Tackling Epilepsy With High-definition Precision Medicine: A Review

ImportanceVarious types of epilepsy are a leading cause of neurological disability worldwide; they have in common a propensity to recurrent unprovoked seizures. There is increasing interest in the concept of precision medicine for therapy. While treatment aimed at the level of an ion channel or single pathway has provided benefits for a small number of individuals with genetically mediated cases, a high-definition approach extending beyond genes to a broader array of personalized factors may improve outcomes. ObservationsAdvances in sequencing technologies have driven genetic discovery in epilepsy. This has provided targets for precision medicine in monogenic types of epilepsy. However, these typically represent a small subset of all types of epilepsy, and to date, precision medicine in epilepsy has primarily focused on seizure reduction. Such a unifocal view may overlook neurodevelopmental and neuropsychiatric comorbidities, which can be more challenging than the seizures themselves. Therefore, a panoramic approach to treatment encompassing both molecular diagnostic techniques and amelioration of network function by addressing factors beyond seizure reduction may be considered as part of a high-definition approach to tackling epilepsy. Conclusions and RelevanceHigh-definition medicine will require the development of analytical techniques, including artificial intelligence, that use and combine behavioral, environmental, molecular genomic, chronotype, and microbiomic data to offer the best individualized therapeutic options for disease management in each person with epilepsy. While an accurate molecular diagnosis remains the first step of the iterative process to the development of a precision medicine for an epilepsy, treatment targeted at a single molecular pathway may reduce seizure frequency but are not likely to address the multiple comorbidities associated with involved aberrant neural networks. To provide an improvement in precision medicine for epilepsy, a high-definition approach may be required that encompasses a panoramic view of factors that can be manipulated either directly or indirectly, now and in the future. This narrative review describes precision medicine derived from research that uses cellular and animal models to define the genetic factors that underlie various types of epilepsy.