Exploring early life social and executive function development in infants and risk for autism: a prospective cohort study protocol of NICU graduates and infants at risk for cerebral palsy.

BACKGROUND: Delays in early social and executive function are predictive of later developmental delays and eventual neurodevelopmental diagnoses. There is limited research examining such markers in the first year of life. High-risk infant groups commonly present with a range of neurodevelopmental challenges, including social and executive function delays, and show higher rates of autism diagnoses later in life. For example, it has been estimated that up to 30% of infants diagnosed with cerebral palsy (CP) will go on to be diagnosed with autism later in life. METHODS: This article presents a protocol of a prospective longitudinal study. The primary aim of this study is to identify early life markers of delay in social and executive function in high-risk infants at the earliest point in time, and to explore how these markers may relate to the increased risk for social and executive delay, and risk of autism, later in life. High-risk infants will include Neonatal Intensive Care Unit (NICU) graduates, who are most commonly admitted for premature birth and/or cardiovascular problems. In addition, we will include infants with, or at risk for, CP. This prospective study will recruit 100 high-risk infants at the age of 3-12 months old and will track social and executive function across the first 2 years of their life, when infants are 3-7, 8-12, 18 and 24 months old. A multi-modal approach will be adopted by tracking the early development of social and executive function using behavioural, neurobiological, and caregiver-reported everyday functioning markers. Data will be analysed to assess the relationship between the early markers, measured from as early as 3-7 months of age, and the social and executive function as well as the autism outcomes measured at 24 months. DISCUSSION: This study has the potential to promote the earliest detection and intervention opportunities for social and executive function difficulties as well as risk for autism in NICU graduates and/or infants with, or at risk for, CP. The findings of this study will also expand our understanding of the early emergence of autism across a wider range of at-risk groups.

Mathematics Skills in Epilepsy: A Systematic Review and Meta-Analysis.

Mathematics incorporates a broad range of skills, which includes basic early numeracy skills, such as subitizing and basic counting to more advanced secondary skills including mathematics calculation and reasoning. The aim of this review was to undertake a detailed investigation of the severity and pattern of early numeracy and secondary mathematics skills in people with epilepsy. Searches were guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Twenty adult studies and 67 child studies were included in this review. Overall, meta-analyses revealed significant moderate impairments across all mathematics outcomes in both adults (g= -0.676), and children (g= -0.593) with epilepsy. Deficits were also observed for specific mathematics outcomes. For adults, impairments were found for mathematics reasoning (g= -0.736). However, two studies found that mathematics calculation was not significantly impaired, and an insufficient number of studies examined early numeracy skills in adults. In children with epilepsy, significant impairments were observed for each mathematics outcome: early numeracy (g= -0.383), calculation (g= -0.762), and reasoning (g= -0.572). The gravity of impairments also differed according to the site of seizure focus for children and adults, suggesting that mathematics outcomes were differentially vulnerable to the location of seizure focus.

Working Memory in Pediatric Epilepsy: A Systematic Review and Meta-Analysis.

Working memory is a multicomponent system that is supported by overlapping specialized networks in the brain. Baddeley's working memory model includes four components: the phonological loop, visuo-spatial sketchpad, the central executive, and episodic buffer. The aim of this review was to establish the gravity and pattern of working memory deficits in pediatric epilepsy. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guided electronic searches. Sixty-five studies were included in the review. Meta-analyses revealed significant impairments across each working memory component: phonological loop (g = 0.739), visuo-spatial sketchpad (g = 0.521), and central executive (g = 0.560) in children with epilepsy compared to controls. The episodic buffer was not examined. The pattern of impairments, however, differed according to the site and side of seizure focus. This suggests that working memory components are differentially vulnerable to the location of seizure focus in the developing brain.

The persistence of sleep disturbance and its correlates in children with moderate to severe traumatic brain injury: A longitudinal study.

OBJECTIVES: The primary aim was to examine whether sleep disturbances persist in children in the chronic stage of recovery from moderate or severe traumatic brain injury (TBI). The secondary aim was to examine whether memory difficulties and/or other previously identified factors relate to sleep disturbances in children with moderate to severe TBI. METHODS: This longitudinal study included 21 children with moderate to severe TBI, 8-18 years old, recruited from an urban tertiary paediatric specialised brain injury rehabilitation unit. Participants were seen 5 years and again 7 years post-injury, on average. Sleep disturbances were assessed with Sleep Disturbance Scale for Children (SDSC). Correlates that were considered included indicators of TBI severity, and questionnaires assessing everyday memory, fatigue, internalizing and externalizing behaviors and pain intensity. RESULTS: The SDSC scores of children with moderate to severe TBI indicated greater disturbances in initiating and maintaining sleep, arousal, sleep-wake transition, and excessive somnolence relative to the norms, at follow-up. The mean SDSC scores and the number of participants with subclinical to clinical sleep disturbances on the SDSC remained unchanged from baseline to follow-up. At follow-up, the SDSC initiating and maintaining sleep, and excessive somnolence scales were associated with poorer everyday memory and greater fatigue. CONCLUSIONS: Children with moderate to severe TBI experience ongoing sleep disturbances for years post-injury. Greater sleep disturbances are associated with worse functional outcomes. Further research into sleep disturbances and development of treatments is important, as it could improve the outcomes of children with TBI.

A feasibility and acceptability study of cognitive behavioural treatment for insomnia in adolescents with traumatic brain injury: A-B with follow up design, randomized baseline, and replication across participants.

Difficulties falling asleep or staying asleep (symptoms of insomnia) are common following paediatric traumatic brain injury (TBI). Yet, interventions to treat insomnia in this population have not yet been reported. This single-case series examined the feasibility and acceptability of cognitive behavioral treatment for insomnia (CBT-I) for adolescents (n = 5, aged 11-13 years) with TBI, and explored changes in sleep and fatigue post-treatment. Adolescents were randomly assigned to two conditions: a 7- or 14-days baseline, followed by 4 weeks of manualised CBT-I delivered individually. To assess feasibility and acceptability we compared recruitment and retention rates, and questionnaire scores to a-priori set criteria. We explored treatment efficacy and functional gains in sleep and fatigue from baseline to follow-up using structured visual analysis of time-series graphs, and reliable change indices or changes in clinical classification. Feasibility and acceptability indicators met a-priori criteria, but therapists noticed limited adolescent engagement in sessions. Clinically significant improvements were found in sleep, in 3 out of 4 cases, and fatigue, in all cases. Our study provides preliminary evidence that CBT-I is feasible for insomnia treatment in adolescents with TBI and provides directions for development of future treatment studies.

Longitudinal changes in emotional functioning following pediatric resective epilepsy surgery: 2-Year follow-up.

OBJECTIVE: To examine longitudinal changes and predictors of depression and anxiety 2 years following resective epilepsy surgery, compared to no surgery, in children with drug-resistant epilepsy (DRE). METHOD: This multicenter cohort study involved 128 children and adolescents with DRE (48 surgical, 80 nonsurgical; 8-18 years) who completed self-report measures of depression and anxiety at baseline and follow-up (6-month, 1-year, 2-year). Child demographic (age, sex, IQ) and seizure (age at onset, duration, frequency, site and side) variables were collected. RESULTS: Linear mixed-effects models controlling for age at enrolment found a time by treatment by seizure outcome interaction for depression. A negative linear trend across time (reduction in symptoms) was found for surgical patients, irrespective of seizure outcome. In contrast, the linear trend differed depending on seizure outcome in nonsurgical patients; a negative trend was found for those with continued seizures, whereas a positive trend (increase in symptoms) was found for those who achieved seizure freedom. Only a main effect of time was found for anxiety indicating a reduction in symptoms across patient groups. Multivariate regressions failed to find baseline predictors of depression or anxiety at 2-year follow-up in surgical patients. Older age, not baseline anxiety or depression, predicted greater symptoms of anxiety and depression at 2-year follow-up in nonsurgical patients. CONCLUSION: Children with DRE reported improvement in anxiety and depression, irrespective of whether they achieve seizure control, across the 2 years following surgery. In contrast, children with DRE who did not undergo surgery, but achieved seizure freedom, reported worsening of depressive symptoms, which may indicate difficulty adjusting to life without seizures and highlight the potential need for ongoing medical and psychosocial follow-up and support.

Changes in caregiver depression, anxiety, and satisfaction with family relationships in families of children who did and did not undergo resective epilepsy surgery.

OBJECTIVE: To evaluate longitudinal changes in caregiver depression, anxiety, and family relationships following resective surgery for pediatric drug-resistant epilepsy (DRE). METHODS: This multicenter cohort study involved 177 caregivers of children with DRE aged 4-18 years (63 surgical and 114 nonsurgical). Caregivers completed measures of depression (Quick Inventory of Depressive Symptomatology), anxiety (Generalized Anxiety Disorder 7-item scale), and satisfaction with family relationships (Family Adaptability, Partnership, Growth, Affective, and Resolve scale) at baseline, 6 months, and 1 year. Additional data collected at baseline included child, caregiver, and family sociodemographic and clinical factors as well as family environment (demands and resources). RESULTS: At 1 year, 64% and 27% of surgical and nonsurgical patients were seizure-free, respectively. Linear mixed-effects models found a reduction in caregiver depression (b = -0.85, P = .004) and anxiety (b = -1.09, P = .003), but not family satisfaction (b = 0.18, P = .31) over time. There was no effect of treatment. When seizure outcome was added to the model, seizure freedom was associated with fewer depressive symptoms (b = -1.15, P = .005) and greater family satisfaction (b = 0.65, P = .006), but not anxiety (b = -0.41, P = .42). A greater proportion of caregivers of patients who achieved seizure freedom (32%) versus continued seizures (18%) reported clinically meaningful improvement in depression at 1 year (P = .03). Lower baseline depression (ß = 0.42, P < .001), greater family resources (ß = -0.18, P = .04), and male caregiver (ß = 0.15, P = .02) predicted lower caregiver depression, and lower baseline anxiety (ß = 0.47, P < .001), greater family resources (ß = -0.24, P = .01), and higher education (ß = -0.13, P = .04) predicted lower caregiver anxiety at 1 year. Baseline functioning was the only predictor of family relationships at 1 year (ß = 0.49, P < .001). SIGNIFICANCE: Caregivers of children who achieved seizure freedom, irrespective of surgical treatment, report fewer depressive symptoms and greater satisfaction with family relationships. Baseline functioning is the strongest predictor of outcome; however, caregivers of families with fewer resources and supports are also at risk of poor psychosocial outcomes.

Family resources moderate the relationship between seizure control and health-related quality of life in children with drug-resistant epilepsy.

OBJECTIVE: Pediatric drug-resistant epilepsy (DRE) is associated with poor health-related quality of life (HRQOL). Achieving seizure control, however, does not improve HRQOL in all children. This study sought to evaluate whether (1) baseline caregiver and family factors are associated with child HRQOL at 1-year follow-up over and above epilepsy characteristics, treatment, and seizure outcome; and (2) baseline family factors moderate the association between seizure outcome and child HRQOL at 1-year follow-up. METHODS: This multicenter longitudinal cohort study recruited 152 children with DRE who were being evaluated for surgical candidacy. Child HRQOL was rated by caregivers using the Quality of Life in Childhood Epilepsy Questionnaire at baseline and 1-year follow-up. Additional data collected at baseline included child epilepsy characteristics, caregiver demographics, caregiver mood, and family environment. RESULTS: Seizure freedom was achieved in 68% and 28% of patients 1 year after surgery and medical treatment, respectively. Caregiver and family factors were not associated with higher child HRQOL at follow-up after accounting for epilepsy characteristics, treatment, seizure outcome, and baseline child HRQOL, F11, 131  = 1.34, P = .21, ΔR2  = .04. Family resources moderated the association between seizure outcome and child HRQOL at follow-up (b = .41, 95% confidence interval [CI] = 0.09-0.74, P = .03); seizure freedom was strongly associated with higher HRQOL when family resources were high (b = 13.50, 95% CI = 8.35-18.54, P < .001), relative to when family resources were low (b = 5.17, 95% CI = -0.18 to 10.52, P = .06). Family relationships and demands did not moderate the relationship between seizure outcome and HRQOL. SIGNIFICANCE: Achieving seizure freedom was associated with better HRQOL in children with DRE, but this association was reduced for those children who presented with limited family resources. These results highlight the importance of assessing the family environment during presurgical evaluation and implementing early family-based intervention and supports to promote better outcomes for children in the long term.

Behavioral interventions for sleep disturbances in children with neurological and neurodevelopmental disorders: a systematic review and meta-analysis of randomized controlled trials.

STUDY OBJECTIVES: Sleep disturbances are common and associated with negative functional and health consequences in children with neurological and neurodevelopmental disorders (NNDDs) and represent an important potential target for behavioral interventions. This systematic review examined the efficacy of behavioral sleep interventions (BSIs) for children with NNDDs and comorbid sleep disturbances. METHODS: A systematic search of MEDLINE, EMBASE, PsychINFO, and CENTRAL was conducted in April 2019. Randomized controlled trials (RCTs) of BSI for children with NNDDS were included. Meta-analysis and GRADE quality ratings were performed on sleep and secondary functional outcomes (cognition, academics, and behavior). RESULTS: Nine RCTs were identified (n = 690; Mage = 8.39 ±â€…2.64years; 71.11% male). The quality of the evidence was predominantly rated as moderate. Posttreatment improvements in sleep were found on self-reported sleep disturbances (total sleep disturbance [standardized mean difference, i.e. SMD = 0.89], night wakings [SMD = 0.52], bedtime resistance [SMD = 0.53], parasomnias [SMD = 0.34], sleep anxiety [SMD = 0.50]) and self-reported sleep patterns (sleep duration [SMD = 0.30], sleep onset duration [SMD = 0.75]) and (2) objectively measured actigraphic sleep patterns (total sleep time [MD = 18.09 min; SMD = 0.32], sleep onset latency [MD = 11.96 min; SMD = 0.41]). Improvements in sleep (self-reported, not actigraphy) were maintained at follow-up, but few studies conducted follow-up assessments resulting in low-quality evidence. Reduction in total behavioral problems (SMD = 0.48) posttreatment and attention/hyperactivity (SMD = 0.28) at follow-up was found. Changes in cognition and academic skills were not examined in any studies. CONCLUSIONS: BSIs improve sleep, at least in the short term, in children with NNDDs. Benefits may extend to functional improvements in behavior. More rigorous RCTs involving placebo controls, blinded outcome assessment, longer follow-up durations, and assessment of functional outcomes are required.

Impact of resective surgery for pediatric drug-resistant epilepsy on emotional functioning.

OBJECTIVE: The objective of the study was to evaluate emotional functioning following surgical and medical treatment in children with drug-resistant epilepsy (DRE; i.e., uncontrolled seizures despite treatment with ≥2 antiepileptic drugs [AED]). METHOD: This prospective, longitudinal, multicenter study involved 128 children and adolescents (8-18 years) with DRE who were assessed for surgical candidacy; 48 went on to have surgery and 80 continued medical treatment. Participants completed child-validated self-report measures of anxiety and depression at baseline, 6, and 12 month follow-up. Standardized z-scores were calculated with higher scores indicative of greater symptoms. RESULTS: At baseline, 16% and 22% of all patients reported elevated symptoms of depression and anxiety, respectively (i.e., z ≥ 1.00). Seizure freedom was higher in the surgical, compared with the medical, group at 6 (64 vs. 11%) and 12 month (77 vs. 24%) follow-up. Linear mixed effects models controlling for age found a main effect of time for both depression and anxiety; scores decreased over time for all patients. A main effect of seizure outcome was found for depression, but not anxiety; seizure freedom was associated with lower scores overall. There were no main effects of treatment or significant interactions. Multiple regression analyses found baseline mood predicted outcomes at 6 and 12 month follow-up; higher anxiety and depression scores at baseline were associated with higher scores at follow-up. Older age and greater number of AEDs at baseline was associated with higher depression scores at 12 month follow-up. CONCLUSION: Overall, patients reported a reduction in anxiety and depressive symptoms over the first 12 months, irrespective of treatment, and baseline level of functioning was the best predictor of outcome. Despite more children achieving seizure freedom with surgery compared with medical treatment, surgery was not associated with better outcomes over time. It may be that changes in anxiety and depression require a longer time to emerge postsurgery; however, being seizure-free is associated with fewer depressive symptoms, irrespective of treatment type.

Risk assessment of self- and other-directed aggression in adolescent psychiatric inpatient units.

OBJECTIVE: To examine the predictive validity of unstructured clinical risk assessment and associated risk factors for aggression in predicting self- and other-directed aggression in the first 4 weeks of admission for patients admitted to an Australian adolescent psychiatric inpatient facility. METHOD: A retrospective review of patient records was conducted at the Marian Drummond Adolescent Unit during late 2009 for the period of September 2006 to July 2009. Information collected included admission risk assessment ratings, aggressive incident reports, patient diagnoses, sex and history of aggression and self-harming behaviour. RESULTS: A total of 193 adolescents (aged 13-18 years old) were included in retrospective analyses. The hypothesis that unstructured clinical risk assessment would be predictive of self- and other-directed aggression was partially supported. High risk assessment scores were predictive of engagement in other-directed aggression. A history of physical aggression was also found to be predictive of engagement in other-directed aggression; however, it was not as predictive as the risk assessment rating. High risk assessment scores were not predictive of self-directed aggression. A history of engaging in one or more acts of self-harm or suicide was the most predictive of engagement in self-directed aggression during inpatient stay. Female sex also predicted engagement in self-directed aggression. CONCLUSIONS: Based on professional expertise, prior experience and intuition, clinicians are relatively good predictors of other-directed aggression in adolescent inpatient units; however, they are less successful at predicting self-directed aggression in this population. It is possible that, unlike other-directed aggression, self-harming behaviour is heavily dependent on environmental factors and that admission to the inpatient unit removes these triggers from the individual's environment.