Seasonal Malaria Vaccination with or without Seasonal Malaria Chemoprevention.

BACKGROUND: Malaria control remains a challenge in many parts of the Sahel and sub-Sahel regions of Africa. METHODS: We conducted an individually randomized, controlled trial to assess whether seasonal vaccination with RTS,S/AS01E was noninferior to chemoprevention in preventing uncomplicated malaria and whether the two interventions combined were superior to either one alone in preventing uncomplicated malaria and severe malaria-related outcomes. RESULTS: We randomly assigned 6861 children 5 to 17 months of age to receive sulfadoxine-pyrimethamine and amodiaquine (2287 children [chemoprevention-alone group]), RTS,S/AS01E (2288 children [vaccine-alone group]), or chemoprevention and RTS,S/AS01E (2286 children [combination group]). Of these, 1965, 1988, and 1967 children in the three groups, respectively, received the first dose of the assigned intervention and were followed for 3 years. Febrile seizure developed in 5 children the day after receipt of the vaccine, but the children recovered and had no sequelae. There were 305 events of uncomplicated clinical malaria per 1000 person-years at risk in the chemoprevention-alone group, 278 events per 1000 person-years in the vaccine-alone group, and 113 events per 1000 person-years in the combination group. The hazard ratio for the protective efficacy of RTS,S/AS01E as compared with chemoprevention was 0.92 (95% confidence interval [CI], 0.84 to 1.01), which excluded the prespecified noninferiority margin of 1.20. The protective efficacy of the combination as compared with chemoprevention alone was 62.8% (95% CI, 58.4 to 66.8) against clinical malaria, 70.5% (95% CI, 41.9 to 85.0) against hospital admission with severe malaria according to the World Health Organization definition, and 72.9% (95% CI, 2.9 to 92.4) against death from malaria. The protective efficacy of the combination as compared with the vaccine alone against these outcomes was 59.6% (95% CI, 54.7 to 64.0), 70.6% (95% CI, 42.3 to 85.0), and 75.3% (95% CI, 12.5 to 93.0), respectively. CONCLUSIONS: Administration of RTS,S/AS01E was noninferior to chemoprevention in preventing uncomplicated malaria. The combination of these interventions resulted in a substantially lower incidence of uncomplicated malaria, severe malaria, and death from malaria than either intervention alone. (Funded by the Joint Global Health Trials and PATH; ClinicalTrials.gov number, NCT03143218.).

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.

The protective effect of breastfeeding on febrile seizures: a systematic review with meta-analysis.

Several potential risk factors have been identified in the etiopathogenesis of febrile seizures (FS), including the type and extent of breastfeeding (BF). Given the lack of conclusive data, this study aims to systematically evaluate the evidence on the association between BF and FS. We conducted a systematic review and meta-analysis according to PRISMA guidelines. The search was conducted using descriptors for FS, BF, and formula feeding in MEDLINE, Embase, and Web of Science databases. We included observational studies that compared the incidence of FS between those who had ever breastfed and those who were formula fed. The study protocol was registered on the PROSPERO platform under the number CRD42023474906. A total of 1,893,079 participants from 8 datasets were included. Our main analysis showed no significant association of any type of BF on the incidence of FS compared with formula-fed children (OR: 0.84; CI: 0.67-1.04; I2 = 78%; Cochran's Q = 0.0001), although meta-regression showed that BF was associated with a lower incidence of FS in preterm infants. Our secondary outcome showed a significantly reduced incidence of FS in children who received BF exclusively (OR: 0.80; CI: 0.65-0.99; I2 = 70%; Cochran's Q = 0.02).    Conclusion: There was no significant reduction in the incidence of FS in those who were breastfed compared to formula feeding. However, our meta-regression analysis indicated an association between BF and a lower incidence of FS in preterm infants. Additionally, children who exclusively received BF had a significantly reduced incidence of FS. These findings should be further investigated in prospective cohorts. What is Known: • Breastfeeding can modify risk factors for febrile seizures, such as susceptibility to viral and bacterial infections, micronutrient deficiencies, and low birth weight. • However, studies have shown conflicting results regarding the impact of breastfeeding on febrile seizures. What is New: • When comparing any breastfeeding pattern with no breastfeeding, there is no significant difference in the incidence of febrile seizures. • When comparing exclusive breastfeeding with no breastfeeding, there may be a decrease in the occurrence of febrile seizures.

Predicting factors for acute encephalopathy in febrile seizure children with SARS-CoV-2 omicron variant: a retrospective study.

BACKGROUND: SARS-CoV-2 posed a threat to children during the early phase of Omicron wave because many patients presented with febrile seizures. The study aimed to investigate predicting factors for acute encephalopathy of children infected by SARS-CoV-2 Omicron variant presenting with febrile seizures. METHODS: The retrospective study analyzed data from pediatric patients who visited the emergency department of Chang Gung Memorial Hospital in Taiwan between April and July 2022. We specifically focused on children with COVID-19 who presented with febrile seizures, collecting demographic, clinical, and laboratory data at the pediatric emergency department, as well as final discharge diagnoses. Subsequently, we conducted a comparative analysis of the clinical and laboratory characteristics between patients diagnosed with acute encephalopathy and those with other causes of febrile seizures. RESULTS: Overall, 10,878 children were included, of which 260 patients presented with febrile seizures. Among them, 116 individuals tested positive for SARS-CoV-2 and of them, 14 subsequently developed acute encephalopathy (12%). Those with acute encephalopathy displayed distinctive features, including older age (5.1 vs. 2.6 years old), longer fever duration preceding the first seizure (1.6 vs. 0.9 days), cluster seizure (50% vs. 16.7%), status epilepticus (50% vs. 13.7%) and occurrences of bradycardia (26.8% vs. 0%) and hypotension (14.3% vs. 0%) in the encephalopathy group. Besides, the laboratory findings in the encephalopathy group are characterized by hyperglycemia (mean (95% CI) 146 mg/dL (95% CI 109-157) vs. 108 mg/dL (95% CI 103-114) and metabolic acidosis (mean (95% CI) pH 7.29(95% CI 7.22-7.36) vs. 7.39 (95%CI 7.37-7.41)). CONCLUSIONS: In pediatric patients with COVID-19-related febrile seizures, the occurrence of seizures beyond the first day of fever, bradycardia, clustered seizures, status epilepticus, hyperglycemia, and metabolic acidosis should raise concerns about acute encephalitis/encephalopathy. However, the highest body temperature and the severity of leukocytosis or C-reactive protein levels were not associated with poor outcomes.

Effect of environmental exposome and influenza infection on febrile seizure in children over 22 years: a time series analysis.

Febrile seizures are convulsions predominately occurring in young children. The effects of various exposomes, including influenza infection and external environmental factors, on febrile seizures have not been well-studied. In this study, we elucidated the relationships between ambient temperature, air pollutants, influenza infection, and febrile seizures using 22-year territory-wide hospitalization data in Hong Kong. The aggregated data were matched with the meteorological records and air pollutant concentrations. All-type and type-specific influenza-like illness positive (ILI+) rates were used as proxies for influenza activity. Distributed lag non-linear model in conjunction with the quasi-poisson generalized additive model was used to examine the associations of interest. According to the results, all-type influenza infections were significantly associated with an increased risk of hospital admissions for febrile seizures (cumulative adjusted relative risk [ARR] = 1.59 at 95th percentile vs. 0; 95% CI, 1.51-1.68). The effect of ILI + A/H3N2 on febrile seizure was more pronounced than other type-specific ILI + rates. A low mean ambient temperature was identified as a significant risk factor for febrile seizures (cumulative ARR = 1.50 at 5th percentile vs. median; 95% CI, 1.35-1.66), while the redox-weighted oxidant capacity and sulfur dioxide were not associated with febrile seizures. In conclusion, our study underscores that influenza infections and exposure to cold conditions were related to an increased risk of febrile seizures in children. Thus, we advocate for influenza vaccination before the onset of the cold season for children to mitigate the burden of febrile seizures.

Characteristics and Risk Factors of Central Nervous System Infection in Children With Febrile Seizures.

OBJECTIVE: The aim of the present study is to evaluate the necessity of performing lumbar puncture in patients experiencing febrile seizures, considering the epidemiology specific to Brazil. METHODS: A retrospective cross-sectional study was performed from January 2017 to December 2021. RESULTS: A total of 469 children with seizure and fever were analyzed. The identified event was the first in 65.9% (n = 309). A total of 54.2% (n = 254) of patients had a simple febrile seizure. Infectious focus, excluding previous central nervous system (CNS) infection, was identified in 35.6% (n = 167) patients. Meningitis was identified in 7.7% (n = 36) patients, all of them were viral. Patients with CNS infection had a higher frequency of symptoms such as nausea and vomiting, drowsiness, headache, and higher level of leukocytosis. A longer duration of fever was found to be more strongly associated with CNS infection. CONCLUSIONS: When considering the use of lumbar puncture in febrile seizure, it is important to conduct a comprehensive evaluation that considers multiple factors, including clinical signs, symptoms, and the overall clinical context. Meningeal signs may be less prominent, and other symptoms such as lethargy, irritability, and vomiting may serve as more reliable indicators. Although clinical examination suggestive of meningitis remains an important factor, the recurrence of febrile seizures and a longer length of fever can provide additional insights and aid in decision-making regarding lumbar puncture.

Febrile seizures: A clinical review and focus on caregiver education.

ABSTRACT: Febrile seizures are the most common seizure disorder in childhood. Most febrile seizures have a benign course and children have a good prognosis. However, febrile seizures are traumatizing events for a child's family or caregiver to witness. Appropriate caregiver education is crucial to ease anxiety. This article reviews the risk factors, clinical presentation, diagnostics, treatment, and prevention of febrile seizures in addition to providing a guideline for effective caregiver education and support.

Clinical characteristics of unvaccinated or incompletely vaccinated children with neurological manifestations due to SARS-CoV-2 Omicron infection.

Omicron generally causes milder disease than previous strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially in fully vaccinated individuals. However, incompletely vaccinated children may develop Omicron-related complications such as those affecting the central nervous system. To characterize the spectrum of clinical manifestations of neuro-COVID and to identify potential biomarkers associated with clinical outcomes, we recruited 15 children hospitalized for Omicron-related neurological manifestations in three hospitals in Hong Kong (9 boys and 6 girls aged 1-13 years). All were unvaccinated or incompletely vaccinated. Fourteen (93.3%) were admitted for convulsion, including benign febrile seizure (n = 7), complex febrile seizure (n = 2), seizure with fever (n = 3), and recurrent breakthrough seizure (n = 2), and the remaining nonconvulsive patient developed encephalopathic state with impaired consciousness. None of the seven children with benign febrile seizure and six of eight children with other neurological manifestations had residual deficits at 9-month follow-up. SARS-CoV-2 RNA was undetectable in the cerebrospinal fluid (CSF) specimens of seven patients who underwent lumbar puncture. Spike-and-wave/sharp waves affecting the frontal lobes were detected in four of seven (57.1%) patients who underwent electroencephalogram. Children with Omicron-related neurological manifestations had significantly higher blood levels of IL-6 (p < 0.001) and CHI3L1 (p = 0.022) than healthy controls, and higher CSF levels of IL-6 (p = 0.002) than children with non-COVID-19-related febrile illnesses. Higher CSF-to-blood ratios of IL-8 and CHI3L1 were associated with longer length of stay, whereas higher ratios of IL-6 and IL-8 were associated with higher blood tau level. The role of CSF:blood ratio of IL-6, IL-8, and CHI3L1 as prognostic markers for neuro-COVID should be further evaluated.

Decreased NK cell count is a high-risk factor for convulsion in children with COVID-19.

BACKGROUND: The neurological symptoms caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of increasing concern. Convulsions are among the main neurological manifestations reported in children with coronavirus disease-2019 (COVID-19), and cause serious harm to physical and mental health. This study aimed to investigate the risk factors for convulsion in children with COVID-19. METHODS: This prospective study was conducted at the Children's Hospital of Soochow University. In total, 102 COVID-19 patients with convulsion, 172 COVID-19 patients without convulsion, and 50 healthy controls were enrolled in the study. The children's clinical and laboratory data were analyzed to assess the risk factors for convulsion in COVID-19 patients. RESULTS: Convulsions occurred in 37.2% of children, mostly those aged 1-3 years, who were hospitalized with the Omicron variant. The neutrophil count, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume-to-platelet ratio (MPR) were significantly higher in the convulsion group than those in the non-convulsion and control groups (P < 0.01). However, the counts of lymphocytes, eosinophils, platelets, lymphocyte subsets, CD3+ T cells, CD4+ T cells, CD8+ T cells, and NK cells were lower in the convulsion group than those in the non-convulsion and control groups (P < 0.01). Multivariate regression analysis indicated that NK cell count (OR = 0.081, 95% CI: 0.010-0.652) and a history of febrile seizure (OR = 10.359, 95% CI: 2.115-50.746) were independent risk factors for the appearance of convulsions in COVID-19. CONCLUSIONS: History of febrile seizure and decreased NK cell count were high-risk factors for convulsions in COVID-19 patients.

Development of a prediction nomogram model of recurrent febrile seizures in pediatric children.

The purpose of this study is to develop a prediction nomogram of recurrent febrile seizures in pediatric children based on the identified predictors for developing recurrent febrile seizures. This is a retrospective observational study. The medical records of 320 febrile seizure-afflicted children admitted to Zhoushan Women and Children Hospital from March 2019 to January 2023 were retrospectively reviewed. Children were divided into the recurrent febrile seizures group and the non-recurrent febrile seizures group. The predictors of recurrent febrile seizures were identified by univariate and multivariate analyses. A prediction nomogram model was developed via R software. The performance of the nomogram was internally validated to assess the model's discrimination and consistency, and decision curve analysis was employed to assess clinical utility. There were 41 out of 320 cases that had recurrent febrile seizures during the observation period, with a 12.81% prevalence rate of recurrent febrile seizures. The predictors of recurrent febrile seizures were young age at the first febrile seizures, a family history of febrile seizures in a first-degree relative, diurnal variation of initial febrile seizures occurrence, gender, and a low level of C-reactive protein. The area under the receiver operating characteristic curve of the nomogram is 0.795 (95% confidence interval: 0.720-0.871). Calibration plots and the result of the Hosmer-Lemeshow test (P = 0.472) reveal satisfactory consistency. Decision curve analysis showed a significant net benefit of the nomogram. CONCLUSIONS: The prediction nomogram model demonstrates good performance and clinical utility, which would be a convenient tool for the detection of children in pediatrics with high-risk recurrent febrile seizures. It is useful for pediatric medical staff to provide early medical interventions and family counseling. WHAT IS KNOWN: • A proportion of children experience recurrences of febrile seizures. • Recognition of risk factors for recurrent FS in pediatrics would be useful for the prediction of risk probabilities and help provide tailored counseling and follow-up. WHAT IS NEW: • A nomogram model is developed for risk prediction of recurrent febrile seizures in this study, which would be a convenient risk prediction tool in pediatrics. • The predictor of diurnal variation of recurrent febrile seizures is with new ideas.

Frequency and risk factors for febrile seizures during COVID-19 pandemic waves: an observational study.

Febrile seizures (FS) are well-known manifestations of viral illnesses. The purpose of this study is to assess the prevalence and factors associated with FS among pediatric patients with COVID-19 admitted to the National Isolation Centre in Brunei Darussalam. All pediatric patients (< 12 years) during the first (n = 12), second (n = 418), and third (n = 219) waves were included in the study. In Brunei, the first, second, and third waves were caused by the original SARS-CoV-2, Delta, and Omicron variants, respectively. Data was extracted from a prospective database and the national electronic health record system. Patients with and without FS were compared to identify any significant risk factors. FS were only encountered in the third wave (n = 29, 13%) giving an overall prevalence of 4.5%; 24 (83%) occurring in the typical age group for FS (≥ 6 months to < 6 years). Five cases (17%) occurred in children 6 years and older. Comparing patients in the third wave, univariate analyses showed typical age group, previous history of FS, family history of FS, higher temperature (> 38.6 °C), and fewer symptoms on presentation (3 or less) were associated with FS. On multivariate analyses, typical age group, family history of FS, and fewer reported symptoms remained significant (all p < 0.05).  Conclusions: The overall prevalence of FS in COVID-19 patients is comparable to rates reported. However, in Brunei Darussalam, FS only occurred in the third wave that has been associated with Omicron variant. Younger age group, family history of FS, and fewer symptoms on presentation are correlated with risk of FS. What is Known: • Viral infections are the most common cause of FS in children. •Young age and a personal and family history of FS are correlated with the risk of FS. What is New: • There were high rates of FS (13%) among pediatric patients admitted with COVID-19 due to the Omicron variant but not with the original and Delta variants. • FS with COVID-19 were correlated with reporting fewer symptoms on presentation.

Evaluation of patients presenting with febrile seizures in an Iranian referral hospital: emphasis on the frequency of meningitis and co-infections.

INTRODUCTION: Febrile seizures are one of the most common diseases that physicians encounter in pediatric emergency departments. Two important aspects of managing patients presenting with a febrile seizure are meningitis exclusion and co-infection investigation. This study was designed to determine any infection that occurs concomitantly with a febrile seizure episode and also to assess the frequency of meningitis among children presenting with febrile seizures. METHODS: This retrospective cross-sectional study was conducted at the Children's Medical Center, an Iranian pediatric referral hospital. All patients aged 6 months to 5 years presenting with febrile seizures from 2020 to 2021 were included. Patients' data were collected from the medical report files. The presence of respiratory, gastrointestinal, and urinary infections was evaluated. Moreover, the detection of SARS-CoV-2 using reverse transcription polymerase chain reaction (RT-PCR) was performed for suspicious cases. The results of urine and stool analysis, as well as blood, urine, and stool cultures were checked. The frequency of lumbar puncture (LP) performance and its results were studied. The relationship between white blood cells (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein in meningitis was evaluated. RESULTS: A total of 290 patients were referred to the Children's Medical Center, Tehran, Iran, due to fever and seizures. The mean age of the patients was 21.5 ± 13.0 months, and 134 (46.2%) were female. Out of 290 patients, 17% presented with respiratory infections. Nasopharyngeal SARS-CoV-2 RT-PCR was requested for 50 patients (17%), of which nine (3%) were reported positive and two patients had multi-inflammatory syndrome in children (MIS-C). Fever without local signs, gastroenteritis, and urinary tract infections were found in 40%, 19%, and 14% of the patients, respectively. LP was requested for 97 participants (33.4%) to evaluate central nervous system infection, of which 22 cases were suggestive of aseptic meningitis. Among laboratory tests, leukocytosis was significantly related to aseptic meningitis (odds ratio = 11.1, 95% CI = 3.0- 41.5). The blood culture testing result was positive in seven patients; all of them were due to skin contamination. CONCLUSION: Evaluation of patients for possible meningitis is necessary for febrile seizure management. Although the prevalence of bacterial meningitis in these patients is not high, according to this study and other studies conducted in Iran, aseptic meningitis, especially after Measles, Mumps, and Rubella (MMR) vaccination should be considered. Leukocytosis and increased CRP can predict the occurrence of aseptic meningitis in these patients. However, further studies with a larger sample size are highly recommended. Moreover, during the COVID-19 pandemic, it is recommended to pay attention to an acute COVID-19 infection or evidence of MIS-C in children with fever and seizure.

Comparison of febrile seizures in children with or without coronavirus disease-2019: A single-center observational study.

BACKGROUND: Febrile seizure (FS) is one of the most common neurological manifestations of coronavirus disease-2019 (COVID-19) in children. We compared the clinical characteristics of FS in patients with and without COVID-19 during the pandemic period. METHODS: This retrospective single-center study included patients aged 0-18 years who visited the pediatric emergency department (ED) with FS from January 1, 2022, to April 30, 2022. RESULTS: A total of 186 patients visited the pediatric ED with FS during the study period: 123 (66.1%) were positive for COVID-19 and 63 (33.9%) were negative. Patients with COVID-19 were predominantly male (70.7% vs. 50.8%, p = 0.007) and older (2.4 vs. 1.8 years, p = 0.005) than those without COVID-19. A higher proportion of patients with COVID-19 were of atypical age (age > 5 years or <6 months) than those without COVID-19 (26.8% vs. 9.5%, p = 0.006). This was especially true for those aged >5 years (22% vs. 4.8%, p = 0.003). Patients with COVID-19 had a higher probability of multiple episodes of convulsion within 24 h than those without COVID-19 (10.6% vs. 1.6%, p = 0.037). Among patients with COVID-19, males had a shorter fever-to-seizure duration than females (3 h vs. 6.5 h, p = 0.045). CONCLUSIONS: Patients with FS with COVID-19 tend to be predominantly male and have older age of onset than those without COVID-19. Because of the atypical age of onset and probability of multiple convulsion episodes, vigilance for FS is needed in patients with COVID-19, especially males.

The Association Between COVID-19 and Febrile Seizure: A Retrospective Case-Control Study.

BACKGROUND/OBJECTIVE: Throughout the pandemic, febrile seizures have resulted from infection secondary to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The objective of this study is to determine if there is an increased association between COVID-19 and febrile seizures as compared with other causes of febrile seizures. METHODS: This was a retrospective case control study. Data were collected from the National Institute of Health (NIH) supported National COVID Cohort Collaborative (N3C). Patients from 6 to 60 months who were tested for COVID-19 were included; cases were defined as COVID-19-positive patients whereas controls were defined as COVID-19-negative patients. Febrile seizures diagnosed within 48 hours of the COVID-19 test were considered to be associated with the test result. Patients were subjected to a stratified gender and date matching design followed by a logistic regression controlling for age and race. RESULTS: During the study period, 27,692 patients were included. Of those, 6923 patients were COVID-19-positive, among which 189 had febrile seizures (2.7%). After logistic regression, the likelihood of having febrile seizures concurrently with COVID-19 as compared with other causes was 0.96 ( P = 0.949; confidence interval, 0.81, 1.14). CONCLUSIONS: There were 2.7% of the patients with COVID-19 that were diagnosed with a febrile seizure. However, when subjected to a matched case control design with logistic regression controlling for confounding variables, there does not appear to be an increased risk of febrile seizures secondary to COVID-19 as compared with other causes.

[Clinical features of children with febrile seizures caused by Omicron variant infection]. / Omicronå˜å¼‚æ ªæ„ŸæŸ“å¯¼è‡´å„¿ç«¥çƒ­æ€§æƒŠåŽ¥çš„ä¸´åºŠç‰¹å¾åˆ†æž.

OBJECTIVES: To study the clinical features of children with febrile seizures after Omicron variant infection. METHODS: A retrospective analysis was performed on the clinical data of children with febrile seizures after Omicron variant infection who were admitted to the Department of Neurology, Children's Hospital Affiliated to the Capital Institute of Pediatrics, from December 1 to 31, 2022 (during the epidemic of Omicron variant; Omicron group), and the children with febrile seizures (without Omicron variant infection) who were admitted from December 1 to 31, in 2021 were included as the non-Omicron group. Clinical features were compared between the two groups. RESULTS: There were 381 children in the Omicron group (250 boys and 131 girls), with a mean age of (3.2±2.4) years. There were 112 children in the non-Omicron group (72 boys and 40 girls), with a mean age of (3.5±1.8) years. The number of children in the Omicron group was 3.4 times that in the non-Omicron group. The proportion of children in two age groups, aged 1 to <2 years and 6-10.83 years, in the Omicron group was higher than that in the non-Omicron group, while the proportion of children in two age groups, aged 4 to <5 years and 5 to <6 years, was lower in the Omicron group than that in the non-Omicron group (P<0.05).The Omicron group had a significantly higher proportion of children with cluster seizures and status convulsion than the non-Omicron group (P<0.05). Among the children with recurrence of febrile seizures, the proportion of children aged 6-10.83 years in the Omicron group was higher than that in the non-Omicron group, while the proportion of children aged 3 years, 4 years, and 5 years in the Omicron group was lower than that in the non-Omicron group (P<0.05). CONCLUSIONS: Children with febrile seizures after Omicron variant infection tend to have a wider age range, with an increase in the proportion of children with cluster seizures and status convulsion during the course of fever.

Seasonal Variation and Risk of Febrile Seizures: A Danish Nationwide Cohort Study.

INTRODUCTION: Onset of febrile seizures varies with calendar season. However, it has not previously been assessed, how season of birth interacts with age and peak risk of febrile seizures, and whether season of birth correlates with the cumulative risk of febrile seizures at 5 years of age (i.e., when children are no longer of risk of febrile seizures). METHODS: We identified all singleton children born in Denmark between 1977 and 2011 who were alive at 3 months of age (N = 2,103,232). We used the Danish Civil Registration System to identify age and sex of the children and the Danish National Patient Register to identify children hospitalized with febrile seizures from 3 months to 5 years of age. Follow-up ended on December 31, 2016, when all children had reached 5 years of age. RESULTS: The relative risk of admission with a first febrile seizure varied with calendar month; in February (a winter month in Denmark), the risk was more than doubled (hazard ratio: 2.10 [95% confidence interval [CI]: 2.03-2.18]) compared with August (a summer month in Denmark). The age-specific incidence of a first febrile seizure by birth month identified the highest peak incidence of a first febrile seizure among children born in November (reaching a peak incidence of 350 first admissions with a febrile seizure per 100,000 person months at age 16 months) as compared to children born in July (reaching a peak incidence of 200 first admissions with a febrile seizure per 100,000 person months at age 16 months). However, the cumulative incidence of any admission with febrile seizures before 5 years was not correlated with season of birth (3.69% [95% CI: 3.64-3.74%] for winter births, 3.57% [95% CI: 3.52-3.62%] for spring births, 3.55% [95% CI: 3.50-3.59%] for summer births, and 3.64% [95% CI: 3.59-3.69%] for fall births). DISCUSSION/CONCLUSION: The study found a significant seasonal variation in onset of the first febrile seizure and in the age-specific peak incidence of febrile seizures. However, there was no correlation between season of birth and cumulative incidence of febrile seizures at 5 years of age suggesting that children who are predisposed to febrile seizures will eventually go on to experience a febrile seizure regardless of season of birth.

Febrile seizures lead to prolonged epileptiform activity and hyperoxia that when blocked prevents learning deficits.

OBJECTIVE: In adult brain tissue, oxygen levels typically remain in the normoxic zone, but status epilepticus results in hyperoxia, whereas brief self-terminating seizures lead to postictal hypoxia. The dynamic changes in oxygen levels and the underlying mechanisms are unknown in juveniles with febrile seizures. METHODS: Eight-day-old female and male rat pups were implanted with an electrode and oxygen-sensing optode in the hippocampus and then received once daily injections of lipopolysaccharide for 4 days to induce an immune response. Local partial pressure of oxygen (pO2 ) and local field potentials were recorded before, during, and after a heat-induced febrile seizure. Separate groups of pups received injections of vehicle or drugs targeting cyclooxygenase (COX)-1, COX-2, L-type calcium channels (LTCCs), and cannabinoid receptor type 1 (CB1) and transient receptor potential vanilloid-1 (TRPV1) receptors prior to febrile seizure induction to determine pO2 mechanisms. Following febrile seizures, a subset of pups were raised to young adulthood and then tested for learning impairments using the novel object recognition task. RESULTS: Febrile seizures resulted in predictable oxygen dynamics that were related to behavioral seizures and epileptiform activity. During a behavioral seizure, pO2 rapidly increased, rapidly decreased, and then returned to near baseline. When the behavioral seizure terminated, oxygen levels climbed into the hyperoxic zone during a time of prolonged epileptiform activity. When epileptiform activity terminated, oxygen levels slowly returned to baseline. A COX-1 antagonist prevented hyperoxia, whereas a COX-2 antagonist did not. An LTCC antagonist exacerbated hyperoxia. Boosting levels of an endocannabinoid also exacerbated hyperoxia, whereas blocking CB1 receptors and TRPV1 receptors reduced hyperoxia. Inhibiting TRPV1 receptors during a febrile seizure prevented learning deficits in young adult female rats. SIGNIFICANCE: Brain oxygenation during and following a febrile seizure has a distinct pattern and multiple mechanisms. Brain oxygen dynamics may be an important consideration in the development of treatments for febrile seizures.

The baseline risk of multiple febrile seizures in the same febrile illness: a meta-analysis.

The baseline risk for multiple febrile seizures within the same febrile illness is largely unknown. Estimates range from 5 to 30%. Imprecise estimates can lead to incorrectly powering studies investigating the management of febrile seizures. To estimate the risk of multiple febrile seizures in the same febrile illness, we systematically reviewed and conducted a meta-analysis of studies from January 2000 to December 2021 that contained data for the number of children for both simple and complex febrile seizures in the same febrile illness. We searched MEDLINE, EMBASE, and Web of Science for randomized, quasi-randomized, prospective, and retrospective trials that involved children with febrile seizures. A total of 23,131 febrile illnesses with febrile seizures met the inclusion criteria. The estimated baseline risk of multiple febrile seizures in the same febrile illness was 17% (95% CI, 16-19%). However, the 30 cohorts that included both admitted and non-admitted patients had a lower percentage of multiple FSs within the same illness (14%; 95% CI, 12-15%) than the 30 cohorts that enrolled only admitted patients (20%; 95% CI, 16-25%). CONCLUSION: Researchers can use estimates in this paper to design future studies. Taking into the account the substantial heterogeneity between countries and studies, clinicians could cautiously use our estimates in their clinical assessment and be better able to set parental expectations about a child's chances of having another febrile seizure during the current illness. TRIAL REGISTRATION: PROSPERO CRD42020191784. Registered July 18, 2020. WHAT IS KNOWN: • There is renewed interest in the diagnostic workup and prophylactic treatment of febrile seizures to prevent repeat seizures in the same febrile illness. • There is a lack of accurate estimates of the baseline risk for multiple febrile seizures in the same illness to properly design studies investigating management. WHAT IS NEW: • This study provides the most robust estimates for the baseline risk for multiple febrile seizures in the same illness.

Risk factors for acute encephalitis and early seizure recurrence in complex febrile seizures.

The purpose of this study is to elucidate risk factors for central nervous system infection and early seizure recurrence in children with febrile seizures (FSs) and thus facilitate outpatient management of complex FS. This single-center, retrospective cohort study investigated 688 children (6-60 months old) with FSs in Japan during 2011-2021. We investigated the incidence and clinical manifestations of children with acute encephalitis or bacterial meningitis. Logistic regression modeling was used to examine risk factors for seizure recurrence within 24 h. Among children with recurrent FSs, the distribution of intervals between first and second FS was assessed. Among 145 children with complex FSs, 2 patients (1.4%) had acute viral encephalitis and none had bacterial meningitis. Acute encephalitis was found in 2 of 8 patients (25%) with FSs prolonged ≥30 min and 2 of 3 patients (67%) requiring ≥2 intravenous anticonvulsants to stop seizures. Seizure recurrence within 24 h was observed in 16% of participants and was independently associated with preceding use of diazepam and family history of FS. In 82% of patients with FS recurrence within 24 h, early recurrences occurred within 8 h of the first seizure.      Conclusion: Patients with prolonged or refractory FSs are still indicated for hospital admission due to the risk of acute encephalitis. FS patients with a family history of FS may be managed safely by 8-h observation or single-dose rectal diazepam as prophylaxis against early recurrent seizure. What is Known: • Hospitalization has been recommended for children with complex febrile seizures due to the increased risk of central nervous infections. • Recent studies showed low incidences of bacterial meningitis (<1%) in children with complex febrile seizures in the presence of routine immunization. What is New: • Acute encephalitis was identified in 1.4% of children with complex febrile seizures, characterized by prolonged seizures ≥30 min and refractory seizures. • Early recurrent seizures may be safely managed by prophylactic diazepam or 8-h expectant observation.

Perceived causes and diagnosis of febrile convulsion in selected rural contexts in Cape Coast Metropolis, Ghana.

BACKGROUND: Febrile convulsion (FC) is a common seizure disorder among children aged 9 months to 5 years. It is usually benign and self-limiting with favourable prognosis. However, in Ghana, FC is commonly perceived as "not for hospital" and widely diagnosed and managed at home based on several beliefs and practices which are limited in related literature. OBJECTIVE: This study explored the perceived causes and diagnosis of FC in selected rural communities in the Cape Coast Metropolis, Ghana. METHODS: A descriptive phenomenological study design underpinned the study at five selected communities located not more than 2 Kilometres from the University of Cape Coast Hospital. Purposive and snowball sampling techniques were used to interview 42 participants made up of 27 parents, two grandmothers, seven registered traditional health practitioners, four herbalists, and two faith healers in the communities. The data was analysed using QSR NVivo 12. RESULTS: Three perceived causes of FC were identified - biological, social/behavioural, and spiritual. Biological causes include genetic abnormalities and other underlying health conditions. The behavioural factors include poor childcare practices and nutrition. Spiritual causes include harm caused by evil spirits. The diagnosis of FC were observed prior, during and after FC attack, and these includes high body temperature, extreme body jerking, and disability outcomes respectively. CONCLUSION: The perceived causes of FC are interplay of complex natural, social and spiritual factors that were deep-rooted in local socio-cultural beliefs and FC experiences. Unlike the attack stage, pre-attack diagnosis were usually missed, or misconstrued to mean other health conditions. These findings indicate the need to intensify maternal and child health (MCH) education programmes on FC in the study area through improved primary healthcare.