Neurobehavioural comorbidities of epilepsy: towards a network-based precision taxonomy

Cognitive and behavioural comorbidities are prevalent in childhood and adult epilepsies and impose a substantial human and economic burden. Over the past century, the classic approach to understanding the aetiology and course of these comorbidities has been through the prism of the medical taxonomy of epilepsy, including its causes, course, characteristics and syndromes. Although this 'lesion model' has long served as the organizing paradigm for the field, substantial challenges to this model have accumulated from diverse sources, including neuroimaging, neuropathology, neuropsychology and network science. Advances in patient stratification and phenotyping point towards a new taxonomy for the cognitive and behavioural comorbidities of epilepsy, which reflects the heterogeneity of their clinical presentation and raises the possibility of a precision medicine approach. As we discuss in this Review, these advances are informing the development of a revised aetiological paradigm that incorporates sophisticated neurobiological measures, genomics, comorbid disease, diversity and adversity, and resilience factors. We describe modifiable risk factors that could guide early identification, treatment and, ultimately, prevention of cognitive and broader neurobehavioural comorbidities in epilepsy and propose a road map to guide future research. This Review offers a novel theoretical perspective on the neurobehavioural comorbidities of adult and childhood epilepsy, involving new analytical approaches, derivation of new taxonomies and consideration of the diverse forces that influence cognition and behaviour in individuals with epilepsy.

Automated summary

Cognitive and behavioral comorbidities are common in childhood and adult epilepsy, posing a significant burden on individuals and society. The traditional medical taxonomy approach has been challenged by advancements in neuroimaging, neuropathology, neuropsychology, and network science, leading to the development of a new taxonomy and potential precision medicine strategies for addressing these comorbidities.