Neuropediatrics最新文献

Background: Magnetic resonance imaging in fetal alcohol spectrum disorder (FASD) children showed altered connectivity, suggesting underlying deficits in networks, which may be related to cognitive outcome. Functional connectivity has been of interest in neurophysiological research with quantitative electroencephalography (QEEG) as useful tool for measuring pathology, not detectable by normal EEG. The aim of this study was to investigate differences in the EEG interhemispheric coherence (ICoh) in children diagnosed with FASD compared with healthy controls and to relate the results to cognitive scores.

Method: Analysis of ICoh in 81 FASD children (4-Digit Code) compared with 31 controls. The children underwent cognitive assessment, and EEG was performed and used for analysis. Group comparisons and analysis of covariance interaction models were used to test for differences between FASD and controls but also to look for differences between FASD subgroups. Significant findings were correlated to cognitive scores.

Results: Lower ICoh was found in the frontal and temporal derivations in the FASD group. When comparing FASD subgroups, children with fetal alcohol syndrome had lower ICoh occipital. Reduced ICoh in the temporal alpha band was correlated with lower performance IQ in the FASD group.

Conclusion: Our findings could imply hypoconnectivity between the hemispheres with impact on cognition. We suggest that EEG coherence analysis could be a sensitive parameter in the detection of electrophysiological abnormalities in FASD with possible clinical relevance. These results may indicate that QEEG could be used as biomarker for FASD. However, further research is needed to determine the role of QEEG analysis in the diagnosis of FASD.

Cyclic nucleotide phosphodiesterase (PDE) enzymes catalyze the breakdown of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which act as intracellular second messengers for signal transduction pathways and modulate various processes in the central nervous system. Recent discoveries that mutations in genes encoding different PDEs, including PDE10A, are responsible for rare forms of chorea in children led to the recognition of an emerging role of PDEs in the field of pediatric movement disorders. A comprehensive literature review of all reported cases of PDE10A mutations in PubMed and Web of Science was performed in English. We included eight studies, describing 31 patients harboring a PDE10A mutation and exhibiting a hyperkinetic movement disorder with onset in infancy or childhood. Mutations in both GAF-A, GAF-B regulatory domains and outside the GAF domains of the PDE10A gene have been reported to cause hyperkinetic movement disorders. In general, patients with homozygous mutations in either GAF-A domain of PDE10A present with a more severe phenotype and at an earlier age but without any extensive abnormalities of the striata compared with patients with dominant variants in GAF-B domain, indicating that dominant and recessive mutations have different pathogenic mechanisms. PDE10A plays a key role in regulating control of striato-cortical movement. Comprehension of the molecular mechanisms within the cAMP and cGMP signaling systems caused by PDE10A mutations may inform novel therapeutic strategies that could alleviate symptoms in young patients affected by these rare movement disorders.

The association between dystonia and early-onset epileptic encephalopathy (EOEE) may have a genetic basis. Phosphatidylinositol glycan biosynthesis class A protein (PIGA) germline mutations have been described in the last decade and associated with refractory EOEEs. Dysmorphisms and visceral abnormalities have also been reported. Here, we present the case of a now 8-month-old child who was evaluated for dystonia, visual impairment, and developmental delay at 2 months of age, followed by refractory focal seizures when he was 4 months old. The remaining examination was normal, besides an accelerated linear growth. His brain magnetic resonance and an extensive metabolic investigation failed to show any abnormalities. At 7 months of age, the exome sequencing found a hemizygous PIGA pathogenic variant-c.1352T > C (p.(Ile451Thr). Seizures improved after the association of carbamazepine with levetiracetam and the beginning of the ketogenic diet. To our knowledge, this is the first time the phenotype associated with this specific mutation is described. Our patient had the singularity of manifesting with remarkable dystonia, over 2 months before the onset of seizures. We also point to the utility of the gene sequencing approach in the diagnosis of patients with dystonia and EOEEs, since identification of the genetic cause may help in patient's management and families' empowerment.

Background: Teenagers with epilepsy require special attention to ensure a successful treatment journey. Our objective was to delineate the clinical characteristics of adolescent-onset epilepsy (AOE) and investigate the predictive factors influencing first-year seizure freedom.

Methods: We retrospectively analyzed the medical records of patients whose first seizure occurred between the ages of 10 and 19 years and who received antiseizure medication (ASM) treatment for at least 12 months.

Results: A total of 67 patients were included, with an average age of 13.5 ± 2.3 years at the onset of their first seizure. The average follow-up period was 45.2 ± 16.9 months, and comorbid conditions were present in 23 patients (34.3%). The majority of the patient population (83.6%) was affected by generalized epilepsy. The most common epilepsy syndrome was epilepsy with generalized tonic-clonic seizures alone at 70.1% (juvenile myoclonic epilepsy 11.9%, juvenile absence epilepsy 1.5%). Regarding ASM treatment, 31 patients (46.3%) received monotherapy, and 28 (41.8%) received dual therapy. Five patients (7.5%) encountered issues related to medication adherence. First-year seizure freedom was observed in 42 patients (62.7%). In multivariate analysis, a negative family history of epilepsy (odds ratio 12.1, 95% confidence interval 1.27-115.44, p = 0.030) was identified as a strong predictive factor of first-year seizure freedom, along with ASM monotherapy (odds ratio 3.99, 95% confidence interval 1.05-15.21, p = 0.043).

Conclusion: These findings suggest that AOE typically exhibits effective control of seizures. A negative family history of epilepsy and ASM monotherapy emerges as robust predictor of achieving favorable outcomes within the early stage of treatment.

Introduction: Cerebral venous thrombosis (CVT) is a rare but potentially fatal disease in pediatric age with an important morbimortality. In adults several factors have been associated with worse outcomes, however there are still few studies in children. This study aims to identify risk factors associated with clinical manifestations and long-term sequelae in pediatric CVT.

Methods: Retrospective analysis of pediatric inpatients admitted to a tertiary-care hospital due to CVT between 2008 and 2020.

Results: Fifty-four children were included, 56% male, median age of 6.5 years (9 months-17.3 years). Permanent risk factors were identified in 13 patients (malignancy, 8; hematologic condition, 5) and transient risk factors in 47, including head and neck infections (57%) and head trauma (15%). Multiple venous sinuses involvement was present in 65% and the deep venous system was affected in four patients. Seventeen percent had intracranial hemorrhage and 9% cerebral infarction. Sixty-four percent of patients with multiple venous sinuses involvement presented with severe clinical manifestations: impaired consciousness, intracranial hypertension, acute symptomatic seizures or focal deficits. Regarding long-term prognosis, six patients had major sequelae: epilepsy (n = 3), sensory motor deficits (n = 2), and cognitive impairment (n = 3). Permanent risk factors were associated with severe clinical manifestations (p = 0.043). Cerebral infarction and intracranial hemorrhage were associated with major sequelae (p = 0.006 and p = 0.03, respectively, adjusted for age and sex).

Conclusion: Permanent risk factors, involvement of multiple venous sinuses, intracranial hemorrhage, and cerebral infarction, were related to worse prognosis. Detection and early management of risk factors may limit CVT extension and reduce its morbimortality.

Congenital myopathy type 13 (CMYO13), also known as Native American myopathy, is a rare muscle disease characterized by early-onset hypotonia, muscle weakness, delayed motor milestones, and susceptibility to malignant hyperthermia. The phenotypic spectrum of congenital myopathy type 13 is expanding, with milder forms reported in non-native American patients. The first description of the disease dates to 1987 when Bailey and Bloch described an infant belonging to a Native American tribe with cleft palate, micrognathia, arthrogryposis, and general-anesthesia-induced malignant hyperthermia reaction; the cause of the latter remains poorly defined in this rare disease. The pan-ethnic distribution, as well as its predisposition to malignant hyperthermia, makes the identification of CMYO13 essential to avoid life-threatening, anesthesia-related complications. In this article, we are going to review the clinical phenotype of this disease and the pathophysiology of this rare disease with a focus on two unique features of the disease, namely cleft palate and malignant hyperthermia. We also highlight the importance of recognizing this disease's expanding phenotypic spectrum-including its susceptibility to malignant hyperthermia-and providing appropriate care to affected individuals and families.

Objective: The aim of the study is to explore the clinical and genetic characteristics of the combined oxidative phosphorylation defect type 21 (COXPD21) caused by the TARS2 compound heterozygous pathogenic variants, and to improve clinicians' awareness of the disease.

Methods: The proband was a girl of first birth, with repeated refractory hypokalemia, hearing impairment, developmental delay, intellectual disability, developmental retardation after infection, high limb muscle tension, and increased serum lactate as the clinical phenotype. The clinical performance, diagnosis, treatment process, and gene characteristics of COXPD21 caused by TARS2 of the case were analyzed, reviewed, and compared with the literature from the CNKI, Wanfang Data, and biomedical literature database (PubMed) until November 2021.

Results: The child was diagnosed with COXPD21 after two heterozygous variants in the TARS2 gene were found via whole exome sequencing. One of the variants was c.1679(exon14) A > C (p.Asp560Ala) missense, derived from the mother, and the other was c.1036(exon10)C > T (p.Arg346Cys) missense, derived from the father. The literature was searched and reviewed with the keywords "mitochondrial encephalomyopathy," "TARS2," and "combination oxidative phosphorylation deficiency type 21." A total of four complete domestic and foreign cases were collected from the literature search.

Conclusion: COXPD21 onset by a complex heterozygous variant of TARS2 causes refractory hypokalemia, which is rarely reported in China and abroad.

Aim: The study aims to review all the genetically confirmed STAC3-related myopathy being followed in a single center in the Eastern Province of Saudi Arabia.

Methodology: A retrospective review of all genetically confirmed STAC3-related myopathy followed in our clinic has been conducted.

Results: 7 patients with STAC3-related myopathy have been found in our cohort, with all the patients presenting with infantile hypotonia, myopathic facies, and muscle weakness in the first year of life. Feeding difficulties and failure to thrive were found in all patients except one who died during the neonatal period. Respiratory muscle involvement was also found in 5 out of 6 formally tested patients while cleft palate was found in 5 patients.

Conclusion: STAC3-related myopathy is a relatively rare, malignant hyperthermia (MH)--causing muscle disease described in specific, highly consanguineous populations. Making the diagnosis in myopathic patients with cleft palate preoperatively can prevent MH-induced, anesthesia-related perioperative complications.