Visuomotor tracking strategies in children: associations with neurodevelopmental symptoms.

Children with neurodevelopmental disorders (NDDs) often display motor problems that may impact their daily lives. Studying specific motor characteristics related to spatiotemporal control may inform us about the mechanisms underlying their challenges. Fifty-eight children with varying neurodevelopmental symptoms load (median age: 5.6 years, range: 2.7-12.5 years) performed an interactive tablet-based tracking task. By investigating digit touch errors relative to the target's movement direction, we found that a load of neurodevelopmental symptoms was associated with reduced performance in the tracking of abrupt alternating directions (zigzag) and overshooting the target. In contrast, reduced performance in children without neurodevelopmental symptoms was associated with lagging behind the target. Neurodevelopmental symptom load was also associated with reduced flexibility in correcting for lateral deviations in smooth tracking (spiral). Our findings suggest that neurodevelopmental symptoms are associated with difficulties in motor regulation related to inhibitory control and reduced flexibility, impacting motor control in NDDs.

Neurodevelopmental problems, general health and academic achievements in a school-based cohort of 11-year-old Swedish children.

AIM: Assessing rates of neurodevelopmental problems (NDPs) in 11-year-old children and possible association with other health complaints and school performance. METHODS: In-school study of 11-year-old children as an add-on assessment to the 4th grade regular health check-up, comprising a structured physical neurodevelopmental examination, neuropsychological assessment, behavioural ratings, maternal interview, review of medical records and academic achievements. RESULTS: Out of 348 children recruited from eight schools, 223 (64%) participated. Any physical condition was found in 102/222 (46%), most commonly atopy (18%). One in five had a BMI z-score >2 standard deviations over the reference mean. One or more NDP was found in 86/221 (40%) children. The number of failed national tests correlated positively with NDP severity rated with the clinical global impression severity instrument (Spearman's r = 0.41, p < 0.001). The majority of participants with failed national tests, also had co-occurring health complaints (≥2 of: stomach or extremity ache, headache, difficulties sleeping, internalising symptoms or obesity) and NDPs. CONCLUSION: Health complaints, physical conditions and NDPs are very common in 11-year-old children and warrant adequately staffed, thoroughly equipped school healthcare services.

Evaluation of C4 Gene Copy Number in Pediatric Acute Neuropsychiatric Syndrome.

Pediatric acute-onset neuropsychiatric syndrome (PANS) is an abrupt-onset neuropsychiatric disorder. PANS patients have an increased prevalence of comorbid autoimmune illness, most commonly arthritis. In addition, an estimated one-third of PANS patients present with low serum C4 protein, suggesting decreased production or increased consumption of C4 protein. To test the possibility that copy number (CN) variation contributes to risk of PANS illness, we compared mean total C4A and total C4B CN in ethnically matched subjects from PANS DNA samples and controls (192 cases and 182 controls). Longitudinal data from the Stanford PANS cohort (n = 121) were used to assess whether the time to juvenile idiopathic arthritis (JIA) or autoimmune disease (AI) onset was a function of total C4A or C4B CN. Lastly, we performed several hypothesis-generating analyses to explore the correlation between individual C4 gene variants, sex, specific genotypes, and age of PANS onset. Although the mean total C4A or C4B CN did not differ in PANS compared to controls, PANS patients with low C4B CN were at increased risk for subsequent JIA diagnosis (hazard ratio = 2.7, p value = 0.004). We also observed a possible increase in risk for AI in PANS patients and a possible correlation between lower C4B and PANS age of onset. An association between rheumatoid arthritis and low C4B CN has been reported previously. However, patients with PANS develop different types of JIA: enthesitis-related arthritis, spondyloarthritis, and psoriatic arthritis. This suggests that C4B plays a role that spans these arthritis types.

A novel tablet-based motor coordination test performs on par with the Beery VMI subtest and offers superior temporal metrics: findings from children with pediatric acute-onset neuropsychiatric syndrome.

Neuropsychiatric and neurodevelopmental disorders are often associated with coordination problems. Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) constitutes a specific example of acute and complex symptomatology that includes difficulties with motor control. The present proof-of-concept study aimed at testing a new, bespoke tablet-based motor coordination test named SpaceSwipe, providing fine-grained measures that could be used to follow-up on symptoms evolution in PANS. This test enables computationally precise and objective metrics of motor coordination, taking into account both directional and spatial features continuously. We used SpaceSwipe to assess motor coordination in a group of children with PANS (n = 12, assessed on in total of 40 occasions) and compared it against the motor coordination subtest from the Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery VMI) 6th edition, traditionally used to follow-up symptomatology. Using a bivariate linear regression, we found that 33 s of the directional offset from tracking a moving target in SpaceSwipe could predict the Beery VMI motor coordination (VMI MC) raw scores (mean absolute error: 1.75 points). Positive correlations between the predicted scores and the VMI MC scores were found for initial testing (radj = 0.87) and for repeated testing (radj = 0.79). With its short administration time and its close prediction to Beery VMI scores, this proof-of-concept study demonstrates the potential for SpaceSwipe as a patient-friendly tool for precise, objective assessment of motor coordination in children with neurodevelopmental or neuropsychiatric disorders.

A randomized controlled trial of a new intervention in early symptomatic syndromes eliciting neurodevelopmental clinical examinations: PR-ESSENCE.

The need for effective intervention programs for youth with neurodevelopmental problems (ESSENCE) and challenging behaviour is great. This study examines Problem Resolution in ESSENCE (PR-ESSENCE), a newly developed model in which children and parents develop mutual problem resolution strategies. Ten-week randomized controlled trial of PR-ESSENCE for children and adolescents aged 5-18 years, compared to treatment as usual. Outcomes were assessed at baseline and randomized period endpoint. Primary outcome was the Clinical Global Impression-Improvement scale (CGI-I) rated by blinded assessors. Secondary outcomes were rated by parents-SNAP-IV, Eyberg Child Behavior Inventory (ECBI), Relationship Problems Questionnaire, Family Burden of Illness Module, and children-Beck Youth Inventories (BYI). ClinicalTrials.gov identifier: NCT03780413. The study enrolled 108 participants (active n = 72; controls n = 36, randomized 2:1), of whom 95 completed the randomized period. No clinically significant group differences were found in baseline characteristics. More than half had autism and 80% had ADD or ADHD. Large treatment effects were seen on CGI-I (ITT analysis, Effect Size 1.48). Treatment responders, much/very much improved on CGI-I, were 51.4% in active group and 5.6% of controls. Effect sizes were medium to large in parent ratings on SNAP-IV (ODD and ADHD symptoms), ECBI (behaviour problems), and in BYI child self-ratings of disruptive behaviour. PR-ESSENCE treatment improved global symptoms and functioning (CGI-I), behaviour problems, ADHD and ODD symptoms, and disruptive behaviour. Treatment effects were at least equivalent to those in previous studies of well-established Parent Management Training and Collaborative Problem Solving programs.

Paediatric Acute-onset Neuropsychiatric Syndrome (PANS) and intravenous immunoglobulin (IVIG): comprehensive open-label trial in ten children.

BACKGROUND: Treatment with intravenous immunoglobulin (IVIG) in children with Paediatric Acute-onset Neuropsychiatric Syndrome (PANS) has for many years been used on clinical indications, but the research evidence for its efficacy is insufficient. METHODS: Open-label prospective in-depth trial including ten children (median age 10.3 years) with PANS, who received IVIG treatment 2 g/kg monthly for three months. Primary outcomes were changes in symptom severity and impairment from baseline to first and second follow-up visits one month after first and one month after third treatment, using three investigator-rated scales: Paediatric Acute Neuropsychiatric Symptom (PANS) scale, Clinical Global Impression - Severity and Improvement (CGI-S and CGI-I) scales. Secondary outcomes reported here were changes in Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) scores, and side effects. RESULTS: All ten children received three treatments at one-month intervals according to study plan. From baseline to second follow-up marked reductions were seen in mean total PANS scale scores (p = .005), and CGI-S scores (p = .004). CGI-I ratings showed much to very much global improvement (mean CGI-I 1.8). Nine children had clinical response defined as > 30% reduction in PANS Scale scores. Improvements were also noted for CY-BOCS scores (p = .005), and in school attendance. Three children suffered moderate to severe temporary side effects after the first treatment, and the remaining seven had mild to moderate side effects. Side effects were much less severe after second and third treatments. CONCLUSIONS: Considerable and pervasive improvements in symptoms and clinical impairments were seen in these ten children after three monthly IVIG treatments. Moderate to severe transient side effects occurred in three cases. TRIAL REGISTRATION: EudraCT no. 2019-004758-27, Clinicaltrials.gov no. NCT04609761, 05/10/2020.

Paediatric Acute onset Neuropsychiatric Syndrome: Exploratory study finds no evidence of HLA class II association but high rate of autoimmunity in first-degree relatives.

AIM: Paediatric acute-onset neuropsychiatric syndrome (PANS) is defined by an acute onset of obsessive-compulsive disorder and/or eating restrictions and at least two other severe neuropsychiatric symptoms. The condition is suspected to have an immune-mediated pathophysiology, but reliable biomarkers have not been identified. METHODS: We hypothesised that PANS, like narcolepsy, might have a human leucocyte antigen (HLA) association, as found in 95% of children developing narcolepsy after H1N1 immunisation. Low resolution genotyping of the MHC class II antigens HLA-DRB1 and HLA-DQB1 was performed using two different PCR-based methods. In addition, parents were interviewed regarding a detailed family history of autoimmune diseases in first-degree relatives. A total of 18 children, aged 5-14 (mean 8.2) years at onset of PANS met symptom criteria. RESULTS: No evident association between PANS and the specific HLA alleles examined was observed. In first-degree relatives of 10 of the 18 children, an autoimmune disease had been diagnosed, and three of the 18 children themselves had an autoimmune disease. CONCLUSION: No HLA allele association such as seen in children with narcolepsy after H1N1 immunisation could be confirmed in this group of children with PANS. However, more than half the group had a first-degree relative with a diagnosed autoimmune disease.

Neurodevelopmental disorders and somatic diagnoses in a national cohort of children born before 24 weeks of gestation.

AIM: This study investigated childhood diagnoses in children born extremely preterm before 24 weeks of gestation. METHODS: Diagnoses of neurodevelopmental disorders and selected somatic diagnoses were retrospectively retrieved from national Swedish registries for children born before 24 weeks from 2007 to 2018. Their individual medical files were also examined. RESULTS: We studied 383 children born at a median of 23.3 (range 21.9-23.9) weeks, with a median birthweight of 565 (range 340-874) grams. Three-quarters (75%) had neurodevelopmental disorders, including speech disorders (52%), intellectual disabilities (40%), attention deficit hyperactivity disorder (30%), autism spectrum disorders (24%), visual impairment (22%), cerebral palsy (17%), epilepsy (10%) and hearing impairment (5%). More boys than girls born at 23 weeks had intellectual disabilities (45% vs. 27%, p < 0.01) and visual impairment (25% vs. 14%, p < 0.01). Just over half of the cohort (55%) received habilitation care. The majority (88%) had somatic diagnoses, including asthma (63%) and failure to thrive/short stature (39%). CONCLUSION: Most children born before 24 weeks had neurodevelopmental disorders and/or additional somatic diagnoses in childhood and were referred to habilitation services. Clinicians should be aware of the multiple health and developmental problems affecting these children. Resources are needed to identify their long-term support needs at an early stage.

National cohort of infants born before 24 gestational weeks showed increased survival rates but no improvement in neonatal morbidity.

AIM: To describe survival and neonatal morbidities in infants born before 24 weeks of gestation during a 12-year period. METHODS: Data were retrieved from national registries and validated in medical files of infants born before 24 weeks of gestation 2007-2018 in Sweden. Temporal changes were evaluated. RESULTS: In 2007-2018, 282 live births were recorded at 22 weeks and 460 at 23 weeks of gestation. Survival to discharge from hospital of infants born alive at 22 and 23 weeks increased from 20% to 38% (p = 0.006) and from 45% to 67% (p < 0.001) respectively. Caesarean section increased from 12% to 22% (p = 0.038) for infants born at 22 weeks. Neonatal morbidity rates in infants alive at 40 weeks of postmenstrual age (n = 399) were unchanged except for an increase in necrotising enterocolitis from 0 to 33% (p = 0.017) in infants born at 22 weeks of gestation. Bronchopulmonary dysplasia was more common in boys than girls, 90% versus 82% (p = 0.044). The number of infants surviving to 40 weeks doubled over time. CONCLUSION: Increased survival of infants born before 24 weeks of gestation resulted in increasing numbers of very immature infants with severe neonatal morbidities likely to have a negative impact on long-term outcome.

Attention-deficit/hyperactivity disorder with developmental coordination disorder: 24-year follow-up of a population-based sample.

BACKGROUND: Although the body of research concerning neurodevelopmental disorders is vast, there is a scarcity of longitudinal studies beyond late adolescence, and of studies taking co-existing disorders into account. The present study aimed to investigate outcome in adulthood for children with attention-deficit/hyperactivity disorder (ADHD) combined with developmental coordination disorder (DCD) diagnosed at 6.6 years of age. METHODS: Out of a screening-based population cohort of 589 individuals, 62 (10 female) diagnosed with ADHD+DCD at mean age 6.6 years naïve to stimulant treatment were followed into adulthood through national registries. Results were compared to a screen- and assessment negative population matched group from the same cohort (PM group, n = 51) and a registry-matched (RM group, n = 410) group of the same county and age. RESULTS: At 30 to 31 years of age, five deaths had occurred; one in the ADHD+DCD group and two each in the comparison groups. In time to event analyses of the composite outcome of any psychiatric disorder, psychotropic prescription, sick pension or criminal sentence, events occurred at a significantly higher rate in the ADHD+DCD group (p = 0.0032, vs PM group p = 0.0115, vs RM group p = 0.0054). The ADHD+DCD group had significantly higher rates of psychiatric diagnoses, prescriptions of psychoactive medications and occurrence of sick pension than both comparison groups. Further, the ADHD+DCD group had significantly lower educational attainment compared to both comparison groups, more years with unemployment, and overall higher welfare recipiency. Rates of pain diagnoses and analgesic prescriptions did not separate the groups. CONCLUSION: ADHD+DCD entailed a less favorable outcome in adulthood compared to a non-clinical comparison group and a registry-matched population. Neurodevelopmental disorder diagnosed upon school entry is of prognostic utility with respect to function in adulthood, and warrants early identification and management.

Supplementation with polyunsaturated fatty acids (PUFAs) in the management of attention deficit hyperactivity disorder (ADHD).

While pharmacotherapy and psychosocial interventions are recommended as the primary frontline treatment for attention deficit hyperactivity disorder (ADHD), alternative approaches to managing ADHD are becoming increasingly popular among patients and their families. Supplementation with polyunsaturated fatty acids (PUFAs) is an example of this. PUFA supplementation is not recommended by guidelines for managing ADHD; however, patients may still decide to use it. To provide direction to healthcare professionals (HCPs) managing ADHD, eight international experts in the field of adult and child ADHD came together for the Continuum Education Board: Omega Supplements in ADHD meeting. This commentary summarises the panel's consensus that current evidence suggests PUFA supplementation has a small beneficial effect on behaviour in children with ADHD, and that further high-quality research is needed to clearly evaluate and define its role in the management of ADHD of children, adolescents and adults. The panel concluded that in cases where patients use PUFA supplementation, HCPs should be comfortable explaining the potential gains that they may have and their possible side effects. The panel also concluded HCPs should not reinforce the idea that PUFA supplementation should replace treatment approaches with a more robust evidence base for managing ADHD.

Omega 3/6 fatty acids for reading in children: a randomized, double-blind, placebo-controlled trial in 9-year-old mainstream schoolchildren in Sweden.

BACKGROUND: Previous research has shown positive effects of Omega 3/6 fatty acids in children with inattention and reading difficulties. We aimed to investigate if Omega 3/6 improved reading ability in mainstream schoolchildren. METHODS: We performed a 3-month parallel, randomized, double-blind, placebo-controlled trial followed by 3-month active treatment for all subjects. Mainstream schoolchildren aged 9-10 years were randomized 1:1 to receive three Omega 3/6 capsules twice daily or identical placebo. Assessments were made at baseline, 3 months, and 6 months. The primary outcome measure was the Logos test battery for evaluating reading abilities. The trial is registered with ClinicalTrials.gov, number NCT02557477. RESULTS: The study enrolled 154 children (active n = 78; placebo n = 76), of whom 122 completed the first 3 months (active n = 64; placebo n = 58) and 105 completed the whole study (active/active n = 55; placebo/active n = 50). Outcomes were assessed by per protocol (PP) and intention-to-treat (ITT) analyses. Active treatment was superior to placebo at 3 months for improvement in phonologic decoding time (PP active/placebo difference -0.16; 95% CI -0.03, -0.29; effect size (ES) .44; p = .005; and ITT ES .37; p = .036), in visual analysis time (PP active/placebo difference -0.19; 95% CI -0.05, -0.33; ES .49; p = .013; and ITT ES .40; p = .01), and for boys in phonologic decoding time (PP -0.22; 95% CI -0.03, -0.41; ES .62; p = .004). Children with ADHD-RS scores above the median showed treatment benefits in visual analysis time (PP ES .8, p = .009), reading speed per word (PP ES .61, p = .008), and phonologic decoding time per word (PP ES .85, p = .006). Adverse events were rare and mild, mainly stomach pain/diarrhea (active n = 9, placebo n = 2). CONCLUSIONS: Compared with placebo, 3 months of Omega 3/6 treatment improved reading ability - specifically the clinically relevant 'phonologic decoding time' and 'visual analysis time' - in mainstream schoolchildren. In particular, children with attention problems showed treatment benefits.

Extended-release guanfacine hydrochloride in 6-17-year olds with ADHD: a randomised-withdrawal maintenance of efficacy study.

BACKGROUND: Extended-release guanfacine hydrochloride (GXR), a selective α2A-adrenergic agonist, is a nonstimulant medication for attention-deficit/hyperactivity disorder (ADHD). This phase 3, double-blind, placebo-controlled, randomised-withdrawal study evaluated the long-term maintenance of GXR efficacy in children/adolescents with ADHD. METHODS: Children/adolescents (6-17 years) with ADHD received open-label GXR (1-7 mg/day). After 13 weeks, responders were randomised to GXR or placebo in the 26-week, double-blind, randomised-withdrawal phase (RWP). The primary endpoint was the percentage of treatment failure (≥50% increase in ADHD Rating Scale version IV total score and ≥2-point increase in Clinical Global Impression-Severity compared with RWP baseline, at two consecutive visits). The key secondary endpoint was time to treatment failure (TTF). TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01081145; EudraCT 2009-018161-12. RESULTS: A total of 528 participants enrolled; 316 (59.8%) entered the RWP. Treatment failure occurred in 49.3% of the GXR and 64.9% of the placebo group (p = 0.006). TTF was significantly longer in GXR versus placebo (p = 0.003). GXR was well tolerated. CONCLUSIONS: Guanfacine hydrochloride demonstrated long-term maintenance of efficacy compared with placebo in children/adolescents with ADHD. Implications of the placebo substitution design and findings with different ADHD medications are discussed.

Parental attitudes and experiences of dental care in children and adolescents with ADHD--a questionnaire study.

Attention deficit hyperactivity disorder (ADHD) is a common psychiatric condition characterized by age-inappropriate levels of inattention, hyperactivity-impulsiveness or a combination of these. The aim of this study was to analyze parental attitudes to and experience of dental care, oral hygiene and dietary habits in children/adolescents with ADHD. Twenty- six parents of 31 subjects, 20 boys and 11 girls, aged 5-19 years with ADHD registered at the Gothenburg Child Neuropsychiatric Clinic, were invited. The parents answered a questionnaire regarding different oral problems when visiting the Clinic of Pediatric Dentistry, Gothenburg, for an oral examination of their child. The parents felt the dental care at the Public Dental Service was good, but noted a lack of knowledge regarding child neuropsychiatry among the dental staff which may influence the dental treatment. Fifteen parents reported their children had experienced mouth pain and 15 reported their child had suffered from both discomfort and pain from local anesthesia. Thirteen of the children had a dental trauma and 12 parents reported pain in connection to the dental treatment. Pain related to filling therapy was stated by 11 parents. According to the parents, five children suffered from dental fear but 15 reported the child had a general fear. Pursuant to the parents, the beverage for dinner was mainly milk or water, while sweet drinks were more frequent when thirsty. Seventeen parents reported their children had poor oral hygiene or could not manage to brush their teeth and 14 of the 31 children only brushed once a day or less. The results show that the parents experience a lack of child neuropsychiatric knowledge, care and patience from the dental staff, which may influence the treatment. Oral hygiene/tooth brushing is neglected and the frequent consumption of sugar is difficult for the parents to handle.

[Survival and prematurity-related neonatal diagnoses among children born before 24 gestational weeks in Sweden 2007-2018]. / Allt fler barn födda före vecka 24 överlever, men sjukligheten är hög.

Children born before 24 gestational weeks had high neonatal morbidity and a majority had one or more neurodevelopmental disorders in addition to somatic diagnoses in childhood. Active Swedish perinatal care of infants with gestational age <24 weeks has resulted in a survival rate of more than 50 percent. Resuscitation of these immature infants is controversial, and some countries offer comfort care only. In a retrospective review of medical files and registries of 399 Swedish infants born before 24 gestational weeks, a majority had severe prematurity-related neonatal diagnoses. In childhood (2-13 years), 75 percent had at least one neurodevelopmental disorder and 88 percent had one or more prematurity-related somatic diagnosis (permanent or transient) that was likely to affect their quality of life. Long-term consequences for surviving infants should be considered in general recommendations as well as in parental information.

Attention-deficit/hyperactivity disorder with oppositional defiant disorder in Swedish children - an open study of collaborative problem solving.

AIM: To evaluate collaborative problem solving (CPS) in Swedish 6-13-year-old children with attention-deficit/hyperactivity disorder and oppositional defiant disorder (ODD). METHODS: Seventeen families completed 6-10 sessions of CPS training. Primary outcome measures were SNAP-IV [attention-deficit/hyperactivity disorder (ADHD) and ODD scores] and Clinical Global Impression-Improvement (CGI-I) scores at baseline, post-intervention and 6 months later. Secondary outcome measures were the Conners' 10-item scale and the Family Burden of Illness Module (FBIM). RESULTS: All 17 participants completed the intervention. The whole group had significant reductions in SNAP-IV ODD, ADHD, total Conners' and FBIM scores, both at post-intervention and at 6-month follow-up. Eight of the children, although significantly improved on ODD scores and the Conners' emotional lability subscale at post-intervention, had almost no improvement in hyperactivity/impulsivity. Post-intervention, this group received stimulant medication for their ADHD. CGI-I scores of much improved or very much improved were reached by 53% (9/17) of all at post-intervention, and by 81% (13/16) at 6-month follow-up. CONCLUSION: Collaborative problem solving significantly reduced ODD, ADHD and emotional lability symptoms. A subgroup improved in their ADHD symptoms only after adding stimulant medication.

Deficits in attention, motor control and perception childhood to age 30 years: prospective case-control study of outcome predictors.

OBJECTIVE: Investigate predictors of adverse outcome in children with and without attention-deficit/hyperactivity disorder (ADHD) combined with developmental coordination disorder (DCD) at 6 years of age. DESIGN: Prospective population-based cohort study. SETTING: Western Sweden. PARTICIPANTS: From a screening-based population cohort of 589 individuals, 62 (11 female) diagnosed with ADHD+DCD at mean age 6.6 years, and a comparison group of 51 population-matched (10 female) children were followed prospectively. OUTCOME MEASURES: Drawn from a clinical reassessment at age 9 years of 110 of the 113 individuals, neuropsychiatric symptoms, continuous performance test results and measures of motor function were used as predictors of outcome in linear regression models. Participants were followed in national registers up to 30-31 years of age for outcomes in adulthood. Predictors were regressed onto an adverse outcome score (range 0-7) comprising seven binary endpoints, and when applicable onto each continuous outcome separately (low educational attainment, low occupation level, psychiatric disorder, psychotropic medication prescription, sick pension, high dependence on social benefits and criminal conviction). RESULTS: Of the 110 individuals, 3 had died. In univariable regression onto the adverse outcome score, the strongest predictors at age 9 years were symptoms of conduct disorder, oppositional defiant disorder, ADHD and motor dysfunction, with an R2 around 25%, followed by autistic traits (R2=15%) and depressive symptoms (R2=8%). Combining these six strongest predictors in a multivariable model yielded an adjusted R2=38%. Subgroup analyses were similar, except for a strong association of autistic traits with the adverse outcome score in females (n=20, R2=50%). CONCLUSION: Several neurodevelopmental symptoms, including ADHD severity at age 9 years, accounted for a considerable amount of the variance in terms of adulthood adverse outcome. Broad neurodevelopmental profiling irrespective of diagnostic thresholds should inform research and clinical practice. The study highlights the importance of considering associated comorbidities and problems in ADHD.

The ESSENCE-Questionnaire for Neurodevelopmental Problems - A Swedish School-Based Validation Study in 11-Year-Old Children.

Purpose: To determine the prevalence of parent-rated developmental concern using the ESSENCE-Q (Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations-Questionnaire, 12-items, score range 0-24) and to ascertain the predictive validity and optimal cutoff level of the instrument in a school-based sample of 11-year-old children. Methods: In a cross-sectional, school-based study, participants underwent a clinical assessment by a physician and a psychologist, teachers and parents completed the SDQ (Strength and Difficulties Questionnaire), medical health records and national tests were reviewed, and parents independently completed the ESSENCE-Q. In a case-conference outcomes were defined as a) the need for further clinical work-up due to suspected neurodevelopmental problems (NDPs) and b) degree of investigator-rated symptoms/impairment from NDPs on the CGI-S (Clinical Global Impression-Severity instrument, range 1-7, 4-7 defined as clinically symptomatic). Classification and optimal cutoffs of the ESSENCE-Q were determined using ROC (Receiver Operating Characteristic) analysis. Results: Out of 343 eligible children, 223 enrolled, of whom 173 (50% of all eligible) had a parent-rated ESSENCE-Q. At least one of the 12 possible concerns was reported by parents of 36% of participants. Overall, in 101 (57%) participants a work-up was warranted, and 64 (37%) were clinically symptomatic from NDPs. The AUC of the ESSENCE-Q in detecting need for work-up was 0.70 (95% confidence interval [CI] 0.63-0.77), and the AUC in detecting clinically symptomatic participants was 0.82 (95% CI 0.76-0.88). ESSENCE-Q ratings correlated positively with CGI-S scores (r=0.48, p<0.05). A cutoff of ≥3 had the highest accuracy (78%) with a negative predictive value of 82%. Ratings >6 conferred few false positives cases with positive likelihood ratios >10 and positive predictive values of 86% or more. Significance: This study of the ESSENCE-Q in 11-year-old children suggests it might be an acceptable instrument for screening of NDPs in children in middle school, optimally in conjunction with other methods.

Establishment of reference values for plasma neurofilament light based on healthy individuals aged 5-90 years.

The recent development of assays that accurately quantify neurofilament light, a neuronal cytoskeleton protein, in plasma has generated a vast literature supporting that it is a sensitive, dynamic, and robust biomarker of neuroaxonal damage. As a result, efforts are now made to introduce plasma neurofilament light into clinical routine practice, making it an easily accessible complement to its cerebrospinal fluid counterpart. An increasing literature supports the use of plasma neurofilament light in differentiating neurodegenerative diseases from their non-neurodegenerative mimics and suggests it is a valuable biomarker for the evaluation of the effect of putative disease-modifying treatments (e.g. in multiple sclerosis). More contexts of use will likely emerge over the coming years. However, to assist clinical interpretation of laboratory test values, it is crucial to establish normal reference intervals. In this study, we sought to derive reliable cut-offs by pooling quantified plasma neurofilament light in neurologically healthy participants (5-90 years) from eight cohorts. A strong relationship between age and plasma neurofilament light prompted us to define the following age-partitioned reference limits (upper 95th percentile in each age category): 5-17 years = 7 pg/mL; 18-50 years = 10 pg/mL; 51-60 years = 15 pg/mL; 61-70 years = 20 pg/mL; 70 + years = 35 pg/mL. The established reference limits across the lifespan will aid the introduction of plasma neurofilament light into clinical routine, and thereby contribute to diagnostics and disease-monitoring in neurological practice.

Retrospective evaluation of ophthalmological and neurological outcomes for infants born before 24 weeks gestational age in a Swedish cohort.

OBJECTIVES: To retrospectively evaluate ophthalmological and neurological outcomes in a Swedish cohort of infants born before 24 weeks gestational age (GA) and explore risk factors for visual impairment. SETTING: Eye and paediatric clinics in Sweden. PARTICIPANTS: Infants screened for retinopathy of prematurity (ROP) (n=399), born before 24 weeks GA, 2007-2018. Cases were excluded if ophthalmological follow-up records could not be traced. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes were ophthalmological, including visual acuity (VA), refractive error, strabismus, nystagmus and cerebral visual impairment (CVI). Secondary outcomes comprised neonatal and neurological morbidities. Data were retrospectively retrieved from medical records. RESULTS: The 355 assessed children had a median GA of 23 weeks and 2 days and a median birth weight of 565 g. At the last available ophthalmological examination, the median age was 4.8 years (range 0.5-13.2 years). Nystagmus was recorded in 21.1%, strabismus in 34.8%, and 51.0% wore spectacles. Seventy-three of 333 (21.9%) were visually impaired, defined as being referred to a low vision clinic and/or having a VA less than 20/60 at 3.5 years of age or older. ROP treatment was a significant risk factor for visual impairment (OR 2.244, p=0.003). Visually impaired children, compared with children without visual impairment, more often had neurological deficits such as intellectual disability 63.8% versus 33.3% (p<0.001), epilepsy 21.1% versus 7.5% (p=0.001) and autism spectrum disorders 32.8% versus 20.9% (p=0.043). Nine of the 355 children had been diagnosed with CVI. CONCLUSIONS: Children born before 24 weeks GA frequently had visual impairment in association with neurological deficits. CVI was rarely diagnosed. A multidisciplinary approach for the evaluation and habilitation of these vulnerable infants is warranted. National follow-up guidelines need to be developed and implemented.