Journal of Child Neurology最新文献

Synaptic vesicle fusion is a process that involves the release of neurotransmitters from synaptic vesicles into the synaptic cleft. VAMP1 is a protein that mediates synaptic vesicle fusion by forming a complex with other proteins on the presynaptic membrane. Mutations in VAMP1 have been recently identified as a cause of a rare form of hereditary spastic paraplegia (HSP), a group of genetic disorders characterized by the gradual development of muscle stiffness and weakness in the lower extremities. We discuss the current knowledge on the structure and function of VAMP1 and its role in synaptic transmission, the clinical features and genetic findings of patients with VAMP1 mutations, the possible pathogenic mechanisms of VAMP1 mutations, such as impaired SNARE complex formation, calcium signaling, and synaptic vesicle recycling and the potential therapeutic strategies for modulating VAMP1 function and restoring synaptic vesicle fusion in hereditary spastic paraplegia patients. We also highlight the research gaps and emerging technologies that may advance the understanding and treatment of VAMP1-related hereditary spastic paraplegia. Furthermore, the review presents some experimental studies that have investigated the molecular and functional consequences of VAMP1 mutations in various models, such as mice, cell lines, or patient-derived samples. These studies have provided evidence for reduced or altered VAMP1 expression, impaired synaptic vesicle fusion and neurotransmitter release, altered synaptic plasticity and excitability, and neuronal degeneration in VAMP1 mutation carriers. These findings suggest that VAMP1 mutations have a significant impact on synaptic vesicle fusion dynamics and neuronal function and may contribute to the pathogenesis and phenotypic variability of hereditary spastic paraplegia.

PurposeTo assess the efficacy and safety of an updated institutional treatment protocol for convulsive status epilepticus (CSE).MethodsA single-center, retrospective cohort study was designed to investigate the effectiveness of a protocolized approach for the treatment of pediatric convulsive status epilepticus. The revised Ege Pediatric Status Epilepticus Protocol (r-EPSEP) consists of first-line therapy (step 1 and step 2 with benzodiazepines), second-line therapy (step 3 and 4 with levetiracetam /diphenylhydantoin / valproic acid), and third-line therapy (step 5 with midazolam infusion, and step 6 with propofol or thiopental sodium infusion). The success rates of each therapy line of the r-EPSEP were defined with clinical termination of convulsive status epilepticus.ResultsThe convulsive status epilepticus cohort consisted of 293 children treated with the r-EPSEP. The cumulative success rates of each therapy line were as follows; first-line with 55.2%, second-line with 82.9%, and third-line with 96.9%. Benzodiazepine-resistant convulsive status epilepticus was defined in 131 children (44.7%) with convulsive status epilepticus. The r-EPSEP provided successful termination of refractory convulsive status epilepticus in 66 of 75 children (88%) with 3 therapy categorizations: (1) second-line therapy in 29 patients (38.6%), (2) midazolam infusion in 31 (41.3%), and (3) propofol or thiopental infusion in 6 (8%). Super-refractory convulsive status epilepticus evolved in 9 children (12%). A favorable neurologic outcome was defined in 74.7% of children with Modified Rankin Scores at the discharge time of children from the intensive care unit.ConclusionThe timeline-based protocol (r-EPSEP) provided considerable success rates in terminating status epilepticus episodes at predefined time points of each therapy line with a favorable early neurologic outcome.

The 5-Domain Niemann Pick Type C Clinical Severity Scale (5DNPCCSS) is used in clinical practice and trials. Although psychometric data support the clinical meaningfulness of the concepts and the scale's interrater reliability, more information is needed to support its construct validity. Here, we evaluated the convergent validity of the Cognition, Speech, and Fine Motor domains. Data from 121 individuals with Niemann-Pick disease type C were drawn from several studies conducted at 2 US sites. Direct standardized assessments included the Nine-Hole pegboard or Purdue pegboard, a portion of the Clinical Evaluation of Language Fundamentals, and the age-appropriate Wechsler IQ test or the Mullen Scales of Early Learning. The 5DNPCCSS domains were significantly related in the expected directions to their respective direct assessments, supporting their construct validity. In combination with previous evidence presented for the Ambulation and Swallow domains, these results support the fitness of purpose of the (5DNPCCSS for clinical studies in Niemann-Pick disease type C. ClinicalTrials.gov: NCT00344331, NCT01747135, NCT02534844.

IntroductionDuchenne muscular dystrophy, the most common inherited neuromuscular disease in children, typically presents its first symptoms at 3-5 years of age with progressive muscular weakness. However, in some boys, the disease manifests earlier in childhood with developmental delays, such as delays in walking and speech, or signs of an autism spectrum disorder.ObjectiveTo analyze and compare the age and time until diagnosis in boys with Duchenne muscular dystrophy, with or without developmental delays as the first sign of disease.Material and MethodsThis is a retrospective descriptive study. Data were collected from 127 boys with Duchenne muscular dystrophy who were followed at the Outpatient Muscle Clinic of Hospital das Clínicas (FMUSP/SP) from 2015 to 2024. To determine the age and time interval between symptom onset and diagnosis, we analyzed the total sample, and 3 separate groups based on initial symptoms.ResultsIn the total sample, the mean age of diagnosis was 6.9 years, with an average interval of 3.6 years between symptom onset and diagnosis. In patients with developmental delays, initial symptoms were observed at an average age of 1.4 years, and despite a diagnosis delay of 3.4 years, these patients were diagnosed an average of 2.7 years earlier than those with normal development.ConclusionOur findings suggest that Duchenne muscular dystrophy should be considered in the differential diagnosis of boys presenting with developmental delays (motor, speech, or cognitive). In such cases, screening with creatine kinase level measurements is crucial.

BackgroundThe transition from pediatric to adult headache care creates an opportunity for changes in care, although the nature of these changes has not been previously explored. We aim to describe the changes in management during this transition period.MethodsA retrospective chart review was conducted on 80 patients who transitioned from pediatric neurology to adult headache clinic within the span of 1 year. The demographics, diagnoses, and treatment regimens were analyzed.ResultsOn average, patients held their first adult headache clinic visit 118 days following their last pediatric visit. More than half of patients experienced changes in either diagnosis or treatment during transition.ConclusionThis research emphasizes the significant influence of care transitions on the management of patients with primary headache disorders.

This retrospective observational study investigates the clinical and neuroimaging profiles of children with cerebral palsy and explores the contribution of genetic factors to its etiology. We reviewed 302 pediatric cases diagnosed with cerebral palsy in Southern Brazil during 2023. Neuroimaging abnormalities were present in 92.1% of cases, with leukomalacia being most frequent. Neonatal encephalopathy emerged as the leading etiology, followed by prematurity and genetic conditions. Genetic testing was performed in 68 patients, identifying 29 distinct genes, notably in cases with preserved imaging or kernicterus. Dyskinetic and ataxic cerebral palsy were more often associated with normal neuroimaging, although not necessarily with positive genetic findings. Some patients with kernicterus also had genetic etiology, especially G6PD. The study reinforces that normal imaging does not exclude underlying genetic causes, especially in patients lacking perinatal complications or exhibiting dyskinetic patterns. These findings emphasize the complementary roles of neuroimaging and genetic in the multifactorial nature of cerebral palsy.

Neuronal ceroid lipofuscinoses are rare, inherited lysosomal storage disorders characterized by progressive neurodegeneration due to aberrant lysosomal function. This study presents 2 cases of CLN7 and CLN8, illustrating the genetic and clinical heterogeneity of neuronal ceroid lipofuscinoses. The first case involves a patient with CLN7, manifesting developmental regression, epilepsy, and motor impairment. The second case presents CLN8, marked by progressive cognitive decline, intractable seizures, and motor dysfunction. Whole exome sequencing confirmed pathogenic mutations in both cases, reinforcing the critical role of genetic diagnostics in precise disease classification. These cases emphasize the necessity of early genetic screening for timely intervention and accurate neuronal ceroid lipofuscinosis subtype classification, which is vital for prognosis and personalized management. Multidisciplinary care, including genetic counseling, neurologic assessment, and supportive therapies, is paramount in optimizing patient outcomes. Documenting these cases contributes to a deeper understanding of neuronal ceroid lipofuscinosis phenotypic variability, supporting ongoing research into genotype-phenotype correlations and potential disease-modifying therapies.

Spinal muscular atrophy (SMA) is a progressive neuromuscular disorder caused by mutations in the SMN1 gene, leading to motor neuron degeneration. This report presents a case of a 22-day-old infant with spinal muscular atrophy who was found to have elevated troponin I level in preparation for administration of a gene therapy with known cardiac adverse effects. Although initial echocardiogram revealed a left-ventricular ejection fraction of 57% at 22 days old, subsequent comprehensive cardiac evaluation revealed improving troponin I levels with a normal left-ventricular ejection fraction of 70% at 34 days of life prior to starting gene therapy. Although not common, elevated troponin I level in an otherwise asymptomatic newborn can be seen in spinal muscular atrophy. This case underscores that elevated troponins may be intrinsic to newborns with spinal muscular atrophy even before starting therapies for spinal muscular atrophy. In addition, we illustrate no further cardiac abnormalities after infusion of the aforementioned gene therapy in a child with asymptomatic elevated troponin I after cardiac clearance.