Neurodevelopmental Diagnoses Research Articles

The Neurodevelopmental and Motor Phenotype of SCA21 (ATX-TMEM240).

Spinocerebellar ataxia type 21 (SCA21/ATX-TMEM240) is a rare form of cerebellar ataxia that commonly presents with motor, cognitive, and behavioral impairments. Although these features have been identified as part of the clinical manifestations of SCA21, the neurodevelopmental disorders associated with SCA21 have not been well studied or described. Here we present extensive phenotypic data for 3 subjects from an SCA21 family in the United States. Genetic testing demonstrated the c.196 G>A (p.Gly66Arg) variant to be a second recurrent mutation associated with the disorder. Standardized developmental assessment revealed significant deficits in cognition, adaptive function, motor skills, and social communication with 2 of the subjects having diagnoses of autism spectrum disorder, which has never been described in SCA21. Quantitative gait analysis showed markedly abnormal spatiotemporal gait variables indicative of poor gait control and cerebellar as well as noncerebellar dysfunction. Clinical evaluation also highlighted a striking variability in clinical symptoms, with greater ataxia correlating with greater severity of neurodevelopmental disorder diagnoses. Notably, neurodevelopmental outcomes have improved with intervention over time. Taken together, this case series identifies that the manifestation of neurodevelopmental disorders is a key feature of SCA21 and may precede the presence of motor abnormalities. Furthermore, the coexistence of ataxia and neurodevelopmental disorders in these subjects suggests a role for spinocerebellar pathways in both outcomes. The findings in this study highlight the importance of evaluation of neurodevelopmental concerns in the context of progressive motor abnormalities and the need for timely intervention to ultimately improve quality of life for individuals with SCA21.

Quantitative genome-wide association analyses of receptive language in the Danish High Risk and Resilience Study

BackgroundOne of the most basic human traits is language. Linguistic ability, and disability, have been shown to have a strong genetic component in family and twin studies, but molecular genetic studies of language phenotypes are scarce, relative to studies of other cognitive traits and neurodevelopmental phenotypes. Moreover, most genetic studies examining such phenotypes do not incorporate parent-of-origin effects, which could account for some of the heritability of the investigated trait. We performed a genome-wide association study of receptive language, examining both child genetic effects and parent-of-origin effects.ResultsUsing a family-based cohort with 400 children with receptive language scores, we found a genome-wide significant paternal parent-of-origin effect with a SNP, rs11787922, on chromosome 9q21.31, whereby the T allele reduced the mean receptive language score by ~ 23, constituting a reduction of more than 1.5 times the population SD (P = 1.04 × 10−8). We further confirmed that this association was not driven by broader neurodevelopmental diagnoses in the child or a family history of psychiatric diagnoses by incorporating covariates for the above and repeating the analysis.ConclusionsOur study reports a genome-wide significant association for receptive language skills; to our knowledge, this is the first documented genome-wide significant association for this phenotype. Furthermore, our study illustrates the importance of considering parent-of-origin effects in association studies, particularly in the case of cognitive or neurodevelopmental traits, in which parental genetic data are not always incorporated.

'That thing in his head': Aboriginal and non-Aboriginal Australian caregiver responses to neurodevelopmental disability diagnoses.

Little is known about the significance of cultural differences to how caregivers receive a diagnosis of neurodevelopmental disability. As part of a Fetal Alcohol Spectrum Disorder prevalence study among sentenced, detained youth, our qualitative study explored the experiences of diagnostic assessment among detained young people and their caregivers. We present findings from the perspectives of caregivers. In conversation with the sociology of diagnosis literature, we present vignettes of three Aboriginal and two non-Aboriginal caregivers' experiences of the diagnostic assessment process. We found that Aboriginal caregivers conceptualised their children's diagnosis and ongoing management in the context of their family networks and community. In contrast, non-Aboriginal caregivers focused on how the diagnosis would affect their child and interactions with various institutions including healthcare systems and schools. Caregivers' engagement with diagnostic reports and resources also followed cultural lines. Reflections on intergenerational drinking were voiced by Aboriginal caregivers, who expressed shame at receiving diagnosis. These findings advance our appreciation of cultural difference in receiving a diagnosis, the examination of which is in its nascent stages. We also suggest ways to mitigate harm from a stigmatising diagnosis and soften the well-established effects of medical dominance over the process of defining a person's capacity and status.

4107 Implementation and evaluation of a novel protocol that uses clinical biomarkers to promote early diagnosis and treatment of Neurodevelopmental Disabilities

OBJECTIVES/GOALS: Our objective was to establish a new protocol to evaluate new biomarkers to detect Neurodevelopmental Disabilities (NDD) in high-risk infants. As early intervention results in better outcomes, our goal was to implement the protocol to promote earlier NDD diagnosis and referral for treatment. METHODS/STUDY POPULATION: We implemented a new protocol using the General Movement Assessment (GMA), Hammersmith Infant Neurological Examination (HINE), and Capute Scales to evaluate infants who were at high risk of NDD. To determine the success of our protocol with these biomarkers, we studied former premature infants who were evaluated in follow-up clinic from 10/1/2018-10/1/2019. We defined our primary and secondary outcomes as the ages of neurodevelopmental diagnoses and referral to early intervention services before and after implementation of the new protocol, respectively. Our hypotheses were that infants who were evaluated with these biomarkers would be diagnosed with NDD and be referred for treatment at younger ages than their counterparts. RESULTS/ANTICIPATED RESULTS: Approximately 120 patients were evaluated during the time period that was defined. About half were evaluated prior to implementing the GMA and HINE, and the remainder were evaluated using GMA and other developmental measures. We anticipate that infants who underwent GMA will be diagnosed with NDD and referred for therapies at a younger age than their counterparts. DISCUSSION/SIGNIFICANCE OF IMPACT: Through our translational research, we will transform the standard of care for high-risk infants by incorporating clinical biomarkers into day-to-day clinical care for these infants. Implementation of this novel protocol will promote the early diagnosis and referral to treatment for NDD.

Unplanned Readmissions of Children With Epilepsy in the United States

BackgroundThe burden and characteristics of unplanned readmission after epilepsy-related discharge in children in the United States is not known. MethodsWe undertook a retrospective cohort study of children aged one to 17 years discharged after a nonelective hospitalization for epilepsy, sampled from the Healthcare Cost and Utilization Project’s 2013 and 2014 Nationwide Readmissions Database. Descriptive statistics and logistic regression models were used to examine the characteristics of initial hospitalization and risk factors for readmission. ResultsA total of 42,873 admissions for unique patients were identified, with 4470 (10.4%) leading to readmission within 30 days. The most common readmission diagnosis was epilepsy (24.9%). Neurodevelopmental diagnoses including cerebral palsy, intellectual disability, and developmental delay were associated with increased odds of readmission. Longer hospitalization, gastrostomy, and tracheostomy were also associated with readmission, but continuous electroencephalography use was not. Children insured by Medicare had a readmission rate of 34.4%, whereas there were no associations of readmission with other sociodemographic characteristics such as neighborhood, income, and sex. ConclusionsSeizures are among the most frequent reasons for hospitalization in children. Establishing a benchmark readmission rate for pediatric epilepsy of 10.4% may be useful to health systems designing quality improvement efforts. Clinical factors were more strongly associated with readmission than demographic characteristics. Interventions to reduce pediatric epilepsy readmissions may have the highest yield when targeting children with neurodevelopmental comorbidities.

Dynamical properties of elemental metabolism distinguish attention deficit hyperactivity disorder from autism spectrum disorder

Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are neurodevelopmental conditions of overlapping etiologies and phenotypes. For ASD, we recently reported altered elemental metabolic patterns in the form of short and irregular zinc and copper cycles. Here, we extend the application of these biomarkers of prenatal and early postnatal elemental metabolism to distinguish between individuals diagnosed with ADHD and/or ASD and neurotypical controls. We recruited twins discordant for ADHD, ASD and other neurodevelopmental diagnoses from national twin studies in Sweden (N = 74) diagnosed according to DSM-5 clinical consensus and standardized psychiatric instruments. Detailed temporal profiles of exposure to 10 metals over the prenatal and early childhood periods were measured using tooth biomarkers. We used recurrence quantification analysis (RQA) to characterize properties of cyclical metabolic patterns of these metals. Regularity (determinism) and complexity (entropy) of elemental cycles was consistently reduced in ADHD for cobalt, lead, and vanadium (determinism: cobalt, β = −0.03, P = 0.017; lead, β = −0.03, P = 0.016; and vanadium, β = −0.03, P = 0.01. Entropy: cobalt, β = −0.13, P = 0.017; lead, β = −0.18, P = 0.016; and vanadium, β = −0.15, P = 0.008). Further, we found elemental pathways and dynamical features specific to ADHD vs ASD, and unique characteristics associated with ADHD/ASD combined presentation. Dysregulation of cyclical processes in elemental metabolism during prenatal and early postnatal development not only encompasses pathways shared by ADHD and ASD, but also comprise features specific to either condition.

Description of Young Children With Idiopathic Sensory Processing Disorder

Abstract Date Presented 04/05/19 A retrospective, nonexperimental design was conducted to explore and describe the characteristics of children ages two through seven years identified as having sensory processing deficits but no other specific neurodevelopmental or behavioral diagnoses. Relations among specific types of sensory processing disorder, adaptive behavior, and psychosocial-emotional functioning were also identified to increase our understanding of sensory processing disorder as its own diagnostic entity. Primary Author and Speaker: Shelley Mulligan Additional Authors and Speakers: Sarah Douglas

B-50 Frequency of Sports-Related Concussion in Athletes with Neurodevelopmental Conditions

Abstract Objective Research demonstrates that athletes with neurodevelopmental diagnoses may have a higher frequency of lifetime concussions (Iverson et al., 2016; Alosco, Fedor & Gunstad, 2014) possibly due to underlying attention, processing speed, or reaction time difficulties. The present study investigates concussion history and sports-related concussions between athletes with and without a history of neurodevelopmental disorders in a longitudinal, state-wide sample. Method Participants included 39,586 high school athletes (Mage = 15.18; 56.2% males) who were assessed pre and post-concussion with ImPACT between 2008 and 2016. There were 36,880 athletes (55.1% males) who did not report neurodevelopmental disorders and served as the control group and 2,706 athletes (71.4% males) in the clinical group who self-reported diagnosis of ADHD (55.6%), Learning Disability (LD;13.6%), Autism (3.2%), ADHD+LD (4.5%), and athletes in special education but no reported diagnosis (SpEd; 22%). Concussion frequency in each group was analyzed using chi-square analysis. Results Athletes were more likely to report prior concussions if they had a self-reported neurodevelopmental diagnosis (17%) compared to the control group (9%, χ2(1) = 112.11, p < .001). Odds ratios indicated that athletes with neurodevelopmental conditions were 1.43 times more likely to have a sports-related concussion. Conclusions Consistent with past research, results indicate that neurodevelopmental conditions are associated with greater lifetime risk of concussion, including sport-related concussions. Future studies may expand this research by examining underlaying causes of this increased risk in order to develop specific interventions to help reduce rates of concussion for this population.

B-55 Performance of ImPACT Validity Indices for Athletes with Neurodevelopmental Disorders

Abstract Objective Research demonstrates neurodevelopmental diagnoses may increase likelihood of failing scores on ImPACT embedded validity indicators that flag questionable effort. New criteria have been proposed to enhance sensitivity of these indicators although their utility in athletes with neurodevelopmental diagnosis have not been thoroughly examined. This study investigates the effect of neurodevelopmental history on frequency of invalid performance on the standard and three proposed validity indicators. Methods Participants included 41,214 high school athletes (Mage = 15.1; 44.2% female; Meducation = 9.1) who completed baseline ImPACT testing. Athletes included these groups: ADHD (3.7%), Learning Disability (LD; 1.5%), Autism (0.2%), ADHD+LD (0.6%), Autism+ADHD/LD (0.1%), athletes with special education history but no diagnosis reported (SpEd; 2.8%), and healthy athletes (91.1%). Odds ratios were calculated to determine differences in invalid performance by both standard and proposed cutoffs. Results Neurodevelopmental disorder was associated with increased invalid performance using standard and proposed cutoffs with odds ratios ranging from 1.32 to 3.25. Invalid performance differed significantly across groups for both standard and two sets of proposed criteria (chi square p < .00001). For standard cutoffs, athletes with ADHD, LD, and ADHD/LD were significantly more likely than healthy athletes to have invalid performance. This pattern remained similar across the two sets of proposed criteria. Conclusions Results indicate increased incidence of invalid ImPACT performance based on standard and proposed validity indicators in athletes who self-report neurodevelopmental disorders. Findings indicate current and proposed cutoffs may not accurately capture low effort for neurodevelopmental populations. Future research should examine utility of separate cutoff criteria and expanded norms for athletes with neurodevelopmental history.

Executive Function: Cognition and Behaviour in Adults with Autism Spectrum Disorders (ASD)

Studies of executive function (EF) in autism spectrum disorder (ASD) have reported mixed findings. Possible confounds include EF domain assessed and co-occurring neurodevelopmental diagnoses. EF task performance across multiple domains and everyday function of autistic adults (n = 110) was significantly different to age- and IQ-matched controls (n = 31). Although significantly more likely to fall into the clinically impaired range, 35.8% of the ASD group showed no impairment on EF measures. Factor analysis revealed a single unifying EF construct rather than a selective pattern of impairment. Dysexecutive behaviours were frequently reported in the ASD group, unrelated to Autism symptoms, EF task performance or co-occurring conditions. This study suggests autistic adults can experience clinically significant executive function difficulties and co-occuring dysexecutive behaviours that are disabling in everyday life.

A nurse's introduction to attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is currently one of the most prevalent neurodevelopmental psychiatric diagnoses for children and young people in the UK. An NHS series of surveys completed by Forbes et al (2018) found a ‘hyperactivity disorder’ diagnosis rate of 1.6% for children aged between 5 and 19 years. This is much lower than the estimated worldwide diagnostic rate of 5–7% in children and adolescents and did not capture the 47.4% persistence rate into adulthood, or the 2.8% adult diagnostic rate (Polanczyk et al, 2014).With such a relatively common disorder, it is likely that all nurses will at some point in their careers care for a patient with a diagnosis of ADHD, regardless of clinical environment. Furthermore, individuals with ADHD are more likely to be overweight and have less healthy diets than other adults, leading to increased contact with health services because they are likely to need care for other conditions (Barkley, 2010).

The Risk of Offspring Psychiatric Disorders in the Setting of Maternal Obesity and Diabetes.

Prenatal exposure to metabolic disturbances is associated with increased risk of offspring neurodevelopmental impairment and autism spectrum disorder, while little is known about the joint effect of maternal obesity and diabetes. With this study, we aim to assess the joint effect of maternal obesity and diabetes on the risk for offspring psychiatric and mild neurodevelopmental disorders. Nationwide registries were used to link data of all live births in Finland between 2004 and 2014 (n = 649 043). Cox proportional hazards modeling adjusting for potential confounders was applied to estimate the effect of maternal obesity, pregestational diabetes mellitus (PGDM), and gestational diabetes mellitus, as well as their joint effects, on the outcomes of offspring psychiatric and mild neurodevelopmental diagnoses and offspring prescription of psychotropic drugs. Among mothers without diabetes, severely obese mothers had 67% to 88% increased risk of having a child with mild neurodevelopmental disorders (hazard risk ratio [HR] = 1.69; 95% confidence interval [CI] = 1.54-1.86), attention-deficit/hyperactivity disorder or conduct disorder (HR = 1.88; 95% CI = 1.58-2.23), and psychotic, mood, and stress-related disorders (HR = 1.67; 95% CI = 1.31-2.13) compared with mothers with a normal BMI. PGDM implied a further risk increase for all groups of psychiatric diagnoses with onset in childhood or adolescence in mothers with severe obesity. Marked effects were found particularly for autism spectrum disorder (HR = 6.49; 95% CI = 3.08-13.69), attention-deficit/hyperactivity disorder and conduct disorder (HR = 6.03; 95% CI = 3.23-11.24), and mixed disorders of conduct and emotions (HR = 4.29; 95% CI = 2.14-8.60). Gestational diabetes mellitus did not increase the risk highly for these offspring disorders. Maternal PGDM combined with severe maternal obesity markedly increases the risk of several children's psychiatric and mild neurodevelopmental disorders.

Feeding behavior in three-year-old children born

BackgroundFeeding difficulties threaten growth, health and neurodevelopment, and are prevalent among infants born preterm. The literature differs on (i) whether these problems persist into early childhood, and (ii) risk factors in the preterm population. In this study we explore feeding difficulties and risk factors in preterm and term-born three-year-olds. ObjectivesTo determine whether three-year-olds born <30 weeks have poorer feeding outcomes than their term-born peers; and identify predictors of feeding outcomes in children born <30 weeks. MethodsFeeding outcomes were examined in three-year-old children born <30 weeks, and a term-born comparison group, using parent report and the Behavioral Pediatric Feeding Assessment Scale (BPFAS). Factors hypothesized to be associated with feeding difficulties and preterm birth were examined in the preterm group, including: gestational age at birth, birth weight z-score, chronic lung disease (CLD), nasogastric tube (NGT) feeding at hospital discharge, age at breastfeeding cessation, oromotor feeding impairment at 12 months, weight at 12 months in kilograms and neurodevelopmental diagnoses. ResultsIn 217 children (111 born <30 weeks, 106 term-born), parents of children born <30 weeks reported more feeding concerns on parent report questions than parents of term-born peers. CLD, NGT at discharge, neurodevelopmental diagnoses and weight at 12 months predicted these parent-reported outcomes. By contrast, there was no difference in BPFAS results between preterm and term groups, and BPFAS scores were predicted only by birth-weight z-score in the preterm group. ConclusionsBehavioral feeding outcomes for three-year-old children born <30 weeks were equivalent to term-born peers in this study, however parental concerns about feeding differed. Further investigation is required to identify the drivers of parent concerns about feeding. Children displaying core risk factors warrant specific follow-up of feeding outcomes.

Temporal changes in the incidence of treated psychiatric and neurodevelopmental disorders during adolescence: an analysis of two national Finnish birth cohorts

Comprehensive overviews of the temporal changes in treated psychiatric and neurodevelopmental disorders during adolescence are scarce. We reviewed data from two national cohorts, 10 years apart, to establish the change in use of specialised services for psychiatric and neurodevelopmental diagnoses in Finland. We compared the nationwide register-based incidence of psychiatric and neurodevelopmental diagnoses between the 12th birthday and 18th birthday of adolescents born in Finland in 1987 and 1997. Adolescents who emigrated or died before their 12th birthday and those with missing covariate data were excluded, as were those who, when aged 11 years, had lived in a municipality belonging to a hospital district with obviously incomplete data reports during any follow-up years in our study. Our primary outcomes were time to incident specialised service use for any psychiatric or neurodevelopmental disorder and for 17 specific diagnostic classes. We also investigated whether adolescents who died by suicide had accessed specialised services before their deaths. The cumulative incidence of psychiatric or neurodevelopmental disorders increased from 9·8 in the 1987 cohort to 14·9 in the 1997 cohort (difference 5·2 percentage points [95% CI 4·8-5·5]) among girls, and from 6·2 in the 1987 cohort to 8·8 in the 1997 (2·6 percentage points [2·4-2·9]) among boys. The hazard ratio for the overall relative increase in neurodevelopment and psychiatric disorders in the 1997 cohort compared with the 1987 cohort was 1·6 (95% CI 1·5-1·8) among girls and 1·5 (1·4-1·6) among boys. Of the studied diagnostic classes, we noted significant (ie, p<0·001) relative increases for ten of 17 diagnoses among girls and 11 among boys. Of the adolescents who died by suicide before age 18, only five of 16 in the 1987 cohort and two of 12 in the 1997 cohort had used specialised services in the 6 months before their death. The large absolute rise in service use for psychiatric or neurodevelopmental disorders points to the need to deliver effective treatment to a rapidly increased patient population, whereas the relative increase in specific diagnoses should inform clinical practice. Despite increasing service use, identification of adolescents at risk of suicide remains a major public health priority. Academy of Finland, Brain and Behavior Research Foundation, Finnish Medical Foundation.

Monogenic disorders that mimic the phenotype of Rett syndrome.

Rett syndrome (RTT) is caused by mutations in methyl-CpG-binding protein 2 (MECP2), but defects in a handful of other genes (e.g., CDKL5, FOXG1, MEF2C) can lead to presentations that resemble, but do not completely mirror, classical RTT. In this study, we attempted to identify other monogenic disorders that share features with RTT. We performed a retrospective chart review on n = 319 patients who had undergone clinical whole exome sequencing (WES) for further etiological evaluation of neurodevelopmental diagnoses that remained unexplained despite extensive prior workup. From this group, we characterized those who (1) possessed features that were compatible with RTT based on clinical judgment, (2) subsequently underwent MECP2 sequencing and/or MECP2 deletion/duplication analysis with negative results, and (3) ultimately arrived at a diagnosis other than RTT with WES. n = 7 patients had clinical features overlapping RTT with negative MECP2 analysis but positive WES providing a diagnosis. These seven patients collectively possessed pathogenic variants in six different genes: two in KCNB1 and one each in FOXG1, IQSEC2, MEIS2, TCF4, and WDR45. n = 2 (both with KCNB1 variants) fulfilled criteria for atypical RTT. RTT-associated features included the following: loss of hand or language skills (n = 3; IQSEC2, KCNB1 x 2); disrupted sleep (n = 4; KNCB1, MEIS2, TCF4, WDR45); stereotyped hand movements (n = 5; FOXG1, KNCB1 x 2, MEIS2, TCF4); bruxism (n = 3; KCNB1 x 2; TCF4); and hypotonia (n = 7). Clinically based diagnoses can be misleading, evident by the increasing number of genetic conditions associated with features of RTT with negative MECP2 mutations.

Measuring Complexity for Autism Interventions: Tcfd’s Inventory of Neuroeducational Complexity

Autism is a complex condition, whether viewed from etiology, comorbidities, functioning, or interventions. There are numerous approaches for measuring complexity in children and adolescents with neurodevelopmental or medical diagnoses. Interventions, however, create the need for broader and deeper assessment—including the environments in which the young person lives. The Center for Discovery, New York state’s Center of Excellence for Developmental Disabilities, (TCFD) implemented an Assessment, Support, Education and Training (ASSET) grant from the New York Office for People with Developmental Disabilities. This paper will describe the Assessment activity. A major goal was to develop a tool for assessing the characteristics of the young person and pivotal environments. The objective was to promote the delay of or prevent movement to a more restrictive placement including residential placement. The pilot tool was developed over nine months and includes six areas for evaluation—medical/ impairments (8 items), functional profile (11 items), educational profile (5 items), home/family environment (9 items), school environment (6 items), and community environment (4 items). Implementation of CfD’s Inventory of Neuro-educational Complexity (INC) was able to distinguish among 30 pilot subjects those likely to use family and school interventions to maintain family living from those most likely needing at least short term residential placement. The INC is of substantial heuristic value in this time of great interest in effective and resource focused interventions with this population.

Neurodevelopmental disorders are highly over‐represented in children with obesity: A cross‐sectional study

To investigate prevalence of neurodevelopmental disorders in children with obesity and to compare body mass index (BMI) and metabolic profile in the children. Seventy-six children (37 girls, 39 boys) were consecutively recruited from a university outpatient clinic specialized in severe obesity. Neurodevelopmental disorders including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and developmental coordination disorder (DCD) were assessed using interviews and questionnaires. Neurodevelopmental diagnoses were collected retrospectively in medical records. BMI ranged between 1.9 and 5.9 SDS and age between 5.1 and 16.5 years. In 13.2% and 18.4% ASD and ADHD was assigned, respectively. In addition, 25% screened positive for DCD, 31.6% had at least one neurodevelopmental disorder, and 18.4% had a parent who screened positive for adult ADHD. Girls with ASD/ADHD had higher BMI SDS than girls without neurodevelopmental disorder (P = 0.006). One third of children with obesity referred to specialist centers have a neurodevelopmental disorder including deviant motor skills, and these problems may deteriorate weight status. One fifth of the parents exhibit ADHD symptomatology which could partly explain the poor adherence by some families in obesity units. Future obesity therapy could benefit from incorporating a neurodevelopmental treatment approach.

Young children who screen positive for autism: Stability, change and “comorbidity” over two years

BackgroundAutism spectrum disorder (ASD) is a developmental disorder with a wide variety of clinical phenotypes and co-occurrences with other neurodevelopmental conditions. Symptoms may change over time. AimsThe aim of the present study was to prospectively follow 96 children, initially assessed for suspected ASD at an average age of 2.9 years. Methods and proceduresAll children had been identified with autistic symptoms in a general population child health screening program, and had been referred to the Child Neuropsychiatry Clinic in Gothenburg, Sweden for further assessment by a multi-professional team at Time 1 (T1). This assessment included a broad neurodevelopmental examination, structured interviews, a cognitive test and evaluations of the child́s adaptive and global functioning. Two years later, at Time 2 (T2), the children and their parents were invited for a follow-up assessment by the same team using the same methods. Outcomes and resultsOf the 96 children, 76 had met and 20 had not met full criteria for ASD at T1. Of the same 96 children, 79 met full ASD criteria at T2. The vast majority of children with ASD also had other neurodevelopmental symptoms or diagnoses. Hyperactivity was observed in 42% of children with ASD at T2, and Intellectual Developmental Disorder in 30%. Borderline Intellectual Functioning was found in 25%, and severe speech and language disorder in 20%. The children who did not meet criteria for ASD at T2 had symptoms of or met criteria for other neurodevelopmental/neuropsychiatric disorders in combination with marked autistic traits. Changes in developmental profiles between T1 and T2 were common in this group of young children with ASD. The main effect of Cognitive level at T1 explained more than twice as much of the variance in Vineland scores as did the ASD subtype; children with IDD had significantly lower scores than children in the BIF and AIF group. Co-existence with other conditions was the rule. Conclusions and implicationsReassessments covering the whole range of these conditions are necessary for an optimized intervention—adapted to the individual child’s needs.

Quality of Life in Pediatric Moyamoya Disease

BackgroundMoyamoya disease (MMD) is a progressive intracranial arteriopathy with high risk of stroke. Its impact on quality of life is unstudied. We surveyed children with moyamoya disease and compared their quality of life to chronically ill children and children with stroke to better understand the impact of this diagnosis. MethodsChildren with moyamoya disease aged seven to 17 years from Stanford's Moyamoya Clinic between June 2014 and March 2015 were included. Children with syndromic neurodevelopmental diagnoses were excluded. Patients were surveyed using the Pediatric Quality of Life 4.0, in addition to the Pediatric Stroke Outcome Measure or Recovery Recurrence Questionnaire. Mean scores were compared to normative data sets. Linear regression models compared total quality of life scores in patients with and without stroke, after adjusting for confounders. ResultsThis cross-sectional study included 30 children with moyamoya disease; ten were male, and the median age was 13.5 years (range, 7 to 17 years). Twenty children (67%) had a stroke, and 14 of these had good neurological outcome (70%). Mean parent-proxy Pediatric Quality of Life scores were lower in all domains compared to healthy controls (P < 0.05), and all scores were comparable to chronically ill children and children with non–moyamoya disease stroke. There was no significant difference in total quality of life between patients with and without stroke. ConclusionsEven in the absence of stroke, children with moyamoya disease have lower quality of life than healthy controls and a similar quality of life to chronically ill children and those with non–moyamoya disease stroke. Children with moyamoya disease would benefit from mental health support beyond what a mild physical presentation may indicate.

Risk Factors for Attention and Behavioral Issues in Pediatric Sickle Cell Disease.

Children with sickle cell disease have an increased risk of neurodevelopmental disorders such as attention deficit hyperactivity disorder, intellectual disability, and specific learning disabilities. Little research has been done to characterize the sickle cell disease-related characteristics associated with neurodevelopmental disorders in the sickle cell disease population. This study was a retrospective chart review involving the outpatient records of 2 medical centers, Kennedy Krieger Institute and Johns Hopkins Hospital. Participants in the study included 59 children with sickle cell disease with a documented neurodevelopmental diagnosis, specifically attention deficit hyperactivity disorder, attention issues, behavioral issues, executive dysfunction, specific learning disabilities in math, reading, and reading comprehension, intellectual disabilities, developmental delay, fine motor disorders, language disorders, or autism spectrum disorders. Children with sickle cell disease type hemoglobin S-β thalassemia plus had significantly higher odds of attention issues than children with sickle cell disease type hemoglobin SS (OR = 17.0, 95% CI = 1.99-145.00, P < .02). Children with sickle cell disease and a reported history of asthma had significantly higher odds of behavioral issues than children with sickle cell disease without a history of asthma, after adjustment for gender and sickle cell disease type (exact OR = 19.53, 95% CI = 1.16-1369.72, P < .04). Children with sickle cell disease may have increased risk for certain neurodevelopmental diagnoses based on their disease characteristics and associated comorbidities. These preliminary study results should be explored in a larger database.