TBI and Sleep–Wake Disorders: Pathophysiology, Clinical Management, and Moving towards the Future

Abstract

After experiencing a traumatic brain injury (TBI), the majority of patients will develop sleep–wake disorders (SWD). These can include insomnia, pleiosomnia, excessive daytime sleepiness, obstructive and/or central sleep apnea, circadian sleep–wake disorders, and potentially a variety of parasomnias. Untreated SWD may impede the recovery process and can negatively impact attention, executive function, and working memory. Importantly, these patients tend to misperceive their posttraumatic sleep problems. Consequently, interviews performed in standard clinical practice will not sufficiently capture SWD patients, potentially compromising safety and productivity.In this review, the authors outline the state of current TBI-related SWD, highlighting proposed mechanisms, treatment modalities, and areas for further clinical investigation. They highlight data examining a role for slow wave sleep (SWS) in the enhancement of neural repair. They also examine the utility of enhanced cohort recruitment and SWD biomarker discovery via use of social media, smart-devices, and data-sharing networks.

Associations of Chronic Pain With Psychosocial Outcomes After Traumatic Brain Injury: A NIDILRR and VA TBI Model Systems Collaborative Project

“…Sleep disturbances and pain share a bidirectional and mutually exacerbating relationship, although the underlying pathophysiological mechanisms have not been fully elucidated 37,38. Pain itself is inherently disruptive to sleep through discomfort and at the time of injury is associated with a system-wide inflammatory cascade and disruption to neural circuitry that contributes directly to both sleep disturbance, as well as setting individuals on a path that raises their risk for developing chronic pain 36,39–41. Sleep disturbance contributes to the experience of pain via physiological pathways such as intermittent hypoxia, impaired immunity, reduced glymphatic waste clearance, and disruption of endogenous pain modulation 42–44.…”

“…37,38 Pain itself is inherently disruptive to sleep through discomfort and at the time of injury is associated with a system-wide inflammatory cascade and disruption to neural circuitry that contributes directly to both sleep disturbance, as well as setting individuals on a path that raises their risk for developing chronic pain. 36,[39][40][41] Sleep disturbance contributes to the experience of pain via physiological pathways such as intermittent hypoxia, impaired immunity, reduced glymphatic waste clearance, and disruption of endogenous pain modulation. [42][43][44] In addition, psychological and behavioral pathways are implicated, such as dysfunctional beliefs about the pain-sleep relationship, 45 psychiatric comorbidity (eg, depression, PTSD), and maladaptive coping responses (eg, increased time spent in bed).…”

Traumatic Brain Injury, Sleep, and Melatonin—Intrinsic Changes with Therapeutic Potential

“…Proposed mechanisms underlying sleep dysfunction following TBI can be subdivided by chronicity and subsequent microscopic or macroscopic effects. Acute injury mechanisms implicate acceleration-deceleration (blast and/or coup-contrecoup), resulting in axonal shearing and diffuse interruption of affiliated functional networks, theoretically including those associated with wakefulness and sleep, as shown in Figure 1 [ 73 ]. Cranial surface morphology exerts traumatic action in areas of high shear stress, such as the sphenoid ridge, inferior frontal, anterior temporal, and basal forebrain regions.…”

“…Cranial surface morphology exerts traumatic action in areas of high shear stress, such as the sphenoid ridge, inferior frontal, anterior temporal, and basal forebrain regions. These areas are rich in axonal projections mediating sleep and wakefulness, such as those from the locus coeruleus (noradrenergic pathway), the suprachiasmatic nucleus (circadian rhythm disorders), posterior hypothalamus (orexin neurons), and tuberomammillary nucleus (histaminergic pathway) [ 73 ].…”