Neuropediatrics最新文献

Acute motor and sensory axonal neuropathy (AMSAN) is a rare and severe form of acute axonal injury caused by immune damage to the axonal membrane. AMSAN is an axonal variant of GBS. GBS occurs from immune injury to the myelin sheath, axonal variants of GBS (AMSAN and AMAN) differ in that insult is to the axonal membrane. AMSAN is seldom seen, especially in pediatric and adolescent patients. Unlike acute motor axonal neuropathy (AMAN), which has been well-described in literature to be secondary to Campylobacter jejuni infection, there is no known etiology of AMSAN. Here, we present a case of an otherwise healthy 15-year-old female who presented with new-onset facial and bulbar weakness that rapidly progressed to functional paralysis requiring intubation. With no clear diagnosis and after failure in improvement with high-dose steroids, Intravenous Immunoglobulin (IVIG), and plasma exchange transfusion, diagnosis was finally made with electromyography (EMG) and nerve conduction study (NCS). In addition, extensive laboratory work was completed and was only notable for primary acute EBV infection. This case represents a new presenting symptom of AMSAN, a unique finding of concomitant primary EBV infection, the possibility of primary Epstein-Barr virus (EBV) infection as the triggering event in AMSAN and stresses the importance of EMG and NCS when evaluating patients with weakness.

ATP1A2 and CACNA1A genes encode proteins forming transmembrane channels, Na⁺/K⁺/ATPase transporter, and voltage-gated calcium channels, respectively. Pathogenic variants in these genes are associated with hemiplegic migraines, movement disorders, and developmental and epileptic encephalopathy.We report a child presenting epileptic encephalopathy with cognitive and behavioral troubles. He carries a likely pathogenic variant in the ATP1A2 gene, inherited from his mother who presents hemiplegic migraines, and a variant of uncertain significance in the CACNA1A gene, inherited from his asymptomatic father and also found in his brother, who presents a milder neurodevelopmental disorder (NDD). No other significant copy number or single nucleotide variations were identified after an in-depth genetic study including whole exome sequencing, array comparative genomic hybridization, and screening for Fragile X and Prader-Willi/Angelman syndromes.We illustrate the synergetic impact of ATP1A2 and CACNA1A genes in NDDs.

Encephalitis in children is a serious inflammatory brain disease caused by infectious or autoimmune-mediated processes. The frequency of autoimmune variants in pediatric populations is not entirely clear.To study the frequency of myelin oligodendrocyte glycoprotein (MOG) antibody (ab)-mediated autoimmune encephalitis (AE) in children included in the Meningitis/Encephalitis register of Lower Saxony (MERIN).Medical records of 1,341 children treated between 2011 and 2020 in two large children's hospitals participating in a prospective study on encephalitis (MERIN) were reviewed. Children meeting diagnostic criteria for possible AE were finally included if serum samples and informed re-consent were available. Children with pathogen-mediated encephalitis were also included as controls. All available serum samples were tested for MOG- and anti-N-methyl-D-aspartate receptor (NMDAR) antibodies (abs) using cell- and tissue-based assay (TBA).We included 55 children of whom 16 had pathogen-associated meningoencephalitis. Thirty-nine out of fifty-five children were classified as possible AE and 3/39 fulfilled the criteria for MOG ab-associated disease (MOGAD). No patients' sera harbored NMDAR abs. However, 5/39 patients fulfilled the criteria for probable, auto-ab-negative AE.In line with recent research our study suggests that ab-mediated AE and probable ab-negative AE are rare in children. The existing criteria seem suitable for identifying patients with AE but should include the testing of serum MOG abs. Further yet unknown abs may play a role in children with AE.

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.