Neuropediatrics最新文献

The objective is to give an update on the current state of research on the genetics of primary headache in children and adolescents. Investigations of the genetics of migraine in adults have changed our understanding of the pathophysiology of migraine, but knowledge from our adult patients cannot be directly applied to pediatric patients. The study was conducted through searches of PubMed and Web of Science. Our search yielded 10 studies. Some of the included studies elucidated correlations between certain characteristics of the headaches in parents and an elevated risk of headache in their children. The follow-up studies found that about one-third of the participants were headache-free at the time of follow-up and about one in four had shifted to a different headache diagnosis. All studies included in this paper found a familial aggregation or heritability of primary headache in children and adolescents.

Background: Non-selective sodium leak channel (NALCN) protein encoded by the NALCN gene is of key importance for neuronal cell excitability. Previous reports showed that biallelic NALCN pathogenic variants cause infantile hypotonia with psychomotor retardation and characteristic facies 1 (IHPRF1) while monoallelic variants lead to congenital contractures of the limbs and face, hypotonia, and developmental delay (CLIFAHDD). In our work, we aimed to expand the heterozygous NALCN-related clinical spectrum, presenting two affected individuals and a literature review.

Methods: We describe two new unrelated subjects harboring monoallelic NALCN pathogenic variants identified through clinical exome sequencing and review the current literature of other heterozygous NALCN patients.

Results: The c.3542G > A (p.Arg1181Gln) and the novel c.3423C > A (p.Phe1141Leu) heterozygous missense variants were disclosed in two subjects manifesting a similar phenotype characterized by congenital ataxia with progressive cerebellar atrophy, camptodactyly, and hypertrichosis of the arms (CAPCACH). Other NALCN subjects with overlapping features have already been reported. A combination of these clinical and neuroimaging findings suggests the definition of the new CAPCACH phenotype.

Conclusion: We expand the heterozygous NALCN-related clinical spectrum from the more severe CLIFFAHDD to the milder CAPCACH phenotype. These conditions should be considered in the differential diagnosis of syndromic congenital ataxias, and the presence of camptodactyly and/or hypertrichosis may represent peculiar diagnostic clues.

Purpose: Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent episodes of fever and serositis, caused by mutations in the MEFV gene. Inflammatory pathways associated with FMF are linked to increased proinflammatory cytokines, which may be related to primary headaches, including migraine. The aim of this study was to evaluate the frequency of migraine and other primary headaches in FMF patients.

Methods: In this retrospective study, the medical records of FMF patients were analyzed. Demographic data, MEFV gene mutations, and headache histories were collected. The frequency of migraine was compared among patients with these mutations, and statistical analyses were conducted.

Results: The study included 148 FMF patients, comprising 56.1% females and 43.9% males, with a mean age of 11.3 ± 3.7 years. A family history of FMF was reported in 77.7% of patients, and 35.8% had a family history of migraine. Headaches were reported in 52.7% of patients: 24.3% non-specific, 15.5% tension-type, and 12.8% migraine. Of those with migraine, 8.1% had migraine with aura, and 4.7% without aura. Headaches were more frequently frontal in patients under 12 years of age and temporal in those aged ≥12 years (p = 0.011). The most common genetic mutations were M694V heterozygous and homozygous, with M694V and E148Q mutations linked to more frequent migraines, although not statistically significant.

Conclusion: FMF patients should be screened for primary headaches, particularly migraine. The high frequency of migraine observed in this study suggests that clinicians should particularly consider migraine as a diagnosis in headache episodes experienced by FMF patients.

Spinal muscular atrophy (SMA) is a rare autosomal recessive genetic disease caused by Survival Motor Protein 1 (SMN1) gene mutations. Classically divided into three types, SMA is characterized by hypotonia, weakness, and tongue fasciculation in the first 6 months of life in type 1, inability to walk and limb weakness in type 2, and failure to run with proximal weakness in type 3 SMA. With the advent of newborn screening, treating presymptomatic patients with Onasemnogene abeparvovec (OA) is the treatment of choice in some centers worldwide. The incidence of jaundice is high in this age group, with no recommendation to guide the use of OA in newborns with jaundice. To our knowledge, treating an SMA patient with alloimmune hemolytic disease of the newborn (HDN), a relatively common disease in the newborn period, has never been reported in the past. We report our experience with dosing a presymptomatic child with SMA who had neonatal jaundice and hemolytic anemia due to hemolytic disease of the newborn who tolerated the treatment well. To our knowledge, this is the first case to report the safety of this novel treatment for an SMA patient with alloimmune HDN.

Patients with MCT8 deficiency often present with underweight and are prone to frequent pulmonary infections, including aspiration pneumonia. Despite commonly reported swallowing difficulties in this population, specific dysphagia symptoms have not been well-documented. We conducted a flexible endoscopic evaluation of swallowing (FEES) on a young boy diagnosed with MCT8 deficiency, who exhibited recurrent pulmonary infections and failed to achieve substantial weight gain despite an oral energy intake appropriate for his age and height. The FEES revealed generally weakened swallowing mechanisms, characterized by prolonged swallow and cough sequences, along with penetration and aspiration of both fluid and semi-solid test boluses. Given the considerable effort associated with oral intake, we hypothesize that dysphagia contributes to his underweight status, alongside peripheral thyrotoxicosis. In conclusion, FEES proved to be an invaluable tool in identifying underlying swallowing impairments and assessing the need for gastrostomy in this patient. For MCT8 deficiency, patients presenting with underweight, frequent pulmonary infections, and swallowing difficulties, it is recommended that diagnostic evaluations include FEES to thoroughly assess their swallowing function and airway protection.

To identify and evaluate risk factors for psychiatric disorders in pediatric patients with tuberous sclerosis complex (TSC).We recruited 121 children with TSC from the Hangzhou Children's Hospital between April 2021 and December 2023. Four clinical psychiatric scales were used to screen and diagnose the psychiatric comorbidities of TSC: the autism behavior checklist, the SNAP-IV scale, and the self-rating anxiety and depression scales. Risk factors related to each psychiatric disorder were analyzed using univariate and multivariate regression analyses.Comorbid psychiatric disorders were found in 70 (57.85%) children: 51 (42.15%) cases had autism spectrum disorder (ASD), 49 (40.50%) cases had attention-deficit hyperactivity disorder (ADHD), 17 (14.05%) cases had anxiety, and 14 (11.57%) cases had depression. Uni- and multivariate logistic regression analysis revealed that seizure frequency (>1/month; OR = 6.206, P = 0.021), use of anti-seizure medications (≥ 2 types; OR = 118.869, P = 0.003), infantile spasms (OR = 25.748, P = 0.000), ADHD (OR = 11.170, P = 0.001), and intellectual disability (OR = 32.131, P = 0.001) were risk factors for TSC children with ASD; ASD was the only risk factor for occurrence of ADHD (OR = 7.302, P = 0.022). Seizure duration (≥ 2 years; OR = 56.200, P = 0.036) and seizure frequency (>1/month; OR = 25.855, P = 0.027) were closely related to occurrence of anxiety and/or depression disorders in pediatric patients with TSC.The study results showed that psychiatric comorbidities of children with TSC had a high incidence and risk factors. The study provides new insights into the diagnosis and treatment of comorbid psychiatric disorders in pediatric patients with TSC.

The spinal application of intrathecal baclofen (ITB) has been commonly used as treatment for severe dystonia as well spasticity. However, in rare cases, the use of ITB is not possible or ineffective. Therefore, intraventricular application of baclofen (IVB) mostly using endoscopic navigation has been rarely performed over the last years. As a valid alternative, we introduced navigated frameless stereotaxy for intraventricular catheter placement as the most minimally invasive approach feasible.We retrospectively report on surgical technique, clinical outcome, and long-term complications in all pediatric patients with severe generalized dystonia who received IVB using navigated frameless stereotaxy between April 2009 and June 2021 at our institution.Twenty patients (median age: 13 years; range: 2-23 years) were treated with IVB. Dystonia improved in 19/20 patients at the time of discharge (median 51 days; range 2-93 weeks). During the follow-up period (median: 19 months; range: 3-83 months), there was a total of five surgery-associated complications including 3/20 pump infections and 2/20 intraventricular catheter dislocations.This study reveals that navigated frameless catheter positioning in IVB therapy of generalized dystonia is a comparatively low risk and effective surgical procedure.

Prenatal alcohol exposure causes disruptions in brain development. The resulting disorder, fetal alcohol spectrum disorder (FASD), cannot be cured, but interventions can help improve the daily functioning of affected children and adolescents and the quality of life for the entire family.The aim of the German guideline version 2024 is to provide validated and evidence-based recommendations on interventions for children and adolescents with FASD.We searched for international guidelines and performed a systematic literature review and a hand search to identify literature (published 2012-2022) on interventions for children (0-18 years) with FASD. The quality of the literature was assessed for predefined outcomes using the GRADE method (grading of recommendations, assessment, development, and evaluation). We established a multidisciplinary guideline group, consisting of 15 professional societies, a patient support group, and 10 additional experts in the field. The group agreed on recommendations for interventions based on the systematic review of the literature and formulated additional recommendations, based on clinical experience/expert evidence in a formal consensus process.No international guideline focusing on interventions for patients with FASD was found. Thirty-two publications (4 systematic reviews and 28 original articles) were evaluated. The analysis resulted in 21 evidence-based recommendations and 26 expert consensus, covering the following topics: neuropsychological functioning, adverse effects of therapy, complications/secondary conditions, quality of life, caregiver burden, knowledge of FASD, and coping and self-efficacy.The German guideline is the first internationally to provide evidence-based recommendations for interventions in children and adolescents with FASD.

Rhabdomyolysis is a potentially life-threatening condition in pediatric patients, often triggered by various factors, such as infections, trauma, hereditary metabolic disorders, and certain medications. Elevated creatine kinase levels are commonly observed in newborns and are often attributed to factors such as hypoxia, labor dystocia, and birth trauma. However, rhabdomyolysis in this population is rare and typically associated with hereditary metabolic disorders, medications, or infections. In this report, we describe the case of a neonate diagnosed with very long-chain acyl-CoA dehydrogenase deficiency after markedly elevated creatine kinase levels and rhabdomyolysis were identified during the neonatal period. Additionally, we suggested a guideline for the evaluation of creatine kinase elevation and rhabdomyolysis in neonates.