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Background Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pandemic, there have been many reports of increased incidence of venous thromboembolism and arterial events as a complication. Objective To determine the incidence of symptomatic thrombotic events (TEs) in patients hospitalized for SARS-CoV2 disease (coronavirus 19 [Covid-19]). Methods A retrospective single-center cohort study with adult patients with a positive reverse transcriptase-polymerase chain reaction (rt-PCR) for SARS-CoV2, included from the date of diagnosis of Covid-19 and followed for 90 days or until death. Results A total of 1621 patients were included in this study. The median age was 73 years (interquartile range 25th-75th [IQR] 53-87 years) and 57% (913) were female. Overall mortality was 21.6% (348). The overall incidence of symptomatic TEs within 90 days of diagnosis was 1.8% (30 of 1621) occurring in 28 patients, including an incidence of pulmonary embolism of 0.9% (15, 95% confidence interval [CI] 0.60%-1.6%), deep venous thrombosis of 0.61% (10, 95% CI 0.2%-1%), ischemic stroke of 0.25% (4, 95% CI 0.09%-0.65%), and ischemic arterial events of 0.06% (1, 95% CI 0.008%-0.43%). No acute coronary syndrome events were recorded. The incidence of symptomatic TEs was significantly lower in the general ward than in intensive care units (1.2% vs 5.7%; p

Objective: Rescue benzodiazepine medication can be used to treat seizure clusters, which are intermittent, stereotypic episodes of frequent seizure activity that are distinct from a patient's usual seizure pattern. The NeuroPace RNS® System is a device that detects abnormal electrographic activity through intracranial electrodes and administers electrical stimulation to control seizures. Reductions in electrographic activity over days to weeks have been associated with the longer-term efficacy of daily antiseizure medications (ASMs). In this pilot study, electrographic activity over hours to days was examined to assess the impact of a single dose of a proven rescue therapy (diazepam nasal spray) with a rapid onset of action., Methods: Adult volunteers (>18 years old) with clinically indicated RNS (stable settings and ASM usage) received a weight-based dose of diazepam nasal spray in the absence of a clinical seizure. Descriptive statistics for a number of detections and a sum of durations of detections at 10-min, hourly, and 24-h intervals during the 7-day (predose) baseline period were calculated. Post-dose detections at each time interval were compared with the respective baseline-detection intervals using a 1 SD threshold. The number of long episodes that occurred after dosing also were compared with the baseline., Results: Five participants were enrolled, and four completed the study; the excluded participant had recurrent seizures during the study. There were no consistent changes (difference >1 SD) in detections between post-dose and mean baseline values. Although variability was high (1 SD was often near or exceeded the mean), three participants showed possible trends for reductions in one or more electrographic variables following treatment., Significance: RNS-assessed electrographic detections and durations were not shown to be sensitive measures of short-term effects associated with a single dose of rescue medication in this small group of participants. The variability of detections may have masked a measurable drug effect., Plain Language Summary: Rescue drugs are used to treat seizure clusters. Responsive neurostimulation (RNS) devices detect and record epilepsy brain waves and then send a pulse to help stop seizures. This pilot study looked at whether one dose of a rescue treatment changes brain activity detected by RNS. There was a very wide range of detections, which made it difficult to see if or how the drug changed brain activity. New studies should look at other types of brain activity, multiple doses, and larger patient groups., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

We performed a genome-wide association study (GWAS) to identify genetic variation associated with common forms of idiopathic generalized epilepsy (GE) and focal epilepsy (FE). Using a cohort of 2220 patients and 14,448 controls, we searched for single nucleotide polymorphisms (SNPs) associated with GE, FE and both forms combined. We did not find any SNPs that reached genome-wide statistical significance ( p ≤ 5 × 10 -8 ) when comparing all cases to all controls, and few SNPs of interest comparing FE cases to controls. However, we document multiple linked SNPs in the PADI6 - PADI4 genes that reach genome-wide significance and are associated with disease when comparing GE cases alone to controls. PADI genes encode enzymes that deiminate arginine to citrulline in molecular pathways related to epigenetic regulation of histones and autoantibody formation. Although epilepsy genetics and treatment are focused strongly on ion channel and neurotransmitter mechanisms, these results suggest that epigenetic control of gene expression and the formation of autoantibodies may also play roles in epileptogenesis.

The objective of this analysis was to determine possible interactions between lamotrigine (LTG) and coffee or cigarette use. As part of the statistical analysis of factors influencing LTG pharmacokinetics (PK) in the Equigen chronic dose study, we collected prospective data from enrolled patients on their use of coffee and cigarettes. Subjects were part of a crossover replication study of generic LTG products with rigorous blood sampling and were instructed to not change their typical consumption of these products for the duration of the study. A total of 35 subjects were enrolled, with 33 subjects having sufficient data for analysis. Higher consumption of coffee was associated with a significantly lower area under the curve (AUC) and maximum concentration (Cmax) of lamotrigine (LTG). Higher cigarette use did not result in a significant change in AUC or Cmax. Coffee, but not cigarette use, either induces LTG metabolism or inhibits LTG absorption., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Women comprise the majority of subjects with conversion disorders in nearly all studies. The authors previously identified 96 subjects with psychogenic non-epileptic seizures (PNES) and found that female sex, alexithymia and childhood trauma were strongly correlated with the development of PNES. In order to characterize men with PNES, the authors collected questionnaire data on a series of male subjects recruited from an epilepsy monitoring unit (EMU)., Methods: Only male patients admitted to the EMU were asked to complete the Toronto Alexithymia Scale-20 (TAS-20) and the Childhood Trauma Questionnaire (CTQ). Results were correlated with diagnosis at discharge, either epileptic seizures (ES) or PNES., Results: Ninety-two subjects submitted complete questionnaire data. Sixty-nine subjects (74%) were diagnosed with ES, 13 subjects (14%) were diagnosed with PNES and 10 subjects (11%) had an undetermined diagnosis. There were no significant differences on the TAS-20 or the CTQ by diagnosis., Conclusion: In this sample of men admitted to an EMU there was no difference in the extent of alexithymia or childhood trauma between men with ES and PNES. There was a small number of men with a PNES diagnosis, which may have limited our ability to identify differences in the groups. The clear correlation of childhood trauma and alexithymia with development of conversion disorder in women could not be demonstrated in men., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Importance: Switching between generic antiepileptic drugs is a highly debated issue that affects both clinical care and overall health care costs., Objective: To evaluate the single-dose pharmacokinetic bioequivalence of 3 (1 branded and 2 generic drugs) on-market, immediate-release lamotrigine drug products., Design, Setting, and Participants: The Equivalence Among Antiepileptic Drug Generic and Brand Products in People With Epilepsy (EQUIGEN) single-dose study is a crossover, prospective, sequence-randomized, replicate pharmacokinetic study conducted at 5 US academic epilepsy centers. Fifty adults (≥18 years) with epilepsy who were taking concomitant antiepileptic drugs and not currently receiving lamotrigine were enrolled between July 18, 2013, and January 19, 2015. Every participant was randomly assigned to 1 of 3 equivalent sequences, each comprising 6 study periods, during which they had blood draws before and after medication administration. Forty-nine participants were included in intention-to-treat analyses., Interventions: Participants received a single 25-mg dose of immediate-release lamotrigine at the start of each period, with the branded and the 2 most disparate generic products each studied twice. Lamotrigine was selected as the antiepileptic drug of interest because of its wide use, publications indicating problems with generic switches, and complaints to the US Food and Drug Administration regarding generic products. Both participants and study personnel were blinded to the specific generic products selected., Main Outcomes and Measures: The primary outcome was bioequivalence between products. Maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) were compared, and average bioequivalence (ABE) was established if the 90% CIs of the ratios of the 2 products were within equivalence limits (80%-125%)., Results: Of the 50 randomized participants, 49 (98%) received all 3 lamotrigine products and completed at least 3 pharmacokinetic assessments and 46 (92%) completed all 6 pharmacokinetic assessments. Among the 49 participants, 28 (57%) were men and 21 (43%) were women, 42 (86%) self-identified as white, and 46 (16) years was the mean (SD) age. The 3 drug products were considered bioequivalent because the 90% CIs were within equivalence limits (lowest and highest CI limits for Cmax, 92.6% and 110.4%; for AUC0-96, 96.9% and 101.9%). Replicate testing demonstrated no significant differences in within-subject variability across the 3 products (likelihood ratios, χ22 for log-transformed variables: AUC0-96, 2.58; Cmax, 0.64; and AUC0-∞, 4.05; P ≥ .13) and that the 3 products were also bioequivalent according to scaled ABE and individual bioequivalence criteria with no subject × formulation interaction (Cmax, 0.00; AUC0-96, 0.54; and AUC0-∞, 0.36; P ≥ .76)., Conclusions and Relevance: This study provides evidence that the disparate lamotrigine products studied are bioequivalent when tested in people with epilepsy taking concomitant antiepileptic drugs., Trial Registration: clinicaltrials.gov Identifier: NCT01733394.

Purpose: Stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs) are often seen during continuous electroencephalographic (cEEG) monitoring in coma. Given their uncertain clinical significance, our prospective study evaluated incidence of SIRPIDs in comatose patients in the neuroscience intensive care unit (NSICU) who underwent a standard stimulation protocol and defined interreader reliability for cEEG., Methods: Of 146 patients prospectively screened who underwent cEEG during a 6-month period, 53 patients were included and 93 patients were excluded. Our protocol used a sequence of auditory, mild tactile, and painful stimuli tested in a quiet room. Continuous electroencephalogram were then reviewed offline by blinded experts, with interrater agreement assessed by kappa statistic. By Pearson χ and Wilcoxon rank-sum tests, we then compared binary and numerical clinical features between those with and without SIRPIDs., Results: Of 53 patients who underwent our protocol, one patient with a corrupt cEEG file was excluded. Traumatic brain injury was the most common diagnosis. Moderate interrater agreement was observed for 66 total stimulations: 20 patients (38.5%) had possible or definite SIRPIDs by minimum one reviewer. For 19 stimulations reviewed by a third reviewer, consensus was reached in 10 cases making the incidence of SIRPIDs 19.3% in our cohort. There was a moderate interrate agreement with kappa of 0.5 (95% confidence interval: 0.1, 0.7). Median intensive care unit stay was 15 days in patients with SIRPIDs versus 6.5 days in those without (P = 0.021)., Conclusions: Our prospective study of SIRPIDs in the neuroscience intensive care unit found a 19% incidence by cEEG using a standard stimulation protocol, most often rhythmic delta activity, and showed a moderate interrater agreement.

Stress is a common and important seizure precipitant reported by epilepsy patients. Studies to date have used different methodologies to identify relationships between epilepsy and stress. Several studies have identified anxiety, depression, and childhood trauma as being more common in patients with epilepsy who report stress as a seizure precipitant compared to patients with epilepsy who did not identify stress as a seizure precipitant. In one survey study it was found that a majority of patients with stress-triggered seizures had used some type of stress reduction method on their own and, of those who tried this, an even larger majority felt that these methods improved their seizures. Additionally, small to moderate sized prospective trials, including randomized clinical trials, using general stress reduction methods have shown promise in improving outcomes in patients with epilepsy, but results on seizure frequency have been inconsistent. Based on these studies, we recommend that when clinicians encounter patients who report stress as a seizure precipitant, these patients should be screened for a treatable mood disorder. Furthermore, although seizure reduction with stress reduction methods has not been proven in a randomized controlled trial, other important endpoints like quality of life were improved. Therefore, recommending stress reduction methods to patients with epilepsy appears to be a reasonable low risk adjunctive to standard treatments. The current review highlights the need for future research to help further clarify biological mechanisms of the stress-seizure relationship and emphasizes the need for larger randomized controlled trials to help develop evidence based treatment recommendations for our epilepsy patients., (Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Epilepsy is a common neurological disease, affecting 2.4million people in the US. Among the many different forms of the disease, temporal lobe epilepsy (TLE) is one of the most frequent in adults. Recent studies indicate the presence of a hyperactive hypothalamopituitary- adrenocortical (HPA) axis and elevated levels of glucocorticoids in TLE patients. Moreover, in these patients, stress is a commonly reported trigger of seizures, and stress-related psychopathologies, including depression and anxiety, are highly prevalent. Elevated glucocorticoids have been implicated in the development of stress-related psychopathologies. Similarly, excess glucocorticoids have been found to increase neuronal excitability, epileptiform activity and seizure susceptibility. Thus, patients with TLE may generate abnormal stress responses that both facilitate ictal discharges and increase vulnerability for the development of comorbid psychopathologies. Here, we will examine the evidence that the HPA axis is disrupted in TLE, consider potential mechanisms by which this might occur, and discuss the implications of HPA dysfunction for seizuretriggering and psychiatric comorbidities., Competing Interests: Conflict of interest. ACW is supported by NINDS F30-NS-095578 and T32-GM-063483. MBS has funding from K12-HD-051953. MDP receives research support from Eisai, Neuren, UCB, Epilepsy Foundation, American Epilepsy Society and FDA. He has served on data safety monitoring boards for Upsher Smith and Astellas. SCD receives funding from NINDS grants NS-062806 and NS-065020. JPH is supported by MH-049698 and MH-101729. NIH and other funding agencies had no further role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Patients and clinicians share concerns that generic drug substitution might lead to loss of efficacy or emergence of adverse events. In this trial, we assessed US Food and Drug Administration (FDA) bioequivalence standards by studying the effects of switching between two disparate generic immediate-release lamotrigine products in patients with epilepsy., Methods: The Equivalence among Generic Antiepileptic Drugs (EQUIGEN) chronic-dose study was a randomised, double-blind, crossover study that enrolled adults (aged ≥18 years) with epilepsy from six epilepsy centres at academic institutions across the USA who were receiving immediate-release lamotrigine dosed at 100 mg, 200 mg, 300 mg, or 400 mg twice daily. Eligible patients were randomly allocated (1:1) to one of two treatment sequences (sequence 1 or sequence 2), comprising four study periods of 14 days each. During each 14-day treatment period, patients received balanced doses of an oral generic lamotrigine product every 12 h (200-800 mg total, identical to lamotrigine dose prior to study enrolment); after each 14-day period, patients were crossed over to receive the other generic product. Computer-based randomisation was done using random permuted blocks of size two or four for each site to prevent sequence predictability. Both patients and study personnel were masked to the generic products selected, their predicted exposure (ie, "high" vs "low"), and their group allocation. The primary outcome of this trial was bioequivalence between the generic products, which was assessed at the end of the study through a comparison of maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC) for each product in the analysis population (all patients who completed all four treatment periods). Bioequivalence was established if the 90% CIs of the ratios of these two parameters for the two products were within equivalence limits (80-125%) in the analysis population. This study is registered with ClinicalTrials.gov\, number NCT01713777., Findings: Between April 25, 2013, and Aug 12, 2014, 35 eligible patients were enrolled and randomly assigned to treatment sequence 1 (n=15) or treatment sequence 2 (n=20). 33 patients completed all four treatment periods and were included in the primary outcome analysis. The 90% CIs of the ratios of both Cmax and AUC were within equivalence limits (AUC 90% CI 98-103, Cmax 90% CI 99-105), showing that lamotrigine exposures were equivalent between the generic products. No significant changes in seizure frequency or adverse events were recorded. No deaths, study-related serious adverse events, or changes in clinical laboratory values or vital signs occurred during this study., Interpretation: Disparate generic lamotrigine products in patients with epilepsy showed bioequivalence with no detectable difference in clinical effects, confirming that US Food and Drug Administration bioequivalence standards are appropriate., Funding: American Epilepsy Society, Epilepsy Foundation, and US Food and Drug Administration., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: Patients with genetic generalized epilepsy (GGE) frequently continue to have seizures despite appropriate clinical management. GGE is associated with changes in the resting-state networks modulated by clinical factors such as duration of disease and response to treatment. However, the effect of generalized spike and wave discharges (GSWDs) and/or seizures on resting-state functional connectivity (RSFC) is not well understood., Methods: We investigated the effects of GSWD frequency (in GGE patients), GGE (patients vs. healthy controls), and seizures (uncontrolled vs. controlled) on RSFC using seed-based voxel correlation in simultaneous electroencephalography (EEG) and resting-state functional magnetic resonance imaging (fMRI) (EEG/fMRI) data from 72 GGE patients (23 with uncontrolled seizures) and 38 healthy controls. We used seeds in paracingulate cortex, thalamus, cerebellum, and posterior cingulate cortex to examine changes in cortical-subcortical resting-state networks and the default mode network (DMN). We excluded from analyses time points surrounding GSWDs to avoid possible contamination of the resting state., Results: (1) Higher frequency of GSWDs was associated with an increase in seed-based voxel correlation with cortical and subcortical brain regions associated with executive function, attention, and the DMN; (2) RSFC in patients with GGE, when compared to healthy controls, was increased between paracingulate cortex and anterior, but not posterior, thalamus; and (3) GGE patients with uncontrolled seizures exhibited decreased cerebellar RSFC., Significance: Our findings in this large sample of patients with GGE (1) demonstrate an effect of interictal GSWDs on resting-state networks, (2) provide evidence that different thalamic nuclei may be affected differently by GGE, and (3) suggest that cerebellum is a modulator of ictogenic circuits., (Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.)

Study Objective: Non-convulsive seizures/status epilepticus occur in approximately 20% of comatose, non-cardiac arrest intensive care unit (ICU) patients, and are associated with increased mortality. The prevalence and clinical significance of seizures in comatose survivors of cardiac arrest undergoing therapeutic hypothermia is not well described., Methods: At this urban level I trauma center, every patient undergoing therapeutic hypothermia is monitored with continuous video encephalography (cvEEG). We abstracted medical records for all cardiac arrest patients treated with therapeutic hypothermia during 2010. Clinical data were extracted in duplicate. cvEEGs were independently reviewed for seizures by two board-certified epileptologists., Results: There were 33 patients treated with therapeutic hypothermia after cardiac arrest in 2010 who met inclusion criteria for this study. Median age was 58 (range 28-86 years), 63% were white, 55% were male, and 9% had a history of seizures or epilepsy. During cooling, seizures occurred in 5/33 patients (15%, 95%CI 6%-33%). 11/33 patients (33%, 95% CI 19%-52%) had seizures at some time during hospitalization. 13/33 (39%) survived to discharge and of these, 7/13 (54%) survived to 30 days. 9/11 patients with seizures died during hospitalization, compared with 11/22 patients without seizures (82% vs. 50%; difference 32%, CI 951%-63%). No patient with seizures was alive at 30 days., Conclusions: Seizures are common in comatose patients treated with therapeutic hypothermia after cardiac arrest. All patients with seizures were deceased within 30 days of discharge. Routine use of EEG monitoring could assist in early detection of seizures in this patient population, providing an opportunity for intervention to potentially improve outcomes., (Copyright © 2013 Elsevier B.V. All rights reserved.)

A working group was created to address clinical "gaps to care" as well as opportunities for development of new treatment approaches for epilepsy. The working group primarily comprised clinicians, trialists, and pharmacologists. The group identified a need for better animal models for both efficacy and tolerability, and noted that animal models for potential disease-modifying or antiepileptogenic effect should mirror conditions in human trials. For antiseizure drugs (ASDs), current animal models have not been validated with respect to their relationship to efficacy in common epilepsy syndromes. The group performed an "expert opinion" survey of perceived efficacy of the available ASDs, and identified a specific unmet need for ASDs to treat tonic-atonic and myoclonic seizures. No correlation has as yet been demonstrated between animal models of tolerability and adverse effects (AEs), versus tolerability in humans. There is a clear opportunity for improved therapies in relation to dose-related AEs. The group identified common and rare epilepsy syndromes that could represent opportunities for clinical trials. They identified opportunities for antiepileptogenic (AEG) therapies in both adults and children, acknowledging that the presence of a biomarker would substantially improve the chances of a successful trial. However, the group acknowledged that disease-modifying therapies (given after the first seizure or after the development of epilepsy) would be easier to study than AEG therapies., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

Background: It has been theorized that conversion disorder is the result of emotion that cannot be experienced consciously as feeling states or put into words (i.e., alexithymia), but there is little confirming empirical evidence. We sought to characterize subjects with conversion disorder compared to subjects with a distinct medical illness, using the model of psychogenic non-epileptic seizures (PNES) vs. epilepsy (ES), on measures of childhood traumatic experience, alexithymia and maturity of psychological defensive strategies., Methods: All subjects admitted to the Epilepsy Monitoring Unit of the University of Cincinnati Medical Center were offered self-report questionnaires (Childhood Trauma Questionnaire, Toronto Alexithymia Scale-20 and Response Evaluation Measure-71) at the outset of evaluation. Diagnosis of each subject was confirmed by video-EEG and we compared subjects with PNES to those with ES on these measures., Results: 82 subjects had ES AND 96 had PNES. Those with PNES were significantly more likely to have experienced childhood trauma in all domains (p=.005 to p=.05), and were significantly more likely to have alexithymia (p=.0267). There was a significant difference in the capacity to identify feelings, and a trend towards significance in capacity to describe feelings. There were no differences in defensive styles between the two groups., Conclusions: PNES diagnosis was associated with female sex, higher alexithymia scores and higher rates of childhood trauma, but not with differences in defensive styles compared to ES. These findings add empirical evidence for theories regarding the cause of conversion disorder and may aid in the design of prospective treatment trials in patients with conversion disorder., (Copyright © 2013 Elsevier Inc. All rights reserved.)

This report represents a summary of the discussions led by the antiseizure treatment working group of the International League Against Epilepsy (ILAE)/American Epilepsy Society (AES) Working Groups joint meeting in London (London Meeting). We review here what is currently known about the pharmacologic characteristics of current models of refractory seizures, both for adult and pediatric epilepsy. In addition, we address how the National Institute of Neurological Disorders and Stroke (NINDS)-funded Anticonvulsant Screening Program (ASP) is evolving to incorporate appropriate animal models in the search for molecules that might be sufficiently novel to warrant further pharmacologic development. We also briefly address what we believe is necessary, going forward, to achieve the goal of stopping seizures in all patients, with a call to arms for funding agencies, the pharmaceutical industry, and basic researchers., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

Purpose: Up to 30% of patients with idiopathic generalized epilepsy (IGE) have seizures that are refractory to medication despite appropriate therapy that commonly includes valproate (VPA). The aim of this study was to compare patients with VPA-refractory and VPA-responsive IGE in order to determine whether there are group differences in generalized spike and wave discharge (GSWD) generators that may be associated with VPA resistance., Methods: Of 89 IGE patients who underwent electroencephalography (EEG) combined with functional magnetic resonance imaging (fMRI; EEG/fMRI), 25 with GSWDs identified in EEG/fMRI data were included. Simultaneous acquisition of 64 channels of EEG data at 10 kHz was performed using an MRI-compatible EEG cap and amplifier at 4T. VPA resistance was defined as lack of seizure control despite therapeutic dose of VPA., Key Findings: The fMRI blood oxygen-level dependent (BOLD) correlates of GSWD in the entire group involved midline thalamus, frontal regions comprising Brodmann areas 6, 24, and 32, and temporal lobes diffusely. When VPA-responsive and VPA-resistant patients were compared, BOLD signal increases were noted in the VPA-resistant patients in medial frontal cortex, along the paracingulate gyrus (Montreal Neurological Institute; MNI x = 2, y = 13.6, z = 45.9), and anterior insula bilaterally (right MNI x = 37.6, y = 7.8, z = 0.6, left MNI x = -35.3, y = 13.6, z = -5.3)., Significance: Our findings support the hypothesis that VPA-resistant and VPA-responsive patients may have different GSWD generators. Furthermore, we hypothesize that these differences in GSWD generators may be the reason for different responses to VPA., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

Purpose: Idiopathic generalized epilepsy (IGE) resistant to treatment is common, but its neuronal correlates are not entirely understood. Therefore, the aim of this study was to examine resting-state default mode network (DMN) functional connectivity in patients with treatment-resistant IGE., Methods: Treatment resistance was defined as continuing seizures despite an adequate dose of valproic acid (valproate, VPA). Data from 60 epilepsy patients and 38 healthy controls who underwent simultaneous electroencephalography (EEG) and resting-state functional magnetic resonance imaging (fMRI) were included (EEG/fMRI). Independent component analysis (ICA) and dual regression were used to quantify DMN connectivity. Confirmatory analysis using seed-based voxel correlation was performed., Key Findings: There was a significant reduction of DMN connectivity in patients with treatment-resistant epilepsy when compared to patients who were treatment responsive and healthy controls. Connectivity was negatively correlated with duration of epilepsy., Significance: Our findings in this large sample of patients with IGE indicate the presence of reduced DMN connectivity in IGE and show that connectivity is further reduced in treatment-resistant epilepsy. DMN connectivity may be useful as a biomarker for treatment resistance., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

Many patients with epilepsy continue to experience seizures despite taking medication, and stress is a commonly reported trigger for seizures in these individuals. Therefore, a behavioral therapy proven to be effective in epilepsy could be a valuable adjunct to current pharmacotherapy. The challenges in testing such a behavioral intervention for epilepsy are numerous, including lack of consensus about sham designs, maintaining the blind, and powering the study absent known effect sizes. Herein, we present the design of a randomized, controlled, double-blind trial of progressive muscle relaxation as an add-on therapy for refractory epilepsy. Progressive muscle relaxation, which involves the tensing and releasing of muscle groups one at a time, is a well-established technique that relaxes the body and mind, reduces stress, and may improve seizure control. Study design issues discussed may provide insights that will inform future behavioral research in epilepsy., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Electrocortical mapping (ECM) is recognised as an established method for localisation of eloquent cortex in patients undergoing resective surgery for epilepsy management. Functional MRI (fMRI) has been utilised for language and other cortical function localisation. We describe language localisation in two patients using both ECM and fMRI. Co-registration of fMRI and ECM revealed that although two fMRI tasks localised multiple language areas, the verb generation task had an advantage over the semantic decision/tone decision task in that there was a clear overlap between the language areas identified by the verb generation task and ECM. In addition to the language areas detected by ECM, fMRI showed other language-related areas that may be important for post-operative language outcome. Therefore, fMRI may provide additional and complementary information to ECM in presurgical evaluation of patients with epilepsy. The correlation between fMRI and ECM may depend on the language testing methods utilised during the procedures.

Semantic association, an essential element of human language, enables discourse and inference. Neuroimaging studies have revealed localization and lateralization of semantic circuitry, making substantial contributions to cognitive neuroscience. However, because of methodological limitations, these investigations have only identified individual functional components rather than capturing the behavior of the entire network. To overcome these limitations, we have implemented group independent component analysis (ICA) to investigate the cognitive modules used by healthy adults performing the fMRI semantic decision task. When compared with the results of a standard general linear modeling (GLM) analysis, ICA detected several additional brain regions subserving semantic decision. Eight task-related group ICA maps were identified, including left inferior frontal gyrus (BA44/45), middle posterior temporal gyrus (BA39/22), angular gyrus/inferior parietal lobule (BA39/40), posterior cingulate (BA30), bilateral lingual gyrus (BA18/23), inferior frontal gyrus (L>R, BA47), hippocampus with parahippocampal gyrus (L>R, BA35/36), and anterior cingulate (BA32/24). Although most of the components were represented bilaterally, we found a single, highly left-lateralized component that included the inferior frontal gyrus and the medial and superior temporal gyri, the angular and supramarginal gyri, and the inferior parietal cortex. The presence of these spatially independent ICA components implies functional connectivity and can be equated with their modularity. These results are analyzed and presented in the framework of a biologically plausible theoretical model in preparation for similar analyses in patients with right- or left-hemispheric epilepsies., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Stress is a commonly reported seizure precipitant among individuals with epilepsy. Yet, the relationship between stress and seizure susceptibility remains unclear. This study examined the relationship between emotional distress and lifetime seizure load in individuals with temporal lobe epilepsy (TLE), as well as the potential moderating effect of explanatory style on this relationship. Data were collected from 148 individuals with TLE. Scales 2 and 7 of the Minnesota Multiphasic Personality Inventory were used as a measure of emotional distress, and explanatory style was measured using the Revised Optimism-Pessimism Scale. Elevated Scale 2 scores were associated with an increase in seizure load only in subjects with Full Scale IQ scores> or =92. An interaction between emotional distress and explanatory style was not observed. Thus, for individuals with higher levels of intelligence, depression may be an important pathway in linking emotional distress to poor seizure control., (Published by Elsevier Inc.)

In patients with idiopathic generalized epilepsies (IGEs), bursts of generalized spike and wave discharges (GSWDs) lasting > or =2 seconds are considered absence seizures. The location of the absence seizures generators in IGEs is thought to involve interplay between various components of thalamocortical circuits; we have recently postulated that medication resistance may, in part, be related to the location of the GSWD generators [Szaflarski JP, Lindsell CJ, Zakaria T, Banks C, Privitera MD. Epilepsy Behav. 2010;17:525-30]. In the present study we hypothesized that patients with medication-refractory IGE (R-IGE) and continued absence seizures may have GSWD generators in locations other than the thalamus, as typically seen in patients with IGE. Hence, the objective of this study was to determine the location of the GSWD generators in patients with R-IGE using EEG/fMRI. Eighty-three patients with IGE received concurrent EEG/fMRI at 4 T. Nine of them (aged 15-55) experienced absence seizures during EEG/fMRI and were included; all were diagnosed with R-IGE. Subjects participated in up to three 20-minute EEG/fMRI sessions (400 volumes, TR=3 seconds) performed at 4 T. After removal of fMRI and ballistocardiographic artifacts, 36 absence seizures were identified. Statistical parametric maps were generated for each of these sessions correlating seizures to BOLD response. Timing differences between brain regions were tested using statistical parametric maps generated by modeling seizures with onset times shifted relative to the GSWD onsets. Although thalamic BOLD responses peaked approximately 6 seconds after the onset of absence seizures, other areas including the prefrontal and dorsolateral cortices showed brief and nonsustained peaks occurring approximately 2 seconds prior to the maximum of the thalamic peak. Temporal lobe peaks occurred at the same time as the thalamic peak, with a cerebellar peak occurring approximately 1 second later. Confirmatory analysis averaging cross-correlation between cortical and thalamic regions of interest across seizures corroborated these findings. Finally, Granger causality analysis showed effective connectivity directed from frontal lobe to thalamus, supporting the notion of earlier frontal than thalamic involvement. The results of this study support our original hypothesis and indicate that in the patients with R-IGE studied, absence seizures may be initiated by widespread cortical (frontal and parietal) areas and sustained in subcortical (thalamic) regions, suggesting that the examined patients have cortical onset epilepsy with propagation to thalamus., (Copyright 2010 Elsevier Inc. All rights reserved.)

We evaluated the potential moderating effect of emotional distress (Minnesota Multiphasic Personality Inventory 2, scales D and Pt) on language functioning (i.e., Boston Naming Test, phonemic paraphasic error production on the Boston Naming Test, Controlled Oral Word Association Task, Animal Naming, Token Test) in patients with left (N=43) and right (N=34) mesial temporal lobe epilepsy (MTLE) and frontal lobe epilepsy (FLE) (N=30). Video/EEG and brain imaging results confirmed localization. Logistic regression models revealed that perceived emotional distress moderated language performance. Performance of patients with left MTLE and that of patients with FLE were equally poor across language measures. Performance of patients with right MTLE was intact. Depression and anxiety differentially moderated performance. Anxiety was associated with better performance in patients with FLE on classically temporal lobe-mediated tasks (Boston Naming Test). Depression was associated with worse language performance on measures for which impaired performance was traditionally intrinsic to the underlying epileptogenic lesion (word fluency in FLE). Emotional distress influences language performance. Adequate treatment of mood should be considered when managing pharmacoresistant epilepsy., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

In a minority of patients with idiopathic generalized epilepsies (IGEs), seizures continue despite appropriate treatment. We sought to determine the clinical and EEG factors associated with medication response in these patients. All patients with IGEs evaluated by epilepsy specialists between 17 November 2008 and 16 November 2009 were included. We collected information on seizure freedom (dependent variable), EEG asymmetries, response to valproic acid (VPA), MRI characteristics, medication use, demographics, and seizure history (predictors). We identified 322 patients with IGEs; 45 (14%) were excluded from analyses because they had always had a normal EEG (N=26), there were no EEG data (N=3), or they were non-compliant with medication (N=26). Patients with juvenile myoclonic epilepsy were more likely to respond to VPA than were patients with other IGEs, and VPA response was associated with seizure freedom. When EEG characteristics were considered, presence of any focal EEG abnormalities (focal slowing, focal epileptiform discharges, or both) was associated with decreased odds of seizure freedom. These findings suggest that patients with IGEs with poor seizure control may have atypical IGEs with possibly focal, for example, frontal, rather than thalamic onset., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

The aim of this study was to assess whether duration of seizure disorder and lifetime seizure load are associated with deficits in higher cognitive functions in patients with temporal lobe epilepsy (TLE) (N=207) or psychogenic nonepileptic seizures (PNES) (N=216). Multivariate regression analyses revealed that age at onset, duration, and group assignment were significant predictors of neuropsychological performance (all P

We sought to determine significant predictors of seizure and cognitive outcome following surgery for epilepsy. Participants included 41 patients who had undergone anterior temporal lobectomy (ATL). Higher presurgical verbal/language scores and lower nonverbal memory scores were predictive of seizure-free status following ATL. Overall, the presurgical predictors were 93% accurate in discriminating between seizure-free and non-seizure-free patients postsurgery. Surgery in the nondominant-for-language hemisphere was predictive of higher postsurgical verbal/language and verbal memory scores. Higher presurgical visual/construction, nonverbal memory, and verbal/language scores were predictive of better postsurgical verbal/language functioning. Better presurgical verbal/language functioning was predictive of the same skills postsurgically as well as visual/construction outcomes. Exploratory analyses in a subset of participants (n=25) revealed that dominant and nondominant intracarotid amobarbital (Wada) memory scores added unique variance only for predicting nonverbal memory following ATL. Presurgical neuropsychological testing provides significant and unique information regarding postsurgical seizure freedom and cognitive outcome in patients who have undergone ATL.

Distinguishing psychogenic nonepileptic seizures (PNES) from epileptic seizures (ES) is a difficult task that is often aided by neuropsychological evaluation. In the present study, signal detection theory (SDT) was used to examine differences between these groups in neuropsychological performance on the Wechsler Memory Scale, Third Edition, Word List Test (WMS-III WLT). The raw WMS-III WLT scores on this task failed to discriminate the two groups; however, with the use of SDT, patients with PNES were found to have a negative response bias and increased memory sensitivity as compared with patients with ES. When patients with left (LTLE) and right (RTLE) temporal lobe epilepsy were compared, the patients with LTLE demonstrated decreased memory sensitivity but a similar response bias as compared with the patients with RTLE. Memory impairment in patients with PNES may be related to faulty decision-making strategies, rather than true memory impairment, whereas memory performance differences between the LTLE and RTLE groups are likely related to actual differences in memory abilities.

Past research has suggested that pessimistic attributional style may be a risk factor for psychopathology among patients with seizure disorders. In addition, classifying psychogenic nonepileptic seizures (PNES) into subtypes has been found to be clinically relevant. However, very few studies have addressed differences in optimism, pessimism, or neuropsychological performance among PNES subtypes. We previously classified adults with PNES into semiology-based subtypes (catatonic, minor motor, major motor). In the study described here, we compared subtypes on optimism, pessimism, depressive symptoms, and neuropsychological performance. We found that patients with PNES with low optimism had significantly greater depressive symptoms than patients with high optimism, F(2, 39)=36.49, P<0.01). Moreover, patients with high pessimism had significantly greater depressive symptoms than patients with low pessimism, F(2, 39)=13.66, P<0.01. We also found that the catatonic subtype was associated with fewer depressive symptoms and better verbal memory than the other PNES subtypes. Our results support relationships between optimism, pessimism, and depressive symptoms and extend these findings to a PNES sample. Overall, the results of the present study suggest that classification into semiology-based subtypes and study of normal personality traits among patients with PNES may have clinical significance.

The Food and Drug Administration requires rigorous testing of generic formulations of antiepileptic drugs to assure bioequivalence to the brand product and asserts that all approved formulations are interchangeable. Physician surveys, case reports, and "switchback" rates from large-scale generic conversions imply that all generic formulations may not be equal to the brand drug for all patient groups. This review presents the current state of the data on bioequivalence and therapeutic equivalence and proposes a series of studies to better clarify the risks of generic formulation substitution in susceptible populations. Until such studies are completed, when switching to generic formulations, health-care providers and people with epilepsy would do well to proceed cautiously and understand the potential risks and benefits of substitution. Extra caution may be needed for patients at highest risk of seizure complications, such as the pregnant patient, patients with recurrent status epilepticus, or patients who have been seizure-free for long periods of time and are driving.

The efficacy of a self-generation encoding procedure in facilitating the encoding and retrieval of verbal memories was compared with the didactic presentation of information in individuals with seizure disorders. Through a within-subject design, 87 patients (25 left temporal seizure onset, 29 right temporal, 8 frontal, and 25 psychogenic nonepileptic seizures) received a self-generation learning condition and a didactic learning condition and were subsequently tested for verbal paired associate free recall, cued recall, and recognition memory. All patient groups benefited from the use of the self-generation condition relative to the didactic condition. Better performance occurred with the self-generation procedure for cued recall and recognition memory test performance, but not free recall. Individuals with a left temporal seizure onset (patients with the poorest memory performance on the didactic condition) benefited the most from the self-generation condition. A memory encoding strategy that actively involves patient participation enhances memory performance.

Memory difficulties are a frequent cognitive complaint of patients with chronic epilepsy. Previous studies have suggested that the presence of a seizure focus causes reorganization of brain mechanisms underlying memory function. Here we examine whether seizure onset in the left hemisphere and onset in the right hemisphere have different effects on memory lateralization and whether longer duration of epilepsy is associated with increased lateralization of memory functions to the unaffected hemisphere. We hypothesized that hemisphere of onset and duration of epilepsy would influence plasticity of memory mechanisms, similar to the plasticity observed for language mechanisms. Healthy controls (HC, N = 10) and patients with epilepsy (N = 23, 11 with a left- and 12 with a right-hemisphere focus) performed a scene-encoding fMRI task at 4 T. Active voxels (relative to scrambled image viewing) were identified for each participant. Memory laterality indices (LIs) were calculated in three regions of interest (ROIs) designed on the basis of HC group data: a functional ROI, an anatomical-hippocampal ROI, and an anatomical-medial temporal ROI encompassing hippocampus and parahippocampal gyrus. In healthy controls, LIs were suggestive of slight left lateralization of encoding memory for pictures. Patients with right hemisphere epilepsy showed a nonsignificant increase in degree of left lateralization. In contrast, patients with left hemispheric epilepsy showed right-lateralized activation, differing significantly from controls and from patients with right hemispheric epilepsy. Neuropsychological measures of memory (WMS-III Story Recall) across epilepsy patients predicted LIs in the anatomical ROIs: higher scores were associated with more left-lateralized medial temporal fMRI activation. Neither age of onset nor duration of epilepsy was significantly related to LI. These results indicate that focal epilepsy may influence the functional neuroanatomy of memory function.

Many studies have reported on the pattern of neuropsychological test performance across varied seizure diagnosis populations. Far fewer studies have evaluated the accuracy of the clinical neuropsychologist in formulating an impression of the seizure diagnosis based on results of neuropsychological assessment, or compared the accuracy of clinical neuropsychological judgment to results of statistical prediction. Accuracy of clinical neuropsychological versus statistical prediction was investigated in four seizure classification scenarios. While both methods outperformed chance, accuracy of clinical neuropsychological classification was either equivalent or superior to statistical prediction. Results support the utility and validity of clinical neuropsychological judgment in epilepsy treatment settings.

Functional magnetic resonance imaging (fMRI) has the potential to replace the intracarotid amobarbital procedure (IAP) in presurgical evaluation of patients with epilepsy. In this study, we compared fMRI verb generation (VG) and semantic decision/tone decision (SDTD) tasks and the IAP in their ability to localize language functions in patients with epilepsy undergoing presurgical evaluation. We enrolled 50 healthy controls to establish normal language activation patterns for VG and SDTD tasks at 3 or 4 T, and to design language regions of interest (ROIs) that were later applied to 38 patients with epilepsy (28 of 38 also underwent the IAP). We calculated laterality indices (LIs) for each task for each subject based on the ROIs, and we used general linear modeling to analyze the fMRI data. All healthy and epileptic subjects activated language areas with both fMRI tasks. We found significant correlations in language lateralization between the fMRI tasks (r=0.495, P<0.001) and between VG and IAP (r=0.652, P<0.001) and SDTD and IAP (r=0.735, P<0.001). The differences in LIs between SDTD and VG tasks were small and not affected by age, gender, epilepsy status, handedness, or performance. SDTD and VG tasks combined explained approximately 58.4% in the variability of the IAP/language. In the general linear modeling, only the SDTD task significantly contributed to the determination of language lateralization in patients with epilepsy undergoing presurgical evaluation. Results indicate a moderate convergent validity between both fMRI language tasks and between IAP and fMRI tasks. The results of this study indicate that either of these fMRI tasks can be used for language lateralization in patients with epilepsy undergoing presurgical evaluation, but that the SDTD task is likely to provide more information regarding language lateralization than the VG task.

Purpose: Noninvasive tests that accurately localize seizure onset provide great value in the presurgical evaluation of patients with intractable epilepsy. This study examined the diagnostic utility of three expressive language disturbances in lateralizing language-dominant (DOM) temporal lobe complex partial seizures: (1) the postictal language delay (PILD; time taken to correctly read a test phrase out loud immediately following seizures); (2) the production of postictal phonemic paraphasic errors (PostPE); and (3) interictal phonemic paraphasic errors (InterPE)., Methods: All 60 subjects underwent inpatient video/EEG monitoring and had surgically confirmed temporal lobe epilepsy (TLE). We determined the presence and number of PostPE and, PILD times (in s) for 212 seizures, and InterPE on the Boston Naming Test (BNT). Each technique's diagnostic usefulness was evaluated via logistic regression and ROC curve analysis. Sensitivity, specificity, positive predictive value and negative predictive values were computed., Results: PILD, PostPE and InterPE production were equally effective and accurate in lateralizing DOM seizure onset. Patients with DOM TLE had a longer PILD and committed more PostPE and InterPE than those with nondominant (NDOM) TLE. Respective sensitivity and specificity values were as follows: PILD (84%, 86%), PostPE (94%, 64%), and InterPE (97%, 86%). No single predictor was significantly better but a combination model yielded enough incremental utility to collectively outperform each separate predictor model., Conclusions: Interictal language testing is as accurate as postictal language testing in predicting DOM lateralization of TLE. Clinicians should also attend to the quality of errors produced during interictal and postictal language testing.

Subtypes of psychogenic nonepileptic seizures (PNES) have emerged via classification of seizure semiology, psychological variables, or both. PNES subtypes that differ with respect to etiology may be amenable to targeted treatment strategies. The aim of the present study was to investigate the relationship between semiology type and Minnesota Multiphasic Personality Inventory-2 (MMPI-2) profile among patients with PNES. We did so by modifying a classification scheme proposed by Selwa et al. Our main hypothesis was that there would be significant associations of semiology-based subtypes with psychological profiles among patients with PNES. We found significant differences in mean scores on MMPI-2 clinical scales 1 (Hypochondriasis) and 3 (Hysteria) and Harris-Lingoes subscales D5 (Brooding) and Sc5 (Lack of Ego Mastery, Defective Inhibition) across PNES subtypes (catatonic, minor motor, major motor). The results of the present study enhance understanding of the nosology of PNES by identifying psychopathological correlates of semiology-based subtypes of PNES. Our study also may inform the methodology of future investigations of psychopathology among patients with PNES by providing support for content-based interpretation of the MMPI.

Purpose: Patients with psychogenic nonepileptic seizures (PNES) rate their health-related quality of life (HRQOL) more poorly than those with epileptic seizures (ES). This has been explained in part by mood state. We sought to investigate whether HRQOL differences between diagnostic groups (PNES vs. ES) can be explained by additional, perhaps chronic, aspects of mood and personality. An understanding of these relationships may inform treatment designed to improve HRQOL in ES or PNES., Methods: One-hundred fourteen individuals (69 ES and 45 PNES) completed the quality of life in Epilepsy-89. The profile of mood states (POMS) and the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) were employed to measure current and chronic mood symptoms, respectively. Multiple regression analyses determined the contribution of chronic mood symptoms to HRQOL beyond the variance accounted for by current mood state and seizure diagnosis., Results: Similar to previous reports, individuals with PNES reported poorer HRQOL than those with ES. Current mood state was strongly related to HRQOL and appeared to moderate the relationship between seizure diagnosis and HRQOL. However, when more chronic psychological symptoms, such as somatization and emotional distress, were included in a model, the moderating role of mood state was not significant., Conclusion: Analyzed independently, mood state is related to HRQOL, but when chronic indicators of psychological symptoms are included in a model mood is related to HRQOL, but, the moderating effect of mood is no longer significant. Treatments designed to improve HRQOL among individuals with intractable seizures should also address chronic psychological distress and symptoms associated with high levels of somatization.

The prevalence of seizure types among the subpopulation of patients referred for phase I neuropsychological assessment likely differs from the prevalence of specific seizure types within the general seizure population. Understanding the prevalence of clinical diagnoses is critical to maximizing the predictive value of any assessment or diagnostic technique, clinical neuropsychological assessment of patients with seizures being no exception. Data from a series of 835 patients referred for phase I neuropsychological evaluation are used to report the prevalence of specific seizure types, as well as neuropsychological and demographic characteristics. Considerations for clinical neuropsychological research and practice are briefly discussed.

Introduction: Levetiracetam (LEV) is used in the setting of acute brain injury for seizure treatment or prophylaxis but its safety and efficacy in this setting is unknown., Method: We retrospectively analyzed the patterns of use and safety/efficacy of LEV in 379 patients treated in the neuroscience intensive care unit (NSICU). We extracted from the charts clinical data including diagnosis, AED therapy before and during stay in the NSICU, complications of treatment, length of stay, and clinical outcomes (improvement, Glasgow Coma Scale, and death). We analyzed the data using binary and ordered (multi-category) logistic regression., Results: Overall, our findings are that phenytoin used prior to the NSICU admission was frequently replaced with LEV monotherapy (P < 0.001). Patients treated with LEV monotherapy when compared to other AEDs had lower complication rates and shorter NSICU stays. Older patients and patients with brain tumors or strokes were preferentially treated with LEV for prevention and/or management of seizures (all P < or = 0.014)., Discussion: The results of this study suggest that LEV is a frequently used AED in the setting of acute brain injury and that it may be a desirable alternative to phenytoin. Prospective studies evaluating the long-term safety, efficacy and outcomes of LEV in this setting are indicated.

We assessed whether duration (time since diagnosis) of intractable epilepsy is associated with progressive memory loss in 250 individuals with left or right temporal lobe epilepsy and those diagnosed with psychogenic nonepileptic seizures. Verbal and nonverbal memory function was assessed using several memory assessment measures administered to all individuals as part of a larger neuropsychological assessment. Multivariate multiple regression analyses demonstrated that duration of temporal lobe epilepsy and age of seizure onset are significantly related to verbal memory deficits in patients with epilepsy. The interaction between duration of epilepsy and diagnostic group was nonsignificant, as was the interaction between age at spell onset and diagnostic group. As measured by several neuropsychological memory tests, duration of disease adversely affects verbal memory performance in patients diagnosed with temporal lobe epilepsy. Our study also supports the notion that age at seizure onset significantly affects verbal memory performance in this population. These results have implications for the strategy of treatment and counseling of patients with intractable temporal lobe epilepsy.

We examine current understanding of the minority disadvantage in the clinical management of epilepsy. We performed an online literature search using several keywords (race, ethnicity, epilepsy, treatment, and quality of life) and identified additional literature through cross-referencing/manual search. The search produced 58 items published between 1977 and 2005. Of 49 original research studies, 38 were quantitative, 7 were qualitative, and 4 used mixed methods. Three or more articles were published in Epilepsia, Epilepsy &Behavior, Epilepsy Research, Neurology, and Seizure. Research concerning racial/ethnic differences in epilepsy treatment is scarce and limited by methodology, but suggests underutilization of state-of-the-art therapies by minorities. Racial/ethnic minorities also appear to have limited knowledge about epilepsy and its treatment, experience barriers to care, lack social support, and seek alternative therapies for epilepsy. We propose a framework to identify the array of disparities, points of intervention, and interventions.

Objective: The goal of this study was to examine the effects of age, age at seizure onset, and duration of epilepsy on health-related quality of life (HRQOL) in patients with medication-resistant epilepsy., Methods: We analyzed data for a sample of 99 patients with medication-resistant epilepsy drawn from admissions to the Epilepsy Monitoring Unit. Patients had completed the Quality of Life in Epilepsy-89 (QOLIE-89), Profile of Mood States (POMS), and Adverse Events Profile. Number of comorbidities and number of antiepileptic drugs were abstracted from the chart. The dependent variable was QOLIE-89 overall score. The data were analyzed using ordinary least-squares regression., Results: The simple regression results showed no significant effect of patient's age on QOLIE-89 (P=0.354), whereas age at onset and duration had significant effects (P=0.004 and P=0.012, respectively); the higher the age at onset and the shorter the disease duration, the lower the HRQOL. After adding POMS Depression/Dejection, Adverse Events Profile, comorbidities, and antiepileptic drugs, the effects of age at onset and duration were no longer significant (P=0.084 and P=0.207)., Conclusions: Adult-onset epilepsy can disrupt one's established social, economic, and psychological life, while better coping mechanisms and social support may improve HRQOL as the duration of epilepsy increases. The modest association of age at onset and disease duration with HRQOL is explained away by mood states and adverse events, which are much stronger predictors of HRQOL. Interventions to improve HRQOL in patients with medication-resistant epilepsy should, therefore, focus on treating mood disturbances and minimizing medication side effects.

Objectives: To evaluate the efficacy and tolerability of topiramate as monotherapy, using a dose-controlled study design., Materials and Methods: We conducted a multinational, randomized, double-blind trial in adults and children (> or =6 years old) with epilepsy that was not being treated when randomized to 400 or 50 mg/day topiramate as target maintenance dosages. In addition to > or =2 lifetime unprovoked seizures, patients had to have one or two partial-onset seizures or generalized-onset tonic-clonic seizures in the 3-month retrospective baseline. The primary efficacy end point was time to first seizure; a secondary efficacy measure was the seizure-free rate at 6 months and 1 year. Double-blind treatment continued until 6 months after the last patient was randomized., Results: Kaplan-Meier survival analyses for time to first seizure (intent-to-treat, n = 470) favored 400 mg/day over 50 mg/day (P = 0.0002) as a target maintenance dosage. The first evaluation point with a significant difference (P = 0.046) favoring the higher dose was at day 14 when patients were receiving 100 or 25 mg/day. The probability of being seizure-free at 6 months was 83% in patients randomized to 400 mg/day and 71% in those randomized to 50 mg/day (P = 0.005). Seizure-free rates at 12 months were 76% and 59%, respectively (P = 0.001). Differences favoring the higher dose were significant in patients with partial-onset seizures (P = 0.009) and in those with generalized-onset tonic-clonic seizures (P = 0.005). The most common dose-related adverse events were paresthesia, weight loss, and decreased appetite. Discontinuations due to cognitive-related adverse events were 2% in the 50-mg group and 7% in the 400-mg group. Overall, 7% and 19%, respectively, discontinued with adverse events during the median treatment duration of 9 months., Conclusion: Topiramate is effective as monotherapy in adults and children. Because a therapeutic effect emerges during titration, clinicians should adjust dosages in step-wise fashion with intermediate stopping points, e.g., 100 mg/day, to evaluate patient response and achieve the optimal maintenance dosage.

Although confrontation naming deficits have been observed in dominant temporal lobe epilepsy (DTLE), the relative contribution of impoverished phonologic word retrieval and/or semantic knowledge remains unclear. Analysis of verbal-semantic, phonemic-literal, and combination paraphasias produced during confrontation naming by participants with seizure disorders (52 DTLE; 47 nondominant temporal lobe epilepsy [NDTLE]; 54 psychogenic nonepileptic seizures [PNES]) indicated that the frequency of: (a) verbal-semantic paraphasias was similar across groups, (b) phonemic-literal paraphasias was highest in DTLE, and (c) combination paraphasias was lowest in PNES. Confrontation naming ability was most strongly related to phonemic-literal paraphasia frequency in DTLE and to verbal IQ in both NDTLE and PNES. Greater confrontation naming deficits in DTLE may be attributed to impairments in phonological processing., (Copyright (c) 2005 APA, all rights reserved.)

Major depressive disorder (MDD) is the most prevalent psychiatric comorbidity among patients with treatment-resistant seizures. The Beck Depression Inventory-II (BDI-II) is often used to measure the severity of self-reported depressive symptoms among patients with seizure disorders. In contrast, researchers often use the Profile of Mood States (POMS) Depression (D) scale to assess depressed mood among other medical patient groups. The clinical significance of POMS-D scores among seizure disorder patients is not clear. In this study, we computed the correlation of POMS-D and BDI-II scores, determined a formula for converting POMS-D scores to BDI-II scores, and computed the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the POMS-D among seizure disorder patients. Two BDI-II cutoffs (BDI-II16 and 20) were used as criteria for significant reported depressive symptoms. We found a strong correlation between POMS-D and BDI-II scores. Analyses indicated that POMS-D scores strongly predict BDI-II scores. In addition, the sensitivity, specificity, PPV, and NPV values obtained demonstrated that POMS-D scores accurately classify seizure disorder patients who endorse significant depressive symptoms. These results suggest that the POMS-D may be effective in measuring reported depressive symptoms among seizure disorder patients.

The relationship between severity of depressive symptoms and performance on three Wechsler Memory Scale-III auditory memory and learning subtests was examined in 84 inpatients diagnosed with medically intractable seizures of left (n=46, LTLE) or right (n=38, RTLE) temporal lobe origin. Depressive symptom severity was associated with auditory recall test performance in individuals with LTLE, but not RTLE. Multiple regression analyses indicated that severity of depressive symptoms, hippocampal sclerosis, and naming ability were significant predictors of auditory memory test performance in LTLE; however, hippocampal sclerosis was the only significant predictor of auditory memory in RTLE. Results demonstrate the importance of hippocampal sclerosis, greater self-report of depressive symptoms, and poor naming ability as independent predictors of poor auditory memory and learning abilities. Results suggest that a complex relationship exists among multiple risk factors that combine to influence performance on auditory memory tests as a function of side of seizure focus.

The aim of this study was to determine the degree to which subjective ratings of neurocognitive ability accurately reflect objectively measured neuropsychological functioning in patients diagnosed with epileptic (ES, n = 45) or psychogenic nonepileptic (PNES; n = 37) seizures. Patients received a battery of neuropsychological tests, measures of current mood state, and the Quality of Life In Epilepsy-89 questionnaire. Results indicated that subjective ratings of neuropsychological functioning were only partially accurate within each group. Patients with ES accurately rated their memory function, but overestimated language and attention abilities. Patients with PNES accurately rated attention, but underestimated memory and overestimated language. In both groups, poorer self-reported neurocognitive functioning was strongly related to poorer mood state; however, mood state did not predict objectively measured neurocognitive abilities. Given the inaccuracies that exist in patient self-report, results highlight the importance of a comprehensive neuropsychological assessment when evaluating the neurocognitive status of individuals with seizures.

Functional MRI (fMRI) studies of memory with coarse resolution of 4 x 4 x 5 mm often fail to demonstrate blood oxygenation level-dependent (BOLD) activation in the hippocampal formation. This failure occurs when nonactivating white matter is averaged with the signal from hippocampal gray matter, attenuating the total BOLD signal from a single voxel due to the "partial volume effect." In this study, we evaluated the suitability of high-resolution fMRI at 3T (voxel size 2 x 2 x 3 mm) for improved visualization of hippocampal activation during memory encoding in 21 healthy and 6 epilepsy subjects. We used a picture encoding task (block design) that involved memorization of indoor and outdoor scenes along with an appropriate resting task. Region-of-interest (ROI) analysis was performed; laterality indices (LIs) were calculated based on hippocampal ROIs (hROIs) or on global medial temporal ROIs (mtROIs). In 19 healthy subjects, robust bilateral BOLD signal changes within both ROIs were noted. The mean LI+/-SD for the hROIs is -0.12+/-0.06 and that for the medial temporal ROIs -0.12+/-0.05, with correlation between the LIs (r = 0.59, P = 0.009). Good concordance was noted between the surgical outcome and memory lateralization with the fMRI task employed in this study. The preliminary results are encouraging, and with continuing improvements in MRI scanner technology, we expect fMRI of the hippocampal formation at higher resolution to be possible and preferable. Furthermore, these results suggest that a larger study to test the utility of high-resolution fMRI in epilepsy presurgical evaluation is needed.