Traumatic Brain Injury In Infants Research Articles

Pathomechanism of infantile traumatic brain injury with a biphasic clinical course and late reduced diffusion evaluated by MR spectroscopy

BackgroundInfantile traumatic brain injury (TBI) with a biphasic clinical course and late reduced diffusion (TBIRD) has recently been reported as a distinct type of TBI in infancy. However, the pathological and prognostic factors of TBIRD remain unknown. We aimed to compare patients with and without TBIRD and evaluate the pathomechanism of TBIRD using magnetic resonance spectroscopy (MRS). MethodsTen Japanese patients with TBI were admitted to our hospital and underwent MRS between September 2015 and September 2022 (age range, 3–15 months; median age, 8.5 months). TBIRD was diagnosed in six patients. MRS data were compared among patients with TBIRD, patients without TBIRD, and controls. Neurological prognosis was classified into grades 1 (normal) to 3 (severe). ResultsIn patients with TBIRD, MRS revealed an increase in the glutamine (Gln) level on days 3–29, which subsequently became close to normal. The degree of Gln elevation in the non-TBIRD group was smaller (117–158 % of controls) than that in the TBIRD group (210–337 %) within 14 days. MRS in the TBIRD group showed decreased N-acetyl aspartate (NAA) concentrations. The degree of NAA decrease was more prominent in grade 3 than in grades 1 and 2. NAA levels in the non-TBIRD group were almost normal. ConclusionsPatients with TBI and markedly elevated Gln levels on MRS may develop TBIRD. Neuro-excitotoxicity is a possible pathological mechanism of TBIRD. Decreased NAA levels may be useful for predicting the prognosis of patients with TBIRD.

Developmental Outcomes of Traumatic Brain Injury in Infants and Children: A Prospective Study

Abstract Background Traumatic brain injury (TBI) in children is a significant health burden worldwide. Children aged 0 to 4 years have the highest incidence of TBI among the non-elderly. These children suffer from long term neurological deficits that compromise their quality of life and daily living activities. Objective To determine the developmental outcomes of infants and children with TBI. Subjects and Methods A prospective descriptive study on infants and children with TBI was conducted. Developmental outcomes by Age and Stage Questionnaire 3rd edition (ASQ-3) was assessed twice; once at hospital discharge and another time 3 months later. Further, Bayley scales of infants and toddlers’ development III was assessed only once in the second visit. Results at discharge and follow up were compared and correlated. Results Eighty -five patients were included in the study with 63.5% were males and the median age was 24(12-34) months, range (1- 42 months). There were statistically significant difference between ASQ-3 at discharge and follow up which was higher at follow up than at discharge indicating better developmental outcomes(P < 0.001 for all aspects). Comparison between ASQ-3 (problem solving) and Bayley Scale (cognitive) at follow up shows that there was no statistically significant difference between them with kappa agreement and 95% CI of 0.527 (0.218–0.837). Also, comparison between ASQ-3 (motor) at follow-up and Bayley Scale (motor)at follow up shows that there was no statistically significant difference between them with kappa agreement and 95% CI of 0.285 (0.001 - 0.569). Also, comparison between ASQ-3 (communication) and Bayley Scale (language) at follow up shows that there was no statistically significant difference between them with kappa agreement and 95% CI 0.501 (0.235 - 0.766). this means that both tests were comparable Conclusions ASQ-3 can be used as a screening tool for infants and children after TBI before referral to Bayley scale. Developmental milestones improved at follow up in most infants and children after TBI.

Traumatic brain injury in infants and little children (a literature review)

Traumatic brain injury in infants and little children (a literature review)

Abusive head trauma in infants: An observational single centre study comparing developmental and functional outcome between 18 months and 5 years

BackgroundAbusive head trauma (AHT) is a major cause of traumatic brain injury in infancy. This exploratory study compared standardized developmental assessment versus functional outcome assessment between 18 months and 5 years of age following AHT in infancy. MethodsObservational cross-sectional study after surviving AHT in infancy. Seventeen children between 18 months and 5 years of age underwent clinical examination, developmental assessment using the Schedule of Growing Skills II (SGS II) and functional assessment using the Glasgow Outcome Scale-Extended Pediatric Revision (GOS-E Peds). Additional clinical information was extracted from medical records. ResultsAge at assessment ranged from 19 to 53 months (median 26 months). Most (n = 14) were delayed in at least 1 domain, even without neurological or visual impairment or visible cortical injury on neuroimaging, including 8 children with favourable GOS-E Peds scores. The most affected domain was hearing and language. Delay in the manipulative domain (n = 6) was associated with visual and/or neurological impairment and greater severity of delay across multiple domains. Eleven (64.7 %) had GOS-E Peds scores indicating good recovery, with positive correlation between GOS-Peds scores and number of domains delayed (r = 0.805, p < 0.05). ConclusionThe SGS-II detects behavioural and cognitive deficits not picked up by the GOS-E Peds. Combining both tools for assessment of AHT survivors under 5 years of age provides a comprehensive profile which addresses multiple domains of development and function, facilitating targeted intervention. Detection of developmental problems in the majority of survivors makes AHT prevention a public health priority.

Minor head trauma in infants — how accurate is cranial ultrasound performed by trained radiologists?

Correct management of infants after minor head trauma is crucial to minimize the risk to miss clinically important traumatic brain injury (ciTBI). Current practices typically involve CT or in-hospital surveillance. Cranial ultrasound (CUS) provides a radiation-free and fast alternative. This study examines the accuracy of radiologist-performed CUS to detect skull fracture (SF) and/or intracranial hemorrhage (ICH). An inconspicuous CUS followed by an uneventful clinical course would allow exclusion of ciTBI with a great certainty. This monocentric, retrospective, observational study analyzed CUS in infants (< 12 months) after minor head trauma at Bern University Children’s Hospital, between 7/2013 and 8/2020. The primary outcome was the sensitivity and specificity of CUS in detecting SF and/or ICH by comparison to the clinical course and to additional neuroimaging. Out of a total of 325 patients, 73% (n = 241) had a normal CUS, 17% (n = 54) were found with SF, and ICH was diagnosed in 2.2% patients (n = 7). Two patients needed neurosurgery and three patients deteriorated clinically during surveillance. Additional imaging was performed in 35 patients. The sensitivity of CUS was 93% ([0.83, 0.97] 95% CI) and the specificity 98% ([0.95, 0.99] 95% CI). All false-negative cases originated in missed SF without clinical deterioration; no ICH was missed. Conclusion: This study shows high accuracy of CUS in exclusion of SF and ICH, which can cause ciTBI. Therefore, CUS offers a reliable method of neuroimaging in infants after minor head trauma and gives reassurance to reduce the duration of in-hospital surveillance.What is Known:• Minor head trauma can cause clinically important traumatic brain injury in infants, and the management of these cases is a challenge for the treating physician. • Cranial ultrasound (CUS) is regularly used in neonatology, but its accuracy after head trauma in infants is controversial. What is New:• CUS performed by a trained radiologist can exclude findings related to clinically important traumatic brain injury (ciTBI) with high sensitivity and specificity. It therefore offers reassurance in the management of infants after minor head trauma.

Epileptic Seizures or not, that is the question: a case report

IntroductionPsychogenic nonepileptic seizures (PNES) consist of paroxysmal changes in responsiveness, movements, or behaviour that superficially resemble epileptic seizures.ObjectivesPresentation of a clinical case of a PNES in a patient with a diagnose of secondary epilepsy, illustrating the relevance of an adequate evaluation, differential diagnosis, and intervention.MethodsDescription of the clinical case, with brief literature review and discussion. A search was conducted on PubMed and other databases, using the MeSH terms “nonepileptic seizure”, and “epileptic seizure”.ResultsWe report the case of a 45-year-old female patient, brought to the emergency department because of tonic axial and limb nonsynchronous movements, closed eyes, long duration, with immediate awareness, no desaturation, tongue bite, facial flushing, dyspnoea or sphincter incontinency. She was medicated with clonazepam 1 mg and levetiracetam 1000 mg ev. TC-CE had no acute alteration. Bloodwork had no other major alteration except valproic acid below therapeutic levels (her usual medication, along with other antiepileptic drugs, antidepressant and antipsychotic). The antecedents of the patient: mild intellectual disability and an accidental traumatic brain injury in infancy, with secondary epilepsy. She was transferred to Psychiatry department. No electroencephalogram (EEG) was realized, because she had a recent one confirming PNES, and many other emergency observations with the diagnosis of PNES.ConclusionsThis clinical case showcases the diagnostic difficulties that clinicians face when there is an overlap in symptoms, emphasizing the need to combine patient history, witness reports, clinician observations, and ictal and interictal EEG to help distinguish these different clinical identities.DisclosureNo significant relationships.

Computed tomography of traumatic brain injury in infants and young children (a literature review)

Objective . To analyze recent studies related to the use of computed tomography in traumatic brain injury in young children. Results . Traumatic brain injury (TBI) is one of the most common causes of death and disability in children. Pediatric TBI has a number of characteristics different of adults. This is due to age-related anatomical and physiological differences depending on patient's physical condition and on problems with his/her neurological assessment. Young children demonstrate specific pathological reactions to TBI with clear concomitant neurological manifestations. The authors present an important information on current aspects of CT application for all types of isolated blunt TBI in children aged from birth to 3 years with consideration of age-appropriate characteristics and emergency condition. Although TBI mechanisms are similar in young children and adults, visual manifestations of head injury in children have their own specific features due to the developing brain and cranial vault. Radiologist's primary role is to identify and characterize the type and severity of head injury so as to assist the correct management of the patient. Using the information obtained from CT examination and knowing TBI mechanisms in infants and young children, a radiologist can play a key role both in diagnostics and in selection of effective care, thus improving clinical outcomes. Conclusion . Head CT with multifaceted and 3D reconstructions has now replaced X-ray examination of the skull in suspected TBI and has become the most important diagnostic technique in patients with TBI at emergency settings. Radiographs do not provide with additional diagnostic information and may be excluded from the examination, if CT with 3D reconstruction are planned to perform or has already been performed.

Neuroanesthesia Management in Pediatric with Traumatic Brain Injury in Emergency Operation

Background: Pediatric neuroanaesthesia is an exciting and challenging branch of anaesthesia. Because the anatomy and physiology of the neurological system of children are still immature, the management of neuroanaesthesia in children is different from that of adults, from hemodynamic control, selection of anaesthetic drugs used, to endotracheal intubation. Case: In this case report, we report a 1-month-old male infant, weighing 4.6 kg, with a diagnosis of acute on chronic SDH in the frontotemporoparietal region. Physical examination revealed a decrease in consciousness GCS E2V2M5, with a pulse of 157 times per minute, a respiratory rate of 48 times per minute and a 100% SpO2 with oxygen administration of 2 litres per minute through a nasal cannula. On examination of the airway, there was no gurgling, snoring, or hoarseness. The patient was hemodynamically stable during the 90-minute operation. Postoperatively the patient was admitted to the PICU. Conclusion: Anaesthesia treatment for traumatic brain injury in infants has unique problems that require knowledge of the anatomy and physiology of the pediatric brain.

The Infant Scalp Score: A Validated Tool to Stratify Risk of Traumatic Brain Injury in Infants With Isolated Scalp Hematoma.

The objective was to validate the previously derived Infant Scalp Score (ISS) that uses clinical signs in infants with isolated scalp hematoma (ISH) after head trauma to stratify risk for clinically important traumatic brain injury (ciTBI) or TBI on computed tomography (CT). Using the publicly available Pediatric Emergency Care Applied Research Network TBI data set, we selected infants≤1year with GCS 14 to 15 who had ISH (defined as hematoma without other signs/symptoms of TBI). CT scans were obtained at the treating physician's discretion. We calculated ISS based on age, hematoma size, and location (range= 0-8) for each patient and calculated the sensitivity and specificity of the score for ciTBI and TBI on CT across a range of ISS cut-points. We included 1,289 infants≤1year of whom 462 (36%) had CT performed. Twelve had ciTBI and 59 had TBI on CT. An ISS cutoff≥4 had sensitivity of 100% for ciTBI (95% confidence interval [CI]= 0.74 to 1.0) and TBI with specificity of 0.49 (95% CI= 0.46 to 0.51). An ISS cutoff of≥5 had a sensitivity of 100% for ciTBI (95% CI= 0.74 to 1.0) and specificity of 0.68 (95% CI= 0.66 to 0.71), but missed three infants with TBI on CT (none of whom required intervention). The receiver operating characteristic curves for clinical score to detect ciTBI and TBI had areas under the curve of 0.916 and 0.807, respectively. The ISS accurately stratified risk for ciTBI and TBI on CT in infants with ISH and is a useful tool to help guide clinical decision making.

Prognostic factors and profile in traumatic brain injury in the paediatric age

Traumatic brain injury (TBI) is a common cause of death and disability in the paediatric population, although the literature on the Spanish population is scarce. From the perspective of early vulnerability, recent research findings suggest that early brain injury has worse sequelae and a higher risk of impact. To analyse the intelligence profile, executive functions and behaviour, and examine the association between age at the time of the injury, severity of the TBI and environmental factors for cognitive and behavioural outcomes. Seventy-one participants with moderate to severe TBI, from 6 to 16 years of age, were assessed with measures of intelligence (intelligence quotient), executive functions and behaviour. Children with TBI are at increased risk of disability in all aspects of intelligence, executive functions and behaviour. Children who suffered a traumatic brain injury in infancy and the preschool period had more overall effects on intelligence quotient and some aspects of the executive functions. Socioeconomic and cultural factors are the best predictors for intelligence quotient and behaviour. These findings contribute to a better understanding of the sequelae of TBI in children, which will help in rehabilitation planning and re-adaptation to functional life.

Análise Parcial do Conhecimento Médico Acerca de Indicação de Tomografia Computadorizada no Trauma Crânio Encefálico Infantil

Traumatismo cranioencefálico (TCE) constitui-se de uma agressão de ordem traumática que acarreta lesão anatômica e comprometimento funcional do couro cabeludo, crânio, meninges, encéfalo ou seus vasos. A frequência do TCE infantil em estatísticas internacionais evidencia 7.400 mortes anuais. Diante disso, o estudo PECARN (Pediatric Emergency Care Applied Research Network) identificou crianças com TCE leve que não necessitariam de tomografia computadorizada (TC) de crânio, permitindo uma estratificação de risco adequada. Objetivo: Debater a respeito do conhecimento médico sobre os critérios para solicitação da TC no TCE da faixa etária pediátrica dos serviços de emergência no munícipio de Campos dos Goytacazes, Rio de Janeiro. Método: Trata-se de um estudo transversal, seguindo o algoritmo baseado no PECARN. Resultados: Alcançou-se um N amostral de 70 questionários. O tempo médio de exercício profissional foi de 15 anos entre as especialidades. Sessenta e um por cento demonstraram aplicar a escala de coma de Glasgow pediátrica. Em situações nas quais a decisão entre TC de crânio e observação hospitalar dependia do critério médico, cerca de 50% dos profissionais demonstraram-se favoráveis à radiação ionizante. Discussão: A realização excessiva de tomografia pode ocasionar, entre outros problemas, o risco aumentado de tumor cerebral e leucemias em crianças devendo sempre seu uso ponderado principalmente nos TCEs leves. Conclusão: O conhecimento entre os grupos dos médicos é heterogêneo, no entanto há uma tendência ao excesso de realização de TC de crânio na faixa etária pediátrica, corroborando com o impacto da radiação ionizante desnecessária em crianças.

Guidelines for the Management of Pediatric Severe Traumatic Brain Injury, Third Edition: Update of the Brain Trauma Foundation Guidelines.

Severe Traumatic Brain Injury in Infants, Children, and Adolescents in 2019: Some Overdue Progress, Many Remaining Questions, and Exciting Ongoing Work in the Field of Traumatic Brain Injury ResearchIn this Supplement to Pediatric Critical Care Medicine, we are pleased to present the Third Edition o

A Case of Evolutionary Hypopituitarism Following Traumatic Brain Injury in Infancy

The long-term clinical course of hypopituitarism resulting from traumatic brain injury in children is unclear. We here present a case involving a 31-year-old Japanese male with hypopituitarism caused by traumatic brain injury at the age of 5 months. His height velocity began to decrease around 3 years of age. At age 7, growth hormone and thyroid-stimulating hormone deficiencies were diagnosed. At age 10, hydrocortisone therapy was started, and testosterone enanthate therapy was needed at age 14. The secretion of anterior pituitary hormones gradually decreased. We should check endocrinological tests in patients with traumatic brain injury who have retarded growth.

Perioperative Care for Pediatric Patients With Penetrating Brain Injury: A Review.

Traumatic brain injury (TBI) continues to be the leading cause of death and acquired disability in young children and adolescents, due to blunt or penetrating trauma, the latter being less common but more lethal. Penetrating brain injury (PBI) has not been studied extensively, mainly reported as case reports or case series, due to the assumption that both types of brain injury have common pathophysiology and consequently common management. However, recommendations and guidelines for the management of PBI differ from those of blunt TBI in regards to neuroimaging, intracranial pressure (ICP) monitoring, and surgical management including those pertaining to vascular injury. PBI was one of the exclusion criteria in the second edition of guidelines for the acute medical management of severe TBI in infants, children, and adolescents that was published in 2012 (it is referred to as "pediatric guidelines" in this review). Many reviews of TBI do not differentiate between the mechanisms of injury. We present an overview of PBI, its presenting features, epidemiology, and causes as well as an analysis of case series and the conclusions that may be drawn from those and other studies. More clinical trials specific to penetrating head injuries in children, focusing mainly on pathophysiology and management, are needed. The term PBI is specific to penetrating injury only, whereas TBI, a more inclusive term, describes mainly, but not only, blunt injury.

Extended Erythropoietin Treatment Prevents Chronic Executive Functional and Microstructural Deficits Following Early Severe Traumatic Brain Injury in Rats

Survivors of infant traumatic brain injury (TBI) are prone to chronic neurological deficits that impose lifelong individual and societal burdens. Translation of novel interventions to clinical trials is hampered in part by the lack of truly representative preclinical tests of cognition and corresponding biomarkers of functional outcomes. To address this gap, the ability of a high-dose, extended, post-injury regimen of erythropoietin (EPO, 3000U/kg/dose × 6d) to prevent chronic cognitive and imaging deficits was tested in a postnatal day 12 (P12) controlled-cortical impact (CCI) model in rats, using touchscreen operant chambers and regional analysis of diffusion tensor imaging (DTI). Results indicate that EPO prevents functional injury and MRI injury after infant TBI. Specifically, subacute DTI at P30 revealed widespread microstructural damage that is prevented by EPO. Assessment of visual discrimination on a touchscreen operant chamber platform demonstrated that all groups can perform visual discrimination. However, CCI rats treated with vehicle failed to pass reversal learning, and perseverated, in contrast to sham and CCI-EPO rats. Chronic DTI at P90 showed EPO treatment prevented contralateral white matter and ipsilateral lateral prefrontal cortex damage. This DTI improvement correlated with cognitive performance. Taken together, extended EPO treatment restores executive function and prevents microstructural brain abnormalities in adult rats with cognitive deficits in a translational preclinical model of infant TBI. Sophisticated testing with touchscreen operant chambers and regional DTI analyses may expedite translation and effective yield of interventions from preclinical studies to clinical trials. Collectively, these data support the use of EPO in clinical trials for human infants with TBI.

Changes in event-related potential functional networks predict traumatic brain injury in piglets

BackgroundTraumatic brain injury is a leading cause of cognitive and behavioral deficits in children in the US each year. None of the current diagnostic tools, such as quantitative cognitive and balance tests, have been validated to identify mild traumatic brain injury in infants, adults and animals. In this preliminary study, we report a novel, quantitative tool that has the potential to quickly and reliably diagnose traumatic brain injury and which can track the state of the brain during recovery across multiple ages and species. MethodsUsing 32 scalp electrodes, we recorded involuntary auditory event-related potentials from 22 awake four-week-old piglets one day before and one, four, and seven days after two different injury types (diffuse and focal) or sham. From these recordings, we generated event-related potential functional networks and assessed whether the patterns of the observed changes in these networks could distinguish brain-injured piglets from non-injured. FindingsPiglet brains exhibited significant changes after injury, as evaluated by five network metrics. The injury prediction algorithm developed from our analysis of the changes in the event-related potentials functional networks ultimately produced a tool with 82% predictive accuracy. InterpretationThis novel approach is the first application of auditory event-related potential functional networks to the prediction of traumatic brain injury. The resulting tool is a robust, objective and predictive method that offers promise for detecting mild traumatic brain injury, in particular because collecting event-related potentials data is noninvasive and inexpensive.

Pediatric Traumatic Brain Injury: an Update on Management

This article reviews the pathophysiology, evaluation, and management of pediatric TBI, as well as highlights recent updates in the literature. Traumatic brain injury (TBI) is a leading cause of death and permanent disability worldwide, and its prevalence presents a significant public health concern. Since the second edition of the Guidelines for the Acute Medical Management of Severe Traumatic Brain Injury in Infants, Children, and Adolescents was released, several recent studies have broadened our understanding of pediatric TBI. While there remains a paucity of high-level evidence on which to base precise consensus guidelines for care in pediatric patients, recent studies have addressed therapeutic hypothermia, pharmacologic treatment of elevated intracranial pressure, and abusive head trauma. Understanding the pathophysiology and treatment strategies for pediatric TBI, while preventing secondary insults, remains a cornerstone for improving patient outcomes.

Pre-clinical models in pediatric traumatic brain injury-challenges and lessons learned.

Despite the enormity of the problem and the lack of new therapies, research in the pre-clinical arena specifically using pediatric traumatic brain injury (TBI) models is limited. In this review, some of the key models addressing both the age spectrum of pediatric TBI and its unique injury mechanisms will be highlighted. Four topics will be addressed, namely, (1) unique facets of the developing brain important to TBI model development, (2) a description of some of the most commonly used pre-clinical models of severe pediatric TBI including work in both rodents and large animals, (3) a description of the pediatric models of mild TBI and repetitive mild TBI that are relatively new, and finally (4) a discussion of challenges, gaps, and potential future directions to further advance work in pediatric TBI models. This narrative review on the topic of pediatric TBI models was based on review of PUBMED/Medline along with a synthesis of information on key factors in pre-clinical and clinical developmental brain injury that influence TBI modeling. In the contemporary literature, six types of models have been used in rats including weight drop, fluid percussion injury (FPI), impact acceleration, controlled cortical impact (CCI), mechanical shaking, and closed head modifications of CCI. In mice, studies are largely restricted to CCI. In large animals, FPI and rotational injury have been used in piglets and shake injury has also been used in lambs. Most of the studies have been in severe injury models, although more recently, studies have begun to explore mild and repetitive mild injuries to study concussion. Given the emerging importance of TBI in infants and children, the morbidity and mortality that is produced, along with its purported link to the development of chronic neurodegenerative diseases, studies in these models merit greater systematic investigations along with consortium-type approaches and long-term follow-up to translate new therapies to the bedside.

Erythropoietin Reverses Cognitive Deficits Following Infantile Traumatic Brain Injury: A Translational Touchscreen Investigation

Traumatic brain injury (TBI) is a leading cause of death and severe morbidity for infants who are born healthy. No targeted treatment currently exists to actively promote repair after early TBI, despite the high incidence of chronic, debilitating deficits. EPO is a neuro‐reparative agent with multiple mechanisms of action that may benefit infants who suffer TBI. TBI in infants increases EPO receptor expression on neural cells, and extended EPO dosing reduces neuroinflammation and enhances survival and maturation of oligodendrocytes and neurons after injury. Using a translatable preclinical model of infant TBI, we hypothesized that EPO would reverse deficits of cognition as observed on a touchscreen paradigm. Controlled cortical impact (CCI) was performed on postnatal day 12 (P12) rats of both sexes. Anesthetized rats underwent left parietal craniectomy and 0.6mm impact. On post‐injury day (pid) 1, injured rats were randomized to 6 doses of intraperitoneal erythropoietin (EPO) 3000U/kg/dose or vehicle (sterile saline) over pid 1–8. Similar to the Cambridge Neuropsychological Test Automated Battery (CANTAB) in humans, a touchscreen platform was applied to assess multiple cognitive domains. Adult rats were trained on a touchscreen operant platform by blinded investigators. Following successful training, rats performed visual discrimination (VD) and reversal tasks to assess executive function and cognitive flexibility (n=6–8/group, two way ANOVA with Bonferroni correction). Results indicate that Sham, CCI and CCI‐EPO rats are able to successfully perform VD with each group requiring a similar number of sessions to passing criteria and committing similar numbers of discrimination errors. However, when assessing reversal learning, only 57.1% of CCI animals successfully passed criteria compared to 100% of Sham and 83.3% of CCI animals treated with EPO. Notably, CCI animals committed significantly more errors and required more correction trials (1114±132) compared to Sham (730±95) and CCI‐EPO (652±61, p&lt;0.05 for all), concomitant with increased perseveration (all p&lt;0.05). Taken together, EPO treatment ameliorates deficits from TBI on a touchscreen platform, including error reduction and perseveration, and restores cognitive flexibility. EPO, administered in an extended post‐injury dosing paradigm congruent with its mechanisms of action, proved efficacious in reversing functional impairment after TBI in developing rats.Support or Funding InformationDedicated health research funds from the University of New Mexico, Genise Goldenson Foundation and Boston Children's Hospital.

Cerebrospinal Fluid NLRP3 is Increased After Severe Traumatic Brain Injury in Infants and Children.

Inflammasome-mediated neuroinflammation may cause secondary injury following traumatic brain injury (TBI) in children. The pattern recognition receptors NACHT domain-, Leucine-rich repeat-, and PYD-containing Protein 1 (NLRP1) and NLRP3 are essential components of their respective inflammasome complexes. We sought to investigate whether NLRP1 and/or NLRP3 abundance is altered in children with severe TBI. Cerebrospinal fluid (CSF) from children (n=34) with severe TBI (Glasgow coma scale score [GCS] ≤8) who had externalized ventricular drains (EVD) placed for routine care was evaluated for NLRP1 and NLRP3 at 0-24, 25-48, 49-72, and >72h post-TBI and was compared to infection-free controls that underwent lumbar puncture to rule out CNS infection (n=8). Patient age, sex, initial GCS, mechanism of injury, treatment with therapeutic hypothermia, and 6-month Glasgow outcome score were collected. CSF NLRP1 was undetectable in controls and detected in 2 TBI patients at only <24h post-TBI. CSF NLRP3 levels were increased in TBI patients compared with controls at all time points, p<0.001. TBI patients ≤4years of age had higher peak NLRP3 levels versus patients >4 (15.50 [3.65-25.71] vs. 3.04 [1.52-8.87] ng/mL, respectively; p=0.048). Controlling for initial GCS in multivariate analysis, peak NLRP3 >6.63ng/mL was independently associated with poor outcome at 6months. In the first report of NLRP1 and NLRP3 in childhood neurotrauma, we found that CSF NLRP3 is elevated in children with severe TBI and independently associated with younger age and poor outcome. Future studies correlating NLRP3 with other markers of inflammation and response to therapy are warranted.