Sleep and circadian rhythms in the acute phase of moderate to severe traumatic brain injury

Traumatic brain injuries (TBI) are the leading cause of disability among young adults, causing debilitating cognitive, psychological and behavioural impairments. Sleep-wake disturbances (SWD) are among the most persistent sequelae following TBI, and could impede recovery. Indeed, sleep is essential to learning, plasticity and neurogenesis. Clinical observations suggest that these disturbances arise in the first weeks following injury, and could suggest a circadian disturbance. However, no study has yet documented how SWD arise and evolve in the acute phase of TBI, or how they are associated to short-term cognitive and functional recovery.  Consequently, this thesis aims to characterize the sleep and circadian rhythms of patients hospitalized with moderate or severe TBI, and determine whether SWD are caused by a deregulation of the circadian clock. To achieve this goal, we used objective and quantitative measures of sleep and circadian rhythms including actigraphy, polysomnography (PSG), and melatonin, beginning in the awakening stage in the Intensive Care Unit. In order to understand the specific role of TBI on SWD, we compared TBI patients to other hospitalized trauma patients, without TBI. Our comprehensive study protocol led to five research articles. First, we show that the sleep-wake cycle of TBI patients is severely disturbed, but improves for 50% of patients during their hospital stay. Patients whose sleep-wake cycle consolidation improves have better cognitive and functional outcome at hospital discharge. Then, in a single case study, we demonstrate how a patient can have drastically different sleep-wake patterns in the same environment, according to recovery stage. In our third research article, we show that the consolidation of sleep and wake states evolves synchronously with the recovery of consciousness and cognition in the acute phase of TBI.  Our fourth article compares the sleep of TBI patients to that of non-TBI trauma patients using ambulatory PSG at bedside. Contrary to our hypothesis, TBI patients have normal sleep elements and normal proportions of each sleep stages. However, they have earlier sleep onset and longer nighttime sleep duration, but with greater fragmentation, than non-TBI patients. In both groups, sleep quality is poor, which most likely reflects non-specific factors associated with the physical trauma and hospital environment. Therefore, PSG reveals little information able to distinguish TBI patients from other non-TBI trauma patients at this stage post-injury. Our final article shows that TBI patients have poorer sleep-wake cycle consolidation and nighttime sleep quality than non-TBI patients, confirming the role of the TBI in altering sleep and wake states. However, despite having more severe SWD, TBI patients have a normal melatonin rhythm, and this rhythm is not associated with the observed SWD. This article suggests that neural mechanisms other than the circadian clock may be responsible for post-TBI SWD. This thesis is the first to investigate the sleep and circadian clock of hospitalized moderate to severe TBI patients who are medically stable. By isolating the role of the injured brain from that of overall trauma and the hospital setting, these studies contribute to understanding the characteristics, consequences and pathophysiology of post-TBI SWD, unlocking the possibility to design interventions aiming to improve sleep and optimize recovery.

Keyphrases: Cognition, Traumatic brain injury, Sleep, Melatonin, Actigraphy, Polysomnography, Acute care, Recovery, Consciousness, Circadian rhythms