动物模型的心率在清醒时变化不定,而在睡眠时正常或偏高。心率对内部刺激(从睡眠中觉醒、睡眠时腿部运动、防御反应)的反应迟钝。这些改变是由食欲素缺乏引起的,至少在睡眠前的清醒状态下,涉及心率的副交感神经调节减少。另一方面,NC 患者和动物模型与从清醒到睡眠,特别是到 REM 状态时的动脉血压下降减弱有关,同时清醒时的动脉血压也呈多变性下降。前者的影响至少部分是由于心脏控制失调所致,而后者可能是由于血管收缩性交感神经活动减少所致。有必要进行系统研究,以帮助阐明 NC 和自主功能障碍之间的联系是否以及如何影响发作性睡病患者的心血管风险。