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.

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.

Objective:  Epilepsy is common among patients with severe motor and intellectual disabilities (SMID) patients, often taking a prolonged and intractable course. Lacosamide (LCM) is widely used to treat epilepsy in both adults and children. We assess the efficacy and tolerability of LCM among pediatric and young adult epilepsy patients with SMID who suffer from intractable seizures.

Methods:  This retrospective analysis reviewed the medical records of SMID patients undergoing LCM treatment for more than a year. The study included 24 patients (14 males) aged 3 to 29 years. Epilepsy was classified as focal in 17 patients, generalized in 4 patients, and combined generalized and focal in 3 patients.

Results:  The retention rates were 70.8%, 65%, and 52.9% at 1, 2, and 3 years after LCM initiation, respectively. The 50% responder rate (achieving >50% seizure reduction) for LCM treatment was 50%, with two patients experiencing complete seizure control (absence of seizures for 6 months before the follow-up visit). The 50% responders included a higher proportion of patients with focal epilepsy (58.8%) compared to those with generalized epilepsy (25.0%). Treatment-emergent adverse events (TEAEs) included somnolence in five patients and nausea in two patients. TEAEs, particularly nausea, developed within 1 month after treatment initiation in two patients, leading to LCM discontinuation.

Conclusion:  LCM demonstrated good efficacy for intractable epilepsy in pediatric and young adult SMID patients. It was generally well-tolerated, resulting in a favorable retention rate. LCM emerged as a useful antiseizure medication for epilepsy treatment in pediatric and young adult SMID patients.

Aim:  Duchenne muscular dystrophy (DMD) is the most frequently seen muscular disease in childhood. Cardiac involvement is extremely important in terms of morbidity and mortality in these patients. Different studies have shown that mutations occurring in various exons are cardioprotective or increase cardiac involvement in DMD cases. The aim of this study was to examine the effect of genotype differences on cardiac involvement in patients diagnosed with DMD with genetic analysis.

Material and method:  A retrospective analysis of DMD patients followed up in the Muscle Diseases Centre of Health Sciences University Izmir Tepecik Training and Research Hospital was done.

Results:  Evaluation was made of 120 male DMD patients with a mean age of 9.66 ± 5.10 years. According to the genetic analysis results, 76.7% deletions, 15.8% mutations, and 7.5% duplications were determined. Of the mutations determined, 65.8% were between exons 44 and 54, 17.5% between exons 1 and 18, and 9.2% between exons 19 and 43, 5.8% were non-sense mutations, and 1.7% were on exons >54. In the cases determined with cardiac involvement, the mean age of onset was 11.87 ± 3.11 years. When ejection fraction (EF) <56% or fractional shortening (FS) <28% was accepted as systolic dysfunction cardiac effect, 12.5% of the cases were determined with cardiac involvement. Of the cases determined with cardiac effects, 86.7% were aged >10 years. Electrocardiography was evaluated as normal in 54.5%, sinus tachycardia in 24.2%, short PR in 15.2%, and right and left ventricle hypertrophy in 8.1%. No statistically significant difference was determined in mutation types and location according to the age of cardiac involvement. The left ventricle (LV) posterior wall thickness value determined in the exon 44-54 group was higher than in DMD cases with other mutations. Although not statistically significant, an important result was that the LV posterior wall and IVSed values were evaluated to be high.

Conclusion:  The current study results and findings in literature have not found a clear relationship between genotypes and cardiac involvement in DMD cases.

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.

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.

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.

Adult reports of unexpected severe disease worsening, often termed "rebound," shortly after discontinuing fingolimod in a subset of patients with multiple sclerosis (MS), have grown over the last decade. This phenomenon, however, remains poorly described in pediatric MS patients. We present findings of a 15-year-old who experienced a debilitating relapse 4 weeks after stopping fingolimod to switch to ocrelizumab. Imaging revealed multiple large new lesions far exceeding any previously observed activity level in the patient. Despite prompt high-dose corticosteroids, plasma exchange, and prolonged rehabilitation therapy, significant residual deficits involving cognition, balance, and vision remain from the attack. This case underscores that pediatric MS patients are also at risk of severe disease deterioration after fingolimod withdrawal and require close monitoring when switching therapies.

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.