一项初步研究调查了测量 1 型和 2 型发作性睡病患者脑脊液乳酸水平的临床潜力。

A preliminary study investigating the clinical potential of measuring cerebrospinal-fluid lactate levels in patients with narcolepsy type 1 and 2.

机构信息

Department of Systems Medicine, University of Rome Tor Vergata, Italy.

Department of Systems Medicine, University of Rome Tor Vergata, Italy; Sleep Medicine Centre, Neurology Unit, University Hospital of Rome Tor Vergata, Italy.

出版信息

Physiol Behav. 2023 Dec 1;272:114371. doi: 10.1016/j.physbeh.2023.114371. Epub 2023 Oct 5.

DOI:10.1016/j.physbeh.2023.114371

PMID:37802459

Abstract

STUDY OBJECTIVES

Besides the quantification of orexin-A/hypocretin-1 cerebrospinal fluid (CSF) levels in narcolepsy for diagnostic purposes, several other CSF biomarkers have been evaluated, although with controversial results. Since CSF lactate concentrations fluctuate according to the sleep-wake cycle with higher levels during wakefulness and lower levels during sleep, as documented in animal model studies, the present study aimed at quantifying the CSF lactate levels in patients with narcolepsy type 1 (NT1) and 2 (NT2), which are two sleep disorders featured by excessive daytime sleepiness (EDS).

METHODS

Patients with NT1 and NT2 were enrolled in this study and compared to a control group of similar age and sex. All the subjects included in the study underwent a polysomnographic study followed by lumbar puncture for the quantification of CSF lactate levels at awakening.

RESULTS

23 NT1 (43.5 % male; 36.43 ± 11.89 years) and 15 NT2 patients (46.7 % male; 37.8 ± 14.1 years) were compared to 17 controls (58.8 % male; 32.3 ± 8.4 years). CSF lactate concentrations were reduced in patients with NT1 and NT2 compared to controls but no differences were found between the two groups of patients. ROC curves analysis showed that CSF lactate ≤1.3 mmol/l had a sensitivity of 96.49 and a specificity of 82.35 % for discriminating patients with narcolepsy from controls.

CONCLUSIONS

The present study showed a decrease in CSF lactate levels in patients with narcolepsy. Notably, the reduction of lactate levels was present in both NT1 and NT2 patients, independently of CSF orexin levels. Narcolepsy patients present EDS with daytime napping and REM-related episodes, possibly substantiating the CSF lactate levels reduction related to the impaired daytime wakefulness which was demonstrated in animal studies. Moreover, CSF lactate levels present a good sensitivity and adequate specificity for differentiating narcolepsy from controls. Further studies are needed to understand the role of CSF lactate and its usefulness for monitoring daytime vigilance in patients with narcolepsy.

摘要

研究目的

除了定量检测嗜睡症患者的脑脊液（CSF）中食欲素-A/下丘脑分泌素-1 的水平以用于诊断外，还评估了其他几种 CSF 生物标志物，但结果存在争议。由于 CSF 中的乳酸浓度会根据睡眠-觉醒周期而波动，在觉醒时较高，在睡眠时较低，这在动物模型研究中已有记载，因此本研究旨在定量检测 1 型（NT1）和 2 型（NT2）嗜睡症患者的 CSF 中乳酸水平，这两种睡眠障碍均以日间过度嗜睡（EDS）为特征。

方法

本研究纳入了 NT1 和 NT2 患者，并与年龄和性别相匹配的对照组进行比较。所有纳入研究的受试者均接受了多导睡眠图检查，然后在觉醒时进行腰椎穿刺以定量检测 CSF 中的乳酸水平。

结果

23 例 NT1（43.5%为男性；36.43±11.89 岁）和 15 例 NT2 患者（46.7%为男性；37.8±14.1 岁）与 17 例对照组（58.8%为男性；32.3±8.4 岁）进行了比较。与对照组相比，NT1 和 NT2 患者的 CSF 乳酸浓度降低，但两组患者之间无差异。ROC 曲线分析显示，CSF 乳酸≤1.3mmol/l 时，用于区分嗜睡症患者和对照组的敏感度为 96.49%，特异性为 82.35%。

结论

本研究显示嗜睡症患者的 CSF 乳酸水平降低。值得注意的是，无论是 NT1 还是 NT2 患者，CSF 中的乳酸水平均降低，这与脑脊液中食欲素水平无关。嗜睡症患者表现为 EDS，伴有日间小睡和 REM 相关发作，这可能证实了与日间觉醒受损相关的 CSF 乳酸水平降低，这在动物研究中已有证明。此外，CSF 乳酸水平对于区分嗜睡症患者和对照组具有良好的敏感度和足够的特异性。还需要进一步的研究来了解 CSF 乳酸的作用及其在监测嗜睡症患者日间警觉性方面的用途。