Mechanisms of epileptogenesis

Epileptogenesis is the process by which the brain develops epilepsy, often divided into:^2,3

• Acute insult (e.g., head injury, febrile seizures)
• A latent period, lasting months or sometimes years
• Spontaneous seizures

Epileptogenesis appears to be driven by a wide array of changes to neuronal and non-neuronal cells, at the levels of the cell, the pathways within the cell, and genetics.¹ The cause of epilepsy in many cases is unknown, but several factors are known to trigger seizures (e.g., stroke, infections, and inflammation), as well as genetic causes – there are >500 genes that have been associated with epilepsy and an increased risk of epilepsy.¹

Many neurophysiological changes occur within the brain during seizures, a range of interacting changes including some that compensate for others, which together drive epilepsy pathology.¹ The wideness of the range of known epileptogenic mechanisms suggests a complex web of interacting pathology that drives the development of epilepsy.¹ DNA=deoxyribonucleic acid; JAK-STAT=Janus kinase – signal transducer and activator of transcription; mTOR=mechanistic target of rapamycin; REST=RE1‑silencing transcription factor; RNA=ribonucleic acid; TGFβ=transforming growth factor-β