Seizure control and mortality in epilepsy

Abstract

Mortality rates are increased among people with epilepsy, and may be highest in those with uncontrolled seizures. Because epilepsy surgery eliminates seizures in some people, we used an epilepsy surgery population to examine how seizure control influences mortality. We tested the hypothesis that patients with complete seizure relief after surgery would have a lower mortality rate than those who had persistent seizures. Three hundred ninety‐three patients who had epilepsy surgery between January 1986 and January 1996 were followed after surgery to assess long‐term survival; 347 had focal resection or transection, and 46 had anterior or complete corpus callosotomy. A multivariate survival analysis was performed, contrasting survival in those who had seizure recurrence with survival of those who remained seizure free. Standardized mortality ratios and 95% confidence intervals were calculated. Overall, seizure‐free patients had a lower mortality rate than those with persistent seizures. This was true for the subset of patients with localized resection or multiple subpial transection. No patients died among 199 with no seizure recurrence, whereas of 194 patients with seizure recurrence, 11 died. Six of the deaths were sudden and unexplained. Most patients who died had a substantial reduction in postoperative seizure frequency. The standardized mortality ratio for patients with recurrent seizures was 4.69, and the risk of death in these patients was 1.37 in 100 person‐years, whereas among patients who became seizure free, there was no difference in mortality rate compared with the age‐ and sex‐matched population of the United States. Elimination of seizures after surgery reduces mortality rates in people with epilepsy to a level indistinguishable from that of the general population, whereas patients with recurrent seizures continue to suffer from high mortality rates. This suggests that uncontrolled seizures are a major risk factor for excess mortality in epilepsy. Achieving complete seizure control with epilepsy surgery in refractory patients reduces the risk of death, so the long‐term risk of continuing medical treatment appears to be higher than the risk of epilepsy surgery in suitable candidates. Ann Neurol 1999;46:45–50

Temporal Lobe Epilepsy Surgery: Outcome, Complications, and Late Mortality Rate in 215 Patients

“…Previous authors also reported that late mortality was associated with persistent seizures after surgery. Sperling et al (4,12) reported that seizure-free patients had a lower mortality rate than those with persistent seizures. Vickrey (3) studied the mortality rate in patients who had diagnostic evaluations for epilepsy surgery, and found that "surgery patients" had significantly lower mortality at an average follow-up of 6 years compared with nonsurgical patients."…”

Evolution of cranial epilepsy surgery complication rates: a 32-year systematic review and meta-analysis

“…5,8,82,90 Uncontrolled seizures are also associated with an elevated risk for sudden unexpected death in epilepsy (SUDEP). 32,59,75 Pharmacological approaches to reducing seizure frequency, while effective in many cases, are dependent on continued drug compliance through out the course of a person's life. Additionally, in approximately 30%-40% of patients, the epilepsy is pharmacoresistant.…”

The pilocarpine model of epilepsy: what have we learned?

“…The National General Practice Study of Epilepsy (NG-PSE), a community-based study in the United Kingdom, saw the first case of SUDEP after 11,000 person-years of follow-up (Lhatoo and Sander 2001), and the results of the Medical Research Council Antiepileptic Drug Withdrawal Study showed that SUDEP is a rare event among patients with epilepsy in remission (1991). Information concerning risk factors for SUDEP is conflicting, but potential risk factors include: early adulthood, early onset of epilepsy (Nilsson et al 1999), long duration of epilepsy (Walczak et al 2001), uncontrolled seizures (mainly in those with TLE) (Walczak et al 2001, Sperling et al 1999, high seizure frequency (Walczak et al 2001, Langan et al 2005, certain seizure types (Walczak et al 2001, Kloster andEngelskjon 1999), higher numbers of AED (Nilsson et al 1999, Walczak et al 2001) and winter temperatures (Scorza et al 2007). Additionally, potential pathomechanisms for SUDEP are unknown, but it is very probable that cardiac arrhythmias during and between seizures, electrolyte disturbances, arrhythmogenic drugs or transmission of epileptic activity to the heart via the autonomic nervous system potentially play a role for SUDEP (Stollberger and Finsterer 2004).…”