AbstractWe report eight children with de novo pathogenic DNA variants in chromatin‐related genes: MORC2, CHD7, KANSL1, KMT2D, ZMYND11, HIST1HIE, EP300, and KMT2B. All children experienced infection or vaccine‐provoked neuroregression or abrupt‐onset neuropsychiatric syndromes. Most had delayed development (n = 6) before the first regression, and four had immune deficiency or autoimmunity (n = 4). At a mean age of 4 years 2 months (range 1–8 years), symptoms included infection‐provoked autistic/language regression (n = 6), cognitive decline (n = 3), gait deterioration (n = 3), or abrupt‐onset anxiety, obsessive‐compulsive disorder, and/or tics (n = 5). Three children had ongoing infection‐provoked deteriorations. Six children benefited from intravenous immunoglobulin (n = 3) or antibiotics (n = 4). Ribonucleic acid expression of the eight chromatin genes was similar in neuronal, glial, and peripheral leukocytes, unlike non‐chromatin neurodevelopmental genes, which have predominantly neuronal expression. These cases demonstrate the role of chromatin dysregulation in autistic regression and abrupt‐onset neuropsychiatric syndromes, potentially related to brain and immune gene dysregulation.

https://onlinelibrary.wiley.com/doi/10.1111/dmcn.16252

https://onlinelibrary.wiley.com/doi/10.1111/dmcn.16007

https://onlinelibrary.wiley.com/doi/10.1111/dmcn.16255

https://onlinelibrary.wiley.com/doi/10.1111/dmcn.15834

https://onlinelibrary.wiley.com/doi/10.1111/dmcn.15864

https://onlinelibrary.wiley.com/doi/10.1111/dmcn.16042

https://onlinelibrary.wiley.com/doi/10.1111/dmcn.16259

AbstractAimTo establish if the General Movements Assessment (GMA) and Hammersmith Infant Neurological Examination (HINE) support the early diagnosis of cerebral palsy (CP) in a cohort of infants who have undergone therapeutic hypothermia.MethodThis was a retrospective cohort study from a large single center between 2018 and 2022. Sample size included surviving 112 infants with follow‐up (68 males, 44 females) with a mean gestational age of 39 weeks (interquartile range 38–40), diagnosed with moderate or severe neonatal encephalopathy who underwent therapeutic hypothermia. Groups were compared using Fisher's exact and Mann–Whitney U tests.ResultsThe absence of normal fidgety movements at the 3‐month GMA was highly associated with CP (p < 0.001, sensitivity 89%, specificity 89%). HINE scores were associated with CP at 3 months, 6 months, and 9 months (p < 0.001; sensitivity 82%–90%, specificity 95%–100%). The HINE scores, which optimally differentiated those with and without CP, were less than 47 at 3 months, less than 51 at 6 months, and less than 64 at the 9‐month follow‐up.InterpretationThe GMA and HINE were predictive of CP in infants born at term with neonatal encephalopathy who had undergone therapeutic hypothermia. Atypical (absent or abnormal) fidgety movements on the GMA at 3 months and the HINE score at 3 months, 6 months, and 9 months were all highly associated with CP diagnosis with more than 80% sensitivity and more than 90% specificity. The optimal HINE cutoff score for predicting CP may differ from infants born preterm and will benefit from further analysis.

AbstractAimTo investigate the potential risk factors of respiratory illness (ethnicity, oral health, and eating and drinking ability) in children and young adults with cerebral palsy (CP).MethodThis was an observational study using a validated CP Respiratory and Oral Health questionnaire with 90 participants (median age 12 years [range: 1–26 years]; 51 males; and 26 New Zealand Māori).ResultsMultivariate analysis, accounting for ethnicity and Gross Motor Function Classification System (GMFCS) levels, showed that those participants who were classified in Eating and Drinking Ability Classification System (EDACS) levels III to V reported more previous respiratory disease episodes (odds ratio [OR] = 4.13, 95% confidence interval [CI] = 1.12–15.2, p = 0.033), increased daily/weekly respiratory symptoms (OR = 9.14, 95% CI = 2.03–41.2, p = 0.004), and increased mealtime respiratory symptoms (OR = 13.8, 95% CI = 2.48–76.8, p = 0.002). Both EDACS levels III to V and GMFCS levels IV and V were independently associated with increased propensity to reflux or seizures (OR = 8.16, 95% CI = 1.77–37.5, p = 0.007; OR = 3.37, 95% CI = 1.09–10.4, p < 0.034). Mealtime symptoms of vomiting or regurgitation (relative risk = 1.58, 95% CI = 1.17–2.13, p = 0.032) and daily coughing (relative risk = 1.55, 95% CI = 1.14–2.11, p = 0.023) were associated with a higher risk of reporting one or more oral health symptoms. Toothache was more common in participants classified in EDACS levels III to V (χ2, p = 0.021).InterpretationChildren with CP classified in EDACS levels III to V are at a higher risk of respiratory disease and toothache and should be screened appropriately. Regurgitation or vomiting of food and daily coughing are linked with poorer oral health.

AbstractAimTo estimate the cumulative risk of epilepsy after neonatal seizures and identify subpopulations at increased risk.MethodThis was a nationwide register‐based cohort study including all children born in Denmark between 1997 and 2018. The cumulative risk of epilepsy in children with and without neonatal seizures was compared. Furthermore, neonatal seizures were stratified according to aetiology.ResultsWe followed 1 294 377 children and identified 1998 neonatal survivors with neonatal seizures. The cumulative risk of epilepsy was 20.4% (95% confidence interval [CI] = 18.5–22.3) among children with neonatal seizures, compared to 1.15% (95% CI = 1.12–1.18) among children without. Epilepsy was diagnosed before 1 year of age in 11.4% of children with neonatal seizures, in an additional 4.5% between 1 year and 5 years, 3.1% between 5 years and 10 years, and 1.4% between 10 years and 22 years. The aetiologies of neonatal cerebral infarction, haemorrhage, or malformations (adjusted hazard ratio = 2.49, 95% CI = 1.98–3.14) and low Apgar score (1.49, 95% CI = 1.12–1.98) were associated with the highest risk of epilepsy, compared to children with seizures of unknown aetiology.InterpretationEpilepsy after neonatal seizures is common and remains a substantial risk throughout childhood. Aetiological risk factors are identifiable and relevant when planning appropriate information for parents and follow‐up.

AbstractAimTo evaluate the efficacy of the Akwenda Intervention Program on participation attendance and involvement of children and young people with cerebral palsy (CP) in rural Uganda.MethodThis was a cluster‐randomized, controlled, single‐blind, interventional study of 100 participants with CP (aged 2–23 years; 48 females; allocated to the intervention or waiting list control group). Picture My Participation interviews assessed participation attendance and involvement in 20 home and community activities. Group differences were analysed using a Mann–Whitney U test and effect sizes were calculated. Change in attendance was related to age and functional level, and to improvements in child functioning, which was published in a previous report from the same study.ResultsAttendance increased more in the intervention compared to the control group (p < 0.001; r = 0.48; z = −4.62) and across both Gross Motor Function Classification System (GMFCS) subgroups and two age subgroups (2–5 years and 13–23 years). Positive correlations were found between increases in attendance and higher GMFCS levels (ρ = 0.25, p = 0.03) and with all three caregiver assistance scales and the social function child scale of the Ugandan version of the Pediatric Evaluation of Disability Inventory. The intervention group had larger increases in involvement than the controls (p < 0.001; r = 0.41; z = −3.95), although positive changes were seen in both groups.InterpretationThe Akwenda Intervention Program, which intervened at the level of the child, family, and community, was successful in enhancing participation for children with CP.

AbstractAimTo map and critically appraise the literature on the feasibility and current use of functional near‐infrared spectroscopy (fNIRS) to assess cortical activity, functional connectivity, and neuroplasticity in individuals with cerebral palsy (CP).MethodA scoping review methodology was prospectively registered and reported following Preferred Reporting Items for Systematic review and Meta‐Analysis Extension for Scoping Reviews (PRISMA‐ScR) guidelines. A systematic search was conducted in four databases. Empirical studies using fNIRS to assess neural activity, functional connectivity, or neuroplasticity in individuals with CP aged 3 years or older were included.ResultsSixteen studies met the inclusion criteria. Individuals with CP (age range = 3–43 years; 70% unilateral CP) underwent fNIRS‐based assessment for task‐evoked activity (studies [n] = 15) and/or resting‐state functional connectivity (n = 3). Preliminary observations suggest greater magnitude, extent, and ipsilateral hemispheric lateralization of sensorimotor cortex activity in CP, while magnitude and patterns of prefrontal cortex activity in CP appear dependent on task demands. Normalization of fNIRS‐based activity metrics observed postintervention (n = 3) paralleled improvements in functional outcomes, highlighting their potential as promising biomarkers for functional gains in CP.InterpretationThis review details the use of fNIRS in CP, highlights research gaps and technical limitations, and offers recommendations to support fNIRS implementation for ecologically valid functional neuroimaging in individuals with CP.

AbstractAimTo evaluate the construct validity and responsiveness of the Gross Motor Function Measure‐66 Item Set (GMFM‐66‐IS), a standardized criterion‐referenced observational measure, for use with children younger than 24 months with or at high risk for cerebral palsy (CP).MethodNon‐experimental integrative data analysis was performed on secondary data from three clinical trials involving children with or at high risk for CP (n = 79, 42 males, mean corrected age = 11.3 months [SD = 4.9]), and one observational study of typically developing children (n = 32, 14 males, mean age = 5.7 months [SD = 0.8]). The GMFM‐66‐IS and comparator instrument (gross motor subtest from the Bayley Scales of Infant and Toddler Development, Third Edition [Bayley‐III] or Bayley Scales of Infant and Toddler Development, Fourth Edition [Bayley‐4], depending on the study) were administered at baseline and 3 months later. Comparator groups were based on neurological impairment, clinical rating of gross motor change, and CP status. Correlations (r) and regression‐adjusted standardized mean differences (Hedges' g) were computed.ResultsGMFM‐66‐IS and Bayley scores were correlated at baseline (r = 0.83), 3 months later (r = 0.88), and across time (r = 0.83). Children with mild impairment had higher mean GMFM‐66‐IS scores at baseline (g = 0.87) and 3 months later (g = 0.95). Children rated as demonstrating greater than expected gross motor change had larger mean GMFM‐66‐IS change scores than children demonstrating less than expected change (g = 0.62). Typically developing children had larger mean GMFM‐66‐IS change scores (g = 1.00).InterpretationGMFM‐66‐IS scores were supported by evidence of strong construct validity and moderate responsiveness.

AbstractAimTo describe the prevalence and incidence of pain, identify prognostic factors for pain, determine psychometric properties of tools to assess pain, and evaluate effectiveness of interventions for reducing pain among adults with cerebral palsy (CP).MethodSix databases were searched to identify studies published since 1990 in any language that met eligibility criteria defined for each objective. Titles, abstracts, and full texts were screened by two independent reviewers.ResultsSixty‐three studies were identified; 47 reporting prevalence, 28 reporting prognostic factors, four reporting psychometric properties, five evaluating intervention effectiveness. Pain prevalence ranged from 24% to 89%. Prevalence was higher among adults with CP than in adults without it. Communication function, sex, and age were prognostic factors for pain prevalence. Numerical, verbal, and pictorial rating scales were valid for assessing pain intensity in adults with CP. Pharmacological and surgical interventions had no effect on pain. An active lifestyle and sports intervention reduced pain in adults with CP compared with usual care.InterpretationMany adults with CP experience pain, although prevalence estimates vary considerably. The quality of evidence for prognostic factors and interventions is very low to low. There is a lack of evidence about effective pain management among adults with CP.

AbstractAimTo determine reproducibility of the Motor Optimality Score–Revised (MOS‐R) to assess infants at high risk of adverse neurodevelopmental outcomes, including cerebral palsy (CP), autism, and developmental delays.MethodThirty infants (18 males, 12 females, gestational age mean [range] = 32.5 [23–41] weeks) were randomly selected, according to 2‐year outcome (typically developing; CP; or adverse neurodevelopmental outcome [ad‐NDO]) from a prospective cohort. Participants had two General Movements videos between 12 weeks and 15 + 6 weeks corrected age. Six assessors, masked to history and outcomes, independently scored the MOS‐R from videos. Assessors scored either one (Group 1; n = 3) or two videos for each infant (Group 2; n = 3). Intraclass correlation coefficient (ICC), Gwet's agreement coefficient, and limits of agreement were calculated.ResultsCombined interassessor reliability (IRR) over six assessors for total MOS‐R was ‘fair’ (ICC = 0.56, 95% confidence interval [CI] 0.41–0.72), and ‘excellent’ with consensus agreement (ICC = 0.99, 95% CI 0.98–0.99). Analyses demonstrated a mean interrater difference of 0.316 (95% limits of agreement −11.51, 12.14) over 450 comparisons (15 pairs). IRR was ‘moderate’ to ‘almost perfect’ across subcategories, with the highest reliability ‘movement patterns’ (Gwet's agreement coefficient = 0.73–1.00) and the lowest ‘postural patterns’ (0.45–0.73). Assessors who scored two videos (Group 2) demonstrated higher reproducibility. IRR for total MOS‐R was ‘excellent’ when infants were typically developing (ICC = 0.90), and ‘good’ for CP (0.74) and ad‐NDO (0.68).InterpretationThe MOS‐R is a highly reproducible tool for assessing infants at high risk of ad‐NDOs and is feasible for implementation in clinical settings. Reproducibility is best when the tool is used by experienced assessors to gain consensus agreement.

AbstractAimTo conduct a postmarketing surveillance study of patients with Dravet syndrome in Japan to investigate the safety and effectiveness of long‐term, real‐world, clinical use of stiripentol (STP).MethodThis prospective study was conducted over 156 weeks in all patients with Dravet syndrome who started STP treatment from its launch in Japan in November 2012 until August 2017. Adverse drug reactions (ADRs) were investigated by degree of seriousness. Effectiveness was determined based on a comprehensive assessment by the physician in charge as well as on the percentage change in the number of seizures from the pretreatment period.ResultsIn total, 520 patients (266 males, 254 females; mean age [SD] 10 years 6 months [9 years 10 months]; age range 0–50 years) were included in the safety analysis set, and 515 patients in the effectiveness analysis set. ADRs occurred in 69.2%, including somnolence, decreased appetite, dizziness, in order of frequency. Twelve deaths occurred, the rate of which was not higher than the reported rates. No new safety concerns were identified. The rate of overall improvement (marked or moderate) after 156 weeks or at treatment discontinuation was 37.7%. Decreases in the number of all seizure types over the long term were confirmed.InterpretationIn real‐world clinical settings, long‐term STP treatment can be safe and effective in patients with Dravet syndrome.