Premature mortality of epilepsy in low‐ and middle‐income countries: A systematic review from the Mortality Task Force of the International League Against Epilepsy

Abstract

SUMMARYTo determine the magnitude of risk factors and causes of premature mortality associated with epilepsy in low-and middle-income countries (LMICs). We conducted a systematic search of the literature reporting mortality and epilepsy in the World Bank-defined LMICs. We assessed the quality of the studies based on representativeness; ascertainment of cases, diagnosis, and mortality; and extracted data on standardized mortality ratios (SMRs) and mortality rates in people with epilepsy. We examined risk factors and causes of death. The annual mortality rate was estimated at 19.8 (range 9.7-45.1) deaths per 1,000 people with epilepsy with a weighted median SMR of 2.6 (range 1.3-7.2) among higherquality population-based studies. Clinical cohort studies yielded 7.1 (range 1.6-25.1) deaths per 1,000 people. The weighted median SMRs were 5.0 in male and 4.5 in female patients; relatively higher SMRs within studies were measured in children and adolescents, those with symptomatic epilepsies, and those reporting less adherence to treatment. The main causes of death in people with epilepsy living in LMICs include those directly attributable to epilepsy, which yield a mean proportional mortality ratio (PMR) of 27.3% (range 5-75.5%) derived from population-based studies. These direct causes comprise status epilepticus, with reported PMRs ranging from 5 to 56.6%, and sudden unexpected death in epilepsy (SUDEP), with reported PMRs ranging from 1 to 18.9%. Important causes of mortality indirectly related to epilepsy include drowning, head injury, and burns. Epilepsy in LMICs has a significantly greater premature mortality, as in high-income countries, but in LMICs the excess mortality is more likely to be associated with causes attributable to lack of access to medical facilities such as status epilepticus, and preventable causes such as drowning, head injuries, and burns. This excess premature mortality could be substantially reduced with education about the risk of death and improved access to treatments, including AEDs. Key Points • Mortality in people with epilepsy in low-and middleincome countries (LMICs) is estimated to be 2.6-fold higher (range 1.3-7.2) than in general populations of LMICs• The main causes of death in people with epilepsy in LMICs are epilepsy-related complications, that is, status epilepticus, SUDEP, and injuries• Estimates of the public health burden of epilepsyrelated mortality are higher in LMICs than estimates from high-income countries• Insufficient studies of good quality, high heterogeneity, and underrepresentation of diverse LMIC economies and culture were the main limitations of this systematic review• Improving access to medical facilities and antiepileptic drugs, and preventing injuries may substantially reduce premature mortality in epilepsy in LMICs Standardized mortality in people with epilepsy in highincome countries (HICs) is estimated to be up to 4-15 times higher than in the general population in community-based studies and selected high-risk populations, respectively.

Mortality in children with cerebral palsy in rural Bangladesh: a population‐based surveillance study

“…In our cohort, nine children who had died had epilepsy and one died from accidental drowning. Drowning is considered one of the indirect causes of premature mortality in children with epilepsy in LMICs …”

Aging and the Epidemiology of Epilepsy

“…The decreasing mortality of epilepsy in the oldest ages can be explained by the competitive role of other clinical conditions leading to death in aged individuals. Highest SMRs in the youngest age groups were also found in low-income countries, with a continuing decline with increasing age [24]. However, in these countries, data were insufficient to characterize the risk of mortality by age of epilepsy onset.…”

Mortality and morbidity of patients with treated and untreated epilepsy in New Zealand

“…Epilepsy affects 70 million people worldwide . People with epilepsy have increased mortality and more physical and psychological comorbidities . In high‐income countries, their mortality rates are 1.6‐3.0 times higher than the general population, and up to 7.2 times higher in low‐ and middle‐income countries .…”

“…People with epilepsy have increased mortality and more physical and psychological comorbidities . In high‐income countries, their mortality rates are 1.6‐3.0 times higher than the general population, and up to 7.2 times higher in low‐ and middle‐income countries . A substantial proportion of people with epilepsy are either not treated or have delayed antiseizure medication (ASM) treatment .…”