Pediatric Traumatic Brain Injury Research Articles

Epidemiological study of paediatric traumatic brain injury in Brazil

BackgroundTraumatic brain injury (TBI) has a high economic and social impact on the family dynamics, particularly among children. High-quality and comprehensive epidemiological studies about TBI in this population are limited worldwide, specifically in Latin America. Therefore, this study aimed to elucidate the epidemiology of TBI among children in Brazil and its effects on the public health system. MethodsThis epidemiological (cohort) retrospective study collected data from the Brazilian healthcare database between 1992 and 2021. ResultsThe mean annual volume of hospital admission (HA) due to TBI in Brazil was 29,017. Moreover, the incidence of TBI in the paediatric population was 45.35 admissions per 100,000 inhabitants/year. Furthermore, approximately 941 paediatric hospital deaths per year were caused by TBI, with an in-hospital lethality rate of 3.21%. The average annual financial transfer for TBI was 12,376,628 USD, and the mean cost per admission was 417 USD. In addition, the mean length of hospital stay was 4.2 days. Notably, the length of stay in the hospital was longer among males, Afro-Brazilians patients and individuals aged 15–19 years. ConclusionPaediatric TBI is an important public health issue worldwide with high social and economic costs. The incidence of paediatric TBI in Brazil is similar to that in developing countries. Moreover, male predominance (2.3:1) was observed in relation paediatric TBI. Notably, during the pandemic, the incidence of paediatric HA has decreased. To the best of our knowledge, this is the first epidemiological study that specifically evaluates paediatric TBI in Latin America.

Assessing Pediatric Mild Traumatic Brain Injury and Its Recovery Using Resting-State Magnetoencephalography Source Magnitude Imaging and Machine Learning.

The objectives of this machine-learning (ML) resting-state magnetoencephalography (rs-MEG) study involving children with mild traumatic brain injury (mTBI) and orthopedic injury (OI) controls were to define a neural injury signature of mTBI and to delineate the pattern(s) of neural injury that determine behavioral recovery. Children ages 8-15 years with mTBI (n = 59) and OI (n = 39) from consecutive admissions to an emergency department were studied prospectively for parent-rated post-concussion symptoms (PCS) at: 1) baseline (average of 3 weeks post-injury) to measure pre-injury symptoms and also concurrent symptoms; and 2) at 3-months post-injury. rs-MEG was conducted at the baseline assessment. The ML algorithm predicted cases of mTBI versus OI with sensitivity of 95.5 ± 1.6% and specificity of 90.2 ± 2.7% at 3-weeks post-injury for the combined delta-gamma frequencies. The sensitivity and specificity were significantly better (p < 0.0001) for the combined delta-gamma frequencies compared with the delta-only and gamma-only frequencies. There were also spatial differences in rs-MEG activity between mTBI and OI groups in both delta and gamma bands in frontal and temporal lobe, as well as more widespread differences in the brain. The ML algorithm accounted for 84.5% of the variance in predicting recovery measured by PCS changes between 3 weeks and 3 months post-injury in the mTBI group, and this was significantly lower (p < 10-4) in the OI group (65.6%). Frontal lobe pole (higher) gamma activity was significantly (p < 0.001) associated with (worse) PCS recovery exclusively in the mTBI group. These findings demonstrate a neural injury signature of pediatric mTBI and patterns of mTBI-induced neural injury related to behavioral recovery.

Modulating chronic outcomes after pediatric traumatic brain injury: Distinct effects of social and environmental enrichment

Impairments in social and cognitive function are a common consequence of pediatric traumatic brain injury (TBI). Rehabilitation has the potential to promote optimal behavioral recovery. Here, we evaluated whether an enhanced social and/or cognitive environment could improve long-term outcomes in a preclinical model of pediatric TBI. Male C57Bl/6 J mice received a moderately-severe TBI or sham procedure at postnatal day 21. After one week, mice were randomized to different social conditions (minimal socialization, n = 2/cage; or social grouping, n = 6/cage), and housing conditions (standard cage, or environmental enrichment (EE), incorporating sensory, motor, and cognitive stimuli). After 8 weeks, neurobehavioral outcomes were assessed, followed by post-mortem neuropathology. We found that TBI mice exhibited hyperactivity, spatial memory deficits, reduced anxiety-like behavior, and reduced sensorimotor performance compared to age-matched sham controls. Pro-social and sociosexual behaviors were also reduced in TBI mice. EE increased sensorimotor performance, and the duration of sociosexual interactions. Conversely, social housing reduced hyperactivity and altered anxiety-like behavior in TBI mice, and reduced same-sex social investigation. TBI mice showed impaired spatial memory retention, except for TBI mice exposed to both EE and group housing. In the brain, while TBI led to significant regional tissue atrophy, social housing had modest neuroprotective effects on hippocampal volumes, neurogenesis, and oligodendrocyte progenitor numbers. In conclusion, manipulation of the post-injury environment has benefit for chronic behavioral outcomes, but the benefits are specific to the type of enrichment available. This study improves understanding of modifiable factors that may be harnessed to optimize long-term outcomes for survivors of early-life TBI.

802 The Predictive Role of Initial Brain Imaging on Seizure Development in Pediatric Traumatic Brain Injury

INTRODUCTION: Pediatric traumatic brain injury (TBI) poses risk for early post-traumatic seizures (EPTS). Antiepileptic drugs are often prescribed prophylactically, though limited evidence exists regarding their effectiveness in pediatric TBI. Neuroimaging has been predictive of EPTS in adult TBI, but this is not well studied in children. Given the heterogeneous nature of TBIs, injury type and location may serve as predictors of seizure development. METHODS: This is a single-center retrospective analysis of 348 pediatric patients with TBI from January 2011 to June 2021 treated with levetiracetam. Factors analyzed include age, sex, GCS, dosage and date of levetiracetam administration, presence of seizures, medical and surgical management, and findings on CT imaging. The primary outcome was the prevalence of seizures within 7 days of injury. RESULTS: On multivariate analysis, the risk of having seizures any time within 7 days of injury was decreased in children with contusions (OR .425 [.205-.880], p = 0.021), simple skull fractures (OR .226 [.079-.648], p = 0.006), and complex skull fractures (OR .370 [.175-.784], p = 0.009). Findings of SDH, traumatic SAH, and pneumocephalus did not significantly increase the risk of EPTS. On univariate analysis of patients who developed seizures after levetiracetam, the only significant imaging factor for EPTS was SDH (OR 4.398 [1.447-13.370], p = 0.009). On multivariate analysis, no imaging characteristics were predictive of EPTS, but older children had a decreased risk of EPTS (1-2 yo OR .095 [.016-.560], p = 0.009; 3-18 yo; OR .006 [0-.132], p = 0.001) despite levetiracetam prophylaxis. CONCLUSIONS: This study demonstrates that regardless of initial neuroimaging, younger age is associated with an increased risk of seizures despite prophylaxis. Further studies are needed to determine the predictive value of imaging characteristics in developing EPTS in pediatric TBI patients.

804 The Association Between Hyperoxia after TBI and Degree of Disability in Pediatric Patients

INTRODUCTION: Traumatic brain injury (TBI) is a leading cause of death and disability in children worldwide. Hyperoxia has been suggested as a mechanism of secondary injury following adult TBI, but its effect on pediatric patients has not been well-described. METHODS: We conducted a review of all pediatric (≤18yo) TBI patients in a prospective institutional registry from October 2008 to January 2021. PaO2 was extracted from the arterial blood gas report for the first 24 hours after admission to the ICU. The first PaO2, highest PaO2 and the AUC calculation of PaO2 were collected and calculated for each patient. Outcomes 6 months after injury were measured using the modified Rankin Scale (mRS) and dichotomized as favorable (1-2) or unfavorable (3-6). A multivariable logistic regression model was used to determine if minimum PaO2, maximum PaO2, or AUC PaO2, predicted an unfavorable outcome. RESULTS: We identified 122 pediatric patients with severe TBI (GCS 3 – 8) during the study period. The incidence of hyperoxia (PaO2 &gt;300 mmHg) was 25%. Elevated PaO2 values, determined by both maximum and AUC PaO2 within the first 24 hours of hospitalization, was an independent predictor of worse neurological outcome at 6 months. CONCLUSIONS: Using an institutional database, hyperoxia was an independent predictor of poor neurological outcome in pediatric patients. Further studies are needed to determine if efforts to prevent and/or correct hyperoxia are associated with improved outcomes.

Intranasal Leukemia Inhibitory Factor Attenuates Gliosis and Axonal Injury and Improves Sensorimotor Function After a Mild Pediatric Traumatic Brain Injury.

Leukemia inhibitory factor (LIF) is a neuroprotective cytokine that is essential for appropriate glial responses, remyelination, and preservation of neuronal conductance after injury. The intranasal route for delivery of therapeutics to the central nervous system is of particular interest given that it bypasses the blood-brain barrier and peripheral clearance systems. We explored the possibility that LIF might improve neurological function when administered intranasally during the acute phase in a pediatric model of mild traumatic brain injury (mTBI). We tested two doses of LIF and evaluated behavioral outcomes. Here, we show that acute 40-ng intranasal LIF treatment twice a day for 3 days attenuates astrogliosis and microgliosis, protects against axonal damage, significantly improves sensorimotor function, and is well tolerated without detrimental effects on growth. Altogether, our studies provide pre-clinical evidence for the use of acute intranasal LIF treatment as a viable therapeutic for pediatric cases of mTBIs.

Studying Trends of Auto-Regulation in Severe Head Injury in Paediatrics (STARSHIP): protocol to study cerebral autoregulation in a prospective multicentre observational research database study

IntroductionStudying cerebral autoregulation, particularly PRx (Pressure Reactivity Index), is commonly employed in adult traumatic brain injury (TBI) and gives real-time information about intracranial pathophysiology, which can help in patient management....

Early metabolic derangements and unfavorable outcomes in pediatric traumatic brain injury: a retrospective multi-center cohort study.

To study the association in moderate and severe pediatric traumatic brain injury (TBI) between hyperglycemia, hyperlactatemia, acidosis and unfavorable outcome, as assessed by Pediatric Cerebral Performance Category (PCPC) on discharge from the pediatric intensive care unit (PICU). Children <16 years old with TBI and Glasgow Coma Scale (GCS) ≤13 in an Asian multi-center PICU TBI cohort from January 2014 to October 2017 were included in this study. We defined unfavorable outcome as PCPC ≥3-moderate disability, severe disability, vegetative state, and death. We performed logistic regression to investigate the association between metabolic changes with unfavorable outcome. We divided hyperglycemia (glucose >11.1 mmol/L) during PICU admission into early-onset (within 24 h), late-onset (beyond 48 h) and persistent (throughout first 72 h). Among the 305 children analyzed, 136 (44.6%) had unfavorable outcome. Children with unfavorable outcome were more likely to have early hyperglycemia (75/136, 55.1% vs. 33/169, 19.5%; P<0.001), high lactate levels >2.0 mmol/L (74/136, 54.4% vs. 56/169, 32.5%; P<0.001) and initial acidosis (85/136, 62.5% vs. 78/169, 56.1%; P=0.003) compared to those with favorable outcome. After adjusting for gender, GCS ≤8 and presence of polytrauma, early hyperglycemia [adjusted odds ratio (aOR) =3.68, 95% CI: 2.12-6.39, P<0.001] and late hyperglycemia (aOR =13.30, 95% CI: 1.64-107.8, P=0.015] were independently associated with unfavorable outcome. All children with persistent hyperglycemia died. We described unfavorable outcome in pediatric TBI especially with persistent hyperglycemia. Future trials should investigate the causal relationship between glycemic trends, early intervention and outcome in this cohort.

Editorial introductions.

Current Opinion in Psychiatry was launched in 1988. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of psychiatry is divided into 13 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Perminder S. SachdevPerminder S. SachdevPerminder S. Sachdev AM, MBBS, MD, FRANZCP, PhD, FAHMS, is Scientia Professor of Neuropsychiatry, Co-Director of the Centre for Healthy Brain Ageing (CHeBA) in the School of Psychiatry, UNSW Sydney, Australia, and Clinical Director of the Neuropsychiatric Institute (NPI) at the Prince of Wales Hospital, Sydney, Australia. He is co-chair of the Australian Dementia Network (ADNeT), and director of the Centre of Research Excellence in Vascular Contributions to Dementia. His major areas of research are drug-induced movement disorders, brain imaging, cognitive ageing and dementia. He has published over 700 peer-reviewed journal papers and six books, including one for lay readers (The Yipping Tiger and Other Tales from the Neuropsychiatric Clinic) and a book of poems (A Migrant's Musings). He was named NSW Scientist of the Year for Biomedical Sciences in 2010. In 2011, he was appointed Member of the Order of Australia (AM) for services to medical research. In 2018, he won the DARF-Yulgilbar Innovation Award for dementia research. In 2022, he was awarded the Ryman Prize for research concept or initiative that has enhanced quality of life for older people. Roma VasaRoma VasaDr Roma Vasa is an internationally recognized developmental neuropsychiatrist and the Director of Psychiatric Services at the Center for Autism and Related Disorders at the Kennedy Krieger Institute. She is an Associate Professor of Psychiatry and Behavioral Sciences at the Johns Hopkins University School of Medicine. Dr Vasa is co-chair of the Autism and Intellectual Disability Committee of American Academy of Child and Adolescent Psychiatry. Within the field of developmental neuropsychiatry, Dr Vasa specializes in the assessment and treatment of neurodevelopmental disorders and their associated psychiatric conditions, as well as neuropsychiatric outcomes after pediatric traumatic brain injury. Her research focuses on investigating the phenotype and underlying transdiagnostic constructs of anxiety in autism spectrum disorder, notably intolerance of uncertainty. Dr Vasa is committed to training the next generation of psychiatrists, students, and other professionals in developmental neuropsychiatry and has developed innovative educational models in this area. She recently launched the Developmental Neuropsychiatry Scholar Program at the Kennedy Krieger Institute, which provides advanced specialty training to child and adolescent psychiatrists.

Prehospital and emergency management of pediatric traumatic brain injury: a multicenter site survey.

There is a paucity of information on pediatric traumatic brain injury (TBI) care in Asia and Latin America. In this study, the authors aimed to describe the clinical practices of emergency departments (EDs) participating in the Saline in Asia and Latin-America Neurotrauma in the Young (SALTY) study, by comparing designated trauma centers (DTCs) and nontrauma centers (NTCs) in their networks. The authors performed a site survey study on pediatric TBI management in the EDs in 14 countries. Two European centers joined other participating sites in Asia and Latin America. Questions were formulated after a critical review of current TBI guidelines and published surveys. The authors performed a descriptive analysis and stratified centers based on DTC status. Of 24 responding centers (70.6%), 50.0% were DTCs, 70.8% had academic affiliations, and all centers were in urban settings. Patients were predominantly transferred to DTCs by centralized prehospital services compared to those sent to NTCs (83.3% vs 41.7%, p = 0.035). More NTCs received a majority of their patients directly from the trauma scene compared to DTCs (66.7% vs 25.0%, p = 0.041). Ten centers (41.7%) reported the use of a TBI management guideline, and 15 (62.5%) implemented CT protocols. Ten DTCs reported implementation of intervention strategies for suspected raised intracranial pressure (ICP) before conducting a CT scan, and 6 NTCs also followed this practice (83.3% vs 50.0%, p = 0.083). ED management for children with TBI was comparable between DTCs and NTCs in the following aspects: neuroimaging, airway management, ICP monitoring, fluid resuscitation, anticoagulant therapy, and serum glucose control. Hyperventilation therapy for raised ICP was used by 33.3% of sites. This study evaluated pediatric TBI management and infrastructure among 24 centers. Limited differences in prehospital care and ED management for pediatric patients with TBI were observed between DTCs and NTCs. Both DTCs and NTCs showed variation in the implementation of current TBI management guidelines. There is an urgent need to investigate specific barriers to guideline implementation in these regions.

Importance of Control Groups for Evaluating Long-Term Behavioral and Cognitive Outcomes of Controlled Cortical Impact in Immature Rats.

Therapies are limited for pediatric traumatic brain injury (TBI), especially for the very young who can experience long-term consequences to learning, memory, and social behavior. Animal models of pediatric TBI have yielded mechanistic insights, but demonstration of clinically relevant long-term behavioral and/or cognitive deficits has been challenging. We characterized short- and long-term outcomes in a controlled cortical impact (CCI) model of pediatric TBI using a panel of tests between 2 weeks and ∼4 months after injury. Male rats with CCI at postnatal Day (PND) 10 were compared with three control groups: Naïve, Anesthesia, and Craniotomy. Motor testing (PND 25-33), novel object recognition (NOR; PND 40-50), and multiple tasks in water maze (WM; PND 65-100) were followed by social interaction tests (PND 120-140). Anesthesia rats performed the same as Naïve rats in all tasks. TBI rats, when compared with Naïve controls, had functional impairments across most tests studied. The most sensitive cognitive processes affected by TBI included those that required fast one-trial learning (NOR, WM), flexibility of acquired memory traces (reversals in WM), response strategies (WM), or recognition memory in the setting of reciprocal social interactions. Both TBI and Craniotomy groups demonstrated increased rates of decision making across several WM tasks, suggesting disinhibition of motor responses. When the TBI group was compared with the Craniotomy group, however, deficits were detected in a limited number of outcomes. The latter included learning speed (WM), cognitive flexibility (WM), and social recognition memory. Notably, effects of craniotomy, when compared with Naïve controls, spanned across multiple tasks, and in some tasks, could reach the effect sizes observed in TBI. These results highlight the importance of appropriate control groups in pediatric CCI models. In addition, the study demonstrates the high sensitivity of comprehensive cognitive testing to detect long-term effects of early-age craniotomy and TBI and provides a template for future testing of experimental therapies.

Social problems and brain structure development following childhood mild traumatic brain injury

Childhood mild traumatic brain injury (mTBI) is associated with elevated risk of developing social problems, which may be underpinned by changes in the structural developmental trajectory of the social brain, a network of cortical regions supporting social cognition and behavior. However, limited sample sizes and cross-sectional designs generally used in neuroimaging studies of pediatric TBI have prevented explorations of this hypothesis. This longitudinal retrospective study examined the development of parent-reported social problems and cortical thickness in social brain regions following childhood mTBI using data from the large population-based Adolescent Brain Cognitive Development (ABCD) Study. Two-group latent change score models revealed different developmental trajectories from ages 10–12 years in the level of social problems between children with (n = 345) and without (n = 7,089) mTBI. Children with mTBI showed higher, but non-clinical, levels of social problems than controls at age 10. Then, social problems decreased over 2 years, but still remained higher, but non-clinical, than in controls in which they stayed stable. Both groups showed similar decreases in social brain cortical thickness between ages 10 and 12 years. Further studies providing detailed information on the injury mechanism and acute symptoms are needed to better understand individual differences in social functioning and brain development in pediatric TBI.

Cognition and post-concussive symptom status after pediatric mild traumatic brain injury

ABSTRACT Cognitive impairment and post-concussive symptoms (PCS) represent hallmark sequelae of pediatric mild traumatic brain injury (pmTBI). Few studies have directly compared cognition as a function of PCS status longitudinally. Cognitive outcomes were therefore compared for asymptomatic pmTBI, symptomatic pmTBI, and healthy controls (HC) during sub-acute (SA; 1–11 days) and early chronic (EC; approximately 4 months) post-injury phases. We predicted worse cognitive performance for both pmTBI groups relative to HC at the SA visit. At the EC visit, we predicted continued impairment from the symptomatic group, but no difference between asymptomatic pmTBI and HCs. A battery of clinical (semi-structured interviews and self-report questionnaires) and neuropsychological measures were administered to 203 pmTBI and 139 HC participants, with greater than 80% retention at the EC visit. A standardized change method classified pmTBI into binary categories of asymptomatic or symptomatic based on PCS scores. Symptomatic pmTBI performed significantly worse than HCs on processing speed, attention, and verbal memory at SA visit, whereas lower performance was only present for verbal memory for asymptomatic pmTBI. Lower performance in verbal memory persisted for both pmTBI groups at the EC visit. Surprisingly, a minority (16%) of pmTBI switched from asymptomatic to symptomatic status at the EC visit. Current findings suggest that PCS and cognition are more closely coupled during the first week of injury but become decoupled several months post-injury. Evidence of lower performance in verbal memory for both asymptomatic and symptomatic pmTBI suggests that cognitive recovery may be a process separate from the resolution of subjective symptomology.

Barbiturate coma treatment in children with refractory intracranial hypertension due to traumatic brain injury; is it useful?

In pediatric severe Traumatic Brain Injury (TBI) the appearance of refractory intracranial hypertension is related to an unfavourable prognosis. Severe TBI (ECG &lt;8) is present in 60% of polytrauma children and is associated with high morbidity and mortality. The monitoring of intracranial pressure (ICP) and the treatment of intracranial hypertension have been subjects of attention in neurotrauma for years in the evidence-based guidelines currently being a topic of discussion. Currently the guides based on evidenceshowing acceptance of some guidelines for the management of intracranial hypertension, within the most accepted of sedatives/analgesics, hyperosmolar agents (hypertonic saline solution HTS and mannitol) and barbiturates, although the level of evidence of these recommendations is insufficient to standardize such management in the centers of attention.

Cerebrovascular dynamics after pediatric traumatic brain injury.

Objective: We aimed to investigate model-based indices of cerebrovascular dynamics after pediatric traumatic brain injury (TBI) using transcranial Doppler ultrasound (TCD) integrated into multimodality neurologic monitoring (MMM). Methods: We performed a retrospective analysis of pediatric TBI patients undergoing TCD integrated into MMM. Classic TCD characteristics included pulsatility indices and systolic, diastolic and mean flow velocities of the bilateral middle cerebral arteries. Model-based indices of cerebrovascular dynamics included the mean velocity index (Mx), compliance of the cerebrovascular bed (Ca), compliance of the cerebrospinal space (Ci), arterial time constant (TAU), critical closing pressure (CrCP) and diastolic closing margin (DCM). Classic TCD characteristics and model-based indices of cerebrovascular dynamics were investigated in relation to functional outcomes and intracranial pressure (ICP) using generalized estimating equations with repeated measures. Functional outcomes were assessed using the Glasgow Outcome Scale-Extended Pediatrics score (GOSE-Peds) at 12months, post-injury. Results: Seventy-two separate TCD studies were performed on twenty-five pediatric TBI patients. We identified that reduced Ci (estimate -5.986, p = 0.0309), increased CrCP (estimate 0.081, p < 0.0001) and reduced DCM (estimate -0.057, p = 0.0179) were associated with higher GOSE-Peds scores, suggestive of unfavorable outcome. We identified that increased CrCP (estimate 0.900, p < 0.001) and reduced DCM (estimate -0.549, p < 0.0001) were associated with increased ICP. Conclusion: In an exploratory analysis of pediatric TBI patients, increased CrCP and reduced DCM and Ci are associated with unfavorable outcomes, and increased CrCP and reduced DCM are associated with increased ICP. Prospective work with larger cohorts is needed to further validate the clinical utility of these features.

Decompressive Craniectomy in Pediatric Traumatic Brain Injury: A Retrospective Cohort Study

AbstractDecompressive craniectomy (DC) in children with traumatic brain injury (TBI) and refractory raised intracranial pressure (ICP) remains controversial. We aimed to describe the clinical and operative characteristics of children with moderate to severe TBI who underwent DC, and compare outcomes with those who had medical therapy. We performed a retrospective observational cohort study on children &lt; 16 years of age with moderate to severe TBI (Glasgow coma scale [GCS] ≤13) who underwent DC in two pediatric centers in Singapore and China between 2014 and 2017, and compared their outcomes with children who underwent medical treatment, among participating centers of the Pediatric Acute and Critical Care Medicine Asian Network. We defined poor functional outcomes as moderate, severe disability, vegetative or comatose state, or mortality, using the Pediatric Cerebral Performance Category scale. We performed multivariable logistic regression to identify predictors for poor functional outcomes. We analyzed 18 children who underwent DC with 214 who had medical therapy. A greater proportion of children with DC (14, 77.8%) experienced poor functional outcomes, compared with those with medical therapy (87, 41.2%, p = 0.003). Children who underwent DC had fewer median 14-day intensive care unit (ICU)-free days (2.5 days, interquartile range [IQR]: 0.0–5.8 vs. 8.0 days, IQR: 0.0–11.0, p = 0.033), median 28-day hospital-free days (0 day, IQR: 0.0–3.5 vs. 11.0 days, IQR: 0.0–21.0, p = 0.002) and 14-day mechanical ventilation-free days (6.5 days, IQR: 0.0–12.3 vs. 11.0 days, IQR: 3.0–14.0, p = 0.011). After accounting for age, sex, GCS, cerebral edema, uncal herniation, nonaccidental injury, and need for intubation, there was no significant association between DC and poor functional outcomes (adjusted odds ratio: 1.59, 95% confidence interval: 0.35–7.24, p = 0.548). Children with DC had severe injuries, and prolonged hospital and ICU stays. Future studies are needed to understand the effectiveness of DC on children with TBI.

Stress Reactivity After Pediatric Traumatic Brain Injury: Relation With Behavioral Adjustment.

Traumatic injury is linked increasingly to alterations in both stress response systems and psychological health. We investigated reactivity of salivary analytes of the hypothalamic-pituitary-adrenal axis (cortisol) and autonomic nervous system (salivary alpha amylase, sAA) during a psychosocial stress procedure in relation to psychological health outcomes. In a prospective cohort design, stress reactivity of children ages 8 to 15 years hospitalized for traumatic brain injury (TBI; n = 74) or extracranial injury (EI; n = 35) was compared with healthy controls (n = 51) 7 months after injury. Area under the curve increase (AUCinc) assessed pre-stressor to post-stressor cortisol and sAA values. Multi-variable general linear models evaluated demographic, family functioning, group, cortisol, and sAA AUCinc, and their interactions in relation to concurrent child and parent ratings of emotion regulation and internalizing and externalizing problems. Although AUCinc values were similar across groups, their relations with outcomes varied by group. Higher stress reactivity is typically associated with fewer adjustment problems. Relative to controls, greater sAA reactivity was associated with greater emotion dysregulation after TBI. In contrast, the relation of sAA reactivity with internalizing and generalized anxiety scores was flatter for both TBI and EI groups. The flattened and/or reversed direction of sAA reactivity with psychological health outcomes after TBI, and to a lesser degree EI, suggests autonomic nervous system dysregulation. Across groups, sAA reactivity interacted with sex on several psychological health outcomes with greater dysregulation in girls than in boys. Our findings highlight altered sAA, but not cortisol reactivity, as a potential mechanism of biological vulnerability associated with poorer adjustment after TBI.

Regional variations distinguish auditory from visual evoked potentials in healthy 4 week old piglets

Objective. Evoked potentials (EP), measured using electroencephalographic (EEG) recordings provide an opportunity to monitor cognitive dysfunctions after neurological diseases or traumatic brain injury (TBI). The 4 week old piglet is an established model of paediatric TBI; therefore, healthy piglets were studied to establish feasibility of obtaining responses to auditory and visual stimuli. A secondary aim was to input the EEG data into a piglet computational model to localize the brain sources related to processing. We tested the hypotheses: (1) visual, auditory-standard, and auditory-target stimuli elicit responses, (2) there is an effect of stimulus type, day tested, and electrode region on EPs from EEG, (3) there is an effect of stimulus type, day tested, and brain region on localized sources from a computational model. Approach. Eleven 4 week old female piglets were fitted with a 32-electrode net and presented with a simple white light stimulus and an auditory oddball click train (70 standard; 30 target tones). Main results. N1 and P2 amplitudes were consistently observed for all stimulus types. Significant interaction effects between brain region and stimulus for EP and current density demonstrate that cognitive responses are specific to each modality with auditory localizing to the temporal region and visual to the occipital regions. There was a day effect where larger responses were found on the first day than day 2 and 3 and may be due to the novelty of the stimulus on the first day. Visual stimuli had larger P1 amplitudes and earlier latencies (P1, N1) than auditory which coincides with current density results at 50 ms where larger activations were observed for visual. At 85 ms, auditory had significantly larger current densities coincident with larger and longer N1 amplitudes and latencies than visual. Significance. Auditory and visual processing were successfully and consistently obtained in a porcine model and can be evaluated as a diagnostic assessment for TBI.

Risk factors for posttraumatic hydrocephalus after decompressive hemicraniectomy in pediatric patients with traumatic brain injury.

Traumatic brain injuries (TBIs) play a significant role in pediatric mortality and morbidity. Decompressive hemicraniectomy (DHC) is a treatment option for severe pediatric TBI (pTBI) not amenable to medical management of intracranial pressure. Posttraumatic hydrocephalus (PTH) is a known sequela of DHC that may lead to further injury and decreased capacity for recovery if not identified and treated. The goal of this study was to characterize risk factors for PTH after DHC in patients with pTBI by using the Kids' Inpatient Database (KID). The records collected in the KID from 2016 to 2019 were queried for patients with TBI using International Classification of Diseases, 10th Revision codes. Data defining demographics, complications, procedures, and outcomes were extracted. Multivariate regression was used to identify risk factors associated with PTH. The authors also investigated length of stay and hospital charges. Of 68,793 patients with pTBI, 848 (1.2%) patients underwent DHC. Prolonged mechanical ventilation (PMV) was required in 475 (56.0%) patients with pTBI undergoing DHC. Three hundred (35.4%) patients received an external ventricular drain (EVD) prior to DHC. PTH was seen in 105 (12.4%), and 50 (5.9%) received a ventriculoperitoneal shunt. DHC before hospital day 2 was negatively associated with PTH (OR 0.464, 95% CI 0.267-0.804; p = 0.006), whereas PMV (OR 2.204, 95% CI 1.344-3.615; p = 0.002) and EVD placement prior to DHC (OR 6.362, 95% CI 3.667-11.037; p < 0.001) were positively associated with PTH. PMV (OR 7.919, 95% CI 2.793-22.454; p < 0.001), TBI with subdural hematoma (OR 2.606, 95% CI 1.119-6.072; p = 0.026), and EVD placement prior to DHC (OR 4.575, 95% CI 2.253-9.291; p < 0.001) were independent predictors of ventriculoperitoneal shunt insertion. The mean length of stay and total hospital charges were significantly increased in patients with PMV and in those with PTH. PMV, presence of subdural hematoma, and EVD placement prior to DHC are risk factors for PTH in patients with pTBI who underwent DHC. Higher healthcare resource utilization was seen in patients with PTH. Identifying risk factors for PTH may improve early diagnosis and efficient resource utilization.

Low Morbidity and Mortality in Children with Severe Traumatic Brain Injury Treated According to the Lund Concept: A Population-Based Study.

Previous reports of mortality and morbidity in pediatric severe traumatic brain injury (TBI) vary considerably, with few population-based studies. Mortality rates from 3-33 % and varying morbidity have been reported, most commonly using the Extended Glasgow Outcome Scale (eGOS). The Lund concept is a treatment algorithm for severe TBI aiming at controlling intracranial pressure (ICP) by reducing cerebral perfusion pressure (CPP). The aim of the present study was to retrospectively assess mortality and morbidity in a population of pediatric TBI treated according to the Lund concept. All cases of severe pediatric TBI (age <18 years) in the southern region of Sweden during 19 years were identified. Patients were treated according to the Lund concept. Mortality, eGOS, ICP, CPP, time in the neurosurgical intensive care unit (NICU), drugs delivered and surgical procedures were recorded. Data were analyzed both by dichotomized outcomes and by ordinal statistics. A total of 135 cases of severe TBI <18 years of age were recorded (incidence 2.0/100000) and 86 patients were admitted to the tertiary NICU. Mortality including all cases was 43% (mortality rate 0.7/100,000) and in NICU 10%. Outcome was good in 60%, moderate in 25%, unfavorable in 15%, with none in a vegetative status. In both dichotomized and ordinal analyses, CPP <40 mm Hg and ICP >15 were associated with poor outcome, supporting current guidelines. However, high CPP also was associated with increased mortality and morbidity, supporting that elevated CPP might increase cerebral edema. In this study, the Lund concept resulted in low mortality and a favorable outcome in a majority of severe pediatric TBI patients; however, randomized controlled trials are warranted to verify this.