Marcel Heers

MEG-based identification of the epileptogenic zone in occult peri-insular epilepsy

INTRODUCTION Presurgical work-ups of patients with pharmacoresistant epileptic seizures can require multiple diagnostic methods if magnetic resonance imaging (MRI) combined with video-EEG monitoring fails to show an epileptogenic lesion. Yet, the added value of available methods is not clear. In particular, only a minority of epilepsy centres apply magnetoencephalography (MEG). This study explores the potential of MEG for patients whose previous sophisticated work-ups missed deep-seated, peri-insular epileptogenic lesions. PATIENTS AND METHODS Three patients with well documented, frequent, stereotypical hypermotor seizures without clear focus hypotheses after repeated presurgical work-ups including video-EEG-monitoring, 3Tesla (3T) magnetic resonance imaging (MRI), morphometric MRI analysis, PET and SPECT were referred to MEG source localisation. RESULTS In two out of three patients, MEG source localisation identified very subtle morphological abnormalities formerly missed in MRI or classified as questionable pathology. In the third patient, MEG was not reliable due to insufficient detection of epileptic patterns. Here, a 1 mm × 1 mm × 1 mm 3T fluid-attenuated inversion recovery (FLAIR) MRI revealed a potential epileptogenic lesion. A minimal invasive work-up via lesion-focused depth electrodes confirmed the intralesional seizure onset in all patients, and histology revealed dysplastic lesions. Seizure outcomes were Engel 1a in two patients, and Engel 1d in the third. DISCUSSION MEG can contribute to the identification of epileptogenic lesions even when multiple previous methods failed, and when the lesions are located in deep anatomical structures such as peri-insular cortex. For epilepsy centres without MEG capability, referral of patients with cryptogenic focal epilepsies to centres with MEG systems may be indicated.

Combining EEG and MEG for the Reconstruction of Epileptic Activity Using a Calibrated Realistic Volume Conductor Model

To increase the reliability for the non-invasive determination of the irritative zone in presurgical epilepsy diagnosis, we introduce here a new experimental and methodological source analysis pipeline that combines the complementary information in EEG and MEG, and apply it to data from a patient, suffering from refractory focal epilepsy. Skull conductivity parameters in a six compartment finite element head model with brain anisotropy, constructed from individual MRI data, are estimated in a calibration procedure using somatosensory evoked potential (SEP) and field (SEF) data. These data are measured in a single run before acquisition of further runs of spontaneous epileptic activity. Our results show that even for single interictal spikes, volume conduction effects dominate over noise and need to be taken into account for accurate source analysis. While cerebrospinal fluid and brain anisotropy influence both modalities, only EEG is sensitive to skull conductivity and conductivity calibration significantly reduces the difference in especially depth localization of both modalities, emphasizing its importance for combining EEG and MEG source analysis. On the other hand, localization differences which are due to the distinct sensitivity profiles of EEG and MEG persist. In case of a moderate error in skull conductivity, combined source analysis results can still profit from the different sensitivity profiles of EEG and MEG to accurately determine location, orientation and strength of the underlying sources. On the other side, significant errors in skull modeling are reflected in EEG reconstruction errors and could reduce the goodness of fit to combined datasets. For combined EEG and MEG source analysis, we therefore recommend calibrating skull conductivity using additionally acquired SEP/SEF data.

Combined EEG/MEG Can Outperform Single Modality EEG or MEG Source Reconstruction in Presurgical Epilepsy Diagnosis

We investigated two important means for improving source reconstruction in presurgical epilepsy diagnosis. The first investigation is about the optimal choice of the number of epileptic spikes in averaging to (1) sufficiently reduce the noise bias for an accurate determination of the center of gravity of the epileptic activity and (2) still get an estimation of the extent of the irritative zone. The second study focuses on the differences in single modality EEG (80-electrodes) or MEG (275-gradiometers) and especially on the benefits of combined EEG/MEG (EMEG) source analysis. Both investigations were validated with simultaneous stereo-EEG (sEEG) (167-contacts) and low-density EEG (ldEEG) (21-electrodes). To account for the different sensitivity profiles of EEG and MEG, we constructed a six-compartment finite element head model with anisotropic white matter conductivity, and calibrated the skull conductivity via somatosensory evoked responses. Our results show that, unlike single modality EEG or MEG, combined EMEG uses the complementary information of both modalities and thereby allows accurate source reconstructions also at early instants in time (epileptic spike onset), i.e., time points with low SNR, which are not yet subject to propagation and thus supposed to be closer to the origin of the epileptic activity. EMEG is furthermore able to reveal the propagation pathway at later time points in agreement with sEEG, while EEG or MEG alone reconstructed only parts of it. Subaveraging provides important and accurate information about both the center of gravity and the extent of the epileptogenic tissue that neither single nor grand-averaged spike localizations can supply.

Detection of epileptic spikes by magnetoencephalography and electroencephalography after sleep deprivation.

INTRODUCTION In diagnosis of epilepsies electrophysiological findings play a key role. While spontaneous electroencephalography (EEG) and EEG with sleep deprivation (EEGsd) are widely evaluated and used, application of magnetoencephalography (MEG) in this field is primarily limited to presurgical assessment of focal epilepsies. METHODS In this study we retrospectively compared MEG (M/EEG) and EEGsd in 63 (55) patients with focal and generalized epilepsy with regard to occurrence of epileptic spikes. RESULTS MEG could record epileptic spikes in 38 patients (60%), while EEGsd recorded spikes in only 32 patients (51%). In a group of 55 patients simultaneous MEG/EEG (M/EEG) was able to record spikes in 38 patients (71%) compared to epileptic spikes in 28 patients (51%) recorded by EEGsd. In a subgroup of 17 MR-negative patients simultaneous M/EEG could record epileptic spikes in all patients, while EEGsd was successful in only 11 (64%) of them. CONCLUSION In this study, MEG showed a tendency to record epileptic spikes in more patients than EEGsd. Furthermore, simultaneous M/EEG has been shown to be especially successful in detection of epileptic spikes in patients with MR-negative epilepsy. This might at least in parts be explained by neocortical predominance of MR-negative epilepsy. Thus, this study motivates prospective studies to evaluate the substitutability of EEGsd by MEG more extensively.

Spatial correlation of hemodynamic changes related to interictal epileptic discharges with electric and magnetic source imaging

Blood oxygenation level‐dependent (BOLD) signal changes at the time of interictal epileptic discharges (IEDs) identify their associated vascular/hemodynamic responses. BOLD activations and deactivations can be found within the epileptogenic zone but also at a distance. Source imaging identifies electric (ESI) and magnetic (MSI) sources of IEDs, with the advantage of a higher temporal resolution. Therefore, the objective of our study was to evaluate the spatial concordance between ESI/MSI and BOLD responses for similar IEDs.

Increased spike frequency during general anesthesia with etomidate for magnetoencephalography in patients with focal epilepsies

OBJECTIVE Magnetoencephalography (MEG) is used for focus localization in presurgical evaluation of patients with focal epilepsies. In this proof-of-concept study, general anesthesia with etomidate was used to improve effectiveness of MEG-recordings. METHODS MEG-recordings of six patients with focal epilepsy were performed before and after application of etomidate. Spike frequency and localization accuracy of MEG with general anesthesia were compared with spontaneous MEG. RESULTS After application of etomidate, an increase in spike frequency occurred in all patients, and movement artifacts were prevented. In one patient, spikes could only be detected by invasive EEG but not by MEG. The results were in accordance with spontaneous MEG or presurgical hypotheses about localizations of neocortical foci in three patients. Dipole localizations were distributed over fronto-temporal areas in three patients with ipsilateral temporo-mesial focus hypotheses. CONCLUSIONS Etomidate ameliorated spike yield and stopped movement artifacts during MEG recordings in patients with focal epilepsy. Localization results were especially accurate in patients with neocortical epilepsy. SIGNIFICANCE These results could facilitate larger studies on the usefulness and safety of general anesthesia with etomidate that record and localize epileptic activity in patients with focal epilepsy by MEG.

Etomidate activates epileptic high frequency oscillations

OBJECTIVE The short acting anesthetic etomidate has been shown to provoke epileptic spikes and rarely seizures. Influence of etomidate on the occurrence of epileptic HFO (high frequency oscillations) however is unknown. An HFO inducing effect of etomidate would allow further validation of the substance as a provocation measure in presurgical evaluation as well as provide insights into the common mechanisms of HFO, spike and seizure generation. METHODS We retrospectively analyzed EEG data from four patients who underwent etomidate activation during invasive video-EEG monitoring with subdural strip electrodes. Spikes were manually selected in raw data, HFO in band pass filtered data (80-250Hz). Rate and spatial distribution of HFO and spikes in three segments were compared: immediately after etomidate administration, as well as during slow wave sleep and while awake. RESULTS Rates of HFO and spikes increased significantly after etomidate administration: Overall average rates of spikes were 9.7/min during sleep, 10/min while awake and 61.4/min after etomidate. Average HFO rates were 9.5/min during sleep, 8.3/min while awake and 24.4/min after etomidate (p<0.001, non-parametric ANOVA). Spatial distributions of HFO and spikes after administration of etomidate were consistent with the seizure onset zone (SOZ) and area of resection when available (SOZ: two patients; resection: one patient; no information: one patient). Except for spurious events, no additional HFO and spike foci were seen with activation. CONCLUSIONS Etomidate administration activates spikes and HFO. Spatial distributions do not extend beyond electrodes showing spikes and HFO without Etomidate and seem consistent with the epileptic network. SIGNIFICANCE Etomidate activation is a safe procedure to provoke not only epileptic spikes but also HFO, which were shown to have a high specificity for the SOZ.

Monofocal MEG in lesional TLE: Does video EEG monitoring add crucial information?

OBJECTIVE Unilateral monofocal temporal magnetoencephalography (MEG) findings might determine epileptogenicity of a lesion in symptomatic epilepsy during presurgical evaluation. To evaluate the additive effect of video-electroencephalography (vEEG), monofocal temporal lobe MEG findings were compared to electrophysiological findings from vEEGs of patients with lesional epilepsy. METHODS In 28 patients with drug-resistant lesional temporal lobe epilepsy (TLE), epileptogenicity of the lesion was determined by monofocal temporal MEG localisations. Findings for lesions of different aetiologies (20 mesial, 6 lateral, and 2 extended mesiolateral lesions) were compared to electrophysiological findings from long-term vEEG monitoring and validated by histology and postsurgical outcome (mean follow-up: 2 years (range 0.5-5)). RESULTS The mean distance between a lesion and MEG localisation was 11mm (range 0-30mm). The distance to the lesion was on average 5mm (range 0-22mm) in patients with neocortical foci and on average 13mm (range 0-30mm) in patients with mesial foci. Predominant interictal and ictal vEEG findings were consistent with MEG findings in all patients, although they were sometimes distributed over multiple lobes and bilaterally pronounced on the side of the MEG findings. Postsurgical outcome of Engel 1 could be achieved in 82% (23 patients), and none of the patients had an outcome worse than Engel 2. CONCLUSION MEG localisations in lesional TLE are able to determine epileptogenicity of mesial and lateral temporal lobe lesions. MEG results are consistent with predominant electrophysiological findings from long-term vEEG. Future studies should assess the substitutability of vEEG by MEG in selected cases.

MEG Slow Wave Dipole Density (SWDD) in Presurgical Evaluation of Epilepsy Patients: Preliminary Results of a Prospective Study

Main objective(s) The aim of this prospective study is to examine the potential contribution of SWDD localisation in clinical preoperative epilepsy focus localisation. Methods Preoperative MEG-SWDD localisations are calculated and overlaid on MR-images of pharmaco-resistant epilepsy pa- tients undergoing presurgical focus localisation evaluation. For all 10 patients who have been operated within at least 6 months, postsurgical outcomes available up to now, are discussed. SWDD localisation results are compared to other preoperative findings and to MEG-spike results and are corre- lated to postoperative outcome (Engel) after 6 months or 12 months. Results 7 of 10 patients showed significant local increase of SWDD. In these SWDD localisation results were always concordant with preoperative findings. All 7 patients were postoperatively seizure-free or had a worthwhile improvement of seizure situa- tion. 3 of 10 patients showed no significant local increase of SWDD and, therefore, were without SWDD result. Comparison to MEG spike results: Among these 7 patients, 6 showed MEG-spike concordant localisations, one had no spikes in the MEG. Conclusions SWDD is able to localise brain areas exhibiting pathological slow wave activity and might become a useful tool for preoperative epilepsy diagnosis.