Journal of Child Neurology最新文献

β-Propeller protein-associated neurodegeneration (BPAN) is a rare, X-linked condition caused by pathogenic variants in the WDR45 gene that result in a defect of autophagy. Classified as a disorder of neurodegeneration with brain iron accumulation, β-propeller protein-associated neurodegeneration is associated with severe neurologic impairments. With the anticipation of future therapeutic trials, this project characterizes the family's perspective of the impact of disease and defines Health Concepts (HC).Children with a molecularly confirmed diagnosis of β-propeller protein-associated neurodegeneration were enrolled in a prospective natural history study. We administered the Vineland Adaptive Behavior Scales-Third Edition and provided health-related quality of life questionnaires to 42 caregivers. Questionnaires included Pediatric Quality of Life Inventory-Generic Core and Pediatric Quality of Life Inventory-Family Impact modules, Caregiver Priorities and Child Health Index of Life with Disabilities, and Caregiver TBI-CareQoL.The Vineland Adaptive Behavior Scales-Third Edition (n = 42) captured the family's perspective that communication was more affected compared with socialization, activities of daily living (ADL), and motor skills (P < .0001, P < .0001, P = .0053, respectively). Similarly, on the Caregiver Priorities and Child Health Index of Life with Disabilities (n = 26), Pediatric Quality of Life Inventory-Generic Core (n = 27), CareQol (n = 26), and Pediatric Quality of Life Inventory-Family Impact (n = 27), communication abilities, as well as social functioning and activities of daily living, were noted to be most impacted.Through the use of standardized surveys and outcome assessments, we establish the effects of β-propeller protein-associated neurodegeneration on caregiver quality of life. Key health concepts identified by families included overall health, comfort, and communication. The identified HC will inform the future identification of concept of interest and selection of appropriate clinical outcome assessments through the administration of patient-reported outcomes.

Objective: This study aimed to assess the first-drug efficacy rate in newly diagnosed children with epilepsies treated with antiseizure medications. Methods: This retrospective study was conducted on 1003 children (age range: 3-10 years, and the mean duration of follow-up: 22 ± 13 months) with newly diagnosed epilepsy. The following parameters were evaluated: first-drug efficacy rate, first-drug-failure rate, and drug resistance rate in the cohort. Results: The first-drug-failure rate was defined in 335/1003 (33%) of the patients, no seizure control in 315 (31%), and drug withdrawal in 20 (2%). There was no significant difference between the group with focal-onset seizures and the group with generalized onset seizures. The first-drug efficacy rate was 67% in children with focal-onset seizures and 66% in children with generalized-onset seizures. Adjunctive antiseizure medication therapy was initiated in 335 patients-dual therapy with 180 patients (18%) and polytherapy with 155 (15%). Drug-resistant epilepsy was defined as 15% in the follow-up period. Etiology-specific diagnoses of the cohort were structural (n = 165, 17%), genetic (n = 25, 3%), metabolic (n = 15%), immune-infectious (n = 17 (2%), and unknown (n = 781, 77%). With a comparison of the 2 most common etiology subgroups (structural versus unknown), a first-drug efficacy rate of 53% and a higher prevalence of drug-resistant epilepsy at 30% were observed in children with structural etiology. First-drug efficacy was statistically lower in children without well-defined epilepsy syndromes (65%) compared with the rate of those with well-defined epilepsy syndrome (79%). Conclusion: This study revealed a first-drug failure rate (33%) in the presented cohort with a drug-resistance epilepsy rate (15%).

Introduction: Eslicarbazepine (ESL) is a once-daily, third-generation antiseizure medication for focal-onset seizures. The primary mechanism of action is enhancing the slow inactivation of voltage-gated sodium channels. The study objective was to review real-world experience regarding retention rate, efficacy, and tolerability of eslicarbazepine, soon after it became available for children in Canada.

Methods: A retrospective review was performed on all patients prescribed eslicarbazepine from September 2017 to June 2020, with at least 3 years of follow-up data, at 3 Canadian tertiary care pediatric centers.

Results: Fifty patients were identified, and the mean age of eslicarbazepine initiation was 12.4 years (range 3-19 years). Most patients had drug-resistant epilepsy, trying a mean of 5.04 (range 0-14) antiseizure medications before the initiation of eslicarbazepine. Twenty-four patients (48.0%) experienced adverse effects, including dizziness (n = 10), drowsiness (n = 6), dizziness and drowsiness (n = 1), nausea and abdominal pain (n = 4), transient unsteadiness and diplopia (n = 1), and negative mood changes (n = 2). None had serious adverse effects, including rash. The retention rate of eslicarbazepine at last follow-up was 70%. Fifteen (30%) had ≥50% seizure reduction, with 2 of these patients becoming seizure free. Ten (20%) had 25% to 50% reduction, 2 (4%) had worsening of seizures, and 17 (34%) had no change in seizure frequency.

Conclusion: The study results support the long-term effectiveness and tolerability of eslicarbazepine in a cohort of children with predominantly drug-resistant epilepsy in a real-life setting from 3 Canadian centers with initial use after approval. Adverse effects were nonserious, infrequently leading to eslicarbazepine discontinuation.

Epstein-Barr virus meningoencephalitis is a rare central nervous system infection that lacks standardized treatment. Immunocompetent and immunosuppressed individuals with this condition frequently have poor prognostic outcomes, making the need to identify therapeutic interventions high. Here, we report 2 pediatric cases of severe Epstein-Barr virus meningoencephalitis, both unresponsive to immunoglobulin and corticosteroid therapy, who demonstrated rapid clinical recovery following rituximab administration. Prognostic outcomes revealed marked improvements in symptoms, neurologic function, and quality of life. Rituximab may offer therapeutic potential in severe and refractory Epstein-Barr virus meningoencephalitis through the medication's target of Epstein-Barr virus harboring B cells. This report emphasizes the need for timely evaluation and consideration of rituximab therapy in immunocompetent pediatric patients with Epstein-Barr virus meningoencephalitis.

Background: RNA polymerase III (POLR3)-related leukodystrophy is a rare, neurodegenerative disorder characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism. Despite the challenges of caring for a child with POLR3-related leukodystrophy, few studies have examined parents' disease burden. We sought to investigate quality of life and stress levels amongst parents of children with POLR3-related leukodystrophy. Methods: 43 parents of 32 children completed questionnaires on demographics, stress, quality of life, coping mechanisms, and experience of injustice. Detailed clinical data was collected from all patients. Results: Mothers (t[27] = -8.66, P < .001) and fathers (t[16] = -4.47, P < .001) had lower quality of life scores compared to the normative population, yet 80% of parents' stress scores fell within the normal stress range. Parents' experience of injustice scores were high (>60). Correlations were found between and within parents' scores. Years since disease onset and certain life circumstances correlated to mothers' quality of life scores; however, no correlation was found between modifiable factors and fathers' quality of life scores. Helpful coping mechanisms included those that allowed parents to be involved in their child's life. Conclusions: This is the first study to assess stress and quality of life in this population. These results shed light on the importance of implementing services and social support to improve the well-being of parents.

Aim: To evaluate the efficacy and safety of onabotulinumtoxinA for treating upper and lower limb spasticity among pediatric patients in 2 open-label extension trials.

Methods: Patients aged <18 years received ≤5 doses of onabotulinumtoxinA (maximum: 8 U/kg [300 U], cycle 1; 10 U/kg [340 U], cycles 2-5) over 60 weeks. Week 6 efficacy endpoints included mean change from baseline in Modified Ashworth Scale-Bohannon and Modified Tardieu Scale scores, and mean Clinical Global Impression of Overall Change score. Adverse events and laboratory assessments of bone health were monitored.

Results: A total of 580 patients received onabotulinumtoxinA. Modified Ashworth Scale-Bohannon change from baseline ranged from -1.01 to -1.9. Modified Tardieu Scale change from baseline was 13.6 to 18.1 (ankle), 25.8 to 44.1 (elbow), and -5.0 to -26.3 (wrist). Clinical Global Impression of Overall Change scores were 1.5 to 2.2. The most common treatment-emergent adverse events were upper respiratory tract infection (16.9%) and nasopharyngitis (15.7%).

Interpretation: Repeat administration of onabotulinumtoxinA was safe and efficacious for treating upper and lower limb spasticity in children.

Introduction: Pediatric neurology provides care for children with complex developmental disorders with environmental, genetic, metabolic, and teratogenic etiologies. Common neurodevelopmental conditions include attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorder. However, only minimal attention from pediatric neurology journals has been devoted to fetal alcohol spectrum disorder. This is surprising because fetal alcohol spectrum disorder is a common neurodevelopmental disorder with a prevalence of between 1% and 5% of school-age children.

Methods: This scoping review had 2 objectives. Objective 1 was to estimate the number of articles reporting on fetal alcohol spectrum disorder in 8 well-respected pediatric neurology journals. Objective 2 was to determine how many patients from a single pediatric neurology practice referred to a clinic for diagnosis and management of neurobehavioral disorders received a diagnosis of ADHD, autism spectrum disorder, and fetal alcohol spectrum disorder.

Results: Objective 1, a survey of 8 prominent pediatric neurology journals until January 2024, found that a title and abstract search identified 1786 articles on the three topics. Papers on autism spectrum disorder (n =1043) accounted for 58.4% of the total. Papers on ADHD (n = 685) comprised 38.4% and articles on fetal alcohol spectrum disorder (n = 58) contributed just 3.3% of the total.Objective 2, a chart review of 40 patients from a single pediatric neurology clinic who were referred for developmental assessment and management, found that 40% had prenatal alcohol exposure and 20% received a diagnosis of fetal alcohol spectrum disorder. High rates of comorbidity between fetal alcohol spectrum disorder and ADHD of 21% and of fetal alcohol spectrum disorder and autism spectrum disorder of 2.5% were found.

Conclusions: Because fetal alcohol spectrum disorder is one of the most common causes of neurodevelopmental disorders, the limited attention to fetal alcohol spectrum disorder in pediatric neurology journals is concerning. This study suggests that in addition to ADHD and autism spectrum disorder, fetal alcohol spectrum disorder may also be a common diagnosis in pediatric neurology practice. Pediatric neurology journals may need to take active steps to increase content on fetal alcohol spectrum disorder. This could include editorials, invited commentaries, or topical reviews. Early recognition and diagnosis of fetal alcohol spectrum disorder allows for the implementation of specific interventions, which can improve the quality of life for patients and families.

Balamuthia mandrillaris granulomatous amebic encephalitis is a rare disease that is associated with a high rate of mortality. Delays in diagnosis and treatment are common because of limited information on the organism in addition to its nonspecific clinical presentation. Prior reports have demonstrated that the encephalitis presents as multifocal lesions throughout the central nervous system with enhancement and edema. Here we report a case involving a 4-year-old previously healthy female child with a novel pathologic presentation of B mandrillaris infection, including vasculitis involving multiple large intracranial vessels as well as inflammation of multiple cranial nerves. The infection was ultimately fatal despite early diagnosis and initiation of targeted treatment.

Kabuki syndrome is a rare congenital disorder characterized by a distinctive combination of craniofacial features, developmental anomalies, and intellectual disabilities. This study aims to provide a comprehensive exploration of Kabuki syndrome through a meticulous case series analysis focusing on its clinical features and genetic underpinnings. A cohort of 9 Kabuki syndrome patients was identified through a retrospective examination of medical records spanning from 1996 to 2022. These patients underwent various clinical assessments, radiologic investigations, neuropsychological evaluations, and targeted genetic analyses, specifically focusing on the KMT2D and KDM6A genes.The median age of diagnosis was approximately 4.7 years, with a male-to-female ratio of 6:3. Prominent clinical characteristics included distinctive facial features such as arched eyebrows, elongated eyelashes, ear abnormalities, fingertip pads, nasolabial anomalies, and oral alterations. Ophthalmologic and otologic manifestations were notable, alongside a spectrum of cardiovascular, gastrointestinal, and endocrine aberrations. The prevalence of neuropsychological disorders highlighted the cognitive and behavioral challenges experienced by Kabuki syndrome patients. Genetic investigations confirmed the involvement of variants in the KMT2D and KDM6A genes in the pathogenesis of Kabuki syndrome. In conclusion, this study emphasizes the importance of precise diagnosis, the adoption of a multidisciplinary care approach, and the tailored interventions for individuals affected by Kabuki syndrome. Furthermore, it underscores the need for continued research efforts to unravel the genetic intricacies and molecular mechanisms underlying this enigmatic syndrome.

Background: Children with self-limited epilepsy with centrotemporal spikes often face language impairments and central auditory processing difficulties. The correlations between these issues, seizure timing, and neuropsychiatric challenges are not fully understood. This study delves into the connections between language impairments and central auditory processing difficulties in cases with self-limited epilepsy with centrotemporal spikes, examining their links with seizure occurrence and neuropsychiatric function.

Materials and methods: Patients with self-limited epilepsy with centrotemporal spikes were categorized based on seizure timing: group 1 experienced seizures postbedtime, and group 2 prewaking. Both, alongside controls, underwent the Turkish Expressive and Receptive Language Test (TIFALDI) for language skills, and the Frequency Pattern and Duration Pattern tests for central auditory processing difficulties. Neuropsychiatric assessments involved the Wechsler Intelligence Scale for Children-Revised, the Strengths and Difficulties Questionnaire, the Conners Parent Rating Scale-Revised Short, and the Barratt Impulsiveness Scale-11.

Results: The study comprised 56 patients with self-limited epilepsy with centrotemporal spikes (ages 6-13) and 32 healthy controls. Both groups significantly lagged behind controls on the Frequency Pattern and Duration Pattern tests (P < .001). In the TIFALDI, the expressive language scores varied between group 1 and controls (P = .04) but not the receptive language scores or the test's expressive and receptive language results between group 2 and controls (P > .05). In the Strengths and Difficulties Questionnaire, group 1 diverged from controls in behavioral and kind and helpful behavior scores (P = .016 and P = .012). Group 1's Barratt Impulsiveness Scale-11 values surpassed controls' (P = .038).

Conclusion: Children with self-limited epilepsy with centrotemporal spikes have a high central auditory processing difficulties prevalence, regardless of seizure timing. Those with postsleep seizures tend to confront expressive language difficulties, alongside issues in prosocial behavior and impulsivity.