Effect of Training on Visual Identification of High Frequency Oscillations-A Delphi-Style Intervention.

OBJECTIVE: We 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. METHODS: We 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. RESULTS: The intervention, regardless of when it occurred, resulted in a significant reduction in the variability between reviewers in both groups (p GroupDI = 0.037, p GroupEI = 0.003). Prior to the delayed-intervention, the group receiving the early intervention showed a significant reduction in variability (p GroupEI = 0.041), but the delayed-intervention group did not (p GroupDI = 0.414). Following the intervention, the projected number of reviewers required to achieve strong generalizability decreased from 35 to 16. SIGNIFICANCE: This 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.

Validity and reliability of global ratings of satisfaction with epilepsy surgery.

OBJECTIVE: We aimed to assess the reliability and validity of single-item global ratings (GR) of satisfaction with epilepsy surgery. METHODS: 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. RESULTS: 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). SIGNIFICANCE: 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.

Predicting postoperative epilepsy surgery satisfaction in adults using the 19-item Epilepsy Surgery Satisfaction Questionnaire and machine learning.

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.

Primary care electronic medical records can be used to predict risk and identify potentially modifiable factors for early and late death in adult onset epilepsy.

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.

Impact of ictal subtraction SPECT and PET in presurgical evaluation.

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.

Development and validation of the Epilepsy Surgery Satisfaction Questionnaire (ESSQ-19).

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.

Outcomes of stereoelectroencephalography exploration at an epilepsy surgery center.

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.

Long term sequelae of amygdala enlargement in temporal lobe epilepsy.

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.

Prediction Tools for Psychiatric Adverse Effects After Levetiracetam Prescription.

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.

Generalizability of High Frequency Oscillation Evaluations in the Ripple Band.

Objective: We examined the interrater reliability and generalizability of high-frequency oscillation (HFO) visual evaluations in the ripple (80-250 Hz) band, and established a framework for the transition of HFO analysis to routine clinical care. We were interested in the interrater reliability or epoch generalizability to describe how similar the evaluations were between reviewers, and in the reviewer generalizability to represent the consistency of the internal threshold each individual reviewer. Methods: We studied 41 adult epilepsy patients (mean age: 35.6 years) who underwent intracranial electroencephalography. A morphology detector was designed and used to detect candidate HFO events, lower-threshold events, and distractor events. These events were subsequently presented to six expert reviewers, who visually evaluated events for the presence of HFOs. Generalizability theory was used to characterize the epoch generalizability (interrater reliability) and reviewer generalizability (internal threshold consistency) of visual evaluations, as well as to project the numbers of epochs, reviewers, and datasets required to achieve strong generalizability (threshold of 0.8). Results: The reviewer generalizability was almost perfect (0.983), indicating there were sufficient evaluations to determine the internal threshold of each reviewer. However, the interrater reliability for 6 reviewers (0.588) and pairwise interrater reliability (0.322) were both poor, indicating that the agreement of 6 reviewers is insufficient to reliably establish the presence or absence of individual HFOs. Strong interrater reliability (≥0.8) was projected as requiring a minimum of 17 reviewers, while strong reviewer generalizability could be achieved with <30 epoch evaluations per reviewer. Significance: This study reaffirms the poor reliability of using small numbers of reviewers to identify HFOs, and projects the number of reviewers required to overcome this limitation. It also provides a set of tools which may be used for training reviewers, tracking changes to interrater reliability, and for constructing a benchmark set of epochs that can serve as a generalizable gold standard, against which other HFO detection algorithms may be compared. This study represents an important step toward the reconciliation of important but discordant findings from HFO studies undertaken with different sets of HFOs, and ultimately toward transitioning HFO analysis into a meaningful part of the clinical epilepsy workup.

Electroencephalographic and Electrocardiographic Effect of Intravenous Lacosamide in Refractory Focal Epilepsy.

PURPOSE: Lacosamide selectively enhances slow inactivation of voltage-gated sodium channels to achieve seizure reduction. We studied the effect of intravenous lacosamide given as one of three single doses on EEG and electrocardiogram, as well as its tolerability in patients with drug-resistant epilepsy. METHODS: This Canadian, investigator-initiated, multicenter, double-blind study recruited patients with refractory focal epilepsy admitted to a seizure monitoring unit. Participants received a loading dose of 100, 200, or 400 mg lacosamide over 30 minutes during continuous monitoring by video-EEG and 12-lead electrocardiogram. The number of interictal spikes, frequency and quantity of background EEG rhythms, corrected QT interval (QTc), PR interval, heart rate (HR), blood pressure, and respiration rate during 60 minutes before the administration were compared with 60 minutes after the infusion. We documented any adverse event during and after the infusion. RESULTS: Seventy-one patients completed the study. There was a significant decrease in interictal spikes (P = 0.039) and decreased frequency of the alpha rhythm (P = 0.003). No significant difference in beta, theta, and delta frequency or amount was noted. There were significant increases in PR interval (153.4-155.8 ms, P = 0.031) and HR (73.4-75.5 bpm, P = 0.022), but QTc, blood pressure, and respiration rate were not affected. Twelve patients (16.9%) experienced transient and mild adverse events, mainly dizziness and leg tingling. More adverse events occurred with 400 mg lacosamide than with the lower doses (P = 0.048). CONCLUSIONS: Intravenous lacosamide is effective in decreasing interictal spikes. Despite a small effect on EEG and electrocardiogram rhythms, it is well tolerated with no serious adverse events.

Interrater reliability of visually evaluated high frequency oscillations.

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<0.05; 11/15 pairs). Interrater reliability was poor for HFOs alone (κmean=0.403; ICC=0.401) and HFO+IEDs (κmean=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.

An investigation into the psychosocial effects of the postictal state.

OBJECTIVE: To determine whether postictal cognitive and behavioral impairment (PCBI) is independently associated with specific aspects of a patient's psychosocial health in those with epilepsy and nonepileptic events. METHODS: We used the University of Calgary's 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 < 0.001). CONCLUSIONS: PCBI appears to be significantly associated with differing psychosocial outcomes depending on the patient's 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.

Assessment of endothelin and copeptin as biomarkers for vasovagal syncope.

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.

Towards a clinically informed, data-driven definition of elderly onset epilepsy.

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.

Jerking & confused: Leucine-rich glioma inactivated 1 receptor encephalitis.

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.

Feasibility of using an online tool to assess appropriateness for an epilepsy surgery evaluation.

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.

Quality indicators in an epilepsy monitoring unit.

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.

Neurovascular decoupling is associated with severity of cerebral amyloid angiopathy.

OBJECTIVES: 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. METHODS: 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). RESULTS: 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, p < 0.001). 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). CONCLUSIONS: 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.

Networks underlying paroxysmal fast activity and slow spike and wave in Lennox-Gastaut syndrome.

OBJECTIVE: To use EEG-fMRI to determine which structures are critically involved in the generation of paroxysmal fast activity (PFA) and slow spike and wave (SSW) (1.5-2.5 Hz), the characteristic interictal discharges of Lennox-Gastaut syndrome (LGS). METHODS: We studied 13 well-characterized patients with LGS using structural imaging and EEG-fMRI at 3 tesla. Ten patients had cortical structural abnormalities. PFA and SSW were considered as separate events in the fMRI analysis. RESULTS: Simultaneous with fMRI, PFA was recorded in 6 patients and SSW in 9 (in 2, both were recorded). PFA events showed almost uniform increases in blood oxygen level-dependent (BOLD) signal in "association" cortical areas, as well as brainstem, basal ganglia, and thalamus. SSW showed a different pattern of BOLD signal change with many areas of decreased BOLD signal, mostly in primary cortical areas. Two patients with prior callosotomy had lateralized as well as generalized PFA. The lateralized PFA was associated with a hemispheric version of the PFA pattern we report here. CONCLUSION: PFA is associated with activity in a diffuse network that includes association cortices as well as an unusual pattern of simultaneous activation of subcortical structures (brainstem, thalamus, and basal ganglia). By comparison, the SSW pattern is quite different, with cortical and subcortical activations and deactivations. Regardless of etiology, it appears that 2 key, but distinct, patterns of diffuse brain network involvement contribute to the defining electrophysiologic features of LGS.