Cortical excitability correlates with seizure control and epilepsy duration in chronic epilepsy

OBJECTIVE Cortical excitability differs between treatment responders and nonresponders in new-onset epilepsy. Moreover, during the first 3 years of epilepsy, cortical excitability becomes more abnormal in nonresponders but normalizes in responders. Here, we study chronic active epilepsy, to examine whether cortical excitability continues to evolve over time, in association with epilepsy duration and treatment response. METHODS We studied 28 normal subjects, 28 patients with moderately controlled epilepsy (≤4 seizures per year) and 40 patients with poorly controlled epilepsy (≥20 or more seizures per year). Resting motor threshold (RMT), active motor threshold (AMT), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and cortical silent period (CSP) were measured, using transcranial magnetic stimulation (TMS). Disease and treatment covariates were collected (age at onset of epilepsy, epilepsy duration, number of drugs prescribed, total drug load, sodium channel drug load). RESULTS RMT and AMT were higher in patients than in normal subjects; RMT and AMT were higher in poorly controlled than moderately controlled patients. ICF at 12 msec and 15 msec were lower in poorly controlled patients than in normal subjects. Long-interval intracortical inhibition (LICI) at 50 msec was higher in poorly controlled compared to moderately controlled patients. These differences were not explained by antiepileptic drug (AED) treatment or duration of epilepsy. RMT and AMT increased with duration in the poorly controlled group, but did not increase with duration in the moderately controlled group. INTERPRETATION Cortical excitability differs markedly between moderately controlled and poorly controlled patients with chronic epilepsy, not explained by disease or treatment variables. Moreover, the evolution of cortical excitability over time differs, becoming more abnormal in the poorly controlled group.