The significance of ictal depth EEG patterns in patients with temporal lobe epilepsy.

We reviewed 187 depth recorded seizures in 33 patients with non-lesional temporal lobe complex partial seizures. All patients had a minimum of 1 year follow-up following temporal lobectomy. We classified seizure onset pattern as rhythmic activity, attenuation, or repetitive spikes or spike wave complexes. The most common pattern of seizure onset was rhythmic activity and the next most common pattern was repetitive spikes. Seventy-five seizures (49%) had only one seizure onset pattern, and 79 seizures (51%) had a combination of seizure onset patterns. The degree of hippocampal gliosis strongly predicted the type of seizure onset pattern (Chi square = 24.07, 2 d.f., P < 0.01). The rhythmic activity pattern was associated with mild gliosis, and the repetitive spike pattern was associated with severe gliosis. We classified seizure onset as focal or regional based on the number of electrode contacts that were involved by the ictal EEG. A focal seizure onset was associated with an excellent outcome following temporal lobectomy.

Comparative cognitive effects of phenobarbital, phenytoin, and valproate in healthy adults.

The relative effects of antiepileptic drugs (AEDs) on cognition are controversial. We compared the cognitive effects of phenobarbital, phenytoin, and valproate in 59 healthy adults using a randomized, double-blind, incomplete-block, crossover design. Cognitive assessments were conducted at baseline, after 1 month on each drug (two AEDs per subject), and at two repeat baselines 11 weeks after each AED treatment. The neuropsychological battery included 12 tests, yielding 22 variables: Choice Reaction Time, P3 Event-Related Potential, Finger Tapping, Lafayette Grooved Pegboard, Selective Reminding Test, Paragraph Memory, Complex Figures, Symbol Digit Modalities Test, Stroop Test, Visual Serial Addition Test, Hopkins Symptom Checklist, and Profile of Mood States. More than one-half of the variables exhibited AED effects when compared with nondrug baselines, and all three AEDs produced some untoward effects. Differential AED effects on cognition were present for approximately one-third of the variables. Phenobarbital produced the worst performance; there was no clinically significant difference between phenytoin and valproate.

Wada memory asymmetries predict verbal memory decline after anterior temporal lobectomy.

We examined Wada memory and neuropsychological memory function in 34 nonlesional patients who underwent anterior temporal lobectomy (ATL) and who were seizure free at 1-year follow-up. Patients who displayed a decline on verbal memory measures that exceeded 1 SD after left ATL had significantly smaller left/right Wada memory asymmetries than left ATL patients without a significant verbal memory decline. When Wada memory asymmetries were used to predict verbal memory decline after left ATL in individual patients, similar statistically significant effects were present. No significant relationship between Wada memory and postoperative memory was present in right ATL patients, and postoperative memory function was not related to Wada memory performance after either left hemisphere or right hemisphere injection alone. We conclude that Wada memory asymmetries provide one measure of the risk to material-specific decline in verbal memory after left ATL.

Wada memory performance predicts seizure outcome following anterior temporal lobectomy.

We examined the ability of Wada memory testing to predict seizure outcome 1 year following anterior temporal lobectomy. Asymmetry scores for Wada memory performance, using amobarbital doses of 125 mg or less, were calculated for 55 patients under the age of 45 years who had no radiologic evidence of structural lesions other than gliosis. Wada memory asymmetries were significantly greater (p < 0.02) in patients who were seizure free compared with those who continued to experience seizures. Furthermore, patients with Wada memory score asymmetries of at least three objects (maximum = 8) were more likely to be seizure free compared with patients with Wada memory asymmetries less than three (p < 0.01). Of the 36 patients who had Wada memory score asymmetries of at least three objects, 32 (89%) were seizure free. In contrast, of the 19 patients whose Wada memory score asymmetries were less than three, only 12 (63%) were seizure free. These data suggest that Wada memory performance is related to seizure outcome following anterior temporal lobectomy.

Stimulus timing effects on Wada memory testing.

OBJECTIVE: To determine the effects of presenting Wada memory stimuli at different times after intracarotid amobarbital injection on Wada memory asymmetries. DESIGN: Wada memory asymmetries from three timing series were related to the laterality of eventual temporal lobectomy. SETTING: Academic institution epilepsy surgery program. PATIENTS: Forty-three patients with complex partial seizures who later underwent anterior temporal lobectomy (left temporal lobectomy, 24 patients; right temporal lobectomy, 19 patients). No patient included had abnormalities on magnetic resonance imaging scans to suggest a lesion other than gliosis. RESULTS: Memory performance for objects whose presentation began approximately 45 seconds after amobarbital administration differentiated laterality of seizure onset. Memory for items presented later and after partial return of language (on average 3 minutes 40 seconds postinjection) also differed as a function of ipsilateral vs contralateral injection, but at a lower level of statistical significance. Memory for items presented last during the procedure (on average 6 minutes postinjection) discriminated seizure groups at a still lower level of statistical significance. When used to predict lateralized temporal lobe impairment in individual patients, early object memory performance was significantly better than memory performance employing either middle (56%) or late (43%) stimulus presentation timings. CONCLUSION: The results of early object memory testing are superior to those obtained from stimulus presentation later in the procedure in documenting temporal lobe dysfunction associated with a lateralized seizure onset.

Amnesia after unilateral temporal lobectomy: a case report.

We report a mixed handed (L > R) patient with exclusive right cerebral language representation who developed a permanent anterograde amnestic syndrome after right anterotemporal lobectomy. Preoperative neuropsychological performance consisted of impaired verbal memory and normal nonverbal memory. Wada memory performance was asymmetrical for objects presented soon after amobarbital injection in conjunction with no memory asymmetry for items presented later in the Wada evaluation. Pre- and postoperative magnetic resonance imaging (MRI) scans showed no structural lesions; however, postoperative MRI hippocampal volume measurements suggested decreased hippocampal volume for the nonresected temporal lobe. These results confirm the risk of anterograde amnesia after unilateral temporal lobectomy and demonstrate that baseline neuropsychological testing may falsely literalize material-specific memory functions in patients with atypical cerebral language dominance.

Use of scalp-sphenoidal EEG for seizure localization in temporal lobe epilepsy.

We determined the accuracy and sensitivity of scalp-sphenoidal EEG for seizure focus localization in 50 patients who became seizure-free or had rare seizures following temporal lobectomy. EEG localization was based on concordant interpretations of scalp-sphenoidal ictal EEG by three independent interpreters. All patients became seizure-free or had rare seizures following temporal lobectomy. Localization from EEG disagreed with the side of surgery in only 1 (2%) of 50 patients. We identified 3 distinct patient groups with a low, moderate, and high likelihood of having a focal ictal EEG pattern during a seizure. These groups comprised 31% (low likelihood), 44% (moderate likelihood), and 25% (high likelihood) of patients. A model based on these results suggests that with multiple ictal EEG recordings, accurate localization from scalp-sphenoidal EEG is possible in approximately up to 65-70% of patients with temporal lobe epilepsy.

Role of multichannel magnetoencephalography in the evaluation of ablative seizure surgery candidates.

Magnetic source imaging (MSI) was performed on 30 ablative epilepsy surgery candidates. The technique involved high resolution multiplanar MRI images with lipid fiducials attached to the patient's head to define a head-based 3D coordinate space. Magnetoencephalography (MEG) was performed after digitizing the same fiducial points. A 37-channel magnetometer obtained data at two to five sites over each hemisphere. MEG epileptiform data were obtained with and without EEG triggering. A single equivalent current dipole model was used to determine orientation and location of a dipole generator whose surface isocontour map most closely fits the measured dipolar data for each event. The MEG data were then transformed to MRI images for source localization. In five of seven cases with ictal anterior temporal lobe foci, MSI data were localized to the same temporal lobe but did not provide additional spatial data. In 10 of 11 cases with convexity foci, MSI provided additional spatial localizing data. MSI did not verify depth electrode localization in one anterior temporal-orbital frontal and three orbitofrontal cases. In seven of eight cases in which depth EEG recordings were nonlocalizing, MSI provided insufficient localizing data. MSI appears to provide additional spatial localizing data in most cases with a convexity epileptic focus.

Seizure localization in temporal lobe epilepsy: a comparison of scalp-sphenoidal EEG and volumetric MRI.

We determined the accuracy of volumetric MRI (based on identification of unilateral hippocampal atrophy) and scalp-sphenoidal EEG (based on concordant interpretations of scalp-sphenoidal ictal EEG by three independent interpreters) for seizure focus localization in 20 patients with temporal lobe epilepsy. All patients became seizure-free or had rare seizures following temporal lobectomy. Among the 20 patients, nine (45%) met both MRI and EEG localization criteria, six (30%) met MRI localization criteria alone, three (15%) met EEG localization criteria alone, and two patients (10%) did not meet either localization criteria. In the 18 patients meeting MRI or EEG localization criteria, the predicted localization agreed with the side of temporal lobectomy. These results suggest that a noninvasive approach combining MRI and EEG will correctly localize the side of seizure onset in most patients with temporal lobe epilepsy.

Wada memory testing and hippocampal volume measurements in the evaluation for temporal lobectomy.

We examined the relationship of Wada memory performance and MRI hippocampal volume measurements to laterality of ultimate seizure localization in 20 patients with complex partial seizures who later underwent temporal lobectomy. Discriminant function analysis employing both Wada memory test asymmetries and hippocampal volume asymmetries correctly classified 100% of the patients into left and right temporal lobe groups. Wada memory asymmetries alone correctly classified 90% of the sample (80% of the sample when the discriminant function included all patients except the one being classified), and hippocampal volume asymmetries alone correctly classified 90% of the patients. A significant correlation was present between Wada memory asymmetries and hippocampal volume asymmetries (r = 0.78), indicating that structural evidence of reduced hippocampal volume has a functional correlate reflected by Wada memory performance. These data suggest that the combination of functional and structural measures is of value in the preoperative evaluation for epilepsy surgery.

Manganese and epilepsy: brain glutamine synthetase and liver arginase activities in genetically epilepsy prone and chronically seizured rats.

Low blood manganese (Mn2+) concentration is associated with epilepsy in humans and rats. The low Mn2+ concentration is attributed by some investigators to the seizure activity associated with the epilepsy, whereas others propose that the low Mn2+ concentration may be secondary to genetic mechanisms underlying the epilepsy. To begin to differentiate between these possibilities, Mn(2+)-binding enzymes of liver and brain (i.e., arginase and glutamine synthetase, respectively) were assayed in rats exposed to chronically induced seizures and in genetically epilepsy-prone rats (GEPRs). Chronic seizures caused a decrease in whole blood Mn2+ levels but did not affect brain Mn2+ concentrations. Arginase activity was increased in livers of rats with chronic seizure as compared with controls, but this difference was eliminated when Mn2+ was added to the assay. Brain glutamine synthetase activity was unaffected by chronic seizures, but the activity of this enzyme was significantly lower in GEPR brain than in control brain. Liver arginase activity tended to be lower in GEPRs, although the difference was not statistically significant. These data indicate that seizures affect liver arginase activity through changes in liver Mn2+ concentration, but GEPRs show abnormalities in Mn(2+)-dependent enzymes apparently independent of seizure activity.

Localization of temporal lobe seizures with quantitative EEG.

In this study, we describe a quantitative EEG method for localization of seizure onset in 29 patients with temporal lobe epilepsy. We used right-left differences in relative power and a logistic regression to predict the side of seizure onset. The optimum bipolar channels were T4-T6/T3-T5 and the optimum frequency band was 4-10.5 Hz. Using a threshold probability of 0.75 for classification, the best quantitative EEG method classified 23 patients (79%) correctly, 2 patients (7%) incorrectly, and 4 patients (14%) as undetermined localization. In comparison, 3 electroencephalographers visually interpreted these same EEGs and classified 20-25 patients (69-86%) correctly, 1 patient (3%) incorrectly and 3-8 patients (10-28%) as undetermined localization. In the 8 patients classified as undetermined localization by at least one interpreter, the quantitative EEG method classified 5 patients correctly, 1 patient incorrectly and 2 patients as undetermined localization. These results suggest that quantitative EEG might improve the reliability of ictal EEG localization and potentially reduce the need for invasive intracranial EEG monitoring.

Comparison of glutamine synthetases from brains of genetically epilepsy prone and genetically epilepsy resistant rats.

Since glutamine synthetase (GS) has been proposed as the primary enzyme in the regulation of glutamate metabolism in the central nervous system and since inhibition of the activity of this enzyme in vivo leads to seizures, it has been proposed that an abnormality in the structure or function of this enzyme could be responsible for the induction of seizures in epilepsy prone rats. To test this hypothesis the glutamine synthetases were purified from the brains of both genetically epilepsy prone rats (GEPR) and their progenitors, genetically epilepsy resistant rats (GERR). The enzymes were compared using both SDS-PAGE and isoelectric focusing. The immunoreactivities of equal amounts of protein were determined using the ELISA technique, and the regulation of the glutamine synthetase activities by Mn2+/Mg2+ ratios were compared. The only difference found between the glutamine synthetases from the two strains was a slightly lower specific activity of the enzyme from the epilepsy prone animals.

Differential effects of left versus right seizure focus on human hippocampal evoked responses.

Hippocampal evoked potentials were recorded using the P3 tonal oddball paradigm in 30 patients with unilateral temporal lobe seizure focus. Spectral power of the evoked potentials was decreased on the side of seizure focus, but this reduction was much greater when the focus was on the left. The effect of left/right focus does not appear to be due to group differences in age, sex, seizure duration, or operative pathology. Remote or finer left/right structural differences or differential left/right hippocampal processing for the sequential tonal task are possible explanations.

A model for focal magnetic brain stimulation.

In this study, we describe a magnetic coil designed for focal brain stimulation. We determined the distribution of magnetically induced currents using a multi-concentric spherical cranial computer model. The induced currents were primarily linearly oriented and concentrated below the coil's center. In comparison with large coils, small coils were less efficient but produced a more concentrated current distribution. Variations in conductivity among brain, scalp and skull produced secondary currents that reduced the magnetically induced current. This reduction in magnetically induced current was greater for larger coils.

Comparison of CT- versus MRI-guided, computer-assisted depth electrode implantation.

Fourteen candidates for ablative seizure surgery underwent CT-guided, computer-assisted stereotactic depth electrode implantation and 21 underwent MRI-guided, computer-assisted implantation. A hand-held computer with no graphic capability was used for CT-guided procedures. A computer work station which included a high-resolution color graphics terminal with touchscreen interfacing and software capable of simulating targets and trajectories in single or multiple views was used for MRI-guided procedures. Previous phantom studies done with a 1.5-tesla MR scanner suggested acceptable localization error. Localizing information was obtained in 10 (71.4%) of 14 of the CT-guided implants and in 16 (76.2%) of 21 of MRI-guided cases. In the CT group, 7 (70%) were seizure-free and 8 (80%) were greater than 90% improved at 1 year follow-up. In the MRI group, 8 (80%) were seizure-free and 9 (90%) were greater than 90% improved at latest follow-up.

Computerized seizure detection of complex partial seizures.

In this study, we describe a computerized method that uses 3 quantified EEG features and discriminant analysis to automatically detect seizure EEG. The quantified EEG features were relative amplitude, dominant frequency and rhythmicity. Using EEGs recorded from intracranial electrodes, the seizure detection method was applied to consecutive non-overlapping 2-channel EEG epochs. A seizure detection sensitivity, ranging from 90% to 100%, was associated with a false positive detection rate of 1.5-2.5/h. The performance of the seizure detection method remained stable for EEG recorded over variable time periods.

Possible relationship of periodic lateralized epileptiform discharges to thalamic stroke.

A patient with a unilateral thalamic infarct and associated periodic lateralized epileptiform discharges is described. The implications of this for the pathophysiology of PLEDs is discussed.

Behavioral state-specific changes in human hippocampal theta activity.

Although there has been extensive examination of the behavioral and physiologic correlates of hippocampal theta activity in animals, the human literature consists of a single case study. We investigated the differential effects of four behavioral states on human hippocampal theta activity in 16 epilepsy surgery patients. Behavioral conditions included resting eyes closed (RC), resting eyes open (RO), eyes open with auditory word activation (AW), and eyes open with visuospatial activation (VS). Hippocampal theta activity decreased during both RO and VS compared to both RC and AW. There were reciprocal changes in delta activity. Comparisons of RO to VS and of RC to AW were nonsignificant. The results demonstrate state-specific changes in human hippocampal theta and are consistent with the animal literature that relates hippocampal theta to sensorimotor integration and forebrain volitional mechanisms.

Human hippocampal EEG: effects of behavioral activation.

We studied spectral components of human hippocampal EEG in relation to behavioral status in 19 patients with intractable complex partial seizures who had depth electrodes implanted into the anterior hippocampi as a part of their preoperative evaluations. Behavioral conditions included: eyes closed resting, eyes open resting, eyes open with a verbal task, and eyes open with a visuospatial task. Hippocampal EEG spectral power uniformly decreased during behavioral activation. EEG activation was quantitatively different among the 3 activated conditions, with the most prominent change occurring during the visuospatial task. The degree of EEG activation corresponded inversely with the site of epileptic focus during the verbal task. The results demonstrate the response of human hippocampal EEG to behavioral activation. The magnitude of EEG change may reflect the degree of functional activation of the given hippocampus.