Advertisement

Magnetoencephalography (MEG): Past, current and future perspectives for improved differentiation and treatment of epilepsies

Open ArchivePublished:November 15, 2016DOI:https://doi.org/10.1016/j.seizure.2016.10.028

      Abstract

      In addition to visual analysis digital computerized recording of electrical and magnetic fields by using EEG and MEG opened a new window for research concerning improved understanding of pathophysiology, diagnosis and treatment of epilepsies. In the last 25 years MEG was used more and more in clinical studies concerning localization of focal epileptic activity, functional cortex and network analysis. Simultaneous MEG/EEG recording and analysis offer the use of complimentary information increasing the sensitivity for tracing primary epileptic activity. Combined MEG/Stereo-EEG recordings showed that MEG noninvasively identified regional interictal networks. The current role of MEG for presurgical evaluation with regard to noninvasive localization in MRI normal patients, guiding of invasive electrode implantation and correlation to postoperative outcome after epilepsy surgery is stressed. Challenges and future opportunities for MEG in clinical epileptology are discussed.

      Keywords

      1. Introduction

      In addition to visual analysis digital computerized recording of electrical and magnetic fields by using EEG and MEG opened a new window for research concerning improved understanding of pathophysiology, diagnosis and treatment of epilepsies. Cohen recorded brain (alpha) activity by means of MEG already in 1972 [
      • Cohen D.
      MEG: detection of the brain electrical activity with a super conducting magnetometer.
      ], but the practicability for clinical use was limited at this time by one to seven channel recordings. Since multichannel MEG recording became available clinical MEG investigations concerning epilepsy were facilitated [
      • Stefan H.
      • Schneider S.
      • Abraham-Fuchs K.
      • Bauer J.
      • Feistel H.
      • Pawlik G.
      • et al.
      Magnetic source localization in focal epilepsy.
      ]. Later prospective studies with whole head systems proved the value for presurgical evaluation [
      • Sutherling W.W.
      • Mamelak A.N.
      • Thyerlei D.
      • Maleeva T.
      • Minazad T.
      • Philpott L.
      • et al.
      Influence of magnetic source imaging for planning intracranial EEG in epilepsy.
      ,
      • Knowlton B.J.
      • Razdan S.N.
      • Limdi N.
      • Elgavish R.A.
      • Killen J.
      • Blount J.
      • et al.
      Effect of epilepsy magnetic source imaging on intracranial electrode placement.
      ]. After many following studies since 25 years MEG now is used for guiding and in special cases also omitting of invasive electrode implantations, determination of the relation of focal epileptic activity to functional cortex and the extent of resection.

      2. MEG in the network analysis of system epilepsies

      Meanwhile simultaneous MEG/EEG recordings and analysis offer the use of complimentary information of both techniques for increasing the sensitivity with regard to the detection of “primary” epileptic discharges [
      • Badier J.M.
      • Chauvel P.
      Spatio-temporal characteristics of paroxysmal interictal events in human temporal lobe epilepsy.
      ], propagated activity and hidden lesions [
      • Aydin Ü.
      • Vorwerk J.
      • Küpper P.
      • Heers H.
      • Kugel H.
      • Galka A.
      • et al.
      Combining EEG and MEG for the reconstruction of epileptic activity using a calibrated realistic volume conductor model.
      ,
      • Aydin Ü.
      Combined EEG and MEG source analysis of epileptiform activity using calibrated realistic finite element head models, Thesis.
      ].
      MEG studies of previously called “primarily generalized” absence epilepsies revealed regional cortical initial epileptic activity and involvement of the default mode network [
      • Sakurai K.
      • Takeda Y.
      • Tanaka N.
      • Kurita T.
      • Shiraishi H.
      • Takenchi F.
      • et al.
      Generalized spike-wave discharges involve a default mode network in patients with juvenile absence epilepsy: a MEG study.
      ]. Thus contributing to the concept of system related epilepsy differentiation [
      • Avanzini G.
      • Manganotti P.
      • Meletti S.
      • Moshe S.L.
      • Panzica F.
      • Wolf P.
      • et al.
      The system epilepsy: a pathophysiological hypothesis.
      ]. Considering neuronal system networks one may proceed further than just a dichotomy of focal and generalized epilepsies. In this view e.g. absences are fast generalizing epilepsies in a thalamo-cortical system involving the default network whereas other epilepsies may involve in a different way more or less e.g. temporal, perisylvian, limbic, extratemporal or basal ganglia networks or remain in small cortical areas.
      Future approaches can use connectivity analysis not only for the improvement of classification concept but also for individual resective surgery [
      • Englot D.J.
      • Hinkley L.B.
      • Kort N.S.
      • Imber B.S.
      • Miziniri D.
      • Honma S.M.
      • et al.
      Global and regional functional connectivity maps of neural oscillations in focal epilepsy.
      ]. Since the early days of stereo-EEG the delineation of the ictal seizure onset zone has been regarded as gold standard to define the cortical region to be removed by surgery. However, the circumstances under which a seizure is recorded in the epilepsy monitoring unit by longterm monitoring, may be cumbersome, and also risky for the patient [
      • Dobesberger J.
      • Walser G.
      • Unterberger I.
      • Seppi K.
      • Kuchukhidze G.
      • Larch J.
      • et al.
      Video-EEG monitoring: safety and adverse events in 507 consecutive patients.
      ]. In addition the criteria to define the epileptogenic “zone are” not fulfilled in a number of patients, with non-informative ictal EEG. In a systematic review undertaken by the E-PILEPSY network the preliminary analysis of the diagnostic utility of video-EEG yielded a sensitivity estimate of 0.70 (95% CI 0.66–0.73) and a specificity estimate of 0.40 (95% CI 0.33–0.45) for correctly localizing the epileptogenic “zone” and predicting one year seizure freedom (data on file). An increase of information concerning the localization of focal epileptic activities in pharmacoresistant epilepsies was found by combining video EEG longterm recording with interictal MEG [
      • Wu X.
      • Rampp S.
      • Hopfengärtner R.
      • Buchfelder M.
      • Zhou D.
      • Stefan H.
      Complimentary use of video EEG and MEG in frontal lobe epilepsy.
      ]. Thus, there has been a shift towards the localization value of interictal activities as criterion to define a surgical strategy. An approach based on interictal discharges could aim at distinguishing among scattered activities those, which could not only distinguish between a primary irritative zone from a secondary irritative zone [
      • Badier J.M.
      • Chauvel P.
      Spatio-temporal characteristics of paroxysmal interictal events in human temporal lobe epilepsy.
      ], but also aid in predicting the relevant cortical generators. Another advantage of using the interictal information is the high number of analysable interictal discharges, which are much more common in any patient, than ictal events [
      • Malinowska U.
      • Badier J.M.
      • Gavaret M.
      • Bartolomei F.
      • Chauvel P.
      • Bénar C.G.
      Interictal networks in magnetoencephalography.
      ]. In a comparative study of seven patients, who underwent MEG and stereo-EEG during their presurgical workup the spatiotemporal network activities of interictal spikes were analysed. Both, MEG and stereo-EEG involved remote regions, which were acting in synchrony. All MEG regions, were confirmed by stereo-EEG, when an electrode was placed in the vicinity of the MEG region. In fact 71% of MEG leaders were confirmed by stereo-EEG, strongly suggesting, that MEG is capable of identifying noninvasively regional interictal epileptic networks and their pattern of connectivity [
      • Malinowska U.
      • Badier J.M.
      • Gavaret M.
      • Bartolomei F.
      • Chauvel P.
      • Bénar C.G.
      Interictal networks in magnetoencephalography.
      ]. Patients had a significantly higher chance being seizure free when SEEG completely sampled the area identified by MEG clustering (p = 0.012). In patients in whom MEG clusters were completely resected had a much higher chance for postoperative seizure freedom compared to partial or no resection groups (p = 0.007) [
      • Murakami H.
      • Wang S.
      • Marashly A.
      • Krishnan B.
      • Prayson R.A.
      • Kakisaka Y.
      • et al.
      Correlating magnetoencephalography to stereo-electroencephalography in patients undergoing epilepsy surgery.
      ].

      3. Current role of MEG in pre surgical evaluation

      In the presurgical evaluation of drug resistant epilepsies the concept of different “zones” as defined by Lüders et al. [
      • Lüders H.
      • Engel J.
      • Monari C.
      General principles.
      ] has become a widely acknowledged and successful approach. The transformation of a two dimensional zone into a three dimensional irritative, seizure onset or symptomatogenic e.g. network is one of the challenges for the future. Here network analysis including primarily and secondarily spiking activity [
      • Badier J.M.
      • Chauvel P.
      Spatio-temporal characteristics of paroxysmal interictal events in human temporal lobe epilepsy.
      ] in the irritative network and causal direction network analysis may be helpful. In addition to source localizations during spikes or seizures also localizations in spike free epochs are of interest.
      The current role of magnetic source localization (magnetic source imaging, MSI), using MEG data, is not fully established yet, but considered useful as an additional tool in the presurgical pathway awaiting further validation [
      • Englot D.J.
      • Nagarajan S.S.
      • Imber B.S.
      • Raygor K.P.
      • Honma S.M.
      • Mizuiri D.
      • et al.
      Epileptogenic zone localization using magnetoencephalography predicts seizure freedom in epilepsy surgery.
      ,
      • Jayakar P.
      • Gaillard W.D.
      • Tripathi M.
      • Libenson M.H.
      • Mathern G.W.
      • Cross J.H.
      Task force for paediatric epilepsy surgery CfP, the diagnostic commission of the international league against epilepsy: specific diagnostic test utilization in evaluation for resective epilepsy surgery in children.
      ]. A lack of long-term seizure outcomes, small sample size, selection bias of non lesional- or unclear cases, or a combination of these factors has limited many studies. Still, it has been recognized as a useful and accurate clinical tool in several centres in Europe, Japan, Korea, and North America [
      • Stefan H.
      • Hummel C.
      • Scheler G.
      • Genow A.
      • Druschky K.
      • Tilz C.
      • et al.
      Magnetic brain source imaging of focal epileptic activity: a synopsis of 455 cases.
      ,
      • Oishi M.
      • Kameyama S.
      • Masuda H.
      • Tohyama J.
      • Kanazawa O.
      • Sasagawa M.
      • et al.
      Single and multiple clusters of MEG dipoles in neocortical epilepsy: significance of characterizing the epileptogenic zone.
      ,
      • De Tiege X.
      • Carrette E.
      • Legros B.
      • Vonck K.
      • Op de Beeck V.
      • Bourquignon M.
      • et al.
      Clinical added value of magnetic source imaging in presurgical evaluation of refractory focal epilepsies.
      ,
      • Ebersole J.S.
      • Ebersole S.M.
      Combining MEG and EEG source modeling in epilepsy evaluations.
      ,
      • Stefan H.
      • Rampp S.
      • Knowlton R.C.
      Magnetoencephalography adds to the surgical evaluation process.
      ,
      • Mu J.
      • Rampp S.
      • Carrette E.
      • Roessler K.
      • Sommer B.
      • Schmitt F.C.
      • et al.
      Clinical relevance of source localization in frontal lobe epilepsies and prediction of postoperative longterm outcome.
      ,
      • Ramachandrannair R.
      • Ochi A.
      • Imai K.
      • Benifla M.
      • Akiyama T.
      • Holowka S.
      • et al.
      Epileptic spasms in older pediatric patients: MEG and ictal high frequency oscillations suggested focal onset seizures in a subset of epileptic spasms.
      ,
      • Jung J.
      • Bouet R.
      • Delpuech C.
      • Ryvlin P.
      • Isnard J.
      • Guenot M.
      • et al.
      The value of MEG for seizure onset zone localization in MRI negative partial epilepsy.
      ,
      • Ito T.
      • Otsubo H.
      • Shiraishi H.
      • Yagyu K.
      • Takahashi Y.
      • Ueda Y.
      • et al.
      Advantageous information provided by MEG for patients with neocortical epilepsy.
      ,
      • Rubinger L.
      • Chan C.
      • D’Arco D.
      • Moineddin R.
      • Muthaffar O.
      • Rutka J.T.
      • et al.
      Change in presurgical diagnostic imaging evaluation affects subsequent pediatric epilepsy surgery outcome.
      ].
      An epilepsy-specific position paper and on electromagnetic source localization [
      • Bagic A.
      • Funke M.E.
      • Ebersole J.
      • ACMEGS Position Statement Committee
      American Clinical MEG Society (ACMEGS) position statement: the value of magnetoencephalography (MEG)/magnetic source imaging (MSI) in noninvasive presurgical evaluation of patients with medically intractable localization-related epilepsy.
      ] and a Clinical Practice Guideline for recording and analysis of spontaneous cerebral activity are available from the American Clinical Magnetoencephalography Society [
      • Bagić A.I.
      • Knowlton R.C.
      • Rose D.F.
      • Ebersole J.S.
      • ACMEGS Clinical Practice Guideline (CPG) Committee
      American clinical magnetoencephalography society clinical practice guideline 1: recording and analysis of spontaneous cerebral activity.
      ] and several general recommendations on hardware requirements and forward and inverse model selection [
      • Leijten F.S.
      • Huiskamp G.
      Interictal electromagnetic source imaging in focal epilepsy: practices, results and recommendations.
      ,
      • Funke M.
      • Constantino T.
      • Van Orman C.
      • Rodin E.
      Magnetoencephalography and magnetic source imaging in epilepsy.
      ]. In a recent survey conducted among the E-PILEPSY reference centres in Europe it was reported that seven centres apply MEG source localization, and nine centres apply EEG source localization. Fourteen centres use combinations of inverse methods and head models [
      • Mouthon A.L.
      • van Hedel H.J.
      • Meyer-Heim A.
      • Kurth S.
      • Ringli M.
      • Pugin F.
      • et al.
      High-density electroencephalographic recordings during sleep in children with disorders of consciousness.
      ].
      The so-called MRI-negative patients are most challenging for epilepsy surgical management, thus it clear, that this patient group has been investigated most often with MSI. In a retrospective study on 25 MR negative patients, MRI post processing could reveal a subtle lesion by using MR post processing techniques [
      • Wang Z.I.
      • Alexopoulos A.V.
      • Jones S.E.
      • Najm I.M.
      • Ristic A.
      • Wong C.
      • et al.
      Linking MRI postprocessing with magnetic source imaging in MI-negative epilepsy.
      ]. In 7 of these patients MSI was concordant with the suspected lesion on MR post processing. Patients in whom a concordant area was identified by both MR post processing and MSI had a significantly higher chance of achieving a seizure-free outcome following complete resection of this area. A similar utility has been reported in the so far largest series with a long duration of follow-up [
      • Englot D.J.
      • Nagarajan S.S.
      • Imber B.S.
      • Raygor K.P.
      • Honma S.M.
      • Mizuiri D.
      • et al.
      Epileptogenic zone localization using magnetoencephalography predicts seizure freedom in epilepsy surgery.
      ]: They analysed 132 surgical patients with a postoperative follow-up of 3.6 years. MSI was successful in identifying a dipole in 78%. A localising MSI result predicted seizure freedom with an odds ration of 5.11.
      Once these promising result of a non invasive approach has been confirmed and validated one could also envisage a less invasive procedure following identification of epileptogenic generators by MSI: minimal or even non-invasive treatment like laser ablation or focal fractionated low dose radio therapy are further options for patients with epileptic activity in eloquent areas like the central or language region. If MEG can localize the epileptic activity and the functional cortex non-invasively then these innovative treatment approaches are helpful in selected patients.
      Finally new technical developments without low temperature recording e.g. with optically—pumped magnetometers [
      • Knappe S.
      • Sander T.H.
      • Trahms L.
      Optically pumped magnetometers for MEG.
      ] may open a new avenue for simultaneous MEG/EEG prolonged recordings.

      4. Challenges and future opportunities for MEG in clinical epileptology

      Despite the major advances in recording techniques, reliability of the recording systems, and accumulated knowledge around the generation and propagation of signals in the epileptogenic networks the breakthrough in terms of broad utilisation within the healthcare system did not take place yet. One of the major obstacles is the high price of the systems (2–3 million Euro) and the running cost, which can be be another 60–90,000 Euro per year for cooling with helium. In the future the costs are lowered by using a new helium refilling system. Not to mention the cost for data storage, technical maintenance, and last, but not least the high cost for qualifies staff such as physicians and technical experts. By nature this allows only few centres to cover the expenditures and engage in such an adventure. What kind of data and actions do we need to change this situation to let all patients participate across Europe irrespective of the health care system?
      First and foremost, the community has to create the evidence, that MEG and MSI with all the advantages, really pays off the high investments and running costs. This requires prospective studies with blinded outcome assessment to get out of the circular argument of self-fulfilling prediction. When we identify a lesion and this is concordant with electromagnetic source localization, there is no convincing argument. Important tasks are if MEG is able to point to occult lesions or identifies the epileptogenic lesion in case of multiple lesions or predicts the extension of resection (which may be larger than the lesion itself). The question is, whether MEG predicts seizure outcome reliably and safe patients potentially harmful invasive recordings. The current evidence of MEG studies is hampered by lack of standardized outcome reporting and description of the selection bias. It is clear, that these studies cannot be undertaken at a single centre, but would need large cooperative networks, such as the E-PILEPSY reference network for rare and complex epilepsies.
      Secondly, quality criteria are needed for use of MEG in epilepsy centres engaging in presurgical evaluation. There are national consensus based guidelines in some countries and well-recognised trinational (Austria, Germany, Switzerland) quality guideline, in which MEG is recommended as an “optional” tool [
      • Rosenow F.
      • Bast T.
      • Czech T.
      • Feucht M.
      • Hans V.H.
      • Helmstaedter C.
      • et al.
      Revised version of quality guidelines for presurgical epilepsy evaluation and surgical epilepsy therapy issued by Austrian, German and Swiss Working Group on presurgical epilepsy diagnosis and operative treatment.
      ,
      • Rosenow F.
      • Bast T.
      • Czech T.
      • Hans V.
      • Helmstaedter C.
      • Huppertz H.J.
      • et al.
      Qualitiy guidelienes for presurgical epillepsy diagnosis and operative epilepsy therapy: 1st revised version.
      ]. Concerning European standards MEG also is considered as additional tool in special cases [

      EFNS task force presurgical evaluation of epilepsies: European standards. J Neurol 2010;119–122.

      ]. However concise evidence based European Guidelines for MEG in presurgical evaluation are still missing, but are currently under development. A position paper of the American Clinical Magnetoencephalography Society (ACMEGS) in 2009 [
      • Bagic A.
      • Funke M.E.
      • Ebersole J.
      • ACMEGS Position Statement Committee
      American Clinical MEG Society (ACMEGS) position statement: the value of magnetoencephalography (MEG)/magnetic source imaging (MSI) in noninvasive presurgical evaluation of patients with medically intractable localization-related epilepsy.
      ] and subsequent epilepsy specific guidelines for recording and analysis of spontaneous cerebral activity in 2011 [
      • Bagić A.I.
      • Knowlton R.C.
      • Rose D.F.
      • Ebersole J.S.
      • ACMEGS Clinical Practice Guideline (CPG) Committee
      American clinical magnetoencephalography society clinical practice guideline 1: recording and analysis of spontaneous cerebral activity.
      ] are an important step in the right direction. However, in order to have a strong argument to cover the cost, evidence and evidence-based guidelines are needed.
      Thirdly, once the evidence has been created and confirmed in prospective studies, at least in Europe and other governmentally driven health care system, one has to talk about the reimbursement for the individual investigations. It can be estimated that the individual costs vary depending on the cost (especially for staff) at a national level. Nevertheless without evidence-based guidelines the arguments for reimbursement will be weak. Cross boarder health care is dependent of established procedures, clearly delineated clinical pathways and standardized investigation. In Europe and its member stated it is clear, that only some major centres will need to provide an MEG service. Collaborative networks utilizing e-health technologies will facilitate selecting the patients, which may profit most from MEG.
      Finally, MEG with all its established uses in the presurgical workup of drug resistant epilepsies, one has to acknowledge also other clinical indications, such as the assessment of brain tumours, higher cortical function, or neuropsychiatric indications. Irrespective how broad the future of the clinical implications may be, there is a clear necessity to have the MEG units embedded in a fruitful neuroscience context which is inspired by clinical questions. A cross fertilization is only able at centres, which have a critical mass of research groups and clinical services.
      For the time being, we regard MEG at the edge of its breakthrough for broad clinical use, following its unquestioned outstanding role in cognitive neurosciences, just a few years ago. It is the responsibility of the community to enable a smooth transition from a neuroscience tool, to a clinically important investigation of critical relevance.

      Conflict of interest statement

      H.Stefan received grants from deutsche Forschungsgemeinschaft (DFG) and travel reimbursement from ELEKTA.
      Both authors declare no conflict of interest concerning the content of this article.

      References

        • Cohen D.
        MEG: detection of the brain electrical activity with a super conducting magnetometer.
        Science. 1972; 175: 664-666
        • Stefan H.
        • Schneider S.
        • Abraham-Fuchs K.
        • Bauer J.
        • Feistel H.
        • Pawlik G.
        • et al.
        Magnetic source localization in focal epilepsy.
        Brain. 1990; 113: 1347-1359
        • Sutherling W.W.
        • Mamelak A.N.
        • Thyerlei D.
        • Maleeva T.
        • Minazad T.
        • Philpott L.
        • et al.
        Influence of magnetic source imaging for planning intracranial EEG in epilepsy.
        Neurology. 2008; 71: 990-996
        • Knowlton B.J.
        • Razdan S.N.
        • Limdi N.
        • Elgavish R.A.
        • Killen J.
        • Blount J.
        • et al.
        Effect of epilepsy magnetic source imaging on intracranial electrode placement.
        Ann Neurol. 2009; 65: 716-723
        • Badier J.M.
        • Chauvel P.
        Spatio-temporal characteristics of paroxysmal interictal events in human temporal lobe epilepsy.
        J Physiol. 1995; 89: 255-264
        • Aydin Ü.
        • Vorwerk J.
        • Küpper P.
        • Heers H.
        • Kugel H.
        • Galka A.
        • et al.
        Combining EEG and MEG for the reconstruction of epileptic activity using a calibrated realistic volume conductor model.
        PLoS One. 2014; 26: e93153
        • Aydin Ü.
        Combined EEG and MEG source analysis of epileptiform activity using calibrated realistic finite element head models, Thesis.
        University Muenster, 2016
        • Sakurai K.
        • Takeda Y.
        • Tanaka N.
        • Kurita T.
        • Shiraishi H.
        • Takenchi F.
        • et al.
        Generalized spike-wave discharges involve a default mode network in patients with juvenile absence epilepsy: a MEG study.
        Epilepsy Res. 2010; 89: 176-184
        • Avanzini G.
        • Manganotti P.
        • Meletti S.
        • Moshe S.L.
        • Panzica F.
        • Wolf P.
        • et al.
        The system epilepsy: a pathophysiological hypothesis.
        Epilepsia. 2012; 53: 771-778
        • Englot D.J.
        • Hinkley L.B.
        • Kort N.S.
        • Imber B.S.
        • Miziniri D.
        • Honma S.M.
        • et al.
        Global and regional functional connectivity maps of neural oscillations in focal epilepsy.
        Brain. 2015; 138: 2249-2262
        • Dobesberger J.
        • Walser G.
        • Unterberger I.
        • Seppi K.
        • Kuchukhidze G.
        • Larch J.
        • et al.
        Video-EEG monitoring: safety and adverse events in 507 consecutive patients.
        Epilepsia. 2011; 52: 443-452
        • Wu X.
        • Rampp S.
        • Hopfengärtner R.
        • Buchfelder M.
        • Zhou D.
        • Stefan H.
        Complimentary use of video EEG and MEG in frontal lobe epilepsy.
        Seizure. 2012; 21: 426-430
        • Malinowska U.
        • Badier J.M.
        • Gavaret M.
        • Bartolomei F.
        • Chauvel P.
        • Bénar C.G.
        Interictal networks in magnetoencephalography.
        Hum Brain Mapp. 2014; 35: 2789-2805
        • Murakami H.
        • Wang S.
        • Marashly A.
        • Krishnan B.
        • Prayson R.A.
        • Kakisaka Y.
        • et al.
        Correlating magnetoencephalography to stereo-electroencephalography in patients undergoing epilepsy surgery.
        Brain. 2016; (ahead of print)
        • Lüders H.
        • Engel J.
        • Monari C.
        General principles.
        in: Engel J. Surgical treatment of the epilepsies. Raven Press, 1993: 137-153
        • Englot D.J.
        • Nagarajan S.S.
        • Imber B.S.
        • Raygor K.P.
        • Honma S.M.
        • Mizuiri D.
        • et al.
        Epileptogenic zone localization using magnetoencephalography predicts seizure freedom in epilepsy surgery.
        Epilepsia. 2015; 56: 949-958
        • Jayakar P.
        • Gaillard W.D.
        • Tripathi M.
        • Libenson M.H.
        • Mathern G.W.
        • Cross J.H.
        Task force for paediatric epilepsy surgery CfP, the diagnostic commission of the international league against epilepsy: specific diagnostic test utilization in evaluation for resective epilepsy surgery in children.
        Epilepsia. 2014; 55: 507-518
        • Stefan H.
        • Hummel C.
        • Scheler G.
        • Genow A.
        • Druschky K.
        • Tilz C.
        • et al.
        Magnetic brain source imaging of focal epileptic activity: a synopsis of 455 cases.
        Brain. 2003; 126: 2396-2405
        • Oishi M.
        • Kameyama S.
        • Masuda H.
        • Tohyama J.
        • Kanazawa O.
        • Sasagawa M.
        • et al.
        Single and multiple clusters of MEG dipoles in neocortical epilepsy: significance of characterizing the epileptogenic zone.
        Epilepsia. 2006; 47: 355-364
        • De Tiege X.
        • Carrette E.
        • Legros B.
        • Vonck K.
        • Op de Beeck V.
        • Bourquignon M.
        • et al.
        Clinical added value of magnetic source imaging in presurgical evaluation of refractory focal epilepsies.
        J Neurol Neurosurg Psychiatry. 2012; 83: 417-423
        • Ebersole J.S.
        • Ebersole S.M.
        Combining MEG and EEG source modeling in epilepsy evaluations.
        J Clin Neurophysiol. 2010; 27: 360-371
        • Stefan H.
        • Rampp S.
        • Knowlton R.C.
        Magnetoencephalography adds to the surgical evaluation process.
        Epilepsy Behav. 2011; 20: 172-177
        • Mu J.
        • Rampp S.
        • Carrette E.
        • Roessler K.
        • Sommer B.
        • Schmitt F.C.
        • et al.
        Clinical relevance of source localization in frontal lobe epilepsies and prediction of postoperative longterm outcome.
        Seizure. 2014; 23: 553-559
        • Ramachandrannair R.
        • Ochi A.
        • Imai K.
        • Benifla M.
        • Akiyama T.
        • Holowka S.
        • et al.
        Epileptic spasms in older pediatric patients: MEG and ictal high frequency oscillations suggested focal onset seizures in a subset of epileptic spasms.
        Epilepsy Res. 2008; 78: 216-224
        • Jung J.
        • Bouet R.
        • Delpuech C.
        • Ryvlin P.
        • Isnard J.
        • Guenot M.
        • et al.
        The value of MEG for seizure onset zone localization in MRI negative partial epilepsy.
        Brain. 2013; 136: 3176-3186
        • Ito T.
        • Otsubo H.
        • Shiraishi H.
        • Yagyu K.
        • Takahashi Y.
        • Ueda Y.
        • et al.
        Advantageous information provided by MEG for patients with neocortical epilepsy.
        Brain Dev. 2015; 37: 237-240
        • Rubinger L.
        • Chan C.
        • D’Arco D.
        • Moineddin R.
        • Muthaffar O.
        • Rutka J.T.
        • et al.
        Change in presurgical diagnostic imaging evaluation affects subsequent pediatric epilepsy surgery outcome.
        Epilepsia. 2016; 57: 32-40
        • Bagic A.
        • Funke M.E.
        • Ebersole J.
        • ACMEGS Position Statement Committee
        American Clinical MEG Society (ACMEGS) position statement: the value of magnetoencephalography (MEG)/magnetic source imaging (MSI) in noninvasive presurgical evaluation of patients with medically intractable localization-related epilepsy.
        J Clin Neurophysiol. 2009; 26: 290-293
        • Bagić A.I.
        • Knowlton R.C.
        • Rose D.F.
        • Ebersole J.S.
        • ACMEGS Clinical Practice Guideline (CPG) Committee
        American clinical magnetoencephalography society clinical practice guideline 1: recording and analysis of spontaneous cerebral activity.
        J Clin Neurophysiol. 2011; 28: 348-354
        • Leijten F.S.
        • Huiskamp G.
        Interictal electromagnetic source imaging in focal epilepsy: practices, results and recommendations.
        Curr Opin Neurol. 2008; 21: 437-445
        • Funke M.
        • Constantino T.
        • Van Orman C.
        • Rodin E.
        Magnetoencephalography and magnetic source imaging in epilepsy.
        Clin EEG Neurosci. 2009; 40: 271-280
        • Mouthon A.L.
        • van Hedel H.J.
        • Meyer-Heim A.
        • Kurth S.
        • Ringli M.
        • Pugin F.
        • et al.
        High-density electroencephalographic recordings during sleep in children with disorders of consciousness.
        Neuroimage Clin. 2016; 11: 468-475
        • Wang Z.I.
        • Alexopoulos A.V.
        • Jones S.E.
        • Najm I.M.
        • Ristic A.
        • Wong C.
        • et al.
        Linking MRI postprocessing with magnetic source imaging in MI-negative epilepsy.
        Ann Neurol. 2014; 75: 759-770
        • Knappe S.
        • Sander T.H.
        • Trahms L.
        Optically pumped magnetometers for MEG.
        Springer Verlag, 2015
        • Rosenow F.
        • Bast T.
        • Czech T.
        • Feucht M.
        • Hans V.H.
        • Helmstaedter C.
        • et al.
        Revised version of quality guidelines for presurgical epilepsy evaluation and surgical epilepsy therapy issued by Austrian, German and Swiss Working Group on presurgical epilepsy diagnosis and operative treatment.
        Epilepsia. 2016; 57: 1215-1220
        • Rosenow F.
        • Bast T.
        • Czech T.
        • Hans V.
        • Helmstaedter C.
        • Huppertz H.J.
        • et al.
        Qualitiy guidelienes for presurgical epillepsy diagnosis and operative epilepsy therapy: 1st revised version.
        Nervenarzt. 2014; 85: 753-756
      1. EFNS task force presurgical evaluation of epilepsies: European standards. J Neurol 2010;119–122.