Sleep and wake disturbances following traumatic brain injury

Traumatic brain injury (TBI) is a major health concern in industrialised countries. Sleep and wake disturbances are among the most persistent and disabling sequelae after TBI. Yet, despite the widespread complaints of post-TBI sleep and wake disturbances, studies on their etiology, pathophysiology, and treatments remain inconclusive. This narrative review aims to summarise the current state of knowledge regarding the nature of sleep and wake disturbances following TBI, both subjective and objective, spanning all levels of severity and phases post-injury. A second goal is to outline the various causes of post-TBI sleep-wake disturbances. Globally, although sleep-wake complaints are reported in all studies and across all levels of severity, consensus regarding the objective nature of these disturbances is not unanimous and varies widely across studies. In order to optimise recovery in TBI survivors, further studies are required to shed light on the complexity and heterogeneity of post-TBI sleep and wake disturbances, and to fully grasp the best timing and approach for intervention.     

Brief report: parental report of sleep behaviors following moderate or severe pediatric traumatic brain injury

OBJECTIVE: Determine the effect of moderate and severe traumatic brain injuries (TBI) on the sleep of school-aged children. METHODS: A concurrent cohort-prospective design compared children aged 6-12 years who sustained moderate TBI (baseline n = 56), severe TBI (n = 53), or only orthopedic injuries (n = 80). Retrospective parental report of pre-injury sleep was collected about 3 weeks post-injury. Post-injury assessments occurred prospectively a mean of 6, 12, and 48 months later. RESULTS: Growth curve analyses compared the groups over time. The moderate TBI group had worse pre-injury sleep than the other groups. The moderate TBI and orthopedic injury groups displayed a small decline in sleep problems from pre- to post-injury. Children with severe TBI displayed increased post-injury sleep problems. CONCLUSIONS: Children who sustain severe TBI are at elevated risk for post-injury sleep problems. Because sleep problems may result in daytime impairments and family distress, additional clinical and research attention is warranted.     

脑微损伤的影像学进展

脑微损伤是创伤性脑损伤最常见的类型,然而,其潜在的神经生理机制尚未完全阐明,影响患者的早期诊断、治疗及预后评估。近年来,多项磁共振（MRI）新技术不断地涌现并用于评估脑微损伤,如功能磁共振、灌注MRI、弥散张量成像、定量易感性图谱、T2 mapping等。本研究综述了多模态MRI在脑微损伤中的应用,从不同的角度深入地了解脑微损伤的神经病理机制,有助于提高临床医生对脑微损伤的诊断和治疗。     

Sleep deprivation has a neuroprotective role in a traumatic brain injury of the rat

During the process of a brain injury, responses to produce damage and cell death are activated, but self-protective responses that attempt to maintain the integrity and functionality of the brain are also activated. We have previously reported that the recovery from a traumatic brain injury (TBI) is better in rats if it occurs during the dark phase of the diurnal cycle when rats are in the waking period. This suggests that wakefulness causes a neuroprotective role in this type of injury. Here we report that 24 h of total sleep deprivation after a TBI reduces the morphological damage and enhances the recovery of the rats, as seen on a neurobiological scale.     

Sleep disturbances and childhood sexual abuse

OBJECTIVE: This longitudinal, prospective study examined the relationship between childhood sexual abuse and later sleep problems in adolescence while taking into account cooccurring psychopathology that is closely related to sleep disruption [e.g., depression and posttraumatic stress disorder (PTSD)]. METHOD: Sleep disturbances in 147 females (78 sexually abused; 69 comparison) were assessed 10 years after disclosure of substantiated abuse. The follow-up protocol included self-report questions regarding typical sleeping patterns and sleep disturbances as well as measures of depression, PTSD, and lifetime victimization histories. RESULTS: Sleep disturbances correlated significantly with both depression and PTSD. Hierarchical regression analysis showed that sexually abused participants reported significantly greater rates of sleep disturbances than comparison participants above and beyond depression and PTSD. Sleep disturbances were related to revictimization rates independent of sexual abuse, depression, and PTSD. CONCLUSIONS: Assessments of sleep disturbances should be integrated into standard of care for adolescents who have experienced sexual abuse.     

Race as a moderator of parent and family outcomes following pediatric traumatic brain injury

OBJECTIVE: To use data from a prospective, longitudinal study to determine whether race moderates parent and family outcomes during the first year following pediatric traumatic brain injuries (TBI). METHOD: Participants included 73 white and 18 black children with moderate to severe TBI and their families, and 32 white and 23 black children with orthopedic injuries only (OI) and their families. Assessments of parent and family functioning occurred shortly after injury (baseline) and at 6- and 12-month follow-ups. RESULTS: Race was a significant moderator of group differences in parental psychological distress and perceived family burden, by and large independent of socioeconomic status. The negative consequences of TBI were relatively less pronounced for parents of black children than for parents of white children at baseline, but became more pronounced at the two follow-ups. Black and white parents differed in preferred coping strategies, which may partially account for their different reactions to their children's injuries. CONCLUSIONS: The sociocultural factors associated with race may moderate the effects of pediatric TBI and OI on parents and families.     

Impaired emotional contagion following severe traumatic brain injury

Empathy deficits are widely-documented in individuals after severe traumatic brain injury (TBI). This study examined the relationship between empathy deficits and psychophysiological responsivity in adults with TBI to determine if impaired responsivity is ameliorated through repeated emotional stimulus presentations. Nineteen TBI participants (13 males; 41 years) and 25 control participants (14 males; 31 years) viewed five repetitions of six 2-min film clip segments containing pleasant, unpleasant, and neutral content. Facial muscle responses (zygomaticus and corrugator), tonic heart rate (HR) and skin conductance level (SCL) were recorded. Mean responses for each viewing period were compared to a pre-experiment 2-min resting baseline period. Self-reported emotional empathy was also assessed. TBI participants demonstrated identical EMG response patterns to controls, i.e. an initial large facial response to both pleasant and unpleasant films, followed by habituation over repetitions for pleasant films, and sustained response to unpleasant films. Additionally, an increase in both arousal and HR deceleration to stimulus repetitions was found, which was larger for TBI participants. Compared to controls, TBI participants self-reported lower emotional empathy, and had lower resting arousal, and these measures were positively correlated. Results are consistent with TBI producing impairments in emotional empathy and responsivity. While some normalisation of physiological arousal appeared with repeated stimulus presentations, this came at the cost of greater attentional effort.     

An NMR metabolomic investigation of early metabolic disturbances following traumatic brain injury in a mammalian model

The effects of traumatic brain injury (TBI) on brain chemistry and metabolism were examined in three groups of rats using high-resolution (1)H NMR metabolomics of brain tissue extracts and plasma. Brain injury in the TBI group (n = 6) was produced by lateral fluid percussion and regional changes in brain metabolites were analyzed at 1 h after injury in hippocampus, cortex and plasma and compared with changes in both a sham-surgery control group (n = 6) and an untreated control group (n = 6). Evidence was found of oxidative stress (e.g. decreases in ascorbate of 16.4% (p<0.01) and 29.7% (p<0.05) in cortex and hippocampus, respectively) in TBI rats versus the untreated control group, as well as excitotoxic damage (e.g. decreases in glutamate of 14.7% (p<0.05) and 12.3% (p<0.01) in the cortex and hippocampus, respectively), membrane disruption (e.g. decreases in the total level of phosphocholine and glycerophosphocholine of 23.0% (p<0.01) and 19.0% (p<0.01) in the cortex and hippocampus, respectively) and neuronal injury (e.g. decreases in N-acetylaspartate of 15.3% (p<0.01) and 9.7% (p>0.05) in the cortex and hippocampus, respectively). Significant changes in the overall pattern of NMR-observable metabolites using principal components analysis were also observed in TBI animals. Although TBI clearly had an effect on the metabolic profile found in brain tissue, no clear effects could be discerned in plasma samples. This was at least partly due to large variability in dominant glucose and lactate peaks in plasma. However, disruption of the blood-brain barrier and the subsequent movement of metabolites from brain into blood may have been relatively small and below the detection limits of our analytical procedures. Overall, these data indicate that TBI results in several significant changes in brain metabolism early after trauma and that a metabolomic approach based on (1)H NMR spectroscopy can provide a metabolic profile comprising several metabolite classes and allow for relative quantification of such changes within specific brain regions. The results also provide support for further development and application of metabolomic technologies for studying TBI and for the utilization of multivariate models for classifying the extent of trauma within an individual.     

Spatiotemporal changes in diffusion,T2 and susceptibility of white matter following mild traumatic brain injury

Impaired white matter integrity in traumatic brain injury (TBI) can lead to deficits in various neurological functions. The differentiation of the underlying pathological processes, e.g. edema, demyelination, axonal damage, to name a few, is of key clinical interest for the assessment of white matter injury. In this study, a combination of T₂, diffusion and susceptibility MRI was used to study the spatiotemporal changes in white matter at 1 h, 3 h, and 1, 2, 7 and 14 days following TBI, using a rat controlled cortical impact (CCI) model. Based on radial diffusivity (RD), the rats were divided into two groups: group 1 showed widespread increases in RD along the corpus callosum of the ipsilesional hemisphere at day 2, and group 2 showed normal RD. Based on this group separation, group 1 also showed similar widespread changes in fractional anisotropy (FA) and T₂ at day 2, and group 2 showed normal FA and T₂. The widespread changes in RD and T₂ in group 1 on day 2 were apparently dominated by edema, which obscured possible myelin and axonal damage. In contrast, the susceptibility of group 1 showed more localized increases near the impact site on day 2, and otherwise similar contrast to the contralesional hemisphere. The localized susceptibility increase is probably a result of demyelination and axonal injury. The extent of brain damage between the two groups revealed by MRI was consistent with behavioral results, with the first group showing significantly increased forelimb asymmetry and increased forelimb foot fault deficits. Our results suggest that the combination of T₂, diffusion and susceptibility MRI may provide an opportunity for the differential assessment of edema and axonal damage in TBI. Copyright © 2016 John Wiley & Sons, Ltd.     

Long-term potentiation deficits and excitability changes following traumatic brain injury

The effects of traumatic brain injury (TBI) on hippocampal long-term potentiation (LTP) and cellular excitability were assessed at postinjury days 2, 7, and 15. TBI was induced using a well-characterized central fluid-percussion model. LTP of the Schaffer collateral/commissural system was assessed in vivo in urethane-anesthetized rats. Significant LTP of the population excitatory postsynaptic potential (EPSP) slope was found only in controls, and no recovery to control levels was observed for any postinjury time point. Four measurement parameters reflecting pyramidal cell discharges (population spike) indicated that TBI significantly increased cellular excitability at postinjury day 2: (1) pretetanus baseline recording showed that TBI reduced population spike threshold and latency; (2) tetanic stimulation (400 Hz) increased population spike amplitudes to a greater degree in injured animals than in control animals; (3) tetanus-induced population spike latency shifts were greater in injured cases; and (4) tetanic stimulation elevated EPSP to spike ratios (E-S potentiation) to a greater degree in injured animals. These parameters returned to control levels, as measured on postinjury days 7 and 15. These results suggest that TBI-induced excitability changes persist at least through 2 days postinjury and involve a differential impairment of mechanisms subserving LTP of synaptic efficacy and mechanisms related to action potential generation     

Persistent problems 1 year after mild traumatic brain injury: a longitudinal population study in New Zealand

Background

Mild traumatic brain injury (mTBI) is a common problem in general practice settings, yet previous research does not take into account those who do not attend hospital after injury. This is important as there is evidence that effects may be far from mild.

Aim

To determine whether people sustain any persistent effects 1 year after mTBI, and to identify the predictors of health outcomes.

Design and setting

A community-based, longitudinal population study of an mTBI incidence cohort (n = 341) from a mixed urban and rural region (Hamilton and Waikato Districts) of the North Island of New Zealand (NZ).

Method

Adults (>16 years) completed assessments of cognitive functioning, global functioning, post-concussion symptoms, mood, and quality of life over the year after injury.

Results

Nearly half of participants (47.9%) reported experiencing four or more post-concussion symptoms 1 year post-injury. Additionally, 10.9% of participants revealed very low cognitive functioning. Levels of anxiety, depression, or reduced quality of life were comparable with the general population. Having at least one comorbidity, history of brain injury, living alone, non-white ethnic group, alcohol and medication use, and being female were significant predictors of poorer outcomes at 12 months.

Conclusion

Although some people make a spontaneous recovery after mTBI, nearly half continue to experience persistent symptoms linked to their injury. Monitoring of recovery from mTBI may be needed and interventions provided for those experiencing persistent difficulties. Demographic factors and medical history should be taken into account in treatment planning.     

Activation of brain regions using task-state FMRI in patients with mild traumatic brain injury: a meta-analysis

Activation likelihood estimation meta-analysis was performed to examine the activation characteristics of cognition-related brain regions in patients with mild traumatic brain injury (mTBI). The databases PubMed, Ovid, Cochrane Library, Google Scholar, CNKI, WFSD, and VIP were systematically searched. The software Ginger-ALE 3.0.2 was used for coordinate unification and meta-analysis. Seven studies with a total of 314 subjects were included. Meta-analysis results indicated that compared with healthy subjects, mTBI patients had enhanced activation in the left anterior angular gyrus, left occipital joint visual, left midbrain, right temporal angular gyrus, right cerebellar tonsil, left frontal insula, and right inferior frontal gyrus. mTBI patients had attenuated activation in the right dorsolateral prefrontal lobe, left cerebellar anterior lobe, left dorsolateral prefrontal lobe, right middle frontal gyrus, right posterior cingulate gyrus, left joint visual, left supramarginal gyrus, left middle frontal gyrus, right precuneus, left dorsolateral prefrontal cortex, right frontal eye field, right lower parietal gyrus, corpus callosum, right frontal pole region, and left prefrontal lobe. Further joint analysis revealed that the dorsolateral prefrontal lobe of the right middle frontal gyrus was a region of attenuated co-activation. The dorsolateral prefrontal lobe of the right middle frontal gyrus showing attenuated activation was the main brain region distinguishing mTBI patients from healthy subjects. Cognitive deficits could be associated with attenuated activation in the dorsolateral prefrontal lobe of the right middle frontal gyrus, which could be due to a decline in the recruitment ability of the neural network involved in controlling attention.     

Axonal injury following mild traumatic brain injury is exacerbated by repetitive insult and is linked to the delayed attenuation of NeuN expression without concomitant neuronal death in the mouse

Mild traumatic brain injury (mTBI) affects brain structure and function and can lead to persistent abnormalities. Repetitive mTBI exacerbates the acute phase response to injury. Nonetheless, its long‐term implications remain poorly understood, particularly in the context of traumatic axonal injury (TAI), a player in TBI morbidity via axonal disconnection, synaptic loss and retrograde neuronal perturbation. In contrast to the examination of these processes in the acute phase of injury, the chronic‐phase burden of TAI and/or its implications for retrograde neuronal perturbation or death have received little consideration. To critically assess this issue, murine neocortical tissue was investigated at acute (24‐h postinjury, 24hpi) and chronic time points (28‐days postinjury, 28dpi) after singular or repetitive mTBI induced by central fluid percussion injury (cFPI). Neurons were immunofluorescently labeled for NeuroTrace and NeuN (all neurons), p‐c‐Jun (axotomized neurons) and DRAQ5 (cell nuclei), imaged in 3D and quantified in automated manner. Single mTBI produced axotomy in 10% of neurons at 24hpi and the percentage increased after repetitive injury. The fraction of p‐c‐Jun+ neurons decreased at 28dpi but without neuronal loss (NeuroTrace), suggesting their reorganization and/or repair following TAI. In contrast, NeuN+ neurons decreased with repetitive injury at 24hpi while the corresponding fraction of NeuroTrace+ neurons decreased over 28dpi. Attenuated NeuN expression was linked exclusively to non‐axotomized neurons at 24hpi which extended to the axotomized at 28dpi, revealing a delayed response of the axotomized neurons. Collectively, we demonstrate an increased burden of TAI after repetitive mTBI, which is most striking in the acute phase response to the injury. Our finding of widespread axotomy in large fields of intact neurons contradicts the notion that repetitive mTBI elicits progressive neuronal death, rather, emphasizing the importance of axotomy‐mediated change.     

Sleep in overweight adolescents: shorter sleep, poorer sleep quality, sleepiness, and sleep-disordered breathing

OBJECTIVE: To document the sleep of overweight adolescents and to explore the degree to which weight-related sleep pathology might account for diminished psychosocial outcome. METHODS: Sixty children aged 10-16.9 from a weight-management clinic were compared to 22 healthy controls using comprehensive actigraphic, polysomnographic, and parent- and self-report questionnaire assessments. RESULTS: Overweight participants averaged more symptoms of sleep-disordered breathing, later sleep onset, shorter sleep time, and more disrupted sleep than controls. Although the groups did not differ in self-reported sleep habits, multiple concerns were reported by parents of overweight participants, including daytime sleepiness, parasomnias, and inadequate sleep. Group differences in academic grades and depressive symptoms were at least partially accounted for by short sleep and daytime sleepiness. CONCLUSIONS: Excessive weight is associated with an increased risk of sleep problems. There is a need for further research in this area and for clinicians who work with overweight children to evaluate their sleep.     

Persistent neurobehavioral problems following mild traumatic brain injury.

Accumulating research documents typical rates in the range of 85% of mild traumatic brain injury (MTBI) showing prompt, complete resolution with 15% suffering from persistent neurobehavioral impairments. Studies of neurobehavioral symptoms of MTBI have not separated these two populations, resulting in either inconclusive or contradictory conclusions concerning the relationship of MTBI with residual behavioral problems. This project studied 70 MTBI patients with persistent neurobehavioral problems at two time intervals post-injury to determine whether there are consistent neurobehavioral patterns considered to be sequelae of MTBI. A matched group of 40 normal subjects provided control data. While most behavioral problems showed improvement, 21% tended to show significant behavioral impairment compared to controls at 12 or more months post-injury. Neurochemical bases of neuronal degeneration may account for some of the behavioral deterioration following MTBI.     

Regional difference of reactive astrogliosis following traumatic brain injury revealed by hGFAP-GFP transgenic mice

Reactive astrocytes greatly influence the wound healing and neuronal regeneration processes following brain injury. However, the origin and fate of reactive astrocytes appear to be different depending on the type, severity and duration of brain injury. Using the cryogenic traumatic brain injury model, here we comprehensively addressed the regional differences of reactive astrocytes in the injured cortex. In the proximal region of injury site, NG2-expressing and cytoplasmic Olig2-labeled cells were densely localized 3 days after the injury. Next to this proximal layer, most of reactive astrocytes did not express NG2 but exhibited radial glia-like shape with elongated processes. Accordingly, they expressed the progenitor or radial glial markers, such as vimentin, brain lipid binding protein (BLBP) and the green fluorescent protein (GFP) under the control of the human GFAP (hGFAP) promoter. However, only few glial fibrillary acidic protein (GFAP) expressing astrocytes were found in this layer. Distal to the injury site, most of astrocytes strongly expressed GFAP with hypertonic morphology. At day 15 after injury, all layers expressing GFAP and other marker expressions disappeared, indicating the termination of reactive astrogliosis. Taken together, our data suggest that reactive astrogliosis occurs in a regionally segregated manner in the early phase of brain injury.     

Long-term parental and family adaptation following pediatric brain injury

OBJECTIVE: To determine whether parents of children with traumatic brain injuries (TBI) report increased injury-related burden, distress, and family dysfunction and to examine the effects of attrition on the results. METHODS: Children with severe TBI, moderate TBI, and orthopedic injuries were followed at six time points from baseline to 6 years after injury. Parents completed measures of injury-related burden, psychological distress, and family functioning at each assessment. Mixed model analysis was used to examine long-term changes. RESULTS: Attrition was higher among families in the severe TBI group with lower burden thereby amplifying group differences. The severe TBI group reported higher injury-related burden over time after injury than the other groups. Family functioning was moderated by social resources. Families of children with severe TBI and low resources reporting deteriorating functioning over the follow-up interval. CONCLUSIONS: Although environmental advantages moderate long-term effects on family functioning, families of children with severe TBI experience long-standing injury-related burden.     

Slow wave activity moderates the association between new learning and traumatic brain injury severity

Study ObjectivesSleep–wake complaints and difficulties in making new learning are among the most persistent and challenging long-term sequelea following moderate to severe traumatic brain injury (TBI). Yet, it is unclear whether, and to what extent, sleep characteristics during the chronic stage of TBI contribute to sleep–wake and cognitive complaints. We aimed to characterize sleep architecture in chronic moderate to severe TBI adults and assess whether non-rapid eye movement slow wave activity (SWA) is associated to next day performance in episodic memory tasks according to TBI severity.MethodsForty-two moderate to severe TBI participants, 12–47 months post-injury, and 38 healthy controls were tested with one night of in-laboratory polysomnography, followed the next morning by questionnaires (sleep quality, fatigue, and sleepiness) and neuropsychological assessment. We used multiple regression analyses to assess the moderator effect of SWA power on TBI severity and next-day memory performance.ResultsWe found that TBI participants reported worse sleep quality and fatigue, and had worse cognitive performance than controls. No between group differences were found on macro- and micro-architecture of sleep. However, SWA significantly interacted with TBI severity to explain next-day memory performance: higher SWA was more strongly associated to better memory performance in more severe TBI compared to milder TBI.ConclusionsThis study provides evidence that the injured brain is able to produce macro- and micro-architecture of sleep comparable to what is seen in healthy controls. However, with increasing TBI severity, lower non-rapid eye movement SWA power is associated with reduced ability to learn and memorise new information the following day.