New Functional Impairment After Hospital Discharge by Traumatic Brain Injury Mechanism in Younger Than 3 Years Old Admitted to the PICU in a Single Center Retrospective Study.

OBJECTIVES: Children who suffer traumatic brain injury (TBI) are at high risk of morbidity and mortality. We hypothesized that in patients with TBI, the abusive head trauma (AHT) mechanism vs. accidental TBI (aTBI) would be associated with higher frequency of new functional impairment between baseline and later follow-up. DESIGN: Retrospective single center cohort study. SETTING AND PATIENTS: Children younger than 3 years old admitted with TBI to the PICU at a level 1 trauma center between 2014 and 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient characteristics, TBI mechanism, and Functional Status Scale (FSS) scores at baseline, hospital discharge, short-term (median, 10 mo [interquartile range 3-12 mo]), and long-term (median, 4 yr [3-6 yr]) postdischarge were abstracted from the electronic health record. New impairment was defined as an increase in FSS greater than 1 from baseline. Patients who died were assigned the highest score (30). Multivariable logistic regression was performed to determine the association between TBI mechanism with new impairment. Over 6 years, there were 460 TBI children (170 AHT, 290 aTBI), of which 13 with AHT and four with aTBI died. Frequency of new impairment by follow-up interval, in AHT vs. aTBI patients, were as follows: hospital discharge (42/157 [27%] vs. 27/286 [9%]; p < 0.001), short-term (42/153 [27%] vs. 26/259 [10%]; p < 0.001), and long-term (32/114 [28%] vs. 18/178 [10%]; p < 0.001). Sensory, communication, and motor domains were worse in AHT patients at the short- and long-term timepoint. On multivariable analysis, AHT mechanism was associated with greater odds (odds ratio [95% CI]) of poor outcome (death and new impairment) at hospital discharge (4.4 [2.2-8.9]), short-term (2.7 [1.5-4.9]), and long-term timepoints (2.4 [1.2-4.8]; p < 0.05). CONCLUSIONS: In patients younger than 3 years old admitted to the PICU after TBI, the AHT mechanism-vs. aTBI-is associated with greater odds of poor outcome in the follow-up period through to ~5 years postdischarge. New impairment occurred in multiple domains and only AHT patients further declined in FSS over time.

Effectiveness of Fosphenytoin and Levetiracetam to Prevent Posttraumatic Seizures in Young Children with Accidental or Abusive Traumatic Brain Injury.

BACKGROUND: Seizures occur frequently in pediatric patients with traumatic brain injury (TBI), particularly abusive head trauma (AHT). There are limited data on the effectiveness of fosphenytoin and levetiracetam to prevent posttraumatic seizures. METHODS: We performed a retrospective single center cohort study of children < 3 years old admitted with mild [Glasgow Coma Scale (GCS) score 13-15], moderate (GCS 9-12), and severe (GCS 3-8) TBI at a level I trauma center from 2011 to 2021. Antiseizure medications were used at the discretion of the treating physicians. Nonparametric tests were used to compare antiseizure medication prophylaxis and TBI etiology. RESULTS: A total of 717 patients (263 with AHT, 454 with accidental TBI) were included, of whom 135 (19%) received fosphenytoin, 152 (21%) received levetiracetam, and 430 (60%) did not receive any seizure prophylaxis. Over the study period, the use of fosphenytoin prophylaxis decreased (R2 = 0.67, p = 0.004), whereas the use of levetiracetam increased (R2 = 0.51, p = 0.008). Additionally, the occurrence of early posttraumatic seizures decreased (R2 = 0.58, p = 0.006). Children with AHT were more likely to receive any seizure prophylaxis than those with accidental TBI (52% vs. 27%; p < 0.001) and were more likely to have ≥ 1 seizure during hospitalization (22% vs. 4%; p < 0.001). Among children who received seizure prophylaxis, those who received fosphenytoin had a higher occurrence of seizures than those who received levetiracetam (33% vs.18%; p = 0.004). After controlling for age, admission year, TBI mechanism, and severity of injury, we observed no differences in seizure occurrence between groups. CONCLUSIONS: In children < 3 years old with TBI, no differences were observed in occurrence of seizures between patients who received fosphenytoin and patients who received levetiracetam prophylaxis after controlling for patient factors including severity of injury. Levetiracetam may be an equally effective alternative to fosphenytoin for seizure prophylaxis for early posttraumatic seizure prevention in this age group.

Multiorgan Dysfunction Syndrome in Abusive and Accidental Pediatric Traumatic Brain Injury.

BACKGROUND: Abusive head trauma (AHT) is a mechanism of pediatric traumatic brain injury (TBI) with high morbidity and mortality. Multiorgan dysfunction syndrome (MODS), defined as organ dysfunction in two or more organ systems, is also associated with morbidity and mortality in critically ill children. Our objective was to compare the frequency of MODS and evaluate its association with outcome between AHT and accidental TBI (aTBI). METHODS: This was a single center, retrospective cohort study including children under 3 years old admitted to the pediatric intensive care unit with nonpenetrating TBI between 2014 and 2021. Presence or absence of MODS on days 1, 3, and 7 using the Pediatric Logistic Organ Dysfunction-2 score and new impairment status (Functional Status Scale score change > 1 compared with preinjury) at hospital discharge (HD), short-term timepoint, and long-term timepoint were abstracted from the electronic health record. Multiple logistic regression was performed to examine the association between MODS and TBI mechanism with new impairment status. RESULTS: Among 576 children, 215 (37%) had AHT and 361 (63%) had aTBI. More children with AHT had MODS on days 1 (34% vs. 23%, p = 0.003), 3 (28% vs. 6%, p < 0.001), and 7 (17% vs. 3%, p < 0.001) compared with those with aTBI. The most common organ failures were cardiovascular ([AHT] 66% vs. [aTBI] 66%, p = 0.997), neurologic (33% vs. 16%, p < 0.001), and respiratory (34% vs. 15%, p < 0.001). MODS was associated with new impairment in multivariable logistic regression at HD (odds ratio 19.1 [95% confidence interval 9.8-38.6, p < 0.001]), short-term discharge (7.4 [3.7-15.2, p < 0.001]), and long-term discharge (4.3 [2.0-9.4, p < 0.001])]. AHT was also associated with new impairment at HD (3.4 [1.6-7.3, p = 0.001]), short-term discharge (2.5 [1.3-4.7, p = 0.005]), and long-term discharge (2.1 [1.1-4.1, p = 0.036]). CONCLUSIONS: Abusive head trauma as a mechanism was associated with MODS following TBI. Both AHT mechanism and MODS were associated with new impairment at all time points.

The Likelihood of an Occult Fracture in Skeletal Surveys Obtained in Children More Than 2 Years Old With Concerns of Physical Abuse.

OBJECTIVES: Skeletal surveys are necessary in the evaluation for physical abuse in children less than 2 years old, but when to obtain a skeletal survey in older children is less clear. METHODS: A retrospective study of patients older than 2 years who underwent skeletal survey over a 3-year period after implementation of an electronic health record physical abuse order set was conducted. Data were analyzed using descriptive statistics and compared with data from a cohort before order set implementation. The radiation dose of a skeletal survey in a 5-year old was calculated using a previously published technique. RESULTS: There were 325 skeletal surveys, a marked increase in the rate of skeletal surveys compared with before order set implementation. Less than 2% (6/325) of skeletal surveys demonstrated an occult fracture. Of the 6 patients with occult fractures, 4 were physically abused; in each case, the diagnosis of abuse was evident before the skeletal survey. The other 2 patients fell from windows. The radiation exposure was 0.34 mSv. CONCLUSIONS: The rate of occult fractures on skeletal survey is significantly lower than previously reported. This is likely because our population included all children who underwent skeletal survey and not the subset referred to a child abuse pediatrician. In addition, our data demonstrate that in children older than 2 years, skeletal surveys are unlikely to assist in making a diagnosis of physical abuse. The radiation exposure in a 5-year-old is 70% greater than in an infant, but still a dose, which represents a negligible health risk.

Injuries Suggestive of Physical Abuse in Young Children With Subconjunctival Hemorrhages.

OBJECTIVE: The aim of this study was to compare the demographic characteristics, clinical presentations, medical evaluation, and injuries identified in a cohort of children with and without subconjunctival hemorrhage who were evaluated by a child abuse specialist. METHODS: This was a case-control study that used data from the ExSTRA (Examining Siblings to Recognize Abuse) research network. Subjects with a subconjunctival hemorrhage(s) were designated as cases. Four controls matched for age and participating center were included for each case. Descriptive statistics were used to compare cases and controls. RESULTS: Fifty of the 2890 subjects in the parent study had a subconjunctival hemorrhage(s) and were designated as cases. The cases had a median (interquartile range) age of 5.0 months (2.0-23.6 months). Two hundred controls were matched to the cases. There was no difference in the demographics, clinical characteristics, medical evaluation, or rate of occult injuries identified in cases and controls. Almost one-quarter of children with subconjunctival hemorrhages had no other external sign of trauma but had the same rate of occult injuries as children with bruises. CONCLUSIONS: These data suggest that subconjunctival hemorrhages are relatively rare among children undergoing evaluation by a child abuse specialist, but that they are often an indicator of occult injury. Even in the absence of other external signs of trauma, the presence of subconjunctival hemorrhages should prompt an age-appropriate evaluation for physical abuse.

Cervical Spine Imaging and Injuries in Young Children With Non-Motor Vehicle Crash-Associated Traumatic Brain Injury.

OBJECTIVES: The aim of this study was to evaluate cervical magnetic resonance imaging (MRI) and computed tomography (CT) practices and cervical spine injuries among young children with non-motor vehicle crash (MVC)-associated traumatic brain injury (TBI). METHODS: We performed a retrospective study of a stratified, systematic random sample of 328 children younger than 2 years with non-MVC-associated TBI at 4 urban children's hospitals from 2008 to 2012. We defined TBI etiology as accidental, indeterminate, or abuse. We reported the proportion, by etiology, who underwent cervical MRI or CT, and had cervical abnormalities identified. RESULTS: Of children with non-MVC-associated TBI, 39.4% had abusive head trauma (AHT), 52.2% had accidental TBI, and in 8.4% the etiology was indeterminate. Advanced cervical imaging (CT and/or MRI) was obtained in 19.1% of all children with TBI, with 9.3% undergoing MRI and 11.7% undergoing CT. Cervical MRI or CT was performed in 30.9% of children with AHT, in 11.7% of accidental TBI, and in 10.7% of indeterminate-cause TBI. Among children imaged by MRI or CT, abnormal cervical findings were found in 22.1%, including 31.3% of children with AHT, 7.1% of children with accidental TBI, and 0% of children with indeterminate-cause TBI. Children with more severe head injuries who underwent cervical imaging were more likely to have cervical injuries. CONCLUSIONS: Abusive head trauma victims appear to be at increased risk of cervical injuries. Prospective studies are needed to define the risk of cervical injury in children with TBI concerning for AHT and to inform development of imaging guidelines.

Identification of Abusive Head Trauma in High-Risk Infants: A Cost-Effectiveness Analysis.

OBJECTIVES: To evaluate the cost-effectiveness of abusive head trauma detection strategies in emergency department settings with and without rapid magnetic resonance imaging (rMRI) availability. STUDY DESIGN: A Markov decision model estimated outcomes in well-appearing infants with high-risk chief complaints. In an emergency department without rMRI, we considered 3 strategies: clinical judgment, universal head computed tomography (CT) scan, or the Pittsburgh Infant Brain Injury Score (PIBIS) with a CT scan. In an emergency department with rMRI for brain availability, we considered additional strategies: universal rMRI, universal rMRI with a CT scan, PIBIS with rMRI, and PIBIS with rMRI followed by a CT scan. Correct diagnosis eliminated future risk; missed abusive head trauma led to reinjury risk with associated poor outcomes. Cohorts were followed for 1 year from a healthcare perspective. One-way and probabilistic sensitivity analyses were performed. The main outcomes evaluated in this study were abusive head trauma correctly identified and incremental cost per quality-adjusted life-year. RESULTS: Without rMRI availability, PIBIS followed by a CT scan was the most cost-effective strategy. Results were sensitive to variation of CT scan-induced cancer parameters and abusive head trauma prevalence. When rMRI was available, universal rMRI followed by a confirmatory CT scan cost $25 791 to gain 1 additional quality-adjusted life-year compared with PIBIS followed by rMRI with a confirmatory CT scan. In both models, clinical judgement was less effective than alternative strategies. CONCLUSIONS: By applying CT scans to a more targeted population, PIBIS decreases radiation exposure and is more effective for the identification of abusive head trauma compared with clinical judgment. When rMRI is available, universal rMRI with a CT scan is more effective than PIBIS and is economically favorable.

The Presence of Anemia in Children with Abusive Head Trauma.

OBJECTIVES: To evaluate the incidence of anemia in patients with abusive head trauma (AHT), noninflicted traumatic brain injury (TBI), and physical abuse without AHT and the effect of anemia on outcome. STUDY DESIGN: In a retrospective, single-center cohort study, we included children under the age of 3 years diagnosed with either AHT (n = 75), noninflicted TBI (n = 77), or physical abuse without AHT (n = 60) between January 1, 2014, and December 31, 2016. Neuroimaging was prospectively analyzed by pediatric neuroradiologists. Primary outcome was anemia at hospital presentation. Secondary outcomes included unfavorable outcome at hospital discharge, defined as a Glasgow Outcome Scale between 1 and 3, and intracranial hemorrhage (ICH) volume. RESULTS: Patients with AHT had a higher rate of anemia on presentation (47.3%) vs noninflicted TBI (15.6%) and physical abuse without AHT (10%) (P < .001). Patients with AHT had larger ICH volumes (33.3 mL [10.1-76.4 mL] vs 1.5 mL [0.6-5.2 mL] ; P < .001) and greater ICH/total brain volume percentages than patients with noninflicted TBI (4.6% [1.4-8.2 %] vs 0.2% [0.1-0.7%]; P < .001). Anemia was associated with AHT (OR, 4.7; 95% CI, 2.2-10.2) and larger ICH/total brain volume percentage (OR, 1.1; 95% CI, 1.1-1.2) in univariate analysis. Unfavorable outcome at hospital discharge was associated with anemia (OR, 4.4; 95% CI, 1.6-12.6) in univariate analysis, but not after controlling for covariates. CONCLUSIONS: Patients with AHT were more likely to present to the hospital with anemia and increased traumatic ICH volume than patients with noninflicted TBI or physical abuse without AHT. Children with anemia and AHT may be at increased risk for an unfavorable outcome.

Implementation of a brain injury screen MRI for infants at risk for abusive head trauma.

BACKGROUND: Head computed tomography (CT) is the current standard of care for evaluating infants at high risk of abusive head trauma. OBJECTIVE: To both assess the feasibility of using a previously developed magnetic resonance imaging (MRI) brain injury screen (MRBRscreen) in the acute care setting in place of head CT to identify intracranial hemorrhage in high-risk infants and to compare the accuracy of a rapid imaging pulse sequence (single-shot T2 fast spin echo [ssT2FSE]) to a conventional pulse sequence (conventional T2 fast spin echo [conT2FSE]). MATERIALS AND METHODS: This was a quality improvement initiative to evaluate infants <12 months of age who were screened for intracranial hemorrhage using an MRBRscreen as part of clinical care. The MRBRscreen included axial conT2FSE, axial gradient recalled echo, coronal T1-weighted inversion recovery, axial diffusion-weighted image and an axial ssT2FSE. A comparison of ssT2FSE to conT2FSE with respect to lesion detection was also performed. RESULTS: Of 158 subjects, the MRBRscreen was able to be completed in 155 (98%); 9% (14/155) were abnormal. Ninety-four percent (137/145) of subjects underwent only an MRBRscreen and avoided both radiation from head CT and sedation from MRI. The axial ssT2FSE and conT2FSE results were congruent 99% of the time. CONCLUSION: An MRBRscreen in place of a head CT is feasible and potentially could decrease head CT use by more than 90% in this population. Using a rapid ssT2FSE in place of a conT2FSE can reduce total scan time without losing lesion detection. If an MRBRscreen is readily available, physicians' threshold to perform neuroimaging may be lowered and lead to earlier detection of abusive head trauma.

Classifying Injuries in Young Children as Abusive or Accidental: Reliability and Accuracy of an Expert Panel Approach.

OBJECTIVE: To assess interrater reliability and accuracy of an expert panel in classifying injuries of patients as abusive or accidental based on comprehensive case information. STUDY DESIGN: Data came from a prospective, observational, multicenter study investigating bruising characteristics of children younger than 4 years. We enrolled 2166 patients with broad ranges of illnesses and injuries presenting to one of 5 pediatric emergency departments in whom bruises were identified during examination. We collected comprehensive data regarding current and past injuries and illnesses, and provided deidentified, standardized case information to a 9-member multidisciplinary panel of experts with extensive experience in pediatric injury. Each panelist classified cases using a 5-level ordinal scale ranging from definite abuse to definite accident. Panelists also assessed whether report to child protective services (CPS) was warranted. We calculated reliability coefficients for likelihood of abuse and decision to report to CPS. RESULTS: The interrater reliability of the panelists was high. The Kendall coefficient (95% CI) for the likelihood of abuse was 0.89 (0.87, 0.91) and the kappa coefficient for the decision to report to CPS was 0.91 (0.87, 0.94). Reliability of pairs and subgroups of panelists were similarly high. A panel composite classification was nearly perfectly accurate in a subset of cases having definitive, corroborated injury status. CONCLUSIONS: A panel of experts with different backgrounds but common expertise in pediatric injury is a reliable and accurate criterion standard for classifying pediatric injuries as abusive or accidental in a sample of children presenting to a pediatric emergency department.

Effective Radiation Dose in a Skeletal Survey Performed for Suspected Child Abuse.

Effective dose of a skeletal survey in infants using digital radiography was estimated to be 0.2 mSv using Monte Carlo simulation. Radiation risk from this procedure is, therefore, low. Radiation concern should not be an overriding factor when deciding whether skeletal survey is needed in cases of possible physical abuse.

Principal components derived from CSF inflammatory profiles predict outcome in survivors after severe traumatic brain injury.

Studies have characterized absolute levels of multiple inflammatory markers as significant risk factors for poor outcomes after traumatic brain injury (TBI). However, inflammatory marker concentrations are highly inter-related, and production of one may result in the production or regulation of another. Therefore, a more comprehensive characterization of the inflammatory response post-TBI should consider relative levels of markers in the inflammatory pathway. We used principal component analysis (PCA) as a dimension-reduction technique to characterize the sets of markers that contribute independently to variability in cerebrospinal (CSF) inflammatory profiles after TBI. Using PCA results, we defined groups (or clusters) of individuals (n=111) with similar patterns of acute CSF inflammation that were then evaluated in the context of outcome and other relevant CSF and serum biomarkers collected days 0-3 and 4-5 post-injury. We identified four significant principal components (PC1-PC4) for CSF inflammation from days 0-3, and PC1 accounted for the greatest (31%) percentage of variance. PC1 was characterized by relatively higher CSF sICAM-1, sFAS, IL-10, IL-6, sVCAM-1, IL-5, and IL-8 levels. Cluster analysis then defined two distinct clusters, such that individuals in cluster 1 had highly positive PC1 scores and relatively higher levels of CSF cortisol, progesterone, estradiol, testosterone, brain derived neurotrophic factor (BDNF), and S100b; this group also had higher serum cortisol and lower serum BDNF. Multinomial logistic regression analyses showed that individuals in cluster 1 had a 10.9 times increased likelihood of GOS scores of 2/3 vs. 4/5 at 6 months compared to cluster 2, after controlling for covariates. Cluster group did not discriminate between mortality compared to GOS scores of 4/5 after controlling for age and other covariates. Cluster groupings also did not discriminate mortality or 12 month outcomes in multivariate models. PCA and cluster analysis establish that a subset of CSF inflammatory markers measured in days 0-3 post-TBI may distinguish individuals with poor 6-month outcome, and future studies should prospectively validate these findings. PCA of inflammatory mediators after TBI could aid in prognostication and in identifying patient subgroups for therapeutic interventions.

Development of a screening MRI for infants at risk for abusive head trauma.

BACKGROUND: Abusive head trauma (AHT) is an important cause of morbidity in infants. Identifying which well-appearing infants are at risk for AHT and need neuroimaging is challenging, and concern about radiation exposure limits the use of head CT. Availability of an MRI protocol that is highly sensitive for intracranial hemorrhage would allow for AHT screening of well-appearing infants without exposing them to radiation. OBJECTIVE: To develop a screening MRI protocol to identify intracranial hemorrhage in well-appearing infants at risk for AHT. MATERIALS AND METHODS: Infants enrolled in a parent study of well-appearing infants at increased risk for AHT were eligible for the current study if they underwent both head CT and conventional brain MRI. A derivation cohort of nine infants with AHT was used to identify sequences that provided the highest sensitivity for intracranial hemorrhage. A validation cohort of 78 infants including both controls with normal neuroimaging and cases with AHT was used to evaluate the accuracy of the selected sequences. RESULTS: Three pulse sequences - axial T2, axial gradient recalled echo (GRE) and coronal T1-W inversion recovery - were 100% sensitive for intracranial hemorrhage in the derivation cohort. The same sequences were 100% sensitive (25/25) and 83% specific (44/53) for intracranial hemorrhage in the validation cohort. CONCLUSION: A screening MRI protocol including axial T2, axial GRE and coronal T1-W inversion recovery sequences is highly sensitive for intracranial hemorrhage and may be useful as a screening tool to differentiate well-appearing infants at risk for AHT who should undergo head CT from those who can safely be discharged without head CT. Additional research is needed to evaluate the feasibility of this approach in clinical practice.

Serum D-dimer concentrations are increased after pediatric traumatic brain injury.

OBJECTIVE: To determine whether D-dimer would be increased in children with traumatic brain injury (TBI), specifically mild abusive head trauma. STUDY DESIGN: D-dimer was measured using multiplex bead technology in 195 children <4 years old (n = 93 controls without TBI, n = 102 cases with TBI) using previously collected serum. D-dimer was then measured prospectively in a clinical setting in 44 children (n = 24 controls, n = 20 cases). Receiver operator curves were generated for prospective data. RESULTS: In both the retrospective and prospective cohorts, median (25th-75th percentile) D-dimer was significantly higher in cases vs controls. A receiver operator curve demonstrated an area under the curve of 0.91 (95% CI 0.83-0.99) in the prospective cohort. At a cut-off of 0.59 µg/L, the sensitivity and specificity for identification of a case was 90% and 75%, respectively. CONCLUSIONS: Our data suggest that serum D-dimer may be able to be used to identify which young children at risk for abusive head trauma might benefit from a head computed tomography or other additional evaluation. Additional data are needed to better identify the clinical scenarios that may result in false positive or false negative D-dimer concentrations.

Assessing the accuracy of the International Classification of Diseases codes to identify abusive head trauma: a feasibility study.

OBJECTIVE: To assess the accuracy of an International Classification of Diseases (ICD) code-based operational case definition for abusive head trauma (AHT). METHODS: Subjects were children <5 years of age evaluated for AHT by a hospital-based Child Protection Team (CPT) at a tertiary care paediatric hospital with a completely electronic medical record (EMR) system. Subjects were designated as non-AHT traumatic brain injury (TBI) or AHT based on whether the CPT determined that the injuries were due to AHT. The sensitivity and specificity of the ICD-based definition were calculated. RESULTS: There were 223 children evaluated for AHT: 117 AHT and 106 non-AHT TBI. The sensitivity and specificity of the ICD-based operational case definition were 92% (95% CI 85.8 to 96.2) and 96% (95% CI 92.3 to 99.7), respectively. All errors in sensitivity and three of the four specificity errors were due to coder error; one specificity error was a physician error. CONCLUSIONS: In a paediatric tertiary care hospital with an EMR system, the accuracy of an ICD-based case definition for AHT was high. Additional studies are needed to assess the accuracy of this definition in all types of hospitals in which children with AHT are cared for.

Minor and repetitive head injury.

Traumatic brain injury (TBI) is the leading cause of death and disability in the young, active population and expected to be the third leading cause of death in the whole world until 2020. The disease is frequently referred to as the silent epidemic, and many authors highlight the "unmet medical need" associated with TBI.The term traumatically evoked brain injury covers a heterogeneous group ranging from mild/minor/minimal to severe/non-salvageable damages. Severe TBI has long been recognized to be a major socioeconomical health-care issue as saving young lives and sometimes entirely restituting health with a timely intervention can indeed be extremely cost efficient.Recently it has been recognized that mild or minor TBI should be considered similarly important because of the magnitude of the patient population affected. Other reasons behind this recognition are the association of mild head injury with transient cognitive disturbances as well as long-term sequelae primarily linked to repeat (sport-related) injuries.The incidence of TBI in developed countries can be as high as 2-300/100,000 inhabitants; however, if we consider the injury pyramid, it turns out that severe and moderate TBI represents only 25-30 % of all cases, while the overwhelming majority of TBI cases consists of mild head injury. On top of that, or at the base of the pyramid, are the cases that never show up at the ER - the unreported injuries.Special attention is turned to mild TBI as in recent military conflicts it is recognized as "signature injury."This chapter aims to summarize the most important features of mild and repetitive traumatic brain injury providing definitions, stratifications, and triage options while also focusing on contemporary knowledge gathered by imaging and biomarker research.Mild traumatic brain injury is an enigmatic lesion; the classification, significance, and its consequences are all far less defined and explored than in more severe forms of brain injury.Understanding the pathobiology and pathomechanisms may aid a more targeted approach in triage as well as selection of cases with possible late complications while also identifying the target patient population where preventive measures and therapeutic tools should be applied in an attempt to avoid secondary brain injury and late complications.

The challenge of mild traumatic brain injury: role of biochemical markers in diagnosis of brain damage.

During the past decade there has been an increasing recognition of the incidence of mild traumatic brain injury (mTBI) and a better understanding of the subtle neurological and cognitive deficits that may result from it. A substantial, albeit suboptimal, effort has been made to define diagnostic criteria for mTBI and improve diagnostic accuracy. Thus, biomarkers that can accurately and objectively detect brain injury after mTBI and, ideally, aid in clinical management are needed. In this review, we discuss the current research on serum biomarkers for mTBI including their rationale and diagnostic performances. Sensitive and specific biomarkers reflecting brain injury can provide important information regarding TBI pathophysiology and serve as candidate markers for predicting abnormal computed tomography findings and/or the development of residual deficits in patients who sustain an mTBI. We also outline the roles of biomarkers in settings of specific interest including pediatric TBI, sports concussions and military injuries, and provide perspectives on the validation of such markers for use in the clinic. Finally, emerging proteomics-based strategies for identifying novel markers will be discussed.