Viral etiology and cytokine responses of infections leading to febrile seizures

Febrile seizures are seizures or convulsions that occur in young children during fever. The symptoms typically involve unconsciousness and stiffness or convulsions of the limbs. Febrile seizures occur in 2-5% of children before school age, usually between 6 months and 5 years old. Altogether, 20-30% of children get recurrent febrile seizures. The underlying cause of febrile seizures remains unknown, but there is genetic predisposition. Febrile seizures most commonly occur in association with typical respiratory infections. Consequently, the pathomechanism of febrile seizures includes both host-related and pathogen-related factors. The aim of this thesis was to clarify the role of viral infections and host inflammatory response, as well as their interplay in the pathomechanism of febrile seizures.

The respiratory virus study showed that febrile seizures are more likely to occur during certain respiratory viral infections. In this study, influenza viruses, coronaviruses, parainfluenza viruses, and enteroviruses caused more febrile seizure-related emergency room visits than other viruses examined. The febrile responses of children with febrile seizures were higher and more prolonged than those of febrile children without seizures with the same respiratory viral infection, suggesting that children with febrile seizures generate stronger inflammatory responses to common respiratory viral infections than children without febrile seizures.

By examining blood inflammatory mediator levels, we found evidence that children with febrile seizures produce stronger inflammatory responses specifically during febrile seizure episodes compared to febrile children without febrile seizures. There were no differences between children with febrile seizures and controls fever episodes without seizures. Our research indicated activation of the interleukin-1 inflammatory mediator axis. However, it appears that the balance of several inflammatory mediators is significant in the development of febrile seizures. The effect of individual inflammatory mediators may vary, for example, among different ethnic groups.

This thesis clarified the pathomechanism of febrile seizures, which may also help in understanding the causes of other central nervous system diseases with inflammatory components. The results of the dissertation also indicated potential targets for the prevention of febrile seizures related to controlling the pathogens and the host inflammatory response.