Disentangling the relationship between epilepsy and its behavioral comorbidities - the need for prospective studies in new-onset epilepsies.

It has been long recognized that there is more to epilepsy than seizures. The prevalence of such neurobehavioral abnormalities as cognitive and mood disorders, autism spectrum disorder, and attention deficit and hyperactivity disorder (ADHD) is significantly higher among patients with epilepsy than in the general population. A long-held view that comorbidities of epilepsy represent mere epiphenomena of seizures has undergone substantial transformation during the past decade, as emerging clinical evidence and experimental evidence suggest the involvement of specific neurobiological mechanisms in the evolution of neurobehavioral deficits in patients with epilepsy. Developmental aspects of both epilepsy and its comorbidities, as well as the frequently reported reciprocal connection between these disorders, both add other dimensions to the already complex problem. In light of progress in effective seizure management in many patients with epilepsy, the importance of neurobehavioral comorbidities has become acute, as the latter are frequently more detrimental to patients' quality of life compared with seizures. This calls for a serious increase in efforts to effectively predict, manage, and ideally cure these comorbidities. Coordinated multicenter clinical, translational, and basic research studies focusing on epidemiology, neuropsychology, neurophysiology, imaging, genetics, epigenetics, and pharmacology of neurobehavioral comorbidities of epilepsy are absolutely instrumental for ensuring tangible progress in the field. Clinical research should focus more on new-onset epilepsy and put particular emphasis on longitudinal studies in large cohorts of patients and groups at risk, while translational research should primarily focus on the development of valid preclinical systems which would allow investigating the fundamental mechanism of epilepsy comorbidities. The final goal of the described research efforts would lie in producing an armamentarium of evidence-based diagnostic tools and therapeutic interventions which would at minimum mitigate and at maximum prevent or abolish neurobehavioral comorbidities of epilepsy and, thus, improve the quality of life of those patients with epilepsy who suffer from the said comorbidities.