Epilepsy Surgery Patients Research Articles

Epilepsy surgery in patients with additional psychogenic seizures.

To assess whether surgery to reduce or control epileptic seizures is safe and effective in patients known to have additional psychogenic seizures. We reviewed our computerized database of 1342 patients examined for epilepsy surgery and identified 13 patients with both epileptic and psychogenic seizures on whom postoperative outcome data were available. Data were gathered from the patients' records. Mean postoperative follow-up was 56 months. Epilepsy surgery led to clinically relevant improvements in 11 of 13 patients. Seven patients became free of epileptic and psychogenic seizures, 2 patients became free of epileptic seizures but continued to have infrequent psychogenic seizures, 1 patient reported more than an 80% improvement in epileptic seizure frequency and an abolishment of psychogenic attacks, and in 1 patient nondisabling epileptic seizures persisted at lower frequency but psychogenic seizures stopped. In 2 of 13 patients, epilepsy surgery failed to produce notable improvements. Although 1 patient became free of epileptic attacks and the other had fewer than 3 epileptic seizures per year, the severity or frequency of psychogenic seizures and pseudo-status epilepticus increased postoperatively. One of these patients had a preoperative diagnosis of somatization disorder; in the other, pathological illness behavior had been noted. A diagnosis of additional psychogenic seizures should not be considered an absolute contraindication to epilepsy surgery, although patients should undergo careful preoperative psychiatric evaluation.

Focal cortical dysplasias in eloquent cortex: functional characteristics and correlation with MRI and histopathologic changes.

Focal cortical dysplasia (CD) is increasingly recognized as a common pathologic substrate of medically intractable epilepsy. As these lesions are often localized in the frontal lobe (therefore in potentially eloquent cortex), an understanding of the functional status of the involved region(s) and of its anatomic and pathologic correlates is of prime importance. The purpose of this study is to assess the function of focal CD in relation to magnetic resonance imaging (MRI) and histopathologic features. Eight patients operated on for medically intractable epilepsy with histologically proven focal CD involving putative eloquent cortex in the frontal lobe (perirolandic and Broca's areas) were included in the study. Functional regions (motor and language) and epileptogenic areas were assessed by extraoperative electrocorticographic recording and electrical cortical mapping. Cortical functions were correlated with the extent of epileptogenicity on electrocorticographic recordings, MRI features, and histologic characteristics. Language or motor areas were colocalized with epileptogenic regions (n=6 of 8, 75%), but were not mapped in regions of increased signal on fluid-attenuated inversion recovery (FLAIR) MRI (when they were identified) on preoperative MRI (n=5 of 5, 100%). Histologically, balloon cells were almost exclusively found in nonfunctional regions with FLAIR MRI abnormalities. When resected, regions of motor cortex were characterized by cortical dyslamination, columnar disorganization, and dysmorphic neurons, but were devoid of balloon cells. We found an absence of language or motor functions in perirolandic and Broca's areas that showed decreased epileptogenicity, histopathological evidence of CD with balloon cells and FLAIR MRI signal increase. Language and motor functions were present in epileptogenic and dysplastic areas with no balloon cells and no FLAIR signal abnormalities. These findings have implications on options for epilepsy surgery in patients with CD.

Insertion of depth electrodes with or without subdural grids using frameless stereotactic guidance systems -- technique and outcome

Over recent years frameless stereotactic systems have begun replacing framed systems for many neurosurgical procedures. However, little has been published regarding the use of these systems to guide intracranial electrode implantation for epilepsy surgery patients. Here we report our experience utilising such a system to insert depth electrodes and subdural grid electrodes. The SteathStation Image-Guided System TM (SSIGS) (Sofamor Danek, Memphis TN.) was used to insert bilateral depth electrodes in 13 patients, of whom 5 also underwent the insertion of subdural grids or strip electrodes. Initially, a surgical plan based on an entry and target point on axial and sagittal images was performed for the insertion of electrodes. Navigational views, using three-planar images, were then performed to determine which structures the electrodes would pass through to be correctly placed in the amygdala and hippocampus. The correct site of electrode implantation was confirmed post-operatively by spiral CT scans in 4 patients (which were then co-registered to the preimplantation MRI using a surface matching technique) and the other 9 patients by post-implantation MRI. The SSIGS was found to have a mean registration error of 2.0 mm (range 1.8-2.5) in 10 cases; in the 3 cases where the error was greater than 2.5 mm a surfacemerge technique was used with a mean error 0.9 (0.8-1.00). The post-implantation MRI or CT-MRI co-registration confirmed an accurate electrode placement in the mesial temporal region in all cases. Seizure onset lateralisation was achieved in 11 patients, all of whom went onto formal resections based on these results. The only long-term complication was a case of osteomyelitis which required removal of the bone flap. 73% of patients had an excellent seizure outcome. Frameless stereotactic systems can be safely used to intracranial electrodes, avoid the disadvantages of the framed system and have the added advantage of the surgeon being able to visualise the trajectory and to adjust this to avoid vital structures. As well they eliminate surgical obstruction to the insertion of subdural grids at the same operation, which may be caused by a framed system.

The ontogeny of partial seizures in infants and young children.

To describe the clinical manifestations of partial seizures in the pediatric population as a function of age. Using the database of the pediatric epilepsy monitoring unit (Children's Hospital of New York), clinical and EEG characteristics of partial seizures were distributed by age groups 0-2, 2-6, and 6+ years for 123 patients who had at least one such seizure with a clear EEG correlate during their admission. chi2 tests for trend were used to examine clinical and EEG features as a function of age. The frequency of aura, limb automatisms, dystonic posturing, secondary generalization, and unresponsiveness increased with age, whereas asymmetric clonus and symmetric tonic posturing decreased with age. There were no clear changes in the types of EEG ictal patterns observed with age; however, partial seizures emanating from the anterior regions of the brain tended to increase with age, whereas those from the posterior regions tended to decrease with age. Important differences exist in the clinical expression of seizures between young children and adults. These findings will contribute to a better understanding of ictal ontogeny that will promote more accurate classification of seizures and of the epilepsies in young patients. Such efforts can be used to identify young patients for focal epilepsy surgery and to select appropriate anticonvulsive medications.

Cerebral substrates of musical imagery.

Musical imagery refers to the experience of "replaying" music by imagining it inside the head. Whereas visual imagery has been extensively studied, few people have investigated imagery in the auditory domain. This article reviews a program of research that has tried to characterize auditory imagery for music using both behavioral and cognitive neuroscientific tools. I begin by describing some of my behavioral studies of the mental analogues of musical tempo, pitch, and temporal extent. I then describe four studies using three techniques that examine the correspondence of brain involvement in actually perceiving vs. imagining familiar music. These involve one lesion study with epilepsy surgery patients, two positron emission tomography (PET) studies, and one study using transcranial magnetic stimulation (TMS). The studies converge on the importance of the right temporal neocortex and other right-hemisphere structures in the processing of both perceived and imagined nonverbal music. Perceiving and imagining songs that have words also involve structures in the left hemisphere. The supplementary motor area (SMA) is activated during musical imagery; it may mediate rehearsal that involves motor programs, such as imagined humming. Future studies are suggested that would involve imagery of sounds that cannot be produced by the vocal tract to clarify the role of the SMA in auditory imagery.

Pre--and postoperative general neurocognitive status and memory in 70 epilepsy surgery patients.

To describe cognitive function preoperatively and cognitive change 2 years postoperatively in 70 consecutive adults in the Göteborg epilepsy surgery series. Analysis of general neurocognitive status and memory for the total group and for three subgroups: 26 patients with seizure onset in dominant temporal lobe, 28 patients with onset in non-dominant temporal lobe and 12 with frontal lobe onset. Preoperative performance was compared with a control group (n=30). Preoperatively, patients were more impaired in general neurocognitive status than controls. Patients in the temporal lobe subgroups performed worse than controls in two memory variables. No postoperative negative change was found at group level. There was a small increase in Full Scale IQ and Performance IQ for the total patient group, and in Performance IQ for the frontal lobe subgroup. At individual level, many patients suffered losses or obtained gains in a number of memory variables without any consistent intra-pattern. Cognitive stability was the main postoperative result. The importance of considering inter- and intra-individual variability of negative as well as positive change is emphasized.

Neurons recorded from pediatric epilepsy surgery patients with cortical dysplasia.

Cortical dysplasia (CD) is a common pathological substrate in patients with early-onset childhood epilepsy. In CD tissue, little is known about the mechanisms responsible for cellular hyperexcitability. In this study, we report initial electrophysiological and morphological observations from normal and dysmorphic cells in pediatric CD patients. Neocortical "most" and "least" epileptogenic areas were sampled based on neuroimaging and electrocorticography from 15 CD patients (ages 0.3 to 14 years). Whole-cell voltage clamp recordings combined with infrared videomicroscopy sampled abnormal cells (cytomegalic neurons, cells with bifurcated dendrites, disoriented pyramidal cells, etc.) compared with normal-appearing neurons from the same patient. Cells were filled with biocytin, and adjacent tissue blocks were stained for neuronal and glial markers. About 15% of the 161 recorded cells were abnormal in appearance. Abnormal cells showed electrophysiological irregularities ranging from intrinsic cellular hyperexcitability to hyposensitivity after application of ionotropic receptor agonists. Other findings included increased excitatory postsynaptic currents and alterations in gamma-aminobutyric acid reversal potentials. In pediatric CD tissue, these preliminary results indicate that abnormal-appearing cells showed abnormalities in electrophysiological measures compared with normal-appearing neurons. The abnormalities varied from hyperexcitability to hypoexcitability. More detailed results and conclusions will be forthcoming as additional patient material is analyzed.

Measuring Quality of Life in Epilepsy Surgery Patients

Treatment of chronic conditions often entails trade-offs between benefits and risks or side effects. This is of particular importance in epilepsy. Consequently, assessment of effectiveness must incorporate this trade-off as perceived by the recipient of the intervention, ie., the patient. Measurement of health related quality of life (HRQOL) aims at capturing such patient-centred effects of therapy. Conceptual aspects of HRQOL are described and issues relevant to outcomes of epilepsy surgery are addressed. Finally, practical aspects of measurement in the context of epilepsy surgery are discussed.

Scalp EEG in temporal lobe epilepsy surgery.

Electroencephalography (EEG) with standard scalp and additional noninvasive electrodes plays a major role in the selection of patients for temporal lobe epilepsy surgery. Recent studies have provided data supporting the value of interictal and postictal EEG in assessing the site of ictal onset. Scalp ictal rhythms are morphologically complex but at least one pattern (a five cycles/second rhythm maximum at the sphenoidal or anterior temporal electrode) occurs in >50% of patients and has a high predictive value and interobserver reliability for temporal lobe originating seizures. Thorough interictal and ictal scalp EEG evaluation, in conjunction with modern neuroimaging, is sufficient for proceeding to surgery without invasive recordings in some patients. Further studies are required to define the scalp ictal characteristics of mesial vs. lateral temporal lobe epilepsy.

Localizing and lateralizing value of epileptic symptoms in temporal lobe epilepsy.

The symptoms and signs associated with all stages of a temporal lobe seizure may be helpful in determining both the localization and lateralization of seizure onset. Auras, when present, may be very suggestive of temporal lobe onset and may further localize to a mesiobasal or lateral temporal lobe site of onset. During the ictus, automatisms and motor phenomena may be highly indicative of temporal lobe seizure activity and may even help lateralize the discharge. In the post-ictal period, motor paresis and aphasia are helpful in lateralization. Video E.E.G. data has provided extensive information on the utility of ictal symptomatology in seizure localization. Thus, the seizure semiology provides important adjunctive information in evaluating patients for epilepsy surgery and should be concordant with information obtained from ictal EEG, neuroimaging and neuropsychology.

Relation of cortical language distribution and cognitive function in surgical epilepsy patients.

To investigate the relation between the number and spatial distribution of language sites and specific patient-and epilepsy-related variables. Patients with stimulation-induced reading or naming errors from anterior or inferior temporal cortex (i.e., atypical temporal language sites) were compared with those with language sites confined to Wernicke's area (WA) in the posterosuperior temporal and inferior parietal perisylvian area. In a consecutive series of 44 left hemisphere language dominant patients with complex partial seizures before left temporal lobectomy, correlations were compared between cortical language distribution and measures of cognitive function. Patients with atypical temporal language sites (group 1) had significantly fewer years of education that did patients with language sites in WA (group 2). Patients in group 1 had poorer verbal learning and fluency than did patients in group 2. Patients with IQ <80 were significantly more likely to have multiple sites where stimulation disrupted language than did patients with normal IQ. Number of language sites had significant negative correlations with full-scale IQ, and measures of confrontation naming, verbal fluency, and immediate verbal memory. Language cortex has a wider spatial distribution in epilepsy surgery patients with lower intelligence, poorer education, and worse verbal and memory skills.

The role of the intracarotid amobarbital procedure in evaluation of patients for epilepsy surgery.

To examine the role of the intracarotid amobarbital procedure (IAP) in the presurgical evaluation of patients with medically refractory localization-related epilepsy. We retrospectively studied 111 patients who underwent cortical resective surgery at our center between 1991 and 1996. In patients with mesial temporal lobe epilepsy (mTLE), a presurgical determination of the epileptogenic zone was compared with localization based on IAP memory asymmetry scores, and with ultimate localization after resective surgery. In patients with neocortical or mesial frontal epilepsy, the IAP was evaluated for evidence of unilateral or bilateral poor memory performance. Of 68 patients with mTLE localized by noninvasive tests, 60 had concordant lateralized memory deficits on IAP. Eight patients had lateralized memory deficits on IAP that were discordant with noninvasive tests and with localization as determined by surgical outcome. All 11 mTLE patients requiring invasive EEG monitoring were correctly lateralized by IAP, including one patient in whom the noninvasive evaluation otherwise provided false lateralization. Of 32 patients with neocortical or mesial frontal lobe epilepsy, 21 displayed memory deficits on IAP. Of 10 patients with bilateral deficits, five had mesial frontal lobe epilepsy. In 13 patients with lateralized memory deficits, seven underwent electrode implantation in the mesial temporal lobe, and four ultimately underwent resection of an epileptogenic mesial temporal lobe in addition to a neocortical resection. In patients with mTLE, lateralized memory deficits on IAP usually confirm localization provided by noninvasive tests. However, in mTLE not well lateralized by the noninvasive evaluation, and in neocortical or mesial frontal epilepsy, the IAP may provide information regarding localization that ultimately alters surgical management.

Intracranial EEG seizure-onset patterns in neocortical epilepsy.

We investigated neocortical seizure-onset patterns recorded by intracranial EEG with regard to anatomic location, pathologic substrate, and prognostic value for surgical outcome. Seizure onset was analyzed in 53 neocortical resective epilepsy surgery patients. Anatomic location was divided into temporal and extratemporal. Pathologic substrate was classified as developmental, mature, and negative or non-specific gliosis. Onset frequency was categorized by visual analysis into tradition EEG frequency bands. Spatial extent was divided into focal (fewer than four contacts) and regional (more than five contacts). Waveform at seizure onset was divided into several types based on their morphology. Onset features were examined with respect to anatomic location, pathologic substrate, and surgical outcome. Seizure-onset frequency was significantly related to spatial distribution and to anatomic location. Extratemporal and regional onset were more commonly in the gamma range, and temporal and focal onset in the beta frequency range or slower. Waveform could be categorized into five different patterns, of which low voltage fast activity (LVFA) was the most common form (57%). LVFA and rhythmic alpha-theta spike activity were more common in developmental than in mature pathology, whereas rhythmic sinusoidal waves at onset were found in only mature substrates. Waveform pattern showed a possible correlation with surgical outcome (p = 0.097): LVFA and rhythmic sinusoidal waves onset patterns were associated with favorable outcome more often (40.4%) than the other three patterns (6.3%). Slow onset suggested poor outcome in the subgroup of developmental pathology (p = 0.062). Certain electrographic seizure-onset features are associated with specific substrates and outcomes, whereas others reflect the anatomic location and its connections independent of the pathology.

The EEG evaluation of single photon emission computed tomography abnormalities in epilepsy.

Single photon emission computed tomography (SPECT) has increasingly been used as a diagnostic procedure for localizing epileptic seizure foci and as a research tool for investigating the physiologic mechanisms underlying seizure activity. With increasing use of SPECT in localizing the seizure focus for epilepsy surgery, there arises a need to critically assess its current role in the evaluation of patients for epilepsy surgery, especially as it relates to other clinical and laboratory data used in presurgical evaluation. Ictal EEG discharge has traditionally been used as the "gold standard" against which SPECT studies are compared in assessing the latter's localizing value. However, this practice presents a major challenge because SPECT studies are often reserved for patients with nonlocalizing EEG or magnetic resonance imaging findings. Nonetheless, SPECT studies in evaluation for epilepsy surgery should always be performed with the knowledge of the patient's EEG activity preceding, during, and after the injection of the radiotracer. The advent of techniques such as subtraction SPECT with co-registration on magnetic resonance imaging (SISCOM) and computer image-guided surgery has great potential in enhancing the clinical electrophysiologic evaluation of SPECT-detected abnormalities in epilepsy. These techniques permit accurate spatial correlation between intracranial EEG activity and SPECT perfusion patterns. The techniques can also be used to evaluate the effect of the extent of EEG focus resection compared with that of SISCOM focus resection to determine which has more prognostic importance in postsurgical control of seizures. Both animal and human studies are warranted to advance our knowledge of the electrophysiology associated with the various SPECT perfusion patterns.

Nonepileptic seizures after resective epilepsy surgery.

To identify factors that are associated with the emergence of nonepileptic seizures (NES) after resective epilepsy surgery. Twenty-two patients with medically refractory epilepsy in whom NESs were documented by EEG after resective surgery were compared with a larger series of epilepsy surgery patients on demographic, neurologic, and psychiatric variables. NES tended to become apparent in the first few months after surgery. Patients who developed NESs did not differ from other epilepsy surgery patients in terms of age, IQ, or preoperative psychiatric diagnoses. However, surgical NES patients' neurologic problems and seizures began later in life, the NES group included a larger proportion of female subjects and patients with right hemisphere surgery, and NES patients were more likely to develop non-NES psychiatric problems after surgery. The heterogeneous collection of behaviors subsumed under the label NESs are determined by multiple factors. Several variables were found to be specifically associated with the development of NES after resective epilepsy surgery: A disproportionate number of postsurgical NES patients are female, they have primary neurologic dysfunction in the right hemisphere, and their epileptic seizures often began after adolescence. We propose that at least one group of patients with somatoform tendencies develop NESs as part of the psychiatric instability that occurs often in the few months after resective surgery.

Marital status after epilepsy surgery.

To characterize features influencing marital status in a group of patients with refractory epilepsy before and after epilepsy surgery and to assess the effect of seizure control on marital status after epilepsy surgery. We analyzed marital status in 430 epilepsy surgery patients and in a subset with temporal lobe epilepsy. Marital status was assessed in relation to gender and age of epilepsy onset and compared with marital rates for the U.S. population. Patients who had > or =4 years of postsurgical follow-up were examined for change in marital status after surgery. Those patients who changed marital status were then evaluated for change in employment. Marital rates were lower than expected in men. Men with onset of epilepsy by age 11 years were less likely to be married than men whose seizures began after age 11 or women whose seizures began at any age. Men and women with temporal lobe epilepsy had higher marriage rates than those with extratemporal lobe epilepsy. More than 4 years after epilepsy surgery (n = 190), patients who had no recurrent seizures were more likely to change marital status (28 of 124, 23%), than those who had recurrent seizures (five of 66, 8%). Seizure-free women were more likely to divorce (n = 9) than were seizure-free men (n = 1). Most men who married were employed (77%), whereas women who divorced were usually unemployed (67%). The age at which seizures begin influences later marital status in men, who have reduced marriage rates. The abolition of seizures by epilepsy surgery creates new opportunities for changing social relationships. Location of the epileptic focus may influence psychosocial function.

Postoperative seizure control and antiepileptic drug use in pediatric epilepsy surgery patients: the UCLA experience, 1986-1997.

Young children with refractory symptomatic epilepsy are at risk for developing neurologic and cognitive disabilities. Stopping the seizures may prevent these disabilities, but it is unclear whether resective surgery is associated with adequate long-term seizure control. This study determined pre- and postsurgery seizure frequency and antiepileptic drug (AED) use (6 months to 10 years) in children with symptomatic seizures from unilateral cortical dysplasia (CD; n = 64) and non-CD etiologies (i.e., ischemia, infection; n = 71), and compared them with older temporal lobe epilepsy (TLE; n = 31) patients with complex partial seizures. Compared with presurgery, postsurgery seizure frequencies were decreased for CD, non-CD, and TLE patients (p < 0.002), and there were no differences between the three groups from 6 to 24 months after surgery (p > 0.12). At 5 years after surgery, seizure frequencies were greater in CD compared with TLE cases (p = 0.009). Compared with presurgery, the number of AEDs declined after surgery in all three groups (p < 0.002), and positively correlated with seizure frequencies (p = 0.0001). This study indicates that seizure relief and AED use after resective surgery for symptomatic CD and non-CD etiologies was comparable with complex partial TLE cases up to 2 years after surgery. Furthermore, at 5 years after surgery, CD patients had outcomes better than those before surgery, but worse than TLE cases. In young children, these findings support the concept that early removal of symptomatic pathologic substrates is associated with seizure control and reduced AED use, similar to that noted in older TLE cases up to 2 years after surgery. Seizure control may reduce the risk of developing the seizure-related encephalopathy associated with severe symptomatic early-onset childhood epilepsy.

Identification of electrocorticogram patterns as the basis for a direct brain interface.

This study reports on the first step in the development of a direct brain interface based on the identification of event-related potentials (ERPs) from an electrocorticogram obtained from the surface of the cortex. Ten epilepsy surgery patients, undergoing monitoring with subdural electrode strips and grid arrays, participated in this study. Electrocorticograms were continuously recorded while subjects performed multiple repetitions for each of several motor actions. ERP templates were identified from action-triggered electrocorticogram averages using an amplitude criterion. At least one ERP template was identified for all 10 subjects and in 56% of all electrode-recording sets resulting from a subject performing an action. These results were obtained with electrodes placed solely for clinical purposes and not for research needs. Eighty-two percent of the identified ERPs began before the trigger, indicating the presence of premovement ERP components. The regions yielding the highest probability of valid ERP identification were the sensorimotor cortex (precentral and postcentral gyri) and anterior frontal lobe, although a number were recorded from other areas as well. The recording locations for multiple ERPs arising from the performance of a specific action were usually found on close-by electrodes. ERPs associated with different actions were occasionally identified from the same recording site but often had noticeably different characteristics. The results of this study support the use of ERPs recorded from the cortical surface as a basis for a direct brain interface.

Depression in Temporal Lobe Epilepsy Before Epilepsy Surgery

This study examined the association of depression with laterality of epilepsy surgery in patients with temporal lobe epilepsy before standard lobectomy. Forty-nine patients presented for EEG telemetry for localization of epilepsy and eventual temporal lobectomy. Patients underwent routine neuropsychiatric evaluation blinded for epileptic focus, including ratings on depression. Patients were grouped according to right (n = 25, M = 10/F = 15) and left (n = 24, M = 13/F = 11) temporal lobectomy. Analysis of variance included side of surgery as grouping variable and sex, general depressive, cognitive depressive, and vegetative depressive symptoms as dependent variables. Chi2 analyses included categoric variables of sex, handedness, education, neuropathologic findings, and current affective disorders. t Tests were performed on variables of age, epilepsy duration, and cognitive function. Right and left temporal epilepsy groups did not differ with regard to sex, handedness, age, duration of epilepsy, education, cognitive function, and neuropathology. Patients with right temporal epilepsy rated higher on general, cognitive. and vegetative depression scores. Women scored higher on general, cognitive, and vegetative depression scores. Current affective disorders were more common in the right temporal epilepsy group. Depression ratings and diagnoses were more prominent in patients with right temporal lobe epilepsy and in women in particular. The strength of this laterality finding lies in the selection of patients, as all underwent epilepsy surgery. The finding on gender difference partly reflects the higher incidence of depression in women and needs further exploration. The laterality finding contrasts with recent findings in epilepsy, stroke, and trauma that associate depression with left hemispheric lesions. However, our results are consistent with findings in electrically hyperactive lesions such as gelastic and dacrystic epilepsy.

Neuroactive amino acids in focally epileptic human brain: a review.

Studies of neuroactive amino acids and their regulatory enzymes in surgically excised focally epileptic human brain are reviewed. Concentrations of glutamate, aspartate and glycine are significantly increased in epileptogenic cerebral cortex. The activities of the enzymes, glutamate dehydrogenase and aspartate aminotransferase, involved in glutamate and aspartate metabolism are also increased. Polyamine synthesis is enhanced in epileptogenic cortex and may contribute to the activation of N-methyl-D-aspartate (NMDA) receptors. Nuclear magnetic resonance spectroscopy (NMRS) reveals that patients with poorly controlled complex partial seizures have a significant diminution in occipital lobe gamma aminobutyric acid (GABA) concentration. The activity of the enzyme GABA-aminotransaminase (GABA-T) which catalyzes GABA degradation is not altered in epileptogenic cortex. NMRS studies show that vigabatrin, a GABA-T inhibitor and effective antiepileptic, significantly increases brain GABA. Glutamate decarboxylase (GAD), responsible for GABA synthesis, is diminished in interneurons in discrete regions of epileptogenic cortex and hippocampus. In vivo microdialysis performed in epilepsy surgery patients provides measurements of extracellular amino acid levels during spontaneous seizures. Glutamate concentrations are higher in epileptic hippocampi and increase before seizure onset reaching potentially excitotoxic levels. Frontal or temporal cortical epileptogenic foci also release aspartate, glutamate and serine particularly during intense seizures or status epilepticus. GABA in contrast, exhibits a delayed and feeble rise in the epileptic hippocampus possibly due to a reduction in the number and/or efficiency of GABA transporters.