Complex Febrile Seizures Research Articles

Frequency of Meningitis Among Infants and Young Children With Clinically Diagnosed First Time Febrile Seizure

Background: Patients with bacterial meningitis (BM) frequently present with febrile seizures (FS) without any signs or symptoms of BM. To perform a lumbar puncture on all FS patients to rule out meningitis is still debatable. The goal of this study was to estimate the frequency of meningitis among first-time febrile seizures (FTFS). Methods: From July 2013 to June 2014, a cross-sectional study was conducted at Sir Salimullah Medical College and Mitford Hospital, Dhaka. CSF and blood reports and detailed histories and examinations were examined in children aged 6 months to 36 months with FTFS (simple or complex). Results: The first complex febrile seizure (FCFS) and the first simple febrile seizure (FSFS) occurred in 58% and 42% of the 73 children included in this study. 11 (15%) cases had meningitis based on CSF and blood reports, where 2 (3%) had confirmed BM, 2 (3%) had probable BM, and 7 (10%) had viral meningitis (PVM). One of two children with confirmed BM had Klebsiella spp. in CSF culture and Streptococcus pneumoniae in CSF gram stain. Others with probable BM had CSF pleocytosis with low sugar and high protein levels. Leukocytosis was found in all four children with BM. Two of the seven children with PVM had isolated pleocytosis, one had low sugar, and four had high protein CSF. Blood cultures were negative in all 11 meningitis cases. Conclusion: Although meningitis is common in FCFS, this study found no cases of BM children with FSFS, though PVM was not uncommon. Sir Salimullah Med Coll J 2022; 30: 108-114

The Impact of Neutrophil-Lymphocyte Ratio in Febrile Seizures: A Systematic Review and Meta-Analysis.

This meta-analysis was conducted to determine the relationship between neutrophil to lymphocyte ratio (NLR) and febrile seizure (FS). Our study was registered with the PROSPERO (ID: CRD42021259944). Web of Science, Embase, PubMed, Scopus, and ProQuest Central were searched, and finally, 17 studies were included. Standardized mean difference (SMD) was reported with a 95% confidence interval (CI) for the NLR levels. Compared with the febrile control group, the FS patients' NLR levels were significantly higher (SMD = 0.49; 95%CI = 0.26 to 0.72, P < 0.001). Furthermore, we conducted a comparison of NLR levels between febrile controls against simple and complex FS cases separately and found that NLR levels of children with either simple or complex FS were higher compared with those of febrile controls (SMD = 0.42, 95%CI = 0.14 to 0.69, P = 0.003 and SMD = 0.90, 95%CI = 0.71 to 1.09, P < 0.001, respectively). Also, in comparison with the NLR levels of the simple FS group, the complex FS patients' NLR levels were significantly higher (SMD = 0.59, 95%CI = 0.34 to 0.85, P < 0.001). Our study indicated that NLR could be recommended as an inexpensive diagnostic biomarker for FS. In addition, it can be useful when distinguishing between simple FS and complex FS.

Evaluation of the risk factors for recurrence and the development of epilepsy in patients with febrile seizure.

Although febrile seizure (FS) is generally considered benign and self-limiting, there are differences regarding the risk factors, the prognosis, and the development of epilepsy. To examine the clinical and sociodemographic characteristics of patients diagnosed with FS, and to determine the risks of recurrence and the development of epilepsy. Between 2015 and 2019, we performed a retrospective evaluation of 300 patients with FS followed for at least 24 months. The first episode of FS was simple in 72.7% of the patients and complex in 27.3%, and it recurred in 40%. Age under 12 months in the first FS, complex FS, and neurodevelopmental delay were found to statistically increase the risk of recurrence (p < 0.05). A total of 7% of the patients developed epilepsy, and this rate was found to be higher in patients with neurodevelopmental delay and long-term use of antiepileptic drugs (p < 0.001). The development of epilepsy was also observed in 77.8% of the patients with abnormal electroencephalogram (EEG). Epilepsy developed more frequently in those with abnormal EEG (p<0.001). Neurodevelopmental delay was an important risk factor for FS recurrence and the development of epilepsy. Abnormality in the EEG is an important risk factor for the development of epilepsy. We found that the long-term prophylactic treatment did not cause decreases in the recurrence of FS nor in the development of epilepsy.

Clinical and Laboratory Characteristics of Febrile Seizure in Children Presenting with Seizure

Introduction: Febrile seizures are generally defined as seizures occurring in children from 6 months to 60 months of age in association with a fever greater than 38°C (100.4°F), who do not have evidence of an intracranial cause (e.g. infection, head trauma, and epilepsy), another metabolic cause of seizure (e.g. electrolyte imbalance, hypoglycemia, drug use, or drug withdrawal), or a history of an afebrile seizure.&#x0D; Aims: To find clinical and laboratory characteristics of febrile seizure.&#x0D; Methods: A hospital based cross sectional study was performed in Nepalgunj Medical College, Kohalpur, Banke from March 2021 to February 2022. Children of aged 6 months to 60 months, with fever and seizure admitted in Department of Pediatrics and visiting in outdoor fulfilling inclusion criteria were taken for the study. Detailed history and examination was performed, Data related to age, sex, family history, recurrence and relevant investigations was carried out in all patients.&#x0D; Results: Out of 3294 admitted patients, 82 children with febrile seizure were studied, in which 55 (67.1%) male and 27 (32.9%) were female respectively which accounts for 2.03:1 ratio. Majority of 34 (41.46%) belongs to 13-24 months of age. 70 (85.4%) had children simple febrile seizure and 12 (14.6%) had complex febrile seizure. 25 (30.5%) had recurrence history. Majority of children had history of cough 26 (31.7%). Mean total leukocyte count (TLC) was slightly higher and other are within normal range.&#x0D; Conclusion: Febrile seizure is more common in male, majority of children affected are below two years of age. Simple febrile seizure is more common variety.

Evaluation of Clinical, EEG, and Lumbar Puncture Findings of Patients with Complicated Febrile Seizure

Introduction: Febrile seizure (convulsion) (FC) is a type of seizure which is accompanied by fever, without a history of neurological disease and central nervous system infection. It occurs in approximately 2–5% of children aged between 6 months and 5 years. Complex FC is a type of convulsion which is often accompanied by focal seizures, occurs again within 24 h, and/or lasts longer than 15 min. About 20–25% of patients experience complex FC. Materials and Methods: Our study included 45 patients who applied to Ayd?n State Hospital Pediatric Neurology Clinic between July 2018 and July 2020 and Mersin City Training and Research Hospital between October 2020 and October 2021 with complex febrile seizures. Demographic and laboratory findings of the patients were evaluated retrospectively. Results: Two hundred and seven patients with FC applied to our clinic. Forty-five (21.7%) of these patients had complex FC. Forty-five patients, who were diagnosed with complex FC, were included in the study. The mean age was 16.6 months. LP was performed in 29 (64.4%) patients, EEG was performed in 40 (88.9%) patients. Pleocytosis was detected in three (6.7%) patients, Streptococcus pneumonia was detected in CSF culture in one patient. H1N1 encephalitis was also observed in one of our patients. EEG was taken in all patients within the first 7 days. EEG abnormalities were detected in 5 (11.1%) patients. Conclusion: The presence of postictal neurologic findings was considered as the most important risk factor for CNS infections in our study. It was thought that the detection of epileptiform abnormality in the EEGs of the patients might be relat

A Comparative Study of Febrile Seizures and Febrile Convulsions Associated With Mild Gastroenteritis

BackgroundChildren presenting with complex febrile seizures (FS) have an increased risk of developing epilepsy. This study aimed to investigate the occurrence of complex seizures in children presenting with FS and those with both convulsions associated with mild gastroenteritis (CwG) and fever. MethodsChildren admitted to our Pediatric Emergency Department between January 2017 and April 2019 with seizures were enrolled in this cross-sectional study. Patients were grouped according to the etiology as FS and febrile CwG. FS classification criteria of simple FS and complex FS was applied to both groups to allow a comparison between them. Prevalence ratios (PRs) of complex seizures, estimated through a log binomial model, were used to compare the occurrence of complex seizures between the two groups, using the FS group as reference category. ResultsA total of 294 patients were enrolled: 231 with FS and 63 with febrile CwG. Complex seizures occurred in 31 patients with FS (13.4%) and 21 patients (33.3%) with febrile CwG. The PR of complex seizures was 2.48 (95% confidence interval, 1.54 to 4.01). ConclusionsChildren with febrile CwG showed a higher rate of complex seizures when compared with those with FS.

Etiological profile of seizure in children of age group 1 month to 18 years with special reference to neuroimaging in a tertiary care hospital

Background: Seizure is a common cause of childhood hospitalization. Neuroimaging studies help in identifying etiologies, including the rare ones, and planning management. Purpose: The aim of this study is to determine the etiology of seizures in pediatric patients and the utility of neuroimaging in the same. Materials and Methods: A prospective study was carried out on 100 children who were admitted with seizures (including recurrent episodes) in our tertiary care institute. The sociodemographic profile, clinical features, neuroimaging findings, and findings of other investigations were documented and analyzed, to classify the type and etiology of seizures. Results: The male–female ratio among patients was 1.94: 1. Seizures of generalized onset were most common (95%), affecting mostly the age group of 1–5 years (50.53%), followed by the 5–18 years (29.47%) and the 1 month to 1 year (20%) groups. The etiologies were simple febrile seizure (51%), seizure disorder (8%), cerebral palsy (8%), acute viral meningoencephalitis (7%), pyogenic meningitis (6%), and complex febrile seizure (5%). Neuroimaging was carried out in 30 children, in which 14 showed abnormal reports, and abnormal electroencephalogram (EEG) report was found in 6 out of 10 patients. The analysis of the distribution of the types of seizures concerning age, gender, family history of seizure, history of seizure, socioeconomic status, and developmental milestones did not reveal any statistically significant relationships (P &gt; 0.05). Conclusion: Seizure of generalized onset was the most common type, and the most common etiology was a simple febrile seizure. Abnormal neuroimaging/EEG findings were more pronounced in patients with focal seizures.

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 (6-60months 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 24h. 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 ≥30min and 2 of 3 patients (67%) requiring ≥2 intravenous anticonvulsants to stop seizures. Seizure recurrence within 24h 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 24h, early recurrences occurred within 8h 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.

Efficacy of melatonin for febrile seizure prevention: A clinical trial study

Background: Prophylactic treatment for recurrence of febrile seizure generally consists of intermittent administration of diazepam or clobazam, or long-term treatment with valproic acid or phenobarbital. However, the adverse effects outweigh the benefits. A newer, effective, more tolerable drug treatment is warranted.Objective: To study melatonin efficacy in prevention of recurrence of one or more episodes of either simple or complex febrile seizure compared to a control group.Methods: A quasi-experimental study in children who were diagnosed with febrile seizure in Bhumibol Adulyadej Hospital, between 6 months to 5 years old, divided into two groups, melatonin group and control group, depending upon parental convenience. Melatonin was given 0.3 mg/kg/dose every 8 hours for 48 to 72 hours during febrile illness to melatonin group if body temperature was more than 37.5°C. Control group had no medicine. Patients were followed at 3 and 6 months.Results: The study included 23 patients in the melatonin group and 41 in the control group. Mean age of diagnosed of febrile seizure onset was 17.3 and 21.6 months, respectively. In the melatonin group, 8.7% of patients had recurrent febrile seizure compared to 36.6% in the control group, which is statistically significant (P-value 0.015, RD −0.28(95%CI: −0.46 to −0.09)). There was no statistically significant difference in adverse effects between the two groups.Conclusion: This study demonstrates the efficacy and safety of short-term melatonin use to prevent the recurrence of one or more episodes of either simple or complex-febrile seizure in children.

Changes of biochemical biomarkers in the serum of children with convulsion status epilepticus: a prospective study

BackgroundConvulsive status epilepticus (CSE) is a common neurologic emergency with high morbidity and mortality. This single center study is aimed to assess changes of serum biochemical biomarkers after seizure, and their associations with the development of CSE.MethodsFrom January 2015 to October 2016, a total of 57 CSE patients, and 30 healthy controls without central nervous system diseases were enrolled in Children’s Hospital of Soochow University. CSE patients were further divided into viral encephalitis (VEN, 13 cases), primary generalized epilepsy (PGE, 30 cases), and complex febrile seizures (CFS, 14 cases). The levels of serum biochemical biomarkers were measured using the corresponding commercial ELISA kits. Logistic regression analysis was performed to identify the associations between these biomarkers and diseases.ResultsAt the 1st and 4th day of CSE, neuron-specific enolase (NSE; 1st day: 20.553 ± 5.360, 4th day: 10.094 ± 3.426) and vascular endothelial growth factor (VEGF; 1st day: 153.504 ± 31.246, 4th day: 138.536 ± 25.221) in the CSE group were increased compared to the control (NSE: 6.138 ± 1.941; VEGF: 119.210 ± 31.681). Both the levels of S-100 calcium binding protein B (S-100B; 1st day: 0.738 ± 0.391) and C-reactive protein (CRP; 1st day: 11.128 ± 12.066) were elevated at 1st day of CSE (S-100B: 0.387 ± 0.040; CRP: 3.915 ± 2.064). For glial fibrillary acidic protein (GFAP), it was remarkably upregulated at 4th day of CSE (3.998 ± 1.211). NSE (P = 0.000), S-100B (P = 0.000), CRP (P = 0.011), and VEGF (P = 0.000) at 1st day of CSE, and NSE (P = 0.000), VEGF (P = 0.005), and GFAP (P = 0.000) at 4th day of CSE were significantly associated with the occurrence of CSE. Besides, NSE (P = 0.002), S-100B (P = 0.001), and VEGF (P = 0.002) at 4th day of CSE were significantly associated with VEN.ConclusionsThe levels of serum NSE, S-100B, CRP, VEGF, and GFAP are associated with CSE.

Establishment of achievable benchmarks of care in the neurodiagnostic evaluation of simple febrile seizures.

Current guidelines recommend against neurodiagnostic testing for the evaluation of simple febrile seizures. (1) Assess overall and institutional rates of neurodiagnostic testing and (2) establish achievable benchmarks of care (ABCs) for children evaluated for simple febrile seizures at children's hospitals. Cross-sectional study of children 6 months to 5 years evaluated in the emergency department (ED) 2016-2019 with simple febrile seizures at 38 children's hospitals in Pediatric Health Information System database. We excluded children with epilepsy, complex febrile seizures, complex chronic conditions, and intensive care. Proportions of children who received neuroimaging, electroencephalogram (EEG), or lumbar puncture (LP) and rates of hospitalization for study cohort and individual hospitals. Hospital-specific outcomes were adjusted for patient demographics and severity of illness. We utilized hospital-specific values for each measure to calculate ABCs. We identified 51,015 encounters. Among the study cohort 821 (1.6%) children had neuroimaging, 554 (1.1%) EEG, 314 (0.6%) LP, and 2023 (4.0%) were hospitalized. Neurodiagnostic testing rates varied across hospitals: neuroimaging 0.4%-6.7%, EEG 0%-8.2%, LP 0%-12.7% in patients <1-year old and 0%-3.1% in patients ≥1 year. Hospitalization rate ranged from 0%-14.5%. Measured outcomes were higher among hospitalized versus ED-only patients: neuroimaging 15.3% versus 1.0%, EEG% 24.7 versus 0.1% (p < .001). Calculated ABCs were 0.6% for neuroimaging, 0.1% EEG, 0% LP, and 1.0% hospitalization. Rates of neurodiagnostic testing and hospitalization for simple febrile seizures were low but varied across hospitals. Calculated ABCs were 0%-1% for all measures, demonstrating that adherence to current guidelines is attainable.

Fever-Associated Seizures or Epilepsy: An Overview of Old and Recent Literature Acquisitions.

In addition to central nervous system infections, seizures and fever may occur together in several neurological disorders. Formerly, based on the clinical features and prognostic evolution, the co-association of seizure and fever included classical febrile seizures (FS) divided into simple, complex, and prolonged FS (also called febrile status epilepticus). Later, this group of disorders has been progressively indicated, with a more inclusive term, as “fever-associated seizures or epilepsy” (FASE) that encompasses: (a) FS divided into simple, complex, and prolonged FS; (b) FS plus; (c) severe myoclonic epilepsy in infancy (Dravet syndrome); (d) genetic epilepsy with FS plus; and (e) febrile infection-related epilepsy syndrome (FIRES). Among the FASE disorders, simple FS, the most common and benign condition, is rarely associated with subsequent epileptic seizures. The correlation of FS with epilepsy and other neurological disorders is highly variable. The pathogenesis of FASE is unclear but immunological and genetic factors play a relevant role and the disorders belonging to the FASE group show to have an underlying common clinical, immunological, and genetic pathway. In this study, we have reviewed and analyzed the clinical data of each of the heterogeneous group of disorders belonging to FASE.

Functional network connectivity imprint in febrile seizures

Complex febrile seizures (CFS), a subset of paediatric febrile seizures (FS), have been studied for their prognosis, epileptogenic potential and neurocognitive outcome. We evaluated their functional connectivity differences with simple febrile seizures (SFS) in children with recent-onset FS. Resting-state fMRI (rs-fMRI) datasets of 24 children with recently diagnosed FS (SFS-n = 11; CFS-n = 13) were analysed. Functional connectivity (FC) was estimated using time series correlation of seed region–to-whole-brain-voxels and network topology was assessed using graph theory measures. Regional connectivity differences were correlated with clinical characteristics (FDR corrected p < 0.05). CFS patients demonstrated increased FC of the bilateral middle temporal pole (MTP), and bilateral thalami when compared to SFS. Network topology study revealed increased clustering coefficient and decreased participation coefficient in basal ganglia and thalamus suggesting an inefficient-unbalanced network topology in patients with CFS. The number of seizure recurrences negatively correlated with the integration of Left Thalamus (r = − 0.58) and FC of Left MTP to 'Right Supplementary Motor and left Precentral' gyrus (r = − 0.53). The FC of Right MTP to Left Amygdala, Putamen, Parahippocampal, and Orbital Frontal Cortex (r = 0.61) and FC of Left Thalamus to left Putamen, Pallidum, Caudate, Thalamus Hippocampus and Insula (r 0.55) showed a positive correlation to the duration of the longest seizure. The findings of the current study report altered connectivity in children with CFS proportional to the seizure recurrence and duration. Regardless of the causal/consequential nature, such observations demonstrate the imprint of these disease-defining variables of febrile seizures on the developing brain.

Factors associated with febrile seizures among children

ObjectiveFebrile seizures are usually benign and are not presented with neurological manifestation. However, complex febrile seizures are presented with recurrence and might require meticulous management. The aim of this study was to evaluate the demographic, clinical, and laboratory parameters of children with febrile seizures and the correlation between these factors. MethodsIn this retrospective study, children presented with febrile seizure in 2019 presented (XXX) were included. Data based on their history, physical examination, and laboratory tests and discharge recommendations were recorded in a checklist. Data were computerized and statistically analyzed using SPSSv25. ResultsOf 77 patients were studied, the mean age of the patients was 29.4 ± 17.6. The mean duration of seizures was 5.09 ± 3.78 min and the mean temperature during seizures was 38.41 ± 0.83 °C. In 44 (57.14%) patients no cause of the fever was recorded. 10 (12.99%) patients had multiple seizures within 24 h 70 (90.91%) seizures ended without medication, and 5 (6.49%) patients were treated with diazepam. The gender of the patients was only correlated with white blood cells, p = 0.014. Other laboratory parameters did not show significant correlation with the gender, p > 0.05. The discharge recommendation was significantly correlated with recurrence within 24 h and type of seizure, p < 0.001, respectively. Lab parameters were significantly associated with family history, p = 0.036 and post-seizure drug, p = 0.005. ConclusionOur study showed that biochemical findings may not be suggestive of febrile seizures and recurrence of seizures and family history is associated with the course of treatment in terms of drugs and imaging.

Hospital-Based Prevalence, Electroencephalogram (EEG), and Neuroimaging Correlation in Seizures Among Children in Odisha, India.

Background: Febrile seizures are very common in pediatric practice. We need to differentiate between febrile seizures and other seizures due to central nervous system (CNS) infection by various means of investigation. Though approximately 30% of patients with febrile seizure have later epilepsy and the risk is around 20% even if electroencephalogram (EEG), and neuro-imagings are normal. But data regarding this is laking in developing countries like India.Aim: The primary objective of this study is to determine the hospital-based prevalence among various types and etiologies of seizures in children admitted to the pediatric department in a teaching hospital of a developing country, India. Besides, the different types of seizures were correlated with the EEG and neuroimaging findings along with the acute onset of seizures among children.Methods: In this prospective observational study, children from two months to 15 years of age admitted to the Pediatrics Department, KIMS, Bhubaneswar in India between September 2017 and September 2019 were taken. The patients having seizures were included in the study based on the inclusion criteria. Neurological and systemic examinations of the children were recorded and the neuroimaging reports were analyzed.Results: A total of 19,553 patients aged two months to 15 years were admitted during the study period. Of that, 1,192 cases were diagnosed with febrile and unprovoked seizures. It was observed that the hospital-based prevalence of seizures among children in Odisha was 6%. Besides, it is found that generalized seizure disorder was the most common among the children. It was found that abnormal EEG, magnetic resonance imaging (MRI), and computed tomography (CT) brain in 60% (202/340), 49% (113/230), and 47% (136/288) of cases, respectively. MRI is a better modality of investigation in partial seizure cases 22 (64%) to detect CNS abnormality. Also, MRI of the brain is better in evaluating CNS abnormality in complex febrile cases 4 (31%) than CT brain (0%).Conclusion: The study concluded that EEG must be the standard modality of test for patients' diagnosis of seizure in children with seizures. CT/MRI scan can give a better supplement to the results but MRI findings are more accurate in cases of complex febrile seizures.

Risk factors of epilepsy in children with complex febrile seizures: A retrospective cohort study.

Febrile seizures are the most common seizures in children. Children with complex febrile seizures have a higher risk of subsequent epilepsy compared with children with simple febrile seizures. Multiple risks factors for epilepsy, including focal status epilepticus, family history of epilepsy, neurodevelopmental abnormalities and abnormal electroencephalogram findings, have been found with inconsistent results. The aim of this study is to identify risk factors for developing epilepsy in children with complex febrile seizures. The study included 248 children aged 3-72-months, diagnosed with complex febrile seizures at Chiang Mai University Hospital. Demographic data, seizure characteristics, electroencephalogram and neuroimaging findings were identified, and assessed to establish whether they were risk factors for subsequent epilepsy. Fifty-five patients (22.1%) had subsequent epilepsy. Using Cox regression-survival analysis, factors associated with epilepsy were prolonged seizures >15 min (P = 0.006; Hazard Ratio (HR): 2.475; 95% Confidence Interval (CI): 1.294-4.735), developmental delay (P = 0.019; HR: 4.476; 95% CI: 2.280-15.646), epileptiform discharges on electroencephalogram (P = 0.023; HR: 1.391; 95%CI: 1.174-1.876), and abnormal neuroimaging (computed tomography or magnetic resonance imaging; P = 0.028; HR: 1.355; 95% CI: 1.034-1.776). Age at onset, peak febrile temperature, duration between the onset of fever and the occurrence of seizure, recurrent seizures within 24 h, focal seizures, abnormal neurological exams and family history of febrile seizure or epilepsy were not associated with increased risk of subsequent epilepsy in this study. Risk factors associated with increased risk of epilepsy in children with complex febrile seizures are prolonged seizures or febrile status epilepticus, developmental delay, electroencephalogram epileptiform discharges, and abnormal neuroimaging. Their presence would merit close clinical monitoring.

KCC2 rs2297201 Gene Polymorphism Might be a Predictive Genetic Marker of Febrile Seizures.

Introduction: Febrile seizures (FS) are the most common neurological disease in childhood. The etiology of FS is the subject of numerous studies including studies regarding genetic predisposition. Aim: The aim of the study was to analyze the association of TRPV1 rs222747 and KCC2 rs2297201 gene polymorphisms with the occurrence of FS. Materials and Methods: The study included 112 patients diagnosed with FS classified as simple febrile seizures (SFS) or complex febrile seizures (CFS). We analyzed selected polymorphisms of KCC2 and TRPV1 genes using the Real-time PCR method. Results: The CT and TT genotypes of the rs2297201 polymorphism of the KCC2 gene are significantly more common in the group of children with FS than the control group (p = .002) as well as the allele T of this polymorphism (p = .045). Additionally, genotypes CT and TT of the rs2297201 polymorphism of the KCC2 gene were more frequent in the group of children with CFS compared to the control group (p < .001). Different genotypes and alleles of the rs222747 TRPV1 gene polymorphism were not associated with the occurrence of febrile seizures or epilepsy, nor were associated with the occurrence of a particular type of febrile seizure (p = .252). Conclusion: These results indicate that the CT and TT genotypes, as well as the T allele of rs2297201 polymorphism of the KCC2 gene, could be a predisposing factor for the FS, as well as the occurrence of CFS.

Fever, Seizures and Encephalopathy: From Bush Fires to Firestorms.

Fever-associated seizures and febrile encephalopathy are common neurological problems in children. Infections of the nervous system are responsible for the majority of cases. However, there is a spectrum of infection-associated and inflammatory conditions associated with the triad of fever, seizures, and encephalopathy. Apart from complex febrile seizures and febrile status epilepticus, fever infection-related epilepsy syndrome of childhood (FIRES), infantile hemiconvulsion hemiplegia epilepsy syndrome (IHHE), acute encephalopathy with delayed diffusion restriction (AESD), acute necrotizing encephalopathy of childhood (ANE), and reversible splenial lesion syndrome (RESLES) are age-related clinical phenotypes of fever-related epilepsy and encephalopathy. Awareness of these entities is important for appropriate diagnosis and the prompt use of immunomodulatory/immunosuppressive therapies. In this review, we discuss the pathophysiology, clinical phenotypes, and management approaches of these fever-related seizure and encephalopathy states.

Protective effect of Toll-like receptor 4 antagonist on inflammation, EEG, and memory changes following febrile seizure in Wistar rats

Neuroinflammation and fever are the main triggers in febrile seizures (FS). Focusing on inflammatory pathways and anti-inflammatory drugs could compensate for the limitations of existing medications. The aim of this study is to evaluate the neuroprotective effect of specific antagonizing Toll-like receptor 4 (TLR4), as a prominent inflammatory axis, on the consequences of FS and adulthood using animal models. Complex FS was induced on 9–11 day old male rat pups using a heated chamber. TAK-242, as a specific TLR4 inhibitor, was injected intraperitoneally before seizure induction. Seizure threshold, duration, and spike number were measured by electrocorticography. The levels of inflammatory cytokines, TLR4 protein expression, and oxidative stress markers were detected by enzyme-linked immunosorbent assay, western blotting, malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) assessments in the cortex and hippocampus. Also, spatial and non-spatial memory were evaluated using the novel object recognition test (NORT) and double Y-maze test during adulthood.The results revealed that provoked inflammatory responses in neonate rats, after FS, were associated with the increase of the tumor necrosis factor alpha, interleukin-1β, and enhanced TLR4 protein expression. Meanwhile, based on performed behavioral tests, the inflammatory process was also involved in adulthood memory deficit. Pretreatment with TAK-242 reduced the inflammatory cytokines and TLR4 protein expression in the cortex and hippocampus of neonate rats and improvement in memory deficit in NORT and double Y-maze tasks. Also, pretreatment with TAK-242 elevated seizure threshold, SOD, and CAT activities, and decreased seizure duration and MDA level with no significant change in spike number. TAK-242 possibly controlled FS via inhibiting inflammation.

Cognitive impairment following experimental febrile seizures is determined by sex and seizure duration

BackgroundFebrile seizures are the most common type of seizures in children. While in most children the outcome is favorable, children with febrile status epilepticus may exhibit modest cognitive impairment. Whether children with other forms of complex febrile seizure, such as repetitive febrile seizures within the same illness are at risk of cognitive deficits is not known. In this study, we used a well-established model of experimental febrile seizures in rat pups to compare the effects of febrile status epilepticus and recurrent febrile seizures on subsequent spatial cognition and anxiety. MethodsMale and female rat pups were subjected to hyperthermic seizures at postnatal day 10 and were divided into groups of rats with continuous seizures for ≥40 min or recurrent febrile seizures. They were then tested as adults in the active avoidance and spatial accuracy tests to assess spatial learning and memory and the elevated plus maze to measure anxiety. ResultsFebrile status epilepticus rats demonstrated impaired spatial cognition in active avoidance and spatial accuracy and exhibited reduced anxiety-like behavior in the elevated plus maze. Rats with recurrent febrile seizures did not differ significantly from the controls on any measures. There were also significant sex-related differences with females with FSE performing far better than males with FSE in active avoidance but demonstrating a navigational learning impairment relative to CTL females in spatial accuracy. However, once learned, females with FSE performed the spatial accuracy task as well as CTL females. ConclusionThere is a duration-dependent effect of febrile seizures on subsequent cognitive and behavioral outcomes. Febrile status epilepticus resulted in spatial cognitive deficits and reduced anxiety-related behaviors whereas rats with recurrent febrile seizures did not differ from controls. Sex had a remarkable effect on spatial cognitive outcome where males with FSE fared worse than females with FSE. The results demonstrate that sex should be considered as a biological variable in studies evaluating the effects of seizures on the developing brain.