Traumatic Brain Injury and Subsequent Risk of Brain Cancer in US Veterans of the Iraq and Afghanistan Wars.

Importance: While brain cancer is rare, it has a very poor prognosis and few established risk factors. To date, epidemiologic work examining the potential association of traumatic brain injury (TBI) with the subsequent risk of brain cancer is conflicting. Further data may be useful. Objective: To examine whether a history of TBI exposure is associated with the subsequent development of brain cancer. Design, Setting, and Participants: A retrospective cohort study was conducted from October 1, 2004, to September 20, 2019, and data analysis was performed between January 1 and June 26, 2023. The median follow-up for the cohort was 7.2 (IQR, 4.1-10.1) years. Veterans Affairs (VA) and Department of Defense (DoD) administrative data on 1 919 740 veterans from the Long-Term Impact of Military-Relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium were included. Exposure: The main exposure of interest was TBI severity (categorized as mild, moderate or severe [moderate/severe], and penetrating). Main Outcomes and Measures: The outcome of interest was the development of brain cancer based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnostic codes in either the DoD/VA medical records or from the National Death Index. Results: After 611 107 exclusions (predominately for no encounter during the study period), a cohort including 1 919 740 veterans was included, most of whom were male (80.25%) and non-Hispanic White (63.11%). Median age at index date was 31 (IQR, 25-42) years. The cohort included 449 880 individuals with TBI (mild, 385 848; moderate/severe, 46 859; and penetrating, 17 173). Brain cancer occurred in 318 individuals without TBI (0.02%), 80 with mild TBI (0.02%), 17 with moderate/severe TBI (0.04%), and 10 or fewer with penetrating TBI (≤0.06%). After adjustment, moderate/severe TBI (adjusted hazard ratio [AHR], 1.90; 95% CI, 1.16-3.12) and penetrating TBI (AHR, 3.33; 95% CI, 1.71-6.49), but not mild TBI (AHR, 1.14; 95% CI, 0.88-1.47), were associated with the subsequent development of brain cancer. Conclusions and Relevance: In this cohort study of veterans of the Iraq and Afghanistan wars, moderate/severe TBI and penetrating TBI, but not mild TBI, were associated with the subsequent development of brain cancer.

A Multicenter Study on the Clinical Characteristics and Outcomes Among Children With Moderate to Severe Abusive Head Trauma.

INTRODUCTION: We aimed to identify clinical characteristics, risk factors for diagnosis, and describe outcomes among children with AHT. METHODS: We performed an observational cohort study in tertiary care hospitals from 14 countries across Asia and Ibero-America. We included patients <5 years old who were admitted to participating pediatric intensive care units (PICUs) with moderate to severe traumatic brain injury (TBI). We performed descriptive analysis and multivariable logistic regression for risk factors of AHT. RESULTS: 47 (12%) out of 392 patients were diagnosed with AHT. Compared to those with accidental injuries, children with AHT were more frequently < 2 years old (42, 89.4% vs 133, 38.6%, p < 0.001), more likely to arrive by private transportation (25, 53.2%, vs 88, 25.7%, p < 0.001), but less likely to have multiple injuries (14, 29.8% vs 158, 45.8%, p = 0.038). The AHT group was more likely to suffer subdural hemorrhage (SDH) (39, 83.0% vs 89, 25.8%, p < 0.001), require antiepileptic medications (41, 87.2% vs 209, 60.6%, p < 0.001), and neurosurgical interventions (27, 57.40% vs 143, 41.40%, p = 0.038). Mortality, PICU length of stay, and functional outcomes at 3 months were similar in both groups. In the multivariable logistic regression, age <2 years old (aOR 8.44, 95%CI 3.07-23.2), presence of seizures (aOR 3.43, 95%CI 1.60-7.36), and presence of SDH (aOR 9.58, 95%CI 4.10-22.39) were independently associated with AHT. CONCLUSIONS: AHT diagnosis represented 12% of our TBI cohort. Overall, children with AHT required more neurosurgical interventions and the use of anti-epileptic medications. Children younger than 2 years and with SDH were independently associated with a diagnosis of AHT. TYPE OF STUDY: Observational cohort study. LEVEL OF EVIDENCE: III.

War-related traumatic brain injuries during the Syrian armed conflict in Damascus 2014-2017: a cohort study and a literature review.

BACKGROUND: The decade-long Syrian armed conflict killed or injured more than 11% of the Syrian population. Head and neck injuries are the most frequent cause of war-related trauma, about half of which are brain injuries. Reports about Syrian brain trauma victims were published from neighboring countries; However, none are available from Syrian hospitals. This study aims to report war-related traumatic brain injuries from the Syrian capital. METHODS: We conducted a retrospective cohort study between 2014 and 2017 at Damascus Hospital, the largest public hospital in Damascus, Syria. Target patients were the victims of combat-related traumatic brain injuries who arrived alive and were admitted to the neurosurgery department or to another department but followed by the neurosurgery team. The collected data included the mechanism, type, and site of injury based on imaging findings; types of invasive interventions; intensive-care unit (ICU) admissions; as well as neurological status at admission and discharge including several severity scales. RESULTS: Our sample consisted of 195 patients; Ninety-six of them were male young adults, in addition to 40 females and 61 children. Injuries were caused by shrapnel in 127 (65%) cases, and by gunshots in the rest, and most of them (91%) were penetrating. Sixty-eight patients (35%) were admitted to the ICU, and 56 (29%) underwent surgery. Neurological impairment was reported in 49 patients (25%) at discharge, and the mortality rate during hospitalization was 33%. Mortality and neurological impairment associated significantly with higher values on clinical and imaging severity scores. CONCLUSIONS: This study captured the full spectrum of war-related brain injuries of civilians and armed personnel in Syria without the delay required to transport patients to neighboring countries. Although the clinical presentation of injuries at admission was not as severe as that in previous reports, the inadequate resources (i.e., ventilators and operation rooms) and the lack of previous experience with similar injuries might have resulted in the higher mortality rate. Clinical and imaging severity scales can provide a handy tool in identifying cases with low probability of survival especially with the shortage of personal and physical resources.

Traumatic brain injuries and maxillofacial fractures: a systematic review and meta-analysis.

Traumatic brain injuries (TBIs) associated with maxillofacial fractures (MFFs) are a public health concern worldwide, especially among adult-aged males. There is an urgent need for early detection of associated TBIs in patients with MFFs during the initial assessment and treatment stage to reduce morbidity and mortality. The objective of the present study was to systematically review the literature to determine specific MFF situations associated with TBIs and to identify the factors associated with TBIs in patients with MFFs. The protocol was developed in accord with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) and was registered to the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42020155912. Overall, of 26,774 patients recorded, 13,667 patients (51.04%) sustained MFFs with an associated TBI. The male to female ratio was 4.8:1. RTA was the most common cause. The most common TBIs were concussions, contusions, and closed brain injuries. Within the limits of this study, it was concluded that TBI-related MFFs should be suspected whenever maxillary or mandibular bone fractures occur, especially among adults, males, and people with injuries caused by RTAs and assaults. There is a need to increase the awareness of maxillofacial surgeons on the possible associations of combined maxillofacial trauma and brain injuries.

A systematic review of the timing of intubation in patients with traumatic brain injury: pre-hospital versus in-hospital intubation.

PURPOSE: The objective of this systematic review was to examine current evidence on the risks versus benefit of pre-hospital intubation when compared with in-hospital intubation in adult patients with traumatic brain injuries. METHODS: We conducted electronic searches of PubMed, Medline, Embase, CIANHL and the Cochrane library up to March 2021. Data extracted compared mortality, length of hospital and intensive care stay, pneumonia and functional outcomes in traumatic brain injured patients undergoing pre-hospital intubation versus in-hospital intubation. The risk of bias was assessed using the Grading of Recommendations Assessment, Development and Evaluation. RESULTS: Ten studies including 25,766 patients were analysed. Seven were retrospective studies, two prospective cohort studies and one randomised control study. The mean mortality rate in patients who underwent pre-hospital intubation was 44.5% and 31.98% for in-hospital intubation. The odds ratio for an effect of pre-hospital intubation on mortality ranged from 0.31 (favouring in-hospital intubation) to 3.99 (favouring pre-hospital). The overall quality of evidence is low; however, the only randomised control study showed an improved functional outcome for pre-hospital intubation at 6 months. CONCLUSIONS: The existing evidence does not support widespread pre-hospital intubation in all traumatic brain injured patients. This does not, however, contradict the need for the intervention when there is severe airway compromise; instead, it must be assessed by experienced personnel if a time critical transfer to hospital is more advantageous. Favourable neurological outcomes highlighted by the randomised control trial favours pre-hospital intubation, but further research is required in this field.

Factors influencing the outcomes of patients with severe traumatic brain injury following road traffic crashes.

BACKGROUND: Traumatic brain injury (TBI) is one of the leading causes of mortality and morbidity in South Africa. Road traffic crashes (RTCs) are among the commonest aetiology of TBI in South Africa. This study aimed to determine the factors influencing the outcomes in patients with severe TBI following RTCs. METHODS: A retrospective study was conducted of patients who were admitted to the neurosurgery department at Inkosi Albert Luthuli Central Hospital between January 2013 and December 2017 with TBI following RTCs and with a Glasgow Coma Scale (GCS) < 9. Demographic, clinical, and radiological information was obtained. The outcome at discharge was categorised into favourable and unfavourable, using the Glasgow outcome score. Statistical analysis was performed to determine factors contributing to the outcome. RESULTS: The study population consisted of 100 patients. The mean age was 29.5 ± 14.1 years old (range 3-81 years). The majority of patients (85%) were males. Pedestrian vehicle accidents accounted for 46%, compared to motor vehicle collisions (54%). The mean hospital stay duration was 14.2 ± 8.8 days (range 1-43 days). The median postresuscitation GCS was 6 (range 3-8), (p = 0.52). Fifty-two patients had an unfavourable outcome compared to 48 who had a favourable outcome. Eleven patients presented with pupillary abnormalities (p = 0.88), which included unilateral dilated non-reactive (DNR) pupil in seven patients, whilst four patients had bilateral. Five patients developed refractory intracranial hypertension (RIC-HTN), all these patients had unfavourable outcomes, (p = 0.03). Thirty-eight patients developed systemic hypotension (SBP < 90 mmHg), 32 out of these patients had unfavourable outcomes (p < 0.001). In female patients, 80% had unfavourable outcomes compared to 47% of male patients (p = 0.02). Extracranial injuries were diagnosed in 50 patients, and 24 patients had unfavourable outcomes (p = 0.42). CONCLUSION: The outcomes in patients with severe TBI following road traffic crashes are influenced by hypotension (SBP <90 mmHg), RIC-HTN and female gender, which have a negative influence on outcomes.

Self-reported respiratory outcomes associated with blast exposure in post 9/11 veterans.

BACKGROUND: Blast lung overpressure has received interest as a cause of chronic respiratory disease in Service members who deployed in support of U.S. military operations in Southwest Asia and Afghanistan since 2001. We studied whether veterans who experienced blast exposure report more chronic respiratory symptoms and diagnoses compared to deployed veterans who did not. METHODS: 9,000 veterans included in the Department of Veterans Affairs Toxic Embedded Fragment Registry were invited to complete a survey assessing chronic respiratory symptoms, diagnoses, and exposures. Blast exposure was assessed using the Brief Traumatic Brain Injury Screen and by presence of other symptoms such as blast-induced loss of consciousness. RESULTS: Participants (n = 2147) were predominantly <40 years old, served in the Army, and injured on average 12.8 years previously. 91% reported blast exposure. Blast-exposed veterans were significantly more likely to report cough (OR 1.8), wheeze (OR 2.4), and dyspnea (OR 1.8), even after adjustment for covariates including smoking and occupational exposures to dust, fume, and gas. Veterans reporting higher severity of blast impact, such as traumatic brain injury or loss of consciousness, were more likely to report cough, wheeze, or dyspnea. Veterans with higher severity of blast impact by multiple measures were also more likely to report having COPD. Those reporting a physician-diagnosis of traumatic brain injury were significantly more likely to report having both asthma (OR 1.5) and COPD (OR 1.5). CONCLUSIONS: Blast exposure is associated with respiratory symptoms and COPD. Respiratory system evaluation may warrant inclusion as a standard part of barotrauma health assessment.

Analyzing pediatric bicycle injuries using geo-demographic data.

PURPOSE: Bicycle accidents are potentially preventable, and helmets can mitigate the severity of injuries. The purpose of the study it to investigate geo-demographic areas to establish prevention policies and targeted programs. METHODS: From October 2013 to March 2020 all bicycle injuries at a Level 1 trauma center were collected for ages ≤18 years. Demographics, injuries, and outcomes were analyzed. Incidents were aggregated to zip codes and the Local Indicators of Spatial Association (LISA) statistic was used to test for spatial clustering of injury rates per 10,000 children. RESULTS: Over the 8-year time period, 77 cases were identified with an average age of 13±4 years, 83% male and 48% non-Hispanic white. The majority of patients (98%) were not wearing a helmet. Loss of consciousness was reported in 44% and 21% sustained a traumatic brain injury. Twenty-eight percent required ICU care and 36% required operative interventions. There was only 1 mortality in the cohort (<1%).Injuries were more common in lower household income zip codes (Figure 1). Six zip codes encompassing several interstate exits and the connected heavy-traffic roadways comprise a statistically significant cluster of pediatric bicycle accidents (Figure 1). CONCLUSION: Low-income neighborhoods and those near major roadways held the highest risk for pediatric bicycle accidents. Use of helmets was extremely low in the patient population, with high rates of traumatic brain injury. With this information, targeted programs to address high-risk intersections, helmet access, and safety education can be implemented locally.

Hippocampal Expression of Cytochrome P450 1B1 in Penetrating Traumatic Brain Injury.

Hippocampal dysfunction contributes to multiple traumatic brain injury sequala. Female rodents' outcome is superior to male which has been ascribed the neuroprotective sex hormones 17ß-estradiol and progesterone. Cytochrome P450 1B1 (CYP1B1) is an oxidative enzyme influencing the neuroinflammatory response by creating inflammatory mediators and metabolizing neuroprotective 17ß-estradiol and progesterone. In this study, we aimed to describe hippocampal CYP1B1 mRNA expression, protein presence of CYP1B1 and its key redox partner Cytochrome P450 reductase (CPR) in both sexes, as well as the effect of penetrating traumatic brain injury (pTBI). A total 64 adult Sprague Dawley rats divided by sex received pTBI or sham-surgery and were assigned survival times of 1-, 3-, 5- or 7 days. CYP1B1 mRNA was quantified using in-situ hybridization and immunohistochemistry performed to verify protein colocalization. CYP1B1 mRNA expression was present in all subregions but greatest in CA2 irrespective of sex, survival time or intervention. At 3-, 5- and 7 days post-injury, expression in CA2 was reduced in male rats subjected to pTBI compared to sham-surgery. Females subjected to pTBI instead exhibited increased expression in all CA subregions 3 days post-injury, the only time point expression in CA2 was greater in females than in males. Immunohistochemical analysis confirmed neuronal CYP1B1 protein in all hippocampal subregions, while CPR was limited to CA1 and CA2. CYP1B1 mRNA is constitutively expressed in both sexes. In response to pTBI, females displayed a more urgent but brief regulatory response than males. This indicates there may be sex-dependent differences in CYP1B1 activity, possibly influencing inflammation and neuroprotection in pTBI.

Multiple Brain Abscesses by an Air Gun Shot: A Case Report

Introduction Low-velocity penetrating brain injury is not prevalent. In some conditions such as childhood, and with the penetration of a pellet in weak spots of skull, low-velocity penetrating brain injury is expected; however, high-velocity projectiles have also been reported as the cause of severe brain injuries. One of the complications of penetrating brain injury is infection, in which different types ofmicroorganisms play a role. The Streptococcus genus is the leading cause of abscess formation in nontraumatic patients. Multiple brain abscesses are not common. Case Presentation A 10-year-old boy with penetrating brain injury caused by an air gun pellet, who developed signs and symptoms of high intracranial pressure 18 days after the trauma. After the imaging scans and the detection of multiple brain abscesses and severe brain edema, prompt surgical intervention was performed for all three lesions in a single operation. The culture of a pus specimen was positive for Streptococcus species, and, with adequate antibiotic therapy, the patient was discharged from the hospital in good condition. Conclusion Brain injurywith air gun shot is not prevalent. The penetration of a low-velocity air gun pellet in weak points of the skull (such as the orbit, the squamous portion of the temporal bone, and the cranial suture), specially in children, can cause significant brain injuries.

Occupational Risk of Low-Level Blast Exposure and TBI-Related Medical Diagnoses: A Population-Based Epidemiological Investigation (2005-2015).

Because traumatic brain injury (TBI)-most often caused by exposure to high-level blast (HLB)-is a leading cause of medical evacuations of deployed U.S. service members in recent conflicts, researchers seek to identify risk factors for TBI. Previous research using self-reported data has identified low-level blast (LLB) as one such risk factor and suggests an association with susceptibility to and symptoms associated with TBI. This article presents a population-based study of all branches of military service that examines the association between occupational risk for LLB and both clinically diagnosed TBIs-from concussions to severe and penetrating TBIs-and conditions commonly comorbid with concussion. Using archival medical and career records from >2 million service members between 2005-2015, this work demonstrates that occupational risk of LLB is associated with any TBI, mild TBI, moderate TBI, cognitive problems, communication problems, hearing problems, headaches, any behavioral health condition, anxiety, drug abuse/dependence, alcohol abuse/dependence, delirium/dementia, posttraumatic stress disorder, post-concussive syndrome, tinnitus, fatigue, and migraines. Understanding the full scope of the effects of LLB on service members will help ensure the health and readiness of service members and may influence both military policy and clinical practice guidelines for blast-induced injuries.

CBF oscillations induced by trigeminal nerve stimulation protect the pericontusional penumbra in traumatic brain injury complicated by hemorrhagic shock.

Traumatic peri-contusional penumbra represents crucial targets for therapeutic interventions after traumatic brain injury (TBI). Current resuscitative approaches may not adequately alleviate impaired cerebral microcirculation and, hence, compromise oxygen delivery to peri-contusional areas. Low-frequency oscillations in cerebral blood flow (CBF) may improve cerebral oxygenation in the setting of oxygen deprivation. However, no method has been reported to induce controllable oscillations in CBF and it hasn't been applied as a therapeutic strategy. Electrical stimulation of the trigeminal nerve (TNS) plays a pivotal role in modulating cerebrovascular tone and cerebral perfusion. We hypothesized that TNS can modulate CBF at the targeted frequency band via the trigemino-cerebrovascular network, and TNS-induced CBF oscillations would improve cerebral oxygenation in peri-contusional areas. In a rat model of TBI complicated by hemorrhagic shock, TNS-induced CBF oscillations conferred significant preservation of peri-contusional tissues leading to reduced lesion volume, attenuated hypoxic injury and neuroinflammation, increased eNOS expression, improved neurological recovery and better 10-day survival rate, despite not significantly increasing CBF as compared with those in immediate and delayed resuscitation animals. Our findings indicate that low-frequency CBF oscillations enhance cerebral oxygenation in peri-contusional areas, and play a more significant protective role than improvements in non-oscillatory cerebral perfusion or volume expansion alone.

Brain Protection after Anoxic Brain Injury: Is Lactate Supplementation Helpful?

While sudden loss of perfusion is responsible for ischemia, failure to supply the required amount of oxygen to the tissues is defined as hypoxia. Among several pathological conditions that can impair brain perfusion and oxygenation, cardiocirculatory arrest is characterized by a complete loss of perfusion to the brain, determining a whole brain ischemic-anoxic injury. Differently from other threatening situations of reduced cerebral perfusion, i.e., caused by increased intracranial pressure or circulatory shock, resuscitated patients after a cardiac arrest experience a sudden restoration of cerebral blood flow and are exposed to a massive reperfusion injury, which could significantly alter cellular metabolism. Current evidence suggests that cell populations in the central nervous system might use alternative metabolic pathways to glucose and that neurons may rely on a lactate-centered metabolism. Indeed, lactate does not require adenosine triphosphate (ATP) to be oxidated and it could therefore serve as an alternative substrate in condition of depleted energy reserves, i.e., reperfusion injury, even in presence of adequate tissue oxygen delivery. Lactate enriched solutions were studied in recent years in healthy subjects, acute heart failure, and severe traumatic brain injured patients, showing possible benefits that extend beyond the role as alternative energetic substrates. In this manuscript, we addressed some key aspects of the cellular metabolic derangements occurring after cerebral ischemia-reperfusion injury and examined the possible rationale for the administration of lactate enriched solutions in resuscitated patients after cardiac arrest.

Roles of Cytokines in the Temporal Changes of Microglial Membrane Currents and Neuronal Excitability and Synaptic Efficacy in ATP-Induced Cortical Injury Model.

Cytokines are important neuroinflammatory modulators in neurodegenerative brain disorders including traumatic brain injury (TBI) and stroke. However, their temporal effects on the physiological properties of microglia and neurons during the recovery period have been unclear. Here, using an ATP-induced cortical injury model, we characterized selective effects of ATP injection compared to needle-control. In the damaged region, the fluorescent intensity of CX3CR1-GFP (+) cells, as well as the cell density, was increased and the maturation of newborn BrdU (+) cells continued until 28 day-post-injection (dpi) of ATP. The excitability and synaptic E/I balance of neurons and the inward and outward membrane currents of microglia were increased at 3 dpi, when expressions of tumor necrosis factor (TNF)-α/interleukin (IL)-1ß and IL-10/IL-4 were also enhanced. These changes of both cells at 3 dpi were mostly decayed at 7 dpi and were suppressed by any of IL-10, IL-4, suramin (P2 receptor inhibitor) and 4-AP (K+ channel blocker). Acute ATP application alone induced only small effects from both naïve neurons and microglial cells in brain slice. However, TNF-α alone effectively increased the excitability of naïve neurons, which was blocked by suramin or 4-AP. TNF-α and IL-1ß increased and decreased membrane currents of naïve microglia, respectively. Our results suggest that ATP and TNF-α dominantly induce the physiological activities of 3 dpi neurons and microglia, and IL-10 effectively suppresses such changes of both activated cells in K+ channel- and P2 receptor-dependent manner, while IL-4 suppresses neurons preferentially.

Head Computed Tomography Scans in Elderly Patients with Low Velocity Head trauma after a Fall.

BACKGROUND: Recommendations for a head computed tomography (CT) scan in elderly patients without a loss of consciousness after a traumatic brain injury and without neurological findings on admission and who are not taking oral anticoagulant therapy, are discordant. OBJECTIVES: To determine variables associated with intracranial hemorrhage (ICH) and the need for neurosurgery in elderly patients after low velocity head trauma. METHODS: In a regional hospital, we retrospectively selected 206 consecutive patients aged ≥ 65 years with head CT scans ordered in the emergency department because of low velocity head trauma. Outcome variables were an ICH and neurological surgery. Independent variables included age, sex, disability, neurological findings, facial fractures, mental status, headache, head sutures, loss of consciousness, and anticoagulation therapy. RESULTS: Fourteen patients presented with ICH (6.8%, 3.8-11.1%) and three (1.5%, 0.3-4.2%) with a neurosurgical procedure. One patient with a coma (0.5, 0.0-2.7) died 2 hours after presentation. All patients who required surgery or died had neurological findings. Reducing head CT scans by 97.1% (93.8-98.9%) would not have missed any patient with possible surgical utility. Twelve of the 14 patients (85.7%) with an ICH had neurological findings, post-trauma loss of consciousness or a facial fracture were not present in 83.5% (95% confidence interval 77.7-88.3) of the cohort. CONCLUSIONS: None of our patients with neurological findings required neurosurgery. Careful palpation of the facial bones to identify facial fractures might aid in the decision whether to perform a head CT scan.

Sensitivity of unilateral- versus bilateral-onset spike-wave discharges to ethosuximide and carbamazepine in the fluid percussion injury rat model of traumatic brain injury.

Unilateral-onset spike-wave discharges (SWDs) following fluid percussion injury (FPI) in rats have been used for nearly two decades as a model for complex partial seizures in human posttraumatic epilepsy (PTE). This study determined if SWDs with a unilateral versus bilateral cortical onset differed. In this experiment, 2-mo-old rats received severe FPI (3 atm) or sham surgery and were instrumented for chronic video-electrocorticography (ECoG) recording (up to 9 mo). The antiseizure drug, carbamazepine (CBZ), and the antiabsence drug, ethosuximide (ETX), were administered separately to determine if they selectively suppressed unilateral- versus bilateral-onset SWDs, respectively. SWDs did not significantly differ between FPI and sham rats on any measured parameter (wave-shape, frequency spectrum, duration, or age-related progression), including unilateral (∼17%) versus bilateral (∼83%) onsets. SWDs with a unilateral onset preferentially originated ipsilateral to the craniotomy in both FPI and sham rats, suggesting that the unilateral-onset SWDs were related to surgical injury and not specifically to FPI. ETX profoundly suppressed SWDs with either unilateral or bilateral onsets, and CBZ had no effect on either type of SWD. These results suggest that SWDs with either a unilateral or bilateral onset have a pharmacosensitivity similar to absence seizures and are very different from the complex partial seizures of PTE. Therefore, SWDs with a unilateral onset after FPI are not a model of the complex partial seizures that occur in PTE, and their use for finding new treatments for PTE could be counterproductive, particularly if their close similarity to normal brain oscillations is not acknowledged.NEW & NOTEWORTHY Unilateral-onset spike-wave discharges (SWDs) in rats have been used to model complex partial seizures in human posttraumatic epilepsy (PTE), compared to bilateral-onset SWDs thought to reflect human absence seizures. Here, we show that both unilateral- and bilateral-onset SWDs following traumatic brain injury are suppressed by the antiabsence drug ethosuximide and are unaffected by the antiseizure drug carbamazepine. We propose that unilateral-onset SWDs are not useful for studying mechanisms of, or treatments for, PTE.

Saving the brain after mild-to-moderate traumatic injury: A report on new insights of the physiology underlying adequate maintenance of cerebral perfusion.

ABSTRACT: Traumatic brain injury (TBI) is associated with increased morbidity and mortality in civilian trauma and battlefield settings. It has been classified across a continuum of dysfunctions, with as much as 80% to 90% of cases diagnosed as mild to moderate in combat casualties. In this report, a framework is presented that focuses on the potential benefits for acute noninvasive treatment of reduced cerebral perfusion associated with mild TBI by harnessing the natural transfer of negative intrathoracic pressure during inspiration. This process is known as intrathoracic pressure regulation (IPR) therapy, which can be applied by having a patient breath against a small inspiratory resistance created by an impedance threshold device. Intrathoracic pressure regulation therapy leverages two fundamental principles for improving blood flow to the brain: (1) greater negative intrathoracic pressure enhances venous return, cardiac output, and arterial blood pressure; and (2) lowering of intracranial pressure provides less resistance to cerebral blood flow. These two effects work together to produce a greater pressure gradient that results in an improvement in cerebral perfusion pressure. In this way, IPR therapy has the potential to counter hypotension and hypoxia, potentially significant contributing factors to secondary brain injury, particularly in conditions of multiple injuries that include severe hemorrhage. By implementing IPR therapy in patients with mild-to-moderate TBI, a potential exists to provide early neuroprotection at the point of injury and a bridge to more definitive care, particularly in settings of prolonged delays in evacuation such as those anticipated in future multidomain operations. LEVEL OF EVIDENCE: Report.

Increased mortality in very young children with traumatic brain injury due to abuse: A nationwide analysis of 10,965 patients.

BACKGROUND: Traumatic brain injury (TBI) is the leading cause of death and disability in young children; however, the impact of mechanism on outcomes has not been fully evaluated. We hypothesized that children with TBI due to abuse would have a higher mortality than children with accidental TBI due to motor vehicle collisions (MVC). METHODS: We performed a retrospective review of the National Kids' Inpatient (KID) hospitalizations database of children <2 years old with TBI due to abuse or MVC (2000-2016). The primary outcome was mortality. Secondary outcomes were length of stay (LOS) and hospital charges. We investigated predictors of mortality with multivariable regression. RESULTS: Of 10,965 children with TBI, 65.2% were due to abuse. Overall mortality was 9.8% (n = 1074). Abused children had longer LOS (5.7 vs 1.6 days, p < 0.0001) and higher hospital charges ($34,314 vs $19,360, p < 0.0001) than children with TBI due to MVC. The odds of mortality were 42% higher in children with abusive head trauma (OR 1.42, 95% CI 1.10-1.83, p = 0.007) compared to MVCs after adjusting for age, race, sex, neurosurgical intervention, injury severity, and insurance. CONCLUSION: Children with abusive traumatic brain injury have increased risk of mortality, longer LOS, and higher hospital charges compared to children with TBI due to motor vehicle collision after adjusting for relevant confounders. Resources must be directed at prevention and early identification of abuse.

Granulocyte Colony-Stimulating Factor Enhances Brain Repair Following Traumatic Brain Injury Without Requiring Activation of Cannabinoid Receptors.

Introduction: Treatment of traumatic brain injury (TBI) with granulocyte colony-stimulating factor (G-CSF) has been shown to enhance brain repair by direct neurotrophic actions on neural cells and by modulating the inflammatory response. Administration of cannabinoids after TBI has also been reported to enhance brain repair by similar mechanisms. Objectives: The primary objective of this study was to test the hypothesis that G-CSF mediates brain repair by interacting with the endocannabinoid system. Methods and Results: (i) Mice that underwent controlled cortical impact (CCI) were treated with G-CSF for 3 days either alone or in the presence of selective cannabinoid receptor 1 (CB1-R) or cannabinoid receptor 2 (CB2-R) agonists and antagonists. The trauma resulted in decreased expression of CB1-R and increased expression of CB2-R in the cortex, striatum, and hippocampus. Cortical and striatal levels of the major endocannabinoid ligand, 2-arachidonoyl-glycerol, were also increased by the CCI. Administration of the hematopoietic cytokine, G-CSF, following TBI, resulted in mitigation or reversal of trauma-induced CB1-R downregulation and CB2-R upregulation in the three brain regions. Treatment with CB1-R agonist (WIN55) or CB2-R agonist (HU308) mimicked the effects of G-CSF. (ii) Pharmacological blockade of CB1-R or CB2-R was not effective in preventing G-CSF's mitigation or reversal of trauma-induced alterations in these receptors. Conclusions: These results suggest that cellular and molecular mechanisms that mediate subacute effects of G-CSF do not depend on activation of CB1 or CB2 receptors. Failure of selective CB receptor antagonists to prevent the effects of G-CSF in this model has to be accepted with caution. CB receptor antagonists can interact with other CB and non-CB receptors. Investigation of the role of CB receptors in this TBI model will require studies with CB1-R and in CB2-R knockout mice to avoid nonspecific interaction of CB receptor agents with other receptors.