Neuropediatrics最新文献

This retrospective, dual-center Italian study assessed the incidence, electroclinical characteristics, and risk factors for post-neonatal epilepsy among neonates with hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH). The study aims to better define the long-term risk factors for developing epilepsy or neurodevelopmental issues.We included neonates with HIE who underwent TH. Neurological examination and general movements were assessed before and after TH. Amplified-integrated EEGs (aEEG) or polygraphic EEGs (pEEG) were performed within 6 hours of life; a pEEG was performed after TH (72 hours to 10 days) and at 3, 9 to 12, and 24 months, and then yearly. Brain MRI was conducted within 30 days. The 24-month developmental outcome was evaluated using Griffiths Mental Development Scales. The median follow-up duration was 48 months. Epilepsy was classified according to ILAE criteria.We enrolled 159 patients: 15 (9.4%) developed epilepsy. Nine (5.6%) had onset before 24 months; three of them developed infantile epileptic spasm syndrome (IESS). Seizure onset was after 24 months in 6/159 individuals (3.8%). At the last follow-up, all 15 patients had focal epilepsy. Global development was pathological in 11/15 (10/15 <2SD; 1/15 <1SD). Risk factors for post-neonatal epilepsy included: MRI lesions involving the basal ganglia and thalamus (p < 0.0001), severe HIE (p = 0.0008), and severe anomalies on the pEEG recorded pre-TH (p = 0.0032) and post-TH (p = 0.0071).Our study confirms that post-neonatal epilepsy is rare and generally well-controlled. MRI, HIE-3, and early pEEGs are key predictors. High-risk patients should be screened for IESS in the early months, and patients with electroclinical and neuroradiological risk factors should continue long-term neurological follow-up beyond 24 months.

Pompe disease is a rare lysosomal storage disorder with a wide clinical spectrum ranging from infantile-onset Pompe disease (IOPD) with early severe cardiomyopathy to late-onset Pompe disease (LOPD) with progressive muscle weakness. This study aimed to evaluate clinical features, genotype-phenotype correlations, treatment outcomes, and significant events in a real-life pediatric cohort of Pompe patients.We retrospectively analyzed 30 pediatric patients diagnosed with Pompe disease (27 IOPD, 3 LOPD). Demographic, clinical, biochemical, genetic, and radiologic data were collected. Recurrent clinical events were assessed using the Andersen-Gill extension of the Cox model to evaluate the effect of enzyme replacement therapy (ERT).The median age at diagnosis was 5 (range 20 days to 80 months) months, and consanguinity was present in 83% of cases. IOPD cases predominantly showed hypotonia and cardiac involvement, whereas LOPD cases were asymptomatic or mildly symptomatic, with delayed motor development and increased CK levels. Novel GAA mutations were identified in seven patients. ERT was administered to 24 IOPD patients, leading to improved cardiac function and prolonged survival. Event incidence was significantly lower in the ERT group (HR = 0.06, p < 0.005), despite a longer follow-up. However, 56% of patients-all with IOPD-died during follow-up. Non-muscular findings such as neurogenic bladder in 6.6% (2/30), sensorineural hearing loss in 13.3% (4/30), and white matter abnormalities in 40.9% (9/21) were also documented.This real-life evidence reinforces the central role of early, individualized ERT and comprehensive multidisciplinary care in altering the natural course of Pompe disease.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) poses challenges for affected children and young people (CYP) and their parents. There is often a lack of knowledge about the illness. Education programs can help address this by providing knowledge and supporting the independent management of the condition. For this reason, two online education programs-one for affected CYP and one for their parents-were developed, implemented, and evaluated in terms of acceptance, format, and benefits.A total of 24 CYP with ME/CFS, aged of up to 20 years, and their parents were recruited for this study. Of these 22 CYP with ME/CFS and 20 parents participated in the online education program. After development and conduct of the programs, six affected CYP were interviewed using written questions, which were answered via an audio device. Furthermore, six semi-structured interviews were obtained with parents. All parents also received an online questionnaire to evaluate the program. Data were analyzed using both quantitative and qualitative methods.Both CYP and their parents expressed overall satisfaction with the program, highlighting aspects such as knowledge acquisition or reinforcement and, importantly, the opportunity to connect with other affected CYP or their parents. The online format was also perceived very positively.The online education program met the expectations and needs of both affected CYP and parents regarding content and format. It facilitated exchange and provided practical knowledge. In this format, the online program appears to be a valuable component of care for those affected.

Continuous electroencephalography (cEEG) is increasingly used in pediatric intensive care units (PICUs), but data on its diagnostic yield and prognostic value in critically ill children remain limited. This study evaluated EEG monitoring practices, seizure detection, treatment changes, and long-term epilepsy outcomes in a tertiary PICU.We retrospectively analyzed 184 children (1 month-18 years) who underwent intermittent EEG or cEEG in a tertiary PICU between 2018 and 2022. Demographic and clinical features, EEG indications and findings, antiseizure treatment modifications, and outcomes were obtained from medical records. Primary outcomes were acute seizure control, occurrence of nonconvulsive status epilepticus (NCSE), and development of drug-resistant epilepsy (DRE) during follow-up.Ninety-eight patients (53.2%) had clinical seizures, and 86 (46.8%) underwent EEG for altered mental status or suspected encephalopathy. cEEG was used in 102/184 and intermittent EEG in 82/184 patients. Electrographic seizures were detected in 22/184 (12.0%); antiseizure therapy was modified in 17/22 based on EEG, and previously unsuspected nonconvulsive seizures were identified in 5/184 (2.7%). Acute seizure control during the PICU stay was achieved in 99/101 (98.0%) patients with documented seizures. Over a median follow-up of 8.0 months, newly diagnosed DRE occurred in 38/184 (20.7%), predominantly in patients with acute encephalopathy, hypoxic-ischemic injury, or central nervous system (CNS) infection.In this pediatric PICU cohort, EEG-especially cEEG in high-risk patients-provided relevant information by improving electrographic seizure detection and guiding antiseizure management, while revealing a long-term burden of DRE. Prospective multicenter studies are needed to define the optimal role of EEG in pediatric neurocritical care.

Alexander disease represents a rare genetic leukodystrophy caused by abnormal astrocytic accumulations of intracytoplasmic proteinaceous inclusions with astrocyte dysfunction. With neonatal onset, survival ranges from 1.5 months to more than 7.5 years, with a possible association between the underlying point mutation, the level of protein accumulation in the cerebral white matter, disease progression, and survival time. We describe the clinical and cerebral imaging features of a female newborn with neonatal-onset Alexander disease caused by a heterozygous de novo point mutation c.1106T > C; p.(Leu369Pro) located in the coil 2B area of the glial fibrillary acidic protein (GFAP). Early-onset seizures, lethargy, and rapid loss of spontaneous movements were accompanied by rapidly evolving brain morphologic abnormalities and early death. The progression of cerebral abnormalities was monitored by magnetic resonance imaging and serial cranial ultrasound exams. As shown in this case study and the accompanying literature review, rapid accumulation of GFAP, as indicated by volume expansion of affected structures on brain imaging, combined with early onset of seizures and rapid clinical deterioration, seems to be associated with poor prognosis. In this case, high-resolution ultrasound offered an easily accessible, serial bedside imaging tool for the detection and follow-up of pathognomonic features of Alexander disease. We observed a close genotype-phenotype interaction in neonatal-onset Alexander disease, with the c.1106T > C; p.(Leu369Pro) mutation in coil2B associated with early death.

Intellectual disability (ID) and epilepsy are often comorbid, but the pathways that lead to epilepsy in individuals with ID remain unclear. This study aims to explore the molecular pathways linked to epilepsy development in ID, providing insights into shared genetic mechanisms.Definitive ID-related genes were extracted from the SysNDD database, and their association with epilepsy pathways was assessed using gene set overrepresentation analysis. Enrichment was performed using Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Disease Ontology (DO) terms. Pathways were classified based on their relevance to epilepsy, and the involvement of specific genes was analyzed.Approximately 75% of ID-related genes were associated with epilepsy. Enriched pathways in ID-related epilepsy genes included neurotransmitter signaling, ion channel regulation, and metabolic pathways such as "nicotine addiction" and "thermogenesis." Key genes like GRIN2A, CACNA1A, and PIGB were found to be involved in multiple pathways, suggesting their potential as therapeutic targets. DO and GO terms indicated shared and distinct mechanisms between ID and epilepsy, with significant overlap in pathways such as "intellectual disability."We performed overrepresentation analyses on curated gene sets; the results are descriptive and hypothesis-generating rather than causal. These insights provide potential targets for therapeutic interventions and highlight the need for further research into the genetic underpinnings of epilepsy in this population.

Spinocerebellar ataxia-21 (SCA21) is an autosomal dominant neurodegenerative disorder due to pathogenic variants of the TMEM240 gene. Its clinical presentation usually includes slowly progressive cerebellar ataxia, myoclonus-dystonia syndrome, cognitive impairment, and behavioral problems. Here, we reported the first patient with SCA21 presenting with a developmental and epileptic encephalopathy with seizure onset during late childhood, a seizure semeiology including atonic, clonic, myoclonic seizures, and absences with eyelid myoclonia and an EEG pattern characterized by diffuse spike and wave discharges. Epilepsy was associated with a progressive motor deterioration (the International Cooperative Ataxia Rating Scale-ICARS Total Ataxia score switched from 23/100 to 35/100 over a period of 2 years), a worsening of a preexisting tremor, and a disabling drowsiness. Nonverbal measure of intellectual functioning revealed a moderate intellectual disability (Leiter-R: brief IQ 40; fluid reasoning 52). The epileptogenic mechanisms involving TMEM240 might be correlated with disinhibition of excitotoxic networks due to the loss of Purkinje cells in the cerebellum, but also damage in neuronal bioenergetic pathways and synaptic vesicular trafficking within cortico-cerebellar and thalamo-cerebellar circuits.

Consensus on the first-line treatment of pediatric-onset multiple sclerosis (POMS) remains unresolved. Recently, dimethyl fumarate (DMF) and anti-CD20 therapies have been among the favorable options for pediatric multiple sclerosis (MS).This study aimed to determine the effectiveness and safety of DMF versus anti-CD20 therapies for POMS.We conducted a retrospective cohort study from July 2012 to July 2022 in the Isfahan MS clinic. MS cases under the age of 18 years old who received DMF or anti-CD20 agents as first-line treatment and were followed for at least 12 months were included.About 124 POMS cases were screened, of which 39 met the inclusion criteria. About 23 patients received DMF, while 16 patients received anti-CD20 (rituximab or ocrelizumab). The median (interquartile range, IQR) annualized relapse rate (ARR) decreased significantly (both with p < 0.0001) from 2.63 (0.68) to 0.0 (1.0) in the DMF group and from 2.89 (1.39) to 0.0 (1.0) in the anti-CD20 group. The median (IQR) expanded disability status score insignificantly changed from 1.0 (1.0) to 1.0 (0.5) in the DMF group, while it changed from 1.25 (1.0) to 1.0 (0.5) in the anti-CD20 group. After 12 months of follow-up, 12/16 in the anti-CD20 group and 17/23 in the DMF group were relapse-free. None of the treatment outcomes were different between the two treatment cohorts. Our study also assessed adverse events (AEs).While subject to replication in future clinical trials, both DMF and anti-CD20 therapies had a significant effect on reducing ARR and disease activity with an acceptable safety profile, but in our study, there were no differences in their efficacy.