Short-Term Impact of Seizures and Mitigation Opportunities.

PURPOSE OF REVIEW: The burden of epilepsy is complex and consists of elements directly related to acute seizures as well as those associated with living with a chronic neurologic disorder. The purpose of this systematic review was to characterize short-term burdens of seizures and to explore the potential value of acute treatments to mitigate these burdens apart from reducing the risk of status epilepticus. RECENT FINDINGS: A systematic literature search was conducted using PubMed to identify articles published from January 1, 2017, to June 22, 2023, that described short-term burdens and acute treatments of seizures. Primary outcomes included those related to short-term burdens of seizures and the benefits of acute treatments to reduce short-term burdens. Of the 1332 articles identified through PubMed and 17 through other sources, 27 had relevant outcomes and were included in the qualitative synthesis. Seizure emergencies negatively affected short-term quality of life and the ability to conduct normal daily living activities and were associated with physical (injury) and financial (emergency transport, hospitalization) burdens. The use of acute treatment was associated with a rapid return (≤ 1 h) to normal function/self for both patients and caregivers and potentially lower healthcare utilization and costs. Seizure action plans may improve knowledge and comfort with seizure care, empowering patients and caregivers. The short-term burden of seizures can create a substantial negative impact on patients and caregivers. Acute treatments may reduce the short-term burdens of seizures in addition to their well-described role to reduce seizure activity and the risk for status epilepticus.

Enhanced sensitivity of electrocorticography during awake craniotomy using a novel circular grid electrode.

PURPOSE: Awake craniotomy with intraoperative functional brain mapping (FBM) bedside neurological testing is an important technique used to optimize resective brain surgeries near eloquent cortex. Awake craniotomy performed with electrocorticography (ECoG) and direct electrical stimulation (DES) for FBM can delineate eloquent cortex from lesions and epileptogenic regions. However, current electrode technology demonstrates spatial limitations. Our group has developed a novel circular grid with the goal of improving spatial recording of ECoG to enhance detection of ictal and interictal activity. METHODS: This retrospective study was approved by the institutional review board at Mayo Clinic Florida. We analyzed patients undergoing awake craniotomy with ECoG and DES and compared ECoG data obtained using the 22 contact circular grid to standard 6 contact strip electrode. RESULTS: We included 144 cases of awake craniotomy with ECoG, 73 using circular grid and 71 with strip electrode. No significant differences were seen regarding preoperative clinical and demographic data, duration of ECoG recording (p = 0.676) and use of DES (p = 0.926). Circular grid was more sensitive in detecting periodic focal epileptiform discharges (PFEDs) (p = 0.004), PFEDs plus (p = 0.032), afterdischarges (ADs) per case (p = 0.022) at lower minimum (p = 0.012) and maximum (p < 0.0012) intensity stimulation, and seizures (p = 0.048). PFEDs (p < 0.001), PFEDs plus (p < 0.001), and HFOs (p < 0.001) but not ADs (p = 0.255) predicted electrographic seizures. CONCLUSION: We demonstrate higher sensitivity in detecting ictal and interictal activity on ECoG during awake craniotomy with a novel circular grid compared to strip electrode, likely due to better spatial sampling during ECoG. We also found association between PFEDs and intraoperative seizures.

The influence of social determinants of health on epilepsy treatment delays in an Arizona Medicaid population.

OBJECTIVE: The purpose of this study was to better understand the role of social determinants of health (SDoH) in both treatment delays and treatment gaps for individuals with epilepsy (IWE) enrolled in Arizona's Medicaid program using predictive models at the population and individual levels. METHODS: In this retrospective cohort study, two statistical regression models were developed using Arizona Medicaid medical and pharmacy claims records from 2015-2019 and selected census tract-level SDoH data. Three treatment outcomes were defined: timely treatment (treated within thirty days); delayed treatment (treated after thirty days); and untreated. For the first model, least squares regression was used to regress the epilepsy treatment delays on selected SDoH factors at the population-level. For the second model, multinomial logistic regression was used to estimate associations between epilepsy treatment delays and individual-level sociodemographic factors. RESULTS: Of the 5965 IWE identified with a new epilepsy diagnosis during the study period, 43.1% were treated with a mean delay of 180 days. Among the treated population, 42% received timely treatment. A treatment gap of at least 40.6% and potentially up to 56.9% was calculated. Individuals with epilepsy diagnosed in an inpatient setting or in emergency departments were more likely to be treated and receive timely treatment than those diagnosed in an office or clinic setting. Individuals with epilepsy diagnosed in "other" settings were more likely to go untreated or receive delayed treatment than a patient diagnosed in an office or clinic. Compared to IWE aged 31-50 years, IWE aged 0-30 years were more likely to receive timely treatment, IWE aged 51-64 years were more likely to receive delayed treatment, and IWE aged 65 years or older were more likely to go untreated. Widowed IWE were more likely to go untreated relative to single patients. Individuals with epilepsy experiencing homelessness were also more likely to go untreated. Unemployed IWE were more likely to go untreated or receive delayed treatment. Native American IWE were more likely to go untreated compared to White patients. CONCLUSIONS: Treatment gaps and treatment delays are experienced by IWE in the Arizona Medicaid population. The SDoH factors predicted to impact treatment delays include care setting, age, race, marital status, homelessness, and employment.

Behavioral adverse events with brivaracetam, levetiracetam, perampanel, and topiramate: A systematic review.

PURPOSE: To understand the currently available post-marketing real-world evidence of the incidences of and discontinuations due to the BAEs of irritability, anger, and aggression in people with epilepsy (PWE) treated with the anti-seizure medications (ASMs) brivaracetam (BRV), levetiracetam (LEV), perampanel (PER), and topiramate (TPM), as well as behavioral adverse events (BAEs) in PWE switching from LEV to BRV. METHODS: A systematic review of published literature using the Cochrane Library, PubMed/MEDLINE, and Embase was performed to identify retrospective and prospective observational studies reporting the incidence of irritability, anger, or aggression with BRV, LEV, PER, or TPM in PWE. The incidences of these BAEs and the rates of discontinuation due to each were categorized by ASM, and where possible, weighted means were calculated but not statistically assessed. Behavioral and psychiatric adverse events in PWE switching from LEV to BRV were summarized descriptively. RESULTS: A total of 1500 records were identified in the searches. Of these, 44 published articles reporting 42 studies met the study criteria and were included in the data synthesis, 7 studies were identified in the clinical trial database, and 5 studies included PWE switching from LEV to BRV. Studies included a variety of methods, study populations, and definitions of BAEs. While a wide range of results was reported across studies, weighted mean incidences were 5.6% for BRV, 9.9% for LEV, 12.3% for PER, and 3.1% for TPM for irritability; 3.3%* for BRV, 2.5% for LEV, 2.0% for PER, and 0.2%* for TPM for anger; and 2.5% for BRV, 2.6% for LEV, 4.4% for PER, and 0.5%* for TPM for aggression. Weighted mean discontinuation rates were 0.8%* for BRV, 3.4% for LEV, 3.0% for PER, and 2.2% for TPM for irritability and 0.8%* for BRV, 2.4% for LEV, 9.2% for PER, and 1.2%* for TPM for aggression. There were no discontinuations for anger. Switching from LEV to BRV led to improvement in BAEs in 33.3% to 83.0% of patients (weighted mean, 66.6%). *Denotes only 1 study. CONCLUSIONS: This systematic review characterizes the incidences of irritability, anger, and aggression with BRV, LEV, PER, and TPM, and it provides robust real-world evidence demonstrating that switching from LEV to BRV may improve BAEs. While additional data remain valuable due to differences in methodology (which make comparisons difficult), these results improve understanding of the real-world incidences of discontinuations due to these BAEs in clinical practice and can aid in discussions and treatment decision-making with PWE.

Recommendations for development of acute seizure action plans (ASAPs) from an expert panel.

PURPOSE OF REVIEW: Disease-related treatment action plans for acute exacerbations providing information that may be helpful for self-management for patients and caregivers are commonly used for chronic conditions such as asthma and diabetes. However, among patients with epilepsy, a review of the literature suggested that the majority did not have an action plan in place for acute seizure treatment. RECENT FINDINGS: Currently, there is a lack of unified guidance on seizure action plans (SAPs) in the literature. In the authors' opinion, available formats have limitations for practical use and may not be easily customizable to individual patients, and they are not often designed to provide simple-to-follow steps for rapid immediate steps to determine and initiate appropriate treatment of seizure emergencies. Our group reviewed current examples of SAPs and provided guidance on the development of acute seizure action plans (ASAPs) designed to facilitate rapid, appropriate acute care in the community and to be as useful as possible for a wide range of care partners, including those with limited experience. SUMMARY: This paper provides agreed upon expert opinion recommendations and considerations for goals, development process, types of content, and format for an ASAP.

Innovative approaches reaching underserved and rural communities to improve epilepsy care: A review of the methodology of the Connectors Project.

OBJECTIVE: The Connectors Project, a collaboration between the Epilepsy Foundation and UCB Pharma, was a multiyear project designed to improve epilepsy care in underserved communities. A core objective of the Connectors Project was to pilot new and innovative approaches to epilepsy awareness and education in rural and underserved areas, including standardized curricula for healthcare providers and patients. METHODS: A series of consensus conferences explored opportunities and barriers to epilepsy care throughout the United States including access to local Epilepsy Foundations, neurologists, and epilepsy centers. Data from QuintilesIMS™ were examined for access to newer antiepileptic drugs (AEDs)-a proxy for quality of epilepsy care-in different regions. State factors (e.g., local epilepsy foundation office, access to newer vs. older AEDs, and geographic density and diversity) were used in selecting four states as examples of rural and underserved areas to pilot the awareness and educational programs. For each state, a work team assessed challenges and opportunities, tailored educational curricula, and developed strategies for effective delivery of the educational programs. Interventions were held between June 2016 and June 2017. Interventions consisted of outreach and awareness programs, in-person health education to healthcare providers and patients/families, and digital health education. RESULTS: Michigan, Nevada, Oklahoma, and West Virginia were identified as pilot states representing geographically diverse areas, ranging from a state with a large high-density population center with several epilepsy centers and a local Epilepsy Foundation office (Michigan) to a state with predominately rural areas and a few small urban cores, two epilepsy centers, and no in-state Epilepsy Foundation office (West Virginia). State work teams tailored interventions and examined options for type, intent, ease of use, and impact. All states implemented outreach and awareness initiatives and in-person health education for patients and healthcare providers; use of digital health education was variable. Measurement of the interventions was agreed to be performed by the use of patient and physician surveys and reevaluation of data from QuintilesIMS for access to newer AEDs. CONCLUSION: Local Epilepsy Foundation offices successfully connected healthcare providers in rural and underserved areas to epilepsy education designed to enhance quality care in epilepsy. Educational opportunities for people with epilepsy and their families addressed critical gaps in accessing quality epilepsy care and self-management. Tailored and innovative educational approaches can be used to increase awareness levels and to overcome geographic challenges in reaching underserved populations. Relationship building and repeated, consistent engagement with healthcare providers and patients can assist in improving communication and self-management skills among patients with epilepsy.

Current state of the union of epilepsy care in the United States: Antiepileptic drugs - An introduction to the Connectors Project.

PURPOSE: How antiepileptic drugs (AEDs) are used in the United States (US) is one proxy public health indicator for the current state of epilepsy management. The use of phenytoin, other older AEDs, and newer AEDs may act as an indicator for the quality of epilepsy practice in addition to the current American Academy of Neurology quality measures. Data on AED used by states and populations can help identify which public health interventions are necessary to improve the status of epilepsy care. The Connectors Project, a collaboration between the Epilepsy Foundation and UCB Pharma, is a multiyear project designed to improve epilepsy awareness and management in underserved communities. The objective of the first phase of the Connectors Project was to assess geographic variation in epilepsy care and identify locations in need of improved epilepsy care by initially evaluating AED use in the US. METHODS: A retrospective cross-sectional administrative claim analysis was conducted using the QuintilesIMS™ database which included US longitudinal retail prescription and office medical claims data. Patients with a confirmed epilepsy diagnosis who were prescribed AEDs were identified. Patients with an AED prescription over a 3-year period from January 2013 to December 2015 were included if they had an epilepsy diagnosis in the 2-year period before their first AED prescription in the reporting period. The percentages of patients initially prescribed phenytoin, other older AEDs (carbamazepine and valproate), and newer AEDs (eslicarbazepine, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, topiramate) were calculated and stratified by US state and Washington, DC. Patients were considered newly treated if they had an epilepsy diagnosis code and had not received an epilepsy drug in the 1-year period preceding the first AED prescription in the reporting period. Data are reported using the moving annual total ending December 2015. RESULTS: Approximately 2.5 million US patients with epilepsy and their AED prescriptions were identified from 2013 to 2015. Predictably, states with the largest population had the highest number of patients with epilepsy who were prescribed an AED, including California, Texas, Florida, and New York. Regions with the highest total proportion of phenytoin use with a low proportion of newer AED use were Mississippi (24.4% and 53.1%, respectively) and Washington, DC (24.7% and 58.1%). Montana had the lowest proportion of phenytoin use with the highest proportion of newer AED use (7.9% and 70.4%). Among newly treated patients (N=237,347), Hawaii (39.1%) and Alaska (38.8%) had the highest percentage of phenytoin use compared with all other states. Idaho (86.1%) and Montana (84.4%) had the highest proportion of newer AED use. Washington, DC (50.9%) and Hawaii (60.9%) had the lowest proportion of patients treated with newer AEDs. North Dakota (29.6%) and Washington, DC (27.9%) had the highest rates of other older AEDs use. CONCLUSIONS: A substantial proportion of newly treated US patients with epilepsy are underserved regarding newer AED use with Mississippi and Washington, DC having the highest proportion of phenytoin use relative to newer AED use. Understanding the socioeconomic and demographic barriers for these observations is essential in planning interventions to improve the quality of life and care for patients with epilepsy, including newly treated patients. These data provide a baseline to target educational and clinical interventions for improving the quality of US epilepsy care.

Usage of EpiFinder clinical decision support in the assessment of epilepsy.

BACKGROUND: The diagnosis of epilepsy is at times elusive for both neurologists and nonneurologists, resulting in delays in diagnosis and therapy. The development of screening methods has been identified as a priority in response to this diagnostic and therapeutic gap. EpiFinder is a novel clinical decision support tool designed to enhance the process of information gathering and integration of patient/proxy respondent data. It is designed specifically to take key terms from a patient's history and incorporate them into a heuristic algorithm that dynamically produces differential diagnoses of epilepsy syndromes. OBJECTIVE: The objective of this study was to test the usability and diagnostic accuracy of the clinical decision support application EpiFinder in an adult population. METHODS: Fifty-seven patients were prospectively identified upon admission to the Epilepsy Monitoring Unit (EMU) for episode classification from January through June of 2017. Based on semiologic input, the application generates a list of epilepsy syndromes. The EpiFinder-generated diagnosis for each subject was compared to the final diagnosis obtained via continuous video electroencephalogram (cVEEG) monitoring. RESULTS: Fifty-three patients had habitual events recorded during their EMU stay. A diagnosis of epilepsy was confirmed (with cVEEG monitoring) in 26 patients while 27 patients were found to have a diagnosis other than epilepsy. The algorithm appropriately predicted differentiation between the presence of an epilepsy syndrome and an alternative diagnosis with 86.8% (46/53 participants) accuracy. EpiFinder correctly identified the presence of epilepsy with a sensitivity of 86.4% (95% confidence interval [CI]: 65.0-97.1) and specificity of 85.1% (95% CI: 70.2-96.4). CONCLUSION: The initial testing of the EpiFinder algorithm suggests possible utility in differentiating between an epilepsy syndrome and an alternative diagnosis in adult patients.

Diagnostic utility of the Minnesota Multiphasic Personality Inventory-2 Restructured Form in the epilepsy monitoring unit: Considering sex differences.

Psychological assessment measures are frequently used to evaluate patients in epilepsy monitoring units. One goal of that assessment is to contribute information that may help with differential diagnosis between epilepsy and psychogenic nonepileptic seizures (PNES). The Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF) is one such measure. Del Bene et al. (2017) recently published an analysis that was the first to compare MMPI-2-RF scale elevations between diagnostic groups stratified by sex. The purpose of the present study was to replicate that analysis in a larger sample. Similar to previous work, we found that both men and women with PNES were more likely than men and women with epilepsy to report high levels of somatic complaints (2 to 5 times greater odds of somatic symptom reporting) and a variety of types of complaints. Mood disturbance scales were not significantly elevated in our PNES sample. Results contribute to the small body of research on sex differences in patients with PNES and suggest that somatization is a key characterization across sexes.

Social factors in marijuana use for medical and recreational purposes.

Of all the various treatment options for epilepsy, no other therapy comes close to the polarity that cannabis engenders. The rationale for this reaction is firmly rooted in the social factors that enshroud the use of marijuana for both medical and recreational purposes. In order to best understand how to approach this controversial treatment, it is essential to explore the social, demographic, and historical variables that have led to the current opinions on cannabis therapy and how this has converged on epilepsy treatment. Utilizing a sociological conceptual framework, this review discusses in depth the social, cultural, and historical dimensions of cannabis use in the US for medical purposes and its impact on epilepsy treatment. Moreover, it posits that cannabis therapy and the opinions surrounding its use are products of history and assesses this treatment option through the lens of our current times. This article is part of a Special Issue titled Cannabinoids and Epilepsy.

Historical perspective on the medical use of cannabis for epilepsy: Ancient times to the 1980s.

There has been a dramatic surge in the interest of utilizing cannabis for epilepsy treatment in the US. Yet, access to cannabis for research and therapy is mired in conflicting regulatory policies and shifting public opinion. Understanding the current state of affairs in the medical cannabis debate requires an examination of the history of medical cannabis use. From ancient Chinese pharmacopeias to the current Phase III trials of pharmaceutical grade cannabidiol, this review covers the time span of cannabis use for epilepsy therapy so as to better assess the issues surrounding the modern medical opinion of cannabis use. This article is part of a Special Issue titled Cannabinoids and Epilepsy.

The Epilepsy Foundation's 4th Biennial Epilepsy Pipeline Update Conference.

On June 5 and 6, 2014, the Epilepsy Foundation held its 4th Biennial Epilepsy Pipeline Update Conference, an initiative of the Epilepsy Therapy Project, which showcased the most promising epilepsy innovations from health-care companies and academic laboratories dedicated to pioneering and advancing drugs, biologics, technologies, devices, and diagnostics for epilepsy. Speakers and attendees included emerging biotech and medical technology companies, major pharmaceutical and device companies, as well as investigators and innovators at the cutting-edge of epilepsy. The program included panel discussions on collaboration between small and large companies, how to get products in need of funding to the marketplace, who is currently funding epilepsy and CNS innovation, and how the NIH facilitates early-stage drug development. Finally, the conference featured the third annual "Shark Tank" competition. The presentations are summarized in this paper, which is followed by a compilation of the meeting poster abstracts.

Fall prevention and bathroom safety in the epilepsy monitoring unit.

Falls are one of the most common adverse events occurring in the epilepsy monitoring unit (EMU) and can result in significant injury. Protocols and procedures to reduce falls vary significantly between institutions as it is not yet known what interventions are effective in the EMU setting. This study retrospectively examined the frequency of falls and the impact of serial changes in fall prevention strategies utilized in the EMU between 2001 and 2014 at a single institution. Overall fall rate was 2.81 per 1000 patient days and varied annually from 0 to 9.02 per 1000 patient days. Both seizures and psychogenic nonepileptic events occurring in the bathroom were more likely to result in falls compared with events occurring elsewhere in the room. With initiation of increased patient education, hourly nurse rounding, nocturnal bed alarms, having two persons assisting for high fall risk patients when out of bed, and immediate postfall team review between 2001 and 2013, there was a trend of decreasing fall frequency; however, no specific intervention could be identified as having a particular high impact. In late 2013, a ceiling lift system extending into the bathroom was put in place for use in all EMU patients when out of bed. In the subsequent 15 months, there have been zero falls. The results reinforce both the need for diligent safety standards to prevent falls in the EMU as well as the challenges in identifying the most effective practices to achieve this goal.

Quality of life in psychogenic nonepileptic seizures and epilepsy: the role of somatization and alexithymia.

It is clear that many individuals with psychogenic nonepileptic seizures (PNESs) often present with poorer quality of life compared with those with epileptic seizures (ESs). However, the mechanisms linking seizure diagnosis to quality-of-life outcomes are much less clear. Alexithymia and somatization are emotional markers of psychological functioning that may explain these differences in quality of life. In the current study, patients from an epilepsy monitoring unit with vEEG-confirmed diagnosis of PNESs or ESs were compared on measures of alexithymia, somatization, quality of life, and a variety of demographic and medical variables. Two models using alexithymia and somatization individually as mediators of the relations between diagnosis and quality of life were tested. Results indicated that patients with PNESs had significantly poorer quality of life compared with those with ESs. Alexithymia was associated with poor quality of life in both groups but did not differentiate between diagnostic groups. Further, alexithymia did not mediate the relationship between diagnosis and quality of life. Somatization was associated with poor quality of life, and patients with PNESs reported greater somatization compared with patients with ESs. Somatization also significantly mediated the relationship between diagnosis and quality of life. In conclusion, somatization may be one mechanism affecting poor quality of life among patients with PNESs compared with ESs and should be a target of comprehensive treatments for PNESs. Alexithymia proved to be an important factor impacting quality of life in both groups and should also be targeted in treatment for patients with PNESs and patients with ESs.

Early versus late antiepileptic drug withdrawal for people with epilepsy in remission.

BACKGROUND: Epilepsy is a chronic neurological disorder which affects millions of people around the world. Antiepileptic drugs (AED) are the main interventions used to prevent seizures and control epilepsy. Although effective in most cases, AEDs are related to long-term adverse effects, such as cognitive and behavioural alterations. Thus when epilepsy is in remission, it may be in the individual's best interest to discontinue medication. However, the optimal timing of AED discontinuation is still unknown.This is an updated version of the original Cochrane review published in Issue 3, 2001. OBJECTIVES: (1) To quantify and compare risk of seizure recurrence, status epilepticus and mortality after early and late AED discontinuation in adult and pediatric epilepsy patients.(2) To assess which variables modify the risk of seizure recurrence.(3) To define a subpopulation in which early AED discontinuation is safe. SEARCH METHODS: We searched the Cochrane Epilepsy Group Specialised Register (June 2014); CENTRAL (Issue 5, The Cochrane Library, May 2014); MEDLINE (1946 to June 2014); CINAHL (23 June 2014); Scopus (1823 to June 2014); ClinicalTrials.gov (23 June 2014); and WHO International Clinical Trials Registry Platform (23 June 2014). We also checked the reference lists of studies found through the electronic searches. SELECTION CRITERIA: Randomised controlled trials that evaluate withdrawal of AEDs after varying periods of seizure remission in adults and children with epilepsy. Included studies compared an early AED discontinuation time (defined as a period of remission of seizures of less than two years) versus a late AED discontinuation time (defined as a period of remission of seizures of more than two years). DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed trial quality. Risk ratio (RR) with 95% confidence interval (CI) was calculated for each trial. Summary RRs and 95% CIs for dichotomous data were calculated using a fixed-effect model. A test of statistical heterogeneity was conducted for each pooled risk ratio calculation. Each included study underwent a 'Risk of bias' assessment, based on the Cochrane Handbook recommendations, and we examined the overall quality of information through the GRADE system, presented in two 'Summary of Findings' tables. MAIN RESULTS: Five trials were included in this review, representing 924 randomised children with epilepsy, all under 16 years of age at randomisation, with a median follow-up of 5.6 years. No eligible trial evaluated adults or assessed mortality or status epilepticus as outcomes. The pooled risk ratio for seizure relapse after AED withdrawal was 1.34 (95% CI 1.13 to 1.59, P = 0.0007). Conforming to this estimate, the number needed to harm, that is expose an individual to a higher risk of seizure relapse because of early withdrawal of AED, is 8 (95% CI 5 to 20). Early discontinuation was associated with greater relapse rates in people with partial seizures with a pooled risk ratio of 1.51 (95% CI 0.97 to 2.35, P = 0.07). Absence type epilepsy showed a lower risk of relapse. Variables associated with higher risk of seizure relapse were abnormal EEG findings (pooled RR 1.44, 95% CI 1.13 to 1.83, P = 0.003), especially epileptiform activity (RR 2.58, 95% CI 2.03 to 3.28, P < 0.0001); epilepsy onset before 2 years or after 10 years of age; history of status epilepticus; intellectual disability (IQ < 70); and high seizure frequency before and during treatment. Gender and family history did not show any significant influence over seizure relapse. Overall, the included trials were classified as low or unclear risk of bias where methodological information was not reported and could not be provided by original study authors. AUTHORS' CONCLUSIONS: There is evidence to support waiting for at least two seizure-free years before discontinuing AEDs in children, particularly if individuals have an abnormal EEG or partial seizures, or both. There is insufficient evidence to establish when to withdraw AEDs in children with generalised seizures. There is no evidence to guide the timing of withdrawal of AEDs in seizure-free adults. Further high-quality randomised controlled trials are needed, particularly recruiting adults and recruiting those with generalised seizure types, to identify the optimal timing of AED withdrawal and risk factors predictive of relapse.

Research implications of the Institute of Medicine Report, Epilepsy Across the Spectrum: Promoting Health and Understanding.

In March 2012 the Institute of Medicine (IOM) released the report, Epilepsy Across The Spectrum: Promoting Health and Understanding. This report examined the public health dimensions of the epilepsies with a focus on the following four areas: public health surveillance and data collection and integration; population and public health research; health policy, health care, and human services; and education for providers, people with epilepsy and their families, and the public. The report provided recommendations and research priorities for future work in the field of epilepsy that relate to increasing the power of data on epilepsy; prevention of epilepsy; improving health care for people with epilepsy; improving health professional education about epilepsy; improving quality of life for people with epilepsy; improving education about epilepsy for people with epilepsy and families; and raising public awareness about epilepsy. For this article, the authors selected one research priority from each of the major chapter themes in the IOM report: expanding and improving the quality of epidemiologic surveillance in epilepsy; developing improved interventions for people with epilepsy and depression; expanding early identification/screening for learning impairments in children with epilepsy; evaluating and promoting effective innovative teaching strategies; accelerating research on the identification of risk factors and interventions that increase employment and improve quality of life for people with epilepsy and their families; assessing the information needs of people with epilepsy and their families associated with epilepsy-related risks, specifically sudden unexpected death in epilepsy; and developing and conducting surveys to capture trends in knowledge, awareness, attitudes, and beliefs about epilepsy over time and in specific population subgroups. For each research priority selected, examples of research are provided that will advance the field of epilepsy and improve the lives of people with epilepsy. The IOM report has many other research priorities for researchers to consider developing to advance the field of epilepsy and better the lives of people with epilepsy.

The evolution of antiseizure medication therapy selection in adults: Is artificial intelligence -assisted antiseizure medication selection ready for prime time?

Antiseizure medications (ASMs) are the mainstay of symptomatic epilepsy treatment. The primary goal of pharmacotherapy with ASMs in epilepsy is to achieve complete seizure remission while minimizing therapy-related adverse events. Over the years, more ASMs have been introduced, with approximately 30 now in everyday use. With such a wide variety, much guidance is needed in choosing ASMs for initial therapy, subsequent replacement monotherapy, or adjunctive therapy. The specific ASMs are typically tailored by the patient's related factors, including epilepsy syndrome, age, sex, comorbidities, and ASM characteristics, including the spectrum of efficacy, pharmacokinetic properties, safety, and tolerability. Weighing these key clinical variables requires experience and expertise that may be limited. Furthermore, with this approach, patients may endure multiple trials of ineffective treatments before the most appropriate ASM is found. A more reliable way to predict response to different ASMs is needed so that the most effective and tolerated ASM can be selected. Soon, alternative approaches, such as deep machine learning (ML), could aid the individualized selection of the first and subsequent ASMs. The recognition of epilepsy as a network disorder and the integration of personalized epilepsy networks in future ML platforms can also facilitate the prediction of ASM response. Augmenting the conventional approach with artificial intelligence (AI) opens the door to personalized pharmacotherapy in epilepsy. However, more work is needed before these models are ready for primetime clinical practice.

Treatment of Seizure Clusters in Epilepsy: A Narrative Review on Rescue Therapies.

Epilepsy is a common neurological disorder in the United States, affecting approximately 1.2% of the population. Some people with epilepsy may experience seizure clusters, which are acute repetitive seizures that differ from the person's usual seizure pattern. Seizure clusters are unpredictable, are emotionally burdensome to patients and caregivers (including care partners), and require prompt treatment to prevent progression to serious outcomes, including status epilepticus and associated morbidity (e.g., lacerations, fractures due to falls) and mortality. Rescue medications for community use can be administered to terminate a seizure cluster, and benzodiazepines are the cornerstone of rescue treatment. Despite the effectiveness of benzodiazepines and the importance of a rapid treatment approach, as many as 80% of adult patients do not use rescue medication to treat seizure clusters. This narrative review provides an update on rescue medications used for treatment of seizure clusters, with an emphasis on clinical development and study programs for diazepam rectal gel, midazolam nasal spray, and diazepam nasal spray. Results from long-term clinical trials have shown that treatments for seizure clusters are effective. Intranasal benzodiazepines provide ease of use and patient and caregiver satisfaction in pediatric and adult patients. Adverse events attributed to acute rescue treatments have been characterized as mild to moderate, and no reports of respiratory depression have been attributed to treatment in long-term safety studies. The implementation of an acute seizure action plan to facilitate optimal use of rescue medications provides an opportunity for improved management of seizure clusters, allowing those affected to resume normal daily activities more quickly.

Some people with epilepsy who take antiseizure medications may still have seizures. These seizures might happen in clusters. Seizure clusters are emergencies that need to be treated quickly to lower the risk of status epilepticus and hospitalization. Also, these clusters can be stressful. Approved rescue medications are diazepam rectal gel, midazolam nasal spray, and diazepam nasal spray. They can all be used by family and other caregivers, and nasal sprays may be preferred in a public setting. All of these treatments can be used for adults, but each has a different age limit for children. Overall, these therapies are underused; however, all have been shown to work in stopping seizure clusters and have mild to moderate side effects. Nasal treatments offer ease of use and satisfaction for patients and caregivers (care partners). However, data for some effects and patient groups are not available for all treatments. Seizure action plans are designed to give step-by-step instructions about when and how to use rescue medication. Increased use of action plans may improve at-home treatment of seizure clusters and allow patients to perform their normal daily activities and avoid injury or hospitalizations.