A prospective, long-term population-based study was performed to determine whether seizure clustering (3 or more afebrile seizures during a 24 hour period) is associated with drug resistance and increased mortality in childhood-onset epilepsy, in a study at University of Turku, Finland, and the Epilepsy Research Group, Berlin, Germany. At an average 37 years follow-up, 26 (22%) of 120 childhood-onset epilepsy patients had recorded clusters of seizures. Patients with clusters had at least one seizure per week at the initial stage in 63% vs 32% of those without clusters (P=0.0178) and during follow-up. During drug therapy, patients with clusters were (1) more likely to have drug resistant epilepsy compared to those without (42% vs 13%, P=0.01); (2) less likely to enter 5-year remission (P=0.0230); and (3) had a higher risk of death (42% vs 14%, P=0.0299). In contrast, patients with seizure clustering before but not during treatment showed no difference in seizure outcome or mortality risk. The causes of death included dissection of the aorta and pneumonia (nonepilepsy related), and accidental drowning, and SUDEP. Five of the patients with clusters during treatment died, whereas none with pre-treatment clusters died. 
COMMENT. Clustering of seizures during treatment is associated with a less favorable long-term outcome compared to clustering prior to treatment. Patients with seizure clustering during treatment compared to those without are four times more likely to have drug resistant epilepsy and an increased risk of mortality. Patients with clustering before beginning treatment is not associated with a poor prognosis. Clustering was not associated with status epilepticus in this study. The authors favor trials of aggressive treatment of seizure clustering.