Sequelae Of Traumatic Brain Injury Research Articles

A Systematic Review of the Relationship Between Traumatic Brain Injury and Disruptions in Heart Rate Variability.

Autonomic nervous system dysfunction is increasingly recognized as a common sequela of traumatic brain injury (TBI). Heart rate variability (HRV) is a specific measure of autonomic nervous system functioning that can be used to measure beat-to-beat changes in heart rate following TBI. The objective of this systematic review was to determine the state of the literature on HRV dysfunction following TBI, assess the level of support for HRV dysfunction following TBI, and determine if HRV dysfunction predicts mortality and the severity and subsequent recovery of TBI symptoms. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two raters coded each article and provided quality ratings with discrepancies resolved by consensus. Eighty-nine papers met the inclusion criteria. Findings indicated that TBI of any severity is associated with decreased (i.e., worse) HRV; the severity of TBI appears to moderate the relationship between HRV and recovery; decreased HRV following TBI predicts mortality beyond age; HRV disturbances may persist beyond return-to-play and symptom resolution following mild TBI. Overall, current literature suggests HRV is decreased following TBI and may be a good indicator of physiological change and predictor of important outcomes including mortality and symptom improvement following TBI.

Exploring the biological basis of acupuncture treatment for traumatic brain injury: a review of evidence from animal models.

Traumatic brain injury (TBI) occurs when external physical forces impact the brain, potentially causing long-term issues such as post-traumatic stress disorders and cognitive and physical dysfunctions. The diverse nature of TBI pathology and treatment has led to a rapid acceleration in research on its biological mechanisms over the past decade. This surge presents challenges in assessing, managing, and predicting outcomes for TBI cases. Despite the development and testing of various therapeutic strategies aimed at mitigating neurological decline after TBI, a definitive cure for these conditions remains elusive. Recently, a growing focus has been on preclinical research investigating acupuncture as a potential treatment method for TBI sequelae. Acupuncture, being a cost-effective non-pharmacological therapy, has demonstrated promise in improving functional outcomes after brain injury. However, the precise mechanisms underlying the anticipated improvements induced by acupuncture remain poorly understood. In this study, we examined current evidence from animal studies regarding acupuncture's efficacy in improving functional outcomes post-TBI. We also proposed potential biological mechanisms, such as glial cells (microglia astrocytes), autophagy, and apoptosis. This information will deepen our understanding of the underlying mechanisms through which acupuncture exerts its most beneficial effects post-TBI, assisting in forming new clinical strategies to maximize benefits for these patients.

Post-Traumatic Epilepsy: Observations from an Urban Level 1 Trauma Center.

There are approximately 2.5 million cases of traumatic brain injury (TBI) in the U.S. each year. Post-traumatic epilepsy (PTE), a sequela of TBI, has been shown to occur in approximately 15% of TBI patients. Pre-disposing risk factors for the development of PTE include severe TBI and penetrating head injury. PTE is associated with poor functional outcomes, increased negative social factors, and mental illness. We conducted a retrospective chart review with a 5-year timeframe at an urban Level 1 Trauma Center. Patients with ICD-10-CM codes associated with TBI were identified. Patients were coded as TBI with or without PTE by the presence of codes associated with PTE. Datapoints collected included risk factors for PTE and encounters with neurologists. A total of 1886 TBI patients were identified, with 178 (9.44%) classified as TBI with PTE. The most significant risk factor associated with PTE was severe brain injury, with an odds ratio (OR) of 2.955 (95% CI [2.062,4.236]; p < 0.0001). Only 19 of 178 patients (10.7%) visited a neurologist beyond 6 months after TBI. Our results suggest the presence of a significant population of patients with PTE and the need for better follow-up.

Menopause and Traumatic Brain Injury: A NIDILRR Collaborative Traumatic Brain Injury Model Systems Study

ObjectiveTo examine the experience of menopause symptoms in women with traumatic brain injury (TBI). DesignCross-sectional descriptive study. SettingFive sites of the TBI Model Systems (TBIMS) program. ParticipantsParticipants were 210 women, aged 40-60 years, who were not taking systemic hormones and did not have both ovaries removed: 61 participants were enrolled in the TBIMS, who were at least 2 years post-TBI and living in the community. One hundred forty-nine participants without TBI were recruited from a research registry and the metropolitan Detroit community. InterventionsNot applicable. Main Outcome MeasuresA checklist comprised of 21 menopause symptoms assessing 4 symptom clusters (vasomotor, somatic, psychological, and cognitive). ResultsTBI and non-TBI groups did not significantly differ and showed small effect sizes on vasomotor symptoms. On the remaining symptom clusters, women with TBI showed greater presence and severity of symptoms than women without TBI, as well as fewer differences between premenopausal and postmenopausal women on those symptoms. A profile indicating an additive or potentiating effect of TBI on menopause symptoms was not observed. ConclusionsFindings support a conceptual model of menopause and TBI indicating that symptoms most closely associated with estrogen decline are similar for women with and without TBI, whereas symptoms that overlap with common TBI sequelae are generally more frequent and severe among these women. Likely because of lower baseline of symptoms premenopause, postmenopausal women without TBI reported more numerous and severe symptoms relative to their premenopausal counterparts without TBI. Overall, it may be that women without TBI experience menopause as more of a “change” of life, whereas women with TBI chronically face significantly more of these symptoms than women without TBI.

Pharmacologic Management of the Sequelae of Traumatic Brain Injuries.

Pharmacologic Management of the Sequelae of Traumatic Brain Injuries.

Longitudinal changes in sodium concentration and in clinical outcome in mild traumatic brain injury.

Ionic imbalances and sodium channel dysfunction, well-known sequelae of traumatic brain injury (TBI), promote functional impairment in affected subjects. Therefore, non-invasive measurement of sodium concentrations using 23Na MRI has the potential to detect clinically relevant injury and predict persistent symptoms. Recently, we reported diffusely lower apparent total sodium concentrations (aTSC) in mild TBI patients compared to controls, as well as correlations between lower aTSC and worse clinical outcomes. The main goal of this study was to determine whether these aTSC findings, and their changes over time, predict outcomes at 3- and 12-month from injury. Twenty-seven patients previously studied with 23Na MRI and outcome measures at 22 ± 10 days (average ± standard deviation) after injury (visit-1, v1) were contacted at 3- (visit-2, v2) and 12-month after injury (visit-3, v3) to complete the Rivermead post-concussion symptoms questionnaire (RPQ), the extended Glasgow outcome scale (GOSE), and the brief test of adult cognition by telephone (BTACT). Follow-up 1H and 23Na MRI were additionally scheduled at v2. Linear regression was used to calculate aTSC in global grey and white matters. Six hypotheses were tested in relation to the serial changes in outcome measures and in aTSC, and in relation to the cross-sectional and serial relationships between aTSC and outcome. Twenty patients contributed data at v2 and fifteen at v3. Total RPQ and composite BTACT z-scores differed significantly for v2 and v3 in comparison to v1 (each P < 0.01), reflecting longitudinally reduced symptomatology and improved performance on cognitive testing. No associations between aTSC and outcome were observed at v2. Previously lower grey and white matter aTSC normalized at v2 in comparison to controls, in line with a statistically detectable longitudinal increase in grey matter aTSC between v1 and v2 (P = 0.0004). aTSC values at v1 predicted a subset of future BTACT subtest scores, but not future RPQ scores nor GOSE-defined recovery status. Similarly, aTSC rates of change correlated with BTACT rates of change, but not with those of RPQ. Tissue aTSC, previously shown to be diffusely decreased compared to controls at v1, was no longer reduced by v2, suggesting normalization of the sodium ionic equilibrium. These changes were accompanied by marked improvement in outcome. The results support the notion that early aTSC from 23Na MRI predicts future BTACT, but not RPQ scores, nor future GOSE status.

Gender Disparities in Neurobehavioral Symptoms and the Role of Post-Traumatic Symptoms in US Service Members Following Mild Traumatic Brain Injury.

Women are more directly involved in combat operations today than ever before, currently making up 18.6% of officers and 16.8% of enlisted personnel in the United States military. However, women continue to be under-represented in military research. Studies that do consider gender differences in traumatic brain injury (TBI) outcomes have shown that women report significantly more post-concussive symptoms than men. Conclusions for true gender differences related to TBI are hard to make without controlling for non-TBI factors. The effects previously identified in the literature may be an artifact of how men and women differ in their response to injury, unrelated to the neurological recovery process associated with TBI. The objective of this study was to examine the effects of gender specifics on mild TBI (mTBI) sequelae on injured and uninjured control groups, and to investigate the role of post-traumatic stress disorder (PTSD) on symptom reporting. It should be noted that the terms "gender" and "men/women" are used in this article in place of "sex" or "males/females" given that we are not discussing biological attributes. A total of 966 United States military service members and veterans were included in the study. Of the total sample, 455 men and 46 women were in the mTBI group, 285 men and 31 women were in the injured controls group (IC), and 111 men and 38 women in the non-injured controls group (NIC). Post-concussive and quality of life symptoms were compared for men and women while controlling for combat exposure. MTBI and IC groups were also stratified by PTSD presentation. Measures used included the Neurobehavioral Symptom Inventory (NSI), PTSD Checklist (PCL-C), Traumatic Brain Injury Quality of Life (TBI-QOL), and Combat Exposure Scale. In the mTBI group, women had worse scores on NSI total, NSI Somatosensory and Affective clusters, and the TBI-QOL Anxiety, Fatigue, and Headache scales (n2 = 0.018-0.032, small to small-medium effect sizes). When PTSD was present, women had worse scores on the NSI Somatosensory cluster only (n2 = 0.029, small-medium effect size). In contrast, when PTSD was absent, women had worse scores than men on the NSI Somatosensory and Affective clusters, and the TBI-QOL Anxiety and Headache scales (n2 = 0.032-0.063, small to medium effect sizes). In the IC group, women had worse scores on the NSI Cognitive cluster and the TBI-QOL Fatigue and Pain Interference scales (n2 = 0.024-0.042, small to small-medium effect sizes). However, group differences were no longer found when stratified by PTSD sub-groups. In the NIC group, there were no significant group differences for any analyses. We were able to identify symptoms unique to women recovering from mTBI that were not present following other forms of physical injury or in healthy controls. However, the impact of PTSD exacerbates the symptom profile and its comorbidity with mTBI equates to most of the noted gender differences.

Head Injury and Risk of Incident Ischemic Stroke in Community-Dwelling Adults.

While stroke is a recognized short-term sequela of traumatic brain injury, evidence about long-term ischemic stroke risk after traumatic brain injury remains limited. The Atherosclerosis Risk in Communities Study is an ongoing prospective cohort comprised of US community-dwelling adults enrolled in 1987 to 1989 followed through 2019. Head injury was defined using self-report and hospital-based diagnostic codes and was analyzed as a time-varying exposure. Incident ischemic stroke events were physician-adjudicated. We used Cox regression adjusted for sociodemographic and cardiovascular risk factors to estimate the hazard of ischemic stroke as a function of head injury. Secondary analyses explored the number and severity of head injuries; the mechanism and severity of incident ischemic stroke; and heterogeneity within subgroups defined by race, sex, and age. Our analysis included 12 813 participants with no prior head injury or stroke. The median follow-up age was 27.1 years (25th-75th percentile=21.1-30.5). Participants were of median age 54 years (25th-75th percentile=49-59) at baseline; 57.7% were female and 27.8% were Black. There were 2158 (16.8%) participants with at least 1 head injury and 1141 (8.9%) participants with an incident ischemic stroke during follow-up. For those with head injuries, the median age to ischemic stroke was 7.5 years (25th-75th percentile=2.2-14.0). In adjusted models, head injury was associated with an increased hazard of incident ischemic stroke (hazard ratio [HR], 1.34 [95% CI, 1.12-1.60]). We observed evidence of dose-response for the number of head injuries (1: HR, 1.16 [95% CI, 0.97-1.40]; ≥2: HR, 1.94 [95% CI, 1.39-2.71]) but not for injury severity. We observed evidence of stronger associations between head injury and more severe stroke (National Institutes of Health Stroke Scale score ≤5: HR, 1.31 [95% CI, 1.04-1.64]; National Institutes of Health Stroke Scale score 6-10: HR, 1.64 [95% CI, 1.06-2.52]; National Institutes of Health Stroke Scale score ≥11: HR, 1.80 [95% CI, 1.18-2.76]). Results were similar across stroke mechanism and within strata of race, sex, and age. In this community-based cohort, head injury was associated with subsequent ischemic stroke. These results suggest the importance of public health interventions aimed at preventing head injuries and primary stroke prevention among individuals with prior traumatic brain injuries.

Modified Mouse Model of Repetitive Mild Traumatic Brain Injury Incorporating Thinned-Skull Window and Fluid Percussion.

Mild traumatic brain injury is a clinically highly heterogeneous neurological disorder. Highly reproducible traumatic brain injury (TBI) animal models with well-defined pathologies are urgently needed for studying the mechanisms of neuropathology after mild TBI and testing therapeutics. Replicating the entire sequelae of TBI in animal models has proven to be a challenge. Therefore, the availability of multiple animal models of TBI is necessary to account for the diverse aspects and severities seen in TBI patients. CHI is one of the most common methods for fabricating rodent models of rmTBI. However, this method is susceptible to many factors, including the impact method used, the thickness and shape of the skull bone, animal apnea, and the type of head support and immobilization utilized. The aim of this protocol is to demonstrate a combination of the thinned-skull window and fluid percussion injury (FPI) methods to produce a precise mouse model of CHI-associated rmTBI. The primary objective of this protocol is to minimize factors that could impact the accuracy and consistency of CHI and FPI modeling, including skull bone thickness, shape, and head support. By utilizing a thinned-skull window method, potential inflammation due to craniotomy and FPI is minimized, resulting in an improved mouse model that replicates the clinical features observed in patients with mild TBI. Results from behavior and histological analysis using hematoxylin and eosin (HE) staining suggest that rmTBI can lead to a cumulative injury that produces changes in both behavior and gross morphology of the brain. Overall, the modified CHI-associated rmTBI presents a useful tool for researchers to explore the underlying mechanisms that contribute to focal and diffuse pathophysiological changes in rmTBI.

An overview of preclinical models of traumatic brain injury (TBI): relevance to pathophysiological mechanisms.

Traumatic brain injury (TBI) is a major cause of morbidity and mortality, affecting millions annually worldwide. Although the majority of TBI patients return to premorbid baseline, a subset of patient can develop persistent and often debilitating neurocognitive and behavioral changes. The etiology of TBI within the clinical setting is inherently heterogenous, ranging from sport related injuries, fall related injuries and motor vehicle accidents in the civilian setting, to blast injuries in the military setting. Animal models of TBI, offer the distinct advantage of controlling for injury modality, duration and severity. Furthermore, preclinical models of TBI have provided the necessary temporal opportunity to study the chronic neuropathological sequelae of TBI, including neurodegenerative sequelae such as tauopathy and neuroinflammation within the finite experimental timeline. Despite the high prevalence of TBI, there are currently no disease modifying regimen for TBI, and the current clinical treatments remain largely symptom based. The preclinical models have provided the necessary biological substrate to examine the disease modifying effect of various pharmacological agents and have imperative translational value. The current review will include a comprehensive survey of well-established preclinical models, including classic preclinical models including weight drop, blast injury, fluid percussion injury, controlled cortical impact injury, as well as more novel injury models including closed-head impact model of engineered rotational acceleration (CHIMERA) models and closed-head projectile concussive impact model (PCI). In addition to rodent preclinical models, the review will include an overview of other species including large animal models and Drosophila. There are major neuropathological perturbations post TBI captured in various preclinical models, which include neuroinflammation, calcium dysregulation, tauopathy, mitochondrial dysfunction and oxidative stress, axonopathy, as well as glymphatic system disruption. The preclinical models of TBI continue to offer valuable translational insight, as well as essential neurobiological basis to examine specific disease modifying therapeutic regimen.

Sleepiness in retired male boxers: daytime sleepiness and its relationship with impulsiveness and depression symptomatology in retired professional male boxers

Background Boxing exposes fighters to head impacts and potential traumatic brain injury (TBI). Though research has explored the neuropsychiatric consequences of contact sports, there is limited research into Excessive Daytime Sleepiness (EDS) and its relationship to other outcomes, such as impulsiveness and depression. Therefore, this study aimed to describe EDS in retired boxers using the Epworth Sleepiness Scale (ESS) and to examine how boxing and sleepiness relate to impulsiveness and depression symptomatology. Methods 86 male retired professional boxers from the Professional Fighters Brain Health Study (PFBHS) met the inclusion criteria. Adjusted multivariable models analyzed relationships between professional boxing bouts, EDS (ESS), impulsiveness (Barratt Impulsiveness Scale Version 11 (BIS-11)), and/or depression (Patient Health Questionnaire-9 (PHQ-9)). A causal mediation analysis was performed to assess whether boxing bouts and ESS scores predicted BIS-11 and PHQ-9 scores. Results Mean age was ∼51 years, fighters averaged ∼36 professional bouts, and ESS mean(SD) was 7.5(5.3). ESS scores were significantly associated with raw BIS-11 (Beta = 1.26, 95%CI = 0.77–1.75, p < 0.001) and ordinal PHQ-9 (OR = 1.20, 95%CI = 1.11–1.31, p < 0.001) scores in adjusted models, and the significant relationship between boxing bouts and BIS-11/PHQ-9 was mediated by ESS. Conclusions EDS in retired male professional boxers may be strongly associated with other neuropsychiatric sequelae of TBI (impulsiveness and depression). Sleepiness; sleep; boxing; contact sports; impulsiveness; impulsivity; depression; Epworth sleepiness scale box

Analysis of middle meningeal artery embolization for the treatment of chronic, acute on chronic, and subacute subdural hematomas.

Chronic subdural hematoma (cSDH) is a common sequela of traumatic brain injury. Middle meningeal artery embolization (MMAE) has shown promising results as an emerging minimally invasive alternative treatment. The purpose of this study is to examine the safety and efficacy of MMAE performed in patients with cSDH, acute-on-chronic, and subacute SDH with a traumatic etiology. This retrospective study included cases performed at a Level II Trauma Center between January 2019 and December 2020 for MMAE of cSDHs. Data collected included patient demographic characteristics and comorbidities, SDH characteristics, complications, and efficacy outcomes. The lesion measurements were collected before the procedure, 4-6 weeks and 3-6 months post-procedure. In our patient population, 78% (39) either had lesions improve or completely resolved. The sample included 50 patients with a mean age of 74 years old. Statistically significant reductions in lesion size were found from pre- to post-procedure in the left lesions, right lesions, and midline shifts. The left lesions decreased from 13.88 ± 5.70 mm to 3.19 ± 4.89 mm at 3-6 months with P < 0.001. The right lesions decreased from 13.74 ± 5.28 mm to 4.93 ± 7.46 mm at 3-6 months with P = 0.02. Midline shifts decreased from 3.78 ± 3.98 mm to 0.48 ± 1.31 mm at 3-6 months with P = 0.02. No complications were experienced for bleeding, hematoma, worsening SDH, pseudoaneurysm, or stroke. Our pilot study from a single center utilizing MMAE demonstrates that MMAE is successful without increasing treatment-related complications not only for cSDH but also in acute-on-cSDH and SDH with a subacute component.

Tracing the path of disruption: 13C isotope applications in traumatic brain injury-induced metabolic dysfunction.

Cerebral metabolic dysfunction is a critical pathological hallmark observed in the aftermath of traumatic brain injury (TBI), as extensively documented in clinical investigations and experimental models. An in-depth understanding of the bioenergetic disturbances that occurfollowing TBI promises to reveal novel therapeutic targets, paving the way for the timely development ofinterventions to improve patient outcomes. The 13C isotope tracing technique represents a robust methodological advance, harnessing biochemical quantification to delineate the metabolic trajectories of isotopically labeled substrates. This nuanced approach enables real-time mapping of metabolic fluxes, providing a window into the cellular energetic state and elucidating the perturbations in key metabolic circuits. By applying this sophisticated tool, researchers can dissect the complexities of bioenergetic networks within the central nervous system, offering insights into the metabolic derangements specific to TBI pathology. Embraced by both animal studies and clinical research, 13C isotope tracing has bolstered our understanding of TBI-induced metabolic dysregulation. This review synthesizes current applications of isotope tracing and its transformative potential in evaluating and addressing the metabolic sequelae of TBI.

Caregiver report of social-emotional functioning in infants and young children after inflicted traumatic brain injury

ABSTRACT Social-emotional difficulties are common sequelae of traumatic brain injury (TBI). Children who have experienced inflicted TBI (iTBI) may be at increased risk for social-emotional problems due to the risk factors associated with both early neurologic injury and with child maltreatment. We characterized the associations among injury severity, caregiver type (i.e., biological parents, non-kinship, kinship), and child social-emotional functioning in 41 infants and young children who had sustained iTBI and were seen in a large, regional children’s hospital. This study was a retrospective analysis, utilizing data collected from the medical record as part of routine clinical care. Social-emotional functioning was assessed with the Bayley Scales of Infant and Toddler Development-Third Edition. Children with more severe injuries were rated as having worse social-emotional functioning. Caregiver type was associated with child social-emotional scores, above and beyond injury and demographic predictors. Biological parents were more likely to report better social-emotional skills than non-kinship caregivers, with the pattern of results suggesting that rater bias plays a role in this difference. In order to ensure that children are accurately identified for supports, these relationships should be considered when interpreting caregiver report of social-emotional skills.

Coverage of education and training of traumatic brain injury-induced growth hormone deficiency in US residency and fellowship programs: a cross-sectional study

BackgroundHypopituitarism, including growth hormone deficiency (GHD), is a common sequela of traumatic brain injury (TBI). This study explored the coverage of education and training of TBI-induced hypopituitarism in general and GHD in particular, in postgraduate program curricula to identify knowledge gaps and opportunities.MethodsAn online survey and qualitative interviews (focus groups) were conducted among endocrinology, neurology, and physiatry postgraduate program directors in the United States (US). The study received an IRB exemption.ResultsA total of 419 fellowship and residency programs were invited to participate; 60 program directors completed the survey and 11 of these participated in the focus groups. About half of the respondents considered TBI-induced hypopituitarism important or fairly important to include in the curriculum, and nearly two-thirds considered it an appropriate training component. Neurology program directors considered education regarding hypopituitarism following TBI less important and relevant for their curricula compared with endocrinology and physiatry program directors. About half (53%) of the programs responded that they included TBI-induced pituitary disorders in their curricula. About two-thirds (68%) of endocrinology programs, compared with only one-quarter (25%) of neurology programs, covered TBI-induced pituitary disorders. Respondents identified multiple barriers to expanding hypopituitarism following TBI in the curriculum, including the rarity of condition and lack of time/room in the curriculum. Respondents reported that consensus clinical guidelines and the availability of more data on TBI-induced hypopituitarism, including GHD, would greatly impact the development of educational curricula on this topic.ConclusionsTo improve the management of TBI-induced hypopituitarism, education and training should be expanded in US fellowship and residency programs to prepare trainees to effectively screen, diagnose, and treat TBI-induced hypopituitarism, including GHD.

Management of Traumatic Cerebral Venous Sinus Thrombosis: A United Kingdom and Ireland Survey on Practice Variation.

Traumatic cerebral venous sinus thrombosis (tCVST) is an increasingly recognized sequela of traumatic brain injury (TBI), with skull fractures and extradural hematomas overlying venous sinuses recognized as risk factors. Although it may be treated with anticoagulation, the decision to treat tCVST is nuanced by the risk of new or worsening hemorrhage. Presently, there are no guidelines on the investigation and management of tCVST. Therefore, we conducted a UK- and Ireland-wide practice variation survey. A 17-question survey was sent via Google Forms to neurosurgeons and intensive care doctors of at least ST3 (registrar) level and above in the UK and Ireland and distributed by the Society of British Neurological Surgeons and investigators of the Sugar or Salt trial between May 9, 2023, and September 15, 2023. Data were extracted from the survey for both qualitative and quantitative analyses. There were 41 respondents to the survey, 18 (43.9%) of whom were consultant neurosurgeons. Fifty-four percent of the respondents performed a computed tomography intracranial venogram to investigate for tCVST where there was a skull fracture overlying or adjacent to a venous sinus, whereas 43.9% performed these at the time of TBI diagnosis. Around three-fourth of the respondents anticoagulate for tCVST, largely within 3 days post-TBI. A range of hemorrhagic and thrombotic complications have been observed following decisions to treat and withhold treatment of tCVST, respectively. Around two-third of the respondents conducted follow-up imaging in confirmed tCVST. None of the respondents had an established departmental protocol for the management of tCVST. This UK- and Ireland-wide survey on the management of tCVST revealed a variation in its diagnosis, treatment, and follow-up with no departmental protocol established. The optimal diagnostic pathway, management protocol, and follow-up of patients with tCVST remain unknown and should be the subject of future studies.

Pseudobulbar affect - an often overlooked and under-diagnosed debilitating sequelae of traumatic brain injury: A case report

Pseudobulbar affect - an often overlooked and under-diagnosed debilitating sequelae of traumatic brain injury: A case report

Serum amyloid P component accumulates and persists in neurones following traumatic brain injury.

The mechanisms underlying neurodegenerative sequelae of traumatic brain injury (TBI) are poorly understood. The normal plasma protein, serum amyloid P component (SAP), which is normally rigorously excluded from the brain, is directly neurocytotoxic for cerebral neurones and also binds to Aβ amyloid fibrils and neurofibrillary tangles, promoting formation and persistence of Aβ fibrils. Increased brain exposure to SAP is common to many risk factors for dementia, including TBI, and dementia at death in the elderly is significantly associated with neocortical SAP content. Here, in 18 of 30 severe TBI cases, we report immunohistochemical staining for SAP in contused brain tissue with blood-brain barrier disruption. The SAP was localized to neurofilaments in a subset of neurones and their processes, particularly damaged axons and cell bodies, and was present regardless of the time after injury. No SAP was detected on astrocytes, microglia, cerebral capillaries or serotoninergic neurones and was absent from undamaged brain. C-reactive protein, the control plasma protein most closely similar to SAP, was only detected within capillary lumina. The appearance of neurocytotoxic SAP in the brain after TBI, and its persistent, selective deposition in cerebral neurones, are consistent with a potential contribution to subsequent neurodegeneration.

3 The Menopause Transition in Women with Traumatic Brain Injury

Objective:All premenopausal women who survive traumatic brain injury (TBI) will eventually experience menopause. Challenges experienced by women with TBI are superimposed on challenges associated with hormonal changes in midlife. Some women with stressful life contexts such as TBI are more vulnerable to the added burdens of the menopause transition, potentiating its effects. Although it may be argued that TBI research correctly overrepresents the male experience given disparities in injury rates (4:1), there are important differences in how females and males age, their specific health needs, and the psychosocial context of midlife. Development of evidence-based interventions begins with understanding the experience of menopause after TBI, including where and when key problems may emerge.Participants and Methods:All participants were women 40-60 years old, not taking hormones (i.e., replacement therapy or other systematic hormones), with intact ovaries. Women with TBI were &gt; 2 years post injury, whose menstrual period returned after injury, and were living in the community. Severity of injury ranged from complicated-mild to severe TBI. Pre/peri and postmenopausal status was determined by presence/absence of menstrual period in previous 6 months, respectively. Eighteen common menopause symptoms (vasomotor, somatic, psychological, and cognitive) were assessed for presence and frequency (rarely-always), along with Quality of Life in Neurological Disorders (Neuro-QOL) Sleep Disturbance and Traumatic Brain Injury Quality of Life (TBIQOL) Anxiety, Depression, and Fatigue scales.Results:Overall, women with TBI (n = 68) showed greater presence and frequency of symptoms than women without TBI (n = 153), with fewer within-group differences by menopausal status. Among pre/peri-menopausal women, TBI and non-TBI groups did not significantly differ and showed small effect sizes on symptoms associated with changes in estrogen during menopause, including hot flashes, night sweats, bowel and bladder sequelae, and breast tenderness. However, pre/peri-menopausal women with TBI also endorsed body aches and headaches, as well as troubles with memory, focus, fatigue, cognitive concerns, sleep, and anxiety significantly more than their pre/peri-menopausal counterparts (all medium effect sizes). Among postmenopausal women, those with TBI had significantly greater frequency of hot flashes, crying spells, poor memory, worry, moodiness, panic attacks, sleep disturbance, and anxiety than women without TBI. Within TBI, only hot flashes and breast tenderness were greater in postmenopausal versus pre/peri-menopausal women. Within non-TBI, postmenopausal status was associated with significantly greater hot flashes, night sweats, restlessness, poor memory, irritability, sleep disturbance, and anxiety, with greater fatigue but not significantly.Conclusions:The findings support a model of TBI and menopause in which symptoms most closely associated with estrogen decline in pre/peri-menopause are generally similar between women with and without TBI, and symptoms that overlap with common TBI sequelae were generally more often present and frequently experienced among women with TBI versus non-TBI. We did not observe a synergistic or potentiating effect of TBI on menopause symptoms in post-menopause. These findings offer insight that contextualizes the experience of menopause symptoms among women with TBI. Such insights are essential for the development of treatment approaches that maximize health and wellbeing during the menopause transition for women with TBI.

The Nociceptin/Orphanin FQ peptide receptor antagonist, SB-612111, improves cerebral blood flow in a rat model of traumatic brain injury.

Traumatic brain injury (TBI) affects more than 2.5 million people in the U.S. each year and is the leading cause of death and disability in children and adults ages 1 to 44. Approximately 90% of TBI cases are classified as mild but may still lead to acute detrimental effects such as impaired cerebral blood flow (CBF) that result in prolonged impacts on brain function and quality of life in up to 15% of patients. We previously reported that nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor antagonism reversed mild blast TBI-induced vestibulomotor deficits and prevented hypoxia. To explore mechanisms by which the NOP receptor-N/OFQ pathway modulates hypoxia and other TBI sequelae, the ability of the NOP antagonist, SB-612111 (SB), to reverse TBI-induced CBF and associated injury marker changes were tested in this study. Male Wistar rats randomly received sham craniotomy or craniotomy + TBI via controlled cortical impact. Injury severity was assessed after 1h (modified neurological severity score (mNSS). Changes in CBF were assessed 2h post-injury above the exposed cortex using laser speckle contrast imaging in response to the direct application of increasing concentrations of vehicle or SB (1, 10, and 100µM) to the brain surface. TBI increased mNSS scores compared to baseline and confirmed mild TBI (mTBI) severity. CBF was significantly impaired on the ipsilateral side of the brain following mTBI, compared to contralateral side and to sham rats. SB dose-dependently improved CBF on the ipsilateral side after mTBI compared to SB effects on the respective ipsilateral side of sham rats but had no effect on contralateral CBF or in uninjured rats. N/OFQ levels increased in the cerebral spinal fluid (CSF) following mTBI, which correlated with the percent decrease in ipsilateral CBF. TBI also activated ERK and cofilin within 3h post-TBI; ERK activation correlated with increased CSF N/OFQ. In conclusion, this study reveals a significant contribution of the N/OFQ-NOP receptor system to TBI-induced dysregulation of cerebral vasculature and suggests that the NOP receptor should be considered as a potential therapeutic target for TBI.