Neuropediatrics最新文献

We investigated the racial and ethnic distribution of participants in Duchenne muscular dystrophy (DMD) phases II and III clinical trials.A total of 36 DMD phases II and III clinical trials were analyzed for racial and ethnic information. Publicly available demographic information was collected from DMD phases II and III clinical trials registered between 2005 and 2018 from the clinical trials database (clinicaltrials.gov). Clinical trial participation was also analyzed based on geographic location (international vs. United States) and funding source (industry vs. academia).White participants accounted for 84% of study participants in DMD phases II and III clinical trials in both multinational studies and within the continental United States. Among the 36 trials, 22% (8/36) did not report racial data, and 44% (16/36) did not report ethnicity. Most DMD phases II and III clinical trials were funded by industry (89%) compared with the National Institutes of Health (3%) and other sources (8%).White participants are most represented in DMD phases II and III clinical trials. The documentation of racial and ethnic information in DMD clinical trials is insufficient. These data highlight the need for further approaches to diversify and include equitable representation in DMD clinical trials.

Hematopoietic stem cell transplantation (HSCT) is frequently the sole curative treatment for a range of hematologic and nonhematologic disorders. One of the most notable neurological complications associated with HSCT is posterior reversible encephalopathy syndrome (PRES), which affects approximately 1 to 10% of pediatric recipients. Although usually reversible, PRES can lead to serious morbidity and lethality. This systematic review and individual participant data (IPD) meta-analysis aims to evaluate risk factors for lethality and characterize the clinical course of PRES in pediatric HSCT patients. Studies reporting PRES in pediatric HSCT recipients with data on outcomes and risk factors were included. Data were sourced from PubMed, Web of Science, Scopus, and Embase (last search: October 20, 2024). IPD were extracted from articles or requested from corresponding authors. Risk of bias was assessed using the Newcastle-Ottawa Scale. A one-stage IPD meta-analysis evaluated associations between risk factors and lethality and descriptive analyses reported the clinical course of PRES in the included population. Among 175 pediatric patients with PRES across 15 studies, the mean age was 8.68 years, and 64.8% were male. PRES occurred on average 73.08 days post-HSCT presenting with seizures (90.3%), hypertension (87.8%), altered mental status (31.9%), headache (28.5%), visual disturbances (27.1%), and atypical presentations (24.3%). Neuroimaging findings indicated that 12.3% of cases involved only anterior or posterior brain circulation, while most (75.4%) demonstrated dual circulation involvement, with bilateral cerebral involvement observed in 89.8% of patients. The overall lethality rate was 32.5%. The meta-analysis reported an overall prevalence of 7% for PRES among pediatric recipients of HSCT. The IPD meta-analysis revealed no significant associations between lethality and factors such as age (p = 0.590), sex (p = 0.516), atypical PRES presentations (p = 0.642), or the specific cerebral circulation involved (p = 0.758). Conversely, acute graft-versus-host disease demonstrated a trend toward statistical significance for association with lethality (p = 0.056). Additionally, underlying malignant disease (odds ratio [OR]: 2.635, 95% confidence interval [95% CI]: 1.256-5.529, p = 0.01), the use of cord blood as a cell source (OR: 5.692, 95% CI: 1.241-26.109, p = 0.025), and transplantation from an unrelated donor (OR: 4.948, 95% CI: 2.176-11.249, p < 0.001) were significantly associated with increased lethality risk. Malignant underlying disease, cord blood transplantation, and unrelated donors significantly increase lethality risk in pediatric HSCT recipients with PRES. These findings underscore the importance of tailored management strategies to identify and monitor at-risk pediatric HSCT recipients.

To analyze neurodevelopmental outcome of children born very preterm (born 2012 to 2018) aged 5 years in Vorarlberg, Austria. To identify medical risk factors and compare with (inter)national data.In this population-based study with prospectively collected data very preterm children underwent neurodevelopmental assessment: Kaufman Assessment Battery for Children (KABC-II) for cognitive functioning, Movement Assessment Battery for Children (M-ABC-2) for motor skills, Strengths and Difficulties Questionnaire (SDQ) and Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P) for deficits in behavior and executive functions. Risk factors were identified using multiple linear regression.The study population (n = 114, 46.5% completed follow-up) showed moderate to severe neurodevelopmental disability (KABC-II IQ score <70), mild (KABC-II IQ score 70-84, M-ABC-2 total score <7, SDQ total score >90th percentile or BRIEF-P Global Executive Function score T >65), and no neurodevelopmental disability in 2.9, 31.4, and 65.7% of the children, respectively. Results were more disadvantageous for children born extremely preterm than for very preterm born children. Regarding risk factors, abnormal hearing screening, male gender, and ICH grades 3-4 were associated with poorer cognitive and motor skills.In our state-wide cohort of very preterm children, we observed a small proportion of moderate to severe neurodevelopmental disabilities of 2.9%, whereby 65.7% had no disability at 5 years. Disadvantageous outcomes are more pronounced in extremely preterm children.

Disease-causing variants in KCNMA1 are associated with a spectrum of epilepsy and/or movement disorders, often with additional developmental issues or intellectual impairment. Monoallelic gain-of-function variants often lead to paroxysmal nonkinesigenic dyskinesia (PNKD). While the treatment mechanism is unknown, dextroamphetamine and its prodrug lisdexamfetamine have been shown to successfully control the debilitating PNKD with up to several hundred daily incidents in one patient with the KCNMA1 (NM_001161352.2) c.1606A > C p.(Asn536His) and six patients with the c.3158A > G p.(Asn1053Ser) variant. Via exome sequencing, a monoallelic KCNMA1 c.2367C > A, p.(Asp789Glu) variant was detected in a 7-year-old girl with daily behavioral arrests, tremors, and drop attacks/PNKD occurring every 8 weeks. The girl had moderate difficulties in mainstream school and experienced challenges in her social life as she was easily fatigued. Additionally, she was heat-intolerant and unable to sweat. Lisdexamfetamine treatment led to cessation of the neuro(psycho)logical symptoms, better functioning in daily life and at school during more than 2 years of follow-up. This report illustrates the importance of an exact, genetic diagnosis for successful individual treatment. It adds another previously unreported variant in KCNMA1. Furthermore, this case increases the evidence for a broader treatment effect of lisdexamfetamine for KCNMA1 variants beyond its known effects on the control of muscle tone, in this case illustrated by better social interaction, improved attention/school performance, and mood. Finally, the previously unreported findings of heat intolerance and inability to sweat may extend the phenotypic spectrum associated with KCNMA1 variants.

Congenital nephrotic syndrome (CNS) is a severe renal disorder in newborns, characterized by complications such as albuminuria, hypoalbuminemia, and hypercoagulability. While CNS is known to predispose patients to thrombosis over time, to our knowledge, cerebrovascular complications such as cerebral sinovenous thrombosis (CSVT) within the first week after birth have rarely been reported before in neonates with confirmed CNS. We present here an infant, born by normal vaginal delivery, which was complicated by the retention of a large placenta. She was first admitted on day 3 with perioral cyanosis and polycythemia. She developed apneas that were later confirmed with amplitude integrated EEG to be seizures and was found to have multiple thrombotic complications, including extensive CSVT and bilateral thalamic hemorrhages. Serum albumin level was very low, with high urinary levels suspicious for Finnish-type CNS, which was confirmed by NPHS1 pathogenic variants p.Cys623Phe and p.Asn870Profs*36. Despite partial exchange transfusions and anticoagulation therapy, the infant developed severe cerebral abnormalities. This case underscores the importance of considering CNS in neonates with a large placenta, severe polycythemia, proteinuria, and hypoalbuminemia, as they may be at risk of developing CSVT.

We aim to identify the associated abnormalities, underlying etiology, and risk factors that may lead to motor/cognitive impairment in children with corpus callosum (CC) malformations. This will provide clinicians with data to predict the prognosis of children with CC malformations in the prenatal and/or neonatal period.Children with agenesis or hypoplasia of any part of the CC on neuroimaging within 11 years at a tertiary care university hospital were retrospectively evaluated for demographic and clinical characteristics, other associated systemic abnormalities, etiologies, and prognosis. Children with a history of hypoxia, intracranial hemorrhage, hydrocephaly, stroke, or brain tumor were excluded. Data analysis was performed with SPSS software. Univariate and multivariate analyses were used to evaluate risk factors for the development of motor/cognitive impairment.A total of 165 children were included, 44% of whom were girls. The most common associated abnormality was ocular. Microcephaly was present in 42% (n = 69). Regarding the genetic etiology, five children were diagnosed by karyotype analysis, two by trinucleotide repeat analysis, one by fluorescence in situ hybridization analysis, seven by array comparative genomic hybridization, 11 by single gene mutations, and 15 by whole-exome sequencing. The presence of microcephaly, epilepsy, abnormal electroencephalogram (EEG) findings, and abnormal neurological examination was associated with the risk of developing both cognitive and motor delay. Involvement of a body part of the CC was slightly associated with the risk of motor delay (p = 0.043).Malformations of the CC can result in varying degrees of neurodevelopmental disability. The presence of microcephaly, epilepsy, abnormal EEG findings, and abnormal neurological examination can be used to predict the outcome.

Related issues, such as sleep disturbance, are also frequently reported by children with autism spectrum disorder (ASD). This study systematically reviewed the influences of exercise on sleep and anxiety in children with ASD. Search for eligible studies through four databases, and then proceed with screening. The inclusion criteria are as follows: 1) children with ASD; 2) age 3 to 14 years; 3) randomized controlled trial (RCT); 4) the intervention group received exercise training; 5) conducted pre-and posttest, which includes sleep and anxiety. Use the Cochrane bias risk assessment tool to evaluate the quality of the selected study. Select standardized mean difference (SMD) as the appropriate effect scale index, and use Revman 5.4 software to analyze the mean difference of the selected article data. A total of seven studies fulfilled the inclusion criteria and were selected for the meta-analysis. The included studies involved 387 males and 79 females. The results demonstrated that the EXP group benefited from improved sleep (SMD, -1.05 [-1.25, -0.85], p < 0.05, I² = 27%, p for heterogeneity = 0.22) and anxiety (SMD, -1.14 [-1.56, -0.72], p < 0.05, I² = 95%, p for heterogeneity < 0.01) than the CON group. According to the findings, physical activities could offer nonpharmacological interventions for improving sleep and anxiety in children diagnosed with ASD. Sports training could also be considered to promote the rehabilitation of children patients with ASD, which might provide valuable insights.

To determine the effects of empiric antibiotic therapy within the first 72 hours after birth, in cases of suspected early-onset sepsis without positive blood cultures, on the neurodevelopment of VLBW infants.Cohort study conducted from January 2014 to December 2021, included neonates from 24 to 32 weeks' gestation. They were categorized based on receiving early antibiotics. Outcomes measured included neonatal morbidities and scores on the Bayley Scales of Infant Development, Third Edition (BSID-III), at 12 to 36 months corrected age.Of 261 VLBW infants 52.9% (n = 138) received empiric antibiotics within the first 72 hours, while 47.1% (n = 123) did not. Multivariate analysis revealed no association between early antibiotics and neurodevelopmental delay. Severe intraventricular hemorrhage independently correlated with delays, while late-onset sepsis and bronchopulmonary dysplasia contributed to specific motor and cognitive delays. Propensity score matching (PSM) was conducted using various models that included gestational age, late-onset sepsis, severe intraventricular hemorrhage, bronchopulmonary dysplasia, and clinical chorioamnionitis. However, antibiotic use was not independently associated with an increased risk of developmental delay in the applied models.Although the use of antibiotics did not emerge as an independent factor contributing to developmental delay, VLBW infants who received antibiotics had more morbidities during their NICU stay.

This study aimed to compare two distinct consciousness evaluation scores (the pediatric Glasgow coma scale [GCS] scale and the full outline of unresponsive [FOUR] score) to predict outcomes for children admitted to the pediatric intensive care unit with impaired consciousness.Children aged between 2 and 18 years who presented with impaired consciousness were included in this longitudinal study. The lead investigator evaluated the pediatric GCS score and the FOUR score. The first 3 days' score readings of both the scores were taken for analysis. The primary outcome of children was recorded as in-hospital mortality. The secondary outcome was functional outcome measured by the modified Rankin scale.A total of 78 children presented with impaired consciousness were eligible for statistical analysis. Survivors and nonsurvivors had significantly different FOUR and GCS scores at admission, 24 and 48 hours (p < 0.0001). The predictive accuracy of the FOUR scale at admission was slightly higher than GCS considering that the area under the curve (AUC) for the FOUR score was higher (AUC = 0.850; 95% confidence interval [CI]: 0.735-0.956) than GCS (AUC = 0.834; 95% CI: 0.735-0.934). The projected outcome based on the FOUR score and the actual patient outcomes were statistically significantly correlated (p = 0.021). Results showed that the FOUR scores had higher sensitivity (89%) specificity (84%), and negative predictive value (83%) than the GSC scale.The FOUR at admission was a better predictor of the outcome as compared with the Glasgow coma scale. More sensitivity of the FOUR scores than GCS makes it an advisable predictive model for children with impaired consciousness.