A longitudinal evaluation of a penetrating traumatic brain injury: Theories of plasticity and vulnerability.

Penetrating traumatic brain injury (TBI) is uncommon in infancy. The consequences may be devastating, especially when the injury is extensive and affects eloquent areas of the brain. There is the potential for neuropsychological dysfunction that may impact the individual's development and well-being into adulthood. In the context of early brain injury, the developing brain is both remarkably resilient and vulnerable. The present case study describes a patient who experienced a penetrating TBI at 9 days of age, subsequently developed intractable seizures, and underwent left hemispherectomy. Neuropsychological testing at ages 5, 10, 11, and 19 years are presented alongside fMRI and Wada testing. While the patient initially developed cognitive functions in the low-average range by age 5, scores on neuropsychological assessments began to decrease thereafter. This case is discussed with attention to vulnerability and plasticity theories. It highlights the ability of the brain to reorganize and allow the development of functions that would normally be sub-served by damaged areas and the limits of plasticity. Further, this case illustrates the vulnerability of the early brain to insult, the potential to grow into deficits, and the need to consider a variety of factors when predicting outcomes for cases of pediatric brain injury.

Differential antiseizure medication sensitivity of the Affective Reactivity Index: A randomized controlled trial in new-onset pediatric focal epilepsy.

BACKGROUND: Irritability is a adverse effect of many antiseizure medications (ASMs), but there are no validated measures currently available to characterize this behavioral risk. We examined both child and parent/guardian versions of the Affective Reactivity Index (ARI), a validated measure developed for application in adolescent psychiatry, to determine its sensitivity to ASM-related irritability. We hypothesized irritability increases associated with levetiracetam (LEV) but not lamotrigine (LTG) or oxcarbazepine (OXC). METHOD: The ARI was administered to 71 child and parent/guardian pairs randomized to one of three common ASMs (LEV, LTG, OXC) used to treat new-onset focal (localization-related) epilepsy. Subjects were recruited as part of a prospective multicenter, randomized, open-label, parallel group design. The ARI was administered at baseline prior to treatment initiation and again at 3 months after ASM initiation. RESULTS: There was a significant increase in ARI ratings for both child and parent/guardian ratings for LEV but not LTG or OXC when assessed 3 months after treatment initiation. When examined on the individual subject level using a criterion of at least a 3-point ARI increase, there was an increase associated with LEV for child ratings but not parent/guardian scores. CONCLUSION: Both child and parent/guardian versions of the ARI appear sensitive to medication-induced irritability associated with LEV on both the group and individual levels. The findings extend the applicability of ARI from characterizing the presence of clinical irritability as a psychiatric diagnostic feature to a more modifiable aspect of behavior change related to medication management and support its use in clinical trial applications.

Longitudinal Changes in Resting State Connectivity and White Matter Integrity in Adolescents With Sports-Related Concussion.

OBJECTIVES: The aim of this study was to investigate alterations in functional connectivity, white matter integrity, and cognitive abilities due to sports-related concussion (SRC) in adolescents using a prospective longitudinal design. METHODS: We assessed male high school football players (ages 14-18) with (n=16) and without (n=12) SRC using complementary resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI) along with cognitive performance using the Immediate Post-Concussive Assessment and Cognitive Testing (ImPACT). We assessed both changes at the acute phase (<7 days post-SRC) and at 21 days later, as well as, differences between athletes with SRC and age- and team-matched control athletes. RESULTS: The results revealed rs-fMRI hyperconnectivity within posterior brain regions (e.g., precuneus and cerebellum), and hypoconnectivity in more anterior areas (e.g., inferior and middle frontal gyri) when comparing SRC group to control group acutely. Performance on the ImPACT (visual/verbal memory composites) was correlated with resting state network connectivity at both time points. DTI results revealed altered diffusion in the SRC group along a segment of the corticospinal tract and the superior longitudinal fasciculus in the acute phase of SRC. No differences between the SRC group and control group were seen at follow-up imaging. CONCLUSIONS: Acute effects of SRC are associated with both hyperconnectivity and hypoconnectivity, with disruption of white matter integrity. In addition, acute memory performance was most sensitive to these changes. After 21 days, adolescents with SRC returned to baseline performance, although chronic hyperconnectivity of these regions could place these adolescents at greater risk for secondary neuropathological changes, necessitating future follow-up. (JINS, 2018, 24, 781-792).

Posterior Cerebellar Volume and Executive Function in Young Adults With Congenital Heart Disease.

OBJECTIVES: As the number of adolescents and young adults (AYAs) surviving congenital heart disease (CHD) grows, studies of long-term outcomes are needed. CHD research documents poor executive function (EF) and cerebellum (CB) abnormalities in children. We examined whether AYAs with CHD exhibit reduced EF and CB volumes. We hypothesized a double dissociation such that the posterior CB is related to EF while the anterior CB is related to motor function. We also investigated whether the CB contributes to EF above and beyond processing speed. METHODS: Twenty-two AYAs with CHD and 22 matched healthy controls underwent magnetic resonance imaging and assessment of EF, processing speed, and motor function. Volumetric data were calculated using a cerebellar atlas (SUIT) developed for SPM. Group differences were compared with t tests, relationships were tested with Pearson's correlations and Fisher's r to z transformation, and hierarchical regression was used to test the CB's unique contributions to EF. RESULTS: CHD patients had reduced CB total, lobular, and white matter volume (d=.52-.99) and poorer EF (d=.79-1.01) compared to controls. Significant correlations between the posterior CB and EF (r=.29-.48) were identified but there were no relationships between the anterior CB and motor function nor EF. The posterior CB predicted EF above and beyond processing speed (ps<.001). CONCLUSIONS: This study identified a relationship between the posterior CB and EF, which appears to be particularly important for inhibitory processes and abstract reasoning. The unique CB contribution to EF above and beyond processing speed alone warrants further study. (JINS, 2018, 24, 939-948).

Effects of Developmental Age on Symptom Reporting and Neurocognitive Performance in Youth After Sports-Related Concussion Compared to Control Athletes.

There is increased necessity to focus research on school-aged athletes with sports-related concussion (SRC). This study assessed differences in symptom reporting and neurocognitive performance in youth athletes who sustained a sports-related concussion. A total of 1345 concussed and 3529 nonconcussed athletes (ages 8-21) completed the Immediate Post-concussive Assessment and Cognitive Testing (ImPACT). Analyses of covariance were conducted in order to assess differences in neurocognitive performance and symptom reporting between the sports-related concussion and control groups across age ranges. Longitudinal hierarchical linear modeling was employed to examine age and its relationship with rates of sports-related concussion recovery in neurocognitive performance. Results revealed athletes aged 13 to 15 had significantly lower neurocognitive performance scores compared to same-aged athletes without a history of sports-related concussion. With respect to the hierarchical linear modeling results, age was identified as a unique predictor of symptom recovery, particularly for ages 8 to 12. Results provide a better understanding of typical symptom reporting and neurocognitive outcomes for younger athletes across different ages.

Assessment of Sleep Quantity and Sleep Disturbances During Recovery From Sports-Related Concussion in Youth Athletes.

OBJECTIVE: To determine the relation between sleep quantity and sleep disturbances on symptoms and neurocognitive ability during the acute phase (<7d) and after sports-related concussion (SRC; >21d). DESIGN: Prospective inception cohort study. SETTING: General community setting of regional middle and high schools. PARTICIPANTS: A sample (N=971) including youth athletes with SRC (n=528) and controls (n=443) (age, 10-18y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Athletes completed the Immediate Post-Concussion Assessment and Cognitive Testing battery. Partial correlation analyses and independent t tests were conducted to assess sleep quantity the night before testing. Multivariate analysis of covariance was used to assess sleep disturbances and their interaction with age. RESULTS: Less sleep quantity was correlated with greater report of cognitive (P=.001) and neuropsychological (P=.024) symptoms specific to prolonged recovery from SRC. Sleep disturbances significantly affect each migraine, cognitive, and neuropsychological symptoms (P<.001). A significant interaction was found between sleep disturbances and age (P=.04) at >21 days post-SRC. CONCLUSIONS: Findings emphasize that the continued presence of low sleep quantity and sleep disturbances in youth athletes with SRC should be a specific indicator to health professionals that these athletes are at an increased risk of protracted recovery. Further research should identify additional factors that may interact with sleep to increase the risk of protracted recovery.

Cognitive and behavioral outcomes among seizure-controlled children with partial epilepsy on antiepileptic drug monotherapy.

The objective of this study was to assess cognitive performance and behavioral symptoms in a sample of children diagnosed with partial epilepsy who were seizure controlled on AED monotherapy for one year. Ninety-eight seizure-controlled children on AED monotherapy were included in this study. Specific AEDs examined included topiramate, divalproex sodium, lamotrigine, levetiracetam, and oxcarbazepine. Groups did not differ on age, region of focal epilepsy, or Full-Scale IQ. Direct measures included the WISC-IV and selected tests from the DKEFS (Verbal Fluency and Trail Making Test). Parent report measures included the BRIEF and the BASC-PRS. A series of ANOVAs revealed significant differences across the AED cohorts within many domains of cognitive functioning and behavioral presentation. Children prescribed divalproex sodium or topiramate demonstrated weaker working memory and verbal fluency, when compared with children prescribed other AEDs. Additionally, parents of children prescribed topiramate reported greater executive functioning and adaptive skills deficits. The pattern of findings suggests that children prescribed divalproex sodium or topiramate generally demonstrated a higher risk of cognitive and behavioral impairments compared to the other AEDs. Future prospective studies are required in order to better understand the relationship between AED type and these outcomes to inform clinical practice.

Quality Improvement in Concussion Care: Influence of Guideline-Based Education.

OBJECTIVE: To evaluate the potential impact of a concussion management education program on community-practicing pediatricians. STUDY DESIGN: We prospectively surveyed 210 pediatricians before and 18 months after participation in an evidence-based, concussion education program. Pediatricians were part of a network of 38 clinically integrated practices in metro-Atlanta. Participation was mandatory for at least 1 pediatrician in each practice. We assessed pediatricians' self-reported concussion knowledge, use of guidelines, and comfort level, as well as self-reported referral patterns for computed tomography (CT) and/or emergency department (ED) evaluation of children who sustained concussion. RESULTS: Based on responses from 120 pediatricians participating in the 2 surveys and intervention (response rate, 57.1%), the program had significant positive effects from pre- to postintervention on knowledge of concussions (-0.26 to 0.56 on -3 to +1 scale; P < .001), guideline use (0.73-.06 on 0-6 scale; P < .01), and comfort level in managing concussions (3.76-4.16 on 1-5 scale; P < .01). Posteducation, pediatricians were significantly less likely to self-report referral for CT (1.64-1.07; P < .001) and CT/ED (4.73-3.97; P < .01), but not ED referral alone (3.07-3.09; P = ns). CONCLUSIONS: Adoption of a multifaceted, evidence-based, education program translated into a positive modification of self-reported practice behavior for youth concussion case management. Given the surging demand for community-based youth concussion care, this program can serve as a model for improving the quality of pediatric concussion management.

fMRI investigation of working memory in adolescents with surgically treated congenital heart disease.

Adolescents and young adults with surgically treated congenital heart disease (CHD) have been shown to exhibit difficulties with executive functions; however, the neural underpinnings of these impairments have not been previously examined with functional magnetic resonance imaging (fMRI). The current study employed fMRI to examine the neural mechanisms during a letter n-back task of working memory compared to vigilance. Seventeen participants with CHD (Mage = 17.76 ± 1.72 years; 88% Caucasian; 30% female; mean IQ = 104.12 ± 15.15) were compared to 17 controls (Mage = 18.40 ± 1.74 years; 70% Caucasian; 30% female; mean IQ = 110.59 ± 5.28) with similar declining performance as the n-back became more challenging. Overall, both groups activated similar frontal-parietal working-memory networks as seen in previous literature; however, some significant differences were detected between the groups. Specifically, the participants with CHD demonstrated differences within the left precuneus and the right inferior frontal gyrus. Secondary analyses indicated that this difference appeared to be due to less task-induced deactivation (TID) in the CHD group during working memory and greater working-memory TID in the control group. In CHD, prefrontal fMRI deactivation on working-memory tasks correlated with improved working-memory performance. Future complementary neuroimaging research with functional connectivity is warranted to further examine the neural underpinnings of disrupted executive function in the long-term outcomes of CHD.

Sex-Based Differences as a Predictor of Recovery Trajectories in Young Athletes After a Sports-Related Concussion.

BACKGROUND: To date, few studies have delineated clear sex-based differences in symptom resolution after a sports-related concussion (SRC), and equivocal results have been identified in sex-based differences on baseline assessments. PURPOSE: To assess whether female athletes displayed prolonged recovery and more symptoms at baseline and after an SRC compared with male athletes. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The current study assessed 135 male and 41 female athletes (10-18 years old) who participated in high-impact sports in metropolitan Atlanta middle and high schools. All athletes completed a baseline assessment and at least 1 postconcussion assessment from the Immediate Post-Concussion Assessment and Cognitive Testing battery. Longitudinal hierarchical linear modeling was employed to examine individual-level variables and their associations with adolescents' rates of recovery in concussive symptoms after controlling for age and number of prior concussions. RESULTS: Aggregate symptoms were rated as higher in female athletes compared with male athletes at baseline (mean ± SD: females, 13.49 ± 11.20; males, 4.88 ± 8.74; F(1,175) = 10.59, P < .001) and immediately after a concussion (females: 16.75 ± 18.08; males: 10.58 ± 14.21; F(1,175) = 3.99, P = .05). There were no group differences in the slope of recovery between male and female athletes, indicating generally similar trajectories of change for both groups. Post hoc analyses revealed higher baseline levels of migraine and neuropsychological symptoms in female athletes. CONCLUSION: Although female athletes in the current study reported increased symptoms, identical recovery patterns were observed in both sexes, suggesting that sex-based differences in concussion recovery are better explained by increased symptom frequency among female athletes when compared with their male counterparts.

Wechsler Intelligence Scale for Children-V: Test Review.

Changes from the fourth edition of the Wechsler Intelligence Scale for Children (WISC) to the fifth edition are discussed, with particular emphasis on how the electronic administration facilitated assessment. The hierarchical organization and conceptualization of primary indices have been adjusted, based on recent theory and research on the construct of intelligence. Changes also include updates to psychometric properties and consideration of cultural bias. The scoring program allows intelligence scores to be linked statistically to achievement measures to aid in diagnoses of learning disabilities. Electronic assessment was clunky at times but overall delivered on its promise of quicker and more accurate administration and scoring.

White Matter Integrity Dissociates Verbal Memory and Auditory Attention Span in Emerging Adults with Congenital Heart Disease.

White matter disruptions have been identified in individuals with congenital heart disease (CHD). However, no specific theory-driven relationships between microstructural white matter disruptions and cognition have been established in CHD. We conducted a two-part study. First, we identified significant differences in fractional anisotropy (FA) of emerging adults with CHD using Tract-Based Spatial Statistics (TBSS). TBSS analyses between 22 participants with CHD and 18 demographically similar controls identified five regions of normal appearing white matter with significantly lower FA in CHD, and two higher. Next, two regions of lower FA in CHD were selected to examine theory-driven differential relationships with cognition: voxels along the left uncinate fasciculus (UF; a tract theorized to contribute to verbal memory) and voxels along the right middle cerebellar peduncle (MCP; a tract previously linked to attention). In CHD, a significant positive correlation between UF FA and memory was found, r(20)=.42, p=.049 (uncorrected). There was no correlation between UF and auditory attention span. A positive correlation between MCP FA and auditory attention span was found, r(20)=.47, p=.027 (uncorrected). There was no correlation between MCP and memory. In controls, no significant relationships were identified. These results are consistent with previous literature demonstrating lower FA in younger CHD samples, and provide novel evidence for disrupted white matter integrity in emerging adults with CHD. Furthermore, a correlational double dissociation established distinct white matter circuitry (UF and MCP) and differential cognitive correlates (memory and attention span, respectively) in young adults with CHD.

Neurocognitive improvements following endovascular repair of vein of Galen malformation in a child.

Cognitive regression is a well-described presentation of vein of Galen aneurysmal malformations (VGAMs) in childhood. However, it remains unclear whether successful treatment of the malformation can reverse cognitive regression. Here, the authors present the case of a 5-year-old girl with a VGAM that was treated with staged endovascular embolization procedures. Comprehensive neurocognitive assessments were completed before intervention and approximately 6 years after initial presentation. There were significant age-matched improvements in this child's neurocognitive profile over this period. The authors believe that timely and successful treatment of VGAM in children may not only stabilize the associated cognitive deterioration but, in some cases, may ameliorate these deficits. Details of this case and a discussion of neurocognitive deficits related to VGAM are presented.

Pediatric sports specific return to play guidelines following concussion.

PURPOSE/BACKGROUND: In 2010, the American Academy of Pediatrics officially adopted the recommended return to play guidelines proposed by the International Conference on Concussion in Sport. The guidelines include a six-step process that provides structure to guide an athlete who is recovering from a concussion in a gradual return to play (RTP) by allowing participation in increasingly difficult physical activities. Unfortunately, the guidelines fail to take into account the variability that occurs within different sports and the resulting challenges medical professionals face in making sure each athlete is able to withstand the rigors of their specific sport, without return of symptoms. Therefore, the purpose of this clinical commentary is to expand upon the current general consensus guidelines for treatment of concussed pediatric athletes and provide sport specific RTP guidelines. DESCRIPTION OF TOPIC: The intention of the sport specific guidelines is to maintain the integrity of the current six-step model, add a moderate activity phase highlighted by resistance training, and to provide contact and limited contact drills specific to the athlete's sport and/or position. The drills and activities in the proposed seven-step programs are designed to simulate sport specific movements; the sports include: football, gymnastics, cheerleading, wrestling, soccer, basketball, lacrosse, baseball, softball, and ice hockey. These activities will provide sports specific challenges to each athlete while simultaneously accomplishing the objectives of each stage of the RTP progression. The final RTP determination should occur with documented medical clearance from a licensed healthcare provider who has been trained in the evaluation and management of concussions. DISCUSSION/RELATION TO CLINICAL PRACTICE: There have been significant strides in the management and care of concussed athletes. However, there continues to be a lot of confusion among, athletes, parents, and coaches regarding the proper management of an athlete with a concussion, particularly in the pediatric population. In an effort to eliminate ambiguity and help further promote adherence to the RTP guidelines, the authors developed several sports-specific RTP guidelines. LEVEL OF EVIDENCE: 5.

CHOA concussion consensus: establishing a uniform policy for academic accommodations.

Concussion research generally centers on physical challenges, though aspects such as social functioning and returning to school also warrant attention in pediatric populations. Restoring academic performance postconcussion remains a challenge. Here we provide recommendations addressing a uniform policy for pediatric concussion patients in academic institutions. Tools that may minimize difficulty with academic re-entry include independent educational evaluations, individualized educational programs (IEPs), student support teams (SSTs), letters of academic accommodation, time off, and 504 Plans. Recognition and treatment is crucial for symptom relief and prevention of functional disruption, as is specialist referral during the acute window. We recommend early intervention with a letter of academic accommodation and SST and suggest that 504 Plans and IEPs be reserved for protracted or medically complicated cases. Students with concussion should be observed for anxiety and depression because these symptoms can lead to prolonged recovery, decreased quality of life, and other social challenges.

Mullen scales of early learning: the utility in assessing children diagnosed with autism spectrum disorders, cerebral palsy, and epilepsy.

A group of 47 patients diagnosed with neurodevelopmental disorders were compared to 47 age-, gender-, and racially matched typically developing children to examine the frequency of impairment across domains of the Mullen Scales of Early Learning (MSEL). The MSEL is a comprehensive measure of cognitive functioning designed to assess infants and preschool children between the ages of birth to 68 months. In the neurodevelopmental group, the sample was composed of children 2 to 4 years of age who were diagnosed with autism spectrum disorders (ASD; n = 19), cerebral palsy (CP; n = 14), and epilepsy (EPI; n = 14). A sample of 47 matched controls, taken from the normative sample of the MSEL, was used as a comparison group. Each one of the clinical groups comprising the neurodevelopmental sample demonstrated statistically significant delays across domains relative to the respective matched control group (p < .001). Children failed to demonstrate a "signature" profile for a diagnosis of ASD, CP, or EPI. The clinical sensitivity of the MSEL and the need for obtaining specific intervention services for children diagnosed with these conditions are presented. Finally, these results are discussed within the context of the clinical sensitivity of the MSEL in working with these clinical populations.

Age association of language task induced deactivation induced in a pediatric population.

Task-induced deactivation (TID) potentially reflects the interactions between the default mode and task specific networks, which are assumed to be age dependent. The study of the age association of such interactions provides insight about the maturation of neural networks, and lays out the groundwork for evaluating abnormal development of neural networks in neurological disorders. The current study analyzed the deactivations induced by language tasks in 45 right-handed normal controls aging from 6 to 22 years of age. Converging results from GLM, dual regression and ROI analyses showed a gradual reduction in both the spatial extent and the strength of the TID in the DMN cortices as the brain matured from kindergarten to early adulthood in the absence of any significant change in task performance. The results may be ascribed to maturation leading to either improved multi-tasking (i.e. reduced deactivation) or reduced cognitive demands due to greater experience (affects both control and active tasks but leads to reduced overall difference). However, other effects, such as changes in the DMN connectivity that were not included in this study may also have influenced the results. In light of this, researchers should be cautious when investigating the maturation of DMN using TID. With a GLM analysis using the concatenated fMRI data from several paradigms, this study additionally identified an age associated increase of TID in the STG (bilateral), possibly reflecting the role of this area in speech perception and phonological processing.