Neuropediatrics最新文献

Progressive myoclonus epilepsy (PME) is a rare, clinically and genetically heterogeneous epilepsy syndrome, and pathogenic variants in the semaphorin 6B (SEMA6B) gene have recently been reported to be among the causes of PME. Cases with pathogenic variants in the SEMA6B gene are extremely rare, only a limited number of cases have been reported in the literature. In this systematic review, we aimed to present a summary of a PME case in which a heterozygous nonsense variant of c.2086C > T p.(Gln696*) in the SEMA6B gene was detected in the etiology and other cases with SEMA6B pathogenic variant in the literature. Except for our case, 35 cases from 12 studies were included. The main clinical findings in these patients were cognitive problems, seizures, gait and speech disturbances, and cognitive and/or motor regression, and they had a wide spectrum of severity. Response to antiseizure medications was also highly variable, almost half of the patients had pharmacoresistant seizures. Patients were divided into four different phenotypic groups according to their clinical presentations: PME (18/36), developmental and epileptic encephalopathy (13/36), neurodevelopmental disorder (4/36), and epilepsy (1/36), respectively. In conclusion, although SEMA6B has been associated with PME, it may actually cause a much broader phenotypic spectrum. Due to their extreme rarity, our knowledge of SEMA6B-related disorders is limited. As with all other rare diseases, each new SEMA6B-related disorder case could contribute to a better understanding of the disease. A better understanding of the disease may allow the development of specific treatment options in the future.

Objective:  The study aimed to interpret and establish patterns of amplitude-integrated electroencephalogram (aEEG) in stable preterm neonates and compare the aEEG among different gestational age groups using three standard classifications.

Methods:  This prospective cohort study included stable preterm neonates between 24^0/7 and 36^6/7 weeks of gestation. aEEG was recorded in the first and second week of life and interpreted using the L. Hellström-Westas, Burdjalov, and Magalhães classification for background pattern, continuity, upper and lower margin amplitude, sleep-wake cycle, bandwidth, and presence of seizures. Subgroup analysis was performed based on ≤30 and >30 weeks' gestation.

Results:  A total of 76 aEEG recordings were analyzed from 45 preterm neonates. In the first week, 60% of the neonates had normal voltage patterns, which increased to 80% in the second week. All infants ≤30 weeks displayed discontinuous wave patterns during the first week, and half transitioned to continuous waves in the second week. The lower margin amplitude increased, and the upper margin amplitude decreased with increased gestational age. Additionally, 65% of neonates had a mature sleep-wake cycle in the second week compared with 22% in the first week. The median (interquartile range) CFM score in the second week was 12 (4.5) compared with 8 (4) in the first week, and the CFM score positively correlated with gestation (Spearman correlation coefficient, 0.8; 95% confidence interval, 0.7-0.86). Magalhães grading in both groups was predominantly normal.

Conclusion:  aEEG is predominantly a continuous normal voltage pattern in >30 weeks' gestation and discontinuous in ≤30 weeks' gestation. CFM score correlates positively with advancing gestation gestational age.

Background:  Global developmental delay (GDD) is a common pediatric disorder that affects up to 3% of children. Due to the heterogeneous etiology of GDD, diagnostic procedures and algorithms are complex and diverse. The aim of our study was to investigate the diagnostic yield of genetic, metabolic, and imaging studies in establishing the etiology of unexplained GDD (UGDD).

Methods:  In this retrospectively observational study, we examined the medical records of all children diagnosed with UGDD at the Department of Pediatric Neurology, University Medical Centre Ljubljana, Slovenia, between January and December 2019. We evaluated the effectiveness of various genetic, metabolic, and magnetic resonance imaging (MRI) tests in identifying the underlying cause of GDD. Additionally, we assessed subgroups of patients to determine whether any of the studied tests were particularly beneficial based on their clinical symptoms.

Results:  A total of 123 patients met the inclusion criteria, with a median age of 4.3 years (range, 0-16 years), of which 71 (57.7%) were males. Genetic diagnosis was established in 47.1% (58/123) of patients. Metabolic laboratory testing did not identify a metabolic disease in any of the tested participants (114/123) and MRI was critical for diagnosis in only 1/81 (1.2%) patient.

Conclusion:  Our findings strongly suggest that genetic testing surpasses MRI and metabolic testing in establishing the etiology of UGDD in a pediatric neurology outpatient setting. This information will help guide the diagnostic evaluation of these children.

Aicardi-Goutières syndrome (AGS) is a rare genetic early-onset progressive encephalopathy with variable clinical manifestations. The IFIH1 mutation has been confirmed to be responsible for type I interferon production and activation of the Janus kinase signaling pathway. We herein stress neurological observations and neuroimaging findings in a severe case report of an infant with AGS type 7 due to an IFIH1 mutation who was diagnosed in the first month of life. We also review neurological characteristics of IFIH1 mutations through recent literature.

Objectives: We aimed to assess the serum levels of caspase-3 as a marker of apoptosis and microtubule-associated protein 1A/1B-light chain 3 (MAP1-LC3) as an autophagy marker in epileptic children with various clinical and pharmacological types.

Methods: This case-control study was carried out on 90 participants (50 pediatric patients with epilepsy and 40 healthy matched children), the patients were categorized into three groups: Group (A): 25 pharmacosensitive epilepsy, Group (B): 25 pharmacoresistant epilepsy, and Group (C): 40 (age, sex, and body mass index) matched healthy children selected as controls. Serum caspase-3 and MAP1-LC3 were measured in all study groups, using commercially available ELISA kits.

Results: Serum caspase-3 was significantly higher among epileptic children, especially in the pharmacoresistant group, cases managed with multiple antiepileptic drugs, and cases with abnormal EEG findings. Conversely, circulating MAP1-LC3 levels showed a significant reduction in epilepsy cases, particularly in pharmacoresistant cases, in cases treated with multiple antiepileptic drugs, and in cases with abnormal EEG data. A significant negative correlation between serum caspase-3 and MAP1-LC3 was found among epileptic children (r =  -0.369, p = 0.0083). Serum caspase-3 was a more valid biomarker in helping diagnose childhood epilepsy, while serum MAP1-LC3 was more valid in predicting pharmacoresistant type.

Conclusion: The study reveals that serum caspase-3 levels were significantly elevated, particularly in pharmacoresistant cases and those managed with multiple drugs. Conversely, MAP1-LC3 levels were significantly reduced in epilepsy cases, suggesting potential involvement of altered apoptosis and autophagy in childhood epilepsy.

Introduction: Neuronal ceroid lipofuscinoses (CLNs) are a group of lysosomal storage disorders of genetic origin, characterized by progressive neurodegeneration and intracellular accumulation of autofluorescent lipopigment. Thirteen genes related to CLNs are currently described, showing genetic and allelic heterogeneity, most of them with an autosomal recessive pattern. Due to the few descriptions of cases related to CLNs in Brazil, it is necessary to describe the phenotypic and genotypic characteristics of these patients. This study aims to evaluate the genotypic profile and correlate it with the phenotypic characteristics of patients with CLN in a children's hospital.

Methods: This study was performed as a descriptive cross-sectional study with analysis of medical records, imaging, and laboratory tests of patients who had a confirmed molecular diagnosis of CLN.

Results: The sample consisted of 11 patients from nine families with different subtypes of CLNs (CLN2, 5, 6, 7, and 8), with CLN2 being the most prevalent in the study. A total of 16 mutation variants were identified in genes associated with the five CLNs described in this study, with typical and atypical clinical phenotypes depending on the subtype and its variants.

Conclusion: Novel mutations identified in the patients in this study showed phenotypes of rapid and severe progression in the CLN2 patient and similar characteristics in CLN6 and CLN7 patients, as previously described in the literature.

Background: Autoimmune encephalitis (AE) is the third most common encephalitis in children. Diagnosis can be challenging due to overlapping and diverse clinical presentations as well as various investigation results. This study aims to characterize the clinical, diagnostic features, as well as treatment and outcomes of AE in children and determine the incidence of pediatric AE in Latvia.

Methods: The study was conducted at the Children's Clinical University Hospital in Riga. The study participants were patients under the age of 18 years diagnosed with AE from 2014 to 2022. Data regarding clinical characteristics, investigation findings, treatment strategy, and outcomes were retrospectively collected from the medical history data system.

Results: We included 18 pediatric patients diagnosed with AE. The mean incidence of pediatric AE in Latvia was 0.56 per 100,000 children. Most patients (66.6%) had seronegative AE. In the seropositive group, the most common was anti-methyl-D-aspartate receptor AE, with two patients having other antibodies. The most prevalent clinical features were personality change, cognitive impairment, autonomic dysfunction, and movement disorders. The majority of patients (58.8%) received first-line treatment only. More than half (55.6%) of our AE patient group had long-term sequelae.

Conclusions: Our study shows that the pediatric AE incidence in Latvia is similar to what has been previously reported in other studies. A relatively high proportion of seronegative AE was present in our cohort, indicating that awareness of possible misdiagnosis should be raised. Further research is needed to better understand the underlying mechanisms, characterize clinical features, and determine the treatment of choice in different situations to improve long-term outcomes.

Hereditary spastic paraplegias (HSPs) are a genetically heterogeneous group of neurodegenerative disorders clinically characterized by progressive lower limb spasticity with pyramidal weakness. Around a dozen potential molecular mechanisms are recognized. Childhood HSP is a significant diagnostic challenge in clinical practice. Mutations in AP5Z1, which are associated with spastic paraplegia type 48 (SPG48), are extremely rare and seldom described in children.We report the clinical, radiologic, and molecular studies performed in a child harboring novel biallelic mutations in AP5Z1.The child presented a neurodevelopmental disorder with slight lower limb pyramidal signs. Brain magnetic resonance imaging (MRI) showed minimal white matter changes in the frontal horns of the lateral ventricles and a normally shaped corpus callosum. Western blotting in cultured skin fibroblasts indicated reduced protein expression, which confirmed the genetic diagnosis and framed this as a case of protein reduction in a context of impaired autophagy.Our findings expand the spectrum of phenotypes associated with mutations in AP5Z1, highlighting their clinical and pathophysiologic overlap with lysosomal storage disorders. SPG48 should be considered in the differential diagnosis of neurodevelopmental disorders even when pyramidal signs are minimal and brain MRI not fully informative.

Surgery remains a critical and often necessary intervention for a subset of patients with epilepsy. The overarching objective of surgical treatment has consistently been to enhance the quality of life for these individuals, either by achieving seizure freedom or by eliminating debilitating seizure types. This review specifically examines minimally invasive surgical approaches for epilepsy. Contemporary advancements have introduced a range of treatments that offer increased safety and efficacy compared to traditional open resective epilepsy surgeries. This manuscript provides a comprehensive review of these techniques and technologies.