IQ After Pediatric Concussion.

OBJECTIVES: This study investigated IQ scores in pediatric concussion (ie, mild traumatic brain injury) versus orthopedic injury. METHODS: Children (N = 866; aged 8-16.99 years) were recruited for 2 prospective cohort studies from emergency departments at children's hospitals (2 sites in the United States and 5 in Canada) ≤48 hours after sustaining a concussion or orthopedic injury. They completed IQ and performance validity testing postacutely (3-18 days postinjury; United States) or 3 months postinjury (Canada). Group differences in IQ scores were examined using 3 complementary statistical approaches (linear modeling, Bayesian, and multigroup factor analysis) in children performing above cutoffs on validity testing. RESULTS: Linear models showed small group differences in full-scale IQ (d [95% confidence interval] = 0.13 [0.00-0.26]) and matrix reasoning (0.16 [0.03-0.30]), but not in vocabulary scores. IQ scores were not related to previous concussion, acute clinical features, injury mechanism, a validated clinical risk score, pre- or postinjury symptom ratings, litigation, or symptomatic status at 1 month postinjury. Bayesian models provided moderate to very strong evidence against group differences in IQ scores (Bayes factor 0.02-0.23). Multigroup factor analysis further demonstrated strict measurement invariance, indicating group equivalence in factor structure of the IQ test and latent variable means. CONCLUSIONS: Across multisite, prospective study cohorts, 3 complementary statistical models provided no evidence of clinically meaningful differences in IQ scores after pediatric concussion. Instead, overall results provided strong evidence against reduced intelligence in the first few weeks to months after pediatric concussion.

Longitudinal trajectories of posttraumatic headache after pediatric mild traumatic brain injury.

OBJECTIVE: This prospective, longitudinal cohort study examined the trajectory, classification, and features of posttraumatic headache after pediatric mild traumatic brain injury. METHODS: Children (N = 213; ages 8.00 to 16.99 years) were recruited from two pediatric emergency departments <24 hours of sustaining a mild traumatic brain injury or mild orthopedic injury. At 10 days, three months, and six months postinjury, parents completed a standardized questionnaire that was used to classify premorbid and posttraumatic headache as migraine, tension-type headache, or not otherwise classified. Multilevel mixed effects models were used to examine posttraumatic headache rate, severity, frequency, and duration in relation to group, time postinjury, and premorbid headache, controlling for age, sex, and site. RESULTS: PTH risk was greater after mild traumatic brain injury than mild orthopedic injury at 10 days (odds ratio = 197.41, p < .001) and three months postinjury (odds ratio = 3.50, p = .030), especially in children without premorbid headache. Posttraumatic headache was more frequent after mild traumatic brain injury than mild orthopedic injury, ß (95% confidence interval) = 0.80 (0.05, 1.55). Groups did not differ in other examined headache features and classification any time postinjury. CONCLUSIONS: Posttraumatic headache risk increases after mild traumatic brain injury relative to mild orthopedic injury for approximately three months postinjury, but is not clearly associated with a distinct phenotype.

Social determinants of participant recruitment and retention in a prospective cohort study of pediatric mild traumatic brain injury.

Background: Prior studies have shown poor recruitment and retention of minoritized groups in clinical trials. Objective: To examine several social determinants as predictors of consent to participate and retention as part of a prospective, longitudinal cohort study of children 8-16 with either mild traumatic brain injury (mild TBI) or orthopedic injury (OI). Methods: Children and families were recruited during acute visits to emergency departments (ED) in two large children's hospitals in the midwestern United States for a prospective, longitudinal cohort study of children 8-16 with either mild TBI or OI. Results: A total of 588 (mild TBI = 307; OI = 281) eligible children were approached in the ED and 315 (mild TBI = 195; OI = 120) were consented. Children who consented did not differ significantly from those who did not consent in sex or age. Consent rates were higher among Black (60.9%) and multi-racial (76.3%) children than white (45.3%) children. Among the 315 children who consented, 217 returned for a post-acute assessment (mild TBI = 143; OI = 74), a retention rate of 68.9%. Participants who were multi-racial (96.6%) or white (79.8%) were more likely to return for the post-acute visit than those who were Black (54.3%). Conclusions: Racial differences exist in both recruitment and retention of participants in a prospective, longitudinal cohort of children with mild TBI or OI. Further work is needed to understand these differences to ensure equitable participation of minoritized groups in brain injury research.

Sex Differences in the Outcomes of Mild Traumatic Brain Injury in Children Presenting to the Emergency Department.

Sex differences after concussion have been studied largely in high school and college athletes, often without reference to comparison groups without concussion. This study sought to evaluate sex differences in outcomes among all children and adolescents presenting to the Emergency Department (ED) for either mild traumatic brain injury (TBI) or orthopedic injury (OI), regardless of mechanism of injury. The study involved a concurrent cohort, prospective study design with longitudinal follow-up. Participants were eight to 16 years old with mild TBI (n = 143) or OI (n = 73). They were recruited and completed an initial assessment at EDs at two children's hospitals. They returned for a post-acute assessment within two weeks of injury and for follow-up assessments at three and six months. Outcomes included child and parent proxy ratings of somatic and cognitive symptoms, and standardized tests of cognitive functioning and balance. Sex did not moderate group differences in balance, fluid or crystallized cognitive ability, or child or parent proxy ratings of somatic or cognitive symptoms. Both parents and children reported more somatic symptoms in girls than boys, but in both groups. Compared with the OI group, the mild TBI group showed significantly lower fluid cognitive ability at the post-acute assessment and significantly higher somatic and cognitive symptoms according to both child and parent proxy ratings across the first two weeks post-injury. The results suggest that sex does not moderate the outcomes of mild TBI in a pediatric ED population. Previous research pointing to sex differences after concussion may reflect the lack of comparison groups, as well as a focus on adolescents and young adults and sport-related concussion. Future research should investigate whether sex moderates the outcomes of pediatric mild TBI in adolescents but not in pre-adolescent children.

Cognitive Outcomes in Children with Mild Traumatic Brain Injury: An Examination Using the National Institutes of Health Toolbox Cognition Battery.

This study is the first to examine cognitive outcomes after pediatric mild TBI using the National Institutes of Health Toolbox Cognition Battery (NIHTB-CB), a computerized cognitive test battery. The NIHTB-CB includes two complex measures of attention and executive function that allow differentiation of accuracy and response speed. We compared performance on the NIHTB-CB among children 8-16 years of age with mild TBI (n = 143) versus children with orthopedic injuries (OIs; n = 74) recruited in emergency departments and followed for 6 months post-injury. Mixed-model analyses showed that the mild TBI group showed significantly lower Fluid Cognition composite scores than the OI group at 10 days (group intercept, p = 0.018); the magnitude of group differences declined modestly over time (group × time interaction, p = 0.055). Effect sizes were d = 0.34 at 10 days post-injury, d = 0.27 at 3 months, and d = 0.10 at 6 months. No significant effects of group or time were found for the Crystallized Cognition composite. Analyses of Fluid Cognition subtests indicated that children with mild TBI displayed deficits for as long as 3 months on measures of attention and executive function (e.g., cognitive flexibility, inhibitory control), but not on measures of explicit memory, working memory, or processing speed. The poorer performance of the mild TBI group on measures of attention and executive function was attributable largely to slowed reaction time, not decreased accuracy. The findings suggest that children with mild TBI demonstrate persistent deficits in fluid cognition that are most apparent on tasks that combine demands for both speed and executive function.

Post-Acute Cortical Thickness in Children with Mild Traumatic Brain Injury versus Orthopedic Injury.

Studies of brain morphometry may illuminate the effects of pediatric mild traumatic brain injury (TBI; e.g., concussion). However, no published studies have examined cortical thickness in the early injury phases of pediatric mild TBI using an appropriate comparison group. The current study used an automated approach (i.e., FreeSurfer) to determine whether cortical thickness differed in children following a mild TBI or a mild orthopedic injury (OI), and to examine whether post-acute cortical thickness predicted post-acute and chronic post-concussive symptoms (PCS). Children ages 8.00-16.99 years with mild TBI (n = 136) or OI (n = 70) were recruited at emergency department visits to two children's hospitals, during which parents rated children's pre-injury symptoms retrospectively. Children completed a post-acute (3-24 days post-injury) assessment, which included a 3 Tesla MRI, and 3- and 6-month post-injury assessments. Parents and children rated PCS at each assessment. Cortical thickness was estimated using FreeSurfer. Linear mixed effects and multi-variable negative binomial regression models were used to test study aims, with false discovery rate (FDR) correction for multiple comparisons. Groups differed significantly on left parietal cortical thickness (TBI > OI) after FDR correction. Cortical thickness also varied by brain subregion and age, but not sex. Groups differed significantly on PCS post-acutely (TBI > OI), but not at 3 or 6 months. Right frontal thickness was positively related to post-acute PCS in both groups. Right cingulum thickness predicted chronic PCS in the OI group only. Results highlight the complexity of predicting outcomes of pediatric mild TBI from post-acute neuroimaging biomarkers.

Post-acute white matter microstructure predicts post-acute and chronic post-concussive symptom severity following mild traumatic brain injury in children.

INTRODUCTION: Mild traumatic brain injury (TBI) is a global public health concern that affects millions of children annually. Mild TBI tends to result in subtle and diffuse alterations in brain tissue, which challenges accurate clinical detection and prognostication. Diffusion tensor imaging (DTI) holds promise as a diagnostic and prognostic tool, but little research has examined DTI in post-acute mild TBI. The current study compared post-acute white matter microstructure in children with mild TBI versus those with mild orthopedic injury (OI), and examined whether post-acute DTI metrics can predict post-acute and chronic post-concussive symptoms (PCS). MATERIALS AND METHODS: Children aged 8-16.99 years with mild TBI (n = 132) or OI (n = 69) were recruited at emergency department visits to two children's hospitals, during which parents rated children's pre-injury symptoms retrospectively. Children completed a post-acute (<2 weeks post-injury) assessment, which included a 3T MRI, and 3- and 6-month post-injury assessments. Parents and children rated PCS at each assessment. Mean diffusivity (MD) and fractional anisotropy (FA) were derived from diffusion-weighted MRI using Automatic Fiber Quantification software. Multiple multivariable linear and negative binomial regression models were used to test study aims, with False Discovery Rate (FDR) correction for multiple comparisons. RESULTS: No significant group differences were found in any of the 20 white matter tracts after FDR correction. DTI metrics varied by age and sex, and site was a significant covariate. No interactions involving group, age, and sex were significant. DTI metrics in several tracts robustly predicted PCS ratings at 3- and 6-months post-injury, but only corpus callosum genu MD was significantly associated with post-acute PCS after FDR correction. Significant group by DTI metric interactions on chronic PCS ratings indicated that left cingulum hippocampus and thalamic radiation MD was positively associated with 3-month PCS in the OI group, but not in the mild TBI group. CONCLUSIONS: Post-acute white matter microstructure did not differ for children with mild TBI versus OI after correcting for multiple comparisons, but was predictive of post-acute and chronic PCS in both injury groups. These findings support the potential prognostic utility of this advanced DTI technique.

Radiologic common data elements rates in pediatric mild traumatic brain injury.

OBJECTIVE: The nosology for classifying structural MRI findings following pediatric mild traumatic brain injury (pmTBI) remains actively debated. Radiologic common data elements (rCDE) were developed to standardize reporting in research settings. However, some rCDE are more specific to trauma (probable rCDE). Other more recently proposed rCDE have multiple etiologies (possible rCDE), and may therefore be more common in all children. Independent cohorts of patients with pmTBI and controls were therefore recruited from multiple sites (New Mexico and Ohio) to test the dual hypothesis of a higher incidence of probable rCDE (pmTBI > controls) vs similar rates of possible rCDE on structural MRI. METHODS: Patients with subacute pmTBI (n = 287), matched healthy controls (HC; n = 106), and orthopedically injured (OI; n = 71) patients underwent imaging approximately 1 week postinjury and were followed for 3-4 months. RESULTS: Probable rCDE were specific to pmTBI, occurring in 4%-5% of each sample, rates consistent with previous large-scale CT studies. In contrast, prevalence rates for incidental findings and possible rCDE were similar across groups (pmTBI vs OI vs HC). The prevalence of possible rCDE was also the only finding that varied as a function of site. Possible rCDE and incidental findings were not associated with postconcussive symptomatology or quality of life 3-4 months postinjury. CONCLUSION: Collectively, current findings question the trauma-related specificity of certain rCDE, as well how these rCDE are radiologically interpreted. Refinement of rCDE in the context of pmTBI may be warranted, especially as diagnostic schema are evolving to stratify patients with structural MRI abnormalities as having a moderate injury.

Insular resection may lead to autonomic function changes.

OBJECTIVE: The aim of this study was to determine if insular damage is associated with markers of autonomic dysfunction. METHODS: We studied patients who underwent temporal lobe and/or insular resections for epilepsy surgery between April 2010 and June 2015 at University Hospitals Cleveland Medical Center (UHCMC). Presurgical T1-weighted MPRAGE, standard T1, T2 and FLAIR sequences were compared with postsurgical MRI by a neuroradiologist and classified as type 0 (no involvement of insula), type 1 (minimal involvement of insular margin), type 2 (insular involvement <25%), and type 3 (insular involvement ≥25%). Analysis of heart rate variability (HRV) was carried out in pre- and postoperative video-electroencephalography (vEEG) recording. Time-domain parameters were calculated: (mean of the RR intervals (MNN), root mean square difference of successive RR intervals (RMSSD), standard deviation of the RR intervals (SDNN), and coefficient of variation (CV)). In addition, frequency-domain parameters were calculated: low frequency (LF), high frequency (HF), and low frequency/high frequency (LF/HF). RESULTS: Twenty-one patients (14 females) with mean age of 36.2 ±â€¯14.4 years (30; 22-75) were studied. Insular involvement was classified as type 0 (4 patients [19%]), type 1 (9 [43%]), type 2 (7 [33%]), and type 3 (1 [5%]). Significant decrease in RMSSD (p = 0.025) and CV (p = 0.008) was seen in insular damage types 2 and 3 compared with no or minimal insular involvement (types 0 and 1). Right-sided resections were associated with increase in LF power (p = 0.010) and the LF/HF ratio (p = 0.017). CONCLUSIONS: This study indicates that insular resection may lead to autonomic function changes.

Age- and sex-related effects in children with mild traumatic brain injury on diffusion magnetic resonance imaging properties: A comparison of voxelwise and tractography methods.

Although there are several techniques to analyze diffusion-weighted imaging, any technique must be sufficiently sensitive to detect clinical abnormalities. This is especially critical in disorders like mild traumatic brain injury (mTBI), where pathology is likely to be subtle. mTBI represents a major public health concern, especially for youth under 15 years of age. However, the developmental period from birth to 18 years is also a time of tremendous brain changes. Therefore, it is important to establish the degree of age- and sex-related differences. Participants were children aged 8-15 years with mTBI or mild orthopedic injuries. Imaging was obtained within 10 days of injury. We performed tract-based spatial statistics (TBSS), deterministic tractography using Automated Fiber Quantification (AFQ), and probabilistic tractography using TRACULA (TRActs Constrained by UnderLying Anatomy) to evaluate whether any method provided improved sensitivity at identifying group, developmental, and/or sex-related differences. Although there were no group differences from any of the three analyses, many of the tracts, but not all, revealed increases of fractional anisotropy and decreases of axial, radial, and mean diffusivity with age. TBSS analyses resulted in age-related changes across all white matter tracts. AFQ and TRACULA revealed age-related changes within the corpus callosum, cingulum cingulate, corticospinal tract, inferior and superior longitudinal fasciculus, and uncinate fasciculus. The results are in many ways consistent across all three methods. However, results from the tractography methods provided improved sensitivity and better tract-specific results for identifying developmental and sex-related differences within the brain.

Synchronized navigation of current and prior studies using image registration improves radiologist's efficiency.

PURPOSE: The purpose of this study was to investigate how the use of multi-modal rigid image registration integrated within a standard picture archiving and communication system affects the efficiency of a radiologist while performing routine interpretations of cases including prior examinations. METHODS: Six radiologists were recruited to read a set of cases (either 16 neuroradiology or 14 musculoskeletal cases) during two crossover reading sessions. Each radiologist read each case twice, one time with synchronized navigation, which enables spatial synchronization across examinations from different study dates, and one time without. Efficiency was evaluated based upon time to read a case and amount of scrolling while browsing a case using Wilcoxon signed rank test. RESULTS: Significant improvements in efficiency were found considering either all radiologists simultaneously, the two sections separately and the majority of individual radiologists for time to read and for amount of scrolling. The relative improvement for each individual radiologist ranged from 4 to 32% for time to read and from 14 to 38% for amount of scrolling. CONCLUSION: Image registration providing synchronized navigation across examinations from different study dates provides a tool that enables radiologists to work more efficiently while reading cases with one or more prior examinations.

Symptoms of Persistent Behavior Problems in Children With Mild Traumatic Brain Injury.

OBJECTIVE: To investigate the effects of mild traumatic brain injury (mTBI) in children on symptom ratings of behavior problems across the first-year postinjury. SETTING: Emergency departments of 2 regional children's hospitals. PARTICIPANTS: Parents of 176 children with mTBI and 90 children with orthopedic injury aged 8 to 15 years. DESIGN: Group comparisons of postinjury parent and teacher ratings of child behavior problems controlling for background factors. MAIN MEASURES: Child Behavior Checklist and Teacher's Report Form. RESULTS: For younger but not older children in the sample, children with mTBI compared with children with orthopedic injury had higher postinjury ratings on the Child Behavior Checklist Total Behavior Problem scale (t264 = 3.34, P < .001) and higher rates of T-scores of 60 or more on this scale (odds ratio = 3.00; 95% confidence interval, 1.33-6.77; P = .008). For children with mTBI, hospitalization, motor vehicle accidents, loss of consciousness, and magnetic resonance imaging abnormality were associated with higher parent or teacher ratings. CONCLUSIONS: School-aged children with mTBI are at risk for persistent symptoms of behavior problems, especially if mTBI is more severe or occurs at a younger age. The findings justify monitoring of behavior long after injury and further research to identify risk factors for these symptoms and their association with clinical disorders.

Relation of neural structure to persistently low academic achievement: a longitudinal study of children with differing birth weights.

OBJECTIVE: This study examined the relation of cerebral tissue reductions associated with VLBW to patterns of growth in core academic domains. METHOD: Children born <750 g, 750 to 1,499 g, or >2,500 g completed measures of calculation, mathematical problem solving, and word decoding at time points spanning middle childhood and adolescence. K. A. Espy, H. Fang, D. Charak, N. M. Minich, and H. G. Taylor (2009, Growth mixture modeling of academic achievement in children of varying birth weight risk, Neuropsychology, Vol. 23, pp. 460-474) used growth mixture modeling to identify two growth trajectories (clusters) for each academic domain: an average achievement trajectory and a persistently low trajectory. In this study, 97 of the same participants underwent magnetic resonance imaging (MRI) in late adolescence, and cerebral tissue volumes were used to predict the probability of low growth cluster membership for each domain. RESULTS: Adjusting for whole brain volume (wbv), each 1-cm(3) reduction in caudate volume was associated with a 1.7- to 2.1-fold increase in the odds of low cluster membership for each domain. Each 1-mm(2) decrease in corpus callosum surface area increased these odds approximately 1.02-fold. Reduced cerebellar white matter volume was associated specifically with low calculation and decoding growth, and reduced cerebral white matter volume was associated with low calculation growth. Findings were similar when analyses were confined to the VLBW groups. CONCLUSIONS: Reduced volume of structures involved in connectivity, executive attention, and motor control may contribute to heterogeneous academic trajectories among children with VLBW.

Injury versus noninjury factors as predictors of postconcussive symptoms following mild traumatic brain injury in children.

OBJECTIVE: To examine the relative contributions of injury characteristics and noninjury child and family factors as predictors of postconcussive symptoms (PCS) following mild traumatic brain injury (TBI) in children. METHOD: Participants were 8- to 15-year-old children, 186 with mild TBI and 99 with mild orthopedic injuries (OI). Parents and children rated PCS shortly after injury and at 1, 3, and 12 months postinjury. Hierarchical regression analyses were conducted to predict PCS from (1) demographic variables; (2) premorbid child factors (WASI IQ; WRAT-3 Reading; Child Behavior Checklist; ratings of preinjury PCS); (3) family factors (Family Assessment Device General Functioning Scale; Brief Symptom Inventory; and Life Stressors and Social Resources Inventory); and (4) injury group (OI, mild TBI with loss of consciousness [LOC] and associated injuries [AI], mild TBI with LOC but without AI, mild TBI without LOC but with AI, and mild TBI without LOC or AI). RESULTS: Injury group predicted parent and child ratings of PCS but showed a decreasing contribution over time. Demographic variables consistently predicted symptom ratings across time. Premorbid child factors, especially retrospective ratings of premorbid symptoms, accounted for the most variance in symptom ratings. Family factors, particularly parent adjustment, consistently predicted parent, but not child, ratings of PCS. CONCLUSIONS: Injury characteristics predict PCS in the first months following mild TBI but show a decreasing contribution over time. In contrast, noninjury factors are more consistently related to persistent PCS.

Rhombencephalosynapsis: embryopathology and management strategies of associated neurosurgical conditions with a review of the literature.

OBJECT: Rhombencephalosynapsis (RS) is a rare congenital posterior fossa malformation characterized by dorsal fusion of the cerebellar hemispheres, hypogenesis or agenesis of the vermis, and fusion of the dentate nuclei and superior cerebellar peduncles. The objective of this institutional study is to review the clinical conditions associated with RS and analyze the varied biological profile of this unique condition. METHODS: The study data were collected retrospectively from the medical records of patients at Rainbow Babies and Children's Hospital. After required institutional review board approval, the authors obtained information regarding the cases of RS reviewed by the Departments of Radiology, Genetics, and/or Pediatric Neurology. Medical charts were systematically reviewed, and 9 patients were analyzed in detail. RESULTS: The authors describe 6 cases of RS and 3 cases of partial RS. This case series demonstrates an association between RS and symptomatic hydrocephalus (7 of 9 patients) and RS and Chiari malformation (5 of 9 patients). Patients with symptomatic hydrocephalus underwent endoscopic third ventriculostomy or ventriculoperitoneal shunt insertion. One of the patients with an associated Chiari malformation underwent foramen magnum decompression. CONCLUSIONS: The authors present a large case series of RS. Patients with RS often had hydrocephalus and/or a Chiari Type I or II hindbrain malformation. Neuroimaging findings of RS are presented along with hypotheses to explain the embryopathology of this unusual condition.

Reliable change in postconcussive symptoms and its functional consequences among children with mild traumatic brain injury.

OBJECTIVE To examine reliable change in postconcussive symptoms and its functional consequences among children with mild traumatic brain injury (TBI) over the first year postinjury as compared with children with orthopedic injuries. DESIGN Prospective, longitudinal cohort. SETTING Emergency departments at 2 children's hospitals. PARTICIPANTS Eight- to 15-year-old children with mild TBI (n = 186) or orthopedic injuries (n = 99). MAIN EXPOSURE Closed-head or orthopedic trauma. MAIN OUTCOME MEASURES Parents rated preinjury symptoms retrospectively shortly after injury and postconcussive symptoms at 2 weeks and 3 and 12 months postinjury. A regression-based approach was used to determine whether each child displayed reliable increases in postconcussive symptoms at each postinjury occasion. Health-related quality of life was assessed at 3 and 12 months postinjury. Information regarding children's educational programming was collected at the initial and 12-month assessments. RESULTS Children with mild TBI were significantly more likely than those with orthopedic injuries to show reliable increases in both cognitive and somatic symptoms. Group differences in the likelihood of reliable increases became less common with time for somatic symptoms but persisted to 12 months postinjury for cognitive symptoms. Among children with mild TBI, reliable increases in symptoms were more common among children with loss of consciousness or abnormalities on neuroimaging. Reliable increases in symptoms were associated with significant declines in health-related quality of life and an increased likelihood of educational intervention. CONCLUSION Many children with mild TBI show reliable increases in postconcussive symptoms that are associated with significant functional impairment in their daily lives.

Phase II trial of radiosurgery to magnetic resonance spectroscopy-defined high-risk tumor volumes in patients with glioblastoma multiforme.

PURPOSE: To determine the efficacy of a Gamma Knife stereotactic radiosurgery (SRS) boost to areas of high risk determined by magnetic resonance spectroscopy (MRS) functional imaging in addition to standard radiotherapy for patients with glioblastoma (GBM). METHODS AND MATERIALS: Thirty-five patients in this prospective Phase II trial underwent surgical resection or biopsy for a GBM followed by SRS directed toward areas of MRS-determined high biological activity within 2 cm of the postoperative enhancing surgical bed. The MRS regions were determined by identifying those voxels within the postoperative T2 magnetic resonance imaging volume that contained an elevated choline/N-acetylaspartate ratio in excess of 2:1. These voxels were marked, digitally fused with the SRS planning magnetic resonance image, targeted with an 8-mm isocenter per voxel, and treated using Radiation Therapy Oncology Group SRS dose guidelines. All patients then received conformal radiotherapy to a total dose of 60 Gy in 2-Gy daily fractions. The primary endpoint was overall survival. RESULTS: The median survival for the entire cohort was 15.8 months. With 75% of recursive partitioning analysis (RPA) Class 3 patients still alive 18 months after treatment, the median survival for RPA Class 3 has not yet been reached. The median survivals for RPA Class 4, 5, and 6 patients were 18.7, 12.5, and 3.9 months, respectively, compared with Radiation Therapy Oncology Group radiotherapy-alone historical control survivals of 11.1, 8.9, and 4.6 months. For the 16 of 35 patients who received concurrent temozolomide in addition to protocol radiotherapeutic treatment, the median survival was 20.8 months, compared with European Organization for Research and Treatment of Cancer historical controls of 14.6 months using radiotherapy and temozolomide. Grade 3/4 toxicities possibly attributable to treatment were 11%. CONCLUSIONS: This represents the first prospective trial using selective MRS-targeted functional SRS combined with radiotherapy for patients with GBM. This treatment is feasible, with acceptable toxicity and patient survivals higher than in historical controls. This study can form the basis for a multicenter, randomized trial.

Quality of life in pediatric mild traumatic brain injury and its relationship to postconcussive symptoms.

OBJECTIVES: Mild traumatic brain injury (TBI) and injury-related outcomes such as postconcussive symptoms (PCS) may influence health-related quality of life (HRQOL) in children. METHODS: We evaluated HRQOL in 186 8- to 15-year-old children with mild TBI and 99 children with orthopedic injuries (OI). Parents rated the frequency and severity of PCS at an initial assessment within 2-weeks postinjury and rated HRQOL at 3- and 12-months postinjury. RESULTS: The mild TBI and OI groups did not differ in psychosocial HRQOL, but the mild TBI group showed lower physical HRQOL at the 12-month follow-up. Somatic PCS were a significant predictor of physical HRQOL over time, and both cognitive and somatic PCS were significant predictors of psychosocial HRQOL over time. Children with higher PCS at the initial assessment had lower HRQOL scores at later time points. CONCLUSIONS: Effective management of PCS may be associated with improvements in HRQOL following pediatric mild TBI.

Premorbid child and family functioning as predictors of post-concussive symptoms in children with mild traumatic brain injuries.

STUDY AIM: This study sought to determine whether premorbid child and family functioning accounts for or moderates group differences in post-concussive symptoms following mild traumatic brain injury (TBI) in childhood. METHODS: This prospective, longitudinal cohort study recruited 8- to 15-year-old children, 186 with mild TBI and 99 with orthopedic injuries (OI), from consecutive emergency department admissions. Parents and children rated post-concussive symptoms within 3 weeks of injury and at 1, 3, and 12 months post injury. Parents also provided retrospective ratings of pre-injury symptoms, as well as of premorbid child behavioral adjustment, overall family functioning, and other stressors and resources in the family environment. RESULTS: Children with mild TBI reported more post-concussive symptoms than those with OI, as did their parents, although premorbid child behavioral adjustment and symptoms also were significant predictors of post-concussive symptoms. Group differences in somatic symptoms as reported by parents were more pronounced among children from families that were higher functioning and had more environmental resources. DISCUSSION: Mild TBI during childhood results in more post-concussive symptoms than OI, even after children's premorbid adjustment is taken into account. Counter to expectations, post-concussive symptoms following mild TBI may actually be more apparent among children from higher-functioning families with greater resources.