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WHAT ADVANCEMENTS IN CLINICAL NEUROSCIENCES NEED TO OCCUR IN THE NEXT 10 YEARS?

Introduction: Temporal lobe epilepsy (TLE) is the commonest focal epilepsy. Acquired TLE is considered to occur as the result of a 3-phase process called epileptogenesis. Firstly, an ‘epileptogenic event’ occurs, for example traumatic brain injury. Next follows a latent period whereby hyperexcitable networks form and lower the seizure threshold. Finally, TLE emerges. The objective of this review is to investigate how gene dysregulation drives hyperexcitability during epileptogenesis. Methods: Searches were conducted using keywords and medical subject headings on bibliographic databases and complemented by Google searches and manual revision of reference lists of retrieved articles. Results: Multiple pathogenic processes occur during the latent phase of epileptogenesis, before acquired TLE is diagnosed. These are hippocampal sclerosis, synaptic reorganisation including mossy fibre sprouting, neuroinflammation, aberrant neurogenesis and astrogliosis. Furthermore, epigenetic signalling pathways including DNA methylation, histone modifications, transcriptional and post-transcriptional dysregulation drive these pathogenic brain changes. Discussion: The epigenetic pathways that drive pathogenic brain changes following epileptogenic events are potential therapeutic targets for novel antiepileptic drugs. Targeting molecular pathways could prevent many cases of acquired TLE by halting epileptogenesis in the latent phase, meaning new therapies for acquired TLE have the potential to be antiepileptogenic rather than simply anticonvulsant.