Aura interruption: the Andrews/Reiter behavioral intervention may reduce seizures and improve quality of life - a pilot trial.

Patients with epilepsy frequently experience depression and emotional stress and these may function as seizure triggers in epileptogenic frontotemporal cortex, which serves in emotional processing. Eight patients enrolled in a pilot trial of a 6-month epilepsy-specific behavioral approach comprising counseling and relaxation to recognize and eliminate emotional seizure triggers. Potential participants with psychogenic seizures were excluded by long-term EEG and/or the MMPI profile. One participant became seizure free, another had an approximately 90% reduction in seizures, and two additional participants achieved a greater than 50% reduction in seizure frequency (total responder rate=50%), stable during 6 months of observation after the intervention. All completers showed marked and stable improvement of quality of life (Quality of Life in Epilepsy-89 inventory) and temporary improvement in the Profile of Mood States. An adequately powered randomized controlled trial is needed to confirm our findings, which suggest that behavioral approaches may hold promise for motivated patients with epilepsy.

Vigilance, alertness, or sustained attention: physiological basis and measurement.

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.

Effects of topiramate and gabapentin on cognitive abilities in healthy volunteers.

OBJECTIVE: To evaluate the cognitive effects of topiramate (TPM) and gabapentin (GBP). METHODS: Forty healthy volunteers were randomized to a 12-week course of TPM, GBP, or placebo. Doses were gradually escalated over 10 weeks to a maximum of 400 mg/day of TPM or 3,600 mg/day of GBP or to the highest tolerated dose. Subjects were interviewed and examined biweekly. Cognitive testing was performed prior to initiating the drug and again 12 weeks later, at least 2 weeks after achieving plateau dosing. For each subject and cognitive measure, test-retest Z scores were calculated based on regression equations derived from 73 healthy volunteers. Group comparisons utilized the Wilcoxon test. RESULTS: There were significant TPM vs GBP and TPM vs placebo differences in test-retest Z scores for four of six target cognitive measures (Digit Symbol, Story Recall, Selective Reminding, Controlled Oral Word Association), always indicating worse retest performance for subjects receiving TPM. Overall, 12 of 24 cognitive measures were similarly affected. TPM effects were large, and several target measures averaged >2 SD of negative change. One measure was significantly affected by GBP. CONCLUSIONS: Topiramate (TPM) impaired cognitive test performance, whereas gabapentin had minimal effects. The effects of TPM were of sufficient magnitude potentially to affect daily and occupational function.

Effects of oxcarbazepine and phenytoin on the EEG and cognition in healthy volunteers.

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.

Test-retest bias, reliability, and regression equations for neuropsychological measures repeated over a 12-16-week period.

The interpretation of neurobehavioral change over time requires knowledge of the test-retest characteristics of the measures. Without this information it is not possible to distinguish a true change (i.e., one reflecting the occurrence or resolution of an intervening process) from that occurring on the basis of chance or systematic bias. We tested a group of 72 healthy young to middle aged adults twice over a 12-to-16-week interval in order to observe the change in scores over time when there was no known intervention. The test battery consisted of seven commonly used cognitive measures and the Profile of Mood States (POMS). Test-retest regression equations were calculated for each measure using initial performance, age, education, and a measure of general intellectual function (Wonderlic Personnel Test) as regressors. Test-retest correlations ranged from .39 (POMS Fatigue) to .89 (Digit Symbol). Cognitive measures generally yielded higher correlations than did the POMS. Univariate regressions based only on initial performance adequately predicted retest performance for the majority of measures. Age and education had a relatively minor influence. Practice effects and regression to the mean were common. These test-retest regression equations can be used to predict retest scores when there has been no known intervention. They can also be used to generate statistical statements regarding the significance of change in an individual's performance over a 12-to-16-week interval.

Improved prediction of nonepileptic seizures with combined MMPI and EEG measures.

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.

Comparison of MMPI-2 profiles of Gulf War veterans with epileptic and nonepileptic seizure patients.

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.

Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial.

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.

Neuropsychologic impairment in patients with nonepileptic 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.

A practical analysis of computer based seizure detection during continuous video-EEG monitoring.

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.

Vagus nerve stimulation for the treatment of medically intractable seizures. Results of a 1-year open-extension trial. Vagus Nerve Stimulation Study Group.

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 long-term 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 long-term response.

Assessment of drowsiness in epilepsy patients receiving chronic antiepileptic drug therapy.

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 with < or = 12 s for each of the three control groups (P < 0.001). One third of the AED-treated patients had > 120 s of drowsiness, in contrast to only 1 of 63 controls (p < 0.001). 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.

Pharmacologically induced changes in arousal: effects on behavioral and electrophysiologic measures of alertness and attention.

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.

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.

Intraindividual analysis of antiepileptic drug effects on EEG background rhythms.

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)

Family history of seizures in posttraumatic and alcohol-associated seizure disorders.

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.

Vagus nerve stimulation has no effect on awake EEG rhythms in humans.

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.

A comparison of quantitative EEG frequency analysis and conventional EEG in patients with focal brain lesions.

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 yield for EEGFA was associated with the use of longer edited EEG lengths, longitudinal bipolar montage, and normative data based 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.

Epilepsy, driving laws, and patient disclosure to physicians.

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.

Test-retest reliability in EEG frequency analysis.

This study was performed to gain a better understanding of EEG frequency analysis test-retest reliability in normal healthy adults, and to evaluate factors which could influence the measured inter-record differences. Nineteen subjects underwent serial EEG recordings at 5 min and 12-16 week intervals. Records were visually edited using a standardized protocol, and FFT frequency analysis performed on segments of 60, 40, or 20 sec total length. Correlation coefficients for broad band features averaged 0.92 over the 5 min retest interval and 0.84 over the 12-16 week interval. There was essentially no difference between correlation coefficients of absolute and relative power features. Coefficients based on 60 sec records were marginally higher than those of 40 or 20 sec records. On the other hand, test-retest percent differences were typically lower for relative as opposed to absolute power features, and 60 sec records showed consistently lower percent differences than did 40 or particularly 20 sec records. Peak alpha frequency and mean frequency were the most stable EEG features at either interval. Montage had significant effects on test-retest differences at the 12-16 week interval. A significant association between intra-record and inter-record variability could not be demonstrated.