Long-term neuroplasticity effects of febrile seizures in the developing brain

Febrile seizures (FS) are the most common seizure disorder in childhood, occurring in 2%-5% of children. Regarding the large number of children with FS, it is important to delineate whether early-life FS alters long-term neuroplasticity, especially the neurocognitive function and subsequent temporal lobe epilepsy (TLE). Recent epidemiological studies reassure that most FS do not adversely affect global intelligence and hippocampal function, such as memory. However, there are concerns regarding those children who experience FS during the first postnatal year, having prior developmental delay and pre- or peri-natal events. The epidemiological data do not support a causal relationship between FS and TLE. However, magnetic resonance imaging studies confirmed that prolonged and focal FS can occasionally produce acute hippocampal injury that evolves into atrophy. Moreover, the common coexistence of hippocampal sclerosis and asymmetric cortical dysgenesis in TLE patients argues for a 'double-hit' theory for TLE. Animal studies have revealed that the exposure of hippocampal neurons to FS early in life, particularly prolonged or frequently repetitive FS, or together with brain malformation, may lead to sustained dysfunction of these cells including long-term memory impairment or epileptogenesis, in spite of the absence of neuronal damage. Recent clinical and molecular genetic studies suggest that the relationship between FS and later epilepsy is frequently genetic, and there are a number of syndrome-specific genes for FS. However, these channelopathies account for a small proportion of FS cases. The clinical management, therefore, is based mainly on the phenotypic features of FS and the subsequent seizures.