Study of Sleep Patterns Might Advance Our Knowledge on Alertness in Traumatic Brain Injury

Loss of consciousness in TBI occurs due to electrophysiological dysfunction of the ascending reticular activating system (ARAS), a fundamental structure that maintains tonic arousals as a prelude to alertness [6]. Urakami simultaneously used electroencephalography (EEG) and magneto encephalography (MEG) in patients with chronic diffuse axonal injury (i.e. a pattern of brain damage characterized by lesion in the corpus callosum and dorsolateral brain stem accompanied by widespread damage in the white matter in patients who were unconscious from the injury) [7] and found that, in the acute stage of diffuse axonal injury, both the frequency of fast spindles and cortical activation source strength were significantly lower in patients with TBI than in healthy controls; the alpha activity reflected the severity of disturbed consciousness [8]. In that study, the presence of sleep spindles was found to serve as an indicator of recovery in the chronic phase after injury [8]. Similarly, Cologan and colleagues proposed that the presence of EEG patterns resembling normal human sleep [9] (i.e. wellstructured patterns of non rapid eye movement (NREM) and/or rapid eye movement(REM) sleep) can be markers of a favorable outcome after brain injury [10]. Moreover, the quality and quantity of spindles can provide a new index of the severity of thalamocortical injury, in accordance with brain imaging studies showing the correlation between the extent of thalamus damage and behavioral disability and outcome in disorders of consciousness [10-13]. Gosselin and colleagues observed increased delta and decreased alpha activity during wakefulness in patients with mild TBI and proposed sleep intrusions in the waking state might indicate continuous sleep inertia, manifesting as fatigue and impaired functioning [14]. The clinical significance of the utility of EEG in TBI is reflected in a recent study by Teel et al. [15]. While concussed participants passed all clinical concussion testing tools, they showed path physiological dysfunction with evaluation of EEG variables, supporting the hypothesis of diminished brain resources to compensate appropriately during activity [15]. The results of the study are particularly relevant to clinicians who make return-to-play or return-to-work decisions (i.e. in sport, first respondents, and other occupations that require sustained attention). An advanced study of sleep and wake EEG offers a new opportunity to define the robust sleep parameters that need to be compared among different patient populations. Another important advance menthes been made by studies exploring the role of neurotransmitters involved in arousal regulation after TBI. Several brain neurotransmitters, including noradrenergic, serotoninergic, cholinergic, histaminergic, hypocretin/orexin, and dopamine systems, are known to be involved in this process [16]. Recent findings suggest that severe brain injury can affect the hypothalamic system to such an extent that the neuropeptides hypocretin-1 and hypocretin-2 (also known as orexin-A and orexin-B) are altered, either transiently or permanently [17-19]. Hypocretins play an essential role in promoting wakefulness. Nardone and colleagues recently studied cortical excitability in patients affected by different sleep-wake disturbances after TBI in order to determine whether the changes in cortical excitability are associated with the development of post-traumatic excessive daytime sleepiness [20]. They reported that, similar to that in patients with narcolepsy [21,22], cortical hypo excitability in patients with TBI might reflect the deficiency of the excitatory hypocretin/orexin-neurotransmitter system [20]. Though not experimentally tested yet in the TBI population, the pre-existing level of alertness should be factored into the conclusions. This is highly relevant to study alertness in the TBI population, when taking into account symptom overlap between impaired alertness and daytime sleepiness; nearly half of patients with excessive sleepiness report automobile accidents, with half reporting occupational accidents and other life threatening situations [23] which can result in a TBI outcome. Studies have been focusing on understanding how factors other than those associated with TBI, including sleep disorders, psychiatric comorbidity, and medications, can impact the ability of TBI patients to maintain alertness during the day [24-26]. Sleep disorders such as sleep apnea, narcolepsy, insomnia, and circadian rhythms disorders are of particular interest at present, since their incidence in TBI has been shown to be significantly higher than those in the general populations [27,28]. Of particular interest in the TBI population is REM sleep behavior disorder (RBD) which is characterized by dramatic REM motor activation resulting in dream enactment, often with violent or injurious results. Verma et al. [29] examined the spectrum of sleep disorders in chronic TBI patients and reported complaints of parasomnia in 25% of participants, with RBD to be the most commonly reported disorder (13%). It has been proposed that the increased RBD incidence relative to that of the general population after brain injury is attributed to damage to brainstem mechanisms mediating descending motor