Pediatric Brain Injury Patients Research Articles

Management of severe traumatic brain injury in pediatric patients: an evidence-based approach.

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. The decision-making process in the management of severe TBI must be based on the best available evidence to minimize the occurrence of secondary brain injuries. However, healthcare approaches to managing TBI patients exhibit considerable variation. Over an 18-month period, a multidisciplinary panel consisting of medical doctors, physiotherapists, nutritional therapists, and nurses performed a comprehensive review on various subtopics concerning TBI. The panel identified primary questions to be addressed using the Population, Intervention, Control, and Outcome (PICO) format and applied the Evidence to Decision (EtD) framework criteria for evaluating interventions. Subsequently, the panel formulated recommendations for the management of severe TBI in children. Fourteen evidence-based recommendations have been devised for the management of severe TBI in children, covering nine topics, including imaging studies, neuromonitoring, prophylactic anticonvulsant use, hyperosmolar therapy, sedation and analgesia, mechanical ventilation strategies, nutritional therapy, blood transfusion, and decompressive craniectomy. For each topic, the panel provided clinical recommendations and identified research priorities. This review offers evidence-based strategies aimed to guide practitioners in the care of children who suffer from severe TBI.

Post cardiotomy extracorporeal membrane oxygenation in pediatric patients: Results and neurodevelopmental outcomes.

The increasing complexity of congenital cardiac surgery has led to greater utilization of extracorporeal membrane oxygenation (ECMO) support for children post-surgery. This study aims to identify risk factors for mortality and brain injury in pediatric patients requiring post-cardiotomy ECMO and to evaluate their neurological outcomes. This retrospective study includes pediatric patients with congenital heart diseases who required ECMO after surgery. Risk factors for in-hospital mortality and brain injury were assessed. Neurodevelopmental status was determined using the Pediatric Cerebral Performance Category (PCPC) Scale at discharge and during follow-up. Between October 2014 and May 2021, 2651 pediatric patients underwent cardiac surgery, with 90 (3.4%) requiring ECMO. The mean age was 0.6 years, ranging from 1 day to 13 years and 7 months. ECMO was implemented for 45 patients due to CPB weaning failure (NW-CPB), 24 due to postoperative low-cardiac output syndrome (LCOS), and 21 for extracorporeal cardiopulmonary resuscitation (E-CPR). ECMO weaning was achieved in 73 patients (81%), with an overall mortality rate of 36%. Pre-implant lactate levels (OR: 1.13, 95% CI: 1.03-1.25; p = 0.009) and peak bilirubin levels (OR: 1.04, 95% CI: 0.87-1.24; p = 0.69) were risk factors for in-hospital mortality. Survival rates were 79% for LCOS, 60% for NW-CPB, and 48% for E-CPR. Brain injury incidence was 33%, with E-CPR being a significant risk factor (p = 0.006) and NW-CPB being protective (p = 0.001). Follow-up in November 2023 showed significant improvement in neurodevelopmental status (p < 0.001). Elevated pre-implant lactate and elevated bilirubin levels during ECMO are major risk factors for mortality. E-CPR is the primary risk factor for brain injury. Follow-up revealed significant improvements in neurodevelopmental outcomes.

Tics Temporally Associated with Mild Traumatic Brain Injury in Pediatric Patients: A Sui Generis Case Series

Traumatic brain injury (TBI) is a major public health concern in Canada, with falls, blows to the head, car accidents, and sports-related injuries being the leading causes. Post-traumatic movement disorders, such as tics, can occur after a TBI, but their association with mild TBIs has been less explored. This manuscript presents two pediatric cases of de novo tics following mild TBIs, shedding light on this unique phenomenon. Possible mechanisms linking mild TBI and tics, such as genetic predisposition and stress-induced activation of the hypothalamic-pituitary-adrenal axis, are discussed. This paper emphasizes the importance of recognizing tics as a potential consequence of mild TBIs in children, and underscores the need for further research to shed light on the mechanism involved.

The usefulness of S100ß protein and fractalkin in predicting traumatic brain injury in pediatric patients with minor head trauma

Aims: In this study it was aimed to demonstrate the effectiveness of S100B protein levels which are biomarkers related to central nervous system, and fractalkin levels, which are known to play a role in inflammation processes in prediction trauma induced brain damage. Methods: Patient aged 2 to 18 years who came to the emergency department due to minor head trauma and underwent brain ct were included in our study. It was investigated whether there was a relationship between the two groups, according to the causes of trauma, symptoms at presentation and the level of serum s100b and FCN according to the lesions detected in CCT. Results: The other symptoms including Vomiting, retrograde amnesia, loss of consciousness, confusion, post traumatic amnesia is significantly higher in patients with brain lesions (p&lt;0,05). Patients with lesions on BCT have significantly low Glassgow coma score. (p&lt;0,05). Patients with lesions on BCT have a significantly high S100B and FKN levels. (p&lt;0,05). S100B area under the curve (CUA) 0.700 sensivity is 55%, spesificity is 87.5%. FKN CUA 0,785, sensitivity is 62.5% specifisity is 85%. Conclusions: As a result, the child patients with BCT lesions from minor cranial trauma levels for S100B and FKN levels are significantly higher and can be a criteria for BCT usage in emergency medicine.

Use of donepezil for neurocognitive recovery after brain injury in adult and pediatric populations: a scoping review.

There are few pharmacologic options for the treatment of cognitive deficits associated with traumatic brain injury in pediatric patients. Acetylcholinesterase inhibitors such as donepezil have been evaluated in adult patients after traumatic brain injury, but relatively less is known about the effect in pediatric populations. The goal of this review is to identify knowledge gaps in the efficacy and safety of acetylcholinesterase inhibitors as a potential adjuvant treatment for neurocognitive decline in pediatric patients with traumatic brain injury. Investigators queried PubMed to identify literature published from database inception through June 2023 describing the use of donepezil in young adult traumatic brain injury and pediatric patients with predefined conditions. Based on preselected search criteria, 340 unique papers were selected for title and abstract screening. Thirty-two records were reviewed in full after eliminating preclinical studies and papers outside the scope of the project. In adult traumatic brain injury, we review results from 14 papers detailing 227 subjects where evidence suggests donepezil is well tolerated and shows both objective and patient-reported efficacy for reducing cognitive impairment. In children, 3 papers report on 5 children recovering from traumatic brain injury, showing limited efficacy. An additional 15 pediatric studies conducted in populations at risk for cognitive dysfunction provide a broader look at safety and efficacy in 210 patients in the pediatric age group. Given its promise for efficacy in adults with traumatic brain injury and tolerability in pediatric patients, we believe further study of donepezil for children and adolescents with traumatic brain injury is warranted.

Serum Markers of Brain Injury in Pediatric Patients with Congenital Heart Defects Undergoing Cardiac Surgery: Diagnostic and Prognostic Role.

Introduction: The objectives of this study were to assess the role of neuromarkers like glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF), protein S100 (pS100), and neuron-specific enolase (NSE) as diagnostic markers of acute brain injury and also as prognostic markers for short-term neurodevelopmental impairment. Methods: Pediatric patients with congenital heart defects (CHDs) undergoing elective cardiac surgery were included. Neurodevelopmental functioning was assessed preoperatively and 4-6 months postoperatively using the Denver Developmental Screening Test II. Blood samples were collected preoperatively and postoperatively. During surgery, regional cerebral tissue oxygen saturation was monitored using near-infrared spectroscopy (NIRS). Results: Forty-two patients were enrolled and dichotomized into cyanotic and non-cyanotic groups based on peripheric oxygen saturation. Nineteen patients (65.5%) had abnormal developmental scores in the non-cyanotic group and eleven (84.6%) in the cyanotic group. A good diagnostic model was observed between NIRS values and GFAP in the cyanotic CHD group (AUC = 0.7). A good predicting model was observed with GFAP and developmental scores in the cyanotic CHD group (AUC = 0.667). A correlation was found between NSE and developmental quotient scores (r = 0.09, p = 0.046). Conclusions: From all four neuromarkers studied, only GFAP was demonstrated to be a good diagnostic and prognostic factor in cyanotic CHD patients. NSE had only prognostic value.

Glial fibrillary acidic protein as a serum neuromarker of brain injury in pediatric patients with congenital heart defects undergoing cardiac surgery

Abstract Objective: The aim of this study was to assess glial fibrillary acidic protein (GFAP) as a marker of short-term neurodevelopmental delay in pediatric patients with congenital defects (CHD) after cardiovascular surgical intervention. Methods: Included patients were screened by Denver Developmental Screening Test II scale a few days before and then at 4 to 6 months after the surgical intervention. Blood samples were collected preoperatory and at 24 hours after surgery; GFAP levels were assessed by enzyme-linked immunosorbent assay using commercial kit form BioVendor. Results: Forty children were enrolled and dichotomized into two groups based on peripheric oxygen saturation: cyanotic (&lt;95%) and non-cyanotic (&gt;=95%) group. 63% from our population had an abnormal neurodevelopmental outcome. Significant differences between groups were found in language domain scores preoperatory (p=0.03) and in fine motor domain postoperatory (p=0.03). In the postoperatory period, GFAP had significantly higher values (p=0.0248) in the cyanotic CHD group. Association between GFAP and NIRS were analyzed and significant differences were found in both groups with a good predicting model in the non-cyanotic CHD group (aria under curve of 0.7 for receiver operative characteristic). Higher GFAP levels from the postoperatory period correlated with neurodevelopmental impairment (mean value of: 0.66 ± 0.02ng/ml in those with good neurodevelopmental score, 0.69 ± 0.02ng/ml in those with low neurodevelopmental score, p=0.01). Conclusions: GFAP could be a reliable neuromarker in identifying early acute brain injury documented by NIRS monitorization during perioperatory period and it also could identify short term neurodevelopmental impairment documented by lower neurodevelopmental scores.

Increased Use of Hyperosmolar Therapy for Suspected Clinically Apparent Brain Injury in Pediatric Patients with Diabetic Ketoacidosis during the Peak of the COVID-19 Pandemic.

The incidence of pediatric diabetic ketoacidosis (DKA) increased during the peak of the COVID-19 pandemic. The objective of this study was to investigate whether rates of hyperosmolar therapy administration for suspected clinically apparent brain injury (CABI) complicating DKA also increased during this period as compared to the three years immediately preceding the pandemic and to compare the characteristics of patients with suspected CABI before the pandemic, patients with suspected CABI during the peak of the pandemic, and those with DKA but without suspected CABI during the pandemic. Patients aged ≤18 years presenting with DKA before (March 11, 2017-March 10, 2020) and during the peak of the pandemic (March 11, 2020-March 10, 2021) were identified through a rigorous search of two databases. Predefined criteria were used to diagnose suspected CABI. Biochemical, clinical, and sociodemographic data were collected from a comprehensive review of the electronic medical record. The proportion of patients with DKA who received hyperosmolar therapy was significantly higher (P = 0.014) during the pandemic compared to the prepandemic period; however, this was only significant among patients with newly diagnosed diabetes. Both groups with suspected CABI had more severe acidosis, lower Glasgow Coma Scale scores, and longer hospital admissions (P< 0.001 for all) than cases without suspected CABI. During the pandemic, the blood urea nitrogen concentration was significantly higher in patients with suspected CABI than those without suspected CABI, suggesting they were more severely dehydrated. The clinical, biochemical, and sociodemographic characteristics of patients with suspected CABI were indistinguishable before and during the pandemic. In conclusion, administration of hyperosmolar therapy for suspected CABI was more common during the peak of the COVID-19 pandemic, possibly a result of delayed presentation, highlighting the need for increased awareness and early recognition of the signs and symptoms of diabetes and DKA, especially during future surges of highly transmissible infections.

Traumatic brain injury in pediatric patients –Clinical manifestations and outcome

Background: Pediatric traumatic brain injury (TBI) is a global public health concern and is preventable, but there are no approved therapies to treat it definitely until date. Falls are the most frequent mode of injuries followed by road traffic accidents (RTA). Most of the TBIs have favorable outcome, though this is influenced by geographical, environmental, societal, and ethnic differences. Aims and Objectives: The aims of this study were to determine the several modes of injury, severity of injury, outcomes, and complications in the Eastern Indian population. Materials and Methods: Children-aged &lt;18 years suffering from TBI who were attended to in Bangur Institute of Neurosciences, Institute of Post-Graduate Medical Education and Research, Kolkata, were prospectively studied for 1 year. Detailed history, clinical examinations, assessment of pupillary status, and Glasgow Coma Scale (GCS) score was recorded. Severity of TBI was done based on GCS score for each case. Computed tomography (CT) scan of head without contrast was the initial mode of neuro imaging and findings were recorded diligently. Patients were treated conservatively and surgically as required. Outcome was assessed in relation to age group, gender, initial GCS score, pupillary status, CT findings, intervention, and associated injuries. Simple statistical analysis was done. Results: Among the total 150 patients aged 1–18 years, most common mode of injury was fall in 56.66% followed by RTA in 23.33%, assault in 6.66%, and other modes such as sports, hit by object on head, and firearm injury in 13.33%. RTAs had a poor outcome in 14.29% and fall had a poor outcome in 14.12%. Poor outcome was associated with the highest (68%) being midline shift (MLS)&gt;3 mm and it was 12.77% with MLS of &lt;3 mm and it was 10.26% in patients with no MLS. It was noticed that chest, spinal, and multiple injuries were associated with poor outcome. Conclusion: The most important prognostic factors regarding pediatric TBI are GCS at presentation, pupillary status, associated injuries, and CT scan findings.

Management of Severe Traumatic Brain Injury in Pediatric Patients.

The optimal management of severe traumatic brain injury (TBI) in the pediatric population has not been well studied. There are a limited number of research articles studying the management of TBI in children. Given the prevalence of severe TBI in the pediatric population, it is crucial to develop a reference TBI management plan for this vulnerable population. In this review, we seek to delineate the differences between severe TBI management in adults and children. Additionally, we also discuss the known molecular pathogenesis of TBI. A better understanding of the pathophysiology of TBI will inform clinical management and development of therapeutics. Finally, we propose a clinical algorithm for the management and treatment of severe TBI in children using published data.

Impact of intracranial pressure monitoring on outcome of traumatic brain injury in pediatric patients: a 15-year single center experience and literature review

Impact of intracranial pressure monitoring on outcome of traumatic brain injury in pediatric patients: a 15-year single center experience and literature review

Promising candidate cerebrospinal fluid biomarkers of seizure disorder, infection, inflammation, tumor, and traumatic brain injury in pediatric patients.

Cerebrospinal fluid (CSF) is a dynamic metabolically active body fluid that has many important roles and is commonly analyzed in pediatric patients, mainly to diagnose central nervous system infection and inflammation disorders. CSF components have been extensively evaluated as biomarkers of neurological disorders in adult patients. Circulating microRNAs in CSF are a promising class of biomarkers for various neurological diseases. Due to the complexity of pediatric neurological disorders and difficulty in acquiring CSF samples from pediatric patients, there are challenges in developing CSF biomarkers of pediatric neurological disorders. This review aimed to provide an overview of novel CSF biomarkers of seizure disorders, infection, inflammation, tumor, traumatic brain injuries, intraventricular hemorrhage, and congenital hydrocephalus exclusively observed in pediatric patients.

Changes in NSE and S-100β during the perioperative period and effects on brain injury in infants with biliary atresia undergoing parent donor liver transplantation.

The present study aimed to investigate the effects of parental donor liver transplantation on the perioperative changes of serum calcium-binding protein β (S-100β) and neuron-specific enolase (NSE) levels, two markers of brain injury, and on postoperative cognitive function. The present study was a prospective observational study of infants with congenital biliary atresia who underwent selective liver transplantation in 2017 at Tianjin First Central Hospital (Tianjin, China). Blood samples were collected prior to, during and following surgery, and S-100β and NSE levels were measured using ELISA. The pediatric patients were assessed using the Bayley Scales of Infant Development 1 day prior to and 3 months after surgery. Additionally, the pediatric anesthesia emergence delirium scores were evaluated. The results demonstrated that serum NSE and S100β were increased during and after surgery compared with prior to surgery (P<0.05). Furthermore, serum S-100β and NSE levels peaked 1 h after the neohepatic phase compared with prior to surgery (P<0.05). Compared with 1 day before surgery, mental development index (MDI) and psychomotor development index (PDI) were decreased 3 months after surgery (MDI, 87.7±8.4 vs. 84.5±8.5, P=0.015; PDI, 82.9±8.7 vs. 79.6±8.8, P=0.016). In conclusion, parental donor liver transplantation may cause a certain degree of brain injury in pediatric patients with end-stage liver disease, as revealed by increased serum NSE and S100β levels.

Neural Networks to Predict Radiographic Brain Injury in Pediatric Patients Treated with Extracorporeal Membrane Oxygenation.

Brain injury is a significant source of morbidity and mortality for pediatric patients treated with Extracorporeal Membrane Oxygenation (ECMO). Our objective was to utilize neural networks to predict radiographic evidence of brain injury in pediatric ECMO-supported patients and identify specific variables that can be explored for future research. Data from 174 ECMO-supported patients were collected up to 24 h prior to, and for the duration of, the ECMO course. Thirty-five variables were collected, including physiological data, markers of end-organ perfusion, acid-base homeostasis, vasoactive infusions, markers of coagulation, and ECMO-machine factors. The primary outcome was the presence of radiologic evidence of moderate to severe brain injury as established by brain CT or MRI. This information was analyzed by a neural network, and results were compared to a logistic regression model as well as clinician judgement. The neural network model was able to predict brain injury with an Area Under the Curve (AUC) of 0.76, 73% sensitivity, and 80% specificity. Logistic regression had 62% sensitivity and 61% specificity. Clinician judgment had 39% sensitivity and 69% specificity. Sequential feature group masking demonstrated a relatively greater contribution of physiological data and minor contribution of coagulation factors to the model's performance. These findings lay the foundation for further areas of research directions.

Traumatic Pediatric Extradural Hematoma: An Institutional Study of 228 Patients in Tertiary Care Center

Background: Extradural hematoma (EDH) is one of the most common causes of mortality and morbidity after traumatic brain injury in pediatric patients. Early surgical intervention in these patients produces excellent results. Objective: We reviewed surgical experience at our center, examining and presenting symptomatology and outcome analysis. Materials and Methods: A retrospective study of 228 pediatric patients of EDH from July 2007 to August 2017 was performed. Patients were evaluated in terms of demographic profile, clinical features, pupillary size and reaction, computed tomography findings, operative measures, and several other parameters. Neurological status was assessed using motor component (M) of Glasgow Coma Scale score. Best motor response was considered as a criterion to classify severity of traumatic brain injury and for the assessment of outcome. Results: Most of the patients were in the age group of 13–18 years (n = 122, 53.5%). Majority of them were male (n = 182, 79.8%). The commonest mode of injury was fall from height (n = 116, 50.9%) followed by road traffic accident (n = 92, 40.4%). Most common site of hematoma was frontal region (n = 66, 28.9%) followed by parietal region (n = 54, 23.7%). The volume of hematoma was between 30 and 50 mL in majority of the patients (n = 186, 81.6%), and most of the patients had a motor responses of M5 (n = 88, 38.6%) and M6 (n = 108, 47.4%). The association between hematoma site and volume was not significant (χ² = 5.910, p = 0.749), whereas statistically significant association was noted between volume of hematoma and motor response (χ² = 93.468, p ≤ 0.001), volume and age (χ² = 7.380, p ≤ 0.05), and volume to time between trauma and surgery (χ² = 8.469, p ≤ 0.05). Maximum mortality was in patients of low motor (M1–M3) response and who were operated 24 h after injury. Conclusion: Mortality in patients of EDH can be significantly reduced with gratifying results if operated early. Best motor response at presentation, pupillary abnormalities, time between injury to surgery, and location of hematoma have been identified as the important factors determining outcome in patients of EDH.

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

The purpose of this work is to identify and synthesize research produced since the second edition of these Guidelines was published and incorporate new results into revised evidence-based recommendations for the treatment of severe traumatic brain injury in pediatric patients. This document provides an overview of our process, lists the new research added, and includes the revised recommendations. Recommendations are only provided when there is supporting evidence. This update includes 22 recommendations, 9 are new or revised from previous editions. New recommendations on neuroimaging, hyperosmolar therapy, analgesics and sedatives, seizure prophylaxis, temperature control/hypothermia, and nutrition are provided. None are level I, 3 are level II, and 19 are level III. The Clinical Investigators responsible for these Guidelines also created a companion algorithm that supplements the recommendations with expert consensus where evidence is not available and organizes possible interventions into first and second tier utilization. The complete guideline document and supplemental appendices are available electronically (https://doi.org/10.1097/PCC.0000000000001735). The online documents contain summaries and evaluations of all the studies considered, including those from prior editions, and more detailed information on our methodology. New level II and level III evidence-based recommendations and an algorithm provide additional guidance for the development of local protocols to treat pediatric patients with severe traumatic brain injury. Our intention is to identify and institute a sustainable process to update these Guidelines as new evidence becomes available.

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

The purpose of this work is to identify and synthesize research produced since the second edition of these Guidelines was published and incorporate new results into revised evidence-based recommendations for the treatment of severe traumatic brain injury in pediatric patients. This document provides an overview of our process, lists the new research added, and includes the revised recommendations. Recommendations are only provided when there is supporting evidence. This update includes 22 recommendations, nine are new or revised from previous editions. New recommendations on neuroimaging, hyperosmolar therapy, analgesics and sedatives, seizure prophylaxis, temperature control/hypothermia, and nutrition are provided. None are level I, three are level II, and 19 are level III. The Clinical Investigators responsible for these Guidelines also created a companion algorithm that supplements the recommendations with expert consensus where evidence is not available and organizes possible interventions into first and second tier utilization. The purpose of publishing the algorithm as a separate document is to provide guidance for clinicians while maintaining a clear distinction between what is evidence based and what is consensus based. This approach allows, and is intended to encourage, continued creativity in treatment and research where evidence is lacking. Additionally, it allows for the use of the evidence-based recommendations as the foundation for other pathways, protocols, or algorithms specific to different organizations or environments. The complete guideline document and supplemental appendices are available electronically from this journal. These documents contain summaries and evaluations of all the studies considered, including those from prior editions, and more detailed information on our methodology. New level II and level III evidence-based recommendations and an algorithm provide additional guidance for the development of local protocols to treat pediatric patients with severe traumatic brain injury. Our intention is to identify and institute a sustainable process to update these Guidelines as new evidence becomes available.

Efficacy of a novel eye tracking system to evaluate mild traumatic brain injury in pediatric patients

Efficacy of a novel eye tracking system to evaluate mild traumatic brain injury in pediatric patients

Clinical features and biomarkers of concussion and mild traumatic brain injury in pediatric patients.

There has been increasing awareness of the incidence and potential long-term consequences of mild traumatic brain injury (mTBI) in children and young adults. While parents, school systems, and athletic programs are clamoring for evidence-based guidelines, the field remains primitive in understanding the factors resulting in a spectrum of individual outcomes, most of which are complete, but some of which are not. In this article, we discuss the definition, epidemiology, clinical presentation, course, and outcomes of mTBI, with a focus on the pediatric population as the context for reviewing the mechanisms and pathophysiology mediating, and biomarkers reflective of, more significant concussion-induced brain injury. Our goal is to present a general overview of the features of mTBI in the pediatric population in order to provide a conceptual model for pediatricians and pediatric subspecialists. This model emphasizes the importance of establishing actionable, noninvasive biomarkers that are reflective of brain injury and that may identify those pediatric patients who can benefit from earlier and more aggressive interventions. We will focus on the specific features of mTBI in pediatric patients; although given the relative lack of research in the pediatric population, we will also extrapolate from research on adults.

Abnormalities of the Attentional Network Following Traumatic Brain Injury in Pediatric Patients: A fMRI Study (S42.002)

Abnormalities of the Attentional Network Following Traumatic Brain Injury in Pediatric Patients: A fMRI Study (S42.002)