Adaptive functioning and academic achievement in pediatric survivors of acute lymphoblastic leukemia: Associations with executive functioning, socioeconomic status, and academic support.

OBJECTIVES: This study examines associations of functional outcomes (adaptive functioning and academic achievement) with executive functioning (EF), socioeconomic status (SES), and academic support in pediatric acute lymphoblastic leukemia (ALL) survivors. METHODS: Fifty survivors of B-lineage ALL treated with chemotherapy-only (42% female, 76% NHW, ages 6-19) were evaluated on performance-based EF and academic achievement, and parent-rated EF and adaptive functioning. Area deprivation and child opportunity (i.e., SES) were extracted using census blocks and tracts. Academic support data were extracted from chart review. RESULTS: Compared to population norms, pediatric ALL survivors demonstrated significantly lower overall adaptive skills and performance in word reading and math calculation (all p ≤ .011). Frequencies of impairment were significantly elevated on all adaptive scales and in math calculation compared to the population (all p ≤ .002). Parent-rated EF significantly predicted overall adaptive skills (p < .001), while performance-based EF significantly predicted word reading and math calculation (all p < .05). Adaptive functioning was not associated with neighborhood-specific variables or academic support. However, academic support predicted word reading (p < .001), while area deprivation and academic support predicted performance-based EF (all p ≤ .02). CONCLUSIONS: Screening of functional outcomes, targeted intervention, and neuropsychological monitoring are necessary to support pediatric ALL survivors' neurocognitive and psychosocial development.

The relationship between pain and sleep in pediatric sickle cell disease.

BACKGROUND: Pain and sleep disturbances are prevalent complications experienced by pediatric patients with sickle cell disease (SCD). This study aims to identify associations between pain and sleep, and to characterize sleep chronotype and social jetlag in children and adolescent patients with SCD. METHODS: We performed a cross-sectional survey of 105 pediatric patients with SCD aged 8-17 years using PROMIS (Patient Reported Outcomes Measurement System) pain interference, sleep disturbance, and sleep-related impairment item banks. The µMCTQ (Ultra-short Munich Chronotype Questionnaire) assessed chronotype and social jetlag. Analyses were performed to assess associations between PROMIS measures, sleep patterns, and clinical variables. RESULTS: Female participants reported higher T-scores for sleep-related impairment than males (females: 56.7 ± 10 vs. males 50.2 ± 9.4, p = .0009). Patients with one or more emergency department (ED) visits for pain in the last 12 months reported greater sleep disturbance (55.0 ± 8.5 vs. 50.7 ± 10, p = .046) and sleep-related impairment (57.1 ± 9.3 vs. 52.1 ± 10.2, p = .03) than patients without any ED visits for pain in the last 12 months. Pain interference was significantly associated with both sleep disturbance (r = .49, p < .0001) and sleep-related impairment (r = .46, p < .0001). The average mid-sleep time was 4:14 ± 1:44 a.m. and the average social jetlag (hh:mm) was 2:32 ± 1:35. CONCLUSION: Our study demonstrates that pain interference is associated with both sleep disturbance and sleep-related impairment. PROMIS measures can identify patients that suffer from pain and sleep disturbances and highlights the need to conduct longitudinal prospective studies to define the directionality of pain and sleep in SCD.

Inflammation, Executive Function, and Adiposity in Children With or at Risk for Obesity: A Pilot Study.

OBJECTIVE: Obesity is associated with executive function (EF) deficits across the lifespan. Higher body mass index (BMI), obesity severity, and poorer adherence and weight outcomes in obesity treatment have all been associated with EF deficits. Adult literature has begun to emphasize neuroinflammation in obesity as a possible pathway to later cognitive impairment in EF. However, pediatric obesity literature has yet to establish associations between peripheral inflammation and EF. Thus, the present study examined associations and variability in inflammation, EF, and adiposity in children with or at risk for obesity. Additionally, inflammation was examined as a mediator of the relationship between adiposity and EF. METHODS: Children (N = 39) aged 8-12 years with BMI ≥ 50th percentile were recruited. The NIH Toolbox Cognitive Battery was used to assess performance-based EF. Peripheral inflammation was assessed in fasted sera. Dual-energy X-ray absorptiometry scans were conducted to assess body composition. Linear regression and Hayes' PROCESS Model 4 (Hayes, 2017) were used to evaluate associations between adiposity and inflammation, inflammation and EF, and whether adiposity effects EF through its effect on inflammation. RESULTS: Positive associations were identified between adiposity and inflammation, and negative to null associations were identified between inflammation and EF. Medium indirect effects of adiposity on EF through inflammation were detected. CONCLUSION: Pilot evidence suggests greater adiposity is linked with greater inflammation, which in turn is associated with less EF in some domains. Directionality and causality cannot yet be established, but with replication, findings may inform efforts to target EF in pediatric obesity.

Quantifying and reporting outcome measures in pediatric epilepsy surgery: A systematic review.

Several instruments and outcomes measures have been reported in pediatric patients undergoing epilepsy surgery. The objective of this systematic review is to summarize, evaluate, and quantify outcome metrics for the surgical treatment of pediatric epilepsy that address seizure frequency, neuropsychological, and health-related quality of life (HRQL). We performed a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify publications between 2010 and June 2021 from PubMed, Embase, and the Cochrane Database of Systematic Reviews that report clinical outcomes in pediatric epilepsy surgery. Eighty-one articles were included for review. Overall, rates of postoperative seizure frequency were the most common metric reported (n = 78 studies, 96%). Among the seizure frequency metrics, the Engel Epilepsy Surgery Outcome Scale (n = 48 studies, 59%) was most commonly reported. Neuropsychological outcomes, performed in 32 studies (40%) were assessed using 36 different named metrics. HRQL outcomes were performed in 16 studies (20%) using 13 different metrics. Forty-six studies (57%) reported postoperative changes in antiepileptic drug (AED) regimen, and time-to-event analysis was performed in 15 (19%) studies. Only 13 outcomes metrics (1/5 seizure frequency, 6/13 HRQL, 6/36 neuropsychological) have been validated for use in pediatric patients with epilepsy and only 13 have been assessed through reliability studies (4/5 seizure frequency, 6/13 HRQL, and 3/36 neuropsychological). Of the 81 included studies, 17 (21%) used at least one validated metric. Outcome variable metrics in pediatric epilepsy surgery are highly variable. Although nearly all studies report seizure frequency, there is considerable variation in reporting. HRQL and neuropsychological outcomes are less frequently and much more heterogeneously reported. Reliable and validated outcomes metrics should be used to increase standardization and accuracy of reporting outcomes in pediatric patients undergoing epilepsy surgery.

Self-endorsed cognitive problems versus objectively assessed cognitive impairment in blood or bone marrow transplantation recipients: A longitudinal study.

BACKGROUND: Cognitive impairment in survivors of blood or bone marrow transplantation (BMT) is well documented. However, to the authors' knowledge, the clinical relevance of self-endorsed cognitive problems and their relation to objectively assessed cognitive impairment is not known. METHODS: The authors assessed cognitive impairment in 378 BMT recipients (median age, 52.2 years, 40% of whom were female and 68% of whom were non-Hispanic white) and 98 healthy controls at 5 predetermined time points: at baseline (before BMT) and at 6 months, 1 year, 2 years, and 3 years after BMT. Self-endorsed cognitive problems were evaluated using the Neuropsychological Impairment Scale (NIS) and correlated with a standardized 2-hour battery of objective cognitive testing at each time point. The authors examined the magnitude of difference in self-endorsed cognitive problems between BMT recipients and healthy controls, and the rate of change in scores over time. Multivariable analyses were used to identify clinical and/or demographic variables associated with self-endorsed cognitive problems. The authors also examined the association between cognitive impairment and returning to work after BMT. RESULTS: Compared with healthy controls, BMT recipients endorsed more cognitive problems (P < .001) at all time points, and the rate of change in NIS scores was found to be significantly greater in BMT recipients. Fatigue was associated with greater endorsement of cognitive problems at 1 year after BMT (odds ratio, 4.23; 95% CI, 2.1-8.3 [P < .001]). Overall, there was a statistically significant, modest correlation noted between self-endorsed cognitive problems and objective cognitive impairment (range, 0.401-0.445 [P ≤ .01]). Higher self-endorsed cognitive problems were associated with a 3.7-fold (P = .02) higher odds of not returning to work at 3 years after BMT. CONCLUSIONS: The results of the current study demonstrated that self-endorsed cognitive problems can help to identify vulnerable patient subpopulations for detailed cognitive assessment and possible cognitive remediation.

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).

Tracking of neurocognitive outcomes over time in children with perinatal stroke and associated complex medical conditions: a case series.

Neurocognitive outcomes in children with perinatal stroke are complicated by additional neurological/medical factors. The main objective of this study was to retrospectively examine long-term neurocognitive outcomes in five children with perinatal stroke with increasingly complex comorbidities; ages 5-7 at first evaluation. Results revealed that intelligence and academic skills were significantly decreased in cases with combined perinatal stroke and comorbidities. Early language development was particularly vulnerable to disruption over time in children with increasing medical complexity. The delayed emergence of neurocognitive deficits emphasizes the need for serial assessment of neurocognitive development to identify early services and interventions.

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.

Changes in intrinsic connectivity of the brain's reading network following intervention in children with autism.

While task-based neuroimaging studies have identified alterations in neural circuitry underlying language processing in children with autism spectrum disorders [ASD], resting state functional magnetic resonance imaging [rsfMRI] is a promising alternative to the constraints posed by task-based fMRI. This study used rsfMRI, in a longitudinal design, to study the impact of a reading intervention on connectivity of the brain regions involved in reading comprehension in children with ASD. Functional connectivity was examined using group independent component analysis (GICA) and seed-based correlation analysis of Broca's and Wernicke's areas, in three groups of participants: an experimental group of ASD children (ASD-EXP), a wait list control group of ASD children (ASD-WLC), and a group of typically developing (TD) control children. Both GICA and seed-based analyses revealed stronger functional connectivity of Broca's and Wernicke's areas in the ASD-EXP group postintervention. Additionally, improvement in reading comprehension in the ASD-EXP group was correlated with greater connectivity in both Broca's and Wernicke's area in the GICA identified reading network component. In addition, increased connectivity between the Broca's area and right postcentral and right STG, and the Wernicke's area and LIFG, were also correlated with greater improvement in reading comprehension. Overall, this study revealed widespread changes in functional connectivity of the brain's reading network as a result of intervention in children with ASD. These novel findings provide valuable insights into the neuroplasticity of brain areas underlying reading and the impact of intensive intervention in modifying them in children with ASD.

Reading comprehension improvement in autism.

Introduction: A subset of autistic children excel at word decoding but have difficulty with reading comprehension (i.e., the discrepant poor comprehender reading profile). Prior research suggests the Visualizing and Verbalizing (V/V) for language comprehension and thinking intervention helps improve reading comprehension in autistic children with this reading profile. Previous studies have demonstrated the role of vocabulary, memory, and social functioning in reading comprehension; however, predictors and moderators of reading comprehension within this specific profile of autistic readers have not been thoroughly explored. Methods: In this study, we examined the effectiveness of the V/V intervention by comparing reading comprehension scores between groups and across time. Participants included a sample of autistic children (AUT-EXP; n=22) and a waitlist control group of autistic children (AUT-WLC; n=17) with reading comprehension difficulties, as well as a sample of non-autistic children (Non-AUT; n=26) (all age 8-13 years). AUT-EXP and AUT-WLC groups completed a battery of cognitive assessments during pre and post tests. We also analyzed whether cognitive assessment scores predicted reading comprehension, and examined the moderating effects of group (AUT-EXP vs. AUT-WLC) on these relationships. Results: The AUT-EXP group significantly improved in their pre to post reading comprehension scores (t(21)=4.19, p<.001, d=.89), whereas the AUT-WLC group did not. Verbal memory significantly predicted reading comprehension, though group did not moderate relationships between cognitive test performance and reading comprehension. Discussion: Results suggest that the V/V intervention may help improve reading comprehension for autistic children with the discrepant poor comprehender reading profile. Additionally, strategies for improving verbal memory may indirectly enhance reading comprehension in autistic children with this reading profile.

Volumetric brain assessment of long-term head and neck cancer survivors.

BACKGROUND: Radiation therapy (RT) for locally advanced head and neck cancer (HNC) often exposes subcortical brain structures to radiation. We performed this study to assess region-specific brain volumetrics in a population of long term HNC survivors. METHODS AND MATERIALS: Forty HNC survivors were enrolled at a mean of 6.4 years from completion of RT. Patients underwent a research MRI protocol that included a 3D T1- weighted whole-brain scan on a 3 Tesla MRI scanner. Voxel based morphometry was performed using the Computational Anatomy Toolbox with the Neuromorphometrics atlas. Healthy controls from the Human Connectome Project were used as a comparison cohort. Study participants also completed a comprehensive neurocognitive assessment. RESULTS: The final study cohort consisted of 38 participants after excluding 2 participants due to image quality. HNC survivors displayed widespread reduction in gray matter (GM) brain region volumes that included bilateral medial frontal cortex, temporal lobe, hippocampus, supplemental motor area, and cerebellum. Greater radiation exposure was associated with reduced GM volume in the left ventral diencephalon (r = -0.512, p = 0.003). Associations between cognition and regional GM volumes were identified for motor coordination and bilateral cerebellum (left, r = 0.444, p = 0.009; right, r = 0.372, p = 0.030), confrontation naming and left amygdala (r = 0.382, p = 0.026), verbal memory and bilateral thalamus (left, r = 0.435, p = 0.010; right, r = 0.424, p = 0.012), right amygdala (r = 0.339, p = 0.050), and right putamen (r = 0.364, p = 0.034). CONCLUSIONS: Reductions in GM were observed within this cohort of primarily non-nasopharyngeal HNC survivors as compared to a control sample. GM volumes were associated with performance in multiple cognitive domains. Results of this exploratory study support the need for investigation of anatomic brain changes as an important translational corollary to cognitive problems among HNC survivors.

Longitudinal brain volumetrics in glioma survivors.

OBJECTIVE: Radiation therapy (RT) is used selectively for patients with low-grade glioma (LGG) given the concerns for potential cognitive effects in survivors, but prior cognitive outcome studies among LGG survivors have had inconsistent findings. Translational studies that characterize changes in brain anatomy and physiology after treatment of LGG may help to both contextualize cognitive findings and improve the overall understanding of radiation effects in normal brain tissue. This study aimed to investigate the hypothesis that patients with LGG who are treated with RT will experience greater brain volume loss than those who do not receive RT. METHODS: This retrospective longitudinal study included all patients with WHO grade 2 glioma who received posttreatment surveillance MRI at the University of Alabama at Birmingham. Volumetric analysis of contralateral cortical white matter (WM), cortical gray matter (GM), and hippocampus was performed on all posttreatment T1-weighted MRI sequences using the SynthSeg script. The effect of clinical and treatment variables on brain volumes was assessed using two-level hierarchical linear models. RESULTS: The final study cohort consisted of 105 patients with 1974 time points analyzed. The median length of imaging follow-up was 4.6 years (range 0.36-18.9 years), and the median number of time points analyzed per patient was 12 (range 2-40). Resection was performed in 79 (75.2%) patients, RT was administered to 61 (58.1%) patients, and chemotherapy was administered to 66 (62.9%) patients. Age at diagnosis (ß = -0.06, p < 0.001) and use of RT (ß = -1.12, p = 0.002) were associated with the slope of the contralateral cortical GM volume model (i.e., change in GM over time). Age at diagnosis (ß = -0.08, p < 0.001), midline involvement (ß = 1.31, p = 0.006), and use of RT (ß = -1.45, p = 0.001) were associated with slope of the contralateral cortical WM volume model. Age (ß = -0.0027, p = 0.001), tumor resection (ß = -0.069, p < 0.001), use of chemotherapy (ß = -0.0597, p = 0.003), and use of RT (ß = -0.0589, p < 0.001) were associated with the slope of the contralateral hippocampus volume model. CONCLUSIONS: This study demonstrated volume loss in contralateral brain structures among LGG survivors, and patients who received RT experienced greater volume loss than those who did not. The results of this study may help to provide context for cognitive outcome research in LGG survivors and inform the design of future strategies to preserve cognition.

fMRI reactivity to high-calorie food pictures predicts short- and long-term outcome in a weight-loss program.

Behavioral studies have suggested that food cues have stronger motivating effects in obese than in normal-weight individuals, which may be a risk factor underlying obesity. Previous cross-sectional neuroimaging studies have suggested that this difference is mediated by increased reactivity to food cues in parts of the reward system in obese individuals. To date, however, only a few prospective neuroimaging studies have been conducted to examine whether individual differences in brain activation elicited by food cues can predict differences in weight change. We used functional magnetic resonance imaging (fMRI) to investigate activation in reward-system as well as other brain regions in response to viewing high-calorie food vs. control pictures in 25 obese individuals before and after a 12-week psychosocial weight-loss treatment and at 9-mo follow-up. In those obese individuals who were least successful in losing weight during the treatment, we found greater pre-treatment activation to high-calorie food vs. control pictures in brain regions implicated in reward-system processes, such as the nucleus accumbens, anterior cingulate, and insula. We found similar correlations with weight loss in brain regions implicated by other studies in vision and attention, such as superior occipital cortex, inferior and superior parietal lobule, and prefrontal cortex. Furthermore, less successful weight maintenance at 9-mo follow-up was predicted by greater post-treatment activation in such brain regions as insula, ventral tegmental area, putamen, and fusiform gyrus. In summary, we found that greater activation in brain regions mediating motivational and attentional salience of food cues in obese individuals at the start of a weight-loss program was predictive of less success in the program and that such activation following the program predicted poorer weight control over a 9-mo follow-up period.

fMRI reactivity on a delay discounting task predicts weight gain in obese women.

Obesity can be accompanied by abnormalities in executive function and related neural circuitry. A useful task for studying executive function is delay discounting (DD), in which an individual chooses between sooner and delayed, but greater, amounts of money or other commodities. We previously found that obese compared to normal-weight women made more immediate choices on a monetary DD task, or had greater delay discounting. In the present study, we performed functional magnetic resonance imaging (fMRI) of obese women during performance of a DD of money task. Confirming the results of previous studies, we found that more difficult compared to easy DD trials resulted in activation in putative executive function areas of the brain, the middle and inferior frontal gyri, and medial prefrontal cortex. Most interestingly, we also found that less activation in executive function areas such as the inferior, middle, and superior frontal gyri on difficult vs. easy DD trials predicted a greater rate of weight gain over the subsequent 1.3-2.9 years. These results suggest that suboptimal functioning of executive function areas such as prefrontal cortex contributes to the progression of obesity.

Processing efficiency in pediatric cancer survivors: A review and operationalization for outcomes research and clinical utility.

OBJECTIVE: Childhood cancer and cancer-related treatments disrupt brain development and maturation, placing survivors at risk for cognitive late effects. Given that assessment tools vary widely across researchers and clinicians, it has been daunting to identify distinct patterns in outcomes across diverse cancer types and to implement systematic neurocognitive screening tools. This review aims to operationalize processing efficiency skill impairment-or inefficient neural processing as measured by working memory and processing speed abilities-as a worthwhile avenue for continued study within the context of childhood cancer. METHODS: A comprehensive literature review was conducted to examine the existing research on cognitive late effects and biopsychosocial risk factors in order to conceptualize processing efficiency skill trends in childhood cancer survivors. RESULTS: While a frequently reported pattern of neurobiological (white matter) and cognitive (working memory and processing speed) disruption is consistent with processing efficiency skill impairment, these weaknesses have not yet been fully operationalized in this population. We offer a theoretical model that highlights the impacts of a host of biological and environmental factors on the underlying neurobiological substrates of cancer survivors that precede and may even predict long-term cognitive outcomes and functional abilities following treatment. CONCLUSION: The unified construct of processing efficiency may be useful in assessing and communicating neurocognitive skills in both outcomes research and clinical practice. Deficits in processing efficiency may serve as a possible indicator of cognitive late effects and functional outcomes due to the unique relationship between processing efficiency skills and neurobiological disruption following cancer treatment. Continued research along these lines is crucial for advancing childhood cancer outcomes research and improving quality of life for survivors.

Prevalence of attention-deficit/hyperactivity disorder and intellectual disability among children with hydrocephalus.

OBJECTIVE: Little is known about the prevalence of attention-deficit/hyperactivity disorder (ADHD) in children with hydrocephalus. In this study, the authors assessed the prevalence of ADHD and its association with clinical and demographic factors, including intellectual disability (ID), a potential factor that can confound the diagnosis of ADHD. METHODS: The authors conducted a cross-sectional study of children 6-12 years of age with hydrocephalus using parent telephone surveys. The Child and Adolescent Intellectual Disability Screening Questionnaire (CAIDS-Q) and the National Institute for Children's Health Quality (NICHQ) Vanderbilt Assessment Scale were used to screen for ID and ADHD, respectively. Among children without ID, the authors identified those with ADHD and calculated a prevalence estimate and 95% confidence interval (Wald method). Logistic regression analysis was conducted to compare children with ADHD with those without ADHD based on demographics, family income, parental educational, etiology of hydrocephalus, and primary treatment. As a secondary analysis, the authors compared subjects with ID with those without using the same variables. Multivariable analysis was used to identify factors with independent association with ADHD and ID. RESULTS: A total of 147 primary caregivers responded to the telephone questionnaire. Seventy-two children (49%) met the cutoff score for ID (CAIDS-Q). The presence of ID was significantly associated with lower family income (p < 0.001). Hydrocephalus etiology (p = 0.051) and initial treatment (p = 0.06) approached significance. Of children without ID (n = 75), 25 demonstrated a likely diagnosis of ADHD on the NICHQ, yielding a prevalence estimate of 0.33 (95% CI 0.22-0.44). No clinical or demographic variable showed significant association with ADHD. CONCLUSIONS: These data indicate that the prevalence of ADHD among children with hydrocephalus (33%) is higher than among the general population (estimated prevalence in Alabama is 12.5%). ID is also common (49%). Routine screening for ADHD and ID in children with hydrocephalus may help to ensure that adequate resources are provided to optimize functional outcomes across development.

A biobehavioural and social-structural model of inflammation and executive function in pediatric chronic health conditions.

ABSTRACTEvidence indicates that pediatric chronic health conditions (CHCs) often impair executive functioning (EF) and impaired EF undermines pediatric CHC management. This bidirectional relationship likely occurs due to biobehavioural and social-structural factors that serve to maintain this feedback loop. Specifically, biobehavioural research suggests that inflammation may sustain a feedback loop that links together increased CHC severity, challenges with EF, and lower engagement in health promoting behaviours. Experiencing social and environmental inequity also maintains pressure on this feedback loop as experiencing inequities is associated with greater inflammation, increased CHC severity, as well as challenges with EF and engagement in health promoting behaviours. Amidst this growing body of research, a model of biobehavioural and social-structural factors that centres inflammation and EF is warranted to better identify individual and structural targets to ameliorate the effects of CHCs on children, families, and society at large. This paper proposes this model, reviews relevant literature, and delineates actionable research and clinical implications.

Clinical Presentation, Risk Factors, and Outcomes of Immune Effector Cell-Associated Neurotoxicity Syndrome Following Chimeric Antigen Receptor T Cell Therapy: A Systematic Review.

Chimeric antigen receptor (CAR) T cell therapy is a novel therapy for patients with relapsed or refractory hematologic malignancies. Most CAR T cell therapy recipients will experience clinical features of the immune effector cell-associated neurotoxicity syndrome (ICANS), a potentially life-threatening condition. Here we describe the clinical, biological, and radiological findings associated with ICANS in adults with hematologic malignancies treated with CAR T cell therapy, as well as the acute and long-term outcomes of ICANS. A literature search of Ovid Medline, Embase, PubMed, Scopus, Web of Science Core Collection, Cochrane Library, and Google Scholar was conducted from each database's inception through February 1, 2022, using search terms reflecting CAR T cell therapy and ICANS. We included studies that enrolled adults (age ≥18 years) who received CAR T cell therapy as management for hematologic malignancies and reported the clinical presentation, predictors, and/or acute or long-term outcomes of ICANS. Two reviewers independently extracted data following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) reporting guidelines. Quality was assessed using the Joanna Briggs Institute critical appraisal tool for cohort studies. Of the 2928 studies screened, 23 observational studies (10 prospective, 11 retrospective, 1 mixed design, and 1 cross-sectional) with a total of 1666 participants met our eligibility criteria and were included in our review. The most common hematologic malignancies were diffuse large B cell lymphoma, acute lymphocytic leukemia, non-Hodgkin lymphoma, and chronic lymphocytic leukemia. ICANS onset was most often associated with the presence and severity of cytokine release syndrome, as well as with C-reactive protein and ferritin levels. Aphasia was the most common ICANS-related symptom reported, although the neurologic manifestations of ICANS were highly variable. Neuroimaging studies (magnetic resonance imaging or computed tomography) were often normal in cases of ICANS; however, electroencephalography often showed generalized background slowing, abnormal rhythmic, and periodic discharge patterns. The pooled mean (± SD) onset of ICANS was 6.4 ± 3.2 days, with a pooled mean duration of 8.3 ± 10.5 days. Two of the 23 studies (9%) reported 5 ICANS-related deaths among 233 participants. A subset of patients experienced persistent neurocognitive complaints at ≥1-year after CAR T cell therapy. The clinical presentation, onset, severity, long-term sequelae, and grading system of ICANS are variable. Future studies should consider using a consensus grading/reporting scale that would permit cross-trial comparisons of the safety profile of various CAR T cell products and enable the development of interventions to mitigate or manage these neurotoxicities. © 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. This systematic review was conducted according to a published protocol (PROSPERO CRD42020207864) and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and Synthesis without Meta-Analysis (SWiM) in systematic review reporting guidelines (Supplementary Table S1) [15,16].