OBJECTIVE: To describe the prescription patterns of home, non-intravenous rescue benzodiazepines (non-IV-rBZDs) for febrile seizures and the factors associated with their prescription.
METHODS: Retrospective descriptive study using the MarketScan Commercial Database, a large database of employer-sponsored privately insured patients in the United States. We used data from January 1st 2006 to December 31st 2022. We studied patients with febrile seizures as the main code for the healthcare encounter (identified with International Classification of Diseases codes) with age from 6 months to 5 years of age and with at least 1 month of follow-up.
RESULTS: There were a total of 82,835 patients [median (p25-p75) age 1.0 (1.0-2.0) years, 56.7 % males] with at least one febrile seizure, of whom 9,737 (11.8 %) filled at least one non-IV-rBZD prescription. Among the 9,737 patients who filled at least one prescription, the median (p25-p75) time from first febrile seizure to non-IV-rBZD prescription was 27 (2-186) days. Among the factors known at the time of the first febrile seizure, complex febrile seizure (OR: 3.51, 95 % CI: 3.24-3.79), and an initial inpatient hospitalization for febrile seizure (OR: 3.53, 95 % CI: 3.29-3.79) were the factors most strongly associated with filling a non-IV-rBZD prescription. In contrast, sex, rural patient\'s residence, and salary employment (versus other employment class) were not independently associated with filling a non-IV-rBZD prescription. Among the factors known at the end of follow-up, complex febrile seizures, type of initial encounter, and an eventual diagnosis of epilepsy were major independent factors associated with filling a non-IV-rBZD prescription.
CONCLUSIONS: Only approximately 12 % of children with a febrile seizure filled a prescription for a home non-IV-rBZD. The major factors independently associated with prescription were complex febrile seizure, hospital admission, recurrent febrile seizures, and an eventual diagnosis of epilepsy.

BACKGROUND: SCN1A channelopathy is the most well-known cause for epileptic encephalopathies and contributes to a wide phenotypic spectrum. The variable expressivity is troublesome for the interpretation of clinical significance and prognoses. To investigate the clinical manifestations, medications and outcomes of patients with SCN1A channelopathies, we conducted this observation retrospective study in Taiwan.
METHODS: A cohort consisting of 16 patients (5 males and 11 females) from multiple centers with identified SCN1A variants was investigated and phenotypically relevant factors were recorded. The variants were identified using NGS and confirmed by Sanger sequencing. A panel of 90 epileptic-related genes was used to identify SCN1A variants and to evaluate some of the potential SCN1A modifier genes.
RESULTS: The mean age of seizure onset was 10.4 months. Twelve of the sixteen patients (75%) had different degrees of neurocognitive sequela and psychobehavioral comorbidity in our cohort. Cognitive impairment was noted in all ten patients with Dravet syndrome (DS) and in two of the patients with non-DS phenotypes. A lower response rate to medications was also noted in patients with DS. Notably, a medication-specific tendency towards valproic acid (VPA), clobazam (CLB), and levetiracetam (LEV) was observed, revealing the effective pharmacotherapies for SCN1A-related seizures. An asymptomatic carrier with a reported pathogenic SCN1A variant was reviewed along with her monozygotic twin sister with DS. Nine novel SCN1A mutations are herein reported, eight of which being classified as pathogenic.
CONCLUSIONS: Our study revealed unfavorable outcomes for patients with SCN1A variants. Some patients with SCN1A channelopathy showed specific responsiveness to the pharmacotherapies previously either recommended or contraindicated for these patients. Our study also expands the genotype and provides valuable prognostic insights in patients with SCN1A channelopathy.

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.
CONCLUSIONS: 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.

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.
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.
CONCLUSIONS: 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.

Febrile seizures (FS) can be frightening for parents, even though they are usually harmless. Various questionnaires have been used to assess parental reactions and awareness about FS, revealing insufficient knowledge. Studies have shown that educational interventions significantly reduce parental concerns, improve knowledge, and promote better first-aid measures. Providing clear information and emotional support to parents is important to reduce their concerns and improve FS management. Healthcare providers should give comprehensive information about FS, including the risk of recurrence, and provide clear instructions on their management. The economic impact of FS includes direct and indirect costs. Studies have shown a decrease of hospitalizations and associated costs due to improved clinical adherence to guidelines, which also reduces the inappropriate use of healthcare resources. This systematic review provides a comprehensive overview of the existing literature on parental anxiety and education about FS, as well as their economic impact, aiming at identifying areas for improvement in the management of FS and providing valuable insights for healthcare providers and policymakers to better address the non-clinical burden of this condition.

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.

Febrile seizures (FS) are commonly seen in younger age groups. The cause of seizures is multifactorial, including viral illnesses, certain vaccines such as MMR (measles, mumps, rubella), family history of FS, and certain mineral deficiencies like zinc. Iron deficiency anemia (IDA) is the most common cause of anemia in children of the same age group. The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. This review aimed to investigate the correlation between IDA and fever convulsions. A systematic literature search was conducted using PubMed and Google Scholar databases for studies published between January 2013 and September 2023. The following keywords were used to search the articles: \"children\", \"febrile seizures\", and \"iron deficiency anemia\", using all possible combinations and using the word \"and\" between them. Following the inclusion and exclusion criteria application, we included 23 case-control studies written in the English language in this study. Quality assessment of studies was done using the Newcastle Ottawa Scale.

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.
CONCLUSIONS: 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.

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.
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.
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).
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.
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.

BACKGROUND: Febrile seizures (FS) are the most common neurologic disorder seen in children. Caused mainly by fever without any damage to the central nervous system (CNS). The associations of several factors, which we can find in the inflammatory response and genetic predisposition, are involved in the occurrence of FS.
OBJECTIVE: This review provides insight into risk factors, particularly the involvement of the inflammatory response and genetic susceptibility in the occurrence of FS.
METHODS: A PubMed search was performed using the keywords « febrile seizures », « inflammatory response », « Pro-inflammatory cytokines », «And anti-inflammatory cytokines ». The search strategy included meta-analyses, prospective case-control studies, clinical trials, observational studies, and reviews.
RESULTS: Febrile seizures with a peak incidence of 18 months usually occur between 6 months and 5 years. A variety of genetic, inflammatory, and environmental factors, including viruses and vaccines, trigger FS. A positive family history of febrile seizures increases the risk for FS occurrence with (20%) in siblings and (33%) in one parent. The involvement of inflammatory response genes, including the cytokine genes IL1B, IL1R, IL6, and IL4. According to these findings, FS is associated with the activation of a cascade of pro- and anti-inflammatory cytokines and the unbalance between these cytokines in the inflammation regulation plays a role in the development of FS.
CONCLUSIONS: Current knowledge suggests that genetic susceptibility and inflammatory response dysregulation contribute to FS\'s genesis.