Neuropediatrics最新文献

NPRL3 (nitrogen permease regulator-like 3) variants are associated with focal epilepsy syndromes, including sleep-related hypermotor epilepsy (SHE) and familial focal epilepsy with variable foci (FFEVF), with or without focal cortical dysplasia (FCD). The NPRL3 gene encodes a protein that forms the GATOR1 complex, which regulates the mTOR signaling pathway.To characterize the epilepsy phenotype associated with NPRL3, assess treatment strategies, and evaluate patient prognosis.We conducted a multicenter, retrospective study using an online questionnaire to collect clinical data on seizure onset, crisis-like seizure exacerbations, MRI findings, neuropsychological assessment, treatment, and genetic variants. Variants were classified per ACMG guidelines. The study was part of the Network for Therapy in Rare Epilepsies (NETRE).Data from 37 patients with NPRL3-associated epilepsy were analyzed. Mean age at seizure onset was 3.7 years (median with interquartile range [IQR] 1.3-4.9). Over 1 to 45 years of follow-up (mean 13.6, IQR 5.4-18), 21/37 (57%) experienced crisis-like seizure exacerbations. MRI abnormalities were present in 10/36 (28%) cases: 8 FCD, 1 hippocampal sclerosis, and 1 hippocampal asymmetry. Persistent focal epileptiform discharges were present on serial EEGs in 20/37 patients (54%). Highest drug response rates were seen with lacosamide, followed by clobazam, carbamazepine/oxcarbazepine, and lamotrigine. Epilepsy surgery (n = 8) led to seizure freedom in four and significant reduction in one case.Crisis-like seizure exacerbations were common in NPRL3-associated epilepsy. Sodium channel blockers showed notable efficacy. Epilepsy surgery was beneficial even in MRI-negative cases. No distinct genotype-phenotype correlation was identified.

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.

Subacute sclerosing panencephalitis (SSPE) is a neurodegenerative disease caused by the measles virus. An affected child typically presents with cognitive decline and abnormal movements, described as myoclonia. Early diagnosis is crucial for prognosis, but can be challenging because early symptoms may be subtle, and EEG findings are not always typical. We propose that better description and documentation of motor symptoms may facilitate earlier recognition of SSPE.A 4-year-old boy presented with cognitive decline and motor symptoms evolving over 6 months. The patient had a history of measles at 2 months of age. Initial investigations, conducted when he developed clinical regression and abnormal movements, were inconclusive. After a partial recovery, he relapsed with further regression, worsening of abnormal movements, and seizures. At our hospital, we diagnosed SSPE based on Dyken's criteria. EEG and EMG recordings showed movements beginning after a diffuse slow wave, followed by a flattening of the EEG line, with a typical diamond pattern on the EMG lasting 0.5 to 1 second. Movements were classified as epileptic spasms.We propose that patients with SSPE may present epileptic spasms as the abnormal motor phenomena, and not only myoclonus. Raising awareness about epileptic spasms as a clinical manifestation may aid early diagnosis of SSPE.

The term "neuromonitoring" denotes several methods that are used to monitor the state of the central nervous system. It is mainly used in intensive care units to mitigate the limitations of the clinical neurological examination, which arise in the context of critical illness, sedation, and neuromuscular blockade. In the pediatric intensive care units, neuromonitoring methods are increasingly used across all age groups. This article aims to give an overview of the four most frequently used technical noninvasive neuromonitoring modalities (electroencephalogram, near-infrared spectroscopy, transcranial Doppler, and automated pupillometry) and the evidence for their use in three clinical scenarios: seizures, increased intracranial pressure, and stroke.

Early treatment improves long-term outcomes for persons living with multiple sclerosis (MS). Patients with pediatric-onset multiple sclerosis (POMS) experience delays in diagnosis and treatment with disease-modifying therapy (DMT). Here, we explore how a dedicated nurse care coordinator decreases time to treatment in POMS.We included a retrospective cohort of 60 POMS at a single center between 2018 and 2024. The primary outcome was time to DMT initiation. Secondary outcomes included relapse rates and Extended Disability Status Scale (EDSS) scores.In 60 participants, 39 were in the precoordinator group and 21 were in the postcoordinator group. Age, race, ethnicity, insurance, and the area deprivation index did not affect outcomes. However, the postcoordinator group had a shorter time from diagnosis to initiation of DMT (median: 49 days, interquartile range [IQR]: 40-57 days) compared to the precoordinator group (median: 126 days, IQR: 57-254 days, p < 0.001).Here, we found that a care coordinator decreased time to DMT initiation and should be implemented in clinical care.Having a dedicated nurse coordinator to help patients with MS with obtaining their treatments, including their DMTs, can result in a shorter time to starting a DMT.

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.