Center for Sleep Sciences and Medicine and Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California, USA.
JAMA Neurol. 2013 Jul;70(7):891-902. doi: 10.1001/jamaneurol.2013.1589.
Narcolepsy, a disorder associated with HLA-DQB1*06:02 and caused by hypocretin (orexin) deficiency, is diagnosed using the Multiple Sleep Latency Test (MSLT) following nocturnal polysomnography (NPSG). In many patients, a short rapid eye movement sleep latency (REML) during the NPSG is also observed but not used diagnostically.
To determine diagnostic accuracy and clinical utility of nocturnal REML measures in narcolepsy/hypocretin deficiency.
DESIGN, SETTING, AND PARTICIPANTS: Observational study using receiver operating characteristic curves for NPSG REML and MSLT findings (sleep studies performed between May 1976 and September 2011 at university medical centers in the United States, China, Korea, and Europe) to determine optimal diagnostic cutoffs for narcolepsy/hypocretin deficiency compared with different samples: controls, patients with other sleep disorders, patients with other hypersomnias, and patients with narcolepsy with normal hypocretin levels. Increasingly stringent comparisons were made. In a first comparison, 516 age- and sex-matched patients with narcolepsy/hypocretin deficiency were selected from 1749 patients and compared with 516 controls. In a second comparison, 749 successive patients undergoing sleep evaluation for any sleep disorders (low pretest probability for narcolepsy) were compared within groups by final diagnosis of narcolepsy/hypocretin deficiency. In the third comparison, 254 patients with a high pretest probability of having narcolepsy were compared within group by their final diagnosis. Finally, 118 patients with narcolepsy/hypocretin deficiency were compared with 118 age- and sex-matched patients with a diagnosis of narcolepsy but with normal hypocretin levels.
Sensitivity and specificity of NPSG REML and MSLT as diagnostic tests for narcolepsy/hypocretin deficiency. This diagnosis was defined as narcolepsy associated with cataplexy plus HLA-DQB1*06:02 positivity (no cerebrospinal fluid hypocretin-1 results available) or narcolepsy with documented low (≤ 110 pg/mL) cerebrospinal fluid hypocretin-1 level.
Short REML (≤15 minutes) during NPSG was highly specific (99.2% [95% CI, 98.5%-100.0%] of 516 and 99.6% [95% CI, 99.1%-100.0%] of 735) but not sensitive (50.6% [95% CI, 46.3%-54.9%] of 516 and 35.7% [95% CI, 10.6%-60.8%] of 14) for patients with narcolepsy/hypocretin deficiency vs population-based controls or all patients with sleep disorders undergoing a nocturnal sleep study (area under the curve, 0.799 [95% CI, 0.771-0.826] and 0.704 [95% CI, 0.524-0.907], respectively). In patients with central hypersomnia and thus a high pretest probability for narcolepsy, short REML remained highly specific (95.4% [95% CI, 90.4%-98.3%] of 132) and similarly sensitive (57.4% [95% CI, 48.1%-66.3%] of 122) for narcolepsy/hypocretin deficiency (area under the curve, 0.765 [95% CI, 0.707-0.831]). Positive predictive value in this high pretest probability sample was 92.1% (95% CI, 83.6%-97.0%).
Among patients being evaluated for possible narcolepsy, short REML (≤15 minutes) at NPSG had high specificity and positive predictive value and may be considered diagnostic without the use of an MSLT; absence of short REML, however, requires a subsequent MSLT.
发作性睡病是一种与 HLA-DQB1*06:02 相关的疾病，由下丘脑分泌素（食欲素）缺乏引起，通过多导睡眠图（PSG）后的多次小睡潜伏期试验（MSLT）进行诊断。在许多患者中，PSG 期间也观察到 REM 潜伏期短（REML），但不用于诊断。
确定夜间 REML 测量在发作性睡病/下丘脑分泌素缺乏症中的诊断准确性和临床实用性。
设计、地点和参与者：使用接受者操作特征曲线对 PSG REML 和 MSLT 结果进行观察性研究（1976 年 5 月至 2011 年 9 月在美国、中国、韩国和欧洲的大学医疗中心进行的睡眠研究），以确定与不同样本相比，诊断发作性睡病/下丘脑分泌素缺乏症的最佳诊断截止值：对照组、其他睡眠障碍患者、其他过度嗜睡症患者和下丘脑分泌素水平正常的发作性睡病患者。进行了越来越严格的比较。在第一次比较中，从 1749 名患者中选择了 516 名年龄和性别匹配的发作性睡病/下丘脑分泌素缺乏症患者，与 516 名对照进行比较。在第二次比较中，对因任何睡眠障碍进行睡眠评估的 749 例连续患者按最终诊断为发作性睡病/下丘脑分泌素缺乏症进行组内比较。在第三次比较中，按最终诊断将 254 例具有高发作性睡病可能性的患者进行组内比较。最后，将 118 例下丘脑分泌素缺乏的发作性睡病患者与 118 例年龄和性别匹配的下丘脑分泌素水平正常的发作性睡病患者进行比较。
PSG REML 和 MSLT 作为发作性睡病/下丘脑分泌素缺乏症诊断试验的敏感性和特异性。该诊断定义为伴有猝倒症的发作性睡病（HLA-DQB1*06:02 阳性）（无脑脊液下丘脑分泌素-1 结果）或伴有记录到低（≤110 pg/ml）脑脊液下丘脑分泌素-1 水平的发作性睡病。
夜间 PSG 时 REML 短（≤15 分钟）具有高度特异性（516 例中的 99.2%[95%CI，98.5%-100.0%]和 735 例中的 99.6%[95%CI，99.1%-100.0%]），但不敏感（516 例中的 50.6%[95%CI，46.3%-54.9%]和 14 例中的 35.7%[95%CI，10.6%-60.8%]）诊断为发作性睡病/下丘脑分泌素缺乏症患者与基于人群的对照组或所有接受夜间睡眠研究的睡眠障碍患者（曲线下面积，0.799[95%CI，0.771-0.826]和 0.704[95%CI，0.524-0.907]）。在中枢性过度嗜睡症患者中，即发作性睡病的可能性较高，夜间 REML 仍然具有高度特异性（132 例中的 95.4%[95%CI，90.4%-98.3%]）和类似的敏感性（122 例中的 57.4%[95%CI，48.1%-66.3%]）（曲线下面积，0.765[95%CI，0.707-0.831]）。在该高可能性样本中，阳性预测值为 92.1%（95%CI，83.6%-97.0%）。
在接受可能的发作性睡病评估的患者中，夜间 PSG 时的 REML 短（≤15 分钟）具有高特异性和阳性预测值，可考虑不使用 MSLT 进行诊断；然而，REML 缺失需要进行随后的 MSLT。
