EANM practice guidelines for an appropriate use of PET and SPECT for patients with epilepsy.

Epilepsy is one of the most frequent neurological conditions with an estimated prevalence of more than 50 million people worldwide and an annual incidence of two million. Although pharmacotherapy with anti-seizure medication (ASM) is the treatment of choice, ~30% of patients with epilepsy do not respond to ASM and become drug resistant. Focal epilepsy is the most frequent form of epilepsy. In patients with drug-resistant focal epilepsy, epilepsy surgery is a treatment option depending on the localisation of the seizure focus for seizure relief or seizure freedom with consecutive improvement in quality of life. Beside examinations such as scalp video/electroencephalography (EEG) telemetry, structural, and functional magnetic resonance imaging (MRI), which are primary standard tools for the diagnostic work-up and therapy management of epilepsy patients, molecular neuroimaging using different radiopharmaceuticals with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) influences and impacts on therapy decisions. To date, there are no literature-based praxis recommendations for the use of Nuclear Medicine (NM) imaging procedures in epilepsy. The aims of these guidelines are to assist in understanding the role and challenges of radiotracer imaging for epilepsy; to provide practical information for performing different molecular imaging procedures for epilepsy; and to provide an algorithm for selecting the most appropriate imaging procedures in specific clinical situations based on current literature. These guidelines are written and authorized by the European Association of Nuclear Medicine (EANM) to promote optimal epilepsy imaging, especially in the presurgical setting in children, adolescents, and adults with focal epilepsy. They will assist NM healthcare professionals and also specialists such as Neurologists, Neurophysiologists, Neurosurgeons, Psychiatrists, Psychologists, and others involved in epilepsy management in the detection and interpretation of epileptic seizure onset zone (SOZ) for further treatment decision. The information provided should be applied according to local laws and regulations as well as the availability of various radiopharmaceuticals and imaging modalities.

Evidence for interictal blood-brain barrier dysfunction in people with epilepsy.

OBJECTIVE: Interictal blood-brain barrier dysfunction in chronic epilepsy has been demonstrated in animal models and pathological specimens. Ictal blood-brain barrier dysfunction has been shown in humans in vivo using an experimental quantitative magnetic resonance imaging (MRI) protocol. Here, we hypothesized that interictal blood-brain barrier dysfunction is also present in people with drug-resistant epilepsy. METHODS: Thirty-nine people (21 females, mean age at MRI ± SD = 30 ± 8 years) with drug-resistant epilepsy were prospectively recruited and underwent interictal T1-relaxometry before and after administration of a paramagnetic contrast agent. Likewise, quantitative T1 was acquired in 29 people without epilepsy (12 females, age at MRI = 48 ± 18 years). Quantitative T1 difference maps were calculated and served as a surrogate imaging marker for blood-brain barrier dysfunction. Values of quantitative T1 difference maps inside hemispheres ipsilateral to the presumed seizure onset zone were then compared, on a voxelwise level and within presumed seizure onset zones, to the contralateral side of people with epilepsy and to people without epilepsy. RESULTS: Compared to the contralateral side, ipsilateral T1 difference values were significantly higher in white matter (corrected p < .05), gray matter (uncorrected p < .05), and presumed seizure onset zones (p = .04) in people with epilepsy. Compared to people without epilepsy, significantly higher T1 difference values were found in the anatomical vicinity of presumed seizure onset zones (p = .004). A subgroup of people with hippocampal sclerosis demonstrated significantly higher T1 difference values in the ipsilateral hippocampus and in regions strongly interconnected with the hippocampus compared to people without epilepsy (corrected p < .01). Finally, z-scores reflecting the deviation of T1 difference values within the presumed seizure onset zone were associated with verbal memory performance (p = .02) in people with temporal lobe epilepsy. SIGNIFICANCE: Our results indicate a blood-brain barrier dysfunction in drug-resistant epilepsy that is detectable interictally in vivo, anatomically related to the presumed seizure onset zone, and associated with cognitive deficits.

Use, experience and perspectives of high-density EEG among Italian epilepsy centers: a national survey.

INTRODUCTION: High-density EEG (hdEEG) is a validated tool in presurgical evaluation of people with epilepsy. The aim of this national survey is to estimate diffusion and knowledge of hdEEG to develop a network among Italian epilepsy centers. METHODS: A survey of 16 items (and 15 additional items) was distributed nationwide by email to all members of the Italian League Against Epilepsy and the Italian Society of Clinical Neurophysiology. The data obtained were analyzed using descriptive statistics. RESULTS: A total of 104 respondents were collected from 85 centers, 82% from the Centre-North of Italy; 27% of the respondents had a hdEEG. The main applications were for epileptogenic focus characterization in the pre-surgical evaluation (35%), biomarker research (35%) and scientific activity (30%). The greatest obstacles to hdEEG were economic resources (35%), acquisition of dedicated personnel (30%) and finding expertise (17%). Dissemination was limited by difficulties in finding expertise and dedicated personnel (74%) more than buying devices (9%); 43% of the respondents have already published hdEEG data, and 91% of centers were available to participate in multicenter hdEEG studies, helping in both pre-processing and analysis. Eighty-nine percent of respondents would be interested in referring patients to centers with established experience for clinical and research purposes. CONCLUSIONS: In Italy, hdEEG is mainly used in third-level epilepsy centers for research and clinical purposes. HdEEG diffusion is limited not only by costs but also by lack of trained personnel. Italian centers demonstrated a high interest in educational initiatives on hdEEG as well as in clinical and research collaborations.

FDG-PET/MRI in the presurgical evaluation of pediatric epilepsy.

In patients with drug-resistant epilepsy, difficulties in identifying the epileptogenic zone are well known to correlate with poorer clinical outcomes post-surgery. The integration of PET and MRI in the presurgical assessment of pediatric patients likely improves diagnostic precision by confirming or widening treatment targets. PET and MRI together offer superior insights compared to either modality alone. For instance, PET highlights abnormal glucose metabolism, while MRI precisely localizes structural anomalies, providing a comprehensive understanding of the epileptogenic zone. Furthermore, both methodologies, whether utilized through simultaneous PET/MRI scanning or the co-registration of separately acquired PET and MRI data, present unique advantages, having complementary roles in lesional and non-lesional cases. Simultaneous FDG-PET/MRI provides precise co-registration of functional (PET) and structural (MR) imaging in a convenient one-stop-shop approach, which minimizes sedation time and reduces radiation exposure in children. Commercially available fusion software that allows retrospective co-registration of separately acquired PET and MRI images is a commonly used alternative. This review provides an overview and illustrative cases that highlight the role of combining 18F-FDG-PET and MRI imaging and shares the authors' decade-long experience utilizing simultaneous PET/MRI in the presurgical evaluation of pediatric epilepsy.

Estimation of fMRI responses related to epileptic discharges using Bayesian hierarchical modeling.

Simultaneous electroencephalography-functional MRI (EEG-fMRI) is a unique and noninvasive method for epilepsy presurgical evaluation. When selecting voxels by null-hypothesis tests, the conventional analysis may overestimate fMRI response amplitudes related to interictal epileptic discharges (IEDs), especially when IEDs are rare. We aimed to estimate fMRI response amplitudes represented by blood oxygen level dependent (BOLD) percentage changes related to IEDs using a hierarchical model. It involves the local and distributed hemodynamic response homogeneity to regularize estimations. Bayesian inference was applied to fit the model. Eighty-two epilepsy patients who underwent EEG-fMRI and subsequent surgery were included in this study. A conventional voxel-wise general linear model was compared to the hierarchical model on estimated fMRI response amplitudes and on the concordance between the highest response cluster and the surgical cavity. The voxel-wise model overestimated fMRI responses compared to the hierarchical model, evidenced by a practically and statistically significant difference between the estimated BOLD percentage changes. Only the hierarchical model differentiated brief and long-lasting IEDs with significantly different BOLD percentage changes. Overall, the hierarchical model outperformed the voxel-wise model on presurgical evaluation, measured by higher prediction performance. When compared with a previous study, the hierarchical model showed higher performance metric values, but the same or lower sensitivity. Our results demonstrated the capability of the hierarchical model of providing more physiologically reasonable and more accurate estimations of fMRI response amplitudes induced by IEDs. To enhance the sensitivity of EEG-fMRI for presurgical evaluation, it may be necessary to incorporate more appropriate spatial priors and bespoke decision strategies.

Interictal HFO and FDG-PET correlation predicts surgical outcome following SEEG.

OBJECTIVE: This study aimed to investigate the quantitative relationship between interictal 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET) and interictal high-frequency oscillations (HFOs) from stereo-electroencephalography (SEEG) recordings in patients with refractory epilepsy. METHODS: We retrospectively included 32 patients. FDG-PET data were quantified through statistical parametric mapping (SPM) t test modeling with normal controls. Interictal SEEG segments with four, 10-min segments were selected randomly. HFO detection and classification procedures were automatically performed. Channel-based HFOs separating ripple (80-250 Hz) and fast ripple (FR; 250-500 Hz) counts were correlated with the surrounding metabolism T score at the individual and group level, respectively. The association was further validated across anatomic seizure origins and sleep vs wake states. We built a joint feature FR × T reflecting the FR and hypometabolism concordance to predict surgical outcomes in 28 patients who underwent surgery. RESULTS: We found a negative correlation between interictal FDG-PET and HFOs through the linear mixed-effects model (R2  = .346 and .457 for ripples and FRs, respectively, p < .001); these correlations were generalizable to different epileptogenic-zone lobar localizations and vigilance states. The FR × T inside the resection volume could be used as a predictor for surgical outcomes with an area under the curve of 0.81. SIGNIFICANCE: The degree of hypometabolism is associated with HFO generation rate, especially for FRs. This relationship would be meaningful for selection of SEEG candidates and for optimizing SEEG scheme planning. The concordance between FRs and hypometabolism inside the resection volume could provide prognostic information regarding surgical outcome.

Artificial intelligence for the detection of focal cortical dysplasia: Challenges in translating algorithms into clinical practice.

Focal cortical dysplasias (FCDs) are malformations of cortical development and one of the most common pathologies causing pharmacoresistant focal epilepsy. Resective neurosurgery yields high success rates, especially if the full extent of the lesion is correctly identified and completely removed. The visual assessment of magnetic resonance imaging does not pinpoint the FCD in 30%-50% of cases, and half of all patients with FCD are not amenable to epilepsy surgery, partly because the FCD could not be sufficiently localized. Computational approaches to FCD detection are an active area of research, benefitting from advancements in computer vision. Automatic FCD detection is a significant challenge and one of the first clinical grounds where the application of artificial intelligence may translate into an advance for patients' health. The emergence of new methods from the combination of health and computer sciences creates novel challenges. Imaging data need to be organized into structured, well-annotated datasets and combined with other clinical information, such as histopathological subtypes or neuroimaging characteristics. Algorithmic output, that is, model prediction, requires a technically correct evaluation with adequate metrics that are understandable and usable for clinicians. Publication of code and data is necessary to make research accessible and reproducible. This critical review introduces the field of automatic FCD detection, explaining underlying medical and technical concepts, highlighting its challenges and current limitations, and providing a perspective for a novel research environment.

Clinical added value of interictal automated electrical source imaging in the presurgical evaluation of MRI-negative epilepsy: A real-life experience in 29 consecutive patients.

OBJECTIVE: During the presurgical evaluation, manual electrical source imaging (ESI) provides clinically useful information in one-third of the patients but it is time-consuming and requires specific expertise. This prospective study aims to assess the clinical added value of a fully automated ESI analysis in a cohort of patients with MRI-negative epilepsy and describe its diagnostic performance, by evaluating sublobar concordance with stereo-electroencephalography (SEEG) results and surgical resection and outcome. METHODS: All consecutive patients referred to the Center for Refractory Epilepsy (CRE) of St-Luc University Hospital (Brussels, Belgium) for presurgical evaluation between 15/01/2019 and 31/12/2020 meeting the inclusion criteria, were recruited to the study. Interictal ESI was realized on low-density long-term EEG monitoring (LD-ESI) and, whenever available, high-density EEG (HD-ESI), using a fully automated analysis (Epilog PreOp, Epilog NV, Ghent, Belgium). The multidisciplinary team (MDT) was asked to formulate hypotheses about the epileptogenic zone (EZ) location at sublobar level and make a decision on further management for each patient at two distinct moments: i) blinded to ESI and ii) after the presentation and clinical interpretation of ESI. Results leading to a change in clinical management were considered contributive. Patients were followed up to assess whether these changes lead to concordant results on stereo-EEG (SEEG) or successful epilepsy surgery. RESULTS: Data from all included 29 patients were analyzed. ESI led to a change in the management plan in 12/29 patients (41%). In 9/12 (75%), modifications were related to a change in the plan of the invasive recording. In 8/9 patients, invasive recording was performed. In 6/8 (75%), the intracranial EEG recording confirmed the localization of the ESI at a sublobar level. So far, 5/12 patients, for whom the management plan was changed after ESI, were operated on and have at least one-year postoperative follow-up. In all cases, the EZ identified by ESI was included in the resection zone. Among these patients, 4/5 (80%) are seizure-free (ILAE 1) and one patient experienced a seizure reduction of more than 50% (ILAE 4). CONCLUSIONS: In this single-center prospective study, we demonstrated the added value of automated ESI in the presurgical evaluation of MRI-negative cases, especially in helping to plan the implantation of depth electrodes for SEEG, provided that ESI results are integrated into the whole multimodal evaluation and clinically interpreted.

Electroencephalography-functional magnetic resonance imaging of epileptiform discharges: Noninvasive investigation of the whole brain.

Simultaneous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) is a unique and noninvasive method for investigating epileptic activity. Interictal epileptiform discharge-related EEG-fMRI provides cortical and subcortical blood oxygen level-dependent (BOLD) signal changes specific to epileptic discharges. As a result, EEG-fMRI has revealed insights into generators and networks involved in epileptic activity in different types of epilepsy, demonstrating-for instance-the implication of the thalamus in human generalized spike and wave discharges and the role of the default mode network in absences and focal epilepsy, and has suggested a mechanism for the cortico-subcortical interactions in Lennox-Gastaut syndrome discharges. EEG-fMRI can find deep sources of epileptic activity not available to scalp EEG or magnetoencephalography, and provides critical new information to delineate the epileptic focus when considering surgical treatment or electrode implantation. In recent years, methodological advances, such as artifact removal and automatic detection of events, have rendered this method easier to implement, and its clinical potential has since been established by evidence of the impact of BOLD response on clinical decision-making and of the relationship between concordance of BOLD responses with extent of resection and surgical outcome. This review presents the recent developments in EEG-fMRI methodology and EEG-fMRI studies in different types of epileptic disorders as follows: EEG-fMRI acquisition, gradient and pulse artifact removal, statistical analysis, clinical applications, presurgical evaluation, altered physiological state in generalized genetic epilepsy, and pediatric EEG-fMRI studies.

Seizure outcome determinants in children after surgery for single unilateral lesions on magnetic resonance imaging: Role of preoperative ictal and interictal electroencephalography.

OBJECTIVE: To determine whether an ictal electroencephalographic (EEG) recording as part of presurgical evaluation of children with a demarcated single unilateral magnetic resonance imaging (MRI) lesion is indispensable for surgical decision-making, we investigated the relationship of interictal/ictal EEG and seizure semiology with seizure-free outcome. METHODS: Data were obtained retrospectively from consecutive patients (≤18 years old) undergoing epilepsy surgery with a single unilateral MRI lesion at our institution over a 6-year period. Video-telemetry EEG (VT-EEG) was classified as concordant or nonconcordant/noninformative in relation to the MRI lesion location. The odds of seizure-free outcome associated with nonconcordant versus concordant for semiology, interictal EEG, and ictal EEG were compared separately. Multivariate logistic regression was conducted to correct for confounding variables. RESULTS: After a median follow-up of 26 months (interquartile range = 17-37.5), 73 (69%) of 117 children enrolled were seizure-free. Histopathological diagnoses included low-grade epilepsy-associated tumors, n = 46 (39%); focal cortical dysplasia (FCD), n = 33 (28%); mesial temporal sclerosis (MTS), n = 23 (20%); polymicrogyria, n = 3 (3%); and nondiagnostic findings/gliosis, n = 12 (10%). The odds of seizure freedom were lower with a nonconcordant interictal EEG (odds ratio [OR] = .227, 95% confidence interval [CI] = .079-.646, p = .006) and nonconcordant ictal EEG (OR = .359, 95% CI = .15-.878, p = .035). In the multivariate logistic regression model, factors predicting lower odds for seizure-free outcome were developmental delay/intellectual disability and higher number of antiseizure medications tried, with a nonsignificant trend for "nonconcordant interictal EEG." In the combined subgroup of patients with FCD and tumors (n = 79), there was no significant relationship of VT-EEG factors and seizure outcomes, whereas in children with MTS and acquired lesions (n = 25), a nonconcordant EEG was associated with poorer seizure outcomes (p = .003). SIGNIFICANCE: An ictal EEG may not be mandatory for presurgical evaluation, particularly when a well-defined single unilateral MRI lesion has been identified and the interictal EEG is concordant.

Multimodal Presurgical Evaluation of Medically Refractory Focal Epilepsy in Adults: An Update for Radiologists.

Surgery is a potentially curative treatment option for patients with medically refractory focal epilepsy. Advanced neuroimaging modalities often improve surgical outcomes by contributing key information during the highly individualized surgical planning process and intraoperative localization. Hence, neuroradiologists play an integral role in the multidisciplinary management team. In this review, we initially present the conceptual background and practical framework of the presurgical evaluation process, including a description of the surgical treatment approaches used for medically refractory focal epilepsy in adults. This background is followed by an overview of the advanced modalities commonly used during the presurgical workup at level IV epilepsy centers, including diffusion imaging techniques, blood oxygenation level-dependent functional MRI (fMRI), PET, SPECT, and subtraction ictal SPECT, and by introductions to 7-T MRI and electrophysiologic techniques including electroencephalography and magnetoencephalography. We also provide illustrative case examples of multimodal neuroimaging including PET/MRI, PET/MRI-diffusion-tensor imaging (DTI), subtraction ictal SPECT, and image-guided stereotactic planning with fMRI-DTI.

Outlines to Initiate Epilepsy Surgery in Low- and Middle-Income Countries.

Surgery is an essential treatment option for patients with drug-resistant epilepsy. While most epilepsy patients worldwide live in low- and middle-income countries (LMIC), most of these countries do not have epilepsy surgery, and those that do have surgical epilepsy services lack capacities. The rapidly growing population in LMIC further widens the gap between the number of patients who can potentially benefit from surgery and those who can actually receive it. This makes the initiation of new surgical epilepsy centers in those countries an urgent issue. Epilepsy surgery is feasible in LMIC, even in resource-poor settings, but lack of local expertise is a major obstacle to the introduction of new surgical services. Importantly, expertise deficits can be compensated by collaborating with a well-established epilepsy center for knowledge transfer, skill building and mentoring. Such projects need to be organized in a multidisciplinary team, should focus on the given circumstances, and should use technologies and personnel that are reasonably available and can function sustainably. Local cultural factors and improvement of patients' quality of life are further spotlights reflected by an increasing number of studies. As a general outline for a new surgical epilepsy program in LMIC, it is recommended to initially focus on patients with mesial temporal lobe epilepsy due to hippocampal sclerosis or other well defined pathologies. These constellations have an excellent surgical outcome in terms of seizure control, can be diagnosed by non-invasive methods, and can be reliably identified even under low-resource conditions. Moreover, surgery can be performed with a highly standardized approach and at reasonable costs, and the vast majority of patients will benefit from surgical intervention. The range of services can then be gradually expanded, depending on growing expertise, local needs, prospects and constraints. Although the introduction of surgical epilepsy services in LMIC can face several challenges, none of them should be a permanent barrier for further establishments.

Reasons for not having epilepsy surgery.

OBJECTIVE: This study was undertaken to determine reasons for adults with drug-resistant focal epilepsy who undergo presurgical evaluation not proceeding with surgery, and to identify predictors of this course. METHODS: We retrospectively analyzed data on 617 consecutive individuals evaluated for epilepsy surgery at a tertiary referral center between January 2015 and December 2019. We compared the characteristics of those in whom a decision not to proceed with surgical treatment was made with those who underwent definitive surgery in the same period. Multivariate logistic regression was performed to identify predictors of not proceeding with surgery. RESULTS: A decision not to proceed with surgery was reached in 315 (51%) of 617 individuals evaluated. Common reasons for this were an inability to localize the epileptogenic zone (n = 104) and the presence of multifocal epilepsy (n = 74). An individual choice not to proceed with intracranial electroencephalography (icEEG; n = 50) or surgery (n = 39), risk of significant deficit (n = 33), declining noninvasive investigation (n = 12), and coexisting neurological comorbidity (n = 3) accounted for the remainder. Compared to 166 surgically treated patients, those who did not proceed to surgery were more likely to have a learning disability (odds ratio [OR] = 2.35, 95% confidence interval [CI] = 1.07-5.16), normal magnetic resonance imaging (OR = 4.48, 95% CI = 1.68-11.94), extratemporal epilepsy (OR = 2.93, 95% CI = 1.82-4.71), bilateral seizure onset zones (OR = 3.05, 95% CI = 1.41-6.61) and to live in more deprived socioeconomic areas (median deprivation decile = 40%-50% vs. 50%-60%, p < .05). SIGNIFICANCE: Approximately half of those evaluated for surgical treatment of drug-resistant focal epilepsy do not proceed to surgery. Early consideration and discussion of the likelihood of surgical suitability or need for icEEG may help direct referral for presurgical evaluation.

Surgery in intractable epilepsy-physicians' recommendations and patients' decisions.

OBJECTIVES: To identify demographic and clinical variables independently associated with patients' decisions against their physicians' recommendations for resective epilepsy surgery or further scalp video-EEG monitoring (sca-VEM), semi-invasive (sem-)VEM with foramen ovale and/or peg electrodes, and invasive (in-)VEM. METHODS: Consecutive patients, who underwent presurgical assessment with at least one sca-VEM between 2010 and 2014, were included into this retrospective analysis. Multivariate analysis was used to identify independent variables associated with patients' decisions. RESULTS: Within the study period, 352 patients underwent 544 VEM sessions comprising 451 sca-, 36 sem-, and 57 in-VEMs. Eventually, 96 patients were recommended resective surgery, and 106 were ineligible candidates; 149 patients denied further necessary VEMs; thus, no decision could be made. After sca- or additional sem-VEM, nine out of 51 eligible patients (17.6%) rejected resection. One hundred and ten patients were recommended in-VEM, 52 of those (47.2%) declined. Variables independently associated with rejection of in-VEM comprised intellectual disability (OR 4.721, 95% CI 1.047-21.284), extratemporal focal aware non-motor seizures ("aura") vs. no "aura" (OR 0.338, 95% CI 0.124-0.923), and unilateral or bilateral vs. no MRI lesion (OR 0.248, 95% CI 0.100-0.614 and 0.149, 95% CI 0.027-0.829, respectively). CONCLUSIONS: During and after presurgical evaluation, patients with intractable focal epilepsy declined resections and intracranial EEGs, as recommended by their epileptologists, in almost 20% and 50% of cases. This calls for early and thorough counseling of patients on risks and benefits of epilepsy surgery. Future prospective studies should ask patients in depth for specific reasons why they decline their physicians' recommendations.

Trends in pediatric epilepsy surgery: A lower-middle-income country perspective.

OBJECTIVE: To study the trends for pediatric epilepsy surgery between 2000 and 2014 in a tertiary epilepsy surgery center in India in order to gain a lower- and middle-income country (LMIC) perspective. METHODS: Children aged <18 years and undergoing epilepsy surgery were divided into three groups based on the year that they underwent surgery-group 1: year 2000-2004; group 2: year 2005-2009; and group 3: year 2010-2014. Data including the rate of surgery, type of surgery, and duration of epilepsy before referral were analyzed from the medical records and compared. RESULTS: Between 2000 and 2014, 463 pediatric epilepsy surgeries were performed. The proportion of pediatric epilepsy surgeries showed an increasing trend-218 (total 510 surgeries, 42.74%) in group 3, compared with 115 (total 375 surgeries, 30.66%) in group 1 and 130 (total 466 surgeries, 27.9%) in group 2. A significant decrease in the age at evaluation and duration of epilepsy before referral was noted between 2000 and 2014, particularly in patients belonging to the lowest income group. There was a two-fold increase in the number of extratemporal surgeries over time. The proportion of children undergoing surgery for benign tumors, cortical malformations, and gliosis/atrophy showed an upward trend while that for mesial temporal sclerosis did not show an increase. SIGNIFICANCE: Promising trends in pediatric epilepsy surgery were noted with increasing number of surgeries and decreasing age at presurgical evaluation. Seen from an LMIC perspective, this reflects an evolution in the practice of pediatric epilepsy surgery, mirroring trends in high-income countries.

Injection of prophylactic lorazepam versus antiseizure drugs on the localization value of ictal SPECT studies and treatment-emergent adverse events: A single-center prospective study.

OBJECTIVE: We aimed to examine the impact of resumption of home antiseizure drugs alone (ASD-) compared with adjunct administration of scheduled intravenous (IV) lorazepam 2 mg every 6 h (ASD+) following ictal single-photon emission computed tomography (SPECT) injection on the localization value of SPECT studies and treatment-emergent adverse events (TEAEs). METHODS: We conducted a prospective study at Mayo Clinic inpatient epilepsy monitoring unit (EMU) between January 2018 and May 2020 in Jacksonville, Florida. The ASD- and ASD+ groups were compared for concordance of SPECT studies with the epilepsy surgical conference (ESC) consensus or intracranial electroencephalography (icEEG) findings as reference. Treatment-emergent adverse events, obtained from surveys at 24 h and one week postictal SPECT injection, were also compared between both groups. RESULTS: Twenty-two consecutive patients with temporal (eight patients, 36%) and extratemporal (14 patients, 64%) epilepsy were included: 12 ASD+ and 10 ASD-. The two groups were well matched with regard to clinical and ictal SPECT injection characteristics including the occurrence of seizure between ictal and interictal SPECT injections. The localization value of SPECT studies was similar in the two groups. Patients in the ASD+ group reported higher rates of dizziness and excessive sedation at 24 h (p-value = 0.008). Fourteen patients (64%) underwent icEEG monitoring. For the entire cohort, the localization concordance of SPECT analysis by statistical parametric mapping (SPM) was superior to raw ictal SPECT (p-value = 0.003) and subtraction ictal SPECT coregistered to magnetic resonance imaging (MRI) (SISCOM; p-value = 0.021). Eventually, seven patients (31.8%) underwent resective brain surgery of whom four (57.1%) became seizure-free (median follow-up = 22 months). CONCLUSIONS: Our findings suggest that resuming home ASDs without the addition of scheduled IV lorazepam following inpatient ictal SPECT injection is equally efficacious for seizure onset zone (SOZ) localization on SPECT studies, especially SPM. This approach is also associated with fewer transient TEAEs and lower financial cost with no difference in preventing seizure between ictal and interictal SPECT injections.

Accuracy and spatial properties of distributed magnetic source imaging techniques in the investigation of focal epilepsy patients.

Source localization of interictal epileptiform discharges (IEDs) is clinically useful in the presurgical workup of epilepsy patients. We aimed to compare the performance of four different distributed magnetic source imaging (dMSI) approaches: Minimum norm estimate (MNE), dynamic statistical parametric mapping (dSPM), standardized low-resolution electromagnetic tomography (sLORETA), and coherent maximum entropy on the mean (cMEM). We also evaluated whether a simple average of maps obtained from multiple inverse solutions (Ave) can improve localization accuracy. We analyzed dMSI of 206 IEDs derived from magnetoencephalography recordings in 28 focal epilepsy patients who had a well-defined focus determined through intracranial EEG (iEEG), epileptogenic MRI lesions or surgical resection. dMSI accuracy and spatial properties were quantitatively estimated as: (a) distance from the epilepsy focus, (b) reproducibility, (c) spatial dispersion (SD), (d) map extension, and (e) effect of thresholding on map properties. Clinical performance was excellent for all methods (median distance from the focus MNE = 2.4 mm; sLORETA = 3.5 mm; cMEM = 3.5 mm; dSPM = 6.8 mm, Ave = 0 mm). Ave showed the lowest distance between the map maximum and epilepsy focus (Dmin lower than cMEM, MNE, and dSPM, p = .021, p = .008, p < .001, respectively). cMEM showed the best spatial features, with lowest SD outside the focus (SD lower than all other methods, p < .001 consistently) and high contrast between the generator and surrounding regions. The average map Ave provided the best localization accuracy, whereas cMEM exhibited the lowest amount of spurious distant activity. dMSI techniques have the potential to significantly improve identification of iEEG targets and to guide surgical planning, especially when multiple methods are combined.

Value of 7T MRI and post-processing in patients with nonlesional 3T MRI undergoing epilepsy presurgical evaluation.

OBJECTIVE: Ultra-high-field 7-Tesla (7T) magnetic resonance imaging (MRI) offers increased signal-to-noise and contrast-to-noise ratios, which may improve visualization of cortical malformations. We aim to assess the clinical value of in vivo structural 7T MRI and its post-processing for the noninvasive identification of epileptic brain lesions in patients with pharmacoresistant epilepsy and nonlesional 3T MRI who are undergoing presurgical evaluation. METHODS: Sixty-seven patients were included who had nonlesional 3T MRI by official radiology report. Epilepsy protocols were used for the 3T and 7T acquisitions. Post-processing of the 7T T1-weighted magnetization-prepared two rapid acquisition gradient echoes sequence was performed using the morphometric analysis program (MAP) with comparison to a normal database consisting of 50 healthy controls. Review of 7T was performed by an experienced board-certified neuroradiologist and at the multimodal patient management conference. The clinical significance of 7T findings was assessed based on intracranial electroencephalography (ICEEG) ictal onset, surgery, postoperative seizure outcomes, and histopathology. RESULTS: Unaided visual review of 7T detected previously unappreciated subtle lesions in 22% (15/67). When aided by 7T MAP, the total yield increased to 43% (29/67). The location of the 7T-identified lesion was identical to or contained within the ICEEG ictal onset in 13 of 16 (81%). Complete resection of the 7T-identified lesion was associated with seizure freedom (P = .03). Histopathology of the 7T-identified lesions encountered mainly focal cortical dysplasia (FCD). 7T MAP yielded 25% more lesions (6/24) than 3T MAP, and showed improved conspicuity in 46% (11/24). SIGNIFICANCE: Our data suggest a major benefit of 7T with post-processing for detecting subtle FCD lesions for patients with pharmacoresistant epilepsy and nonlesional 3T MRI.

Initiating a new national epilepsy surgery program: Experiences gathered in Georgia.

Surgery is the most effective therapeutic approach for medically refractory epilepsies and a safe and cost-efficient treatment in terms of long-term expenses of direct, indirect, and intangible costs. Georgia is a Caucasian low- to middle-income country with a remarkable effort to deal with epileptic diseases, but without an appropriate epilepsy surgery program. To address the needs for such a service in this country, two joint German-Georgian projects were initiated in 2017 and 2019. In the framework of these projects, a productive exchange program involving German and Georgian experts was undertaken in the past two years. This program included training and mentoring for Georgian clinical colleagues, as well as joint case conferences and workshops with the aim of optimizing presurgical diagnostics and preparing for an epilepsy surgery program in Georgia. Finally, a postsurgical medium- and long-term follow-up scheme was organized as the third component of this comprehensive approach. As a result of our efforts, the first patients underwent anterior temporal lobectomy and all of them remain seizure-free up to the present day. Hence, epilepsy surgery is not only feasible, but also already available in Georgia. In this report, we aim to share our experiences in the initiation and implementation of surgical epilepsy intervention in Georgia and illustrate our recent endeavor and achievements.

The Epilepsy Surgery Grading Scale: Validation in an independent population with drug-resistant focal epilepsy.

The Epilepsy Surgery Grading Scale (ESGS) is a simple tool that predicts a patient's likelihood of progressing to resective surgery and becoming seizure-free. The aim of our study was to validate the ESGS in an independent patient cohort. We retrospectively calculated the ESGS score for adult patients with drug-resistant focal epilepsy undergoing presurgical evaluation at two reference centers for drug-resistant epilepsy in Belgium. We classified patients into ESGS grade 1 (most favorable), grade 2 (intermediate), and grade 3 (least favorable). We assessed progression to surgery and postsurgical seizure freedom. A total of 238 patients underwent presurgical evaluation (presurgical cohort), of whom 140 progressed to surgery (surgical cohort). In the presurgical cohort, we observed significant differences in rates of surgery and in rates of seizure freedom between grades 1, 2, and 3. In the surgical cohort, we observed significant differences in rates of seizure freedom between grades 1 and 2 and between grades 1 and 3. We confirm the usefulness of the ESGS for the prognostic stratification of patients with drug-resistant focal epilepsy undergoing presurgical evaluation. Our results support the use of the ESGS in the decision process of presurgical evaluation in clinical practice.