Guy's, King's & St Thomas' School of Medicine, King's College, London, UK.
Expert Rev Neurother. 2010 Jun;10(6):879-84. doi: 10.1586/ern.10.56.
Non-motor symptoms in Parkinson's disease (PD), such as excessive daytime sleepiness, 'sleep attacks', insomnia, restless legs syndrome and rapid eye movement sleep behavior disorder, are common and provide a challenge to treatment. These sleep symptoms are also described in patients suffering from the sleep/wake disorder, narcolepsy. The International Classification of Sleep Disorders (ICSD-2) narcolepsy criteria uses a number of markers for diagnosis, of which lack or deficiency of cerebrospinal fluid (CSF) hypocretin-1 levels is a key marker. Hypocretin neurons prominently located in the lateral hypothalamus and perifornical nucleus have been proposed to interact with mechanisms involving sleep and arousal. Low hypocretin-1 levels in the CSF have been shown to correlate with hypothalamic hypocretin cell loss in narcolepsy and other forms of hypersomnia; therefore, it has been proposed that degenerative damage to hypocretin neurons (such as in PD) may be detected by low CSF hypocretin-1 concentrations, and may also explain the sleep symptoms experienced by some PD patients. To date, there is mixed conflicting data describing hypocretin-1 levels in the CSF of patients with parkinsonism associated with sleep symptoms, with most studies showing no significant decrease when compared with controls. However, hypocretin-1 CSF deficiency has been shown in some studies to be more prominent in PD patients with sleep symptoms versus those without. Notably, the hypocretin system has been shown not to be selectively disrupted, with one study showing melanin concentrating hormone cell loss in the same patients with hypocretin loss. It is likely that hypocretin deficiency in PD patients occurs secondary to collateral damage caused by the neurodegenerative process involving the hypothalamus. Awareness of narcoleptic events in PD is important for driving related advice, in addition to the possible use of dopamine D3 receptor active agonists.
帕金森病（PD）的非运动症状，如日间过度嗜睡、“睡眠发作”、失眠、不宁腿综合征和快速眼动睡眠行为障碍，较为常见，且给治疗带来了挑战。患有睡眠/觉醒障碍（如发作性睡病）的患者也存在这些睡眠症状。国际睡眠障碍分类（ICSD-2）中的发作性睡病诊断标准使用了多种标志物，其中脑脊液（CSF）中下丘脑泌素-1 水平的缺乏或减少是一个关键标志物。位于外侧下丘脑和穹隆周核的下丘脑泌素神经元被认为与涉及睡眠和觉醒的机制相互作用。CSF 中低水平的下丘脑泌素-1 已被证明与发作性睡病和其他形式的嗜睡症中的下丘脑泌素细胞丢失相关；因此，有人提出，下丘脑泌素神经元的退行性损伤（如在 PD 中）可能通过 CSF 中低水平的下丘脑泌素-1 来检测，并且也可能解释一些 PD 患者的睡眠症状。迄今为止，描述与睡眠症状相关的帕金森病患者 CSF 中下丘脑泌素-1 水平的研究数据相互矛盾，大多数研究显示与对照组相比并无显著降低。然而，一些研究表明，与没有睡眠症状的 PD 患者相比，CSF 中下丘脑泌素-1 缺乏症在有睡眠症状的 PD 患者中更为明显。值得注意的是，下丘脑泌素系统并未被选择性破坏，一项研究表明在有下丘脑泌素丧失的同一患者中存在黑色素聚集激素细胞丧失。PD 患者的下丘脑泌素缺乏可能继发于涉及下丘脑的神经退行性过程中的侧支损伤。除了可能使用多巴胺 D3 受体激动剂外，了解 PD 中的发作性睡病事件对于提供相关建议也很重要。
