Extratemporal Lobe Epilepsy Research Articles

Interictal alterations of cytokines and leukocytes in patients with active epilepsy

BackgroundInvolvement of the innate immune system in the pathogenesis of epilepsies has been suggested but possible interactions between the immune system and human epilepsy remain unclear. We analyzed the interictal immuno-phenotype of leukocyte subsets and proinflammatory cytokine profiles in epileptic patients and correlated them with the epilepsy syndrome. Methods101 patients with active focal or generalized epilepsy were prospectively included and compared to 36 healthy controls. Immuno-phenotype of leukocyte subsets and cytokines IL-1β, IL-6 and tnfα were measured in peripheral blood. Multivariate analyses were performed to test group differences. ResultsAs compared to controls, the patients showed an elevated percentage of monocytes (18.06±7.08% vs. 12.68±4.55%, p<0.001), NK cells (14.88±7.08% vs. 11.43±5.41%, p=0.019) and IL-6 concentration (3.33±3.11pg/ml vs. 1.5±1.36pg/ml, p=0.002). This remained true when focal epilepsies or generalized epilepsies were compared separately to controls but only focal epilepsies showed additionally a decrease in B lymphocyts (8.16±3.76% vs. 11.54±4.2%, p<0.001). Treatment with lamotrigine was associated with a higher percentage of B lymphocytes and valproate with an increased percentage of CD4+ T lymphocytes. Therapy with levetiracetam showed a trend towards decreased CD8+ T cell counts. No significant differences were seen between focal and generalized epilepsies and between temporal and extratemporal lobe epilepsies. ConclusionPatients with active epilepsy revealed interictal alterations of the immune system which varied among specific syndromes and were influenced by antiepileptic drug treatment.

Resistant epilepsy

Pharmacoresistant epilepsy is defined as the persistence of seizures despite adequate use of antiepileptic drugs, with a minimum of two first-line drugs either as monotherapy or in combination as appropriate to the epileptic syndrome. We present the case of a 31 years old male, with extratemporal lobe epilepsy, MRI negative who proved to be resistant to medical treatment. A benefit-and-risk assessment of all treatment alternatives should consider also epilepsy surgery in this case.

Prevalence of interictal psychiatric disorders in patients with refractory temporal and extratemporal lobe epilepsy in Spain. A comparative study

We aim to investigate whether temporal origin of epilepsy increases the risk of developing a psychiatric disorder and more specifically a major depressive disorder. The lack of standardized diagnostic instruments and the methodologic differences between studies highlight the fact that this issue warrants further, systematic, study. Three-hundred eight patients with complex partial seizures were classified according to temporal or extratemporal origin, following the Commission on Classification and Terminology of the International League Against Epilepsy (ILAE), 1989 localization-related concept. All patients were assessed using the Structured Interview for DSM-IV axis I psychiatric disorders (SCID-I). Lifetime and previous-year prevalence of psychiatric disorders were compared in temporal and extratemporal subgroups, using multivariate analysis. Previous-year major depression was significantly associated with temporal lobe origin. Our results do not support the hypothesis that patients with temporal lobe epilepsy (TLE) have more psychiatric illness in general, although they do suggest a specific connection between TLE and major depression.

Reasons for reoperation after epilepsy surgery: a review based on a complex clinical case with three operations

The results of surgical treatment of epileptic seizures have gradually improved in the past decade, approaching 60% to 90% seizure-free outcome in temporal lobe epilepsy and 45% to 66% in extratemporal lobe epilepsy. Unfortunately some patients continue with seizures after epilepsy surgery and the studies have shown that approximately the 3% to 15% of patients with a previous failed surgical procedure are reoperated. Selected patients may be candidates for further surgery, potentially leading to a significant decrease in the frequency and severity of seizures. In patients with intractable partial epilepsy there are many possible factors, alone or in combination, that could be related to the failure of resection. Some of the factors could be genetic or acquired predisposition to epileptogenicity. In this article we report a case with intractable epilepsy that required three interventions to render seizure free. We analyzed our specific case in the light of previous reports on reoperation and enumerate the potential reasons for reoperation that could apply to all patients with failure of an initial procedure.

Surgery for extratemporal nonlesional epilepsy in adults: an outcome meta-analysis

To better evaluate surgery for extratemporal lobe epilepsy (ETLE) in adults, we conducted a meta-analysis of previous studies that analyzed postoperative seizure outcomes for ETLE. After searching PubMed for appropriate studies, patient data were reviewed, and data on patients who fit the authors' criteria were extracted. Statistical analysis compared each variable with surgical outcome to determine if an association existed. For the 131 patients who were included in the analysis, the age at surgery, age of seizure onset, and duration of epilepsy were not found to be statistically and significantly related to seizure outcome. Similarly, seizure semiology, abnormality on magnetic resonance imaging, lateralization of the seizures, the need for intracranial monitoring, pathological findings, and the type and location of surgery did not appear to be associated with outcome. This meta-analysis confirms the findings of other centers: ETLE surgical outcomes are less desirable than those for temporal lobe epilepsy. None of the factors studied in adults showed significant association with outcome. Contrary to some reports, shortening the duration of epilepsy by pursuing surgery as early as possible also does not appear to improve outcomes. The creation of standard protocols among epilepsy centers is needed to allow for a detailed evaluation of outcomes across different centers and, ultimately, to better assess the factors associated with improved outcomes.

Extent of neocortical resection and surgical outcome of epilepsy: Intracranial EEG analysis

Intracranial electroencephalography (EEG) monitoring is an important process in the presurgical evaluation for epilepsy surgery. The objective of this study was to identify the ideal resection margin in neocortical epilepsy guided by subdural electrodes. For this purpose, we investigated the relationship between the extent of resection guided by subdural electrodes and the outcome of epilepsy surgery. Intracranial EEG studies were analyzed in 177 consecutive patients who had undergone resective epilepsy surgery. We reviewed various intracranial EEG findings and resection extent. We analyzed the relationships between the surgical outcomes and intracranial EEG factors: the frequency, morphology, and distribution of ictal-onset discharges, the propagation speed, and the time lag between clinical and intracranial ictal onset. We also investigated whether the extent of resection, including the area showing ictal rhythm and various interictal abnormalities--such as frequent interictal spikes, pathologic delta waves, and paroxysmal fast activity--influenced the surgical outcome. Seventy-five patients (42%) were seizure free. A seizure-free outcome was significantly associated with a resection that included the area showing ictal spreading rhythm during the first 3 s or included all the electrodes showing pathologic delta waves or frequent interictal spikes. However, subgroup analysis revealed that the extent of resection did not affect the surgical outcome in lateral temporal lobe epilepsy. The extent of resection is closely associated with surgical outcome, especially in extratemporal lobe epilepsy. Resection that includes the area with total pathologic delta waves and frequent interictal spikes predicts a good surgical outcome.

Interictal EEG Spikes Identify Seizure Focus

A computerized spike detector was used to measure and localize interictal epileptiform discharges (IEDs) over prolonged, representative segments of recordings in 19 children with intractable, mostly extratemporal lobe epilepsy.

Interictal EEG spikes identify the region of electrographic seizure onset in some, but not all, pediatric epilepsy patients

The role of sharps and spikes, interictal epileptiform discharges (IEDs), in guiding epilepsy surgery in children remains controversial, particularly with intracranial electroencephalography (IEEG). Although ictal recording is the mainstay of localizing epileptic networks for surgical resection, current practice dictates removing regions generating frequent IEDs if they are near the ictal onset zone. Indeed, past studies suggest an inconsistent relationship between IED and seizure-onset location, although these studies were based upon relatively short EEG epochs. We employ a previously validated, computerized spike detector to measure and localize IED activity over prolonged, representative segments of IEEG recorded from 19 children with intractable, mostly extratemporal lobe epilepsy. Approximately 8 h of IEEG, randomly selected 30-min segments of continuous interictal IEEG per patient, were analyzed over all intracranial electrode contacts. When spike frequency was averaged over the 16-time segments, electrodes with the highest mean spike frequency were found to be within the seizure-onset region in 11 of 19 patients. There was significant variability between individual 30-min segments in these patients, indicating that large statistical samples of interictal activity were required for improved localization. Low-voltage fast EEG at seizure onset was the only clinical factor predicting IED localization to the seizure-onset region. Our data suggest that automated IED detection over multiple representative samples of IEEG may be of utility in planning epilepsy surgery for children with intractable epilepsy. Further research is required to better determine which patients may benefit from this technique a priori.

Electrical source imaging for presurgical focus localization in epilepsy patients with normal MRI

Patients with magnetic resonance (MR)-negative focal epilepsy (MRN-E) have less favorable surgical outcomes (between 40% and 70%) compared to those in whom an MRI lesion guides the site of surgical intervention (60-90%). Patients with extratemporal MRN-E have the worst outcome (around 50% chance of seizure freedom). We studied whether electroencephalography (EEG) source imaging (ESI) of interictal epileptic activity can contribute to the identification of the epileptic focus in patients with normal MRI. We carried out ESI in 10 operated patients with nonlesional MRI and a postsurgical follow-up of at least 1 year. Five of the 10 patients had extratemporal lobe epilepsy. Evaluation comprised surface and intracranial EEG monitoring of ictal and interictal events, structural MRI, [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET), ictal and interictal perfusion single photon emission computed tomography (SPECT) scans. Eight of the 10 patients also underwent intracranial monitoring. ESI correctly localized the epileptic focus within the resection margins in 8 of 10 patients, 9 of whom experienced favorable postsurgical outcomes. The results highlight the diagnostic value of ESI and encourage broadening its application to patients with MRN-E. If the surface EEG contains fairly localized spikes, ESI contributes to the presurgical decision process.

Uzun Dönemli Video-EEG Görüntülemenin Epilepsili Çocuklarda Sonuçları

Objective: This aim of this study was to evaluate usefulness and diagnostic efficacy of video-EEG monitoring in children with epilepsy in terms of differential diagnosis, epilepsy classification, management, presurgical evaluation, and nonepileptic events. Material and Methods: Three hundred eighty two children were evaluated concerning the nature of clinical behaviour, seizure classification, or work-up prior to epilepsy surgery. The patients were divided into two groups as younger than 6 years of age and older than 6.1. Seizure classification was performed using both ILAE 1981 and 1989 classifications. Localizing and lateralizing signs and nonepileptic events were also investigated. Results: One-hundred and seven (28%) of the patients were seizure free, 74 (19.4%) of them had nonepileptic events, 201 (52.6%) of them had real seizures. While the children younger than 6 years had more primary generalized seizures (37.2%) and epileptic spasm (16.3%), the children older than 6 years had more complex partial seizures (55.7%) and temporal lobe epilepsy (27.8%) (p<0.05). Contralateral head version (14.4%) was the most frequent lateralizing sign in both groups, and ipsilateral automatism (16.9%), contralateral dystonia (12.9%), and nose wiping (11.4%), were noted as well. Sixty eight percent of children with behaviour arrest had extratemporal lobe epilepsy, and 24% of them were younger than 6 years of age. Ictal fear was more common in temporal lobe epilepsy (64.2%). Forty three patients underwent epilepsy surgery. While 24 (56%) of them were performed resective surgery, 19 (44%) of them had vagal nerve stimulation. Conclusion: Prolonged video EEG monitoring is a mandatory method for assessment and successful management of children with refractory epilepsy, especially in patients enrolled for epilepsy surgery or suspected of having pseudoseizures and nonepileptic events.

Nonconvulsive Status Epilepticus Presenting with Throat Clearing as Part of Clinical Seizure Semiology

Oro-alimentary automatisms such as chewing movements, lip-smacking, repeated snuffling, swallowing and retching have been reported with seizures usually of temporal lobe origin. Throat clearing, usually along with other vegetative signs, has been reported in patients with temporal and rarely extra-temporal lobe epilepsy. We report a case of a 93-year-old woman admitted with acute right temporo-occipital stroke. Repeated throat clearing episodes raised suspicion for complex partial seizures. Video-EEG recording confirmed frequent right hemispheric focal seizures originating from the right posterior temporal area concordant with her cortical stroke. The value of throat clearing as a sign of complex partial seizures of temporal lobe origin and its lateralizing and localizing value is discussed.

Objective evaluation of personality and psychopathology in temporal lobe versus extratemporal lobe epilepsy

Previous research has been equivocal on personality trait and psychopathology differences between temporal lobe and other types of epilepsy, as well as between patients with right and left temporal lobe seizure foci. In this study, personality differences between patients with right temporal ( n = 23), left temporal ( n = 21), and extratemporal ( n = 24) epilepsy were investigated using the NEO Personality Inventory—Revised (NEO-PI-R). No statistically significant differences were found on any of the NEO-PI-R domains or facet trait scales. There were also no significant differences between groups on the Minnesota Multiphasic Personality Inventory 2 (MMPI-2), a measure of psychopathology. However, mild elevations were seen in all groups on clinical scales related to physical symptoms, health concern, and depression. These data suggest there are no consistent personality or psychopathology differences, as measured by the NEO-PI-R and the MMPI-2, between patients with left temporal, right temporal, and extratemporal epilepsy whose seizures are localized using video/EEG monitoring.

Seizure‐related injuries are underreported in pharmacoresistant localization‐related epilepsy

To investigate and compare injury rates, associated risk factors, circumstances, and medical record documentation in patients with pharmacoresistant temporal lobe epilepsy (TLE) and extratemporal lobe epilepsy (ETLE). The study cohort consisted of fifty-two consecutive adults with treatment-resistant epilepsy and seizure classification confirmed by video-electrocardiography (EEG) (28 with TLE and 24 with ETLE) who consented to participate. All subjects had their seizures classified with prior video-EEG monitoring, were followed in a tertiary-care center in northwest New York City, and received a semistructured phone interview regarding injuries experienced since being diagnosed with epilepsy. Injuries were reported in 16 (57%) of the patients with TLE and 4 (17%) of the patients with ETLE (p = 0.004 after controlling for duration of epilepsy and seizure burden); 83% of all injuries were designated by patients as seizure-related. Most injuries (22 of 41; 54%) were classified as moderate or greater in severity. In addition, one motor vehicle accident (MVA) was reported in the TLE group and one episode of sudden unexpected death (SUDEP) was identified in the ETLE group. More than half (55%) of the injuries were not documented as seizure-related in medical records. A substantial number of potentially serious injuries are not documented as seizure related, even in a tertiary-care setting. Patients with pharmacoresistant TLE may be at higher risk for experiencing an injury than patients with pharmacoresistant ETLE.

Surgery for extratemporal nonlesional epilepsy in children: a meta-analysis

Previous small studies have demonstrated that seizure outcomes following surgery for extratemporal lobe epilepsy (ETLE) in children are worse than those for temporal lobe epilepsy. We have conducted a meta-analysis of the available literature to better understand ETLE surgical outcomes in children. We searched PubMed (1990-2009) for appropriate studies using the following terms: ETLE, ETLE surgery, ETLE surgery outcome, frontal lobe epilepsy, occipital lobe epilepsy, and parietal lobe epilepsy. Our collected data included patient age at seizure onset and surgery, the cerebral lobe involved with epileptogenesis, MRI findings, predominant seizure semiology, intracranial monitoring use (electrode implantation), epileptic region histopathology, and postoperative seizure outcome. Statistical analysis was performed to determine associations among these variables and postoperative outcome. Ninety-five patients from 17 studies satisfied the inclusion criteria. Pathological findings (p = 0.039) and seizure type (p = 0.025) were significantly associated with outcome: A larger proportion of patients with cortical dysplasia and complex partial seizures experienced better outcomes. Age at surgery (p = 0.073) and the cerebral resection site (p = 0.059) were marginally associated with seizure outcome. This study confirms previous reports: Surgical outcomes for ETLE epilepsy are significantly worse than those for temporal lobe epilepsy. The reasons for this difference may include the diffuse nature of the pathology involved in ETLE, difficulty in localizing the seizure focus in young children, and involvement of "eloquent" nonresectable cortex in epileptogenesis. Because of the reporting variability among different epilepsy centers, more uniform protocols are necessary for fair evaluation and comparison of outcomes among the different centers.

Long‐term seizure outcome of surgery versus no surgery for drug‐resistant partial epilepsy: A review of controlled studies

A majority of patients with formerly drug-resistant temporal lobe epilepsy become seizure-free after surgery. However, apart from one 12-month randomized trial, it is unclear how many become seizure-free because of surgery. To determine the net benefit of surgery, we performed a systematic review and meta-analysis of the published evidence of how many patients in similar studies become seizure-free without surgery. Of 155 potentially eligible articles reviewed in full text, 29 (19%) fulfilled eligibility criteria. After excluding 9 publications, 20 studies form the base of evidence. Overall, 719 of 1,621 (44%) of patients with mostly temporal lobe surgery were seizure-free compared to 139 of 1113 (12%) of nonoperated controls [pooled random effects relative risk (RR) 4.26, 95% confidence interval (CI) 3.03-5.98]. The pooled risk difference in favor of surgery was 42% (95% CI 32-51%). We found no comparative outcome data in patients with extratemporal lobe epilepsy only. The available evidence from mostly nonrandomized observational studies indicates that in appropriately selected patients with drug-resistant temporal lobe epilepsy, the combination of surgery with medical treatment is 4 times as likely as medical treatment alone to achieve freedom from seizures.

Intracranial electroencephalography seizure onset patterns and surgical outcomes in nonlesional extratemporal epilepsy

Patients with normal MR imaging (nonlesional) findings and medically refractory extratemporal epilepsy make up a disproportionate number of nonexcellent outcomes after epilepsy surgery. In this paper, the authors investigated the usefulness of intracranial electroencephalography (iEEG) in the identification of surgical candidates. Between 1992 and 2002, 51 consecutive patients with normal MR imaging findings and extratemporal epilepsy underwent intracranial electrode monitoring. The implantation of intracranial electrodes was determined by seizure semiology, interictal and ictal scalp EEG, SPECT, and in some patients PET studies. The demographics of patients at the time of surgery, lobar localization of electrode implantation, duration of follow-up, and Engel outcome score were abstracted from the Mayo Rochester Epilepsy Surgery Database. A blinded independent review of the iEEG records was conducted for this study. Thirty-one (61%) of the 51 patients who underwent iEEG ultimately underwent resection for their epilepsy. For 28 (90.3%) of the 31 patients who had epilepsy surgery, adequate information regarding follow-up (> 1 year), seizure frequency, and iEEG recordings was available. Twenty-six (92.9%) of 28 patients had frontal lobe resections, and 2 had parietal lobe resections. The most common iEEG pattern at seizure onset in the surgically treated group was a focal high-frequency discharge (in 15 [53.6%] of 28 patients). Ten (35.7%) of the 28 surgically treated patients were seizure free. Fourteen (50%) had Engel Class I outcomes, and overall, 17 (60.7%) had significant improvement (Engel Class I and IIAB with > or =80% seizure reduction). Focal high-frequency oscillation at seizure onset was associated with Engel Class I surgical outcome (12 [85.7%] of 14 patients, p = 0.02), and it was uncommon in the nonexcellent outcome group (3 [21.4%] of 14 patients). A focal high-frequency oscillation (> 20 Hz) at seizure onset on iEEG may identify patients with nonlesional extratemporal epilepsy who are likely to have an Engel Class I outcome after epilepsy surgery. The prospect of excellent outcome in nonlesional extratemporal lobe epilepsy prior to intracranial monitoring is poor (14 [27.5%] of 51 patients). However, iEEG can further stratify patients and help identify those with a greater likelihood of Engel Class I outcome after surgery.

Contribution of subtraction ictal SPECT coregistered to MRI to epilepsy surgery: a multicenter study

A multicenter prospective study was performed to assess the additional value of a subtraction ictal SPECT coregistered to MRI (SISCOM) technique to traditional side-by-side comparison of ictal- and interictal SPECT images in epilepsy surgery. One hundred and twenty-three patients with temporal and extratemporal lobe epilepsy who had undergone epilepsy surgery after evaluation of scalp ictal and interictal electroencephalogram (EEG), MRI, and ictal and interictal SPECT scans were followed up in terms of postsurgical outcome for a period of at least 1 year. Three reviewers localized the epileptogenic focus using ictal and interictal SPECT images first by side-by-side comparison and subsequently by SISCOM. Concordance of the localization of the epileptogenic focus by SPECT diagnosis with the surgical site and inter-observer agreement between reviewers was compared between side-by-side comparison and SISCOM. Logistic regression analysis was performed in predicting the surgical outcome with the dependent variable being the achievement of a good postsurgical outcome and the independent variables using the SISCOM, side-by-side comparison of ictal and interictal SPECT images, MRI, and scalp ictal EEG. The SISCOM presented better concordance in extratemporal lobe epilepsy and less concordance in temporal lobe epilepsy than side-by-side comparison. Inter-observer concordance was higher in SISCOM than in side-by-side comparison. Much higher concordance of the epileptogenic focus by SPECT diagnosis with the surgical site was obtained in patients with good surgical outcome than in those with poor surgical outcome. These differences in concordance between good and poor surgical outcomes were greater in SISCOM than in side-by-side comparison. Logistic regression analysis showed the highest odds ratio of 12.391 (95% confidence interval; 3.319, 46.254) by SISCOM evaluation for concordance of the epileptogenic focus with the surgical site in predicting good surgical outcome. A SISCOM technique of ictal and interictal SPECT images provides higher predictive value of good surgical outcome and more reliability on the diagnosis of the epileptogenic focus than side-by-side comparison in medically intractable partial epilepsy.

Interleukin-6, interleukin-1 receptor antagonist and interleukin-1beta production in patients with focal epilepsy: A video–EEG study

Experimental and clinical studies have shown that prolonged seizures result in increased cytokine production in the central nervous system. The purpose of this study was to examine plasma concentrations of interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1Ra), and interleukin-1 beta (IL-1β) in 20 patients with epilepsy undergoing a video–EEG study. Plasma samples were obtained at the onset of the recordings and 3, 6, 12 and 24 h after the index seizure. Localization of the seizure focus and classification of epilepsy was based on concordant electroclinical findings in the video–EEG study, and on MRI examination. Patients were divided into two groups: temporal lobe epilepsy (TLE) ( n = 11), and extratemporal lobe epilepsy (XLE) ( n = 9). Results Only the TLE group showed significant increase in plasma levels of IL-6 peaking at 6 h postictally. Postictal plasma levels of IL-1RA and IL-1β did not significantly differ from baseline levels in either of the patient groups. IL-1RA showed a decreasing trend ( p > 0.059) in TLE patients during 12 to 24 postictal hours. Conclusions This study further supports the role of focal seizures in regulation of cytokine responses.

Interleukin-6 levels are increased in temporal lobe epilepsy but not in extra-temporal lobe epilepsy

Previous studies have reported activation of inflammatory cytokines in seizures, but clinical characteristics of epilepsy associated with cytokine activation have not been well established. In this study, serum levels of interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1RA) were measured, and clinical characteristics of epilepsy were assessed in 86 well-evaluated patients with refractory focal epilepsy and in 5 patients with controlled focal epilepsy. Epilepsy was evaluated based on patient histories, electroclinical findings, and high-resolution brain MRI scans. Sixty-three healthy blood donors served as controls. IL-6 concentrations were chronically increased in epilepsy patients (11%) compared with healthy controls (0%) (P = 0.007). Increased levels of IL-6 were more prevalent in patients with temporal lobe epilepsy (TLE) compared to patients with extra-TLE (P = 0.028). Also the mean and the median serum levels of IL-6 were higher in patients with TLE than in patients with extra-TLE (P = 0.042). Concentrations of IL-1RA were not significantly different in patients compared with controls. Indicated by increased levels of IL-6 in TLE, epilepsy type is important in determining chronic overproduction of cytokines in refractory focal epilepsy. The results may reflect a chronic immunological process in the brain in patients with refractory epilepsy.

PET and SPECT in epilepsy: A critical review

Molecular imaging with ictal and interictal single-photon emission computed tomography (SPECT) as well as positron emission tomography (PET) rank among the established functional imaging tests for the presurgical evaluation of epileptic onset zone in patients with intractable partial epilepsy. In temporal lobe epilepsy the sensitivity of these methods was shown to be excellent, in particular if a multimodal platform is used, which combines the functional imaging with the additional morphological information of magnetic resonance imaging (MRI), but was lower in extra temporal lobe epilepsy. Functional imaging with SPECT and PET reflects seizure related changes of cerebral perfusion, glucose-metabolism and neuroreceptor status. In this review the usefulness of SPECT and PET imaging in clinical routine in epilepsy as well as the role of different neuroreceptor PET-tracer, which were used in epilepsy are discussed. The use of perfusion SPECT tracer allows the investigation of ictal activations, but the low temporal resolution of ictal perfusion SPECT often results in the detection of both the ictal onset zone as well as the propagation pathways, an area that has not always need to be resected in order to render a patient seizure free. The additional use of interictal PET with fluorine-18 fluorodeoxyglucose which measures regional cerebral metabolism or interictal perfusion SPECT enhance the informational value of ictal SPECT and were shown to be important tools to better define the ictal onset and surround inhibition zones. In recent years PET imaging of different cerebral neuroreceptor-systems inter alia GABA(A) receptors, serotonin receptors (5-HT(1A)), opioid receptors as well as dopamine receptors was used to investigate the neurochemical basis of epilepsy, the role of these neurotransmitters for the epileptogenesis as well as the spread of epileptic activity during seizures and partially entered in clinical routine. Currently some of these radioligands are also used to investigate new treatment approaches.