Uncovering the neurobehavioural comorbidities of epilepsy over the lifespan

Abstract

Epilepsy is a common neurological disorder that is complicated by psychiatric, cognitive, and social comorbidities that have become a major target of concern and investigation in view of their adverse effect on the course and quality of life. In this report we define the specific psychiatric, cognitive, and social comorbidities of paediatric and adult epilepsy, their epidemiology, and real life effects; examine the relation between epilepsy syndromes and the risk of neurobehavioural comorbidities; address the lifespan effect of epilepsy on brain neurodevelopment and brain ageing and the risk of neurobehavioural comorbidities; consider the overarching effect of broader brain disorders on both epilepsy and neurobehavioural comorbidities; examine directions of causality and the contribution of selected epilepsy-related characteristics; and outline clinic-friendly screening approaches for these problems and recommended pharmacological, behavioural, and educational interventions.

Figure 1

Theoretical framework for understanding the major mediators of the neurobehavioral comorbities of epilepsy (psychiatric, cognitive and social). The potential mediators include epilepsy syndrome, brain development and brain aging, underlying brain disorders and core epilepsy characteristics (e.g., early age of seizure onset, longer epilepsy duration, epileptiform discharges and seizure medication).

Figure 2

Altered neurodevelopmental trajectory in pediatric epilepsy. A) Gray matter pruning during normal brain development, with red areas denoting thicker and blue areas denoting thinner cortical regions. B) Children with new-onset idiopathic generalized epilepsy over prospective 2 years exhibited reduced gray matter pruning (red regions) and white matter expansion (blue regions), when compared to their healthy peers.

Figure 3

The impact of aging on brain structure and cognition. C) Accumulation of tau protein (stained with AT8) in the temporal pole (C1) hippocampus (C2) as well as inflammatory changes (stained with GFAP, C3 and HLA-DR, C4) in the hippocampus of patients with TLE. D) These age-related changes might increase epilepsy induced cognitive changes and brain atrophy, in which patients start and persist at a lower cognitive level and brain volume than healthy controls. Cognitive reserve is a potential mediator of these age-related changes. Abbreviations: TLE, temporal lobe epilepsy; CONTR, controls; AT8, anti-phosphorylated tau antibody; GFAP, glial fibrillary acidic protein; HLA, antihuman leucocyte antigen. Part A modified with permission from National Academy of Science, USA; Parts B, C, D1 modified with permission from Oxford University Press; Part D2 modified with permission from Wiley-Blackwell.