The mechanisms of epileptogenesis in pediatric
epileptic syndromes are diverse, and may involve disturbances of neurodevelopmental trajectories, synaptic homeostasis, and cortical connectivity, which may occur during brain development, early infancy, or childhood. Although genetic or structural/metabolic factors are frequently associated with age-specific
epileptic syndromes, such as
infantile spasms and
West syndrome, other syndromes may be determined by the effect of immunopathogenic mechanisms or energy-dependent processes in response to environmental challenges, such as
infections or
fever in normally-developed children during early or late childhood. Immune-mediated mechanisms have been suggested in selected pediatric
epileptic syndromes in which acute and rapidly progressive
encephalopathies preceded by
fever and/or
infections, such as febrile
infection-related
epilepsy syndrome, or in chronic progressive
encephalopathies, such as
Rasmussen encephalitis. A definite involvement of adaptive and innate immune mechanisms driven by cytotoxic CD8(+) T lymphocytes and neuroglial responses has been demonstrated in
Rasmussen encephalitis, although the triggering factor of these responses remains unknown. Although the beneficial response to
steroids and
adrenocorticotropic hormone of
infantile spasms, or preceding
fever or
infection in FIRES, may support a potential role of
neuroinflammation as pathogenic factor, no definite demonstration of such involvement has been achieved, and genetic or metabolic factors are suspected. A major challenge for the future is discovering pathogenic mechanisms and etiological factors that facilitate the introduction of novel targets for
drug intervention aimed at interfering with the disease mechanisms, therefore providing putative disease-modifying treatments in these pediatric
epileptic syndromes.