Developing precision treatments for epilepsy using patient and animal models.

ABSTRACT

Introduction: Phenytoin was the first antiepileptic drug (AED) discovered in an animal model of seizures whose clinical efficacy was subsequently confirmed. This clearly indicated that a search for other AEDs had to consider animal studies.Areas covered Main seizure tests used for the evaluation of possible anticonvulsive activity of potential anticonvulsants and their predictive values have been reviewed. Procedures used for the estimation of antiepileptogenic effects have been also included.Expert opinion First-line seizure models comprise maximal electroshock (MES)-, pentylenetetrazol (PTZ)- and kindling-induced convulsions in rodents. The MES test may be considered as a convenient and easy model of generalized tonic-clonic seizures, PTZ test - as a model of generalized myoclonic seizures and to a certain degree - absence seizures. Kindled seizures (for example, from amygdala) may be regarded as a model of focal seizures. Some tests have been suggested for the search of AEDs effective in drug-resistant seizures - for instance, 6 Hz (44 mA) test or intrahippocampal kainate model of mesial temporal lobe epilepsy. There are also recommendations from experimental epileptology on synergistic AED combinations for patients with drug-resistant seizures. The clinical evidence on this issue is scarce and favors a combined treatment with valproate + lamotrigine.