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Objective: The absence of MRI-lesion reduces considerably the probability of having an excellent outcome (International League Against Epilepsies [ILAE] class I-II) after epilepsy surgery. Surgical success in magnetic-resonance imaging (MRI)-negative cases relies therefore mainly on non-invasive techniques such as positron-emission tomography (PET), subtraction ictal/inter-ictal single-photon-emission-computed-tomography co-registered to MRI (SISCOM), electric source imaging (ESI) and morphometric MRI analysis (MAP). We were interested in identifying the optimal imaging technique or combination to achieve post-operative class I-II in patients with MRI-negative focal epilepsy., Methods: We identified 168 epileptic patients without MRI lesion. Thirty-three (19.6%) were diagnosed with unifocal epilepsy, underwent surgical resection and follow-up ⩾ 2 years. Sensitivity, specificity, predictive values, and diagnostic odds ratio (OR) were calculated for each technique individually and in combination (after co-registration)., Results: 23/33 (70%) were free of disabling seizures (75.0% with temporal and 61.5% extratemporal lobe epilepsy). None of the individual modalities presented an OR > 1.5, except ESI if only patients with interictal epileptiform discharges (IEDs) were considered (OR 3.2). On a dual combination, SISCOM with ESI presented the highest outcome (OR = 6). MAP contributed to detecting indistinguishable focal cortical dysplasia in particular in extratemporal epilepsies with a sensitivity of 75%. Concordance of PET, ESI on interictal epileptic discharges, and SISCOM was associated with the highest chance for post-operative seizure control (OR = 11)., Conclusion: If MRI is negative, the chances to benefit from epilepsy surgery are almost as high as in lesional epilepsy, provided that multiple established non-invasive imaging tools are rigorously applied and co-registered together., (© 2023. The Author(s).)

In patients with drug-resistant epilepsy who are considering surgery, intracranial EEG (iEEG) helps delineate the putative epileptogenic zone. In a minority of patients, iEEG fails to identify seizure onsets. In such cases, it might be worthwhile to reimplant more iEEG electrodes. The consequences of such a strategy for the patient are unknown. We matched 12 patients in whom the initially implanted iEEG electrodes did not delineate the seizure onset zone precisely enough to offer resective surgery, and in whom additional iEEG electrodes were implanted during the same inpatient stay, to controls who did not undergo reimplantation. Seven cases and eight controls proceeded to resective surgery. No intracranial infection occurred. One control suffered an intracranial hemorrhage. Three cases and two controls suffered from a post-operative neurological or neuropsychological deficit. We found no difference in post-operative seizure control between cases and controls. Compared to an ILAE score of 5 (ie, stable seizure frequency in the absence of resective surgery), cases showed significant improvement. Reimplantation of iEEG electrodes can offer the possibility of resective epilepsy surgery to patients in whom the initial iEEG investigation was inconclusive, without compromising on the risk of complications or seizure control., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: Structure-function coupling remains largely unknown in brain disorders. We studied this coupling during interictal epileptic discharges (IEDs), using graph signal processing in temporal lobe epilepsy (TLE)., Methods: We decomposed IEDs of 17 patients on spatial maps, i.e. network harmonics, extracted from a structural connectome. Harmonics were split in smooth maps (long-range interactions reflecting integration) and coarse maps (short-range interactions reflecting segregation) and were used to reconstruct the part of the signal coupled (Xc) and decoupled (Xd) from the structure, respectively. We analysed how Xc and Xd embed the IED energy over time, at global and regional level., Results: For Xc, the energy was smaller than for Xd before the IED onset (p < .001), but became larger around the first IED peak (p < .05, cluster 2, C2). Locally, the ipsilateral mesial regions were significantly coupled to the structure over the whole epoch. The ipsilateral hippocampus increased its coupling during C2 (p < .01)., Conclusions: At whole-brain level, segregation gives way to integrative processes during the IED. Locally, brain regions commonly involved in the TLE epileptogenic network increase their reliance on long-range couplings during IED (C2)., Significance: In TLE, integration mechanisms prevail during the IED and are localized in the ipsilateral mesial temporal regions., (Copyright © 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objective: Electric source imaging (ESI) of interictal epileptiform discharges (IEDs) has shown significant yield in numerous studies; however, its implementation at most centers is labor- and cost-intensive. Semiautomatic ESI analysis (SAEA) has been proposed as an alternative and has previously shown benefit. Computer-assisted automatic spike cluster retrieval, averaging, and source localization are carried out for each cluster and are then reviewed by an expert neurophysiologist, to determine their relevance for the individual case. Here, we examine its yield in a prospective single center study., Method: Between 2017 and 2022, 122 patients underwent SAEA. Inclusion criteria for the current study were unifocal epilepsy disorder, epilepsy surgery with curative purpose, and postoperative follow-up of 2 years or more. All patients (N=40) had continuous video-electroencephalographic (EEG) monitoring with 37 scalp electrodes, which underwent SAEA. Forty patients matched our inclusion criteria., Results: Twenty patients required intracranial monitoring; 13 were magnetic resonance imaging (MRI)-negative. Mean duration of analyzed EEG was 4.3 days (±3.1 days), containing a mean of 12 749 detected IEDs (±22 324). The sensitivity, specificity, and accuracy of SAEA for localizing the epileptogenic focus of the entire group were 74.3%, 80%, and 75%, respectively, leading to an odds ratio (OR) of 11.5 to become seizure-free if the source was included in the resection volume (p < .05). In patients with extratemporal lobe epilepsy, our results indicated an accuracy of 68% (OR=11.7). For MRI-negative patients (n = 13) and patients requiring intracranial EEG (n = 20), we found a similarly high accuracy of 84.6% (OR=19) and 75% (OR = 15.9), respectively., Significance: In this prospective study of SAEA of long-term video-EEG, spanning several days, we found excellent localizing information and a high yield, even in difficult patient groups. This compares favorably to high-density ESI, most likely due to marked improved signal-to-noise ratio of the averaged IEDs. We propose including ESI, or SAEA, in the workup of all patients who are referred for epilepsy surgery., (© 2022 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background and Purpose: The purpose was to evaluate whether intracranial interictal epileptiform discharges (IEDs) that are not visible on the scalp are associated with changes in the frequency spectrum on scalp electroencephalograms (EEGs)., Methods: Simultaneous scalp high-density EEG and intracranial EEG recordings were recorded in nine patients undergoing pre-surgical invasive recordings for pharmaco-resistant temporal lobe epilepsy. Epochs with hippocampal IED visible on intracranial EEG (ic-IED) but not on scalp EEG were selected, as well as control epochs without ic-IED. Welch's power spectral density was computed for each scalp electrode and for each subject; the power spectral density was further averaged across the canonical frequency bands and compared between the two conditions with and without ic-IED. For each patient the peak frequency in the delta band (the significantly strongest frequency band in all patients) was determined during periods of ic-IED. The five electrodes showing strongest power at the peak frequency were also determined., Results: It was found that intracranial IEDs are associated with an increase in delta power on scalp EEGs, in particular at a frequency ≥1.4 Hz. Electrodes showing slow frequency power changes associated with IEDs were consistent with the hemispheric lateralization of IEDs. Electrodes with maximum power of slow activity were not limited to temporal regions but also involved frontal (bilateral or unilateral) regions., Conclusions: In patients with a clinical picture suggestive of temporal lobe epilepsy, the presence of delta slowing ≥1.4 Hz in anterior temporal regions can represent a scalp marker of hippocampal IEDs. To our best knowledge this is the first study that demonstrates the co-occurrence of ic-IED and increased delta power., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objective: In patients with epilepsy, interictal epileptic discharges are a diagnostic hallmark of epilepsy and represent abnormal, so-called "irritative" activity that disrupts normal cognitive functions. Despite their clinical relevance, their mechanisms of generation remain poorly understood. It is assumed that brain activity switches abruptly, unpredictably, and supposedly randomly to these epileptic transients. We aim to study the period preceding these epileptic discharges, to extract potential proepileptogenic mechanisms supporting their expression., Methods: We used multisite intracortical recordings from patients who underwent intracranial monitoring for refractory epilepsy, the majority of whom had a mesial temporal lobe seizure onset zone. Our objective was to evaluate the existence of proepileptogenic windows before interictal epileptic discharges. We tested whether the amplitude and phase synchronization of slow oscillations (.5-4 Hz and 4-7 Hz) increase before epileptic discharges and whether the latter are phase-locked to slow oscillations. Then, we tested whether the phase-locking of neuronal activity (assessed by high-gamma activity, 60-160 Hz) to slow oscillations increases before epileptic discharges to provide a potential mechanism linking slow oscillations to interictal activities., Results: Changes in widespread slow oscillations anticipate upcoming epileptic discharges. The network extends beyond the irritative zone, but the increase in amplitude and phase synchronization is rather specific to the irritative zone. In contrast, epileptic discharges are phase-locked to widespread slow oscillations and the degree of phase-locking tends to be higher outside the irritative zone. Then, within the irritative zone only, we observe an increased coupling between slow oscillations and neuronal discharges before epileptic discharges., Significance: Our results show that epileptic discharges occur during vulnerable time windows set up by a specific phase of slow oscillations. The specificity of these permissive windows is further reinforced by the increased coupling of neuronal activity to slow oscillations. These findings contribute to our understanding of epilepsy as a distributed oscillopathy and open avenues for future neuromodulation strategies aiming at disrupting proepileptic mechanisms., (© 2021 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: Preoperative workup aims at localizing the epileptogenic focus to achieve postoperative seizure-freedom. We studied the predictive value of non-invasive techniques, i.e. structural magnetic resonance imaging [MRI], high-density electric source imaging [HD-ESI] and metabolic imaging (positron emission tomography [PET]; single-photon emission computed tomography [SPECT]), in surgically treated patients., Methods: A prospective study of 190 epileptic operated patients, with >12 months follow-up and analyzed with state-of-the-art algorithms. 58 patients underwent all techniques. We computed sensitivity, specificity, predictive value and diagnostic odds ratio (OR) in relation to postoperative outcome., Results: Of 190 patients, 148 (77.9%) were seizure-free at follow-up. Resection of the epileptogenic focus was associated with favorable postsurgical outcome (p<0.05). Among 58 patients who underwent all tests, only MRI and HD-ESI were favorable outcome predictors (MRI: OR 10.9, p=0.004; HD-ESI: OR 13.1, p=0.004). Patients with concordant structural MRI and HD-ESI results had 92.3% (24/26) probability of favorable outcome. When both results were negative, probability was 0% (0/5); and when they disagreed, it was 63.0% (17/27)., Conclusions: Combination of MRI and HD-ESI offered the highest predictive value for postoperative seizure-freedom., Significance: This finding highlights the added value of HD-ESI in the presurgical workup, in particular in combination with an informative MRI., (Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Electrical source imaging (ESI) aims at reconstructing the electrical brain activity from scalp EEG. When applied to interictal epileptiform discharges (IEDs), this technique is of great use for identifying the irritative zone in focal epilepsies. Inaccuracies in the modeling of electro-magnetic field propagation in the head (forward model) may strongly influence ESI and lead to mislocalization of IED generators. However, a systematic study on the influence of the selected head model on the localization precision of IED in a large number of patients with known focus localization has not yet been performed. We here present such a performance evaluation of different head models in a dataset of 38 epileptic patients who have undergone high-density scalp EEG, intracranial EEG and, for the majority, subsequent surgery. We compared ESI accuracy resulting from three head models: a Locally Spherical Model with Anatomical Constraints (LSMAC), a Boundary Element Model (BEM) and a Finite Element Model (FEM). All of them were computed from the individual MRI of the patient and ESI was performed on averaged IED. We found that all head models provided very similar source locations. In patients having a positive post-operative outcome, at least 74% of the source maxima were within the resection. The median distance from the source maximum to the nearest intracranial electrode showing IED was 13.2, 15.6 and 15.6 mm for LSMAC, BEM and FEM, respectively. The study demonstrates that in clinical applications, the use of highly sophisticated and difficult to implement head models is not a crucial factor for an accurate ESI.

Complex auditory hallucinations are often characterized by hearing voices and are then called auditory verbal hallucinations (AVHs). While AVHs have been extensively investigated in psychiatric patients suffering from schizophrenia, reports from neurological patients are rare and, in most cases, incomplete. Here, we characterize AVHs in 9 patients suffering from pharmacoresistant epilepsy by analyzing the phenomenology of AVHs and patients' neuropsychological and lesion profiles. From a cohort of 352 consecutively examined patients with epilepsy, 9 patients suffering AVHs were identified and studied by means of a semistructured interview, neuropsychological tests, and multimodal imaging, relying on a combination of functional and structural neuroimaging data and surface and intracranial EEG. We found that AVHs in patients with epilepsy were associated with prevalent language deficits and damage to posterior language areas and basal language areas in the left temporal cortex. Auditory verbal hallucinations, most of the times, consisted in hearing a single voice of the same gender and language as the patient and had specific spatial features, being, most of the times, perceived in the external space, contralateral to the lesion. We argue that the consistent location of AVHs in the contralesional external space, the prominence of associated language deficits, and the prevalence of lesions to the posterior temporal language areas characterize AVHs of neurological origin, distinguishing them from those of psychiatric origin., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: Patients with tuberous sclerosis complex (TSC) often suffer from medically refractory epilepsy. Despite the multifocality of the disease, resection of the most epileptogenic tuber can lead to major improvement of seizure control. Therefore, non-invasive imaging methods are needed for detecting epileptogenic sources. We assessed the utility of electric source imaging (ESI) in the presurgical work-up of TSC patients and its combination with Positron Emission Tomography (PET) and ictal/interictal Single Photon Emission Computed Tomography (SISCOM)., Methods: Thirteen patients underwent high density ESI (8/13) and/or low density ESI (13/13). We investigated the concordance between ESI, PET, SISCOM and the resection area in the 11 operated patients (nine seizure-free)., Results: High resolution ESI was partially or completely concordant with the resected area in 5/5 seizure free patients. Low resolution ESI was partially or completely concordant in 7/9 seizure free patients. PET and SPECT were concordant (partially or completely) in 8/9 and 6/9 cases, respectively. We found multifocal ESI sources in 2/9 seizure free patients, marked multifocal PET hypometabolism in 3/9 and multifocal SISCOM in 4/9. The region of concordant ESI and PET accurately predicted the dominant epileptogenic source in 6/9 patients. The same was true for concordant ESI and SISCOM in 4/9 patients, whereas the coregistration of only PET and SISCOM was insufficient in 3/9 successfully operated cases. The combination of all three imaging modalities could successfully identify the resection area in all but one patient with a favorable post-operation outcome., Conclusion: ESI is an important tool for the pre-surgical evaluation of TSC patients. It complements PET and SPECT results and can improve the management of candidates for surgery when integrated with electro-clinical information., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Functional magnetic resonance imaging (fMRI) has become part of routine brain mapping in patients with epilepsy or tumor undergoing resective surgery. However, robust localization of crucial functional areas is required., Objective: To establish a simple, short fMRI task that reliably localizes crucial language areas in individual patients who undergo respective surgery., Methods: fMRI was measured during an 8-minute auditory semantic decision task in 28 healthy controls and 35 consecutive patients who had focal epilepsy or a brain tumor. Nineteen underwent resective surgery. Group and individual analyses were performed. Results in patients were compared with postsurgical language outcome and electrocortical stimulation when available., Results: fMRI activations concordant with the anterior and posterior language areas were found in 96% and 89% of the controls, respectively. The anterior and posterior language areas were both activated in 93% of the patients. These results were concordant with electrocortical stimulation results in 5 patients. Transient postsurgical language deficits were found in 2 patients in whom surgery was performed in the vicinity of the fMRI activations or who had postsurgical complications implicating areas of fMRI activations., Conclusion: The proposed fast fMRI language protocol reliably localized the most relevant language areas in individual subjects. It appears to be a valuable complementary tool for surgical planning of epileptogenic foci and of brain tumors.

Deep brain stimulation (DBS) of different nuclei is being evaluated as a treatment for epilepsy. While encouraging results have been reported, the effects of changes in stimulation parameters have been poorly studied. Here the effects of changes of pulse waveform in high frequency DBS (130 Hz) of the amygdala-hippocampal complex (AH) are presented. These effects were studied on interictal epileptic discharge rates (IEDRs). AH-DBS was implemented with biphasic versus pseudo monophasic charge balanced pulses, in two groups of patients: six with temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS) and six with non lesional (NLES) temporal epilepsy. In patients with HS, IEDRs were significantly reduced with AH-DBS applied with biphasic pulses in comparison with monophasic pulse. IEDRs were significantly reduced in only two patients with NLES independently to stimulus waveform. Comparison to long-term seizure outcome suggests that IEDRs could be used as a neurophysiological marker of chronic AH-DBS and they suggest that the waveform of the electrical stimuli can play a major role in DBS. We concluded that biphasic stimuli are more efficient than pseudo monophasic pulses in AH-DBS in patients with HS. In patients with NLES epilepsy, other parameters relevant for efficacy of DBS remain to be determined., (Copyright © 2011 Elsevier B.V. All rights reserved.)

In patients with medically refractory focal epilepsy who are candidates for epilepsy surgery, concordant non-invasive neuroimaging data are useful to guide invasive electroencephalographic recordings or surgical resection. Simultaneous electroencephalography and functional magnetic resonance imaging recordings can reveal regions of haemodynamic fluctuations related to epileptic activity and help localize its generators. However, many of these studies (40-70%) remain inconclusive, principally due to the absence of interictal epileptiform discharges during simultaneous recordings, or lack of haemodynamic changes correlated to interictal epileptiform discharges. We investigated whether the presence of epilepsy-specific voltage maps on scalp electroencephalography correlated with haemodynamic changes and could help localize the epileptic focus. In 23 patients with focal epilepsy, we built epilepsy-specific electroencephalographic voltage maps using averaged interictal epileptiform discharges recorded during long-term clinical monitoring outside the scanner and computed the correlation of this map with the electroencephalographic recordings in the scanner for each time frame. The time course of this correlation coefficient was used as a regressor for functional magnetic resonance imaging analysis to map haemodynamic changes related to these epilepsy-specific maps (topography-related haemodynamic changes). The method was first validated in five patients with significant haemodynamic changes correlated to interictal epileptiform discharges on conventional analysis. We then applied the method to 18 patients who had inconclusive simultaneous electroencephalography and functional magnetic resonance imaging studies due to the absence of interictal epileptiform discharges or absence of significant correlated haemodynamic changes. The concordance of the results with subsequent intracranial electroencephalography and/or resection area in patients who were seizure free after surgery was assessed. In the validation group, haemodynamic changes correlated to voltage maps were similar to those obtained with conventional analysis in 5/5 patients. In 14/18 patients (78%) with previously inconclusive studies, scalp maps related to epileptic activity had haemodynamic correlates even when no interictal epileptiform discharges were detected during simultaneous recordings. Haemodynamic changes correlated to voltage maps were spatially concordant with intracranial electroencephalography or with the resection area. We found better concordance in patients with lateral temporal and extratemporal neocortical epilepsy compared to medial/polar temporal lobe epilepsy, probably due to the fact that electroencephalographic voltage maps specific to lateral temporal and extratemporal epileptic activity are more dissimilar to maps of physiological activity. Our approach significantly increases the yield of simultaneous electroencephalography and functional magnetic resonance imaging to localize the epileptic focus non-invasively, allowing better targeting for surgical resection or implantation of intracranial electrode arrays.

Electroencephalography is mandatory to determine the epilepsy syndrome. However, for the precise localization of the irritative zone in patients with focal epilepsy, costly and sometimes cumbersome imaging techniques are used. Recent small studies using electric source imaging suggest that electroencephalography itself could be used to localize the focus. However, a large prospective validation study is missing. This study presents a cohort of 152 operated patients where electric source imaging was applied as part of the pre-surgical work-up allowing a comparison with the results from other methods. Patients (n = 152) with >1 year postoperative follow-up were studied prospectively. The sensitivity and specificity of each imaging method was defined by comparing the localization of the source maximum with the resected zone and surgical outcome. Electric source imaging had a sensitivity of 84% and a specificity of 88% if the electroencephalogram was recorded with a large number of electrodes (128-256 channels) and the individual magnetic resonance image was used as head model. These values compared favourably with those of structural magnetic resonance imaging (76% sensitivity, 53% specificity), positron emission tomography (69% sensitivity, 44% specificity) and ictal/interictal single-photon emission-computed tomography (58% sensitivity, 47% specificity). The sensitivity and specificity of electric source imaging decreased to 57% and 59%, respectively, with low number of electrodes (<32 channels) and a template head model. This study demonstrated the validity and clinical utility of electric source imaging in a large prospective study. Given the low cost and high flexibility of electroencephalographic systems even with high channel counts, we conclude that electric source imaging is a highly valuable tool in pre-surgical epilepsy evaluation.

Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive method for brain stimulation. Group-studies applying rTMS in epilepsy patients aiming to decrease epileptic spike- or seizure-frequency have led to inconsistent results. Here we studied whether therapeutic trains of rTMS have detectable effects on individual spike pattern and/or frequency in patients suffering from focal epilepsy. Five patients with focal epilepsy underwent one session of rTMS online with EEG using a 6 Hz prime/1 Hz rTMS protocol (real and sham). The EEG was recorded continuously throughout the stimulation, and the epileptic spikes recorded immediately before (baseline) and after stimulation (sham and real) were subjected to further analysis. Number of spikes, spike-strength and spike-topography were examined. In two of the five patients, real TMS led to significant changes when compared to baseline and sham (decrease in spike-count in one patient, change in topography of the after-discharge in the other patient). Spike-count and topography remained unchanged the remaining patients. Overall, our results do not indicate a consistent effect of rTMS stimulation on interictal spike discharges, but speak in favor of a rather weak and individually variable immediate effect of rTMS on focal epileptic activity. The individuation of most effective stimulation patterns will be decisive for the future role of rTMS in epilepsies and needs to be determined in larger studies.

Simultaneous EEG-fMRI acquisitions in patients with epilepsy often reveal distributed patterns of Blood Oxygen Level Dependant (BOLD) change correlated with epileptiform discharges. We investigated if electrical source imaging (ESI) performed on the interictal epileptiform discharges (IED) acquired during fMRI acquisition could be used to study the dynamics of the networks identified by the BOLD effect, thereby avoiding the limitations of combining results from separate recordings. Nine selected patients (13 IED types identified) with focal epilepsy underwent EEG-fMRI. Statistical analysis was performed using SPM5 to create BOLD maps. ESI was performed on the IED recorded during fMRI acquisition using a realistic head model (SMAC) and a distributed linear inverse solution (LAURA). ESI could not be performed in one case. In 10/12 remaining studies, ESI at IED onset (ESIo) was anatomically close to one BOLD cluster. Interestingly, ESIo was closest to the positive BOLD cluster with maximal statistical significance in only 4/12 cases and closest to negative BOLD responses in 4/12 cases. Very small BOLD clusters could also have clinical relevance in some cases. ESI at later time frame (ESIp) showed propagation to remote sources co-localised with other BOLD clusters in half of cases. In concordant cases, the distance between maxima of ESI and the closest EEG-fMRI cluster was less than 33 mm, in agreement with previous studies. We conclude that simultaneous ESI and EEG-fMRI analysis may be able to distinguish areas of BOLD response related to initiation of IED from propagation areas. This combination provides new opportunities for investigating epileptic networks.

Objective: To test the accuracy of EEG source imaging in epilepsy patients with large cerebral lesions. It is hypothesized that lesions are most likely to change conductivity properties and to significantly impair the accuracy of electromagnetic source imaging (ESI) based on the EEG. This has, however, not been tested in patients' EEG., Methods: Fourteen patients with focal epilepsy and large cerebral lesions underwent high-resolution (128-256 channels) interictal EEG recordings. Thirteen patients were operated, leading to seizure freedom in 12. The spike sources were localized with a distributed linear inverse solution (LAURA) and compared to the post-operative MRI or the results of other invasive or non-invasive exams., Results: In 12 patients ESI indicated the maximum source of the epileptic activity to be located within the epileptogenic zone (85%). One of the remaining cases was not seizure free after surgery. According to the ESI result, however, the focus was incompletely removed., Conclusion: High resolution ESI constrained to the individual anatomy identifies the epileptogenic focus in patients with volume relevant brain lesions with excellent accuracy, comparable to that of other non-invasive methods., Significance: Our results are of particular clinical importance, as they show that ESI can be extended to patients with large inhomogeneous lesions.

Unlabelled: Multiple structural and functional imaging modalities are available to localize the epileptogenic focus. In pre-surgical evaluation of children with pharmacoresistant epilepsy, investigations with the maximum yield should be considered in order to reduce the complexity of the workup., Objective: To determine the extent to which PET, ictal/interictal SPECT and its co-registration with the patient's MRI contributes to correct localization of the epileptogenic focus, surgical intervention and to the post surgical outcome in paediatric patients., Methods: The study population included children and adolescents with pharmacoresistant epilepsy (n = 50) who underwent preoperative evaluation, surgery and had postoperative follow-up for at least 12 months. Outcome was measured by postoperative seizure frequency using Engel's classification., Results: Thirty-nine patients (78%) became completely seizure free after surgical intervention. The likelihood to benefit from surgical treatment was significantly higher if localization with more imaging modalities (MRI, PET, SPECT) were concordant with respect to the resected brain area (p < 0.01). Preoperative PET examination provided better localizing information in patients with extratemporal epilepsy and/or dysplastic lesions, whereas SPECT was found to be superior to PET in patients with temporal lobe epilepsy and/or tumors (p < 0.05). No significant difference was noted in the surgical outcome in younger or older age group, in children with or without special education needs., Conclusion: In paediatric epilepsy pre-surgical evaluation, the combined use of multiple functional imaging modalities for a precise localisation of the epileptogenic focus is worthwhile for both extratemporal and temporal lobe epilepsy, also when EEG and MRI alone are non-contributive, given the potential benefit of complete postoperative seizure control.

Purpose: Epilepsy is a relatively frequent disease in children, with considerable impact on cognitive and social life. Successful epilepsy surgery depends on unambiguous focus identification and requires a comprehensive presurgical workup, including several neuroimaging techniques [magnetic resonance imaging, positron emission tomography (PET), and single-photon emission computed tomography (SPECT)]. These may be difficult to apply in younger or developmentally delayed children or both, requiring sedation, and hence, a significant workforce. Modern electric source imaging (ESI) provides accurate epileptic source-localization information in most patients, with minimal patient discomfort or need for cooperation. The purpose of the present study was to determine the usefulness of ESI in pediatric EEG recordings performed with routine electrode arrays., Methods: Preoperative EEGs recorded from 19 to 29 scalp electrodes were reviewed, and interictal epileptiform activity was analyzed by using a linear source-imaging procedure (depth-weighted minimum norm) in combination with statistical parametric mapping., Results: In 27 (90%) of 30 patients, the ESI correctly localized the epileptogenic region. These numbers compare favorably with the results from other imaging techniques in the same patients (PET, 82%; ictal SPECT, 70%). In extratemporal epilepsy, ESI was correct in all cases, and in temporal lobe epilepsy, in 10 of 13 cases. In two temporal lobe patients showing less-accurate ESI results, 128-electrode data could be analyzed, and in both cases, the 128-electrode ESI was correct., Conclusions: ESI with standard clinical EEG recordings provides excellent localizing information in pediatric patients, in particular in extratemporal lobe epilepsy. The lower yield in temporal lobe epilepsy seems to be due to undersampling of basal temporal areas with routine scalp recordings.

The authors present a patient in whom electrical cortical stimulation of the posterior temporal cortex induced speech arrest, comprehension deficits, and other language-related impairments. This area was ultimately resected because of persistence of a severe seizure disorder. No postoperative aphasia was observed despite the cortical stimulation results, and the patient is since seizure free. These findings question the well-established principle that corticography directly reflects local cortical functions in all patients.

The authors evaluated the feasibility, clinical yield, and localization precision of high-resolution EEG source imaging of interictal epileptic activity. A consecutive series of 44 patients with intractable epilepsy of various causes, who underwent a comprehensive presurgical epilepsy evaluation, were subjected to a 128-channel EEG recording. A standardized source imaging procedure constrained to the individual gray matter was applied to the averaged spikes of each patient. In 32 patients, the presurgical workup identified a focal epileptogenic area. The 128-channel EEG source imaging correctly localized this area in 30 of these patients (93.7%). Imprecise localization was explained by simplifications of the recordings and analysis procedure, which was accepted for the benefit of speed and standardization. In a subgroup of 24 patients who underwent operations, the sublobar precision of the 128-channel EEG source imaging was evaluated by calculating the distance of the source maximum to the resected area. This analysis revealed zero distance in 19 cases (79%). The authors conclude that high-resolution interictal EEG source imaging is a valuable noninvasive functional neuroimaging technique. The speed, ease, flexibility, and low cost of this technique warrant its use in clinical practice.

Objective: Electroencephalography (EEG) source reconstruction is becoming recognized as a useful technique to non-invasively localize the epileptic focus. Whereas, large array magnetoencephalography (MEG) systems are available since quite some time, application difficulties have previously prevented multichannel EEG recordings. Recently, however, EEG systems which allow for quick (10-20min) application of, and recording from, up to 125 electrodes have become available. The purpose of the current investigation was to systematically compare the accuracy of epileptic source localization with high electrode density to that obtained with sparser electrode setups., Methods: Interictal epileptiform activity was recorded with 123 electrodes in 14 epileptic patients undergoing presurgical evaluation. Each single epileptiform potential was down sampled to 63 and 31 electrodes, and a distributed source model (EPIFOCUS) was used to reconstruct the sources with the 3 different electrode configurations. The localization accuracy with the 3 electrode setups was then assessed, by determining the distance from the inverse solution, maximum of each single spike to the epileptogenic lesion., Results: In 9/14 patients, the distance from the EEG source to the lesion was significantly smaller with 63 than with 31 electrodes, and increasing the number of electrodes to 123 increased this number of patients from 9 to 11. Simulations confirmed the relation between the number of electrodes and localization accuracy., Conclusions: The results illustrate the necessity of multichannel EEG recordings for high source location accuracy in epileptic patients.

The major goal of presurgical epilepsy evaluation is the correct and precise identification of the epileptic focus. Functional magnetic resonance imaging (fMRI) and EEG source analysis (EEG mapping) are two recent developments that are increasingly used in this particular clinical context. fMRI yields anatomically precise information but low temporal resolution, whereas the inverse situation is true for EEG mapping. Important complementary information is therefore obtained by integrating the results from each technique. Recent advances in these two fields are discussed, with particular reference to epileptic focus localization. Such a combined approach is shown to be a powerful tool, in particular in patients with non-lesional and/or extratemporal epilepsy still considered to be difficult surgical candidates.

Objectives: Characterization of the EEG pattern during the early phase of a seizure is crucial for identifying the epileptic focus. The purpose of the present investigation was to evaluate a method that divides ictal EEG activity into segments of relatively constant surface voltage distribution, and to provide a 3-dimensional localization of the activity during the different segments., Methods: For each timepoint the electrical voltage distribution on the scalp (the voltage map) was determined from the digitized EEG recording. Through a spatial cluster analysis time sequences where the maps did not change much (segments) were identified, and a 3-dimensional source reconstruction of the activity corresponding to the different mean maps was performed using a distributed linear inverse solution algorithm., Results: Segments dominating early in seizure development were identified, and source reconstruction of the EEG activity corresponding to the maps of these segments yielded results which were consistent with the results from invasive recordings. In some cases a sequence of consecutive segments was obtained, which might reflect ictal propagation., Conclusions: Segmentation of ictal EEG with subsequent 3-dimensional source reconstruction is a useful method to non-invasively determine the initiation and perhaps also the spread of epileptiform activity in patients with epileptic seizures.

In the attempts to localize electric sources in the brain on the basis of multichannel EEG and/or MEG measurements, distributed source estimation procedures have become of increasing interest. Several commercial software packages offer such localization programs and results using these methods are seen more and more frequently in the literature. It is crucial that the users understand the similarities and differences of these methods and that they become aware of the advantages and limitations that are inherent to each approach. This review provides this information from a theoretical as well as from a practical point of view. The theoretical part gives the algorithmic basis of the electromagnetic inverse problem and shows how the different a priori assumptions are formally integrated in these equations. The authors restrict this formalism to the linear inverse solutions i.e., those solutions in which the inversion procedure can be represented as a matrix applied to the data. It will be shown that their properties can be best characterized by their resolution kernels and that methods with optimal resolution matrices can be designed. The authors also discuss the important problem of regularization strategies that are used to minimize the influence of noise. Finally, a new kind of inverse solution, termed ELECTRA (for ELECTRical Analysis), is presented that is based on constraining the source model on the basis of the currents that can actually be measured by the scalp recorded EEG. The practical part of the review illustrates the localization procedures with different clinical data sets. Three aspects become important when working with real data: 1) Clinical data is usually far from ideal (limited number of electrodes, noise, etc.). The behavior of inverse procedures in such unfortunate situations has to be evaluated. 2) The selection of the time points or time periods of interest is crucial, especially in the analysis of spontaneous EEG. 3) Additional information coming from other modalities is usually available and can be incorporated. The authors are illustrating these important points in the case of interictal and ictal epileptiform activity. Spike averaging, frequency domain source localization, and temporal segmentation based on electric field topographies will be discussed. Finally, the technique of EEG-triggered functional magnetic resonance imaging (fMRI) will be illustrated, where EEG is recorded in the magnet and is used to synchronize fMRI acquisition with interictal events. The analysis of both functional data, i.e. the EEG in terms of three-dimensional source localization and the EEG-triggered fMRI, combines the advantages of the two techniques: the temporal resolution of the EEG and the spatial resolution of the fMRI.

It is well recognized that epileptic patients are at higher risk for acute or chronic psychotic states than non-epileptic subjects. Here we present intracranial depth electrode recordings during a psychotic episode in a 20-year-old woman who was referred for presurgical evaluation. Unrelated to her seizures, she presented acoustic hallucinations and delusions and became agitated for a duration of 18-24 hours. During this period, a new unusual pattern of sharp slow waves was seen semi-rhythmically every 2-3 sec from left anterior neocortical temporal areas. Her condition responded well to a treatment with Haloperidol, but not with Benzodiazepines. Ictal and interictal scalp- and depth-EEG recordings outside the psychotic episode as well as MRI-based volumetry, PET, SPECT and neuropsychological testing gave evidence of bilateral temporal and frontal dysfunction. This case report suggests that psychosis in epileptic patients may be based on a bilateral cerebral dysfunction linked together in a pathological network, but with a focal (here: left temporal) driving mechanism.

Abstract: To screen for patients at risk for memory decline after temporal lobe epilepsy (TLE) surgery, selective amobarbital procedures, such as injection into the anterior choroidal artery (ACA-IAT), are sometimes used. We investigated the extent of the territory affected during ACA-IAT and its predictive value with respect to postoperative memory. Seventeen patients with TLE underwent ACA-IAT. In 9 of 17 patients, intraarterial SPECT co-registrated to MRI allowed delineation of amobarbital-perfused structures. Another subgroup of 9 of 17 patients underwent anterior temporal lobectomy. Verbal memory was tested pre- and postoperatively and during ACA-IAT. Major variations in the ACA-IAT perfusion pattern occurred and were not correlated with the verbal memory scores during ACA-IAT. Postoperatively, no patient experienced a severe verbal memory decline, but individual postoperative performance was not correlated with results during ACA-IAT. Our study suggests that ACA-IAT can be used to screen for severe postoperative amnesia in inconclusive cases, but cannot predict individual outcome, even when the perfusion pattern is taken into account. [Copyright &y& Elsevier]