Diagnostic Accuracy of Ambulatory EEG vs Routine EEG in Patients With First Single Unprovoked Seizure.

Background and Objective: To evaluate the diagnostic accuracy of the ambulatory EEG (aEEG) at detecting interictal epileptiform discharges (IEDs)/seizures compared with routine EEG (rEEG) and repetitive/second rEEG in patients with a first single unprovoked seizure (FSUS). We also evaluated the association between IED/seizures on aEEG and seizure recurrence within 1 year of follow-up. Methods: We prospectively evaluated 100 consecutive patients with FSUS at the provincial Single Seizure Clinic. They underwent 3 sequential EEG modalities: first rEEG, second rEEG, and aEEG. Clinical epilepsy diagnosis was ascertained based on the 2014 International League Against Epilepsy definition by a neurologist/epileptologist at the clinic. An EEG-certified epileptologist/neurologist interpreted all 3 EEGs. All patients were followed up for 52 weeks until they had either second unprovoked seizure or maintained single seizure status. Accuracy measures (sensitivity, specificity, negative and positive predictive values, and likelihood ratios), receiver operating characteristic (ROC) analysis, and area under the curve (AUC) were used to evaluate the diagnostic accuracy of each EEG modality. Life tables and the Cox proportional hazard model were used to estimate the probability and association of seizure recurrence. Results: Ambulatory EEG captured IED/seizures with a sensitivity of 72%, compared with 11% for the first rEEG and 22% for the second rEEG. The diagnostic performance of the aEEG was statistically better (AUC: 0.85) compared with the first rEEG (AUC: 0.56) and second rEEG (AUC: 0.60). There were no statistically significant differences between the 3 EEG modalities regarding specificity and positive predictive value. Finally, IED/seizure on the aEEG was associated with more than 3 times the hazard of seizure recurrence. Discussion: The overall diagnostic accuracy of aEEG at capturing IED/seizures in people presenting with FSUS was higher than the first and second rEEGs. We also found that IED/seizures on the aEEG were associated with an increased risk of seizure recurrence. Classification of Evidence: This study provides Class I evidence supporting that, in adults with First Single Unprovoked Seizure (FSUS), 24-h ambulatory EEG has increased sensitivity when compared with routine and repeated EEG.

Definitions and Risk Factors for Drug-Resistant Epilepsy in an Adult Cohort.

Background: Less than one-third of people with epilepsy will develop drug-resistant epilepsy (DRE). Establishing the prognosis of each unique epilepsy case is an important part of evaluation and treatment.Most studies on DRE prognosis have been based on a pooled, heterogeneous group, including children, adults, and older adults, in the absence of clear recognition and control of important confounders, such as age group. Furthermore, previous studies were done before the 2010 definition of DRE by the International League Against Epilepsy (ILAE), so data based on the current definitions have not been entirely elucidated. This study aimed to explore the difference between 3 definitions of DRE and clinical predictors of DRE in adults and older adults. Methods: Patients with a new diagnosis of epilepsy ascertained at a Single Seizure Clinic (SSC) in Saskatchewan, Canada were included if they had at least 1 year of follow-up. The first study outcome was the diagnosis of DRE epilepsy at follow-up using the 2010 ILAE definition. This was compared with 2 alternative definitions of DRE by Kwan and Brodie and Camfield and Camfield. Finally, risk factors were analyzed using the ILAE definition. Results: In total, 95 patients with a new diagnosis of epilepsy and a median follow-up of 24 months were included. The median age of patients at the diagnosis of epilepsy was 33 years, and 51% were men. In the cohort, 32% of patients were diagnosed with DRE by the Kwan and Brodie definition, 10% by Camfield and Camfield definition, and 15% by the ILAE definition by the end of follow-up. The only statistically significant risk factor for DRE development was the failure to respond to the first anti-seizure medication (ASM). Conclusion: There were important differences in the percentage of patients diagnosed with DRE when using 3 concurrent definitions. However, the use of the ILAE definition appeared to be the most consistent through an extended follow-up. Finally, failure to respond to the first ASM was the sole significant risk factor for DRE in the cohort after considering the age group.

The Concept of an Epilepsy Brain Bank.

Epilepsy comprises more than 40 clinical syndromes affecting millions of patients and families worldwide. To decode the molecular and pathological framework of epilepsy researchers, need reliable human epilepsy and control brain samples. Brain bank organizations collecting and supplying well-documented clinically and pathophysiologically tissue specimens are important for high-quality neurophysiology and neuropharmacology studies for epilepsy and other neurological diseases. New development in molecular mechanism and new treatment methods for neurological disorders have evoked increased demands for human brain tissue. An epilepsy brain bank is a storage source for both the frozen samples as well as the formaldehyde fixed paraffin embedded (FFPE) tissue from epilepsy surgery resections. In 2014, the University of Saskatchewan have started collecting human epilepsy brain tissues for the first time in Canada. This review highlights the necessity and importance of Epilepsy Brain bank that provides unique access for research to valuable source of brain tissue and blood samples from epilepsy patients.

Evaluation of wait times for assessment and epilepsy surgery according the geographic area of residence in the province of Saskatchewan, Canada.

PURPOSE: The aim of this study was to determine and compare the waiting times for surgical assessment, neuropsychological testing and epilepsy surgery between people with epilepsy who live in cities with available neurologists vs not. METHODS: We reviewed all cases referred for epilepsy surgery between 2007 and 2017 at the Saskatchewan Epilepsy Program Royal University Hospital (SEP) (n = 98; Saskatchewan, Canada). Mann-Whitney U test was used to compare wait times from first diagnosis of epilepsy to epilepsy surgery between patients who live in cities with neurologists (mainly urban areas) vs cities without neurologists (mainly rural areas). RESULTS: The mean age of patients who enrolled in SEP was 37.8 ± 12.8 years. The median wait time from date of epilepsy diagnosis to referral was 9.5 years in Saskatoon and Regina (cities with available neurologists) and 14 years in other areas of Saskatchewan (small cities and rural areas with no available neurologists) (p = 0.03). The median wait time from date of epilepsy diagnosis to first consult with the epileptologist was 10 years in Saskatoon and Regina and 15.5 years in other areas of Saskatchewan (p = 0.03). The median wait time from date of first diagnosis to epilepsy surgery was 13.2 years in Saskatoon and Regina and 18.2 years in other areas of Saskatchewan (p = 0.05). CONCLUSION: A notable difference was observed in surgical wait times between patients who live in cities with available neurologists compared with people living in rural areas and cities with no neurologists. This suggests that delayed surgical treatment for epilepsy is related with the availability of neurologists.

Diagnostic Accuracy of the Ambulatory EEG vs. Routine EEG for First Single Unprovoked Seizures and Seizure Recurrence: The DX-Seizure Study.

Background: The DX-Seizure study aims to evaluate the diagnostic accuracy (sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio) of the ambulatory EEG in comparison with the first routine EEG, and a second routine EEG right before the ambulatory EEG, on adult patients with first single unprovoked seizure (FSUS) and define the utility of ambulatory EEG in forecasting seizure recurrence in these patients after 1-year follow-up. Methods: The DX-Seizure study is a prospective cohort of 113 adult patients (≥18-year-old) presenting with FSUS to the Single Seizure Clinic for evaluation. These patients will be assessed by a neurologist/epileptologist with the first routine EEG (referral EEG) and undergo a second routine EEG and ambulatory EEG. The three EEG (first routine EEG as gold standard) will be compared and evaluated their diagnostic accuracy (sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratios) with respect of epileptiform activity and other abnormalities. One-year follow-up of each patient will be used to assess recurrence of seizures after a FSUS and the utility of the ambulatory EEG to forecast these recurrences. Discussion: To the best of our knowledge, this will be the first study to prospectively examine the use of ambulatory EEG for a FSUS in adults and its use for prediction of recurrence of seizures. The overarching goal is to improve diagnostic accuracy with the use of ambulatory EEG in patients with their FSUS. We anticipate that this will decrease incorrect or uncertain diagnoses with resulting psychological and financial cost to the patient. We also anticipate that an improved method to predicting the recurrence of seizures will reduce the chances of repeated seizures and their consequences.

The Use of Cannabis as a Treatment for Epilepsy in Adult Patients: Are Side Effects a Limitation of Use?

Marijuana is the dried leaves, stems, and flowers of a 1- to 5-m weed originating from Central Asia. The most common varieties are Cannabis sativa and Cannabis indica. It is usually inhaled as smoke but can also be used as a vapor, taken by mouth as a spray, ingested in tea or as butter in baked goods, or in capsule form and used as an oil. Cannabis has been widely used to treat many medical conditions such as multiple sclerosis symptoms, mood disorders, pain, sleep disorders, and seizures among others. Preclinical and clinical studies have been done over the past decade, among them there are few randomized placebo-controlled trials. In the last few years, Cannabis has been proposed as a potential therapy for patients with drug-resistant epilepsy. This review analyzes the best information about the use of cannabis in adult patients, reviewing aspects of efficacy and safety.

Secular trends and population differences in the incidence of epilepsy. A population-based study from Saskatchewan, Canada.

PURPOSE: To estimate the incidence of epilepsy in Saskatchewan, Canada between 2005 and 2010 by using provincial administrative health database stratifying gender, age, self-reported Registered Indian (RI) status and secular trends. METHODS: An epilepsy database was created through linkage of services claims data from the provincial health database of Saskatchewan, Canada between 2005 and 2010 with a four years washout period (2001-2004). The algorithm used was at least two physician visit with the diagnosis of epilepsy on a different date within 730 days or at least one hospital separation with the diagnosis of epilepsy. RESULTS: Between 2005 and 2010 the overall crude and age-standardized incidences of epilepsy were 63 new epilepsy patients per 100,000 person-years and 62 per 100,000 person-years respectively. The overall age-specific incidence showed a gradual increase toward a high point in elderly. The incidence rate was slightly higher in men than in women who were older than 39 years. There was a significant downward trend over time in the incidence of epilepsy from 2005 to 2010 in Saskatchewan. For self-declared RI the overall age-standardized incidence of epilepsy was 122 per 100,000 person-years. The rate ratio (RR) incidence difference between self-identified Registered Indian (RI) and non-self-identified RI was 1.6. CONCLUSIONS: The incidence of epilepsy in Saskatchewan, Canada was comparable to previous incidence studies from developed countries. This study is the first Canadian study calculating the secular trends and all-age group incidence of epilepsy and one of the few studies showing the incidence of epilepsy in a self-declared Registered Indian population.

Epilepsy in an elderly population: Classification, etiology and drug resistance.

PURPOSE: To characterize epilepsy in an elderly population and describe the prevalence of drug resistant epilepsy (DRE) using recently validated International League Against Epilepsy (ILAE) criteria. METHODS: Using a case-control design, 72 patients aged 60 years and older (cases) and 223 patients under age 60 (controls) were identified from the Saskatchewan Epilepsy Program database. Patients' charts were retrospectively reviewed. Bivariate and multiple logistic regression analyses were performed to identify variables that were associated with epilepsy in elderly patients. RESULTS: Forty-seven elderly patients (65%) had focal epilepsy, while 9 (13%) had generalized epilepsy. The most common etiology in elderly patients with epilepsy was unknown in 30 (48%) patients. Other identified etiologies included brain tumors in 14 (19.4%), genetic in 6 (8%), degenerative disease in 4 (5%), stroke in 6 (8%) and head injury in 3 (4%). Significantly fewer elderly patients met criteria for DRE compared to non-elderly patients (26% vs. 51%, p = 0.001). In the multiple logistic regression analysis, elderly patients with epilepsy were more likely to have the presence of stroke, psychiatric comorbidity and to be on monotherapy. CONCLUSION: In our sample, elderly patients with epilepsy were more likely to have seizures resulting from brain tumors and stroke, and less likely to have DRE than non-elderly patients. These unique features of elderly patients strongly suggest that clinical practice guidelines are needed to facilitate the highest quality of care in elderly patients with epilepsy.

Efficacy of Vagal Nerve Stimulation for Drug-Resistant Epilepsy: Is it the Stimulation or Medication?

BACKGROUND: Vagus nerve stimulation (VNS) therapy has been widely recognized as an alternative for the treatment of drug-resistant epilepsy, although modification of antiepileptic drugs (AEDs) during VNS treatment could explain the improvement in patients. METHODS: We retrospectively assessed the efficacy of VNS in 30 adult patients with epilepsy treated with >6 months of follow-up. The criteria for implantation were the following: (1) not a candidate for resective epilepsy surgery, (2) drug-resistant epilepsy, (3) impairment of quality of life, (4) no other option of treatment, and (5) patients with idiopathic generalized epilepsy who fail to be controlled with appropriate AEDs. We assessed sociodemographics, seizure etiology, seizure classification, and AEDs used during treatment with VNS. We assessed adverse effects and efficacy. Responder rate was defined as >50% seizure improvement from baseline. RESULTS: Thirty patients (females, 18; males, 12; age, 35.1±13.3 years) were included. After 6, 12, 24, and 36 months of follow-up, the response rates were: 13/30 (43%), 13/27 (48%), 9/22 (41%), and 8/16 (50%), respectively; none was seizure free. Fifty-seven percent, 33%, 59%, and 81% of patients had changes of medication type or dose at 6, 12, 24, and 36 months respectively. In the majority of patients, the change of medication consisted of an increase in the dose of AEDs. CONCLUSIONS: Our study shows that VNS is an effective therapy, although significant changes in medications were done along with the therapy; therefore, the real effect of VNS could be controversial.

Epidemiology of neurocysticercosis and epilepsy, is everything described?

In recent years clinical and epidemiological research on cysticercosis has gained significant interest in some countries, especially in Latin American countries and some countries in Asia and Africa. For many years it has been proposed that the higher prevalence of epilepsy seen in some regions such as Latin-America could be explained by parasitic infections, particularly neurocysticercosis (NCC). In this review we discussed selected epidemiological topics of the association of NCC and epilepsy, such as global distribution around the world, identification of NCC in developed countries, drug resistant epilepsy and NCC. Finally this review presents a critical review of biases of the published literature in NCC. This article is part of a Special Issue entitled "Neurocysticercosis and Epilepsy".

Epidemiology of early stages of epilepsy: Risk of seizure recurrence after a first seizure.

A single unprovoked seizure is a frequent phenomenon in the general population and the rate of seizure recurrence can vary widely. Individual risk prognostication is crucial in predicting patient outcomes and guiding treatment decisions. In this article, we review the most important risk factors associated with an increased likelihood of seizure recurrence after a single unprovoked seizure. In summary, the presence of focal seizure, nocturnal seizure, history of prior brain injury, family history of epilepsy, abnormal neurological exam, epileptiform discharges on electroencephalography and neuroimaging abnormalities, portend increased risk of seizure recurrence. Elucidation of these risk factors in patient assessment will augment clinical decision-making and may help determine the appropriateness of instituting anti-epilepsy treatment. We also discuss the Canadian model of single seizure clinics and the potential use to assess these patients.

Update on Minimal Standards for Electroencephalography in Canada: A Review by the Canadian Society of Clinical Neurophysiologists.

Surface electroencephalogram (EEG) recording remains the gold standard for noninvasive assessment of electrical brain activity. It is the most efficient way to diagnose and classify epilepsy syndromes as well as define the localization of the epileptogenic zone. The EEG is useful for management decisions and for establishing prognosis in some types of epilepsy. Electroencephalography is an evolving field in which new methods are being introduced. The Canadian Society of Clinical Neurophysiologists convened an expert panel to develop new national minimal guidelines. A comprehensive evidence review was conducted. This document is organized into 10 sections, including indications, recommendations for trained personnel, EEG yield, paediatric and neonatal EEGs, laboratory minimal standards, requisitions, reports, storage, safety measures, and quality assurance.

Diagnóstico y tratamiento de la crisis epiléptica única no provocada / Diagnosis and treatment of non-triggered single epileptic seizures

Las crisis epilépticas son una de las principales causas de consulta neurológica en el servicio de urgencias. Un episodio convulsivo representa un evento traumático para el paciente y la familia, con consecuencias médicas y sociales signifi cativas. Por su prevalencia e impacto, el abordaje inicial es de vital importancia. Si bien después de una primera crisis epiléptica la recurrencia temprana disminuye con el inicio de fármacos antiepilépticos, el pronóstico para el desarrollo de epilepsia y los desenlaces a largo plazo no se alteran por ninguna intervención temprana. El interrogatorio detallado basado en la semiología del episodio, los antecedentes del paciente y un estudio completo con electroencefalograma y neuroimagen permiten defi nir el riesgo de recurrencia de la crisis y el posible diagnóstico de epilepsia. Las anormalidades epilépticas, la presencia de lesiones cerebrales con potencial epileptógeno antiguas o nuevas, así como las crisis nocturnas, incrementan el riesgo de recurrencia. Los médicos deben evaluar a cada paciente de manera individual para determinar un tratamiento idóneo, explicando el riesgo de no tratar frente al riesgo existente con el inicio de fármacos antiepilépticos (AU)

Epileptic seizures are one of the main reasons for neurological visits in an emergency department. Convulsions represent a traumatic event for the patient and the family, with signifi cant medical and social consequences. Due to their prevalence and impact, the initial management is of vital importance. Although following the fi rst epileptic seizure, early recurrence diminishes after establishing treatment with antiepileptic drugs, the forecast for developing epilepsy and longterm outcomes are not altered by any early intervention. Detailed questioning based on the symptoms of the convulsions, the patient’s medical history and a full electroencephalogram and neuroimaging study make it possible to defi ne the risk of recurrence of the seizure and the possible diagnosis of epilepsy. Epileptic abnormalities, the presence of old or new potentially epileptogenic brain lesions, as well as nocturnal seizures, increase the risk of recurrence. Physicians must assess each patient on an individual basis to determine the most suitable treatment, and explain the risk of not being treated versus the risk that exists if treatment with antiepileptic drugs is established (AU)

Evaluating the single seizure clinic model: Findings from a Canadian Center.

INTRODUCTION: The effect of the single seizure clinic (SSC) model on patient diagnose, work-up, wait-times, and clinical care is poorly characterized and its efficacy unclear. The present study assesses patient characteristics and evaluates the impact of a single seizure clinic (SSC) model on wait-times and access to care. MATERIAL AND METHODS: A prospective study of all patients (n=200) referred to our SSC for first seizure evaluation. Demographic, clinical, and paraclinicial variables were systematically collected and analyzed against a historical cohort. Binary logistic regression analysis was performed to predict impact of dichotomized variables on diagnosis of epilepsy. Diagnostic concordance between SSC nurses and epileptologists was also assessed. RESULTS: Predominant referral sources were emergency department physicians and general practitioners. Mean wait-time for first assessment was significantly reduced by 70.5% employing the SSC model versus historical usual care. A diagnosis was established at first-contact in 80.5% of cases while 16.0% of patients required a second visit. Eighty-two patients (41.0%) were diagnosed with epilepsy. An abnormal EEG was found in 93.9% of patients diagnosed with epilepsy. Sixty-three patients were started on anti-epileptic drugs (63.5% lamotrigine, 7.0% levetiracetam, 5.0% phenytoin, and 5.0% topiramate). In 18% of cases driving restrictions were initiated by the SSC. The most common non-seizure diagnosis was syncope (24.0%). DISCUSSION: The SSC reduced wait-times for assessment and investigations, clarified diagnoses, affected management decisions with respect to further workup, pharmacotherapy, and driving. There was moderate correlation between SSC nurses and physicians (kappa=0.54; p<0.001) as physicians were significantly more likely to diagnose epilepsy. Key factors identified as predictors of epilepsy were: presence of abnormalities on electroencephalography and imaging studies, patients stratified as high or medium-risk for seizure recurrence, semiological characteristics such as amnesia and limb stiffening, and presence of tongue trauma, or incontinence. CONCLUSIONS: The SSC model reduces wait-times, streamlines assessments, and impacts clinical care decisions.

Clinical Benefit of 3 Tesla Magnetic Resonance Imaging Rescanning in Patients With Focal Epilepsy and Negative 1.5 Tesla Magnetic Resonance Imaging.

BACKGROUND: Magnetic resonance imaging is an essential tool in the pre-surgical evaluation of patients with drug-resistant epilepsy. OBJECTIVE: Our aim was to assess the value of re-imaging patients with focal drug-resistant epilepsy. METHODS: Thirty patients with negative or non-conclusive 1.5 Tesla magnetic resonance imaging were rescanned with 1.5T and 3T. All of them had previous 1.5 scans with no seizure protocol in a non-specialized center. Two neuroradiologists who were blinded to prior imaging results randomly reviewed the magnetic resonance images. Kappa score was used to assess the reliability. RESULTS: Mean age of patients was 30 (SD ± 11) years. The intra-observer agreement for the first radiologist was 0.74 for 1.5T and 0.71 for 3T. In the second radiologist it was 0.82 and 0.66, respectively. Three lesions (10%) were identified by general radiologists in non-specialized centers using a 1.5T standard protocol. In our center a consensus between two neuroradiologists using epilepsy protocol identified seven lesions (23%) using 1.5T and 10 (33%) using 3T (p < 0.01). In 28% of patients this additional information resulted in a change in clinical management. CONCLUSIONS: 3T magnetic resonance imaging rescanning improves the diagnostic yield in patients with focal epilepsy and previous negative 1.5T magnetic resonance imaging. Use of 3T magnetic resonance imaging, epilepsy protocols, and interpretation by experienced neuroradiologists is highly recommended.

How many adults with temporal epilepsy have a mild course and do not require epilepsy surgery?

Temporal lobe epilepsy (TLE) is the most common type of drug-resistant epilepsy in adults and commonly requires surgical treatment. While an overwhelming preponderance of literature supports the notion that a large percentage of patients with TLE benefit from surgery, there is a paucity of outcome data on patients who demonstrate a sustained response to pharmacological treatment. In this study, we present an adult cohort of patients with TLE, with the purpose of identifying the proportion of patients with a mild course of the disease, as well as potential risk factors. A prospective cohort study of all patients with TLE assessed and followed by the Saskatchewan Epilepsy Program, from 1 March 2007 to Jan 29(th) 2014. Patients were dichotomized as having a mild (seizure freedom without surgical intervention) or severe (surgical intervention required and/or failure to achieve seizure remission) course. Descriptive statistics, odds ratios and confidence intervals were calculated to identify predictors of seizure freedom. The cohort consisted of 159 patients. Mean patient age at last follow-up visit was 46±14.4 (range: 19-88) years. Mean follow-up period was 43.4±22.6 (6 to 84) months. Forty-six patients (29%) demonstrated mild-course TLE while 113 (71%) had a severe course of TLE. Patients with a mild course of TLE were more likely to be older (p = 0.002), have late-onset epilepsy (p < 0.001) with shorter evolution (p < 0.001). A good response to the first antiepileptic drug (OR: 6.8; 95% CI: 2.5-19; p < 0.001) was associated with a mild course of TLE. Although a majority of patients with TLE eventually require surgery, operative treatment is not necessary for all patients. This study identifies prognostic factors that may help patients and clinicians characterize long-term outcome.

StatNet Electroencephalogram: A Fast and Reliable Option to Diagnose Nonconvulsive Status Epilepticus in Emergency Setting.

BACKGROUND: The StatNet electrode set is a system that can be applied by a non-electroencephalogram (EEG) technologist after minimal training. The primary objectives of this study are to assess the quality and reliability of the StatNet recordings in comparison to the conventional EEG. METHODS: Over 10 months, 19 patients with suspected nonconvulsive status epilepticus were included from university hospital emergency settings. Each patient received a StatNet EEG by a trained epilepsy fellow and a conventional EEG by registered technologists. We compared the studies in a blinded fashion, for the timeframe from EEG order to the setup time, start of acquisition, amount of artifact, and detection of abnormalities. The nonparametric Mann-Whitney two-sample t test was used for comparisons. The kappa score was used to assess reliability. RESULTS: Mean age of patients was 61±16.3 (25-93) years. The inter-observer agreement for detection of abnormal findings was 0.83 for StatNet and 0.75 for conventional EEG. Nonconvulsive status epilepticus was detected in 10% (2/19) in both studies. The delay from the time of EEG requisition to acquisition was shorter in the StatNet (22.4±2.5 minutes) than the conventional EEG (217.7±44.6 minutes; p<0.0001). The setup time was also shorter in the StatNet (9.9±0.8 minutes) compared with the conventional EEG (17.8±0.8 minutes; p<0.0001). There was no difference in the percentage of artifact duration between the two studies (p=0.89). CONCLUSION: This study demonstrates that StatNet EEG is a practical and reliable tool in the emergency setting, which reduces the delay of testing compared with conventional EEG, without significant compromise of study quality.

Resective focal epilepsy surgery - Has selection of candidates changed? A systematic review.

OBJECTIVE: No standard, widely accepted criteria exist to determine who should be referred for an epilepsy surgical evaluation. As a result, indications for epilepsy surgery evaluation vary significantly between centers. We review the literature to assess what criteria have been used to select patients for resective epilepsy surgery and examine whether these have changed since the publication of the first epilepsy surgery randomized controlled trial in 2001. METHODS: A systematic review was conducted using PubMed and EMBASE, bibliographies of reviews and book chapters identifying focal epilepsy resective series. Abstract, full text review and data abstraction (i.e. indications for surgery) were performed independently by two reviewers. Descriptive historical analysis was done to examine indications over time. RESULTS: Out of 5061 articles related to epilepsy surgery, 384 articles met all eligibility criteria. Most common criteria for selecting patients for evaluation for resective surgery were: AED resistance (n=303, most commonly >2 AEDs=46), epilepsy duration (n=53, most commonly >1 year=42) and seizure frequency (most commonly at least one seizure/month, n=29). Out of the prospective studies the most notable change over time (pre-2000 vs. post-2000) was failure of ≥2 AEDs (8% vs. 43% respectively, p<0.001). CONCLUSIONS: Important variations between studies make it difficult to identify consistent criteria to guide surgical candidacy or changes in indications over time. With increasing evidence that earlier surgery is associated with better outcomes, it is recommended that patients be evaluated as soon as they have failed two AEDs, consistent with the new definition of drug resistant epilepsy. Furthermore, low seizure frequency should not be a barrier to epilepsy surgery. Anyone with drug resistant epilepsy should be promptly evaluated for possible surgery, regardless of seizure frequency.