Activation of TRPV1 Contributes to Recurrent Febrile Seizures via Inhibiting the Microglial M2 Phenotype in the Immature Brain.

Transient receptor potential vanilloid type 1 (TRPV1) is a nonselective cation channel implicated in the nervous system as a key component of several inflammatory diseases. A massive amount of evidence has demonstrated that TRPV1 is extensively expressed in the central nervous system (CNS) and there might be a close relationship between TRPV1 and neuroinflammation, which is a crucial pathogenic factor in seizure generation, although it's signaling mechanism has been less well characterized. Herein, we identified that TRPV1 is functionally expressed in the primary cultured mouse microglia and the membrane expression of TRPV1 is upregulated in rFS mice brain and specifically in activated microglia. Stimulation of TRPV1 promoted microglia activation and indirectly enhanced seizure susceptibility by inhibiting the neuroprotective effects of microglial transforming growth factor-beta1 (TGF-ß1) via interaction with Toll-like receptor 4 (TLR4) in mice. Conversely, genetic deletion of TRPV1 alleviated hyperthermia or LPS-induced abnormal microglial activation and restored a balanced inflammatory microenvironment in the brain. Taken together, these findings show that microglial TRPV1, as a potential pro-inflammatory mediator, and participate in neuroinflammatory response, which will provide a novel therapeutic strategy for controlling the neuroinflammation-induced seizure.

Association of developing childhood epilepsy subsequent to febrile seizure: A population-based cohort study.

PURPOSE: Epilepsy is an important neurological condition that frequently associated with neurobehavioral disorders in childhood. Our aim was to identify the risk of developing epilepsy subsequent to febrile seizure and the association between epilepsy risk factors and neurobehavioral disorders. SUBJECTS AND METHODS: This longitudinal population-based cohort data included 952 patients with a febrile seizure diagnosis and 3808 age- and sex-matched controls. Participants were recruited for the study from 1996 to 2011, and all patients were followed up for maximum 12.34 years. RESULTS: The association of epilepsy was significantly higher (18.76-fold) in individuals that experienced febrile seizure compared to controls. Further, of those individuals who experienced febrile seizure, the frequency of subsequent development of epilepsy was 2.15-fold greater in females, 4.846-fold greater in patients with recurrent febrile seizure, and 11.26-fold greater patients with comorbid autism. CONCLUSIONS: Our study showed that being female, comorbid autism with febrile seizure and recurrent febrile seizure had an increased association with development of epilepsy. Increased recognition the association for epilepsy might be warranted in those febrile seizure children with certain characteristics.

Clinical characteristics of febrile seizures and risk factors of its recurrence in Chiang Mai University Hospital

Background & Objectives: Febrile seizures are the most common convulsive disorder in children under 5 years old. Among these children, some develop recurrent febrile seizures. The objective of this study was to describe clinical characteristics of children with febrile seizures and to identify risk factors for developing recurrent seizures. Methods: A retrospective study was conducted from January 2004 to December 2013 in Chiang Mai University Hospital. Infants and children between 6 months and 5 years of age who were diagnosed with febrile seizures were included in this study. Clinical characteristics of children and all factors associated with seizure recurrence were extensively reviewed using electronic medical records. Results: There were 335 cases included for analysis. The mean age at onset of febrile seizures was 1.85 ± 0.95 years; 64.78 % were males. Among 261 cases who presented with first episode of febrile seizures, 52 cases (19.92%) developed recurrent febrile seizures. Respiratory tract infections were the most frequent etiology of febrile illnesses. Younger age at onset and family history of febrile seizures were statistically significant predictors of developing recurrent febrile seizures (p = <0.001 and 0.02, respectively). After adjusting the confounding variables, similar findings were found from the multiple logistic regression analysis (p = 0.003 and 0.01 respectively). Conclusion: In this study, younger age at onset of first febrile seizure and family history of febrile seizures were found to increase the risk of the recurrence of febrile seizures.

Predictors of Recurrent Febrile Seizure / 대한소아신경학회지

PURPOSE: We performed this study to investigate the clinical features of febrile seizure (FS) and to identify prognostic factors of recurrence of FS on Jeju Island, South Korea. METHODS: A hospital-based retrospective study was performed in 307 children with FS whose first episode developed between July 2005 and June 2013 seen at the Pediatric Department of Jeju National University Hospital. RESULTS: 307 children (189 boys and 118 girls) were enrolled in this study. Based on first FS semiology, 97.1% (298/307) of cases manifested as generalized seizure and 2.9% of cases showed focal seizure. Moreover, 23.5% (72/307) of cases had complex FS as the first FS. The average age at the first FS was 18.4 months. A family history of FS or epilepsy was found in 30.6% and 5.2% of patients, respectively. Recurrence occurred in 67.6% of patients; among them, 93.7% had their first recurrence within 1 year. Multivariate analysis identified the following factors as significant predictors of recurrence of FS: early onset of FS (< or =15 months of age) and a family history of FS. CONCLUSIONS: We identified the following risk factors for recurrence of FS: early onset of FS (< or =15 months of age) and a family history of FS.