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To determine if the number of participants with psychiatric disorders increased in association with failures on symptom validity tests (SVTs) and a performance validity test (PVT) in Veterans admitted for evaluation of possible seizures.The 254 participants were Veterans undergoing inpatient video-EEG monitoring for the diagnosis of possible seizures. DSM-IV psychiatric disorders were diagnosed with the SCID IV. Symptom exaggeration was assessed with the MMPI-2-RF and performance validity with the TOMM.On the MMPI-2-RF, 27.6%-32.7% showed symptom exaggeration. Participants who exaggerated on the MMPI-2-RF were more often diagnosed with psychiatric disorders. The TOMM was failed by 15.4% of the sample. Participants who failed the TOMM were more often diagnosed with an Axis I disorder but not with a personality disorder. The MMPI-2-RF was invalid in more cases than the TOMM, but 7.9% of the sample generated a valid MMPI-2-RF and an invalid TOMM.The correlational design does not allow conclusions about cause and effect. The invalid groups may have had a higher rate of psychopathology. The number of participants with psychiatric disorders increased in association with symptom exaggeration and performance invalidity. Symptom exaggeration was more frequent than performance invalidity, but the TOMM made a unique contribution to identification of invalidity. The routine clinical use of SVTs and PVTs is supported. The results also suggest the need for caution in diagnosing psychiatric disorders when there is symptom exaggeration or performance invalidity, because diagnostic validity is dependent on the accuracy of symptom reporting.

Objective To assess the validity of embedded measures of performance validity, the effort index (EI) and effort scale (ES) of the repeatable battery for the assessment of neuropsychological status (RBANS), in Veterans with seizures; to compare the frequency of failure on the test of memory malingering (TOMM) in patients with epileptic versus psychogenic nonepileptic seizures (PNES). Methods Seizure diagnosis was established for 309 participants in epilepsy monitoring units using conventional diagnostic criteria who completed both the TOMM and RBANS. The criterion for performance invalidity was failure on any trial of the TOMM. We examined multiple EI and ES cutoffs to establish optimal sensitivity and specificity. Results An RBANS EI cutoff score of greater than three was optimal with specificity of .98, sensitivity of.19, and positive Likelihood Ratio of 10 but was not useful when below this cutoff. Confidence intervals indicate the need for confirmation of a failed EI with another performance validity test (PVT). No ES cutoff had sufficient specificity for clinical use. Invalid TOMM performance but not invalid RBANS performance was significantly more common in persons with PNES than in persons with epileptic seizures. Conclusions In Veterans undergoing seizure monitoring, the RBANS EI was useful as a screen when positive that requires confirmation with another PVT. The RBANS ES was not useful. Invalid performance on the TOMM was more common in persons with PNES than in persons with epileptic seizures.

Health-related quality of life (HRQoL) is compromised in civilians with epileptic seizures (ES) or psychogenic nonepileptic seizures (PNES). U.S. Veterans are a distinct patient group with regard to gender, age, and background. We studied HRQoL in Veterans and asked the following: (1) Is there a difference in HRQoL in Veterans with ES vs. PNES?; (2) What factors influence HRQoL in each group?; (3) What factors influenced the difference between seizure groups?We studied consecutive Veterans entering the epilepsy monitoring units (EMUs) of three VA Epilepsy Centers of Excellence. Patients underwent continuous video-EEG monitoring. Seizure diagnoses followed established criteria. Health-related quality of life was measured with the Quality of Life in Epilepsy Inventory-31 (QOLIE-31). Evaluations included the Structured Clinical Interview for Diagnostic and Statistical Manual-IV (DSM IV), the posttraumatic stress disorder (PTSD) Checklist (PCL), the Beck Depression Inventory II (BDI-II), and the Minnesota Multiphasic Personality Inventory-2 Restructured form (MMPI-2RF). Between-group differences were tested with Wilcoxon tests. Nested regression analysis was used to evaluate the influence of demographic, social, military, seizure-related, and psychological factors on QOLIE-31 scores.The median QOLIE-31 total score was 14 points lower in Veterans with PNES vs. ES (p 0.001; Cohen's d = 0.73). Within each seizure group, psychological factors accounted for ≥50% of the variance in QOLIE scores while combined demographic, social, and seizure-related factors accounted for 18% (group with ES) and 7% (PNES). Psychological measures, particularly PCL and the BDI-II scores, accounted for all of the difference in QOLIE-31 total scores between Veterans with ES and those with PNES.Health-related quality of life as measured by the QOLIE-31 is worse in Veterans with PNES as compared with those with ES. Psychological factors account for the most of the variance in QOLIE-31 scores regardless of seizure type and also account for the difference between groups with PNES and ES. Demographic, military, social, and seizure-related factors have minimal influence on HRQoL. These results in U.S. Veterans are similar to those found in civilians despite differences in patient age, gender, and background.

Identification of clinically meaningful subgroups among patients with psychogenic nonepileptic seizures (PNES) or epileptic seizures (ES) is of potential value for assessing prognosis and predicting therapeutic response. Invalid performance on validity tests has been associated with noncredible complaints and worse cognitive test scores, and may be one such classification criteria. We studied invalid performance in Veterans with PNES or ES, and the association of invalid performance with cognitive test scores and subjective complaints.Patients were consecutive admissions to three veterans affairs (VA) epilepsy monitoring units. Evaluations included two validity tests: the Test of Memory Malingering (TOMM); and the Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) over-reporting validity scales. We compared the frequency of invalid performance on the TOMM or MMPI-2-RF in patients diagnosed with PNES vs. ES. We evaluated the association of invalid performance with scores on the Repeatable Battery for Assessment of Neuropsychological Status (RBANS), and four subjective symptom measures including the Beck Depression Inventory-II, and Quality of Life in Epilepsy-31.Invalid TOMM performance was found in 25.3% of Veterans diagnosed with PNES and 10.8% of those with ES (p = .03). Invalid reporting on the MMPI-2-RF was found in 35.9% of the PNES group vs. 15.3% of the ES group (p = .01). Effects of valid vs. invalid reporting on external measures were similar for ES and PNES groups. Patients with invalid vs. valid TOMM performance had lower scores on the RBANS (p .001). Patients with invalid performance had greater complaints on all subjective measures, with largest effect sizes for the MMPI-2-RF validity scales (p .001).In Veterans admitted for evaluation of poorly controlled seizures, invalid performance on validity tests was not uncommon. Cognitive test results and subjective reports from patients with invalid performance may not be credible. These observations have implications for the analysis of clinical trials, where primary and secondary outcomes often rely on self-report measures.

OBJECTIVE To determine the frequency and severity of psychiatric disorders and attribution of seizures to traumatic brain injury (TBI) in veterans with verified psychogenic nonepileptic seizures (PNES) versus epileptic seizures (ES). METHODS We studied 333 consecutive admissions to the monitoring units of three Veterans Administration epilepsy centers. All patients underwent continuous video-electroencephalographic recording to define definite PNES or ES. Evaluations included the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition, PTSD Checklist, Beck Depression Inventory II, and Patient Seizure Etiology Questionnaire. Interviews and questionnaires were completed prior to final seizure type diagnosis and patient debriefing. The primary outcome measure was a comparison of Axis I psychiatric diagnoses in patients diagnosed with PNES versus ES. RESULTS A total of 81 patients were diagnosed with PNES, and 70 with ES. PTSD was the most frequent Axis I diagnosis in veterans with PNES (64%, vs 13% of those with ES; P

Objective To determine the frequency and yield of neuroimaging in patients with known seizure disorders presenting to the emergency department (ED) with recurrent (nonindex) seizures. Methods We reviewed 822 consecutive ED visits for nonindex seizures at the Oregon Health & Science University and the VA Portland Health Care System. For each visit, we abstracted details of the clinical presentation, whether neuroimaging was obtained, the results of neuroimaging, and the results of previous neuroimaging studies, when available. We determined whether ED neuroimaging led to an acute change in patient management (yield). Clinical factors associated with obtaining ED neuroimaging, and with the yield of neuroimaging, were evaluated by multivariate logistic regression. Results A majority (78%) of ED seizure visits were for nonindex seizures. Neuroimaging was obtained in 381 of 822 nonindex seizure visits (46%). Of these, 11 imaging studies (3%) led to an acute change in patient management, 8 (2%) after excluding false-positive scans. Acute head trauma, prolonged alteration of consciousness, and a focal neurologic examination at presentation were associated with an increased yield of ED neuroimaging. Absent any of these 3 clinical factors the true positive yield of neuroimaging was zero. Significance ED neuroimaging was performed in nearly half of all patients presenting with nonindex seizures. A more conservative use of ED neuroimaging for nonindex seizures, based on clinical factors at presentation, could decrease imaging frequency with minimal loss of yield.

Rationale Patients with seizure disorders have relatively high rates of comorbid psychological and sleep disorders. Because these can profoundly affect quality of life, early recognition and treatment are of potential benefit. As a quality improvement project, we evaluated the performance and utility of a set of mental health and sleep quality screening questionnaires in patients admitted to a VA seizure monitoring unit (SMU). Methods Questionnaires, including the Beck Depression Inventory-II (BDI-II), the post-traumatic stress disorder (PTSD) checklist (PCL), the Quality of Life in Epilepsy Inventory-31 (QOLIE-31), and the Pittsburgh Sleep Quality Index (PSQI), were administered to 100 patients admitted to the Portland VAMC SMU. Scored results were entered into the electronic medical record (EMR) within 72 h of hospital admission. We assessed how many patients exceeded questionnaire cutoff scores, and whether these patients had prior mental health or sleep diagnoses or evaluations within the six months preceding admission. Following hospital discharge, providers completed a survey regarding the utility of the questionnaire results. We also reviewed EMR documented mental health and sleep visits during the six months following the SMU admission. Results Forty-seven patients (47.5%) exceeded the cutoff score for the BDI-II, including 15 without an admission diagnosis of depression, and 14 who had not seen a mental health provider in the previous six months. Similarly, 33 patients (33.3%) exceeded the cutoff score for the PCL, including nine without a diagnosis of PTSD. Scores on the BDI-II and PCL were highly correlated with the QOLIE-31 total score (r = 0.7). Seventy patients (70.7%) exceeded the cutoff score for poor sleep quality, and 37 did not have a sleep disorder diagnosis. Providers indicated that the questionnaire results were moderately or very helpful in most cases and influenced discharge recommendations to patients and referring providers in more than 50% of cases. Discharge recommendations for mental health or sleep follow-up were associated with EMR documented consultations within the six months following SMU admission. Conclusions The results suggest that a standard set of screening questionnaires can identify SMU patients at risk for mental health and sleep disorders, including patients not currently diagnosed or recently evaluated. Questionnaire results were perceived as helpful by providers and influenced discharge recommendations. Given that these disorders are treatable and have a major influence on health-related quality of life, the effort to collect and document this information is well justified.

Traumatic brain injury (TBI) is an important cause of epilepsy and has also been associated with psychogenic nonepileptic seizures (PNES). We designed a brief questionnaire assessing patient beliefs regarding TBI as the cause of their seizures (Patient Seizure Etiology Questionnaire; PSEQ). This study reports content validity for the PSEQ.Ninety Veterans undergoing comprehensive evaluation at 3 VA epilepsy centers completed the PSEQ, a series of questions regarding possible causes for their seizures, including TBI. The PSEQ was scored as YES vs. NO for TBI as the proposed cause of seizures. For each patient, two expert reviewers independently completed a structured chart review to determine whether TBI was the proposed cause of seizures (n=180 reviews). Kappa statistic was used to assess agreement between the PSEQ and each chart review and between the PSEQ and combined chart reviews where both reviewers agreed on a TBI seizure etiology.The PSEQ scored higher overall rates for a TBI seizure etiology than did expert chart reviews (40% vs. 28%; p0.001). The PSEQ agreed with 82% of 180 independent chart reviews (sensitivity 88%; specificity 79%). Kappa statistic for agreement was 0.60. The two reviewers agreed on a probable TBI seizure etiology for 83% of chart reviews. The PSEQ sensitivity increased to 100% when both reviewers were in agreement.The PSEQ provides a direct, standardized measure of patient beliefs regarding TBI as the cause of their seizures and has moderate-substantial agreement with expert chart reviews.

OBJECTIVE:: To examine the association of epilepsy with traumatic brain injury (TBI) in Afghanistan and Iraq (Operation Enduring Freedom [OEF]/Operation Iraqi Freedom [OIF]) Veterans. DESIGN:: Cross-sectional observational study. PARTICIPANTS:: A total 256284 OEF/OIF Veterans who received inpatient and outpatient care in the Veterans Health Administration in fiscal years 2009-2010. MAIN OUTCOME MEASURES:: We used algorithms developed for use with International Classification of Diseases, Ninth Revision, Clinical Modification, codes to identify epilepsy, TBI (penetrating TBI [pTBI]/other TBI), and other risk factors for epilepsy (eg, stroke). TBI and other risk factors were identified prior to the index date (first date of seizure or October 1, 2009) for primary analyses. RESULTS:: Epilepsy prevalence was 10.6 per 1000 (N = 2719) in fiscal year 2010; age-adjusted prevalence was 6.1. Of 37718 individuals with a diagnosis of TBI, 29297 Veterans had a diagnosis of TBI prior to the index date. Statistically significant associations were found between epilepsy and prior TBI diagnosis (pTBI: adjusted odds ratio = 18.77 [95% confidence interval, 9.21-38.23]; other TBI: adjusted odds ratio = 1.64 [1.43-1.89]). CONCLUSIONS:: Among OEF/OIF Veterans, epilepsy was associated with previous TBI diagnosis, with pTBI having the strongest association. Because war-related epilepsy in Vietnam War Veterans with TBI continued 35 years postwar, a detailed, prospective study is needed to understand the relationship between epilepsy and TBI severity in OEF/OIF Veterans. Language: en

We describe seizure laterality and temporal seizure patterns in six subjects with bilateral temporal lobe epilepsy (bTLE) implanted with bilateral hippocampal depth electrodes and the NeuroPace RNS™ system over 84 consecutive days. Seizures were disproportionate in laterality in three subjects and disproportionate in time for two subjects. Clustering of seizures did not clearly affect laterality. Some but not all subjects with bTLE displayed nonrandom temporal or lateral clustering of seizures.

We compared MMPI-2 profiles of Gulf War veterans with fibromyalgia (FM) to epileptic seizure (ES) patients, psychogenic non-epileptic seizure (PNES) patients, and Gulf War veteran healthy controls. Both PNES and FM are medically unexplained conditions. In previous MMPI-2 research PNES patients were shown to have significantly higher Hs and Hy clinical scales than ES patients. In the present research the FM group had significantly higher Hs and Hy scale scores than both the ES group and the healthy control group. There was no significant difference between the FM and PNES Hs scale scores; however, the FM Hy scale score was significantly lower than the PNES Hy scale score. Present findings indicate a high level of psychological distress in the FM group.

We compared the MMPI-2 profiles of adults with multiple chemical sensitivity (MCS), epileptic seizures (ES), and nonepileptic seizures (NES). Both NES and MCS are medically unexplained conditions. In previous studies profiles associated with NES were elevated on scales Hs and Hy, compared with profiles associated with ES. We predicted that profiles associated with MCS would be elevated on Hs and Hy compared with the ES group. Patients with ES and NES were diagnosed after intensive EEG monitoring using published criteria. MCS was diagnosed if there was a complaint of illness in response to multiple common odors at levels that are not noxious to most people. All the MCS cases had legal claims for injury related to chemical exposures. The results showed that on MMPI-2 scales Hs, D, and Hy the MCS group had means significantly higher than both the ES and NES groups. Fake Bad Scale scores were elevated in 11 MCS cases, and regression-based estimates of Fake Bad Scale scores showed elevation in the MCS group compared with both seizure groups. We conclude that MMPI-2 data, obtained from people seeking financial compensation, indicate that there is a strong psychological component to MCS symptoms.

Vigilance is a term with varied definitions but the most common usage is sustained attention or tonic alertness. This usage of vigilance implies both the degree of arousal on the sleep-wake axis and the level of cognitive performance. There are many interacting neural and neurotransmitter systems that affect vigilance. Most studies of vigilance have relied on states where the sleep-wake state is altered, e.g. drowsiness, sleep-deprivation, and CNS-active drugs, but there are factors ranging from psychophysics to motivation that may impact vigilance. While EEG is the most commonly studied physiologic measure of vigilance, various measures of eye movement and of autonomic nervous system activity have also been used. This review paper discusses the underlying neural basis of vigilance and its assessment using physiologic tools. Since, assessment of vigilance requires assessment of cognitive function this aspect is also discussed.

The Portland Neurotoxicity Scale (PNS) is a brief patient-based survey of neurotoxicity complaints commonly encountered with the use of antiepileptic drugs (AEDs). The authors present data on the validity of this scale, particularly when used in longitudinal studies. Participants included 55 healthy controls, 23 epilepsy patient controls, and 86 healthy volunteers who took various AEDs or placebos for 12 weeks as part of randomized, double-blind studies of AED effects on cognitive abilities. Test-retest reliability in the control groups averaged .80 (total score). Test-retest changes in the PNS were sensitive to AED usage in general (p < .001) and to each of the five AEDs tested but not to placebo. Test-retest changes in the PNS were strongly correlated with several scales of the Profile of Mood States but only weakly correlated with objective cognitive test measures. The PNS has satisfactory psychometric properties and is sensitive to AED usage in test-retest studies.

We studied the EEG and cognitive effects of oxcarbazepine (OXC) and phenytoin (PHT) using a double-blind, randomized, parallel-group design. Thirty-two healthy volunteers received a maximum of 1200 mg of OXC or 360 mg of PHT. EEG and cognitive testing were performed at baseline and after 12 weeks of treatment. For each subject and measure, test-retest Z scores were calculated from regression equations derived from 73 healthy controls. Twenty-six subjects completed the study. Both the OXC and PHT groups had significant slowing of the EEG peak frequency and increased relative theta and delta power. Differences between AEDs (antiepileptic drugs) were not significant. Significant cognitive effects were seen on 5 of 20 measures, primarily measures of motor speed and reaction time. Again, there were no significant differences between AEDs. The only significant difference between AEDs was for the POMS-Vigor scale, favoring OXC. The small sample size may have contributed to the lack of significant differences between AEDs.

Vagus nerve stimulation is a unique therapy for epileptic seizures. Two randomized controlled trials in patients with medically refractory partial seizures have demonstrated efficacy, leading to US Food and Drug Administration approval of vagus nerve stimulation therapy in 1997. Extensive safety testing has not revealed significant effects on cardiac, respiratory, or gastrointestinal function, though recent reports of intraoperative asystole and sleep-related airway obstruction have raised concerns. Vagus nerve stimulation is indicated for adjunctive therapy of partial-onset seizures in children and individuals older than 12 years (Class I evidence). Based on controlled, randomized trials, approximately 30% of these patients can be expected to have at least a 50% decrease in overall seizure frequency. Vagus nerve stimulation efficacy is similar to that of several newer antiepileptic drugs when used in similar populations in controlled, randomized trials. Long-term follow-up studies suggest continued efficacy over more than 1 year (Class III evidence). Case series suggest similar or greater efficacy in younger children, and in patients with refractory generalized seizures, including those associated with the Lennox-Gastaut syndrome (Class III evidence). Vagus nerve stimulation is appropriate therapy for patients with medically refractory epileptic seizures who are not optimal candidates for resective epilepsy surgery.

Summary: Purpose: Antiepileptic drug (AED) therapy can be associated with neurotoxic side effects including cognitive dysfunction. Objective methods for detection of neurotoxicity in individual patients would be useful. We studied the effects of gabapentin (GBP) and carbamazepine (CBZ) on neurophysiologic and cognitive/behavioral measures in healthy volunteers. Methods: In a 12-week, randomized, double-blind, parallelgroup study of CBZ and GBP in healthy volunteers, 23 subjects completed the protocol. All achieved the target dose of 1,200 mg CBZ or 3,600 mg GBP. A structured EEG for quantitative analysis and a cognitive test battery were administered before AED therapy and again after 12 weeks of therapy. Test–retest differences were compared with those of 72 untreated control subjects. Results: Both CBZ and GBP significantly decreased the peak frequency of the posterior (alpha) rhythm, with CBZ exerting a greater effect. Ten CBZ and six GBP subjects exceeded the 95% confidence interval (CI) for an individual. Cognitive tests revealed AED vs. control group effects for two of seven measures (Digit Symbol, Stroop) and all subjective measures. However, few subjects exceeded the 95% CI for any objective test. Differences between CBZ and GBP were not significant. Greater EEG slowing was associated with greater subjective neurotoxicity and poorer test–retest performance on a cognitive test summary measure. Conclusions: Prolonged CBZ and GBP therapy induced EEG slowing that correlated with cognitive complaints and often exceeded the confidence interval for individual subjects. Quantitative EEG measures may be useful in the objective determination of AED-related neurotoxicity. Key Words: Antiepileptic drugs—Electroencephalography—Cognition— Epilepsy—Gabapentin—Carbamazepine.

To evaluate a proposed seizure etiology of traumatic brain injury (TBI) as a risk factor for psychogenic nonepileptic seizures (PNESs), the effect of reported TBI severity on the diagnosis of PNES versus epileptic seizures (ESs), and the potential moderating role of posttraumatic stress disorder (PTSD).Veterans with a diagnosis of PNES or ES during epilepsy monitoring at a Veterans Affairs Medical Center.Retrospective review of seizure type, proposed seizure etiology, TBI severity, and PTSD.Both PNES and ES groups were compared for TBI history and severity, and prior diagnosis of PTSD.Traumatic brain injury was the proposed seizure etiology for 57% of 67 PNES patients versus 35% of 54 ES patients (P.05). It was mild in 87% of PNES patients and 37% of ES patients (P.001). Posttraumatic stress disorder increased the likelihood of diagnosing PNES versus ES in Veterans with mild TBI as the proposed seizure etiology.Veterans with PNES commonly cite a TBI as the cause for seizures. Mild TBI was strongly associated with PNES versus ES. Posttraumatic stress disorder may moderate the development of PNES in Veterans with a history of mild TBI. Clinicians caring for Veterans with seizures may use these results in selecting patients for early diagnostic evaluation.

Recent diagnostic and treatment advances in psychogenic nonepileptic seizures (PNES) have the potential to improve care for patients, but little is known about the current state of PNES care delivery in the Veterans Health Administration (VA). We conducted semistructured interviews with 74 health-care clinicians and workers in the VA, eliciting provider perceptions of PNES care. Data were analyzed according to principles of Grounded Theory. The results revealed variation in care and two emergent domain themes of frustration and hope. Frustration was manifest in subthemes including Complexity, Patient Acceptance, Uncertainty About Treatment, Need for Evidence-based Treatment, and Failure of Cross-Disciplinary Collaboration between neurologists and mental health providers. Hope encompassed subthemes of Positive Attitudes, Developing Cross-Disciplinary Treatment, and Specific PNES Care. Increased resources for diagnosing, treating, and researching PNES have improved awareness of the disorder. More research is needed to understand patients' and caregivers' perceptions of PNES care.

Summary: Purpose: To determine the long-term efficacy of vagus nerve stimulation (VNS) for refractory seizures. VNS is a new treatment for refractory epilepsy. Two short-term double-blind trials have demonstrated its safety and efficacy, and one long-term study in 114 patients has demonstrated a cumulative improvement in efficacy at 1 year. We report the largest prospective long-term study of VNS to date. Methods: Patients with six or more complex partial or generalized tonic-clonic seizures enrolled in the pivotal EOS study were prospectively evaluated for 12 months. The primary outcome variable was the percentage reduction in total seizure frequency at 3 and 12 months after completion of the acute EO5 trial, compared with the preimplantation baseline. Subjects originally randomized to low stimulation (active-control group) were crossed over to therapeutic stimulation settings for the first time. Subjects initially randomized to high settings were maintained on high settings throughout the 12-month study. Results: The median reduction at 12 months after completion of the initial double-blind study was 45%. At 12 months, 35% of 195 subjects had a >50% reduction in seizures, and 20% of 195 had a >75% reduction in seizures. Conclusions: The efficacy of VNS improves during 12 months, and many subjects sustain >75% reductions in seizures.

Patients with nonepileptic seizures (NES), those with epileptic seizures (ES), and normal controls were compared on a battery of neuropsychologic tests. Diagnoses were made after intensive electroencephalogram (EEG) monitoring. Excluded from the study were patients with both ES and NES, as well as patients with ES who had evidence of structural brain damage. On all neuropsychologic measures, the two seizure groups were significantly impaired relative to the controls, but there were no significant differences between the ES and NES group performances. Additional neuropsychologic measures were obtained on the two seizure groups but not controls, and again there were no significant differences between the two seizure groups. Further analyses suggested that the NES group's impairment was related to emotional factors. The Minnesota Multiphasic Personality Inventory (MMPI)/MMPI-2 and the Portland Digit Recognition Test were helpful in classifying patients by seizure group. Our results, which are consistent with those of previous studies, suggest that neuropsychologic abnormalities are not pathognomonic of brain dysfunction in this population. However, the Portland Digit Recognition Test (PDRT) and measures of personality are useful for classification purposes in the differential diagnosis of epileptic and nonepileptic seizures.

Objective: The purpose of this multicenter, add-on, double-blind, randomized, active-control study was to compare the efficacy and safety of presumably therapeutic (high) vagus nerve stimulation with less (low) stimulation. Background: Chronic intermittent left vagus nerve stimulation has been shown in animal models and in preliminary clinical trials to suppress the occurrence of seizures. Methods: Patients had at least six partial-onset seizures over 30 days involving complex partial or secondarily generalized seizures. Concurrent antiepileptic drugs were unaltered. After a 3-month baseline, patients were surgically implanted with stimulating leads coiled around the left vagus nerve and connected to an infraclavicular subcutaneous programmable pacemaker-like generator. After randomization, device initiation, and a 2-week ramp-up period, patients were assessed for seizure counts and safety over 3 months. The primary efficacy variable was the percentage change in total seizure frequency compared with baseline. Results: Patients receiving high stimulation (94 patients, ages 13 to 54 years) had an average 28% reduction in total seizure frequency compared with a 15% reduction in the low stimulation group (102 patients, ages 15 to 60 year; p = 0.04). The high-stimulation group also had greater improvements on global evaluation scores, as rated by a blinded interviewer and the patient. High stimulation was associated with more voice alteration and dyspnea. No changes in physiologic indicators of gastric, cardiac, or pulmonary functions occurred. Conclusions: Vagus nerve stimulation is an effective and safe adjunctive treatment for patients with refractory partial-onset seizures. It represents the advent of a new, nonpharmacologic treatment for epilepsy.

Psychogenic non-epileptic seizures (PNES) are frequently encountered in epilepsy monitoring units (EMU) at Veterans Affairs Medical Centers (VAMCs) and cause significant long-term disability. An understanding of psychiatric factors associated with PNES could aid in earlier diagnosis and treatment. We studied 50 consecutive veterans diagnosed with PNES and 37 veterans diagnosed with epileptic seizures (ES), evaluated at a VAMC EMU. We reviewed all available mental health evaluations prior to EMU evaluation. Univariate comparisons included axis I diagnoses, axis II diagnoses, and psychiatric hospitalizations. Predictive models of seizure classification were evaluated by logistic regression. A diagnosis of post-traumatic stress disorder (PTSD) preceded the diagnosis of PNES in 58% of patients and the diagnosis of ES in 13.5% (p0.001). On logistic regression, PTSD was the only significant psychiatric diagnosis (odds ratio 9.2). Major depression and alcohol abuse were common diagnoses but did not differentiate PNES and ES groups.

Vagus nerve stimulation (VNS) has demonstrated a significant anticonvulsant effect in preclinical studies, in pilot studies in humans, and in the acute phase of a multicenter, double-blinded, randomized study. After completion of a 14-week, blinded, randomized study, with 31 receiving high (therapeutic) VNS and 36 receiving low (less or noneffective) VNS, 67 patients elected to continue in an open extension phase. During the extension phase, all 67 patients received high VNS. Seizure frequency during the 3-month treatment blocks was compared with a 12-week baseline. For both groups, all periods of high VNS demonstrated a significant decrease in seizure frequency (p < 0.01 level) as compared with baseline. For the 16-18-month period of VNS, data were available for 26 of the 31 patients randomized to high VNS. This group achieved a 52.0% mean seizure frequency percentage reduction as compared with baseline. For those converted from low to high VNS, data were available for 24 of the 36 patients at the 16-18-month time period. This group reported a mean seizure frequency percentage reduction of 38.1% as compared with baseline. No significant change in the safety/side effect profile was reported during long-term follow-up. The previously reported side effects of hoarseness/voice change, coughing, and paresthesia (sensation in neck and jaw) continued to occur during VNS. These side effects were well tolerated. During the follow-up period, 1 patient died of thrombotic thrombocytopenic purpura (TTP) and 5 patients discontinued treatment because of unsatisfactory efficacy.

Antiepileptic drug (AED) therapy with either phenytoin or carbamazepine has been associated with generalized slowing of EEG background rhythms. These effects have been seen in groups of patients undergoing AED manipulation, although the background slowing has been highly variable from patient to patient. Background slowing may represent an objective physiologic measure of drug impact on cerebral function and could be useful in monitoring for AED neurotoxicity in individual patients. This would require an intraindividual analysis of AED effects on EEG background rhythms. The present study was designed to develop a methodology for intraindividual analysis of EEG background changes and to apply this methodology to patients beginning or ending chronic AED therapy. EEG recordings were obtained under controlled conditions in 31 healthy subjects and were repeated after an interval of 12-16 weeks. EEG background rhythms from each record were analyzed using the fast Fourier transform, and test-retest differences for several quantitative measures were calculated from each subject's paired recordings. EEG recordings were also obtained in 6 patients beginning or ending chronic AED therapy. Test-retest differences for each patient's quantitative EEG measures were statistically compared with the distributions of test-retest measures obtained from the healthy controls. AED therapy was associated with an increase in absolute delta and/or theta power and a slowing of the dominant posterior rhythm; however, these EEG background changes varied widely in degree from patient to patient. Intraindividual analysis revealed that 5 patients had statistically significant slowing relative to the control group on at least 1 of the 9 target quantitative EEG measures, as well as a composite measure.(ABSTRACT TRUNCATED AT 250 WORDS)

Summary: Vagus nerve stimulation (VNS) has been shown to have an anticonvulsant effect in several animal models, and clinical trials in patients were recently started. Experimental data have suggested that VNS may act by modulating EEG rhythmic activity. We studied the acute effects of VNS on EEG background rhythms in patients undergoing treatment for poorly controlled partial seizures. Six patients had recordings of satisfactory quality for quantitative EEG analysis. A significant effect of VNS on EEG total power, median frequency, or power in any of the conventional frequency bands, could not be demonstrated. Intraindividual analysis did not show a significant effect of VNS on total power for any patient, including those with apparent clinical response. We conclude that VNS at the parameters in current clinical use does not alter awake EEG background rhythms. The mechanism mediating acute antiepileptic effect remains unknown.

Background : Non-epileptic seizures (NES) are not infrequent in the elderly. However, the data on NES in the elderly is likited. Aim : To study the demographic and historical background of eldely patients with NES and compare the same with the data in the younger patients with NES. Patients and Methods : Patients with NES over 55 years of age and the next two consecutive patients with NES between ages 18 and 45 were compared in terms of demographic and historical features, psychiatric evaluation and MMPI testing. Results : Of all the 128 patients with NES, 13 (10.6%) were over 55 years of age. History of physical/sexual abuse was high in both the groups. The mean length of time for NES diagnosis was longer in the elderly (13.38 ± 15.33 vs. 6.15 ± 8.04 years; P < 0.05). Majority of the patients with NES were on AEDs without evidence of epilepsy and almost half in both the groups were using benzodiazepines. Conclusion : In demographic and historical aspects old and young patients do not display major differences; however, the diagnosis is significantly delayed in the elderly. Early diagnosis with video EEG is recommended to avoid potential long-term risks associated with inappropriate treatments.

Antiepileptic drugs (AEDs) can be associated with neurotoxic side effects including cognitive dysfunction, a problem of considerable importance given the usual long-term course of treatment. Pregabalin is a relatively new AED widely used for the treatment of seizures and some types of chronic pain including fibromyalgia. We measured the cognitive effects of 12 weeks of pregabalin in healthy volunteers.Thirty-two healthy volunteers were randomized in a double-blind parallel study to receive pregabalin or placebo (1:1). Pregabalin was titrated over 8 weeks to 600 mg/d. At baseline, and after 12 weeks of treatment, all subjects underwent cognitive testing. Test-retest changes in all cognitive and subjective measures were Z scored against test-retest regressions previously developed from 90 healthy volunteers. Z scores from the placebo and pregabalin groups were compared using Wilcoxon tests.Thirty subjects completed the study (94%). Three of 6 target cognitive measures (Digit Symbol, Stroop, Controlled Oral Word Association) revealed significant test-retest differences between the pregabalin and placebo groups, all showing negative effects with pregabalin (p0.05). These cognitive effects were paralleled by complaints on the Portland Neurotoxicity Scale, a subjective measure of neurotoxicity (p0.01).At conventional doses and titration, pregabalin induced mild negative cognitive effects and neurotoxicity complaints in healthy volunteers. These effects are one factor to be considered in the selection and monitoring of chronic AED therapy. Class of Evidence: This study provides Class I evidence that pregabalin 300 mg BID negatively impacts cognition on some tasks in healthy volunteers.

The sensitivity and specificity of quantified EEG frequency analysis (EEGFA) were assessed in a group of patients with CT or MRI verified unilateral cerebral lesions and compared with the results of conventional EEG interpretations. Digital EEG recordings were obtained in 25 patients and 25 normal control subjects during performance of an alerting task. Recording artifacts were carefully eliminated. The results of EEGFA were then statistically compared with those of 75 additional normal subjects in the same age range. Complete conventional EEGs were blindly interpreted by two independent electroencephalographers using a structured reporting procedure. We observed similar overall sensitivities for the two methods. Optimal yeild for EEGFA was associated with the use of longer edited EEG lengths, longitudinal bipolar montage, and normative data bases on total EEG power. In those recordings with normal or mildly abnormal EEG backgrounds the two techniques were to an extent complimentary, each detecting abnormalities missed by the other. In such circumstances EEGFA may be useful as an extension of conventional EEG interpretation.

Summary There has been much research in the electrophysiologic correlates of alertness and attention, but it is fragmented into many subfields. This article integrates current knowledge across multiple disciplines and methodologies to provide a broad overview of alertness and attention. First, terms that are related to alertness and attention are clarified. Then, there is a discussion of basic neuroscience, human neurophysiology, and clinical fields that impact on alertness and attention. Areas discussed include thalamic and neurotransmitter-specific ascending pathways, EEG, event-related potentials, and both physiologic and pathologic states of decreased alertness or attention.

Neurological, neurodiagnostic, and neuropsychological aspects of psychogenic nonepileptic seizures (PNES) are reviewed, including psychosocial, psychiatric, cognitive, and MMPI-2 findings.

Objective Previous quantitative EEG (QEEG) studies of carbamazepine (CBZ), oxcarbazepine (OXC), and phenytoin (PHT) revealed a pattern of EEG slowing and an increase in drowsiness on the awake maintenance task (AMT). EEG slowing has been shown to correlate with negative effects on cognitive tests. Topiramate (TPM) is a novel AED with relatively large negative effects on cognitive function. We tested the hypothesis that TPM would induce significant slowing of EEG background rhythms and an increase in AMT drowsiness. Methods Forty healthy volunteers were randomized to TPM, gabapentin (GBP), or placebo. Doses were escalated as tolerated to a maximum of 400 mg/day for TPM or 3600 mg/day for GBP, over a 10-week period, followed by a minimum 2-week plateau period. Volunteers underwent an EEG, cognitive tests, and the AMT prior to starting an AED and again 12 weeks later. The EEG was captured using a structured recording protocol and quantified using the fast Fourier transform. Four target measures were derived from the averaged occipital electrodes (peak frequency of the dominant posterior rhythm, median frequency, percentage theta, and percentage delta). Test–retest changes for all measures were scored against similar test–retest distributions previously obtained from untreated healthy volunteers. Results TPM produced no significant change in any of the four target EEG measures or on the AMT, even though several target cognitive tests revealed moderate or greater negative effects. There were also no significant changes in the placebo group. GBP slowed the peak and median frequency EEG measures and increased the percentage of theta and delta activity. Neither TPM, GBP, nor placebo caused a significant increase in drowsiness on the AMT. Conclusions TPM has a unique neurotoxicity profile. It has no effect on EEG background measures or on the AMT, but induces moderate to large negative changes in many cognitive test scores. This profile differs from those of CBZ, OXC, PHT, and GBP.

Summary: Purpose: Nonepileptic seizures (NESs) are frequently mistaken for epileptic seizures (ESs). Improved detection of patients with NESs could lead to more appropriate treatment and medical cost savings. Previous studies have shown the MMPI/MMPI-2 to be a useful predictor of NES. We hypothesized that combining the MMPI-2 with a physiologic predictor of epilepsy (routine EEG; rEEG) would result in enhanced prediction of NES. Methods: Consecutive patients undergoing CCTV-EEG monitoring underwent rEEG evaluation and completed an MMPI-2. Patients were subsequently classified as having epilepsy (n = 91) or NESs (n = 76) by using standardized criteria. Logistic regression was used to predict seizure type classification. Results: Overall classification accuracy was 74% for rEEG, 71% for MMPI-2 Hs scale, and 77% for MMPI-2 Hy scale. The model that best predicted diagnosis included rEEG, MMPI-2, and number of years since the first spell, resulting in an overall classification accuracy of 86%. Conclusions: The high accuracy achieved by the model suggests that it may be useful for screening candidates for diagnostic telemetry.

As part of a larger study of illnesses related to service in the Gulf War, MMPI-2 profiles of epileptic seizure (ES) patients; nonepileptic seizure (NES) patients; Gulf War veterans with unexplained cognitive, psychological, musculoskeletal, fatigue, or dermatologic symptoms; and asymptomatic Gulf War veterans (Controls) were analyzed. There were 70 people in each group. Seizure diagnosis was based upon intensive EEG monitoring. Gulf War cases were mildly abnormal on MMPI-2 Scales Hs and D and significantly higher than controls on 8 of 10 MMPI-2 clinical scales, but they were significantly lower than NES patients on several scales including Hs and Hy.

Computer based seizure detection (CSD) systems improve the efficiency of CCTV-EEG monitoring by capturing epileptic seizures which would have otherwise been missed. We prospectively evaluated the yield of a commercial CSD system in 83 consecutive CCTV-EEG admissions. All seizures were coded as to the method of detection. the percentage of seizures detected only by CSD was calculated for each patient, and the impact on length of hospital stay was estimated. Overall, 33% of epileptic seizures were signaled by the patient, 45% were directly observed by family or medical personnel, and 22% were captured only by CSD. Forty admissions (48%) had at least one seizure captured only by CSD. The majority of these events were clinical and electrographic seizures (73%) and the remainder were purely electrographic. Five admissions concluded with all seizures captured only by CSD. We estimated an average saving of 1.3 hospital days per admission, based on the percentage of seizures captured only by CSD.

Drowsiness is a common complaint among patients with epilepsy taking antiepileptic drugs (AEDs) and may be of particular importance because of the potential effects on cognitive abilities. We used a novel EEG-based measure (the Awake Maintenance Task, AMT) to determine objectively whether patients on chronic, stable AED therapy had impaired ability to maintain wakefulness. Thirty patients receiving AEDs [carbamazepine (CBZ), phenytoin (PHT), phenobarbital (PB), valproate (VPA)] were compared to 35 healthy controls, 12 seizure patients not taking AEDs, and 16 patients with multiple sclerosis. A structured EEG recording was conducted under controlled conditions, and subjects were tested to determine their ability to maintain wakefulness during a 6-min unstimulated trial. Testing also included Digit Symbol, auditory reaction time, and subjective measures of fatigue or sleepiness [Profile of Mood States (POMS), Stanford Sleepiness Scale (SSS)]. Patients receiving AEDs had a mean total drowsiness score of 101 s compared withor = 12 s for each of the three control groups (P0.001). One third of the AED-treated patients had120 s of drowsiness, in contrast to only 1 of 63 controls (p0.001). Among patients receiving AEDs, objective EEG drowsiness did not correlate with AED levels or performance measures. Untreated seizure patients had significantly greater complaints of lack of vigor despite a near absence of objective drowsiness on the AMT. These results suggest that epilepsy patients receiving chronic AED therapy have impaired ability to maintain wakefulness. Patient self-reports of AED-related sleepiness may not accurately represent this problem.

The relationships between the diffuse subcortical neurotransmitter systems and behavioral and physiologic measures of alertness and attention are not well understood. This study was designed to further understand these relationships. In this double-blind experiment, 23 subjects ingested methylphenidate, diphenhydramine or placebo on 3 different days and performed behavioral and cognitive tasks including covert orienting of spatial attention and visual search tasks. Subjective and physiologic measures of alertness included EEG frequency analysis, EEG event-related desynchronization, and amount of sleep and sleep onset time in the unstimulated eyes closed state. Performance on the cognitive tasks improved with MP and worsened with DPHA, but there were no specific attentional effects. The best measures of alertness were based on self-rated scales and on EEG recorded in the unstimulated eyes closed state. These observations suggest that methylphenidate and diphenhydramine primarily affected overall state and that healthy humans were able to partially compensate for the pharmacologically induced alertness changes during cognitive task performance.

Psychological correlates of psychogenic seizures were studied. The MMPI, Portland Digit Recognition Test (PDRT; a forced choice measure of motivation), disability status, Face-Hand Test, and Finger Agnosia were compared in 53 patients with medically intractable seizure disorders who underwent intensive EEG monitoring. Using conventional neurologic criteria, 64% had diagnoses of epileptic seizures (ES) and 36% had psychogenic seizures (PS). PS patients were significantly higher in number of somatoform MMPI profiles and likelihood of applying for financial benefits, and significantly lower on the PDRT. PS patients made more Finger Agnosia errors. Differences on the Face-Hand Test were of borderline significance. The results support the existence of multiple psychometric correlates of PS.

The potential role of genetic factors in the etiology of posttraumatic and alcohol-associated seizures was studied in 289 male patients with recurrent seizures and in 174 individuals who had never experienced a seizure. The incidence of seizures in first-degree relatives of probands was compared with that in relatives of unaffected individuals. Relatives of patients with alcohol-associated seizures had a rate ratio of 2.45 95% confidence interval (CI) 1.41-4.25, whereas no excess incidence was noted among relatives of posttraumatic epilepsy patients (rate ratio 1.20, 0.64-2.25 CI). Relatives of probands with both antecedents showed an intermediate rate ratio of 1.72 (0.92-3.20 CI). Among probands with alcohol-associated seizures, the rate ratio of 2.05 for patients with alcohol-related seizures (i.e., spontaneously occurring seizures in association with chronic alcohol abuse) was slightly higher than that of 1.85 for probands with alcohol withdrawal seizures. Trauma severity had a slight impact on the incidence of affected relatives; patients with severe head injuries had a rate ratio of 0.73 and probands with milder trauma had a rate ratio of 0.99. The results indicate a limited, if any, role of genetic predisposition in development of posttraumatic seizures. Alcohol-related seizures, however, showed familial aggregation of unprovoked seizures, suggesting an involvement of genetic factors in the origin of such seizures. Language: en

To avoid loss of driving privileges, patients with epilepsy may elect not to report seizures to their physician or to the Department of Motor Vehicles (DMV). Reporting to the physician may differ depending upon the type of law in effect, i.e., mandatory physician reporting versus patient reporting to the DMV. Nondisclosure to the physician may have important consequences with regard to seizure management. We surveyed patients at two adult seizure clinics to determine the effect of driving laws on patients' reporting to their physician. One hundred fifty-eight patients completed an anonymous questionnaire asking whether they would report a breakthrough seizure under a physician versus a patient DMV reporting system. Under patient reporting, 96% would inform their physician and 56% would report to the DMV. Under physician reporting, 84% would inform their physician. This falls to 72% when considering currently driving patients only. An additional 9-17% of patients would continue to drive with a suspended license. In all, 53% would remain driving under patient reporting and 33% under physician reporting; however, with physician reporting, half of the illegally driving patients would have compromised their medical care, potentially increasing driving risk.

Background: Chronic vagus nerve stimulation (VNS) continues to be evaluated as an adjunctive treatment for medically intractable seizures. A previous randomized controlled trial of 114 patients demonstrated a significant decrease in seizure frequency during 3 months of VNS at effective stimulation levels. Objective: To evaluate the efficacy of 1 year of VNS therapy for the treatment of medically refractory partial seizures and the relationship between initial and longterm response. Patients and Methods: All patients exiting the randomized controlled study of VNS for treatment of medically refractory partial seizures were offered indefinite treatment extension as part of an open-label trial. One hundred (88%) of 114 patients completed 12 months of VNS treatment at effective stimulation levels. Fourteen patients discontinued VNS treatment prior to 1 year, principally because of the treatment's lack of efficacy. These 14 patients were retained in the present analysis using an intent-to-treat approach. Antiepileptic drug use was monitored throughout the trial. Seizure frequency was analyzed in 4 sequential 3-month treatment periods. Results: Compared with pretreatment baseline, there was a significant decrease in seizure frequency during each of the 3-month treatment periods. Seizure frequency was reduced by a median of 20% during the first 3 months of VNS treatment and by 32% during stimulation months 10 through 12. Response during the first 3 months of VNS treatment was a statistically significant predictor of response at months 10 through 12. The observed reduction in seizure frequency was not explained by overall changes in antiepileptic drug use. Conclusions: The results indicate that VNS remains an effective adjunctive therapy for medically refractory partial seizures over a period of at least 1 year. Response during the first 3 months of treatment is predictive of longterm response.

We performed computerized EEG frequency analysis (C-EEGFA) in 69 controls and 20 patients with focal brain lesions and focally abnormal conventional EEGs. Individual channel EEG frequency analysis variables that were helpful in differentiating the 2 groups were absolute delta and theta band power, relative delta, theta, and alpha band powers, and median-power frequency. High-frequency beta band power (20 to 32 Hz) was not useful. Changes in EEG with age were seen only after age 50 and generally consisted of an increase in anterior alpha power, with no significant increase in slowing. Correlations of C-EEGFA variables with posterior alpha power were more significant than correlations with age. Calculating normative C-EEGFA data for 5 subsets of controls, each with a different amount of posterior alpha power, increased the sensitivity of the EEG frequency analysis test without altering the specificity. Even with this correction 2 of 20 patients with focal lesions and focally abnormal conventional EEGs had normal C-EEGFA studies. If these obvious focal lesions produced normal results, more subtle diseases might not be detected. A significant clinical utility of C-EEGFA remains to be proven.