Familial aggregation of seizure outcomes in four familial epilepsy cohorts.

OBJECTIVE: To assess the possible effects of genetics on seizure outcome by estimating the familial aggregation of three outcome measures: seizure remission, history of ≥4 tonic-clonic seizures, and seizure control for individuals taking antiseizure medication. METHODS: We analyzed families containing multiple persons with epilepsy in four previously collected retrospective cohorts. Seizure remission was defined as being 5 and 10 years seizure-free at last observation. Total number of tonic-clonic seizures was dichotomized at <4 and ≥4 seizures. Seizure control in patients taking antiseizure medication was defined as no seizures for 1, 2, and 3 years. We used Bayesian generalized linear mixed-effects model (GLMM) to estimate the intraclass correlation coefficient (ICC) of the family-specific random effect, controlling for epilepsy type, age at epilepsy onset, and age at last data collection as fixed effects. We analyzed each cohort separately and performed meta-analysis using GLMMs. RESULTS: The combined cohorts included 3644 individuals with epilepsy from 1463 families. A history of ≥4 tonic-clonic seizures showed strong familial aggregation in three separate cohorts and meta-analysis (ICC .28, 95% confidence interval [CI] .21-.35, Bayes factor 8 × 1016). Meta-analyses did not reveal significant familial aggregation of seizure remission (ICC .08, 95% CI .01-.17, Bayes factor 1.46) or seizure control for individuals taking antiseizure medication (ICC .13, 95% CI 0-.35, Bayes factor 0.94), with heterogeneity among cohorts. SIGNIFICANCE: A history of ≥4 tonic-clonic seizures aggregated strongly in families, suggesting a genetic influence, whereas seizure remission and seizure control for individuals taking antiseizure medications did not aggregate consistently in families. Different seizure outcomes may have different underlying biology and risk factors. These findings should inform the future molecular genetic studies of seizure outcomes.

Incidence of mental health conditions by seizure control among adults with epilepsy in the United States.

BACKGROUND: Mental health conditions (MHCs) are frequent comorbidities among people with epilepsy; however, the influence of seizure control on the incidence of MHCs is not well reported. This retrospective observational cohort study based on claims data evaluated the effects of indicators of poor seizure control on the incidence of MHCs among MHC-naïve people with epilepsy. We hypothesized that poor seizure control is associated with new-onset MHC diagnoses and/or new prescription drugs for MHCs. METHODS: This study utilized a sample of patients from HealthVerity Marketplace, which includes more than 150 US commercial, Medicare, and Medicaid payers, to identify a cohort of adults (age ≥18 years) with prevalent epilepsy. Follow-up started on day 1 (January 1) after a 1-year eligibility assessment period occurring in calendar year 2017 or 2018. Patients were followed up until the occurrence of an incident MHC event (primary outcome), defined as a mental health diagnosis or psychotropic drug prescription. Time from follow-up to incident MHC diagnosis or to a drug prescription specific to depression or anxiety disorder was analyzed as a secondary outcome. Multivariate Cox proportional hazards regressions were estimated with time-varying covariates, measured in 6-month intervals during follow-up. Time-varying covariates were based on the occurrence of 4 variables used as indicators of poor seizure control in the prior period: epilepsy-related emergent care admissions, epilepsy-related inpatient admissions, epilepsy electroencephalography referrals, and exposure to one or more new antiseizure medications (ASMs). RESULTS: From a random sample of 40,000 people with epilepsy, 2563 (mean age 46.1 years; 50.6% male) were included in the analysis. Incident MHC events were observed in 27.7% (incidence rate 24.4 events per 100 person-years over 2,915.7 total person-years of follow-up). Mean (standard deviation [SD]) time to event was 232.7 (186.3) days. Among the 4 variables, epilepsy-related emergent care admissions were associated with an increased risk of incident MHC events in the following 6-month period (hazard ratio [HR] = 1.676, 95% confidence interval [CI]: 1.386, 2.026, p < 0.001) as were prescriptions for new ASMs in the previous period (HR = 1.702, 95% CI: 1.359, 2.132, p < 0.001). Previous epilepsy-related emergent care admissions (HR = 1.650, 95% CI: 1.347, 2.021, p < 0.001) and new ASMs (HR = 1.632, 95% CI: 1.280, 2.081, p < 0.001) also predicted an increased risk of incident depression or anxiety in the following 6-month period. CONCLUSIONS: Previous indicators of poor seizure control, including epilepsy-related emergent care admissions and new ASMs, predicted increased risk of new MHC events, including depression and anxiety, during the following 6-month interval in MHC-naïve patients with prevalent epilepsy. These data suggest that poor seizure control can increase the subsequent risk of new mental health diagnoses and treatment among people with epilepsy.

Interictal dysphoric disorder in people with and without epilepsy.

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.

Exploring the complex associations over time among albendazole treatment, cyst evolution, and seizure outcomes in neurocysticercosis.

OBJECTIVE: To develop a causal model for the occurrence of neurocysticercosis (NC)-related seizures and test hypotheses generated from the model. METHODS: We used data from a randomized controlled trial comparing albendazole with placebo among patients newly diagnosed with NC. Based on our causal model, we explored the associations among albendazole treatment, NC cyst evolution, and seizure outcomes over 24 months of follow-up using generalized linear mixed effect models. RESULTS: We included 153 participants, of whom 51% received albendazole. The association between seizure outcomes and treatment over time demonstrated lack of linearity and heterogeneity, requiring the inclusion of time-treatment interaction terms for valid modeling. Participants in the albendazole group had fewer seizures overall and of partial onset at all time points compared with the placebo group, but the difference increased over the first few months following treatment, then decreased over time. Generalized seizures exhibited a more complex association; those in the albendazole group had fewer seizures compared with those in the placebo group for the first few months after treatment, and then the association reversed and those in the placebo arm had fewer seizures. Adjusting for the number of NC cysts in each phase resulted in an attenuation of the strength of association between albendazole and seizure outcomes, consistent with mediation. Among participants in whom all cysts had disappeared (n = 21), none continued to have seizures. SIGNIFICANCE: Albendazole treatment is associated with a possible reduction in focal seizures in the short term (3-6 months), perhaps by hastening the resolution of the cysts. However, the effect is not discernible over the long term, because most cysts either calcify or resolve completely, regardless of whether treated with albendazole. The stage of evolution of the cysticercus is an important consideration in the evaluation of albendazole effect on seizure outcome.

Fetal growth and premature delivery in pregnant women on antiepileptic drugs.

OBJECTIVE: To evaluate the effects of epilepsy and antiepileptic drugs (AEDs) used during pregnancy on fetal growth and preterm delivery. METHODS: This study included singleton liveborn infants born to women enrolled in the North American Antiepileptic Drug Pregnancy Registry between 1997 and 2016. Data were collected prospectively through telephone interviews. The prevalence of preterm birth (<37 weeks) and small for gestational age status (SGA) among infants exposed prenatally to AEDs when used by women with epilepsy (WWE) or women without epilepsy (WWOE) was compared with that among infants unexposed to AEDs and born to WWOE. Multivariate log-binomial regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: The study population included infants born to 6,777 AED-WWE, 696 AED-WWOE, and 486 no-AED-WWOE. The risk of prematurity was 6.2% for no-AED-WWOE, 9.3% for AED-WWE (RR = 1.5, 95% CI = 1.0-2.1), and 10.5% for AED-WWOE (RR = 1.5, 95% CI = 1.0-2.4). Prenatal exposure to AEDs in WWE and WWOE was associated with a mean lower birth weight of 110 and 136g, respectively, as compared to no-AED-WWOE. The prevalence of SGA was 5.0% for no-AED-WWOE, 10.9% for AED-WWE (RR = 2.0, 95% CI = 1.3-3.0), and 11.0% for AED-WWOE (RR = 1.9, 95% CI = 1.2-2.9). Within users of AEDs in monotherapy, the prevalence of SGA ranged from 7.3% for lamotrigine to 18.5% for topiramate. INTERPRETATION: Women on AEDs during pregnancy, whether for epilepsy or for other neuropsychiatric indications, are at a higher risk of delivering prematurely and giving birth to SGA newborns. The risk may vary by drug. Ann Neurol 2017;82:457-465.

Stress is associated with an increased risk of recurrent seizures in adults.

OBJECTIVE: The literature is sparse on the complex interrelationships between stressors, depression, anxiety disorders, and epilepsy. We hypothesized that a relationship exists between stress and epilepsy. We evaluated whether markers of stress are associated with seizure recurrence in a low income community-based cohort of adults with single unprovoked seizure or newly diagnosed epilepsy. METHODS: We ascertained adult residents of Northern Manhattan and Harlem, New York City, with a first unprovoked seizure or newly diagnosed epilepsy, between December 2010 and January 2013. At enrollment, we collected information about seizure phenomenology, demographics, clinical information, and measures of stress (environmental stress, stressful life events, facets of allostatic load-i.e., the cumulative effect of adaptation to stress, psychiatric disorders, and low collective efficacy). Collective efficacy assesses neighborhood characteristics and incorporates social cohesion and informal social control. All subjects were followed for 2 years for further seizures. Cox proportional hazard regression models were used to estimate the hazard ratios of seizure recurrence during the 2 years of follow-up. RESULTS: We identified 52 subjects (64.2%) with a single unprovoked seizure and 29 (35.9%) with newly diagnosed epilepsy. Seizure recurrence was recorded in 38.5% (N = 20) of subjects with a single unprovoked seizure and in 69% of those with epilepsy (N = 20) (p = 0.01). In the overall sample, the hazard of seizure recurrence was increased by lifetime generalized anxiety disorder (3.0-fold) and by low collective efficacy (2.7-fold). In a second model, the hazard was increased by lifetime mood disorder (2.1-fold) and low collective efficacy (2.5-fold). SIGNIFICANCE: Markers of stress (i.e., low collective efficacy, lifetime mood disorder, and lifetime generalized anxiety disorder) were associated with an increased risk for seizure recurrence in adults with a single unprovoked seizure or newly diagnosed epilepsy. Stress-reducing interventions, such as mindfulness, may be a useful, safe, and inexpensive adjunctive treatment for epilepsy.

Reasons for discontinuation of reversible contraceptive methods by women with epilepsy.

OBJECTIVE: To report the reasons for discontinuation of contraceptive methods by women with epilepsy (WWE). METHODS: These retrospective data come from a web-based survey regarding the contraceptive practices of 1,144 WWE in the community, ages 18-47 years. We determined the frequencies of contraceptive discontinuations and the reasons for discontinuation. We compared risk ratios for rates of discontinuation among contraceptive methods and categories. We used chi-square analysis to test the independence of discontinuation reasons among the various contraceptive methods and categories and when stratified by antiepileptic drug (AED) categories. RESULTS: Nine hundred fifty-nine of 2,393 (40.6%) individual, reversible contraceptive methods were discontinued. One-half (51.8%) of the WWE who discontinued a method discontinued at least two methods. Hormonal contraception was discontinued most often (553/1,091, 50.7%) with a risk ratio of 1.94 (1.54-2.45, p < 0.0001) compared to intrauterine devices (IUDs), the category that was discontinued the least (57/227, 25.1%). Among all individual methods, the contraceptive patch was stopped most often (79.7%) and the progestin-IUD was stopped the least (20.1%). The top three reasons for discontinuation among all methods were reliability concerns (13.9%), menstrual problems (13.5%), and increased seizures (8.6%). There were significant differences among discontinuation rates and reasons when stratified by AED category for hormonal contraception but not for any other contraceptive category. SIGNIFICANCE: Contraception counseling for WWE should consider the special experience profiles that are unique to this special population on systemic hormonal contraception.

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

To 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 higher-quality 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.

The burden of premature mortality of epilepsy in high-income countries: A systematic review from the Mortality Task Force of the International League Against Epilepsy.

Since previous reviews of epidemiologic studies of premature mortality among people with epilepsy were completed several years ago, a large body of new evidence about this subject has been published. We aim to update prior reviews of mortality in epilepsy and to reevaluate and quantify the risks, potential risk factors, and causes of these deaths. We systematically searched the Medline and Embase databases to identify published reports describing mortality risks in cohorts and populations of people with epilepsy. We reviewed relevant reports and applied criteria to identify those studies likely to accurately quantify these risks in representative populations. From these we extracted and summarized the reported data. All population-based studies reported an increased risk of premature mortality among people with epilepsy compared to general populations. Standard mortality ratios are especially high among people with epilepsy aged <50 years, among those whose epilepsy is categorized as structural/metabolic, those whose seizures do not fully remit under treatment, and those with convulsive seizures. Among deaths directly attributable to epilepsy or seizures, important immediate causes include sudden unexpected death in epilepsy (SUDEP), status epilepticus, unintentional injuries, and suicide. Epilepsy-associated premature mortality imposes a significant public health burden, and many of the specific causes of death are potentially preventable. These require increased attention from healthcare providers, researchers, and public health professionals.

Epilepsy and treatment gap in urban and rural areas of the Southern Kazakhstan in adults.

PURPOSE: There are no data in the English literature about the epidemiology of epilepsy in the large countries in the Asian region of the former Soviet Union. This paper presents the results of epidemiological studies of active epilepsy in the population 14years of age and older in the Province of South Kazakhstan. METHODS: The study population consisted of 306.44 thousand persons: 139.42 in the urban Enbekshinskiy district of the city of Shymkent and 167.02 in the rural Sairam district. To collect patient's data, multiple medical sources were used. For each person with epilepsy (PWE), a questionnaire was completed by members of the research team. Clinical profiles, seizure type, clinical syndrome, etiology, seizure frequency, therapy, educational level, and social status were abstracted. RESULTS: Overall, 1351 PWE were identified: 459 in the urban district and 892 in the rural district. The age-adjusted prevalence of epilepsy was 3.14/1000 (CI95%: 2.86-3.45) in the urban district and 4.95/1000 (CI95%: 4.62-5.30) in the rural district. Prevalence for men was higher than for women. Focal seizures predominated in both regions. Traumatic brain injury was the most frequently identified cause of epilepsy. The other important antecedents were pre/perinatal disorders, CNS infection, and cerebrovascular disease. Half of PWE experienced more than 12seizures per year. Substantial social impacts of epilepsy were observed: 44% of PWE received disability pensions from the government; only 15.5% were employed. About a quarter of all PWE were not taking AEDs at the time of the record review. For those on treatment, regimens were frequently suboptimal. CONCLUSION: In the first study performed according to the guidelines for epidemiologic studies on epilepsy of ILAE in the Asian part of the former Soviet Union, poor seizure control and a substantial treatment gap were identified. The need for improvement of epilepsy care was highlighted, especially in the rural regions.

Contraceptive practices of women with epilepsy: Findings of the epilepsy birth control registry.

OBJECTIVE: To report the contraceptive practices of women with epilepsy (WWE) in the community, predictors of highly effective contraception use, and reasons WWE provide for the selection of a particular method. METHODS: These cross-sectional data come from the Epilepsy Birth Control Registry (EBCR) web-based survey regarding the contraceptive practices of 1,144 WWE in the community, ages 18-47 years. We report demographic, epilepsy, and antiepileptic drug (AED) characteristics as well as contraceptive use. We determined the frequency of use of highly effective contraception use, that is, methods with failure rate <10%/year, and conducted binary logistic regression analysis to determine predictors of highly effective contraception use. We report frequencies of WWE who consult various health care providers regarding the selection of a method and the reasons cited for selection. RESULTS: Of the 796 WWE at risk of unintended pregnancy, 69.7% use what is generally considered to be highly effective contraception (hormonal, intrauterine device [IUD], tubal, vasectomy). Efficacy in WWE, especially for the 46.6% who use hormonal contraception, remains to be proven. Significant predictors of highly effective contraception use are insurance (insured 71.6% vs. noninsured 56.0%), race/ethnicity (Caucasian 71.3% vs. minority 51.0%), and age (38-47, 77.5%; 28-37, 71.8%; 18-27, 67.0%). Of the 87.2% who have a neurologist, only 25.4% consult them regarding selection of a method, although AED interaction is cited as the top reason for selection. SIGNIFICANCE: The EBCR web-based survey is the first large-scale study of the contraceptive practices of WWE in the community. The findings suggest a need for the development of evidence-based guidelines that address the efficacy and safety of contraceptive methods in this special population, and for greater discourse between neurologists and WWE regarding contraception.

Differential impact of contraceptive methods on seizures varies by antiepileptic drug category: Findings of the Epilepsy Birth Control Registry.

PURPOSE: The aim of this study was to determine whether categories of contraception differ in their impact on seizures in women with epilepsy and whether the impact varies by antiepileptic drug category. METHODS: Retrospective survey data came from 2712 contraceptive experiences reported by 1144 women with epilepsy. We compared risk ratios for reports of increase and decrease in seizure frequency on hormonal versus nonhormonal contraception, stratified by antiepileptic drug categories. RESULTS: More women with epilepsy reported a change in seizures on hormonal (28.2%) than on nonhormonal contraception (9.7%) (p<0.0001). The risk ratio for seizure increase on hormonal (18.7%) versus nonhormonal contraception (4.2%) was 4.47 (p<0.0001). The risk ratio for seizure decrease on hormonal (9.5%) versus nonhormonal contraception (5.5%) was 1.71, p<0.0001. On hormonal contraception, the risk ratio for seizure increase was greater than for decrease (1.98, p<0.0001). In comparison to combined pills, both hormonal patch and progestin-only pills had greater risk ratios for seizure increase. Depomedroxyprogesterone was the only hormonal method with a greater risk ratio for seizure decrease than combined pills. Seizure increase was greater for hormonal than nonhormonal contraception for each antiepileptic drug category (p<0.001). On hormonal contraception, relative to the non-enzyme-inducing antiepileptic drug category which had the lowest rate, each of the other categories had significantly greater risks for seizure increase, especially the enzyme-inhibiting (valproate) category (risk ratio=2.53, p=0.0002). CONCLUSION: The findings provide community-based, epidemiological survey evidence that contraceptive methods may differ in their impact on seizures and that this impact may vary by antiepileptic drug category.

Familial risk of epilepsy: a population-based study.

Almost all previous studies of familial risk of epilepsy have had potentially serious methodological limitations. Our goal was to address these limitations and provide more rigorous estimates of familial risk in a population-based study. We used the unique resources of the Rochester Epidemiology Project to identify all 660 Rochester, Minnesota residents born in 1920 or later with incidence of epilepsy from 1935-94 (probands) and their 2439 first-degree relatives who resided in Olmsted County. We assessed incidence of epilepsy in relatives by comprehensive review of the relatives' medical records, and estimated age-specific cumulative incidence and standardized incidence ratios for epilepsy in relatives compared with the general population, according to proband and relative characteristics. Among relatives of all probands, cumulative incidence of epilepsy to age 40 was 4.7%, and risk was increased 3.3-fold (95% confidence interval 2.75-5.99) compared with population incidence. Risk was increased to the greatest extent in relatives of probands with idiopathic generalized epilepsies (standardized incidence ratio 6.0) and epilepsies associated with intellectual or motor disability presumed present from birth, which we denoted 'prenatal/developmental cause' (standardized incidence ratio 4.3). Among relatives of probands with epilepsy without identified cause (including epilepsies classified as 'idiopathic' or 'unknown cause'), risk was significantly increased for epilepsy of prenatal/developmental cause (standardized incidence ratio 4.1). Similarly, among relatives of probands with prenatal/developmental cause, risk was significantly increased for epilepsies without identified cause (standardized incidence ratio 3.8). In relatives of probands with generalized epilepsy, standardized incidence ratios were 8.3 (95% confidence interval 2.93-15.31) for generalized epilepsy and 2.5 (95% confidence interval 0.92-4.00) for focal epilepsy. In relatives of probands with focal epilepsy, standardized incidence ratios were 1.0 (95% confidence interval 0.00-2.19) for generalized epilepsy and 2.6 (95% confidence interval 1.19-4.26) for focal epilepsy. Epilepsy incidence was greater in offspring of female probands than in offspring of male probands, and this maternal effect was restricted to offspring of probands with focal epilepsy. The results suggest that risks for epilepsies of unknown and prenatal/developmental cause may be influenced by shared genetic mechanisms. They also suggest that some of the genetic influences on generalized and focal epilepsies are distinct. However, the similar increase in risk for focal epilepsy among relatives of probands with either generalized (2.5-fold) or focal epilepsy (2.6-fold) may reflect some coexisting shared genetic influences.

Prevalence of pediatric epilepsy in low-income rural Midwestern counties.

Epilepsy is one of the most common disabling neurological disorders, but significant gaps exist in our knowledge about childhood epilepsy in rural populations. The present study assessed the prevalence of pediatric epilepsy in nine low-income rural counties in the Midwestern United States overall and by gender, age, etiology, seizure type, and syndrome. Multiple sources of case identification were used, including medical records, schools, community agencies, and family interviews. The prevalence of active epilepsy was 5.0/1000. Prevalence was 5.1/1000 in males and 5.0/1000 in females. Differences by age group and gender were not statistically significant. Future research should focus on methods of increasing study participation in rural communities, particularly those in which research studies are rare.

Increased mortality persists in an adult drug-resistant epilepsy prevalence cohort.

OBJECTIVE: To investigate the cumulative probability of death and the standardised mortality ratio (SMR) in an adult drug-resistant epilepsy (DRE) population. METHODS: In two separate centres during 2003-2006, we identified a total of 433 patients with DRE defined as at least one seizure per month and failure of at least two antiepileptic drugs. These patients were subsequently followed for a total follow-up of 6 years. We examined the cumulative probability of death, using Kaplan-Meier methodology, and the SMR based on mortality data from the Social Security Death Index. Clinical predictors of death were evaluated using Cox regression analysis. RESULTS: The cumulative probability of death was 8.7% (95% CI 6.2% to 12.1%) at 6 years. The overall SMR was 2.4 (95% CI 1.7 to 3.3). It was 3.1; 95% CI 2.0 to 4.6 in subjects with remote or progressive aetiology and 1.7; 95% CI 0.8 to 2.8 in subjects with unknown aetiology. The SMR was significantly increased in those with a known remote aetiology (2.5; 95% CI (1.4 to 3.8)). Older age at enrolment and symptomatic generalised epilepsy syndrome were significant predictors of death. DISCUSSION: Mortality is increased in this drug-resistant population; largely driven by those with a known epilepsy aetiology. The increased mortality remains even after exclusion of those with a progressive aetiology. Previous studies of incident epilepsy cohorts revealed increased mortality that declines to near-normal levels after the first several years, but in our DRE cohort, mortality remains elevated despite a median duration of epilepsy of 25 years at study entry.

Why U.S. epilepsy hospital stays rose in 2006.

OBJECTIVE: We observed a substantial increase in age-adjusted hospitalization rates in the United States National Hospital Discharge Survey data from 1996 to 2010. We aimed to assess reasons for this increase. METHODS: The National Hospital Discharge Survey collected data on a national sample of short-term hospital stays in nonfederal hospitals. We determined epilepsy-related discharge diagnoses by age, gender, and region using weighted analysis, and estimated age-adjusted rates and annual percent changes using regression analysis. We also looked at epilepsy as the principal discharge diagnosis in the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project. RESULTS: In the United States, on average, nearly 110,000 more admissions were reported each year with epilepsy as the principal discharge diagnosis in 2006-2010 than in 1996-2005, a 2.7-fold increase in hospitalization rates from epilepsy. During this period, there were more hospitalizations with principal discharge diagnosis of epilepsy not otherwise specified, and among older patients. The number of discharges with seizure not otherwise specified dropped dramatically after 2006, and was more evident among pediatric patients. The age-adjusted rates of hospital stays combining discharges with any mention of epilepsy (345.XX) or seizures unspecified (780.39) in seven discharge diagnoses, were similar in 1996-2005 and 2006-2010. SIGNIFICANCE: We postulate that the excess in hospitalizations with epilepsy as first discharge diagnosis in 2006-2010 in the United States was related to the changes in coding in 2006. Any use of U.S. hospital discharge data with epilepsy-related diagnosis after that date will require further validation. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Yield of epileptiform electroencephalogram abnormalities in incident unprovoked seizures: a population-based study.

OBJECTIVE: The yield of epileptiform abnormalities in serial electroencephalography (EEG) studies has not been addressed in a population-based setting for subjects with incident epilepsy or a single unprovoked seizure, raising the possibility of methodologic limitations such as selection bias. Our aim was to address these limitations by assessing the yield and predictors of epileptiform abnormalities for the first and subsequent EEG recording in a study of incident epilepsy or single unprovoked seizure in Rochester, Minnesota. METHODS: We used the resources of the Rochester Epidemiology Project to identify all 619 residents of Rochester, Minnesota, born in 1920 or later with a diagnosis of incident epilepsy (n = 478) or single unprovoked seizure (n = 141) between 1960 and 1994, who had at least one EEG study. Information on all EEG studies and their results was obtained by comprehensive review of medical records. RESULTS: Among subjects with epilepsy, the cumulative yield of epileptiform abnormalities was 53% after the first EEG study and 72% after the third. Among subjects with a single unprovoked seizure, the cumulative yield was 39% after the first EEG study and 68% after the third. Young age at diagnosis and idiopathic etiology were risk factors for finding epileptiform abnormalities across all EEG recordings. SIGNIFICANCE: Although the cumulative yield of epileptiform abnormalities increases over successive EEG recordings, there is a decrease in the increment for each additional EEG study after the first EEG study. This is most evident in incident epilepsy and in younger subjects. Clinically it may be worthwhile to consider that the probability of finding an epileptiform abnormality after the third nonepileptiform EEG recording is low.

Seizure frequency and patient-centered outcome assessment in epilepsy.

OBJECTIVE: Seizure frequency represents a commonly assessed epilepsy status, but in the context of the growing trend toward patient-centered care, we examined the adequacy of seizure frequency as a measure of epilepsy status as perceived by the patient. METHODS: Between 2006 and 2008, we assessed seizure frequency, mood, and preference-based health-related quality of life (HRQOL) measured with the visual analog scale metric in 182 adult patients sampled consecutively. Using nonparametric tests and Monte Carlo computer simulations, we analyzed the relationship between preference-based HRQOL and seizure frequency, and using regression analyses, we tested for significant predictors of preference-based HRQOL. RESULTS: Only patients who had been seizure-free for >1 year had significantly higher preference-based HRQOL (p < 0.0001) than those who experienced any recurrent seizure, regardless of their seizure frequency. Among patients with recurrent seizures, preference-based HRQOL and seizure frequency were not monotonically, linearly related. For patients with similar seizure frequency, preference-based HRQOL varied substantially with large overlaps in preference-based HRQOL across different seizure frequency categories. The Monte Carlo simulation found that seizure frequency was a poor predictor of preference-based HRQOL about one third of the time. The presence of depressive symptoms was an independent predictor of preference-based HRQOL measure, accounting for 33.5% of the variation in scores between patients. SIGNIFICANCE: Our findings highlight the importance of attaining complete seizure freedom and the substantial variation in preference-based HRQOL among patients with similar seizure frequencies. To improve assessment of patient-centered outcomes in epilepsy, we encourage adding direct measurement of preference-based HRQOL into clinical care.

Post-stroke epilepsy: From clinical predictors to possible mechanisms.

BACKGROUND: Stroke is the most common cause of newly diagnosed epilepsy in the elderly, ahead of degenerative disorders, brain tumors, and head trauma. Stroke accounts for 30-50% of unprovoked seizures in patients aged ≥ 60 years. This review discusses the current understanding of epidemiology, risk factors, mechanisms, prevention, and treatment opportunities for post-stroke epilepsy (PSE). METHODS: We performed a literature search in the PubMed and Cochrane Library databases. The keywords "stroke, epilepsy", "stroke, seizure", "post-stroke seizure", "post-stroke epilepsy" were used to identify the clinical and experimental articles on PSE. All resulting titles and abstracts were evaluated, and any relevant article was considered. The reference lists of all selected papers and reference lists of selected review papers were manually analyzed to find other potentially eligible articles. RESULTS: PSE occurs in about 6% of stroke patients within several years after the event. The main risk factors are cortical lesion, initial stroke severity, young age and seizures in acute stroke period (early seizures, ES). Other risk factors, such as a cardioembolic mechanism or circulation territory involvement, remain debated. The role of ES as a risk factor of PSE could be underestimated especially in young age. Mechanism of epileptogenesis may involve gliosis scarring, alteration in synaptic plasticity, etc.; and ES may enhance these processes. Statins especially in the acute period of stroke are possible agents for PSE prevention presumably due to their anticonvulsant and neuroprotection effects. Antiepileptic drugs (AED) monotherapy is enough for seizure prevention in most cases of PSE; but no evidence was found for its efficiency against epileptic foci formation. The growing interest in PSE has led to a notable increase in the number of published articles each year. To aid in navigating this expanding body of literature, several tables are included in the manuscript. CONCLUSION: Further studies are needed for better understanding of the pathophysiology of PSE and searching the prevention strategies.