Ictal source localization in presurgical patients with refractory epilepsy.

Source localization of epileptic foci using ictal spatiotemporal dipole modeling (ISDM) yields reliable anatomic information in presurgical candidates. It requires substantial resources from EEG and neuroimaging laboratories. The profile and number of patients who may benefit from it are currently unknown. The purpose of this study is to demonstrate the clinical usefulness of source localization in a prospectively analyzed series. One hundred patients (51 male and 49 female patients) with mean age of 31 years (range, 2 to 63 years) and mean duration of refractory epilepsy of 20 years (range, 1 to 49 years) were enrolled consecutively in a presurgical protocol. Ictal EEG was available in 93 patients. ISDM was performed when suitable ictal EEG files were available. The clinical applicability of ISDM was examined in three patients groups: 37 patients in whom ictal EEG recording and MRI were congruent (group I), 30 patients in whom results were not completely congruent but not incongruent (group II), and 26 patients in whom the results were incongruent (group III). ISDM could be performed in 31 of 100 patients: 11 in group I, 8 in group II, and 12 in group III. ISDM influenced decision making in none of the patients in group I, in 4 of 8 patients in group II, and in 10 of 12 patients in group III. Typically, the results of ISDM directed avoiding intracranial EEG recordings in what appeared to be unsuitable candidates for resection by clearly confirming the incongruency between ictal EEG and MRI findings. In this series of 100 presurgical candidates, ictal source localization could be performed in 31% of patients. In 14% of patients, it proved to be a key element in the surgical decision process.     

Alfentanil-induced activation: a promising tool in the presurgical evaluation of temporal lobe epilepsy patients

Pharmacologic activation of epileptic foci has been used experimentally with the hope that it may accelerate the presurgical evaluation of patients with medically intractable epilepsy. In this article, we will review the existing literature on these activating tests giving emphasis on the opioid analogs, and particularly alfentanil. Alfentanil is an opioid analog with rapid anesthetic effect, which has been known to trigger epileptiform discharges in epilepsy patients. 58 temporal lobe epilepsy (TLE) patients were studied with alfentanil activation during electrocorticography, at the Epilepsy Surgery Unit (ING, Brazil). An increase of the interictal epileptiform discharges was observed originating from hippocampal and parahippocampal regions (96.5%). To a lesser extent, alfentanil activated the basal and lateral temporal regions. Electrographic seizures were observed in 38%. In addition, we performed continuous video-EEG (VT/EEG) monitoring, with scalp and bilateral foramen ovale electrodes, in 12 TLE patients. The results of spontaneously observed seizures were compared with the electrographic changes following alfentanil activation (50–75 μg/kg, i.v.). In seven cases, alfentanil triggered focal electrographic seizures, ipsilaterally to the side generating the spontaneous seizures and in two patients it produced bilateral sequential activation of the temporal lobes. Ictal SPECTs during the alfentanil test showed hyperperfusion at the lateral temporal regions, ipsilaterally to the activated area or bilaterally. In summary, our study confirms the activating effect of alfentanil, and provides a strong evidence for its selective activating effect on the temporal lobes of TLE patients. The ictal SPECT during alfentanil activation did not offer any additional advantage for the localization of the ictal onset.     

Automatic ictal onset source localization in presurgical epilepsy evaluation

Objective

To test the diagnostic accuracy of a new automatic algorithm for ictal onset source localization (IOSL) during routine presurgical epilepsy evaluation following STARD (Standards for Reporting of Diagnostic Accuracy) criteria.

Electrical source imaging for presurgical focus localization in epilepsy patients with normal MRI

Purpose: Patients with magnetic resonance (MR)–negative focal epilepsy (MRN‐E) have less favorable surgical outcomes (between 40% and 70%) compared to those in whom an MRI lesion guides the site of surgical intervention (60–90%). Patients with extratemporal MRN‐E have the worst outcome (around 50% chance of seizure freedom). We studied whether electroencephalography (EEG) source imaging (ESI) of interictal epileptic activity can contribute to the identification of the epileptic focus in patients with normal MRI. Methods: We carried out ESI in 10 operated patients with nonlesional MRI and a postsurgical follow‐up of at least 1 year. Five of the 10 patients had extratemporal lobe epilepsy. Evaluation comprised surface and intracranial EEG monitoring of ictal and interictal events, structural MRI, [¹⁸F]fluorodeoxyglucose positron emission tomography (FDG‐PET), ictal and interictal perfusion single photon emission computed tomography (SPECT) scans. Eight of the 10 patients also underwent intracranial monitoring. Results: ESI correctly localized the epileptic focus within the resection margins in 8 of 10 patients, 9 of whom experienced favorable postsurgical outcomes. Discussion: The results highlight the diagnostic value of ESI and encourage broadening its application to patients with MRN‐E. If the surface EEG contains fairly localized spikes, ESI contributes to the presurgical decision process.     

Using electrocorticography for presurgical language mapping in epilepsy patients

Of five epilepsy patients with implanted subdural electrodes, electrical cortical stimulation (ECS) on left posterior inferior frontal gyri (LPIFG) of dominant language hemisphere, did not elicit language production related symptoms. These patients were then subjected to six language production tasks with simultaneously electrocorticographic (ECoG) recording. Dada analysis revealed several cortical sites showed event-related cortical high gamma activities. These sites were linked to certain functions, e.g., auditory, visual, and sensorimotor, according to their different activation patterns among tasks. Sites labeled as sensorimotor-related by ECoG showed high accordance with those identified via ECS. Yet ECoG identified few extra crucial sites in LPIFG either. These results demonstrated consistency between ECS and ECoG and reaffirmed the utility of ECoG in preoperative functional cortical mapping.     

Intractable pediatric epilepsy: presurgical evaluation

Epilepsy surgery in children requires a multidisciplinary approach. This section examines the role of scalp EEG, video-EEG monitoring, and intracranial EEG in the presurgical evaluation. Concepts central to understanding the basis for surgical treatment, such as the epileptogenic zone, the irritative zone, and the epileptogenic lesion, are discussed. An illustrative case then demonstrates application of the process in clinical practice. Neuroimaging and neuropsychological issues are not discussed herein; rather they are addressed elsewhere in this issue.     

Individual localization value of resting-state fMRI in epilepsy presurgical evaluation: A combined study with stereo-EEG

ObjectiveTo examine the individual-patient-level localization value of resting-state functional MRI (rsfMRI) metrics for the seizure onset zone (SOZ) defined by stereo-electroencephalography (SEEG) in patients with medically intractable focal epilepsies.MethodsWe retrospectively included 19 patients who underwent SEEG implantation for epilepsy presurgical evaluation. Voxel-wise whole-brain analysis was performed on 3.0 T rsfMRI to generate clusters for amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo) and degree centrality (DC), which were co-registered with the SEEG-defined SOZ to evaluate their spatial overlap. Subgroup and correlation analyses were conducted for various clinical characteristics.ResultsALFF demonstrated concordant clusters with SEEG-defined SOZ in 73.7% of patients, with 93.3% sensitivity and 77.8% PPV. The concordance rate showed no significant difference when subgrouped by lesional/non-lesional MRI, SOZ location, interictal epileptiform discharges on scalp EEG, pathology or seizure outcomes. No significant correlation was seen between ALFF concordance rate and epilepsy duration, seizure-onset age, seizure frequency or number of antiseizure medications. ReHo and DC did not achieve favorable concordance results (10.5% and 15.8%, respectively). All concordant clusters showed regional activation, representing increased neural activities.ConclusionALFF had high concordance rate with SEEG-defined SOZ at individual-patient level.SignificanceALFF activation on rsfMRI can add localizing information for the noninvasive presurgical workup of intractable focal epilepsies.     

Comprehensive presurgical functional MRI language evaluation in adult patients with epilepsy

Functional magnetic resonance imaging (fMRI) has the potential to replace the intracarotid amobarbital procedure (IAP) in presurgical evaluation of patients with epilepsy. In this study, we compared fMRI verb generation (VG) and semantic decision/tone decision (SDTD) tasks and the IAP in their ability to localize language functions in patients with epilepsy undergoing presurgical evaluation. We enrolled 50 healthy controls to establish normal language activation patterns for VG and SDTD tasks at 3 or 4 T, and to design language regions of interest (ROIs) that were later applied to 38 patients with epilepsy (28 of 38 also underwent the IAP). We calculated laterality indices (LIs) for each task for each subject based on the ROIs, and we used general linear modeling to analyze the fMRI data. All healthy and epileptic subjects activated language areas with both fMRI tasks. We found significant correlations in language lateralization between the fMRI tasks (r=0.495, P<0.001) and between VG and IAP (r=0.652, P<0.001) and SDTD and IAP (r=0.735, P<0.001). The differences in LIs between SDTD and VG tasks were small and not affected by age, gender, epilepsy status, handedness, or performance. SDTD and VG tasks combined explained approximately 58.4% in the variability of the IAP/language. In the general linear modeling, only the SDTD task significantly contributed to the determination of language lateralization in patients with epilepsy undergoing presurgical evaluation. Results indicate a moderate convergent validity between both fMRI language tasks and between IAP and fMRI tasks. The results of this study indicate that either of these fMRI tasks can be used for language lateralization in patients with epilepsy undergoing presurgical evaluation, but that the SDTD task is likely to provide more information regarding language lateralization than the VG task.     

Foramen ovale recordings: a presurgical investigation in epilepsy

The aim of our study was to determine when foramen ovale recordings add useful information to scalp EEG recordings and magnetic resonance imaging (MRI) with hippocampal measurements. We evaluated the outcome of 79 patients with non-lesional partial epilepsy with presumed temporal seizure onset. Ictal foramen ovale recordings were performed in 16 patients with normal MRI ('MRI-negative group') and 41 patients with lateralizing MRI but non-lateralizing scalp EEG ('discordant group'). 22 patients with concordant MRI and scalp EEG were not investigated with foramen ovale recordings ('concordant group'). The seizure-free rate was higher in concordant than discordant patients despite additional investigation with foramen ovale electrodes (71 and 55% seizure free, respectively). No useful localizing information was added with foramen ovale recordings in MRI-negative patients.     

Use of magnetoencephalography in the presurgical evaluation of epilepsy patients.

Magnetoencephalography (MEG) is used twofold for presurgical evaluation of patients with medically intractable partial epilepsy; to identify epileptogenic focus and to investigate functions of cortical areas at or near the epileptogenic focus or structural lesion. For the precise localization of the current source of epileptic discharge, the question as to whether MEG is superior to electroencephalography (EEG) is often addressed. To answer this question, so many factors, both biologically and technically related, have to be taken into consideration. The biological factors include the magnitude of epileptic discharge, its distribution over the cortex, depth of its source from the head surface, and the proportion of large pyramidal neurons tangentially oriented with respect to the head surface within the cortical area. The technical factors include the quality of the recording instrument such as the number of sensors and the use of gradiometer vs. magnetometer, the employed method of source analysis, and availability of experts in each institute. As far as the importance of ictal recording is emphasized, long-term video/EEG monitoring is of utmost importance. Thus, it is concluded that, once the epileptogenic focus is identified by the video/EEG monitoring, then MEG is superior to EEG in order to precisely localize the current source of the interictal epileptic discharge. Another question often addressed is whether MEG can replace the invasive intracranial EEG recording or not. In addition to the above-described factors, different coverage of the cortical areas by MEG vs. invasive intracranial EEG recording has to be taken into account to explain some of the recent reports related to this question. MEG can be effectively applied to the investigation of cortical functions near the epileptogenic focus. It is especially so when combined with other non-invasive studies like functional magnetic resonance imaging (fMRI). In addition to the source analysis of magnetic fields related to various events or tasks, analysis of the task-related change of rhythmic cortical oscillations is a useful tool for studying higher cortical functions such as language in the presurgical evaluation.     

Magnetoencephalography in the presurgical evaluation of epilepsy

Magnetoencephalography (MEG) is an important tool in the presurgical evaluation of patients with medically refractory epilepsy. The appropriate utilization and interpretation of MEG studies can increase the proportion of patients who may be able to further pursue surgical evaluation, refine surgical planning, and potentially increase the probability of seizure freedom after surgery. The aim of this paper is to provide the reader with a comprehensive but accessible guide to MEG, with particular emphasis on acquiring a working knowledge of MEG analysis, identifying patient groups that are most likely to benefit, and clarifying the limitations of this technology.     

Revised version of quality guidelines for presurgical epilepsy evaluation and surgical epilepsy therapy issued by the Austrian,German, and Swiss working group on presurgical epilepsy diagnosis and operative epilepsy treatment

The definition of minimal standards remains pivotal as a basis for a high standard of care and as a basis for staff allocation or reimbursement. Only limited publications are available regarding the required staffing or methodologic expertise in epilepsy centers. The executive board of the working group (WG) on presurgical epilepsy diagnosis and operative epilepsy treatment published the first guidelines in 2000 for Austria, Germany, and Switzerland. In 2014, revised guidelines were published and the WG decided to publish an unaltered English translation in this report. Because epilepsy surgery is an elective procedure, quality standards are particularly high. As detailed in the first edition of these guidelines, quality control relates to seven different domains: (1) establishing centers with a sufficient number of sufficiently and specifically trained personnel, (2) minimum technical standards and equipment, (3) continuous medical education of employees, (4) surveillance by trained personnel during video electroencephalography (EEG) monitoring (VEM), (5) systematic acquisition of clinical and outcome data, (6) the minimum number of preoperative evaluations and epilepsy surgery procedures, and (7) the cooperation of epilepsy centers. These standards required the certification of the different professions involved and minimum numbers of procedures. In the subsequent decade, quite a number of colleagues were certified by the trinational WG; therefore, the executive board of the WG decided in 2013 to make these standards obligatory. This revised version is particularly relevant given that the German procedure classification explicitly refers to the guidelines of the WG with regard to noninvasive/invasive preoperative video‐EEG monitoring and invasive intraoperative diagnostics in epilepsy.     

Intracranial electrodes in the presurgical evaluation of epilepsy

The resection of the epileptogenic area of brain is very important and useful for the treatment of uncontrolled epilepsy, especially for the patients with stereotyped partial seizures. The critical point for successful epilepsy surgery is the precise identification of epileptogenic zone. Actually, we cannot precisely localize the epileptogenic zone in about 25?% of patient with refractory seizures based on the noninvasive examination; thus for these patients, we mainly use the intracranial EEG to localize the epileptogenic zone which could be useful in 10-15?% of surgical candidates. The intracranial electrodes which are most used currently are depth electrodes, subdural strip electrodes, and subdural grid electrodes. The subject of this paper is to discuss and compare the indications, construction, insertion, interpretation, limitations, risks and accuracy of each of these methods.     

Functionalized magnetonanoparticles for MRI diagnosis and localization in epilepsy

Purpose: The development of nonradioactive and targeted magnetonanoparticles (MNP) capable of crossing the blood–brain barrier (BBB) and of concentrating in the epileptogenic tissues of acute and chronic animal models of temporal lobe epilepsy to render these tissues visible on magnetic resonance imaging (MRI).
Methods: Nonradioactive alpha methyl tryptophan (AMT) was covalently attached to MNP composed of iron oxide and dextran. A rodent model of temporal lobe epilepsy was prepared by injecting kainic acid into the right hippocampus. AMT-MNP or plain MNP was injected in the tail-vein of two animals during the acute stage 3 days after status epilepticus, and AMT-MNP in five animals during the chronic stage. MRIs were obtained before and after particle injection in all animals. Intracranial EEGs were obtained in all chronic animals after completion of MRI studies.
Results: AMT-MNP crossed the BBB and intraparenchymal uptake was visible on MRI. In the acute condition, AMT-MNP appeared to localize to both hippocampi, whereas plain MNP only identified unilateral, presumably inflammatory, changes. In the chronic condition, AMT-MNP uptake correlated with the occurrence of spontaneous seizures, and the location of uptake appeared to agree with bilateral or unilateral epileptogenicity confirmed by subsequent intracranial EEG.
Discussion: Nonradioactive AMT-MNP can cross the BBB and may accurately localize epileptogenic cerebral regions. The MNP-MRI approach is potentially applicable to the use of any bioactive molecules as ligands for imaging normal and abnormal localized cerebral functions, accurately, safely, and inexpensively.     

Antiepileptic drug withdrawal in patients with temporal lobe epilepsy undergoing presurgical video-EEG monitoring

PURPOSE: To investigate antiepileptic drug (AED) withdrawal during video-EEG monitoring in adult patients with temporal lobe epilepsy (TLE). METHODS: Between 1995 and 1997, 102 consecutive patients with refractory TLE were admitted to the epilepsy monitoring unit for presurgical evaluation. Patients were monitored with ongoing AEDs being rapidly decreased and discontinued in 4-6 days. The monitoring was continued until sufficient numbers of seizures were recorded. Serum AED levels were checked at admission and after the first complex partial seizure (CPS). RESULTS: In all, 89 patients had 429 CPSs (mean, 4.8 per patient), including 156 (36.4%) secondarily generalized. A mean of 153.8 h (16-451 h) was required for completing the monitoring in each patient. Forty-three (48.3%) patients experienced seizure clusters, and eight (9.0%) had generalized seizures that had never occurred or had been absent for years. However, none evolved to status epilepticus. Carbamazepine was the most commonly used AED in 71.9% of patients, followed by valproate and phenytoin. When the first CPS occurred, mean 77.2 h since the beginning of the monitoring, serum levels of these three AEDs were mostly subtherapeutic rather than minimal. CONCLUSIONS: Acute AED withdrawal effectively provoked seizures in TLE patients undergoing presurgical video-EEG monitoring. However, nearly 50% of patients had seizure clusters or secondarily generalized seizures. Serum AED levels were mostly subtherapeutic when the first CPS occurred.