Risk Of Brain Injury Research Articles

Brain-Lung Crosstalk: Management of Concomitant Severe Acute Brain Injury and Acute Respiratory Distress Syndrome.

Purpose of ReviewTo summarize pathophysiology, key conflicts, and therapeutic approaches in managing concomitant severe acute brain injury (SABI) and acute respiratory distress syndrome (ARDS).Recent FindingsARDS is common in SABI and independently associated with worse outcomes in all SABI subtypes. Most landmark ARDS trials excluded patients with SABI, and evidence to guide decisions is limited in this population. Potential areas of conflict in the management of patients with both SABI and ARDS are (1) risk of intracranial pressure (ICP) elevation with high levels of positive end-expiratory pressure (PEEP), permissive hypercapnia due to lung protective ventilation (LPV), or prone ventilation; (2) balancing a conservative fluid management strategy with ensuring adequate cerebral perfusion, particularly in patients with symptomatic vasospasm or impaired cerebrovascular blood flow; and (3) uncertainty about the benefit and harm of corticosteroids in this population, with a mortality benefit in ARDS, increased mortality shown in TBI, and conflicting data in other SABI subtypes. Also, the widely adapted partial pressure of oxygen (PaO2) target of > 55 mmHg for ARDS may exacerbate secondary brain injury, and recent guidelines recommend higher goals of 80–120 mmHg in SABI. Distinct pathophysiology and trajectories among different SABI subtypes need to be considered.SummaryThe management of SABI with ARDS is highly complex, and conventional ARDS management strategies may result in increased ICP and decreased cerebral perfusion. A crucial aspect of concurrent management is to recognize the risk of secondary brain injury in the individual patient, monitor with vigilance, and adjust management during critical time windows. The care of these patients requires meticulous attention to oxygenation and ventilation, hemodynamics, temperature management, and the neurological exam. LPV and prone ventilation should be utilized, and supplemented with invasive ICP monitoring if there is concern for cerebral edema and increased ICP. PEEP titration should be deliberate, involving measures of hemodynamic, pulmonary, and brain physiology. Serial volume status assessments should be performed in SABI and ARDS, and fluid management should be individualized based on measures of brain perfusion, the neurological exam, and cardiopulmonary status. More research is needed to define risks and benefits in corticosteroids in this population.

Diffuse correlation spectroscopy blood flow monitoring for intraventricular hemorrhage vulnerability in extremely low gestational age newborns

In premature infants with an extremely low gestational age (ELGA, < 29 weeks GA), dysregulated changes in cerebral blood flow (CBF) are among the major pathogenic factors leading to germinal matrix/intraventricular hemorrhage (GM/IVH). Continuous monitoring of CBF can guide interventions to minimize the risk of brain injury, but there are no clinically standard techniques or tools for its measurement. We report the feasibility of the continuous monitoring of CBF, including measures of autoregulation, via diffuse correlation spectroscopy (DCS) in ELGA infants using CBF variability and correlation with scalp blood flow (SBF, served as a surrogate measure of systemic perturbations). In nineteen ELGA infants (with 9 cases of GM/IVH) monitored for 6–24 h between days 2–5 of life, we found a strong correlation between CBF and SBF in severe IVH (Grade III or IV) and IVH diagnosed within 72 h of life, while CBF variability alone was not associated with IVH. The proposed method is potentially useful at the bedside for the prompt assessment of cerebral autoregulation and early identification of infants vulnerable to GM/IVH.

Early post-traumatic seizures in hospitalized patients with traumatic brain injury.

Early post-traumatic seizures (EPTS) are a well-known complication of traumatic brain injury (TBI). EPTS increase the risk of secondary brain injury and may cause significant challenges during the period of critical care. Routine use of prophylactic anti-seizure medication is controversial due to conflicting reports on efficacy and risk of adverse effects. The purpose of this study was to expand the understanding of EPTS by examining incidence and risk factors in hospitalized patients with TBI. Adult patients with TBI and evidence of intracranial injury admitted to Oslo University Hospital between 2015 and 2019 were identified from the Oslo TBI Registry - Neurosurgery. Demographic and clinical data including occurrence of seizures were retrieved from the registry. The patients did not receive routine seizure prophylaxis. Univariate and multivariable logistic regression analyses were used to investigate risk factors associated with EPTS. 103 of 1827 patients (5.6%) had new-onset seizures within the first week after TBI. The following factors were in multivariable analyses associated with EPTS; alcohol abuse (odds ratio [OR] 3.6, 95% CI 2.3-5.7, p < .001), moderate and severe brain injury (OR 2.2, 95% CI 1.3-3.8, p=.004 and OR 2.1, 95% CI 1.2-3.6, p=.012), brain contusion (OR 1.6, 95% CI 1.0-2.4, p=.046) and subdural hematoma (OR 1.6, 95% CI 1.0-2.6, p=.052). In our material, EPTS occurred in 5.6% of hospital-admitted TBI-patients. Alcohol abuse was the most significant risk factor, followed by moderate and severe brain injury. The results of this study contribute to the discussion about preventive treatment of EPTS in certain risk groups.

Development and Validation of a Deep Learning Method to Predict Cerebral Palsy From Spontaneous Movements in Infants at High Risk

Early identification of cerebral palsy (CP) is important for early intervention, yet expert-based assessments do not permit widespread use, and conventional machine learning alternatives lack validity. To develop and assess the external validity of a novel deep learning-based method to predict CP based on videos of infants' spontaneous movements at 9 to 18 weeks' corrected age. This prognostic study of a deep learning-based method to predict CP at a corrected age of 12 to 89 months involved 557 infants with a high risk of perinatal brain injury who were enrolled in previous studies conducted at 13 hospitals in Belgium, India, Norway, and the US between September 10, 2001, and October 25, 2018. Analysis was performed between February 11, 2020, and September 23, 2021. Included infants had available video recorded during the fidgety movement period from 9 to 18 weeks' corrected age, available classifications of fidgety movements ascertained by the general movement assessment (GMA) tool, and available data on CP status at 12 months' corrected age or older. A total of 418 infants (75.0%) were randomly assigned to the model development (training and internal validation) sample, and 139 (25.0%) were randomly assigned to the external validation sample (1 test set). Video recording of spontaneous movements. The primary outcome was prediction of CP. Deep learning-based prediction of CP was performed automatically from a single video. Secondary outcomes included prediction of associated functional level and CP subtype. Sensitivity, specificity, positive and negative predictive values, and accuracy were assessed. Among 557 infants (310 [55.7%] male), the median (IQR) corrected age was 12 (11-13) weeks at assessment, and 84 infants (15.1%) were diagnosed with CP at a mean (SD) age of 3.4 (1.7) years. Data on race and ethnicity were not reported because previous studies (from which the infant samples were derived) used different study protocols with inconsistent collection of these data. On external validation, the deep learning-based CP prediction method had sensitivity of 71.4% (95% CI, 47.8%-88.7%), specificity of 94.1% (95% CI, 88.2%-97.6%), positive predictive value of 68.2% (95% CI, 45.1%-86.1%), and negative predictive value of 94.9% (95% CI, 89.2%-98.1%). In comparison, the GMA tool had sensitivity of 70.0% (95% CI, 45.7%-88.1%), specificity of 88.7% (95% CI, 81.5%-93.8%), positive predictive value of 51.9% (95% CI, 32.0%-71.3%), and negative predictive value of 94.4% (95% CI, 88.3%-97.9%). The deep learning method achieved higher accuracy than the conventional machine learning method (90.6% [95% CI, 84.5%-94.9%] vs 72.7% [95% CI, 64.5%-79.9%]; P < .001), but no significant improvement in accuracy was observed compared with the GMA tool (85.9%; 95% CI, 78.9%-91.3%; P = .11). The deep learning prediction model had higher sensitivity among infants with nonambulatory CP (100%; 95% CI, 63.1%-100%) vs ambulatory CP (58.3%; 95% CI, 27.7%-84.8%; P = .02) and spastic bilateral CP (92.3%; 95% CI, 64.0%-99.8%) vs spastic unilateral CP (42.9%; 95% CI, 9.9%-81.6%; P < .001). In this prognostic study, a deep learning-based method for predicting CP at 9 to 18 weeks' corrected age had predictive accuracy on external validation, which suggests possible avenues for using deep learning-based software to provide objective early detection of CP in clinical settings.

Investigating Pathways of Ventilation Induced Brain Injury on Cerebral White Matter Inflammation and Injury After 24h in Preterm Lambs.

Initiation of respiratory support in the delivery room increases the risk and severity of brain injury in preterm neonates through two major pathways: an inflammatory pathway and a haemodynamic pathway. The relative contribution of each pathway on preterm brain injury is not known. We aimed to assess the role of the inflammatory and haemodynamic pathway on ventilation-induced brain injury (VIBI) in the preterm lamb. Fetal lambs (125 ± 1 day gestation) were exteriorised, instrumented and ventilated with a high tidal-volume (VT) injurious strategy for 15 min either with placental circulation intact to induce the inflammatory pathway only (INJINF; n = 7) or umbilical cord occluded to induce both the inflammatory and haemodynamic pathways (INJINF+HAE; n = 7). Sham controls were exteriorised but not ventilated (SHAM; n = 5) while unoperated controls (UNOP; n = 7) did not undergo fetal instrumentation. Fetuses were returned in utero following intervention and the ewe allowed to recover. Arterial blood gases and plasma were sampled periodically. Twenty-four hours following intervention, lambs were delivered and maintained on non-injurious ventilation for ∼40 min then brains were collected post-mortem for immunohistochemistry and RT-qPCR to assess inflammation, vascular pathology and cell death within white matter regions. Compared to INJINF lambs, INJINF+HAE lambs achieved a consistently higher VT during injurious ventilation and carotid blood flow was significantly lower than baseline by the end of ventilation. Throughout the 24 h recovery period, systemic arterial IL-6 levels of INJINF+HAE lambs were significantly higher than SHAM while there was no difference between INJINF and SHAM animals. At 24 h, mRNA expression levels of pro-inflammatory cytokines, tight junction proteins, markers of cell death, and histological injury indices of gliosis, blood vessel protein extravasation, oligodendrocyte injury and cell death were not different between groups. Injurious ventilation, irrespective of strategy, did not increase brain inflammation or injury 24 h later when compared to control animals. However, the haemodynamic pathway did influence carotid blood flow adaptations during injurious ventilation and increased systemic arterial IL-6 that may underlie long-term pathology. Future studies are required to further characterise the pathways and their long-term effects on VIBI.

Biomarkers and neuromonitoring for prognosis of development after perinatal brain damage

Das sich entwickelnde Gehirn ist in der Perinatalperiode besonders empfindlich für eine Vielzahl von Insulten, wie z. B. Extremfrühgeburtlichkeit und perinatale Asphyxie. Ihre Komplikationen können zu lebenslangen neurokognitiven, sensorischen und psychosozialen Einschränkungen führen; deren Vorhersage bleibt eine Herausforderung. Eine Schlüsselfunktion kommt der möglichst exakten Identifikation von Hirnläsionen und funktionellen Störungen zu. Die Prädiktion stützt sich auf frühe diagnostische Verfahren und die klinische Erfassung der Meilensteine der Entwicklung. Zur klinischen Diagnostik und zum Neuromonitoring in der Neonatal- und frühen Säuglingsperiode stehen bildgebende Verfahren zur Verfügung. Hierzu zählen zerebrale Sonographie, MRT am errechneten Termin, amplitudenintegriertes (a)EEG und/oder klassisches EEG, Nah-Infrarot-Spektroskopie, General Movements Assessment und die frühe klinische Nachuntersuchung z. B. mithilfe der Hammersmith Neonatal/Infant Neurological Examination. Innovative Biomarker und -muster (Omics) sowie (epi)genetische Prädispositionen sind Gegenstand wissenschaftlicher Untersuchungen. Neben der Erfassung klinischer Risiken kommt psychosozialen Faktoren im Umfeld des Kindes eine entscheidende Rolle zu. Eine möglichst akkurate Prognose ist mit hohem Aufwand verbunden, jedoch zur gezielten Beratung der Familien und der Einleitung von frühen Interventionen, insbesondere vor dem Hintergrund der hohen Plastizität des sich entwickelnden Gehirns, von großer Bedeutung. Diese Übersichtsarbeit fokussiert die Charakterisierung der oben genannten Verfahren und ihrer Kombinationsmöglichkeiten. Zudem wird ein Ausblick gegeben, wie innovative Techniken in Zukunft die Prädiktion der Entwicklung und Nachsorge dieser Kinder vereinfachen können.

Impact of Comorbid Prematurity and Congenital Anomalies: A Review.

Preterm infants are more likely to be born with congenital anomalies than those who are born at full-term. Conversely, neonates born with congenital anomalies are also more likely to be born preterm than those without congenital anomalies. Moreover, the comorbid impact of prematurity and congenital anomalies is more than cumulative. Multiple common factors increase the risk of brain injury and neurodevelopmental impairment in both preterm babies and those born with congenital anomalies. These include prolonged hospital length of stay, feeding difficulties, nutritional deficits, pain exposure and administration of medications including sedatives and analgesics. Congenital heart disease provides a well-studied example of the impact of comorbid disease with prematurity. Impaired brain growth and maturity is well described in the third trimester in this population; the immature brain is subsequently more vulnerable to further injury. There is a colinear relationship between degree of prematurity and outcome both in terms of mortality and neurological morbidity. Both prematurity and relative brain immaturity independently increase the risk of subsequent neurodevelopmental impairment in infants with CHD. Non-cardiac surgery also poses a greater risk to preterm infants despite the expectation of normal in utero brain growth. Esophageal atresia, diaphragmatic hernia and abdominal wall defects provide examples of congenital anomalies which have been shown to have poorer neurodevelopmental outcomes in the face of prematurity, with associated increased surgical complexity, higher relative cumulative doses of medications, longer hospital and intensive care stay and increased rates of feeding difficulties, compared with infants who experience either prematurity or congenital anomalies alone.

Antenatal Magnesium Sulfate for Preterm Neuroprotection: A Single-Center Experience from Kuwait Tertiary NICU

Objectives: The study aimed to evaluate the impact of antenatal exposure of magnesium sulfate (MgSO₄) on short- and long-term outcomes in preterm neonates born less than 32 weeks gestation. Methods: Single-center retrospective cohort study of 229 neonates born between 24 and 32 weeks gestation was conducted from January 2018 through December 2018 in a level III neonatal care unit in Kuwait. Antenatal MgSO₄ exposure was collected from the medical records, and the indication was for neuroprotection effect. Brain MRI was done on 212 neonates (median gestational age 36 weeks), and brain injury was assessed using the Miller’s score. Neurodevelopmental outcome was assessed by Bayley-III scales of infant development at 36 months corrected age (N = 146). The association of exposure to MgSO4 with brain injury and neurodevelopmental outcomes was examined using multivariable regression analysis adjusting for gestational age at MRI and variables with p value <0.05 on univariate analysis. Results: Among the 229 neonates, 47 received antenatal MgSO₄. There were no differences between the groups in gestational age and birth weight. MgSO₄ exposure was not associated with an increased risk of necrotizing enterocolitis, chronic lung disease, retinopathy of prematurity, and mortality. The incidence of cerebellar hemorrhage was significantly less in the MgSO₄ group (0% vs. 16%, p value = 0.002). Neonates who received MgSO₄ had lower risks of grade 3–4 intraventricular hemorrhage (IVH) adjusted OR 0.248 (95% CI: 0.092, 0.66), p = 0.006; moderate-severe white matter injury (WMI) adjusted odd ratio 0.208 (95% CI: 0.044, 0.96), p = 0.046; and grade 3–4 IVH and/or moderate-severe WMI adjusted OR 0.23 (95% CI: 0.06, 0.84), p = 0.027. Neurodevelopmental assessment at 36 months corrected age showed better motor (adjusted beta coefficient 1.08 [95% CI: 0.099, 2.06]; p = 0.031) and cognitive composite scores (adjusted beta coefficient 1.29 [95% CI: 0.36, 2.22]; p = 0.007) in the MgSO₄ group. Conclusion: Antenatal exposure to MgSO₄ in preterm neonates less than 32 weeks was independently associated with lower risks of brain injury and better motor and cognitive outcomes.

Zone 1 REBOA in a combat DCBI swine model does not worsen brain injury

BackgroundZone 1 resuscitative endovascular balloon occlusion of the aorta has been recommended for refractory shock after a dismounted complex blast injury for the austere combat scenario. While resuscitative endovascular balloon occlusion of the aorta should enhance coronary perfusion, there is a potential risk of secondary brain injury due to loss of cerebral autoregulation. We developed a combat casualty relevant dismounted complex blast injury swine model to evaluate the effects of resuscitative endovascular balloon occlusion of the aorta zone I on intracranial pressure and cerebral edema. We hypothesized that zone 1 aortic occlusion with resuscitative endovascular balloon occlusion of the aorta would increase mean arterial pressure transmitted in excessive intracranial pressure, thereby worsening brain injury. Methods50 kg male Yorkshire swine were subjected to a combination dismounted complex blast injury model consisting of blast traumatic brain injury (50 psi, ARA Mobile Shock Laboratory), tissue injury (bilateral femur fractures), and hemorrhagic shock (controlled bleeding to a base deficit goal of 10 mEq/L). During the shock phase, pigs were randomized to no aortic occlusion (n = 8) or to 30 minutes of zone 1 resuscitative endovascular balloon occlusion of the aorta (zone 1 aortic occlusion group, n = 6). After shock, pigs in both groups received a modified Tactical Combat Casualty Care–based resuscitation and were monitored for an additional 240 minutes until euthanasia/death for a total of 6 hours. Intracranial pressure was monitored throughout, and brains were harvested for water content. Linear mixed models for repeated measures were used to compare mean arterial pressure and intracranial pressure between zone 1 aortic occlusion and no aortic occlusion groups. ResultsAfter dismounted complex blast injury, the zone 1 group had a significantly higher mean arterial pressure during hemorrhagic shock compared to the control group (41.2 mm Hg vs 16.7 mm Hg, P = .002). During balloon occlusion, intracranial pressure was not significantly elevated in the zone 1 aortic occlusion group vs control, but intracranial pressure was significantly lower in the zone 1 group at the end of the observation period. In addition, the zone 1 aortic occlusion group did not have increased brain water content (zone 1 aortic occlusion: 3.95 ± 0.1g vs no aortic occlusion: 3.95 ± 0.3 g, P = .87). Troponin levels significantly increased in the no aortic occlusion group but did not in the zone 1 aortic occlusion group. ConclusionZone 1 aortic occlusion using resuscitative endovascular balloon occlusion of the aorta in a large animal dismounted complex blast injury model improved proximal mean arterial pressure while not significantly increasing intracranial pressure during balloon inflation. Observation up to 240 minutes postresuscitation did not show clinical signs of worsening brain injury or cardiac injury. These data suggest that in a dismounted complex blast injury swine model, resuscitative endovascular balloon occlusion of the aorta in zone 1 may provide neuro- and cardioprotection in the setting of blast traumatic brain injury. However, longer monitoring periods may be needed to confirm that the neuroprotection is lasting.

Potential missed opportunities for antenatal corticosteroid exposure and outcomes among periviable births: observational cohort study.

Test the hypothesis potential missed opportunities for antenatal corticosteroids increase as gestational age decreases and are associated with adverse outcomes. Observational cohort study. 24 US centers in the Neonatal Research Network. Actively treated infants 22-25 weeks' gestation and birth weight 401-1000 grams, without major birth defects, born 2006-2018. Potential missed opportunity was defined as no antenatal corticosteroids but did have prenatal antibiotics, and/or magnesium sulfate, and/or prolonged rupture of membranes. Poisson regression models adjusted for baseline characteristics. Antenatal corticosteroid exposure, mortality, and severe intracranial hemorrhage or periventricular leukomalacia. 6966 (87.5%) were exposed to antenatal corticosteroids, 454 (5.7%) had no exposure but potential missed opportunities for antenatal corticosteroid exposure, and 537 (6.7%) had no exposure and no evidence of potential missed opportunities. Compared with infants born at 25 weeks, potential missed opportunities for antenatal corticosteroid exposure were more likely at 22 weeks (adjusted relative risk (aRR) [95% CI] 11.06 [7.52-16.27]) and 23 weeks (3.24 [2.44-4.29]) but did not differ at 24 weeks (1.08 [0.82-1.42]). Potential missed opportunities for antenatal corticosteroids decreased over time at 22-23 weeks' gestation. Antenatal corticosteroid exposed infants had lower risk of death (31.0% vs 54.8%; 0.77 [0.70-0.84]) and survivors had lower risk of severe brain injury (25.0% v 44.5%; 0.64 [0.55-0.73]) compared with infants with potential missed opportunities. Potential missed opportunities for antenatal corticosteroid exposure increased with decreasing gestational age and were associated with higher rates of death and severe brain injury among actively treated periviable births.

Automated soccer head impact exposure tracking using video and deep learning

Head impacts are highly prevalent in sports and there is a pressing need to investigate the potential link between head impact exposure and brain injury risk. Wearable impact sensors and manual video analysis have been utilized to collect impact exposure data. However, wearable sensors suffer from high deployment cost and limited accuracy, while manual video analysis is a long and resource-intensive task. Here we develop and apply DeepImpact, a computer vision algorithm to automatically detect soccer headers using soccer game videos. Our data-driven pipeline uses two deep learning networks including an object detection algorithm and temporal shift module to extract visual and temporal features of video segments and classify the segments as header or nonheader events. The networks were trained and validated using a large-scale professional-level soccer video dataset, with labeled ground truth header events. The algorithm achieved 95.3% sensitivity and 96.0% precision in cross-validation, and 92.9% sensitivity and 21.1% precision in an independent test that included videos of five professional soccer games. Video segments identified as headers in the test data set correspond to 3.5 min of total film time, which can be reviewed through additional manual video verification to eliminate false positives. DeepImpact streamlines the process of manual video analysis and can help to collect large-scale soccer head impact exposure datasets for brain injury research. The fully video-based solution is a low-cost alternative for head impact exposure monitoring and may also be expanded to other sports in future work.

Neuroimaging in professional combat sports: consensus statement from the association of ringside physicians

ABSTRACT Professional boxing, kickboxing, and mixed martial arts (MMA) are popular sports with substantial risk for both acute and chronic traumatic brain injury (TBI). Although rare, combat sports athletes have died in the ring or soon after the completion of a bout. Deaths in these instances are usually the result of an acute catastrophic neurological event such as an acute subdural hematoma (SDH). Other causes may include acute epidural hematoma (EDH), subarachnoid hemorrhage (SAH), intraparenchymal hemorrhage (IPH), or a controversial, rare, and still disputed clinical entity called second-impact syndrome (SIS). Neuroimaging or brain imaging is currently included in the process of registering for a license to compete in combat sports in some jurisdictions of the United States of America and around the world. However, the required imaging specifics and frequency vary with no consensus guidelines. The Association of Ringside Physicians (an international, nonprofit organization dedicated to the health and safety of the combat sports athlete) sets forth this consensus statement to establish neuroimaging guidelines in combat sports. Commissions, ringside physicians, combat sports athletes, trainers, promoters, sanctioning bodies, and other healthcare professionals can use this statement for risk stratification of a professional combat sports athlete prior to licensure, identifying high-risk athletes and for prognostication of the brain health of these athletes over the course of their career. Guidelines are also put forth regarding neuroimaging requirements in the immediate aftermath of a bout.

Individualizing medical suspension after knockout in boxing-no two knockouts are the same

Professional boxing carries high risk of acute traumatic brain injuries (TBIs). Subdural hematoma is the most common neurological cause of boxing related mortality. Other acute TBIs in boxing include epidural hematoma, intracranial hematoma, cerebral contusions, dissection of large vessels of the neck and concussion. Concussion or mild TBI is common in a sport like boxing where every punch thrown at the head is thrown with the idea of winning by causing a knockout (KO) which is nothing but a concussive injury of the brain. After a KO, the boxer is typically given a medical suspension. The adequate duration of medical suspension after a KO has neither been determined nor standardized.

Individualizing medical suspension after knockout in boxing-no two knockouts are the same

Professional boxing carries high risk of acute traumatic brain injuries (TBIs). Subdural hematoma is the most common neurological cause of boxing related mortality. Other acute TBIs in boxing include epidural hematoma, intracranial hematoma, cerebral contusions, dissection of large vessels of the neck and concussion. Concussion or mild TBI is common in a sport like boxing where every punch thrown at the head is thrown with the idea of winning by causing a knockout (KO) which is nothing but a concussive injury of the brain. After a KO, the boxer is typically given a medical suspension. The adequate duration of medical suspension after a KO has neither been determined nor standardized.

Acute histologic chorioamnionitis independently and directly increases the risk for brain abnormalities seen on magnetic resonance imaging in very preterm infants

The independent risk for neurodevelopmental impairments attributed to chorioamnionitis in premature infants remains controversial. Delayed brain maturation or injury identified on magnetic resonance imaging at term-equivalent age can be used as a surrogate measure of neurodevelopmental impairments that is less confounded by postdelivery neonatal intensive care unit environmental factors to investigate this relationship more clearly. This study aimed to determine whether preterm infants born with moderate to severe acute histologic chorioamnionitis would have a higher magnetic resonance imaging-determined global brain abnormality score, independent of early premature birth, when compared with preterm infants with no or mild chorioamnionitis. This was a prospective, multicenter cohort study involving infants born very prematurely ≤32 weeks' gestational age with acute moderate to severe histologic chorioamnionitis, graded using standard histologic criteria. Brain abnormalities were diagnosed and scored using a well-characterized, standardized scoring system captured using a high-resolution 3 Tesla magnetic resonance imaging research magnet. In secondary analyses, total brain volume and 4 magnetic resonance imaging metrics of cortical maturation (cortical surface area, sulcal depth, gyral index, and inner cortical curvature) were calculated using an automated algorithm and correlated with chorioamnionitis. The association of funisitis (any grade) with brain abnormalities was also explored. We investigated if premature birth mediated the relationship between histologic chorioamnionitis and brain abnormality score using mediation analysis. Of 353 very preterm infants, 297 infants had mild or no chorioamnionitis (controls), and 56 were diagnosed with moderate to severe acute histologic chorioamnionitis. The primary outcome brain abnormality score was significantly higher in histologic chorioamnionitis-exposed infants than in the controls (median, 4 vs 7; P<.001). Infants with acute histologic chorioamnionitis had significantly lower brain tissue volume (P=.03) and sulcal depth (P=.04), whereas other morphometric indices did not differ statistically. In the multiple regression analysis, we observed persistent significant relationships between moderate to severe acute histologic chorioamnionitis and brain abnormality scores (β=2.84; 1.51-4.16; P<.001), total brain volume (P=.03), and sulcal depth (P=.02). Funisitis was also significantly associated with brain abnormality score after adjustment for clinical confounders (P=.005). Mediation analyses demonstrated that 50% of brain abnormalities was an indirect consequence of premature birth, and the remaining 50% was a direct effect of moderate to severe acute histologic chorioamnionitis when compared with preterm infants with no or mild chorioamnionitis exposure. Examining gestational age as a mediator, funisitis did not exert a significant direct effect on brain abnormalities after the significant indirect effects of preterm birth were accounted for. Acute histologic chorioamnionitis increases the risk for brain injury and delayed maturation, both directly and indirectly, by inducing premature birth.

AB1144 COGNITIVE AND PSYCHOSOCIAL OUTCOME IN CHILDREN WITH MULTISYSTEM INFLAMMATORY SYNDROME FOLLOWING SARS-CoV-2 INFECTION

BackgroundDespite the low rate of neurological deficits following the SARS-COV-2 infection in the pediatric population, children and adolescents who develop multisystem inflammatory syndrome (MIS-C) after being infected with SARS-COV-2 are at a higher risk for neurological abnormalities and brain injury, increasing the risk of adverse cognitive and psychiatric outcome.ObjectivesGiven the increased risk of central nervous system impairment we chose to conduct a prospective study looking at the cognitive and psychosocial outcome of patients with MIS-C.MethodsOur study included 27 of the 29 patients between 2 to 18 years of age (M = 11.1, SD = 4.4) who were treated for MIS-C from the onset of the SARS-COV-2 pandemic until the beginning of May 2021 at the only tertiary care pediatric immunology center in Slovenia. We assessed these patients 6 months after diagnosis using the age-appropriate Wechsler intelligence scales and a battery of neuropsychological test measuring attention, executive function, memory and fine motor skills. We also asked parents to report on patients’ psychosocial outcome using the Achenbach Child Behavior Checklist.ResultsBy using Bayesian statistics to take into account parental education and any potential pre-morbid learning difficulties we found no evidence of impairment on measures of intelligence. However, the posterior distribution of scores on neuropsychological measures indicated that a significant proportion of patients scored 1SD bellow expected levels on measures of attention (31%), executive function (28%) and visual memory (35%). Increased symptoms of depression, anxiety and attention difficulties were also reported by parents, although their extent did not rise to a clinically significant level.ConclusionThe findings from our cohort suggest that the cognitive and psychosocial outcome of patients with MIS-C is generally favorable, although up to 35% may experience specific neuropsychological deficits more than 6 months after diagnosis. The most commonly impaired cognitive domains seem to be attention, executive function and visual memory.AcknowledgementsFunding for this work was provided by the Slovenian Research Agency grant J3-3061 and University Medical Centre grant 20210069. Support was also provided by Dušica Boben and the publisher Center za psihodiagnostična sredstva by providing the local adaptations of psychological assessment tools.Disclosure of InterestsDavid Gosar Speakers bureau: Biogen, Novartis, Mojca Zajc Avramovič: None declared, Nina Emersic: None declared, Mateja Šušterič: None declared, Maja Maša Šömen: None declared, Damjan Osredkar: None declared, Tadej Avcin: None declared

Analysis head injuries of Vietnamese motorcyclist without a helmet in car to motorbike frontal impact using a computer model

Nowadays, with the increasing demand for travel, the number of people using motorbikes is increasing, especially in Vietnam. People tend to face more injury risks when they are in traffic, such as vulnerable road users (VRU) – pedestrians, cyclists, and motorcyclists. Therefore, the objective of this study is to assess how car crashes influence Vietnamese motorcyclists' bodies, in particular their heads, because they are the most vulnerable parts of their bodies. The result of this study is to let people know what they’re facing in case they are hit by a car. In addition, this research analyzes the injury to the motorcyclist's head when being hit by different configurations of the car. Due to the lack of facilities, car-to-motorcyclist frontal impact simulation has become the best way to resolve this problem. The impact conditions, which were obtained from real motorcyclist accidents in Vietnam, including the speed of vehicle and motorcycle, and impact angle, were defined as initial loading conditions in a simulation of the head striking the windscreen by using a finite element Vietnamese dummy model. Logistic regression models were developed to study brain injury risk with respect to injury-related variables: the head linear acceleration and head injury criterion (HIC) value. In this paper, the deformation of the motorbike structure model was neglected, so the material has been selected as a rigid form. The knowledge from this research could be a prerequisite for developing guidelines to improve motorcyclist safety in Vietnam.

Clinical determinants of cerebrovascular reactivity in very preterm infants during the transitional period

Preterm infants are at enhanced risk of brain injury due to altered cerebral haemodynamics during postnatal transition. This observational study aimed to assess the clinical determinants of transitional cerebrovascular reactivity and its association with intraventricular haemorrhage (IVH). Preterm infants <32 weeks underwent continuous monitoring of cerebral oxygenation and heart rate over the first 72 h after birth. Serial cranial and cardiac ultrasound assessments were performed to evaluate the ductal status and to diagnose IVH onset. The moving correlation coefficient between cerebral oxygenation and heart rate (TOHRx) was calculated. Linear mixed-effect models were used to analyse the impact of relevant clinical variables on TOHRx. The association between TOHRx and IVH development was also assessed. Seventy-seven infants were included. A haemodynamically significant patent ductus arteriosus (hsPDA) (β = 0.044, 95% CI: 0.007-0.081) and ongoing dopamine treatment (β = 0.096, 95% CI: 0.032-0.159) were associated with increasing TOHRx, indicating impaired cerebrovascular reactivity. A significant association between TOHRx, mean arterial blood pressure (β = -0.004, 95% CI: -0.007, -0.001) and CRIB-II score (β = 0.007, 95% CI: 0.001-0.015) was also observed. TOHRx was significantly higher in infants developing high-grade IVH compared to those without IVH. Dopamine treatment, low blood pressure, hsPDA and high CRIB-II are associated with impaired cerebrovascular reactivity during postnatal transition, with potential implications on IVH development. The correlation coefficient between cerebral oxygenation and heart rate (TOHRx) provides a non-invasive estimation of cerebrovascular reactivity, whose failure has a potential pathogenic role in the development of IVH in preterm infants. This study shows that cerebrovascular reactivity during the transitional period improves over time and is affected by specific clinical and therapeutic factors, whose knowledge could support the development of individualized neuroprotective strategies in at-risk preterm infants. The evidence of increased TOHRx in infants developing high-grade compared to low-grade or no IVH during the transitional period further supports the role of impaired cerebrovascular reactivity in IVH pathophysiology.

Investigation of traffic accidents involving seated pedestrians using a finite element simulation-based approach

Pedestrians who use wheelchairs (seated pedestrians) report 36% - 75% higher mortality rates than standing pedestrians in car-to-pedestrian collisions but the cause of this mortality is unknown. This is the first study to investigate the cause of seated pedestrian mortality in vehicle impacts using finite element simulations. In this study a manual wheelchair model was developed using geometry taken from publicly available CAD data, and was tested to meet ISO standards. The GHBMC 50th percentile male simplified occupant model was used as the seated pedestrian and the EuroNCAP family car and sports utility vehicle models were used as the impacting vehicles. The seated pedestrian was impacted by the two vehicles at three different locations on the vehicle and at 30 and 40 km/h. In 75% of the impacts the pedestrian was ejected from the wheelchair. In the rest of the impacts, the pedestrian and wheelchair were pinned to the vehicle and the pedestrian was not ejected. The underlying causes of seated pedestrian mortality in these impacts were head and brain injury. Life-threatening head injury risks (0.0% - 100%) were caused by the ground-pedestrian contact, and life-threatening brain injury risks (0.0 - 97.9%) were caused by the initial vehicle-wheelchair contact and ground-pedestrian contact. Thoracic and abdominal compression reported no risks of life-threatening injuries, but may do so in faster impacts or with different wheelchair designs. Protective equipment such as the wheelchair seatbelt or personal airbag may be useful in reducing injury risks but future research is required to investigate their efficacy.

The brain in pediatric critical care: unique aspects of assessment, monitoring, investigations, and follow-up.

As survival after pediatric intensive care unit (PICU) admission has improved over recent years, a key focus now is the reduction of morbidities and optimization of quality of life for survivors. Neurologic disorders and direct brain injuries are the reason for 11-16% of admissions to PICU. In addition, many critically ill children are at heightened risk of brain injury and neurodevelopmental difficulties affecting later life, e.g., complex heart disease and premature birth. Hence, assessment, monitoring and protection of the brain, using fundamental principles of neurocritical care, are crucial to the practice of pediatric intensive care medicine. The assessment of brain function, necessary to direct appropriate care, is uniquely challenging amongst children admitted to the PICU. Challenges in assessment arise in children who are unstable, or pharmacologically sedated and muscle relaxed, or who have premorbid abnormality in development. Moreover, the heterogeneity of diseases and ages in PICU patients, means that high caliber evidence is harder to accrue than in adult practice, nonetheless, great progress has been made over recent years. In this 'state of the art' paper about critically ill children, we discuss (1) patient types at risk of brain injury, (2) new standardized clinical assessment tools for age-appropriate, clinical evaluation of brain function, (3) latest evidence related to cranial imaging, non-invasive and invasive monitoring of the brain, (4) the concept of childhood 'post intensive are syndrome' and approaches for neurodevelopmental follow-up. Better understanding of these concepts is vital for taking PICU survivorship to the next level.