Not your usual drug-drug interactions: Monoclonal antibody-based therapeutics may interact with antiseizure medications.

Therapeutic monoclonal antibodies (mAbs) have emerged as the fastest growing drug class. As such, mAbs are increasingly being co-prescribed with other drugs, including antiseizure medications (ASMs). Although mAbs do not share direct targets or mechanisms of disposition with small-molecule drugs (SMDs), combining therapeutics of both types can increase the risk of adverse effects and treatment failure. The primary goal of this literature review was identifying mAb-ASM combinations requiring the attention of professionals who are treating patients with epilepsy. Systematic PubMed and Embase searches (1980-2021) were performed for terms relating to mAbs, ASMs, drug interactions, and their combinations. Additional information was obtained from documents from the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Evidence was critically appraised - key issues calling for clinicians' consideration and important knowledge gaps were identified, and practice recommendations were developed by a group of pharmacists and epileptologists. The majority of interactions were attributed to the indirect effects of cytokine-modulating antibodies on drug metabolism. Conversely, strong inhibitors or inducers of drug-metabolizing enzymes or drug transporters could potentially interact with the cytotoxic payload of antibody-drug conjugates, and ASMs could alter mAb biodistribution. In addition, mAbs could potentiate adverse ASM effects. Unfortunately, few studies involved ASMs, requiring the formulation of class-based recommendations. Based on the current literature, most mAb-ASM interactions do not warrant special precautions. However, specific combinations should preferably be avoided, whereas others require monitoring and potentially adjustment of the ASM doses. Reduced drug efficacy or adverse effects could manifest days to weeks after mAb treatment onset or discontinuation, complicating the implication of drug interactions in potentially deleterious outcomes. Prescribers who treat patients with epilepsy should be familiar with mAb pharmacology to better anticipate potential mAb-ASM interactions and avoid toxicity, loss of seizure control, or impaired efficacy of mAb treatment.

Antiseizure Medications Withdrawal Seizures in Patients with Juvenile Myoclonic Epilepsy.

BACKGROUND: Patients with juvenile myoclonic epilepsy (JME) are especially prone to having antiseizure medications (ASMs) withdrawal seizures (WS). OBJECTIVES: To clarify whether WS in JME patients are caused by a high tendency of non-adherence from seizure-free patients or by a constitutive increased sensitivity to drug withdrawal. METHODS: Epilepsy patients followed in a tertiary epilepsy clinic between 2010 and 2013 were included in the study. WS prevalence was compared between drug-responsive and drug-resistant JME patients and patients with other types of epilepsy. RESULTS: The study included 23 JME patients (16 drug-responsive and 7 drug-resistant) and 138 patients with other epilepsies (74 drug-responsive and 64 drug-resistant). JME patients were younger and included more women than non-JME patients. Significantly more WS were seen in JME than in non-JME patients (P = 0.01) and in the drug-resistant fraction of JME patients in comparison to drug-resistant non-JME patients (P = 0.02). On logistic regression, the type of epilepsy, but not the patient's sex, was found to significantly predict WS. No significant difference was found in the prevalence of WS between drug-responsive and drug-resistant JME patients. The main ASM discontinued in JME was valproic acid (VPA), especially in women. CONCLUSIONS: Our findings suggest a higher sensitivity of JME patients to withdrawal of medications. It is important to educate JME patients about treatment adherence and to explain to their physicians how to carefully reduce or replace ASMs to mitigate the morbidity and mortality related to ASM withdrawal.

Bilateral epileptic networks in congenital and acquired corpus callosum defects: EEG-fMRI study.

OBJECTIVES: Electroencephalography-correlated functional magnetic resonance imaging (EEG-fMRI) allows imaging of brain-wide epileptic networks, and demonstrates that focal interictal epileptic activity is sometimes accompanied by bilateral functional activations. The corpus callosum (CC) facilitates bilateral spread of epileptic activity and at times targeted surgically for drug-resistant epilepsy (DRE). We hypothesized that focal epileptic networks are more unilateral in patients lacking intact CC. METHODS: We included focal DRE patients who underwent pre-surgical EEG-fMRI and had CC agenesis (group A, n = 5), patients who previously underwent anterior callosotomy as treatment for drop attacks and continued having seizures (group B, n = 6), and control group of patients with focal epilepsy and intact CC (group C, n = 9). Blood-oxygenation-level-dependent (BOLD) signal maps were generated for interictal epileptic discharges. To quantify bi-hemispheric distribution of epileptic networks, laterality indices were compared between groups. Anatomical and diffusion-weighted imaging demonstrated white matter pathways. RESULTS: 96% of studies demonstrated bilateral activations. Laterality indices were similar in groups A and C, whereas group B demonstrated a more bilateral network than group C (p = 0.028). Diffusion-weighted and anatomical imaging showed aberrant white matter pathways and larger anterior commissure in groups A and B. 68% of studies showed maximal activation cluster concordant with the presumed epileptic focus, 28% showed non-maximal activation at presumed focus. SIGNIFICANCE: Focal epileptic activity is associated with bilateral functional activations despite lack of intact CC, and is associated with stronger contralateral activation in patients after anterior callosotomy compared to controls. These findings disprove our initial hypothesis, and combined with white matter structural imaging, may indicate that the CC is not a sole route of propagation of epileptic activity, which might spread via anterior commissure. Our study demonstrates the utility of EEG-fMRI in assessing epileptic networks and potentially aiding in tailoring surgical treatments in DRE patients with callosal anomalies, and in callosal surgeries.

Deviations from Critical Dynamics in Interictal Epileptiform Activity.

The framework of criticality provides a unifying perspective on neuronal dynamics from in vitro cortical cultures to functioning human brains. Recent findings suggest that a healthy cortex displays critical dynamics, giving rise to scale-free spatiotemporal cascades of activity, termed neuronal avalanches. Pharmacological manipulations of the excitation-inhibition balance (EIB) in cortical cultures were previously shown to result in deviations from criticality and from the power law scaling of avalanche size distribution. To examine the sensitivity of neuronal avalanche metrics to altered EIB in humans, we focused on epilepsy, a neurological disorder characterized by hyperexcitable networks. Using magnetoencephalography, we quantitatively assessed deviations from criticality in the brain dynamics of patients with epilepsy during interictal (between-seizures) activity. Compared with healthy control subjects, epilepsy patients tended to exhibit a higher neural gain and larger avalanches, particularly during interictal epileptiform activity. Moreover, deviations from scale-free behavior were exclusively connected to brief intervals at epileptiform discharges, strengthening the association between deviations from criticality and the instantaneous changes in EIB. The avalanches collected during interictal epileptiform activity had not only a stereotypical size range but also involved particular spatial patterns of activations, as expected for periods of epileptic network dominance. Overall, the neuronal avalanche metrics provide a quantitative novel description of interictal brain activity of patients with epilepsy. SIGNIFICANCE STATEMENT: Healthy brain dynamics requires a delicate balance between excitatory and inhibitory processes. Several brain disorders, such as epilepsy, are associated with altered excitation-inhibition balance, but assessing this balance using noninvasive tools is still challenging. In this study, we apply the framework of critical brain dynamics to data from epilepsy patients, which were recorded between seizures. We show that metrics of criticality provide a sensitive tool for noninvasive assessment of changes in the balance. Specifically, brain activity of epilepsy patients deviates from healthy critical brain dynamics, particularly during abnormal epileptiform activity. The study offers a novel quantitative perspective on epilepsy and its relation to healthy brain dynamics.

Dual array EEG-fMRI: An approach for motion artifact suppression in EEG recorded simultaneously with fMRI.

OBJECTIVE: Although simultaneous recording of EEG and MRI has gained increasing popularity in recent years, the extent of its clinical use remains limited by various technical challenges. Motion interference is one of the major challenges in EEG-fMRI. Here we present an approach which reduces its impact with the aid of an MR compatible dual-array EEG (daEEG) in which the EEG itself is used both as a brain signal recorder and a motion sensor. METHODS: We implemented two arrays of EEG electrodes organized into two sets of nearly orthogonally intersecting wire bundles. The EEG was recorded using referential amplifiers inside a 3T MR-scanner. Virtual bipolar measurements were taken both along bundles (creating a small wire loop and therefore minimizing artifact) and across bundles (creating a large wire loop and therefore maximizing artifact). Independent component analysis (ICA) was applied. The resulting ICA components were classified into brain signal and noise using three criteria: 1) degree of two-dimensional spatial correlation between ICA coefficients along bundles and across bundles; 2) amplitude along bundles vs. across bundles; 3) correlation with ECG. The components which passed the criteria set were transformed back to the channel space. Motion artifact suppression and the ability to detect interictal epileptic spikes following daEEG and Optimal Basis Set (OBS) procedures were compared in 10 patients with epilepsy. RESULTS: The SNR achieved by daEEG was 11.05±3.10 and by OBS was 8.25±1.01 (p<0.00001). In 9 of 10 patients, more spikes were detected after daEEG than after OBS (p<0.05). SIGNIFICANCE: daEEG improves signal quality in EEG-fMRI recordings, expanding its clinical and research potential.

Sensitivity and specificity of seizure-onset zone estimation by ictal magnetoencephalography.

PURPOSE: Ictal video-electroencephalography (EEG) is commonly used to establish ictal onset-zone location. Recently software development has enabled systematic studies of ictal magnetoencephalography (MEG). In this article, we evaluate the ability of ictal MEG signals to localize the seizure-onset zone. METHODS: Twenty-six patients underwent ictal MEG and epilepsy surgery. Prediction of seizure-onset zone by ictal and interictal MEG was retrospectively compared with ictal-onset area found by intracranial EEG in 12 patients. The specificity and sensitivity of the prediction were calculated at hemisphere-lobe (HL) and at hemisphere-lobe-surface (HLS) levels. KEY FINDINGS: The sensitivity of ictal MEG source localization was 0.958 on HL and 0.706 on HLS levels, and its specificity was 0.900 on HL and 0.731 on HLS levels. The interictal MEG dipole cluster, defined as >10 dipoles on one lobar surface, had sensitivity of 0.400 and specificity of 0.769. Ictal MEG was equally sensitive and specific on dorsolateral and nondorsolateral neocortical surfaces up to a depth of 4 cm from the scalp. SIGNIFICANCE: Sources of ictal-onset MEG signals and interictal dipole clusters are essentially equally specific in estimation of the ictal-onset zone on lobar surface resolution, but ictal MEG is more sensitive. On the lobe resolution, ictal MEG estimates ictal-onset zone with high sensitivity and specificity.

What is the optimal duration of home-video-EEG monitoring for patients with <1 seizure per day? A simulation study.

Ambulatory "at home" video-EEG monitoring (HVEM) may offer a more cost-effective and accessible option as compared to traditional inpatient admissions to epilepsy monitoring units. However, home monitoring may not allow for safe tapering of anti-seizure medications (ASM). As a result, longer periods of monitoring may be necessary to capture a sufficient number of the patients' stereotypic seizures. We aimed to quantitatively estimate the necessary length of HVEM corresponding to various diagnostic scenarios in clinical practice. Using available seizure frequency statistics, we estimated the HVEM duration required to capture one, three, or five seizures on different days, by simulating 100,000 annual time-courses of seizure occurrence in adults and children with more than one and <30 seizures per month (89% of adults and 85% of children). We found that the durations of HVEM needed to record 1, 3, or 5 seizures in 80% of children were 2, 5, and 8 weeks (median 2, 12, and 21 days), respectively, and significantly longer in adults -2, 6, and 10 weeks (median 3, 14, and 26 days; p < 10-10 for all comparisons). Thus, longer HVEM than currently used is needed for expanding its clinical value from diagnosis of nonepileptic or very frequent epileptic events to a presurgical tool for patients with drug-resistant epilepsy. Technical developments and further studies are warranted.

Source localization using virtual magnetoencephalography helmets: A simulation study toward a prior-based tailored scheme.

Magnetoencephalography (MEG) source estimation of brain electromagnetic fields is an ill-posed problem. A virtual MEG helmet (VMH), can be constructed by recording in different head positions and then transforming the multiple head-MEG coordinates into one head frame (i.e., as though the MEG helmet was moving while the head remained static). The constructed VMH has sensors placed in various distances and angles, thus improving the spatial sampling of neuromagnetic fields. VMH has been previously shown to increase total information in comparison to a standard MEG helmet. The aim of this study was to examine whether VMH can improve source estimation accuracy. To this end, controlled simulations were carried out, in which the source characteristics are predefined. A series of VMHs were constructed by applying two or three translations and rotations to a standard 248 channel MEG array. In each simulation, the magnetic field generated by 1 to 5 dipoles was forward projected, alongside noise components. The results of this study showed that at low noise levels (e.g., averaged data of similar signals), VMHs can significantly improve the accuracy of source estimations, compared to the standard MEG array. Moreover, when utilizing a priori information, tailoring the constructed VMHs to specific sets of postulated neuronal sources can further improve the accuracy. This is shown to be a robust and stable method, even for proximate locations. Overall, VMH may add significant precision to MEG source estimation, for research and clinical benefits, such as in challenging epilepsy cases, aiding in surgical design.

Interictal Epileptiform Discharge Dynamics in Peri-sylvian Polymicrogyria Using EEG-fMRI.

Polymicrogyria (PMG) is a common malformation of cortical development associated with a higher susceptibility to epileptic seizures. Seizures secondary to PMG are characterized by difficult-to-localize cerebral sources due to the complex and widespread lesion structure. Tracing the dynamics of interictal epileptiform discharges (IEDs) in patients with epilepsy has been shown to reveal the location of epileptic activity sources, crucial for successful treatment in cases of focal drug-resistant epilepsy. In this case series IED dynamics were evaluated with simultaneous EEG-fMRI recordings in four patients with unilateral peri-sylvian polymicrogyria (PSPMG) by tracking BOLD activations over time: before, during and following IED appearance on scalp EEG. In all cases, focal BOLD activations within the lesion itself preceded the activity associated with the time of IED appearance on EEG, which showed stronger and more widespread activations. We therefore propose that early hemodynamic activity corresponding to IEDs may hold important localizing information potentially leading to the cerebral sources of epileptic activity. IEDs are suggested to develop within a small area in the PSPMG lesion with structural properties obscuring the appearance of their electric field on the scalp and only later engage widespread structures which allow the production of large currents which are recognized as IEDs on EEG.

Digital Semiology: A Prototype for Standardized, Computer-Based Semiologic Encoding of Seizures.

Video-EEG monitoring (VEM) is imperative in seizure classification and presurgical assessment of epilepsy patients. Analysis of VEM is currently performed in most institutions using a freeform report, a time-consuming process resulting in a non-standardized report, limiting the use of this essential diagnostic tool. Herein we present a pilot feasibility study of our experience with "Digital Semiology" (DS), a novel seizure encoding software. It allows semiautomated annotation of the videos of suspected events from a predetermined, hierarchal set of options, with highly detailed semiologic descriptions, somatic localization, and timing. In addition, the software's semiologic extrapolation functions identify characteristics of focal seizures and PNES, sequences compatible with a Jacksonian march, and risk factors for SUDEP. Sixty episodes from a mixed adult and pediatric cohort from one level 4 epilepsy center VEM archives were analyzed using DS and the reports were compared with the standard freeform ones, written by the same epileptologists. The behavioral characteristics appearing in the DS and freeform reports overlapped by 78-80%. Encoding of one episode using DS required an average of 18 min 13 s (standard deviation: 14 min and 16 s). The focality function identified 19 out of 43 focal episodes, with a sensitivity of 45.45% (CI 30.39-61.15%) and specificity of 87.50% (CI 61.65-98.45%). The PNES function identified 6 of 12 PNES episodes, with a sensitivity of 50% (95% CI 21.09-78.91%) and specificity of 97.2 (95% CI 88.93-99.95%). Eleven events of GTCS triggered the SUDEP risk alert. Overall, these results show that video recordings of suspected seizures can be encoded using the DS software in a precise manner, offering the added benefit of semiologic alerts. The present study represents an important step toward the formation of an annotated video archive, to be used for machine learning purposes. This will further the goal of automated VEM analysis, ultimately contributing to wider utilization of VEM and therefore to the reduction of the treatment gap in epilepsy.

A functional magnetic resonance imaging investigation of prefrontal cortex deep transcranial magnetic stimulation efficacy in adults with attention deficit/hyperactive disorder: A double blind, randomized clinical trial.

ADHD is one of the most prevalent neurocognitive disorders. Deep Transcranial Magnetic Stimulation (dTMS) is a non-invasive neuromodulation tool that holds promise in treatment of neurocognitive disorders. Hypoactivity of the prefrontal cortex (PFC) has been observed in ADHD. This study examined the clinical, cognitive, and neural effects of dTMS to the PFC in adults with ADHD by using functional magnetic resonance imaging (fMRI). High frequency repetitive dTMS was applied to either the right or left PFC in 62 adults with ADHD in a randomized, double blind, placebo controlled protocol with 3 study groups: 2 treatment arms (rPFC, or lPFC) and a Sham arm. The study included 15 dTMS/cognitive training treatment sessions. Clinical effects were assessed with the Conners Adult ADHD Rating Scale (CAARS) self-report and the Clinical Global Impression score (CGI) as primary outcome measures. Self-report/observer questionnaires and computerized cognitive testing were also performed to assess clinical and cognitive effects. Neural effects were assessed with fMRI using working-memory (WM) and resting-state paradigms. While the study did not show improvement in the primary endpoints, significant improvements were observed in the CAARS (self-report) inattention/memory sub-scale, as well as increased activations in the rDLPFC, right parietal-cortex and right insula/IFG during WM conditions after treatment in the right stimulation group. Increased rDLPFC activation was associated with larger symptom improvement in the right stimulation group. This study indicates that dTMS is effective in modulating attention related brain networks, and is a feasible technique that may improve attention symptoms in adults with ADHD.

Preoperative localization of seizure onset zones by magnetic source imaging, EEG-correlated functional MRI, and their combination.

OBJECTIVE: Preoperative localization of seizure onset zones (SOZs) is an evolving field in the treatment of refractory epilepsy. Both magnetic source imaging (MSI), and the more recent EEG-correlated functional MRI (EEG-fMRI), have shown applicability in assisting surgical planning. The purpose of this study was to evaluate the capability of each method and their combination in localizing the seizure onset lobe (SL). METHODS: The study included 14 patients who underwent both MSI and EEG-fMRI before undergoing implantation of intracranial EEG (icEEG) as part of the presurgical planning of the resection of an epileptogenic zone (EZ) during the years 2012-2018. The estimated location of the SL by each method was compared with the location determined by icEEG. Identification rates of the SL were compared between the different methods. RESULTS: MSI and EEG-fMRI showed similar identification rates of SL locations in relation to icEEG results (88% ± 31% and 73% ± 42%, respectively; p = 0.281). The additive use of the coverage lobes of both methods correctly identified 100% of the SL, significantly higher than EEG-fMRI alone (p = 0.039) and nonsignificantly higher than MSI (p = 0.180). False-identification rates of the additive coverage lobes were significantly higher than MSI (p = 0.026) and EEG-fMRI (p = 0.027). The intersecting lobes of both methods showed the lowest false identification rate (13% ± 6%, p = 0.01). CONCLUSIONS: Both MSI and EEG-fMRI can assist in the presurgical evaluation of patients with refractory epilepsy. The additive use of both tests confers a high identification rate in finding the SL. This combination can help in focusing implantation of icEEG electrodes targeting the SOZ.

Fine tuning the correlation limit of spatio-temporal signal space separation for magnetoencephalography.

Head, jaw and tongue movements contribute to speech artifacts in magnetoencephalography (MEG). Their sources lay close to MEG sensors, therefore, the spatio-temporal signal space separation method (tSSS), specifically suppressing nearby artifacts, can be used for speech artifact suppression. After data reconstruction by signal space separation (referred as SSS), tSSS identifies artifacts by their correlated temporal behavior inside and outside the sensor helmet. The artifacts to be eliminated are thresholded by the quantitative level of this correlation determined by correlation limit (CL). Unnecessarily high CL value may result in suboptimal interference suppression. We evaluated the performance of tSSS with different CLs on MEG data containing speech artifacts. MEG was recorded with 204 planar gradiometers and 102 magnetometers in two subjects counting aloud. The recorded data were processed by tSSS using CLs 0.98, 0.8 and 0.6, and traces were compared. The speech artifact was increasingly suppressed with decreasing CL, but sufficient suppression was achieved at different CL in each subject. Alpha rhythm was not suppressed with CL 0.98 or 0.8; some amplitude reduction with CL 0.6 occurred in one subject. The tSSS is a robust tool suppressing MEG artifacts. It can be fine tuned for challenging artifacts which, after insufficient rejection might resemble brain signals.

Conductive gel bridge sensor for motion tracking in simultaneous EEG-fMRI recordings.

EEG-fMRI allows the localization of the hemodynamic correlates of neural activity and has been shown to be useful as a diagnostic tool in pre-surgical evaluation of refractory epilepsy. However, EEG recordings may be highly contaminated by artifacts induced by movements inside the magnetic field thus rendering the scan difficult for interpretation. Existing methods for motion correction require additional equipment or hardware modification. We introduce a simple method for motion artifact detection, the conductive gel bridge sensor (CGBS), easily applicable using the standard setup. We report examples of CGBS use in two patients with epilepsy and demonstrate the method's ability to successfully differentiate between epochs of brain activity and those of movement.

Virtual MEG Helmet: Computer Simulation of an Approach to Neuromagnetic Field Sampling.

Head movements during an MEG recording are commonly considered an obstacle. In this computer simulation study, we introduce an approach, the virtual MEG helmet (VMH), which employs the head movements for data quality improvement. With a VMH, a denser MEG helmet is constructed by adding new sensors corresponding to different head positions. Based on the Shannon's theory of communication, we calculated the total information as a figure of merit for comparing the actual 306-sensor Elekta Neuromag helmet to several types of the VMH. As source models, we used simulated randomly distributed source current (RDSC), simulated auditory and somatosensory evoked fields. Using the RDSC model with the simulation of 360 recorded events, the total information (bits/sample) was 989 for the most informative single head position and up to 1272 for the VMH (addition of 28.6%). Using simulated AEFs, the additional contribution of a VMH was 12.6% and using simulated SEF only 1.1%. For the distributed and bilateral sources, a VMH can provide a more informative sampling of the neuromagnetic field during the same recording time than measuring the MEG from one head position. VMH can, in some situations, improve source localization of the neuromagnetic fields related to the normal and pathological brain activity. This should be investigated further employing real MEG recordings.

Improving the excess kurtosis (g2) method for localizing epileptic sources in magnetoencephalographic recordings.

OBJECTIVE: To suggest ways to apply the excess kurtosis estimator g2, in the detection of epileptic activity with magnetoencephalography, while avoiding its bias towards detecting high-amplitude, infrequent events. METHODS: Synthetic aperture magnetometry (SAM), combined with g2, was applied using window lengths ranging from 0.125 s to 32 s and with sum and maximum metrics on simulated data and recordings of two focal epilepsy patients. RESULTS: Comparing sources with different spike rates (two per second and one per 2s), the sum metric was most efficient when using a window of 0.25s. Simulations showed that the sum metric is insensitive to spike frequency when the window includes more than one spike. SAM(g2) images from long segments with maximum metric resulted in misleading images, showing the strongest activity away from the lesions. CONCLUSIONS: Using a sliding window and the sum metric is beneficial when imaging interictal spikes and status epilepticus. Windows should be short enough not to include more than one interictal event. For continuous events such as electrographic seizures windows should contain baseline data and the epileptic event. SIGNIFICANCE: The sliding window and metric should be set according to the suggested guidelines when using SAM(g2) for presurgical evaluation.

Interictal MEG reveals focal cortical dysplasias: special focus on patients with no visible MRI lesions.

PURPOSE: To investigate the value of interictal magnetoencephalography (MEG) in localizing epileptogenic cortex in epilepsy surgery patients with focal cortical dysplasias (FCD), particularly in patients having no visible MRI lesions. METHODS: Thirty-four patients with FCD and preoperative MEG were retrospectively evaluated. Interictal MEG spike source localizations in respect to the resected area were studied using postoperative MR imaging. The possible predictive value of MEG-findings in respect to the clinical outcome was evaluated. Results from intracranial recordings were also compared with the MEG localizations. RESULTS: Interictal MEG spikes were observed in all but one patient. 17 of the 34 (50%) patients became seizure free (Engel class I). In patients with MEG dipole clusters (n=20) and Engel class I or II (n=15) 49% of the source clusters were removed on the average; the corresponding value in patients with Engel class III or IV (n=5) was 5.5% (p=0.02). Seven (54%) of the 13 patients with an MRI-negative lesion achieved Engel class I; the outcomes did not differ from patients having a visible MRI lesion (n=21; p=0.82). The concordance between MEG localizations and the invasive studies was good in nine of the 13 patients with no visible MRI lesions CONCLUSION: MEG is particularly useful in finding small FCDs not visible on MRI. A more complete removal of MEG source cluster area is associated with better clinical outcome These features make it a valuable tool in pre-surgical evaluation of patients with intractable focal-type epilepsy and normal MRI.