Seizure clustering during drug treatment affects seizure outcome and mortality of childhood-onset epilepsy

To provide evidence of whether seizure clustering is associated with drug resistance and increased mortality in childhood-onset epilepsy, a prospective, long-term population-based study was performed. One hundred and twenty patients who had been followed since disease onset (average age 37.0 years, SD 7.1, median 40.0, range 11-42; incident cases) were included. At the end of the follow-up period, 26 (11 boys) of these patients (22%) had recorded clusters of seizures. Fourteen recorded pre-treatment clusters, including 10 patients with clusters as first seizures; and in 12 patients, clusters occurred during treatment. In these 12 patients, first clustering began after 16 (range 0-35; median 15) years of treatment. Compared with the patients without clusters, those with clusters more often had at least one seizure per week at the initial stage (63% versus 32%, P = 0.0178) and during the follow-up period (P-value varied from 0.0464 to 0.0064). Patients having seizure clusters during drug therapy were more likely to have drug resistant epilepsy compared to those not experiencing seizure clusters (42% versus 13%; P = 0.0102) and had a lower rate of entering 5-year terminal remission (P = 0.0039) and 5-year remission (P = 0.0230). In addition, the risk of death was significantly increased among patients with seizure clusters during drug therapy compared with those who had not experienced any clustering (42% versus 14%; P = 0.0299 two-sided Fisher's exact test). The risk ratio for patients with clusters was 3.49 (95%CI 1.25-9.78). In contrast, patients with seizure clustering prior to, but not during, treatment versus those with no clustering showed no difference in seizure outcome or mortality risk. In conclusion, clustering of seizures during treatment, but not prior to treatment, is associated with a poorer long-term seizure and mortality outcome.