Prior Traumatic Brain Injury Research Articles

B - 50 Traumatic Brain Injury in Patients with Psychogenic Non-epileptic Seizures and Functioning

Abstract Objective Past studies reveal that many patients with psychogenic non-epileptic seizures (PNES) also have a traumatic brain injury (TBI) history, but the specific influence of prior TBI on patients is presently under examination. This study aims to investigate the relationship between patients with PNES with a TBI history and symptoms/functioning, compared to those without a TBI history. Method Data collected from patients seen for comprehensive neuropsychiatric evaluation was analyzed, including TBI history, TBI severity, and Global Assessment of Functioning (GAF) scores. The GAF scale allows assignment of a numerical rating to patients based on their psychological and social functioning. Results Patients with PNES without TBI (n = 120; mean age 51) had higher average GAF scores (52.4) compared to those with TBI (n = 164, mean age 54, mean GAF 50) (p = 0.0059). Across PNES patients with a history of TBI, those with mild TBI exhibited notably lower GAF scores (43.2) than those with moderate (48.87) or severe (50) history of TBI. Conclusion Patients with PNES and a history of TBI had lower (worse) GAF scores than those without TBI, and worse in cases of mild TBI. Further exploration of demographic variables, education, and employment status will address potential confounds. Understanding the complex interplay between PNES and TBI may improve diagnosis and management strategies, with further research in advancing clinical practice.

Prior traumatic brain injury is a risk factor for in-hospital mortality in moderate to severe traumatic brain injury: a TRACK-TBI cohort study

ObjectivesAn estimated 14–23% of patients with traumatic brain injury (TBI) incur multiple lifetime TBIs. The relationship between prior TBI and outcomes in patients with moderate to severe TBI (msTBI) is...

Age-associated gadolinium leakage into ocular structures in patients with acute traumatic brain injury

BackgroundGadolinium Leakage into Ocular Structures (GLOS) is common following acute cerebrovascular events. The objective of this study was to investigate the occurrence of GLOS in an acute traumatic brain injury (TBI) cohort without acute cerebrovascular injury and to explore associated factors. MethodsEnrolled acute TBI patients had a baseline MRI ≤48 h of injury (TP1) and follow-up MRI ≤72 h after baseline (TP2). Vitreous chamber enhancement and signal intensity ratios (SIRs) were calculated using pre- and post-contrast Fluid Attenuated Inversion Recovery (FLAIR). White matter hyperintensities (WMHs) were assessed using the Fazekas scale. ResultsOf the 128 TBI patients included, median age was 47 years, 70% male, and 66% presented with Glasgow Coma Scale of 15. No GLOS was detected at TP1 but was present in 23% of patients at TP2. GLOS+ patients were older (68 years [56–76] vs 39 years [27–53], p < 0.001), more likely to report falls as injury mechanism (62% vs 36%, p = 0.006), report history of hypertension (41% vs 19%, p = 0.025), and had a higher burden of WMHs (59% vs 14% with a total Fazekas ≥2, p < 0.001). Quantitative SIRs confirmed qualitative assessments: GLOS+ patients had higher SIRs at TP2 (0.43 vs 0.22, p < 0.001). Age (OR 3.28, 95%CI [1.88–5.71], p < 0.001) and prior TBI history (OR 4.99, 95%CI [1.46–17.06], p = 0.010) were independent predictors of GLOS. When age was removed, total Fazekas score (OR 2.53, 95%CI [1.60–4.00], p < 0.001) was an independent predictor of GLOS. ConclusionsGLOS is primarily associated with age and may serve as another imaging marker of chronic vascular disease.

Axonal injury, sleep disturbances, and memory following traumatic brain injury.

Traumatic brain injury (TBI) is associated with sleep deficits, but it is not clear why some report sleep disturbances and others do not. The objective of this study was to assess the associations between axonal injury, sleep, and memory in chronic and acute TBI. Data were acquired from two independent datasets which included 156 older adult veterans (69.8 years) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with prior moderate-to-severe TBIs and 90 (69.2 years) controls and 374 (39.6 years) from Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) with a recent mild TBI (mTBI) and 87 controls (39.6 years), all who completed an MRI, memory assessment, and sleep questionnaire. Older adults with a prior TBI had a significant association between axonal injury and sleep disturbances [β = 9.52, 95% CI (4.1, 14.9), p = 0.01]. Axonal injury predicted changes in memory over 1-year in TBI [β = -8.72, 95% CI (-18, -2.7), p = 0.03]. We externally validated those findings in TRACK-TBI where axonal injury within 2 weeks after mTBI was significantly associated with higher sleep disturbances in the TBI group at 2 weeks[β = -7.2, 95% CI (-14, -0.50), p = 0.04], 6 months [β = -16, 95% CI (-24, -7.6), p ≤ 0.01], and 12 months post-injury [β = -11, 95% CI (-19, -0.85), p = 0.03]. These associations were not significant in controls. Axonal injury, specifically to the left anterior internal capsule is robustly associated with sleep disturbances in multiple TBI populations. Early assessment of axonal injury following mTBI could identify those at risk for persistent sleep disturbances following injury.

Association Between Traumatic Brain Injury and Cognitive Decline Among Middle-to-Older Aged Men in the Vietnam Era Twin Study of Aging.

Traumatic brain injury (TBI) is associated with increased risk of dementia. However, whether TBI is associated with greater cognitive decline over time in specific cognitive domains among older adults is not well understood. This prospective cohort study used data from 1476 male Vietnam Era Twin Study of Aging participants (average age at study entry = 57.9 years, range = 51-71 years; 97.6% non-Hispanic; 92.5% White) collected from 2003 to 2019, who had complete information on prior TBI. Participants completed a comprehensive neuropsychological assessment at up to three visits over up to a 12-year follow-up period during which they also self-reported their history of TBI. Multivariable, linear mixed-effects models were used to assess associations between TBI and cognitive performance trajectories. Effect measure modification by apolipoprotein E (APOE) epsilon 4 (ε4) genotype status was assessed in a subset of participants. Thirty-one percent of participants reported a history of TBI; 29.4% were APOE ε4 carriers. There were no statistically significant associations of TBI with decline in episodic memory, executive function, or processing speed among participants overall. In models stratified by APOE ε4 carrier status, TBI was associated with a larger magnitude of decline in executive function for APOE ε4 carriers (β = -0.0181; 95% confidence interval [CI] -0.0335, -0.0027) compared to noncarriers (β = -0.0031; 95% CI -0.0128, 0.0067; P Interaction = 0.03). In sensitivity analyses, TBI earlier in life (before military induction, average age = 20 years) was associated with faster declines in executive function compared to no TBI, irrespective of APOE ε4 status. In this sample of middle-to-older aged men, TBI was associated with faster declines in executive function among APOE ε4 carriers and among those who reported TBI in early life. These findings support the importance of a life course perspective when considering factors that may influence cognitive health in aging.

Seizure freedom without seizure medication following stereoelectroencephalography implantation: a case report of drug-resistant post-traumatic epilepsy.

Achieving seizure freedom following failure of several antiseizure medications (ASMs) is rare, with the likelihood of achieving further control decreasing with each successive ASM trial. When cases of drug-resistant epilepsy arise, a diagnostic procedure known as stereoelectroencephalography (sEEG) can be used to identify epileptogenic zones (EZ) within the brain. After localization of these zones, they can be targeted for future surgical intervention. Here, we describe a case of complete seizure freedom off medication after sEEG without resection or other therapeutic intervention. In 2017, a 36-year-old right-handed male presented with drug-resistant epilepsy stemming from prior traumatic brain injury. Due to ongoing seizures, in 2020 a robotic-assisted sEEG electrode placement procedure was employed to localize the seizure onset zone. During sEEG monitoring, a single event was captured where the patient had dysarthric speech, left arm dystonic flexion, and difficulty responding to questioning. Notably, this event had no sEEG correlate, suggesting seizure occurrence in a region not monitored by implanted electrodes, which prompted the placement of scalp electrodes following this event. However, no further clinical events consistent with seizure were provoked through the remainder of recording. Following the 13-day admission, the patient chose to self-discontinue all seizure medications and has remained seizure free as of October 2023, more than 3.5 years later. While sEEG is considered a relatively safe procedure for seizure localization in drug resistant epilepsy, the possibility of microlesions created by sEEG depth electrodes remains largely unexplored. Further evaluation should be performed into potential tissue injury produced by depth electrode insertion.

Longitudinal Investigation of Alexithymia as a Predictor of Empathy, Emotional Functioning, Resilience, and Life Satisfaction 2 Years After Brain Injury

ObjectiveTo examine the unique contribution of alexithymia at 1 year after traumatic brain injury (TBI) to the prospective prediction of emotional and social health outcomes at 2 years after injury. DesignMulticenter, longitudinal cohort study. SettingData were collected during year 1 and year 2 postinjury follow-up interviews across 4 TBI Model System centers. ParticipantsPersons with TBI (N=175; 134 men and 41 women) who had English fluency and were capable of providing self-reported data. InterventionsNot applicable. Main Outcome MeasuresPrimary independent variable was the Toronto Alexithymia Scale-20. Outcome measures included the Interpersonal Reactivity Index, National Institute of Health Toolbox Emotion Battery Anger, Difficulty with Emotion Regulation Scale, Connor-Davidson Resilience Scale, Posttraumatic Stress Disorder Checklist – Civilian, Satisfaction with Life Scale, General Anxiety Disorder-7, Patient Health Questionnaire 9, suicidal ideation, and problematic substance use. ResultsSimple adjusted models demonstrated that after controlling for the specific outcome at year 1, Toronto Alexithymia Scale-20 scores significantly predicted year 2 scores for perspective-taking, physical aggression, emotional dysregulation, resilience, anxiety, depression, and suicidal ideation. All of these predictive findings except for physical aggression were maintained in the fully adjusted models that also controlled for age, sex, education level, number of prior TBIs, and motor and cognitive functioning. ConclusionsCompared with those with lower alexithymia scores, persons with TBI who had higher alexithymia scores at 1 year after injury reported poorer emotional health at 2 years after TBI, even after controlling for year 1 outcome scores, sociodemographic characteristics, and injury-related factors. These results support the need to assess for elevated alexithymia and to provide interventions targeting alexithymia early in the TBI recovery process.

176 Repetitive Traumatic Brain Injuries Are Associated With Poorer Outcomes at 1-Year and 3-7 Years After Index Injury

INTRODUCTION: Traumatic brain injury (TBI) patients are at risk for subsequent TBIs. Research on the longitudinal impact of repetitive TBI is limited. METHODS: The 18-center TRACK-TBI study enrolled subjects who presented to hospital and received head computed tomography (CT) within 24-hours of TBI between 2014-2018. Subjects were interviewed regarding post-index TBI during follow-up. Data from subjects aged = 17-years with 1-year or 3-7-year outcomes were extracted. Outcome measures included functional (GOSE:Glasgow Outcome Scale-Extended), post-concussive symptoms (PCS) (RPQ:Rivermead Post-Concussion Symptoms Questionnaire), psychological distress (BSI-18:Brief Symptom Inventory-18), depression (PHQ-9:Patient Health Questionnaire-9), post-traumatic stress disorder (PCL-5:PTSD-Checklist for DSM-5), and quality of life (QOL) (QOLIBRI-OS:Quality of Life After Brain Injury-Overall Scale). Multivariable regressions were adjusted for demographic, socioeconomic, and injury severity factors, and for multiple comparisons. Mean-differences (B), relative risks (RR), and 95% confidence intervals [CI] were reported. RESULTS: In 1,572 subjects, 3.2% and 12.2% sustained post-index TBI at 1-year and 3-7-years, respectively; 2.4% sustained multiple post-index TBIs at 3-7-years. Risk factors included psychiatric history, prior TBI, and extracranial injury severity. At 1-year, post-index TBI was independently associated with incomplete recovery (GOSE&lt;8; RR = 1.75 [1.04-2.94]), decreased QOL (QOLIBRI-OS: B = -15.9 [-22.6, -9.1]), and increased severity of PCS, psychological distress, PTSD, and depression (RPQ: B = 8.1 [4.2-11.9], BSI-18: B = 5.3 [2.1-8.6]; PCL-5: B = 7.8 [3.2-12.4]; PHQ-9: B = 3.0 [1.5-4.4]); effects were conserved at reduced magnitudes at 3-7-years. Multiple (=2 vs. 1) post-index TBIs were associated with greater symptom severities across all outcome measures. CONCLUSIONS: Post-index TBI is associated with incomplete functional recovery, increased PCS, psychological distress, PTSD, and depressive symptom severities, and decreased QOL at 1- and 3-7-years post-injury. Sustaining multiple post-index TBIs further increases symptom severity across all outcome domains. Institutional processes and resources for TBI prevention, education, counseling, and follow-up are greatly needed.

The Effects of Repetitive Head Impact Exposure on Mental Health Symptoms Following Traumatic Brain Injury.

This study aimed to characterize the types and timing of repetitive head impact (RHI) exposures in individuals with moderate to severe traumatic brain injury (TBI) and to examine the effects of RHI exposures on mental health outcomes. TBI Model Systems National Database. 447 patients with moderate to severe TBI who reported RHI exposure between 2015 and 2022. Secondary data analysis. RHI exposures reported on the Ohio State University TBI Identification Method (OSU TBI-ID) were characterized by exposure category, duration, and timing relative to the index TBI. Mental health outcomes were evaluated at the 5-year follow-up assessment using the Patient Health Questionnaire-9 (PHQ-9) for depression symptoms and the Generalized Anxiety Disorder-7 (GAD-7) for anxiety symptoms. The majority of RHI exposures were sports-related (61.1%), followed by other causes (20.8%; including falls), repetitive violence/assault (18.8%), and military exposures (6.7%). Males predominantly reported sports and military exposures, while a larger proportion of females reported violence and falls. Sports exposures were most common before the index TBI, while exposures from falls and violence/abuse were most common after TBI. RHI exposures occurring after the index TBI were associated with higher levels of depression (β = 5.05; 95% CI, 1.59-8.50) and anxiety (β = 4.53; 95% CI, 1.02-8.05) symptoms than exposures before the index TBI. The findings emphasize the need to consider RHI exposures and their interaction with TBI when assessing mental health outcomes. Understanding the prevalence and challenges associated with RHI post-TBI can inform targeted interventions and improve the well-being of individuals with TBI. Preventive measures and ongoing care should be implemented to address the risks posed by RHI, particularly in individuals with prior TBI, especially surrounding fall and violence/abuse prevention.

Traumatic Brain Injury, Psychological Trauma Exposure, and Anxious and Depressive Symptoms in a Clinical Population.

Approximately 90% of adults endorse psychological trauma exposure. However, barriers to assessment of psychological trauma and sequelae include limited access to care, lack of standardized assessments in nonpsychiatric settings, and comorbid diagnoses, such as traumatic brain injury (TBI), that may mimic psychiatric syndromes. This study aims to assess the prevalence rates of psychological trauma exposure and TBI to understand the relationship of these experiences with current psychiatric symptoms. This is a cross-sectional study of a convenience sample of adult patients (age 18years and older) referred for outpatient evaluation at a neuropsychology clinic in the Western United States between September 2021 and October 2022. Patients completed a clinical interview to assess their history of psychological trauma, TBI, and current psychiatric symptoms. A total of 118 patients met inclusion criteria. Patients in the TBI group (n = 83) endorsed significantly higher rates of childhood trauma and prior physical, emotional, and sexual abuse compared with the No TBI group (n = 35). Psychological trauma exposure and TBI significantly predicted current anxiety and depressive symptoms, but there was no interaction between these experiences in predicting current psychiatric symptoms. Individuals with prior TBI experienced psychological trauma, particularly childhood trauma, at a significantly higher rate than those without TBI. Psychological trauma exposure and TBI independently predicted anxious and depressive symptoms, suggesting both may be viable treatment targets. Evaluation of prior psychological trauma exposure during evaluation of TBI may provide opportunities for trauma-informed care and may allow for improved outpatient treatment planning.

Assessing Prevalence of TBI in a Community Setting

Background: Traumatic brain injury (TBI) is often under-reported and thus under-recognized by clinicians. Reports of TBI prevalence have been widely variable based on the methods of data collection and definition of TBI. This study investigates the prevalence of TBI using the Ohio State University TBI Identification Method (OSU TBI-ID), a reliable and valid structured interview designed to elicit lifetime history of TBI. We also assessed relationships between TBI and psychiatric illnesses. Identifying prevalence and effects of TBI on mental health is critical to providing personalized, higher-quality care for psychiatric patients in community settings. &#x0D; &#x0D; Methods: Patients receiving mental health care at the IUSM Psychiatry Residency Clinic in Vincennes, Indiana were asked to participate in a research study assessing history of head or neck injuries. Patients attended their regularly scheduled appointments with resident physicians, and 2–5-minute TBI screenings were conducted during or immediately after their appointment. Following the interview, patient charts were reviewed for documentation of prior TBI and all current psychiatric diagnoses. &#x0D; &#x0D; Results: Prevalence of TBI was reported at 62.3% among patients receiving psychiatric care. 87 total TBI events were recorded, including repetitive TBI events, after 77 patient interviews. The most common cause of acute TBI was vehicular accident. The most common cause of repetitive TBI was sports injury. Of the 87 TBIs, only 5 TBI events were recorded in patient charts. History of TBI was more likely in patients with PTSD as well as substance use disorders, and this was especially evident in patients with repetitive TBI. &#x0D; &#x0D; Conclusion and Potential Impact: This study shows that TBI is quite common among psychiatric patients and is vastly under-reported in patient charts. Increasing clinician awareness of TBI history in their patients is critical to providing high-quality care, and the OSU TBI-ID provides an efficient way to screen patients for TBI.

Blood Markers in Relation to a History of Traumatic Brain Injury Across Stages of Cognitive Impairment in a Diverse Cohort.

Traumatic brain injury (TBI) has been linked to multiple pathophysiological processes that could increase risk for Alzheimer's disease and related dementias (ADRD). However, the impact of prior TBI on blood biomarkers for ADRD remains unknown. Using cross-sectional data, we assessed whether a history of TBI influences serum biomarkers in a diverse cohort (approximately 50% Hispanic) with normal cognition, mild cognitive impairment, or dementia. Levels of glial fibrillary acidic protein (GFAP), neurofilament light (NFL), total tau (T-tau), and ubiquitin carboxy-terminal hydrolase-L1 (UCHL1) were measured for participants across the cognitive spectrum. Participants were categorized based on presence and absence of a history of TBI with loss of consciousness, and study samples were derived through case-control matching. Multivariable general linear models compared concentrations of biomarkers in relation to a history of TBI and smoothing splines modelled biomarkers non-linearly in the cognitively impaired groups as a function of time since symptom onset. Each biomarker was higher across stages of cognitive impairment, characterized by clinical diagnosis and Mini-Mental State Examination performance, but these associations were not influenced by a history of TBI. However, modelling biomarkers in relation to duration of cognitive symptoms for ADRD showed differences by history of TBI, with only GFAP and UCHL1 being elevated. Serum GFAP, NFL, T-tau, and UCHL1 were higher across stages of cognitive impairment in this diverse clinical cohort, regardless of TBI history, though longitudinal investigation of the timing, order, and trajectory of the biomarkers in relation to prior TBI is warranted.

The Relationship between History of Traumatic Brain Injury and Longitudinal Changes in Cortical Thickness among Patients with Alzheimer's Disease.

There has been little direct examination of how traumatic brain injury (TBI) affects the rate of neurodegeneration for individuals with Alzheimer's disease (AD). The study examined 89 cognitively normal adults (65 with and 24 without prior TBI) and 65 with AD (16 with and 49 without prior TBI). Cortical thickness was quantified from T1-weighted MRI scans at baseline and follow-up (mean interval 33.4 months). Partial least squares analysis was used to evaluate the effects of AD and TBI history on the longitudinal change in cortical thickness. Significant group effects were identified throughout the frontal and temporal cortices. Comparison of the AD groups to their control cohorts showed greater relative atrophy for the AD cohort with prior TBI. These results indicate that a history of TBI exacerbates longitudinal declines in cortical thickness among AD patients, providing new insights into the shared pathomechanisms between these neurological conditions.

Tau Imaging in Late Traumatic Brain Injury: A [18F]MK-6240 Positron Emission Tomography Study.

Epidemiological studies have identified prior traumatic brain injury (TBI) as a risk factor for developing Alzheimer's disease (AD). Neurofibrillary tangles (NFTs) are common to AD and chronic traumatic encephalopathy following repetitive mild TBI. However, it is unclear if a single TBI is sufficient to cause accumulation of NFTs. We performed a [18F]MK-6240 positron emission tomography (PET) imaging study to assess NFTs in patients who had sustained a single TBI at least 2 years prior to study inclusion. Fourteen TBI patients (49 ± 20 years; 5 M/9 F; 8 moderate-severe, 1 mild-probable, 5 symptomatic-possible TBI) and 40 demographically similar controls (57 ± 19 years; 19 M/21 F) underwent simultaneous [18F]MK-6240 PET and magnetic resonance imaging (MRI) as well as neuropsychological assessment including the Cambridge Neuropsychological Test Automated Battery (CANTAB). A region-based voxelwise partial volume correction was applied, using parcels obtained by FreeSurfer v6.0, and standardized uptake value ratios (SUVR) were calculated relative to the cerebellar gray matter. Group differences were assessed on both a voxel- and a volume-of-interest-based level and correlations of [18F]MK-6240 SUVR with time since injury as well as with clinical outcomes were calculated. Visual assessment of TBI images did not show global or focal increases in tracer uptake in any subject. On a group level, [18F]MK-6240 SUVR was not significantly different in patients versus controls or between subgroups of moderate-severe TBI versus less severe TBI. Within the TBI group, One Touch Stockings problem solving and spatial working memory (executive function), reaction time (attention), and Mini-Mental State Examination (MMSE) (global cognition) were associated with [18F]MK-6240 SUVR. We found no group-based increase of [18F]MK-6240 brain uptake in patients scanned at least 2 years after a single TBI compared with healthy volunteers, which suggests that no NFTs are building up in the first years after a single TBI. Nonetheless, correlations with cognitive outcomes were found that warrant further investigation.

The Bidirectional Association of TBI and Dementia/MCI among older US Veterans

AbstractBackgroundPrior studies have reported a link between traumatic brain injury (TBI) and risk of adverse neuropsychiatric outcomes including dementia. However it is unclear how prevalent these conditions are prior to TBI and if they are predisposing factors in addition to sequalae.MethodsWe studied older (age &gt;55 years) US veterans who were followed for care at Veterans Affairs Medical Centers across the nation from 2000 to 2019. We first identified all veterans with an incident TBI diagnoses defined as no prior TBI diagnosis, having been seen in an emergency department (ED), having a brain imaging scan (primarily CT) within one day of ED visit and with a subsequent new TBI diagnosis in the electronic medical record (EMR). We then determined 2‐year age‐adjusted prevalence rates (rate per 1000 person‐years and 95% confidence interval or CI) for dementia and mild cognitive impairment (MCI) prior to and post incident TBI. We also compared prior TBI prevalence to prevalence among 1:3 matched (on age and index date) veterans without TBI.ResultsThere were 13,709 primarily male veterans with incident TBI with mean age of 77.7 sd 9.1 years, 81% were non‐Hispanic White. Compared to the 41,127 veterans without TBI (mean age = 77.9, sd 9.1), veterans prior to having an incident TBI had almost a six‐fold greater pre‐TBI age‐adjusted prevalence of dementia (104.9; 95% CI 100.8‐109.0 vs 18.6; 95% CI 17.6‐19.7, p&lt;0.001) and MCI (48.0; 95% CI 45.2‐50.7 vs 8.1; 95% CI 7.4‐8.8, p&lt;0.001). After the incident TBI diagnosis, the age‐adjusted prevalence rates were even higher: dementia (193.5; 95% CI 187.7‐199.2) and MCI (59.3; 95% CI 56.0‐62.6).ConclusionsAmong older US veterans, there is a bidirectional association with dementia/ MCI and TBI with very high prevalence prior to TBI (compared to those without TBI) and even greater prevalence after TBI. These findings highlight the importance of prevention strategies for both pre‐ and post‐TBI cognitive impairment.

57 Traumatic Brain Injury and Concussion in Patients with Frontotemporal Dementia Spectrum Diagnoses

Objective:Traumatic brain injury (TBI) and concussion are associated with increased dementia risk. Accurate TBI/concussion exposure estimates are relatively unknown for less common neurodegenerative conditions like frontotemporal dementia (FTD). We evaluated lifetime TBI and concussion frequency in patients diagnosed with a range of FTD spectrum conditions and related prior head trauma to cavum septum pellucidum (CSP) characteristics observable on MRI.Participants and Methods:We administered the Ohio State University TBI Identification and Boston University Head Impact Exposure Assessment to 108 patients (age 69.5 ± 8.0, 35% female, 93% white or unknown race) diagnosed at the UCSF Memory and Aging Center with one of the following FTD or related conditions: behavioral variant frontotemporal dementia (N=39), semantic variant primary progressive aphasia (N=16), nonfluent variant PPA (N=23), corticobasal syndrome (N=14), or progressive supranuclear palsy (N=16). Data were also obtained from 217 controls (“HC”; age 76.8 ± 8.0, 53% female, 91% white or unknown race). CSP characteristics were defined based on width or “grade” (0-1 vs. 2+) and length of anterior-posterior separation (millimeters). We first describe frequency of any and multiple (2+) prior TBI based on different but commonly used definitions: TBI with loss of consciousness (LOC), TBI with LOC or posttraumatic amnesia (LOC/PTA), TBI with LOC/PTA or other symptoms like dizziness, nausea, “seeing stars,” etc. (“concussion”). TBI/concussion frequency was then compared between FTD and HC using chi-square. Associations between TBI/concussion and CSP characteristics were analyzed with chi-square (CSP grade) and Mann-Whitney U tests (CSP length). We explored sex differences due to typically higher rates of TBI among males.Results:History of any TBI with LOC (FTD=20.0%, HC=19.2%), TBI with LOC/PTA (FTD:32.2%, HC=31.5%), and concussion (FTD: 50.0%, HC=44.3%) was common but not different between study groups (p’s&gt;.4). In both FTD and HC, prior TBI/concussion was nominally more frequent in males but not significantly greater than females. Frequency of repeat TBI/concussion (2+) also did not differ significantly between FTD and HC (repeat TBI with LOC: 6.7% vs. 3.3%, TBI with LOC/PTA: 12.2% vs. 10.3%, concussion: 30.2% vs. 28.7%; p’s&gt;.2). Prior TBI/concussion was not significantly related to CSP grade or length in the total sample or within the FTD or HC groups.Conclusions:TBI/concussion rates depend heavily on the symptom definition used for classifying prior injury. Lifetime symptomatic TBI/concussion is common but has an unclear impact on risk for FTD-related diagnoses. Larger samples are needed to appropriately evaluate sex differences, to evaluate whether TBI/concussion rates differ between specific FTD phenotypes, and to understand the rates and effects of more extensive repetitive head trauma (symptomatic and asymptomatic) in patients with FTD.

The neuropathology of intimate partner violence

Lifelong brain health consequences of traumatic brain injury (TBI) include the risk of neurodegenerative disease. Up to one-third of women experience intimate partner violence (IPV) in their lifetime, often with TBI, yet remarkably little is known about the range of autopsy neuropathologies encountered in IPV. We report a prospectively accrued case series from a single institution, the New York City Office of Chief Medical Examiner, evaluated in partnership with the Brain Injury Research Center of Mount Sinai, using a multimodal protocol comprising clinical history review, ex vivo imaging in a small subset, and comprehensive neuropathological assessment by established consensus protocols. Fourteen brains were obtained over 2 years from women with documented IPV (aged 3rd–8th decade; median, 4th) and complex histories including prior TBI in 6, nonfatal strangulation in 4, cerebrovascular, neurological, and/or psychiatric conditions in 13, and epilepsy in 7. At autopsy, all had TBI stigmata (old and/or recent). In addition, white matter regions vulnerable to diffuse axonal injury showed perivascular and parenchymal iron deposition and microgliosis in some subjects. Six cases had evidence of cerebrovascular disease (lacunes and/or chronic infarcts). Regarding neurodegenerative disease pathologies, Alzheimer disease neuropathologic change was present in a single case (8th decade), with no chronic traumatic encephalopathy neuropathologic change (CTE-NC) identified in any. Findings from this initial series then prompted similar exploration in an expanded case series of 70 archival IPV cases (aged 2nd–9th decade; median, 4th) accrued from multiple international institutions. In this secondary case series, we again found evidence of vascular and white matter pathologies. However, only limited neurodegenerative proteinopathies were encountered in the oldest subjects, none meeting consensus criteria for CTE-NC. These observations from this descriptive exploratory study reinforce a need to consider broad co-morbid and neuropathological substrates contributing to brain health outcomes in the context of IPV, some of which may be potentially modifiable.

Longitudinal Recovery Following Repetitive Traumatic Brain Injury

One traumatic brain injury (TBI) increases the risk of subsequent TBIs. Research on longitudinal outcomes of civilian repetitive TBIs is limited. To investigate associations between sustaining 1 or more TBIs (ie, postindex TBIs) after study enrollment (ie, index TBIs) and multidimensional outcomes at 1 year and 3 to 7 years. This cohort study included participants presenting to emergency departments enrolled within 24 hours of TBI in the prospective, 18-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study (enrollment years, February 2014 to July 2020). Participants who completed outcome assessments at 1 year and 3 to 7 years were included. Data were analyzed from September 2022 to August 2023. Postindex TBI(s). Demographic and clinical factors, prior TBI (ie, preindex TBI), and functional (Glasgow Outcome Scale-Extended [GOSE]), postconcussive (Rivermead Post-Concussion Symptoms Questionnaire [RPQ]), psychological distress (Brief Symptom Inventory-18 [BSI-18]), depressive (Patient Health Questionnaire-9 [PHQ-9]), posttraumatic stress disorder (PTSD; PTSD Checklist for DSM-5 [PCL-5]), and health-related quality-of-life (Quality of Life After Brain Injury-Overall Scale [QOLIBRI-OS]) outcomes were assessed. Adjusted mean differences (aMDs) and adjusted relative risks are reported with 95% CIs. Of 2417 TRACK-TBI participants, 1572 completed the outcomes assessment at 1 year (1049 [66.7%] male; mean [SD] age, 41.6 [17.5] years) and 1084 completed the outcomes assessment at 3 to 7 years (714 [65.9%] male; mean [SD] age, 40.6 [17.0] years). At 1 year, a total of 60 participants (4%) were Asian, 255 (16%) were Black, 1213 (77%) were White, 39 (2%) were another race, and 5 (0.3%) had unknown race. At 3 to 7 years, 39 (4%) were Asian, 149 (14%) were Black, 868 (80%) were White, 26 (2%) had another race, and 2 (0.2%) had unknown race. A total of 50 (3.2%) and 132 (12.2%) reported 1 or more postindex TBIs at 1 year and 3 to 7 years, respectively. Risk factors for postindex TBI were psychiatric history, preindex TBI, and extracranial injury severity. At 1 year, compared with those without postindex TBI, participants with postindex TBI had worse functional recovery (GOSE score of 8: adjusted relative risk, 0.57; 95% CI, 0.34-0.96) and health-related quality of life (QOLIBRI-OS: aMD, -15.9; 95% CI, -22.6 to -9.1), and greater postconcussive symptoms (RPQ: aMD, 8.1; 95% CI, 4.2-11.9), psychological distress symptoms (BSI-18: aMD, 5.3; 95% CI, 2.1-8.6), depression symptoms (PHQ-9: aMD, 3.0; 95% CI, 1.5-4.4), and PTSD symptoms (PCL-5: aMD, 7.8; 95% CI, 3.2-12.4). At 3 to 7 years, these associations remained statistically significant. Multiple (2 or more) postindex TBIs were associated with poorer outcomes across all domains. In this cohort study of patients with acute TBI, postindex TBI was associated with worse symptomatology across outcome domains at 1 year and 3 to 7 years postinjury, and there was a dose-dependent response with multiple postindex TBIs. These results underscore the critical need to provide TBI prevention, education, counseling, and follow-up care to at-risk patients.

Intentional Self-Harm Among US Veterans With Traumatic Brain Injury or Posttraumatic Stress Disorder: Retrospective Cohort Study From 2008 to 2017.

Veterans with a history of traumatic brain injury (TBI) and/or posttraumatic stress disorder (PTSD) may be at increased risk of suicide attempts and other forms of intentional self-harm as compared to veterans without TBI or PTSD. Using administrative data from the US Veterans Health Administration (VHA), we studied associations between TBI and PTSD diagnoses, and subsequent diagnoses of intentional self-harm among US veterans who used VHA health care between 2008 and 2017. All veterans with encounters or hospitalizations for intentional self-harm were assigned "index dates" corresponding to the date of the first related visit; among those without intentional self-harm, we randomly selected a date from among the veteran's health care encounters to match the distribution of case index dates over the 10-year period. We then examined the prevalence of TBI and PTSD diagnoses within the 5-year period prior to veterans' index dates. TBI, PTSD, and intentional self-harm were identified using International Classification of Diseases diagnosis and external cause of injury codes from inpatient and outpatient VHA encounters. We stratified analyses by veterans' average yearly VHA utilization in the 5-year period before their index date (low, medium, or high). Variations in prevalence and odds of intentional self-harm diagnoses were compared by veterans' prior TBI and PTSD diagnosis status (TBI only, PTSD only, and comorbid TBI/PTSD) for each VHA utilization stratum. Multivariable models adjusted for age, sex, race, ethnicity, marital status, Department of Veterans Affairs service-connection status, and Charlson Comorbidity Index scores. About 6.7 million veterans with at least two VHA visits in the 5-year period before their index dates were included in the analyses; 86,644 had at least one intentional self-harm diagnosis during the study period. During the periods prior to veterans' index dates, 93,866 were diagnosed with TBI only; 892,420 with PTSD only; and 102,549 with comorbid TBI/PTSD. Across all three VHA utilization strata, the prevalence of intentional self-harm diagnoses was higher among veterans diagnosed with TBI, PTSD, or TBI/PTSD than among veterans with neither diagnosis. The observed difference was most pronounced among veterans in the high VHA utilization stratum. The prevalence of intentional self-harm was six times higher among those with comorbid TBI/PTSD (6778/58,295, 11.63%) than among veterans with neither TBI nor PTSD (21,979/1,144,991, 1.92%). Adjusted odds ratios suggested that, after accounting for potential confounders, veterans with TBI, PTSD, or comorbid TBI/PTSD had higher odds of self-harm compared to veterans without these diagnoses. Among veterans with high VHA utilization, those with comorbid TBI/PTSD were 4.26 (95% CI 4.15-4.38) times more likely to receive diagnoses for intentional self-harm than veterans with neither diagnosis. This pattern was similar for veterans with low and medium VHA utilization. Veterans with TBI and/or PTSD diagnoses, compared to those with neither diagnosis, were substantially more likely to be subsequently diagnosed with intentional self-harm between 2008 and 2017. These associations were most pronounced among veterans who used VHA health care most frequently. These findings suggest a need for suicide prevention efforts targeted at veterans with these diagnoses.

Traumatic Brain Injury and Long-Term Risk of Stroke Among US Military Veterans.

Traumatic brain injury (TBI) is associated with significant morbidity, but the association of TBI with long-term stroke risk in diverse populations remains less clear. Our objective was to examine the long-term associations of TBI with stroke and to investigate potential differences by age, sex, race and ethnicity, and time since TBI diagnosis. Retrospective cohort study of US military veterans aged 18+ years receiving healthcare in the Veterans Health Administration system between October 1, 2002 and September 30, 2019. Veterans with TBI were matched 1:1 to veterans without TBI on age, sex, race and ethnicity, and index date, yielding 306 796 veterans with TBI and 306 796 veterans without TBI included in the study. In primary analyses, Fine-Gray proportional hazards models adjusted for sociodemographics and medical/psychiatric comorbidities were used to estimate the association between TBI and stroke risk, accounting for the competing risk of mortality. Participants were a mean age of 50 years, 9% were female, and 25% were of non-White race and ethnicity. Overall, 4.7% of veterans developed a stroke over a median follow-up of 5.2 years. Veterans with TBI had 1.69 times (95% CI, 1.64-1.73) increased risk of any stroke (ischemic or hemorrhagic) compared to veterans without TBI. This increased risk was highest in the first-year post-TBI diagnosis (hazard ratio [HR], 2.16 [95% CI, 2.03-2.29]) but remained elevated for 10+ years. Similar patterns were observed for secondary outcomes, with associations of TBI with hemorrhagic stroke (HR, 3.92 [95% CI, 3.59-4.29]) being stronger than with ischemic stroke (HR, 1.56 [95% CI, 1.52-1.61]). Veterans with both mild (HR, 1.47 [95% CI, 1.43-1.52]) and moderate/severe/penetrating injury (HR, 2.02 [95% CI, 1.96-2.09]) had increased risk of stroke compared to veterans without TBI. Associations of TBI with stroke were stronger among older compared to younger individuals (P interaction-by-age<0.001) and were weaker among Black veterans compared to other race and ethnicities (P interaction-by-race<0.001). Veterans with prior TBI are at increased long-term risk for stroke, suggesting they may be an important population to target for primary stroke prevention measures.