The mechanisms of medically refractory temporal lobe epilepsy.

The mechanisms underlying the refractory temporal lobe epilepsy (TLE) are not well understood. Several explanations for refractory TLE are (1) an overexpression of P-glycoprotein (P-gp) encoded by multiple drug resistance 1 (MDR1) gene and other efflux transporters such as multidrug resistance protein (MRP) in the cerebrovascular endothelium in or around the region of the epileptic focus may lead to drug resistance in epilepsy; (2) the loss of antiepileptic drug sensitivity at certain target sites in the brain, including the sodium ion channel and the gamma aminobutyric acid (GABA)A receptor; and (3) seizures beget seizures by means of a cascade of events that include various types of neuronal damage, sprouting of neuronal axons and new synapse formations that establish aberrant glutamatergic synapses. TLE may be a progressive neurological disorder that requires early and effective treatment. Early recognition of refractory TLE and referral for epilepsy surgery may prevent years of unnecessary seizure activity and its consequences.