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Objective: Seizure clusters require prompt medical treatment to minimize possible progression to status epilepticus, increased health care use, and disruptions to daily life. Isolated seizures may exhibit cyclical patterns, including circadian and longer rhythms. However, little is known about the cyclical patterns in seizure clusters. This post hoc analysis of data from a long-term, phase 3, open-label, repeat-dose safety study of diazepam nasal spray modeled the periodicity of treated seizure clusters., Methods: Mixed-effects cosinor analysis evaluated circadian rhythmicity, and single component cosinors using 12 and 24 h were used to calculate cosinor parameters (e.g., midline statistic of rhythm, wave ampitude, and acrophase [peak]). Analysis was completed for the full cohort and a consistent cohort of participants with two or more seizure clusters in each of four, 3-month periods. The influence of epilepsy type on cosinor parameters was also analyzed., Results: Seizure-cluster events plotted across 24 h showed a bimodal distribution with acrophases (peaks) at ~06:30 and ~18:30. A 12-h plot showed a single peak at ~06:30. Cosinor analyses of the full and consistent cohort aligned, with acrophases for both models predicting peak seizure activity at ~23:30 on a 24-h scale and ~07:30 on a 12-h scale. The consistent cohort was associated with increases in baseline and peak seizure-cluster activity. Analysis by epilepsy type identified distinct trends. Seizure clusters in the focal epilepsy group peaked in the evening (acrophase 19:19), whereas events in the generalized epilepsy group peaked in the morning (acrophase 04:46). Together they compose the bimodal clustering observed over 24 h., Significance: This analysis of seizure clusters treated with diazepam nasal spray demonstrated that seizure clusters occur cyclically in 12- and 24-h time frames similar to that reported with isolated seizures. Further elucidation of these patterns may provide important information for patient care, ranging from improved patient-centered outcomes to seizure-cluster prediction., (© 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: An epilepsy monitoring unit (EMU) is a specialized unit designed for capturing and characterizing seizures and other paroxysmal events with continuous video electroencephalography (vEEG). Nearly 260 epilepsy centers in the United States are accredited by the National Association of Epilepsy Centers (NAEC) based on adherence to specific clinical standards to improve epilepsy care, safety, and quality. This study examines EMU staffing, safety practices, and reported outcomes., Method: We analyzed NAEC annual report data and results from a supplemental survey specific to EMU practices reported in 2019 from 341 pediatric or adult center directors. Data on staffing, resources, safety practices and complications were collated with epilepsy center characteristics. We summarized using frequency (percentage) for categorical variables and median (inter-quartile range) for continuous variables. We used chi-square or Fisher's exact tests to compare staff responsibilities., Results: The supplemental survey response rate was 100%. Spell classification (39%) and phase 1 testing (28%) were the most common goals of the 91,069 reported admissions. The goal ratio of EEG technologist to beds of 1:4 was the most common during the day (68%) and off-hours (43%). Compared to residents and fellows, advanced practice providers served more roles in the EMU at level 3 or pediatric-only centers. Status epilepticus (SE) was the most common reported complication (1.6% of admissions), while cardiac arrest occurred in 0.1% of admissions., Significance: EMU staffing and safety practices vary across US epilepsy centers. Reported complications in EMUs are rare but could be further reduced, such as with more effective treatment or prevention of SE. These findings have potential implications for improving EMU safety and quality care., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Improved understanding of physical activity barriersand preferences in people with epilepsyis needed to successfully design and perform larger, more robust effectivenesstrials., Methods: Adult patients at a single tertiary epilepsy center between January and April 2020 were surveyed. The survey included a validated physical activity questionnaire (Physical Activity Scale for the Elderly) plus 15 items aimed to address 1) perceptions and beliefs regarding physical activity, 2) barriers to routine physical activity, and 3) willingness and ability to participate in a physical activity intervention and 4) current physical abilities, activities, and preferences., Results: 95 participants with epilepsy (age 42 ± 16.2, 59 % female) completed the survey. Sixty-five participants (68.4 %) reported that they believe that physical activity could improve their seizure frequency. However, 40 % of those surveyed said their neurologist had never talked to them about physical activity. The most commonly reported barriers to physical activity were lack of time (24.7 %) and fear of having a seizure (19.7 %), while barriers to intervention participation included being unable to come to in-person sessions (53 % of those willing to participate),living far away (39.3 %), time constraints (28.6 %), and lack of transportation (21.4 %)., Conclusion: Future physical activity studies in people with epilepsy should focus on using tailored interventions that accommodate their unique beliefs and barriers., Competing Interests: Declaration of Competing Interest Halley B. Alexander receives compensation from the American Academy of Neurology for her position as Deputy Editor of the Neurology Minute podcast and is funded by National Center for Advancing Translational Sciences, National Institutes of Health, Grant #KL2TR001421. Heidi Munger Clary receives support as a Topic Editor for DynaMed and research support from Eysz, Inc., National Institutes of Health, Department of Defense, The Duke Endowment, and the Suzanne Marcus Collins Foundation. Nathan B. Fountain serves on the board of directors and has stock for Acumen Pharmaceuticals and Hexokine Therapeutics. He receives support from Equilibre, Xenon, Medtronic, Cerebral Therapeutics, and InSightec. Jason Fanning is partially supported by the Wake Forest University Claude D. Pepper Older Americans Independence Center (P30-AG21332)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Well-designed placebo-controlled clinical trials are critical to the development of novel treatments for epilepsy, but their design has not changed for decades. Patients, clinicians, regulators, and innovators all have concerns that recruiting for trials is challenging, in part, due to the static design of maintaining participants for long periods on add-on placebo when there are an increasing number of options for therapy. A traditional trial maintains participants on blinded treatment for a static period (e.g., 12 weeks of maintenance), during which participants on placebo have an elevated risk of sudden unexpected death in epilepsy compared to patients on an active treatment. Time-to-event trials observe participants on blinded treatment until a key event occurs (e.g., post-randomization seizure count matches pre-randomization monthly seizure count). In this article, we review the evidence for these designs based on re-analysis of prior trials, one published trial that used a time-to-second seizure design, and experience from an ongoing blinded trial. We also discuss remaining concerns regarding time-to-event trials. We conclude that, despite potential limitations, time-to-event trials are a potential promising mechanism to make trials more patient friendly and reduce placebo exposure, which are urgent needs to improve safety and increase recruitment to trials., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: The evaluation to determine candidacy and treatment for epilepsy surgery in persons with drug-resistant epilepsy (DRE) is not uniform. Many non-invasive and invasive tests are available to ascertain an appropriate treatment strategy. This study examines expert response to clinical vignettes of magnetic resonance imaging (MRI)-positive lesional focal cortical dysplasia in both temporal and extratemporal epilepsy to identify associations in evaluations and treatment choice., Methods: We analyzed annual report data and a supplemental epilepsy practice survey reported in 2020 from 206 adult and 136 pediatric epilepsy center directors in the United States. Non-invasive and invasive testing and surgical treatment strategies were compiled for the two scenarios. We used chi-square tests to compare testing utilization between the two scenarios. Multivariable logistic regression modeling was performed to assess associations between variables., Results: The supplemental survey response rate was 100% with 342 responses included in the analyses. Differing testing and treatment approaches were noted between the temporal and extratemporal scenarios such as chronic invasive monitoring selected in 60% of the temporal scenario versus 93% of the extratemporal scenario. Open resection was the most common treatment choice; however, overall treatment choices varied significantly (p < .001). Associations between non-invasive testing, invasive testing, and treatment choices were present in both scenarios. For example, in the temporal scenario stereo-electroencephalography (SEEG) was more commonly associated with fluorodeoxyglucose-positron emission tomography (FDG-PET) (odds ratio [OR] 1.85; 95% confidence interval [CI] 1.06-3.29; p = .033), magnetoencephalography (MEG) (OR 2.90; 95% CI 1.60-5.28; p = <.001), high density (HD) EEG (OR 2.80; 95% CI 1.27-6.24; p = .011), functional MRI (fMRI) (OR 2.17; 95% CI 1.19-4.10; p = .014), and Wada (OR 2.16; 95% CI 1.28-3.66; p = .004). In the extratemporal scenario, choosing SEEG was associated with increased odds of neuromodulation over open resection (OR 3.13; 95% CI 1.24-7.89; p = .016)., Significance: In clinical vignettes of temporal and extratemporal lesional DRE, epilepsy center directors displayed varying patterns of non-invasive testing, invasive testing, and treatment choices. Differences in practice underscore the need for comparative trials for the surgical management of DRE., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background and Objective: Nearly one-third of persons with epilepsy will continue having seizures despite trialing multiple antiseizure medications. Epilepsy surgery may be beneficial in these cases, and evaluation at a comprehensive epilepsy center is recommended. Numerous palliative and potentially curative approaches exist, and types of surgery performed may be influenced by center characteristics. This article describes epilepsy center characteristics associated with epilepsy surgery access and volumes in the United States., Methods: We analyzed National Association of Epilepsy Centers 2019 annual report and supplemental survey data obtained with responses from 206 adult epilepsy center directors and 136 pediatric epilepsy center directors in the United States. Surgical treatment volumes were compiled with center characteristics, including US Census region. We used multivariable modeling with zero-inflated Poisson regression models to present ORs and incidence rate ratios of receiving a given surgery type based on center characteristics., Results: The response rate was 100% with individual element missingness less than 4% across 352 observations undergoing univariate analysis. Multivariable models included 319 complete observations. Significant regional differences were present. The rates of laser interstitial thermal therapy (LITT) were lower at centers in the Midwest (incidence rate ratio [IRR] 0.74, 95% CI 0.59-0.92; p = 0.006) and Northeast (IRR 0.77, 95% CI 0.61-0.96; p = 0.022) compared with those in the South. Conversely, responsive neurostimulation implantation rates were higher in the Midwest (IRR 1.45, 95% CI 1.1-1.91; p = 0.008) and West (IRR 1.91, 95% CI 1.49-2.44; p < 0.001) compared with the South. Center accreditation level, institution type, demographics, and resources were also associated with variations in access and rates of potentially curative and palliative surgical interventions., Discussion: Epilepsy surgery procedure volumes are influenced by US epilepsy center region and other characteristics. These variations may affect access to specific surgical treatments for persons with drug resistant epilepsy across the United States., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: Persons with drug-resistant epilepsy may benefit from epilepsy surgery and should undergo presurgical testing to determine potential candidacy and appropriate intervention. Institutional expertise can influence use and availability of evaluations and epilepsy surgery candidacy. This census survey study aims to examine the influence of geographic region and other center characteristics on presurgical testing for medically intractable epilepsy., Methods: We analyzed annual report and supplemental survey data reported in 2020 from 206 adult epilepsy center directors and 136 pediatric epilepsy center directors in the United States. Test utilization data were compiled with annual center volumes, available resources, and US Census regional data. We used Wilcoxon rank-sum, Kruskal-Wallis, and chi-squared tests for univariate analysis of procedure utilization. Multivariable modeling was also performed to assign odds ratios (ORs) of significant variables., Results: The response rate was 100% with individual element missingness < 11% across 342 observations undergoing univariate analysis. A total of 278 complete observations were included in the multivariable models, and significant regional differences were present. For instance, compared to centers in the South, those in the Midwest used neuropsychological testing (OR = 2.87, 95% confidence interval [CI] = 1.2-6.86; p = .018) and fluorodeoxyglucose-positron emission tomography (OR = 2.74, 95% CI = = 1.14-6.61; p = .025) more commonly. For centers in the Northeast (OR = .46, 95% CI = .23-.93; p = .031) and West (OR = .41, 95% CI = .19-.87; p = .022), odds of performing single-photon emission computerized tomography were lower by nearly 50% compared to those in the South. Center accreditation level, demographics, volume, and resources were also associated with varying individual testing rates., Significance: Presurgical testing for drug-resistant epilepsy is influenced by US geographic region and other center characteristics. These findings have potential implications for comparing outcomes between US epilepsy centers and may inject disparities in access to surgical treatment., (© 2022 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background and Objectives: Persons with epilepsy, especially those with drug resistant epilepsy (DRE), may benefit from inpatient services such as admission to the epilepsy monitoring unit (EMU) and epilepsy surgery. The COVID-19 pandemic caused reductions in these services within the US during 2020. This article highlights changes in resources, admissions, and procedures among epilepsy centers accredited by the National Association of Epilepsy Centers (NAEC)., Methods: We compared data reported in 2019, prior to the COVID-19 pandemic, and 2020 from all 260 level 3 and level 4 NAEC accredited epilepsy centers. Data were described using frequency for categorical variables and median for continuous variables and were analyzed by center level, center population category, and geographical location. Qualitative responses from center directors to questions regarding the impact from COVID-19 were summarized utilizing thematic analysis. Responses from the NAEC center annual reports as well as a supplemental COVID-19 survey were included., Results: EMU admissions declined 23% (-21,515) in 2020, with largest median reductions in level 3 centers [-55 admissions (-44%)] and adult centers [-57 admissions (-39%)]. The drop in admissions was more substantial in the East North Central, East South Central, Mid Atlantic, and New England US Census divisions. Survey respondents attributed reduced admissions to re-assigning EMU beds, restrictions on elective admissions, reduced staffing, and patient reluctance for elective admission. Treatment surgeries declined by 371 cases (5.7%), with the largest reduction occurring in VNS implantations [-486 cases (-19%)] and temporal lobectomies [-227 cases (-16%)]. All other procedure volumes increased, including a 35% (54 cases) increase in corpus callosotomies., Discussion: In the US, access to care for persons with epilepsy declined during the COVID-19 pandemic in 2020. Adult patients, those relying on level 3 centers for care, and many persons in the eastern half of the US were most affected., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background and Objectives: Patients with drug-resistant epilepsy (DRE) may benefit from specialized testing and treatments to better control seizures and improve quality of life. Most evaluations and procedures for DRE in the United States are performed at epilepsy centers accredited by the National Association of Epilepsy Centers (NAEC). On an annual basis, the NAEC collects data from accredited epilepsy centers on hospital-based epilepsy monitoring unit (EMU) size and admissions, diagnostic testing, surgeries, and other services. This article highlights trends in epilepsy center services from 2012 through 2019., Methods: We analyzed data reported in 2012, 2016, and 2019 from all level 3 and level 4 NAEC accredited epilepsy centers. Data were described using frequency for categorical variables and median for continuous variables and were analyzed by center level and center population category. EMU beds, EMU admissions, epileptologists, and aggregate procedure volumes were also described using rates per population per year., Results: During the period studied, the number of NAEC accredited centers increased from 161 to 256, with the largest increases in adult- and pediatric-only centers. Growth in EMU admissions (41%), EMU beds (26%), and epileptologists (109%) per population occurred. Access to specialized testing and services broadly expanded. The largest growth in procedure volumes occurred in laser interstitial thermal therapy (LiTT) (61%), responsive neurostimulation (RNS) implantations (114%), and intracranial monitoring without resection (152%) over the study period. Corpus callosotomies and vagus nerve stimulator (VNS) implantations decreased (-12.8% and -2.4%, respectively), while growth in temporal lobectomies (5.9%), extratemporal resections (11.9%), and hemispherectomies/otomies (13.1%) lagged center growth (59%), leading to a decrease in median volumes of these procedures per center., Discussion: During the study period, the availability of specialty epilepsy care in the United States improved as the NAEC implemented its accreditation program. Surgical case complexity increased while aggregate surgical volume remained stable or declined across most procedure types, with a corresponding decline in cases per center. This article describes recent data trends and current state of resources and practice across NAEC member centers and identifies several future directions for driving systematic improvements in epilepsy care., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Introduction: There is scant evidence to quantify the risk of contact sports such as football to patients with epilepsy. This retrospective review was performed to evaluate the incidence of injuries or seizure exacerbation related to football participation in patients with epilepsy., Methods: Between the years 1994 and 2004, 157,709 consecutive clinic notes were searched for mention of "football" and "epilepsy" or "seizure". Resulting notes were reviewed to quantify the number of seizure exacerbations and the number of injuries in this cohort., Results: Seven of 44 subjects with epilepsy (15.9%) experienced injury while playing football. Four of 32 (12.5%) patients experienced seizure exacerbation during a time when they were concurrently participating in football though 3 of these patients stopped taking or were weaned off of their antiepileptic drugs (AEDs). One in 32 patients with epilepsy (3.1%) had an exacerbation of seizures while playing football and consistently taking AEDs., Conclusion: The risk of injury and seizure exacerbation due to participation in football for patients with epilepsy is low. Clinicians should use their best judgment in deciding whether contact sports increase risks for a particular patient based on individual seizure frequency, concurrent neurological and medical issues, and medication adverse effects., Competing Interests: Declaration of competing interest David Taplinger is on the editorial board for epilepsy.com, the advisory board for the Epilepsy Foundation's Wellness Institute. Nathan Fountain has received support from the NIH, Xenon, UCB, GW Pharma, Medtronic, Cerebral Therapeutics, and the Epilepsy Foundation. The remaining authors have no conflicts of interest., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To study the incidence and clinical features of sudden unexpected death in epilepsy (SUDEP) in patients treated with direct brain-responsive stimulation with the RNS System., Methods: All deaths in patients treated in clinical trials (N = 256) or following U.S. Food and Drug Administration (FDA) approval (N = 451) through May 5, 2016, were adjudicated for SUDEP., Results: There were 14 deaths among 707 patients (2208 postimplantation years), including 2 possible, 1 probable, and 4 definite SUDEP events. The rate of probable or definite SUDEP was 2.0/1000 (95% confidence interval [CI] 0.7-5.2) over 2036 patient stimulation years and 2.3/1000 (95% CI 0.9-5.4) over 2208 patient implant years. Stored electrocorticograms around the time of death were available for 4 patients with probable/definite SUDEP and revealed the following: frequent epileptiform activity ending abruptly (n = 2), no epileptiform activity or seizures (n = 1), and an electrographic and witnessed seizure with cessation of postictal electrocorticography (ECoG) activity associated with apnea and pulselessness (n = 1)., Significance: The SUDEP rate of 2.0/1000 patient stimulation years among patients treated with the RNS System is favorable relative to treatment-resistant epilepsy patients randomized to the placebo arm of add-on drug studies or with seizures after resective surgery. Our findings support that treatments that reduce seizures reduce SUDEP risk and that not all SUDEPs follow seizures., (© 2018 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.)

Although the epilepsy and neurology communities have position papers on a number of topics pertaining to epilepsy diagnosis and management, no current paper exists for the rationale and appropriate indications for epilepsy monitoring unit (EMU) evaluation. General neurologists, hospital administrators, and insurers also have yet to fully understand the role this type of testing has in the diagnosis and management of individuals with paroxysmal neurologic symptoms. This review outlines the indications for long-term video-electroencephalography (VEEG) for typical elective admissions to a specialized inpatient setting. The common techniques used in EMUs to obtain diagnostic information are reviewed. The added benefit of safety measures and clinical testing above that available for routine or long-term ambulatory electroencephalography is also discussed. The indications for admission to the EMU include differential diagnosis of paroxysmal spells, characterization of seizure types, presurgical epilepsy evaluations, seizure quantification, monitoring medication adjustment in a safe setting, and differentiation between seizures and side effects. We conclude that the appropriate use of this specialized testing can lead to an early and correct diagnosis in a variety of clinical circumstances. The EMU evaluation is considered the gold standard test for the definitive diagnosis of epilepsy and seizure-like spells., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)

The randomized controlled trial is the unequivocal gold standard for demonstrating clinical efficacy and safety of investigational therapies. Recently there have been concerns raised about prolonged exposure to placebo and ineffective therapy during the course of an add-on regulatory trial for new antiepileptic drug approval (typically ∼6 months in duration), due to the potential risks of continued uncontrolled epilepsy for that period. The first meeting of the Research Roundtable in Epilepsy on May 19-20, 2016, focused on "Reducing placebo exposure in epilepsy clinical trials," with a goal of considering new designs for epilepsy regulatory trials that may be added to the overall development plan to make it, as a whole, safer for participants while still providing rigorous evidence of effect. This topic was motivated in part by data from a meta-analysis showing a 3- to 5-fold increased rate of sudden unexpected death in epilepsy in participants randomized to placebo or ineffective doses of new antiepileptic drugs. The meeting agenda included rationale and discussion of different trial designs, including active-control add-on trials, placebo add-on to background therapy with adjustment, time to event designs, adaptive designs, platform trials with pooled placebo control, a pharmacokinetic/pharmacodynamic approach to reducing placebo exposure, and shorter trials when drug tolerance has been ruled out. The merits and limitations of each design were discussed and are reviewed here., (© 2017 American Academy of Neurology.)

Purpose of Review: The science of quality of care in medicine has been emerging for the past decade, but it has only recently addressed epilepsy care. Quality of care in this sense refers to implementation of policies in large populations to improve care. This can have a large impact on epilepsy patients, as much of their care is delivered by generalists who can improve their care through the explicit direct requirements of quality measures., Recent Findings: Eight epilepsy quality performance measures were recently approved by national organizations, but only three were adopted by Medicare and only one by the National Quality Forum. The main reason for not adopting them is the lack of high-level evidence. However, there is high-level evidence for the efficacy of epilepsy surgery and use of newer antiepileptic drugs for the treatment of intractable epilepsy. Other problems are the lack of information about gaps in care and the imprecision in epilepsy diagnosis coding., Summary: Quality measurement will continue in epilepsy care, so a working knowledge of the topic is required by healthcare providers. Implementation of standardized quality measures can improve the care of people with epilepsy if the measures have demonstrated efficacy and can address gaps in care, and implementation is feasible.

Objective: Epilepsy is a common neurologic condition with significant personal, societal, medical, and economic burdens. There are considerable gaps in the quality of care delivered. Measuring the quality of care delivered is the first step to its improvement. Performance measures are easily identified and quantitated ways to assess whether specific activities were carried out during a patient encounter. Therefore, epilepsy performance measures were derived through a standardized systematic process and may be the basis for pay-for-performance initiatives and maintenance of certification requirements., Methods: Epilepsy measures were developed through the American Medical Association-convened Physician Consortium for Performance Improvement (PCPI) independent measure development process, which marked the first time a medical specialty society followed this process. Guidelines, measures, and consensus papers reviewed for the period 1998 to 2008 using the National Guidelines Clearinghouse, the National Quality Measures Clearinghouse, PubMed, MEDLINE, and the Cochrane Library were evaluated using a framework to determine the acceptability of each guideline or other evidence review document for measures development. Recommendation statements based on level of evidence, importance, validity, and gap in care were developed into candidate measures. A panel of experts from representative organizations vetted the measures. A period of public comment was followed by approval from the American Academy of Neurology and the PCPI., Results: Literature search identified 160 relevant recommendation statements from 19 guidelines and 2 consensus papers. Systematic assessment resulted in 20 recommendation statements that were refined to 8 candidate measures by the expert panel. The measures are relevant to seizure type and frequency, etiology or epilepsy syndrome, EEG, neuroimaging, antiepileptic drug side effects, safety issues, referral for refractory epilepsy, and issues for women of childbearing potential., Conclusion: There is a reasonable evidence base, and consensus for, deriving performance measures for quality of epilepsy care. It is anticipated that implementation of these performance measures will improve care for patients with epilepsy if adopted by providers.

This document was developed by the members of the Committee to Revise the Guidelines for Services, Personnel, and Facilities at Specialized Epilepsy Centers. After discussions with the general membership they were adopted by the Board of the National Association of Epilepsy Centers. The Guidelines will be reviewed and updated when considered necessary by the Board.

The authors debate whether routine EEG is an essential clinical tool for evaluation of a first seizure. One author suggests that because of the positive predictive value of interictal spikes for seizure recurrence, the EEG is a useful tool. The other author argues that since many clinicians would not treat after a single seizure, even if the EEG were abnormal, the EEG is not essential. Both authors agree that the EEG should only be ordered with forethought to answer a specific question.

We discuss the impact of epilepsy on the lives of athletes involved in contact sports. Recommendations for epilepsy patients with regard to contact sports have changed over the years from avoidance to encouragement. It is conceivable that exercise could exacerbate seizures either directly, through hyperventilation, or indirectly by alteration of anticonvulsant levels. Seizures could also be injurious in contact sports, and recurrent minor head trauma could worsen epilepsy. However, evidence to the contrary abounds and very few case reports support these notions. Exercise benefits individuals with epilepsy in many ways including improved seizure control, mood, and quality of life. We suggest that athletes with epilepsy be evaluated on an individual basis, and follow sensible guidelines while participating in contact sports. There is no significant evidence to suggest that contact sports are harmful to athletes with epilepsy; however, common sense rules still apply.

Seizures are common and are treated in all branches of medicine. Approximately 10% of the population will have one or more seizures during their lifetime. Seizures are symptoms that occur in acute illness, ie, provoked seizures, or in epilepsy, ie, unprovoked seizures. Epilepsy is any disorder in which spontaneous recurrence of unprovoked seizures is the main symptom. It is a common chronic neurologic disorder and affects 1% to 3% of the population. Classification of seizure type is important because it enables identification of the region of the brain where the seizure originated and guides initial diagnostic testing. Classification of epilepsy syndrome, rather than only type of seizure, is more important. Epilepsy syndromes are defined by many factors, including type of seizures, age at onset of seizures, family history of seizures, and findings at physical examination, electroencephalography (EEG), and neurologic imaging studies. Identifying the epilepsy syndrome provides insight into natural history, prognosis, diagnostic testing, and therapy of the disorder and facilitates communication between health care professionals. Understanding seizure type provides useful information even when the epilepsy syndrome cannot be classified. Many sudden events are easily confused with seizures, in particular, pseudoseizures, syncope, migraine, cerebrovascular disease, movement disorders, and sleep disorders. In most cases a detailed history and physical examination concentrated on the details of the event, and results of routine EEG and magnetic resonance imaging can aid in determination of which events are seizures. Video EEG monitoring is occasionally necessary to capture events to enable definitive determination of whether they are seizures and to further characterize them. Provoked seizures are treated with relief of the provoking factor. Antiepileptic drugs (AEDs) are not indicated. However, AEDs may be required to treat unprovoked seizures of new onset in patients at high risk for seizure recurrence or when a second seizure can have devastating psychosocial effects. High risk for recurrence is present when there is a history of brain insult, an EEG demonstrates epileptiform abnormalities, and magnetic resonance images demonstrate a structural lesion. AED therapy is the standard treatment for epilepsy, ie, two or more seizures. Selection of the appropriate AED depends on type of seizure and epilepsy present, and individual drug characteristics, including pharmacokinetics, side effects, dosing interval, and cost. All available AEDs except ethosuximide are effective as adjunctive therapy, and most are effective as initial monotherapy for partial seizures. Generalized seizures preferentially respond to valproate, lamotrigine, and topiramate, among other drugs. If trials of more than two AEDs do not control seizures, additional AEDs are unlikely to be effective, and the patient should be referred to an epilepsy center, where other treatment options, in particular, epilepsy surgery, can be offered. Epilepsy surgery renders 60% to 70% of patients with temporal lobe epilepsy free of disabling seizures.

It may seem logical to place restrictions on athletes with epilepsy, but there are no studies to suggest that even contact sports exacerbate seizures, and there is ample evidence that exercise reduces seizure frequency and improves well-being. Thus, sports participation should generally be encouraged for epilepsy patients. The risk-benefit analysis for an individual patient is highly dependent on the athletic activity considered; type of seizure, the likelihood that a seizure will occur during the activity, and comorbid conditions. Water sports (scuba diving, swimming, boating), sports performed at heights (piloting, sky diving, climbing, horseback riding), and motor sports require specific considerations.

Purpose: The pharmacokinetics of the novel antiepileptic drug (AED) levetiracetam and its major metabolite, ucb L057, were studied in children with partial seizures in a multicenter, open-label, single-dose study., Methods: Twenty-four children (15 boys, nine girls), 6 to 12 years old, received a single dose of levetiracetam (20 mg/kg) as an adjunct to their stable regimen of a single concomitant AED, followed by a 24-h pharmacokinetic evaluation., Results: In children, the half-lives of levetiracetam and its metabolite ucb L057 were 6.0 +/- 1.1 and 8.1 +/-2.7 hours, respectively. The Cmax and area under the curve (AUC) of levetiracetam equated for a 1-mg/kg dose were lower in children (Cmax, norm=1.33 plus minus 0.35 microg/ml; AUCnorm=12.4 +/- 3.5 microg/h/ml) than in adults (Cmax, norm=1.38 +/- 0.05 microg/ml; AUCnorm=11.48 +/- 0.63 microg/h/ml), whereas the renal clearance was higher. The apparent body clearance (1.43 +/- 0.36 ml/min/kg) was approximately 30-40% higher in children than in adults. Levetiracetam was generally well tolerated., Conclusions: On the basis of these data, a daily maintenance dose equivalent to 130-140% of the usual daily adult maintenance dosage (1,000-3,000 mg/day) in two divided doses, on a weight-normalized level (mg/kg/day) is initially recommended. Clinical efficacy trials in children are ongoing with dosages of 20 to 60 mg/kg/day.

Purpose: Previous studies of patient-reported seizure precipitants have not evaluated whether different epilepsy syndromes are differentially affected., Methods: Patients of a tertiary-care epilepsy center were consecutively surveyed with the use of a standardized questionnaire that lists precipitants that might trigger or exacerbate seizures (alcohol, caffeine, fasting, fatigue, fever or illness, flashing lights, heat or humidity, menstrual cycle, sleep, sleep deprivation, emotional stress, unknown, or other). Patients were classified into epilepsy syndromes according to International League Against Epilepsy criteria. Age and gender within groups defined by major precipitants were compared. Pearson's correlation was performed to evaluate common patterns of precipitants., Results: Of 400 patients, 62% cited at least one precipitant. In order of frequency, stress (30%), sleep deprivation (18%), sleep (14%), fever or illness (14%), and fatigue (13%) were noted by at least 10% of patients. Stress, fatigue, and sleep deprivation positively correlated, but sleep tended to negatively correlate with other major precipitants. Rankings of precipitants varied within epilepsy syndromes, with patients with temporal lobe epilepsy citing sleep infrequently compared with patients with other epilepsy syndromes. Menstrual effects were ranked highly within major precipitants among women over age 12 and were especially noted by women with temporal lobe epilepsy (28%)., Conclusions: Most patients with epilepsy identify a precipitant that triggers or exacerbates seizures. The high correlation of stress, sleep deprivation, and fatigue suggests that they act through common mechanisms to worsen seizure control. Through identification of the effect of both endogenous and exogenous precipitants among syndromes, more research and counseling can be directed to specific precipitants.

An electroencephalogram (EEG) recorded after sleep deprivation (SDEEG) in epilepsy patients often discloses epileptiform discharges (ED) when routine EEG (REEG) does not, but since sleep alone activates ED, activation during SDEEG may result merely from the induction of sleep. We retrospectively investigated whether SDEEG is useful when REEG containing wakefulness and sleep fails to show ED. Subjects were patients with definite or highly probable epilepsy whose REEG lacked ED and who later underwent SDEEG. All had wakefulness and at least stage II sleep during both REEG and SDEEG. Patients with ED on REEG were specifically excluded to avoid including patients with activation due merely to the occurrence of sleep. Patient and EEG characteristics were studied, including duration of wakefulness and each sleep stage and timing and characteristics of ED. Fifteen of 29 patients (52%) had activation on SDEEG; exclusively during wakefulness in 1, exclusively during sleep in 6 and in both wakefulness and sleep in 8. Activation rates were not significantly different between wakefulness (9, 60%), stage I (11, 74%) and stage II (11, 74%). EEG characteristics were similar for REEG and SDEEG, except that total EEG duration and stage II sleep were longer in SDEEG than in REEG, which did not influence activation by a logistic regression model (p > 0.05). We conclude that sleep deprivation activates ED independent of the activating effects of sleep and therefore is useful in evaluation of suspected epilepsy even when REEG contains sleep.

1. The main purposes of this study are to characterize the intracellular and extracellular responses of cells in superficial layers of entorhinal cortex (EC) in chronically epileptic animals, determine whether their altered physiology is dependent on being connected to hippocampus, and investigate whether there is evidence of augmented excitation and inhibitory interneuron disconnection. 2. Functional connectivity was maintained between the hippocampal area and the EC in vitro in a combined rat hippocampal-parahippocampal slice preparation by slicing with a vibratome at a 30-deg angle to the base of the brain. Three groups of animals were studied: naive animals, animals that had experienced a previous episode of (nonconvulsive) self-sustaining limbic system status epilepticus (SSLSE) induced by electrical stimulation resulting in a chronically epileptic state, and animals in an electrode control group. In chronically epileptic rats and the electrode control group, studies were done on tissue contralateral to the side of electrode implantation. 3. Extracellular and intracellular recordings were made from the superficial layers of EC. Neurons in the superficial layers of the EC were activated by stimulation of the deep layers within the EC or the angular bundle adjacent to the EC, which contains axons from EC neurons. Responses could be elicited by antidromic and synaptic mechanisms by stimulation at either site. In addition, a monosynaptic protocol was used that involved direct activation of interneurons with a stimulating electrode placed near the recording electrode in the presence of the ionotropic glutamate blockers D(-)-2-amino-5-phosphonovaleric acid (APV) and 6,7-dinitroquinoxaline-2-3-dione (DNQX). 4. Responses were collected over a range of stimulus intensities, from very low to high intensities, to construct input/output function (I/O) curves. Amplitudes and durations were measured at the lowest stimulus intensity that elicited a maximum responses. 5. Extracellular field potential responses from electrode controls did not differ from naives qualitatively with respect to morphology of field potential responses or quantitatively with respect to response duration and amplitude. Field potential responses in tissue from post-SSLSE rats differed markedly in morphology from naive and electrode controls, being more complex, significantly longer in duration, and decreased in amplitude. These epileptiform responses were shortened markedly by blockade of N-methyl-D-aspartate (NMDA) receptors with APV, but this manipulation did not convert responses to a normal morphology. These responses were abolished by blockade of non-NMDA mediated ionotropic glutamate receptors with DNQX. 6. During intracellular recordings of neurons in slices from both control and epileptic animals, neurons were quiescent under resting conditions in the absence of electrical stimulation. 7. Intracellular responses in electrode controls were identical to naive, and together were considered "controls." In control tissue, evoked intracellular responses were similar to those previously described and most commonly consisted of an excitatory postsynaptic potential (EPSP) that was blocked partially by the NMDA-receptor antagonist APV, followed by hyperpolarizing potentials, which were identified electrophysiologically and pharmacologically as gamma-aminobuturic acid-A (GABAA)- and GABAB-receptor-mediated inhibitory postsynaptic potentials (IPSPs). EPSPs were blocked completely by DNQX. 8. In chronically epileptic tissue, evoked intracellular responses differed markedly from responses in control animals, exhibiting all-or-none prolonged paroxysmal depolarizing events with multiple superimposed action potentials in response to a single shock. These depolarizing events were reduced in duration and amplitude, but not abolished, in APV. IPSPs were not seen or markedly reduced at all stimulus intensities. These intracellular responses never resembled control responses. Intracellur responss correlated precisely in morphology and duration with extracellular field potentials. (ABSTRACT TRUNCATED)