The worldwide epilepsy treatment gap: A systematic review and recommendations for revised definitions - A report from the ILAE Epidemiology Commission.

OBJECTIVE: In order to more appropriately apply and understand the "epilepsy treatment gap" (ETG) concept in current health systems, revised conceptual and operational definitions of ETG are timely and necessary. This article therefore systematically reviews worldwide studies of the ETG, distinguishing high-, middle-, and low-income regions, and provides recommendations for an updated International League Against Epilepsy (ILAE) definition of ETG. METHODS: A systematic review of the ETG was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. The search was conducted from January 1990 to July 2019, in the online databases of Ovid MEDLINE and Embase. Identified abstracts were reviewed in duplicate and data independently extracted using a standard proforma. Data describing treatment gap information including both diagnostic and therapeutic aspects of access to epilepsy treatment were recorded. Descriptive statistics are presented. RESULTS: The treatment gap reported in the 45 distinctive populations represented 33 countries. Treatment gap definitions varied widely. The reported ETGs ranged broadly from 5.6% in Norway to 100% in parts of Tibet, Togo, and Uganda. The wide range of reported ETGs was multifactorial in origin including true differences in the availability and utilization of health care among study populations, variations in operational definitions of the epilepsy treatment gap, and methodological differences in sampling and identifying representative epilepsy cases in populations. Significance and recommendations For the ETG to be a useful metric to compare levels of unmet epilepsy care across different countries and regions, a standardized definition must be adapted, recognizing some of the limitations of the current definitions. Our proposed definition takes into account the lack of effective health care insurance, the diagnostic gap, the therapeutic gap, quality-of-care, and other unmet health care needs."

Big data in epilepsy: Clinical and research considerations. Report from the Epilepsy Big Data Task Force of the International League Against Epilepsy.

Epilepsy is a heterogeneous condition with disparate etiologies and phenotypic and genotypic characteristics. Clinical and research aspects are accordingly varied, ranging from epidemiological to molecular, spanning clinical trials and outcomes, gene and drug discovery, imaging, electroencephalography, pathology, epilepsy surgery, digital technologies, and numerous others. Epilepsy data are collected in the terabytes and petabytes, pushing the limits of current capabilities. Modern computing firepower and advances in machine and deep learning, pioneered in other diseases, open up exciting possibilities for epilepsy too. However, without carefully designed approaches to acquiring, standardizing, curating, and making available such data, there is a risk of failure. Thus, careful construction of relevant ontologies, with intimate stakeholder inputs, provides the requisite scaffolding for more ambitious big data undertakings, such as an epilepsy data commons. In this review, we assess the clinical and research epilepsy landscapes in the big data arena, current challenges, and future directions, and make the case for a systematic approach to epilepsy big data.

Thirty-day readmission after status epilepticus in the United States: Insights from the nationwide readmission database.

OBJECTIVE: To determine the incidence, causes, predictors, and costs of 30-day readmissions in patients admitted with status epilepticus (SE) from a large representative United States (US) population. METHODS: Adults (age ≥18 years) hospitalized with a primary diagnosis of SE (International Classification of Diseases-Ninth Revision-CM codes 345.2 or 345.3) between January 2013 and September 2015 were identified using the Nationwide Readmissions Database. A multivariable logistic regression model was used to identify predictors of 30-day readmissions. RESULTS: Of 42,232 patients with index SE, 6372 (15.0%) were readmitted within 30 days. In the multivariable analysis, intracranial hemorrhage (odds ratio, 1.56; 95% confidence interval, 1.12-2.18), psychosis (1.26 95%, 1.05-1.50), diabetes mellitus (1.12, 95%, 1.00-1.25), chronic kidney disease (1.50, 95%, 1.31-1.72), chronic liver disease (1.51; 95%, 1.24-1.84), >3 Elixhauser comorbidities (1.18; 95%, 1.06-1.31), length of stay >4 days during index hospitalization (1.41; 95%, 1.28-1.56) and discharge to skilled nursing facility (SNF) (1.14; 95%, 1.01-1.28) were independent predictors of 30-day readmission. The most common reason for readmission was seizures (45.1%). Median length of stay and costs of readmission were 4 days (interquartile range [IQR], 2-7 days) and $7882 (IQR, $4649-$15,012), respectively. CONCLUSION: Thirty-day readmissions after SE occurs in 15% of patients, the majority of which were due to seizures. Readmitted patients are more likely to have multiple comorbidities, a longer length of stay, and discharge to SNF. Awareness of these predictors can help identify and target high-risk patients for interventions to reduce readmissions and costs.

New-onset lesional and nonlesional epilepsy in the US population: Patient characteristics and patterns of antiepileptic drug use.

PURPOSE: Describe treatment patterns in patients from the United States with new-onset epilepsy, comparing those with and without lesional epilepsy. METHODS: In this observational study we used Truven Health MarketScan databases derived from commercial health insurance, Medicare and Medicaid claims covering at least 5 years, commencing in 2008. We identified incident epilepsy cases based on International Classification of Diseases, Ninth Revision, Clinical Modification codes indicating epilepsy or recurrent seizures, taking into account antiepileptic drug (AED) claims, consistent with International League Against Epilepsy Commission on Epidemiology recommendations. We identified patients with lesional epilepsy when associated diagnoses indicated central nervous system infection, neoplasm, traumatic brain injury, stroke, senile dementia and static encephalopathy. Lesional and nonlesional cohorts were matched 1:1 on baseline characteristics of age, sex and insurance type for group comparisons. RESULTS: In unmatched cohorts lesional epilepsy patients (N = 15,302) were more commonly older (mean age 48.7 years) compared with nonlesional epilepsy patients (N = 15,970; mean age 18.5 years). Among lesional patients <20 years of age, the leading putative etiology was static encephalopathy, while among ages ≥20 years and older, the leading putative etiology was stroke or cerebrovascular disease. In matched cohorts (7063 patients each), those with lesional epilepsy were significantly less likely to be untreated at 1 year versus those with nonlesional epilepsy (37.2% vs 56.1%). In children and adults among matched cohorts, levetiracetam was the most common AED prescribed for initial AED therapy for the lesional (39.5%) and nonlesional (32.1%) groups. Lesional epilepsy patients on monotherapy were only slightly less likely than nonlesional epilepsy patients to be on the same AED 1 year after treatment initiation (55.6% vs 59.7%). SIGNIFICANCE: Compared with patients with lesional epilepsy, a higher proportion of patients with nonlesional epilepsy remain untreated 1 year after diagnosis. There were differences in AED selection by epilepsy etiology; levetiracetam is the most commonly prescribed drug for both cohorts.

Assessment and effect of a gap between new-onset epilepsy diagnosis and treatment in the US.

OBJECTIVE: To estimate the treatment gap between a new epilepsy diagnosis and antiepileptic drug (AED) initiation in the United States. METHODS: Retrospective claims-based cohort study using Truven Health MarketScan databases (commercial and supplemental Medicare, calendar years 2010-2015; Medicaid, 2010-2014) and a validation study using PharMetrics Plus Database linked to LRx claims database (2009-2014). Persons met epilepsy diagnostic criteria, had an index date (first epilepsy diagnosis) with a preceding 2-year baseline (1 year for persons aged 1 to <2 years; none for persons <1 year), and continuous medical and pharmacy enrollment without epilepsy/seizure diagnosis or AED prescription during baseline. Outcomes included percentage of untreated persons (no AED prescription) up to 3 years' follow-up and comparative outcomes (incidence rate ratio: untreated persons/treated persons), including medical events and health care resource utilization. RESULTS: In the primary study, 59,970 persons met selection (or inclusion) criteria; 36.7% of persons with newly diagnosed epilepsy remained untreated up to 3 years after diagnosis. In the validation study (N = 30,890), 31.8% of persons remained untreated up to 3 years after diagnosis. Lack of AED treatment was associated with an adjusted incidence rate ratio (95% confidence interval) of 1.2 (1.2-1.3) for medical events, 2.3 (2.2-2.3) for hospitalizations, and 2.8 (2.7-2.9) for emergency department visits. CONCLUSIONS: One-third of newly diagnosed persons remain untreated up to 3 years after epilepsy diagnosis. The increased risk of medical events and health care utilization highlights the consequences of delayed treatment after epilepsy diagnosis, which might be preventable.

Antiepileptic Drug Treatment Patterns in Women of Childbearing Age With Epilepsy.

Importance: Limited population-based data are available on antiepileptic drug (AED) treatment patterns in women of childbearing age with epilepsy; the current population risk is not clear. Objectives: To examine the AED treatment patterns and identify differences in use of valproate sodium and topiramate by comorbidities among women of childbearing age with epilepsy. Design, Setting, and Participants: A retrospective cohort study used a nationwide commercial database and supplemental Medicare as well as Medicaid insurance claims data to identify 46 767 women with epilepsy aged 15 to 44 years. The eligible study cohort was enrolled between January 1, 2009, and December 31, 2013. Data analysis was conducted from January 1, 2017, to February 22, 2018. Exposures: Cases required an International Classification of Diseases, Ninth Revision, Clinical Modification-coded epilepsy diagnosis with continuous medical and pharmacy enrollment. Incident cases required a baseline of 2 or more years without an epilepsy diagnosis or AED prescription before the index date. For both incident and prevalent cases, focal and generalized epilepsy cohorts were matched by age, payer type, and enrollment period and then compared. Main Outcomes and Measures: Antiepileptic drug treatment pattern according to seizure type and comorbidities. Results: Of the 46 767 patients identified, there were 8003 incident cases (mean [SD] age, 27.3 [9.4] years) and 38 764 prevalent cases (mean [SD] age, 29.7 [9.0] years). Among 3219 women in the incident epilepsy group who received AEDs for 90 days or more, 3173 (98.6%) received monotherapy as first-line treatment; among 28 239 treated prevalent cases, 18 987 (67.2%) received monotherapy. In 3544 (44.3%) incident cases and 9480 (24.5%) prevalent cases, AED treatment was not documented during 180 days or more of follow-up after diagnosis. Valproate (incident: 35 [5.81%]; prevalent: 514 [13.1%]) and phenytoin (incident: 33 [5.48%]; prevalent: 178 [4.53%]) were more commonly used for generalized epilepsy and oxcarbazepine (incident: 53 [8.03%]; prevalent: 386 [9.89%]) was more often used for focal epilepsy. Levetiracetam (incident: focal, 267 [40.5%]; generalized, 271 [45.0%]; prevalent: focal, 794 [20.3%]; generalized, 871 [22.2%]), lamotrigine (incident: focal, 123 [18.6%]; generalized, 106 [17.6%]; prevalent: focal, 968 [24.8%]; generalized, 871 [22.2%]), and topiramate (incident: focal, 102 [15.5%]; generalized, 64 [10.6%]; prevalent: focal, 499 [12.8%]; generalized, 470 [12.0%]) were leading AEDs prescribed for both focal and generalized epilepsy. Valproate was more commonly prescribed for women with comorbid headache or migraine (incident: 53 of 1251 [4.2%]; prevalent: 839 of 8046 [10.4%]), mood disorder (incident: 63 of 860 [7.3%]; prevalent: 1110 of 6995 [15.9%]), and anxiety and dissociative disorders (incident: 57 of 881 [6.5%]; prevalent: 798 of 5912 [13.5%]). Topiramate was more likely prescribed for those with comorbid headache or migraine (incident: 335 of 1251 [26.8%]; prevalent: 2322 of 8046 [28.9%]). Conclusions and Relevance: Many women appear to be treated with valproate and topiramate despite known teratogenicity risks. Comorbidities may affect selecting certain AEDs despite their teratogenicity risks.

Independent role of neonatal seizures in subsequent neurological outcomes: a population-based study.

AIM: This population-based study aimed to estimate the impact of neonatal seizures on subsequent neurological outcomes, regardless of underlying etiology. METHOD: We performed a retrospective cohort study (1st January 2009-31st December 2014), using a USA nationwide claims database. Newborn infants enrolled in 2009 were followed for up to 6 years. Neonatal seizures were identified by combining the International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code of 779.0 (convulsions in newborn), procedure codes of electroencephalogram and brain imaging, and antiepileptic drugs claims. Cox regression models were built to estimate the independent impact of neonatal seizures on developing epilepsy, intellectual disability, psychiatric/behavioral disorders, and headache. RESULTS: Out of 490 071 newborn infants (251 850 males [51.4%], 238 221 females [48.6%]), 800 neonatal seizure cases were identified. After controlling for sex, birthweight, preterm birth status, and underlying etiology, neonates with seizures were more likely to have epilepsy (hazard ratio=32.7; 95% confidence interval [CI]=27.7-38.7; p<0.001), intellectual disability (hazard ratio=2.0; 95% CI=1.8-2.3; p<0.001), and headache (hazard ratio=1.6; 95% CI=1.1-2.2; p=0.013) than those without seizures. INTERPRETATION: Observed covariates being equal, seizures in neonates appeared to play a significant role in developing epilepsy, intellectual disability, and headache. The findings showed a detrimental impact of the event in the very early life on neurological outcomes in later life. WHAT THIS PAPER ADDS: Seizures had their own impact on the development of adverse neurological outcomes. The magnitude of impact was quite large in epilepsy.

Epidemiology of traumatic brain injury-associated epilepsy and early use of anti-epilepsy drugs: An analysis of insurance claims data, 2004-2014.

BACKGROUND: About 2.8 million TBI-related emergency department visits, hospitalizations and deaths occurred in 2013 in the United States. Post-traumatic epilepsy (PTE) can be a disabling, life-long outcome of TBI. OBJECTIVES: The purpose of this study is to address the probability of developing PTE within 9 years after TBI, the risk factors associated with PTE, the prevalence of anti-epileptic drug (AEDs) use, and the effectiveness of using AEDs prophylactically after TBI to prevent the development of PTE. METHODS: Using MarketScan® databases covering commercial, Medicare Supplemental, and multi-state Medicaid enrollees from 2004 to 2014, we examined the incidence of early seizures (within seven days after TBI) and cumulative incidence of PTE, the hazard ratios (HR) of PTE by age, gender, TBI severity, early seizure and AED use (carbamazepine, clonazepam, divalproex sodium, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, phenytoin, pregabalin, topiramate, acetazolamide). We used backward selection to build the final Cox proportional hazard model and conducted multivariable survival analysis to obtain estimates of crude and adjusted HR (cHRs, aHRs) of PTE and 95% confidence intervals (CI). RESULTS: The incidence of early seizure among TBI patients in our study was 0.5%. The cumulative incidence of PTE increased from 1.0% in one year to 4.0% in nine years. Most patients with TBI (93%) were not prescribed any AED. Gender was not associated with PTE. The risk of PTE was higher for individuals with older age, early seizures, and more severe TBI. Only individuals using prophylactic acetazolamide had significantly lower risk of PTE (aHR = 0.6, CI 0.4-0.9) compared to those not using any AED. CONCLUSION: The probability of developing PTE increased within the study period. The risk of developing PTE significantly increased with age, early seizure and TBI severity. Most of the individuals did not receive AED after TBI. There was no evidence suggesting AEDs helped to prevent PTE with the possible exception of acetazolamide. However, further studies may be needed to test the efficacy of acetazolamide in preventing PTE.

Patient characteristics and treatment patterns in patients with newly diagnosed epilepsy: A US database analysis.

OBJECTIVE: The objective of this study was to determine patient characteristics and antiepileptic drug (AED) treatment patterns in patients with newly diagnosed epilepsy in a United States (US) population followed for ≥180 days. METHODS: In this retrospective cohort study, Commercial, Supplemental Medicare, and Medicaid insurance claims from US-based Truven Health MarketScan® claims database were analyzed for incident epilepsy cases (index date: January 2010-June 2013; prior baseline of 2 years [1 year for ages 1 to <2 years; none for those <1 year]). Cases met epilepsy criteria consistent with the International League Against Epilepsy diagnostic guidelines, with continuous medical and pharmacy enrollment without an epilepsy or seizure diagnosis or AED prescription during baseline. Treatment was classified as monotherapy (one AED for ≥90 continuous days), polytherapy (at least two AEDs for ≥90 days), or untreated (no AED claims but other pharmacy or healthcare claims). Treatment pattern comparisons used matched cohorts across seizure types. RESULTS: Of 58,757 incident cases, 50,838 had a follow-up of ≥180 days. The median (range) follow-up duration was 529 (180-1096) days. Patient characteristics were similar across seizure types (matched focal vs. generalized epilepsy, N = 9949 each). At 6 and 12 months post-index, 46.8% and 52.2% of patients, respectively, had received AED treatment. Of 29,226 patients receiving treatment, 74.7% and 1.6% received monotherapy and polytherapy for ≥90 days, respectively, as first-line treatment; remaining patients received AED for <90 days and were excluded. The probability of remaining on initial treatment after 1 year was 61.0% for monotherapy and 36.5% for polytherapy. The most common first-line AEDs were levetiracetam (44.4%), phenytoin (6.5%), valproic acid (6.4%), lamotrigine (6.3%), oxcarbazepine (5.7%), topiramate (5.5%), and gabapentin (5.3%). CONCLUSION: Although the majority of treated patients received AED monotherapy consistent with guidelines, suboptimal rates of AED treatment and persistence of first-line treatment after initial epilepsy diagnosis suggest that efforts are needed to improve patient care.

The primary prevention of epilepsy: A report of the Prevention Task Force of the International League Against Epilepsy.

Among the causes of epilepsy are several that are currently preventable. In this review, we summarize the public health burden of epilepsy arising from such causes and suggest priorities for primary epilepsy prevention. We conducted a systematic review of published epidemiologic studies of epilepsy of 4 preventable etiologic categories-perinatal insults, traumatic brain injury (TBI), central nervous system (CNS) infection, and stroke. Applying consistent criteria, we assessed the quality of each study and extracted data on measures of risk from those with adequate quality ratings, summarizing findings across studies as medians and interquartile ranges. Among higher-quality population-based studies, the median prevalence of active epilepsy across all ages was 11.1 per 1000 population in lower- and middle-income countries (LMIC) and 7.0 per 1000 in high-income countries (HIC). Perinatal brain insults were the largest attributable fraction of preventable etiologies in children, with median estimated fractions of 17% in LMIC and 15% in HIC. Stroke was the most common preventable etiology among older adults with epilepsy, both in LMIC and in HIC, accounting for half or more of all new onset cases. TBI was the attributed cause in nearly 5% of epilepsy cases in HIC and LMIC. CNS infections were a more common attributed cause in LMIC, accounting for about 5% of all epilepsy cases. Among some rural LMIC communities, the median proportion of epilepsy cases attributable to endemic neurocysticercosis was 34%. A large proportion of the overall public health burden of epilepsy is attributable to preventable causes. The attributable fraction for perinatal causes, infections, TBI, and stroke in sum reaches nearly 25% in both LMIC and HIC. Public health interventions addressing maternal and child health care, immunizations, public sanitation, brain injury prevention, and stroke prevention have the potential to significantly reduce the burden of epilepsy.

National Association of Medical Examiners position paper: Recommendations for the investigation and certification of deaths in people with 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.

National Association of Medical Examiners Position Paper: Recommendations for the Investigation and Certification of Deaths in People with Epilepsy.

Sudden unexpected death of an individual with epilepsy (SUDEP) can pose a challenge to death investigators, as most deaths are unwitnessed and the individual is commonly found dead in bed. Anatomic findings (e.g., tongue/lip bite) are commonly absent and of varying specificity, 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 convened 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.

Comorbidities and risk factors associated with newly diagnosed epilepsy in the U.S. pediatric population.

Neurobehavioral comorbidities can be related to underlying etiology of epilepsy, epilepsy itself, and adverse effects of antiepileptic drugs. We examined the relationship between neurobehavioral comorbidities and putative risk factors for epilepsy in children with newly diagnosed epilepsy. We conducted a retrospective analysis of children aged ≤18years in 50 states and the District of Columbia, using the Truven Health MarketScan® commercial claims and encounters database from January 1, 2009 to December 31, 2013. The eligible study cohort was continuously enrolled throughout 2013 as well as enrolled for any days during a baseline period of at least the prior 2years. Newly diagnosed cases of epilepsy were defined by International Classification of Diseases, Ninth Revision, Clinical Modification-coded diagnoses of epilepsy or recurrent seizures and evidence of prescribed antiepileptic drugs during 2013, when neither seizure codes nor seizure medication claims were recorded during baseline periods. Twelve neurobehavioral comorbidities and eleven putative risk factors for epilepsy were measured. More than 6 million children were analyzed (male, 51%; mean age, 8.8years). A total of 7654 children were identified as having newly diagnosed epilepsy (125 per 100,000, 99% CI=122-129). Neurobehavioral comorbidities were more prevalent in children with epilepsy than children without epilepsy (60%, 99% CI=58.1-61.0 vs. 23%, CI=23.1-23.2). Children with epilepsy were far more likely to have multiple comorbidities (36%, 99% CI=34.3-37.1) than those without epilepsy (8%, 99% CI=7.45-7.51, P<0.001). Preexisting putative risk factors for epilepsy were detected in 28% (99% CI=26.9-29.6) of children with epilepsy. After controlling for demographics, neurobehavioral comorbidities, family history of epilepsy, and other risk factors than primary interest, neonatal seizures had the strongest independent association with the development of epilepsy (OR=29.8, 99% CI=23.7-37.3, P<0.001). Compared with children with risk factors but no epilepsy, those with both epilepsy and risk factors were more likely to have intellectual disabilities (OR=13.4, 99% CI=11.9-15.0, P<0.001). The epilepsy and intellectual disabilities could share the common pathophysiology in the neuronal network.

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.

Sudden unexpected death in epilepsy: epidemiology, mechanisms, and prevention.

Sudden unexpected death in epilepsy (SUDEP) can affect individuals of any age, but is most common in younger adults (aged 20-45 years). Generalised tonic-clonic seizures are the greatest risk factor for SUDEP; most often, SUDEP occurs after this type of seizure in bed during sleep hours and the person is found in a prone position. SUDEP excludes other forms of seizure-related sudden death that might be mechanistically related (eg, death after single febrile, unprovoked seizures, or status epilepticus). Typically, postictal apnoea and bradycardia progress to asystole and death. A crucial element of SUDEP is brainstem dysfunction, for which postictal generalised EEG suppression might be a biomarker. Dysfunction in serotonin and adenosine signalling systems, as well as genetic disorders affecting cardiac conduction and neuronal excitability, might also contribute. Because generalised tonic-clonic seizures precede most cases of SUDEP, patients must be better educated about prevention. The value of nocturnal monitoring to detect seizures and postictal stimulation is unproven but warrants further study.

Epilepsy or seizure disorder? The effect of cultural and socioeconomic factors on self-reported prevalence.

Self-reported epilepsy may be influenced by culture, knowledge, and beliefs. We screened 6420 residents of the District of Columbia (DC) for epilepsy to investigate whether socio-demographics were associated with whether they reported their diagnosis as epilepsy or as seizure disorder. Lifetime and active prevalence rates were 0.54% and 0.21%, respectively for 'epilepsy' and 1.30% and 0.70%, respectively for 'seizure disorder'. Seizure disorder was reported significantly more often than epilepsy among blacks, females, respondents≥50years, those with lower level education, respondents who lived alone and in low income neighborhoods, and those who resided in DC for at least five years. Clinicians should assure that patients and caregivers understand that epilepsy is synonymous with seizure disorder and other culturally appropriate terms, in order to optimize compliance with treatment, disease management instructions, and utilization of other resources targeted at persons with epilepsy. Furthermore, education and awareness campaigns aimed at improving access-to-care, reducing stigma, and increasing awareness of adverse events, such as SUDEP, should include a more diverse definition of epilepsy in their messages.

Estimating Epilepsy Incidence and Prevalence in the US Pediatric Population Using Nationwide Health Insurance Claims Data.

This study aims to determine prevalence and incidence of epilepsy in the US pediatric population. We analyzed commercial claims and Medicaid insurance claims data between 2008 and 2012. Over 8 million continuously enrolled lives aged 0 to 19 years were included. Our definition of a prevalent case of epilepsy was based on International Classification of Diseases-coded diagnoses of epilepsy or seizures and evidence of prescribed antiepileptic drugs. Incident cases were identified in subjects continuously enrolled for ≥2 years of which the first 2 years had no indication of epilepsy or seizures. The overall prevalence estimate for 2012 was 6.8 per 1,000 children. The overall incidence estimate for 2012 was 104 per 100,000 pediatric population. This study provides estimates of the prevalence and incidence of epilepsy in the US pediatric population, using large claims datasets from multiple US population sectors. The findings appear reasonably representative of the US-insured pediatric population.