Susceptibility to febrile seizures: More than just a faulty thermostat!

Abstract

Febrile seizures, always a hot topic, continue to fire up the interest of a wide spectrum of clinical and basic neuroscientists. Several clinical investigators, amongst them the Halifax group (spearheaded by the Camfields to whom we owe a great debt of gratitude for their contributions in this field), have provided us with a sound foundation for clinical management. We now need to explore febrile seizures in new ways to clarify factors and identify mechanisms that contribute to the intriguing agedependent susceptibility. The complex processes involved in thermoregulation and the febrile response are important pieces of the puzzle. The contributory factors are likely different for isolated simple febrile, recurrent febrile and complex febrile seizures. A 'systems biology approach' is needed to investigate the intricate genome-proteome- metabolome interaction in determining susceptibility. Population studies that incorporate current clinical, experimental, infectious and molecular genetic knowledge in their concept and design will help to 'conquer' the final frontiers of febrile seizures. In 2006, Engel suggested that febrile seizures could 'encompass many different entities',39 an increasingly plausible opinion. A higher profile for febrile seizures and related syndromes in the ILAE classification scheme will further catalyze progress in the field. The resultant knowledge can only improve management.