Racial and Ethnic Differences in Hospital Admission and Diagnostic Evaluation for Febrile Seizures in the Emergency Department.

OBJECTIVE: To examine differences in hospital admission and diagnostic evaluation for febrile seizure by race and ethnicity. STUDY DESIGN: We conducted a cross-sectional study among children 6 months to 6 years with simple or complex febrile seizure between January 1, 2016, and December 31, 2021, using data from the Pediatric Health Information System. The primary outcome was hospital admission. Secondary outcomes included the proportion of encounters with neuroimaging or lumbar puncture. We used mixed-effects logistic regression model with random intercept for hospital and patient to estimate the association between outcomes and race and ethnicity after adjusting for covariates, including seizure type. RESULTS: In total, 94 884 encounters were included. Most encounters occurred among children of non-Hispanic White (37.0%), Black (23.9%), and Hispanic/Latino (24.6%) race and ethnicity. Black and Hispanic/Latino children had 29% (aOR 0.71; 95% CI 0.66-0.75) and 26% (aOR 0.74; 95% CI 0.69-0.80) lower odds of hospital admission compared with non-Hispanic White children, respectively. Black and Hispanic/Latino children had 21% (aOR 0.79; 95% CI 0.73-0.86) and 22% (aOR 0.78; 95% CI 0.71-0.85) lower adjusted odds of neuroimaging compared with non-Hispanic White children. For complex febrile seizure, the adjusted odds of lumbar puncture was significantly greater among Asian children (aOR 2.12; 95% CI 1.19-3.77) compared with non-Hispanic White children. There were no racial differences in the odds of lumbar puncture for simple febrile seizure. CONCLUSIONS: Compared with non-Hispanic White children, Black and Hispanic/Latino children with febrile seizures are less likely to be hospitalized or receive neuroimaging.

SCN1A-deficient excitatory neuronal networks display mutation-specific phenotypes.

Dravet syndrome is a severe epileptic encephalopathy, characterized by (febrile) seizures, behavioural problems and developmental delay. Eighty per cent of patients with Dravet syndrome have a mutation in SCN1A, encoding Nav1.1. Milder clinical phenotypes, such as GEFS+ (generalized epilepsy with febrile seizures plus), can also arise from SCN1A mutations. Predicting the clinical phenotypic outcome based on the type of mutation remains challenging, even when the same mutation is inherited within one family. This clinical and genetic heterogeneity adds to the difficulties of predicting disease progression and tailoring the prescription of anti-seizure medication. Understanding the neuropathology of different SCN1A mutations may help to predict the expected clinical phenotypes and inform the selection of best-fit treatments. Initially, the loss of Na+-current in inhibitory neurons was recognized specifically to result in disinhibition and consequently seizure generation. However, the extent to which excitatory neurons contribute to the pathophysiology is currently debated and might depend on the patient clinical phenotype or the specific SCN1A mutation. To examine the genotype-phenotype correlations of SCN1A mutations in relation to excitatory neurons, we investigated a panel of patient-derived excitatory neuronal networks differentiated on multi-electrode arrays. We included patients with different clinical phenotypes, harbouring various SCN1A mutations, along with a family in which the same mutation led to febrile seizures, GEFS+ or Dravet syndrome. We hitherto describe a previously unidentified functional excitatory neuronal network phenotype in the context of epilepsy, which corresponds to seizurogenic network prediction patterns elicited by proconvulsive compounds. We found that excitatory neuronal networks were affected differently, depending on the type of SCN1A mutation, but did not segregate according to clinical severity. Specifically, loss-of-function mutations could be distinguished from missense mutations, and mutations in the pore domain could be distinguished from mutations in the voltage sensing domain. Furthermore, all patients showed aggravated neuronal network responses at febrile temperatures compared with controls. Finally, retrospective drug screening revealed that anti-seizure medication affected GEFS+ patient- but not Dravet patient-derived neuronal networks in a patient-specific and clinically relevant manner. In conclusion, our results indicate a mutation-specific excitatory neuronal network phenotype, which recapitulates the foremost clinically relevant features, providing future opportunities for precision therapies.

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.

Development and validation of a nomogram for the estimation of the prognosis of patients presenting with a febrile seizure.

BACKGROUND: Febrile seizures constitute a prevalent emergency in early childhood. Previous studies indicated that certain febrile seizures in children may progress to epilepsy, exerting a substantial impact on children's health and developmental trajectory. The objective of this study was to formulate a predictive nomogram to assess the likelihood of transitioning from febrile seizures to epilepsy in pediatric patients, thereby facilitating informed decisions regarding medical interventions for febrile seizures. METHODS: A total of 306 patients were enrolled and categorized into training (70%) and test (30%) cohorts. Clinical characteristics were subjected to comparison utilizing chi-squared and t tests. Multivariate logistic regression was employed to identify significant factors for predicting the risk of transitioning from febrile seizures to epilepsy, leading to the development of a nomogram. The nomogram's performance was assessed through receiver operating characteristic curves, calibration, and decision curve analysis. RESULTS: Predictive factors associated with the transition to epilepsy encompassed lower Na, elevated RDW, IL-6, and increased background slow rhythm and epileptiform discharges in EEG. The nomogram, incorporating five factors, exhibited commendable predictive value (AUC train = 0.812, AUC test = 0.791) for assessing the risk of transitioning from febrile seizures to epilepsy. Calibration analyses confirmed reliability, and decision curve analysis underscored its clinical utility. CONCLUSIONS: Lower Na, elevated RDW, IL-6, background slow rhythm, and epileptiform discharges are associated with the risk of transitioning from febrile seizures to epilepsy. The nomogram stands as a valuable tool for predicting this risk, aiding in the strategic implementation of medical interventions to enhance outcomes for patients with febrile seizures.

Uncertainty, knowledge, and anxiety of mothers concerning febrile seizure: A comparison between affected and unaffected mothers.

BACKGROUND: Febrile seizures are the most common type of convulsions affecting children aged six months to five years. However, febrile seizures can be difficult to identify due to the vague nature of the symptoms, which can lead to incorrect diagnosis and treatment. Thus, this study explores febrile seizure-related uncertainty, knowledge, and anxiety among mothers. DESIGN AND METHODS: A cross-sectional design included 190 Jordanian mothers, about half with children having febrile seizure history. Instruments included the State-Trait Anxiety Inventory (STAI), Parental Perception of Uncertainty Scale (PPUS), and Parental Knowledge, Attitudes, Concerns, and Practices (KACP). RESULTS: Mothers exhibited poor febrile seizure knowledge, with affected mothers significantly scoring higher than unaffected. Affected mothers had higher state and trait anxiety and uncertainty. Correlations showed uncertainty positively correlated with anxiety. Regression analysis showed that trait anxiety and knowledge predicted uncertainty in affected mothers, while only trait anxiety predicted uncertainty in unaffected mothers. CONCLUSION: Mothers, especially those with affected children, demonstrated low febrile seizure knowledge, high anxiety, and uncertainty. Lack of knowledge may contribute to ineffective febrile seizure management. The study identifies trait anxiety and knowledge as predictors of uncertainty, emphasizing the need for tailored interventions. PRACTICE IMPLICATIONS: Healthcare professionals can design interventions targeting febrile seizure education and anxiety reduction. Policymakers should focus on raising awareness and allocating resources for effective interventions, potentially improving children with febrile seizure outcomes. This study underscores the importance of addressing maternal knowledge gaps, anxiety, and uncertainty related to febrile seizures, suggesting the need for comprehensive educational programs and support strategies for mothers.

Distinguishing features of COVID-19 and non-COVID-19 febrile seizures in hospitalised children.

INTRODUCTION: Febrile seizures in children can be associated with various underlying conditions, including COVID-19. Differentiating COVID-19 and non-COVID-19 related febrile seizures is crucial for tailored patient management and for implementing appropriate infection control measures to prevent nosocomial transmission. This study aimed to describe the clinical features of children hospitalised for COVID-19 and non-COVID-19 febrile seizures and to identify factors that differentiate between the two groups. MATERIALS AND METHODS: This retrospective cross-sectional study involved children aged 6 months to 6 years who were hospitalised for febrile seizures in Hospital Tuanku Ja'afar Seremban (HTJS) from January 2021 to June 2022. Descriptive statistics were used to summarise the differences in demographics and clinical presentations. Logistic regression analyses were performed to identify factors associated with COVID-19 and non-COVID-19 febrile seizures. RESULTS: Of the 345 patients (median age 22 months, IQR 15- 32; 59.7% were males) included in the study, 130 (37.7%) tested positive for COVID-19, while 215 (62.3%) tested negative. There were no significant differences between both groups based on age, comorbidities, history of febrile seizures, seizure types, temperature on arrival, cough and rhinorrhoea. Multivariate analysis revealed that a family history of febrile seizures and leucocytosis were associated with increased odds of non-COVID-19 febrile seizures. In contrast, lymphopenia was associated with decreased odds. CONCLUSION: The clinical presentation of COVID-19 and non- COVID-19 febrile seizures are remarkably similar, highlighting the importance of including COVID-19 screening in febrile seizures workup. Full blood count readings may be potentially useful for differentiating between these conditions.

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.

Core Features Differentiate Dravet Syndrome from Febrile Seizures.

An 11-month-old girl with febrile seizures and first unprovoked seizures was evaluated in the hospital. Relevant history included developmental delay and strong family history of febrile seizures and migraines. A routine electroencephalogram was performed and was abnormal due to the presence of a slowed posterior dominant rhythm, generalized spike-wave discharges, and multifocal sharp waves. The findings were concerning for a developmental and epileptic encephalopathy. Given the concern for a developmental and epileptic encephalopathy, a next generation sequence epilepsy gene panel was ordered which identified a pathogenic variant in SCN1A. The clinical history, electroencephalogram, and pathogenic variant were compatible with a diagnosis of Dravet syndrome. This Grand Rounds manuscript highlights the thought process, evaluation, differential diagnosis, treatment, and prognosis in Dravet syndrome.

Clinical and laboratory characteristics of complex febrile seizures in the acute phase: a case-series study in Japan.

BACKGROUND: Patients with complex febrile seizures (CFS) often display abnormal laboratory results, unexpectedly prolonged seizures, and/or altered consciousness after admission. However, no standardized values have been established for the clinical and laboratory characteristics of CFS in the acute phase, making the management of CFS challenging. This study aimed to determine the clinical and laboratory characteristics of children with CFS during the acute phase. In particular, the duration of impaired consciousness and the detailed distribution of blood test values were focused. METHODS: We retrospectively reviewed medical records of a consecutive pediatric cohort aged 6-60 months who were diagnosed with CFS and admitted to Kobe Children's Hospital between October 2002 and March 2017. During the study period, 486 seizure episodes with confirmed CFS were initially reviewed, with 317 seizure episodes included in the analysis. Detailed clinical and laboratory characteristics were summarized. RESULTS: Among 317 seizure episodes (296 children with CFS), 302 required two or fewer anticonvulsants to be terminated. In 296 episodes showing convulsive seizures, median seizure duration was 30.5 min. The median time from onset to consciousness recovery was 175 min. Impaired consciousness lasting > 6, 8, and 12 h was observed in 13.9%, 7.6%, and 1.9% patients with CFS, respectively. Additionally, the distribution of aspartate aminotransferase, lactate dehydrogenase, creatinine, and glucose were clarified with 3, 10, 50, 90, and 97 percentile values. CONCLUSION: This study detailed the clinical and laboratory findings of acute-phase CFS using the data of the largest 15-year consecutive cohort of children with CFS. These results provide important information for appropriate acute management of CFS.

Epilepsy diagnosis using a clinical decision tool and artificially intelligent electroencephalography.

OBJECTIVE: To construct a tool for non-experts to calculate the probability of epilepsy based on easily obtained clinical information combined with an artificial intelligence readout of the electroencephalogram (AI-EEG). MATERIALS AND METHODS: We performed a chart review of 205 consecutive patients aged 18 years or older who underwent routine EEG. We created a point system to calculate the pre-EEG probability of epilepsy in a pilot study cohort. We also computed a post-test probability based on AI-EEG results. RESULTS: One hundred and four (50.7%) patients were female, the mean age was 46 years, and 110 (53.7%) were diagnosed with epilepsy. Findings favoring epilepsy included developmental delay (12.6% vs 1.1%), prior neurological injury (51.4% vs 30.9%), childhood febrile seizures (4.6% vs 0.0%), postictal confusion (43.6% vs 20.0%), and witnessed convulsions (63.6% vs 21.1%); findings favoring alternative diagnoses were lightheadedness (3.6% vs 15.8%) or onset after prolonged sitting or standing (0.9% vs 7.4%). The final point system included 6 predictors: Presyncope (-3 points), cardiac history (-1), convulsion or forced head turn (+3), neurological disease history (+2), multiple prior spells (+1), postictal confusion (+2). Total scores of ≤1 point predicted <5% probability of epilepsy, while cumulative scores ≥7 predicted >95%. The model showed excellent discrimination (AUROC: 0.86). A positive AI-EEG substantially increases the probability of epilepsy. The impact is greatest when the pre-EEG probability is near 30%. SIGNIFICANCE: A decision tool using a small number of historical clinical features accurately predicts the probability of epilepsy. In indeterminate cases, AI-assisted EEG helps resolve uncertainty. This tool holds promise for use by healthcare workers without specialty epilepsy training if validated in an independent cohort.

What is the safe observation period for seizure recurrence in pediatric emergency departments?

BACKGROUND: Afebrile seizures are the common causes of emergency department (ED) admissions in childhood, and there is limited data on the observation period in emergency service follow-up of these patients in terms of seizure recurrence in the literature. This study aims to determine the seizure recurrence time in afebrile seizures and the risk factors that determine it. METHODS: Patients aged between 1 month and 18 years with afebrile seizures were included in the study. Seizure recurrence times, demographic data, diagnosis of epilepsy, use of antiseizure medications, Electroencephalography (EEG) and imaging results, structural abnormalities, hospitalizations, and treatments were recorded. RESULTS: The median age of 623 patients included in the study was 42 months (16.0-94.0 months) and 59.9% were male. Epilepsy was diagnosed in 372 (59.7%) of the patients. Short-acting benzodiazepine was administered in 249 of the cases. The mean observation time of the patients was 36 hours (24-98 hours). Electroencephalography (EEG) was applied in 437 (70.1%) of the patients and abnormality was detected in 53.5%. Seizure recurrence was observed in 149 patients (23.9%). The median time of seizure recurrence was 1.0 hour (0.5-4.0 hours). Eighty-six percent of the seizure recurrences (n = 129) occurred within the first six hours and 95.3% (n = 142) within the first 12 hours. Risk factors included a history of febrile seizures (p = 0.001, OR = 2.7), not receiving short-acting benzodiazepine therapy (p = 0.026, OR 1.7), previous structural abnormalities (p = 0.018, OR 1.8), and cluster seizures (p = 0.001, OR 6.7) for all patients and also EEG abnormalities in pediatric ED for first seizure (p = 0.012, OR 2.4). CONCLUSION: Patients with a history of febrile seizure, previous structural abnormalities, cluster seizures, EEG abnormalities in pediatric ED, and patients who didn't receive BZD treatment were at risk for seizure recurrence in the early period. Since most seizure recurrences occur within the first 6 hours, this period is the most critical time for recurrence risk.

Management of children with febrile seizures: a Greek nationwide survey.

The purpose of this study was to investigate knowledge, principles, and practices concerning the management of children with febrile seizures among pediatricians in Greece. A cross-sectional study was performed across Greece. Pediatricians completed an anonymous and voluntary 11-item questionnaire about their knowledge, attitudes, and practices with respect to the management of febrile seizures; the survey also collected demographic data. It was first administered in paper form in October 2017. This was followed by an online survey performed between June and August of 2018 and publicized by medical boards across Greece. Descriptive statistics and comparisons between groups were conducted with the significance level set at p ≤ 0.05. We recorded 457 responses. Pediatricians admitted to modifying their advice to the parents of children with febrile seizures by suggesting more "aggressive" fever management at low temperatures or systematically (63%), referral to a specialist after any episode of febrile seizures (63%), or hospitalization in a subsequent episode (67%), even though 72% admitted these practices were of no efficacy. Almost one in three pediatricians (28%) believed aggressive management of fever could delay the onset of febrile seizures; increasing age was associated with this perception. A minority (28%) would make parents aware of febrile seizures before a first episode regardless of family history; 38% would do so in the event of family history. CONCLUSIONS: Several pediatricians in Greece use outdated and ineffective practices for the management of febrile seizures, despite the availability of updated evidence-based guidelines. Further training of practitioners is needed to bridge this gap. WHAT IS KNOWN: •Aggressive management of fever at low temperatures with antipyretics, referral to a neurologist, and hospitalization are not supported by evidence or recent guidelines on childhood febrile seizures. •Febrile seizures are especially disturbing to uninformed parents, who may be inclined to pursue aggressive but ineffective treatments as a result. WHAT IS NEW: •Pediatricians in Greece use non-evidence-based practices for the management of febrile seizures, even when they are aware that these practices are not effective. •Older age increases the likelihood that a pediatrician will pursue guideline non-compliant practices in Greece. At the same time, physicians with over 20 years of experience are more likely to inform parents in advance about febrile seizures.

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.

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.

The Impact of Omicron Wave on Pediatric Febrile Seizure.

BACKGROUND: The coronavirus disease 2019 (COVID-19) omicron (B.1.1.529) variant reduced the risk of severe disease compared with the original strain and other variants, but it appeared to be highly infectious, which resulted in an exponential increase in confirmed cases in South Korea. As the number of confirmed cases increased, so did the number of pediatric patients' hospitalization. This study aims to evaluate the frequency and clinical features of febrile seizure associated with the COVID-19 omicron variant in children. METHODS: We retrospectively reviewed the medical records of children aged under 18 years with febrile seizure who were tested for COVID-19 from February 2020 to April 2022 at Ajou University Hospital, South Korea. Based on the dominant variants, we divided the period into the pre-omicron (from February 2020 to December 2021) and omicron periods (from January 2022 to April 2022) and compared the clinical characteristics between the two. Also, we compared the clinical characteristics of febrile seizure between COVID-19 positive and negative group during the omicron period. RESULTS: Among the 308 children, 211 patients (9.2 patients/months) and 97 patients (24.3 patients/months) were grouped into pre-omicron and omicron periods, respectively. Compared with the pre-omicron period, patients in the omicron period showed significantly higher mean age (pre-omicron vs. omicron, 22.0 vs. 28.0 months; P = 0.004) and COVID-19 positive results (pre-omicron vs. omicron, 0.5% vs. 62.9%; P < 0.001). As the COVID-19 confirmed cases in the omicron period increased, the number of COVID-19 associated febrile seizure also increased. In the omicron period, 61 children were confirmed to be positive for COVID-19, and COVID-19 positive group showed statistically significant higher mean age (positive vs. negative, 33.0 vs. 23.0 months; P = 0.003) and peak body temperature than the negative group (positive vs. negative, 39.1°C vs. 38.6°C; P = 0.030). Despite the lack of significance, COVID-19 positive group showed longer seizure time, multiple seizure episodes, and higher prevalence of complex febrile seizure. CONCLUSION: The frequency of COVID-19 associated febrile seizure increased in the omicron periods. In addition, in this period, children with febrile seizure diagnosed with COVID-19 had a higher mean age and higher peak body temperature.

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.

Cerebral blood flow abnormalities with central sparing on arterial spin labeling in mild encephalopathy associated with excitotoxicity: a case report.

BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and mild encephalopathy associated with excitotoxicity (MEEX) are the most frequent acute encephalopathies in pediatric patients in Japan. AESD typically presents with biphasic seizures and delayed reduced diffusion in the subcortical area, called bright tree appearance (BTA), on radiological examination. In patients with AESD, arterial spin labeling (ASL) shows decreased cerebral blood flow (CBF) in the hyperacute stage and increased CBF in the acute stage, suggesting the usefulness of ASL for the early diagnosis of AESD. Additionally, proton magnetic resonance spectroscopy (MRS) shows elevated glutamate (Glu) and glutamine (Gln) in AESD. MEEX is a group of mild encephalopathies with transient elevation of Gln on MRS similar to that in AESD; however, MEEX does not include any clinical biphasic course or abnormalities, including BTA on diffusion-weighted imaging. Although the usefulness of ASL for AESD has been reported, there are no reports for patients with MEEX. In this study, we report our experience with a 4-year-old girl diagnosed with MEEX who showed unique findings on ASL. CASE PRESENTATION: The patient was a 4-year-old girl admitted to the emergency room with febrile status epilepticus. Considering the possibility of AESD, vitamin therapy was initiated. ASL-MR imaging (MRI) of the brain performed on the second day showed increased blood flow in the frontal, temporal, and occipital regions with spared central sulcus, which indicated AESD with central sparing. The patient was diagnosed with AESD, and the treatment included pulse steroid therapy and immunoglobulin therapy from day 3. The patient remained mildly unconscious but gradually became conscious by day 7 with no seizures. Brain MRI performed on day 8 did not show any characteristic AESD findings, such as BTA. Furthermore, MRS showed elevated Gln, which, along with the clinical course, led to the diagnosis of MEEX. The patient was discharged on day 16 without obvious sequelae. CONCLUSIONS: ASL may be useful in the early diagnosis of MEEX as well as AESD, facilitating early intervention.

Status epilepticus following vaccination in children aged ≤24 months: A five-year retrospective observational study.

BACKGROUND: Status epilepticus is associated with significant morbidity and mortality. While vaccine-proximate status epilepticus (VP-SE) has rarely been associated with cases of Dravet syndrome, it is not known whether VP-SE differs clinically from non-vaccine proximate status epilepticus (NVP-SE). METHODS: Medical records of children aged ≤24 months, presenting to one of five Australian tertiary pediatric hospitals with their first episode of status epilepticus from 2013 to 2017 were identified using ICD-coded discharge diagnoses. Vaccination history was obtained from the Australian Immunisation Register. Hospitalization details, subsequent epilepsy diagnosis, and vaccination uptake were compared between VP-SE and NVP-SE cases. RESULTS: Of 245 first status epilepticus hospitalization with immunization records, 35 (14%) were VP-SE and 21 (60%) followed measles-containing vaccines. Vaccine-proximate status epilepticus cases had a median age of 12.5 months [IQR 7.1-14.73], 23 (66%) were in males, 15 (43%) were febrile status epilepticus and 17 (49%) had an infection confirmed. There were no significant differences in hospitalization duration (P = 0.50) or intensive care unit admission (P = 0.42) between children with VP-SE compared to children with NVP-SE. Children with no history of seizures at their first VP-SE had longer hospitalizations, were more likely to require intensive care unit admission, but were less likely to have a subsequent diagnosis of epilepsy than children with previous seizures at their first VP-SE. CONCLUSION: First VP-SE was predominantly associated with a measles-containing vaccine at 12-months of age. Seizure severity was no different between first VP-SE and first NVP-SE. In children with VP-SE, subsequent seizure admissions and epilepsy diagnosis were associated with having seizure prior to their first SE.

Prehospital capillary lactate in children differentiates epileptic seizure from febrile seizure, syncope, and psychogenic nonepileptic seizure.

PURPOSE: The aim of the study was to examine prehospital capillary lactate in children as a diagnostic biomarker to differentiate epileptic seizures from febrile seizures, syncope, and psychogenic nonepileptic seizures (PNES). METHODS: Capillary lactate concentrations taken in a pediatric prehospital setting within 2 h of the paroxysmal event were compared retrospectively between patients with epileptic seizure, febrile seizure, syncope, and PNES, based on the final diagnosis from the hospitalization report. RESULTS: One hundred and two patients were included, 53 (52%) with epileptic seizures, 41 (40%) with febrile seizures, and 8 (8%) with syncope or PNES. Capillary lactate in patients with a final diagnosis of epileptic seizure was significantly increased in comparison to the concentrations in patients with febrile seizure (p < 0.0007) and in comparison to the concentrations in patients with syncope or PNES (p < 0.0204). The area under the ROC-curve was 0.71 (95% CI 0.61-0.80). For a cutoff concentration of prehospital capillary lactate >3.9 mmol/l (Youden index), the sensitivity was 49% and the specificity 92%. CONCLUSION: Prehospital capillary lactate concentrations are a useful tool for differentiating the nature of a paroxysmal event in children.

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.