33 Mortality in Epilepsy

Elizabeth J. Donner

Division of Neurology, Department of Paediatrics, The Hospital for Sick Children
University of Toronto, Toronto, Ontario, Canada

Introduction

Although most people with epilepsy live long lives, their risk of a premature death is increased compared to that of the general population. Both the Joint American Epilepsy Society/Epilepsy Foundation Task Force and the UK National Institute of Clinical Excellence Guidelines recommend that physicians discuss the risk of premature mortality with people with epilepsy as part of the delivery of comprehensive epilepsy education. A critical review of the relevant literature, including population-based studies and reports on epilepsy subgroups, is necessary to inform discussions of mortality with patients and their families.

TIPS AND TRICKS

Despite the apprehension physicians feel about discussing mortality with their patients, people with epilepsy and their families report that they want to discuss mortality, especially the difficult issue of sudden unexpected death in epilepsy (SUDEP), with their physicians. There are several opportunities to discuss mortality and SUDEP in the course of epilepsy care. For example, upon witnessing a seizure, family members often wonder whether a seizure may be fatal, and they may initiate the conversation. A simple message can be used: Although people with epilepsy are at an increased risk of premature death, the best way to reduce that risk is to work with the healthcare team to reduce seizures.

People with epilepsy have a two to three times increased risk of premature death

Population-based studies have demonstrated that people with epilepsy have a two to three times increased risk of premature death compared with that of the general population. A UK study that followed more than 1000 people for a median followup of greater than 20 years calculated an overall standardized mortality ratio (SMR) of 2.2. A similar study evaluated risk in people with chronic epilepsy of at least 4 years’ duration and those with newly diagnosed epilepsy. In that study, the SMR was 3.1 for the chronic epilepsy group and 2.6 for the new-onset epilepsy group.

Standard mortality ratios are significantly higher for children than for adults with epilepsy, ranging from 5.3 to 9.0. The higher rate reflects the high mortality among children with significant neurological impairment as well as the overall lower mortality rate among children in the general population.

SCIENCE REVISITED

Study design determines how mortality is measured and reported. Population-based studies aim to include all people with epilepsy in a defined geographic area. These studies compare the rate of death among people with epilepsy to the rate of death in the general population as a standardized mortality ratio (SMR). The SMR is the ratio of observed deaths in the study population to expected deaths among people of the same age and sex in the general population. When there is no increased rate of death compared to the general population, the SMR equals one. It is only possible to calculate an SMR if there is available information about a reference population.

Cohort studies often report case fatality rates that describe the rate of death in a specific group. For example, a study may report a 12% case fatality among 120 adults who presented with status epilepticus, which means that 12% of the subjects died. Many studies report rates of death in person-years. One person-year is equal to one person living with epilepsy for 1 year. For example, the rate of SUDEP is estimated to be 1 in 1000 person-years. This means that if we follow 1000 people with epilepsy for 1 year, one will die of SUDEP.

Another way to describe premature mortality is to consider the life expectancy of people with epilepsy compared to that of people of the same age and sex in the general population. The life expectancy of people with idiopathic epilepsy is possibly reduced by up to 2 years, and the life expectancy of people with a symptomatic epilepsy can be reduced by as much as 10 years. Reduction in life expectancy declines over the duration of epilepsy. The longer a person survives with epilepsy, the higher the likelihood of survival.

In resource-poor areas of the world, the SMRs for people with epilepsy are even higher. For example, a study from rural China determined an SMR of 4.92, significantly higher than the SMR for epilepsy in European and North American studies. In the rural Chinese cohort, drowning was the leading cause of death.

Risk factors for mortality in epilepsy

The strongest predictor of mortality in people with epilepsy is seizure etiology. Most of the increased risk of death in people with epilepsy is attributable to the inclusion of those with a secondary or symptomatic epilepsy (Table 33.1).

There is conflicting evidence on the risk of premature mortality in people with idiopathic epilepsy, as some studies have failed to demonstrate an increase in risk. Mortality risk in idiopathic epilepsy may occur later, as demonstrated by a large UK cohort in which followup at 14 years did not demonstrate an elevated SMR; however, when followup was extended up to 25 years, the SMR was elevated.

Beyond symptomatic etiology, the strongest risk factor for premature mortality is ongoing, persistent, poorly controlled seizures. Failure to obtain 5-year seizure remission was found to be the strongest risk factor for death by any cause in a long-term follow-up study of childhood-onset epilepsy. Younger age and recent diagnosis of epilepsy also increase risk. Nonadherence to antiepileptic drug (AED) therapy has been shown to be a significant risk factor, with an over three times increased risk of mortality.

Many other factors have been studied with conflicting results. Several reports suggest that males are at greater risk. In addition, generalized tonic–clonic seizures may increase risk; however, complex partial and myoclonic seizures have also been shown to increase risk, which is likely related to their underlying causes. Many factors that are associated with symptomatic epilepsy, such as cognitive impairment or developmental delay, and an abnormal neurological examination have also been found to increase mortality risk