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Objective Methods Results Significance Little is known about the incidence of late onset epilepsy (LOE) across different racial/ethnic groups in the USA, particularly in the Hispanic population. Stroke, a strong predictor of LOE, is more common in non‐Hispanic Blacks (NHBs) and Hispanics than in non‐Hispanic Whites (NHWs). We assessed the incidence of LOE across racial/ethnic groups and examined whether the associations of stroke with LOE risk differ by race/ethnicity.The Northern Manhattan Study is a population‐based longitudinal study of older adults enrolled between 1993 and 2001. Participants free of history of stroke or epilepsy at baseline (n = 3419) were followed prospectively for incidence of LOE. We estimated LOE incidence per 1000 person‐years in each racial/ethnic group. We used Cox proportional hazards regression to assess the association of race/ethnicity with LOE and multiplicative interactions of race/ethnicity with incident stroke in relation to LOE, adjusting for demographics and comorbid diagnoses.During 51 176 person‐years of follow‐up, 183 individuals developed LOE. Incidence of LOE was significantly higher in NHBs (6.2 per 1000 person‐years) than in NHWs (3.3 per 1000 person‐years, p = .004). There was no significant difference in LOE incidence between NHWs (3.3 per 1000 person‐years) and Hispanics (2.6 per 1000 person‐years, p = .875). However, following incident stroke, the risk of LOE differed across racial/ethnic groups. Incident stroke was associated with 2.55 times the risk of LOE among NHWs (95% confidence interval [CI] = .88–7.35), 8.53 times the risk of LOE among Hispanics (95% CI = 5.36–13.57, p = .04 for stronger association than that in NHWs), and 6.46 times the risk of LOE among NHBs (95% CI = 3.79–11.01, p = .12 for stronger association than that in NHWs).We found a stronger association of incident stroke with LOE risk in Hispanics and NHBs than in NHWs, offering some insight into the racial/ethnic disparities of LOE incidence. [ABSTRACT FROM AUTHOR]

Objective: Cognitive decline is a major concern for older adults with epilepsy. Whether and how much faster older adults with epilepsy experience cognitive decline beyond expected age‐related cognitive change remain unclear. We sought to estimate and compare rates of cognitive decline in older adults with and without epilepsy. Methods: The Cardiovascular Health Study is a population‐based longitudinal cohort study of 5888 US adults aged 65+. Cognitive function was assessed annually with Modified Mini‐Mental State Exam (3MS) and Digit Symbol Substitution Test (DSST). We used linear mixed models to estimate average rates of decline in 3MS and DSST scores by epilepsy status (prevalent, incident, or no epilepsy), adjusted for risk factors associated with cognitive decline. Results: The rate of decline in 3MS was significantly faster in prevalent epilepsy (P <.001) and after incident epilepsy (P =.002) compared with no epilepsy. Prevalent epilepsy and apolipoprotein E gene (APOE) ε4 (ApoE4) had a synergistic interaction, whereby prevalent epilepsy and ApoE4 together were associated with 1.51 points faster annual decline in 3MS than would be expected if prevalent epilepsy and ApoE4 did not interact (P <.001). Older adults with prevalent epilepsy had a significantly lower initial DSST score and faster rate of decline compared to those with no epilepsy (P <.001). Significance: Faster decline in global cognitive ability seen in this study validates concerns of patients. ApoE4 allele status was an effect modifier of the relationship between cognitive decline and prevalent epilepsy. Further research is warranted to explore biological mechanisms and possible interventions to mitigate cognitive decline. [ABSTRACT FROM AUTHOR]

Objective: Carbamazepine, widely used in the treatment of partial and generalized tonic–clonic seizures, has been associated with life‐threatening Stevens‐Johnson syndrome/toxic epidermal necrolysis among some Asians. The HLA‐B*1502 genotype that occurs with varying frequency among Asians is recommended for screening prior to starting carbamazepine. Our goal is to explore the cost‐effectiveness of screening for the presence of this genetic allele. Methods: We constructed a Markov model in a hypothetical cohort of adult Asian patients with epilepsy in the United States being considered for carbamazepine to investigate the cost‐effectiveness of two alternative strategies: (1) no HLA‐B*1502 gene allele screening and using carbamazepine and (2) HLA‐B*1502 gene allele screening and starting levetiracetam in the case of a positive screen. Results: For the lifetime horizon, HLA‐B*1502 gene screening was the cost‐effective choice compared to no gene screening, with an incremental cost‐effectiveness ratio of $27 058 per quality‐adjusted life‐year (QALY), below the $50 000/QALY threshold in 99.69% of probabilistic sensitivity analyses. Although gene screening strategy was more expensive than a no screening strategy, it was more effective, yielding more QALYs, across all Asian ethnic groups. Significance: Our analysis confirms the 2007 US Food and Drug Administration recommendation to screen for HLA‐B*1502 allele before starting treatment with carbamazepine in patients of Asian ancestry in the United States. [ABSTRACT FROM AUTHOR]

• A quarter of patients gave responses indicating that they had high adherence to their ASM regimen. • The odds of high adherence increased with increases in patients' understanding of their epilepsy. • The odds of high adherence decreased with increases in overall life impact and emotional impact of epilepsy. We assessed the relationship of epilepsy illness perceptions to antiseizure medication (ASM) adherence. Surveys were completed by 644 adult patients with epilepsy of unknown cause. We used the Morisky Medication Adherence Scale-8 (MMAS-8) to define "high" adherence (score = 8) and "low-medium" adherence (score < 8). We evaluated epilepsy illness perceptions using seven items from the Brief Illness Perception Questionnaire (BIPQ), each scored from 0-10, measuring participants' views of the overall effect of epilepsy on their lives, how long it would last, how much control they had over their epilepsy, the effectiveness of their treatment, level of concern about epilepsy, level of understanding of epilepsy, and emotional impact of epilepsy. We investigated the association of each BIPQ item with medication adherence using logistic regression models that controlled for potential confounders (age, race/ethnicity, income, and time since the last seizure). One hundred forty-nine patients (23%) gave responses indicating high adherence. In the adjusted models, for each 1-unit increase in participants' BIPQ item scores, the odds of high adherence increased by 17% for understanding of their epilepsy (OR = 1.17, 95% CI 1.07–1.27, p < 0.001), decreased by 11% for overall life impact of epilepsy (OR = 0.89, 95% CI 0.82–0.97, p = 0.01) and decreased by 6% for emotional impact of epilepsy (OR = 0.94, 95% CI 0.86–0.99, p = 0.03). No other illness perception was associated with high adherence. Depression, anxiety, and stigma mediated the inverse relationships of high adherence to the overall life impact of epilepsy and the emotional impact of epilepsy. These measures did not mediate the relationship of high adherence to the perceived understanding of epilepsy. These results indicate that a greater perceived understanding of epilepsy is independently associated with high ASM adherence. Programs aimed at improving patients' understanding of their epilepsy may help improve medication adherence. [ABSTRACT FROM AUTHOR]

Purpose Psychiatric and behavioral side effects (PBSEs) are common, undesirable effects associated with antiepileptic drug (AED) use. The objective of the study was to compare the PBSE profiles of older and newer AEDs in a large specialty practice-based sample of patients diagnosed with epilepsy. Methods As part of the Columbia and Yale AED Database Project, we reviewed patient records including demographics, medical history, AED use, and side effects for 4085 adult patients (age: 18 years) newly started on an AED regimen. Psychiatric and behavioral side effects were determined by patient or physician report in the medical record, which included depressive mood, psychosis, anxiety, suicidal thoughts, irritability, aggression, and tantrum. Significant non-AED predictors of PBSE rate were first determined from 83 variables using logistic regression. Predictors were then controlled for in the comparison analysis of the rate of PBSEs and intolerable PBSEs (PBSEs that led to dosage reduction or discontinuation) between 18 AEDs. Results Psychiatric and behavioral side effects occurred in 17.2% of patients and led to intolerability in 13.8% of patients. History of psychiatric condition(s), secondary generalized seizures, absence seizures, and intractable epilepsy were associated with increased incidence of PBSE. Levetiracetam (LEV) had the greatest PBSE rate (22.1%). This was statistically significant when compared with the aggregate of the other AEDs (P < 0.001, OR = 6.87). Levetiracetam was also significantly (P < 0.001) associated with higher intolerability rate (17.7%), dose decreased rate (9.4%), and complete cessation rate (8.3%), when compared with the aggregate of the other AEDs. Zonisamide (ZNS) was also significantly associated with a higher rate of PBSE (9.7%) and IPBSE (7.9%, all P < 0.001). On the other hand, carbamazepine (CBZ), clobazam (CLB), gabapentin (GBP), lamotrigine (LTG), oxcarbazepine (OXC), phenytoin (PHT), and valproate (VPA) were significantly associated with a decreased PBSE rates (P < 0.001). Carbamazepine, GBP, LTG, PHT, and VPA were also associated with lower IPBSE rates when compared individually with the aggregate of other AEDs. All other AEDs were found to have intermediate rates that were not either increased or decreased compared with other AEDs. When each AED was compared to LTG, only CBZ had a significantly lower PBSE rate. The main limitations of this study were that the study design was retrospective and not blinded, and the AEDs were not randomly assigned to patients. Conclusions Psychiatric and behavioral side effects occur more frequently in patients taking LEV and ZNS than any other AED and led to higher rates of intolerability. Lower PBSE rates were seen in patients taking CBZ, CLB, GBP, LTG, OXC, PHT, and VPA. Our findings may help facilitate the AED selection process. [ABSTRACT FROM AUTHOR]

Purpose In the current study, we explored the prevalence of physician-confirmed seizure clusters. We also investigated potential clinical factors associated with the occurrence of seizure clusters overall and by epilepsy type. Methods We reviewed medical records of 4116 adult (≥16 years old) outpatients with epilepsy at our centers for documentation of seizure clusters. Variables including patient demographics, epilepsy details, medical and psychiatric history, AED history, and epilepsy risk factors were then tested against history of seizure clusters. Patients were then divided into focal epilepsy, idiopathic generalized epilepsy (IGE), or symptomatic generalized epilepsy (SGE), and the same analysis was run. Results Overall, seizure clusters were independently associated with earlier age of seizure onset, symptomatic generalized epilepsy (SGE), central nervous system (CNS) infection, cortical dysplasia, status epilepticus, absence of 1-year seizure freedom, and having failed 2 or more AEDs (P < 0.0026). Patients with SGE (27.1%) were more likely to develop seizure clusters than patients with focal epilepsy (16.3%) and IGE (7.4%; all P < 0.001). Analysis by epilepsy type showed that absence of 1-year seizure freedom since starting treatment at one of our centers was associated with seizure clustering in patients across all 3 epilepsy types. In patients with SGE, clusters were associated with perinatal/congenital brain injury. In patients with focal epilepsy, clusters were associated with younger age of seizure onset, complex partial seizures, cortical dysplasia, status epilepticus, CNS infection, and having failed 2 or more AEDs. In patients with IGE, clusters were associated with presence of an aura. Only 43.5% of patients with seizure clusters were prescribed rescue medications. Conclusion Patients with intractable epilepsy are at a higher risk of developing seizure clusters. Factors such as having SGE, CNS infection, cortical dysplasia, status epilepticus or an early seizure onset, can also independently increase one’s chance of having seizure clusters. [ABSTRACT FROM AUTHOR]

Objective: To examine the seizure trajectories of adults with epilepsy developing drug-resistant epilepsy (DRE) and to identify the predictors of seizure trajectory outcome. Methods: Adult patients failing two antiepileptic drugs (AEDs) due to inefficacy and starting their third AED at a tertiary epilepsy center were followed for seizure trajectory outcome during medical management. Seizure trajectories were categorized into one of four patterns: (1) course with constant seizures; (2) fluctuating course; (3) delayed attainment of seizure freedom (seizure freedom delayed for >12 months after start of the study, but patient stayed in seizure freedom); and (4) early attainment of seizure freedom (within 12 months of starting study). Multiple ordinal logistic regression models were used to estimate the association between trajectory categories and clinical factors. Results: Four hundred three adult patients met the eligibility criteria. Of these, 212 (53%) never achieved a seizure-free period of a year or more. The trajectories of 63 patients (16%) had a complex fluctuating trajectory, 62 (15%) had delayed onset of seizure freedom, and 66 (16%) had an early seizure freedom. Independent predictors associated with more favorable outcome trajectories were epilepsy type and length of follow-up. Specifically, compared to patients with focal epilepsy of temporal lobe, patients with focal epilepsy of occipital lobe (OR 3.80, 95% confidence interval [CI] 1.00-14.51, p = 0.04), generalized genetic (OR 3.23, 95% CI 1.88-5.57, p < 0.0001), unclear epilepsy type (OR 3.82, 95% CI 1.53-9.52, p < 0.005), and both focal and generalized epilepsy(OR 11.73, 95% CI 1.69-81.34, p = 0.01) were significantly more likely to experience a better trajectory pattern. Significance: Examination of patterns of seizure trajectory of patients with incident DRE showed that 31% were in continuous seizure freedom at the end of the observation period. [ABSTRACT FROM AUTHOR]

Objective This study tested whether perceived epilepsy-related stigma is associated with adherence in people living with epilepsy and if information, motivation, and behavioral skills are potential pathways underlying the stigma–adherence link. Methods We surveyed persons living with epilepsy between the ages of 18 and 65 ( N = 140) using an online questionnaire to assess medication adherence and perceived epilepsy-related stigma. In addition, participants reported their level of information, motivation, and behavioral skills. Results Higher perceived epilepsy-related stigma was associated with lower medication adherence ( r = − 0.18, p < .05). Higher perceived stigma was associated with lower levels of information ( r = − 0.28, p < .05), motivation ( r = − 0.55, p < .05), and behavioral skills ( r = − 0.41, p < .05), and the link between stigma and adherence was fully explained by information, motivation, and behavioral skills, i.e., the effect of stigma on adherence was fully mediated ( c = − 0.18, p < .05 reduced to c′ = 0.06, p = .48). Conclusion Perceived epilepsy-related stigma is problematic for maintaining the prescribed medication regimen in people living with epilepsy. The information–motivation–behavioral skills model is a useful framework for understanding the pathways linking perceived stigma and adherence in this population. [ABSTRACT FROM AUTHOR]

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.. A PowerPoint slide summarizing this article is available for download in the Supporting Information section . [ABSTRACT FROM AUTHOR]

Abstract: What are the health status and health needs of people with epilepsy? How do clinicians and patients choose between alternative interventions for the same condition? Are health interventions used effectively in the community, and do they improve health? How can we translate findings from regulatory clinical trials to the real world? These and similar questions are the subject of applied translational research. This evolving and broad-ranging area of research involves the application of basic sciences such as epidemiology, biostatistics, economics, and behavioral science to the assessment of health, health interventions, and outcomes. However, despite its palpable importance, applied translational research remains underfunded and underutilized. Using their own innovative research as a prototype, two young and promising investigators provide insights not only into the enormous potential but also the gaps and hurdles of two specific areas of applied translational research, i.e., clinical decision analysis and health services research. The message is clear that if we are to understand and improve the health of people with epilepsy in clinics, hospitals, and communities, we must substantially increase research capacity to address the many gaps that thwart our progress in applied research in epilepsy. This article is part of a Special Issue entitled “The Future of Translational Epilepsy Research”. [Copyright &y& Elsevier]

Abstract: Patients with pharmacoresistant temporal lobe epilepsy (TLE) contemplating brain surgery must make a complex treatment decision involving trade-offs. Patient decision aids, containing information on the risks and benefits of treatment interventions, increase patient knowledge and facilitate shared decision making between patients and physicians. We conducted five focus groups to describe the information patients need to make informed decisions about TLE surgery. Twenty patients who had undergone TLE surgery described the information used in their decision-making process, and evaluated the potential for a patient decision aid to assist other patients who are considering surgery. Thematic analysis revealed information needs that were both experiential (i.e., learning about other patients’ experiences through testimonials) and factual (i.e., individualized statistical information). Patients also made suggestions on how this information should be delivered to patients. These data will accelerate the development of a patient decision aid designed to assist TLE patients in their decision making about epilepsy surgery. [Copyright &y& Elsevier]

Summary: Recent studies have provided much needed data on the probability of seizure remission among adults with chronic intractable epilepsy treated medically. Here we provide an extended follow-up to our earlier study in order to provide a more comprehensive picture of long-term prognosis in this patient population during medical treatment. The prevalence cohort was followed for two outcomes—complete seizure remission for ≥12 months and subsequent seizure relapse among those attaining a seizure remission. The study outcomes were estimated using Kaplan–Meier analysis. We found that the probability of attaining a ≥12 months of complete seizure freedom to be approximately 3–4% per year through 8 years of follow-up. By year 5 since the start of seizure remission, the cumulative probability of seizure relapse was 81%, although only half of the patients with seizure relapse went on to experience their previous seizure frequency. [ABSTRACT FROM AUTHOR]

Abstract: Patients with epilepsy are frequently confronted with complex treatment decisions. Communicating treatment risks is often difficult because patients may have difficulty with basic statistical concepts (i.e., low numeracy) or might misconceive the statistical information based on the way information is presented, a phenomenon known as “framing bias.” We assessed numeracy and framing bias in 95 adults with chronic epilepsy and explored cognitive correlates of framing bias. Compared with normal controls, patients with epilepsy had significantly poorer performance on the Numeracy scale (P =0.02), despite a higher level of education than normal controls (P <0.001). Compared with patients with higher numeracy, patients with lower numeracy were significantly more likely to exhibit framing bias. Abstract problem solving performance correlated with the degree of framing bias (r =0.631, P <0.0001), suggesting a relationship between aspects of executive functioning and framing bias. Poor numeracy and susceptibility framing bias place patients with epilepsy at risk for uninformed decisions. [ABSTRACT FROM AUTHOR]

Summary: We examined whether duration of epilepsy prior to temporal lobe resection has decreased over the years as a result of increasing body of evidence in the literature showing the benefits of anterior temporal resection. We stratified the 213 patients, who had their first temporal lobe resection at our center between 1996 and 2007 into three groups in order to detect any trends in duration of epilepsy: group A (surgery between 1996 and 1999); group B (surgery between 2000 and 2003); group C (surgery between 2004 and 2007). No difference in mean duration of epilepsy was detected between the three groups (p =0.54). The mean duration in epilepsy prior to temporal lobe resection has persisted at greater than 20 years during the past two decades. [Copyright &y& Elsevier]

To investigate the cumulative probabilities of ≥12 month seizure remission and seizure relapse following remission, and to test the associations of clinical characteristics with these two study end points in a prevalence cohort of intractable adult epilepsy patients during medical management. A retrospective cohort study of intractable epilepsy patients seen in 2001 at a single center was conducted. Kaplan–Meier analysis was used to estimate the cumulative probabilities of seizure remission and subsequent seizure relapse. Cox proportional hazards models were used to estimate the association (1) between clinical factors and ≥12 month seizure remission and (2) between clinical factors and seizure relapse following remission. One hundred eighty-seven subjects met the eligibility criteria for intractable epilepsy. The estimate of probability of remission was about 4% per year. Seizure remission was temporary for some individuals, as 5 out of 20 subjects with remission ultimately relapsed. No clinical factors predicted the likelihood of achieving ≥12 month seizure remission or subsequent seizure relapse. Some people with intractable epilepsy achieve ≥12 month seizure remission during medical treatment. Remission, however, is only temporary for some individuals. We were unable to identify clear predictors for remission. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to characterize antiseizure medication (ASM) treatment pathways in Medicare beneficiaries with newly treated epilepsy. Methods: This was a retrospective cohort study using Medicare claims. Medicare is the United States' federal health insurance program for people aged 65 years and older plus younger people with disabilities or end‐stage renal disease. We included beneficiaries with newly treated epilepsy (International Classification of Diseases codes for epilepsy/convulsions 2014–2017, no ASM in the previous 2 years). We displayed the sequence of ASM fills using sunburst plots overall, then stratified by mood disorder, age, and neurologist prescriber. We tabulated drug costs for each pathway. Results: We included 21 458 beneficiaries. Levetiracetam comprised the greatest number of pill days (56%), followed by gabapentin (11%) and valproate (8%). There were 22 288 unique treatment pathways. The most common pathways were levetiracetam monotherapy (43%), gabapentin monotherapy (10%), and valproate monotherapy (5%). Gabapentin was the most common second‐ and third‐line ASM. Whereas only 2% of pathways involved first‐line lacosamide, those pathways accounted for 19% of cost. Gabapentin and valproate use was increased and levetiracetam use was decreased in beneficiaries with mood disorders compared to beneficiaries without mood disorders. Levetiracetam use was increased and gabapentin, valproate, lamotrigine, and topiramate use was decreased in beneficiaries aged >65 years compared with those aged 65 years or less. Lamotrigine, levetiracetam, and lacosamide use was increased and gabapentin use was decreased in beneficiaries whose initial prescriber was a neurologist compared to those whose prescriber was not a neurologist. Significance: Levetiracetam monotherapy was the most common pathway, although substantial heterogeneity existed. Lacosamide accounted for a small percentage of ASMs but a disproportionately large share of cost. Neurologists were more likely to prescribe lamotrigine compared with nonneurologists, and lamotrigine was prescribed far less frequently than may be endorsed by guidelines. Future work may explore patient‐ and physician‐driven factors underlying ASM choices. [ABSTRACT FROM AUTHOR]

Objective: New‐onset refractory status epilepticus (NORSE) is a rare but severe clinical syndrome. Despite rigorous evaluation, the underlying cause is unknown in 30%–50% of patients and treatment strategies are largely empirical. The aim of this study was to describe clinical outcomes in a cohort of well‐phenotyped, thoroughly investigated patients who survived the initial phase of cryptogenic NORSE managed in specialist centers. Methods: Well‐characterized cases of cryptogenic NORSE were identified through the EPIGEN and Critical Care EEG Monitoring Research Consortia (CCEMRC) during the period 2005–2019. Treating epileptologists reported on post‐NORSE survival rates and sequelae in patients after discharge from hospital. Among survivors >6 months post‐discharge, we report the rates and severity of active epilepsy, global disability, vocational, and global cognitive and mental health outcomes. We attempt to identify determinants of outcome. Results: Among 48 patients who survived the acute phase of NORSE to the point of discharge from hospital, 9 had died at last follow‐up, of whom 7 died within 6 months of discharge from the tertiary care center. The remaining 39 patients had high rates of active epilepsy as well as vocational, cognitive, and psychiatric comorbidities. The epilepsy was usually multifocal and typically drug resistant. Only a minority of patients had a good functional outcome. Therapeutic interventions were heterogenous during the acute phase of the illness. There was no clear relationship between the nature of treatment and clinical outcomes. Significance: Among survivors of cryptogenic NORSE, longer‐term outcomes in most patients were life altering and often catastrophic. Treatment remains empirical and variable. There is a pressing need to understand the etiology of cryptogenic NORSE and to develop tailored treatment strategies. [ABSTRACT FROM AUTHOR]

A response from the authors of the article "Drug-resistant epilepsy in adults: Outcome trajectories after failure of two medications" is presented.

Objective: Hispanics continue to face challenges when trying to access health care, including epilepsy care and genetic‐related health care services. This study examined epilepsy genetic knowledge and beliefs in this historically underserved population. Methods: Questionnaires were completed by 641 adults with epilepsy without identified cause, of whom 122 self‐identified as Hispanic or Latino and 519 as non‐Hispanic. Participants were asked about their views on the contribution of genetics to the cause of their epilepsy ("genetic attribution"), optimism for advancements in epilepsy genetic research ("genetic optimism"), basic genetic knowledge, and epilepsy‐specific genetic knowledge. Generalized linear models were used to compare the two groups in the means of quantitative measures and percents answered correctly for individual genetic knowledge items. Analyses were adjusted for age, sex, education, religion, family history of epilepsy, and time since last seizure. Results: Hispanics did not differ from non‐Hispanics in genetic attribution, genetic optimism, or number of six basic genetic knowledge items answered correctly. The number of nine epilepsy‐specific genetic knowledge items answered correctly was significantly lower for Hispanics than non‐Hispanics (adjusted mean = 6.0 vs. 6.7, p <.001). After adjustment for education and other potential mediators, the proportion answered correctly was significantly lower for Hispanics than non‐Hispanics for only two items related to family history and penetrance of epilepsy‐related genes. Only 54% of Hispanics and 61% of non‐Hispanics answered correctly that "If a person has epilepsy, his or her relatives have an increased chance of getting epilepsy." Significance: Despite large differences in sociodemographic variables including education, most attitudes and beliefs about genetics were similar in Hispanics and non‐Hispanics. Epilepsy‐specific genetic knowledge was lower among Hispanics than non‐Hispanics, and this difference was mostly mediated by differences in demographic variables. Genetic counseling should address key concepts related to epilepsy genetics to ensure they are well understood by both Hispanic and non‐Hispanic patients. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to determine areas of consensus among an international panel of experts for the clinical presentation and diagnosis of epilepsy with eyelid myoclonia (EEM; formerly known as Jeavons syndrome) to improve a timely diagnosis. Methods: An international steering committee was convened of physicians and patients/caregivers with expertise in EEM. This committee summarized the current literature and identified an international panel of experts (comprising 25 physicians and five patients/caregivers). This international expert panel participated in a modified Delphi process, including three rounds of surveys to determine areas of consensus for the diagnosis of EEM. Results: There was a strong consensus that EEM is a female predominant generalized epilepsy syndrome with onset between 3 and 12 years of age and that eyelid myoclonia must be present to make the diagnosis. There was a strong consensus that eyelid myoclonia may go unrecognized for years prior to an epilepsy diagnosis. There was consensus that generalized tonic–clonic and absence seizures are typically or occasionally seen in patients. There was a consensus that atonic or focal seizures should lead to the consideration of reclassification or alternate diagnoses. There was a strong consensus that electroencephalography is required, whereas magnetic resonance imaging is not required for diagnosis. There was a strong consensus to perform genetic testing (either epilepsy gene panel or whole exome sequencing) when one or a combination of factors was present: family history of epilepsy, intellectual disability, or drug‐resistant epilepsy. Significance: This international expert panel identified multiple areas of consensus regarding the presentation and evaluation of EEM. These areas of consensus may be used to inform clinical practice to shorten the time to the appropriate diagnosis. [ABSTRACT FROM AUTHOR]

Objective: There are limited data about the treatment and management of epilepsy with eyelid myoclonia (EEM). The objective of this study was to determine areas of consensus among an international panel of experts for the management of EEM (formerly known as Jeavons syndrome). Methods: An international steering committee was convened of physicians and patients/caregivers with expertise in EEM. This committee summarized the current literature and identified an international panel of experts (comprising 25 physicians and five patients/caregivers). This panel participated in a modified Delphi process, including three rounds of surveys to determine areas of consensus for the treatment, other areas of management, and prognosis for EEM. Results: There was a strong consensus for valproic acid as the first‐line treatment, with levetiracetam or lamotrigine as preferable alternatives for women of childbearing age. There was a moderate consensus that ethosuximide and clobazam are also efficacious. There was a strong consensus to avoid sodium channel‐blocking medications, except for lamotrigine, as they may worsen seizure control. There was consensus that seizures typically persist into adulthood, with remission occurring in <50% of patients. There was less agreement about other areas of management, including dietary therapy, lens therapy, candidacy for driving, and outcome. Significance: This international expert panel identified multiple areas of consensus regarding the optimal management of EEM. These areas of consensus may inform clinical practice to improve the management of EEM. In addition, multiple areas with less agreement were identified, which highlight topics for further research. [ABSTRACT FROM AUTHOR]

Objective: Genetic factors have long been debated as a cause of failure of surgery for mesial temporal lobe epilepsy (MTLE). We investigated whether rare genetic variation influences seizure outcomes of MTLE surgery. Methods: We performed an international, multicenter, whole exome sequencing study of patients who underwent surgery for drug‐resistant, unilateral MTLE with normal magnetic resonance imaging (MRI) or MRI evidence of hippocampal sclerosis and ≥2‐year postsurgical follow‐up. Patients with either sustained seizure freedom (favorable outcome) or ongoing uncontrolled seizures since surgery (unfavorable outcome) were included. Exomes of controls without epilepsy were also included. Gene set burden analyses were carried out to identify genes with significant enrichment of rare deleterious variants in patients compared to controls. Results: Nine centers from 3 continents contributed 206 patients operated for drug‐resistant unilateral MTLE, of whom 196 (149 with favorable outcome and 47 with unfavorable outcome) were included after stringent quality control. Compared to 8,718 controls, MTLE cases carried a higher burden of ultrarare missense variants in constrained genes that are intolerant to loss‐of‐function (LoF) variants (odds ratio [OR] = 2.6, 95% confidence interval [CI] = 1.9–3.5, p = 1.3E‐09) and in genes encoding voltage‐gated cation channels (OR = 2.4, 95% CI = 1.4–3.8, p = 2.7E‐04). Proportions of subjects with such variants were comparable between patients with favorable outcome and those with unfavorable outcome, with no significant between‐group differences. Interpretation: Rare variation contributes to the genetic architecture of MTLE, but does not appear to have a major role in failure of MTLE surgery. These findings can be incorporated into presurgical decision‐making and counseling. ANN NEUROL 2023;93:752–761 [ABSTRACT FROM AUTHOR]

Objective: More than one third of appropriately treated patients with epilepsy have continued seizures despite two or more medication trials, meeting criteria for drug‐resistant epilepsy (DRE). Accurate and reliable identification of patients with DRE in observational data would enable large‐scale, real‐world comparative effectiveness research and improve access to specialized epilepsy care. In the present study, we aim to develop and compare the performance of computable phenotypes for DRE using the Observational Medical Outcomes Partnership (OMOP) Common Data Model. Methods: We randomly sampled 600 patients from our academic medical center's electronic health record (EHR)‐derived OMOP database meeting previously validated criteria for epilepsy (January 2015–August 2021). Two reviewers manually classified patients as having DRE, drug‐responsive epilepsy, undefined drug responsiveness, or no epilepsy as of the last EHR encounter in the study period based on consensus definitions. Demographic characteristics and codes for diagnoses, antiseizure medications (ASMs), and procedures were tested for association with DRE. Algorithms combining permutations of these factors were applied to calculate sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for DRE. The F1 score was used to compare overall performance. Results: Among 412 patients with source record‐confirmed epilepsy, 62 (15.0%) had DRE, 163 (39.6%) had drug‐responsive epilepsy, 124 (30.0%) had undefined drug responsiveness, and 63 (15.3%) had insufficient records. The best performing phenotype for DRE in terms of the F1 score was the presence of ≥1 intractable epilepsy code and ≥2 unique non‐gabapentinoid ASM exposures each with ≥90‐day drug era (sensitivity =.661, specificity =.937, PPV =.594, NPV =.952, F1 score =.626). Several phenotypes achieved higher sensitivity at the expense of specificity and vice versa. Significance: OMOP algorithms can identify DRE in EHR‐derived data with varying tradeoffs between sensitivity and specificity. These computable phenotypes can be applied across the largest international network of standardized clinical databases for further validation, reproducible observational research, and improving access to appropriate care. [ABSTRACT FROM AUTHOR]

We retrospectively explored patients with drug-resistant epilepsy (DRE) who previously underwent presurgical evaluation to identify correlations between surgical outcomes and pathogenic variants in epilepsy genes. Through an international collaboration, we evaluated adult DRE patients who were screened for surgical candidacy. Patients with pathogenic (P) or likely pathogenic (LP) germline variants in genes relevant to their epilepsy were included, regardless of whether the genetic diagnosis was made before or after the presurgical evaluation. Patients were divided into two groups: resective surgery (RS) and non-resective surgery candidates (NRSC), with the latter group further divided into: palliative surgery (vagus nerve stimulation, deep brain stimulation, responsive neurostimulation or corpus callosotomy) and no surgery. We compared surgical candidacy evaluations and postsurgical outcomes in patients with different genetic abnormalities. We identified 142 patients with P/LP variants. After presurgical evaluation, 36 patients underwent RS, while 106 patients were NRSC. Patients with variants in ion channel and synaptic transmission genes were more common in the NRSC group (48 %), compared with the RS group (14 %) (p<0.001). Most patients in the RS group had tuberous sclerosis complex. Almost half (17/36, 47 %) in the RS group had Engel class I or II outcomes. Patients with channelopathies were less likely to undergo a surgical procedure than patients with mTORopathies, but when deemed suitable for resection had better surgical outcomes (71 % versus 41 % with Engel I/II). Within the NRSC group, 40 underwent palliative surgery, with 26/40 (65 %) having ≥50 % seizure reduction after mean follow-up of 11 years. Favourable palliative surgery outcomes were observed across a diverse range of genetic epilepsies. Genomic findings, including a channelopathy diagnosis, should not preclude presurgical evaluation or epilepsy surgery, and appropriately selected cases may have good surgical outcomes. Prospective registries of patients with monogenic epilepsies who undergo epilepsy surgery can provide additional insights on outcomes. • Germline genetic variants can influence epilepsy surgery outcomes and must be a part of presurgical investigations. • Channelopathy patients with structural lesions may benefit from epilepsy surgery. • Palliative goals should be prioritized over epilepsy surgery for patients with TSC and multiple tubers. • Neuromodulation and corpus callosotomy are acceptable treatments for a broad spectrum of genetic epilepsies. • Larger studies on surgical outcomes are needed to study impact of genotype on surgical success. [ABSTRACT FROM AUTHOR]

Inconsistent access to healthcare for people with epilepsy results in reduced adherence to antiseizure medications, increased seizure frequency, and fewer appropriate referrals for epilepsy surgery. Identifying and addressing factors that impede access to care should consequently improve patient outcomes. We hypothesized that health insurance and transportation affect access to outpatient neurology care for adults living with epilepsy in the United States (US). We conducted a retrospective cross-sectional study of US adults with active epilepsy surveyed via the National Health Interview Survey (NHIS) in 2015 and 2017. We established whether patients reported seeing a neurologist in the past year and used multiple logistic regression to determine whether health insurance status and transportation access were associated with this outcome. We identified 735 respondents from 2015 and 2017, representing an estimated 2.98 million US adults with active epilepsy. After adjusting for socioeconomic and seizure-related co-variates, we found that a lack of health insurance coverage was associated with no epilepsy care in the past year (adjusted odds ratio [aOR] 0.22; 95 % confidence interval [CI]: 0.09 – 0.54). Delayed care due to inadequate transportation (aOR 0.42; 95 % CI: 0.19 – 0.93) also resulted in reduced patient access to a neurologist. Due to the inherent nature of their condition, people with epilepsy are less likely to have employer-sponsored health insurance or consistent driving privileges. Yet, these factors also impact patient access to neurological care. We must address transportation and insurance barriers through long-term investment and partnership between community, healthcare, and government stakeholders. • 64.8 % of US adults with active epilepsy saw a neurologist in 2015 and 2017. • Patients without insurance were less likely to see a neurologist. • Transportation barriers also contribute to decreased access to epilepsy care. [ABSTRACT FROM AUTHOR]

Objective: This study addresses the contribution of genetics‐related concerns to reduced childbearing among people with epilepsy. Methods: Surveys were completed by 606 adult patients with epilepsy of unknown cause at our medical center. Poisson regression analysis was used to assess the relations of number of offspring to: (1) genetic attribution (GA: participants' belief that genetics was a cause of their epilepsy), assessed via a novel scale developed from four survey items (Cronbach's alpha =.89), (2) participants' estimates of epilepsy risk in the child of a parent with epilepsy (1%, 5%–10%, 25%, and 50%–100%), and (3) participants' reports of the influence on their reproductive decisions of "the chance of having a child with epilepsy" (none/weak/moderate, strong/very strong). Analyses were adjusted for age, education, race/ethnicity, religion, type of epilepsy (generalized, focal, and both/unclassifiable), and age at epilepsy onset (<10, 10–19, and ≥20 years). Results: Among participants 18–45 years of age, the number of offspring decreased significantly with increasing GA (highest vs lowest GA quartile rate ratio [RR] =.5, p <.001), and increasing estimated epilepsy risk in offspring (with 5%–10% as referent because it is closest to the true value, RR for 25%:.7, p =.05; RR for 50%–100%:.6, p =.03). Number of offspring was not related to the reported influence of "the chance of having a child with epilepsy" on reproductive decisions. Among participants >45 years of age, the number of offspring did not differ significantly according to GA quartile or estimated offspring epilepsy risk. However, those reporting a strong/very strong influence on their reproductive decisions of "the chance of having a child with epilepsy" had only 60% as many offspring as others. Significance: These findings suggest that overestimating the risk of epilepsy in offspring can have important consequences for people with epilepsy. Patient and provider education about recurrence risks and genetic testing options to clarify risks are critical, given their potential influence on reproductive decisions. [ABSTRACT FROM AUTHOR]

Objective: We sought to determine which combination of clinical and electroencephalography (EEG) characteristics differentiate between an antiseizure medication (ASM)–resistant vs ASM‐responsive outcome for patients with idiopathic generalized epilepsy (IGE). Methods: This was a case‐control study of ASM‐resistant cases and ASM‐responsive controls with IGE treated at five epilepsy centers in the United States and Australia between 2002 and 2018. We recorded clinical characteristics and findings from the first available EEG study for each patient. We then compared characteristics of cases vs controls using multivariable logistic regression to develop a predictive model of ASM‐resistant IGE. Results: We identified 118 ASM‐resistant cases and 114 ASM‐responsive controls with IGE. First, we confirmed our recent finding that catamenial epilepsy is associated with ASM‐resistant IGE (odds ratio [OR] 3.53, 95% confidence interval [CI] 1.32–10.41, for all study subjects) after covariate adjustment. Other independent factors seen with ASM resistance include certain seizure‐type combinations (absence, myoclonic, and generalized tonic‐clonic seizures [OR 7.06, 95% CI 2.55–20.96]; absence and generalized tonic‐clonic seizures [OR 4.45, 95% CI 1.84–11.34]), as well as EEG markers of increased generalized spike‐wave discharges (GSWs) in sleep (OR 3.43, 95% CI 1.12–11.36 for frequent and OR 7.21, 95% CI 1.50–54.07 for abundant discharges in sleep) and the presence of generalized polyspike trains (GPTs; OR 5.49, 95% CI 1.27–38.69). The discriminative ability of our final multivariable model, as measured by area under the receiver‐operating characteristic curve, was 0.80. Significance: Multiple clinical and EEG characteristics independently predict ASM resistance in IGE. To improve understanding of a patient's prognosis, clinicians could consider asking about specific seizure‐type combinations and track whether they experience catamenial epilepsy. Obtaining prolonged EEG studies to record the burden of GSWs in sleep and assessing for the presence of GPTs may provide additional predictive value. [ABSTRACT FROM AUTHOR]

The main objective of this study was to assess the efficacy, safety, and retention rates of levetiracetam monotherapy in children with epilepsy. A retrospective review of pediatric patients receiving levetiracetam monotherapy at 2 large tertiary epilepsy centers over an 11-year period was conducted. One hundred two patients using levetiracetam monotherapy with a mean age of 13.1 years were identified. For the entire cohort, a 6-month retention rate was 61.1% and a 12-month retention rate 53.1%. With regard to seizure freedom, 46.8% of those patients that remained on monotherapy for at least 6 months became seizure free. Twelve-month seizure freedom was reached by 41.2%. About one-third (32.4%) of patients reported adverse effects, with irritability, moodiness, and depression being the most common. Despite a number of patients that reported adverse events, levetiracetam monotherapy was found to be potentially effective in this cohort of children with epilepsy and warrants further, prospective studies. [ABSTRACT FROM AUTHOR]

Summary: Objective: The Epilepsy Genetics Initiative (EGI) was formed in 2014 to create a centrally managed database of clinically generated exome sequence data. EGI performs systematic research‐based reanalysis to identify new molecular diagnoses that were not possible at the time of initial sequencing and to aid in novel gene discovery. Herein we report on the efficacy of this approach 3 years after inception. Methods: One hundred sixty‐six individuals with epilepsy who underwent diagnostic whole exome sequencing (WES) were enrolled, including 139 who had not received a genetic diagnosis. Sequence data were transferred to the EGI and periodically reevaluated on a research basis. Results: Eight new diagnoses were made as a result of updated annotations or the discovery of novel epilepsy genes after the initial diagnostic analysis was performed. In five additional cases, we provided new evidence to support or contradict the likelihood of variant pathogenicity reported by the laboratory. One novel epilepsy gene was discovered through dual interrogation of research and clinically generated WES. Significance: EGI's diagnosis rate of 5.8% represents a considerable increase in diagnostic yield and demonstrates the value of periodic reinterrogation of whole exome data. The initiative's contributions to gene discovery underscore the importance of data sharing and the value of collaborative enterprises. [ABSTRACT FROM AUTHOR]

Summary: Objective: The dynamics of the postictal period, which may demonstrate such dramatic clinical phenomena as focal neurological deficits, prolonged coma and immobility, and even sudden death, are poorly understood. We sought to classify and characterize postictal phases of bilateral tonic–clonic seizures based on electroencephalographic (EEG) criteria and associated clinical features. Methods: We performed a detailed electroclinical evaluation of the postictal period in a series of 31 bilateral tonic–clonic seizures in 16 patients undergoing epilepsy surgery evaluations for focal pharmacoresistant epilepsy with intracranial electrodes and time‐locked video. Results: The postictal EEG demonstrated three clearly differentiated phases as follows: attenuation, a burst‐attenuation pattern, and a return to continuous background, with abrupt, synchronized transitions between phases. Postictal attenuation was common, occurring in 84% of seizures in 94% of patients in this study. There was increased power in gamma frequencies (>25 Hz) during postictal attenuation periods relative to preictal baseline in 88% of seizures demonstrating the attenuation pattern (n = 25 seizures, P < 0.002). Such increases were seen in >90% of channels in 13 seizures (52%) and <10% of channels in three seizures (12%). Postictal immobility was seen in 87% of seizures, with either a flaccid (58%) or rigid/dystonic (29%) appearance. Clinical motor manifestations, including focal dystonic posturing, automatisms, head and eye deviation, and myoclonic jerking, continued or emerged within the first minute following seizure termination in 48% of seizures, regardless of EEG appearance. Significance: Intracranial postictal attenuation, which may be diffuse or focal, is so common that it should be regarded as a ubiquitous feature of bilateral tonic‐clonic seizures, rather than an unusual event. The prominence of high‐frequency activity coupled with emerging clinical features, including rigid immobility and semiologies such as automatisms, during the postictal period supports the presence of ongoing seizure‐related neuronal activity in unrecorded brain regions. [ABSTRACT FROM AUTHOR]

Summary: Objective: There is little detailed phenotypic characterization of bilateral hippocampal sclerosis (HS). We therefore conducted a multicenter review of people with pharmacoresistant epilepsy and bilateral HS to better determine their clinical characteristics. Methods: Databases from 11 EPIGEN centers were searched. For identified cases, clinicians reviewed the medical notes, imaging, and electroencephalographic (EEG), video‐EEG, and neuropsychometric data. Data were irretrievably anonymized, and a single database was populated to capture all phenotypic information. These data were compared with phenotyped cases of unilateral HS from the same centers. Results: In total, 96 patients with pharmacoresistant epilepsy and bilateral HS were identified (43 female, 53 male; age range = 8‐80 years). Twenty‐five percent had experienced febrile convulsions, and 27% of patients had experienced status epilepticus. The mean number of previously tried antiepileptic drugs was 5.32, and the average number of currently prescribed medications was 2.99; 44.8% of patients had cognitive difficulties, and 47.9% had psychiatric comorbidity; 35.4% (34/96) of patients continued with long‐term medical therapy alone, another 4 being seizure‐free on medication. Sixteen patients proceeded to, or were awaiting, neurostimulation, and 11 underwent surgical resection. One patient was rendered seizure‐free postresection, with an improvement in seizures for 3 other cases. By comparison, of 201 patients with unilateral HS, a significantly higher number (44.3%) had febrile convulsions and only 11.4% had experienced status epilepticus. Importantly, 41.8% (84/201) of patients with unilateral HS had focal aware seizures, whereas such seizures were less frequently observed in people with bilateral HS, and were never observed exclusively (P = .002; Fisher's exact test). Significance: The current work describes the phenotypic spectrum of people with pharmacoresistant epilepsy and bilateral HS, highlights salient clinical differences from patients with unilateral HS, and provides a large platform from which to develop further studies, both epidemiological and genomic, to better understand etiopathogenesis and optimal treatment regimes in this condition. [ABSTRACT FROM AUTHOR]

Objective To compare efficacy of unique antiepileptic drug (AED) polytherapy regimens among patients with focal epilepsy. Methods From a longitudinal study of AED treatment, we identified patients with active focal epilepsy who had attempted at least two unique AED regimens (mono-, duo-, or tri-therapy). Efficacy was defined as the presence of at least one six-month period of continuous seizure freedom during exposure to a regimen. To control for individual variations in response and epilepsy severity, we used within-patient comparison approaches, in which we: 1) compared head-to-head unique regimens tried within the same patients; 2) compared one regimen versus aggregate of other regimens attempted in that patient; and 3) compared aggregated monotherapy versus polytherapy regimens. Results 757 patients met our criteria and had collectively attempted 170 unique regimens. In the head-to-head analysis, lamotrigine monotherapy was more effective than phenytoin monotherapy. Two regimens were more effective than the aggregate of other regimens attempted: levetiracetam/lamotrigine duotherapy and lamotrigine monotherapy. Two other regimens exhibited slightly better efficacy but did not reach statistical significance: clobazam/levetiracetam/lamotrigine and levetriacetam/oxcarbazepine. Patients who previously attempted at least four regimens had slightly better outcomes on polytherapy than monotherapy, though this was not significant. Significance We identified two unique regimens more likely to be associated with ≥6 months of seizure freedom: levetiracetam/lamotrigine duotherapy and lamotrigine monotherapy. Polytherapy may be an effective alternative to monotherapy for patients with focal epilepsy and persistent seizures. [ABSTRACT FROM AUTHOR]

Epilepsy with eyelid myoclonia (EEM) is a generalized epilepsy syndrome with childhood-onset and 2:1 female predominance that consists of: 1. eyelid myoclonia with or without absence seizures, 2. eye closure induced seizures or EEG paroxysms, 3. clinical or EEG photosensitivity. While eyelid myoclonia is the disease hallmark, other seizure types, including absence seizures and generalized tonic-clonic seizures, may be present. It is thought to have a genetic etiology, and around one-third of patients may have a positive family history of epilepsy. Recently, specific genetic mutations have been recognized in a minority patients, including in SYNGAP1 , NEXMIF , RORB , and CHD2 genes. There are no randomized controlled trials in EEM, and the management literature is largely restricted to small retrospective studies. Broad-spectrum antiseizure medications such as valproate, levetiracetam, lamotrigine, and benzodiazepines are typically used. Seizures typically persist into adulthood, and drug-resistant epilepsy is reported in over 50%. • Epilepsy with eyelid myoclonia is an under-recognized generalized epilepsy syndrome. • Eyelid myoclonia are frequent and may occur multiple times a day. • Specific genetic mutations have been found in some patients. • There is limited data about treatment, and drug-resistant epilepsy is common. [ABSTRACT FROM AUTHOR]

• Access to the EMU in NJ differs by race/ethnicity and primary payer. • Patients without health insurance had the lowest EMU admission rates. • Minority race/ethnic groups also had lower admission rates, which varied by payer. Elective admission to the epilepsy monitoring unit (EMU) is an essential service provided by epilepsy centers, particularly for those with drug-resistant epilepsy. Given previously characterized racial and socioeconomic healthcare disparities in the management of epilepsy, we sought to understand access and utilization of this service in New Jersey (NJ). We examined epilepsy hospitalizations in NJ between 2014 and 2016 using state inpatient and emergency department (ED) databases. We stratified admissions by race/ethnicity and primary payer and used these to estimate and compare (1) admission rates per capita in NJ, as well as (2) admission rates per number of ED visits for each group. Patients without insurance underwent elective EMU admission at the lowest rates across all racial/ethnic groups and payer types studied. Black patients with Medicaid and private insurance were admitted at disproportionately low rates relative to their number of ED visits. Hispanic/Latino and Asian/Pacific Islanders with private insurance, Hispanic/Latinos with Medicaid, and Asian/Pacific Islanders with Medicare were also admitted at low rates per capita within each respective payer category. Future studies should focus on addressing causal factors driving healthcare disparities in epilepsy, particularly for patients without adequate health insurance coverage and those who have been historically underserved by the healthcare system. [ABSTRACT FROM AUTHOR]

Objective The extent to which adverse cognitive effects (ACEs) to a specific antiepileptic drug (AED) affect the chance of developing ACEs to other AEDs (i.e., cross-sensitivity) is unknown. We investigated the rates of cross-sensitivity of ACEs among AEDs and examined the association between clinical characteristics and occurrence of having ACEs to multiple AEDs in adults with epilepsy. Methods The rates of cross-sensitivity of intolerable ACEs (IACEs; i.e., ACEs leading to dosage reduction or discontinuation) and the non-AED predictors of IACEs were investigated in 2269 patients who had taken at least two AEDs at a single center. We accounted for AED load and looked for specific cross-sensitivities between AEDs as well as cross-sensitivity based on the AED mechanism of action. Results Among the 2269 patients, the highest rates of IACEs were seen with TPM (26.3%), ZNS (9.8%), PHT (8.8%), and VPA (8.5%). Intolerable ACEs to two or more AEDs occurred in 100 patients (4.4%). History of psychiatric condition(s) and absence seizure type were independent predictors of IACEs to two or more AEDs. High rates of cross-sensitivity of IACEs were seen between phenytoin (PHT) and lamotrigine (LTG), valproate (VPA) and phenytoin, and valproate and zonisamide (ZNS). For example, of patients who had IACEs to VPA and were also prescribed ZNS, 46.2% had IACEs to ZNS (abbreviated as VPA → ZNS: 46.2%); of patients who had IACEs to ZNS and were also prescribed VPA, 37.5% had IACEs to VPA (abbreviated as ZNS → VPA: 37.5%). Other results are as follows: LTG → PHT: 28.6%, PHT → LTG: 20.0%, PHT → VPA: 42.9%, and VPA → PHT: 27.3%. No specific cross-sensitivities were found among AEDs sharing a similar mechanism of action. Significance The probability of ACE intolerability to an AED can increase if a patient developed ACE intolerability to another AED. The cross-sensitivity rates for ACE intolerability between LTG and PHT, PHT and VPA, and VPA and ZNS were found to be particularly high. The cross-sensitivity rates provided here may be clinically useful for predicting ACE intolerability in patients taking certain AEDs and for AED selection in individual patients. [ABSTRACT FROM AUTHOR]

• Comparisons of epilepsy treatment pathways are limited by available data standards. • The Common Data Model (CDM) offers an international clinical data sharing standard. • We validated a CDM phenotype to identify epilepsy in electronic health record data. • Levetiracetam replaced phenytoin as the most common first-line agent over time. • Significant variability persisted in first and subsequent antiseizure medication use. Efforts to characterize variability in epilepsy treatment pathways are limited by the large number of possible antiseizure medication (ASM) regimens and sequences, heterogeneity of patients, and challenges of measuring confounding variables and outcomes across institutions. The Observational Health Data Science and Informatics (OHDSI) collaborative is an international data network representing over 1 billion patient records using common data standards. However, few studies have applied OHDSI's Common Data Model (CDM) to the population with epilepsy and none have validated relevant concepts. The goals of this study were to demonstrate the feasibility of characterizing adult patients with epilepsy and ASM treatment pathways using the CDM in an electronic health record (EHR)-derived database. We validated a phenotype algorithm for epilepsy in adults using the CDM in an EHR-derived database (2001–2020) against source records and a prospectively maintained database of patients with confirmed epilepsy. We obtained the frequency of all antecedent conditions and procedures for patients meeting the epilepsy phenotype criteria and characterized ASM exposure sequences over time and by age and sex. The phenotype algorithm identified epilepsy with 73.0–85.0% positive predictive value and 86.3% sensitivity. Many patients had neurologic conditions and diagnoses antecedent to meeting epilepsy criteria. Levetiracetam incrementally replaced phenytoin as the most common first-line agent, but significant heterogeneity remained, particularly in second-line and subsequent agents. Drug sequences included up to 8 unique ingredients and a total of 1,235 unique pathways were observed. Despite the availability of additional ASMs in the last 2 decades and accumulated guidelines and evidence, ASM use varies significantly in practice, particularly for second-line and subsequent agents. Multi-center OHDSI studies have the potential to better characterize the full extent of variability and support observational comparative effectiveness research, but additional work is needed to validate covariates and outcomes. [ABSTRACT FROM AUTHOR]

Context: Patients with pharmacoresistant epilepsy have increased mortality compared with the general population, but patients with pharmacoresistant temporal lobe epilepsy who meet criteria for surgery and who become seizure-free after anterior temporal lobe resection have reduced excess mortality vs those with persistent seizures.Objective: To quantify the potential survival benefit of anterior temporal lobe resection for patients with pharmacoresistant temporal lobe epilepsy vs continued medical management.Design: Monte Carlo simulation model that incorporates possible surgical complications and seizure status, with 10,000 runs. The model was populated with health-related quality-of-life data obtained directly from patients and data from the medical literature. Insufficient data were available to assess gamma-knife radiosurgery or vagal nerve stimulation.Main Outcome Measures: Life expectancy and quality-adjusted life expectancy.Results: Compared with medical management, anterior temporal lobe resection for a 35-year-old patient with an epileptogenic zone identified in the anterior temporal lobe would increase survival by 5.0 years (95% CI, 2.1-9.2) with surgery preferred in 100% of the simulations. Anterior temporal lobe resection would increase quality-adjusted life expectancy by 7.5 quality-adjusted life-years (95%, CI, -0.8 to 17.4) with surgery preferred in 96.5% of the simulations, primarily due to increased years spent without disabling seizures, thereby reducing seizure-related excess mortality and improving quality of life. The results were robust to sensitivity analyses.Conclusion: The decision analysis model suggests that on average anterior temporal lobe resection should provide substantial gains in life expectancy and quality-adjusted life expectancy for surgically eligible patients with pharmacoresistant temporal lobe epilepsy compared with medical management. [ABSTRACT FROM AUTHOR]

Epilepsy surgery is considered to reduce the risk of epilepsy-related mortality, including sudden unexpected death in epilepsy (SUDEP), though data from existing surgical series are conflicting. We retrospectively examined all-cause mortality and SUDEP in a population of 590 epilepsy surgery patients and a comparison group of 122 patients with pharmacoresistant focal epilepsy who did not undergo surgery, treated at Columbia University Medical Center between 1977 and 2014. There were 34 deaths in the surgery group, including 14 cases of SUDEP. Standardized mortality ratio (SMR) for the surgery group was 1.6, and SUDEP rate was 1.9 per 1000 patient-years. There were 13 deaths in the comparison group, including 5 cases of SUDEP. Standardized mortality ratio for the comparison group was 3.6, and SUDEP rate was 4.6 per 1000 patient-years. Both were significantly greater than in the surgery group (p < 0.05). All but one of the surgical SUDEP cases, and all of the comparison group SUDEP cases, had a history of bilateral tonic–clonic seizures (BTCS). Of postoperative SUDEP cases, one was seizure-free, and two were free of BTCS at last clinical follow-up. Time to SUDEP in the surgery group was longer than in the comparison group (10.1 vs 5.9 years, p = 0.013), with 10 of the 14 cases occurring > 10 years after surgery. All-cause mortality was reduced after epilepsy surgery relative to the comparison group. There was an early benefit of surgery on the occurrence of SUDEP, which was reduced after 10 years. A larger, multicenter study is needed to further investigate the time course of postsurgical SUDEP. • All-cause mortality is reduced after surgery in patients with pharmacoresistant focal epilepsy. • Sudden unexpected death in epilepsy (SUDEP) rate is reduced after surgery in patients with pharmacoresistant focal epilepsy. • The benefit of epilepsy surgery on SUDEP occurrence is seen early but is reduced after 10 years. [ABSTRACT FROM AUTHOR]