Extratemporal Lobe Epilepsy Research Articles

The Regulation of Plasma Interleukin-6 Levels Is Modified by Hippocampal Sclerosis and Its Lateralization in Drug-Resistant Temporal Lobe Epilepsy

Background. Several studies have reported the association of the proinflammatory cytokine IL-6 with temporal lobe epilepsy (TLE), but the regulation of IL-6 in hippocampal sclerosis (HS) is less studied. Objectives. To analyse IL-6 levels and the IL-6/IL-10 ratio in a larger, well-characterized group of patients with drug-resistant focal epilepsy (DRE), focusing especially on TLE and TLE-associated HS. Methods. IL-6 levels were measured by ELISA in plasma in a cross-sectional cohort of 265 patients comprising TLE with HS ( n = 34 ), TLE without HS ( n = 103 ), extratemporal lobe epilepsy ( n = 92 ), and idiopathic generalized epilepsy ( n = 36 ). Results. The IL-6/IL-10 ratio was higher in TLE with HS than in TLE without HS (3.1 vs. 1.6, p = 0.042 ), whereas the median levels of IL-6 did not differ among epilepsy types. TLE without HS patients had a higher proportion of increased IL-6 levels than TLE with HS patients ( p = 0.021 ). Additionally, IL-6 levels were higher in patients with right-sided HS than in those with left lateralization (1.71 vs. 0.80 pg/mL, p = 0.04 ). In TLE with HS patients, IL-6 levels showed a negative correlation with seizure frequency during the last month ( r = − 0.342 ; p = 0.047 ), whereas in TLE without HS patients, the correlation was positive but did not reach significance ( r = 0.136 ; p = 0.169 ). Conclusion. IL-6 levels and the IL-6/IL-10 ratio are differentially regulated among patients with TLE depending on the presence of HS and its lateralization, suggesting that TLE with HS is a distinct category regarding cytokine activation.

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

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

Spike patterns surrounding sleep and seizures localize the seizure-onset zone in focal epilepsy.

Interictal spikes help localize seizure generators as part of surgical planning for drug-resistant epilepsy. However, there are often multiple spike populations whose frequencies change over time, influenced by brain state. Understanding state changes in spike rates will improve our ability to use spikes for surgical planning. Our goal was to determine the effect of sleep and seizures on interictal spikes, and to use sleep and seizure-related changes in spikes to localize the seizure-onset zone (SOZ). We performed a retrospective analysis of intracranial electroencephalography (EEG) data from patients with focal epilepsy. We automatically detected interictal spikes and we classified different time periods as awake or asleep based on the ratio of alpha to delta power, with a secondary analysis using the recently published SleepSEEG algorithm. We analyzed spike rates surrounding sleep and seizures. We developed a model to localize the SOZ using state-dependent spike rates. We analyzed data from 101 patients (54 women, age range 16-69). The normalized alpha-delta power ratio accurately classified wake from sleep periods (area under the curve=.90). Spikes were more frequent in sleep than wakefulness and in the post-ictal compared to the pre-ictal state. Patients with temporal lobe epilepsy had a greater wake-to-sleep and pre- to post-ictal spike rate increase compared to patients with extra-temporal epilepsy. A machine-learning classifier incorporating state-dependent spike rates accurately identified the SOZ (area under the curve=.83). Spike rates tended to be higher and better localize the seizure-onset zone in non-rapid eye movement (NREM) sleep than in wake or REM sleep. The change in spike rates surrounding sleep and seizures differs between temporal and extra-temporal lobe epilepsy. Spikes are more frequent and better localize the SOZ in sleep, particularly in NREM sleep. Quantitative analysis of spikes may provide useful ancillary data to localize the SOZ and improve surgical planning.

Interictal localization of the epileptogenic zone: Utilizing the observed resonance behavior in the spectral band of surrounding inhibition.

The gold standard for identification of the epileptogenic zone (EZ) continues to be the visual inspection of electrographic changes around seizures' onset by experienced electroencephalography (EEG) readers. Development of an epileptogenic focus localization tool that can delineate the EZ from analysis of interictal (seizure-free) periods is still an open question of great significance for improved diagnosis (e.g., presurgical evaluation) and treatment of epilepsy (e.g., surgical outcome). We developed an EZ interictal localization algorithm (EZILA) based on novel analysis of intracranial EEG (iEEG) using a univariate periodogram-type power measure, a straight-forward ranking approach, a robust dimensional reduction method and a clustering technique. Ten patients with temporal and extra temporal lobe epilepsies, and matching the inclusion criteria of having iEEG recordings at the epilepsy monitoring unit (EMU) and being Engel Class I ≥12 months post-surgery, were recruited in this study. In a nested k-fold cross validation statistical framework, EZILA assigned the highest score to iEEG channels within the EZ in all patients (10/10) during the first hour of the iEEG recordings and up to their first typical clinical seizure in the EMU (i.e., early interictal period). To further validate EZILA's performance, data from two new (Engel Class I) patients were analyzed in a double-blinded fashion; the EZILA successfully localized iEEG channels within the EZ from interictal iEEG in both patients. Out of the sampled brain regions, iEEG channels in the EZ were most frequently and maximally active in seizure-free (interictal) periods across patients in specific narrow gamma frequency band (∼60-80 Hz), which we have termed focal frequency band (FFB). These findings are consistent with the hypothesis that the EZ may interictally be regulated (controlled) by surrounding inhibitory neurons with resonance characteristics within this narrow gamma band.

Yield and risk associated with prolonged presurgical video-EEG monitoring: a systematic review

Presurgical long-term video-EEG monitoring (LT-VEEG) is an important part of the presurgical evaluation in patients with focal epilepsy. Multiple seizures need to be recorded, often in limited time and with the need to taper anti-seizure medication (ASM). The aim of this study was to systematically study the yield – in terms of success – and risks associated with presurgical LT-VEEG, and to identify all previously reported contributing variables. A systematic review of the databases of PubMed Medline, Embase, Cochrane Central, and the Cochrane Database of Systematic Reviews were searched following the Preferred Reporting Items for Systematic Reviews (PRISMA) guideline. Publications about presurgical LT-VEEG reporting on variables contributing to yield and risk were included. Study characteristics of all included studies were extracted following a standardized template. Within these articles, studies presenting multivariable analyses of factors contributing to the risk of adverse events or the success of LT-VEEG were identified. We found 36 articles reporting on LT-VEEG, including 4,703 presurgical patients, both children and adults. Presurgical LT-VEEG monitoring led to an average yield of 85%. Adverse events occurred with an averaged total event rate of 17%, but the type of included events was variable among studies. Factors reported to independently contribute to successful LT-VEEG were: baseline seizure frequency, a shorter interval from the most recent seizure, extratemporal lobe epilepsy, and no requirement for ASM reduction. Factors independently contributing to the occurrence of adverse events were: ASM tapering, a history of status epilepticus, a history of focal to bilateral tonic-clonic seizures, psychiatric comorbidity, and ASM taper rate. This study reveals that the data on factors contributing to yield and risk of adverse events is significant and variable, and often reported with inadequate statistics. Future research is warranted to develop guidelines for ASM withdrawal during presurgical video-EEG monitoring, taking predefined factors for success and risks of adverse events into account.

The anterior nucleus of the thalamus plays a role in the epileptic network.

We investigated both the metabolic differences and interictal/ictal discharges of the anterior nucleus of the thalamus (ANT) in patients with epilepsy to clarify the relationship between the ANT and the epileptic network. Nineteen patients with drug-resistant epilepsy who underwent stereoelectroencephalography were studied. Metabolic differences in ANT were analyzed using [18F] fluorodeoxyglucose-positron emission tomography with three-dimensional (3D) visual and quantitative analyses. Interictal and ictal discharges in the ANT were analyzed using visual and time-frequency analyses. The relationship between interictal discharge and metabolic differences was analyzed. We found that patients with temporal lobe epilepsy (TLE) showed significant metabolic differences in bilateral ANT compared with extratemporal lobe epilepsy in 3D visual and quantitative analyses. Four types of interictal activities were recorded from the ANT: spike, high-frequency oscillation (HFO), slow-wave, and α-rhythmic activity. Spike and HFO waveforms were recorded mainly in patients with TLE. Two spike patterns were recorded: synchronous and independent. In 83.3% of patients, ANT was involved during seizures. Three seizure onset types of ANT were recorded: low-voltage fast activity, rhythmic spikes, and theta band discharge. The time interval of seizure onset between the seizure onset zone and ANT showed two patterns: immediate and delayed. ANT can receive either interictal discharges or ictal discharges which propagate from the epileptogenic zones. Independent epileptic discharges can also be recorded from the ANT in some patients. Metabolic anomalies and epileptic discharges in the ANT indicate that the ANT plays a role in the epileptic network in most patients with epilepsy, especially TLE.

Intraoperative electrocorticography using high-frequency oscillations or spikes to tailor epilepsy surgery in the Netherlands (the HFO trial): a randomised, single-blind, adaptive non-inferiority trial

Intraoperative electrocorticography is used to tailor epilepsy surgery by analysing interictal spikes or spike patterns that can delineate epileptogenic tissue. High-frequency oscillations (HFOs) on intraoperative electrocorticography have been proposed as a new biomarker of epileptogenic tissue, with higher specificity than spikes. We prospectively tested the non-inferiority of HFO-guided tailoring of epilepsy surgery to spike-guided tailoring on seizure freedom at 1 year. The HFO trial was a randomised, single-blind, adaptive non-inferiority trial at an epilepsy surgery centre (UMC Utrecht) in the Netherlands. We recruited children and adults (no age limits) who had been referred for intraoperative electrocorticography-tailored epilepsy surgery. Participants were randomly allocated (1:1) to either HFO-guided or spike-guided tailoring, using an online randomisation scheme with permuted blocks generated by an independent data manager, stratified by epilepsy type. Treatment allocation was masked to participants and clinicians who documented seizure outcome, but not to the study team or neurosurgeon. Ictiform spike patterns were always considered in surgical decision making. The primary endpoint was seizure outcome after 1 year (dichotomised as seizure freedom [defined as Engel 1A-B] vs seizure recurrence [Engel 1C-4]). We predefined a non-inferiority margin of 10% risk difference. Analysis was by intention to treat, with prespecified subgroup analyses by epilepsy type and for confounders. This completed trial is registered with the Dutch Trial Register, Toetsingonline ABR.NL44527.041.13, and ClinicalTrials.gov, NCT02207673. Between Oct 10, 2014, and Jan 31, 2020, 78 individuals were enrolled to the study and randomly assigned (39 to HFO-guided tailoring and 39 to spike-guided tailoring). There was no loss to follow-up. Seizure freedom at 1 year occurred in 26 (67%) of 39 participants in the HFO-guided group and 35 (90%) of 39 in the spike-guided group (risk difference -23·5%, 90% CI -39·1 to -7·9; for the 48 patients with temporal lobe epilepsy, the risk difference was -25·5%, -45·1 to -6·0, and for the 30 patients with extratemporal lobe epilepsy it was -20·3%, -46·0 to 5·4). Pathology associated with poor prognosis was identified as a confounding factor, with an adjusted risk difference of -7·9% (90% CI -20·7 to 4·9; adjusted risk difference -12·5%, -31·0 to 5·9, for temporal lobe epilepsy and 5·8%, -7·7 to 19·5, for extratemporal lobe epilepsy). We recorded eight serious adverse events (five in the HFO-guided group and three in the spike-guided group) requiring hospitalisation. No patients died. HFO-guided tailoring of epilepsy surgery was not non-inferior to spike-guided tailoring on intraoperative electrocorticography. After adjustment for confounders, HFOs show non-inferiority in extratemporal lobe epilepsy. This trial challenges the clinical value of HFOs as an epilepsy biomarker, especially in temporal lobe epilepsy. Further research is needed to establish whether HFO-guided intraoperative electrocorticography holds promise in extratemporal lobe epilepsy. UMCU Alexandre Suerman, EpilepsieNL, RMI Talent Fellowship, European Research Council, and MING Fund.

Focal epilepsy impacts rapid eye movement sleep microstructure.

Whereas there is plenty of evidence on the influence of epileptic activity on non-rapid eye movement (NREM) sleep macro- and micro-structure, data on the impact of epilepsy on rapid eye movement (REM) sleep remains sparse. Using high-density electroencephalography (HD-EEG), we assessed global and focal disturbances of sawtooth waves (STW) as cortically generated sleep oscillations of REM sleep in patients with focal epilepsy. Twenty-two patients with drug-resistant focal epilepsy (13 females; mean age, 32.6 ± 10.7 years; 12 temporal lobe epilepsy) and 12 healthy controls (3 females; 24.0 ± 3.2 years) underwent combined overnight HD-EEG and polysomnography. STW rate, duration, frequency, power, spatial extent, IED rates and sleep homeostatic properties were analyzed. STW rate and duration were reduced in patients with focal epilepsy compared to healthy controls (rate: 0.64/min ± 0.46 vs. 1.12/min ± 0.41, p = .005, d = -0.98; duration: 3.60 s ± 0.76 vs. 4.57 ± 1.00, p = .003, d = -1.01). Not surprisingly given the fronto-central maximum of STW, the reductions were driven by extratemporal lobe epilepsy patients (rate: 0.45/min ± 0.31 vs. 1.12/min ± 0.41, p = .0004, d = -1.35; duration: 3.49 s ± 0.92 vs. 4.57 ± 1.00, p = .017, d = -0.99) and were more pronounced in the first vs. the last sleep cycle (rate first cycle patients vs. controls: 0.60/min ± 0.49 vs. 1.10/min ± 0.55, p = .016, d = -0.90, rate last cycle patients vs. controls: 0.67/min ± 0.51 vs. 0.99/min ± 0.49, p = .11, d = -0.62; duration first cycle patients vs. controls: 3.60s ± 0.76 vs. 4.57 ± 1.00, p = .003, d = -1.01, duration last cycle patients vs. controls: 3.66s ± 0.84 vs. 4.51 ± 1.26, p = .039, d = -0.80). There was no regional decrease of STWs in the region with the epileptic focus vs. the contralateral side (all p > .05). Patients with focal epilepsy and in particular extratemporal lobe epilepsy show a global reduction of STW activity in REM sleep. This may suggest that epilepsy impacts cortically generated sleep oscillations even in REM sleep when epileptic activity is low.

Changes in heart rate during the peri-ictal period in focal epilepsy

We explored changes in heart rate during the peri-ictal period in patients with focal epilepsy, and differences in heart rate changes according to epileptic site and side were assessed. A total of 198 epileptic seizures in 102 patients with focal epilepsy, who had a definite epileptogenic focus and had undergone surgical treatment, were assessed from 2014 to 2019. Heart rate was measured manually during the peri-ictal period. Change in heart rate and the time it occurred were assessed and compared between different epileptic sites and sides. Heart rate increased in 177 (89.4%) of 198 seizures. In 82 (44.8%) of 183 seizures, the change in heart rate occurred before seizure onset. The median period of heart rate change was seven seconds (interquartile range: 3–11 seconds) in seizures with heart rate change before seizure onset. The number of seizures with heart rate increase before seizure onset was significantly greater for medial temporal lobe epilepsy compared to lateral temporal lobe epilepsy (p=0.019) and extratemporal lobe epilepsy (p=0.002). A change in heart rate prior to seizure onset is more likely to occur in patients with medial temporal lobe epilepsy, compared to those with lateral temporal lobe epilepsy and extratemporal lobe epilepsy. Patients with medial temporal lobe epilepsy may likely benefit from seizure warning and detection devices.

Amygdala subnuclear volumes in temporal lobe epilepsy with hippocampal sclerosis and in non-lesional patients.

Together with hippocampus, the amygdala is important in the epileptogenic network of patients with temporal lobe epilepsy. Recently, an increase in amygdala volumes (i.e. amygdala enlargement) has been proposed as morphological biomarker of a subtype of temporal lobe epilepsy patients without MRI abnormalities, although other data suggest that this finding might be unspecific and not exclusive to temporal lobe epilepsy. In these studies, the amygdala is treated as a single entity, while instead it is composed of different nuclei, each with peculiar function and connection. By adopting a recently developed methodology of amygdala’s subnuclei parcellation based of high-resolution T1-weighted image, this study aims to map specific amygdalar subnuclei participation in temporal lobe epilepsy due to hippocampal sclerosis (n = 24) and non-lesional temporal lobe epilepsy (n = 24) with respect to patients with focal extratemporal lobe epilepsies (n = 20) and healthy controls (n = 30). The volumes of amygdala subnuclei were compared between groups adopting multivariate analyses of covariance and correlated with clinical variables. Additionally, a logistic regression analysis on the nuclei resulting statistically different across groups was performed. Compared with other populations, temporal lobe epilepsy with hippocampal sclerosis showed a significant atrophy of the whole amygdala (pBonferroni = 0.040), particularly the basolateral complex (pBonferroni = 0.033), while the non-lesional temporal lobe epilepsy group demonstrated an isolated hypertrophy of the medial nucleus (pBonferroni = 0.012). In both scenarios, the involved amygdala was ipsilateral to the epileptic focus. The medial nucleus demonstrated a volume increase even in extratemporal lobe epilepsies although contralateral to the seizure onset hemisphere (pBonferroni = 0.037). Non-lesional patients with psychiatric comorbidities showed a larger ipsilateral lateral nucleus compared with those without psychiatric disorders. This exploratory study corroborates the involvement of the amygdala in temporal lobe epilepsy, particularly in mesial temporal lobe epilepsy and suggests a different amygdala subnuclei engagement depending on the aetiology and lateralization of epilepsy. Furthermore, the logistic regression analysis indicated that the basolateral complex and the medial nucleus of amygdala can be helpful to differentiate temporal lobe epilepsy with hippocampal sclerosis and with MRI negative, respectively, versus controls with a consequent potential clinical yield. Finally, the present results contribute to the literature about the amygdala enlargement in temporal lobe epilepsy, suggesting that the increased volume of amygdala can be regarded as epilepsy-related structural changes common across different syndromes whose meaning should be clarified.

Atrophy of the hippocampal CA1 subfield relates to long-term forgetting in focal epilepsy.

The mechanisms underlying accelerated long-term forgetting (ALF) in patients with epilepsy are still under investigation. We examined the contribution of hippocampal subfields and their morphology to long-term memory performance in patients with focal epilepsy. We prospectively assessed long-term memory and performed magnetic resonance imaging in 80 patients with focal epilepsy (61 with temporal lobe epilepsy and 19 with extratemporal lobe epilepsy) and 30 healthy controls. The patients also underwent electroencephalography recording. Verbal and visuospatial memory was tested 30 s, 10min, and 1week after learning. We assessed the volumes of the whole hippocampus and seven subfields and deformation of the hippocampal shape. The contributions of the hippocampal volumes and shape deformation to long-term forgetting, controlling for confounding factors, including the presence of interictal epileptiform discharges, were assessed by multiple regression analyses. Patients with focal epilepsy had lower intelligence quotients and route recall scores at 10min than controls. The focal epilepsy group had smaller volumes of both the right and left hippocampal tails than the control group, but there were no statistically significant group differences for the volumes of the whole hippocampus or other hippocampal subfields. Multiple regression analyses showed a significant association between the left CA1 volume and the 1-week story retention (β=7.76; Bonferroni-corrected p=0.044), but this was not found for the whole hippocampus or other subfield volumes. Hippocampal shape analyses revealed that atrophy of the superior-lateral, superior-central, and inferior-medial regions of the left hippocampus, corresponding to CA1 and CA2/3, was associated with the verbal retention rate. Our results suggest that atrophy of the hippocampal CA1 region and its associated structures disrupts long-term memory consolidation in focal epilepsy. Neuronal cell loss in specific hippocampal subfields could be a key underlying cause of ALF in patients with epilepsy.

Prevalence of Depression and Generalized Anxiety Disorder in the Epileptic Adults: A Case-Control Study

Aims: The present study aims the determination the frequency of generalized anxiety disorder (GAD) and depression in epileptic individuals and its association with the duration of the disease and frequency of episodes of seizures. Study type: A case-control study Place and Duration: This study was conducted at Ghulam Mohammad Mahar Medical College Sukkur SMBBMU Larkana from February 2021 to February 2022 Methodology: A total of 110 individuals were considered in the study. All of them were young males with a mean age of 23.2±2.5 years. A total of 55 participants were diagnosed with cases of epilepsy and 55 participants were healthy. The healthy individuals were allocated to the control group. Out of the epileptic 55 participants, 15 had temporal lobe epilepsy (TLE) and 40 had extra-temporal lobe epilepsy (ETLE). All the participants had to complete Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI). Results: The frequency of GAD in the epileptic group was 14 (25.45%) and the frequency of depression was 19 (34.55%) which was higher, compared to the control group. The frequency of depression and GAD was more in the TLE group (p&lt;0.276) compared to the ETLE group despite no statistical significance. There was no remarkable correlation between the duration of the disease with depression inventory score and anxiety inventory score. However, a correlation between the frequency of seizures with the BDI and BAI was found in the TLE group. Conclusion: The frequency of depression and GAD seems to be higher in epileptic individuals. An interdisciplinary and multidisciplinary approach is helpful in the treatment of such patients. Keywords: Epilepsy, Generalized Anxiety Disorder, Frequency, Depression, males

Statistical asymmetry analysis of volumetric MRI and FDG PET in temporal lobe epilepsy

PurposeTo analyze statistically derived threshold values of volumetric MRI and 18F fluorodeoxyglucose (FDG) PET asymmetry, independent of normative data, for non-invasive detection/exclusion of temporal lobe epilepsy (TLE). MethodsWe retrospectively analyzed amygdalohippocampal volumetry and temporal FDG PET metabolism in 33 patients (age: 29.27 ± 8.56 years) who underwent surgery following Stereo-EEG implantation and had postsurgical seizure freedom lasting >12 months. The temporal lobe epilepsy group and the extratemporal lobe epilepsy (ETLE) group were compared. Percentage volume loss (PVL) was calculated from manually traced amygdalohippocampal volumetry whereas percentage metabolic loss (PML) was calculated from PET using amygdalohippocampal trace and temporal neocortical Brodmann areas (BA) template. ResultsReceiver operating characteristic (ROC) curve analysis identified a cutoff hippocampal PVL of 4.21% as the minimum indicating probable hippocampal involvement in seizure onset, with sensitivity of 88.89% and the specificity of 100% (p < 0.001). Region of interest (ROI)-based PML values in PET imaging showed a significant correlation with the presence of TLE in the TLE group of patients and its absence in the ETLE group of patients. Region of interest curve analysis yielded PML cutoffs of 5.77% and 8.36%, respectively, for the hippocampus and BA 38 (temporopolar neocortex) to detect TLE with the sensitivity of 72.7% and specificity of 77.8%. ConclusionWe describe statistical thresholds for asymmetry analysis of hippocampal volumetry and FDG PET to improve detection of TLE. These threshold parameters warrant further validation in prospective studies.

Withdrawal of Antiepileptic Drugs After MRI–Guided Laser Interstitial Thermal Therapy in Extra-Temporal Lobe Epilepsy (P8-8.005)

Withdrawal of Antiepileptic Drugs After MRI–Guided Laser Interstitial Thermal Therapy in Extra-Temporal Lobe Epilepsy (P8-8.005)

Epilepsy Surgery in Extratemporal vs Temporal Lobe Epilepsy: Changes in Surgical Volumes and Seizure Outcome Between 1990 and 2017.

Seizure outcome after extratemporal lobe epilepsy (exTLE) surgery has often been poorer than after temporal lobe epilepsy (TLE) surgery, but recent improvements in diagnostics and surgery may have changed this. Our aim was to analyze the changes in presurgical and surgical volumes and seizure outcome 2 years after surgery for patients with exTLE compared with those with TLE. We performed a retrospective, single-center cohort study including patients from the Bethel presurgical-surgical-postsurgical database from 1990 to 2017. We used logistic regression to analyze factors influencing the odds for surgery and the odds for seizure freedom after surgery. We included 3,822 patients with presurgical evaluation, 2,404 of whom had subsequently undergone surgery. The proportion of patients with exTLE in presurgical evaluation increased from 41% between 1990 and 1993 to 64% in 2014-2017. The odds for surgery decreased over time (2003-2011: odds ratio [OR] 0.50 [95% CI 0.36-0.70]; 2012-2017: OR 0.24 [CI 0.17-0.35]; reference: 1990-2002) and patients with exTLE had lower odds for surgery than patients with TLE, but this difference diminished over time (exTLE vs TLE 1990-2002: OR 0.14 [CI 0.09-0.20]; 2003-2011: OR 0.32 [CI 0.24-0.44]; 2012-2017: OR 0.46 [CI 0.34-0.63]). Etiology, the side of the epileptogenic lesion, and invasive recordings influenced the odds for surgery. The most frequent reasons for not undergoing surgery were missing identification of a circumscribed epileptogenic zone or an unacceptable risk of postsurgical deficits in patients with exTLE and the patient's decision in patients with TLE. Compared with patients with TLE, the odds for seizure freedom after surgery started lower for patients with exTLE in earlier years, but increased (≤2 lobes 1990-2002: OR 0.47 [CI 0.33-0.68]; 2003-2011: OR 0.62 [CI 0.44-0.87]; 2012-2017: OR 0.78 [CI 0.53-1.15]; ≥3 lobes 1990-2002: OR 0.37 [CI 0.22-0.62]; 2003-2011: OR 0.73 [CI 0.43-1.23]; 2012-2017: OR 1.46 [CI 0.91-2.42]). Etiology, age at surgery, and invasive recordings were further predictors for the odds for seizure freedom. Over the past 28 years, the success of resective surgery for patients with exTLE has improved. At the same time, the number of patients with exTLE being evaluated for surgery increased, as well as their odds for undergoing surgery.

Seizure latency and epilepsy localization as predictors of recurrence following epilepsy surgery

The primary purpose is to determine whether the time between epilepsy surgery and first seizure recurrence can estimate the timing of the next seizure event for temporal and extratemporal epilepsy. A secondary endpoint aimed to compare temporal and extratemporal epilepsy surgery and examine which subgroup has a higher hazard of subsequent seizure recurrence. Data used were from a retrospective database at Thomas Jefferson University Hospital. Records were stratified into temporal (n=943) and extratemporal (n=125) surgeries. Analyses were done using SAS and utilized Cox proportional hazards models while controlling for demographics and clinical factors. The primary predictor of time between surgery and first recurrence was treated as a nominal variable binned into six segments, whereas secondary endpoints used a categorical predictor of epilepsy location while controlling for seizure latency. Generally, as seizure latency following surgery increased, the time between first seizure and second seizure increased. These results were statistically meaningful in the temporal set (Wald chi-squared = 40.4715, df=5, p<.0001). Outcomes could also be interpreted based on predictor group; for instance, if Seizure 1 occurred 1-2 months following surgery in the temporal set, the median number of days until the next seizure was 35.5days (95% confidence interval [CI] = 21-89days). Secondary analysis showed that temporal lobe epilepsy had a lower hazard of a second seizure than extratemporal lobe epilepsy (89.2% reduction in hazard; 95% CI = .015-.795). This analysis provides a framework to use initial seizure latency to predict the median number of days until the next seizure event, while stratifying based on epilepsy location and controlling for multiple variables. It also suggests that the hazard of seizure recurrence in temporal lobe epilepsy is lower than in extratemporal lobe epilepsy.

Estimation of seizure onset zone from ictal scalp EEG using independent component analysis in extratemporal lobe epilepsy

Objective. The purpose of this study is to localize the seizure onset zone of patients suffering from drug-resistant epilepsy. During the last two decades, multiple studies proposed the use of independent component analysis (ICA) to analyze ictal electroencephalogram (EEG) recordings. This study aims at evaluating ICA potential with quantitative measurements. In particular, we address the challenging step where the components extracted by ICA of an ictal nature must be selected. Approach. We considered a cohort of 10 patients suffering from extratemporal lobe epilepsy who were rendered seizure-free after surgery. Different sets of pre-processing parameters were compared and component features were explored to help distinguish ictal components from others. Quantitative measurements were implemented to determine whether some of the components returned by ICA were located within the resection zone and thus likely to be ictal. Finally, an assistance to the component selection was proposed based on the implemented features. Main results. For every seizure, at least one component returned by ICA was localized within the resection zone, with the optimal pre-processing parameters. Three features were found to distinguish components localized within the resection zone: the dispersion of their active brain sources, the ictal rhythm power and the contribution to the EEG variance. Using the implemented component selection assistance based on the features, the probability that the first proposed component yields an accurate estimation reaches 51.43% (without assistance: 24.74%). The accuracy reaches 80% when considering the best result within the first five components. Significance. This study confirms the utility of ICA for ictal EEG analysis in extratemporal lobe epilepsy, and suggests relevant features to analyze the components returned by ICA. A component selection assistance is proposed to guide clinicians in their choice for ictal components.

Simultaneously Acquired MRI Arterial Spin-Labeling and Interictal FDG-PET Improves Diagnosis of Pediatric Temporal Lobe Epilepsy.

Interictal FDG-PET scans are a routine diagnostic technique for the identification of epileptogenic foci in the presurgical work-up of medically refractory pediatric epilepsy. With the advent of PET/MR imaging, it has become possible to simultaneously acquire FDG-PET and arterial spin-labeling perfusion data. The objective of this study was to evaluate whether the incorporation of arterial spin-labeling data with interictal FDG-PET could improve the diagnostic performance metrics of FDG-PET for identification of epileptogenic foci. Forty-five pediatric patients with a mean age of 10.8 years were retrospectively included in this study. These patients all underwent PET/MR imaging to diagnose suspected focal epilepsy. When compared to interpretations of interictal FDG findings alone, FDG combined with arterial spin-labeling findings resulted in significantly decreased sensitivity (0.64 versus 0.52, P = .02), significantly increased specificity (0.50 versus 0.75, P = .04), and an increased positive predictive value (0.59 versus 0.75). The decreased sensitivity was found to be primarily driven by patients with extratemporal lobe epilepsy, as a subgroup analysis showed decreased sensitivity for patients with extratemporal epilepsy (0.52 versus 0.38, P = .04), but not for temporal epilepsy (0.83 versus 0.75, P = .16). Additionally, substantial agreement between focal FDG hypometabolism and arterial spin-labeling hypoperfusion was demonstrated with the Cohen κ (0.70, P < .01). These findings suggest that simultaneously acquired interictal FDG-PET and arterial spin-labeling data can improve the diagnosis of epileptogenic foci, especially in the setting of temporal lobe epilepsy where they improve specificity and positive predictive value, with preservation of sensitivity.

Neuropsychological features of mind wandering in left-, right- and extra temporal lobe epilepsy

PurposeMind wandering, i.e. mental time-travelling and imagery unrelated to the current situation has recently been related to mesial temporal lobe (memory) function. In this regard we evaluated as to whether parameters of mind wandering are related to material specific memory in patients with a left-, right-, or extra- temporal lobe epilepsy. MethodsIn this prospective controlled study we analyzed mind wandering, material specific memory, and executive functions in 29 right-handed patients with right-, left-, or extra-temporal lobe epilepsies. Mind wandering was assessed with a sustained attention to response task containing embedded inquiries on mind wandering. In addition, verbal list learning and memory (VLMT), design list learning (DCS-R), and executive function (EpiTrack) were assessed. ResultsIn patients with right temporal lobe epilepsy, the propensity to mind wander was positively related to verbal memory performance, while in left temporal lobe epilepsy, the propensity and future related mind wandering were positively correlated to the performance in visual/figural memory. Generally, the propensity of MW was related to executive function as well. ConclusionThe results suggest that mind wandering in lateralized temporal lobe epilepsy appears to be non-specifically driven by executive function and specifically by the mode and functionality of the memory system of the non-epileptic hemisphere. Repeated assessments would be required to discern as to how much such patterns depend on lesions versus epileptic dysfunction and whether they change with successful medical or surgical treatment.

Hippocampal spindles and barques are normal intracranial electroencephalographic entities

ObjectiveTo assess whether hippocampal spindles and barques are markers of epileptogenicity. MethodsFocal epilepsy patients that underwent stereo-electroencephalography implantation with at least one electrode in their hippocampus were selected (n = 75). The occurrence of spindles and barques in the hippocampus was evaluated in each patient. We created pairs of pathologic and pathology-free groups according to two sets of criteria: 1. Non-invasive diagnostic criteria (patients grouped according to focal epilepsy classification). 2. Intracranial neurophysiological criteria (patient’s hippocampi grouped according to their seizure onset involvement). ResultsHippocampal spindles and barques appear equally often in both pathologic and pathology-free groups, both for non-invasive (Pspindles = 0.73; Pbarques = 0.46) and intracranial criteria (Pspindles = 0.08; Pbarques = 0.26). In Engel Class I patients, spindles occurred with similar incidence both within the non-invasive (P = 0.67) and the intracranial criteria group (P = 0.20). Barques were significantly more frequent in extra-temporal lobe epilepsy defined by either non-invasive (P = 0.01) or intracranial (P = 0.01) criteria. ConclusionsBoth spindles and barques are normal entities of the hippocampal intracranial electroencephalogram. The presence of barques may also signify lack of epileptogenic properties in the hippocampus. SignificanceUnderstanding that hippocampal spindles and barques do not reflect epileptogenicity is critical for correct interpretation of epilepsy surgery evaluations and appropriate surgical treatment selection.