Repeat Traumatic Brain Injury Research Articles

Repeat traumatic brain injury exacerbates acute thalamic hyperconnectivity in humans.

Repeated mild traumatic brain injury is of growing interest regarding public and sporting safety and is thought to have greater adverse or cumulative neurological effects when compared with single injury. While epidemiological links between repeated traumatic brain injury and outcome have been investigated in humans, exploration of its mechanistic substrates has been largely undertaken in animal models. We compared acute neurological effects of repeat mild traumatic brain injury (n = 21) to that of single injury (n = 21) and healthy controls (n = 76) using resting-state functional MRI and quantified thalamic functional connectivity, given previous identification of its prognostic potential in human mild traumatic brain injury and rodent repeat mild traumatic brain injury. Acute thalamocortical functional connectivity showed a rank-based trend of increasing connectivity with number of injuries, at local and global scales of investigation. Thus, history of as few as two previous injuries can induce a vulnerable neural environment of exacerbated hyperconnectivity, in otherwise healthy individuals from non-specialist populations. These results further establish thalamocortical functional connectivity as a scalable marker of acute injury and long-term neural dysfunction following mild traumatic brain injury.

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>.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>.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.

Lifetime Traumatic Brain Injury and Risk of Post-Concussive Symptoms in the Millennium Cohort Study.

Traumatic brain injury (TBI) is prevalent among active duty military service members, with studies reporting up to 23% experiencing at least one TBI, with 10-60% of service members reporting at least one subsequent repeat TBI. A TBI has been associated with an increased risk of cumulative effects and long-term neurobehavioral symptoms, impacting operational readiness in the short-term and overall health in the long term. The association between multiple TBI and post-concussive symptoms (PCS), however, defined as symptoms that follow a concussion or TBI, in the military has not been adequately examined. Previous studies in military populations are limited by methodological issues including small sample sizes, the use of non-probability sampling, or failure to include the total number of TBI. To overcome these limitations, we examined the association between the total lifetime number of TBI and total number of PCS among U.S. active duty military service members who participated in the Millennium Cohort Study. A secondary data analysis was conducted using the Millennium Cohort Study's 2014 survey (n = 28,263) responses on self-reported TBI and PCS (e.g., fatigue, restlessness, sleep disturbances, poor concentration, or memory loss). Zero-inflated negative binomial models calculated prevalence ratios (PRs) and 95% confidence intervals (CIs) for the unadjusted and adjusted associations between lifetime TBIs and PCS. A third of military participants reported experiencing one or more TBIs during their lifetime with 72% reporting at least one PCS. As the mean number of PCS increased, mean lifetime TBIs increased. The mean number of PCS by those with four or more TBI (4.63) was more than twice that of those with no lifetime TBI (2.28). One, two, three, and four or more TBI had 1.10 (95% CI: 1.06-1.15), 1.19 (95% CI: 1.14-1.25), 1.23 (95% CI: 1.17-1.30), and 1.30 times (95% CI: 1.24-1.37) higher prevalence of PCS, respectively. The prevalence of PCS was 2.4 (95% CI: 2.32-2.48) times higher in those with post-traumatic stress disorder than their counterparts. Active duty military service members with a history of TBI are more likely to have PCS than those with no history of TBI. These results suggest an elevated prevalence of PCS as the number of TBI increased. This highlights the need for robust, longitudinal studies that can establish a temporal relationship between repetitive TBI and incidence of PCS. These findings have practical relevance for designing both workplace safety prevention measures and treatment options regarding the effect on and from TBI among military personnel.

Repeat Traumatic Brain Injury Complications with Localized Dissociative Amnesia of Twenty-Two Years

A 53-year-old male with history of traumatic brain injury (TBI) presented with localized dissociative amnesia following a second head injury. While memory loss due to TBI is present in the literature, presentations of this type are very rare. Although fully independent in activities of daily living, this patient demonstrated severe deficits in visual memory and processing speed upon neurocognitive evaluation. Effort testing was unremarkable. Increased awareness and study of memory loss following TBI can contribute to enhanced understanding and improved care for patients experiencing these deficits. The authors present this unique case’s profile, clinical history, and discuss their findings.

The effect of birth order on length of hospitalization for pediatric traumatic brain injury: an analysis of the 1987 Finnish birth cohort

PurposeThis study examines the relationship between birth order and length of hospitalization due to pediatric traumatic brain injury (TBI).MethodsWe prospectively followed 59,469 Finnish newborns from 1987 until age 18 years. Data on first diagnosis of TBI was recorded within the 1987 Finnish Birth Cohort (FBC). Hospitalization period was divided into two categories: 2 days or less and more than 2 days. The latter was considered in this study as longer hospitalization.ResultsCompared with first born siblings, later born siblings had an increased risk of a longer hospitalization for TBI (12.7% of fourth or higher born birth children diagnosed with TBI were hospitalized for 2 or more days, 11.3% of first born, 10.4% of third born and 9.0% of second born). Fourth or higher born children were more likely to experience a repeat TBI; 13.4% of fourth or higher born children diagnosed with TBI had 2–3 TBIs during the study period compared to 9% of third born, 7.8% of second born and 8.8% of the first born. Injuries in the traffic environment and falls were the most common contributors to pediatric TBI and occurred most frequently in the fourth or higher birth category; 29.3% of TBIs among fourth or higher birth order were due to transport accidents and 21% were due to falls.ConclusionsThis study revealed a significant increase in risk for longer hospitalization due to TBI among later born children within the same sibling group. The study provides epidemiological evidence on birth order as it relates to TBI, and its potential to help to explain some of the statistical variability in pediatric TBI hospitalization over time in this population.

Estimating Repeat Traumatic Brain Injury in the U.S. Military, 2015-2017.

Traumatic brain injury (TBI) is a significant health issue among deployed and non-deployed U.S. military service members (SMs). Since 2000, an estimated 413,858 SMs have been diagnosed with at least one TBI. Due to the difficulty in distinguishing new incident TBIs from follow-up TBI-related medical encounters in the Military Health System (MHS), the official TBI case definition also includes an incidence rule considering an individual an incident case only once per lifetime. We sought to examine patterns in medical records of SMs with at least one TBI encounter, in an effort to identify repeat TBIs in individual SMs and to estimate the incidence of repeat TBIs within the study cohort as a whole. Using the official DoD TBI case definition, we obtained a list of SMs who sustained their first active duty TBI between October 1, 2015, and September 30, 2017. We identified the SM's diagnosing encounter (index TBI). Subsequently, we identified patterns associated with diagnosing medical encounters, as opposed to encounters associated with follow-up TBI care. We flagged external cause of injury records and the presence of TBI-related symptom codes at the diagnosing encounter. Traumatic brain injury-related symptoms included memory issues, alteration of cognition, hearing loss, vertigo, headache, anxiety, depression, emotional lability, weakness, insomnia, and vision disturbance. Data discovery results were shared with a group of clinicians at the Defense and Veterans Brain Injury Center, and the list of variables was further refined based on clinical expertise. Subsequently, we conducted stepwise logistic regression, and best fitting model was used to create a probability score to be applied to all TBI-related medical encounters. To validate the accuracy of the model-derived probability score, a stratified random sample of medical records was reviewed by trained clinician. At the 0.5 probability cutoff point, the model had an area under the curve of 0.69. We applied the final model portability scores to all identified TBI encounters to estimate the incidence of repeat TBI within the cohort. Between October 1, 2015, and September 30, 2017, we identified 36,440 SMs and their first lifetime TBI encounter. Study follow-up period was 2 years. Predictors of repeat TBI (rTBI) encounters included the presence of TBI diagnosis extender codes "A" (odds ratio [OR] = 4.67, 95% CI 2.15-10.12); W and V series codes (OR = 4.05, 95% CI 2.05-7.95 and OR = 2.86, 95% CI 1.40-5.83, respectively); patient's disposition at home/quarters; and admission or immediate referral (OR = 3.67, 95% CI 1.79-7.51). Number of diagnosis codes in patient's medical record was inversely associated with a repeat TBI encounter (OR = 0.84, 95% CI 0.76-0.96). Applying model-derived probability score onto identified medical records, we estimate that 804 unique SMs sustained an rTBI during the follow-up period, yielding a rate of 260 rTBIs per 10,000 person-years or approximately 2.32% of SMs annually. Probability scores based on statistical modeling can provide reasonable estimates of repeat incidences of TBI using medical billing data when formerly only the first TBI was thought to be measurable. With 100% sensitivity and 69% specificity, application of these models can inform estimates of repeat TBI across the MHS. This effort shows initial success if estimating repeat TBI, and further modeling work is encouraged to increase the predictive characteristics of the models as these efforts show promise in estimating repeat TBI across the MHS.

The Impact of Preexisting Illness and Substance Use on Functional and Neuropsychological Outcomes Following Traumatic Brain Injury

Traumatic brain injury (TBI) is a significant public health problem in the US. Specific preexisting medical illnesses delay recovery after TBI and increase mortality or risk of repeat TBI. This study examined the impact of preexisting illness and substance use on patient rehabilitation outcomes following TBI. The Functional Independence Measure total score and Disability Rating Scale score measured functional outcomes at discharge from inpatient rehabilitation, while the Trail Making Test A and B and Total Trials 1-5 of the California Verbal Learning Test-II measured neuropsychological outcomes in 128 TBI survivors with moderate or severe TBI. Results showed that the presence of a heart condition or diabetes/high blood sugar was associated with lower functional outcomes by discharge. A history of a heart condition, stroke, or respiratory condition prior to TBI was associated with reduced cognitive flexibility. Those with preexisting diabetes/high blood sugar demonstrated poorer visual attention, visuomotor processing speed, and ability to learn and recall verbal information. Those with pre-TBI cancer also had greater auditory-verbal memory deficits. The findings showed that specific preexisting medical conditions are independently associated with lower functional and cognitive outcomes for patients with TBI. By screening patients for preexisting medical conditions, multidisciplinary TBI rehabilitation teams can identify patients who require more aggressive treatments or greater length of stay.

Adolescent TBI-induced hypopituitarism causes sexual dysfunction in adult male rats.

Adolescents are at greatest risk for traumatic brain injury (TBI) and repeat TBI (RTBI). TBI-induced hypopituitarism has been documented in both adults and juveniles and despite the necessity of pituitary function for normal physical and brain development, it is still unrecognized and untreated in adolescents following TBI. TBI induced hormonal dysfunction during a critical developmental window has the potential to cause long-term cognitive and behavioral deficits and the topic currently remains unaddressed. The purpose of this study was to determine if four mild TBIs delivered to adolescent male rats disrupts testosterone production and adult behavioral outcomes. Plasma testosterone was quantified from 72 hrs preinjury to 3 months postinjury and pubertal onset, reproductive organ growth, erectile function and reproductive behaviors were assessed at 1 and 2 months postinjury. RTBI resulted in both acute and chronic decreases in testosterone production and delayed onset of puberty. Significant deficits were observed in reproductive organ growth, erectile function and reproductive behaviors in adult rats at both 1 and 2 months postinjury. These data suggest adolescent RTBI-induced hypopituitarism underlies abnormal behavioral changes observed during adulthood. The impact of undiagnosed hypopituitarism following RTBI in adolescence has significance not only for growth and puberty, but also for brain development and neurobehavioral function as adults.

Abstracts fromThe 32nd AnnualNational Neurotrauma SymposiumJune 29–July 2, 2014San Francisco, California

Abstracts fromThe 32^nd AnnualNational Neurotrauma SymposiumJune 29–July 2, 2014San Francisco, California

The effects of repeat traumatic brain injury on the pituitary in adolescent rats.

Adolescents are one of the highest groups at risk for sustaining both traumatic brain injury (TBI) and repeat TBI (RTBI). Consequences of endocrine dysfunction following TBI have been routinely explored in adults, but studies in adolescents are limited, and show an incidence rate of endocrine dysfunction in 16-61% in patients, 1-5 years after injury. Similar to in adults, the most commonly affected axis is growth hormone (GH) and insulin-like growth hormone 1 (IGF-1). Despite TBI being the primary cause of morbidity and mortality among the pediatric population, there are currently no experimental studies specifically addressing the occurrence of pituitary dysfunction in adolescents. The present study investigated whether a sham, single injury or four repeat injuries (24 h interval) delivered to adolescent rats resulted in disruption of the GH/IGF-1 axis. Circulating levels of basal GH and IGF-1 were measured at baseline, 24 h, 72 h, 1 week, and 1 month after injury, and vascular permeability of the pituitary gland was quantified via Evans Blue dye extravasation. Changes in weight and length of animals were measured as a potential consequence of GH and IGF-1 disruption. The results from the current study demonstrate that RTBI results in significant acute and chronic decreases in circulation of GH and IGF-1, reduction in weight gain and growth, and an increase in Evans Blue dye extravasation in the pituitary compared with sham and single injury animals. RTBI causes significant disruption of the GH/IGF-1 axis that may ultimately affect normal cognitive and physical development during adolescence.

Insights Into Pediatric Concussions From a Novel Repeat Traumatic Brain Injury Mouse Model

Insights Into Pediatric Concussions From a Novel Repeat Traumatic Brain Injury Mouse Model

Repeat Traumatic Brain Injury in the Juvenile Rat Is Associated with Increased Axonal Injury and Cognitive Impairments

Among the enormous population of head-injured children and young adults are a growing subpopulation who experience repeat traumatic brain injury (RTBI). The most common cause of RTBI in this age group is sports-related concussions, and athletes who have experienced a head injury are at greater risk for subsequent TBI, with consequent long-term cognitive dysfunction. While several animal models have been proposed to study RTBI, they have been shown to either produce injuries too severe, were conducted in adults, involved craniotomy, or failed to show behavioral deficits. A closed head injury model for postnatal day 35 rats was established, and single and repeat TBI (1-day interval) were examined histologically for axonal injury and behaviorally by the novel object recognition (NOR) task. The results from the current study demonstrate that an experimental closed head injury in the rodent with low mortality rates and absence of gross pathology can produce measurable cognitive deficits in a juvenile age group. The introduction of a second injury 24 h after the first impact resulted in increased axonal injury, astrocytic reactivity and increased memory impairment in the NOR task. The histological evidence demonstrates the potential usefulness of this RTBI model for studying the impact and time course of RTBI as it relates to the pediatric and young adult population. This study marks the first critical step in experimentally addressing the consequences of concussions and the cumulative effects of RTBI in the developing brain.

Pre-existing Health Conditions and Repeat Traumatic Brain Injury

Saunders LL, Selassie AW, Hill EG, Horner MD, Nicholas JS, Lackland DT, Corrigan JD. Pre-existing health conditions and repeat traumatic brain injury. Objective To assess and compare the effect of Pre-existing epilepsy/seizure disorder and drug/alcohol problem on the hazard of repeat traumatic brain injury (TBI) in persons with TBI who participated in a follow-up study. Design Retrospective cohort. Setting Acute care hospitals in South Carolina. Participants Participants were from the South Carolina Traumatic Brain Injury Follow-up Registry cohort of persons (N=2118) who were discharged from an acute care hospital in South Carolina and who participated in a year-1 follow-up interview. Interventions Not applicable. Main Outcome Measures Repeat TBI was defined by 2 isolated events of TBI in the same person at least 72 hours apart and recorded in hospital discharge or emergency department records from 1999 through 2005. Results A Cox proportional hazards model was used to assess the associations of Pre-existing epilepsy/seizure disorder and drug/alcohol problem with time to repeat TBI, controlling for other confounding factors. There were 2099 persons with information on both Pre-existing conditions. There were 147 (7%) persons who sustained repeat TBI after recruitment to the follow-up study, and 82 (3.9%) had a previous TBI before recruitment for which they were seen in the hospital discharge or emergency department since 1996. The hazard of repeat TBI for persons with Pre-existing epilepsy/seizure disorder was 2.3 times the hazard for those without (hazard ratio, 2.3; 95% confidence interval, 1.2–4.4; P=.011). Pre-existing drug/alcohol problem was not associated with repeat TBI. Other variables significantly associated with repeat TBI were having a prior TBI, being insured under Medicaid, and having no insurance. Conclusions Pre-existing epilepsy/seizure disorder predisposes to repeat TBI. Appropriate management of seizure control may be an important strategy to allay the occurrence of repeat TBI.