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脑脊液食欲素 A 水平与嗜睡症患者夜间睡眠稳定性的关系。

Association of CSF orexin-A levels and nocturnal sleep stability in patients with hypersomnolence.

机构信息

From the Sleep-Wake Disorders Unit, Department of Neurology (L.B., R.L., S.C., A.-L.R., S.S., Y.D.), Gui-de-Chauliac Hospital, CHU Montpellier, University of Montpellier; National Reference Network for Narcolepsy (L.B., R.L., S.C., A.-L.R., S.S., Y.D.), CHU Montpellier; Inserm, Neuropsychiatry: Epidemiological and Clinical Research (L.B., R.L., I.J., Y.D.), University of Montpellier; Department of Biochemistry (M.L., J.-P.C.), Montpellier University Hospital; and PhyMedExp (M.L., J.-P.C.), University of Montpellier, INSERM U1046, CNRS UMR 9214, France.

出版信息

Neurology. 2020 Nov 24;95(21):e2900-e2911. doi: 10.1212/WNL.0000000000010743. Epub 2020 Sep 1.

Abstract

OBJECTIVE

To evaluate the associations between CSF orexin-A (ORX) levels and markers of nocturnal sleep stability, assessed by polysomnography.

METHODS

Nocturnal polysomnography data and ORX levels of 300 drug-free participants (55% men, 29.9±15.5 years, ORX level 155.1±153.7 pg/mL) with hypersomnolence were collected. Several markers of nocturnal sleep stability were analyzed: sleep and wake bouts and sleep/wake transitions. Groups were categorized according to ORX levels, in 2 categories (deficient ≤110; >110), in tertiles (≤26, 26-254, >254), and compared using logistic regression models. Results were adjusted for age, sex, and body mass index.

RESULTS

We found higher number of wake bouts (43 vs 25, < 0.0001), sleep bouts (43 vs 25.5, < 0.0001), and index of sleep bouts/hour of sleep time, but lower index of wake bouts/hour of wake time (41.4 vs 50.6, < 0.0001), in patients with ORX deficiency. The percentage of wake bouts <30 seconds was lower (51.3% vs 60.8%, < 0.001) and of wake bouts ≥1 minutes 30 seconds higher (7.7% vs 6.7%, = 0.02) when ORX deficient. The percentage of sleep bouts ≤14 minutes was higher (2-5 minutes: 23.7% vs 16.1%, < 0.0001), and of long sleep bouts lower (>32 minutes 30 seconds: 7.3% vs 18.3%, < 0.0001), when ORX deficient. These findings were confirmed when groups were categorized according to ORX tertiles, with a dose-response effect of ORX levels in post hoc comparisons, and in adjusted models.

INTERPRETATION

This study shows an association between ORX levels and nocturnal sleep stabilization in patients with hypersomnolence. Sleep and wake bouts are reliable markers of nighttime sleep stability that correlate with CSF ORX levels in a dose-dependent manner.

摘要

目的

评估脑脊液食欲素 A(ORX)水平与通过多导睡眠图评估的夜间睡眠稳定性标志物之间的关联。

方法

收集了 300 名无药物治疗的嗜睡症患者(55%为男性,29.9±15.5 岁,ORX 水平为 155.1±153.7pg/mL)的夜间多导睡眠图数据和 ORX 水平。分析了几种夜间睡眠稳定性标志物:睡眠和觉醒发作以及睡眠/觉醒转换。根据 ORX 水平将患者分为 2 组(不足≤110;>110),分为 3 组(≤26、26-254、>254),并使用逻辑回归模型进行比较。结果按年龄、性别和体重指数进行调整。

结果

我们发现 ORX 缺乏的患者觉醒发作次数更多(43 次比 25 次,<0.0001),睡眠发作次数更多(43 次比 25.5 次,<0.0001),每小时睡眠时间的睡眠发作指数更高,但每小时觉醒时间的觉醒发作指数更低(41.4 比 50.6,<0.0001)。30 秒以下的觉醒发作比例较低(51.3%比 60.8%,<0.001),1 分 30 秒以上的觉醒发作比例较高(7.7%比 6.7%,=0.02)。ORX 缺乏的患者睡眠发作持续时间≤14 分钟的比例较高(2-5 分钟:23.7%比 16.1%,<0.0001),持续时间较长的睡眠发作比例较低(>32 分钟 30 秒:7.3%比 18.3%,<0.0001)。当按 ORX 三分位数对患者进行分组时,这些发现得到了证实,并且在后验比较和调整模型中存在 ORX 水平的剂量反应效应。

结论

这项研究表明,在患有嗜睡症的患者中,ORX 水平与夜间睡眠稳定有关。睡眠和觉醒发作是夜间睡眠稳定性的可靠标志物,与 CSF ORX 水平呈剂量依赖性相关。

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