Epileptogenic Lesions Research Articles

Relative Source Power: A novel method for localizing epileptiform EEG discharges

ObjectiveTo validate relative source power (RSP) imaging of extratemporal interictal epileptiform discharges (IEDs). MethodsThe accuracy of RSP was validated in a cohort of patients with extratemporal focal epilepsy and a confined epileptogenic lesion (<19 cm3) using distance to the lesion, concordance with resected area and postoperative outcome. Performance was compared with three conventional methods: voltage maps, equivalent current dipole and a distributed source model. ResultsThirty-three of 41 consecutive patients (80%) had IED averages suitable for analysis. While the peak negativity in voltage maps localized above the epileptogenic lesion only in 18 cases, RSP-maps matched in 29 cases (88%, p < 0.0026). Source localization showed a median distance of 9.8 mm from the lesion. Source-regions with 20 mm radius included 98% of all source-to-lesion distances. In the 21 surgical cases, outcome showed a sensitivity of 82.35% and specificity of 50% without significant differences between the three source imaging methods. ConclusionsRSP-maps provide a rapid, intuitive and more accurate source estimation than voltage maps. At sublobar level, RSP localizes with an accuracy similar to conventional methods and results of previous studies. SignificanceThe definition of a source region with 20 mm radius helps in guiding further exploration in extratemporal focal epilepsy.

Comparison of pulse pressure variation, stroke volume variation, and plethysmographic variability index in pediatric patients undergoing craniotomy

Objective To compare well-known preload dynamic parameters intraoperatively including stroke volume variation (SVV), pulse pressure variation (PPV), and plethysmographic variability index (PVI) in children who underwent craniotomy for epileptogenic lesion excision. Methods A total of 30 children aged 0 to 14 years undergoing craniotomy for intracranial epileptogenic lesion excision were enrolled. During surgery, we measured PPV, SVV (measured by the Flotrac/Vigileo device), and PVI (measured by the Masimo Radical-7 monitor) simultaneously and continuously. Preload dynamic parameter measurements were collected at predefined steps: after induction of anesthesia, during opening the skull, intraoperative electroencephalogram monitoring, excision of epileptogenic lesion, skull closure, at the end of the operation. After exclusion of outliers, agreement among SVV, PPV, and PVI was assessed using repeated measures of Bland-Altman approach. The 4-quadrant and polar plot techniques were used to assess the trending ability among the changes in the three parameters. Results The mean SVV, PPV, and PVI were 8%±2%, 10%±3%, and 15%±7%, respectively during surgery. We analyzed a total of 834 paired measurements (3 to 8 data sets for each phase per patient). Repeated measures Bland-Altman analysis identified a bias of -2.3 and 95% confidence intervals between -1.9 and -2.7 (95% limits of agreement between -6.0 and 1.5) between PPV and SVV, showing significant correlation at all periods. The bias between PPV and PVI was -5.0 with 95% limits of agreement between -20.5 and 10.5, and that between SVV and PVI was -7.5 with 95% limits of agreement between -22.7 and 7.8, both not showing significant correlation. Reflected by 4-quadrant plots, the con-cordance rates showing the trending ability between the changes in PPV and SVV, PPV and PVI, SVV and PVI were 88.6%, 50.4%, and 50.1%, respectively. The concordance rate between PPV and SVV was higher (92.7%) in children aged less than 3 years compared with those aged 3 and more than 3 years. The mean angular bias, radial limits of agreement, and angular concordance rate in the polar analysis were not clinically acceptable in the changes between arterial pressure waveform-based parameters and volume-based PVI (PPV vs. PVI: angular mean bias 8.4°, angular concordance rate 29.9%; SVV vs. PVI: angular mean bias 2.4°, angular concordance rate 29.1%). There was a high concordance between the two arterial pressure waveform-based parameters reflected by the polar plot (angular mean bias -0.22°, angular concordance rate 86.6%). Conclusion PPV can be viewed as a surrogate for SVV, especially in children aged less than 3 years. The agreement between arterial pressure waveform-based preload parameters (PPV and SVV) and PVI is poor and these two should not be considered interchangeable. Attempt to combine PVI and PPV for improving the anesthesiologist's ability to monitor cardiac preload in major pediatric surgery is warranted.

BCRP Expression with Lipofuscin Accumulation in Abnormal Neurons from a Child with Transmantle Cortical Dysplasia (TMCD) and Refractory Epilepsy

Cerebral cortical development’s malformations, including the transmantel cortical dysplasia (TMCD), have been associated with refractory epilepsy (RE). Several ABC-transporters as “P-glycoprotein (P-gp), Multidrug resistance proteins (MRP-1) and breast Cancer Resistant Protein (BCRP)” are up-regulated in human epileptogenic brain lesions of RE, however they have not been explored in Transmantle cortical dysplasia (TMCD). We describe a 13 years old boy with Refractory Epilepsy (RE) and abnormal Magneic Resonance Image (MRI) (T1, FLAIR and T2) compatible with TMCD. Clinical follow-up, images and pathologic studies were developed by routinely methods. Epilepsy surgical treatment included total lesion resection with complete seizures remission at date. Deeper brain areas related with images findings, showed features of TMCD with abnormal ballooned neurons with high accumulation of PAS+, sudanophilic and autoflourescent lipopigment (LP). Immunohistochemistry, using primary monoclonal antibodies for P-gp, MVP and BCRP proteins, showed high expression of BCRP in several ballooned-LP+ cells. In contrast, P-gp and MVP were negative and MRP-1 has not been investigated. The links of BCRP with LP and AEDs are not known, however, the expression of BCRP in these LP+ ballooned neurons from the epileptogenic brain area, with P-gp/MVP negative results, suggest that BCRP could be associated to refractory epileptic phenotype.

The role of hybrid FDG-PET/MRI on decision-making in presurgical evaluation of drug-resistant epilepsy

BackgroundWhen MRI fails to detect a potentially epileptogenic lesion, the chance of a favorable outcome after epilepsy surgery becomes significantly lower (from 60 to 90% to 20–65%). Hybrid FDG-PET/MRI may provide additional information for identifying the epileptogenic zone. We aimed to investigate the possible effect of the introduction of hybrid FDG-PET/MRI into the algorithm of the decision-making in both lesional and non-lesional drug-resistant epileptic patients.MethodsIn a prospective study of patients suffering from drug-resistant focal epilepsy, 30 nonlesional and 30 lesional cases with discordant presurgical results were evaluated using hybrid FDG-PET/MRI.ResultsThe hybrid imaging revealed morphological lesion in 18 patients and glucose hypometabolism in 29 patients within the nonlesional group. In the MRI positive group, 4 patients were found to be nonlesional, and in 9 patients at least one more epileptogenic lesion was discovered, while in another 17 cases the original lesion was confirmed by means of hybrid FDG-PET/MRI. As to the therapeutic decision-making, these results helped to indicate resective surgery instead of intracranial EEG (iEEG) monitoring in 2 cases, to avoid any further invasive diagnostic procedures in 7 patients, and to refer 21 patients for iEEG in the nonlesional group. Hybrid FDG-PET/MRI has also significantly changed the original therapeutic plans in the lesional group. Prior to the hybrid imaging, a resective surgery was considered in 3 patients, and iEEG was planned in 27 patients. However, 3 patients became eligible for resective surgery, 6 patients proved to be inoperable instead of iEEG, and 18 cases remained candidates for iEEG due to the hybrid FDG-PET/MRI. Two patients remained candidates for resective surgery and one patient became not eligible for any further invasive intervention.ConclusionsThe results of hybrid FDG-PET/MRI significantly altered the original plans in 19 of 60 cases. The introduction of hybrid FDG-PET/MRI into the presurgical evaluation process had a potential modifying effect on clinical decision-making.Trial registrationTrial registry: Scientific Research Ethics Committee of the Medical Research Council of Hungary. Trial registration number: 008899/2016/OTIG. Date of registration: 08 February 2016.

Ste20-like Kinase Is Critical for Inhibitory Synapse Maintenance and Its Deficiency Confers a Developmental Dendritopathy

The size and structure of the dendritic arbor play important roles in determining how synaptic inputs of neurons are converted to action potential output. The regulatory mechanisms governing the development of dendrites, however, are insufficiently understood. The evolutionary conserved Ste20/Hippo kinase pathway has been proposed to play an important role in regulating the formation and maintenance of dendritic architecture. A key element of this pathway, Ste20-like kinase (SLK), regulates cytoskeletal dynamics in non-neuronal cells and is strongly expressed throughout neuronal development. However, its function in neurons is unknown. We show that, during development of mouse cortical neurons, SLK has a surprisingly specific role for proper elaboration of higher, ≥ third-order dendrites both in male and in female mice. Moreover, we demonstrate that SLK is required to maintain excitation-inhibition balance. Specifically, SLK knockdown caused a selective loss of inhibitory synapses and functional inhibition after postnatal day 15, whereas excitatory neurotransmission was unaffected. Finally, we show that this mechanism may be relevant for human disease, as dysmorphic neurons within human cortical malformations revealed significant loss of SLK expression. Overall, the present data identify SLK as a key regulator of both dendritic complexity during development and inhibitory synapse maintenance.SIGNIFICANCE STATEMENT We show that dysmorphic neurons of human epileptogenic brain lesions have decreased levels of the Ste20-like kinase (SLK). Decreasing SLK expression in mouse neurons revealed that SLK has essential functions in forming the neuronal dendritic tree and in maintaining inhibitory connections with neighboring neurons.

Factors influencing the detection of treatable epileptogenic lesions on MRI. A randomized prospective study

BackgroundTo prospectively analyze factors associated with detecting epileptogenic lesions on MRI within the work-sharing process of neurologists, epileptologists, radiologists and neuroradiologists.MethodsWe assembled four sets of six MRI scans, each set representing five typical epileptogenic lesions (hippocampal sclerosis or limbic encephalitis; focal cortical dysplasias; periventricular nodular or other heterotopias; long-term epilepsy associated tumors; gliotic scar, hemosiderin or cavernoma), and non - lesional epilepsy.At professional conferences, we invited neurologists, epileptologists, radiologists, and neuroradiologists to read two out of four MRI sets, one of which was presented with a clinical focus hypothesis. Participants were randomly assigned to MRI sets. Effects of examiners’ specialty, duration of training and professional experience on detection rate of epileptogenic lesions were investigated.ResultsFourty-eight neurologists, 22 epileptologists, 20 radiologists and 21 neuroradiologists read 1323 MRI scans. Overall, 613 of 1101 (55.7%) epileptogenic lesions were detected. Long-term epilepsy associated tumors (182/221, 82.4%) were found more frequently than gliotic scar, hemosiderin or cavernoma (157/220, 71.4%), hippocampal sclerosis or limbic encephalitis (141/220, 64.1%), nodular heterotopia (68/220, 30.9%) and focal cortical dysplasias (65/220, 29.5%, p < 0.001). Provision of a focus hypothesis improved the detection of hippocampal sclerosis or limbic encephalitis (86/110, 78.2% vs 55/110, 50%, p < 0.001) and focal cortical dysplasias (40/110, 36.4% vs 25/110, 22.7%, p = 0.037). Neuroradiologists and epileptologists were more likely than radiologists and neurologists to be amongst the most successful readers. In multivariable analysis, type of epileptogenic lesion, specialty of MRI reader, and provision of focus hypothesis predicted correct identification of epileptogenic lesions.ConclusionsEpileptogenic lesions are often not recognized on MRI even by expert readers. Their detection can be improved by providing a focus hypothesis. These results stress the need for training in the MRI characteristics of epilepsy - specific pathology, and, most importantly, interdisciplinary communication between neurologists/epileptologists and (neuro)radiologists to improve detection of epileptogenic lesions.

Sensitivity of long-term EEG monitoring as a second diagnostic step in the initial diagnosis of epilepsy.

In this retrospective study, we aimed to evaluate the sensitivity and negative predictive value of long-term EEG (L-EEG) in patients being assessed for epilepsy, who had already undergone non-specific standard EEG(s) (S-EEG). Secondary endpoints of this study were: (1) the correlation of non-specific changes on EEG with epileptiform patterns on L-EEG; and (2) the correlation of clinical parameters such as subjective frequency of seizures or epileptogenic lesions on cerebral imaging with epileptiform changes on L-EEG. We retrospectively analysed clinical and electrophysiological data of 75 patients, assessed for epilepsy at the University Hospital Zurich, who had undergone an L-EEG for at least 48 hours, between 2010 and 2015. All patients had already undergone S-EEG(s) before L-EEG, which showed no epileptic changes. Furthermore, the association with clinical parameters, such as frequency of presumptive seizures, abnormalities on standard-EEG, AED intake and cerebral imaging with the final diagnosis, was analysed. Out of 75 patients, 14 (19%) patients were finally diagnosed with epilepsy. In eight of these patients, L-EEGs showed typical ictal/interictal patterns, with a sensitivity of 57% and negative predictive value of 91%. Neither the subjective frequency of seizures nor potentially epileptogenic lesions on cerebral imaging were associated with a positive epilepsy diagnosis. In this preselected cohort of patients, who had already undergone a non-diagnostic S-EEG, the sensitivity of L-EEG remained considerable. Nonetheless, our study also revealed a significant false-negative rate. Based on the high negative predictive value in this study, L-EEG appears to be most useful at excluding epilepsy. Nevertheless, thorough evaluation of seizure history and clinical findings remain crucial for a reliable diagnosis.

Surgical candidates in children with epileptic spasms can be selected without invasive monitoring: A report of 70 cases

ObjectivePrior surgical series in children with drug-resistant epileptic spasms have reported use of intracranial EEG monitoring in up to two-third of patients. We report outcome after epilepsy surgery for drug-resistant epileptic spasms in a cohort of children without the use of intracranial EEG monitoring in any of the patients. MethodsMedical records of all consecutive children aged 5 years or under who had epilepsy surgery for epileptic spasms at Cleveland Clinic between 2000 and 2018 were reviewed. Post-operative seizure outcome and predictors of prognosis of seizure outcome were analyzed. ResultsSeventy children with active epileptic spasms underwent surgical resections during the study period. Mean age at seizure onset was 6.8 (+9.31) months and median age at surgery was 18.5 months. An epileptogenic lesion was identified on brain MRI in all patients; 17 (24%) had bilateral abnormalities. Etiologies included malformations of cortical development (58%), perinatal infarct/encephalomalacia (39%), and tumor (3%). None of the patients had intracranial EEG. Surgical procedures included hemispherectomy (44%), lobectomy/ lesionectomy (33%), and multilobar resections (23%). Twelve children needed repeat surgery; six (50%) became seizure free after the second surgery. At six months follow-up, 73% (51/70) were seizure-free since surgery. At a mean follow-up of 4.7 years, 60% (42/70) had Engel 1 outcome. In those with seizure recurrence, 17 (60%) reported improvement. Shorter epilepsy duration (p = 0.05) and lobar or sub-lobar epileptogenic lesions (p = 0.02) predicted favorable seizure outcome at 6 months after surgery. For long term outcome, patients with bilateral abnormalities on MRI (p = 0.001), and multilobar extent on MRI (p = 0.02) were at higher risk for recurrence. SignificanceChildren with drug-resistant epileptic spasms secondary to an epileptogenic lesion detected on MRI could be selected for epilepsy surgery without undergoing intracranial EEG monitoring. A surgical selection paradigm without intracranial monitoring may allow early surgery without the risks of invasive monitoring.

Making the Invisible Visible: Advanced Neuroimaging Techniques in Focal Epilepsy.

It has been a clinically important, long-standing challenge to accurately localize epileptogenic focus in drug-resistant focal epilepsy because more intensive intervention to the detected focus, including resection neurosurgery, can provide significant seizure reduction. In addition to neurophysiological examinations, neuroimaging plays a crucial role in the detection of focus by providing morphological and neuroanatomical information. On the other hand, epileptogenic lesions in the brain may sometimes show only subtle or even invisible abnormalities on conventional MRI sequences, and thus, efforts have been made for better visualization and improved detection of the focus lesions. Recent advance in neuroimaging has been attracting attention because of the potentials to better visualize the epileptogenic lesions as well as provide novel information about the pathophysiology of epilepsy. While the progress of newer neuroimaging techniques, including the non-Gaussian diffusion model and arterial spin labeling, could non-invasively detect decreased neurite parameters or hypoperfusion within the focus lesions, advances in analytic technology may also provide usefulness for both focus detection and understanding of epilepsy. There has been an increasing number of clinical and experimental applications of machine learning and network analysis in the field of epilepsy. This review article will shed light on recent advances in neuroimaging for focal epilepsy, including both technical progress of images and newer analytical methodologies and discuss about the potential usefulness in clinical practice.

Multivariate analysis and machine learning in pediatric epilepsy research: A literature review

Due to brain immaturity, pediatric epilepsy has some unique challenges and opportunities in seizure management. Multivariate analysis and machine learning methods have been increasingly used in childhood epilepsy, mainly in seizure detection and prediction, epileptogenic lesion identification, and clinical outcome prediction. In order to provide an overview of this field, this paper reviewed such studies and found that these methods have made it possible to detect seizures on electroencephalogram (EEG) and detect lesions on imaging automatically. In addition, although seizure occurrence has been regarded as random or unpredictable for long, it has been found that seizures may occur non-randomly in complex patient-specific patterns. Preictal changes on EEG can be detected and distinguished from interictal activities by machine learning approaches, which makes it possible to predict seizure occurrence, but there are significant obstacles in seizure prediction, for example, sufficient clinical data and good machine learning algorithms are needed to identify complex seizure occurrence patterns. Further, outcome studies using multivariate analysis and machine learning methods have identified outcome predictors for seizure outcome prediction. To make these relatively new methods accurate and reliable, confirmatory studies are warranted and further research is needed to improve these methods. It is anticipated that multivariate analysis and machine learning will contribute more to identifying complex seizure patterns, epileptogenic lesions, and outcome predictors to improve seizure detection/prediction, lesion detection, and seizure outcome prediction, which will lead to better seizure control to prevent seizure-related accidents/injury in children with epilepsy, reduce mortality rate, improve quality of life and eventually set them free from seizures.

Adopting MR-guided stereotactic laser ablations for epileptic lesions: initial clinical experience and lessons learned.

MR-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive technique for ablating brain lesions under real-time MRI feedback and control of the ablation process. The Medtronic Visualase system was recently approved for use in Europe and Israel. We report our initial technical experience using the system in the first 16 cases in which the system was used to ablate focal epileptogenic lesions. We included all consecutive patients with intractable epilepsy who underwent MRgLITT procedures between 2018 and 2020. We reviewed medical charts and imaging studies of patients. Post-ablation MRIs were used to calculate ablation volumes. Seventeen MRgLITT procedures were performed in 16 patients. One cooling catheter/laser fiber assemblies were placed per patient. Indications for surgery were intractable epilepsy due to TLE (n = 7),suspected low-grade glioma (n = 4), radiological cortical dysplasia (n = 1), hypothalamic hamartoma (n = 1), and MR-negative foci (n = 3). Ablations were made using 30 to 70% of the maximal energy of the Visualase system. We used serial ablations as needed along the tract of the catheter by pulling back the optic fiber; the length of the lesion ranged between 7.4 and 38.1mm. Ablation volume ranged between 0.27 and 6.78 mm3. Immediate post-ablation MRI demonstrated good ablation of the epileptic lesion in 16/17 cases. In one case with mesial temporal sclerosis, no ablation was performed due to suboptimal position of the catheter. That patient was successfully reoperated at a later date. Mean follow-up was 14.9months (± 11.6months). Eleven patients had follow-up longer than 12months. Good seizure control (Engel I, A) was achieved in 7/11 patients (63%) and 1/11 (9%) had significant improvement in seizure frequency (Angle IIIa). Three patients (27%) did not experience improvement in their seizure frequency (Engel IV, B), and one of these patients died during the follow-up period from sudden unexpected death of epilepsy (SUDEP). No immediate or delayed neurological complications were documented in any of the cases during the follow-up period. MRgLITT is a promising technique and can be used safely as an alternative to open resection in both lesional and non-lesional intractable epilepsy cases. In our local series, the success rate of epilepsy surgery was comparable to recent publications.

Laser interstitial thermal therapy (LITT) for intracranial lesions: a single-institutional series, outcomes, and review of the literature

Introduction Laser interstitial thermal therapy (LITT) is a minimally invasive treatment method in managing primary brain neoplasms, brain metastases, radiation necrosis, and epileptogenic lesions, many of which are located in operative corridors that would be difficult to address. Although the use of lasers is not a new concept in neurosurgery, advances in technology have enabled surgeons to perform laser treatment with the aid of real-time MRI thermography as a guide. In this report, we present our institutional series and outcomes of patients treated with LITT. Methods We retrospectively evaluated 19 patients (age range, 28–77 years) who underwent LITT at one or more targets from 2015 to 2019. Primary endpoint observed was mean progression free survival (PFS) and overall survival (OS). Results Seven patients with glial neoplasms and 12 patients with metastatic disease were reviewed. Average hospitalization was 2.4 days. Median PFS was 7 and 4 months in the metastatic group and primary glial neoplasm group, respectively (p = 0.01). Median OS from time of diagnosis was 41 and 32 months (p = 0.02) and median OS after LITT therapy was 25 and 24 months (p = 0.02) for the metastatic and primary glial neoplasm groups, respectively. One patient experienced immediate post-procedural morbidity secondary to increased intracerebral edema peri-lesionally while one patient experienced post-operative mortality and expired secondary to hemorrhage 1-month post-procedure. Median follow-up was 10 months. Conclusion Laser interstitial thermal therapy (LITT) is a safe, minimally invasive treatment method that provides surgeons with cytoreductive techniques to treat neurosurgical conditions. Both PFS and OS appear to be more favorable after LITT in patients with metastatic disease. In properly selected patients, this modality offers improved survival outcomes in conjunction with other salvage therapies.

New-onset seizures in adults: Low diagnostic yield of gadolinium contrast in initial brain MRI evaluation.

The diagnostic utility of contrast MR-imaging in adult new-onset seizures without clinically suspected neoplasia or infection is not well defined in the literature. Imaging guidelines consider both contrast and noncontrast MR-imaging examinations appropriate in this clinical scenario. The purpose of this study was to evaluate the utility of contrast MR-sequences in evaluation of seizure in patients without suspicion for neoplasia or infection. Imaging and clinical data were reviewed for 103 consecutive patients admitted for phase-1 seizure monitoring with the following criteria: (1) MRI-brain performed with/without intravenous contrast; (2) no clinical suspicion for central nervous system (CNS) infection; and (3) no history of CNS neoplasia, or suspected metastatic disease. Readers designated cases as lesional or nonlesional. Lesional cases were further categorized as either visualized on noncontrast sequences only, contrast sequences only, or both. 29/103 (28%) patients had epileptogenic lesions, 74/103 (72%) were nonlesional studies. 29/29 (100%) lesional abnormalities were detected on noncontrast sequences (sensitivity 100% [95 confidence interval (CI): 88-100], specificity 100% [95 CI: 95-100]). 23/29 (79.3%) lesional cases were visualized on both noncontrast and postcontrast sequences. 6/29 (20.7%) were visualized only on noncontrast sequences. No lesional cases were detected exclusively on postcontrast MR sequences. With an observed nonlesional extraneous contrast MR-imaging rate of 72%, estimated excess cost of contrast MR-imaging per 1000 patients using Medicare data was $103,680 USD. Contrast MR-imaging has limited diagnostic utility in initial screening of adult new-onset seizure patients without clinically suspected neoplasia or infection. More judicious use of contrast MR-imaging in this patient population may reduce unnecessary exposure to gadolinium and lower associated healthcare costs.

Progress Toward Obtaining Seizure Freedom With New Medications in Older Adults.

Characteristics and Treatment Outcomes of Newly Diagnosed Epilepsy in Older People: A 30-Year Longitudinal Cohort Study Alsfouk BAA, Hakeem H, Chen Z, Walters M, Brodie MJ, Kwan P. Epilepsia. 2020;61(12):2720-2728. doi:10.1111/epi.16721Objectives:To describe the clinical characteristics and evaluate the long-term treatment outcomes in older people with newly diagnosed epilepsy over the past 30 years. Methods: We included patients newly diagnosed with epilepsy and commenced on anti-seizure medications (ASMs) at age 65 years or older between July 1982 and October 2012 at the Western infirmary in Glasgow, Scotland. They were followed up until April 2016 or death. Seizure freedom was defined as no seizure for at least 1 year on unchanged medication at the last follow-up. Results: A total of 201 patients (median age 73 years, 59% male) were included. The median duration from initial seizure to starting treatment was 8 months (interquartile range: 3.0-24.0 months); 42.2% (85/201) patients had more than 5 seizures before commencing treatment. Brain imaging showed potentially epileptogenic lesions in 19.7% (38/193) of patients and other abnormalities in 56.5% (109/193); 78.6% patients (158/201) were seizure-free at the last follow-up, of whom 94.9% were taking monotherapy. Concomitant aspirin use (n = 80) was associated with a lower probability of being seizure-free (relative risk 0.82, 95% confidence interval 0.70-0.97; P = .02). The use of second-generation ASMs as the initial monotherapy increased from 31.5% (23/73) before 2000 to 70.3% (90/128, P < .001) from 2000 onward. However, the seizure freedom rates (67.1% vs 55.5%; P = .35) and intolerable adverse-effect rates (16.4% vs 19.5%; P = .45) did not show any significant difference. Significance: There was often a long interval between seizure onset and the initiation of treatment in older people with new-onset epilepsy, although the majority responded well to ASM treatment. Brain imaging showed a high rate of abnormalities. Despite the increased use of second-generation ASMs, treatment outcomes in later-onset epilepsy have not improved over time. The possible effect of aspirin on treatment response warrants further investigation.

Fluid and White Matter Suppression Imaging and Voxel-Based Morphometric Analysis in Conventional Magnetic Resonance Imaging-Negative Epilepsy.

Purpose: Delineation of subtle lesions in magnetic resonance imaging (MRI)-negative patients is of great importance in preoperative epilepsy evaluation. The aim of our study was to explore the diagnostic value of the novel fluid and white matter suppression (FLAWS) sequence in comparison with a voxel-based MRI postprocessing morphometric analysis program (MAP) in a consecutive cohort of non-lesional patients.Methods: Surgical candidates with a negative finding on an official neuroradiology report were enrolled. High-resolution FLAWS image and MAP maps generated based on high-resolution three-dimensional (3D) T1 image were visually inspected for each patient. The findings of FLAWS or MAP-positive (FLAWS/MAP+) regions were compared with the surgical resection cavity in correlation with surgical outcome and pathology.Results: Forty-five patients were enrolled; the pathological examination revealed focal cortical dysplasia (FCD) in 32 patients and other findings in 13 patients. The positive rate, sensitivity, and specificity were 48.9%, 0.43, and 0.87, respectively, for FLAWS and 64.4%, 0.57, and 0.8, respectively, for MAP. Concordance between surgical resection and FLAWS+ or MAP+ regions was significantly associated with a seizure-free outcome (FLAWS: p = 0.002; MAP: p = 0.0003). A positive finding in FLAWS and MAP together with abnormalities in the same gyrus (FLAWS–MAP gyral+) was detected in 31.1% of patients. FLAWS+ only and MAP+ only were found in 7 (15.5%) and 14 (31.1%) patients, respectively.Conclusions: FLAWS showed a promising value for identifying subtle epileptogenic lesions and can be used as a complement to current MAP in patients with MRI-negative epilepsy.

Hybrid Convolutional Neural Network for Localization of Epileptic Focus Based on iEEG.

Epileptic focus localization by analysing intracranial electroencephalogram (iEEG) plays a critical role in successful surgical therapy of resection of the epileptogenic lesion. However, manual analysis and classification of the iEEG signal by clinicians are arduous and time-consuming and excessively depend on the experience. Due to individual differences of patients, the iEEG signal from different patients usually shows very diverse features even if the features belong to the same class. Accordingly, automatic detection of epileptic focus is required to improve the accuracy and to shorten the time for treatment. In this paper, we propose a novel feature fusion-based iEEG classification method, a deep learning model termed Time-Frequency Hybrid Network (TF-HybridNet), in which short-time Fourier transform (STFT) and 1d convolution layers are performed on the input iEEG in parallel to extract features of the time-frequency domain and feature maps. And then, the time-frequency features and feature maps are fused and fed to a 2d convolutional neural network (CNN). We used the Bern-Barcelona iEEG dataset for evaluating the performance of TF-HybridNet, and the experimental results show that our approach is able to differentiate the focal from nonfocal iEEG signal with an average classification accuracy of 94.3% and demonstrates an improved accuracy rate compared to the model using only STFT or one-dimensional convolutional layers as feature extraction.

Continuous Intraoperative Neurophysiological Monitoring of the Motor Pathways Using Depth Electrodes During Surgical Resection of an Epileptogenic Lesion: A Novel Technique.

Intraoperative neurophysiological monitoring of the motor pathways during epilepsy surgery is essential to safely achieve maximal resection of the epileptogenic zone. Motor evoked potential (MEP) recording is usually performed intermittently during resection using a handheld stimulator or continuously through an electrode array placed on the motor cortex. We present a novel variation of continuous MEP acquisition through previously implanted depth electrodes in the perirolandic cortex. A 60-yr-old woman with a history of a left frontal meningioma (World Health Organization [WHO] grade II) treated with surgical resection and radiation presented with residual right hemiparesis and refractory epilepsy. Imaging demonstrated a perirolandic lesion with surrounding edema and mass effect in the prior surgical site, suspicious for radiation necrosis versus tumor recurrence. Presurgical electrocorticography (ECoG) with orthogonal, stereotactically implanted depth electrodes (stereoelectroencephalography [SEEG]) of the perirolandic cortex captured seizure onsets from the supplementary motor area (SMA) and primary motor cortex (PMC). The patient underwent a left frontal craniotomy for repeat resection and tissue diagnosis. Intraoperative ECoG and MEPs were obtained continuously with direct cortical stimulation through the indwelling SEEG electrodes in the PMC. Maximal resection was achieved with preservation of direct cortical MEPs and without deterioration of her baseline hemiparesis. Biopsy revealed radiation necrosis. At 30-mo follow-up, the patient had only rare seizures (Engel class IIB). Intraoperative cortical MEP acquisition through implanted SEEG electrode arrays is a potentially safe and effective alternative approach to continuously monitor the motor pathways during the resection of a perirolandic epileptogenic lesion, without the need for surgical interruptions.

Commentary: Continuous Intraoperative Neurophysiologic Monitoring of the Motor Pathways Using Depth Electrodes During Surgical Resection of an Epileptogenic Lesion: A Novel Technique.

Commentary: Continuous Intraoperative Neurophysiologic Monitoring of the Motor Pathways Using Depth Electrodes During Surgical Resection of an Epileptogenic Lesion: A Novel Technique.

Surgical treatment of epilepsy at the Russian Children’s Clinical Hospital: substrates and imaging aspects

Introduction. MRI revealing the epileptogenic foci is the central part of the presurgical evaluation of children with focal-resistant epilepsy. Besides that, MRI seems to be a reliable instrument of treatment optimization and good prognosis. Aim. To identify epileptogenic lesions in children with resistant focal epilepsy by high resolution (HR) MRI and comparing obtained data with postsurgical morphology. Materials and methods. We assessed the results of neuroimaging, EEG, clinical neurological status, and postsurgical morphological data in 65 children with focal epilepsy who had undergone antiepileptic surgery in Russian State Children Hospital, neurosurgery department (Moscow, Russia) from 2016 to 2020. Results. The broad spectrum of epileptogenic lesions was revealed by HR MRI, including focal and diffuse cortical dysplasias (44.6%), cortical post hypoxic gliosis (27.7%), glial tumors (7.7%), Rasmussen encephalitis (10.8%), tuberous sclerosis, and Sturge-Weber syndrome (3%), small angiodysplasias (4.6%) and other. Focal cerebral dysplasia had an obvious superiority as the main etiological factor in focal epilepsy and was approved in 33.8% of all patients. In all cases, epilepsy is characterized by frequent and resistant seizures, inflicting motor arrest, and psycho-emotional deterioration. Conclusion. HR MRI and multidisciplinary investigation have to be unchangeable standards in the presurgical evaluation of children with focal epilepsy. This approach’s effectiveness has reassuring confirmation by high level (95.2%) of total coincidence MRI and morphological results.

Automated fusion of multimodal imaging data for identifying epileptogenic lesions in patients with inconclusive magnetic resonance imaging.

Many methods applied to data acquired by various imaging modalities have been evaluated for their benefit in localizing lesions in magnetic resonance (MR) negative epilepsy patients. No approach has proven to be a stand‐alone method with sufficiently high sensitivity and specificity. The presented study addresses the potential benefit of the automated fusion of results of individual methods in presurgical evaluation. We collected electrophysiological, MR, and nuclear imaging data from 137 patients with pharmacoresistant MR‐negative/inconclusive focal epilepsy. A subgroup of 32 patients underwent surgical treatment with known postsurgical outcomes and histopathology. We employed a Gaussian mixture model to reveal several classes of gray matter tissue. Classes specific to epileptogenic tissue were identified and validated using the surgery subgroup divided into two disjoint sets. We evaluated the classification accuracy of the proposed method at a voxel‐wise level and assessed the effect of individual methods. The training of the classifier resulted in six classes of gray matter tissue. We found a subset of two classes specific to tissue located in resected areas. The average classification accuracy (i.e., the probability of correct classification) was significantly higher than the level of chance in the training group (0.73) and even better in the validation surgery subgroup (0.82). Nuclear imaging, diffusion‐weighted imaging, and source localization of interictal epileptic discharges were the strongest methods for classification accuracy. We showed that the automatic fusion of results can identify brain areas that show epileptogenic gray matter tissue features. The method might enhance the presurgical evaluations of MR‐negative epilepsy patients.