The aging brain and late onset drug-refractory epilepsies

While late-onset epilepsies are characterized by a good pharmacoresponsiveness, a relevant subgroup of this patient population suffers from drug-refractory epilepsy with its impact on overall quality of life and a high risk of seizure-related injuries. Particular attention should be paid to accurate diagnosis and thorough exclusion of pseudoresistance. Challenges include the likelihood of multimorbidities and polypharmacotherapy in an elderly patient population. Network, cellular, molecular, and metabolic alterations associated with aging and age-related disorders have the potential to affect the intrinsic severity of late-onset epilepsies, neural network function, and the pharmacodynamics and pharmacokinetics of antiseizure medications (ASMs). Whereas age-related changes in pharmacokinetics tend to favor responsiveness to low doses, respective changes in network excitability and pharmacodynamics of ASMs are more likely to contribute to drug resistance. There are particular gaps in our knowledge of the mechanisms of drug resistance and the impact of influencing factors in this patient population. Therefore, experimental and clinical research needs to be intensified to advance our understanding of drug-resistant epilepsy in patients with late-onset epilepsies and to develop multivariate prediction algorithms. In this context, the heterogeneity of an elderly patient population should be taken into account, considering differences in etiology, comorbidities, co-medications, frailty, activity and environmental factors.