Drug-resistant Focal Epilepsy Research Articles

Value of ultra-high field MRI in patients with suspected focal epilepsy and negative 3\xa0T MRI (EpiUltraStudy): protocol for a prospective, longitudinal therapeutic study

PurposeResective epilepsy surgery is a well-established, evidence-based treatment option in patients with drug-resistant focal epilepsy. A major predictive factor of good surgical outcome is visualization and delineation of a potential epileptogenic lesion by MRI. However, frequently, these lesions are subtle and may escape detection by conventional MRI (≤ 3 T). MethodsWe present the EpiUltraStudy protocol to address the hypothesis that application of ultra-high field (UHF) MRI increases the rate of detection of structural lesions and functional brain aberrances in patients with drug-resistant focal epilepsy who are candidates for resective epilepsy surgery. Additionally, therapeutic gain will be addressed, testing whether increased lesion detection and tailored resections result in higher rates of seizure freedom 1 year after epilepsy surgery. Sixty patients enroll the study according to the following inclusion criteria: aged ≥ 12 years, diagnosed with drug-resistant focal epilepsy with a suspected epileptogenic focus, negative conventional 3 T MRI during pre-surgical work-up.ResultsAll patients will be evaluated by 7 T MRI; ten patients will undergo an additional 9.4 T MRI exam. Images will be evaluated independently by two neuroradiologists and a neurologist or neurosurgeon. Clinical and UHF MRI will be discussed in the multidisciplinary epilepsy surgery conference. Demographic and epilepsy characteristics, along with postoperative seizure outcome and histopathological evaluation, will be recorded.ConclusionThis protocol was reviewed and approved by the local Institutional Review Board and complies with the Declaration of Helsinki and principles of Good Clinical Practice. Results will be submitted to international peer-reviewed journals and presented at international conferences.Trial registration numberwww.trialregister.nl: NTR7536.

Incidence and prevalence of major epilepsy-associated brain lesions.

Epilepsy surgery is an effective treatment option for drug-resistant focal epilepsy patients with associated structural brain lesions. However, little epidemiological data are available regarding the number of patients with these lesions. We reviewed data regarding (1) the prevalence and incidence of epilepsy; (2) the proportion of epilepsy patients with focal epilepsy, drug-resistant epilepsy, and drug-resistant focal epilepsies; and (3) the number of epilepsy presurgical evaluations and surgical resections. We also assessed the relative proportion of brain lesions using post-surgical histopathological findings from 541 surgical patients from the Cleveland Clinic and 9,523 patients from a European multi-center cohort. Data were combined to generate surgical candidate incidence and prevalence estimates and the first lesion-specific estimates for hippocampal sclerosis (HS), low-grade epilepsy-associated brain tumors (LEAT), malformations of cortical development (MCD), glial scars, vascular malformations, and encephalitis. The most frequently diagnosed brain lesions were HS (incidence=2.32±0.26 in 100,000, prevalence=19.40±2.16 in 100,000) for adults and MCD (incidence=1.15±0.34 in 100,000, prevalence=6.52±1.89 in 100,000) for children. Our estimates can guide patient advocacy groups, clinicians, researchers, policymakers in education, development of health care strategy, resource allocation, and reimbursement schedules.

Epilepsy surgery in patient with monogenic epilepsy related to SCN8A mutation.

Epilepsy surgery is superior to prolonged medical therapy in patients with drug-resistant focal epilepsy, but reports on epilepsy surgery outcomes for patients with a genetic etiology are limited, especially in adults. This is the first documented report of a stereoelectroencephalography (SEEG) evaluation and resective surgery outcome in an adult patient with epilepsy related to SCN8A mutation. We describe a patient with epilepsy related to SCN8A mutation which was reported as a variant of uncertain significance at time of his pre-surgical evaluation and reclassified as likely pathogenic about 3years after resective epilepsy surgery. Most of his pre-surgical evaluation results suggested right temporal lobe epilepsy, but few reported semiological symptoms, ictal SPECT, and neuropsychology results were discordant, and brain MRI was non-lesional. Therefore, SEEG was recommended; ultimately, seizures were localized to the right hippocampus. He was seizure-free for 1.5years after right anterior temporal lobectomy, then reported three focal to bilateral tonic-clonic (FBTC) seizures in the subsequent 12months (preoperatively, 6 focal impaired awareness seizures and 4-6 FBTC per year). This case demonstrates that epilepsy surgery reduced seizure burden in a patient with SCN8A-related epilepsy granting him short-term seizure freedom after resection, and then decreased seizure frequency after relapse compared to the preoperative baseline.

The presurgical evaluation of patients with drug-resistant epilepsy

Comprehensive multimodal examination of patients with focal refractory epilepsies is currently a prerequisite for high-quality pre-surgical diagnostics, which aims not only to expand the indications for radical treatment of epilepsy, but also to avoid the appearance of severe postoperative deficits. High-resolution MRI plays a key role in preoperative assessment. In this review, we illustrate the modern aspects of a pre-surgical diagnostical complex in examinations of patients with focal drug-resistant epilepsy, including the possibilities of neuroimaging.

Rituximab in Rasmussen's encephalitis: A single center experience and review of the literature.

Rasmussen's encephalitis (RE) is a rare chronic inflammatory disease of the brain resulting in unilateral hemispheric atrophy with drug-resistant focal epilepsy associated with a variable degree of progressive hemiparesis and cognitive decline. The precise etiology of RE is unknown but presumed to have a neuroinflammatory pathobiological basis. Only surgery halts progression of the disease, but may occur at the expense of a fixed but otherwise inevitable neurological deficit. Therefore, the question of medical management is an important consideration. Reports of rituximab use in patients with RE were presented at the American Epilepsy Society annual meeting in 2008. Good published evidence for its usage has been very slow to emerge since then. However, rituximab continues to be listed in discussions of treatment options for patients with RE, though other monoclonal antibodies have since been used with comparable outcomes. We describe a series of nine patients including two with adult-onset RE. Rituximab was used early in the disease course (range 1-108months; mean 32months). Of nine patients with RE, there was significant benefit in their seizure burden with rituxamab. Seizure freedom occurred in 3 patients. Epilepsia partialis continua (EPC) was present in 4/9 and no focal motor deficit noted in 4/9. No progression of a neurological deficit was present in 2/9 and evidence of progression with neuroimaging was terminated with rituxamab in 5/9 supporting early use of rituxamab in patients with RE.

Histopathological Findings in Brain Tissue of Patients with Pharmacoresistant Focal Epilepsy

Background: Pharmacoresistant epilepsy represents 30-40% of cases with intractable epilepsy in children, and up to 20% of adult cases. Various cerebral lesions can lead to drug-resistant focal epilepsy. They are medically refractory but the complete surgical resection correlates with good outcome.

7T versus 3T MRI in the presurgical evaluation of patients with drug-resistant epilepsy.

MRI has a crucial role in presurgical evaluation of drug-resistant focal epilepsy patients. Whether and how much 7T MRI further improves presurgical diagnosis compared to standard of care 3T MRI remains to be established. We investigate the added value 7T MRI offers in surgical candidates with remaining clinical uncertainty after 3T MRI. 7T brain MRI was obtained on sequential patients with drug-resistant focal epilepsy undergoing presurgical evaluation at a comprehensive epilepsy center, including patients with and without suspected lesions on standard 3T MRI. Clinical information and 3T images informed the interpretation of 7T images. Detection of a new lesion on 7T or better characterization of a suspected lesion was considered to add value to the presurgical workup. Interpretable 7T MRI was acquired in 19 patients. 7T MRI identified a lesion relevant to the seizures in three of eight patients (38%) without a lesion on 3T MRI; no lesion in 7/11 patients (64%) with at least one suspected lesion on 3T MRI, contributing to the final classification of all seven as nonlesional; and confirmed and better characterized the lesion suspected at 3T MR in the remaining 4/11 patients. 7T MRI detected new lesions in over a third of 3T MRI nonlesional patients, confirmed and better characterized a 3T suspected lesion in one third of patients, and helped exclude a 3T suspected lesion in the remainder. Our initial experience suggests that 7T MRI adds value to surgical planning by improving detection and characterization of suspected brain lesions in drug-resistant focal epilepsy patients.

Coffee consumption and seizure frequency in patients with drug-resistant focal epilepsy

ObjectiveTo assess the relation between coffee consumption and seizure frequency in patients with drug-resistant focal epilepsy. MethodsCross-sectional analysis of data collected in the SAVE study, which included patients with drug-resistant focal epilepsy during long-term EEG monitoring. Patients in whom both coffee consumption and data about seizure frequency, including focal to bilateral tonic-clonic seizures (FBTCS), were available were selected. Coffee consumption was collected using a standardized self-report questionnaire and classified into four groups: none, rare (from less than 1 cup/week to up 3 cups/week), moderate (from 4 cups/week to 3 cups/day), and high (more than 4 cups/day). ResultsSix hundred and nineteen patients were included. There was no relation between coffee consumption and total seizure frequency (p = 0.902). In contrast, the number of FBTCS reported over the past year was significantly associated with usual coffee consumption (p = 0.029). Specifically, number of FBCTS in patients who reported moderate coffee consumption was lower than in others. In comparison with patients with moderate coffee consumption, the odds ratio (95%CI) for reporting at least 1 FBTCS per year was 1.6 (1.03–2.49) in patients who never take coffee, 1.62 (1.02–2.57) in those with rare consumption and 2.05 (1.24–3.4) in those with high consumption. Multiple ordinal logistic regression showed a trend toward an association between coffee consumption and number of FBTCS (p = 0.08). Conclusions and relevanceOur data suggest that effect of coffee consumption on seizures might depend on dose with potential benefits on FBTCS frequency at moderate doses. These results will have to be confirmed by prospective studies.

Neuromodulation for Refractory Epilepsy.

Three neuromodulation therapies, all using implanted device and electrodes, have been approved to treat adults with drug-resistant focal epilepsy, namely, the vagus nerve stimulation in 1995, deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) in 2018 (2010 in Europe), and responsive neurostimulation (RNS) in 2014. Indications for VNS have more recently extended to children down to age of 4. Limited or anecdotal data are available in other epilepsy syndromes and refractory/super-refractory status epilepticus. Overall, neuromodulation therapies are palliative, with only a minority of patients achieving long-term seizure freedom, justifying favoring such treatments in patients who are not good candidates for curative epilepsy surgery. About half of patients implanted with VNS, ANT-DBS, and RNS have 50% or greater reduction in seizures, with long-term data suggesting increased efficacy over time. Besides their impact on seizure frequency, neuromodulation therapies are associated with various benefits and drawbacks in comparison to antiseizure drugs. Yet, we lack high-level evidence to best position each neuromodulation therapy in the treatment pathways of persons with difficult-to-treat epilepsy.

Intraoperative electrocorticography: variants of periodic patterns in the structural epilepsy

The results of intraoperative electrocorticography for patients with the structural epilepsy are influenced by two main factors: the action of general anesthetic and the mechanisms of epileptogenesis. Under the general anesthesia, there is a dose-dependent suppression of the bioelectrical activity of the brain; you could even register the outburst-diminution and outburst-suppression types of the periodic patterns. The study was carried out to classify the variants of periodic activity registered on the intraoperative electrocorticogram for patients with a structural epilepsy. The work was carried out during the examination and surgical treatment of the two groups of patients: 1) 19 patients (men/women 10/9, 1945 years old) with focal drug-resistant epilepsy; 2) 19 patients (men/women 8/11, 2868 years old) with structural epilepsy associated with the intracerebral tumors. All patients underwent surgical removal of the epileptic focus under a neurophysiological control. Surgical interventions were performed under the sevoflurane-based inhalation anesthesia in doses from 1.01.5 MAC (minimum alveolar concentration). Periodic activity on intraoperative electrocorticography was represented with the outburst-suppression type of patterns and patterns containing epileptiform discharge graph elements: discharge- postdischarge depression, outburst-suppression with discharges against the background of depression, small electrical elements with epileptiform discharges. The presence of discharge graph elements in the periodic patterns has a neurophysiological correlation with a drug-resistance in the structural epilepsy.

Resective, Ablative and Radiosurgical Interventions for Drug Resistant Mesial Temporal Lobe Epilepsy: A Systematic Review and Meta-Analysis of Outcomes

Objectives: One-third of individuals with focal epilepsy do not achieve seizure freedom despite best medical therapy. Mesial temporal lobe epilepsy (MTLE) is the most common form of drug resistant focal epilepsy. Surgery may lead to long-term seizure remission if the epileptogenic zone can be defined and safely removed or disconnected. We compare published outcomes following open surgical techniques, radiosurgery (SRS), laser interstitial thermal therapy (LITT) and radiofrequency ablation (RF-TC).Methods: PRISMA systematic review was performed through structured searches of PubMed, Embase and Cochrane databases. Inclusion criteria encompassed studies of MTLE reporting seizure-free outcomes in ≥10 patients with ≥12 months follow-up. Due to variability in open surgical approaches, only comparative studies were included to minimize the risk of bias. Random effects meta-analysis was performed to calculate effects sizes and a pooled estimate of the probability of seizure freedom per person-year. A mixed effects linear regression model was performed to compare effect sizes between interventions.Results: From 1,801 screened articles, 41 articles were included in the quantitative analysis. Open surgery included anterior temporal lobe resection as well as transcortical and trans-sylvian selective amygdalohippocampectomy. The pooled seizure-free rate per person-year was 0.72 (95% CI 0.66–0.79) with trans-sylvian selective amygdalohippocampectomy, 0.59 (95% CI 0.53–0.65) with LITT, 0.70 (95% CI 0.64–0.77) with anterior temporal lobe resection, 0.60 (95% CI 0.49–0.73) with transcortical selective amygdalohippocampectomy, 0.38 (95% CI 0.14–1.00) with RF-TC and 0.50 (95% CI 0.34–0.73) with SRS. Follow up duration and study sizes were limited with LITT and RF-TC. A mixed-effects linear regression model suggests significant differences between interventions, with LITT, ATLR and SAH demonstrating the largest effects estimates and RF-TC the lowest.Conclusions: Overall, novel “minimally invasive” approaches are still comparatively less efficacious than open surgery. LITT shows promising seizure effectiveness, however follow-up durations are shorter for minimally invasive approaches so the durability of the outcomes cannot yet be assessed. Secondary outcome measures such as Neurological complications, neuropsychological outcome and interventional morbidity are poorly reported but are important considerations when deciding on first-line treatments.

Working Memory and Language Contribution to Verbal Learning and Memory in Drug-Resistant Unilateral Focal Temporal Lobe Epilepsy.

We aimed to investigate the working memory (WM) and language separate contributions to verbal learning and memory in patients with unilateral drug-resistant temporal lobe epilepsy (drTLE); additionally, we explored the mediating role of WM on the relationship between the number of antiepileptic drugs (AEDs) and short-term verbal memory. We retrospectively enrolled 70 patients with left (LTLE; n = 44) and right (RTLE; n = 26) drTLE. About 40 similar (age and education) healthy controls were used to determine impairments of groups at WM, language (naming and verbal fluency), and verbal learning and memory (five trials list-learning, story memory—immediate recall). To disentangle the effect of learning from the short-term memory, we separately analyzed performances at the first trial, last trial, and delayed-recall list-learning measures, in addition to the total learning capacity (the sum of the five trials). Correlation and regression analyses were used to assess the contribution of potential predictors while controlling for main clinical and demographic variables, and ascertain the mediating role of WM. All patients were impaired at WM and story memory, whereas only LTLE showed language and verbal learning deficits. In RTLE, language was the unique predictor for the most verbal learning performances, whereas WM predicted the results at story memory. In LTLE, WM was the sole predictor for short-term verbal learning (list-learning capacity; trial 1) and mediated the interaction between AED number and the performance at these measures, whereas language predicted the delayed-recall. Finally, WM confounded the performance at short-term memory in both groups, although at different measures. WM is impaired in drTLE and contributes to verbal memory and learning deficits in addition to language, mediating the relationship between AED number and short-term verbal memory in LTLE. Clinicians should consider this overlap when interpreting poor performance at verbal learning and memory in drTLE.

Carisbamate add-on therapy for drug-resistant focal epilepsy.

Epilepsy is one of the most common neurological disorders. Many people with epilepsy are drug-resistant and require add-on therapy, meaning that they concomitantly take multiple antiepileptic drugs. Carisbamate is a drug which is taken orally and inhibits voltage-gated sodium channels. Carisbamate may be useful for drug-resistant focal epilepsy. To evaluate the efficacy and tolerability of carisbamate when used as an add-on therapy for drug-resistant focal epilepsy. We searched the following databases on 8 April 2021: Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid) 1946 to April 07, 2021. CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, WHO ICTRP, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane review groups including Epilepsy. We also searched ongoing trials registers, checked reference lists, and contacted authors of the included trials. Double-blind randomised controlled trials (RCTs) comparing carisbamate versus placebo or another antiepileptic drug, as add-on therapy for drug-resistant focal epilepsy. Trials could have a parallel-group or cross-over design. Two review authors independently selected the trials for inclusion, assessed trial quality, and extracted data. The primary outcome was 50% or greater reduction in seizure frequency (responder rate). The secondary outcomes were: seizure freedom, treatment withdrawal (for any reason and due to adverse events); adverse events, and quality of life. We analysed data using the Mantel-Haenszel statistical method and according to the intention-to-treat population. We presented results as risk ratios (RRs) with 95% confidence intervals (CIs). We included four RCTs involving a total of 2211 participants. All four trials compared carisbamate with placebo for drug-resistant focal epilepsy. Participants in all trials were over 16 years of age and received at least one other antiepileptic drug concomitantly. We detected substantial risk of bias across the included trials. All four trials were at high risk of attrition bias due to the incomplete reporting of attrition and the high treatment withdrawal rates noted, especially with higher doses. All four trials also had unclear risk of detection bias, as they did not specify whether outcome assessors were blinded. Meta-analysis suggested that carisbamate produced a higher responder rate compared to placebo (RR 1.36, 95% CI 1.14 to 1.62; 4 studies; moderate-certainty evidence). More participants in the carsibamate group achieved seizure freedom (RR 2.43, 95% CI 0.84 to 7.03; 1 study); withdrew from treatment for any reason (RR 1.32, 95% CI 0.82 to 2.12; 4 studies); and withdrew from treatment due to adverse events (RR 1.80, 95% CI 0.78 to 4.17; 4 studies) than in the placebo group. However, the evidence for the three outcomes was very low-certainty. There was no difference between treatment groups for the proportion of participants experiencing at least one adverse event (RR 1.10, 95% CI 0.93 to 1.30; 2 studies; low-certainty evidence). More participants in the carisbamate group than in the placebo group developed dizziness (RR 2.06, 95% CI 1.23 to 3.44; 4 studies; very low-certainty evidence) and somnolence (RR 1.82, 95% CI 1.28 to 2.58; 4 studies; low-certainty evidence), but not fatigue (RR 1.11, 95% CI 0.73 to 1.68; 3 studies); headache (RR 1.13, 95% CI 0.92 to 1.38; 4 studies); or nausea (RR 1.19, 95% CI 0.81 to 1.75; 3 studies). None of the included trials reported quality of life. The results suggest that carisbamate may demonstrate efficacy and tolerability as an add-on therapy for drug-resistant focal epilepsy. Importantly, the evidence for all outcomes except responder rate was of low to very low certainty, therefore we are uncertain of the accuracy of the reported effects. The certainty of the evidence is limited by the significant risk of bias associated with the included studies, as well as the statistical heterogeneity detected for some outcomes. Consequently, it is difficult for these findings to inform clinical practice. The studies were all of short duration and only included adult study populations. There is a need for further RCTs with more clear methodology, long-term follow-up, more clinical outcomes, more seizure types, and a broader range of participants.

Atlas of lesion locations and postsurgical seizure freedom in focal cortical dysplasia: A MELD study.

ObjectiveDrug‐resistant focal epilepsy is often caused by focal cortical dysplasias (FCDs). The distribution of these lesions across the cerebral cortex and the impact of lesion location on clinical presentation and surgical outcome are largely unknown. We created a neuroimaging cohort of patients with individually mapped FCDs to determine factors associated with lesion location and predictors of postsurgical outcome.MethodsThe MELD (Multi‐centre Epilepsy Lesion Detection) project collated a retrospective cohort of 580 patients with epilepsy attributed to FCD from 20 epilepsy centers worldwide. Magnetic resonance imaging‐based maps of individual FCDs with accompanying demographic, clinical, and surgical information were collected. We mapped the distribution of FCDs, examined for associations between clinical factors and lesion location, and developed a predictive model of postsurgical seizure freedom.ResultsFCDs were nonuniformly distributed, concentrating in the superior frontal sulcus, frontal pole, and temporal pole. Epilepsy onset was typically before the age of 10 years. Earlier epilepsy onset was associated with lesions in primary sensory areas, whereas later epilepsy onset was associated with lesions in association cortices. Lesions in temporal and occipital lobes tended to be larger than frontal lobe lesions. Seizure freedom rates varied with FCD location, from around 30% in visual, motor, and premotor areas to 75% in superior temporal and frontal gyri. The predictive model of postsurgical seizure freedom had a positive predictive value of 70% and negative predictive value of 61%.SignificanceFCD location is an important determinant of its size, the age at epilepsy onset, and the likelihood of seizure freedom postsurgery. Our atlas of lesion locations can be used to guide the radiological search for subtle lesions in individual patients. Our atlas of regional seizure freedom rates and associated predictive model can be used to estimate individual likelihoods of postsurgical seizure freedom. Data‐driven atlases and predictive models are essential for evidence‐based, precision medicine and risk counseling in epilepsy.

Cytokine profile in the peripheral blood and the brain in patients with focal drug-resistant epilepsy

Aim. To study markers of blood-brain barrier dysfunction (BBB) in patients with pharmacoresistant epilepsy (PhRE) – the amount of VEGF in endotheliocytes of brain capillaries, TNF-α in brain tissue and cytokine profile in blood serum.Materials and methods. The study included 30 patients with PhRE who underwent anterior temporal bloc resection. Histological samples of the brain were examined to assess the amount of VEGF and TNF-α; the concentration of cytokines in the blood serum was determined.Results. In the PhRE group, the densitometric density of cells expressing VEGF and the amount of TNF-α in the epileptogenic focus were higher than in the control groups (p < 0.001; p < 0.05). Compared with the control, the serum concentrations of IL-2 (0.98 ± 0.28 pg/ml vs. 2.80 ± 0.71 pg/ml; p < 0.001), IL-8 (14.04 ± 1.46 pg/ml vs. 26.13 ± 3.80 pg/ml; p < 0.001) and EGF (43.72 ± 5.63 pg/ml vs. 83.62 ± 24.06 pg/ml; p < 0.05) were statistically significantly lower in the PhRE group, and the amount of TNF-α (33.09 ± 1.23 pg/ml vs. 24.85 ± 1.32 pg/ml, p < 0.05), IL-4 (43.73 ± 2.57 pg/ml vs. 32.37 ± 5.80 pg/ml, p < 0.05), IL-5 (43.73 ± 2.57 pg/ml vs. 32.37 ± 5.80 pg/ml; p < 0.05), IL-7 (16.65 ± 3.07 pg/ml vs. 8.13 ± 1.67 pg/ml; p < 0.05), GRO (growth-regulated protein) (3054.0 ± 200.8 pg/ml vs. 1367.0 ± 187.3 pg/ml; p < 0.001), VEGF (316.10 ± 55.28 pg/ml vs. 95.22 ± 15.78 pg/ml; p < 0.01) are statistically significantly higher. There were no significant differences in the concentration of IL-1β, IL-1RA, IL-10 and IFN-γ between the PhRE group and the control.Conclusion. Based on the studied cytokine profile, there is no systemic inflammation in patients with PhRE. The established overexpression of VEGF in the brain and an increase in its concentration in the blood, combined with a decrease in serum EGF concentrations and an increase in GRO, as well as pro-inflammatory factors, indicates damage to the BBB. A high amount of TNF-α in the epileptic focus indicates neuroinflammation, and an increased concentration of this marker can be found in the blood of patients with BBB dysfunction.

Imaging the extent and location of spatiotemporally distributed epileptiform sources from MEG measurements

Non-invasive MEG/EEG source imaging provides valuable information about the epileptogenic brain areas which can be used to aid presurgical planning in focal epilepsy patients suffering from drug-resistant seizures. However, the source extent estimation for electrophysiological source imaging remains to be a challenge and is usually largely dependent on subjective choice. Our recently developed algorithm, fast spatiotemporal iteratively reweighted edge sparsity minimization (FAST-IRES) strategy, has been shown to objectively estimate extended sources from EEG recording, while it has not been applied to MEG recordings. In this work, through extensive numerical experiments and real data analysis in a group of focal drug-resistant epilepsy patients’ interictal spikes, we demonstrated the ability of FAST-IRES algorithm to image the location and extent of underlying epilepsy sources from MEG measurements. Our results indicate the merits of FAST-IRES in imaging the location and extent of epilepsy sources for pre-surgical evaluation from MEG measurements.

Seizure outcomes in people with drug-resistant focal epilepsy evaluated for surgery but do not proceed

ObjectiveTo ascertain seizure outcomes in people with drug-resistant focal epilepsy considered for epilepsy surgery but who did not proceed. MethodsWe identified people discussed at a weekly presurgical epilepsy multi-disciplinary (MDT) meeting from January 2015 to December 2019 and in whom a decision not to proceed to surgery was made. Seizure outcomes were obtained from individuals, primary care physicians and attending neurologists at a minimum of 12 months following the not to proceed decision. ResultsWe considered 315 people who did not proceed to surgery after evaluation. Nine died, and 25 were lost to follow-up. We included 281 people with a median follow-up of 2.4 (IQR 1.5–4) years. In total, 83 (30%) people reported that seizures had improved or resolved since the MDT meeting. Thirteen (5%) were seizure-free over the last 12 months of follow-up, 70 (25%) had experienced more than 50% reduction in seizure frequency, 180 (64%) had no meaningful change, and 18 (6%) reported a doubling of seizure frequency. Of the 53 (16%) who had vagal nerve stimulation, 19/53 (37%) reported more than 50% reduction in frequency, including one seizure-free. SignificanceThe chances of seizure freedom with further medications and neurostimulation are low for people with drug-resistant focal epilepsy who have been evaluated for surgery and do not proceed, but improvement may still occur. Up to a quarter have a > 50% reduction in seizures, and one in twenty become seizure-free eventually. Trying additional anti-seizure medication and neurostimulation is worthwhile in this population.

18F-FDG PET/MR in focal epilepsy: A new step for improving the detection of epileptogenic lesions

PurposeHybrid PET/MR is a promising tool in focal drug-resistant epilepsy, however the additional value for the detection of epileptogenic lesions and surgical decision-making remains to be established. MethodsWe retrospectively compared 18F-FDG PET/MR images with those obtained by a previous 18F-FDG PET co-registered with MRI (PET+MR) in 25 consecutive patients (16 females, 13–60 years) investigated for focal drug-resistant epilepsy. Visual analysis was performed by two readers blinded from imaging modalities, asked to assess the technical characteristics (co-registration, quality of images), the confidence in results, the location of PET abnormalities and the presence of a structural lesion on MRI. Clinical impact on surgical strategy and outcome was assessed independently. ResultsThe location of epileptic focus was temporal in 9 patients and extra-temporal in 16 others. MRI was initially considered negative in 21 patients. PET stand-alone demonstrated metabolic abnormalities in 19 cases (76%), and the co-registration with MRI allowed the detection of 4 additional structural lesions. Compared to PET+MR, the PET/MR sensitivity was increased by 13% and new structural lesions (mainly focal cortical dysplasias) were detected in 6 patients (24%). Change of surgical decision-making was substantial for 10 patients (40%), consisting in avoiding invasive monitoring in 6 patients and modifying the planning in 4 others. Seizure-free outcome (follow-up>1 year) was obtained in 12/14 patients who underwent a cortical resection. ConclusionHybrid PET/MR may improve the detection of epileptogenic lesions, allowing to optimize the presurgical work-up and to increase the proportion of successful surgery even in the more complex cases.

Future of Neurology & Technology: Stereoelectroencephalography in Presurgical Epilepsy Evaluation.

Stereoelectroencephalography (SEEG) is not only a sophisticated and highly technological investigation but a new and better way to conceptualize the spatial and temporal dynamics of epileptic activity. The first intracranial investigations with SEEG were performed in France in the mid-twentieth century; however, its use in North America is much more recent. Given its significantly lower risk of complications and its ability to sample both superficial and deep structures and both hemispheres simultaneously, SEEG has become the preferred method to conduct intracranial EEG monitoring in most comprehensive epilepsy centers in North America. SEEG is an invasive neurophysiologic methodology used for advanced presurgical workup in the 20% of drug-resistant patients with more complex focal epilepsy in whom noninvasive investigations do not allow to decide on surgical candidacy. SEEG uses stereotactically implanted depth electrodes to map the origin and propagation of epileptic seizures by creating a 3-dimensional representation of the abnormal electrical activity in the brain. SEEG analysis takes into account the background, interictal, and ictal activity, as well as the results of cortical electrical stimulation procedures, to reliably delineate the epileptogenic network. By means of a clinical vignette, this article will walk general neurologists, but especially neurology trainees through the immense potential of this methodology. In summary, SEEG enables to accurately identify the epileptogenic zone in patients with drug-resistant focal epilepsy who otherwise would be not amenable to surgical treatment. In this patient population, SEEG is the best way to improve seizure control and achieve seizure freedom.

Comparison of Resampling Techniques for Imbalanced Datasets in Machine Learning: Application to Epileptogenic Zone Localization From Interictal Intracranial EEG Recordings in Patients With Focal Epilepsy.

Aim: In neuroscience research, data are quite often characterized by an imbalanced distribution between the majority and minority classes, an issue that can limit or even worsen the prediction performance of machine learning methods. Different resampling procedures have been developed to face this problem and a lot of work has been done in comparing their effectiveness in different scenarios. Notably, the robustness of such techniques has been tested among a wide variety of different datasets, without considering the performance of each specific dataset. In this study, we compare the performances of different resampling procedures for the imbalanced domain in stereo-electroencephalography (SEEG) recordings of the patients with focal epilepsies who underwent surgery.Methods: We considered data obtained by network analysis of interictal SEEG recorded from 10 patients with drug-resistant focal epilepsies, for a supervised classification problem aimed at distinguishing between the epileptogenic and non-epileptogenic brain regions in interictal conditions. We investigated the effectiveness of five oversampling and five undersampling procedures, using 10 different machine learning classifiers. Moreover, six specific ensemble methods for the imbalanced domain were also tested. To compare the performances, Area under the ROC curve (AUC), F-measure, Geometric Mean, and Balanced Accuracy were considered.Results: Both the resampling procedures showed improved performances with respect to the original dataset. The oversampling procedure was found to be more sensitive to the type of classification method employed, with Adaptive Synthetic Sampling (ADASYN) exhibiting the best performances. All the undersampling approaches were more robust than the oversampling among the different classifiers, with Random Undersampling (RUS) exhibiting the best performance despite being the simplest and most basic classification method.Conclusions: The application of machine learning techniques that take into consideration the balance of features by resampling is beneficial and leads to more accurate localization of the epileptogenic zone from interictal periods. In addition, our results highlight the importance of the type of classification method that must be used together with the resampling to maximize the benefit to the outcome.