Preliminary Guidelines for Resuming Electroconvulsive Therapy After a Complication of Status Epilepticus.

ABSTRACT: Electroconvulsive therapy (ECT) is an effective and safe treatment for severe major depressive disorder. However, status epilepticus is a rare yet serious complication that can occur following treatment. We present a case of a patient with severe major depression who experienced convulsive status epilepticus during the first treatment of her fourth ECT course. Electroconvulsive therapy treatment was then discontinued, and the patient underwent unsuccessful medication trials. Due to deterioration of depressive symptoms, ECT resumption was considered 3 months later after the patient had been maintained on an antiepileptic drug and no further seizures had occurred. Electroconvulsive therapy was resumed with a detailed safety protocol that included electroencephalographic monitoring before and after ECT treatment, remaining on an antiepileptic drug during the course of treatment, performing ECT in the operating room, and preparing seizure-terminating drugs before each treatment. The patient completed her ECT course with no tardive seizures or other neurological complications. We present the safety measures taken for resumption of ECT in our patient, and we offer preliminary clinical guidelines for resuming ECT after a complication of status epilepticus.

Reliability of visual review of intracranial electroencephalogram in identifying the seizure onset zone: A systematic review and implications for the accuracy of automated methods.

Visual review of intracranial electroencephalography (iEEG) is often an essential component for defining the zone of resection for epilepsy surgery. Unsupervised approaches using machine and deep learning are being employed to identify seizure onset zones (SOZs). This prompts a more comprehensive understanding of the reliability of visual review as a reference standard. We sought to summarize existing evidence on the reliability of visual review of iEEG in defining the SOZ for patients undergoing surgical workup and understand its implications for algorithm accuracy for SOZ prediction. We performed a systematic literature review on the reliability of determining the SOZ by visual inspection of iEEG in accordance with best practices. Searches included MEDLINE, Embase, Cochrane Library, and Web of Science on May 8, 2022. We included studies with a quantitative reliability assessment within or between observers. Risk of bias assessment was performed with QUADAS-2. A model was developed to estimate the effect of Cohen kappa on the maximum possible accuracy for any algorithm detecting the SOZ. Two thousand three hundred thirty-eight articles were identified and evaluated, of which one met inclusion criteria. This study assessed reliability between two reviewers for 10 patients with temporal lobe epilepsy and found a kappa of .80. These limited data were used to model the maximum accuracy of automated methods. For a hypothetical algorithm that is 100% accurate to the ground truth, the maximum accuracy modeled with a Cohen kappa of .8 ranged from .60 to .85 (F-2). The reliability of reviewing iEEG to localize the SOZ has been evaluated only in a small sample of patients with methodologic limitations. The ability of any algorithm to estimate the SOZ is notably limited by the reliability of iEEG interpretation. We acknowledge practical limitations of rigorous reliability analysis, and we propose design characteristics and study questions to further investigate reliability.

Persistent racial and ethnic disparities as a potential source of epilepsy surgery underutilization: Analysis of large national datasets from 2006-2016.

OBJECTIVE: High volume surgical epilepsy centers have reported a decrease in surgical resections and an increase in intracranial monitoring. Despite this increase in complexity, epilepsy surgery remains significantly underutilized. The goal of this study is to examine the utilization of and access to epilepsy surgery in the United States from 2006 to 2016. METHODS: We used administrative datasets from the National Inpatient Sample (NIS) and Center for Medicare and Medicaid Services (CMS) to report national estimates of epilepsy surgery and changes in surgery types. We also examined disparities and barriers in access to epilepsy surgery. RESULTS: Inpatient epilepsy admissions increased from 2.41 to 5.78 per 100,000 between 2006 and 2016, while surgical epilepsy admissions plateaued after 2011. Open resections comprised 75 % of all surgical cases from 2006 to 2011 then decreased each year to 50 % in 2016 with both temporal and extratemporal resections decreasing proportionally. Intracranial monitoring increased in the last two years of the study due to an increase in SEEG/depth electrode cases. The multivariate analysis showed that patients with Medicaid (OR 0.75, 95 % CI 0.67-0.83) and Medicare (OR 0.62, 95 % CI 0.54-0.70) were significantly less likely to undergo epilepsy surgery compared to those with private insurance. Black patients were less likely to undergo epilepsy surgery than White or Hispanic patients (OR 0.57, 95 % CI 0.49-0.67). No significant difference was found in epilepsy surgery rates after implementation of the Affordable Care Act (ACA) in 2014. CONCLUSION: This study identifies recent trends in epilepsy surgical approaches and suggests that improving access to care does not necessarily address disparities present in the treatment of epilepsy patients who need surgical care.

Sudden Unexpected Death in Epilepsy: A Personalized Prediction Tool.

OBJECTIVE: To develop and validate a tool for individualized prediction of sudden unexpected death in epilepsy (SUDEP) risk, we reanalyzed data from 1 cohort and 3 case-control studies undertaken from 1980 through 2005. METHODS: We entered 1,273 epilepsy cases (287 SUDEP, 986 controls) and 22 clinical predictor variables into a Bayesian logistic regression model. RESULTS: Cross-validated individualized model predictions were superior to baseline models developed from only average population risk or from generalized tonic-clonic seizure frequency (pairwise difference in leave-one-subject-out expected log posterior density = 35.9, SEM ± 12.5, and 22.9, SEM ± 11.0, respectively). The mean cross-validated (95% bootstrap confidence interval) area under the receiver operating curve was 0.71 (0.68-0.74) for our model vs 0.38 (0.33-0.42) and 0.63 (0.59-0.67) for the baseline average and generalized tonic-clonic seizure frequency models, respectively. Model performance was weaker when applied to nonrepresented populations. Prognostic factors included generalized tonic-clonic and focal-onset seizure frequency, alcohol excess, younger age at epilepsy onset, and family history of epilepsy. Antiseizure medication adherence was associated with lower risk. CONCLUSIONS: Even when generalized to unseen data, model predictions are more accurate than population-based estimates of SUDEP. Our tool can enable risk-based stratification for biomarker discovery and interventional trials. With further validation in unrepresented populations, it may be suitable for routine individualized clinical decision-making. Clinicians should consider assessment of multiple risk factors, and not focus only on the frequency of convulsions.

Presurgical depression and anxiety are not associated with worse epilepsy surgery outcome five years postoperatively.

PURPOSE: Anxiety and depression have been associated with poor seizure control after epilepsy surgery. This study explored the effect of presurgical anxiety or depression on two- and five-year seizure control outcomes. METHODS: Adult subjects were enrolled between 1996 and 2001 in a multicenter prospective study to evaluate outcomes of resective epilepsy surgery. A Poisson regression was used to analyze the association of depression and anxiety with surgical outcome, while adjusting for gender, age, ethnicity, number of years with seizures, and presence of mesial temporal sclerosis. RESULTS: The relative risk (RR) of presurgical depression on two-year seizure-free outcome in this cohort is 1.12 (95% confidence interval (CI), 0.84-1.49) and 1.06 (CI, 0.73-1.55) on five-year seizure free outcome. The RR of presurgical anxiety on two-year seizure outcome is 0.73 (CI, 0.50-1.07) and 0.70 (CI, 0.43-1.17) on five-year seizure outcome. When including Engel classes I and II, the RRs of presurgical depression, anxiety, or both two years after surgery were 0.96 (p=0.59), 0.73 (p<0.05), and 0.97 (p=0.70), respectively, and they were 0.97 (p=0.82), 0.84 (p=0.32), and 0.89 (p=0.15), respectively, five years after surgery. Only presurgical anxiety was associated with worse epilepsy surgery outcome two year after surgery but not at five years postsurgery. Depression was not a risk factor for poor epilepsy surgical outcome in the long term. CONCLUSION: These findings from a prospective study that utilized a standardized protocol for psychiatric and seizure outcome assessment suggest that presurgical mood disorders have no substantial impact on postsurgical seizure outcome for up to five years after surgery.

Practice Guideline Summary: Sudden Unexpected Death in Epilepsy Incidence Rates and Risk Factors: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society.

OBJECTIVE: To determine the incidence rates of sudden unexpected death in epilepsy (SUDEP) in different epilepsy populations and address the question of whether risk factors for SUDEP have been identified. METHODS: Systematic review of evidence; modified Grading Recommendations Assessment, Development and Evaluation process for developing conclusions; recommendations developed by consensus. RESULTS: Findings for incidence rates based on 12 Class I studies include the following: SUDEP risk in children with epilepsy (aged 0-17 years) is 0.22/1,000 patient-years (95% CI 0.16-0.31) (high confidence in evidence). SUDEP risk increases in adults to 1.2/1,000 patient-years (95% CI 0.64-2.32) (low confidence in evidence). The major risk factor for SUDEP is the occurrence of generalized tonic-clonic seizures (GTCS); the SUDEP risk increases in association with increasing frequency of GTCS occurrence (high confidence in evidence). RECOMMENDATIONS: Level B: Clinicians caring for young children with epilepsy should inform parents/guardians that in 1 year, SUDEP typically affects 1 in 4,500 children; therefore, 4,499 of 4,500 children will not be affected. Clinicians should inform adult patients with epilepsy that SUDEP typically affects 1 in 1,000 adults with epilepsy per year; therefore, annually 999 of 1,000 adults will not be affected. For persons with epilepsy who continue to experience GTCS, clinicians should continue to actively manage epilepsy therapies to reduce seizures and SUDEP risk while incorporating patient preferences and weighing the risks and benefits of any new approach. Clinicians should inform persons with epilepsy that seizure freedom, particularly freedom from GTCS, is strongly associated with decreased SUDEP risk.

Practice guideline summary: Sudden unexpected death in epilepsy incidence rates and risk factors: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society.

OBJECTIVE: To determine the incidence rates of sudden unexpected death in epilepsy (SUDEP) in different epilepsy populations and address the question of whether risk factors for SUDEP have been identified. METHODS: Systematic review of evidence; modified Grading Recommendations Assessment, Development, and Evaluation process for developing conclusions; recommendations developed by consensus. RESULTS: Findings for incidence rates based on 12 Class I studies include the following: SUDEP risk in children with epilepsy (aged 0-17 years) is 0.22/1,000 patient-years (95% confidence interval [CI] 0.16-0.31) (moderate confidence in evidence). SUDEP risk increases in adults to 1.2/1,000 patient-years (95% CI 0.64-2.32) (low confidence in evidence). The major risk factor for SUDEP is the occurrence of generalized tonic-clonic seizures (GTCS); the SUDEP risk increases in association with increasing frequency of GTCS occurrence (high confidence in evidence). RECOMMENDATIONS: Level B: Clinicians caring for young children with epilepsy should inform parents/guardians that in 1 year, SUDEP typically affects 1 in 4,500 children; therefore, 4,499 of 4,500 children will not be affected. Clinicians should inform adult patients with epilepsy that SUDEP typically affects 1 in 1,000 adults with epilepsy per year; therefore, annually 999 of 1,000 adults will not be affected. For persons with epilepsy who continue to experience GTCS, clinicians should continue to actively manage epilepsy therapies to reduce seizures and SUDEP risk while incorporating patient preferences and weighing the risks and benefits of any new approach. Clinicians should inform persons with epilepsy that seizure freedom, particularly freedom from GTCS, is strongly associated with decreased SUDEP risk.

Mood, anxiety, and incomplete seizure control affect quality of life after epilepsy surgery.

OBJECTIVE: We examined the complex relationship between depression, anxiety, and seizure control and quality of life (QOL) outcomes after epilepsy surgery. METHODS: Seven epilepsy centers enrolled 373 patients and completed a comprehensive diagnostic workup and psychiatric and follow-up QOL evaluation. Subjects were evaluated before surgery and then at 3, 6, 12, 24, 48, and 60 months after surgery. Standardized assessments included the Quality of Life in Epilepsy Inventory-89, Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). A mixed-model repeated-measures analysis was used to analyze associations of depression, anxiety, seizure outcome, and seizure history with overall QOL score and QOL subscores (cognitive distress, physical health, mental health, epilepsy-targeted) prospectively. RESULTS: The groups with excellent and good seizure control showed a significant positive effect on the overall QOL compared to the groups with fair and poor seizure control. The BDI and BAI scores were both highly and negatively associated with overall QOL; increases in BDI and BAI scores were associated with decreased overall QOL score. CONCLUSIONS: Depression and anxiety are strongly and independently associated with worse QOL after epilepsy surgery. Interestingly, even partial seizure control, controlling for depression and anxiety levels, improved QOL. Management of mood and anxiety is a critical component to postsurgical care.

Do antiepileptic drugs or generalized tonic-clonic seizure frequency increase SUDEP risk? A combined analysis.

PURPOSE: In an analysis of four case-control studies of sudden unexpected death in epilepsy (SUDEP), we found that yearly frequency of generalized tonic-clonic seizures (GTCS) and antiepileptic drug (AED) polytherapy were associated with an increased risk for SUDEP. The prior analysis, however, did not evaluate AEDs and GTCS frequency concurrently. METHODS: We combined data from the three case-control studies with information on the frequency of GTCS and AED therapy, that is, carbamazepine, phenytoin, valproic acid, and other AED therapy. Number of AEDs was also considered. Lamotrigine and GTCS frequency were considered separately in two of the case-control studies. Logistic regression analysis was used to evaluate GTCS frequency, each of the AEDs, and number of AEDs. Adjusted analysis of the different AEDs accounted for study, age at death, gender, and GTCS frequency. KEY FINDINGS: In crude analysis, GTCS frequency, AED polytherapy, and number of AEDs were associated with an increased risk for SUDEP. Analysis of individual AEDs and of number of AEDs, adjusting for GTCS frequency, revealed no increased risk associated with AEDs as monotherapy, polytherapy, or total number. GTCS frequency remained strongly associated with an increased risk for SUDEP. SIGNIFICANCE: Our findings-that none of the AEDs considered were associated with increased SUDEP risk as monotherapy or as polytherapy when GTCS frequency was taken into account-provide a consistent message that number of GTCS increases SUDEP risk and not AEDs. These results suggest that prevention of SUDEP must involve increased efforts to decrease GTCS frequency in order to avert the occurrence of this devastating epilepsy outcome.

Combined analysis of risk factors for SUDEP.

PURPOSE: To pool data from four published case-control studies of sudden unexpected death in epilepsy (SUDEP) with live controls, to increase the power to determine risk factors. METHODS: Case-control studies from the United States, Sweden, Scotland, and England were combined. SUDEP was defined as (1) a history of epilepsy (>1 epileptic seizure during a period of < 5 years); (2) death occurring suddenly; (3) death unexpected (i.e., no life-threatening illness); and (4) death remained unexplained after all investigative efforts, including autopsy. Definite SUDEP required all criteria. Logistic regression analyses adjusted for study. Further analysis simultaneously adjusted for study, age at death, gender, and duration of epilepsy. KEY FINDINGS: Of the risk factors that could be analyzed across some or all studies, those that were statistically significant were increased frequency of generalized tonic-clonic seizures (GTCS), use of polytherapy, duration of epilepsy, young age at onset, gender, symptomatic etiology, and lamotrigine therapy. Results persisted when epilepsy onset was younger than 16 years and when it was 16 years or older. In univariate analysis, lamotrigine therapy was associated with significantly increased risk for SUDEP among individuals with idiopathic generalized epilepsy. SIGNIFICANCE: This analysis refines the identification of people with epilepsy that are at particular risk of SUDEP. The emerging profile indicates that people with early onset refractory symptomatic epilepsy with frequent GTCS and antiepileptic drug (AED) polytherapy are at higher risk. The results suggest that reduction of the number of GTCS is a priority, of more importance than reducing the number of AEDs. The role of AEDs and other treatment should be analyzed further in future studies.

Suicide outcomes after resective epilepsy surgery.

People with epilepsy have a higher risk for suicide than people without epilepsy. The relationship between seizure control and suicide is controversial. A standardized protocol to record history, diagnostic testing, and neuropsychiatric assessments was administered. The Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) were administered presurgically and yearly for up to 5 years. Among the 396 enrolled, 4 of 27 deaths were attributed to suicide. The standardized mortality ratio, compared with suicides in the U.S. population and adjusted for age and gender, was 13.3 (95% CI=3.6-34.0). Only one patient had a BDI score suggestive of severe depression (BDI=33), one had depressive symptoms that did not the meet the depressive range (BDI=7), and the other two reported no depressive symptoms. Two of the patients reported moderate to severe anxiety symptoms (BAI=17 and 21, respectively). Suicide may occur after epilepsy surgery, even when patients report excellent seizure control.

Essential services, personnel, and facilities in specialized epilepsy centers--revised 2010 guidelines.

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.

Long-term use of felbamate: clinical outcomes and effect of age and concomitant antiepileptic drug use on its clearance.

PURPOSE: To determine the effects of long-term use of felbamate (FBM) on weight, complete blood count, liver function tests, and seizure control, and also to determine the effect of age on FBM clearance. METHODS: A computerized prospective database was used to identify all subjects who had FBM listed as one of their antiepileptic drugs (AEDs) during their most recent clinic visit. Medical records from each patient were then reviewed for inclusion criteria [treatment >2 years, FBM initiated at the study clinic, data for pre-FBM (Time-1; T1), one-year exposure to FBM (Time-2; T2), and the latest visit (Time-3; T3)]. Clinical information was abstracted from clinic charts. RESULTS: Seventy-seven patients (F = 41, M = 36; ages 10-69 years) met entry criteria. Mean treatment time was 7.4 years, with the longest 20.3 years. Significant weight loss (mean 5.1 kg; p < 0.001) occurred from T1 to T2, but weight was regained by T3. No clinically significant changes in laboratory parameters occurred. Older age was associated with a significant decrease in FBM clearance (p = 0.01). Significant reduction in generalized tonic-clonic seizures was seen at both T2 (p < 0.001) and T3 (p < 0.001) compared with seizure frequency at T1. DISCUSSION: Our results suggest that long-term FBM use is associated with persistent decrease of seizures and no clinically significant changes in major laboratory parameters. Older age correlated with reduced apparent clearance of FBM. The patient population described in this study were long-term users of FBM who were continuing to use the drug, and thus this study does not constitute an "intent to treat" study.

Bone health in women with epilepsy: clinical features and potential mechanisms.

Bone disease is recognized as an important pathologic process to identify and treat in women. Women are at greater risk than men secondary to multiple factors including estrogen loss in menopause. The most important consequence of bone disease is fracture. Fracture rates are higher in persons with epilepsy treated with antiepileptic drugs (AEDs). Increased bone turnover secondary to AED exposure, higher rates of osteoporosis, adverse effects on bone quality, seizures, and impaired coordination may all contribute. There is a differential effect of AEDs on bone. Although results are mixed for some AEDs, phenytoin use is consistently associated with lower bone mineral density (BMD). As most evidence associates cytochrome P450 enzyme-inducing AEDs with abnormalities in bone, the induction of these enzymes has been proposed as the main mechanism to describe this effect. However, data suggest that this theory does not explain all findings. Many therapies are available for the treatment of bone disease, but there is limited study in persons with epilepsy. All patients should receive at least the recommended daily allowance of calcium and vitamin D and obtain vitamin D status screening. For prolonged AED exposure, BMD screening is available, particularly if the patient has other risk factors.

Employment outcomes following resective epilepsy surgery.

PURPOSE: Analyze determinates of employment changes from before to 2 years after surgery in refractory focal epilepsy patients. METHODS: Preoperative employment was prospectively assessed in 375 adults with refractory epilepsy. Two-year postsurgical employment status was obtained for 299; factors potentially associated with employment status change among subgroups unemployed and employed at baseline were analyzed. RESULTS: Presurgical employment status was full-time (n = 148, 39.5%), part-time (n = 26, 6.9%), disabled and unemployed (n = 100, 26.7%), unemployed (n = 44, 11.7%), and other (n = 57, 15.2%). Those with and without 2-year follow-up did not differ on baseline characteristics (all p > 0.10). Two years after surgery, 42.8% were employed full-time and 12.4%, part-time. Among those unemployed before surgery, better seizure outcome was associated with gaining employment at 2 years (p = 0.03). CONCLUSIONS: Net employment gains were modest 2 years after surgery and higher with better seizure outcomes, reinforcing the need for optimizing surgical candidate selection, long-term follow-up studies, and postsurgical vocational rehabilitation.

Health-related quality of life over time since resective epilepsy surgery.

OBJECTIVE: Health-related quality of life (HRQOL) improves after resective epilepsy surgery, but data are limited to short follow-up in mostly retrospective reports, with minimal consideration of other potential factors that might influence HRQOL. METHODS: In a prospective multicenter study, 396 patients underwent resective epilepsy surgery. They completed the Quality of Life in Epilepsy Inventory-89 (QOLIE-89) before surgery, within 6 months, and at approximately yearly intervals after surgery. Seizure outcome was ascertained by phone calls every 3 months, and dates of postoperative seizures were chronicled. Overall HRQOL as measured by the QOLIE-89 was evaluated with respect to seizure outcome using logistic regression. RESULTS: QOLIE-89 scores increased significantly at the first postoperative measurement (within 6 months after surgery) in the cohort overall; subsequent changes over time were sensitive to seizure-free and aura-free status. After adjusting for baseline scores, the corresponding postsurgical QOLIE-89 overall, and four dimension scores, increased as a function of square root of time seizure-free, and independently as a function of square root of time aura free, leveling by 2 years of stable seizure (aura) status. HRQOL was not independently related to duration of epilepsy, duration of intractable epilepsy, or continuation of medications. INTERPRETATION: HRQOL improves early after surgery, regardless of seizure outcome. Subsequent changes parallel length of time seizure free or aura free, stabilize after 2 years, and are unrelated to duration of epilepsy, duration of intractable epilepsy, or continued medication use.

Reduction of AEDs in postsurgical patients who attain remission.

PURPOSE: Little evidence guides practice regarding the reduction of antiepileptic drugs (AEDs) in individuals who achieve significant periods of remission after resective surgery. METHODS: In a prospective study of 396 individuals who underwent resective surgery for intractable seizures, the impact of reducing AEDs on relapse and predictors of relapse were examined. RESULTS: Of 301 study subjects who attained a 1-year seizure remission after surgery, 129 reduced from two to one or from one to no AEDs after achieving remission, and 162 did not reduce drugs. Ten patients who stopped all AEDs before attaining remission were excluded from analysis. In all, 114 (39%) patients relapsed: 73 (45%) of 162 in the nonreduction group and 41 (32%) of 129 in the reduction group (p = 0.02). Patients who reduced drugs were more likely to have remitted immediately after hospital discharge (p<0.0001). After adjustment for this factor, little or no apparent impact of drug reduction on the rate of relapse was noted [rate ratio (RR), 1.1; 95% CI, 0.72-1.71; p=0.64 for reducing from two to one AED, and RR, 0.85; 95% CI, 0.50-1.45; p=0.56 for reducing from one to no AEDs]. Within the 129 patients who reduced AEDs, only delayed remission after hospital discharge was significantly associated with an increased rate of relapse (RR, 2.26; 95% CI, 1.15- 4.48; p=0.02). Continued auras had a marginally significant association with relapse (RR, 2.06; p=0.07) CONCLUSIONS: Although many relapses in this cohort of postsurgical patients who achieved remission occurred in the context of reducing or completely eliminating AEDs, the risk was no higher than in those who continued AEDs. Randomized studies are needed to test the impact of drug reduction in seizure-free postsurgical patients.

The multicenter study of epilepsy surgery: recruitment and selection for surgery.

PURPOSE: Multiple studies have examined predictors of seizure outcomes after epilepsy surgery. Most are single-center series with limited sample size. Little information is available about the selection process for surgery and, in particular, the proportion of patients who ultimately have surgery and the characteristics that identify those who do versus those who do not. Such information is necessary for providing the epidemiologic and clinical context in which epilepsy surgery is currently performed in the United States and in other developed countries. METHODS: An observational cohort of 565 surgical candidates was prospectively recruited from June 1996 through January 2001 at six Northeastern and one Midwestern surgical centers. Standardized eligibility criteria and protocol for presurgical evaluations were used at all seven sites. RESULTS: Three hundred ninety-six (70%) study subjects had resective surgery. Clinical factors such as a well-localized magnetic resonance imaging (MRI) abnormality and consistently localized EEG findings were most strongly associated with having surgery. Of those who underwent intracranial monitoring (189, 34%), 85% went on to have surgery. Race/ethnicity and marital status were marginally associated with having surgery. Age, education, and employment status were not. Demographic factors had little influence over the surgical decision. More than half of the patients had intractable epilepsy for >/=10 years and five or more drugs had failed by the time they initiated their surgical evaluation. During the recruitment period, eight new antiepileptic drugs were approved by the Food and Drug Administration for use in the United States and came into increasing use in this study's surgical candidates. Despite the increased availability of new therapeutic options, the proportion that had surgery each year did not fluctuate significantly from year to year. This suggests that, in this group of patients, the new drugs did not provide a substantial therapeutic benefit. CONCLUSIONS: Up to 30% of patients who undergo presurgical evaluations for resective epilepsy surgery ultimately do not have this form of surgery. This is a group whose needs are not currently met by available therapies and procedures. Lack of clear localizing evidence appears to be the main reason for not having surgery. To the extent that these data can address the question, they suggest that repeated attempts to control intractable epilepsy with new drugs will not result in sustained seizure control, and eligible patients will proceed to surgery eventually. This is consistent with recent arguments to consider surgery earlier rather than later in the course of epilepsy. Postsurgical follow-up of this group will permit a detailed analysis of presurgical factors that predict the best and worst seizure outcomes.

Do antiepileptic drugs play a role in sudden unexpected death in epilepsy?

Sudden unexpected death in epilepsy (SUDEP) accounts for approximately 2% of deaths in population-based cohorts of epilepsy, and up to 25% of deaths in cohorts of more severe epilepsy. When it occurs, SUDEP usually follows a generalised tonic-clonic seizure. Unresponsiveness, apnoea, and cardiac arrest occur in SUDEP, rather than the typical gradual recovery. The great majority of tonic-clonic seizures occur without difficulty and how the rare seizure associated with SUDEP differs from others is unknown.Three mechanisms have been proposed for SUDEP: cardiac arrhythmia, neurogenic pulmonary oedema, and postictal suppression of brainstem respiratory centres leading to central apnoea. Recent studies have found that the incidence of SUDEP increases with the severity of epilepsy in the population studied. The duration of epilepsy, number of tonic-clonic seizures, mental retardation, and simultaneous treatment with more than two antiepileptic drugs are independent risk factors for SUDEP. Some studies have reported that carbamazepine use, carbamazepine toxicity, and frequent, rapid changes in carbamazepine levels, may be associated with SUDEP. Other evidence indicates that carbamazepine could potentially increase the risk for SUDEP by causing arrhythmia or by altering cardiac autonomic function. However, this evidence is tenuous and most studies have not found an association between the use of carbamazepine or any other individual antiepileptic drug and SUDEP. There is little information regarding antiepileptic drugs other than phenytoin and carbamazepine. The incidence of SUDEP with gabapentin, tiagabine, and lamotrigine clinical development programmes is in the range found in other populations with refractory epilepsy. This suggests that these individual antiepileptic drugs are no more likely to cause SUDEP than antiepileptic drugs in general. Best current evidence indicates that the risk of SUDEP can be decreased by aggressive treatment of tonic-clonic seizures with as few antiepileptic drugs as necessary to achieve complete control. At present there is no strong reason to avoid any particular antiepileptic drug. Further studies are needed to elucidate the potential role of individual antiepileptic drugs in SUDEP and establish clinical relevance, if any. These studies may be challenging to conduct and interpret because SUDEP is relatively uncommon and large numbers will be necessary to narrow confidence intervals to determine the clinical relevance. Also adjustments will be needed to account for the potent risks associated with other independent factors.