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Objective: Interictal dysphoric disorder (IDD) has been regarded as an affective disorder occurring only in people with epilepsy (PWE). Data showing similar characteristics and similar prevalence of IDD in patients with migraine and with psychogenic nonepileptic seizures question the epilepsy-specific nature of IDD. The aim of the study was to investigate the nature of IDD in people with prevalent epilepsy with mood disorders and people with mood disorders who are free of neurological disease., Methods: This is a case-control study, with 142 patients with a confirmed diagnosis of epilepsy and major depressive disorder (MDD; cases) and 222 patients with MDD only (controls). MDD diagnosis was confirmed by a structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition (SCID-I-RV). We used the Beck Depression Inventory and the Beck Anxiety Inventory to estimate anxiety and depression levels and the Interictal Dysphoric Disorder Inventory (IDDI) to confirm the presence of IDD. Mann-Whitney U test, Pearson chi-squared, Spearman correlation, and logistic regression were used., Results: No differences were found in the prevalence of IDD between PWE with MDD and people with MDD alone (88.73% vs. 85.13%, χ2 = .96, p = .32). There were no differences between the groups overall or for any IDDI subscales (all p > .05). In both groups, IDD symptoms were grouped with the same incidence and had the same duration and periodicity. IDD was not associated with epilepsy (odds ratio = .84, 95% confidence interval = .40-1.98, p = .72). No significant correlation was found between epilepsy, demographic characteristics, and all IDDI subscales (all p > .05). Notably, patients with IDD suffered from affective disorders longer (6.68 ± 6.82 years vs. 3.7 ± 3.97 years, p = .001) and also received higher scores on all psychometric scales (all p < .05)., Significance: This study does not confirm the specificity of IDD for epilepsy. The presence of IDD symptoms may be associated with a more severe course of MDD and significant anxiety distress., (© 2021 International League Against Epilepsy.)

Objective: To examine the consistency of applying the Nashef et al (2012) criteria to classify sudden unexpected death in epilepsy (SUDEP)., Methods: We reviewed cases from the North American SUDEP Registry (n = 250) and Medical Examiner Offices (n = 1301: 698 Maryland, 457 New York City, 146 San Diego). Two epileptologists with expertise in SUDEP and epilepsy-related mortality independently reviewed medical records, scene investigation, autopsy, and toxicology and assigned a SUDEP class., Results: Major areas of disagreement arose between adjudicators concerned differentiating (1) Definite SUDEP Plus Comorbidity from Possible SUDEP and (2) Resuscitated (Near) SUDEP from SUDEP. In many cases, distinguishing between contributing and competing causes of death when trying to classify Definite SUDEP Plus Comorbidity versus Possible SUDEP is ambiguous and relies on judgement. Similarly, determining if an intervention was lifesaving or not (Resuscitated SUDEP or Not SUDEP), or if resuscitation merely delayed SUDEP (Resuscitated SUDEP or SUDEP) is often a judgement call and can differ between experienced adjudicators. Given these persisting ambiguities, we propose more explicit criteria for distinguishing these categories., Significance: Accurate and consistent classification of cause of death among individuals with epilepsy remains a dire public health concern. SUDEP is likely underestimated in national health statistics. Greater standardization of criteria among epilepsy researchers, medical examiners, and epidemiologists to determine cause and classify death will lead to more accurate tracking of SUDEP and other epilepsy-related mortalities., (Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.)

Sudden unexpected death of an individual with epilepsy can pose a challenge to death investigators, as most deaths are unwitnessed, and the individual is commonly found dead in bed. Anatomic findings (eg, tongue/lip bite) are commonly absent and of varying specificity, thereby limiting the evidence to implicate epilepsy as a cause of or contributor to death. Thus it is likely that death certificates significantly underrepresent the true number of deaths in which epilepsy was a factor. To address this, members of the National Association of Medical Examiners, North American SUDEP Registry, Epilepsy Foundation SUDEP Institute, American Epilepsy Society, and the Centers for Disease Control and Prevention constituted an expert panel to generate evidence-based recommendations for the practice of death investigation and autopsy, toxicological analysis, interpretation of autopsy and toxicology findings, and death certification to improve the precision of death certificate data available for public health surveillance of epilepsy-related deaths. The recommendations provided in this paper are intended to assist medical examiners, coroners, and death investigators when a sudden unexpected death in a person with epilepsy is encountered., (© 2018 National Association of Medical Examiners. This paper has been simultaneously published in Epilepsia. Volume 59, #3 and Academic Forensic Pathology: The Official Publication of the National Association of Medical Examiners, Volume 8, #1.)

The Commission on Classification and Terminology and the Commission on Epidemiology of the International League Against Epilepsy (ILAE) have charged a Task Force to revise concepts, definition, and classification of status epilepticus (SE). The proposed new definition of SE is as follows: Status epilepticus is a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms, which lead to abnormally, prolonged seizures (after time point t1 ). It is a condition, which can have long-term consequences (after time point t2 ), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures. This definition is conceptual, with two operational dimensions: the first is the length of the seizure and the time point (t1 ) beyond which the seizure should be regarded as "continuous seizure activity." The second time point (t2 ) is the time of ongoing seizure activity after which there is a risk of long-term consequences. In the case of convulsive (tonic-clonic) SE, both time points (t1 at 5 min and t2 at 30 min) are based on animal experiments and clinical research. This evidence is incomplete, and there is furthermore considerable variation, so these time points should be considered as the best estimates currently available. Data are not yet available for other forms of SE, but as knowledge and understanding increase, time points can be defined for specific forms of SE based on scientific evidence and incorporated into the definition, without changing the underlying concepts. A new diagnostic classification system of SE is proposed, which will provide a framework for clinical diagnosis, investigation, and therapeutic approaches for each patient. There are four axes: (1) semiology; (2) etiology; (3) electroencephalography (EEG) correlates; and (4) age. Axis 1 (semiology) lists different forms of SE divided into those with prominent motor systems, those without prominent motor systems, and currently indeterminate conditions (such as acute confusional states with epileptiform EEG patterns). Axis 2 (etiology) is divided into subcategories of known and unknown causes. Axis 3 (EEG correlates) adopts the latest recommendations by consensus panels to use the following descriptors for the EEG: name of pattern, morphology, location, time-related features, modulation, and effect of intervention. Finally, axis 4 divides age groups into neonatal, infancy, childhood, adolescent and adulthood, and elderly., (Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.)

The World Health Organization (WHO) International Classification of Diseases (ICD) has been used to classify causes of morbidity and mortality such as epilepsy for more than 50 years. The aims of this critical commentary are to do the following: (1) Introduce the ICD classification, summarize the ICD-9 and ICD-10 codes for epilepsy and seizures, and discuss the challenges of mapping epilepsy codes between these two versions; (2) discuss how the ICD-9 and ICD-10 relate to the revised International League Against Epilepsy (ILAE) terminology and concepts for classification of seizures and epilepsies; (3) discuss how ICD-coded data have been used for epilepsy care and research and briefly examine the potential impact of the international ICD-10 clinical modifications on research; (4) discuss the upcoming ICD-11 codes and the role of the epilepsy community in their development; and (5) discuss how the ICD-11 will conform more closely to the current ILAE terminology and classification of the epilepsies and seizures and its potential impact on clinical care, surveillance, and public health and research., (Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.)

The incidence, prevalence, and mortality of epilepsy vary across countries with different economies. Differences can be explained by methodological problems, premature mortality, seizure remission, socioeconomic factors, and stigma. Diagnostic misclassification-one possible explanation-may result from inclusion of patients with acute symptomatic or isolated unprovoked seizures. Other sources of bias include age and ethnic origin of the target population, definitions of epilepsy, retrospective versus prospective ascertainment, sources of cases, and experienced and perceived stigma. Premature mortality is an issue in low-income countries (LICs), where treatment gap, brain infections, and traumatic brain injuries are more common than in high-income countries (HICs). Death rates may reflect untreated continued seizures or inclusion of acute symptomatic seizures. Lack of compliance with antiepileptic drugs has been associated with increased risk for death, increased hospital admissions, motor vehicle accidents, and fractures in poor communities. Epilepsy is a self-remitting clinical condition in up to 50% of cases. Studies in untreated individuals from LICs have shown that the proportion of remissions overlaps that of countries where patients receive treatment. When the identification of patients is based on spontaneous reports (e.g., door-to-door surveys), patients in remission may be less likely to disclose the disease for fear of stigmatization with no concurrent benefits. This might lead to underascertainment of cases when assessing the lifetime prevalence of epilepsy. In LICs, the proportion of people living in poverty is greater than in HICs. Poverty is associated with risk factors for epilepsy, risk for developing epilepsy, and increased mortality. The high incidence and prevalence of epilepsy found in LICs is also observed in low income individuals from HICs. Epileptogenic conditions are associated with an increased mortality. This may partly explain the difference between incidence and lifetime prevalence of epilepsy in LICs. Poverty within LICs and HICs could be a preventable cause of mortality in epilepsy., (Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.)

Purpose: To determine the persistence of disparities in health care use and outcomes in socioeconomically diverse populations of epilepsy patients., Methods: We followed patients for a year at one clinic in Houston and two in New York City that serve predominantly low-income, minority, Medicaid-insured, or uninsured patients, and a fourth clinic in Houston that serves a more balanced racial/ethnic and higher socioeconomic status (SES) population. We interviewed the patients several times regarding health care use, seizures, side effects, and outcomes, and examined differences between the patients at the three low-SES clinics and the patients at the high-SES clinic., Key Findings: After controlling for patients' age, gender, race/ethnicity, marital status, seizures, and side effects we found that low SES patients had consistently higher use of the hospital emergency room and more visits to a general practitioner. Hospitalizations were also consistently higher but the differences were not significant in most periods. Neurologist visits were relatively similar. Patients at the low SES sites also had a greater likelihood of having uncontrolled seizures, drug-related side effects, to be stigmatized, and have a lower overall quality of life throughout the study period., Significance: These findings suggest the persistence of SES-related disparities in health care use and outcomes among patients with epilepsy who are receiving regular care., (Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.)

Purpose: We investigated the cumulative probability of seizure remission and relapse in an adult population with drug-resistant epilepsy and frequent seizures. In addition, we determined clinical predictors of remission and relapse in this population., Methods: IN 2003, we identified 246 patients at a single center with drug-resistant epilepsy defined as at least one seizure per month and failure of at least two antiepileptic drugs. These patients were followed prospectively (cohort design). We examined the cumulative probability of seizure remission and relapse in this population using Kaplan-Meier methodology. Clinical predictors of remission and relapse were also evaluated using Cox regression analysis., Key Findings: The estimated cumulative probability of 12-month seizure remission was 34.6% at 7 years in the entire population and 33.4% when limited to those without surgery. The risk for relapse after a 12-month period of seizure remission was 71.2% at 5 years. Negative predictors of seizure remission included developmental delay, symptomatic generalized epilepsy syndrome, duration of intractability, and number of antiepileptic drugs failed. Localization-related epilepsy was the only negative predictor of relapse., Significance: Among patients with drug-resistant epilepsy, 5% per year enter seizure remission even with a follow-up of 6 years. However, a substantial proportion of these patients relapse after the first year following a remission. The large proportion of patients entering a significant remission gives these patients hope; however, caution should be advised when discussing the likelihood of future seizures., (Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.)

Purpose: The purpose of this study was to identify sociodemographic disparities in health care use among epilepsy patients receiving care at different sites and the extent to which the disparities persisted after adjusting for patient characteristics and site of care., Methods: Three months of health care use data were obtained from baseline interviews of approximately 560 patients at four sites. One-half of the patients were from a Houston site and two NYC sites that serve predominantly low-income, minority, publicly insured, or uninsured patients. The other half were at the remaining site in Houston that serves a more balanced racial/ethnic and higher sociodemographic population. Differences in general and specialist visits, hospital emergency room (ER) care, and hospitalizations were associated with race/ethnicity, income, and coverage. Logistic regression was used to assess the extent to which the differences persisted when adjusting for individual patient characteristics and site of care., Results: Compared to whites, blacks and Hispanics had higher rates of generalist visits [odds ratio (OR) = 5.3 and 4.9, p < 0.05), ER care (OR = 3.1 and 2.9, p < 0.05) and hospitalizations (OR = 5.4 and 6.2, p < 0.05), and lower rates of specialist visits (OR = 0.3 and 0.4, p < 0.05). A similar pattern was found related to patient income and coverage. The magnitude and significance of the disparities persisted when adjusting for individual characteristics but decreased substantially or were eliminated when site of care was added to the model., Discussion: There are sociodemographic disparities in health care for people with epilepsy that are largely explained by differences in where patients receive care.

Problem: The prevalence of epilepsy is high in many areas of Africa. This condition is stigmatized, and there are limited health personnel and facilities for diagnosis and treatment. A huge treatment gap is suspected for epilepsy, and data suggest that nearly 80-85% of people with epilepsy have never been diagnosed or treated. It is reported worldwide that the mortality among people with epilepsy is two- to threefold higher than in general population. An increase of at least this magnitude is suspected in Africa, but there are very few data. Verbal autopsy studies may be one way of carrying out studies of mortality for epilepsy in Africa because these methods do not rely on autopsies, which are rare, or upon death certificates, which are a poor source of information on death in Africa., Methods: This paper presents the literature on mortality after seizures in Africa, although there are few studies of mortality among people with epilepsy in Africa., Results: The existing studies suggest an increased risk of dying and a greater proportion of deaths that are epilepsy-related. One study reports a sixfold increase in mortality in people with epilepsy. This is higher than the two- to threefold increase reported in developed countries., Conclusions: Considering the high prevalence of this condition, the public health impact of epilepsy mortality is likely to be enormous.

Purpose: Status epilepticus (SE) is a medical emergency associated with a high mortality. Clinical series have suggested that mortality after SE has decreased. No studies have systematically examined trends in incidence, mortality, and case fatality after SE in a well-defined population., Methods: All first episodes of SE receiving medical attention between January 1, 1935, and December 31, 1984, were ascertained through the Rochester Epidemiology Project Records-Linkage System and followed up until death or study termination (February 1, 1996). We calculated incidence rates in the 50-year period (1935-1984), while we considered mortality and case-fatality in the last 30-year period (1955-1984)., Results: Incidence of SE increased over time to 18.1/100,000 (1975 through 1984). The increase was related to an increased incidence in the elderly and to the advent of myoclonic SE after cardiac arrest, a condition not seen in the early decades. In the last decade, approximately 16% of the incidence was due to myoclonic SE. The mortality rates increased from 3.6 per year in the decade 1955-1965 to 4.0/100,000 per year between 1975 and 1984. The 30-day case-fatality (CF) was unchanged, although a trend toward improvement was shown after excluding myoclonic SE., Conclusions: Incidence and mortality rates of SE have increased in the last 30 years. Case fatality remained the same. The increased incidence and mortality are due to the occurrence in the last decade of myoclonic SE after cardiac arrest. The mortality in the elderly was twice that of the youngest age group, across all study periods. Changes in the age and cause distribution of SE over time are responsible for the stable survivorship. There is improvement in survivorship in the last decade when myoclonic SE is excluded.

Purpose: To determine whether an increased risk of status epilepticus (SE) and complex partial status epilepticus (CPSE) is associated with tiagabine (TGB) therapy., Methods: Thirteen cases in which an EEG, performed on patients with altered mental status taking TGB, was reported to demonstrate spike-and-wave discharges (SWDs) were reviewed by a panel of experts. In addition, all cases of suspected SE from TGB clinical trials were reviewed. The occurrence of SE in four epidemiologic cohorts from Rochester, Minnesota, Turku, Finland, Bronx, New York, and New Haven, Connecticut was analyzed as an external comparison., Results: Review of the 13 cases with reported SWDs found that the majority had had prior EEGs with similar findings, and only three were thought to have electrographic evidence of SE. There was no difference in the frequency of SE or CPSE in the placebo-controlled clinical trials between the TGB-treated (1.0% SE, 0.8% CPSE) and placebo-treated (1.5% SE, 1.5% CPSE) groups. The 5% frequency of SE and 3% frequency of CPSE in the TGB-treated patients in the long-term safety studies, which included 2,248 patients, were very similar to the rates of occurrence of SE and CPSE in the four external cohorts. The major risk factor for the occurrence of SE and CPSE in all groups was a prior episode of SE (p < 0.0001)., Conclusions: Over a 3-year period, SE will occur in 5-10% of patients with epilepsy not in remission. At highest risk are those who have had a prior episode of SE. Treatment with TGB in recommended doses does not increase the risk of SE in patients with partial seizures.

Purpose: To analyze the nonfatal adverse events (AE) associated with a first episode of status epilepticus (SE)., Methods: We performed a population-based retrospective cohort study to determine the morbidity of SE. Participants included 184 residents of Rochester, Minnesota who experienced nonfebrile SE between 1965 and 1984., Results: The etiology of SE was acute symptomatic in 100 patients and unprovoked in 84 patients. The most common seizure-types were continuous partial (n=56, 30%), generalized convulsive (n=52, 28%), and generalized with focal features (n=32, 17%). Morbidity related to SE was noted in 5 of the 146 patients (3.4%) surviving 30 days. The AE included hemiparesis (n=3), encephalopathy (n=2), mental retardation (n=1), and aphasia (n=1). All patients with morbidity had an acute symptomatic (n=4) or remote symptomatic (n=1) etiology. Thirty-four patients (18.5%) had a second episode of SE., Conclusions: Based on this retrospective study, significant morbidity related to SE is uncommon and is associated with the underlying etiology.

Purpose: Studies evaluating short-term mortality among people who experience status epilepticus (SE) have produced conflicting results. Most studies are derived from clinical series with results affected by unspecified follow-up period and select referral of cases. This study was planned to evaluate short-term mortality after a first episode of SE., Methods: We performed a population-based retrospective cohort study to determine the short-term mortality following a first episode of SE. Between January 1, 1965 and December 31, 1984, we studied all first episodes of afebrile SE who received medical attention in Rochester, Minnesota. Cases were followed until death or end of the study (February 1996)., Results: Mortality within the first 30 days was 19% (38 deaths out of 201 incident SE). Thirty-four deaths (89%) occurred among those with nonfebrile acute symptomatic SE, while 4 deaths (11%) occurred among those with unprovoked SE. Within the acute symptomatic group, after adjusting for age, there was a decreased risk of death in women (RR = 0.4; 95% CI: 0.2-0.9). No effect of duration or seizure type was shown after adjusting for other risk factors., Conclusions: One out of 5 subjects with SE died within the first 30 days. Short-term mortality is associated with the presence of an underlying acute etiology. Among acute symptomatic cases, women had a decreased risk of dying.

Purpose: Hypertension is an established risk factor for clinically detected stroke, which is in turn a risk factor for epilepsy. This relation suggested that hypertension, particularly severe and uncontrolled, might increase the risk of epilepsy in the absence of prior clinically detected stroke., Methods: Subjects in this population-based case-control study were the 145 incident cases of first unprovoked seizure aged 55 years or older and 290 controls matched to cases on age, gender, and duration of medical follow-up. Using the records-linkage system of the Rochester Epidemiology Project, we obtained, for both cases and matched controls, all blood pressure readings before each case's first seizure came to medical attention. Subjects were classified as hypertensive if they had at least two readings of > or = 160/95 mm Hg or if there was electrocardiographic evidence for left ventricular hypertrophy., Results: Severe uncontrolled hypertension increased the risk of unprovoked seizure. Left ventricular hypertrophy without diuretic treatment was associated with an 11-fold increased risk of unprovoked seizure: left ventricular hypertrophy treated with diuretics did not increase the risk., Conclusions: In the absence of clinically detected stroke, left ventricular hypertrophy without diuretic use may increase the risk of unprovoked seizures, and diuretic treatment may protect against this increased risk.