Yelden Kudret, James Leon M, Duport Sophie, Kempny Agnieszka, Farmer Simon F, Leff Alex P, Playford E Diane
Neurological Rehabilitation, Royal Hospital for Neuro-Disability, London, United Kingdom.
Department of Neuroscience, King's College Hospital, London, United Kingdom.
Front Neurol. 2022 Jul 22;13:824880. doi: 10.3389/fneur.2022.824880. eCollection 2022.
Sleep is a physiological state necessary for memory processing, learning and brain plasticity. Patients with disorders of consciousness (DOC) show none or minimal sign of awareness of themselves or their environment but appear to have sleep-wake cycles. The aim of our study was to assess baseline circadian rhythms and sleep in patients with DOC; to optimize circadian rhythm using an intervention combining blue light, melatonin and caffeine, and to identify the impact of this intervention on brain function using event related potentials. We evaluated baseline circadian rhythms and sleep in 17 patients with DOC with 24-h polysomnography (PSG) and 4-hourly saliva melatonin measurements for 48 h. Ten of the 17 patients (5 female, age 30-71) were then treated for 5 weeks with melatonin each night and blue light and caffeine treatment in the mornings. Behavioral assessment of arousal and awareness [Coma recovery scale-revised (CRS-R)], 24-h polysomnography and 4-hourly saliva melatonin measurements, oddball mismatch negativity (MMN) and subject's own name (SON) experiments were performed twice at baseline and following intervention. Baseline sleep was abnormal in all patients. Cosinor analysis of saliva melatonin results revealed that averaged baseline % rhythmicity was low (: 31%, Range: 13-66.4%, : 18.4). However, increase in % Melatonin Rhythm following intervention was statistically significant ( = 0.012). 7 patients showed improvement of CRS-R scores with intervention and this was statistically significant ( = 0.034). All the patients who had improvement of clinical scores also had statistically significant improvement of neurophysiological responses on MMN and SON experiments at group level ( = 0.001). Our study shows that sleep and circadian rhythms are severely deranged in DOC but optimization is possible with melatonin, caffeine and blue light treatment. Clinical and physiological parameters improved with this simple and inexpensive intervention. Optimization of sleep and circadian rhythms should be integrated into rehabilitation programs for people with DOC.
睡眠是记忆处理、学习和大脑可塑性所必需的生理状态。意识障碍（DOC）患者对自身或其环境表现出无或极少的意识迹象，但似乎有睡眠-觉醒周期。我们研究的目的是评估DOC患者的基线昼夜节律和睡眠；使用蓝光、褪黑素和咖啡因相结合的干预措施优化昼夜节律，并使用事件相关电位确定该干预对脑功能的影响。我们通过24小时多导睡眠图（PSG）和48小时每4小时一次的唾液褪黑素测量，评估了17例DOC患者的基线昼夜节律和睡眠。然后，这17例患者中的10例（5名女性，年龄30 - 71岁）每晚接受褪黑素治疗5周，并在早晨接受蓝光和咖啡因治疗。在基线和干预后，进行了两次唤醒和意识的行为评估[昏迷恢复量表修订版（CRS-R）]、24小时多导睡眠图和每4小时一次的唾液褪黑素测量、奇偶数失配负波（MMN）和受试者自己名字（SON）实验。所有患者的基线睡眠均异常。唾液褪黑素结果的余弦分析显示，平均基线节律百分比很低（：31%，范围：13 - 66.4%，：18.4）。然而，干预后褪黑素节律百分比的增加具有统计学意义（ = 0.012）。7例患者在干预后CRS-R评分有所改善，且具有统计学意义（ = 0.034）。所有临床评分有所改善的患者在组水平上MMN和SON实验的神经生理反应也有统计学意义的改善（ = 0.001）。我们的研究表明，DOC患者的睡眠和昼夜节律严重紊乱，但通过褪黑素、咖啡因和蓝光治疗可以实现优化。这种简单且廉价的干预改善了临床和生理参数。睡眠和昼夜节律的优化应纳入DOC患者的康复计划。
