PHARMACO-RESISTANT EPILEPSY: UNDERLYING MECHANISMS TREATMENT OPTIONS

摘要

Epilepsy is the moet mmon chronic neurological disorder in both humans and dogs (Chandler, 2006). Most epileptic dogs are treaed successfully for life, with the standard seizure suppressing drugs ("antiepileptic drugs", AEDs) phenobarbitone (PB) and/or potassium bromide (KBr). However, in about 20-30% of treated dogs, seizures are poorly responsive to treatment with a combination of PB and KBr (Schwartz-Porsche et al., 1985; Podell and Fenner, 1993; Trepanier et al., 1998). Increasing the dosage of PB and KBr may improve seizure control but this is not always possible due to side-effects and toxicity (e.g. polyuria/polydipsia, polyphagia, ataxia, lethargy and hepatotoxicity) (Dewey, 2006). In human medicine there has been progress in developing better tolerated epilepsy treatment over recent decades (Beghi, 2004; Rogawski and Loscher, 2004). Conversely, in veterinary medicine there is still a lack of data concerning new treatment options for epileptic patients, especially for pharmacoresistant patients. Many of the newer AEDs that show some effect and are well tolerated in humans (Beghi, 2004), are not efficacious in small animals due to inappropriate pharmacokmetics or life-threatening side-effects; these include vigabatrin, lamotrigine, tiagabine, oxcarbazepine (Podell, 1998).