Long-term neuropsychological trajectories in children with epilepsy: does surgery halt decline?

Neuropsychological impairments are common in children with drug-resistant epilepsy. It has been proposed that epilepsy surgery might alleviate these impairments by providing seizure freedom; however, findings from prior studies have been inconsistent. We mapped long-term neuropsychological trajectories in children before and after undergoing epilepsy surgery, to measure the impact of disease course and surgery on functioning. We performed a retrospective cohort study of 882 children who had undergone epilepsy surgery at Great Ormond Street Hospital (1990-2018). We extracted patient information and neuropsychological functioning [obtained from IQ tests (domains: full-scale IQ, verbal IQ, performance IQ, working memory and processing speed) and tests of academic attainment (reading, spelling and numeracy)] and investigated changes in functioning using regression analyses. We identified 500 children (248 females) who had undergone epilepsy surgery [median age at surgery = 11.9 years, interquartile range = (7.8, 15.0)] and neuropsychological assessment. These children showed declines in all domains of neuropsychological functioning in the time leading up to surgery (all P-values ≤0.001; e.g. ßFSIQ = -1.9, SEFSIQ = 0.3, PFSIQ < 0.001). Children lost on average one to four points per year, depending on the domain considered; 27%-43% declined by ≥10 points from their first to their last preoperative assessment. At the time of presurgical evaluation, most children (46%-60%) scored one or more standard deviations below the mean (<85) on the different neuropsychological domains; 37% of these met the threshold for intellectual disability (full-scale IQ < 70). On a group level, there was no change in performance from pre- to postoperative assessment on any of the domains (all P-values ≥0.128). However, children who became seizure free through surgery showed higher postoperative neuropsychological performance (e.g. rrb-FSIQ = 0.37, P < 0.001). These children continued to demonstrate improvements in neuropsychological functioning over the course of their long-term follow-up (e.g. ßFSIQ = 0.9, SEFSIQ = 0.3, PFSIQ = 0.004). Children who had discontinued antiseizure medication treatment at 1-year follow-up showed an 8- to 13-point advantage in postoperative working memory, processing speed and numeracy, and greater improvements in verbal IQ, working memory, reading and spelling (all P-values ≤0.034) over the postoperative period compared with children who were seizure free and still receiving antiseizure medication. In conclusion, by providing seizure freedom and the opportunity for antiseizure medication cessation, epilepsy surgery might not only halt but reverse the downward trajectory that children with drug-resistant epilepsy display in neuropsychological functioning. To halt this decline as soon as possible or, potentially, to prevent it from occurring in the first place, children with focal epilepsy should be considered for epilepsy surgery as early as possible after diagnosis.

The clinical, imaging, pathological and genetic landscape of bottom-of-sulcus dysplasia.

Bottom-of-sulcus dysplasia (BOSD) is increasingly recognized as a cause of drug-resistant, surgically-remediable, focal epilepsy, often in seemingly MRI-negative patients. We describe the clinical manifestations, morphological features, localization patterns and genetics of BOSD, with the aims of improving management and understanding pathogenesis. We studied 85 patients with BOSD diagnosed between 2005-2022. Presenting seizure and EEG characteristics, clinical course, genetic findings and treatment response were obtained from medical records. MRI (3 T) and 18F-FDG-PET scans were reviewed systematically for BOSD morphology and metabolism. Histopathological analysis and tissue genetic testing were performed in 64 operated patients. BOSD locations were transposed to common imaging space to study anatomical location, functional network localization and relationship to normal MTOR gene expression. All patients presented with stereotyped focal seizures with rapidly escalating frequency, prompting hospitalization in 48%. Despite 42% patients having seizure remissions, usually with sodium channel blocking medications, most eventually became drug-resistant and underwent surgery (86% seizure-free). Prior developmental delay was uncommon but intellectual, language and executive dysfunction were present in 24%, 48% and 29% when assessed preoperatively, low intellect being associated with greater epilepsy duration. BOSDs were missed on initial MRI in 68%, being ultimately recognized following repeat MRI, 18F-FDG-PET or image postprocessing. MRI features were grey-white junction blurring (100%), cortical thickening (91%), transmantle band (62%), increased cortical T1 signal (46%) and increased subcortical FLAIR signal (26%). BOSD hypometabolism was present on 18F-FDG-PET in 99%. Additional areas of cortical malformation or grey matter heterotopia were present in eight patients. BOSDs predominated in frontal and pericentral cortex and related functional networks, mostly sparing temporal and occipital cortex, and limbic and visual networks. Genetic testing yielded pathogenic mTOR pathway variants in 63% patients, including somatic MTOR variants in 47% operated patients and germline DEPDC5 or NPRL3 variants in 73% patients with familial focal epilepsy. BOSDs tended to occur in regions where the healthy brain normally shows lower MTOR expression, suggesting these regions may be more vulnerable to upregulation of MTOR activity. Consistent with the existing literature, these results highlight (i) clinical features raising suspicion of BOSD; (ii) the role of somatic and germline mTOR pathway variants in patients with sporadic and familial focal epilepsy associated with BOSD; and (iii) the role of 18F-FDG-PET alongside high-field MRI in detecting subtle BOSD. The anatomical and functional distribution of BOSDs likely explain their seizure, EEG and cognitive manifestations and may relate to relative MTOR expression.

Spike ripples localize the epileptogenic zone best: an international intracranial study.

We evaluated whether spike ripples, the combination of epileptiform spikes and ripples, provide a reliable and improved biomarker for the epileptogenic zone compared with other leading interictal biomarkers in a multicentre, international study. We first validated an automated spike ripple detector on intracranial EEG recordings. We then applied this detector to subjects from four centres who subsequently underwent surgical resection with known 1-year outcomes. We evaluated the spike ripple rate in subjects cured after resection [International League Against Epilepsy Class 1 outcome (ILAE 1)] and those with persistent seizures (ILAE 2-6) across sites and recording types. We also evaluated available interictal biomarkers: spike, spike-gamma, wideband high frequency oscillation (HFO, 80-500 Hz), ripple (80-250 Hz) and fast ripple (250-500 Hz) rates using previously validated automated detectors. The proportion of resected events was computed and compared across subject outcomes and biomarkers. Overall, 109 subjects were included. Most spike ripples were removed in subjects with ILAE 1 outcome (P < 0.001), and this was qualitatively observed across all sites and for depth and subdural electrodes (P < 0.001 and P < 0.001, respectively). Among ILAE 1 subjects, the mean spike ripple rate was higher in the resected volume (0.66/min) than in the non-removed tissue (0.08/min, P < 0.001). A higher proportion of spike ripples were removed in subjects with ILAE 1 outcomes compared with ILAE 2-6 outcomes (P = 0.06). Among ILAE 1 subjects, the proportion of spike ripples removed was higher than the proportion of spikes (P < 0.001), spike-gamma (P < 0.001), wideband HFOs (P < 0.001), ripples (P = 0.009) and fast ripples (P = 0.009) removed. At the individual level, more subjects with ILAE 1 outcomes had the majority of spike ripples removed (79%, 38/48) than spikes (69%, P = 0.12), spike-gamma (69%, P = 0.12), wideband HFOs (63%, P = 0.03), ripples (45%, P = 0.01) or fast ripples (36%, P < 0.001) removed. Thus, in this large, multicentre cohort, when surgical resection was successful, the majority of spike ripples were removed. Furthermore, automatically detected spike ripples localize the epileptogenic tissue better than spikes, spike-gamma, wideband HFOs, ripples and fast ripples.

Basal temporal language area revisited in Japanese language with a language function density map.

We revisited the anatomo-functional characteristics of the basal temporal language area (BTLA), first described by Lüders et al. (1986), using electrical cortical stimulation (ECS) in the context of Japanese language and semantic networks. We recruited 11 patients with focal epilepsy who underwent chronic subdural electrode implantation and ECS mapping with multiple language tasks for presurgical evaluation. A semiquantitative language function density map delineated the anatomo-functional characteristics of the BTLA (66 electrodes, mean 3.8 cm from the temporal tip). The ECS-induced impairment probability was higher in the following tasks, listed in a descending order: spoken-word picture matching, picture naming, Kanji word reading, paragraph reading, spoken-verbal command, and Kana word reading. The anterior fusiform gyrus (FG), adjacent anterior inferior temporal gyrus (ITG), and the anterior end where FG and ITG fuse, were characterized by stimulation-induced impairment during visual and auditory tasks requiring verbal output or not, whereas the middle FG was characterized mainly by visual input. The parahippocampal gyrus was the least impaired of the three gyri in the basal temporal area. We propose that the BTLA has a functional gradient, with the anterior part involved in amodal semantic processing and the posterior part, especially the middle FG in unimodal semantic processing.

Dynamic functional connectivity in verbal cognitive control and word reading.

Cognitive control processes enable the suppression of automatic behaviors and the initiation of appropriate responses. The Stroop color naming task serves as a benchmark paradigm for understanding the neurobiological model of verbal cognitive control. Previous research indicates a predominant engagement of the prefrontal and premotor cortex during the Stroop task compared to reading. We aim to further this understanding by creating a dynamic atlas of task-preferential modulations of functional connectivity through white matter. Patients undertook word-reading and Stroop tasks during intracranial EEG recording. We quantified task-related high-gamma amplitude modulations at 547 nonepileptic electrode sites, and a mixed model analysis identified regions and timeframes where these amplitudes differed between tasks. We then visualized white matter pathways with task-preferential functional connectivity enhancements at given moments. Word reading, compared to the Stroop task, exhibited enhanced functional connectivity in inter- and intra-hemispheric white matter pathways from the left occipital-temporal region 350-600 ms before response, including the posterior callosal fibers as well as the left vertical occipital, inferior longitudinal, inferior fronto-occipital, and arcuate fasciculi. The Stroop task showed enhanced functional connectivity in the pathways from the left middle-frontal pre-central gyri, involving the left frontal u-fibers and anterior callosal fibers. Automatic word reading largely utilizes the left occipital-temporal cortices and associated white matter tracts. Verbal cognitive control predominantly involves the left middle frontal and precentral gyri and its connected pathways. Our dynamic tractography atlases may serve as a novel resource providing insights into the unique neural dynamics and pathways of automatic reading and verbal cognitive control.

Reduced long-term mortality after successful resective epilepsy surgery: a population-based study.

BACKGROUND: We investigated all-cause and epilepsy-related mortality in patients operated with resective epilepsy surgery and in non-operated patients with drug-resistant epilepsy. Our hypothesis was that patients who proceed to surgery have lower mortality over time compared with non-operated patients. METHOD: Data from 1329 adults and children from the Swedish National Epilepsy Surgery Register and 666 patients with drug-resistant epilepsy who had undergone presurgical work-up but not been operated were analysed. The operated patients had follow-ups between 2 and 20 years. We used the Swedish Cause of Death Register to identify deaths. Autopsy reports were collected for patients with suspected sudden unexpected death in epilepsy (SUDEP). Kaplan-Meier and Cox regression analyses were performed to identify predictors for mortality and SUDEP. RESULTS: SUDEP accounted for 30% of all deaths. Surgery was associated with lower all-cause mortality (HR 0.7, 95% CI 0.5 to 0.9), also when adjusted for age, sex and tonic-clonic seizures at inclusion. The benefit of surgery seemed to persist and possibly even increase after 15 years of follow-up. Risk factors of mortality for operated patients were persisting seizures and living alone. Of the operated patients, 37% had seizures, and these had a higher risk of mortality (HR 2.1, 95% CI 1.4 to 3.0) and SUDEP (HR 3.5, 95% CI 1.7 to 7.3) compared with patients with seizure freedom at last follow-up. CONCLUSIONS: In this large population-based epilepsy surgery cohort, operated patients had a lower all-cause mortality compared with non-operated patients with drug-resistant epilepsy. Seizure freedom was the most important beneficial factor for both all-cause mortality and SUDEP among operated patients.

Impact of white matter networks on risk for memory decline following resection versus ablation in temporal lobe epilepsy.

BACKGROUND: With expanding neurosurgical options in epilepsy, it is important to characterise each options' risk for postoperative cognitive decline. Here, we characterise how patients' preoperative white matter (WM) networks relates to postoperative memory changes following different epilepsy surgeries. METHODS: Eighty-nine patients with temporal lobe epilepsy with T1-weighted and diffusion-weighted imaging as well as preoperative and postoperative verbal memory scores (prose recall) underwent either anterior temporal lobectomy (ATL: n=38) or stereotactic laser amygdalohippocampotomy (SLAH; n=51). We computed laterality indices (ie, asymmetry) for volume of the hippocampus and fractional anisotropy (FA) of two deep WM tracts (uncinate fasciculus (UF) and inferior longitudinal fasciculus (ILF)). RESULTS: Preoperatively, left-lateralised FA of the ILF was associated with higher prose recall (p<0.01). This pattern was not observed for the UF or hippocampus (ps>0.05). Postoperatively, right-lateralised FA of the UF was associated with less decline following left ATL (p<0.05) but not left SLAH (p>0.05), while right-lateralised hippocampal asymmetry was associated with less decline following both left ATL and SLAH (ps<0.05). After accounting for preoperative memory score, age of onset and hippocampal asymmetry, the association between UF and memory decline in left ATL remained significant (p<0.01). CONCLUSIONS: Asymmetry of the hippocampus is an important predictor of risk for memory decline following both surgeries. However, asymmetry of UF integrity, which is only severed during ATL, is an important predictor of memory decline after ATL only. As surgical procedures and pre-surgical mapping evolve, understanding the role of frontal-temporal WM in memory networks could help to guide more targeted surgical approaches to mitigate cognitive decline.

Prediction tools and risk stratification in epilepsy surgery.

OBJECTIVE: This study was undertaken to conduct external validation of previously published epilepsy surgery prediction tools using a large independent multicenter dataset and to assess whether these tools can stratify patients for being operated on and for becoming free of disabling seizures (International League Against Epilepsy stage 1 and 2). METHODS: We analyzed a dataset of 1562 patients, not used for tool development. We applied two scales: Epilepsy Surgery Grading Scale (ESGS) and Seizure Freedom Score (SFS); and two versions of Epilepsy Surgery Nomogram (ESN): the original version and the modified version, which included electroencephalographic data. For the ESNs, we used calibration curves and concordance indexes. We stratified the patients into three tiers for assessing the chances of attaining freedom from disabling seizures after surgery: high (ESGS = 1, SFS = 3-4, ESNs > 70%), moderate (ESGS = 2, SFS = 2, ESNs = 40%-70%), and low (ESGS = 2, SFS = 0-1, ESNs < 40%). We compared the three tiers as stratified by these tools, concerning the proportion of patients who were operated on, and for the proportion of patients who became free of disabling seizures. RESULTS: The concordance indexes for the various versions of the nomograms were between .56 and .69. Both scales (ESGS, SFS) and nomograms accurately stratified the patients for becoming free of disabling seizures, with significant differences among the three tiers (p < .05). In addition, ESGS and the modified ESN accurately stratified the patients for having been offered surgery, with significant difference among the three tiers (p < .05). SIGNIFICANCE: ESGS and the modified ESN (at thresholds of 40% and 70%) stratify patients undergoing presurgical evaluation into three tiers, with high, moderate, and low chance for favorable outcome, with significant differences between the groups concerning having surgery and becoming free of disabling seizures. Stratifying patients for epilepsy surgery has the potential to help select the optimal candidates in underprivileged areas and better allocate resources in developed countries.

Depth versus surface: A critical review of subdural and depth electrodes in intracranial electroencephalographic studies.

Intracranial electroencephalographic (IEEG) recording, using subdural electrodes (SDEs) and stereoelectroencephalography (SEEG), plays a pivotal role in localizing the epileptogenic zone (EZ). SDEs, employed for superficial cortical seizure foci localization, provide information on two-dimensional seizure onset and propagation. In contrast, SEEG, with its three-dimensional sampling, allows exploration of deep brain structures, sulcal folds, and bihemispheric networks. SEEG offers the advantages of fewer complications, better tolerability, and coverage of sulci. Although both modalities allow electrical stimulation, SDE mapping can tessellate cortical gyri, providing the opportunity for a tailored resection. With SEEG, both superficial gyri and deep sulci can be stimulated, and there is a lower risk of afterdischarges and stimulation-induced seizures. Most systematic reviews and meta-analyses have addressed the comparative effectiveness of SDEs and SEEG in localizing the EZ and achieving seizure freedom, although discrepancies persist in the literature. The combination of SDEs and SEEG could potentially overcome the limitations inherent to each technique individually, better delineating seizure foci. This review describes the strengths and limitations of SDE and SEEG recordings, highlighting their unique indications in seizure localization, as evidenced by recent publications. Addressing controversies in the perceived usefulness of the two techniques offers insights that can aid in selecting the most suitable IEEG in clinical practice.

Bilateral centromedian nucleus of thalamus responsive neurostimulation for pediatric-onset drug-resistant epilepsy.

Neuromodulation therapies offer an efficacious treatment alternative for patients with drug-resistant epilepsy (DRE), particularly those unlikely to benefit from surgical resection. Here we present our retrospective single-center case series of patients with pediatric-onset DRE who underwent responsive neurostimulation (RNS) depth electrode implantation targeting the bilateral centromedian nucleus (CM) of the thalamus between October 2020 and October 2022. Sixteen patients were identified; seizure outcomes, programming parameters, and complications at follow-up were reviewed. The median age at implantation was 13 years (range 3.6-22). Six patients (38%) were younger than 12 years of age at the time of implantation. Ictal electroencephalography (EEG) patterns during patients' most disabling seizures were reliably detected. Ten patients (62%) achieved 50% or greater reduction in seizure frequency at a median 1.3 years (range 0.6-2.6) of follow-up. Eight patients (50%) experienced sensorimotor side effects, and three patients (19%) had superficial pocket infection, prompting the removal of the RNS device. Side effects of stimulation were experienced mostly in monopolar-cathodal configuration and alleviated with programming change to bipolar configuration or low-frequency stimulation. Closed-loop neurostimulation using RNS targeting bilateral CM is a feasible and useful therapy for patients with pediatric-onset DRE.

Incomplete resection of the intracranial electroencephalographic seizure onset zone is not associated with postsurgical outcomes.

Delineation of seizure onset regions using intracranial electroencephalography (icEEG) is vital in the surgical workup of drug-resistant epilepsy cases. However, it is unknown whether the complete resection of these regions is necessary for seizure freedom, or whether postsurgical seizure recurrence can be attributed to the incomplete removal of seizure onset regions. To address this gap, we retrospectively analyzed icEEG recordings from 63 subjects, identifying seizure onset regions visually and algorithmically. We assessed onset region resection and correlated this with postsurgical seizure control. The majority of subjects had more than half of their onset regions resected (82.46% and 80.65% of subjects using visual and algorithmic methods, respectively). There was no association between the proportion of the seizure onset zone (SOZ) that was subsequently resected and better surgical outcomes (area under the receiver operating characteristic curve [AUC] < .7). Investigating the spatial extent of onset regions, we found no substantial evidence of an association with postsurgical seizure control (all AUC < .7). Although seizure onset regions are typically resected completely or in large part, incomplete resection is not associated with worse postsurgical outcomes. We conclude that postsurgical seizure recurrence cannot be attributed to an incomplete resection of the icEEG SOZ alone. Other network mechanisms beyond icEEG seizure onset likely contribute.

Predictors of long-term memory and network connectivity 10 years after anterior temporal lobe resection.

OBJECTIVE: Anterior temporal lobe resection (ATLR) effectively controls seizures in medically refractory temporal lobe epilepsy but risks significant episodic memory decline. Beyond 1 year postoperatively, the influence of preoperative clinical factors on episodic memory and long-term network plasticity remain underexplored. Ten years post-ATLR, we aimed to determine biomarkers of successful memory network reorganization and establish presurgical features' lasting impact on memory function. METHODS: Twenty-five ATLR patients (12 left-sided) and 10 healthy controls underwent a memory-encoding functional magnetic resonance imaging paradigm alongside neuropsychometry 10 years postsurgery. Generalized psychophysiological interaction analyses modeled network functional connectivity of words/faces remembered, seeding from the medial temporal lobes (MTLs). Differences in successful memory connectivity were assessed between controls and left/right ATLR. Multivariate regressions and mixed-effect models probed preoperative phenotypes' effects on long-term memory outcomes. RESULTS: Ten years post-ATLR, lower baseline functioning (verbal and performance intelligence quotient) and a focal memory impairment preoperatively predicted worse long-term memory outcomes. Poorer verbal memory was significantly associated with longer epilepsy duration and earlier onset age. Relative to controls, successful word and face encoding involved increased functional connectivity from both or remnant MTL seeds and contralesional parahippocampus/hippocampus after left/right ATLR. Irrespective of surgical laterality, successful memory encoding correlated with increased MTL-seeded connectivity to frontal (bilateral insula, right anterior cingulate), right parahippocampal, and bilateral fusiform gyri. Ten years postsurgery, better memory performance was correlated with contralateral frontal plasticity, which was disrupted with longer epilepsy duration. SIGNIFICANCE: Our findings underscore the enduring nature of functional network reorganizations to provide long-term cognitive support. Ten years post-ATLR, successful memory formation featured stronger connections near resected areas and contralateral regions. Preoperative network disruption possibly influenced effectiveness of postoperative plasticity. These findings are crucial for enhancing long-term memory prediction and strategies for lasting memory rehabilitation.

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

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

Low prevalence of neural autoantibodies in perioperative cerebrospinal fluid samples of epilepsy surgery patients: A multicenter prospective study.

OBJECTIVE: Refractory epilepsy may have an underlying autoimmune etiology. Our aim was to assess the prevalence of neural autoantibodies in a multicenter national prospective cohort of patients with drug-resistant epilepsy undergoing epilepsy surgery utilizing comprehensive clinical, serologic, and histopathological analyses. METHODS: We prospectively recruited patients undergoing epilepsy surgery for refractory focal epilepsy not caused by a brain tumor from epilepsy surgery centers in the Czech Republic. Perioperatively, we collected cerebrospinal fluid (CSF) and/or serum samples and performed comprehensive commercial and in-house assays for neural autoantibodies. Clinical data were obtained from the patients' medical records, and histopathological analysis of resected brain tissue was performed. RESULTS: Seventy-six patients were included, mostly magnetic resonance imaging (MRI)-lesional cases (74%). Mean time from diagnosis to surgery was 21 ± 13 years. Only one patient (1.3%) had antibodies in the CSF and serum (antibodies against glutamic acid decarboxylase 65) in relevant titers; histology revealed focal cortical dysplasia (FCD) III (FCD associated with hippocampal sclerosis [HS]). Five patients' samples displayed CSF-restricted oligoclonal bands (OCBs; 6.6%): three cases with FCD (one with FCD II and two with FCD I), one with HS, and one with negative histology. Importantly, eight patients (one of them with CSF-restricted OCBs) had findings on antibody testing in individual serum and/or CSF tests that could not be confirmed by complementary tests and were thus classified as nonspecific, yet could have been considered specific without confirmatory testing. Of these, two had FCD, two gliosis, and four HS. No inflammatory changes or lymphocyte cuffing was observed histopathologically in any of the 76 patients. SIGNIFICANCE: Neural autoantibodies are a rare finding in perioperatively collected serum and CSF of our cohort of mostly MRI-lesional epilepsy surgery patients. Confirmatory testing is essential to avoid overinterpretation of autoantibody-positive findings.

Neurological morbidity of surgery for suprasylvian operculoinsular epilepsy.

OBJECTIVE: The objective of this study was to identify risk factors associated with surgery-related neurological morbidity in patients with drug-resistant epilepsy undergoing suprasylvian operculoinsular resections. As secondary outcomes, we also analyzed the risk factors for ischemic lesion (IL) of corona radiata and seizure recurrence. METHODS: A retrospective analysis was conducted on a cohort of patients who underwent suprasylvian operculoinsular resections for drug-resistant epilepsy. The association of several presurgical, surgical, and postsurgical factors with both primary (persistent neurological deficits) and secondary (structural abnormalities on postoperative magnetic resonance imaging [MRI] and seizure recurrence) postoperative outcomes was investigated with univariate and multivariate statistical analysis. RESULTS: The study included a total of 65 patients; 46.2% of patients exhibited postoperative neurological deficits, but only 12.3% experienced persistent deficits. On postoperative MRI, IL in the corona radiata and corticospinal tract Wallerian degeneration (CSTWd) were seen in 68% and 29% of cases, respectively. Only CSTWd was significantly associated with persistent neurological deficits (relative risk [RR] = 2.6). Combined operculoinsular resection (RR = 3.62) and surgery performed on the left hemisphere (RR = .37) were independently associated with IL in the corona radiata. Variables independently associated with CSTWd were the presence of malacic components in the IL (RR = 1.96), right central operculum resection (RR = 1.79), and increasing age at surgery (RR = 1.03). Sixty-two patients had a postoperative follow-up > 12 months (median = 56, interquartile range = 30.75-73.5), and 62.9% were in Engel class I at last outpatient control. The risk of seizure recurrence was reduced by selective opercular resection (RR = .25) and increased by the histological diagnosis of aspecific gliosis (RR = 1.39). SIGNIFICANCE: This study provides insights into the risk factors associated with surgery-related neurological morbidity, as well as further evidence on the postoperative occurrence of subcortical injury and seizure recurrence in epileptic patients undergoing suprasylvian operculoinsular resections. The findings highlighted in this study may be useful to better understand the processes supporting the increased surgical risk in the operculoinsular region.

Hemispheric epilepsy surgery for hemimegalencephaly: The UCLA experience.

OBJECTIVES: Hemimegalencephaly (HME) is a rare congenital brain malformation presenting predominantly with drug-resistant epilepsy. Hemispheric disconnective surgery is the mainstay of treatment; however, little is known about how postoperative outcomes compare across techniques. Thus we present the largest single-center cohort of patients with HME who underwent epilepsy surgery and characterize outcomes. METHODS: This observational study included patients with HME at University of California Los Angeles (UCLA) from 1984 to 2021. Patients were stratified by surgical intervention: anatomic hemispherectomy (AH), functional hemispherectomy (FH), or less-than-hemispheric resection (LTH). Seizure freedom, functional outcomes, and operative complications were compared across surgical approaches. Regression analysis identified clinical and intraoperative variables that predict seizure outcomes. RESULTS: Of 56 patients, 43 (77%) underwent FH, 8 (14%) underwent AH, 2 (4%) underwent LTH, 1 (2%) underwent unknown hemispherectomy type, and 2 (4%) were managed non-operatively. At median last follow-up of 55 months (interquartile range [IQR] 20-92 months), 24 patients (49%) were seizure-free, 17 (30%) required cerebrospinal fluid (CSF) shunting for hydrocephalus, 9 of 43 (21%) had severe developmental delay, 8 of 38 (21%) were non-verbal, and 15 of 38 (39%) were non-ambulatory. There was one (2%) intraoperative mortality due to exsanguination earlier in this cohort. Of 12 patients (29%) requiring revision surgery, 6 (50%) were seizure-free postoperatively. AH, compared to FH, was not associated with statistically significant improved seizure freedom (hazard ratio [HR] = .48, p = .328), although initial AH trended toward greater odds of seizure freedom (75% vs 46%, p = .272). Younger age at seizure onset (HR = .29, p = .029), lack of epilepsia partialis continua (EPC) (HR = .30, p = .022), and no contralateral seizures on electroencephalography (EEG) (HR = .33, p = .039) independently predicted longer duration of seizure freedom. SIGNIFICANCE: This study helps inform physicians and parents of children who are undergoing surgery for HME by demonstrating that earlier age at seizure onset, absence of EPC, and no contralateral EEG seizures were associated with longer postoperative seizure freedom. At our center, initial AH for HME may provide greater odds of seizure freedom with complications and functional outcomes comparable to those of FH.

High-gamma modulation language mapping and cognitive outcomes after epilepsy surgery.

OBJECTIVE: We evaluated changes in cognitive domains after neurosurgical lesioning of cortical sites with significant high-gamma power modulations (HGM) during a visual naming task, although these sites were found language-negative on standard-of-care electrical stimulation mapping (ESM). METHODS: In drug-resistant epilepsy patients who underwent resection/ablation after stereo-electroencephalography (SEEG), we computed reliable change indices (RCIs) from a battery of presurgical and 1-year postsurgical neuropsychological assessments. We modeled RCIs as a function of lesioning even one HGM language site, number of HGM language sites lesioned, and the magnitude of naming-related HGM. The analyses were adjusted for 1-year seizure freedom, operated hemispheres, and the volumes of surgical lesions. RESULTS: In 37 patients with 4455 SEEG electrode contacts (1839 and 2616 contacts in right and left hemispheres, respectively), no ESM language sites were lesioned. Patients with lesioning of even one HGM language site showed significantly lower RCIs for Peabody Picture Vocabulary Test (PPVT), working memory, and verbal learning immediate (VLI) scores. RCI declines with higher number of HGM language sites lesioned were seen in PPVT (slope [ß] = -.10), working memory (ß = -.10), VLI (ß = -.14), and letter-word identification (LWI; ß = -.14). No neuropsychological domains improved after lesioning of HGM language sites. Significant effects of the HGM magnitude at lesioned sites were seen on working memory (ß = -.31), story memory immediate (ß = -.27), verbal learning recognition (ß = -.18), LWI (ß = -.16), spelling (ß = -.49), and passage comprehension (ß = -.33). Because working memory was significantly affected in all three analyses, patients with maximal working memory decline were examined post hoc, revealing that all such patients had HGM naming sites lesioned in the posterior quadrants of either hemisphere. SIGNIFICANCE: HGM language mapping should be used as an adjunct to ESM in clinical practice and may help counsel patients/families about postsurgical cognitive deficits.

Racial disparities in the utilization of invasive neuromodulation devices for the treatment of drug-resistant focal epilepsy.

Racial disparities affect multiple dimensions of epilepsy care including epilepsy surgery. This study aims to further explore these disparities by determining the utilization of invasive neuromodulation devices according to race and ethnicity in a multicenter study of patients living with focal drug-resistant epilepsy (DRE). We performed a post hoc analysis of the Human Epilepsy Project 2 (HEP2) data. HEP2 is a prospective study of patients living with focal DRE involving 10 sites distributed across the United States. There were no statistical differences in the racial distribution of the study population compared to the US population using census data except for patients reporting more than one race. Of 154 patients enrolled in HEP2, 55 (36%) underwent invasive neuromodulation for DRE management at some point in the course of their epilepsy. Of those, 36 (71%) were patients who identified as White. Patients were significantly less likely to have a device if they identified solely as Black/African American than if they did not (odds ratio = .21, 95% confidence interval = .05-.96, p = .03). Invasive neuromodulation for management of DRE is underutilized in the Black/African American population, indicating a new facet of racial disparities in epilepsy care.

Outcomes of surgical resection and vagus nerve stimulation in patients with medically refractory epilepsy and glutamic acid decarboxylase 65 antibody positivity.

Epilepsy associated with high-titer glutamic acid decarboxylase 65 (GAD65) IgG is often refractory to immunotherapies and antiseizure medication. This study sought to determine the efficacy of vagus nerve stimulation (VNS) and surgical resection in patients with drug-resistant epilepsy associated with GAD65-IgG. We retrospectively identified 15 patients with drug-resistant epilepsy and high serum GAD65 antibody titers (>20 nmol·L-1) who underwent VNS implantation (n = 6), surgical resection (n = 7), or both (n = 2). A responder to VNS was defined as someone with a ≥50% reduction in seizure frequency, and a favorable surgical outcome was defined as Engel I-II. Of the eight patients who underwent VNS implantation, three (37.5%) were initially responders, but this was not sustained in two. Of the nine patients who underwent surgical resection, three (33.3%) had a favorable outcome; however, only one patient was seizure-free at last follow-up. Pathology was available in six patients, and only one had evidence of inflammation; this patient had seizure onset 1 year prior to surgery. Favorable seizure outcome correlated with older age at time of resective surgery, with a trend favoring later age of seizure onset. Taken together, surgical resection and VNS implantation may have limited efficacy in this patient population but can be considered in carefully selected cases.

Investigating current clinical opinions in stereoelectroencephalography-informed epilepsy surgery.

OBJECTIVE: Stereoelectroencephalography (SEEG) is increasingly utilized worldwide in epilepsy surgery planning. International guidelines for SEEG terminology and interpretation are yet to be proposed. There are worldwide differences in SEEG definitions, application of features in epilepsy surgery planning, and interpretation of surgical outcomes. This hinders the clinical interpretation of SEEG findings and collaborative research. We aimed to assess the global perspectives on SEEG terminology, differences in the application of presurgical features, and variability in the interpretation of surgery outcome scores, and analyze how clinical expert demographics influenced these opinions. METHODS: We assessed the practices and opinions of epileptologists with specialized training in SEEG using a survey. Data were qualitatively analyzed, and subgroups were examined based on geographical regions and years of experience. Primary outcomes included opinions on SEEG terminology, features used for epilepsy surgery, and interpretation of outcome scores. Additionally, we conducted a multilevel regression and poststratification analysis to characterize the nonresponders. RESULTS: A total of 321 expert responses from 39 countries were analyzed. We observed substantial differences in terminology, practices, and use of presurgical features across geographical regions and SEEG expertise levels. The majority of experts (220, 68.5%) favored the Lüders epileptogenic zone definition. Experts were divided regarding the seizure onset zone definition, with 179 (55.8%) favoring onset alone and 135 (42.1%) supporting onset and early propagation. In terms of presurgical SEEG features, a clear preference was found for ictal features over interictal features. Seizure onset patterns were identified as the most important features by 265 experts (82.5%). We found similar trends after correcting for nonresponders using regression analysis. SIGNIFICANCE: This study underscores the need for standardized terminology, interpretation, and outcome assessment in SEEG-informed epilepsy surgery. By highlighting the diverse perspectives and practices in SEEG, this research lays a solid foundation for developing globally accepted terminology and guidelines, advancing the field toward improved communication and standardization in epilepsy surgery.