Magnetoencephalography for Epilepsy Presurgical Evaluation.

PURPOSE OF THE REVIEW: Magnetoencephalography (MEG) is a functional neuroimaging technique that records neurophysiology data with millisecond temporal resolution and localizes it with subcentimeter accuracy. Its capability to provide high resolution in both of these domains makes it a powerful tool both in basic neuroscience as well as clinical applications. In neurology, it has proven useful in its ability to record and localize epileptiform activity. Epilepsy workup typically begins with scalp electroencephalography (EEG), but in many situations, EEG-based localization of the epileptogenic zone is inadequate. The complementary sensitivity of MEG can be crucial in such cases, and MEG has been adopted at many centers as an important resource in building a surgical hypothesis. In this paper, we review recent work evaluating the extent of MEG influence of presurgical evaluations, novel analyses of MEG data employed in surgical workup, and new MEG instrumentation that will likely affect the field of clinical MEG. RECENT FINDINGS: MEG consistently contributes to presurgical evaluation and these contributions often change the plan for epilepsy surgery. Extensive work has been done to develop new analytic methods for localizing the source of epileptiform activity with MEG. Systems using optically pumped magnetometry (OPM) have been successfully deployed to record and localize epileptiform activity. MEG remains an important noninvasive tool for epilepsy presurgical evaluation. Continued improvements in analytic methodology will likely increase the diagnostic yield of the test. Novel instrumentation with OPM may contribute to this as well, and may increase accessibility of MEG by decreasing cost.

From theory to practical fundamentals of electroencephalographic source imaging in localizing the epileptogenic zone.

With continued advancement in computational technologies, the analysis of electroencephalography (EEG) has shifted from pure visual analysis to a noninvasive computational technique called EEG source imaging (ESI), which involves mathematical modeling of dipolar and distributed sources of a given scalp EEG pattern. ESI is a noninvasive phase I test for presurgical localization of the seizure onset zone in focal epilepsy. It is a relatively inexpensive modality, as it leverages scalp EEG and magnetic resonance imaging (MRI) data already collected typically during presurgical evaluation. With an adequate number of electrodes and combined with patient-specific MRI-based head models, ESI has proven to be a valuable and accurate clinical diagnostic tool for localizing the epileptogenic zone. Despite its advantages, however, ESI is routinely used at only a minority of epilepsy centers. This paper reviews the current evidence and practical fundamentals for using ESI of interictal and ictal epileptic activity during the presurgical evaluation of drug-resistant patients. We identify common errors in processing and interpreting ESI studies, describe the differences in approach needed for localizing interictal and ictal EEG discharges through practical examples, and describe best practices for optimizing the diagnostic information available from these studies.

EEG Source Imaging in Presurgical Evaluations.

SUMMARY: Presurgical evaluations to plan intracranial EEG implantations or surgical therapies at most epilepsy centers in the United States currently depend on the visual inspection of EEG traces. Such analysis is inadequate and does not exploit all the localizing information contained in scalp EEG. Various types of EEG source modeling or imaging can provide sublobar localization of spike and seizure sources in the brain, and the software to do this with typical long-term monitoring EEG data are available to all epilepsy centers. This article reviews the fundamentals of EEG voltage fields that are used in EEG source imaging, the strengths and weakness of dipole and current density source models, the clinical situations where EEG source imaging is most useful, and the particular strengths of EEG source imaging for various cortical areas where spike/seizure sources are likely.

Tonic phase of a generalized convulsive seizure is an independent predictor of postictal generalized EEG suppression.

PURPOSE: To determine the incidence, duration, risk factors for, and clinical correlates of postictal generalized electroencephalography (EEG) suppression (PGES), and to further delineate the significance of PGES in the pathogenesis of sudden unexpected death in epilepsy (SUDEP). METHODS: We retrospectively reviewed the video-EEG studies of 109 consecutive patients with 151 generalized convulsive seizures (GCS) during video-EEG monitoring. We determined the incidence, duration, and clinical correlates of PGES. We also investigated whether factors such as age, sex, seizure type, total seizure duration, and duration of tonic and clonic phases influenced PGES. KEY FINDINGS: PGES was observed in 64 (58.7%) of 109 patients and in 98 (64.9%) of 151 GCS. Average duration of PGES was 42.4 ± 19.1 s. Statistical analysis showed that patients with PGES had no difference in age, gender, total seizure duration, total convulsive duration, clonic phase, seizure type, and seizure termination, as compared to those without PGES. However, tonic phase was significantly prolonged in patients with PGES than in those without PGES (p = 0.00086). A 1 s increase in tonic phase duration was associated with a 0.06 increase in log odds of PGES (odds ratio = 1.1, p = 0.00055). Clinically, 95.3% patients were unresponsive or immobile during PGES, whereas only 26.7% patients without PGES were unresponsive or immobile immediately after seizure termination. SIGNIFICANCE: PGES is a common EEG pattern of GCS. Tonic phase of GCS is an independent predictor of PGES, which is well correlated with postictal unresponsiveness or immobile, and may play a significant role in the mechanism of SUDEP.

Interictal regional delta slowing is an EEG marker of epileptic network in temporal lobe epilepsy.

PURPOSE: Several studies have suggested that interictal regional delta slowing (IRDS) carries a lateralizing and localizing value similar to interictal spikes and is associated with favorable surgical outcomes in patients with temporal lobe epilepsy (TLE). However, whether IRDS reflects structural dysfunction or underlying epileptic activity remains controversial. The objective of this study is to determine the cortical electroencephalography (EEG) correlates of scalp-recorded IRDS, in so doing, to further understand its clinical and biologic significances. METHODS: We examined the cortical EEG substrates of IRDS with electrocorticography (ECoG-IRDS) and delineated the spatiotemporal relationship between ECoG-IRDS and both interictal and ictal discharges by recording simultaneously scalp and intracranial EEG in 18 presurgical candidates with TLE. KEY FINDINGS: Our results demonstrated that ECoG-IRDS is typically a mixture of delta/theta slowing and spike-wave potentials. ECoG-IRDS was predominantly recorded from basal and anterolateral temporal cortex, occasionally in mesial, posterior temporal, and extratemporal regions. Abundant IRDS was most commonly observed in patients with neocortical temporal lobe epilepsy (NTLE), whereas infrequent to moderate IRDS was usually observed in patients with mesial temporal lobe epilepsy (MTLE). The anatomic distribution of ECoG-IRDS was highly correlated with the irritative and seizure-onset zones in 10 patients with NTLE. However, it was poorly correlated with the irritative and seizure-onset zones in the 8 patients with MTLE. SIGNIFICANCE: These findings demonstrate that IRDS is an EEG marker of epileptic network in patients with TLE. Although IRDS and interictal/ictal discharges likely arise from the same neocortical generator in patients with NTLE, IRDS in patients with MTLE may reflect a network disease that involves temporal neocortex.

Practical Fundamentals of Clinical MEG Interpretation in Epilepsy.

Magnetoencephalography (MEG) is a neurophysiologic test that offers a functional localization of epileptic sources in patients considered for epilepsy surgery. The understanding of clinical MEG concepts, and the interpretation of these clinical studies, are very involving processes that demand both clinical and procedural expertise. One of the major obstacles in acquiring necessary proficiency is the scarcity of fundamental clinical literature. To fill this knowledge gap, this review aims to explain the basic practical concepts of clinical MEG relevant to epilepsy with an emphasis on single equivalent dipole (sECD), which is one the most clinically validated and ubiquitously used source localization method, and illustrate and explain the regional topology and source dynamics relevant for clinical interpretation of MEG-EEG.

SUDEP, suspected positional airway obstruction, and hypoventilation in postictal coma.

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of mortality in patients with chronic uncontrolled epilepsy. Despite intense interest in SUDEP from the medical and scientific communities in recent years, its etiologies are still largely unresolved. A 35-year-old woman had SUDEP after having a generalized seizure in the prone position. The cause of her death was likely asphyxia from the convergence of postictal coma and suspected positional airway obstruction and hypoventilation, rather than the commonly suspected periictal cardiac arrhythmia or central apnea. SUDEP may share a similar etiology with sudden infant death syndrome (SIDS) and is likely preventable, at least in a proportion of cases.

Relative Yield of MEG and EEG Spikes in Simultaneous Recordings.

PURPOSE: Most clinical magnetoencephalography (MEG) centers record both MEG and EEG, but model only MEG sources. This may be related to the belief that MEG spikes are more prevalent, MEG is more sensitive, or to proprietary software limitations. Biophysics would contend, however, that EEG, being sensitive to radial and tangential source orientations, would provide complementary data for analysis. METHODS: We recorded 306 channels of MEG and 25 channels of EEG simultaneously in 297 consecutive patients over 3 years. We inspected the MEG and EEG recordings separately, identified spikes in both, determined whether their voltage and/or magnetometer magnetic fields were dipolar and thus model-worthy, and segregated them into types based on similar and distinct field topography. We placed for each patient their spike types into categories, including those with both a recognizable MEG and EEG signal and those with only an MEG and only an EEG signal. RESULTS: Eighty-three percent of patients had spikes recorded, and these patients had an average of 2.7 spike types each. Fifty-six percent of spike types were present in both MEG and EEG. However, 36% of spike types were only evident in EEG, whereas 8% were noted in MEG alone. In 49% of patients with spikes, MEG review missed at least one spike type, whereas in 17% of patients, EEG review missed at least one spike type. CONCLUSIONS: To obtain an optimal yield of diagnostic information, EEG should also be subjected to source analysis in any clinical MEG study. EEG and MEG data are indeed complementary.

Localizing value of scalp EEG spikes: a simultaneous scalp and intracranial study.

OBJECTIVE: To determine the relationship between cortical origins of interictal and ictal EEG discharges in patients with temporal lobe epilepsy. METHODS: Simultaneous cortical and scalp EEG recordings were obtained from six patients with temporal lobe epilepsy. Subdural electrode contacts active at seizure onset and when scalp ictal rhythms became evident were identified. Similarly, cortical substrates of scalp EEG spikes were identified at spike peak and at the initial rising phase of the potential. RESULTS: Intracranial seizure onsets were commonly focal and involved only a few electrode contacts, as opposed to scalp ictal rhythms, which required synchronous activation of multiple electrode contacts. At the peak of scalp spikes, multiple electrode contacts were similarly active. However, at spike onset, cortical substrates were more discrete and commonly involved electrodes similar to that of seizure onsets. CONCLUSIONS: Scalp EEG ictal rhythms and the peak of a scalp spike may poorly localize the epileptogenic focus because of propagation. Cortical source area at scalp spike onset is more discrete, however, and the seizure onset zone often lies within this area. SIGNIFICANCE: Analysis of scalp spikes, such as source modeling, at their initial rising phase might provide useful localizing information about seizure origins in the same patient.

Clinical application of dipole models in the localization of epileptiform activity.

SUMMARY: Routine clinical interpretation of EEG using visual inspection of traces is a time-honored, but simplistic, form of analysis. This is particularly true in attempts to localize an epileptogenic focus by means of EEG spike or seizure waveforms. Improved understanding of the cortical substrates of these potentials has allowed us to identify their likely cerebral origins through spatio-temporal analysis of scalp voltage fields. Equivalent dipole modeling is one such technique. Although an imperfect representation of spike or seizure sources, proper interpretation of dipole models can lead to a far better characterization of their localization and propagation. Modern techniques of 3-D MRI reconstruction and realistic head models have both improved localization accuracy and provided a means of displaying results in an image of the individual's brain.

Cortical substrates of scalp EEG epileptiform discharges.

SUMMARY: Scalp EEG is an essential component of epilepsy presurgical evaluation during the lateralization and localization of epileptogenic focus. Scalp EEG epileptiform discharges may either guide direct surgical intervention or provide necessary information to further localize the epileptic focus with intracranial EEG recording. Despite the importance and widespread use of scalp EEG epileptiform discharges, the cortical EEG substrates underlying these spikes and seizure discharges are mostly speculative. Misconceptions are therefore prevalent regarding the necessary cortical area, synchrony, and amplitude required to generate those that are recordable at the scalp. Using contemporary EEG recording techniques such as simultaneous scalp and intracranial EEG recording, the authors' recent studies have shown that the cortical area of epileptiform discharges required for the scalp recording is considerably larger than commonly thought. A cortical area of 10 to 20 cm is often required to generate a scalp recognizable interictal spike or ictal rhythm. Sufficient cortical source area and synchrony are mandatory factors for the corresponding scalp EEG epileptiform recording. The amplitude is primarily dependent on source area and synchrony; therefore it is a less important factor. The authors review the previous literatures in conjunction with their recent investigations on this topic.

gamma-Aminobutyric acid-serotonin interactions in healthy men: implications for network models of psychosis and dissociation.

BACKGROUND: This study tested the hypothesis that deficits in gamma-aminobutyric acid type A (GABA(A)) receptor function might create a vulnerability to the psychotogenic and perceptual altering effects of serotonergic (5-HT(2A/2C)) receptor stimulation. The interactive effects of iomazenil, an antagonist and partial inverse agonist of the benzodiazepine site of the GABA(A) receptor complex, and m-chlorophenylpiperazine (m-CPP), a partial agonist of 5-HT(2A/2C) receptors, were studied in 23 healthy male subjects. METHODS: Subjects underwent 4 days of testing, during which they received intravenous infusions of iomazenil/placebo followed by m-CPP/placebo in a double-blind, randomized crossover design. Behavioral, cognitive, and hormonal data were collected before drug infusions and periodically for 200 min after. RESULTS: Iomazenil and m-CPP interacted in a synergistic manner to produce mild psychotic symptoms and perceptual disturbances without impairing cognition. Iomazenil and m-CPP increased anxiety in an additive fashion. Iomazenil and m-CPP interacted in a synergistic manner to increase serum cortisol. CONCLUSIONS: Gamma-aminobutyric acid-ergic deficits might increase the vulnerability to the psychotomimetic and perceptual altering effects of serotonergic agents. These data suggest that interactions between GABA(A) and 5-HT systems might contribute to the pathophysiology of psychosis and dissociative-like perceptual states.

Association of prone position with sudden unexpected death in epilepsy.

OBJECTIVE: To examine the association between prone position and sudden unexpected death in epilepsy (SUDEP). METHODS: We conducted a systematic review and meta-analysis based on a literature search from databases PubMed, Web of Science, and Scopus, using keywords "SUDEP" or "sudden unexpected death in epilepsy" or "sudden unexplained death syndromes in epilepsy." Twenty-five publications met the inclusion and exclusion criteria and were enrolled in this study. RESULTS: Body positions were documented in 253 cases of SUDEP. Of these patients, 73.3% (95% confidence interval [CI] = 65.7%, 80.9%) died in the prone position, whereas 26.7% (95% CI = 16.3%, 37.1%) died in nonprone positions. Binary random-effects analysis showed that prone position is significantly associated with SUDEP, as compared with nonprone position (p < 0.001). In addition, the prone position was reported in all 11 cases of video-EEG-monitored SUDEP. Moreover, in a subgroup of 88 cases of SUDEP in which demographics and circumstances of death were documented, the prone position was observed in 85.7% (95% CI = 74.6%, 93.3%) of patients aged 40 years or younger, but in only 60% (95% CI = 38.7%, 78.9%) of patients older than 40 years. Statistical analysis confirmed that the prone position was significantly more prevalent in the younger patient group, as compared with the older patient group (odds ratio 3.9; 95% CI = 1.4%, 11.4%; p = 0.009). CONCLUSION: There is a significant association between prone position and SUDEP, which suggests that prone position is a major risk factor for SUDEP, particularly in patients aged 40 years and younger. As such, SUDEP may share mechanisms similar to sudden infant death syndrome.

A standardized boundary element method volume conductor model.

OBJECTIVES: We used a 3-compartment boundary element method (BEM) model from an averaged magnetic resonance image (MRI) data set (Montreal Neurological Institute) in order to provide simple access to realistically shaped volume conductor models for source reconstruction, as compared to individually derived models. The electrode positions were transformed into the model's coordinate system, and the best fit dipole results were transformed back to the original coordinate system. The localization accuracy of the new approach was tested in a comparison with simulated data and with individual BEM models of epileptic spike data from several patients. METHODS: The standard BEM model consisted of a total of 4770 nodes, which describe the smoothed cortical envelope, the outside of the skull, and the outside of the skin. The electrode positions were transformed to the model coordinate system by using 3-5 fiducials (nasion, left and right preauricular points, vertex, and inion). The transformation consisted of an averaged scaling factor and a rigid transformation (translation and rotation). The potential values at the transformed electrode positions were calculated by linear interpolation from the stored transfer matrix of the outer BEM compartment triangle net. After source reconstruction the best fit dipole results were transformed back into the original coordinate system by applying the inverse of the first transformation matrix. RESULTS: Test-dipoles at random locations and with random orientations inside of a highly refined reference BEM model were used to simulate noise-free data. Source reconstruction results using a spherical and the standardized BEM volume conductor model were compared to the known dipole positions. Spherical head models resulted in mislocation errors at the base of the brain. The standardized BEM model was applied to averaged and unaveraged epileptic spike data from 7 patients. Source reconstruction results were compared to those achieved by 3 spherical shell models and individual BEM models derived from the individual MRI data sets. Similar errors to that evident with simulations were noted with spherical head models. Standardized and individualized BEM models were comparable. CONCLUSIONS: This new approach to head modeling performed significantly better than a simple spherical shell approximation, especially in basal brain areas, including the temporal lobe. By using a standardized head for the BEM setup, it offered an easier and faster access to realistically shaped volume conductor models as compared to deriving specific models from individual 3-dimensional MRI data.