Pharmakoresistence – view of the clinician

Children and adolescents have a pharmakoresistent epilepsy in such cases, in which epileptic seizures can not sufficiently be managed by application of antiepileptic drugs. This is also the case when the successful anticonvulsant treatment negatively influences the somatic, cognitive, psychic and/or social development and relevant side effects occur. A prerequisite of the antiepileptic pharmacotherapy is the correct, sufficiently high dosed, seizure- and syndrome-adequate medication. Epilepsy surgery with resection of the epileptogenic brain lesion is the therapy of first choice for pharmacoresistent symptomatic epilepsies. Whether pharmacoresistence is defined after treatment with two, three or more drugs, given as mono- or polytherapy, has to be considered in individual cases and remains arbitrary. If there is a clear indication for epilepsy surgery with congruent findings of the semiology, of the EEG and (MR-) imaging findings in non-eloquent brain areas, the lesionectomy should not be delayed. Etiopathogenetically, there are age-, syndrome-specific, metabolic, patient-related and other so far unknown categories of pharmacoresistent epilepsies. Age- and syndrome-specific epilepsies are e.g. the Pseudo-Lennox-, the Dravet-, the PEHO-syndrome, the malignant migrating epilepsy of infancy and several kryptogenic focal epilepsies (e.g. of frontal lobe). Metabolic epilepsies are seen e.g. in the neuronal lipofuscinoses and sulfit-oxidase deficiency. The induction of drug transporters in the blood brain barrier leads to increased excretion of (antiepileptic) drugs from the brain and pharmacoresistence. Despite treatment with new antiepileptic drugs there still are patients with pharmacoresistent epileptic status and fatal prognosis, often without etiopathogenetic diagnosis. The knowledge of the balance of inhibitory and excitatory mechanisms in the developing brain has increased multifold during the last years, nevertheless many of the basic principles of pharmacoresistence in (pediatric) epileptology are still unknown.