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      Global, regional, and national burden of epilepsy, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

      research-article
      GBD 2016 Epilepsy Collaborators
      The Lancet. Neurology
      Lancet Pub. Group

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          Summary

          Background

          Seizures and their consequences contribute to the burden of epilepsy because they can cause health loss (premature mortality and residual disability). Data on the burden of epilepsy are needed for health-care planning and resource allocation. The aim of this study was to quantify health loss due to epilepsy by age, sex, year, and location using data from the Global Burden of Diseases, Injuries, and Risk Factors Study.

          Methods

          We assessed the burden of epilepsy in 195 countries and territories from 1990 to 2016. Burden was measured as deaths, prevalence, and disability-adjusted life-years (DALYs; a summary measure of health loss defined by the sum of years of life lost [YLLs] for premature mortality and years lived with disability), by age, sex, year, location, and Socio-demographic Index (SDI; a compound measure of income per capita, education, and fertility). Vital registrations and verbal autopsies provided information about deaths, and data on the prevalence and severity of epilepsy largely came from population representative surveys. All estimates were calculated with 95% uncertainty intervals (UIs).

          Findings

          In 2016, there were 45·9 million (95% UI 39·9–54·6) patients with all-active epilepsy (both idiopathic and secondary epilepsy globally; age-standardised prevalence 621·5 per 100 000 population; 540·1–737·0). Of these patients, 24·0 million (20·4–27·7) had active idiopathic epilepsy (prevalence 326·7 per 100 000 population; 278·4–378·1). Prevalence of active epilepsy increased with age, with peaks at 5–9 years (374·8 [280·1–490·0]) and at older than 80 years of age (545·1 [444·2–652·0]). Age-standardised prevalence of active idiopathic epilepsy was 329·3 per 100 000 population (280·3–381·2) in men and 318·9 per 100 000 population (271·1–369·4) in women, and was similar among SDI quintiles. Global age-standardised mortality rates of idiopathic epilepsy were 1·74 per 100 000 population (1·64–1·87; 1·40 per 100 000 population [1·23–1·54] for women and 2·09 per 100 000 population [1·96–2·25] for men). Age-standardised DALYs were 182·6 per 100 000 population (149·0–223·5; 163·6 per 100 000 population [130·6–204·3] for women and 201·2 per 100 000 population [166·9–241·4] for men). The higher DALY rates in men were due to higher YLL rates compared with women. Between 1990 and 2016, there was a non-significant 6·0% (−4·0 to 16·7) change in the age-standardised prevalence of idiopathic epilepsy, but a significant decrease in age-standardised mortality rates (24·5% [10·8 to 31·8]) and age-standardised DALY rates (19·4% [9·0 to 27·6]). A third of the difference in age-standardised DALY rates between low and high SDI quintile countries was due to the greater severity of epilepsy in low-income settings, and two-thirds were due to a higher YLL rate in low SDI countries.

          Interpretation

          Despite the decrease in the disease burden from 1990 to 2016, epilepsy is still an important cause of disability and mortality. Standardised collection of data on epilepsy in population representative surveys will strengthen the estimates, particularly in countries for which we currently have no or sparse data and if additional data is collected on severity, causes, and treatment. Sizeable gains in reducing the burden of epilepsy might be expected from improved access to existing treatments in low-income countries and from the development of new effective drugs worldwide.

          Funding

          Bill & Melinda Gates Foundation.

          Related collections

          Most cited references20

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          Global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 1970–2016: a systematic analysis for the Global Burden of Disease Study 2016

          Summary Background Detailed assessments of mortality patterns, particularly age-specific mortality, represent a crucial input that enables health systems to target interventions to specific populations. Understanding how all-cause mortality has changed with respect to development status can identify exemplars for best practice. To accomplish this, the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) estimated age-specific and sex-specific all-cause mortality between 1970 and 2016 for 195 countries and territories and at the subnational level for the five countries with a population greater than 200 million in 2016. Methods We have evaluated how well civil registration systems captured deaths using a set of demographic methods called death distribution methods for adults and from consideration of survey and census data for children younger than 5 years. We generated an overall assessment of completeness of registration of deaths by dividing registered deaths in each location-year by our estimate of all-age deaths generated from our overall estimation process. For 163 locations, including subnational units in countries with a population greater than 200 million with complete vital registration (VR) systems, our estimates were largely driven by the observed data, with corrections for small fluctuations in numbers and estimation for recent years where there were lags in data reporting (lags were variable by location, generally between 1 year and 6 years). For other locations, we took advantage of different data sources available to measure under-5 mortality rates (U5MR) using complete birth histories, summary birth histories, and incomplete VR with adjustments; we measured adult mortality rate (the probability of death in individuals aged 15–60 years) using adjusted incomplete VR, sibling histories, and household death recall. We used the U5MR and adult mortality rate, together with crude death rate due to HIV in the GBD model life table system, to estimate age-specific and sex-specific death rates for each location-year. Using various international databases, we identified fatal discontinuities, which we defined as increases in the death rate of more than one death per million, resulting from conflict and terrorism, natural disasters, major transport or technological accidents, and a subset of epidemic infectious diseases; these were added to estimates in the relevant years. In 47 countries with an identified peak adult prevalence for HIV/AIDS of more than 0·5% and where VR systems were less than 65% complete, we informed our estimates of age-sex-specific mortality using the Estimation and Projection Package (EPP)-Spectrum model fitted to national HIV/AIDS prevalence surveys and antenatal clinic serosurveillance systems. We estimated stillbirths, early neonatal, late neonatal, and childhood mortality using both survey and VR data in spatiotemporal Gaussian process regression models. We estimated abridged life tables for all location-years using age-specific death rates. We grouped locations into development quintiles based on the Socio-demographic Index (SDI) and analysed mortality trends by quintile. Using spline regression, we estimated the expected mortality rate for each age-sex group as a function of SDI. We identified countries with higher life expectancy than expected by comparing observed life expectancy to anticipated life expectancy on the basis of development status alone. Findings Completeness in the registration of deaths increased from 28% in 1970 to a peak of 45% in 2013; completeness was lower after 2013 because of lags in reporting. Total deaths in children younger than 5 years decreased from 1970 to 2016, and slower decreases occurred at ages 5–24 years. By contrast, numbers of adult deaths increased in each 5-year age bracket above the age of 25 years. The distribution of annualised rates of change in age-specific mortality rate differed over the period 2000 to 2016 compared with earlier decades: increasing annualised rates of change were less frequent, although rising annualised rates of change still occurred in some locations, particularly for adolescent and younger adult age groups. Rates of stillbirths and under-5 mortality both decreased globally from 1970. Evidence for global convergence of death rates was mixed; although the absolute difference between age-standardised death rates narrowed between countries at the lowest and highest levels of SDI, the ratio of these death rates—a measure of relative inequality—increased slightly. There was a strong shift between 1970 and 2016 toward higher life expectancy, most noticeably at higher levels of SDI. Among countries with populations greater than 1 million in 2016, life expectancy at birth was highest for women in Japan, at 86·9 years (95% UI 86·7–87·2), and for men in Singapore, at 81·3 years (78·8–83·7) in 2016. Male life expectancy was generally lower than female life expectancy between 1970 and 2016, and the gap between male and female life expectancy increased with progression to higher levels of SDI. Some countries with exceptional health performance in 1990 in terms of the difference in observed to expected life expectancy at birth had slower progress on the same measure in 2016. Interpretation Globally, mortality rates have decreased across all age groups over the past five decades, with the largest improvements occurring among children younger than 5 years. However, at the national level, considerable heterogeneity remains in terms of both level and rate of changes in age-specific mortality; increases in mortality for certain age groups occurred in some locations. We found evidence that the absolute gap between countries in age-specific death rates has declined, although the relative gap for some age-sex groups increased. Countries that now lead in terms of having higher observed life expectancy than that expected on the basis of development alone, or locations that have either increased this advantage or rapidly decreased the deficit from expected levels, could provide insight into the means to accelerate progress in nations where progress has stalled. Funding Bill & Melinda Gates Foundation, and the National Institute on Aging and the National Institute of Mental Health of the National Institutes of Health.
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            The epidemiology of the comorbidity of epilepsy in the general population.

            To describe the epidemiology of somatic and psychiatric conditions in adults with epilepsy in the community and compare it to that of people without epilepsy. A cross-sectional population-based study extracting data from the UK General Practice Research Database for the period 1995-1998. Age- and sex-standardized prevalence rates were estimated for selected conditions and groups of conditions (categorized by ICD-9 chapters) in adults with epilepsy registered with primary care physicians. Results were compared with those in adults without epilepsy in the cohort, and prevalence ratios were calculated according to two broad age groups (16-64 and older than 64 years). Conditions common in the general population also were common in adults with epilepsy. Psychiatric disorders occurred twice as often, and the risk of somatic disorders was increased in people with epilepsy, with the exception of musculoskeletal and connective tissue disorders in older adults. The prevalence ratio of neoplasia, excluding intracranial tumors, was not increased in epilepsy. The prevalence ratio of brain tumors was particularly increased in young adults [prevalence ratio (PR), 70.7] and of meningiomas in older adults (PR, 91.9). Neurodegenerative conditions, particularly dementias and Alzheimer' disease (PR, 6.3 and 8, respectively) and Parkinson' disease (PR, 3.2), appeared more frequently in people with epilepsy. Upper gastrointestinal bleed occurred more frequently in epilepsy (PR, 4.3), as did cardio- and cerebrovascular disorders, fractures, pneumonia and chronic lung diseases, and diabetes. Eczema, osteoarthritis, and rheumatoid arthritis did not occur more frequently in epilepsy. The prevalence ratio of many common psychiatric and somatic conditions is increased in adults with epilepsy who consult a primary care physician in the U.K. These findings may have implications in the diagnosis and management of epilepsy and coexisting conditions, as well as in health care provision.
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              The natural history and prognosis of epilepsy.

              Epilepsy is a brain condition characterized by the recurrence of unprovoked seizures. Generally, prognosis refers to the probability of attaining seizure freedom on treatment and little is known about the natural history of the untreated condition. Here, we summarize aspects of the prognosis and prognostic predictors of treated and untreated epilepsy and of its different syndromes. Usually, epilepsy is a fairly benign condition. Most epilepsies have a good prognosis for full seizure control and eventual discontinuation of AEDs, but epilepsy syndromes have differing outcomes and responses to treatment. Prognostic factors include aetiology, EEG abnormalities, type of seizures and the number of seizures experienced before treatment onset, and poor early effects of drugs. Early response to treatment is an important positive predictor of long-term prognosis, while the history of a high number of seizures at the time of diagnosis, intellectual disability, and symptomatic aetiology are negative predictors. Different prognostic patterns can be identified, suggesting that the epileptogenic process is not static. Epilepsy carries a greater than expected risk of premature death. Aetiology is the single most important risk factor for premature death.
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                Author and article information

                Journal
                Lancet Neurol
                Lancet Neurol
                The Lancet. Neurology
                Lancet Pub. Group
                1474-4422
                1474-4465
                1 April 2019
                April 2019
                : 18
                : 4
                : 357-375
                Author notes
                [* ]Correspondence to: Dr Ettore Beghi, Laboratory of Neurological Disorders, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, 20156 Milan, Italy ettore.beghi@ 123456marionegri.it
                [†]

                Collaborators listed at the end of the Article

                Article
                S1474-4422(18)30454-X
                10.1016/S1474-4422(18)30454-X
                6416168
                30773428
                d2bf2d97-d276-43f3-a026-5ad990e7be5f
                © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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                Neurology
                Neurology

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