Traumatic Brain Injury In Adolescents Research Articles

Smartphone App-Delivered Mindfulness-Based Intervention for Mild Traumatic Brain Injury in Adolescents: Protocol for a Feasibility Randomized Controlled Trial.

Concussion in children and adolescents is a significant public health concern, with 30% to 35% of patients at risk for prolonged emotional, cognitive, sleep, or physical symptoms. These symptoms negatively impact a child's quality of life while interfering with their participation in important neurodevelopmental activities such as schoolwork, socializing, and sports. Early psychological intervention following a concussion may improve the ability to regulate emotions and adapt to postinjury symptoms, resulting in the greater acceptance of change; reduced stress; and recovery of somatic, emotional, and cognitive symptoms. The primary objective of this study is to assess the feasibility of conducting a parallel-group (1:1) randomized controlled trial (RCT) to evaluate a digital therapeutics (DTx) mindfulness-based intervention (MBI) in adolescents aged 12 to <18 years. The attention-matched comparator intervention (a math game also used in previous RCTs) will be delivered on the same DTx platform. Both groups will be provided with the standard of care guidelines. The secondary objective is to examine intervention trends for quality of life; resilience; self-efficacy; cognition such as attention, working memory, and executive functioning; symptom burden; and anxiety and depression scores at 4 weeks after concussion, which will inform a more definitive RCT. A subsample will be used to examine whether those randomized to the experimental intervention group have different brain-based imaging patterns compared with those randomized to the control group. This study is a double-blind Health Canada-regulated trial. A total of 70 participants will be enrolled within 7 days of concussion and randomly assigned to receive the 4-week DTx MBI (experimental group) or comparator intervention. Feasibility will be assessed based on the recruitment rate, treatment adherence to both interventions, and retention. All outcome measures will be evaluated before the intervention (within 7 days after injury) and at 1, 2, and 4 weeks after the injury. A subset of 60 participants will undergo magnetic resonance imaging within 72 hours and at 4 weeks after recruitment to identify the neurophysiological mechanisms underlying the potential benefits from MBI training in adolescents following a concussion. The recruitment began in October 2022, and the data collection is expected to be completed by September 2024. Data collection and management is still in progress; therefore, data analysis is yet to be conducted. This trial will confirm the feasibility and resolve uncertainties to inform a future definitive multicenter efficacy RCT. If proven effective, a smartphone-based MBI has the potential to be an accessible and low-risk preventive treatment for youth at risk of experiencing prolonged postconcussion symptoms and complications. ClinicalTrials.gov NCT05105802; https://classic.clinicaltrials.gov/ct2/show/NCT05105802. DERR1-10.2196/57226.

Traumatic brain injury, working memory-related neural processing, and alcohol experimentation behaviors in youth from the ABCD cohort

Adolescent traumatic brain injury (TBI) has long-term effects on brain functioning and behavior, impacting neural activity under cognitive load, especially in the reward network. Adolescent TBI is also linked to risk-taking behaviors including alcohol misuse. It remains unclear how TBI and neural functioning interact to predict alcohol experimentation during adolescence. Using Adolescent Brain Cognitive Development (ABCD) study data, this project examined if TBI at ages 9–10 predicts increased odds of alcohol sipping at ages 11–13 and if this association is moderated by neural activity during the Emotional EN-Back working memory task at ages 11–13. Logistic regression analyses showed that neural activity in regions of the fronto-basal ganglia network predicted increased odds of sipping alcohol by ages 11–13 (p < .05). TBI and left frontal pole activity interacted to predict alcohol sipping (OR = 0.507, 95% CI [0.303 - 0.846], p = .009) – increased activity predicted decreased odds of alcohol sipping for those with a TBI (OR = 0.516, 95% CI [0.314 - 0.850], p = .009), but not for those without (OR = 0.971, 95% CI [0.931 −1.012], p = .159). These findings suggest that for youth with a TBI, increased BOLD activity in the frontal pole, underlying working memory, may be uniquely protective against the early initiation of alcohol experimentation. Future work will examine TBI and alcohol misuse in the ABCD cohort across more time points and the impact of personality traits such as impulsivity on these associations.

Adolescent traumatic brain injury leads to incremental neural impairment in middle-aged mice: role of persistent oxidative stress and neuroinflammation.

Traumatic brain injury (TBI) increases the risk of mental disorders and neurodegenerative diseases in the chronic phase. However, there is limited neuropathological or molecular data on the long-term neural dysfunction and its potential mechanism following adolescent TBI. A total of 160 male mice aged 8 weeks were used to mimic moderate TBI by controlled cortical impact. At 1, 3, 6 and 12 months post-injury (mpi), different neurological functions were evaluated by elevated plus maze, forced swimming test, sucrose preference test and Morris water maze. The levels of oxidative stress, antioxidant response, reactive astrocytes and microglia, and expression of inflammatory cytokines were subsequently assessed in the ipsilateral hippocampus, followed by neuronal apoptosis detection. Additionally, the morphological complexity of hippocampal astrocytes was evaluated by Sholl analysis. The adolescent mice exhibited persistent and incremental deficits in memory and anxiety-like behavior after TBI, which were sharply exacerbated at 12 mpi. Depression-like behaviors were observed in TBI mice at 6 mpi and 12 mpi. Compared with the age-matched control mice, apoptotic neurons were observed in the ipsilateral hippocampus during the chronic phase of TBI, which were accompanied by enhanced oxidative stress, and expression of inflammatory cytokines (IL-1β and TNF-α). Moreover, the reactive astrogliosis and microgliosis in the ipsilateral hippocampus were observed in the late phase of TBI, especially at 12 mpi. Adolescent TBI leads to incremental cognitive dysfunction, and depression- and anxiety-like behaviors in middle-aged mice. The chronic persistent neuroinflammation and oxidative stress account for the neuronal loss and neural dysfunction in the ipsilateral hippocampus. Our results provide evidence for the pathogenesis of chronic neural damage following TBI and shed new light on the treatment of TBI-induced late-phase neurological dysfunction.

Delirium following traumatic brain injury in adolescents: Symptomatology and prediction of ability to return to school or employment 1-year post-injury.

There is a limited evidence-base describing clinical features of delirium in youth. What is known is largely extrapolated from studies of adults or samples with heterogeneous etiologies. It is unclear if the symptoms experienced by adolescents differ from those experienced by adults, or the degree to which delirium impacts the ability of adolescents to return to school or work. To describe delirium symptomatology among adolescents following a severe traumatic brain injury (TBI). Symptoms were compared by adolescent delirium status and across age groups. Delirium and its relationship with adolescent employability 1 year post-injury was also examined. Exploratory secondary analysis of prospectively collected data. Free-standing rehabilitation hospital. Severely injured TBI Model Systems neurorehabilitation admissions (n = 243; median Glasgow Coma Scale = 7). The sample was divided into three age groups (adolescents, 16-21 years, n = 63; adults 22-49 years, n = 133; older adults ≥50 years, n = 47). Not applicable. We assessed patients using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnostic criteria and the Delirium Rating Scale-Revised 98 (DRS-R-98). The employability item from the Disability Rating Scale was the primary 1-year outcome. Most items on the DRS-R-98 differentiated delirious from non-delirious adolescents. Only "delusions" differed among age groups. Among adolescents, delirium status 1 month post-TBI provided acceptable classification of employability prediction 1 year later (area under the curve [AUC]: 0.80, 95% confidence interval [CI]: 0.69-0.91, p < .001). Delirium symptom severity (AUC: 0.86, 95% CI: 0.68-1.03, SE: 0.09; p < .001) and days of post-traumatic amnesia (AUC: 0.85, 95% CI: 0.68-1.01, SE: 0.08; p < .001) provided excellent prediction of outcomes for TBI patients in delirium. Delirium symptomatology was similar among age groups and useful in differentiating the delirium status within the adolescent TBI group. Delirium and symptom severity at 1 month post-TBI were highly predictive of poor outcomes. Findings from this study support the utility of DRS-R-98 at 1 month post-injury to inform treatment and planning.

You only get one brain: adult reflections on coping and recovery after traumatic brain injury in adolescence

ABSTRACT Background TBI during adolescence can result in significant acute symptoms that can persist into adulthood. This research analyzed retrospective qualitative accounts of young adults who had sustained a TBI in adolescence to explore coping and recovery processes specific to this developmental stage. Methods Thirteen adults (aged 20–25 years; mean 23 years) who sustained a mild (n = 12) or moderate (n = 1) TBI during adolescence (aged 13–17 years at injury), approximately 7.7 years (range = 6.7–8.0 years) prior, participated. Semi-structured individual interviews, analyzed using thematic analysis, explored participants’ experiences following their TBIs. Results Thematic data analysis produced two key categories of themes relating to recovery processes: (1) Individual factors impacting coping, with themes of learning to cope with difficulties, seeking acceptance and balance, and finding meaning; and (2) Social factors impacting coping, which included themes of feeling included, relying on family, professionals didn’t get it, and lacking someone who understands. Conclusions Recovery following TBI sustained during adolescence could be maximized by facilitating greater understanding of specific impacts on young people among clinicians and family, longer term monitoring of symptoms including emotional reactions to symptoms, and the provision of emotional support.

Prehospital care of pediatric traumatic brain injury

Traumatic brain injury (TBI) in children and adolescents is associated with significant morbidity and, in severe TBI, mortality. The aim of this article is to provide an overview of the spectrum of TBI, its pathophysiology, and current treatment recommendations for prehospital management of children and adolescents with TBI. The current literature was reviewed for studies on the management of TBI in children and adolescents. In recent years, alarge number of scientific studies have been published that have resulted in evidence-based guidelines for primary care of children with TBI. The primary aim is to minimize secondary brain damage following TBI, for which immediate assessment of the severity of TBI at the scene based on clinical findings and the accident mechanism and initiation of specific treatment measures to prevent hypoxia, hypotension, and hypothermia are critical. Not only prehospital management, but also the rapid transfer of children with severe TBI to centers with high neurosurgical, pediatric surgical, and pediatric intensive care expertise is of particular importance to improve survival and neurological outcome after severe TBI. Structured prehospital management may help reduce secondary brain injury after TBI and lead to improved clinical outcomes.

Brief Oxygen Exposure after Traumatic Brain Injury Hastens Recovery and Promotes Adaptive Chronic Endoplasmic Reticulum Stress Responses.

Traumatic brain injury (TBI) is a major public health concern, particularly in adolescents who have a higher mortality and incidence of visual pathway injury compared to adult patients. Likewise, we have found disparities between adult and adolescent TBI outcomes in rodents. Most interestingly, adolescents suffer a prolonged apneic period immediately post-injury, leading to higher mortality; therefore, we implemented a brief oxygen exposure paradigm to circumvent this increased mortality. Adolescent male mice experienced a closed-head weight-drop TBI and were then exposed to 100% O2 until normal breathing returned or recovered in room air. We followed mice for 7 and 30 days and assessed their optokinetic response; retinal ganglion cell loss; axonal degeneration; glial reactivity; and retinal ER stress protein levels. O2 reduced adolescent mortality by 40%, improved post-injury visual acuity, and reduced axonal degeneration and gliosis in optical projection regions. ER stress protein expression was altered in injured mice, and mice given O2 utilized different ER stress pathways in a time-dependent manner. Finally, O2 exposure may be mediating these ER stress responses through regulation of the redox-sensitive ER folding protein ERO1α, which has been linked to a reduction in the toxic effects of free radicals in other animal models of ER stress.

Salt diet Induces Neuroinflammatory Response, Microbiome Dysregulation and Associated with Long-term Anxiety Following Repetitive Closed Head Injury. (S28.003)

<h3>Objective:</h3> Investigate the effects of salt diet on neuroinflammatory response, behavior, and microbiome dysregulation following repetitive closed head injury model. <h3>Background:</h3> Concussions continue to be a prominent public health concern, with an estimated 1.6–3.8 million incidences annually in the United States. Younger populations are experiencing the highest rates of concussion and nearly all athletic endeavors have some risk of concussive injury. Concerns surrounding the potential risks of long-term cognitive and medical outcomes made adolescent traumatic brain injury (TBI) a central focus of public attention. Coupled to these events, recent clinical studies have shown that lifestyle factors, including salt diet, constitute additional risk affecting TBI consequences and neuropathophysiological outcomes. However, the impact of salt diet on the pathophysiology of TBI and whether it exacerbates post-injury outcomes is still largely unknown. <h3>Design/Methods:</h3> We investigated if the exposure to a high salt diet (HSD) would alter hemodynamics, behavior, innate immune response and microbiome diversity after repetitive mild closed head injury in adolescent mice. Mice were injured with a three hit model (3HD) and then maintained on a HSD or standard diet (STD) for 12 weeks. <h3>Results:</h3> We found that HSD didn’t change systolic and diastolic blood pressure, and heart rate compared with STD group. HSD group was associated with worsening anxiety-like behavior at 12 weeks post diet administration. HSD induced microgliosis and proinflammatory microglial transcriptomic signature including upregulation in interferon gamma, Interferon beta, T cells proliferation pathways. Consistently, we found upregulation of proinflammatory Tumor necrotic factor (TNF) in brain compared to Sham-HSD and TBI-STD groups. HSD was the main driver of microbiome dysregulation in both TBI and Sham groups. We found that Eubacterium xylanophilum and Lachnospiraceae bacterium associated with an anxiety phenotype following injury at 12 weeks post diet administration. <h3>Conclusions:</h3> Salt diet associated with increasing risk of worsening anxiety and exacerbating chronic neuroinflammation post repetitive head injury. <b>Disclosure:</b> Dr. Izzy has received publishing royalties from a publication relating to health care. Taha Yahya has nothing to disclose. Dr. Cao has nothing to disclose. Mr. Albastaki has nothing to disclose. Dr. Waed has nothing to disclose. Ms. Chopra has nothing to disclose. Miss EKWUDO has nothing to disclose. Miss Kurdeikaite has nothing to disclose. Ms. Moraes Verissimo has received personal compensation for serving as an employee of Brigham and Women’s Hospital. Ms. Moraes Verissimo has received personal compensation for serving as an employee of Brigham and Women’s Hospital and Harvard Medical School. Ms. Moraes Verissimo has received personal compensation for serving as an employee of Von Medical, Inc.. Ms. Moraes Verissimo has received personal compensation for serving as an employee of Nova Southeastern University. Ms. Moraes Verissimo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Montachem Company. Dr. Cox has received personal compensation for serving as an employee of Anaerobe Systems. The institution of Dr. Cox has received research support from Infectious Disease Society. The institution of Dr. Cox has received research support from BrightFocus Foundation. Dr. Cox has received intellectual property interests from a discovery or technology relating to health care. Dr. Zafonte has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MYOMO. Dr. Zafonte has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Kisbee. Dr. Zafonte has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers in Neurology. The institution of Dr. Zafonte has received research support from NIDILRR. The institution of Dr. Zafonte has received research support from NIH. The institution of Dr. Zafonte has received research support from FPHS study. Dr. Zafonte has received publishing royalties from a publication relating to health care. Michael J. Whalen has nothing to disclose.

Memory Impairments Associated With Mild Traumatic Brain Injury: A Critically Appraised Topic

Clinical Question: Do sports-related mild traumatic brain injury in adolescents and young adults produce changes that can be identified with functional magnetic resonance imaging that are associated with memory impairment? Clinical Bottom Line: After sport-related mild traumatic brain injury, functional magnetic resonance imaging identified inconsistent structural changes (e.g., cortical thickness changes, brain activation patterns), and negative performance changes in memory function (e.g., lower neuropsychological scores) in adolescents and young adults 9 days to more than a year following injury.

Repetitive Mild Closed Head Injury in Adolescent Mice Is Associated with Impaired Proteostasis, Neuroinflammation, and Tauopathy.

Repetitive mild traumatic brain injury (mTBI) in children and adolescents leads to acute and chronic neurologic sequelae and is linked to later life neurodegenerative disease. However, the biological mechanisms connecting early life mTBI to neurodegeneration remain unknown. Using an adolescent mouse repetitive closed head injury model that induces progressive cognitive impairment in males and anxiety in females in the absence of overt histopathology, we examined transcriptional and translational changes in neurons isolated from sham and injured brain in the chronic phase after injury. At 14 months, single-nuclei RNA sequencing of cortical brain tissue identified disruption of genes associated with neuronal proteostasis and evidence for disrupted ligand-receptor signaling networks in injured mice. Western blot analysis of isolated neurons showed evidence of inflammasome activation and downstream IL-1β processing, as previously demonstrated in acute CNS injury models, and accumulation of misfolded, hyperphosphorylated tau, and changes in expression of proteins suggestive of impaired translation in males but not in females. At 6 months, injured IL-1 receptor 1 (IL-1R1) KO mice, which are protected from postinjury cognitive deficits, had decreased accumulation of pro-IL-1β and misfolded tau in cortex and cerebellum, suggesting that IL-1R1 is upstream of inflammasome priming (defined as increase in pro-IL-1β) and abnormal tau phosphorylation. Together, our findings provide evidence for neuronal inflammasome activation and impaired proteostasis as key mechanisms linking repetitive mTBI in adolescence to later life neurologic dysfunction and neurodegeneration.SIGNIFICANCE STATEMENT Repetitive mild closed head injury in adolescent male mice leads to impaired proteostasis, tau phosphorylation, and inflammasome activation in neurons later in adulthood through mechanisms involving IL-1 receptor 1. The data are the first to link repetitive mild traumatic brain injury in adolescence to neurodegeneration and suggest molecular targets and pathways to prevent neurologic sequelae in the chronic period after injuries.

Longitudinal assessment of hemodynamic alterations after mild traumatic brain injury in adolescents: Selected case study review

Alterations in the neurovasculature after traumatic brain injury (TBI) represents a significant sequelae. However, despite theoretical and empirical evidence supporting the near-ubiquity of vascular injury, its pathophysiology remains elusive. Although this has been shown for all grades of TBI, the vascular changes after injuries with the broad mild traumatic brain injuries (mTBI) classification, remain particularly difficult to describe. Our group has previously demonstrated hemodynamic alterations in mTBI by utilizing transcranial Doppler ultrasound and cerebrovascular reactivity in a cross-sectional study. That work identified a phasic progression of deviations over varying days post-injury. These phases were then characterized by a set of inverse models that provided a hypothetical process of hemodynamic dysfunction after mTBI. This model set provides a framework with the potential for guiding clinical treatment over the course of recovery. However, it is still unclear if individual patients will progress through the phases of dysfunction similar to that found at the population level. The work presented here explores six individual patients with high-density data collected during their post-injury recovery. Breath-hold index (BHI) was found to be the most robust feature related to mTBI longitudinally. All six subjects exhibited BHI recovery curves that followed the population model's progression. The changes in pulsatile features lacked the universality of BHI, but were present in subjects with higher self-reported symptom scores and longer periods of recovery. This work suggests neurovascular dysfunction after an mTBI may be a robust phenomenon. Additionally, the capabilities of TCD in capturing these changes highlights its potential for aiding clinicians in monitoring patient's recovery post mTBI.

Alcohol is not associated with increased mortality in adolescent traumatic brain injury patients

PurposeCompared to adults, there is a paucity of data regarding the association of a positive alcohol screen (PAS) and outcomes in adolescent patients with traumatic brain injury (TBI). We hypothesize adolescent TBI patients with a PAS on admission to have increased mortality compared to patients with a negative alcohol screen.MethodsThe 2017 Trauma Quality Improvement Program database was queried for patients aged 13–17 years presenting with a TBI and serum alcohol screen. Patients with missing information regarding midline shift on imaging and Glasgow Coma Scale (GCS) score were excluded. A multivariable logistic regression analysis for mortality was performed.ResultsFrom 2553 adolescent TBI patients with an alcohol screen, 220 (8.6%) had a PAS. Median injury severity scores and rates of penetrating trauma (all p > 0.05) were similar between alcohol positive and negative patients. Patients with a PAS had a similar mortality rate (13.2% vs. 12.1%, p = 0.64) compared to patients with a negative screen. Multivariate logistic regression controlling for risk factors associated with mortality revealed a PAS to confer a similar risk of mortality compared to alcohol negative patients (p = 0.40).ConclusionAdolescent TBI patients with a PAS had similar associated risk of mortality compared to patients with a negative alcohol screen.

Diffusion Tensor Imaging Correlates of Resilience Following Adolescent Traumatic Brain Injury.

Traumatic brain injury (TBI) is associated with considerable mortality and morbidity in adolescents, but positive outcomes are possible. Resilience is the concept that some individuals flourish despite significant adversity. To determine if there is a relationship between resilience-promoting factors that are known to promote resilience and white matter (WM) microstructure 1 year after complicated mild TBI or moderate or severe TBI that is sustained by adolescents. We examined the relationship between performance on a self-report measure of resilience-promoting factors and WM integrity assessed by diffusion tensor imaging in a group of adolescents who had sustained either a TBI (n = 38) or an orthopedic injury (OI) (n = 23). Immediately following injury, the individuals with TBI and the OI controls had comparable levels of resilience-promoting factors; however, at 1 year post injury, the TBI group endorsed fewer resilience-promoting factors and exhibited WM disruption compared with the OI controls. The individuals with TBI who had more resilience-promoting factors at 1 year post injury exhibited increased WM integrity, but the OI controls did not. Findings were particularly strong for the following structures: anterior corona radiata, anterior limb of the internal capsule, and genu of the corpus callosum-structures that are implicated in social cognition and are frequently disrupted after TBI. Relationships were notable for caregiver and community-level resilience-promoting factors. The current findings are some of the first to indicate neurobiological evidence of previously noted buffering effects of resilience-promoting factors in individuals with TBI.

You Only Get One Brain: Adult Reflections on the Long-Term Impacts of Traumatic Brain Injury in Adolescence

AbstractBackground:This research adds to scarce literature regarding adolescent experiences of traumatic brain injury (TBI). Retrospective accounts of young adults who had sustained a TBI in adolescence were analysed to explore the perceived impact this had on their lives and forming identities during this important developmental stage.Methods:Thirteen adults (aged 20–25 years; mean 23 years) who sustained a mild or moderate TBI during adolescence (i.e. aged 13–17 years at injury), approximately 7.7 years (range = 6.7–8.0 years) prior, participated in the research. Semi-structured individual interviews, analysed using thematic analysis, explored participants’ experiences following their TBIs.Results:Thematic analysis of interview data produced two categories of themes: (1) Impacts on Important Areas of Life, which included: schoolwork suffered, career opportunities became limited, struggling with work and missing out socially; and (2) Impacts on Identity: with themes including feeling ‘stupid’, feeling self-conscious, loss of social identity and being dependent.Conclusions:TBI sustained during adolescence can have broad impacts on important areas of life and on developing identity.

You only get one brain. Adult reflections on acute and ongoing symptom experiences after traumatic brain injury in adolescence

ABSTRACT Background This research adds to the scarce literature regarding adolescent experiences of traumatic brain injury (TBI). It uses a qualitative methodology to explore the symptoms experienced after sustaining a TBI at this unique stage of development including their persistence into adulthood. Methods Thirteen adults (aged 20–25 years; mean 23 years) who sustained a mild-moderate TBI during adolescence (aged 13–17 years at injury), approximately 7.7 years (range = 6.7–8.0 years) prior, participated in the research. Semi-structured individual interviews, analyzed using thematic analysis, explored participants’ experiences surrounding and following their TBIs. Results TBI during adolescence can result in significant acute symptoms, particularly headaches, fatigue, and difficulties in thinking. Participants’ descriptions of the extent and impact of these symptoms reflected feelings of frustration and often anxiety and/or depression. Difficulties could persist for years post-TBI and sometimes had not resolved at all. Conclusions Even mild TBI during adolescence can result in significant acute and ongoing symptoms, which can contribute to emotional distress in the long term.

The experience of families following traumatic brain injury in adult populations: A meta-synthesis of narrative structures

BackgroundTraumatic brain injury has a significant effect on uninjured family members. Typically, this has been examined with a focus on psychopathological outcomes including stress, depression and anxiety. However, in recent years there has been increasing interest in the subjective experiences of families post-injury leading to a plethora of qualitative studies. Therefore, an in-depth examination and synthesis of this literature is now relevant and timely. ObjectiveTo examine the subjective experiences of families following traumatic brain injury in adult populations in the sub/post-acute period through the synthesis of original qualitative research. DesignThis paper presents a meta-synthesis using Thomas and Harden's framework of ‘thematic synthesis’ rooted in a critical realist philosophy. Data sourcesIn July 2019 five electronic databases, were searched for the terms ‘traumatic brain injury’, ‘family’ and ‘qualitative’. Studies were included if the primary research reported qualitative data about the subjective experiences of family members of adults with traumatic brain injury and had been published in a peer reviewed journal. Studies with mixed brain injury samples, child or adolescent traumatic brain injury or disorders of consciousness were excluded. Hand searching and citation searches were also completed. Review methodsTwo reviewers screened titles, abstracts and full text and reached consensus through critical discussion. Thirty papers were finally agreed for inclusion in this review. Each study was then assessed for relevance, resonance and rigour using the Critical Appraisal Skills Programme (CASP) tool. Line by line coding of the findings in each paper was conducted as the basis for a thematic analysis and synthesis. ResultsDescriptive themes were identified followed later by analytical themes. This final stage was informed by a narrative lens and from these, eight narrative functions belonging to four dimensions were identified from the subjective experiences of families post-traumatic brain injury. Specifically, these were: (1) Displacing and Anchoring; (2) Rupturing and Stabilising; (3) Isolating and Connecting; (4) Harming and Healing. ConclusionsThe interpretation of the narrative functions revealed the substantial existential work involved in negotiating lives, maintaining family system equilibrium and moving forward. As such, family members have their own unique narrative needs. Despite contemporary service models built around the injured person, service providers are well placed to support families in this everyday narrative work through actively attending to narrative structures and understanding the implications of these for family experience.The study protocol was registered with PROSPERO (International prospective register of systematic reviews) in July 2018 (Registration number: CRD42018085824).Tweetable abstract: This synthesis showed the immense and invisible work required for family members to maintain family system equilibrium and negotiate their lives post-TBI.

Paternal exposure to exercise and/or caffeine and alcohol modify offspring behavioral and pathophysiological recovery from repetitive mild traumatic brain injury in adolescence.

Only recently has the scope of parental research expanded to include the paternal sphere with epidemiological studies implicating stress, nutrition and alcohol consumption in the neurobiological and behavioral characteristics of offspring. This study was designed to determine if paternal exposure to caffeine, alcohol and exercise prior to conception would improve or exacerbate offspring recovery from adolescent repetitive mild traumatic brain injury (RmTBI). Sires received 7 weeks of standard drinking water, or caffeine and ethanol and were housed in regular cages or cages with running wheels, prior to being mated to control females. At postnatal day 40, offspring were administered RmTBI or sham injuries and were assessed for post concussive symptomology. Post-mortem quantitative real-time polymerase chain reaction (qRT-PCR) was used to assess gene expression in the prefrontal cortex (PFC), nucleus accumbens (NAc) and changes in telomere length. Additionally, enzyme-linked immunosorbent assay (ELISA's) were run on serum to detect levels of cytokines, chemokines and sex hormones. Paternal experience did not improve or exacerbate RmTBI behavioral outcomes. However, female and male offspring displayed unique responses to RmTBI and paternal experience, resulting in changes in physical, behavioral and molecular outcomes. Injury and paternal exercise modified changes in female offspring, whereas male offspring were affected by paternal exercise, caffeine and alcohol treatment. Additionally, paternal experience and RmTBI modified expression of many genes in the PFC, NAc, telomere length and levels of sex hormones. Although further exploration is required to understand the heterogeneity that exists in disease risk and resiliency, this study provides corroborating evidence that paternal experiences prior to conception influences offspring development.

Sex Differences in the Outcomes of Mild Traumatic Brain Injury in Children Presenting to the Emergency Department.

Sex differences after concussion have been studied largely in high school and college athletes, often without reference to comparison groups without concussion. This study sought to evaluate sex differences in outcomes among all children and adolescents presenting to the Emergency Department (ED) for either mild traumatic brain injury (TBI) or orthopedic injury (OI), regardless of mechanism of injury. The study involved a concurrent cohort, prospective study design with longitudinal follow-up. Participants were eight to 16 years old with mild TBI (n = 143) or OI (n = 73). They were recruited and completed an initial assessment at EDs at two children's hospitals. They returned for a post-acute assessment within two weeks of injury and for follow-up assessments at three and six months. Outcomes included child and parent proxy ratings of somatic and cognitive symptoms, and standardized tests of cognitive functioning and balance. Sex did not moderate group differences in balance, fluid or crystallized cognitive ability, or child or parent proxy ratings of somatic or cognitive symptoms. Both parents and children reported more somatic symptoms in girls than boys, but in both groups. Compared with the OI group, the mild TBI group showed significantly lower fluid cognitive ability at the post-acute assessment and significantly higher somatic and cognitive symptoms according to both child and parent proxy ratings across the first two weeks post-injury. The results suggest that sex does not moderate the outcomes of mild TBI in a pediatric ED population. Previous research pointing to sex differences after concussion may reflect the lack of comparison groups, as well as a focus on adolescents and young adults and sport-related concussion. Future research should investigate whether sex moderates the outcomes of pediatric mild TBI in adolescents but not in pre-adolescent children.

Effects of Remote Immune Activation on Performance in the 5-Choice Serial Reaction Time Task Following Mild Traumatic Brain Injury in Adolescence

In adult pre-clinical models, traumatic brain injury (TBI) has been shown to prime microglia, exaggerating the central inflammatory response to an acute immune challenge, worsening depressive-like behavior, and enhancing cognitive deficits. Whether this phenomenon exists following mTBI during adolescence has yet to be explored, with age at injury potentially altering the inflammatory response. Furthermore, to date, studies have predominantly examined hippocampal-dependent learning domains, although pre-frontal cortex-driven functions, including attention, motivation, and impulsivity, are significantly affected by both adolescent TBI and acute inflammatory stimuli. As such, the current study examined the effects of a single acute peripheral dose of LPS (0.33 mg/kg) given in adulthood following mTBI in mid-adolescence in male Sprague–Dawley rats on performance in the 5-choice serial reaction time task (5-CSRTT). Only previously injured animals given LPS showed an increase in omissions and reward collection latency on the 5-CSRTT, with no effect noted in sham animals given LPS. This is suggestive of impaired motivation and a prolonged central inflammatory response to LPS administration in these animals. Indeed, morphological analysis of myeloid cells within the pre-frontal cortex, via IBA1 immunohistochemistry, found that injured animals administered LPS had an increase in complexity in IBA1+ve cells, an effect that was seen to a lesser extent in sham animals. These findings suggest that there may be ongoing alterations in the effects of acute inflammatory stimuli that are driven, in part by increased reactivity of microglial cells.

Reading Abilities Post Traumatic Brain Injury in Adolescents and Adults: A Systematic Review and Meta-Analysis.

Purpose People with traumatic brain injury (TBI) often struggle with complex reading, limiting participation in work and educational settings. This systematic review and meta-analysis examined studies of reading conducted with adolescents and adults with TBI to describe reading problems post TBI and investigate underlying factors for the effects of TBI on reading abilities. Method The search was conducted in EBSCO (including MEDLINE, PsycINFO, etc.), BIOSIS, ProQuest, and Web of Science. Empirical studies that used samples with a mean age greater than 10 years, reported injury characteristics, and investigated complex reading abilities (defined as greater than single-word reading) were eligible for this review. Study quality was evaluated using QualSyst. Study and sample characteristics, measures, and outcomes of interest were extracted and synthesized in the review. Studies that compared reading abilities between people with and without TBI were included in the meta-analysis. Results Twenty-four studies met inclusion criteria, six of which addressed reading in pediatric samples. Findings from heterogeneous samples supported the existence of reading deficits post TBI, including mild TBI. In studies of children, comprehension was examined most frequently, whereas reading speed was the focus of most adult studies. Oculomotor functions and processing speed were related to reading speed; cognitive functions, such as attention and memory, were associated with reading comprehension. Intervention studies were limited, but most reported positive effects. The meta-analysis confirmed the impact of TBI on reading with a large effect size (g = 1.23). Demographic, injury, and study variables did not moderate overall reading outcomes, but male sex was a significant moderator of impairment in reading speed. Discussion Global reading ability, including both comprehension and speed, is negatively impacted by TBI. Future research should continue to explore reading after TBI, including its underlying mechanisms, effects on complex reading activities such as inferencing, development of screening and assessment tools that address a range of functional reading needs, and efficacy of reading-related interventions.