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We aimed to assess the reliability and validity of single-item global ratings (GR) of satisfaction with epilepsy surgery.We recruited 240 patients from four centers in Canada and Sweden who underwent epilepsy surgery ≥1 year earlier. Participants completed a validated questionnaire on satisfaction with epilepsy surgery (the ESSQ-19), plus a single-item GR of satisfaction with epilepsy surgery twice, 4-6 weeks apart. They also completed validated questionnaires on quality of life, depression, health state utilities, epilepsy severity and disability, medical treatment satisfaction and social desirability. Test-retest reliability of the GR was assessed with the intra-class correlation coefficient (ICC). Construct and criterion validity were examined with polyserial correlations between the GR measure of satisfaction and validated questionnaires and with the ESSQ-19 summary score. Non-parametric rank tests evaluated levels of satisfaction, and ROC analysis assessed the ability of GRs to distinguish among clinically different patient groups.Median age and time since surgery were 42 years (IQR 32-54) and 5 years (IQR 2-8), respectively. The GR demonstrated good to excellent test-retest reliability (ICC = 0.76; 95% CI 0.67-0.84) and criterion validity (0.85; 95% CI 0.81-0.89), and moderate correlations in the expected direction with instruments assessing quality of life (0.59; 95% CI 0.51-0.63), health utilities (0.55; 95% CI 0.45-0.65), disability (-0.51; 95% CI -0.41, -0.61), depression (-0.48; 95% CI -0.38, -0.58), and epilepsy severity (-0.48; 95% CI -0.38, -0.58). As expected, correlations were lower for social desirability (0.40; 95% CI 0.28-0.52) and medical treatment satisfaction (0.33; 95% CI 0.21-0.45). The GR distinguished participants who were seizure-free (AUC 0.75; 95% CI 0.67-0.82), depressed (AUC 0.75; 95% CI 0.67-0.83), and self-rated as having more severe epilepsy (AUC 0.78; 95% CI 0.71-0.85) and being more disabled (AUC 0.82; 95% CI 0.74-0.90).The GR of epilepsy surgery satisfaction showed good measurement properties, distinguished among clinically different patient groups, and appears well-suited for use in clinical practice and research.

Objective To use clinically informed machine learning to derive prediction models for early and late premature death in epilepsy. Methods This was a population-based primary care observational cohort study. All patients meeting a case definition for incident epilepsy in the Health Improvement Network database for inclusive years 2000-2012 were included. A modified Delphi process identified 30 potential risk factors. Outcome was early (within 4 years of epilepsy diagnosis) and late (4 years or more from diagnosis) mortality. We used regularized logistic regression, support vector machines, Gaussian naive Bayes, and random forest classifiers to predict outcomes. We assessed model calibration, discrimination, and generalizability using the Brier score, mean area under the receiver operating characteristic curve (AUC) derived from stratified fivefold cross-validation, plotted calibration curves, and extracted measures of association where possible. Results We identified 10 499 presumed incident cases from 11 194 182 patients. All models performed comparably well following stratified fivefold cross-validation, with AUCs ranging from 0.73 to 0.81 and from 0.71 to 0.79 for early and late death, respectively. In addition to comorbid disease, social habits (alcoholism odds ratio [OR] for early death = 1.54, 95% confidence interval [CI] = 1.12-2.11 and OR for late death = 2.62, 95% CI = 1.66-4.16) and treatment patterns (OR for early death when no antiseizure medication [ASM] was prescribed at baseline = 1.33, 95% CI = 1.07-1.64 and OR for late death after receipt of enzyme-inducing ASM at baseline = 1.32, 95% CI = 1.04-1.66) were significantly associated with increased risk of premature death. Baseline ASM polytherapy (OR = 0.55, 95% CI = 0.36-0.85) was associated with reduced risk of early death. Significance Clinically informed models using routine electronic medical records can be used to predict early and late mortality in epilepsy, with moderate to high accuracy and evidence of generalizability. Medical, social, and treatment-related risk factors, such as delayed ASM prescription and baseline prescription of enzyme-inducing ASMs, were important predictors.

OBJECTIVE To assess the relative contribution of ictal subtraction single-photon emission computed tomography (ISSPECT) and 18 F-fluorodeoxyglucose positron emission tomography computed tomography (PET) in epilepsy surgery decision making. MATERIALS AND METHODS A retrospective 3-year study of consecutive patients with resistant focal epilepsy who underwent ISSPECT and PET to evaluate to what extent these modalities influence decisions in epilepsy surgery and outcomes. ISSPECT imaging was performed in 106 patients and 58 (55%) had PET also. The clinical consensus (ClinC) was the final arbiter for decisions. Post-surgical outcomes were collected from follow-up clinics. Non-parametric statistics were used to assess association and logistic regression to evaluate prediction of outcomes. RESULTS Of 106 patients, 60 were males (57%). MRI was non-lesional in 46 (43%). Concordance with ClinC was seen in 80 patients (76%) for ISSPECT, in 46 patients (79%) for PET, and in 37 patients (64%) for ISSPECT + PET. Fifty-six patients (53%) were planned for intracranial video-electroencephalography monitoring (IVEM). Those with ClinC-PET concordance were likely to proceed to IVEM (p = 0.02). ClinC-PET concordance and ClinC-ISSPECT concordance did not predict decision to proceed to surgery, but VEM-MRI concordance did in lesional cases (p = 0.018). Forty-five (42%) underwent surgery of which 29 had minimum follow-up for 1 year (mean, 20 months; SD, 8) and 22 (76%) had Engel class I outcomes. ClinC-ISSPECT concordance (p = 0.024) and VEM-MRI concordance (p = 0.016) predicted Engel class I outcomes. CONCLUSION Those with ClinC-PET concordance were more likely to proceed with IVEM. ClinC-ISSPECT concordance and VEM-MRI concordance predicted good surgical outcomes.

Objective No validated tools exist to assess satisfaction with epilepsy surgery. We aimed to develop and validate a new measure of patient satisfaction with epilepsy surgery, the 19-item Epilepsy Surgery Satisfaction Questionnaire (ESSQ-19). Methods An initial 31-item measure was developed based on literature review, patient focus groups, thematic analysis, and Delphi panels. The questionnaire was administered twice, 4-6 weeks apart, to 229 adults (≥18 years old) who underwent epilepsy surgery ≥1 year earlier, at three centers in Canada and one in Sweden. Participants also completed seven validated questionnaires to assess construct validity. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) assessed the factorial structure of the questionnaire. Cronbach alpha and intraclass correlation coefficients (ICCs) assessed the internal consistency and test-retest reliability of the ESSQ-19. Spearman and polyserial correlations assessed construct validity. Results Median age of participants and time since surgery were 42 years (interquartile range [IQR] = 32-54) and 5 years (IQR = 2-8.75), respectively. EFA and CFA yielded 18 items that segregated into four domains (mean score [SD]), namely, seizure control (76.4 [25]), psychosocial functioning (67.3 [26]), surgical complications (84 [22]), and recovery from surgery (73 [24]), one global satisfaction item, and a summary global score (74 [21]). The domain and summary scores demonstrated good to excellent internal reliability (Cronbach ⍺ range = .84-.95) and test-retest reliability (ICC range = 0.71-0.85). Construct validity was supported by predicted correlations with other instruments. Significance The ESSQ-19 is a new, valid, and reliable measure of patient satisfaction with epilepsy surgery that can be used in clinical and research settings.

ObjectiveWe examined the effect of a simple Delphi-method feedback on visual identification of high frequency oscillations (HFOs) in the ripple (80–250 Hz) band, and assessed the impact of this training intervention on the interrater reliability and generalizability of HFO evaluations.MethodsWe employed a morphology detector to identify potential HFOs at two thresholds and presented them to visual reviewers to assess the probability of each epoch containing an HFO. We recruited 19 board-certified epileptologists with various levels of experience to complete a series of HFO evaluations during three sessions. A Delphi-style intervention was used to provide feedback on the performance of each reviewer relative to their peers. A delayed-intervention paradigm was used, in which reviewers received feedback either before or after the second session. ANOVAs were used to assess the effect of the intervention on the reviewers' evaluations. Generalizability theory was used to assess the interrater reliability before and after the intervention.ResultsThe intervention, regardless of when it occurred, resulted in a significant reduction in the variability between reviewers in both groups (pGroupDI = 0.037, pGroupEI = 0.003). Prior to the delayed-intervention, the group receiving the early intervention showed a significant reduction in variability (pGroupEI = 0.041), but the delayed-intervention group did not (pGroupDI = 0.414). Following the intervention, the projected number of reviewers required to achieve strong generalizability decreased from 35 to 16.SignificanceThis study shows a robust effect of a Delphi-style intervention on the interrater variability, reliability, and generalizability of HFO evaluations. The observed decreases in HFO marking discrepancies across 14 of the 15 reviewers are encouraging: they are necessarily associated with an increase in interrater reliability, and therefore with a corresponding decrease in the number of reviewers required to achieve strong generalizability. Indeed, the reliability of all reviewers following the intervention was similar to that of experienced reviewers prior to intervention. Therefore, a Delphi-style intervention could be implemented either to sufficiently train any reviewer, or to further refine the interrater reliability of experienced reviewers. In either case, a Delphi-style intervention would help facilitate the standardization of HFO evaluations and its implementation in clinical care.

Purpose Amygdala enlargement (AE) has been reported in drug resistant lesional and non-lesional temporal lobe epilepsy (TLE). Its contribution to development of intractability of epilepsy is at best uncertain. Our aim was to study the natural course of AE in a heterogenous group of TLE patients with follow-up imaging and clinical outcomes. Methods A prospective observational study in patients with TLE with imaging features of AE recruited from epilepsy clinics between 1994 and 2018. Demographic data, details of epilepsy syndrome, outcomes and follow up neuroimaging were extracted. Results Forty-two patients were recruited including 19 males (45 %). Mean age at onset of epilepsy was 30.6 years and mean duration of epilepsy was 19.9 years. On MRI, 33 patients had isolated unilateral AE and eleven had AE with hippocampal enlargement (HE). Twenty (48 %) underwent temporal resections with most common histopathology being amygdalar gliosis (40 %). Engel Class IA outcome at last follow up (mean, 10 years) was 60 %. Thirty-four patients had neuroimaging follow up of at least 1 year (mean, 5 years). AE resolved in 6, persisted in 25, evolved into bilateral HS in 1, bilateral mesial temporal atrophy in 1 and ipsilateral mesial temporal atrophy in 1. Resolution of AE was associated with better seizure free outcomes (p = 0.013). Conclusions TLE with AE is associated with favourable prognosis yet not benign. Over 50 % were drug resistant and surgical outcomes were similar to mTLE. Resolution of AE on follow up neuroimaging was associated with better seizure free outcomes.

Seizures are often followed by a period of transient neurological dysfunction and postictal alterations in cerebral blood flow may underlie these symptoms. Recent animal studies have shown reduced local cerebral blood flow at the seizure onset zone (SOZ) lasting approximately 1 h following seizures. Using arterial spin labelling (ASL) MRI, we observed postictal hypoperfusion at the SOZ in 75% of patients. The clinical implementation of ASL as a tool to identify the SOZ is hampered by the limited availability of MRI on short notice. Computed tomography perfusion (CTP) also measures blood flow and may circumvent the logistical limitations of MRI. Thus, we aimed to measure the extent of postictal hypoperfusion using CTP. Fourteen adult patients with refractory focal epilepsy admitted for presurgical evaluation were prospectively recruited and underwent CTP scanning within 80 min of a habitual seizure. Patients also underwent a baseline scan after they were seizure-free for > 24 h. The acquired scans were qualitatively assessed by two reviewers by visual inspection and quantitatively assessed through a subtraction pipeline to identify areas of significant postictal hypoperfusion. Postictal blood flow reductions of > 15 ml/100 g−1/min−1 were seen in 12/13 patients using the quantitative method of analysis. In 10/12 patients, the location of the hypoperfusion was partially or fully concordant with the presumed SOZ. In all patients, additional areas of scattered hypoperfusion were seen in areas corresponding to seizure spread. CTP can reliably measure postictal hypoperfusion which is maximal at the presumed SOZ.

Objective The 19-item Epilepsy Surgery Satisfaction Questionnaire (ESSQ-19) is a validated and reliable post hoc means of assessing patient satisfaction with epilepsy surgery. Prediction models building on these data can be used to counsel patients. Methods The ESSQ-19 was derived and validated on 229 patients recruited from Canada and Sweden. We isolated 201 (88%) patients with complete clinical data for this analysis. These patients were adults (≥18 years old) who underwent epilepsy surgery 1 year or more prior to answering the questionnaire. We extracted each patient's ESSQ-19 score (scale is 0-100; 100 represents complete satisfaction) and relevant clinical variables that were standardized prior to the analysis. We used machine learning (linear kernel support vector regression [SVR]) to predict satisfaction and assessed performance using the R2 calculated following threefold cross-validation. Model parameters were ranked to infer the importance of each clinical variable to overall satisfaction with epilepsy surgery. Results Median age was 41 years (interquartile range [IQR] = 32-53), and 116 (57%) were female. Median ESSQ-19 global score was 68 (IQR = 59-75), and median time from surgery was 5.4 years (IQR = 2.0-8.9). Linear kernel SVR performed well following threefold cross-validation, with an R2 of .44 (95% confidence interval = .36-.52). Increasing satisfaction was associated with postoperative self-perceived quality of life, seizure freedom, and reductions in antiseizure medications. Self-perceived epilepsy disability, age, and increasing frequency of seizures that impair awareness were associated with reduced satisfaction. Significance Machine learning applied postoperatively to the ESSQ-19 can be used to predict surgical satisfaction. This algorithm, once externally validated, can be used in clinical settings by fixing immutable clinical characteristics and adjusting hypothesized postoperative variables, to counsel patients at an individual level on how satisfied they will be with differing surgical outcomes.

Objectives Epilepsy surgery is offered in resistant focal epilepsy. Non-invasive investigations like scalp video EEG monitoring (SVEM) help delineate epileptogenic zone. Complex cases may require intracranial video EEG monitoring (IVEM). Stereoelectroencephalography (SEEG)-based intracerebral electrode implantation has better spatial resolution, lower morbidity, better tolerance, and superiority in sampling deep structures. Our objectives were to assess IVEM using SEEG with regard to reasoning behind implantation, course, surgical interventions, and outcomes. Materials and methods Seventy-two admissions for SEEG from January 2014 to December 2018 were included in the study. Demographic and clinical data were retrospectively collected. Results The cohort comprised of 69 adults of which 34 (47%) had lesional MRI. Reasons for SEEG considering all cases included non-localizing ictal onset (76%), ictal-interictal discordance (21%), discordant semiology (17%), proximity to eloquent cortex (33%), nuclear imaging discordance (34%), and discordance with neuropsychology (19%). Among lesional cases, additional reasons included SVEM discordance (68%) and dual or multiple pathology (47%). Forty-eight patients (67%) were offered resective surgery, and 41 underwent it. Twenty-three (56%) had at least one year post-surgical follow-up of which 14 (61%) had Engels class I outcome. Of the remaining 23 who were continued on medical management, 4 (17%) became seizure-free and 12 (51%) had reduction in seizure frequency. Conclusion SEEG monitoring is an important and safe tool for presurgical evaluation with good surgical and non-surgical outcomes. Whether seizure freedom following non-surgical management could be related to SEEG implantation, medication change, or natural course needs to be determined.

Objective: To determine whether postictal cognitive and behavioral impairment (PCBI) is independently associated with specific aspects of a patient9s psychosocial health in those with epilepsy and nonepileptic events. Methods: We used the University of Calgary9s Comprehensive Epilepsy Clinic prospective cohort database to identify patients reporting PCBI. The cohort was stratified into those diagnosed with epilepsy or nonepileptic events at first clinic visit. Univariate comparisons and stepwise multiple logistic regression with backward elimination method were used to identify factors associated with PCBI for individuals with epilepsy and those with nonepileptic events. We then determined if PCBI was independently associated with depression and the use of social assistance when controlling for known risk factors. Results: We identified 1,776 patients, of whom 1,510 (85%) had epilepsy and 235 had nonepileptic events (13%). PCBI was independently associated with depression in those with epilepsy (odds ratio [OR] 1.73; 95% confidence interval [CI] 1.06–2.83; p = 0.03) and with the need for social assistance in those with nonepileptic events (OR 4.81; 95% CI 2.02–11.42; p Conclusions: PCBI appears to be significantly associated with differing psychosocial outcomes depending on the patient9s initial diagnosis. Although additional research is necessary to examine causality, our results suggest that depression and employment concerns appear to be particularly important factors for patients with PCBI and epilepsy and nonepileptic attacks, respectively.

Summary Objective Elderly onset epilepsy represents a distinct subpopulation that has received considerable attention due to the unique features of the disease in this age group. Research into this particular patient group has been limited by a lack of a standardized definition and understanding of the attributes associated with elderly onset epilepsy. Methods We used a prospective cohort database to examine differences in patients stratified according to age of onset. Linear support vector machine learning incorporating all significant variables was used to predict age of onset according to prespecified thresholds. Sensitivity and specificity were calculated and plotted in receiver-operating characteristic (ROC) space. Feature coefficients achieving an absolute value of 0.25 or greater were graphed by age of onset to define how they vary with time. Results We identified 2,449 patients, of whom 149 (6%) had an age of seizure onset of 65 or older. Fourteen clinical variables had an absolute predictive value of at least 0.25 at some point over the age of epilepsy-onset spectrum. Area under the curve in ROC space was maximized between ages of onset of 65 and 70. Features identified through machine learning were frequently threshold specific and were similar, but not identical, to those revealed through simple univariable and multivariable comparisons. Significance This study provides an empirical, clinically informed definition of “elderly onset epilepsy.” If validated, an age threshold of 65–70 years can be used for future studies of elderly onset epilepsy and permits targeted interventions according to the patient's age of onset.

Importance Levetiracetam is a commonly used antiepileptic drug, yet psychiatric adverse effects are common and may lead to treatment discontinuation. Objective To derive prediction models to estimate the risk of psychiatric adverse effects from levetiracetam use. Design, Setting, and Participants Retrospective open cohort study. All patients meeting the case definition for epilepsy after the Acceptable Mortality Reporting date in The Health Improvement Network (THIN) database based in the United Kingdom (inclusive January 1, 2000, to May 31, 2012) who received a first-ever prescription for levetiracetam were included. Of 11 194 182 patients registered in THIN, this study identified 7400 presumed incident cases (66.1 cases per 100 000 persons) over a maximum of 12 years' follow-up. The index date was when patients received their first prescription code for levetiracetam, and follow-up lasted 2 years or until an event, loss to follow-up, or censoring. The analyses were performed on April 22, 2018. Exposure A presumed first-ever prescription for levetiracetam. Main Outcomes and Measures The outcome of interest was a Read code for any psychiatric sign, symptom, or disorder as reached through consensus by 2 authors. This study used regression techniques to derive 2 prediction models, one for the overall population and one for those without a history of a psychiatric sign, symptom, or disorder during the study period. Results Among 1173 patients with epilepsy receiving levetiracetam, the overall median age was 39 (interquartile range, 25-56) years, and 590 (50.3%) were female. A total of 14.1% (165 of 1173) experienced a psychiatric symptom or disorder within 2 years of index prescription. The odds of reporting a psychiatric symptom were significantly elevated for women (odds ratio [OR], 1.41; 95% CI, 0.99-2.01; P = .05) and those with a preexposure history of higher social deprivation (OR, 1.15; 95% CI, 1.01-1.31; P = .03), depression (OR, 2.20; 95% CI, 1.49-3.24; P < .001), anxiety (OR, 1.74; 95% CI, 1.11-2.72; P = .02), or recreational drug use (OR, 2.02; 95% CI, 1.20-3.37; P = .008). The model performed well after stratified k = 5-fold cross-validation (area under the curve [AUC], 0.68; 95% CI, 0.58-0.79). There was a gradient in risk, with probabilities increasing from 8% for 0 risk factors to 11% to 17% for 1, 17% to 31% for 2, 30% to 42% for 3, and 49% when all risk factors were present. For those free of a preexposure psychiatric code, a second model performed comparably well after k = 5-fold cross-validation (AUC, 0.72; 95% CI, 0.54-0.90). Specificity was maximized using threshold cutoffs of 0.10 (full model) and 0.14 (second model); a score below these thresholds indicates safety of prescription. Conclusions and Relevance This study derived 2 simple models that predict the risk of a psychiatric adverse effect from levetiracetam. These algorithms can be used to guide prescription in clinical practice.

This is a case of autoimmune encephalitis with features of faciobrachial dystonic seizures (FBDS) pathognomonic for Leucine Rich Glioma inactivated (LGI)1 antibody encephalitis. This voltage-gated potassium channel complex encephalitis is marked by rapid onset dementia, FBDS and hyponatremia, which is sensitive to management with immunotherapy including steroids, IVIG and other agents. In this case report we review the clinical features, imaging and management of this condition.

Objective High frequency oscillations (HFOs) and interictal epileptiform discharges (IEDs) have been shown to be markers of epileptogenic regions. However, there is currently no ‘gold standard' for identifying HFOs. Accordingly, we aimed to formally characterize the interrater reliability of HFO markings to validate the current practices. Methods A morphology detector was implemented to detect events (candidate HFOs, lower-threshold events, and distractors) from the intracranial EEG (iEEG) of ten patients. Six electroencephalographers visually evaluated these events for the presence of HFOs and IEDs. Interrater reliability was calculated using pairwise Cohen's Kappa ( κ ) and intraclass correlation coefficients (ICC). Results The HFO evaluation distributions were significantly different for most pairs of reviewers ( p . 05; 11/15 pairs). Interrater reliability was poor for HFOs alone ( κ mean =0 . 403; ICC=0.401) and HFO+IEDs ( κ mean =0 . 568; ICC=0.570). Conclusions The current practice of using two visual reviewers to identify HFOs is prone to bias arising from the poor agreement between reviewers, limiting the extrinsic validity of studies using these markers. Significance The poor interrater reliability underlines the need for a framework to reconcile the important findings of existing studies. The present epoched design is an ideal candidate for the implementation of such a framework.

Objective While there are well-established guidelines for optimum video-EEG monitoring (VEM), the process of reviewing VEM data varies amongst centres. In this study, we compared continuous with sampled reviewing of VEM data to assess whether their diagnostic yield differs. Methods VEM data acquired from 50 consecutive patients (31 females) admitted for VEM were reviewed by two independent electroencephalographers, one using the continuous review method, and the other sampling the first five minutes of each hour together with events identified by push buttons and automated spike detection software. Overall agreement between reviewers was calculated using the Kappa statistic. Comparison between the total number of clinical events detected by the two methods was done by Pearson’s correlation coefficient. Results A substantial number of events were missed using sampled review. Despite this, there was excellent agreement between the two methods on the final electro-clinical diagnosis for each patient (Kappa = 0.89). Conclusion In our laboratory, continuous VEM more comprehensively captured information of interest, but it did not substantially alter the final electro-clinical diagnosis. Significance Sampled review of VEM data captures sufficient data to reliably make accurate clinical decisions. It may be considered as a more cost and labor efficient alternative to continuous review.

Background The diagnosis of vasovagal syncope continues to be difficult despite the use of accurate histories, tilt testing and implantable loop recorders. A circulating biomarker might be useful to facilitate diagnoses. Both endothelin-1 and vasopressin are increased during positive tilt tests resulting in syncope. Copeptin is a stable cleavage product of vasopressin formation. We conducted a pilot study to assess the utility of endothelin-1 and copeptin as circulating biomarkers of vasovagal syncope. Methods Three populations were studied: syncope patients, epilepsy patients and controls. Vasovagal syncope diagnosis was ascertained with the Calgary Syncope Score and epilepsy diagnosis was confirmed with EEG. Plasma levels of endothelin-1 were measured using by ELISA and copeptin levels were determined using an EIA kit. Results Asymptomatic control subjects had mean age 35 ± 11 years (7/22 male); epileptic subjects had mean age 32 ± 7 years (4/15 male); and syncope subjects had mean age 33 ± 16 years (4 of 21 male). Circulating plasma levels of endothelin-1 and copeptin were no different among the three groups. Mean concentrations of endothelin-1 were as follows: syncope, 23 ± 32 pg/mL; controls, 21 ± 17 pg/mL; and epileptics, 18 ± 12 pg/mL. Mean concentrations of copeptin were as follows: syncope, 1·29 ± 0·79 ng/mL; controls, 1·25 ± 0·79 ng/mL; and seizures, 1·23 ± 0·45 ng/mL. There were no significant correlations between syncope frequency and copeptin or endothelin-1 levels. Conclusion Circulating plasma endothelin-1 and copeptin levels are not significantly different among populations of controls, syncope patients and seizure patients.

We assessed the impact of vagus nerve stimulation on a cohort of patients with intractable epilepsy. A 1-year prospective trial of vagus nerve stimulation for intractable epilepsy was done in 26 patients. Seizure frequency, anti-epileptic drugs, and quality of life were assessed using QOLIE-89, ELDQOL, and a Likert scale of impact of treatment. Seizures were reduced by more than 50% in 19% of the patients, by less than 50% in 46%, and were unchanged in 35% of them. Antiepileptic drugs were reduced in 43% of the patients. There was a significant improvement in the mean overall QOLIE-89 score and other measures of quality of life, but these did not correlate with changes in seizure frequency. Subjective improvement occurred in 84% of the patients. The quality of life improves in some patients following vagus nerve stimulation for intractable epilepsy. The favorable effects of this treatment may be attributable to additional factors besides seizure control which in this study was modest.

Although in clinical use for many years, the validity of intraoperative electrocorticography (ECoG) in guiding resective temporal lobe epilepsy (TLE) surgery is uncertain. Advances in neuroimaging and extraoperative intracranial recordings have contributed greatly to the identification of epileptogenic lesions and cortex, clarifying the limitations of a brief intraoperative interictal recording. Studies of undifferentiated ECoG findings (which classify all interictal cortical spike discharges as equal) tend to not support this method. This article reviews ECoG and presents data from 86 TLE surgeries at the University of British Columbia suggesting that differentiation of ECoG features may enhance the contribution of this time honored method. Specifically, independent foci may be more important for epileptogenesis than synchronous foci, and postexcision activation appears to be a benign phenomenon, while residual spikes unaltered by the resection correlate with a greater proportion of seizure recurrence.

The electroencephalogram (EEG) plays an important diagnostic role in epilepsy and provides supporting evidence of a seizure disorder as well as assisting with classification of seizures and epilepsy syndromes. Emerging evidence suggests that the EEG may also provide useful prognostic information regarding seizure recurrence after a single unprovoked attack and following antiepileptic drug withdrawal. Continuous EEG video telemetry monitoring has an established role in the diagnosis of non-epileptic pseudo-seizures and in localizing the seizure focus for epilepsy surgery. Newer tools such as EEG mapping and magneto-encephalogram, although still investigational, appear potentially useful for defining the seizure focus in epilepsy. This review examines the traditional concepts of clinical EEG in the light of newly available data.

Examining and improving the quality of care in epilepsy monitoring units (EMUs) is essential to delivering the best possible care and to mitigating undesirable outcomes. Epilepsy monitoring units are unique in that an admission to an EMU often involves the induction of symptoms (seizures) rather than minimizing and/or treating symptoms, which can lead to an increased risk to patient safety. Very little research has addressed the quality of care and safety in EMUs. The objective of this study was to examine quality indicators in a large population of patients admitted to an EMU in a large health region. Data were collected prospectively on 396 consecutive patients admitted to the EMU for scalp EEG recording from 2008 to 2011 using a standardized data abstraction form. Variables examined included the following: patient demographics, baseline clinical characteristics, EMU admission statistics, and EMU quality indicators. We found that an admission to the EMU was a safe and effective tool in the management of patients with epilepsy and seizure-like events. The number of adverse events during the study period was low at 4.9%. The admission question was answered in 78.8% of cases, and it was partially answered in 6.6%. The need for systematically developed and validated quality indicators in EMUs is emphasized. The research in this area is sparse, and thus these data aid in supporting the utility of EMUs in the management and care of those with seizures and seizure-like events.

We used functional MRI (fMRI), transcranial Doppler ultrasound, and visual evoked potentials (VEPs) to determine the nature of blood flow responses to functional brain activity and carbon dioxide (CO2) inhalation in patients with cerebral amyloid angiopathy (CAA), and their association with markers of CAA severity.In a cross-sectional prospective cohort study, fMRI, transcranial Doppler ultrasound CO2 reactivity, and VEP data were compared between 18 patients with probable CAA (by Boston criteria) and 18 healthy controls, matched by sex and age. Functional MRI consisted of a visual task (viewing an alternating checkerboard pattern) and a motor task (tapping the fingers of the dominant hand).Patients with CAA had lower amplitude of the fMRI response in visual cortex compared with controls (p = 0.01), but not in motor cortex (p = 0.22). In patients with CAA, lower visual cortex fMRI amplitude correlated with higher white matter lesion volume (r = -0.66, p = 0.003) and more microbleeds (r = -0.78, p0.001). VEP P100 amplitudes, however, did not differ between CAA and controls (p = 0.45). There were trends toward reduced CO2 reactivity in the middle cerebral artery (p = 0.10) and posterior cerebral artery (p = 0.08).Impaired blood flow responses in CAA are more evident using a task to activate the occipital lobe than the frontal lobe, consistent with the gradient of increasing vascular amyloid severity from frontal to occipital lobe seen in pathologic studies. Reduced fMRI responses in CAA are caused, at least partly, by impaired vascular reactivity, and are strongly correlated with other neuroimaging markers of CAA severity.

Purpose Despite evidence that carefully selected patients with refractory focal epilepsy benefit from epilepsy surgery, significant delays remain. We examined patient knowledge and perceptions regarding epilepsy surgery. Methods A 5-minute questionnaire was administered to consecutive adults with focal epilepsy seen in the epilepsy clinic in a large Canadian health region. Survey items assessed the following: (1) knowledge of surgical options, (2) perceptions about the risks of surgery vs. ongoing seizures, (3) disease disability, (4) treatment goals, and (5) demographic and socioeconomic variables. Patient responses were compiled to calculate a “Barriers to Epilepsy Surgery Composite” (BESC) score. Results Of 129 eligible patients, 107 completed the questionnaire (response rate: 83%). The average BESC score was 60/100. Apprehension about epilepsy surgery was less likely among patients who had previously undergone epilepsy surgery and those born in Canada. Discussion People with epilepsy often have hindering perceptions that can contribute to delays in surgical care.

Introduction: Cerebral amyloid angiopathy (CAA) is marked by accumulation of vascular beta-amyloid which is toxic to smooth muscle cells. An animal study and a pilot study in humans suggest decreased vasodilation in CAA. We studied patients with CAA and matched controls to determine whether neurovascular coupling is impaired in CAA. Methods: Patients with CAA and controls underwent task-related fMRI with a visual task (viewing a flashing alternating checkerboard pattern) or a motor task (tapping the fingers of the dominant hand) using a block design, and visual evoked potentials (VEPs). CAA patients were diagnosed by Boston criteria and had normal corrected visual acuity, no visual field deficits and no paresis of the dominant arm. Controls were recruited by community advertising and were matched by gender and age (±5 years) to CAA cases. Results: Eighteen CAA patients (12 M, 6F; 72±7 yrs) and eighteen controls (12 M, 6F; 70±7 yrs) were studied. For the visual task, CAA patients had reduced activity in the occipital lobe (Figure) and lower amplitude of the BOLD response vs. controls (28% reduced, p=0.005). By contrast, for the motor task CAA patients had a similar response of the primary motor cortex vs. controls (9.6% reduced BOLD response, p=0.53). VEP P100 latencies and amplitudes did not differ between CAA and controls (p=0.49 and p=0.74). Lower visual cortex BOLD amplitudes were correlated with greater white matter lesion volumes in CAA (r=-0.66, p=0.003). Conclusions: Neurovascular coupling is impaired in the occipital lobe in CAA. BOLD signal amplitudes are reduced despite normal evoked potentials, suggesting impaired vasodilation. The association with white matter lesion volume raises the possibility that impaired vasodilation may be involved in the pathogenesis of these lesions. BOLD responses in the primary motor cortex in CAA were not reduced, likely reflecting the known posterior predominance of CAA with lesser involvement of the frontal lobe.

The purpose of this study was to investigate staff experience and satisfaction in the seizure monitoring unit (SMU) of a large health region serving a population of 1.4 million. A staff satisfaction questionnaire was administered yearly between 2007 and 2010 with an average response rate of 58.4%. The majority of staff perceived the SMU to be a positive workplace. Strengths of the SMU were interdisciplinary teamwork and patient-centred care. Satisfaction with professional development opportunities increased from 2007 to 2010, likely reflecting the implementation of training sessions. The physical environment was the least satisfactory. This study highlights aspects of staff experience that have improved or still need to be improved since implementing a quality and safety program in our SMU.

Background:Non-convulsive seizures have been reported to be common in neurocritical care patients. Many jurisdictions do not have sufficient resources to enable routine continuous electroencephalography (cEEG) and instead use primarily intermittent EEG, for which the diagnostic yield remains uncertain. Determining risk factors for epileptiform activity and seizures could help identify patients who might particularly benefit from EEG monitoring.Methods:We performed a cohort study involving neurocritical care patients with admission Glascow Coma Scale (GCS) scores =≤ 12, who underwent ≥ 1 EEG. EEGs were reviewed for presence of interictal discharges, periodic epileptiform discharges (PEDs), and seizures. Multivariate analysis was used to identify predictors of these findings and to describe their prognostic implications.Results:393 patients met inclusion criteria. 34 underwent cEEG, usually because epileptiform activity was first detected on a routine EEG. The prevalence of PEDs or electrographic seizures was 13%, and was highest with anoxic encephalopathy and central nervous system infections. Other independent predictors for epileptiform activity included a history of convulsive seizure(s), increasing age, deeper coma, and female gender. Although patients with epileptiform activity had higher mortality, this association disappeared after adjustment for confounders.Conclusion:Approximately 7-8 neurocritical care patients must undergo intermittent EEG monitoring in order to diagnose one with PEDs or seizures. The predictors we identified could potentially help guide use of resources. Repeated intermittent studies, or cEEG, should be considered in patients with multiple risk factors, or when interictal discharges are identified on an initial EEG. It remains unclear whether aggressive prevention and treatment of electrographic seizures improves neurologic outcomes.

Seizure monitoring unit (SMU) research typically focuses on diagnostic utility and medical management of epilepsy. However, patient safety and satisfaction are also imperative to high-quality SMU care. This study uses a standardized tool to evaluate patient experience on a SMU compared to a general neurology unit (GNU). The 27-item Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey was telephone-administered post-discharge to a sample of patients from our SMU and GNU. Data from a 33-month period were reviewed, encompassing 217 SMU patient admissions and 317 GNU patient admissions. On average, SMU patients were 14.7 years younger and stayed in the hospital 4.2 days longer than GNU patients. SMU patients provided lower overall mental health ratings (p

Summary: The effect of domoic acid-induced seizure activity on energy metabolism and on brain pH in mice was studied by continuous EEG recording and in vivo 31P nuclear magnetic resonance (NMR) spectroscopy. Mice were divided into ventilated (n = 6) and nonventilated (n = 7) groups. Baseline EEG was 0.1-mV amplitude with frequence of >30-Hz and of 4-5 Hz. After intraperitoneal (i.p.) administration of domoic acid (6 mglkg), electrographic spikes appeared at increasing frequency, progressing to high-amplitude (0.1-0.8 mV) continuous seizure activity (status epilepticus). In ventilated mice, the ["PJNMR spectra showed that high-energy phosphate levels and tissue pH did not change after domoic acid administration or during the intervals of spiking or status epilepticus. Nonventilated mice showed periods of EEG suppression accompanied by decreases in the levels of high-energy phosphate metabolites and in pH, corresponding to episodic respiratory suppression during the spiking interval. In all animals, status epilepticus was followed by a marked decrease in EEG amplitude that progressed rapidly to isoelectric silence. [3 IPINMR spectra obtained after this were indicative of total energy failure and tissue acidosis. In a separate group of ventilated mice (n = 4), domoic acid-induced status epilepticus was accompanied initially by an increase in mean arterial blood pressure (MAP) that slowly returned to baseline level. Isoelectric silence was accompanied by a decrease in MAP to 75 ? 8 mm Hg. These experiments suggest that domoic acid-induced seizures are not accompanied by an increase in substrate demand that exceeds supply. Key Words: Domoic acid-"P Spectroscopy-Status epilepticus-Neurologic models.

A community survey and subsequent clinical assessment of 192 Cree aged 65 years and over registered in two Reserves in Northern Manitoba identified only one case of probable Alzheimer's disease among eight cases of dementia, giving a prevalence of 0.5% for Alzheimer's disease and 4.2% for all dementias. This contrasted with an age-adjusted prevalence of 3.5% for Alzheimer's disease and 4.2% for all dementias in an age-stratified sample of 241 English-speaking residents of Winnipeg. Although it was not so for all dementias, the difference between the groups for prevalence of Alzheimer's disease was highly significant (p < .001). The age-specific patterns of all dementias in the two groups were significantly different, however (p = .0254).

Summary: Epilepsy-prone and epilepsy-resistant substrains were selectively bred from a strain of BALB/c mice; audiogenic-sensitive epilepsy-prone animals showed enhanced sensitivity to chemical convulsants. Treatment with pyridoxine (100 mg/L in drinking water) initiated at mating and continued throughout pregnancy and the life of the offspring abolished the enhanced sensitivity to chemical convulsants and reduced the severity of audiogenic seizures. Withdrawal of pyridoxine restored the enhanced seizure sensitivity. [1H] Nuclear magnetic resonance (NMR) spectroscopy of perchloric acid extracts of tissue was used to determine the concentrations of several compounds [N-acetylaspartate (NAA), GABA, glutamate, aspartate, alanine, taurine, creatine, cholines, inositol] in the hippocampus, neocortex, brainstem, and cerebellum of untreated and pyridoxine-treated 6-week-old female animals. The ratios of the concentrations of excitatory to inhibitory putative neurotransmitteramino acids tended to be higher in epilepsy-prone animals, with the most pronounced difference being a significantly elevated glutamate/GABA ratio in every brain region examined. Pyridoxine treatment abolished this imbalance in the hippocampus, brainstem, and cerebellum, but not in the neocortex. Treatment of epilepsy-resistant animals with pyridoxine using the same protocol decreased the glutamate/GABA concentration ratio in the hippocampus, brainstem, and neocortex and resulted in impaired development of the animals. The amino acid imbalance and the accompanying seizure susceptibility in these genetically epilepsy prone mice may originate from an inborn error in pyridoxine metabolism or in a pyridoxine-dependent enzyme system. ReSUMe A partir d'une souche de souris BALB/c, des pedigrees de souris predisposees a l'epilepsie et resistantes a l'epilepsie ont ete selectivement obtenus avec des animaux predisposes a l'epilepsie, sensibles aux stimulations audiogeniques, qui presentaient une sensibilite augmentee aux convulsivants chimiques. Le traitement par la pyridoxine (100 mg/L dans l'eau de boisson) commence au moment de la copulation, poursuivi pendant la gestation et pendant toute la vie du rat a aboli l'augmentation de sensibilite aux convulsivants chimiques, et a reduit la severite des crises audiogtnes. L'arret de la pyridoxine a retabli l'augmentation de sensibilite aux crises. La spectroscopie RMN [1H] d'extraits de tissus traites par acide perchlorique a ete utilisee pour determiner les concentrations de differents composes (N-acetylaspartate, GABA, glutamate, aspartate, alanine, taurine, creatine, cholines, inositol) au niveau de l'hippocampe, du neocortex, du tronc cerebral et du cervelet, chez des souris femelles non traitees et traitees par pyridoxine, âgees de 6 semaines. Les rapports de concentration des acides amines neurotransmetteurs excitateurshnhibiteurs tendaient B ttre plus eleves chez les animaux predisposes B l'epilepsie, la difference la plus importante representant un rapport significativement augmente glutamate/GABA au niveau de chaque region cerebrale examinee. Le traitement par pyridoxine a aboli ce desequilibre au niveau de l'hippocampe, du tronc cerebral et du cervelet mais pas au niveau du neocortex. Le traitement des animaux resistant B l'epilepsie par la pyridoxine, suivant le mtme protocole a diminue les rapports de concentrations de glutamate/GABA au niveau de l'hippocampe, du tronc cerebral et du neocortex et a entraino un trouble du developpement de ces animaux. Le desequilibre des amino-acides et la susceptibilite aux crises, qui semblent associCs chez ces rats genetiquement predisposes B l'epilepsie, peut provenir d'une erreur innee du metabolisme de la pyridoxine ou d'un systeme enzymatique pyridoxino-dependant. RESUMEN Se han seleccionado sub-cepas resistentes a la epilepsia y tambikn cepas de ratones BALB/c que tenian epilepsia sensible a estimulos radiogknicos y mostraron un aumento de su sensibilidad a convulsivantes quimicos. Un tratamiento con piridoxina (100 mg/L administrada en agua) iniciado en el momento de la copulacion y continuada a lo largo del embarazo y de la vida de los animales-hijo elimino el incremento de la sensibilidad a convulsivantes quimicos y redujo la severidad de los ataques audiogknicos. La interrupcion de la piridoxina restauro el incremento de la sensibilidad de los ataques. Se ha utilizado la espectroscopia con Resonancia Magnetica para extractos de acido perclorico de los tejidos con intention de determinar las concentraciones de varios compuestos (N-acetilaspartato, GABA, glutamato, aspartato, alanina, taurina, creatina, colina, inositol) en el hipocampo, neocortex, tronco cerebral y cerebelo de los animales hembras de 6 semanas de edad tratados y no tratados con piridoxina. Las relaciones entre la concentracion de aminoacidos neurotransmisores putativamente considerados como excitatorios o inhibitorios, mostraron una tendencia a estar mas elevadas en animales con tendencia a la epilepsia con una diferencia mas pronunciada demostrada por una elevation significativa de la relacion glutamato-GABA en cada region cerebral examinada. El tratamiento con piridoxina elimino este desequilibrio en el hipocampo, el tronco cerebral y el cerebelo per0 no en el neocortex. El tratamiento de los animales resistentes a la epilepsia con piridoxina utilizando el mismo protocolo redujo la concentracion de la relacion glutamatolGABA en el hipocampo, tronco cerebral y neocortex, y condujo a un desarrollo de los animales sin ningdn tip0 de trastorno. El desequilibrio de aminoacidos y la asociada susceptibilidad para los ataques en estos ratones con una tendencia genktica a la epilepsia puede originarse a traves de un error congenito del metabolismo de la piridoxina o en sistemas enzimaticos piridoxina-dependientes. ZUSAMMENFASSUNG Epilepsieanfallige und Epilepsieresistente Untergruppen wurden von einem Stamm BALB/c-Mausen gezuchtet, wobei die Tiere mit einer audiogen-sensitiven Epilepsieneigung eine erhohte Empfindlichkeit gegenuber chemischen Konvulsiva zeigten. Eine Behandlung mit Pyridoxin (100 mg/l Trinkwasser), die bei der Paarung begonnen wurde und wahrend der Tragezeit und dem ganzen Leben der Nachkommen aufrecht erhalten wurde, brachte die erhohte Empfindlichkeit gegenuber chemischen Konvulsiva zum Verschwinden und reduzierte den Schweregrad der audiogenen Anfalle. Ein Pyridoxin-Entzug stellte die erhohte Anfallsempfindlichkeit wieder her. Mit Hilfe einer [1H] NMR-Spektroskopie von Perchlorsaureextrakten wurden die Konzentrationen von verschiedenen Bestandteilen (N-Acethylaspartat, GABA, Glutamat, Aspartat, Alanin, Taurin, Kreatin, Cholinen, Inositol) im Hippokampus, Neokortex, Hirnstamm und Cerebellum von unbehandelten und Pyridoxinbehandelten 6 Wochen alten weiblichen Tieren bestimmt. Das Verhaltnis in den Konzentrationen von exzitatorischen zu inhibitorischen moglichen Neurotransmitter-Aminosauren zeigte bei den Epilepsie-anfalligen Tieren eine Tendenz zur Erhohung, mit der deutlichsten Differenz in Form einer signifikanten Erhohung des Glutamat/GABA Verhaltnisses in jeder untersuchten Hirnregion. Die Pyridoxin-Behandlung brachte dieses Ungleichgewicht im Hippokampus, Hirnstamm und Kleinhirn zum Verschwinden, jedoch nicht im Neokortex. Die Behandlung von Epilepsie -resistenten Tieren mit Pyridoxin unter dem gleichen Protokoll fuhrte zu einer Verminderung des Glutamat/GABA- Konzentrationsverhaltnisses im Hippokampus, Hirnstamm und Neokortex und resultierte in einer behinderten Entwicklung der Tiere. Die Aminosaurenimbalance und die begleitende Anfallsempfindlichkeit bei diesen genetisch zu einer Epilepsie neigenden Mausen rahrt moglicherweise von einer angeborenen Storung im Pyridoxinmetabolismus oder in einem Pyridoxin- abhangigen Enzymsystem her.

Summary Purpose: Lesion-negative refractory partial epilepsy is a major challenge in the assessment of patients for potential surgery. Finding a potential epileptogenic lesion simplifies assessment and is associated with good outcome. Here we describe imaging features of subtle parahippocampal dysplasia in five cases that were initially assessed as having imaging-negative frontal or temporal lobe epilepsy. Methods: We analyzed the clinical and imaging features of five patients with seizures from the parahippocampal region. Results: Five patients had subtle but distinctive magnetic resonance imaging (MRI) abnormalities in the parahippocampal gyrus. This was a unilateral signal abnormality in the parahippocampal white matter extending into gray matter on heavily T1- and T2-weighted images with relative preservation of the gray–white matter boundary on T1-weighted volume sequences. Only one of these patients had typical electroclinical unilateral temporal lobe epilepsy (TLE); one mimicked frontal lobe epilepsy, two showed bitemporal seizures, and one had unlocalized partial seizures. All have had surgery; four are seizure-free (one has occasional auras only, follow-up 6 months to 10 years), and one has a >50% seizure reduction. Histopathologic evaluation suggested dysplastic features in the surgical specimens in all. Discussion: In patients with lesion-negative partial epilepsy with frontal or temporal semiology, or in cases with apparent bitemporal seizures, subtle parahippocampal abnormalities should be carefully excluded. Recognizing the MRI findings of an abnormal parahippocampal gyrus can lead to successful surgery without invasive monitoring, despite apparently incongruent electroclinical features.

Summary Purpose: High frequency oscillations (HFOs) >200 Hz are believed to be associated with epileptic processes. The spatial distribution of HFOs and their evolution over time leading up to seizure onset is unknown. Also, recording HFOs through conventional intracranial electrodes is not well established. We therefore wished to determine whether HFOs could be recorded using commercially available depth macroelectrodes. We also examined the spatial distribution and temporal progression of HFOs during the transition to seizure activity. Methods: Intracranial electroencephalography (EEG) recordings of 19 seizures were obtained from seven patients with temporal lobe epilepsy using commercial depth or subdural electrodes. EEG recordings were analyzed for frequency content in five spectral bands spanning DC-500 Hz. We examined the spatial distribution of the different spectral bands 5 s before and 5 s after seizure onset. Temporal changes in the spectral bands were studied in the 30-s period leading up to seizure onset. Results: Three main observations were made. First, HFOs (100–500 Hz) can be recorded using commercial depth and subdural grid electrodes. Second, HFOs, but not

Background. Periodic lateralized epileptiform discharges (PLEDs) are a rare phenomenon in electroencephalography, occurring in acute structural brain lesions. In general, PLEDs appear transiently in acute lesions, but a few reports have described persistent PLEDs in chronic lesions. Case report. An 86-year-old female was admitted, in 1999, with a left MCA stroke associated with right hand focal motor seizures. The first EEG in February of 2002 showed PLEDs over the left hemisphere associated with rhythmic discharges (PLEDs-plus). The patient was admitted on a second occasion in 2003 because of three sequential seizures and the EEG showed a similar pattern. Finally in 2006, the patient was admitted again because of sequential complex partial seizures and an EEG showed the same PLEDS-plus pattern as the EEGs of 2002 and 2003. Discussion. We report an unusual case of chronic PLEDs associated with rhythmic discharges in a patient with recurrent seizures and remote stroke.

The association of movement disorders with hypoglycemia has been rarely noted in the past. We recently observed 2 patients with documented hypoglycemia and paroxysmal dyskinesias. One patient had evidence of an insulin-secreting tumor. The other patient had insulin-dependent diabetes, and also experienced recurrent episodes of hypoglycemic hemiparesis. Classical adrenergic symptoms of hypoglycemia were absent in both patients. Our observations support the concept that the development of neuroglycopenic symptoms cannot be predicted from blood glucose measurements alone, but must depend on other factors controlling the availability or metabolism of glucose in the brain.

Purpose Extending perampanel long-term safety/tolerability data, with an additional 10 months (cut-off Oct 2011). Methods Participants in study 307 (NCT00735397) had completed a Phase III perampanel trial, and were titrated to 12 mg/day (or individual maximum tolerated dose) during blinded titration, followed by open-label maintenance. Results Of 1216 patients, 1122 (92.3%) reached 10 or 12 mg/day (mean maintenance dose 10.61 mg/day). Median exposure was 1.5 years (1 week–3.3 years), totalling 21635 patient-months. Treatment retention was 58.5% at cut-off. Subject choice or inadequate efficacy drove most discontinuations. AEs occurred in 1110 patients (91.3%); majority (80.2%) were mild/moderate. AEs seen in ≥10% of patients were dizziness (46.8%), somnolence (21.2%), headache (18.3%), fatigue (13.1%), irritability (11.5%) and weight increase (10.9%). Only dizziness and irritability caused discontinuation in >1% (48/1216, 3.9%, and 16/1216, 1.3%, respectively). 227 patients (18.7%) had serious AEs (SAEs). The only individual SAEs in >1% of patients were epilepsy-related; others (in >5 patients) were aggression (n=12, 0.99%; 5 resolved, 7 withdrew), head injury (11, 0.90%), pneumonia (10, 0.82%), psychotic disorders (6, 0.49%), and suicidal ideation (6, 0.49%). Two patients died since previous cut-off (5 total; none study-drug-related). At 122 weeks, mean weight gain was 2.96±6.6 Kg (N=200). No clinically relevant changes in vital signs, ECG parameters, or labs were seen. Conclusions No new safety signals identified, with 7260 additional patient-months. Acknowledgements This study was sponsored by Eisai Inc. Medical writing support in developing the abstract was provided by Lisa Henry, of Choice Healthcare Solutions, and funded by Eisai Ltd.

The purpose of this study was to identify differences in family functioning between subjects with pseudoseizures and their families, and control subjects with epilepsy. Thirty-one adult subjects with pseudoseizures and 31 controls with intractable epilepsy, whose diagnoses were confirmed using video-EEG, were recruited from the epilepsy unit of a tertiary care hospital over a 4-year period. Each study participant and their first-degree adult family members completed two standardized questionnaires designed to measure family functioning: the McMaster Family Assessment Device (FAD) and the Beavers Self-Report Family Inventory (SFI). Individuals with pseudoseizures, when compared with epileptic subjects, exhibited significantly elevated scores in three scales of the FAD and in one scale of the SFI, indicating greater psychopathology within the family, as perceived by the individual. Statistically significant differences with the FAD were on measures of affective involvement (p = .044), communication (p = .004), and general functioning (p = .013). The SFI revealed significantly greater difficulty with conflict (p = .050). No differences were noted between subjects with both pseudoseizures and epilepsy and subjects with pseudoseizures alone. In comparison with the families of the epileptic group, the families of subjects with pseudoseizures displayed statistically significant elevations in their responses on the roles scale (p = .003) of the FAD. The responses of the family members did not differ in regard to the role they assumed within the family unit (i.e., spouse, parent). In summary, individuals with pseudoseizures view their families as being more dysfunctional, particularly in the area of communication, whereas their family members perceived difficulties in defining roles. This suggests that family education and interventions focusing on these areas, may be an important aspect of the treatment of patients with pseudoseizures.

Background The potential adverse central nervous system effects of H 1 -receptor antagonists have not been optimally studied in the elderly. Objective We hypothesized that newer H 1 -receptor antagonists such as cetirizine and loratadine would cause less central nervous system dysfunction than the older H 1 -receptor antagonists diphenhydramine and chlorpheniramine in this population, as they do in younger subjects. Methods We performed a randomized, double-blind, single-dose, placebo-controlled, 5-way crossover study in 15 healthy elderly subjects (mean age 71 ± SD 5 years). On study days at least 1 week apart, they received cetirizine 10 mg, loratadine 10 mg, diphenhydramine 50 mg, chlorpheniramine 8 mg, or placebo. Outcome measures, recorded before and 2 to 2.5 hours after dosing were latency of the P300 event-related potential in which increased latency reflects a decreased rate of cognitive processing, visual analogue scale for subjective somnolence, and histamine skin tests for measurement of peripheral H 1 -blockade. Results The changes in P300 following each treatment yielded variances that were not equal ( P > .05), precluding usual statistical analysis of the means. These variances were ranked: chlorpheniramine > diphenhydramine > loratadine > placebo > cetirizine. The rank of mean differences in the visual analogue scale increase from pre-dose baseline was: diphenhydramine > chlorpheniramine > cetirizine > loratadine > placebo. All H 1 -receptor antagonists suppressed the histamine-induced wheal and flare significantly compared to baseline. Conclusion In the elderly, the new H 1 -receptor antagonists cetirizine and loratadine are less likely to cause adverse central nervous system effects than the old H 1 -antagonists chlorpheniramine or diphenhydramine, but this requires confirmation using additional objective tests of central nervous system function.

Objective: To develop a classification tree to predict those patients with epilepsy who have higher or lower chances of experiencing side effects on antiepileptic drugs. Background Controversy surrounds the factors associated with the occurrence of side effects (SE) related to antiepileptic drugs (AEDs). Previous studies have uncovered difficulties using the classical approach of logistic regression in developing a predictive model for SE due to multiple issues including colinearity of predictors. Design/Methods: Self-reported SE to AEDs were prospectively collected from outpatients attending a large Canadian epilepsy clinic. Potential predictor variables were selected by epileptologists from their clinical experience. These included AED types, AED drug load (sum of the prescribed daily dose/defined daily dose (DDD) ratios), mono-therapy, history of psychiatric disorders/treatment, clinical and socio-demographic factors. Using recursive partitioning a hierarchical tree of variables was created based on their ability to discriminate the risk of SE between subgroups. The tree is pruned based on 10-fold cross-validation and the risk (95% confidence interval) of SE is determined within subgroups. Results: 801 patients taking at least one AED were used to develop the classification tree containing the following predictive factors. First was DDD Conclusions: The classification tree yielded important clinical factors that can be used to discriminate between patients9 risk of SE. Next, the classification tree will be validated in an external sample and evaluated for its predictive ability. Disclosure: Dr. Dykeman has nothing to disclose. Dr. Lowerison has nothing to disclose. Dr. Faris has nothing to disclose. Dr. Jette has received research support from various sources. Dr. Pillay has nothing to disclose. Dr. Klassen has nothing to disclose. Dr. Hanson has nothing to disclose. Dr. Murphy has nothing to disclose. Dr. Federico has nothing to disclose. Dr. Wiebe has nothing to disclose.

Three patients are described with pathologically verified Creutzfeldt-Jakob disease (CJD) who presented with localizing clinical signs accompanied by focal electroencephalographic abnormalities including periodic lateralized epileptiform discharges (PLEDS). With further progression of the disease, diffuse background slowing and continuous bisynchronous periodic discharges appeared in all three cases. There was good correlation between the initial focal clinical manifestations and the EEG findings.

Summary Rationale Dysembryoplastic neuroepithelial tumors (DNET) are benign, localized lesions that typically cause localization-related epilepsy of childhood onset. Although excellent seizure outcomes are expected following surgical resection of focal, benign lesions, reports in pediatric epilepsy series suggest that this may not be the case with DNETs, which may exhibit complex and often multifocal epileptogenesis. We report the characteristics and surgical outcome of an adult- and childhood-onset cohort with this condition. Methods Retrospective cohort of 23 patients seen at two major epilepsy centers, with localization-related epilepsy associated with histopathologically demonstrated DNETs. We assessed clinical, electrographic and surgical outcome features in patients with adult- and childhood-onset epilepsy. We were particularly interested in the level of congruence of EEG and MRI data and the need for intracranial recordings. We evaluated seizure outcomes at last follow-up. Results The mean age was 33.3 years (range: 5–56 years). Ten patients had adult-onset epilepsy. Thirteen patients (57%) had simple partial, 21 (91%) had complex partial, 16 (70%) had secondarily generalized seizures and 5 patients had only simple partial seizures. Status epilepticus did not occur. Non-enhancing lesions on MRI were located in the temporal lobe in 17 patients, the frontal lobe in 3 patients and the parietal/occipital region in 2 patients. One patient had a DNET that involved both frontal and temporal areas. Ictal scalp EEG and MRI were congruent in 17 patients (74%). Eleven patients (48%) underwent lesionectomies, while the rest required some resection of extralesional cortex as well. Five patients required intracranial EEG. There was no association with cortical dysplasia. Seventeen patients (74%) had an Engel class 1 outcome, in a follow-up period that ranging from 5 to 98 months. Conclusions We found no difference in outcomes between adult- and childhood-onset cases. Although epileptogenicity was complex, congruence between electro-clinical and neuroimaging studies was high and allowed good surgical outcomes at 1 year of follow-up.

A number of reports have suggested that some cases of multiple personality disorder might be due to temporal lobe epileptic discharges. We have administered a structured interview, the Dissociative Disorders Interview Schedule, to 20 subjects with multiple personality disorder, 20 with complex partial seizures, and 28 neurologic controls. Subjects also completed the Dissociative Experiences Scale. Results show that multiple personality can be differentiated from complex partial seizures on a large number of items. The seizure patients did not differ from controls. The data indicate that the phenomenologies of these two disorders are distinct, and, therefore, there is little reason to assume a common etiology.

Reverting to the more strict definition of secondary bilateral synchrony (SBS) of Tukel and Jasper (1952), we reexamined clinical and EEG correlates of this phenomenon. SBS occurred in 57 of 10,410 consecutive patients (0.5%) recorded in our laboratory. SBS originated in the frontal lobe in 51% of patients, significantly more often than the incidence of frontal spikes among controls. The best indicator of SBS origin was the most active spike focus which localized the onset in 52 of the 57 patients (91%) and falsely identified the origin in only one. Other focal or lateralizing clinical and EEG features appeared each in a minority of patients and lateralized and/or localized SBS origin with the following incidences when present: seizure manifestations (86%), neurological examination (95%), focal delta (100%), focal or unilateral theta (100%), and offset of bisynchronous paroxysms (96%). However, the most active spike focus triggered SBS in all but two instances when these other features appeared. Reliability of such indicators of SBS origin may obviate the need for depth electroencephalography in such patients. The presence of more than one spike focus in 96% of patients and three or more foci in 77% suggests that SBS results from a complex interaction of multiple potentially epileptogenic regions, instead of spread from a single focus as previously thought.

Objectives: To examine the applicability of applying an online tool to determine the appropriateness of referral for an epilepsy surgical evaluation and to determine whether appropriateness scores are concordant with the clinical judgment of epilepsy specialists. Methods: We prospectively applied the tool in 107 consecutive patients with focal epilepsy seen in an epilepsy outpatient clinic. Variables collected included seizure type, epilepsy duration, seizure frequency, seizure severity, number of antiepileptic drugs (AEDs) tried, AED-related side effects, and the results of investigations. Appropriateness ratings were then compared with retrospectively collected information concerning whether a surgical evaluation had been considered. Results: Thirty-nine patients (36.4%) were rated as appropriate for an epilepsy surgical evaluation, all of whom had adequately tried 2 or more appropriate AEDs. The majority of patients (84.6%) rated as appropriate had previously been considered or referred for an epilepsy surgical evaluation. Tool feasibility of use was high, with the exception of assessing whether previous AED trials had been adequate and discrepancies between physician and patient reports of AED side effects. Conclusions: Our evidence-based, online clinical decision tool is easily applied and able to determine whether patients with focal epilepsy are appropriate for a surgical evaluation. Future validation of this tool will require application in clinical practice and assessment of potential improvements in patient outcomes.