Decline in seizure propensity in seizure-free patients as reflected in the evolution of the therapeutic antiepileptic drug threshold

To better understand mechanisms of remission, the decline in seizure propensity in seizure-free patients was investigated. Plasma antiepileptic drug levels were measured in 199 adults seizure-free for 2 or more years, who consented to reduction and eventual discontinuation of therapy. Among 117 patients on monotherapy, drug dosage was reduced in 82 and therapy was terminated in 35. The initial therapeutic threshold was known in 51 cases, and the new threshold was determined in all cases of relapse. Four types of evolution were observed: no decline in seizure propensity; restricted decline and relapse; greater decline but relapse; and decline below the intrinsic seizure threshold (no relapse). Patients with seizure control immediately after onset of treatment were more likely to obtain remission. Our findings indicate that in seizure-free patients, seizure propensity only rarely remains unchanged, remission is attained by both qualitative and quantitative mechanisms, and there may be different mechanisms underlying quantitative declines in seizure propensity.