Drug-resistant epilepsy is associated with a significant increase in mortality that persists for decades after diagnosis, particularly among individuals with a known etiology, according to data from a retrospective, multicenter cohort study.
Dr. Brian Callaghan of the University of Michigan, Ann Arbor, and his colleagues identified 433 patients with drug-resistant epilepsy, which was defined as one or more seizures per month for 3 months prior to inclusion and failure on at least two antiepileptic drugs prior to the index date.
The authors said that a consensus exists, based on previous studies, that patients with epilepsy have increased mortality, compared with the general population. However, these studies also suggest that this mortality decreases over time.
"Ours is a prevalent cohort of drug-resistant epilepsy, and mortality was evaluated after the period of increased mortality risk in an incident cohort with epilepsy (i.e., the first 5 years after diagnosis)," the investigators wrote in their report.
"In our study, we also demonstrate increased mortality. Thus, in this group with a median duration of epilepsy at entry of 25 years, elevated mortality persists."
Over the 6-year follow-up period, there were 33 deaths (7.6%). However, in patients with a known etiology, the case fatality rate was 10.1%, compared with 5.1% among patients with unknown etiology, the researchers reported (J. Neurol. Neurosurg. Psychiatry 2014 Feb. 19 [doi:10.1136/jnnp-2013-307074]).
Among those whose epilepsy had a known etiology, the case fatality rate was 45.5% for progressive etiologies and 8.2% for remote etiologies (P less than .001).
The standardized mortality ratio for the entire cohort was 2.4 (95% confidence interval, 1.7-3.3), while for those with a remote or progressive etiology, the ratio was 3.1 (95% CI, 2.0-4.6), and 1.7 (95% CI, 0.8-2.8) for those with an unknown etiology.
The majority of patients had focal epilepsy (82.5%), 10.6% had symptomatic generalized epilepsy, 5.8% had genetic generalized epilepsy, and 1.2% had another epilepsy syndrome.
Ten of the 33 deaths were definitely or potentially epilepsy related, including 5 cases of sudden unexplained death in epilepsy (3 with unknown and 2 with known etiology), 3 cases of status epilepticus, 1 accident, and 1 suicide.
Ten patients who died had known active cancer at the index date, two other patients had known neurodegenerative conditions, and seven deaths were linked to the underlying cause of the epilepsy such as brain tumors and strokes.
The remaining 16 deaths were unrelated to epilepsy or the underlying etiology.
"The two clinical factors associated with an increased risk of death were older age at study entry and ‘symptomatic generalized epilepsy syndrome’ (in pre-2010 terminology)," the researchers wrote.
"Gender, age of epilepsy onset, and number of [antiepileptic drugs] failed were not associated with mortality, providing further evidence that epilepsy syndrome and etiology are the most important risk factors for death."
The authors also noted that in 11 of the 33 deaths, the epileptologist did not know that the patient had died, and 12% of patients recorded on their medical charts as lost to follow-up were in fact dead.
Some authors reported grant funding and support from a range of pharmaceutical companies, including Lundbeck, Vertex Pharmaceuticals, SK Life Science, Pfizer, Medtronic, GlaxoSmithKline, Eisai, Cyberonics, Neuropace, and Upsher-Smith.