Risk factors and predictors of recurrence of febrile seizures in children in Nantong, China: a retrospective cohort study.

BACKGROUND: Although most children with febrile seizures (FS) have a favorable prognosis, some experience recurrence within 1-3 years. Age, peak temperature, and family history are now recognized as important risk factors for FS recurrence, yet studies in this area are lacking in China. This study aimed to investigate the risk factors for FS recurrence in children in Nantong, China, and to develop a prediction model. METHODS: This retrospective cohort study analyzed 463 children diagnosed with febrile seizures (FS) who presented to the Affiliated Hospital of Nantong University between January 2015 and June 2020. Basic information, disease characteristics, and laboratory and imaging data were collected. A follow-up survey was conducted one year post-discharge to assess the recurrence status of FS in children. Univariate logistic regression and random forest models were used to identify and rank the predictive ability of risk factors for recurrence. RESULTS: Of the 463 children with FS, 70 experienced recurrences within 1 year of discharge, resulting in a one-year recurrence rate of 15%. Age (OR = 0.61, 95% CI: 0.46, 0.80, P < 0.001), duration of the first episode (OR = 1.03, 95% CI: 1.00, 1.06, P = 0.040), and peak temperature (OR = 0.68, 95% CI: 0.47, 0.98, P = 0.036) were identified as independent risk factors for FS recurrence. Age had the highest relative importance in predicting FS recurrence, followed by the duration of the first episode, with an area under the ROC curve of 0.717. CONCLUSION: Young age and duration of the first seizure are important independent risk factors for FS recurrence and are key considerations for predicting recurrence. Further research is needed to confirm the potential use of Neutrophil-lymphocyte ratio (NLR) as a predictor of FS recurrence.

A preliminary study on the association between prognostic nutritional index and neutrophil-to-lymphocyte ratio with nutritional status and inflammation in febrile children's susceptibility to seizures.

OBJECTIVE: The aim of this study was to evaluate the association between nutritional status, inflammation, and susceptibility to seizures in febrile children. METHODS: This observational single-center study was carried out from January 2020 to December 2023 with 324 children aged 6 months and 6 years; 106 were diagnosed with febrile seizure, 108 were febrile children, and 110 were healthy controls. The prognostic nutritional index and neutrophil-to-lymphocyte ratio were calculated, and the cutoff threshold was established through receiver operating characteristics. The study utilized correlation and univariate-multivariate logistic regression analysis. The comparison between simple and complex febrile seizure was conducted to analyze differences. RESULTS: The optimal cutoff values were identified as 61.25 for prognostic nutritional index and 1.04 for neutrophil-to-lymphocyte ratio. Our findings showed a significant negative association between febrile seizure and platelet count, high C-reactive protein, and high ferritin levels. Additionally, the febrile seizure group showed a significant positive correlation with high neutrophil-to-lymphocyte ratio values (≥1.04) and body temperature (≥38). Our findings revealed that high neutrophil-to-lymphocyte ratio, high C-reactive protein, and age less than 18 months were independently associated with seizure susceptibility in febrile children. CONCLUSION: High neutrophil-to-lymphocyte ratio values and low prognostic nutritional index scores may serve as novel surrogate independent factors for seizure susceptibility in febrile children. Febrile children who are less than 18 months old are more prone to experience seizures than older febrile children. Moreover, there was a correlation between febrile seizures and elevated C-reactive protein levels and neutrophil-to-lymphocyte ratio values.

Neurological Manifestations of Acute SARS-CoV-2 Infection in Pediatric Patients: A 3-Year Study on Differences between Pandemic Waves.

This study analyzed the neurological manifestation profiles of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across pandemic waves in pediatric patients. The study collected data on patients aged between 0 and 18 years, diagnosed with acute SARS-CoV-2 infection, admitted to a pediatric tertiary hospital between 1 March 2020 and 28 February 2023. This study included 1677 patients. Neurological manifestations were noted in 10% (n = 168) of patients with a median age of 3.2 years (interquartile range: 1-11.92). Neurological manifestations were significantly associated with the pandemic waves (p = 0.006) and age groups (p < 0.001). Seizures were noted in 4.2% of cases and reached an increasing frequency over time (p = 0.001), but were not associated with age groups. Febrile seizures accounted for the majority of seizures. Headache was reported in 2.6% of cases and had similar frequencies across the pandemic waves and age groups. Muscular involvement was noted in 2% of cases, reached a decreasing frequency over time (p < 0.001), and showed different frequencies among the age groups. Neurological manifestations of acute SARS-CoV-2 infection exhibit distinct patterns, depending on the pandemic wave and patient age group. The Wuhan and Omicron waves involved the nervous system more often than the other waves.

Serum HMGB1 in febrile seizures.

The role of high-mobility group box 1 (HMGB1) in the pathogenesis of febrile seizures (FSs) is unclear. In our controlled follow-up study, we compared serum levels of HMGB1 (s-HMGB1) in the same individuals after the first FS, during febrile episodes without a FS, after recurrent FS, during healthy periods after FS, and between patients and controls. In all, 122 patients with FSs were included in the final analysis, including 18 with recurrent FSs with a complete follow-up protocol. We recruited 30 febrile children and 18 matched febrile children without seizures as controls. S-HMGB1 was lower in patients with recurrent FSs after the first FS than that in matched febrile control children (median 1.12 µg/L (0.14-2.95) vs 1.79 µg/L (0.33-47.90), P<0.04). We did not find any other differences in s-HMGB1 between the groups. S-HMGB1 did not differ in different types of FSs. We updated a meta-analysis of s-HMGB1 in patients with FSs and found that the differences were significant only in the studies conducted in East Asian populations. We conclude that S-HMGB1 does not seem to be a key factor in the pathogenesis of FSs but differences in HMGB1 concentrations could explain some of the ethnicity related susceptibility to FSs.

Has the Incidence of Febrile Convulsions in Childhood Changed During the SARS-CoV-2 Pandemic?

Introduction: SARS-CoV-2 infection in children is usually asymptomatic or only mild symptoms are typical. The aim of our study was to assess the incidence of febrile convulsions in our own patients with COVID-19. Patients and Methods: In our retrospective study, we reviewed the data of children who presented at our University Hospital from March 2020 to March 2022 with febrile convulsion. The control group were children admitted to the hospital because of febrile convulsions from January 2018 to January 2020. Results: During the coronavirus pandemic, 51 patients were examined with febrile convulsions. The majority (86.3%) of children had their first febrile convulsion during this period. We diagnosed simple febrile convulsions in 40 cases and complicated ones in 11 cases. The family history of febrile convulsion or epilepsy was present in 12 (23.5%) patients. In addition to febrile convulsion, SARS-CoV-2 infection was confirmed by laboratory testing in 4 cases (7.8%). Three of them had febrile convulsion during the Omicron variant period. Conclusions: During the coronavirus pandemic, the number of children examined because of having febrile convulsions was not higher than in the control period. The coronavirus is unlikely to increase the risk of febrile convulsions.

FADD gene pathogenic variants causing recurrent febrile infection-related epilepsy syndrome: Case report and literature review.

FIRES and NORSE are clinical presentations of disease processes that, to date, remain unexplained without an established etiology in many cases. Neuroinflammation is thought to have paramount importance in the genesis of these conditions. We hereby report the clinical, EEG, brain MRI, and genetic findings of a nuclear family with recurrent febrile-related encephalopathy with refractory de novo Status Epilepticus. Whole-exome sequencing (WES) revealed a homozygous p.C105W pathogenic variant of FADD gene (FAS-associated protein with death domain, FADD), known to cause ultrarare forms of autosomal recessive immunodeficiency that could be associated with variable degrees of lymphoproliferation, cerebral atrophy, and cardiac abnormalities. The FADD-related conditions disrupt FAS-mediated apoptosis and can cause a clinical picture with the characteristics of FIRES. This observation is important because, on one hand, it increases the number of reported patients with FADD deficiency, showing that this disorder may present variable expressivity, and on the other hand, it demonstrates a genetic cause of FIRES involving a cell-mediated inflammation regulatory pathway. This finding supports early treatment with immunomodulatory therapy and could represent a new avenue of research in the field of new onset refractory status epilepticus and related conditions.

Sex differences in cholinergic signaling affect functional outcomes for theta-gamma coordination in hippocampal subcircuits following experimental febrile status epilepticus.

OBJECTIVE: Sex determines cognitive outcome in animal models of early life seizure, where males exhibit impaired hippocampal-dependent learning and memory compared with females. The physiological underpinnings of this sex effect are unclear. Cholinergic signaling is essential for the generation of hippocampal oscillations, and supplementation of cholinergic precursors prior to status epilepticus in immature male rats prevents subsequent memory deficits. We hypothesized that there are sex differences in acetylcholine circuits and their response to experimental febrile status epilepticus (eFSE). METHODS: eFSE was induced in male and female rat pups. We transversed the hippocampus of postnatal day >60 control (CTL) and eFSE rats with a 64-channel laminar silicon probe to assay cholinergic-dependent theta oscillations under urethane anesthesia. Local field potential properties were compared during (1) baseline sensory stimulation, (2) pharmacological stimulation via acetylcholine reuptake blockade, and (3) sensory stimulation after muscarinic acetylcholine receptor block (atropine). RESULTS: In all groups, a baseline tail pinch could elicit theta oscillations via corticohippocampal synaptic input. Following atropine, a tail pinch response could no longer be elicited in CTL male, CTL female, or eFSE female rats. In contrast, induced slow theta power in eFSE males after atropine was not decreased to spontaneous levels. Analysis of oscillation bandwidths revealed sex differences in acetylcholine modulation of theta frequency and slow gamma frequency and power. This study also identified significant effects of both sex and eFSE on baseline theta-gamma comodulation, indicating a loss of coupling in eFSE males and a potential gain of function in eFSE females. SIGNIFICANCE: There are differences in cholinergic modulation of theta and gamma signal coordination between male and female rats. These differences may underlie worse cognitive outcomes in males following eFSE. Promoting the efficacy of muscarinic acetylcholine signaling prior to or following early life seizures could elucidate a mechanism for the temporal discoordination of neural signals within and between hippocampus and neocortex and provide a novel therapeutic approach for improving cognitive outcomes.

Best practices for the management of febrile seizures in children.

Febrile seizures (FS) are commonly perceived by healthcare professionals as a self-limited condition with a generally 'benign' nature. Nonetheless, they frequently lead to pediatric consultations, and their management can vary depending on the clinical context. For parents and caregivers, witnessing a seizure can be a distressing experience, significantly impacting their quality of life. In this review, we offer an in-depth exploration of FS management, therapeutic interventions, and prognostic factors, with the aim of providing support for physicians and enhancing communication with families. We conducted a comprehensive literature search using the PubMed and Web of Science databases, spanning the past 50 years. The search terms utilized included "febrile seizure," "complex febrile seizure," "simple febrile seizure," in conjunction with "children" or "infant." Only studies published in English or those presenting evidence-based data were included in our assessment. Additionally, we conducted a cross-reference search to identify any additional relevant data sources. Our thorough literature search resulted in a compilation of references, with carefully selected papers thoughtfully integrated into this review.

Seizure control via pH manipulation: a phase II double-blind randomised controlled trial of inhaled carbogen as adjunctive treatment of paediatric convulsive status epilepticus (Carbogen for Status Epilepticus in Children Trial (CRESCENT)).

BACKGROUND: Paediatric convulsive status epilepticus is the most common neurological emergency presenting to emergency departments. Risks of resultant neurological morbidity and mortality increase with seizure duration. If the seizure fails to stop within defined time-windows, standard care follows an algorithm of stepwise escalation to more intensive treatments, ultimately resorting to induction of general anaesthesia and ventilation. Additionally, ventilatory support may also be required to treat respiratory depression, a common unwanted effect of treatment. There is strong pre-clinical evidence that pH (acid-base balance) is an important determinant of seizure commencement and cessation, with seizures tending to start under alkaline conditions and terminate under acidic conditions. These mechanisms may be particularly important in febrile status epilepticus: prolonged fever-related seizures which predominantly affect very young children. This trial will assess whether imposition of mild respiratory acidosis by manipulation of inhaled medical gas improves response rates to first-line medical treatment. METHODS: A double-blind, placebo-controlled trial of pH manipulation as an adjunct to standard medical treatment of convulsive status epilepticus in children. The control arm receives standard medical management whilst inhaling 100% oxygen; the active arm receives standard medical management whilst inhaling a commercially available mixture of 95% oxygen, 5% carbon dioxide known as 'carbogen'. Due to the urgent need to treat the seizure, deferred consent is used. The primary outcome is success of first-line treatment in seizure cessation. Planned subgroup analyses will be undertaken for febrile and non-febrile seizures. Secondary outcomes include rates of induction of general anaesthesia, admission to intensive care, adverse events, and 30-day mortality. DISCUSSION: If safe and effective 95% oxygen, 5% carbon dioxide may be an important adjunct in the management of convulsive status epilepticus with potential for pre-hospital use by paramedics, families, and school staff. TRIAL REGISTRATION: EudraCT: 2021-005367-49. CTA: 17136/0300/001. ISRCTN: 52731862. Registered on July 2022.

Comparison of clinical characteristics and disease burden of febrile seizures in children with and without COVID-19.

BACKGROUND: Febrile seizures (FS) are the most common seizure disorder in children and a common neurologic complication in children with coronavirus disease 2019 (COVID-19). This study aimed to identify differences in clinical characteristics and disease burden between FS with and without COVID-19. MATERIALS AND METHODS: We conducted a retrospective analysis of medical data at our hospital from December 2019 to July 2023, focusing on hospitalized patients under the age of 14 diagnosed with FS who underwent COVID-19 polymerase chain reaction (PCR) testing. Descriptive statistics and analysis of variance were employed to compare the COVID-19 and non-COVID-19 groups in terms of clinical characteristics and disease burden. RESULTS: A total of 514 patients were included, with 106 testing positive for COVID-19 and 408 testing negative. Patients with COVID-19 were older (34.87 ± 6.16 vs. 28.61 ± 11.35 months, P < 0.001) and had a higher proportion of males (79.2% vs. 62.3%, P = 0.001). The COVID-19 group had longer seizure durations (4.57 ± 4.38 vs. 3.22 ± 2.91 min, P = 0.006) and more complex FS (25.5% vs. 15.9%, P = 0.022). Laboratory tests showed lower lymphocyte counts in the COVID-19 group (1.87 ± 1.48 vs. 2.75 ± 1.51 × 103/µL, P < 0.001) and higher creatine kinase levels (158.49 ± 82.89 vs. 110.89 ± 56.11 U/L, P < 0.001). No significant differences were found in hospital costs, length of hospitalization, and intensive care unit admissions. CONCLUSION: Clinicians should be knowledgeable about the distinct clinical characteristics of FS in children with COVID-19. Despite distinct features, the prognosis remains favorable and does not require excessive intervention. Ongoing monitoring and research are needed to fully understand the impact of COVID-19 on FS and optimize management strategies.

Modulating Endoplasmic Reticulum Chaperones and Mutant Protein Degradation in GABRG2(Q390X) Associated with Genetic Epilepsy with Febrile Seizures Plus and Dravet Syndrome.

A significant number of patients with genetic epilepsy do not obtain seizure freedom, despite developments in new antiseizure drugs, suggesting a need for novel therapeutic approaches. Many genetic epilepsies are associated with misfolded mutant proteins, including GABRG2(Q390X)-associated Dravet syndrome, which we have previously shown to result in intracellular accumulation of mutant GABAA receptor γ2(Q390X) subunit protein. Thus, a potentially promising therapeutic approach is modulation of proteostasis, such as increasing endoplasmic reticulum (ER)-associated degradation (ERAD). To that end, we have here identified an ERAD-associated E3 ubiquitin ligase, HRD1, among other ubiquitin ligases, as a strong modulator of wildtype and mutant γ2 subunit expression. Overexpressing HRD1 or knockdown of HRD1 dose-dependently reduced the γ2(Q390X) subunit. Additionally, we show that zonisamide (ZNS)-an antiseizure drug reported to upregulate HRD1-reduces seizures in the Gabrg2+/Q390X mouse. We propose that a possible mechanism for this effect is a partial rescue of surface trafficking of GABAA receptors, which are otherwise sequestered in the ER due to the dominant-negative effect of the γ2(Q390X) subunit. Furthermore, this partial rescue was not due to changes in ER chaperones BiP and calnexin, as total expression of these chaperones was unchanged in γ2(Q390X) models. Our results here suggest that leveraging the endogenous ERAD pathway may present a potential method to degrade neurotoxic mutant proteins like the γ2(Q390X) subunit. We also demonstrate a pharmacological means of regulating proteostasis, as ZNS alters protein trafficking, providing further support for the use of proteostasis regulators for the treatment of genetic epilepsies.

Febrile Seizures: A Systematic Review of Different Guidelines.

BACKGROUND: Febrile seizures (FS) are the most common neurological disorder in pediatric age. FS affect 2% to 12% of children and result from a complex interplay of genetic and environmental factors. Effective management and unambiguous recommendations are crucial for allocating health care resources efficiently and ensuring cost-effectiveness in treating FS. METHODS: This systematic review compares existing guidelines to provide insights into FS management. Seven guidelines published between 1991 and 2021, from Japan, United Kingdom, United States, Mexico, India, and Italy, were included. Data extraction covered definitions, diagnostic criteria, hospital admission criteria, diagnostic tests, management, and prophylaxis recommendations. RESULTS: Hospital admission criteria varied but typically included age <18 months and complex FS. Neuroimaging and lumbar puncture recommendations varied, with most guidelines suggesting limited use. Pharmacologic prophylaxis was generally discouraged for simple FS but considered only for high-risk cases, due to the benign nature of FS and the potential side effects of antiseizure medications. CONCLUSIONS: Guidelines on FS exhibit similarities and differences, highlighting the need for standardized management and improved parental education to enhance clinical outcomes and reduce economic and social costs associated with FS. Future research should focus on creating updated international guidelines and ensuring their practical implementation.

Comparative analysis of patients with new onset refractory status epilepticus preceded by fever (febrile infection-related epilepsy syndrome) versus without prior fever: An interim analysis.

Febrile infection-related epilepsy syndrome (FIRES) is a subset of new onset refractory status epilepticus (NORSE) that involves a febrile infection prior to the onset of the refractory status epilepticus. It is unclear whether FIRES and non-FIRES NORSE are distinct conditions. Here, we compare 34 patients with FIRES to 30 patients with non-FIRES NORSE for demographics, clinical features, neuroimaging, and outcomes. Because patients with FIRES were younger than patients with non-FIRES NORSE (median = 28 vs. 48 years old, p = .048) and more likely cryptogenic (odds ratio = 6.89), we next ran a regression analysis using age or etiology as a covariate. Respiratory and gastrointestinal prodromes occurred more frequently in FIRES patients, but no difference was found for non-infection-related prodromes. Status epilepticus subtype, cerebrospinal fluid (CSF) and magnetic resonance imaging findings, and outcomes were similar. However, FIRES cases were more frequently cryptogenic; had higher CSF interleukin 6, CSF macrophage inflammatory protein-1 alpha (MIP-1a), and serum chemokine ligand 2 (CCL2) levels; and received more antiseizure medications and immunotherapy. After controlling for age or etiology, no differences were observed in presenting symptoms and signs or inflammatory biomarkers, suggesting that FIRES and non-FIRES NORSE are very similar conditions.

Hippocampal sclerosis and temporal lobe epilepsy following febrile status epilepticus: The FEBSTAT study.

OBJECTIVE: This study was undertaken to determine whether hippocampal T2 hyperintensity predicts sequelae of febrile status epilepticus, including hippocampal atrophy, sclerosis, and mesial temporal lobe epilepsy. METHODS: Acute magnetic resonance imaging (MRI) was obtained within a mean of 4.4 (SD = 5.5, median = 2.0) days after febrile status on >200 infants with follow-up MRI at approximately 1, 5, and 10 years. Hippocampal size, morphology, and T2 signal intensity were scored visually by neuroradiologists blinded to clinical details. Hippocampal volumetry provided quantitative measurement. Upon the occurrence of two or more unprovoked seizures, subjects were reassessed for epilepsy. Hippocampal volumes were normalized using total brain volumes. RESULTS: Fourteen of 22 subjects with acute hippocampal T2 hyperintensity returned for follow-up MRI, and 10 developed definite hippocampal sclerosis, which persisted through the 10-year follow-up. Hippocampi appearing normal initially remained normal on visual inspection. However, in subjects with normal-appearing hippocampi, volumetrics indicated that male, but not female, hippocampi were smaller than controls, but increasing hippocampal asymmetry was not seen following febrile status. Forty-four subjects developed epilepsy; six developed mesial temporal lobe epilepsy and, of the six, two had definite, two had equivocal, and two had no hippocampal sclerosis. Only one subject developed mesial temporal epilepsy without initial hyperintensity, and that subject had hippocampal malrotation. Ten-year cumulative incidence of all types of epilepsy, including mesial temporal epilepsy, was highest in subjects with initial T2 hyperintensity and lowest in those with normal signal and no other brain abnormalities. SIGNIFICANCE: Hippocampal T2 hyperintensity following febrile status epilepticus predicted hippocampal sclerosis and significant likelihood of mesial temporal lobe epilepsy. Normal hippocampal appearance in the acute postictal MRI was followed by maintained normal appearance, symmetric growth, and lower risk of epilepsy. Volumetric measurement detected mildly decreased hippocampal volume in males with febrile status.

Clinical Profile and Predictors of Recurrent Simple Febrile Seizure.

BACKGROUND: Recurrent simple febrile seizure (SFS) refers to febrile seizure (FS) that recurs within 24 hours. Patients with recurrent SFS often undergo unnecessary neurodiagnostic tests. To address this, we compared the clinical characteristics of recurrent SFS with those of SFS and investigated the risk factors associated with recurrent SFS. METHODS: We retrospectively reviewed electronic medical records of patients aged six to 60 months who had been hospitalized for FS at two training hospitals between January 2016 and December 2019. The primary outcome was a comparison of the clinical features of patients with SFS and recurrent SFS. Additionally, the risk factors associated with seizure recurrence within 24 hours were evaluated. RESULTS: Three quarters (n = 191, 75.2%) of the 254 enrolled patients experienced a single seizure episode during the febrile illness period. The remaining 63 patients (24.8%) were diagnosed with recurrent SFS. Significant differences between SFS and recurrent SFS were observed in the history of recurrent SFS, time from fever onset to seizure, and body temperature on hospital arrival. Multiple logistic regression analysis revealed that a history of previous recurrent SFS (odds ratio [OR] 10.161) and a body temperature below 39°C on arrival (OR 2.377) were significantly associated with early seizure recurrence. CONCLUSIONS: This study highlights that early FS recurrence is common and has a self-limiting clinical course similar to that of SFS. We recommend close monitoring of the patient for six to eight hours when a history of early recurrence is present or if the seizure occurs at a low body temperature.

Additive interaction between birth asphyxia and febrile seizures on autism spectrum disorder: a population-based study.

BACKGROUND: Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental disorder that can significantly impact an individual's ability to socially integrate and adapt. It's crucial to identify key factors associated with ASD. Recent studies link both birth asphyxia (BA) and febrile seizures (FS) separately to higher ASD prevalence. However, investigations into the interplay of BA and FS and its relationship with ASD are yet to be conducted. The present study mainly focuses on exploring the interactive effect between BA and FS in the context of ASD. METHODS: Utilizing a multi-stage stratified cluster sampling, we initially recruited 84,934 Shanghai children aged 3-12 years old from June 2014 to June 2015, ultimately including 74,251 post-exclusion criteria. A logistic regression model was conducted to estimate the interaction effect after controlling for pertinent covariates. The attributable proportion (AP), the relative excess risk due to interaction (RERI), the synergy index (SI), and multiplicative-scale interaction were computed to determine the interaction effect. RESULTS: Among a total of 74,251 children, 192 (0.26%) were diagnosed with ASD. The adjusted odds ratio for ASD in children with BA alone was 3.82 (95% confidence interval [CI] 2.42-6.02), for FS alone 3.06 (95%CI 1.48-6.31), and for comorbid BA and FS 21.18 (95%CI 9.10-49.30), versus children without BA or FS. The additive interaction between BA and FS showed statistical significance (P < 0.001), whereas the multiplicative interaction was statistically insignificant (P > 0.05). LIMITATIONS: This study can only demonstrate the relationship between the interaction of BA and FS with ASD but cannot prove causation. Animal brain experimentation is necessary to unravel its neural mechanisms. A larger sample size, ongoing monitoring, and detailed FS classification are needed for confirming BA-FS interaction in ASD. CONCLUSION: In this extensive cross-sectional study, both BA and FS were significantly linked to ASD. The coexistence of these factors was associated with an additive increase in ASD prevalence, surpassing the cumulative risk of each individual factor.

Ascorbic acid mitigates the impact of oxidative stress in a human model of febrile seizure and mesial temporal lobe epilepsy.

Prolonged febrile seizures (FS) in children are linked to the development of temporal lobe epilepsy (MTLE). The association between these two pathologies may be ascribed to the long-term effects that FS exert on neural stem cells, negatively affecting the generation of new neurons. Among the insults associated with FS, oxidative stress is noteworthy. Here, we investigated the consequences of exposure to hydrogen peroxide (H2O2) in an induced pluripotent stem cell-derived neural stem cells (iNSCs) model of a patient affected by FS and MTLE. In our study, we compare the findings from the MTLE patient with those derived from iNSCs of a sibling exhibiting a milder phenotype defined only by FS, as well as a healthy individual. In response to H2O2 treatment, iNSCs derived from MTLE patients demonstrated an elevated production of reactive oxygen species and increased apoptosis, despite the higher expression levels of antioxidant genes and proteins compared to other cell lines analysed. Among the potential causative mechanisms of enhanced vulnerability of MTLE patient iNSCs to oxidative stress, we found that these cells express low levels of the heat shock protein HSPB1 and of the autophagy adaptor SQSTM1/p62. Pre-treatment of diseased iNSCs with the antioxidant molecule ascorbic acid restored HSBP1 and p62 expression and simultaneously reduced the levels of ROS and apoptosis. Our findings suggest the potential for rescuing the impaired oxidative stress response in diseased iNSCs through antioxidant treatment, offering a promising mechanism to prevent FS degeneration in MTLE.

Higher Risk of Psychiatric Disorders in Children With Febrile Seizures: A Nationwide Cohort Study in Taiwan.

BACKGROUND: Febrile seizures occur commonly in children aged between six months and six years. A previous Danish study found a positive correlation between febrile seizures and the overall incidence of psychiatric disorders. This population-based nationwide observational study was conducted to investigate the association between febrile seizures and different psychiatric disorders in Taiwan and the associated risk factors. METHODS: This cohort study used data from the National Health Insurance Research Database in Taiwan-a nationwide claims database covering >99% of the Taiwanese population. The study period was from January 2000 to December 2015; the overall median follow-up time was 11.04 ± 10.95 years. Overall, 2464 children with febrile seizures diagnosed between 2000 and 2015 met the inclusion criteria, and 7392 children without febrile seizures matched by index year, age, and sex were included in the control cohorts. Febrile seizures and psychiatric disorders were measured as the exposure and main outcomes, respectively. RESULTS: Children with febrile seizures (n = 2463) were at a high risk of psychiatric disorders (adjusted hazard ratio, 4.70; 95% confidence interval [CI], 2.44 to 7.30; P < 0.001). The risk for anxiety was the highest (adjusted hazard ratio, 21.92; 95% CI, 11.40 to 34.05; P < 0.001). CONCLUSIONS: When treating children with febrile seizures, particular attention should be paid to the symptoms of psychiatric disorders, as early referral may be beneficial for these children.

[Analysis of three Chinese pedigrees affected with Genetic epilepsy with febrile seizures plus due to variants of SCN1A gene].

OBJECTIVE: To analyze the clinical and genetic characteristics of three Chinese pedigrees affected with Genetic epilepsy with febrile seizures plus (GEFS+). METHODS: Three GEFS+ probands and their pedigree members presented at the Children's Hospital of Zhengzhou University from January 2020 to December 2021 were selected as the study subjects. Clinical data of the pedigrees were collected. Whole exome sequencing was carried out for the probands, and Sanger sequencing was used to verify the candidate variants. RESULTS: Proband 1 was a 3-year-and-2-month-old male with febrile seizure plus. His father, two aunts, grandmother, aunt grandmother, uncle grandfather, and paternal great-grandmother also had onset of febrile seizures at 1 ~ 2 years of age with remission before 6 years old. Proband 2 was a 1-year-and-4-month-old male with complex febrile seizure. His mother, maternal uncle, and maternal grandmother also had febrile seizures before 5 ~ 6 years of age. Proband 3 was a 3-year-and-11-month-old male with febrile seizure plus. His father and grandfather also had febrile seizures plus with remission at 7 ~ 8 years of age. Genetic testing revealed that proband 1 had harbored a paternally derived heterozygous SCN1A: c.1613T>C variant, proband 2 had harbored a maternally derived heterozygous SCN1A: c.2804A>G variant, and proband 3 had harbored a paternally derived heterozygous SCN1A: c.1271T>C variant. All of the three variants were predicted as likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (PM1+PM2_Supporting+PP1+PP3+PP4). CONCLUSION: The c.1613T>C, c.2804A>G and c.1271T>C variants probably underlay the pathogenesis of GEFS+ in these pedigrees.