Chronic headaches after traumatic brain injury: Diagnostic complexity associated with increased cost.

BACKGROUND: Chronic headache after traumatic brain injury (TBI) is a common, yet disabling, disorder whose diverse clinical characteristics and treatment needs remain poorly defined. OBJECTIVE: To examine diagnostic coding patterns and cost among military Veterans with comorbid chronic headache and TBI. METHODS: We identified 141,125 post-9/11 era Veterans who served between 2001 and 2019 with a headache disorder diagnosed after TBI. We first identified patterns of Complex Headache Combinations (CHC) and then compared the patterns of healthcare costs in 2022-dollar values in the three years following the TBI diagnosis. RESULTS: Veterans had diverse individual headache and CHC diagnoses with uniformly high cost of care. Post-whiplash and post-TBI CHCs were common and consistently associated with higher costs after TBI than those with other types of headache and CHCs. Post-TBI migraine had the highest unadjusted mean inpatient ($27,698), outpatient ($61,417), and pharmacy ($4,231) costs, which persisted even after adjustment for confounders including demographic, military, and clinical characteristics. CONCLUSION: Headache diagnoses after TBI, particularly those diagnosed with post-traumatic headache, are complex, and associated with dual high cost and care burdens. More research is needed to examine whether this higher expenditure reflects more intensive treatment and better outcomes or refractory headache with worse outcomes.

Prognostic Value of Dynamic Segmented Neutrophil to Monocyte (SeMo) Ratio Changes in Patients with Moderate to Severe Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in trauma patients, necessitating reliable prognostic tools. The segmented neutrophil-to-monocyte (SeMo) ratio, indicative of the inflammatory response, has emerged as a valuable biomarker. This study evaluates the prognostic value of dynamic changes in the SeMo ratio in predicting outcomes for patients with moderate to severe TBI. METHODS: A retrospective analysis was conducted on data from 1118 TBI patients admitted to the surgical intensive care unit at a level I trauma center between January 2009 and December 2020. Patients were selected based on an Abbreviated Injury Scale (AIS) score ≥ 3 in the head region. Initial and follow-up SeMo ratios were calculated upon admission and 48-72 h later, respectively. The dynamic SeMo ratio was defined as the difference between the second and initial SeMo ratios. Statistical analyses included receiver operating characteristic (ROC) curve analysis to determine the optimal threshold for mortality prediction, and comparative analysis of clinical outcomes. RESULTS: The study cohort included 121 deceased and 997 surviving patients. Deceased patients had significantly higher second SeMo ratios (20.9 ± 16.1 vs. 15.8 ± 17.2, p = 0.001) and dynamic SeMo ratios (2.4 ± 19.8 vs. -2.1 ± 19.5, p = 0.019) than those survival patients. In the multivariate analysis, the dynamic SeMo is a significant independent risk factor for in-hospital mortality (OR 1.01, 95%CI: 1.01-1.03, p = 0.031). The optimal cut-off for the dynamic SeMo ratio was 5.96, above which patients exhibited higher mortality (21.4% vs. 8.5%, p < 0.001), higher adjusted mortality (adjusted odds ratio: 2.98; 95% confidence interval: 1.95-4.56; p = 0.005), and longer hospital stays (23.6 days vs. 19.7 days, p = 0.005). DISCUSSION: Dynamic SeMo ratio changes serve as a prognostic marker for in-hospital mortality and hospital stay duration in moderate to severe TBI patients. A higher dynamic SeMo ratio indicates increased risk, highlighting the importance of early monitoring and intervention. Future prospective studies should validate these findings and explore integration with other biomarkers for enhanced prognostication.

Revealing the role of material properties in impact-related injuries: Investigating the influence of brain and skull density variations on head injury severity.

Traumatic brain injuries (TBI) resulting from head impacts are a major public health concern, which prompted our research to investigate the complex relationship between the material properties of brain tissue and the severity of TBI. The goal of this research is to investigate how variations in brain and skull density influence the vulnerability of brain tissue to traumatic injury, thereby enhancing our understanding of injury mechanism. To achieve this goal, we employed a well-validated finite element head model (FEHM). The current investigation was divided into two phases: in the first one, three distinct brain viscoelastic materials that had been utilized in prior studies were analyzed. The review of the properties of these three materials has been meticulous, encompassing both the spectrum of mechanical properties and the behaviors that are relevant to the way in which brain tissue reacts to traumatic loading conditions. In the second phase, the material properties of both the brain and skull tissue, alongside the impact conditions, were held constant. After this step, the focus was directed towards the variation of density in the brain and skull, which was consistent with the results obtained from previous experimental investigations, in order to determine the precise impact of these variations in density. This approach allowed a more profound comprehension of the impacts that density had on the simulation results. In the first phase, Material No. 2 exhibited the highest maximum first principal strain value in the frontal region (εmax=15.41%), indicating lower stiffness to instantaneous deformation. This characteristic suggests that Material No. 2 may deform more extensively upon impact, potentially increasing the risk of injury due to its viscoelastic behavior. In contrast, Material No. 1, with a lower maximum first principal strain in the frontal region (εmax=7.87%), displayed greater stiffness to instantaneous deformation, potentially reducing the risk of brain injury upon head impact. The second phase provided quantitative findings revealing a proportional relationship between brain tissue density and the pressures experienced by the brain. A 2 % increase in brain tissue density corresponded to approximately a 1 % increase in pressure on the brain tissue. Similarly, changes in skull density exhibited a similar quantitative relationship, with a 6 % increase in skull density leading to a 2.5 % increase in brain pressure. This preliminary approximate ratio of 2 to 1 between brain and skull density variations provides an initial quantitative framework for assessing the impact of density changes on brain vulnerability. These findings have several implications for the development of protective measures and injury prevention strategies, particularly in contexts where head trauma is a major issue.

Advances in neuroproteomics for neurotrauma: unraveling insights for personalized medicine and future prospects.

Neuroproteomics, an emerging field at the intersection of neuroscience and proteomics, has garnered significant attention in the context of neurotrauma research. Neuroproteomics involves the quantitative and qualitative analysis of nervous system components, essential for understanding the dynamic events involved in the vast areas of neuroscience, including, but not limited to, neuropsychiatric disorders, neurodegenerative disorders, mental illness, traumatic brain injury, chronic traumatic encephalopathy, and other neurodegenerative diseases. With advancements in mass spectrometry coupled with bioinformatics and systems biology, neuroproteomics has led to the development of innovative techniques such as microproteomics, single-cell proteomics, and imaging mass spectrometry, which have significantly impacted neuronal biomarker research. By analyzing the complex protein interactions and alterations that occur in the injured brain, neuroproteomics provides valuable insights into the pathophysiological mechanisms underlying neurotrauma. This review explores how such insights can be harnessed to advance personalized medicine (PM) approaches, tailoring treatments based on individual patient profiles. Additionally, we highlight the potential future prospects of neuroproteomics, such as identifying novel biomarkers and developing targeted therapies by employing artificial intelligence (AI) and machine learning (ML). By shedding light on neurotrauma's current state and future directions, this review aims to stimulate further research and collaboration in this promising and transformative field.

Traumatic Brain Injury Positive Strategies for Families: A Pilot Randomized Controlled Trial of an Online Parent-Training Program.

OBJECTIVE: To determine program satisfaction and preliminary efficacy of Traumatic Brain Injury Positive Strategies (TIPS), a web-based training for parenting strategies after child brain injury. DESIGN: A randomized controlled trial with parallel assignment to TIPS intervention or usual-care control (TAU). The three testing time-points were pretest, posttest within 30 days of assignment, and 3-month follow-up. Reported in accordance with CONSORT extensions to randomized feasibility and pilot trials SETTING: Online. PARTICIPANTS: Eighty-three volunteers recruited nationally who were 18 years of age or older, U.S. residents, English speaking and reading, had access to high-speed internet, and were living with and caring for a child who was hospitalized overnight with a brain injury (ages 3-18 years, able to follow simple commands; N=83). INTERVENTIONS: Eight interactive behavioral training modules on parent strategies. The usual-care control was an informational website. MAIN OUTCOME MEASURES: The proximal outcomes were User Satisfaction, Usefulness, Usability, Feature Preference, Strategy Utilization and Effectiveness, and Learning and Self-Efficacy for TIPS program participants. The primary outcomes were: Strategy Knowledge, Application, and Strategy-Application Confidence; Family Impact Module of Pediatric Quality of Life Inventory (PedsQL); and Caregiver Self-Efficacy Scale. The secondary outcomes were TIPS vs TCore PedsQL and Health Behavior Inventory (HBI) RESULTS: Pre- and posttest assessments were completed by 76 of 83 caregivers; 74 completed their 3-month follow-up. Linear growth models indicated that relative to TAU, TIPS yielded greater increases in Strategy Knowledge over the 3-month study (d=.61). Other comparisons did not reach significance. Outcomes were not moderated by child age, SES, or disability severity measured by Cognitive Function Module of PedsQL. All TIPS participants were satisfied with the program. CONCLUSIONS: Of the 10 outcomes tested, only TBI knowledge significantly improved relative to TAU.

Are GABAergic drugs beneficial in providing neuroprotection after traumatic brain injuries? A comprehensive literature review of preclinical studies.

Traumatic brain injuries (TBI) caused by physical impact to the brain can adversely impact the welfare and well-being of the affected individuals. One of the leading causes of mortality and dysfunction in the world, TBI is a major public health problem facing the human community. Drugs that target GABAergic neurotransmission are commonly used for sedation in clinical TBI yet their potential to cause neuroprotection is unclear. In this paper, I have performed a rigorous literature review of the neuroprotective effects of drugs that increase GABAergic currents based on the results reported in preclinical literature. The drugs covered in this review include the following: propofol, benzodiazepines, barbiturates, isoflurane, and other drugs that are agonists of GABAA receptors. A careful review of numerous preclinical studies reveals that these drugs fail to produce any neuroprotection after a primary impact to the brain. In numerous circumstances, they could be detrimental to neuroprotection by increasing the size of the contusional brain tissue and by severely interfering with behavioral and functional recovery. Therefore, anesthetic agents that work by enhancing the effect of neurotransmitter GABA should be administered with caution of TBI patients until a clear and concrete picture of their neuroprotective efficacy emerges in the clinical literature.

The Outcome Predictors of the Patients with Traumatic Brain Injury; A Cross-Sectional Study.

Objective: To probe the factors associated with the outcomes of traumatic brain injury (TBI) patients admitted to emergency department (ED). Methods: This is a cross-sectional study that data gathering was performed via census methods, retrospectively. During one year, all head injury's patients who admitted to the ED of a tertiary center in Tehran, Iran were included. Age, gender, mechanism of injury, Glasgow coma scale (GCS) and injury severity score (ISS) on admission, presence of extra-cranial injuries, findings of brain computed tomography (CT), duration of hospitalization, and in hospital outcomes were recorded. Outcome's assessment for survivors was performed within a 6 months-period after discharge based on Glasgow outcome scale (GOS). The variables and outcomes' association were assessed. Results: Totally, 506 patients were evaluated with the mean age of 36.77±21.1 years that 411 (81.2%) were men. Follow up at 6-months post injury was feasible in 487 (96.2%) patients; 59 (11.7%) out of 506 eligible patients died. Logistic regression analysis showed the association between assessed variables and patients' outcome as follows: age>65 years (OR: 12.21; p<0.001), GCS on admission <8 (OR: 62.99; p<0.001), presence of traumatic Intracerebral hemorrhage (ICH) in brain CT scan (OR: 20.11; p=0.010), duration of hospitalization ≥ 5 days (OR: 0.28; p=0.001). Conclusion: The findings of the current study distinguished some variables that were associated with the poor outcome of the patients with TBI. Therefore, TBI patients with any of these risk factors may need close continues monitoring, early ICU admission, and some other special extra care in ED.

"We have no magic bullet": Diagnostic ideals in veterans' mild traumatic brain injury evaluations.

OBJECTIVE: To understand military veterans' and healthcare providers' experiences identifying veterans' personal histories of combat-related mild traumatic brain injury (mTBI) months or years after the injury. METHODS: Patients and clinical staff of a Veterans Health Administration (VA) Polytrauma/TBI clinic participated in a seven-month ethnographic study, which combined direct observation and interviews with veterans (n = 12) and VA clinicians (n = 11). Data were analyzed thematically. RESULTS: Veterans and staff have different understandings of the value of neuroimaging in care for patients with post-acute mTBI, and different understandings of the role of diagnostic certainty in clinical care. Veterans sought to understand the relationship between their past head injuries and their current symptoms. Clinicians educated veterans that their symptoms could be caused by multiple factors and embraced ambiguity as part of treating this patient population. CONCLUSIONS: Patient-provider communication may be enhanced by conversations about common norms of diagnosis and why evaluating mTBI histories departs from these norms. PRACTICE IMPLICATIONS: Clinicians should anticipate that patients may expect a diagnostic process that entails neuroimaging and resolves their uncertainty. In the case of post-acute mTBI, patients would likely benefit from education about the diagnostic process, itself.

Exploring Traumatic Brain Injuries and Aggressive Antisocial Behaviors in Young Male Violent Offenders.

Background: Traumatic brain injury (TBI) is a major cause of disabilities and mortality worldwide, with higher prevalence in offender populations than in the general population. Previous research has strongly advocated increased awareness of TBI in offender populations. The aim of this study was to explore the prevalence and characteristics of TBI, and to investigate associations and interactions between TBI, aggressive antisocial behaviors, general intellectual functioning, and substance use disorders (SUD) in a well-characterized group of young violent offenders. Methods: The study investigated a cohort (n = 269) of 18 to 25-year-old male violent offenders in Sweden. Data on TBI (files + self-report), aggressive antisocial behaviors (Life History of Aggression), SUD (clinical interviews), and general intellectual functioning (General Ability Index, Wechsler Adult Intelligence Scales Third Edition) were collected between 2010 and 2012. Parametric (Student's t-test) and non-parametric (Mann-Whitney U-test, Spearman's rho, χ2, Kruskal Wallis test) inferential statistics were applied and effect sizes reported. Results: TBI, both with and without loss of consciousness, was common, with 77.5% of the offenders reporting having suffered at least one TBI during their lifetime. TBI was associated with an increased occurrence of aggressive antisocial behaviors and SUD, and offenders with both TBI and SUD evidenced the largest amount of aggressive antisocial behaviors. No clinically meaningful associations were found between TBI and general intelligence. Effect sizes were in the small to medium range. Conclusions: Our study confirms an increased prevalence of TBI among young violent offenders compared to the general population, as well as associations between TBI, aggressive antisocial behaviors, and SUD. However, it provides no information on the severity of the TBI, nor on the causality of the demonstrated associations. Nevertheless, TBI, and possible related deficits, need to be considered in the assessment and treatment of young violent offenders.

Dietary Supplementation With the Ketogenic Diet Metabolite Beta-Hydroxybutyrate Ameliorates Post-TBI Aggression in Young-Adult Male Drosophila.

Traumatic brain injury (TBI), caused by repeated concussive head trauma can induce chronic traumatic encephalopathy (CTE), a neurodegenerative disease featuring behavioral symptoms ranging from cognitive deficits to elevated aggression. In a Drosophila model, we used a high-impact trauma device (Katzenberger et al., 2013, 2015) to induce TBI-like symptoms and to study post-TBI behavioral outcomes. Following TBI, aggression in banged male flies was significantly elevated as compared with that in unbanged flies. These increases in aggressive behavior were not the result of basal motility changes, as measured by a negative geotaxis assay. In addition, the increase in post-TBI aggression appeared to be specific to concussive trauma: neither cold exposure nor electric shock-two alternate types of trauma-significantly elevated aggressive behavior in male-male pairs. Various forms of dietary therapy, especially the high-fat, low-carbohydrate ketogenic diet (KD), have recently been explored for a wide variety of neuropathies. We thus hypothesized that putatively neuroprotective dietary interventions might be able to suppress post-traumatic elevations in aggressive behavior in animals subjected to head-trauma-inducing strikes, or "bangs". We supplemented a normal high-carbohydrate Drosophila diet with the KD metabolite beta-hydroxybutyrate (ß-HB)-a ketone body (KB). Banged flies raised on a KB-supplemented diet exhibited a marked reduction in aggression, whereas aggression in unbanged flies was equivalent whether dieted with KB supplements or not. Pharmacological blockade of the ATP-sensitive potassium (KATP) channel abrogated KB effects reducing post-TBI aggression while pharmacological activation mimicked them, suggesting a mechanism by which KBs act in this model. KBs did not significantly extend lifespan in banged flies, but markedly extended lifespan in unbanged flies. We have thus developed a functional model for the study of post-TBI elevations of aggression. Further, we conclude that dietary interventions may be a fruitful avenue for further exploration of treatments for TBI- and CTE-related cognitive-behavioral symptoms.

Autoimmunity After Ischemic Stroke and Brain Injury.

Ischemic Stroke is a major cause of morbidity and mortality worldwide. Sterile inflammation occurs after both stroke subtypes and contributes to neuronal injury and damage to the blood-brain barrier with release of brain antigens and a potential induction of autoimmune responses that escape central and peripheral tolerance mechanisms. In stroke patients, the detection of T cells and antibodies specific to neuronal antigens suggests a role of humoral adaptive immunity. In experimental models stroke leads to a significant increase of autoreactive T and B cells to CNS antigens. Lesion volume and functional outcome in stroke patients and murine stroke models are connected to antigen-specific responses to brain proteins. In patients with traumatic brain injury (TBI) a range of antibodies against brain proteins can be detected in serum samples. In this review, we will summarize the role of autoimmunity in post-lesional conditions and discuss the role of B and T cells and their potential neuroprotective or detrimental effects.

Risk factors predicting prognosis and outcome of elderly patients with isolated traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI), particularly in the elderly patient population, is known to be the single largest cause of death and disability worldwide. The purpose of this retrospective study was to evaluate clinical factors predicting poor outcome with special emphasis on the impact of respiratory failure (RF) on mortality in elderly patients with isolated severe TBI. METHODS: All elderly patients (age ≥ 65 years) with isolated severe head injury, admitted to this level I trauma center, during a period of 18 years (from January 1992 to December 2010) were identified from the trauma registry. The medical records were reviewed for demographics, mechanism of injury (MOI), GCS score at admission, RF, pupillary light reflex (LR), CT findings (subdural hematoma, subarachnoid hematoma, edema, midline-shift), and whether there was conservative treatment or surgical intervention and the Glasgow Outcome Score (GOS) at hospital discharge. Stepwise logistic regression analysis was used to identify risk factors for a poor prognosis and outcome. RESULTS: The following variables influenced the mortality: respiratory failure, pupillary response, and the injury severity score (ISS). A significant increased risk of death was also found for patients with a midline shift of over 15 mm. CONCLUSIONS: The present study predicts a strong correlation between respiratory failure, pathological pupillary response, a higher ISS, and substantial midline shift with poor outcomes in elderly patients sustaining an isolated severe TBI. TRIAL REGISTRATION: Clinical trials: ID: NCT02386865 . Registered 12 March 2015-retrospectively registered.

Emerging from an unresponsive wakefulness syndrome: brain plasticity has to cross a threshold level.

Unresponsive wakefulness syndrome (UWS, previously known as vegetative state) occurs after patients survive a severe brain injury. Patients suffering from UWS have lost awareness of themselves and of the external environment and do not retain any trace of their subjective experience. Current data demonstrate that neuronal functions subtending consciousness are not completely reset in UWS; however, they are reduced below the threshold required to experience consciousness. The critical factor that determines whether patients will recover consciousness is the distance of their neuronal functions from this threshold level. Recovery of consciousness occurs through functional and/or structural changes in the brain, i.e., through neuronal plasticity. Although some of these changes may occur spontaneously, a growing body of evidence indicates that rehabilitative interventions can improve functional outcome by promoting adaptive functional and structural plasticity in the brain, especially if a comprehensive neurophysiological theory of consciousness is followed. In this review we will focus on the pathophysiological mechanisms involved in UWS and on the plastic changes operating on the recovery of consciousness.