Barbara Bangert

Longitudinal trajectories of postconcussive symptoms in children with mild traumatic brain injuries and their relationship to acute clinical status

OBJECTIVE. We examined whether mild traumatic brain injuries in children and adolescents, especially when associated with acute clinical features reflecting more severe injury, result in different postinjury trajectories of postconcussive symptoms compared with mild orthopedic injuries. PARTICIPANTS AND METHODS. Participants in this prospective and longitudinal cohort study were 8- to 15-year-old children, 186 with mild traumatic brain injuries and 99 with mild orthopedic injuries, who were recruited from consecutive admissions to emergency departments in 2 large childrens hospitals. Parents rated current postconcussive symptoms within 3 weeks of injury and at 1, 3, and 12 months after injury. At the initial assessment, parents also provided retrospective ratings of preinjury symptoms, and children with mild traumatic brain injuries received MRI of the brain. Clinical features examined as predictors of postconcussive symptoms included loss of consciousness, Glasgow Coma Scale score below 15, other injuries, acute symptoms of concussion, and intracranial abnormalities on the MRI. RESULTS. Finite mixture modeling identified 4 longitudinal trajectories of postconcussive symptoms (ie, no postconcussive symptoms, moderate persistent postconcussive symptoms, high acute/resolved postconcussive symptoms, high acute/persistent postconcussive symptoms). The mild traumatic brain injuries and orthopedic injuries groups demonstrated a different distribution of trajectories. Children with mild traumatic brain injuries were more likely than those with orthopedic injuries to demonstrate high acute/resolved and high acute/persistent trajectories relative to the no postconcussive symptoms group. The 2 trajectories with high acute levels of postconcussive symptoms were especially likely among children with mild traumatic brain injuries whose acute clinical presentation reflected more severe injury. CONCLUSIONS. Mild traumatic brain injuries, particularly those that are more severe, are more likely than orthopedic injuries to result in transient or persistent increases in postconcussive symptoms in the first year after injury. Additional research is needed to elucidate the range of factors, both injury related and non–injury related, that place some children with mild traumatic brain injuries at risk for postconcussive symptoms.

Post-Concussive Symptoms in Children with Mild Traumatic Brain Injury

To investigate postconcussive symptoms (PCS) following pediatric mild traumatic brain injury (mTBI), 8- to 15-year-old children with mTBI (n = 186) and a comparison group with uncomplicated orthopedic injuries (OI, n = 99) were recruited from two emergency departments. Parent and child ratings of PCS and symptom counts were obtained within 3 weeks after injury (baseline) and at 1, 3, and 12 months postinjury. The mTBI group also completed magnetic resonance imaging at baseline. Group differences were examined using growth modeling, controlling for age at injury, sex, socioeconomic status, and (for parent-based measures) preinjury symptom levels. Relative to the OI group, the mTBI group had higher ratings of somatic PCS and parent counts of PCS at the initial assessments, but higher parent ratings of cognitive PCS and child counts of PCS throughout follow-up. Higher levels of PCS in the mTBI group were associated with motor-vehicle-related trauma, loss of consciousness, neuroimaging abnormalities, and hospitalization. The findings validate both transient and persistent PCS in children with mTBI and document associations of symptoms with injury and noninjury factors.

Long-term neuropsychological outcomes of very low birth weight: associations with early risks for periventricular brain insults.

Few follow-up studies of children with very low birth weight (VLBW, <1,500 g) have examined neuropsychological sequelae at later ages or neonatal risks as predictors of these outcomes. The present study assessed cognitive skills at mean age 16 years in 48 participants with <750 g birth weight, 47 with 750-1,499 g birth weight, and 52 term-born controls. Our major objectives were to delineate the long-term cognitive consequences of VLBW, and to determine if risks for periventricular brain insults accounted for variations in outcomes. Analysis revealed poorer outcomes for the <750 g group than for term-born controls on nearly all measures, with specific impairments in visual-motor skills, spatial memory, and executive function. Predictors of outcome for participants with VLBW included lower birth weight, lower weight for gestational age, and a longer period of oxygen requirement for chronic lung disease. The longer-term consequences of VLBW are consistent with expectations based on early brain pathology and suggest limitations to functional plasticity.

Cognitive reserve as a moderator of postconcussive symptoms in children with complicated and uncomplicated mild traumatic brain injury

The occurrence of postconcussive symptoms (PCS) following mild traumatic brain injury (TBI) in children may depend on cognitive reserve capacity. This prospective, longitudinal study examined whether the relationship between mild TBI and PCS is moderated by cognitive ability, which served as a proxy for cognitive reserve. Participants included 182 children with mild TBI and 99 children with orthopedic injuries (OI), ranging from 8 to 15 years of age when injured. Mild TBI were classified as complicated (n = 32) or uncomplicated (n = 150) depending on whether they were associated with trauma-related intracranial abnormalities on magnetic resonance imaging. PCS were assessed initially within 3 weeks of injury, and again at 1, 3, and 12 months post injury. The initial assessment also included standardized tests of childrens cognitive skills and retrospective parent ratings of pre-injury symptoms. Hierarchical linear modeling indicated that ratings of PCS were moderated jointly by cognitive ability and injury severity. Children of lower cognitive ability with a complicated mild TBI were especially prone to cognitive symptoms across time according to parents and to high acute levels of PCS according to childrens self-ratings. Cognitive reserve is an important moderator of the outcomes of mild TBI in children and adolescents.

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.

Brain Volumes in Adolescents With Very Low Birth Weight: Effects on Brain Structure and Associations With Neuropsychological Outcomes

The aims of this study were to examine abnormalities in brain structure in adolescents and young adults with very low birth weight (VLBW, <1,500 g) and associations of these abnormalities with neuropsychological outcomes. The sample of 108 participants from 14 to 19 years of age included 37 participants with <750 g birth weight, 35 with 750–1,499 g birth weight, and 36 normal birth weight (NBW) controls. One or both of the VLBW groups had smaller brain volumes, larger lateral ventricles, and a small surface area of the corpus callosum than the NBW controls. Group differences in white matter (WM) structures, subcortical gray matter (GM), and the cerebellum were found even when controlling for whole brain volume (WBV), and were most pronounced in the <750 g group. WM reductions in the two VLBW groups relative to NBW controls were associated with more pervasive cognitive deficits than were reductions in subcortical GM. Associations of cognitive outcomes with structural abnormalities remained when controlling for WBV or neonatal risks. The results are consistent with previous findings of residual brain abnormalities in adolescents and young adults with VLBW and provide new information on their cognitive correlates.

Apolipoprotein E4 as a Predictor of Outcomes in Pediatric Mild Traumatic Brain Injury

The epsilon4 allele of the apolipoprotein E (APOE) gene has been linked to negative outcomes among adults with traumatic brain injury (TBI) across the spectrum of severity, with preliminary evidence suggesting a similar pattern among children. This study investigated the relationship of the APOE epsilon4 allele to outcomes in children with mild TBI. Participants in this prospective, longitudinal study included 99 children with mild TBI between the ages of 8 and 15 recruited from consecutive admissions to Emergency Departments at two large childrens hospitals. Outcomes were assessed acutely in the Emergency Department and at follow-ups at 2 weeks, 3 months, and 12 months post-injury. Among the 99 participants, 28 had at least one epsilon4 allele. Children with and without an epsilon4 allele did not differ demographically. Children with an epsilon4 allele were significantly more likely than those without an epsilon4 allele to have a Glasgow Coma Scale score of less than 15, but the groups did not differ on any other measures of injury severity. Those with an epsilon4 allele exhibited better performance than children without an epsilon4 allele on a test of constructional skill, but the groups did not differ on any other neuropsychological tests. Children with and without an epsilon4 allele also did not differ on measures of post-concussive symptoms. Overall, the findings suggest that the APOE epsilon4 allele is not consistently related to the outcomes of mild TBI in children.

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.

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

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.

Agreement between Parents and Children on Ratings of Post-Concussive Symptoms Following Mild Traumatic Brain Injury

The level of parent-child agreement on post-concussive symptoms (PCS) was examined in children following mild traumatic brain injuries (TBI). As part of a larger longitudinal study, 186 children with mild TBI and 99 with orthopedic injuries (OI), from 8 to 15 years of age, were recruited prospectively. Parents and children completed the PCS Interview (PCS-I) and the Health and Behavior Inventory (HBI) at 2 weeks, 1 month, 3 months, and 12 months postinjury. Item-level correlations between child and parent ratings on both measures of PCS were significant but modest in both groups. Parent-child correlations for composite scales on the HBI and the total score on the PCS-I were significant in both groups, but somewhat higher in the OI group than in the mild TBI group. Mean symptom ratings tended to be significantly higher for children as compared to parents, especially for somatic symptoms. Parents and children display modest agreement when reporting PCS; their ratings correlate significantly, but children report higher mean levels of symptoms than parents.