Abstract：
The Maintenance of Wakefulness Test (MWT) is a widely accepted objective test used to evaluate daytime somnolence and is commonly used in clinical studies evaluating novel therapeutics for excessive daytime sleepiness. In the latter, sleep onset latency (SOL) is typically the sole MWT endpoint. Here, we explored microsleeps, sleep probability measures derived from automated sleep scoring, and quantitative electroencephalography (qEEG) features as additional MWT biomarkers of daytime sleepiness, using data from a phase 1B trial of the selective orexin receptor 2 agonist danavorexton (TAK-925) in people with narcolepsy type 1 (NT1) or type 2 (NT2). Danavorexton treatment reduced the rate and duration of microsleeps during the MWT in NT1 (days 1 and 7; p ≤ 0.005) and microsleep rate in NT2 (days 1 and 7; p < 0.0001). Use of an EEG-sleep-staging-derived measure to determine the probability of wakefulness for each minute revealed a novel metric to track changes in daytime sleepiness, which were consistent with the θ/α ratio, a known biomarker of drowsiness. The slopes of line-fits to both the log-transformed sleepiness score or log-transformed θ/α ratio correlated well to (inverse) MWT SOL for NT1 (R = 0.93 and R = 0.83, respectively) and NT2 (R = 0.97 and R = 0.84, respectively), suggesting that individuals with narcolepsy have increased sleepiness immediately after lights-off. These analyses demonstrate that novel EEG-based biomarkers can augment SOL as predictors of sleepiness and its response to treatment and provide a novel framework for the analysis of wake EEG in hypersomnia disorders.
摘要：
保持清醒测试（MWT）是一种广泛接受的客观测试，用于评估白天的嗜睡，通常用于评估白天过度嗜睡的新疗法的临床研究。在后者中,睡眠开始延迟（SOL）通常是唯一的MWT终点。这里,我们探索了微睡眠，从自动睡眠评分中得出的睡眠概率度量，和定量脑电图（qEEG）特征作为白天嗜睡的额外MWT生物标志物，使用选择性食欲素受体2激动剂danavorexton（TAK-925）在发作性睡病1型（NT1）或2型（NT2）患者中的1B期试验数据。Danavorexton治疗降低了MWT期间NT1（第1天和第7天；p≤0.005）和NT2（第1天和第7天；p<0.0001）的微睡眠率和持续时间。使用EEG睡眠分期得出的度量来确定每分钟的清醒概率，揭示了一种新颖的指标来跟踪白天嗜睡的变化，与θ/α比一致，一种已知的嗜睡生物标志物.对于NT1（分别为R=0.93和R=0.83）和NT2（分别为R=0.97和R=0.84），对数变换的困倦得分或对数变换的θ/α比的线性拟合斜率与（逆）MWTSOL密切相关，这表明发作性睡病患者在关灯后立即增加了嗜睡。这些分析表明，基于EEG的新型生物标志物可以增强SOL作为嗜睡及其对治疗反应的预测因子，并为失眠症中唤醒EEG的分析提供了新的框架。
