Grading system for assessing the confidence in the epileptogenic zone reported in published studies: A Delphi consensus study.

OBJECTIVE: This study was undertaken to develop a standardized grading system based on expert consensus for evaluating the level of confidence in the localization of the epileptogenic zone (EZ) as reported in published studies, to harmonize and facilitate systematic reviews in the field of epilepsy surgery. METHODS: We conducted a Delphi study involving 22 experts from 18 countries, who were asked to rate their level of confidence in the localization of the EZ for various theoretical clinical scenarios, using different scales. Information provided in these scenarios included one or several of the following data: magnetic resonance imaging (MRI) findings, invasive electroencephalography summary, and postoperative seizure outcome. RESULTS: The first explorative phase showed an overall interrater agreement of .347, pointing to large heterogeneity among experts' assessments, with only 17% of the 42 proposed scenarios associated with a substantial level of agreement. A majority showed preferences for the simpler scale and single-item scenarios. The successive Delphi voting phases resulted in a majority consensus across experts, with more than two thirds of respondents agreeing on the rating of each of the tested single-item scenarios. High or very high levels of confidence were ascribed to patients with either an Engel class I or class IA postoperative seizure outcome, a well-delineated EZ according to all available invasive EEG (iEEG) data, or a well-delineated focal epileptogenic lesion on MRI. MRI signs of hippocampal sclerosis or atrophy were associated with a moderate level of confidence, whereas a low level was ascribed to other MRI findings, a poorly delineated EZ according to iEEG data, or an Engel class II-IV postoperative seizure outcome. SIGNIFICANCE: The proposed grading system, based on an expert consensus, provides a simple framework to rate the level of confidence in the EZ reported in published studies in a structured and harmonized way, offering an opportunity to facilitate and increase the quality of systematic reviews and guidelines in the field of epilepsy surgery.

Yield of non-invasive imaging in MRI-negative focal epilepsy.

OBJECTIVE: The absence of MRI-lesion reduces considerably the probability of having an excellent outcome (International League Against Epilepsies [ILAE] class I-II) after epilepsy surgery. Surgical success in magnetic-resonance imaging (MRI)-negative cases relies therefore mainly on non-invasive techniques such as positron-emission tomography (PET), subtraction ictal/inter-ictal single-photon-emission-computed-tomography co-registered to MRI (SISCOM), electric source imaging (ESI) and morphometric MRI analysis (MAP). We were interested in identifying the optimal imaging technique or combination to achieve post-operative class I-II in patients with MRI-negative focal epilepsy. METHODS: We identified 168 epileptic patients without MRI lesion. Thirty-three (19.6%) were diagnosed with unifocal epilepsy, underwent surgical resection and follow-up ⩾ 2 years. Sensitivity, specificity, predictive values, and diagnostic odds ratio (OR) were calculated for each technique individually and in combination (after co-registration). RESULTS: 23/33 (70%) were free of disabling seizures (75.0% with temporal and 61.5% extratemporal lobe epilepsy). None of the individual modalities presented an OR > 1.5, except ESI if only patients with interictal epileptiform discharges (IEDs) were considered (OR 3.2). On a dual combination, SISCOM with ESI presented the highest outcome (OR = 6). MAP contributed to detecting indistinguishable focal cortical dysplasia in particular in extratemporal epilepsies with a sensitivity of 75%. Concordance of PET, ESI on interictal epileptic discharges, and SISCOM was associated with the highest chance for post-operative seizure control (OR = 11). CONCLUSION: If MRI is negative, the chances to benefit from epilepsy surgery are almost as high as in lesional epilepsy, provided that multiple established non-invasive imaging tools are rigorously applied and co-registered together.

Semiautomatic interictal electric source localization based on long-term electroencephalographic monitoring: A prospective study.

OBJECTIVE: Electric source imaging (ESI) of interictal epileptiform discharges (IEDs) has shown significant yield in numerous studies; however, its implementation at most centers is labor- and cost-intensive. Semiautomatic ESI analysis (SAEA) has been proposed as an alternative and has previously shown benefit. Computer-assisted automatic spike cluster retrieval, averaging, and source localization are carried out for each cluster and are then reviewed by an expert neurophysiologist, to determine their relevance for the individual case. Here, we examine its yield in a prospective single center study. METHOD: Between 2017 and 2022, 122 patients underwent SAEA. Inclusion criteria for the current study were unifocal epilepsy disorder, epilepsy surgery with curative purpose, and postoperative follow-up of 2 years or more. All patients (N=40) had continuous video-electroencephalographic (EEG) monitoring with 37 scalp electrodes, which underwent SAEA. Forty patients matched our inclusion criteria. RESULTS: Twenty patients required intracranial monitoring; 13 were magnetic resonance imaging (MRI)-negative. Mean duration of analyzed EEG was 4.3 days (±3.1 days), containing a mean of 12 749 detected IEDs (±22 324). The sensitivity, specificity, and accuracy of SAEA for localizing the epileptogenic focus of the entire group were 74.3%, 80%, and 75%, respectively, leading to an odds ratio (OR) of 11.5 to become seizure-free if the source was included in the resection volume (p < .05). In patients with extratemporal lobe epilepsy, our results indicated an accuracy of 68% (OR=11.7). For MRI-negative patients (n = 13) and patients requiring intracranial EEG (n = 20), we found a similarly high accuracy of 84.6% (OR=19) and 75% (OR = 15.9), respectively. SIGNIFICANCE: In this prospective study of SAEA of long-term video-EEG, spanning several days, we found excellent localizing information and a high yield, even in difficult patient groups. This compares favorably to high-density ESI, most likely due to marked improved signal-to-noise ratio of the averaged IEDs. We propose including ESI, or SAEA, in the workup of all patients who are referred for epilepsy surgery.

High density electric source imaging in childhood-onset epilepsy due to focal cortical dysplasia.

Objective: The goal of this study was to investigate the diagnostic utility of electric source imaging (ESI) in the presurgical evaluation of children with focal cortical dysplasia (FCD) and to compare it with other imaging techniques. Methods: Twenty patients with epilepsy onset before 18 years, surgically treated focal epilepsy with a minimal follow-up of 2 years, and histologically proven FCD were retrospectively selected. All patients underwent MRI, positron emission tomography (PET), and 16 patients also had ictal single-photon emission computed tomography (iSPECT). ESI, using EEG with 64 electrodes or more (HD-ESI), was performed in all 20 patients. We determined sensitivity, specificity and accuracy of ESI, and compared its yield to that of other imaging techniques. Results: Twelve patients were seizure-free post-operatively (60%). Among all patients, highest localization accuracy (80%) was obtained with ESI, followed by PET and iSPECT (75%). When results from ESI and SPECT were concordant 100% of patients achieved Engel I outcome. If ESI and PET showed concordant localization, 90% of patients achieved postoperative seizure freedom. Conclusions: Our findings demonstrate that HD-ESI allows accurate localization of the epileptogenic zone in patients with FCD. Significance: In combination with other imaging modalities, ESI helps with planning a more accurate surgery and therefore, the chances of postoperative seizure control are higher. Since it is based on EEG recordings, it does not require sedation, which is particularly interesting in pediatric patients. ESI represents an important imaging tool in focal epilepsies due to cortical dysplasia, which might be difficult to detect on standard imaging.

Linear distributed inverse solutions for interictal EEG source localisation.

OBJECTIVE: To compare the spatial accuracy of 6 linear distributed inverse solutions for EEG source localisation of interictal epileptic discharges: Minimum Norm, Weighted Minimum Norm, Low-Resolution Electromagnetic Tomography (LORETA), Local Autoregressive Average (LAURA), Standardised LORETA, and Exact LORETA. METHODS: Spatial accuracy was assessed clinically by retrospectively comparing the maximum source of averaged interictal discharges to the resected brain area in 30 patients with successful epilepsy surgery, based on 204-channel EEG. Additionally, localisation errors of the inverse solutions were assessed in computer simulations, with different levels of noise added to the signal in both sensor space and source space. RESULTS: In the clinical evaluations, the source maximum was located inside the resected brain area in 50-57% of patients when using LORETA or LAURA, while all other inverse solutions performed significantly worse (17-30%; corrected p < 0.01). In the simulation studies, when noise levels exceeded 10%, LORETA and LAURA had substantially smaller localisation errors than the other inverse solutions. CONCLUSIONS: LORETA and LAURA provided the highest spatial accuracy both in clinical and simulated data, alongside with a comparably high robustness towards noise. SIGNIFICANCE: Among the different linear inverse solution algorithms tested, LORETA and LAURA might be preferred for interictal EEG source localisation.

Automated interictal source localisation based on high-density EEG.

PURPOSE: To study the accuracy of automated interictal EEG source localisation based on high-density EEG, and to compare it to low-density EEG. METHODS: Thirty patients operated for pharmacoresistant focal epilepsy were retrospectively examined. Twelve months after resective brain surgery, 18 were seizure-free or had 'auras' only, while 12 had persistence of disabling seizures. Presurgical 257-channel EEG lasting 3-20 h was down-sampled to 25, 40, and 204 channels for separate analyses. For each electrode setup, interictal spikes were detected, clustered, and averaged automatically before validation by an expert reviewer. An individual 6-layer finite difference head model and the standardised low-resolution electromagnetic tomography were used to localise the maximum source activity of the most prevalent spike. Sublobar concordance with the resected brain area was visually assessed and related to favourable vs. unfavourable postsurgical outcome. RESULTS: Depending on the EEG setup, epileptic spikes were detected in 21-24 patients (70-80%). The median number of single spikes per average was 470 (range 17-15,066). Diagnostic sensitivity of EEG source localisation was 58-75%, specificity was 50-67%, and overall accuracy was 55-71%. There were no significant differences between low- and high-density EEG setups with 25 to 257 electrodes. CONCLUSION: Automated high-density EEG source localisation provides meaningful information in the majority of cases. With hundreds of single spikes averaged, diagnostic accuracy is similar in high- and low-density EEG. Therefore, low-density EEG may be sufficient for interictal EEG source localisation if high numbers of spikes are available.

Blinded study: prospectively defined high-frequency oscillations predict seizure outcome in individual patients.

Interictal high-frequency oscillations are discussed as biomarkers for epileptogenic brain tissue that should be resected in epilepsy surgery to achieve seizure freedom. The prospective classification of tissue sampled by individual electrode contacts remains a challenge. We have developed an automated, prospective definition of clinically relevant high-frequency oscillations in intracranial EEG from Montreal and tested it in recordings from Zurich. We here validated the algorithm on intracranial EEG that was recorded in an independent epilepsy centre so that the analysis was blinded to seizure outcome. We selected consecutive patients who underwent resective epilepsy surgery in Geneva with post-surgical follow-up > 12 months. We analysed long-term recordings during sleep that we segmented into intervals of 5 min. High-frequency oscillations were defined in the ripple (80-250 Hz) and the fast ripple (250-500 Hz) frequency bands. Contacts with the highest rate of ripples co-occurring with fast ripples designated the relevant area. As a validity criterion, we calculated the test-retest reliability of the high-frequency oscillations area between the 5 min intervals (dwell time ≥50%). If the area was not fully resected and the patient suffered from recurrent seizures, this was classified as a true positive prediction. We included recordings from 16 patients (median age 32 years, range 18-53 years) with stereotactic depth electrodes and/or with subdural electrode grids (median follow-up 27 months, range 12-55 months). For each patient, we included several 5 min intervals (median 17 intervals). The relevant area had high test-retest reliability across intervals (median dwell time 95%). In two patients, the test-retest reliability was too low (dwell time < 50%) so that outcome prediction was not possible. The area was fully included in the resected volume in 2/4 patients who achieved post-operative seizure freedom (specificity 50%) and was not fully included in 9/10 patients with recurrent seizures (sensitivity 90%), leading to an accuracy of 79%. An additional exploratory analysis suggested that high-frequency oscillations were associated with interictal epileptic discharges only in channels within the relevant area and not associated in channels outside the area. We thereby validated the automated procedure to delineate the clinically relevant area in each individual patient of an independently recorded dataset and achieved the same good accuracy as in our previous studies. The reproducibility of our results across datasets is promising for a multicentre study to test the clinical application of high-frequency oscillations to guide epilepsy surgery.

7T Epilepsy Task Force Consensus Recommendations on the Use of 7T MRI in Clinical Practice.

Identifying a structural brain lesion on MRI has important implications in epilepsy and is the most important factor that correlates with seizure freedom after surgery in patients with drug-resistant focal onset epilepsy. However, at conventional magnetic field strengths (1.5 and 3T), only approximately 60%-85% of MRI examinations reveal such lesions. Over the last decade, studies have demonstrated the added value of 7T MRI in patients with and without known epileptogenic lesions from 1.5 and/or 3T. However, translation of 7T MRI to clinical practice is still challenging, particularly in centers new to 7T, and there is a need for practical recommendations on targeted use of 7T MRI in the clinical management of patients with epilepsy. The 7T Epilepsy Task Force-an international group representing 21 7T MRI centers with experience from scanning over 2,000 patients with epilepsy-would hereby like to share its experience with the neurology community regarding the appropriate clinical indications, patient selection and preparation, acquisition protocols and setup, technical challenges, and radiologic guidelines for 7T MRI in patients with epilepsy. This article mainly addresses structural imaging; in addition, it presents multiple nonstructural MRI techniques that benefit from 7T and hold promise as future directions in epilepsy. Answering to the increased availability of 7T MRI as an approved tool for diagnostic purposes, this article aims to provide guidance on clinical 7T MRI epilepsy management by giving recommendations on referral, suitable 7T MRI protocols, and image interpretation.

Electrical stimulation of the medial orbitofrontal cortex in humans elicits pleasant olfactory perceptions.

BACKGROUND: Olfactory hallucinations can be part of epileptic seizures of orbitofrontal origin. Olfactory hallucinations, however, are rare and therefore the semiology, localization and lateralization characteristics are underdetermined. In addition, many discrepancies are found in the literature regarding olfactory processing and orbitofrontal (OF) functions and olfactory function. Particularly, the questions of laterality and affective component in coding of odors in the OF cortex remain controversial. AIMS: This study explored whether cortical electrical stimulation of the OF and mesiotemporal brain can trigger olfactory hallucinations with special focus on olfactory percepts in terms of laterality and hedonics. MATERIALS AND METHODS: Eight patients with temporal lobe epilepsy participated in the study, at the time of invasive exploration of their epilepsy. The most distal contact of the OF and anterior hippocampus depth electrodes were stimulated (50 Hz, 0.2 ms biphasic pulse; maximal stimulation 4 mA). Patients were instructed to report any kind of sensation they might experience. Intracranial depth electrodes were localized (iElectrodes): subject-specific brain mask, subcortical segmentation and cortical parcellation based on the Destrieux atlas (FreeSurfer) were superposed to the coregistered T1-weighted MRI and CT images (SPM). The center of mass of each electrode-artifact cluster determined the electrode localization. The electrode labeling was done in patient space. To obtain the electrode coordinates in Montreal Neurological Institute (MNI) space, the images obtained previously in the patient space were first segmented and normalized (SPM). Then, the localization procedure (iElectrodes) was run again with these new normalized images in MNI space. RESULTS: No hallucination was evoked by stimulation, neither of the right nor the left hippocampus (8/8 patients). Pleasant olfactory hallucinations were evoked by OF stimulation in 5/8 patients in either hemisphere. Patients named the percept as the smell of lemon or coffee for example. Among those 5 patients, electrodes were localized in the cortex of the olfactory sulcus, medial orbital sulcus or medial OF gyrus. Increasing stimulation amplitude changed the olfactory percept identification in 3 out of those 5 patients. No affective judgement or change in perceived odor intensity was reported by the patients. No hallucination was evoked by the stimulation of the white matter of the medial OF brain in 3/8 patients independently of the hemisphere stimulated. CONCLUSIONS: This study demonstrated that stimulation of the cortex of the medial OF brain and not of its white matter elicits specific pleasant olfactory hallucinations independently of the hemisphere stimulated, supporting one symmetrical olfactory processing in human.

High-density Electric Source Imaging of interictal epileptic discharges: How many electrodes and which time point?

OBJECTIVE: To assess the value of caudal EEG electrodes over cheeks and neck for high-density electric source imaging (ESI) in presurgical epilepsy evaluation, and to identify the best time point during averaged interictal epileptic discharges (IEDs) for optimal ESI accuracy. METHODS: We retrospectively examined presurgical 257-channel EEG recordings of 45 patients with pharmacoresistant focal epilepsy. By stepwise removal of cheek and neck electrodes, averaged IEDs were downsampled to 219, 204, and 156 EEG channels. Additionally, ESI at the IED's half-rise was compared to other time points. The respective sources of maximum activity were compared to the resected brain area and postsurgical outcome. RESULTS: Caudal channels had disproportionately more artefacts. In 30 patients with favourable outcome, the 204-channel array yielded the most accurate results with ESI maxima < 10 mm from the resection in 67% and inside affected sublobes in 83%. Neither in temporal nor in extratemporal cases did the full 257-channel setup improve ESI accuracy. ESI was most accurate at 50% of the IED's rising phase. CONCLUSION: Information from cheeks and neck electrodes did not improve high-density ESI accuracy, probably due to higher artefact load and suboptimal biophysical modelling. SIGNIFICANCE: Very caudal EEG electrodes should be used for ESI with caution.

Visual analysis of high density EEG: As good as electrical source imaging?

OBJECTIVE: In this study, we sought to determine whether visual analysis of high density EEG (HD-EEG) would provide similar localizing information comparable to electrical source imaging (ESI). METHODS: HD-EEG (256 electrodes) recordings from 20 patients suffering from unifocal, drug-resistant epilepsy (13 women, mean age 29.1 ±â€¯2.62 years, 11 with temporal lobe epilepsy) were examined. In the visual analysis condition, we identified the 5 contacts with maximal spike amplitude and determined their localization with respect to the underlying cortex. ESI was computed using the LAURA algorithm of the averaged spikes in the patient's individual MRI. We considered the localization "correct" if all 5 contacts were concordant with the resection volume underneath or if ESI was located within the resection as determined by the postoperative MRI. RESULTS: Twelve patients were postoperatively seizure-free (Engel Class IA), while the remaining eight were in class IB to IV. Visual analysis and ESI showed sensitivity of 58% and 75%, specificity of 75% and 87%, and accuracy of 65% and 80%, respectively. In 70% of cases, visual analysis and ESI provided concordant results. CONCLUSIONS: Localization of the electrodes with maximal spike amplitude provides very good estimation of the localization of the underlying source. However, ESI has a higher accuracy and adds 3D information; therefore, it should remain the tool of choice for presurgical evaluation. SIGNIFICANCE: The present study proposes the possibility to analyze HD-EEG visually, in tandem with ESI or alone, if ESI is not accessible.

Postoperative memory prognosis in temporal lobe epilepsy surgery: The contribution of postictal memory.

OBJECTIVE: The prediction of verbal memory decline after temporal lobe epilepsy (TLE) surgery remains difficult at an individual level. We evaluated the prognostic value of postictal memory testing in predicting the postoperative verbal memory function. METHODS: Sixty-three consecutive patients were included in the analysis who underwent TLE surgery at our center with preoperative interictal/postictal and postoperative memory testing. Verbal memory was evaluated using the Rey Auditory Verbal Learning Test (RAVLT). We used reliable change indices with 90% confidence interval (90% RCIs) to evaluate a significant postoperative memory decline. The sensitivity (Sn), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), area under the curve (AUC), and accuracy (ACC) were calculated. The analysis was performed for all TLE patients and for the subgroup with hippocampal sclerosis (HS). RESULTS: Left-TLE patients (n = 31) had lower verbal memory scores on RAVLT than right-TLE at 3 months (57% vs 78%) and 12 months (53% vs 78%) after surgery. The 90% RCI was estimated to be a loss of 4 out of 15 items. The predictive value was Sn = 42%, Sp = 84%, PPV = 39%, NPV = 86%, AUC = 0.630, and ACC = 76% to predict a verbal memory decline in the whole group (n = 63). In HS patients (n = 41), the postictal verbal memory test had Sn = 50%, Sp = 88%, PPV = 50%, NPV = 88%, AUC = 0.689, and ACC = 81% to predict a significant postoperative decline. SIGNIFICANCE: Postictal memory is a noninvasive bedside memory test that can help predict the postoperative verbal memory decline in patients with HS with an overall accuracy of 81%.

[Pharmacology and epilepsy†: update on the new antiepileptic drugs]. / Pharmacologie et épilepsie†: un point sur les nouveaux-nouveaux antiépileptiques.

New antiepileptic drugs are regularly approved for treatment and offer large therapeutic opportunities. Efficacy of these drugs is relatively similar on-label with different mechanisms to be combined for a synergic effect. Treatments such as cannabidiol have benefitted from large media coverage despite limited clinical evidence so far. The objective of antiepileptic drugs is to stop the recurrence of epileptic seizures with as few adverse events as possible. When confronted to a difficult-to-treat epilepsy, referral to a specialised centre is strongly advised. The aim is to confirm that the diagnosis is correct, that the treatment is well adapted (indication, pharmacokinetic and compliance) and to evaluate the indication for non-pharmacological treatments such as epilepsy surgery.

De nouveaux traitements médicamenteux antiépileptiques arrivent régulièrement sur le marché, et permettent d'offrir une large palette thérapeutique. Les efficacités sont relativement similaires dans les indications approuvées, avec différents mécanismes à utiliser de façon synergique. Certains traitements, comme le cannabidiol, ont bénéficié d'un succès médiatique dépassant l'évidence clinique à ce jour. L'objectif du traitement est l'arrêt des crises d'épilepsie d'une part, et l'absence d'effet secondaire invalidant de l'autre. Devant une situation d'épilepsie difficile à traiter, une évaluation dans un centre spécialisé est indiquée. Le but est de confirmer le diagnostic d'épilepsie, vérifier l'adéquation du traitement (indication, pharmacocinétique, compliance) et évaluer l'indication aux traitements non pharmacologiques, comme une chirurgie de l'épilepsie.

Diagnostic accuracy of interictal source imaging in presurgical epilepsy evaluation: A systematic review from the E-PILEPSY consortium.

OBJECTIVE: Interictal high resolution (HR-) electric source imaging (ESI) and magnetic source imaging (MSI) are non-invasive tools to aid epileptogenic zone localization in epilepsy surgery candidates. We carried out a systematic review on the diagnostic accuracy and quality of evidence of these modalities. METHODS: Embase, Pubmed and the Cochrane database were searched on 13 February 2017. Diagnostic accuracy studies taking post-surgical seizure outcome as reference standard were selected. Quality appraisal was based on the QUADAS-2 framework. RESULTS: Eleven studies were included: eight MSI (n = 267), three HR-ESI (n = 127) studies. None was free from bias. This mostly involved: selection of operated patients only, interference of source imaging with surgical decision, and exclusion of indeterminate results. Summary sensitivity and specificity estimates were 82% (95% CI: 75-88%) and 53% (95% CI: 37-68%) for overall source imaging, with no statistical difference between MSI and HR-ESI. Specificity is higher when partially concordant results were included as non-concordant (p < 0.05). Inclusion of indeterminate test results as non-concordant lowered sensitivity (p < 0.05). CONCLUSIONS: Source imaging has a relatively high sensitivity but low specificity for identification of the epileptogenic zone. SIGNIFICANCE: We need higher quality studies allowing unbiased test evaluation to determine the added value and diagnostic accuracy of source imaging in the presurgical workup of refractory focal epilepsy.

European trends in epilepsy surgery.

OBJECTIVE: Resective surgery is effective in treating drug-resistant focal epilepsy, but it remains unclear whether improved diagnostics influence postsurgical outcomes. Here, we compared practice and outcomes over 2 periods 15 years apart. METHODS: Sixteen European centers retrospectively identified 2 cohorts of children and adults who underwent epilepsy surgery in the period of 1997 to 1998 (n = 562) or 2012 to 2013 (n = 736). Data collected included patient (sex, age) and disease (duration, localization and diagnosis) characteristics, type of surgery, histopathology, Engel postsurgical outcome, and complications, as well as imaging and electrophysiologic tests performed for each case. Postsurgical outcome predictors were included in a multivariate logistic regression to assess the strength of date of surgery as an independent predictor. RESULTS: Over time, the number of operated cases per center increased from a median of 31 to 50 per 2-year period (p = 0.02). Mean disease duration at surgery decreased by 5.2 years (p < 0.001). Overall seizure freedom (Engel class 1) increased from 66.7% to 70.9% (adjusted p = 0.04), despite an increase in complex surgeries (extratemporal and/or MRI negative). Surgeries performed during the later period were 1.34 times (adjusted odds ratio; 95% confidence interval 1.02-1.77) more likely to yield a favorable outcome (Engel class I) than earlier surgeries, and improvement was more marked in extratemporal and MRI-negative temporal epilepsy. The rate of persistent neurologic complications remained stable (4.6%-5.3%, p = 0.7). CONCLUSION: Improvements in European epilepsy surgery over time are modest but significant, including higher surgical volume, shorter disease duration, and improved postsurgical seizure outcomes. Early referral for evaluation is required to continue on this encouraging trend.

MP2RAGE and Susceptibility-Weighted Imaging in Lesional Epilepsy at 7T.

BACKGROUND AND PURPOSE: Surgery is the first choice therapeutic approach in case of drug-resistant epilepsy. Unfortunately, up to 43% of patients referred for presurgical assessment do not have a lesion detectable by routine 3T magnetic resonance imaging (MRI) (MRI-negative), although most of them likely have an underlying epileptogenic lesion. Thus, new MRI modalities with increased sensibility for epileptogenic lesions are required. This paper describes the magnetization-prepared two rapid acquisition gradient echoes (MP2RAGE) and susceptibility-weighted imaging (SWI) findings at 7T in a series of patients with drug-resistant epilepsy of different etiologies. METHODS: Prospective pilot study of 7 patients with drug-resistant lesional epilepsy and absence of contraindications for MRI underwent a research 7T head-only scanner. Qualitative analysis of the high-resolution MP2RAGE and SWI sequences is given for each case. This study was approved by the local ethics committee. Written informed consent was obtained from each participant. RESULTS: This study shows that such sequences at ultra-high field are new and valuable approaches to unravel and characterize epileptogenic lesions. Particularly, MP2RAGE shows a better delineation of lesions due to high gray-white matter contrast and structural resolution, and SWI reveals new imaging signs related to improved magnitude and phase contrast imaging. CONCLUSION: MRI at ultra-high field is very promising for the detection of inconspicuous epileptogenic lesions and may facilitate epilepsy surgery of a great number of to-date MRI-negative patients.

EEG source connectivity to localize the seizure onset zone in patients with drug resistant epilepsy.

Electrical source imaging (ESI) from interictal scalp EEG is increasingly validated and used as a valuable tool in the presurgical evaluation of epilepsy as a reflection of the irritative zone. ESI of ictal scalp EEG to localize the seizure onset zone (SOZ) remains challenging. We investigated the value of an approach for ictal imaging using ESI and functional connectivity analysis (FC). Ictal scalp EEG from 111 seizures in 27 patients who had Engel class I outcome at least 1 year following resective surgery was analyzed. For every seizure, an artifact-free epoch close to the seizure onset was selected and ESI using LORETA was applied. In addition, the reconstructed sources underwent FC using the spectrum-weighted Adaptive Directed Transfer Function. This resulted in the estimation of the SOZ in two ways: (i) the source with maximal power after ESI, (ii) the source with the strongest outgoing connections after combined ESI and FC. Next, we calculated the distance between the estimated SOZ and the border of the resected zone (RZ) for both approaches and called this the localization error ((i) LEpow and (ii) LEconn respectively). By comparing LEpow and LEconn, we assessed the added value of FC. The source with maximal power after ESI was inside the RZ (LEpow = 0 mm) in 31% of the seizures and estimated within 10 mm from the border of the RZ (LEpow ≤ 10 mm) in 42%. Using ESI and FC, these numbers increased to 72% for LEconn = 0 mm and 94% for LEconn ≤ 10 mm. FC provided a significant added value to ESI alone (p < 0.001). ESI combined with subsequent FC is able to localize the SOZ in a non-invasive way with high accuracy. Therefore it could be a valuable tool in the presurgical evaluation of epilepsy.

Personalized structural image analysis in patients with temporal lobe epilepsy.

Volumetric and morphometric studies have demonstrated structural abnormalities related to chronic epilepsies on a cohort- and population-based level. On a single-patient level, specific patterns of atrophy or cortical reorganization may be widespread and heterogeneous but represent potential targets for further personalized image analysis and surgical therapy. The goal of this study was to compare morphometric data analysis in 37 patients with temporal lobe epilepsies with expert-based image analysis, pre-informed by seizure semiology and ictal scalp EEG. Automated image analysis identified abnormalities exceeding expert-determined structural epileptogenic lesions in 86% of datasets. If EEG lateralization and expert MRI readings were congruent, automated analysis detected abnormalities consistent on a lobar and hemispheric level in 82% of datasets. However, in 25% of patients EEG lateralization and expert readings were inconsistent. Automated analysis localized to the site of resection in 60% of datasets in patients who underwent successful epilepsy surgery. Morphometric abnormalities beyond the mesiotemporal structures contributed to subtype characterisation. We conclude that subject-specific morphometric information is in agreement with expert image analysis and scalp EEG in the majority of cases. However, automated image analysis may provide non-invasive additional information in cases with equivocal radiological and neurophysiological findings.

Drug-Level Monitoring on Admission for Presurgical Epilepsy Evaluation.

OBJECTIVE: Evaluation for surgical treatment is offered to patients who do not respond to antiepileptic drugs. Pseudo-pharmacoresistance (PPR) has been described in the context of impaired compliance, incorrect diagnosis of epilepsy or pharmacological interference resulting in too low blood levels. We were interested to determine the frequency and causes of PPR in patients admitted for presurgical evaluation. METHODS: We reviewed 553 drug levels in 199 patients and analyzed the relative frequency of drugs below reference range (10 and 20% below the range). RESULTS: Patients who had at least one serum level below the 10% cut-off amounted to 33% and 9% of patients had at least one serum level below the 20% cut-off. Only in 2 patients (1%), this was due to poor compliance. Low levels were equally frequent in mono- or polytherapy. Drugs that were most frequently found out of range were phenytoin, valproate, and topiramate. In monotherapy, lamotrigine was often prescribed in too low dosages. CONCLUSION: Low drug levels are frequently observed in surgical candidates due to pharmacological interference or insufficient dosing. Poor compliance or incorrect diagnosis does not appear to be a significant concern in this patient group. Our data strengthen the need for regular drug monitoring even in advanced chronic epilepsy to avoid unnecessary health costs by too low and ineffective dosages.