Penetrating Traumatic Brain Injury Research Articles

Physiological and radiological parameters predicting outcome from penetrating traumatic brain injury treated in the deployed military setting

IntroductionPenetrating traumatic brain injury (TBI) is the most common cause of death in current military conflicts, and results in significant morbidity in survivors. Identifying those physiological and radiological parameters associated...

Revert total protein normalization method offers a reliable loading control for mitochondrial samples following TBI

Owing to evidence that mitochondrial dysfunction plays a dominant role in the traumatic brain injury (TBI) pathophysiology, the Western blot (WB) based immunoblotting method is widely employed to identify changes in the mitochondrial protein expressions after neurotrauma. In WB method, the housekeeping proteins (HKPs) expression is routinely used as an internal control for sample normalization. However, the traditionally employed HKPs can be susceptible to complex cascades of TBI pathogenesis, leading to their inconsistent expression. Remarkably, our data illustrated here that mitochondrial HKPs, including Voltage-dependent anion channels (VDAC), Complex-IV, Cytochrome C and Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) yielded altered expressions following penetrating TBI (PTBI) as compared to Sham. Therefore, our goal was to identify more precise normalization procedure in WB. Adult male Sprague Dawley rats (N = 6 rats/group) were used to perform PTBI, and the novel REVERT Total Protein (RTP) method was used to quantify mitochondrial protein load consistency between samples at 6 h and 24 h post-injury. Notably, the RTP method displayed superior protein normalization compared to HKPs method with higher sensitivity at both time-points between experimental groups. Our data favors application of RTP based normalization to accurately quantify protein expression where inconsistent HKPs may be evident in neuroscience research.

Intracranial Pressure and Brain Tissue Oxygen Multimodality Neuromonitoring in Gunshot Wounds to the Head in Children

Gunshot wounds to the head (GSWH) are a cause of severe penetrating traumatic brain injury (TBI). Although multimodal neuromonitoring has been increasingly used in blunt pediatric TBI, its role in the pediatric population with GSWH is not known. We report on 3 patients who received multimodal neuromonitoring as part of clinical management at our institution and review the existing literature on pediatric GSWH. We identified 3 patients ≤18 years of age who were admitted to a quaternary children's hospital from 2005 to 2021 with GSWH and received invasive intracranial pressure (ICP) and Pbto2 (brain tissue oxygenation) monitoring with or without noninvasive near-infrared spectroscopy (NIRS). We analyzed clinical and demographic characteristics, imaging findings, and ICP, Pbto2, cerebral perfusion pressure, and rSo2 (regional cerebral oxygen saturation) NIRS trends. All patients were male with an average admission Glasgow Coma Scale score of 4. One patient received additional NIRS monitoring. Episodes of intracranial hypertension (ICP ≥20 mm Hg) and brain tissue hypoxia (Pbto2 <15 mm Hg) or hyperemia (Pbto2 >35 mm Hg) frequently occurred independently of each other, requiring unique targeted treatments. rSo2 did not consistently mirror Pbto2. All children survived, with favorable Glasgow Outcome Scale-Extended score at 6 months after injury. Use of ICP and Pbto2 multimodality neuromonitoring enabled specific management for intracranial hypertension or brain tissue hypoxia episodes that occurred independently of one another. Multimodality neuromonitoring has not been studied extensively in pediatric GSWH; however, its use may provide a more complete picture of patient injury and prognosis without significant added procedural risk.

EFFECTS OF TRANEXAMIC ACID ON NEUROPATHOLOGY, ELECTROENCEPHALOGRAPHY, AND CEREBRAL FIBRIN DEPOSITION IN A RAT MODEL OF POLYTRAUMA WITH CONCOMITANT PENETRATING TRAUMATIC BRAIN INJURY.

Several studies have demonstrated the clinical utility of tranexamic acid (TXA) for use in trauma patients presenting with significant hemorrhage. Tranexamic acid is an antifibrinolytic that inhibits plasminogen activation, and plasmin activity has been shown to mitigate blood loss and reduce all-cause mortality in the absence of adverse vascular occlusive events. Recent clinical developments indicate TXA is safe to use in patients with concomitant traumatic brain injury (TBI); however, the prehospital effects are not well understood. Importantly, TXA has been associated with seizure activity. Therefore, this study sought to evaluate the effects of early administration of TXA on neurological recovery and electroencephalogram (EEG) abnormalities following penetrating TBI with concomitant hypoxemia and hemorrhagic shock. We hypothesized that early administration of TXA will provide hemodynamic stabilization and reduce intracerebral hemorrhage, which will result in improved neurological function. To test this hypothesis, Sprague-Dawley rats received a unilateral, frontal penetrating ballistic-like brain injury by inserting a probe into the frontal cortex of the anesthetized rat. Five minutes following brain injury, animals underwent 30 min of respiratory distress and 30 min of hemorrhage. Upon completion of the hemorrhage phase, animals received the initial dose of drug intravenously over 10 min after which the prehospital phase was initiated. During the prehospital phase, animals received autologous shed whole blood as needed to maintain a MAP of 65 mm Hg. After 90 min, "in-hospital" resuscitation was performed by administering the remaining shed whole blood providing 100% oxygen for 15 min. Upon recovery from surgery, animals were administered their second dose of vehicle or TXA intravenously over 8 h. Tranexamic acid induced an early improvement in neurologic deficit, which was statistically significant compared with vehicle at 24, 48, and 72 h at three doses tested. Analysis of cerebral hemoglobin content and intracerebral lesion progression revealed 100 mg/kg provided the optimal effects for improvement of neuropathology and was continued for determination of adverse treatment effects. We observed no exacerbation of cerebral thrombosis, but TXA treatment caused an increased risk of EEG abnormalities. These results suggest that TXA following polytrauma with concomitant brain injury may provide mild neuroprotective effects by preventing lesion progression, but this may be associated with an increased risk of abnormal EEG patterns. This risk may be associated with TXA inhibition of glycine receptors and may warrant additional considerations during the use of TXA in patients with severe TBI.

Comprehensive evaluation of mitochondrial redox profile, calcium dynamics, membrane integrity and apoptosis markers in a preclinical model of severe penetrating traumatic brain injury.

Traumatic Brain Injury (TBI) is caused by the external physical assaults damages the brain. It is a heterogeneous disorder that remains a leading cause of death and disability in the military and civilian population of the United States. Preclinical investigations of mitochondrial responses in TBI have ascertained that mitochondrial dysfunction is an acute indicator of cellular damage and plays a pivotal role in long-term injury progression through cellular excitotoxicity. The current study was designed to provide an in-depth evaluation of mitochondrial endpoints with respect to redox and calcium homeostasis, and cell death responses following penetrating TBI (PTBI). To evaluate these pathological cascades, anesthetized adult male rats (N=6/group) were subjected to either 10% unilateral PTBI or Sham craniectomy. Animals were euthanized at 24h post-PTBI, and purified mitochondrial fractions were isolated from the brain injury core and perilesional areas. Overall, increased reactive oxygen and nitrogen species (ROS/RNS) production, and elevated oxidative stress markers such as 4-hydroxynonenal (4-HNE), 3-nitrotyrosine (3-NT), and protein carbonyls (PC) were observed in the PTBI group compared to Sham. Mitochondrial antioxidants such as glutathione, peroxiredoxin (PRX-3), thioredoxin (TRX), nicotinamide adenine dinucleotide phosphate (NADPH), superoxide dismutase (SOD), and catalase (CAT) levels were significantly decreased after PTBI. Likewise, PTBI mitochondria displayed significant loss of Ca2+ homeostasis, early opening of mitochondrial permeability transition pore (mPTP), and increased mitochondrial swelling. Both, outer and inner mitochondrial membrane integrity markers, such as voltage-dependent anion channels (VDAC) and cytochrome c (Cyt C) expression were significantly decreased following PTBI. The apoptotic cell death was evidenced by significantly decreased B-cell lymphoma-2 (Bcl-2) and increased glyceraldehyde 3-phosphate dehydrogenase (GAPDH) expression after PTBI. Collectively, current results highlight the comprehensive picture of mitochondria-centric acute pathophysiological responses following PTBI, which may be utilized as novel prognostic indicators of disease progression and theragnostic indicators for evaluating neuroprotection therapeutics following TBI.

Cross-Walk Comparison of the DVBIC-TBICoE and LIMBIC-CENC Combat-Related Concussion Prospective Longitudinal Study Datasets

ObjectiveTo describe and compare cohorts between 2 large, longitudinal, federally-funded TBI studies of Service members and veterans across demographic, self-report, and neuropsychological variables. DesignAnalysis of data from the DVBIC-TBICoE and LIMBIC-CENC prospective longitudinal studies (PLS). SettingRecruitment locations spanning Department of Defense and Veterans Affairs hospitals across the U.S. Participants1463 participants (N=1463) enrolled in the DVBIC-TBICoE study and divided among non-injured (NIC) (n=191), injured control (IC) (n=349), mild TBI (mTBI) (n=682), and (severe, moderate, penetrating, and complicated mild traumatic brain injury (smcTBI) (n=241) subgroups. 1550 participants enrolled in the LIMBIC-CENC study and divided between IC (n=285) and mTBI (n=1265) subgroups. IC and mTBI study groups were compared across demographic and military characteristics, self-reported symptoms, and neuropsychological test scores. InterventionsNone. Main Outcome MeasuresNeurobehavioral Symptom Inventory, PTSD Checklist-Military Version, TBI quality of life, Test of Premorbid Functioning, Wechsler Adult Intelligence Scale-IV Visual Puzzles, Symbol Search, Coding, Letter-Number Sequencing, and Digit Span, Trail Making Test, Delis-Kaplan Executive Functioning System Verbal Fluency, Letter Fluency, and Category Fluency, California Verbal Learning Test-II, and Grooved Pegboard. ResultsCompared with DVBIC-TBICoE, LIMBIC-CENC participants have higher enrollment age, education level, proportion of Black race, and time from injury as well as less combat deployments and are less likely to be married. The distribution of military service branches also differed. Further, symptom profiles differed between cohorts. LIMBIC-CENC participants endorsed higher posttraumatic stress disorder symptomatology. DVBIC-TBICoE study IC participants endorsed higher somatosensory and vestibular symptoms (medium effect sizes). Other symptom measure differences had very small effect sizes (≤0.2). Differences were found on many cognitive test results, but are difficult to interpret given the demographic differences and generally very small effect sizes. ConclusionsThe heavy use of National Institutes of Health common data elements in both studies and collaboration with the DVBIC-TBICoE study team on development of the LIMBIC-CENC assessment battery enabled this comparative analysis. Results highlight unique differences in study cohorts and add perspective and interpretability for assimilating past and future findings.

Civilian penetrating traumatic brain injury: A 5-year single-center experience.

The aim of this study was to report the demographics and clinical features of patients with penetrating traumatic brain injury (PTBI) during the past 5 years in Rajaee Hospital, a tertiary referral trauma center in Shiraz, southern Iran. We conducted a 5-year retrospective evaluation of all patients diagnosed with PTBI who were referred to Rajaee Hospital. We retrieved the following items from the hospital's database and PACS system: patients' demographics, on-admission Glasgow Coma Scale (GCS), presence of trauma to other organs, duration of the hospital and ICU stay, the neurosurgical interventions, any necessity of tracheostomy, duration of ventilator dependency, the entrance point of the trauma in the skull, type of assault, length of trajectory in the brain parenchyma, the number of remaining objects in the brain, the occurrence of any hemorrhagic phenomenon, the cross of the bullet from the midline or coronal suture, and the presence of the pneumocephalus. A total of 59 patients with a mean age of 28.75 ± 9.40 had PTBI over the 5 years. The mortality rate was 8.5%. Stab wounds, shotguns, gunshots, and airguns were the cause of injury in 33 (56%), 14 (23.7%), 10 (17%), and 2 (3.4%) patients, respectively. The median initial GCS of patients was 15 (3-15). Intracranial hemorrhage was observed in 33 cases, subdural hematoma in 18 cases, intraventricular hemorrhage in eight cases, and subarachnoid hemorrhage in four cases. The mean duration of hospitalization was 10.05 ± 10.75 (ranging from 1 to 62 days). Furthermore, 43 patients experienced ICU admission with mean days of 6.5 ± 5.62 (1-23). The temporal and frontal regions were the most common entrance points, in 23 and 19 patients, respectively. The incidence of PTBI is relatively low in our center, possibly due to the prohibition of possession or using warm weapons in Iran. Further, multicenter studies with larger sample sizes are needed to determine prognostic factors associated with worse clinical outcomes after PTBI.

Risk-adjusted mortality in severely injured adult trauma patients in Sweden

BackgroundRisk-adjusted mortality (RAM) analysis and comparisons of clinically relevant subsets of trauma patients allow hospitals to assess performance in different processes of care. The aim of the study was to develop a RAM model and compare RAM ratio (RAMR) in subsets of severely injured adult patients treated in university hospitals (UHs) and emergency hospitals (EHs) in Sweden.MethodsThis was a retrospective study of the Swedish trauma registry data (2013 to 2017) comparing RAMR in patients (aged 15 years or older and New Injury Severity Score (NISS) of more than 15) in the total population (TP) and in multisystem blunt (MB), truncal penetrating (PEN), and severe traumatic brain injury (STBI) subsets treated in UHs and EHs. The RAM model included the variables age, NISS, ASA Physical Status Classification System Score, and physiology on arrival.ResultsIn total, 6690 patients were included in the study (4485 from UHs and 2205 from EHs). The logistic regression model showed a good fit. RAMR was 4.0, 3.8, 7.4, and 8.5 percentage points lower in UH versus EH for TP (P < 0.001), MB (P < 0.001), PEN (P = 0.096), and STBI (P = 0.005), respectively. The TP and MB subsets were subgrouped in with (+) and without (−) traumatic brain injury (TBI). RAMR was 7.5 and 7.0, respectively, percentage points lower in UHs than in EHs in TP + TBI and MB + TBI (both P < 0.001). In the TP–TBI (P = 0.027) and MB–TBI (P = 0.107) subsets the RAMR was 1.6 and 1.8 percentage points lower, respectively.ConclusionThe lower RAMR in UHs versus EH were due to differences in TBI-related mortality. No evidence supported that Swedish EHs provide inferior quality of care for trauma patients without TBI or for patients with penetrating injuries.

Performance of the Modified Rapid Emergency Medicine Score in Patients With and Without Traumatic Brain Injury.

BACKGROUND: The modified Rapid Emergency Medicine Score (mREMS) is a recently published index to estimate the severity of trauma patients; however, little is known about its performance in patients with different types of trauma. This study verified the predictive capacity of mREMS in-hospital mortality in patients of blunt and penetrating trauma with and without traumatic brain injury (TBI) and the performance of this index compared with the Rapid Emergency Medicine Score, Injury Severity Score, New Injury Severity Score, and Trauma and Injury Severity Score. METHODS: This is a retrospective, correlational study that analyzed trauma patients 18 years or older, who attended at a hospital in Rio de Janeiro, Brazil. The receiver operating characteristic (ROC) curve was applied in the analyses. RESULTS: The sample consisted of 987 patients, 359 (36.4%) with TBI (225 blunt and 134 penetrating trauma). Regarding mREMS, the area under the ROC curve for TBI patients for in-hospital mortality was 0.506 (95% confidence interval [CI], 0.404-0.609) for penetrating injuries and 0.486 (95% CI, 0.402-0.571) for blunt injuries; the values in patients without TBI were 0.629 (95% CI, 0.554-0.703) and 0.618 (95% CI, 0.552-0.684), respectively. In relation to the other indices the mREMS presented the lowest area under the curve/ROC for penetrating and blunt TBI, and the Rapid Emergency Medicine Score for extracranial injuries. CONCLUSION: The mREMS showed no prognostic capacity for patients with TBI, and it presented the worst performance in relation to the Injury Severity Score, New Injury Severity Score, and Trauma and Injury Severity Score to discriminate cases of in-hospital mortality when considering trauma patients with and without TBI.

Stimulating and Analyzing Adult Neurogenesis in the Drosophila Central Brain.

The molecular and cellular mechanisms underlying neurogenesis in response to disease or injury are not well understood. However, understanding these mechanisms is crucial for developing neural regenerative therapies. Drosophila melanogaster is a leading model for studies of neural development but historically has not been exploited to investigate adult brain regeneration. This is primarily because the adult brain exhibits very low mitotic activity. Nonetheless, penetrating traumatic brain injury (PTBI) to the adult Drosophila central brain triggers the generation of new neurons and new glia. The powerful genetic tools available in Drosophila combined with the simple but rigorous injury protocol described here now make adult Drosophila brain a robust model for neural regeneration research. Provided here are detailed instructions for (1) penetrating injuries to the adult central brain and (2) dissection, immunohistochemistry, and imaging post-injury. These protocols yield highly reproducible results and will facilitate additional studies to dissect mechanisms underlying neural regeneration.

Stimulating and Analyzing Adult Neurogenesis in the &lt;em&gt;Drosophila&lt;/em&gt; Central Brain

The molecular and cellular mechanisms underlying neurogenesis in response to disease or injury are not well understood. However, understanding these mechanisms is crucial for developing neural regenerative therapies. Drosophila melanogaster is a leading model for studies of neural development but historically has not been exploited to investigate adult brain regeneration. This is primarily because the adult brain exhibits very low mitotic activity. Nonetheless, penetrating traumatic brain injury (PTBI) to the adult Drosophila central brain triggers the generation of new neurons and new glia. The powerful genetic tools available in Drosophila combined with the simple but rigorous injury protocol described here now make adult Drosophila brain a robust model for neural regeneration research. Provided here are detailed instructions for (1) penetrating injuries to the adult central brain and (2) dissection, immunohistochemistry, and imaging post-injury. These protocols yield highly reproducible results and will facilitate additional studies to dissect mechanisms underlying neural regeneration.

Prevalence of Comorbidities in Active and Reserve Service Members Pre and Post Traumatic Brain Injury, 2017-2019.

To understand the prevalence of comorbidities associated with traumatic brain injury (TBI) patients among active and reserve service members in the U.S. Military. Active and reserve SMs diagnosed with an incident TBI from January 2017 to October 2019 were selected. Nineteen comorbidities associated with TBI as identified in the literature and by clinical subject matter experts were described in this article. Each patient's medical encounters were evaluated from 6months before to 2years following the initial TBI diagnoses date in the Military Data Repository, if data were available. Time-to-event analyses were conducted to assess the cumulative prevalence over time of each comorbidity to the incident TBI diagnosis. We identified 47,299 TBI patients, of which most were mild (88.8%), followed by moderate (10.5%), severe (0.5%), and of penetrating (0.2%) TBI severity. Two years from the initial TBI diagnoses, the top five comorbidities within our cohort were cognitive disorders (51.9%), sleep disorders (45.0%), post-traumatic stress disorder (PTSD; 36.0%), emotional disorders (22.7%), and anxiety disorders (22.6%) across severity groups. Cognitive, sleep, PTSD, and emotional disorders were the top comorbidities seen within each TBI severity group. Comorbidities increased pre-TBI to post-TBI; the more severe the TBI, the greater the prevalence of associated comorbidities. A large proportion of our TBI patients are afflicted with comorbidities, particularly post-TBI, indicating many have a complex profile. The military health system should continue tracking comorbidities associated with TBI within the U.S. Military and devise clinical practices that acknowledge the complexity of the TBI patient.

Neurogenesis in the adult Drosophila brain

Neurodegenerative diseases such as Alzheimer's and Parkinson's currently affect ∼25 million people worldwide. The global incidence of traumatic brain injury (TBI) is estimated at ∼70 million/year. Both neurodegenerative diseases and TBI remain without effective treatments. We are utilizing adult Drosophila melanogaster to investigate the mechanisms of brain regeneration with the long-term goal of identifying targets for neural regenerative therapies. We specifically focused on neurogenesis, i.e., the generation of new cells, as opposed to the regrowth of specific subcellular structures such as axons. Like mammals, Drosophila have few proliferating cells in the adult brain. Nonetheless, within 24 hours of a penetrating traumatic brain injury (PTBI) to the central brain, there is a significant increase in the number of proliferating cells. We subsequently detect both new glia and new neurons and the formation of new axon tracts that target appropriate brain regions. Glial cells divide rapidly upon injury to give rise to new glial cells. Other cells near the injury site upregulate neural progenitor genes including asense and deadpan and later give rise to the new neurons. Locomotor abnormalities observed after PTBI are reversed within 2 weeks of injury, supporting the idea that there is functional recovery. Together, these data indicate that adult Drosophila brains are capable of neuronal repair. We anticipate that this paradigm will facilitate the dissection of the mechanisms of neural regeneration and that these processes will be relevant to human brain repair.

Risk factors of persistent insomnia among survivors of traumatic injury: a retrospective cohort study.

Insomnia is a diagnosis with broad health and economic implications that has been increasingly recognized in military service members. This trend was concurrent with an increase in traumatic wartime injuries. Accordingly, we sought to determine longitudinal predictors of persistent insomnia in combat veterans who sustained traumatic injuries. Retrospective cohort study of service members deployed to conflict zones from 2002 to 2016, with longitudinal follow-up in the Veterans Affairs and Military Health Systems. Two cohorts were derived: (1) service members who sustained traumatic injuries and (2) an age-, sex-, and service component-matched cohort of uninjured service members who deployed to a combat zone. Insomnia was defined using International Classification of Diseases, Ninth Revision or International Classification of Diseases, 10th Revision-Clinical Modification codes. The final population of 17,374 service members was followed from date of injury (or date of matched participant's injury) for a median of 8.4 (interquartile range, 5.3-10.7) years. Service members with traumatic injury were at significantly greater risk of developing insomnia than uninjured service members (hazard ratio = 1.43; 95% confidence interval, 1.30-1.58) after adjustment. Traumatic brain injury was associated with insomnia compared with patients without traumatic brain injury in the multivariable model: mild/unclassified traumatic brain injury (hazard ratio = 2.07; 95% confidence interval, 1.82-2.35) and moderate/severe/ penetrating traumatic brain injury (hazard ratio = 2.43; 95% confidence interval, 2.06-2.86). Additionally, burn injury (hazard ratio = 1.95; 95% confidence interval, 1.47-2.59) and amputation (hazard ratio = 1.61; 95% confidence interval, 1.26-2.06) significantly increased the risk of a diagnosis. Traumatic injuries significantly predicted a diagnosis of insomnia after controlling for mental health disorders. Our findings strongly suggest the need for long-term surveillance of sleep disorders in trauma survivors. Haynes ZA, Collen JF, Poltavskiy EA, etal. Risk factors of persistent insomnia among survivors of traumatic injury: a retrospective cohort study. J Clin Sleep Med. 2021;17(9):1831-1840.

Syllabic Diadochokinesis in Adults With and Without Traumatic Brain Injury: Severity, Stability, and Speech Considerations.

Purpose Syllabic diadochokinesis (DDK) is a standard assessment task for motor speech disorders. This study aimed to compare rate and regularity of DDK according to the presence or absence of traumatic brain injury (TBI) and severity of TBI, examine the stability of DDK over time, and explore associations between DDK and extemporaneous speech. Method Military service members and veterans were categorized into three groups: no history of TBI (control), uncomplicated mild TBI (mTBI), and moderate through severe (including penetrating) TBI (msTBI). Participants produced rapid alternating-motion and sequential-motion syllable repetitions during one or two sessions. A semi-automated protocol determined syllabic rate and regularity. Perceptual ratings of selected participants' connected speech samples were compared to DDK results. Results Two hundred sixty-three service members and veterans provided data from one session and 69 from two sessions separated by 1.9 years (SD = 1.0). DDKs were significantly slower overall for mTBI and msTBI groups compared to controls. Regularity of productions did not differ significantly across groups. A significant Group × Task interaction revealed that the msTBI group produced sequential-motion syllable repetitions but not alternating-motion repetitions with greater regularity, whereas the opposite occurred for control and mTBI groups. DDK results did not differ significantly between sessions. Perceptual speech analysis for 30 participants, including 20 with atypical or questionable DDK performance, revealed two participants with mildly abnormal speech. Conclusions Overall, DDK productions are slower than normal in adults with moderate, severe, and penetrating TBI and are stable over time. Regularity of productions did not differentiate groups, although this result differed according to task. There were surprisingly few people identified with disordered speech, making comparisons to DDK data tenuous, and indicating that dysarthria is a rare complication in a population of adults with mostly uncomplicated mTBI who are not selected from referrals to a speech-language pathology clinic.

Determinants of caregiver burden in male patients with epilepsy following penetrating traumatic brain injury

PurposeWe determined burden of caring for patients with post-traumatic epilepsy (PTE) following penetrating traumatic brain injury (TBI) and identified factors predicting higher burden. MethodWe assessed 331 caregiver-veteran dyads in Phase 2 (136 PTE, 136 non-PTE, and 59 HC dyads), 133 in Phase 4 (47 PTE, 56 non-PTE, and 30 HC dyads) – 30 years later, and 46 dyads in the follow-up study (18 PTE, 19 non-PTE, and 9 HC). Caregiver’s burden was measured by Zarit Burden Index and a questionnaire. Veterans completed demographic, mental and physical well-being, quality-of-life, and medical-related information. Caregivers provided information about burden and their assessments of cognitive decline and neuropsychiatric status of the veterans. ResultsPTE caregivers perceived significantly more burden than comparison groups at all phases. Bivariate analyses revealed that caregiver distress due to the veteran’s neuropsychiatric state including cognitive decline, apathy, and disinhibition and the veteran’s characteristics including older age at epilepsy onset and role limitation due to physical problems were associated with higher burden. Finally, we revealed disinhibition distress, and role imitation due to physical problems as the predictors in a model of caregiver burden. ConclusionElevated PTE caregiver burden is persistent across the life span suggesting that caregivers could benefit from counseling and targeted psychosocial interventions to reduce their burden.

Transcranial Doppler Ultrasound Use in Pediatric Patients With Penetrating Traumatic Brain Injuries

The purpose of this article is to increase awareness of the usefulness of transcranial Doppler (TCD) ultrasound as a noninvasive neuromonitor and bedside ultrasound in pediatric patients who have experienced a penetrative traumatic brain injury (TBI) as a result of a firearm. To date, the use of TCD is not standard of care in pediatric TBI patients. TCD is a portable ultrasound that can be performed in any care environment. The use of TCD in pediatric TBI studies have demonstrated abnormalities in cerebral blood flow velocity, autoregulation, and embolic events; all of which have been associated with poor neurocognitive and functional outcomes. A penetrating brain injury as a result of a firearm is associated with ongoing vascular injury and thereby an increased risk for poor neurologic sequelae. We discuss two exemplars of TCD use in children who experienced a firearm-related penetrating TBI and their TCD findings. Both exemplars identified the unique insights provided by TCD that were unappreciated by clinical observation. This article provides early evidence for the use of TCD as a neuromonitor in pediatric penetrating TBI.

Penetrating traumatic brain injury resulting from a cockerel attack: case report and literature review

Traumatic brain injury is common in children and can lead to death or considerable, long-lasting morbidity. We present the case of a 10-month-old female child who presented after being attacked by a cockerel in a chicken coop. Following a seizure, an MRI scan revealed an intracerebral haemorrhage underlying a stab-type wound inflicted by the bird. Animal bite injuries are common worldwide but they rarely cause intracranial injuries. Domestic hens are rarely dangerous but can become defensive or aggressive during breeding periods or when protecting their territory. To date, only a handful of articles have reported on wounds inflicted by chicken beaks. Those reported were largely facial or ocular injuries. Infectious complications have also been encountered post-injury. This is to our knowledge the first report of a bird attack resulting in significant penetrating traumatic brain injury. Children should be cautioned by guardians to avoid unsupervised contact with chickens, particularly during breeding. Attacks to the neurocranium when they occur must be taken seriously and not treated as humorous or insignificant. Imaging appropriate to the child's clinical condition should be pursued and appropriate intervention and antibiotic treatment should be implemented.

Prognostic performance of computerized tomography scoring systems in civilian penetrating traumatic brain injury: an observational study

BackgroundThe prognosis of penetrating traumatic brain injury (pTBI) is poor yet highly variable. Current computerized tomography (CT) severity scores are commonly not used for pTBI prognostication but may provide important clinical information in these cohorts.MethodsAll consecutive pTBI patients from two large neurotrauma databases (Helsinki 1999–2015, Stockholm 2005–2014) were included. Outcome measures were 6-month mortality and unfavorable outcome (Glasgow Outcome Scale 1–3). Admission head CT scans were assessed according to the following: Marshall CT classification, Rotterdam CT score, Stockholm CT score, and Helsinki CT score. The discrimination (area under the receiver operating curve, AUC) and explanatory variance (pseudo-R2) of the CT scores were assessed individually and in addition to a base model including age, motor response, and pupil responsiveness.ResultsAltogether, 75 patients were included. Overall 6-month mortality and unfavorable outcome were 45% and 61% for all patients, and 31% and 51% for actively treated patients. The CT scores’ AUCs and pseudo-R2s varied between 0.77–0.90 and 0.35–0.60 for mortality prediction and between 0.85–0.89 and 0.50–0.57 for unfavorable outcome prediction. The base model showed excellent performance for mortality (AUC 0.94, pseudo-R2 0.71) and unfavorable outcome (AUC 0.89, pseudo-R2 0.53) prediction. None of the CT scores increased the base model’s AUC (p > 0.05) yet increased its pseudo-R2 (0.09–0.15) for unfavorable outcome prediction.ConclusionExisting head CT scores demonstrate good-to-excellent performance in 6-month outcome prediction in pTBI patients. However, they do not add independent information to known outcome predictors, indicating that a unique score capturing the intracranial severity in pTBI may be warranted.

Human neural stem cell transplant location-dependent neuroprotection and motor deficit amelioration in rats with penetrating traumatic brain injury.

BACKGROUNDPenetrating traumatic brain injury induces chronic inflammation that drives persistent tissue loss long after injury. Absence of endogenous reparative neurogenesis and effective neuroprotective therapies render injury-induced disability an unmet need. Cell replacement via neural stem cell transplantation could potentially rebuild the tissue and alleviate penetrating traumatic brain injury disability. The optimal transplant location remains to be determined.METHODSTo test if subacute human neural stem cell (hNSC) transplant location influences engraftment, lesion expansion, and motor deficits, rats (n = 10/group) were randomized to the following four groups (uninjured and three injured): group 1 (Gr1), uninjured with cell transplants (sham+hNSCs), 1-week postunilateral penetrating traumatic brain injury, after establishing motor deficit; group 2 (Gr2), treated with vehicle (media, no cells); group 3 (Gr3), hNSCs transplanted into lesion core (intra); and group 4 (Gr4), hNSCs transplanted into tissue surrounding the lesion (peri). All animals were immunosuppressed for 12 weeks and euthanized following motor assessment.RESULTSIn Gr2, penetrating traumatic brain injury effect manifests as porencephalic cyst, 22.53 ± 2.87 (% of intact hemisphere), with p value of <0.0001 compared with uninjured Gr1. Group 3 lesion volume at 17.44 ± 2.11 did not differ significantly from Gr2 (p = 0.36), while Gr4 value, 9.17 ± 1.53, differed significantly (p = 0.0001). Engraftment and neuronal differentiation were significantly lower in the uninjured Gr1 (p < 0.05), compared with injured groups. However, there were no differences between Gr3 and Gr4. Significant increase in cortical tissue sparing (p = 0.03), including motor cortex (p = 0.005) was observed in Gr4 but not Gr3. Presence of transplant within lesion or in penumbra attenuated motor deficit development (p < 0.05) compared with Gr2.CONCLUSIONIn aggregate, injury milieu supports transplanted cell proliferation and differentiation independent of location. Unexpectedly, cortical sparing is transplant location dependent. Thus, apart from cell replacement and transplant mediated deficit amelioration, transplant location–dependent neuroprotection may be key to delaying onset or preventing development of injury-induced disability.LEVEL OF EVIDENCEPreclinical study evaluation of therapeutic intervention, level VI.