Study of Recurrence and in the Long-Term Epilepsy Development, Prevalence, Risk Factors and Prognosis in Patients Presenting with Febrile Convulsion and IL-1β (-511) and IL-10 (-1082) Gene Polymorphism İdentifed

Febrile convulsion (FC) is defined as an event occurring between 6 months and 5 years of age, associated with fever when there is no other cause leading to intracranial infection and seizures. The incidence of FC is between 2-5%. The peak age of FC occurrence is 18 months of age. Although FC is the most common neurological disorder in childhood, underlying pathophysiology remains unclear. It is an age-dependent event caused by the central nervous system, which is immature as a result of genetic predisposition as being sensitive to fever. In our study, 191 patients diagnosed with FC between September 1, 2005, and September 1, 2018, in the Pediatric Emergency Department and Pediatric Neurology Outpatient Clinic of Akdeniz University Medical Faculty were retrospectively scanned and constituted the first study group. Among the children who refered with first FC in 2007; 44 patients with IL-1β (-511) and IL-10 (-1082) gene polymorphisms were obtained as second study group that retrospectively scanned from patient files. We aimed to identify the prevalence, risk factors, and prognosis of epilepsy occurrence in the long-term with FC recurrence for both study groups. In the first group involving 191 patients in our study; the rate of males who applied for the first time with FC was higher than that of females. We determined the male / female ratio as 1.7 / 1. The average age of FC occurrence was 22 months (± 14) and the median was 18 months of age. The age of 111 patients (58%) was 18 months and lower. The most common fever focus of FC was found to be the upper respiratory tract infection. The most common detectable infection cause was found to be influenza A. As the first type of FC, simple FC was detected in 141 patients (74%) and complex FC in 50 patients (26%). LP was performed in 45 patients (24%) referring as the first FC and meningitis was not demonstrated in any case. EEG was performed in 143 patients (75%), and 28 patients (15%) had pathological results. Central imaging was performed in 124 patients (65%) referring as the first FC, and the results of 20 patients (10%) were reported pathological. After the first FC, in 139 patients recurrence of FC is defined and we determined recurrence rate as 73%. Risk factors for FC recurrence in the follow-up after the first FC are patient age 18 month or below, peak fever 38.5°C or below, family history of FC, neuromotor developmental retardation and complex FC application (p <0.05). After the first FC, 44 patients (23%) were diagnosed as epilepsy in the long-term. Generalized seizures were observed in 27 patients (14%) diagnosed with epilepsy, and focal seizures were observed in 17 patients (9%). Risk factors for the development of epilepsy in the follow-up after the first FC included neuromotor developmental retardation, complicated FC, family epilepsy history, family FC history, parental consanguineous history, pathological EEG outcome, accompanying additional disease, an abnormal result of central imaging and recurrent FC history (p <0, 05). In the second group consisting of 44 patients with IL-1β (-511) and IL-10 (-1082) gene polymorphism, in the follow-up after the first FC, the recurrence was detected in 32 patients (73%). No statistically significant difference was found in terms of detection cytokine gene polymorphism and FC recurrence. In the follow-up after first FC, 19 patients (43%) were diagnosed with epilepsy. After the first FC, 13 patients (59%) with G / A polymorphism in the IL-10 (-1082) region, 4 patients (67%) with A / A polymorphism and 2 patients (13%) with G / G polymorphism were diagnosed with epilepsy. Development of epilepsy after first FC and detection polymorphism in the IL-10 (-1082) region was found statistically significant (p = 0.006). The probability of developing epilepsy with G / A and A / A polymorphism was higher than G / G polymorphism. 17 patients (61%) with the A allele genotype in the IL-10 (-1082) region were diagnosed as epilepsy in the follow up after first FC. A statistically significant relationship was found between the development of epilepsy after FC and carrying the A allele genotype in the IL-10 (-1082) region (p = 0.002). The presence of the A allele genotype in the IL-10 (-1082) region increased the development of epilepsy 10.8 times compared to the absence of the A allele genotype (OR = 10.8) (95% CI: 2.04-57). The prognosis of FC is usually good, however, patients under risk should be followed-up more closely due to higher risk of recurrency and epilepsy in the future compared to the general population. In particular, families of children at risk of FC recurrence and epilepsy should be informed in detail, fever should be preserved under control, and necessary precautions should be taken when FC develops. The findings of our study were obtained by a follow-up of 3.5 years in the first group and 13 years in the second group. In our study, determination of polymorphism in the IL-10 (-1082) region in the patients who applied after the first FC was found to be a risk factor for development of epilepsy in the follow-up. Studies are needed with a higher number of cases in terms of the long-term prognosis of children with cytokines gene mutations and clarification of the etiology of epilepsy is required. Our study will lead to new studies on the formation, genetic transition, recurrence, and treatment of FC.