Sleep-Wake Disorders Unit, Department of Neurology, Gui-de-Chauliac Hospital, CHU de Montpellier, Montpellier, France; National Reference Centre for Orphan Diseases, Narcolepsy, Idiopathic Hypersomnia, and Kleine-Levin Syndrome, Montpellier, France; Institute of Neurosciences of Montpellier, University of Montpellier, Inserm, Montpellier, France.
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche, Bologna, Italy.
Rev Neurol (Paris). 2023 Oct;179(7):727-740. doi: 10.1016/j.neurol.2023.08.001. Epub 2023 Aug 25.
Narcolepsy type 1 (NT1) and type 2 (NT2), also known as narcolepsy with and without cataplexy, are sleep disorders that benefited from major scientific advances over the last two decades. NT1 is caused by the loss of hypothalamic neurons producing orexin/hypocretin, a neurotransmitter regulating sleep and wake, which can be measured in the cerebrospinal fluid (CSF). A low CSF level of hypocretin-1/orexin-A is a highly specific and sensitive biomarker, sufficient to diagnose NT1. Orexin-deficiency is responsible for the main NT1 symptoms: sleepiness, cataplexy, disrupted nocturnal sleep, sleep-related hallucinations, and sleep paralysis. In the absence of a lumbar puncture, the diagnosis is based on neurophysiological tests (nocturnal and diurnal) and the presence of the pathognomonic symptom cataplexy. In the revised version of the International Classification of sleep Disorders, 3rd edition (ICSD-3-TR), a sleep onset rapid eye movement sleep (REM) period (SOREMP) (i.e. rapid occurrence of REM sleep) during the previous polysomnography may replace the diurnal multiple sleep latency test, when clear-cut cataplexy is present. A nocturnal SOREMP is very specific but not sensitive enough, and the diagnosis of cataplexy is usually based on clinical interview. It is thus of crucial importance to define typical versus atypical cataplectic attacks, and a list of clinical features and related degrees of certainty is proposed in this paper (expert opinion). The time frame of at least three months of evolution of sleepiness to diagnose NT1 was removed in the ICSD-3-TR, when clear-cut cataplexy or orexin-deficiency are established. However, it was kept for NT2 diagnosis, a less well-characterized disorder with unknown clinical course and absence of biolo biomarkers; sleep deprivation, shift working and substances intake being major differential diagnoses. Treatment of narcolepsy is nowadays only symptomatic, but the upcoming arrival of non-peptide orexin receptor-2 agonists should be a revolution in the management of these rare sleep diseases.
发作性睡病 1 型（NT1）和 2 型（NT2），又称有猝倒和无猝倒的发作性睡病，是过去二十年中受益于重大科学进步的睡眠障碍。NT1 是由下丘脑神经元产生的食欲素/下丘脑分泌素缺失引起的，这种神经递质调节睡眠和觉醒，可以在脑脊液（CSF）中测量。低 CSF 水平的下丘脑分泌素-1/食欲素-A 是一种高度特异性和敏感的生物标志物，足以诊断 NT1。食欲素缺乏是导致主要 NT1 症状的原因：嗜睡、猝倒、夜间睡眠紊乱、睡眠相关幻觉和睡眠瘫痪。在没有腰椎穿刺的情况下，诊断基于神经生理学测试（夜间和日间）和特征性症状猝倒的存在。在修订后的国际睡眠障碍分类，第 3 版（ICSD-3-TR）中，前一次多导睡眠图检查期间出现的睡眠起始快速眼动睡眠（REM）期（即 REM 快速发生）（SOREMP）可替代日间多次小睡潜伏期测试，当明确存在猝倒时。夜间 SOREMP 非常特异但不够敏感，猝倒的诊断通常基于临床访谈。因此，定义典型与非典型猝倒发作至关重要，本文提出了一系列临床特征和相关确定性程度（专家意见）。在 ICSD-3-TR 中，明确的猝倒或食欲素缺乏症建立后，将诊断 NT1 的嗜睡症状演变至少三个月的时间框架删除。然而，对于 NT2 诊断，保留了这一条件，因为这是一种特征不明确的疾病，其临床病程和生物标志物未知；睡眠剥夺、轮班工作和物质摄入是主要的鉴别诊断。发作性睡病的治疗目前仅为对症治疗，但即将到来的非肽类食欲素受体 2 激动剂的到来将是这些罕见睡眠疾病治疗的一场革命。
