Epileptogenic Zone In Patients Research Articles

Diagnostic Evaluation in Patients with Intractable Epilepsy and Normal Findings on MRI: A Decision Analysis and Cost-Effectiveness Study

Patients with focal intractable epilepsy and normal MR imaging findings frequently undergo further diagnostic tests to localize the epileptogenic zone. The aim of this study was to determine the cost-effective diagnostic strategy that will identify the epileptogenic zone in patients with suspected focal intractable epilepsy and normal MR imaging findings by using decision analysis. A Markov decision model was constructed by using sensitivities and specificities of test strategies, seizure outcomes following surgical and medical treatment, cost, utilities, probabilities, and standardized mortality ratios. We compared 6 diagnostic test strategies: PET, ictal SPECT, and MEG individually; and combinations of PET+SPECT, PET+MEG, and SPECT+MEG. The outcomes measured were health care costs, QALY, and ICER. One-way and probabilistic sensitivity analyses were conducted to adjust for uncertainties in model parameters. The preferred strategies were PET+MEG and SPECT. The health care cost of the baseline strategy (PET+MEG) was $95,612 with 16.30 QALY gained. SPECT cost $97,479 with 16.45 QALY gained and an ICER of $12,934/QALY gained compared with those in PET+MEG. One-way sensitivity analyses showed that the decisions of the model were sensitive to variations in sensitivity and specificity of the test strategies. Probabilistic sensitivity analysis showed that when the willingness to pay was <$10,000, PET+MEG was the favored strategy, but the favored strategy changed to SPECT when the willingness to pay was >$10,000. PET+MEG and SPECT were the preferred strategies in the base case. The choice of test was dependent on the sensitivity and specificity of test strategies and willingness to pay. Further study with a larger sample size is needed to obtain better estimates of sensitivity and specificity of diagnostic tests.

Localization of epileptogenic zones in Lennox–Gastaut syndrome using frequency domain source imaging of intracranial electroencephalography: a preliminary investigation

Although intracranial electroencephalography (iEEG) has been widely used to localize epileptogenic zones in epilepsy, visual inspection of iEEG recordings does not always result in a favorable surgical outcome, especially in secondary generalized epilepsy such as Lennox–Gastaut syndrome (LGS). Various computational iEEG analysis methods have recently been introduced to confirm the visual inspection results. Of these methods, high gamma oscillation in iEEG has attracted interest because a series of studies have reported a close relationship between epileptogenic zones and cortical areas with high gamma oscillation. Meanwhile, frequency domain source imaging of EEG and MEG oscillations has proven to be a useful auxiliary tool for identifying rough locations of epileptogenic zones. To the best of our knowledge, however, frequency domain source imaging of high gamma iEEG oscillations has not been studied. In this study, we investigated whether the iEEG-based frequency domain source imaging of high gamma oscillation (60–100 Hz) would be a useful supplementary tool for identifying epileptogenic zones in patients with secondary generalized epilepsy. The method was applied to three successfully operated on LGS patients, whose iEEG contained some ictal events with distinct high gamma oscillations before seizure onset. The resultant cortical source distributions were compared with surgical resection areas and with high gamma spectral power distributions on the intracranial sensor plane. While the results of the sensor-level analyses contained many spurious activities, the results of frequency domain source imaging coincided better with the surgical resection areas, suggesting that the frequency domain source imaging of iEEG high gamma oscillations might help enhance the accuracy of pre-surgical evaluations of patients with secondary generalized epilepsy.

Identifying the Epileptic Network

Identifying the Epileptic Network

Surgery after intracranial investigation with subdural electrodes in patients with drug-resistant focal epilepsy: outcome and complications

Video-EEG monitoring with intracranial subdural electrodes is a useful assessment tool for the localization of the epileptogenic zone in patients with drug-resistant focal epilepsy. We aimed at assessing the morbidity related to electrode implantation and the surgical outcome in patients who underwent epilepsy surgery after intracranial EEG monitoring. All patients (N = 58) admitted to our Epilepsy Surgery Centre for drug-resistant focal epilepsy who underwent resective surgery after intracranial monitoring with subdural electrodes and were followed up for at least 2 years were included in the study. Their mean age was 30.4 years (range 8-60 years), 25 (43 %) were female, and 44 (76 %) had a preoperatively detected structural lesion. The mean duration of invasive recording was 2.3 days (range 1-14 days). Extraoperative ECoG allowed the identification of the epileptogenic focus in all cases. The temporal lobe was involved in 21 (36 %) patients, whereas extratemporal foci were identified in 24 (41 %) patients. Thirteen patients (23 %) had multilobar involvement. Functional brain mapping was performed in 15 (26 %) patients. Transient complications related to electrode implantation occurred in three patients. Among patients with evidence of lesion on preoperative MRI, lesionectomy alone was performed in 12 cases (27 %), while it was combined with tailored cortical resection in the remaining cases. Tailored cortical resection was also performed in patients without evidence of lesion on MRI. After resective surgery, transient neurological deficits occurred in five cases, while another patient experienced permanent lateral homonymous hemianopia. At the last follow-up observation, 34 (57 %) patients were seizure-free (Engel class I). This study suggests that invasive EEG recording with subdural electrodes may be useful and fairly safe for many candidates for epilepsy surgery.

Usefulness of extent analysis for statistical parametric mapping with asymmetry index using inter-ictal FGD-PET in mesial temporal lobe epilepsy

Inter-ictal (18)F-2-fluoro-deoxy-D: -glucose-positron emission tomography (FDG-PET) is widely used for preoperative evaluation to identify epileptogenic zones in patients with temporal lobe epilepsy. In this study, we combined statistical parametric mapping (SPM) with the asymmetry index and volume-of-interest (VOI) based extent analysis employing preoperative FDG-PET in unilateral mesial temporal lobe epilepsy (MTLE) patients. We also evaluated the detection utility of these techniques for automated identification of abnormalities in the unilateral hippocampal area later confirmed to be epileptogenic zones by surgical treatment and subsequent good seizure control. FDG-PET scans of 17 patients (9 males, mean age 35years, age range 16-60years) were retrospectively analyzed. All patients had been preoperatively diagnosed with unilateral MTLE. The surgical outcomes of all patients were Engel class 1A or 1B with postoperative follow-up of 2years. FDG-PET images were spatially normalized and smoothed. After two voxel-value adjustments, one employing the asymmetry index and the other global normalization, had been applied to the images separately, voxel-based statistical comparisons were performed with 20 controls. Peak analysis and extent analysis in the VOI in the parahippocampal gyrus were conducted for SPM. For the extent analysis, a receiver operating characteristic (ROC) curve was devised to calculate the area under the curve and to determine the optimal threshold of extent. The accuracy of the method employing the asymmetry index was better than that of the global normalization method for both the peak and the extent analysis. The ROC analysis results, for the extent analysis, yielded an area under the curve of 0.971, such that the accuracy and optimal extent threshold of judgment were 92 and 32.9%, respectively. Statistical z-score mapping with the asymmetry index was more sensitive for detecting regional glucose hypometabolism and more accurate for identifying the side harboring the epileptogenic zone using inter-ictal FDG-PET in unilateral MTLE than z-score mapping with global normalization. Moreover, the automated determination of the side with the epileptogenic zone in unilateral MTLE showed improved accuracy when the combination of SPM with the asymmetry index and extent analysis was applied based on the VOI in the parahippocampal gyrus.

Versive seizures in occipital lobe epilepsy: Lateralizing value and pathophysiology

To clarify the value of versive seizures in lateralizing and localizing the epileptogenic zone in patients with occipital lobe epilepsy, we studied 13 occipital lobe epilepsy patients with at least one versive seizure recorded during preoperative noninvasive video-EEG monitoring, who underwent occipital lobe resection, and were followed postoperatively for more than 2 years with Engel's class I outcome. The videotaped versive seizures were analyzed to compare the direction of version and the side of surgical resection in each patient. Moreover, we examined other motor symptoms (partial somatomotor manifestations such as tonic and/or clonic movements of face and/or limbs, automatisms, and eyelid blinking) associated with version. Forty-nine versive seizures were analyzed. The direction of version was always contralateral to the side of resection except in one patient. Among accompanying motor symptoms, partial somatomotor manifestations were observed in only five patients. In conclusion, versive seizure is a reliable lateralizing sign indicating contralateral epileptogenic zone in occipital lobe epilepsy. Since versive seizures were accompanied by partial somatomotor manifestations in less than half of the patients, it is suggested that the mechanism of version in occipital lobe epilepsy is different from that in frontal lobe epilepsy.

Histopathology of cortex and white matter in pediatric epileptic spasms: Comparison with those of partial seizures

Epileptic spasms in older children have increasingly been recognized as a distinct seizure type and subset of these patients are considered for surgical resection. This study compares histopathology and magnetic resonance imaging (MRI), especially focusing the difference between the cortical grey matter and the subcortical white matter to understand the extensive epileptic brain in patients with epileptic spasms. We examined 22 patients consisting of 11 patients with epileptic spasms and 11 with partial seizures. Scalp video electroencephalography (EEG) showed interictal generalized epileptiform discharges (9 patients with epileptic spasms vs. 1 with partial seizures) and ictal generalized epileptiform discharges (10 vs. 3). We found MRI abnormalities in a single lobe (6 vs. 7) and multiple lobes (2 vs. 1). Surgical resections were performed across multiple lobes (9 vs. 2), comparing within a single lobe (2 vs. 9), ( p < 0.001). Histopathology showed abnormal cortical organizations as FCD (2 vs. 5) and microdysgenesis (4 vs. 4), normal (4 vs. 1). Two patients with epileptic spasms showed hyaline proteoplasmic astrocytopathy. There were heterotopic neurons (10 vs. 10), cluster of oligodendroglia (8 vs. 7), balloon cells (2 vs. 5) and blurred myelination (1 vs. 4), in the white matter. Seizure-free outcomes were seen in seven patients with epileptic spasms (64%) and four with partial seizures (36%). The multilobar epileptogenic zones existed in patients with epileptic spasms, compared with the focal epileptogenic zone in patients with partial seizures. There was no difference of MRI and histopathology findings in cortex and subcortical white matter between two groups.

Bilateral invasive electroencephalography in patients with tuberous sclerosis complex: a path to surgery?

Many children with epilepsy and tuberous sclerosis complex (TSC) have multiple tubers on MR imaging and poorly localized/lateralized video electroencephalography (EEG) findings. Given the long-term risks associated with frequent seizures and multiple antiepileptic drugs, along with improved success in identifying focal epileptogenic zones in patients with multifocal lesions, the authors used bilateral intracranial EEG to lateralize the epileptogenic zone in patients with nonlateralizable noninvasive preoperative evaluations. A retrospective analysis from January 1, 1998, to June 30, 2008, identified 62 children with TSC who were presented at a surgical conference. Of the 52 patients undergoing diagnostic or therapeutic procedures during the study period, 20 underwent bilateral intracranial EEG. The presurgical testing results, intracranial EEG findings, surgical interventions, and outcomes were reviewed. Fourteen of 20 patients had intracranial EEG findings consistent with a resectable epileptogenic zone. One patient is awaiting further resection. Five patients had findings consistent with a nonresectable epileptogenic zone, and 1 of these patients underwent a callosotomy. Seven patients had Engel Class I outcomes, 1 was Class II, 3 were Class III, and 3 were Class IV (mean follow-up 25 months). Bilateral intracranial EEG can identify potential resectable seizure foci in nonlateralizable epilepsy in TSC. Although 6 of 20 patients did not undergo resection (1 patient is pending future resection), significant improvements in seizures (Engel Class I or II) were noted in 8 patients. In the authors' experience, this invasive monitoring provided a safe method for identifying the ictal onset zone.

Evaluation of Algorithms for Intracranial EEG (iEEG) Source Imaging of Extended Sources: Feasibility of Using iEEG Source Imaging for Localizing Epileptogenic Zones in Secondary Generalized Epilepsy

Precise identification of epileptogenic zones in patients with intractable drug-resistant epilepsy is critical for successful epilepsy surgery. Numerous source-imaging algorithms for localizing epileptogenic zones based on scalp electroencephalography (EEG) and magnetoencephalography (MEG) have been developed and validated in simulation and experimental studies. Recently, intracranial EEG (iEEG)-based imaging of epileptogenic sources has attracted interest as a promising tool for presurgical evaluation of epilepsy; however, most iEEG studies have focused on localization of epileptogenic zones in focal epilepsy. In the present study, we investigated whether iEEG source imaging is a useful supplementary tool for identifying extended epileptogenic sources in secondary generalized epilepsy such as Lennox-Gastaut syndrome (LGS). To this end, we applied four different cortical source imaging algorithms, namely minimum norm estimation (MNE), low-resolution electromagnetic tomography (LORETA), standardized LORETA (sLORETA), and L(p)-norm estimation (p = 1.5, referred to as Lp1.5), to artificial iEEG datasets generated assuming various source sizes and locations. We also applied these four algorithms to clinical ictal iEEG recordings acquired from a pediatric patient with LGS. Interestingly, the traditional MNE algorithm outperformed the other imaging algorithms in most of our experiments, particularly in cases when larger-sized sources were activated. Although sLORETA outperformed both LORETA and Lp1.5, its performance was not as good as that of MNE. Compared to the other algorithms, the performance of Lp1.5 decayed most rapidly as the source size increased. Our findings suggest that iEEG source imaging using MNE is a promising auxiliary tool for the identification of epileptogenic zones in secondary generalized epilepsy. We anticipate that our results will provide useful guidelines for selection of an appropriate imaging algorithm for iEEG source imaging studies.

Subclinical Abnormal Gyration Pattern, a Potential Anatomic Marker of Epileptogenic Zone in Patients With Magnetic Resonance Imaging–Negative Frontal Lobe Epilepsy

Epilepsy surgery for magnetic resonance imaging (MRI)-negative patients has a less favorable outcome. Detection of subclinical abnormal gyration (SAG) patterns and their potential contribution to assessment of the topography of the epileptogenic zone (EZ) is addressed in MRI-negative patients with frontal lobe epilepsy. Between September 1998 and July 2005, 12 MRI-negative frontal lobe epilepsy patients underwent stereoelectroencephalography with postcorticectomy follow-up of longer than 1 year (average, 3.3 years). Original software (BrainVISA/Anatomist, http://brainvisa.info) trained on a database of normal volunteers was used to determine which sulci had morphology out of the normal range (SAG). Topography of the EZ, SAG pattern, corticectomy, postoperative seizure control, and histopathology were analyzed. At last follow-up, 8 of 12 patients (66.7%) were Engel class I (7 IA and 1 IB), 2 class II, and 2 class IV. Small focal cortical dysplasia was histologically diagnosed in 9 of the 12 patients (75%), including 7 of 8 seizure-free patients (87.5%). A SAG pattern was found to be in the EZ area in 9 patients (75%), in the ipsilateral frontal lobe out of the EZ in 2, and limited to the contralateral hemisphere in 1. SAG patterns appear to be associated with the topography of the EZ in MRI-negative frontal lobe epilepsy and may have a useful role in preoperative assessment. Small focal cortical dysplasia not detected with MRI is often found on histopathological examination, particularly in the depth of the posterior part of the superior frontal sulcus and intermediate frontal sulcus, suggesting a specific developmental critical zone in these locations.

Source localization in magnetoencephalography to identify epileptogenic foci

Rationale Magnetoencephalography (MEG) is useful to localize epileptic foci in epilepsy as MEG has higher spatio-temporal resolution than conventional diagnostic imaging studies; positron emission computed tomography, single photon emission computed tomography and magnetic resonance imaging (MRI). Methods We use 204-channel helmet-shaped MEG with a sampling rate of 600 Hz. A single dipole method calculates equivalent current dipoles to localize epileptic sources. The equivalent current dipoles are superimposed onto MRI as magnetic source imaging (MSI). Ictal MEG data are analyzed using time–frequency analysis. The power spectrum density is calculated using short-time Fourier transform and superimposed onto MRI results. Results Clustered equivalent current dipoles represent epileptogenic zones in patients with localization-related epilepsy. The surgical plan is reliably developed from source localizations of dipoles and power spectrum of interictal spike discharges, and ictal frequency. Conclusion MEG is indispensable in diagnosis and surgical resection for epilepsy to accurately localize the epileptogenic zone.

Role of resting state functional connectivity MRI in presurgical investigation of mesial temporal lobe epilepsy

ObjectiveThe authors aimed to determine the ability of resting-state functional connectivity MRI (fcMRI) to lateralise/localise the epileptogenic zone in patients presenting with mesial temporal lobe epilepsy (MTLE) at the individual...

Identification of the epileptogenic zone in patients with tuberous sclerosis: Concordance of interictal and ictal epileptiform activity

In the majority of patients with tuberous sclerosis complex (TSC) multifocal epileptiform activity is present interictally. Therefore, its value in identifying epilepsy surgery candidates has been doubted. We hypothesize that dominant interictal epileptiform foci are concordant with the ictal onset zone in TSC patients. Consistency and dominance of focal interictal epileptiform activity was assessed in 19 patients with a clinical definite diagnosis of TSC. The ictal onset zone was identified. Concordance between interictal en ictal findings was analyzed. If concordance was found epilepsy surgery was proposed. We found dominant, consistently present, focal interictal epileptiform activity in 14 of the 19 patients. Concordance between the dominant interictal focus and the ictal onset zone was found in 11 of the 14 patients (79%). In one patient the ictal onset zone could not be identified and discordance was present in two patients. Epilepsy surgery was performed in six patients rendering three of them seizure free, and one had a seizure reduction >90%. In these patients local concordance was found whereas regional concordance was found in the two patients who did not benefit from epilepsy surgery. A dominant as well as a consistent interictal focus is concordant with the ictal onset zone in the majority of TSC patients. Future studies of TSC patients addressing the value of interictal foci in the consideration of epilepsy surgery, in absence of clear ictal onset zone, are necessary.

Reevaluating the mechanisms of focal ictogenesis: The role of low‐voltage fast activity

The mechanisms that control the transition into a focal seizure are still uncertain. The introduction of presurgical intracranial recordings to localize the epileptogenic zone in patients with drug-resistant focal epilepsies opened a new window to the interpretation of seizure generation (ictogenesis). One of the most frequent focal patterns observed with intracranial electrodes at seizure onset is characterized by low-voltage fast activity in the beta-gamma range that may or may not be preceded by changes of ongoing interictal activities. In the present commentary, the mechanisms of generation of focal seizures are reconsidered, focusing on low-voltage fast activity patterns. Experimental findings on models of temporal lobe seizures support the view that the low-voltage fast activity observed at seizure onset is associated with reinforcement and synchronization of inhibitory networks. A minor role for the initiation of the ictal pattern is played by principal neurons that are progressively recruited with a delay, when inhibition declines and synchronous high-voltage discharges ensue. The transition from inhibition into excitatory recruitment is probably mediated by local increase in potassium concentration associated with synchronized interneuronal firing. These findings challenge the classical theory that proposes an increment of excitation and/or a reduction of inhibition as a cause for the transition to seizure in focal epilepsies. A new definition of ictogenesis mechanisms, as herewith hypothesized, might possibly help to develop new therapeutic strategies for focal epilepsies.

Research priorities in epilepsy for the next decade—A representative view of the European scientific community: Summary of the ILAE Epilepsy Research Workshop, Brussels, 17–18 January 2008

Research priorities in epilepsy for the next decade—A representative view of the European scientific community: Summary of the ILAE Epilepsy Research Workshop, Brussels, 17–18 January 2008

Neuroimaging in Epilepsy: Diagnostic Strategies in Partial Epilepsy

The diagnostic evaluation of the patient with partial or localization-related epilepsy is designed to identify treatment strategies that will permit the individual to be seizure-free. The use of magnetic resonance imaging (MRI) has been pivotal in elucidating the presence of an epileptogenic pathological alteration that may coexist with the site of seizure onset. There are compelling data that MRI is of significant diagnostic and prognostic importance in patients with partial epilepsy. Patients with MRI-negative partial epilepsy may be candidates for additional neuroimaging techniques including positron emission tomography, MR spectroscopy, and single photon emission tomography. Contemporary innovations with peri-ictal imaging may allow identification of the epileptogenic zone in patients with normal MRI scans. This discussion will focus on the management of the adult patient with seizures and epilepsy, emphasizing the neuroimaging evaluation and treatment of patients with medically refractory seizure disorders.

MRI-negative refractory partial epilepsy: Role for diffusion tensor imaging in high field MRI

Our aim is to use the high field MR scanner (3T) to verify whether diffusion tensor imaging (DTI) could help in locating the epileptogenic zone in patients with MRI-negative refractory partial epilepsy. Fifteen patients with refractory partial epilepsy who had normal conventional MRI, and 40 healthy volunteers were recruited for the study. DTI was performed on a 3T MR scanner, individual maps of mean diffusivity (MD) and fractional anisotropy (FA) were calculated, and Voxel-Based Analysis (VBA) was performed for individual comparison between patients and controls. Voxel-based analysis revealed significant MD increase in variant regions in 13 patients. The electroclinical seizure localization was concurred to seven patients. No patient exhibited regions of significant decreased MD. Regions of significant reduced FA were observed in five patients, with two of these concurring with electroclinical seizure localization. Two patients had regions of significant increase in FA, which were distinct from electroclinical seizure localization. Our study's results revealed that DTI is a responsive neuroradiologic technique that provides information about the epileptogenic areas in patients with MRI-negative refractory partial epilepsy. This technique may also helpful in pre-surgical evaluation.

Fast oscillations associated with interictal spikes localize the epileptogenic zone in patients with partial epilepsy

Although interictal epileptic spikes are defined as fast transient activity, the spatial distribution of spike-related high-frequency power changes is unknown. In this study, we localized the sources of spike-locked power increases in the beta and gamma band with magnetoencephalography and an adaptive spatial filtering technique and tested the usefulness of these reconstructions for determining the epileptogenic zone in a population of 27 consecutive presurgical patients with medication refractory partial epilepsies. The reliability of this approach was compared to the performance of conventional MEG techniques such as equivalent current dipole (ECD) models. In patients with good surgical outcome after a mean follow-up time of 16 months (Engel class I or II), the surgically resected area was identified with an accuracy of 85% by sources of spike-locked beta/gamma activity, which compared favorably with the accuracy of 69% found for ECD models of single spikes. In patients with a total of more than 50 spikes in their recordings, the accuracies increased to 100% vs. 88%, respectively. Imaging of spike-locked beta/gamma power changes therefore seems to be a reliable and fast alternative to conventional MEG techniques for localizing epileptogenic tissue, in particular, if more than 50 interictal spikes can be recorded.

Is Behavior in Temporal Lobe Epilepsy Different than in Other Epilepsies? the Jury is Out

Interictal Depression, Anxiety, Personality Traits, and Psychological Dissociation in Patients with Temporal Lobe Epilepsy (TLE) and Extra-TLE. Swinkels WA, van Emde Boas W, Kuyk J, van Dyck R, Spinhoven P. Epilepsia 2006;47(12):2092–2103. PURPOSE: This study was performed to investigate the relation between symptoms of interictal depression, anxiety, personality traits, and psychological dissociation with the localization and lateralization of the epileptogenic zone in patients with partial epilepsy. METHODS: All patients were diagnosed according to the localization-related concept of the 1989 International League Against Epilepsy (ILAE) Classification of Epilepsies and Epileptic Syndromes, and the localization and lateralization of the epileptogenic zone was established by using the clinical criteria for noninvasive presurgical evaluation. This resulted in 67 patients with temporal lobe epilepsy (TLE) and 64 patients with extra-TLE. All patients were assessed on the various aspects of psychopathology by using a comprehensive battery of standardized diagnostic instruments. RESULTS: We did not find the hypothesized excess of psychiatric symptoms in patients with (mesial) TLE in comparison with patients with extra-TLE. We also found no differences between patients with the lateralization of epilepsy in the left versus the right hemisphere. CONCLUSIONS: TLE per se cannot be considered a risk factor in developing more or more severe symptoms of psychopathology in patients with partial epilepsy. Concomitant factors, such as the duration of epilepsy, seizure frequency, and frontal lobe dysfunction may play an additional role. Our findings support the hypothesis of a multifactorial explanation for the psychiatric symptoms in patients with epilepsy.

Expression and cellular distribution of multidrug resistance-related proteins in patients with focal cortical dysplasia

Recent arouse of interest indicated that drug resistant proteins are markedly over-expressed in the epileptogenic tissue and they may be responsible for the one-third of the epileptic patients who were refractory to anti-epileptic drugs (AEDs). Since several AEDs may act as substrates for these drug resistant proteins, the enhanced function of such proteins may increase drug extrusion, resulting in inadequate response to drug therapy in patients with epilepsy. We studied expression of the multidrug resistance protein 1 (MDR1) and multidrug resistance-associated protein 1 (MRP1) in the epileptic tissues resected surgically in 28 patients with focal cortical dysplasia (FCD) by immunohistochemistry. The results were compared with 10 normal necropsy brain tissues. Normal brain showed no MDR1 expression in neurons and astrocytes, while MRP1 expression was very weak, which were encountered in a few samples. MDR1 expression was mainly localized on the vascular endothelial cells. In contrast to normal brain, we found intense MDR1 and MRP1 expression in both neurons and reactive astrocytes in the vast majority of dysplastic tissues. The majority of the dysplastic neurons demonstrated moderate to strong MRP1 immunoreactivity. Endothelial cells showed both MDR1 and MRP1 expression in the majority of the specimens studied. Multidrug transporters are over-expressed in the epileptogenic zone in patients with FCD. These results are concordant with previous studies, in which over-expression of multidrug proteins were shown in epileptogenic brain tissue in patients with FCD, that the over-expression of drug transport proteins in tissue from patients with refractory epilepsy may explain one possible mechanism for drug resistant in these pathologies.