Neuro-Intensive Care Unit, Hospices Civils de Lyon, Neurological Hospital Pierre-Wertheimer, Bron, France.
ImpAct Team (Integrative, Multisensory, Perception, Action & Cognition), Lyon Neuroscience Research Centre (Université Claude Bernard Lyon 1, INSERM U1028, CNRS UMR5292), Bron, France.
J Pineal Res. 2019 Apr;66(3):e12555. doi: 10.1111/jpi.12555. Epub 2019 Feb 6.
Circadian rhythmicity (CR) is involved in the regulation of all integrated functions, from sleep-wake cycle regulation to metabolic function, mood and cognition. However, the interdependence of CR, cognition and consciousness has been poorly addressed. To clarify the state of CR in coma and to determine the chronological relationship between its recovery and consciousness after brain lesions, we conducted a longitudinal observational study investigating how the state of CR was chronologically related with the recovery of behavioural wakefulness, cognition and/or awareness. Among 16 acute comatose patients, we recruited two 37-year-old patients with a persistent disorder of consciousness, presenting diencephalic lesions caused by severe traumatic brain injuries. Two biological urinary markers of CR were explored every 2 hours during 24 hours (6-sulfatoxymelatonin, free cortisol) with a dedicated methodology to extract the endogenous component of rhythmicity (environmental light recording, near-constant-routine protocol, control of beta-blockers). They presented an initial absence of rhythmic secretions and a recovered CR 7-8 months later. This recovery was not associated with the restoration of behavioural wakefulness, but with an improvement of cognition and awareness (up to the minimally conscious state). MRI showed a lesion pattern compatible with the interruption of either the main hypothalamic-sympathetic pathway or the accessory habenular pathway. These results suggest that CR may be a prerequisite for coma recovery with a potential but still unproven favourable effect on brain function of the resorted circadian melatonin secretion and/or the functional recovery of the suprachiasmatic nucleus (SCN). Assessing circadian functions by urinary melatonin should be further explored as a biomarker of cognition reappearance and investigated to prognosticate functional recovery.
昼夜节律（CR）参与所有整合功能的调节，从睡眠-觉醒周期调节到代谢功能、情绪和认知。然而，CR、认知和意识的相互依存关系尚未得到充分解决。为了阐明昏迷状态下的 CR 状态，并确定脑损伤后 CR 恢复与意识之间的时间关系，我们进行了一项纵向观察研究，调查 CR 状态如何与行为觉醒、认知和/或意识的恢复在时间上相关。在 16 名急性昏迷患者中，我们招募了两名 37 岁的持续性意识障碍患者，他们患有严重创伤性脑损伤引起的间脑损伤。使用专门的方法学（环境光记录、近常时方案、β受体阻滞剂的控制）每 2 小时探索了 24 小时内的 2 种 CR 的生物尿液标志物（6-硫酸褪黑素、游离皮质醇）。他们最初表现出节律分泌缺失，7-8 个月后恢复了 CR。这种恢复与行为觉醒的恢复无关，而是与认知和意识的改善（直至最低意识状态）有关。MRI 显示的损伤模式与主要下丘脑-交感神经通路或辅助缰核通路的中断相兼容。这些结果表明，CR 可能是昏迷恢复的先决条件，对恢复的昼夜褪黑素分泌和/或视交叉上核（SCN）的功能恢复可能具有潜在但尚未得到证实的有利影响。通过尿液褪黑素进一步探索评估昼夜节律功能应该作为认知再现的生物标志物进行研究，并研究以预测功能恢复。
