Center for Sleep Sciences and Medicine, and Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, USA.
Sleep. 2012 Sep 1;35(9):1247-55F. doi: 10.5665/sleep.2080.
To compare clinical, electrophysiologic, and biologic data in narcolepsy without cataplexy with low (≤ 110 pg/ml), intermediate (110-200 pg/ml), and normal (> 200 pg/ml) concentrations of cerebrospinal fluid (CSF) hypocretin-1.
University-based sleep clinics and laboratories.
Narcolepsy without cataplexy (n = 171) and control patients (n = 170), all with available CSF hypocretin-1.
Retrospective comparison and receiver operating characteristics curve analysis. Patients were also recontacted to evaluate if they developed cataplexy by survival curve analysis.
The optimal cutoff of CSF hypocretin-1 for narcolepsy without cataplexy diagnosis was 200 pg/ml rather than 110 pg/ml (sensitivity 33%, specificity 99%). Forty-one patients (24%), all HLA DQB106:02 positive, had low concentrations (≤ 110 pg/ml) of CSF hypocretin-1. Patients with low concentrations of hypocretin-1 only differed subjectively from other groups by a higher Epworth Sleepiness Scale score and more frequent sleep paralysis. Compared with patients with normal hypocretin-1 concentration (n = 117, 68%), those with low hypocretin-1 concentration had higher HLA DQB106:02 frequencies, were more frequently non-Caucasians (notably African Americans), with lower age of onset, and longer duration of illness. They also had more frequently short rapid-eye movement (REM) sleep latency (≤ 15 min) during polysomnography (64% versus 23%), and shorter sleep latencies (2.7 ± 0.3 versus 4.4 ± 0.2 min) and more sleep-onset REM periods (3.6 ± 0.1 versus 2.9 ± 0.1 min) during the Multiple Sleep Latency Test (MSLT). Patients with intermediate concentrations of CSF hypocretin-1 (n = 13, 8%) had intermediate HLA DQB1*06:02 and polysomnography results, suggesting heterogeneity. Of the 127 patients we were able to recontact, survival analysis showed that almost half (48%) with low concentration of CSF hypocretin-1 had developed typical cataplexy at 26 yr after onset, whereas only 2% had done so when CSF hypocretin-1 concentration was normal. Almost all patients (87%) still complained of daytime sleepiness independent of hypocretin status.
Objective (HLA typing, MSLT, and sleep studies) more than subjective (sleepiness and sleep paralysis) features predicted low concentration of CSF hypocretin-1 in patients with narcolepsy without cataplexy.
比较无猝倒发作的嗜睡症患者脑脊液（CSF）中低（≤ 110 pg/ml）、中（110-200 pg/ml）和正常（> 200 pg/ml）浓度下丘脑泌素-1 的临床、电生理和生物学数据。
以大学为基础的睡眠诊所和实验室。
无猝倒发作的嗜睡症（n = 171）和对照患者（n = 170），均有可用的 CSF 下丘脑泌素-1。
回顾性比较和受试者工作特征曲线分析。还通过生存曲线分析重新联系患者，以评估他们是否出现猝倒。
无猝倒发作的嗜睡症诊断的 CSF 下丘脑泌素-1 的最佳截断值为 200 pg/ml，而不是 110 pg/ml（敏感性 33%，特异性 99%）。41 名患者（24%），均为 HLA DQB106:02 阳性，下丘脑泌素-1 浓度较低（≤ 110 pg/ml）。只有下丘脑泌素-1 浓度较低的患者在主观上通过更高的 Epworth 嗜睡量表评分和更频繁的睡眠瘫痪与其他组有所不同。与正常下丘脑泌素-1 浓度（n = 117，68%）的患者相比，下丘脑泌素-1 浓度较低的患者 HLA DQB106:02 频率更高，非高加索人（特别是非裔美国人）更常见，发病年龄更小，病程更长。他们还更频繁地出现短快速眼动（REM）睡眠潜伏期（≤ 15 分钟）（64% 对 23%），以及更短的睡眠潜伏期（2.7 ± 0.3 对 4.4 ± 0.2 分钟）和更多的睡眠开始 REM 期（3.6 ± 0.1 对 2.9 ± 0.1 分钟）在多次睡眠潜伏期试验（MSLT）中。CSF 下丘脑泌素-1 浓度中等（n = 13，8%）的患者具有中间 HLA DQB1*06:02 和多导睡眠图结果，表明存在异质性。在我们能够重新联系的 127 名患者中，生存分析显示，近一半（48%）下丘脑泌素-1 浓度较低的患者在发病后 26 年出现典型猝倒，而当 CSF 下丘脑泌素-1 浓度正常时，只有 2%出现这种情况。几乎所有患者（87%）仍有日间嗜睡症状，与下丘脑泌素状态无关。
客观（HLA 分型、MSLT 和睡眠研究）特征而非主观（嗜睡和睡眠瘫痪）特征预测无猝倒发作的嗜睡症患者 CSF 下丘脑泌素-1 浓度较低。
