Josemir W. Sander

The global burden and stigma of epilepsy

Epilepsy is one of the most prevalent neurological conditions and it knows no age, racial, social class, geographic, or national boundaries. The impact of epilepsy rests not only on the individual patient, but also on the family and indirectly on the community. The burden of epilepsy may be due to the physical hazards of epilepsy resulting from the unpredictability of seizures; the social exclusion as a result of negative attitudes of others toward people with epilepsy; and the stigma, as children with epilepsy may be banned from school, adults may be barred from marriage, and employment is often denied, even when seizures would not render the work unsuitable or unsafe. Furthermore, epilepsy is a disorder associated with significant psychological consequences, with increased levels of anxiety, depression, and poor self-esteem compared with people without this condition. Here we discuss some of the aspects of the global burden of epilepsy.

Estimation of the burden of active and life-time epilepsy: A meta-analytic approach

Purpose:  To estimate the burden of lifetime epilepsy (LTE) and active epilepsy (AE) and examine the influence of study characteristics on prevalence estimates.

Standards for epidemiologic studies and surveillance of epilepsy

Worldwide, about 65 million people are estimated to have epilepsy. Epidemiologic studies are necessary to define the full public health burden of epilepsy; to set public health and health care priorities; to provide information needed for prevention, early detection, and treatment; to identify education and service needs; and to promote effective health care and support programs for people with epilepsy. However, different definitions and epidemiologic methods complicate the tasks of these studies and their interpretations and comparisons. The purpose of this document is to promote consistency in definitions and methods in an effort to enhance future population‐based epidemiologic studies, facilitate comparison between populations, and encourage the collection of data useful for the promotion of public health. We discuss: (1) conceptual and operational definitions of epilepsy, (2) data resources and recommended data elements, and (3) methods and analyses appropriate for epidemiologic studies or the surveillance of epilepsy. Variations in these are considered, taking into account differing resource availability and needs among countries and differing purposes among studies.

The psychiatric comorbidity of epilepsy

Several studies have assessed the prevalence of psychiatric disorders in epilepsy. They are characterized by considerable heterogeneity, because of differences in the population setting and type of study. A non‐systematic review of the literature allows us to draw some useful, although not definite, conclusions. Six per cent of people with epilepsy in the general population appear to suffer from a psychiatric disorder, while this rises to 10–20% in populations with temporal lobe and/or refractory epilepsy. Mood disorders are the most common culprit (24–74%), particularly depression (30%), followed by anxiety disorders (10–25%), psychoses (2–7%) and personality disorders (1–2%). This comorbidity appears to be related to endogenous and exogenous (including iatrogenic) factors and to the severity and chronicity of epilepsy. Conditions such as schizophrenia‐like psychosis of epilepsy and interictal dysphoric disorder are represented only in epilepsy. Adequate recognition and treatment of psychiatric conditions in epilepsy is essential for patient management because of their considerable burden in morbidity and quality of life.

The Epidemiology of the Comorbidity of Epilepsy in the General Population

Summary:  Purpose: 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.

The long-term outcome of adult epilepsy surgery, patterns of seizure remission, and relapse: a cohort study

BACKGROUND Surgery is increasingly used as treatment for refractory focal epilepsy; however, few rigorous reports of long-term outcome exist. We did this study to identify long-term outcome of epilepsy surgery in adults by establishing patterns of seizure remission and relapse after surgery. METHODS We report long-term outcome of surgery for epilepsy in 615 adults (497 anterior temporal resections, 40 temporal lesionectomies, 40 extratemporal lesionectomies, 20 extratemporal resections, 11 hemispherectomies, and seven palliative procedures [corpus callosotomy, subpial transection]), with prospective annual follow-up for a median of 8 years (range 1-19). We used Kaplan-Meier survival analysis to estimate time to first seizure, and investigated patterns of seizure outcome. FINDINGS We used survival methods to estimate that 52% (95% CI 48-56) of patients remained seizure free (apart from simple partial seizures [SPS]) at 5 years after surgery, and 47% (42-51) at 10 years. Patients who had extratemporal resections were more likely to have seizure recurrence than were those who had anterior temporal resections (hazard ratio [HR] 2·0, 1·1-3·6; p=0·02); whereas for those having lesionectomies, no difference from anterior lobe resection was recorded. Those with SPS in the first 2 years after temporal lobe surgery had a greater chance of subsequent seizures with impaired awareness than did those with no SPS (2·4, 1·5-3·9). Relapse was less likely the longer a person was seizure free and, conversely, remission was less likely the longer seizures continued. In 18 (19%) of 93 people, late remission was associated with introduction of a previously untried antiepileptic drug. 104 of 365 (28%) seizure-free individuals had discontinued drugs at latest follow-up. INTERPRETATION Neurosurgical treatment is appealing for selected people with refractory focal epilepsy. Our data provide realistic expectations and indicate the scope for further improvements in presurgical assessment and surgical treatment of people with chronic epilepsy. FUNDING UK Department of Health National Institute for Health Research (NIHR) Biomedical Research Centres funding scheme, Epilepsy Society, Dr Marvin Weil Epilepsy Research Fund.

Some Aspects of Prognosis in the Epilepsies: A Review

The traditional view that epilepsy is usually a chronic condition in which the prognosis is consistently poor has been challenged in the last 2 decades. Evidence from population‐based studies and from intervention studies in newly diagnosed patients has produced a wealth of information of a much better prognosis. It is now generally accepted that as many as 70–80% of people developing seizures for the first time will eventually achieve terminal remission, whereas the remaining 20–30% will continue to have recurrent seizures despite all treatment. Despite the high recurrence rate after a first epileptic seizure, remission usually occurs early and for most persons, epilepsy is a short‐lived condition. The exact role of antiepileptic drugs (AEDs) in this good outcome, however, remains open to debate, because the natural history of the untreated condition is largely unknown. In this article, factors that may influence the prognosis of the epilepsies, including the problems of diagnosis, are reviewed. Special emphasis is given to the issue of spontaneous remission and the question of prognosis of different epileptic syndromes.

Mortality from epilepsy : results from a prospective population-based study

Patients with epilepsy may be subject to an increased risk of premature death from the underlying cause, or from the epilepsy itself. The extent and nature of this risk has been insufficiently investigated. Standard mortality ratios (SMRs) of patients with newly diagnosed epilepsy were determined in a prospective national population-based study. 1091 patients with newly diagnosed or suspected epilepsy were ascertained who were attending one of 275 UK general practices from 1984-1987. 1091 patients were classified after 6 months as definite epilepsy (564), possible epilepsy (228), febrile seizures (220), or not epilepsy (79). Over a median follow up of 6.9 years the SMR for patients with definite or possible epilepsy was 2.5 (95% CI 2.1-2.9), and 3.0 (2.5-3.7) for definite epilepsy. The SMR was highest during the first year after diagnosis 5.1 (3.8-6.5), declined to 2.5 (1.5-3.9) at 3 years, and 1.3 (0.7-2.0) at 5 years. The commonest causes of death were pneumonia (SMR 7.2), cancer (3.5), and stroke (3.7). The SMR for patients with idiopathic epilepsy was 1.6 (1.0-2.4), remote symptomatic epilepsy 4.3 (3.3-5.5), and acute symptomatic epilepsy 2.9 (1.7-4.5). Mortality in patients with newly-diagnosed epilepsy was high, mainly due to the underlying cause. The SMR for idiopathic epilepsy was also raised, suggesting that epilepsy per se may carry a small risk of death.

Sudden unexpected death in epilepsy: risk factors and potential pathomechanisms

Sudden unexpected death in epilepsy (SUDEP) is the most common cause of death directly related to epilepsy, and most frequently occurs in people with chronic epilepsy. The main risk factors for SUDEP are associated with poorly controlled seizures, suggesting that most cases of SUDEP are seizure-related events. Dysregulation in cardiac and respiratory physiology, dysfunction in systemic and cerebral circulation physiology, and seizure-induced hormonal and metabolic changes might all contribute to SUDEP. Cardiac factors include bradyarrhythmias and asystole, as well as tachyarrhythmias and alterations to cardiac repolarization. Altered electrolytes and blood pH, as well as the release of catecholamines, modulate cardiac excitability and might facilitate arrhythmias. Respiratory symptoms are not uncommon during seizures and comprise central apnea or bradypnea, and, less frequently, obstruction of the airways and neurogenic pulmonary edema. Alterations to autonomic function, such as a reduction in heart rate variability or disturbed baroreflex sensitivity, can impair the bodys capacity to cope with challenging situations of elevated stress, such as seizures. Here, we summarize data on the incidence of and risk factors for SUDEP, and consider the pathophysiological aspects of chronic epilepsy that might lead to sudden death. We suggest that SUDEP is caused by the fatal coexistence of several predisposing and triggering factors.

National general practice study of epilepsy : newly diagnosed epileptic seizures in a general population

The National General Practice Study of Epilepsy is a prospective population-based cohort study of 1195 patients with newly diagnosed or suspected epileptic seizures. At the time of initial classification (6 months after notification), 104 patients were excluded. Of the remaining 1091 patients, 220 (20% [95% confidence interval 18-23%]) had febrile seizures, 564 (52% [49-55%]) definite epileptic seizures, and 228 (21% [19-23%]) possible epilepsy. In the definite epilepsy group the proportions of males and females were similar, 25% (21-28%) were younger than 15 years and 24% (21-28%) were 60 years or older. The definite seizures were classified as cryptogenic in 62% (58-66%), remote symptomatic in 21% (18-25%), and acute symptomatic in 15% (12-18%). The aetiology of epilepsy was vascular disease in 15% (12-18%) and tumour in 6% (4-8%). Among older subjects the proportion with an identifiable cause was much higher: 49% (41-58%) were due to vascular disease and 11% (6-16%) to tumour. Only 252 (45% [41-49%]) of the 564 patients with definite epileptic seizures were registered at the time of their first seizure. 52% (48-56%) of the patients had partial or secondarily generalised seizures, and only 39% (35-43%) seizures generalised from the outset.