Publications by authors named "Neelan Pillay"

28 Publications

  • Page 1 of 1

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.

Epilepsia 2021 Jan 14;62(1):51-60. Epub 2020 Dec 14.

Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

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.
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http://dx.doi.org/10.1111/epi.16738DOI Listing
January 2021

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

Epilepsia 2020 12 16;61(12):2729-2738. Epub 2020 Oct 16.

Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

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.
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http://dx.doi.org/10.1111/epi.16709DOI Listing
December 2020

Impact of ictal subtraction SPECT and PET in presurgical evaluation.

Acta Neurol Scand 2021 Mar 10;143(3):271-280. Epub 2020 Nov 10.

Comprehensive Epilepsy Program, Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

Objective: To assess the relative contribution of ictal subtraction single-photon emission computed tomography (ISSPECT) and 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.
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http://dx.doi.org/10.1111/ane.13362DOI Listing
March 2021

Outcomes of stereoelectroencephalography exploration at an epilepsy surgery center.

Acta Neurol Scand 2020 Jun 9;141(6):463-472. Epub 2020 Mar 9.

Calgary Comprehensive Epilepsy Program, Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Canada.

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.
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http://dx.doi.org/10.1111/ane.13229DOI Listing
June 2020

Long term sequelae of amygdala enlargement in temporal lobe epilepsy.

Seizure 2020 Jan 28;74:33-40. Epub 2019 Nov 28.

Calgary Comprehensive Epilepsy Program, Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, AB, Canada. Electronic address:

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.
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http://dx.doi.org/10.1016/j.seizure.2019.11.015DOI Listing
January 2020

Prediction Tools for Psychiatric Adverse Effects After Levetiracetam Prescription.

JAMA Neurol 2019 04;76(4):440-446

Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

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.
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http://dx.doi.org/10.1001/jamaneurol.2018.4561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459128PMC
April 2019

Generalizability of High Frequency Oscillation Evaluations in the Ripple Band.

Front Neurol 2018 28;9:510. Epub 2018 Jun 28.

Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada.

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. 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). 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. 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.
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http://dx.doi.org/10.3389/fneur.2018.00510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031752PMC
June 2018

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

J Clin Neurophysiol 2018 Sep;35(5):365-369

Department of Clinical Neurological Sciences, Western University, London, ON, Canada.

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.
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http://dx.doi.org/10.1097/WNP.0000000000000479DOI Listing
September 2018

Interrater reliability of visually evaluated high frequency oscillations.

Clin Neurophysiol 2017 03 30;128(3):433-441. Epub 2016 Dec 30.

Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; Seaman Family MR Research Centre, Foothills Medical Centre, Calgary, AB, Canada; Department of Radiology, University of Calgary, Calgary, AB, Canada. Electronic address:

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 (κ=0.403; ICC=0.401) and HFO+IEDs (κ=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.
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http://dx.doi.org/10.1016/j.clinph.2016.12.017DOI Listing
March 2017

An investigation into the psychosocial effects of the postictal state.

Neurology 2016 Feb 27;86(8):723-30. Epub 2016 Jan 27.

From the Department of Clinical Neurosciences (C.B.J., N.J., Y.A.-K., P.F., W.M., N.P., S.W.), Clinical Research Unit (J.D.T.E., T.T.S., S.W.), and Department of Community Health Sciences (T.T.S., N.J., S.W.), Cumming School of Medicine, Hotchkiss Brain Institute (T.T.S., N.J., P.F., S.W.), and O'Brien Institute of Public Health (T.T.S., N.J., S.W.), University of Calgary, Canada.

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.
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http://dx.doi.org/10.1212/WNL.0000000000002398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4763804PMC
February 2016

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

Epilepsia 2016 Feb 9;57(2):298-305. Epub 2015 Dec 9.

Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.

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.
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http://dx.doi.org/10.1111/epi.13266DOI Listing
February 2016

Assessment of endothelin and copeptin as biomarkers for vasovagal syncope.

Eur J Clin Invest 2016 Feb 18;46(2):141-5. Epub 2016 Jan 18.

Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB, Canada.

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.
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http://dx.doi.org/10.1111/eci.12576DOI Listing
February 2016

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

J Neuroimmunol 2015 Dec 21;289:84-6. Epub 2015 Oct 21.

Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.

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.
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http://dx.doi.org/10.1016/j.jneuroim.2015.10.010DOI Listing
December 2015

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

Neurology 2014 Sep 8;83(10):913-9. Epub 2014 Aug 8.

From the Department of Clinical Neurosciences and Hotchkiss Brain Institute (J.I.R., C.H., S.W., K.S., A.H., P.F., N.P., W.M., M.V., N.J.), Department of Community Health Sciences and Institute for Public Health (J.I.R., S.W., K.S., N.J.), and Department of Radiology (P.F.), University of Calgary; and Department of Medicine (C.H.), Division of Neurology, University of British Columbia, Canada.

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.
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http://dx.doi.org/10.1212/WNL.0000000000000750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4153845PMC
September 2014

Quality indicators in an epilepsy monitoring unit.

Epilepsy Behav 2014 Apr 20;33:7-11. Epub 2014 Feb 20.

Department of Clinical Neuroscience, University of Calgary, Calgary, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Canada; Department of Community Health Sciences, University of Calgary, Calgary, Canada; Institute for Public Health, University of Calgary, Calgary, Canada. Electronic address:

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.
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http://dx.doi.org/10.1016/j.yebeh.2014.01.021DOI Listing
April 2014

Neurovascular decoupling is associated with severity of cerebral amyloid angiopathy.

Neurology 2013 Nov 4;81(19):1659-65. Epub 2013 Oct 4.

From the Department of Radiology, Seaman Family MR Centre (S.P., C.R.M., R.F., B.G.G., E.E.S.), Departments of Clinical Neurosciences (E.D., G.K., N.S., K.S., A.C., N.P., M.J.P., R.F., B.G.G., E.E.S.), Physiology and Pharmacology (C.D.S., A.B., D.F., M.J.P.), and Community Health Sciences (G.H.F., E.E.S.), University of Calgary, Canada; Institute of Human Movement Sciences and Sport (D.F.), ETH Zurich, Switzerland; Hotchkiss Brain Institute (M.J.P., R.F., B.G.G., E.E.S.), and Faculty of Kinesiology (M.J.P.), University of Calgary; Foothills Medical Centre, Alberta Health Services, Canada.

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.
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http://dx.doi.org/10.1212/01.wnl.0000435291.49598.54DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3812103PMC
November 2013

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

Neurology 2013 Aug 17;81(7):665-73. Epub 2013 Jul 17.

Brain Research Institute, Department of Medicine, University of Melbourne, Australia.

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.
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http://dx.doi.org/10.1212/WNL.0b013e3182a08f6aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775693PMC
August 2013

Patient perceptions and barriers to epilepsy surgery: evaluation in a large health region.

Epilepsy Behav 2013 Jul 7;28(1):52-65. Epub 2013 May 7.

Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Calgary, Canada.

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.
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http://dx.doi.org/10.1016/j.yebeh.2013.03.013DOI Listing
July 2013

Experience and satisfaction of staff working in a seizure monitoring unit.

Can J Neurosci Nurs 2012 ;34(2):33-8

Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, AB.

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.
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October 2012

Magnetic resonance imaging of crossed cerebellar diaschisis and bright pulvinar in status epilepticus.

Neurosciences (Riyadh) 2012 Jul;17(3):259-61

Department of Clinical Neurosciences, University of Calgary, Foothills Medical Center, Calgary, Alberta, Canada.

Crossed cerebellar diaschisis and bright pulvinar are rare in patients with status epilepticus. We present a case of a 53-year-old man who was found confused, incontinent, and nonverbal. The EEG findings were consistent with non-convulsive status epilepticus. The brain MR images showed findings consistent with crossed cerebellar diaschisis and bright pulvinar. We report and discuss this case to increase the awareness of these MRI signs in confused and obtunded patients.
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July 2012

Epileptiform activity in neurocritical care patients.

Can J Neurol Sci 2012 May;39(3):328-37

Department of Critical Care Medicine, University of Calgary, Calgary, Alberta, Canada. Andreas.Kramer@AlbertaHealth Services.ca

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.
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http://dx.doi.org/10.1017/s0317167100013469DOI Listing
May 2012

Using a standardized assessment tool to measure patient experience on a seizure monitoring unit compared to a general neurology unit.

Epilepsy Behav 2012 May 4;24(1):54-8. Epub 2012 Apr 4.

Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Calgary, Canada.

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<.001), perceived nursing staff to be more responsive to the call button (p<.001), and assigned higher overall ratings to their stay (p<0.05). Lower education was associated with more favorable hospital ratings on both units (p<0.05).
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http://dx.doi.org/10.1016/j.yebeh.2012.03.002DOI Listing
May 2012

A blinded comparison of continuous versus sampled review of video-EEG monitoring data.

Clin Neurophysiol 2011 Jun 13;122(6):1086-90. Epub 2010 Dec 13.

Department of Medicine, The University of Melbourne, Australia.

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.
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http://dx.doi.org/10.1016/j.clinph.2010.10.048DOI Listing
June 2011

Parahippocampal epilepsy with subtle dysplasia: A cause of "imaging negative" partial epilepsy.

Epilepsia 2009 Dec 12;50(12):2611-8. Epub 2009 May 12.

Brain Research Institute, Heidelberg Heights, Victoria, Australia.

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 T(1)- and T(2)-weighted images with relative preservation of the gray-white matter boundary on T(1)-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.
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http://dx.doi.org/10.1111/j.1528-1167.2009.02103.xDOI Listing
December 2009

Spatial localization and time-dependant changes of electrographic high frequency oscillations in human temporal lobe epilepsy.

Epilepsia 2009 Apr 20;50(4):605-16. Epub 2008 Aug 20.

Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.

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 <100 Hz oscillations, were localized to channels of ictal onset (100-200, 400-500 Hz, p < 0.05; 300-400 Hz, p < 0.001). Third, temporal analysis showed increased HFO power for approximately 8 s prior to electrographic onset (p < 0.05).

Conclusions: These results suggest that HFOs can be recorded by depth macroelectrodes. Also, HFOs are localized to the region of primary ictal onset and can exhibit increased power during the transition to seizure. Thus, HFOs likely represent important precursors to seizure initiation.
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http://dx.doi.org/10.1111/j.1528-1167.2008.01761.xDOI Listing
April 2009

Chronic PLEDs with transitional rhythmic discharges (PLEDs-plus) in remote stroke.

Epileptic Disord 2007 Jun;9(2):164-9

Division of Neurology, Department of Medicine. University of Saskatchewan, Saskatoon, Saskatchewan, Canada.

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.
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http://dx.doi.org/10.1684/epd.2007.0095DOI Listing
June 2007

Medical management of intractable epilepsy.

Adv Neurol 2006 ;97:527-35

Adult Convulsive Disorder Clinic, Glenrose Rehabilitation Hospital, Edmonton, Alberta, Canada.

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February 2006

Quality of life after vagus nerve stimulation for intractable epilepsy: is seizure control the only contributing factor?

Eur Neurol 2003 ;50(1):16-9

Department of Clinical Neurological Sciences, University of Western Ontario, London, Ont., Canada.

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.
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http://dx.doi.org/10.1159/000070853DOI Listing
August 2003