Albert J. Colon

Magnetoencephalography is more successful for screening and localizing frontal lobe epilepsy than electroencephalography.

Purpose: The diagnosis of frontal lobe epilepsy may be compounded by poor electroclinical localization, due to distributed or rapidly propagating epileptiform activity. This study aimed at developing optimal procedures for localizing interictal epileptiform discharges (IEDs) of patients with localization related epilepsy in the frontal lobe. To this end the localization results obtained for magnetoencephalography (MEG) and electroencephalography (EEG) were compared systematically using automated analysis procedures.

EEG-fMRI correlation patterns in the presurgical evaluation of focal epilepsy: A comparison with electrocorticographic data and surgical outcome measures

EEG-correlated functional MRI (EEG-fMRI) visualizes brain regions associated with interictal epileptiform discharges (IEDs). This technique images the epileptiform network, including multifocal, superficial and deeply situated cortical areas. To understand the role of EEG-fMRI in presurgical evaluation, its results should be validated relative to a gold standard. For that purpose, EEG-fMRI data were acquired for a heterogeneous group of surgical candidates (n=16) who were later implanted with subdural grids and strips (ECoG). The EEG-fMRI correlation patterns were systematically compared with brain areas involved in IEDs ECoG, using a semi-automatic analysis method, as well as to the seizure onset zone, resected area, and degree of seizure freedom. In each patient at least one of the EEG-fMRI areas was concordant with an interictally active ECoG area, always including the early onset area of IEDs in the ECoG data. This confirms that EEG-fMRI reflects a pattern of onset and propagation of epileptic activity. At group level, 76% of the BOLD regions that were covered with subdural grids, were concordant with interictally active ECoG electrodes. Due to limited spatial sampling, 51% of the BOLD regions were not covered with electrodes and could, therefore, not be validated. From an ECoG perspective it appeared that 29% of the interictally active ECoG regions were missed by EEG-fMRI and that 68% of the brain regions were correctly identified as inactive with EEG-fMRI. Furthermore, EEG-fMRI areas included the complete seizure onset zone in 83% and resected area in 93% of the data sets. No clear distinction was found between patients with a good or poor surgical outcome: in both patient groups, EEG-fMRI correlation patterns were found that were either focal or widespread. In conclusion, by comparison of EEG-fMRI with interictal invasive EEG over a relatively large patient population we were able to show that the EEG-fMRI correlation patterns are spatially accurate at the level of neurosurgical units (i.e. anatomical brain regions) and reflect the underlying network of IEDs. Therefore, we expect that EEG-fMRI can play an important role for the determination of the implantation strategy.

Use of routine MEG in the primary diagnostic process of epilepsy.

At present, in epilepsy, magnetoencephalography (MEG) is mostly used for presurgical evaluations. It has proven to be robust for detecting and localizing interictal epileptiform discharges. Whether this is also true for first-line investigation in the diagnosis of epilepsy has not been investigated yet. We present our data on the usefulness of MEG in the earliest phase of diagnosing epilepsy. We examined 51 patients with suspicion of neocortical epilepsy and an inconclusive routine EEG. A method to integrate MEG in daily routine was developed. Results of visually assessed MEG recordings were compared, retrospectively, with clinical data and with the results of EEG after sleep deprivation. After a finding of inconclusive, routine MEG generated a gain in diagnostic value of 63% when compared with “final” clinical diagnosis. This is comparable with the added value of EEG after sleep deprivation recorded previously in the same patients. However, MEG is less of a burden for patient and hospital and has no association with risk of increase in seizure frequency. The routine MEG with visual assessment only is a reliable diagnostic tool in the routine diagnosis of epilepsy and may replace or precede EEG after sleep deprivation in daily clinical practice. Furthermore, MEG together with MRI enables magnetic source imaging and, thus, may provide additional information on the cortical localization of the epilepsy of a patient.

A framework to integrate EEG-correlated fMRI and intracerebral recordings.

EEG-correlated functional MRI (EEG-fMRI) has been used to indicate brain regions associated with interictal epileptiform discharges (IEDs). This technique enables the delineation of the complete epileptiform network, including multifocal and deeply situated cortical areas. Before EEG-fMRI can be used as an additional diagnostic tool in the preoperative work-up, its added value should be assessed in relation to intracranial EEG recorded from depth electrodes (SEEG) or from the cortex (ECoG), currently the clinical standard. In this study, we propose a framework for the analysis of the SEEG data to investigate in a quantitative way whether EEG-fMRI reflects the same cortical areas as identified by the IEDs present in SEEG recordings. For that purpose, the data of both modalities were analyzed with a general linear model at the same time scale and within the same spatial domain. The IEDs were used as predictors in the model, yielding for EEG-fMRI the brain voxels that were related to the IEDs and, similarly for SEEG, the electrodes that were involved. Finally, the results of the regression analysis were projected on the anatomical MRI of the patients. To explore the usefulness of this quantitative approach, a sample of five patients was studied who both underwent EEG-fMRI and SEEG recordings. For clinical validation, the results of the SEEG analysis were compared to the standard visual review of IEDs in SEEG and to the identified seizure onset zone, the resected area, and outcome of surgery. SEEG analysis revealed a spatial pattern for the most frequent and dominant IEDs present in the data of all patients. The electrodes with the highest correlation values were in good concordance with the electrodes that showed maximal amplitude during those events in the SEEG recordings. These results indicate that the analysis of SEEG data at the time scale of EEG-fMRI, using the same type of regression model, is a promising way to validate EEG-fMRI data. In fact, the BOLD areas with a positive hemodynamic response function were closely related to the spatial pattern of IEDs in the SEEG recordings in four of the five patients. The areas of significant BOLD that were not located in the vicinity of depth electrodes, were mainly characterized by negative hemodynamic responses. Furthermore, the area with a positive hemodynamic response function overlapped with the resected area in three patients, while it was located at the edge of the resection area for one. To conclude, the results of this study encourage the application of EEG-fMRI to guide the implantation of depth electrodes as prerequisite for successful epilepsy surgery.

Brain imaging in chronic epilepsy patients after depth electrode (stereoelectroencephalography) implantation: magnetic resonance imaging or computed tomography?

BACKGROUND The accurate localization of depth electrodes in epilepsy surgery is important for correct interpretation of stereoelectroencephalography recordings and neurosurgical resection. Unfortunately, image quality in postimplantation magnetic resonance imaging (MRI) is degraded by metal artifacts. The registration of postimplantation computed tomography (CT) or MRI to preimplantation (artifact-free) MRI facilitates electrode imaging and optimal visualization of brain anatomy. However, registration errors negatively affect electrode localization accuracy. OBJECTIVE To compare the relative registration deviation between postimplantation CT and MRI with preimplantation MRI. METHODS Retrospectively, 14 pharmacoresistant epilepsy patients were included who underwent stereotactic insertion of multiple depth electrodes and preimplantation and postimplantation MRI and postimplantation CT. Postimplantation MRI and CT image sets were registered to preimplantation MRI. The registration error between the registered postimplantation MRI and CT was quantified by measuring the geometrical distance between the electrodes of the registered postimplantation CT and the postimplantation MRI. RESULTS The registration error of postimplantation imaging to preimplantation MRI was dependent on the algorithm used. After optimization, the smallest registration error was 1.22 ± 0.29 mm (mean ± SD) at the tip and 2.25 ± 1.18 mm at the base of the electrode. CONCLUSION The good correspondence between the CT/MRI and the MRI/MRI registration suggests that either postimplantation MRI or CT is sufficient for accurate electrode localization. In case of postoperative morphological brain deformations, postimplantation MRI is still recommended.

Network analysis of EEG related functional MRI changes due to medication withdrawal in focal epilepsy

Anti-epileptic drugs (AEDs) have a global effect on the neurophysiology of the brain which is most likely reflected in functional brain activity recorded with EEG and fMRI. These effects may cause substantial inter-subject variability in studies where EEG correlated functional MRI (EEG–fMRI) is used to determine the epileptogenic zone in patients who are candidate for epilepsy surgery. In the present study the effects on resting state fMRI are quantified in conditions with AED administration and after withdrawal of AEDs. EEG–fMRI data were obtained from 10 patients in the condition that the patient was on the steady-state maintenance doses of AEDs as prescribed (condition A) and after withdrawal of AEDs (condition B), at the end of a clinically standard pre-surgical long term video-EEG monitoring session. Resting state networks (RSN) were extracted from fMRI. The epileptic component (ICE) was identified by selecting the RSN component with the largest overlap with the EEG–fMRI correlation pattern. Changes in RSN functional connectivity between conditions A and B were quantified. EEG–fMRI correlation analysis was successful in 30% and 100% of the cases in conditions A and B, respectively. Spatial patterns of ICEs are comparable in conditions A and B, except for one patient for whom it was not possible to identify the ICE in condition A. However, the resting state functional connectivity is significantly increased in the condition after withdrawal of AEDs (condition B), which makes resting state fMRI potentially a new tool to study AED effects. The difference in sensitivity of EEG–fMRI in conditions A and B, which is not related to the number of epileptic EEG events occurring during scanning, could be related to the increased functional connectivity in condition B.

Evaluation of MEG vs EEG after sleep deprivation in epilepsy

MEG and EEG after sleep deprivation (EEG‐SD) are applied as diagnostic tools in the evaluation of patients with possible epilepsy. There is no gold standard to check whether the diagnosis based on these two modalities is correct. The best standard available is the long‐term follow‐up of patients. As follow‐up of an earlier study in which the additional value of MEG vs EEG‐SD diagnosis was evaluated, we investigated the long‐term validity of MEG‐based and EEG‐SD‐based diagnosis.

Evidence on the efficacy of primary radiosurgery or stereotactic radiotherapy for drug-resistant non-neoplastic focal epilepsy in adults: A systematic review

PURPOSE Although the majority of adult epilepsy patients respond well to the current antiepileptic drug treatment, 20-40% of them are drug-resistant. In these patients, resective epilepsy surgery is a curative treatment option, for which, however, only a limited number of patients is eligible. The purpose is to summarize the outcome of radiotherapy for drug-resistant non-neoplastic focal epilepsy and to elucidate its efficacy for seizure outcome and long-term toxicity in adults. METHOD A systematic literature search was performed in Pubmed, Ovid Medline, Cochrane library, Embase and Web of Science. The methodological quality was evaluated using an adapted QUADAS checklist. RESULTS Sixteen out of 170 initially identified studies were included in this systematic literature study (n = 170 patients). Twelve of the 16 studies described a positive effect of radiotherapy on seizure frequency reduction, with 98 of the patients (on average 58%, range 25%-95%) reporting no or rare seizures (defined as radiotherapy-adapted Engel class [RAEC] I and II. In total, 20% (34 patients) of the patients needed subsequent surgery due to radionecrosis, cysts formation, edema, and intracranial hypertension or remaining seizures. A dose-effect model was fitted to the available response data in an attempt to derive a relationship between prescribed dose and RAEC frequency. CONCLUSIONS Radiotherapy is a possible non-invasive treatment option for patients with drug-resistant focal non-neoplastic epilepsy. This systematic review showed that there is only level 4 evidence of primary radiotherapy reducing seizure frequency in adult patients. Prospective randomized trials are needed to determine its exact value compared to other treatment approaches.

Automated identification of intracranial depth electrodes in computed tomography data

Intracranial depth electrodes are commonly used to identify the regions of the brain that are responsible for epileptic seizures. Knowledge of the exact location of the electrodes is important as to properly interpret the EEG in relation to the anatomy. In order to provide fast and accurate identification of these electrodes, a procedure has been developed for automatic detection and localization in computed tomography data. Results indicate that in the vast majority of cases the depth electrodes can be automatically found. The localization of the electrodes versus the anatomy showed an acceptably small error when compared to manual positioning. Furthermore, interactive visualization software is developed to show the detected electrodes together with pre-operative MRI images, which enables the physician to confirm that the electrode is placed at the expected anatomical location.

Connectivity analysis of generalized epileptic discharges

Adresses e-mail : sadeghiye hashem@yahoo.com, sadeghiye@ut.ac.it (H. Sadeghiyeh) The present study aimed to examine the gender differences in empathy for pain at a sensorimotor level. Previous studies using single-pulse TMS have shown a reduction in amplitude of motor-evoked potentials (MEPs) while subjects observing needles penetrating hand of a human model which was specific to the muscle subjects observed being pricked. Twenty-five subjects (thirteen females and twelve males) participated in the study. Their TMS-induced MEPs were recorded from their right first dorsal interosseus (FDI) muscle of index finger during watching various clips depicting needles penetrating the same FDI muscle of right hand of a model. There were twelve types of clips, including pictures of hands of a woman, a man, a child and an apple, which was either pinpricked by a needle, touched by a Q-tip or at rest. Each clip was shown to the subjects eighteen times in a completely random sequence. Electromyography signals were recorded through an amplifier of an ANT ERP recording system and analysed by ASA-Lab software. Results had been shown that women had larger MEP inhibited amplitude than men in all the stimuli. However, there were no significant differences between MEP amplitudes of different types of models’ hands. The gender differences of MEPs between subjects indicate greater sensorimotor empathy in women, which is in correspondence with greater subjective responses of women to the painful clips (state empathy), which were obtained through a Visual Analogue Scale. Therefore, upon these results, we can conclude that women’s stronger empathic response to observing pain in others go beyond just a subjective level and extend to a very automatic and sensorimotor level. Women are hard-wired to embody the pain of others more intensely, and this could prepare them to take action towards others’ pain more rapidly. Further reading