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Neuropsychological profiles are heterogeneous both across and within epilepsy syndromes, but especially in frontal lobe epilepsy (FLE), which has complex semiology and epileptogenicity. This study aimed to characterize the cognitive heterogeneity within FLE by identifying cognitive phenotypes and determining their demographic and clinical characteristics.One hundred and six patients (age 16-66; 44% female) with FLE completed comprehensive neuropsychological testing, including measures within five cognitive domains: language, attention, executive function, processing speed, and verbal/visual learning. Patients were categorized into one of four phenotypes based on the number of impaired domains. Patterns of domain impairment and clinical and demographic characteristics were examined across phenotypes.Twenty-five percent of patients met criteria for the Generalized Phenotype (impairment in at least four domains), 20% met criteria for the Tri-Domain Phenotype (impairment in three domains), 36% met criteria for the Domain-Specific Phenotype (impairment in one or two domains), and 19% met criteria for the Intact Phenotype (no impairment). Language was the most common domain-specific impairment, followed by attention, executive function, and processing speed. In contrast, learning was the least impacted cognitive domain. The Generalized Phenotype had fewer years of education compared to the Intact Phenotype, but otherwise, there was no differentiation between phenotypes in demographic and clinical variables. However, qualitative analysis suggested that the Generalized and Tri-Domain Phenotypes had a more widespread area of epileptogenicity, whereas the Intact Phenotype most frequently had seizures limited to the lateral frontal region.This study identified four cognitive phenotypes in FLE that were largely indistinguishable in clinical and demographic features, aside from education and extent of epileptogenic zone. These findings enhance our appreciation of the cognitive heterogeneity within FLE and provide additional support for the development and use of cognitive taxonomies in epilepsy.

Objective To assess and validate the performance of a new tool developed for segmenting and characterizing lacunas in postoperative MR images of epilepsy patients. Methods A MATLAB‐based pipeline was implemented using SPM12 to produce the 3D mask of the surgical lacuna and estimate its volume. To validate its performance, we compared the manual and automatic lacuna segmentations obtained from 51 MRI scans of epilepsy patients who underwent temporal lobe resections. Results The code is consolidated as a tool named ResectVol, which can be run via a graphical user interface or command line. The automatic and manual segmentation comparison resulted in a median Dice similarity coefficient of 0.77 (interquartile range: 0.71‐0.81). Significance Epilepsy surgery is the treatment of choice for pharmacoresistant focal epilepsies, and despite the extensive literature on the subject, we still cannot predict surgical outcomes accurately. As the volume and location of the resected tissue are fundamentally relevant to this prediction, researchers commonly perform a manual segmentation of the lacuna, which presents human bias and does not provide detailed information about the structures removed. In this study, we introduce ResectVol, a user‐friendly, fully automatic tool to accomplish these tasks. This capability enables more advanced analytical techniques applied to surgical outcomes prediction, such as machine‐learning algorithms, by facilitating coregistration of the resected area and preoperative findings with other imaging modalities such as PET, SPECT, and functional MRI ResectVol is freely available at https://www.lniunicamp.com/resectvol.

This study was undertaken to better understand the long-term palliative and disease-modifying effects of surgical resection beyond seizure freedom, including frequency reduction and both late recurrence and remission, in patients with drug-resistant epilepsy.This retrospective database-driven cohort study included all patients with9 years of follow-up at a single high-volume epilepsy center. We included patients who underwent lobectomy, multilobar resection, or lesionectomies for drug-resistant epilepsy; we excluded patients who underwent hemispherectomies. Our main outcomes were (1) reduction in frequency of disabling seizures (at 6 months, each year up to 9 years postoperatively, and at last follow-up), (2) achievement of seizure remission (6 months,1 year, and longest duration), and (3) seizure freedom at last follow-up.We included 251 patients; 234 (93.2%) achieved 6 months and 232 (92.4%) experienced 1 year of seizure freedom. Of these, the average period of seizure freedom was 10.3 years. A total of 182 (72.5%) patients were seizure-free at last follow-up (defined as1 year without seizures), with a median 11.9 years since remission. For patients not completely seizure-free, the mean seizure frequency reduction at each time point was 76.2%, and ranged from 66.6% to 85.0%. Patients decreased their number of antiseizure medications on average by .58, and 53 (21.2%) patients were on no antiseizure medication at last follow-up. Nearly half (47.1%) of those seizure-free at last follow-up were not seizure-free immediately postoperatively.Patients who continue to have seizures after resection often have considerable reductions in seizure frequency, and many are able to achieve seizure freedom in a delayed manner.

The spectrum of EEG abnormalities in the disconnected hemisphere in seizure-free patients after hemispherectomy has not been well characterized.Fifty consecutive patients who were seizure-free following hemispheric disconnection were identified. Data on preoperative clinical, EEG and neuroimaging findings and postoperative EEG findings and antiseizure medication status were collected.Forty-seven patients (94%) had functional hemispherectomy, and three (6%) had more extensive tissue resection of the posterior quadrant or frontal region along with hemispheric disconnection. Etiologies included: residual effects from vascular lesions including perinatal stroke in 35 patients, Rasmussen encephalitis in six, malformation of cortical development in seven, and Sturge-Weber syndrome in two. Pre-operative EEG showed focal epileptiform discharges in the affected hemisphere in 26 patients and in both hemispheres in 19. Eleven patients had diffuse bisynchronous epileptiform discharges. Postoperative EEGs at six to 12 months after surgery showed slowing and attenuation of physiological rhythms on the operated side in all patients. Thirty-four patients (68%) had epileptiform discharges exclusively from the operated hemisphere, six (12%) had bilateral independent epileptiform discharges, nine (18%) had no epileptiform discharges on either side, and one (2%) had epileptiform discharges from the contralateral hemisphere only. Lateralized periodic discharges from the operated hemisphere were noted in three patients (6%). EEG seizures from the operated hemisphere without clinical signs were noted in four patients (8%). After a median follow-up of three years, 30 patients (60%) were off all antiseizure medications, including 8/9 (89%) patients with no epileptiform discharges, 20/34 (59%) patients with postoperative epileptiform discharges from the operated hemisphere, and 2/7 (28%) patients with contralateral discharges.The majority of patients who are seizure-free after disconnective hemispherectomy will continue to show epileptiform discharges in the operated hemisphere. The presence of such discharges should not preclude tapering, nor prompt restarting of antiseizure medication in seizure-free patients.

ObjectiveTo develop and externally validate models to predict the probability of postoperative verbal memory decline in adults after temporal lobe resection (TLR) for epilepsy using easily accessible preoperative clinical predictors.MethodsMultivariable models were developed to predict delayed verbal memory outcome on 3 commonly used measures: Rey Auditory Verbal Learning Test (RAVLT) and Logical Memory (LM) and Verbal Paired Associates (VPA) subtests from Wechsler Memory Scale–Third Edition. With the use of the Harrell step-down procedure for variable selection, models were developed in 359 adults who underwent TLR at the Cleveland Clinic and validated in 290 adults at 1 of 5 epilepsy surgery centers in the United States or Canada.ResultsTwenty-nine percent of the development cohort and 26% of the validation cohort demonstrated significant decline on at least 1 verbal memory measure. Initial models had good to excellent predictive accuracy (calibration [c] statistic range 0.77–0.80) in identifying patients with memory decline; however, models slightly underestimated decline in the validation cohort. Model coefficients were updated with data from both cohorts to improve stability. The model for RAVLT included surgery side, baseline memory score, and hippocampal resection. The models for LM and VPA included surgery side, baseline score, and education. Updated model performance was good to excellent (RAVLT c = 0.81, LM c = 0.76, VPA c = 0.78). Model calibration was very good, indicating no systematic overestimation or underestimation of risk.ConclusionsNomograms are provided in 2 easy-to-use formats to assist clinicians in estimating the probability of verbal memory decline in adults considering TLR for treatment of epilepsy.Classification of EvidenceThis study provides Class II evidence that multivariable prediction models accurately predict verbal memory decline after TLR for epilepsy in adults.

Objective Patients undergoing frontal lobectomy demonstrate lower seizure-freedom rates than patients undergoing temporal lobectomy and several other resective interventions. We attempted to utilize automated preoperative quantitative analysis of focal and global cortical volume loss to develop predictive volumetric indicators of seizure outcome after frontal lobectomy. Methods Ninety patients who underwent frontal lobectomy were stratified based on seizure freedom at a mean follow-up time of 3.5 (standard deviation [SD] 2.5) years. Automated quantitative analysis of cortical volume loss organized by distinct brain region and laterality was performed on preoperative T1-weighted magnetic resonance imaging (MRI) studies. Univariate statistical analysis was used to select potential predictors of seizure freedom. Backward variable selection and multivariate logistical regression were used to develop models to predict seizure freedom. Results Forty-eight of 90 (53.3%) patients were seizure-free at the last follow-up. Several frontal and extrafrontal brain regions demonstrated statistically significant differences in both volumetric cortical volume loss and volumetric asymmetry between the left and right sides in the seizure-free and non-seizure-free cohorts. A final multivariate logistic model utilizing only preoperative quantitative MRI data to predict seizure outcome was developed with a c-statistic of 0.846. Using both preoperative quantitative MRI data and previously validated clinical predictors of seizure outcomes, we developed a model with a c-statistic of 0.897. Significance This study demonstrates that preoperative cortical volume loss in both frontal and extrafrontal regions can be predictive of seizure outcome after frontal lobectomy, and models can be developed with excellent predictive capabilities using preoperative MRI data. Automated quantitative MRI analysis can be quickly and reliably performed in patients with frontal lobe epilepsy, and further studies may be developed for integration into preoperative risk stratification.

Objective To develop a model to predict the probability of mood decline in adults following temporal lobe resection for the treatment of pharmacoresistant epilepsy. Methods Variable selection was performed on 492 patients from the Cleveland Clinic using best subsets regression. After completing variable selection, a subset of variables was requested from four epilepsy surgery centers across North America (n = 100). All data were combined to develop a final model to predict postoperative mood decline (N = 592). Internal validation with bootstrap resampling was performed. A clinically significant increase in depressive symptoms was defined as a 15% increase in Beck Depression Inventory-Second Edition score and a postoperative raw score > 11. Results Fourteen percent of patients in the Cleveland Clinic cohort and 22% of patients in the external cohort experienced clinically significant increases in depressive symptoms following surgery. The final prediction model included six predictor variables: psychiatric history, resection side, relationship status, verbal fluency score, age at preoperative testing, and presence/absence of malformation of cortical development on magnetic resonance imaging. The model had an optimism-adjusted c-statistic of .70 and good calibration, with slight probability overestimation in higher risk patients. Significance Clinicians can utilize our nomogram via a paper tool or online calculator to estimate the risk of postoperative mood decline for individual patients prior to temporal lobe epilepsy surgery.

Stereoelectroencephalography (SEEG) has gained popularity as an invasive monitoring modality for epileptogenic zone (EZ) localization. The need and indications for SEEG in patients with evident brain lesions or associated abnormalities on imaging is debated. We report our experience with SEEG as a presurgical evaluation tool for patients with lesional epilepsy.A retrospective cohort study was performed of 131 patients with lesional or magnetic resonance imaging abnormality-associated medically refractory focal epilepsy who underwent resections from 2010 to 2017. Seventy-one patients had SEEG followed by resection, and 60 had no invasive recordings. Volumetric analysis of resection cavities from 3T magnetic resonance imaging was performed.Mean lesion and resection volumes for SEEG and non-SEEG were 16.2 (standard deviation [SD] = 29) versus 23.7 cmSeizure outcomes did not correlate with final resection volume after SEEG evaluation. SEEG evaluation presurgically can be used to maintain the efficacy of resection and decrease the volume and subsequent risk of extensive tissue removal. We believe that this technology allows resective surgery to proceed in a subpopulation of patients with lesional epilepsy who may otherwise not have been considered surgical candidates.

The glucocorticoid receptor (GR) at the blood–brain barrier (BBB) is involved in the pathogenesis of drug-resistant epilepsy with focal cortical dysplasia (FCD); however, the roles of GR isoforms GRα and GRβ in the dysplastic brain have not been revealed. We utilized dysplastic/epileptic and non-dysplastic brain tissue from patients who underwent resective epilepsy surgery to identify the GRα and GRβ levels, subcellular localization, and cellular specificity. BBB endothelial cells isolated from the dysplastic brain tissue (EPI-ECs) were used to decipher the key BBB proteins related to drug regulation and BBB integrity compared to control and transfected GRβ-overexpressed BBB endothelial cells. GRβ was upregulated in dysplastic compared to non-dysplastic tissues, and an imbalance of the GRα/GRβ ratio was significant in females vs. males and in patients > 45 years old. In EPI-ECs, the subcellular localization and expression patterns of GRβ, Hsp90, CYP3A4, and CYP2C9 were consistent with GRβ+ brain endothelial cells. Active matrix metalloproteinase levels and activity increased, whereas claudin-5 levels decreased in both EPI-ECs and GRβ+ endothelial cells. In conclusion, the GRβ has a major effect on dysplastic BBB functional proteins and is age and gender-dependent, suggesting a critical role of brain GRβ in dysplasia as a potential biomarker and therapeutic target in epilepsy.

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

OBJECTIVEThe authors sought to describe the long-term recurrence patterns, prognostic factors, and effect of adjuvant or salvage radiotherapy (RT) on treatment outcomes for patients with spinal myxopapillary ependymoma (MPE).METHODSThe authors reviewed a tertiary institution IRB-approved database and collected data regarding patient, tumor, and treatment characteristics for all patients treated consecutively from 1974 to 2015 for histologically confirmed spinal MPE. Key outcomes included relapse-free survival (RFS), postrecurrence RFS, failure patterns, and influence of timing of RT on recurrence patterns. Cox proportional hazards regression and Kaplan-Meier analyses were utilized.RESULTSOf the 59 patients included in the study, the median age at initial surgery was 34 years (range 12–74 years), 30 patients (51%) were female, and the most common presenting symptom was pain (n = 52, 88%). Extent of resection at diagnosis was gross-total resection (GTR) in 39 patients (66%), subtotal resection (STR) in 15 (25%), and unknown in 5 patients (9%). After surgery, 10 patients (17%) underwent adjuvant RT (5/39 GTR [13%] and 5/15 STR [33%] patients). Median follow-up was 6.2 years (range 0.1–35.3 years). Overall, 20 patients (34%) experienced recurrence (local, n = 15; distant, n = 5). The median RFS was 11.2 years (95% CI 77 to not reached), and the 5- and 10-year RFS rates were 72.3% (95% CI 59.4–86.3) and 54.0% (95% CI, 36.4–71.6), respectively.STR was associated with a higher risk of recurrence (HR 6.45, 95% CI 2.15–19.23, p < 0.001) than GTR, and the median RFS after GTR was 17.2 years versus 5.5 years after STR. Adjuvant RT was not associated with improved RFS, regardless of whether it was delivered after GTR or STR. Of the 20 patients with recurrence, 12 (60%) underwent salvage treatment with surgery alone (GTR, n = 6), 4 (20%) with RT alone, and 4 (20%) with surgery and RT. Compared to salvage surgery alone, salvage RT, with or without surgery, was associated with a significantly longer postrecurrence RFS (median 9.5 years vs 1.6 years; log-rank, p = 0.006).CONCLUSIONSAt initial diagnosis of spinal MPE, GTR is key to long-term RFS, with no benefit to immediate adjuvant RT observed in this series. RT at the time of recurrence, however, is associated with a significantly longer time to second disease recurrence. Surveillance imaging of the entire neuraxis remains crucial, as distant failure is not uncommon in this patient population.

Background Hemispherectomy has been shown to be successful in treating medically intractable epilepsy, with favorable seizure-free outcomes. However, the procedure is technically challenging with high rates of in-hospital complications. We present a unique case of functional hemispherectomy complicated by diffuse cerebral vasospasm and subsequent death in a patient with COL4A1 gene mutation. Case Description A 17-year-old boy presented with right hemispheric epilepsy and a previously diagnosed autosomal dominant heterozygous COL4A1 gene mutation (c.4380T>G;p.Cys1460Trp). Functional hemispherectomy was performed without complications. On postoperative day 8, he developed an acute decline in neurologic status requiring urgent intubation for airway protection. Magnetic resonance imaging revealed areas of restricted diffusion throughout bilateral hemispheres that was explained by severe vasospasm and minimal cerebral blood flow seen on cerebral angiography. Intra-arterial calcium channel blocker infusion and balloon angioplasty were attempted without improvement in perfusion. With a worsening clinical picture, he was transitioned to comfort care and died. Conclusions This is the first report in the literature describing global vasospasm and delayed cerebral ischemia following hemispherectomy in a patient carrying COL4A1 gene mutation. We postulate that his COL4A1 gene mutation might have resulted in this exaggerated vasospasm despite minimal residual postoperative subarachnoid hemorrhage burden. This hypothesis needs to be studied in animal models of this genetic disorder.

BACKGROUND AND PURPOSE: NeuroQuant is an FDA-approved software that performs automated MR imaging quantitative volumetric analysis. This study aimed to compare the accuracy of NeuroQuant analysis with visual MR imaging analysis by neuroradiologists with expertise in epilepsy in identifying hippocampal sclerosis. MATERIALS AND METHODS: We reviewed 144 adult patients who underwent presurgical evaluation for temporal lobe epilepsy. The reference standard for hippocampal sclerosis was defined by having hippocampal sclerosis on pathology (n = 61) or not having hippocampal sclerosis on pathology (n = 83). Sensitivities, specificities, positive predictive values, and negative predictive values were compared between NeuroQuant analysis and visual MR imaging analysis by using a McNemar paired test of proportions and the Bayes theorem. RESULTS: NeuroQuant analysis had a similar specificity to neuroradiologist visual MR imaging analysis (90.4% versus 91.6%; P = .99) but a lower sensitivity (69.0% versus 93.0%, P

ObjectiveThe aim was to compare the outcomes of subdural electrode (SDE) implantations versus stereotactic electroencephalography (SEEG), the 2 predominant methods of intracranial electroencephalography (iEEG) performed in difficult-to-localize drug-resistant focal epilepsy.MethodsThe Surgical Therapies Commission of the International League Against Epilepsy created an international registry of iEEG patients implanted between 2005 and 2019 with ≥1 year of follow-up. We used propensity score matching to control exposure selection bias and generate comparable cohorts. Study endpoints were: (1) likelihood of resection after iEEG; (2) seizure freedom at last follow-up; and (3) complications (composite of postoperative infection, symptomatic intracranial hemorrhage, or permanent neurological deficit).ResultsTen study sites from 7 countries and 3 continents contributed 2,012 patients, including 1,468 (73%) eligible for analysis (526 SDE and 942 SEEG), of whom 988 (67%) underwent subsequent resection. Propensity score matching improved covariate balance between exposure groups for all analyses. Propensity-matched patients who underwent SDE had higher odds of subsequent resective surgery (odds ratio [OR]=1.4, 95% confidence interval [CI] 1.05, 1.84) and higher odds of complications (OR=2.24, 95% CI 1.34, 3.74; unadjusted: 9.6% after SDE vs 3.3% after SEEG). Odds of seizure freedom in propensity-matched resected patients were 1.66 times higher (95% CI 1.21, 2.26) for SEEG compared with SDE (unadjusted: 55% seizure free after SEEG-guided resections vs 41% after SDE).InterpretationIn comparison to SEEG, SDE evaluations are more likely to lead to brain surgery in patients with drug-resistant epilepsy but have more surgical complications and lower probability of seizure freedom. This comparative-effectiveness study provides the highest feasible evidence level to guide decisions on iEEG. ANN NEUROL 2021;90:927-939.

Neurosurgery is an effective treatment option for pharmacoresistant epilepsy. Although post-surgical seizure freedom is considered the primary goal of epilepsy surgery, other factors that impact Quality of Life (QOL) are also important to consider, including post-surgical cognitive changes. This study aimed to examine the impact of post-surgical cognitive changes on QOL in the context of seizure outcomes.Participants were 196 adults with focal epilepsy who underwent either frontal (n = 27) or temporal (n = 169) lobe resection. Each participant completed pre- and post-surgical neuropsychological evaluations, and cognitive composites were constructed for the following domains: language, attention/processing speed, memory, executive function, and visuospatial skill. The Quality of Life in Epilepsy (QOLIE-10) questionnaire was used to assess QOL. Seizure outcome was determined by seizure status six months post-surgery.Eighty-one percent of patients were seizure-free post-surgery and generally reported improved QOL. While a significant portion of patient's demonstrated declines in language and verbal memory following surgery, only a decline in verbal memory was associated with worse QOL; however, this relationship was no longer significant after controlling for seizure outcome. Instead, reduced post-surgical QOL was primarily observed in those who experienced both seizure recurrence and a decline in executive function. Notably, depression was a significant covariate in all of the models.The findings from this study improve our ability to counsel patients about the trade-off between cognitive decline and seizure remittance in the greater context of overall QOL. Reassuringly, it appears that QOL is improved regardless of cognitive changes when patients have good seizure outcomes. However, for those that experience a "double hit" (i.e., cognitive decline without seizure remission), post-surgical QOL may be reduced. Changes in depression also appear to play a crucial role in QOL outcomes.

Objective To determine whether brain connectivity differs between focal cortical dysplasia (FCD) types I and II. Methods We compared cortico-cortical evoked potentials (CCEPs) as measures of effective brain connectivity in 25 FCD patients with drug-resistant focal epilepsy who underwent intracranial evaluation with stereo-electroencephalography (SEEG). We analyzed the amplitude and latency of CCEP responses following ictal-onset single-pulse electrical stimulation (iSPES). Results In comparison to FCD type II, patients with type I demonstrated significantly larger responses in the electrodes near the ictal-onset zone (

Objective This study aims to evaluate the role of scalp electroencephalography (EEG; ictal and interictal patterns) in predicting resective epilepsy surgery outcomes. We use the data to further develop a nomogram to predict seizure freedom. Methods We retrospectively reviewed the scalp EEG findings and clinical data of patients who underwent surgical resection at three epilepsy centers. Using both EEG and clinical variables categorized into 13 isolated candidate predictors and 6 interaction terms, we built a multivariable Cox proportional hazards model to predict seizure freedom 2 years after surgery. Harrell's step-down procedure was used to sequentially eliminate the least-informative variables from the model until the change in the concordance index (c-index) with variable removal was less than 0.01. We created a separate model using only clinical variables. Discrimination of the two models was compared to evaluate the role of scalp EEG in seizure-freedom prediction. Results Four hundred seventy patient records were analyzed. Following internal validation, the full Clinical + EEG model achieved an optimism-corrected c-index of 0.65, whereas the c-index of the model without EEG data was 0.59. The presence of focal to bilateral tonic-clonic seizures (FBTCS), high preoperative seizure frequency, absence of hippocampal sclerosis, and presence of nonlocalizable seizures predicted worse outcome. The presence of FBTCS had the largest impact for predicting outcome. The analysis of the models' interactions showed that in patients with unilateral interictal epileptiform discharges (IEDs), temporal lobe surgery cases had a better outcome. In cases with bilateral IEDs, abnormal magnetic resonance imaging (MRI) predicted worse outcomes, and in cases without IEDs, patients with extratemporal epilepsy and abnormal MRI had better outcomes. Significance This study highlights the value of scalp EEG, particularly the significance of IEDs, in predicting surgical outcome. The nomogram delivers an individualized prediction of postoperative outcome, and provides a unique assessment of the relationship between the outcome and preoperative findings.

Multimodal image integration (MMII) is a promising tool to help delineate the epileptogenic zone (EZ) in patients with medically intractable focal epilepsies undergoing presurgical evaluation. We report here the detailed methodology of MMII and an overview of the utility of MMII at the Cleveland Clinic Epilepsy Center from 2014 to 2018, exemplified by illustrative cases. The image integration was performed using the Curry platform (Compumedics Neuroscan™, Charlotte, NC, USA), including all available diagnostic modalities such as Magnetic resonance imaging (MRI), Positron Emission Tomography (PET), single-photon emission computed tomography (SPECT) and Magnetoencephalography (MEG), with additional capability of trajectory planning for intracranial EEG (ICEEG), particularly stereo-EEG (SEEG), as well as surgical resection planning. In the 5-year time span, 467 patients underwent MMII; of them, 98 patients (21%) had a history of prior neurosurgery and recurring seizures. Of the 467 patients, 425 patients underwent ICEEG implantation with further CT co-registration to identify the electrode locations. A total of 351 patients eventually underwent surgery after MMII, including 197 patients (56%) with non-lesional MRI and 223 patients (64%) with extra-temporal lobe epilepsy. Among 269 patients with 1-year post-operative follow up, 134 patients (50%) had remained completely seizure-free. The most common histopathological finding is focal cortical dysplasia. Our study illustrates the usefulness of MMII to enhance SEEG electrode trajectory planning, assist non-invasive/invasive data interpretation, plan resection strategy, and re-evaluate surgical failures. Information presented by MMII is essential to the understanding of the anatomo-functional-electro-clinical correlations in individual cases, which leads to the ultimate success of presurgical evaluation of patients with medically intractable focal epilepsies.

Background Prior studies in the field of epilepsy surgical disparities have examined barriers in undergoing epilepsy surgical resections in disadvantaged populations involving trust in health providers, education level, social support, and fear of treatment. Few studies have analyzed the geographical locations of specialized epilepsy centers and their role in nationwide epilepsy surgical access and disparities. Objective To better visualize the locations of epilepsy level IV centers in the United States with respect to epilepsy prevalence and socioeconomic disadvantage. Methods We created heat maps of the United States to visualize geographical locations of level IV epilepsy centers with respect to the 2015 state-wide epilepsy prevalence and 2017 county-wide Area Deprivation Index (ADI) scores, a composite measure of socioeconomic disadvantage. Univariate logistic regression was used to test for associations between the presence or absence of epilepsy centers and socioeconomic disadvantage. Results We found eight states within the United States without any level IV epilepsy centers. In states with level IV centers, centers were clustered in populated and metropolitan regions. Disadvantaged counties (with increased ADI scores) were less likely to have level IV centers compared to counties that were less disadvantaged (lower ADI scores) (p Conclusion Further work is required to remedy the decreased access to specialized epilepsy care due to geographical disparities, and to better understand its contribution to overall disparities affecting epilepsy surgery referrals.

Quantitative volumetric brain MRI measurement is important in research applications, but translating it into patient care is challenging. We explore the incorporation of clinical automated quantitative MRI measurements in statistical models predicting outcomes of surgery for temporal lobe epilepsy. Four hundred and thirty-five patients with drug-resistant epilepsy who underwent temporal lobe surgery at Cleveland Clinic, Mayo Clinic and University of Campinas were studied. We obtained volumetric measurements from the pre-operative T1-weighted MRI using NeuroQuant, a Food and Drug Administration approved software package. We created sets of statistical models to predict the probability of complete seizure-freedom or an Engel score of I at the last follow-up. The cohort was randomly split into training and testing sets, with a ratio of 7:3. Model discrimination was assessed using the concordance statistic (C-statistic). We compared four sets of models and selected the one with the highest concordance index. Volumetric differences in pre-surgical MRI located predominantly in the frontocentral and temporal regions were associated with poorer outcomes. The addition of volumetric measurements to the model with clinical variables alone increased the model’s C-statistic from 0.58 to 0.70 (right-sided surgery) and from 0.61 to 0.66 (left-sided surgery) for complete seizure freedom and from 0.62 to 0.67 (right-sided surgery) and from 0.68 to 0.73 (left-sided surgery) for an Engel I outcome score. 57% of patients with extra-temporal abnormalities were seizure-free at last follow-up, compared to 68% of those with no such abnormalities (P-value = 0.02). Adding quantitative MRI data increases the performance of a model developed to predict post-operative seizure outcomes. The distribution of the regions of interest included in the final model supports the notion that focal epilepsies are network disorders and that subtle cortical volume loss outside the surgical site influences seizure outcome., Abbreviated summary Morita-Sherman et al. demonstrate how sophisticated research imaging can cross the divide to clinical practice. They show how quantitative MRI can enhance epilepsy surgery outcome prediction. Volume changes in the structures highlighted were identified as outcome predictors, supporting the hypothesis that subtle cortical atrophy outside the resection influences seizure outcome., Graphical Abstract Graphical Abstract

Hemispherectomy in Adults and Adolescents: Seizure and Functional Outcomes in 47 Patients McGovern RA, NV Moosa A, Jehi L, Busch R, Ferguson L, Gupta A, et al. Epilepsia. 2019;60(12):2416-2427. http://doi.org/10.1111/epi.16378.Objective:To examine longitudinal seizure and functional outcomes after hemispherectomy in adults and adolescents.Methods:We reviewed 47 consecutive patients older than 16 years who underwent hemispherectomy between 1996 and 2016 at our center. Clinical, electroencephalographic (EEG), imaging, neuropsychological, surgical, and functional status data were analyzed.Results:Thirty-six patients were 18 years or older at surgery; 11 were aged between 16 and 18 years. Brain injury leading to hemispheric epilepsy occurred before 10 years of age in 41 (87%) patients. At a mean follow-up of 5.3 postoperative years (median = 2.9 years), 36 (77%) had Engel class I outcome. Longitudinal outcome analysis showed 84% seizure freedom (Engel IA) at 6 months, 76% at 2 years, and 76% at 5 years and beyond, with stable longitudinal outcomes up to 12 years from surgery. Multivariate analysis demonstrated that acute postoperative seizures and contralateral interictal spikes at 6-month follow-up EEG were associated with seizure recurrence. Patients who could walk unaided preoperatively and had no cerebral peduncle atrophy on brain magnetic resonance imaging were more likely to experience worsening of motor function postoperatively. Otherwise, postoperative ambulatory status and hand function were unchanged. Of the 19 patients who completed neuropsychological testing, 17 demonstrated stable or improved postoperative outcomes.Significance:Hemispherectomy in adults is a safe and effective procedure, with seizure freedom rates and functional outcome similar to those observed in children.

Objective The objective of this study was to compare the accuracy of clinical judgment in predicting seizure outcome after resective epilepsy surgery relative to two recently published statistical tools [the Epilepsy Surgery Nomogram (ESN) and the modified Seizure-Freedom score (m-SFS)]. Methods Details of presurgical evaluations of 20 patients who underwent epilepsy surgery were presented to 20 epilepsy experts. The final surgical treatment was also disclosed. The clinicians were asked to predict the likelihood of a good outcome (Engel 1) at 2 and 5 years in each case. The ESN and the m-SFS predictions were calculated with the data provided to the clinicians. The discriminative ability of clinical judgment, ESN, and m-SFS was assessed by calculating a concordance index (C-index). Expert opinion, the m-SFS and the ESN performances were compared using a Receiver Operating Characteristic (ROC) curve analysis. Results The mean age at surgery was 29 years (standard deviation [SD] = 14); 40% were male; 70% were right-handed, and thirteen (65%) had an Engel outcome 1 at 2 and 5 years. The mean C-index for the mean physician's prediction was 0.478 with a variance of 0.012. The ESN had an area under the curve (AUC) of 0.528 and 0.533 for the 2-year and 5-year predictions in comparison with the clinicians' predictions that was 0.476, and 0.466, respectively. For the m-SFS, the AUC at 2 years and 5 years was 0.539 and 0.539, respectively. No statistical difference was noted between the ESN and the clinicians or between m-SFS and the ESN, but there is a moderate statistical difference favoring the m-SFS to the clinicians (p 0.0960 and 0.0514, for 2 and 5 years). Significance Clinical judgment was not superior to the ESN nor to the m-SFS. Together with the interphysician's prediction variability, our findings reinforce the need for better tools to predict postoperative outcomes.

OBJECTIVE Drug-resistant epilepsy (DRE) during the first few months of life is challenging and necessitates aggressive treatment, including surgery. Because the most common causes of DRE in infancy are related to extensive developmental anomalies, surgery often entails extensive tissue resections or disconnection. The literature on "ultra-early" epilepsy surgery is sparse, with limited data concerning efficacy controlling the seizures, and safety. The current study's goal is to review the safety and efficacy of ultra-early epilepsy surgery performed before the age of 3 months. METHODS To achieve a large sample size and external validity, a multinational, multicenter retrospective study was performed, focusing on epilepsy surgery for infants younger than 3 months of age. Collected data included epilepsy characteristics, surgical details, epilepsy outcome, and complications. RESULTS Sixty-four patients underwent 69 surgeries before the age of 3 months. The most common pathologies were cortical dysplasia (28), hemimegalencephaly (17), and tubers (5). The most common procedures were hemispheric surgeries (48 procedures). Two cases were intentionally staged, and one was unexpectedly aborted. Nearly all patients received blood products. There were no perioperative deaths and no major unexpected permanent morbidities. Twenty-five percent of patients undergoing hemispheric surgeries developed hydrocephalus. Excellent epilepsy outcome (International League Against Epilepsy [ILAE] grade I) was achieved in 66% of cases over a median follow-up of 41 months (19-104 interquartile range [IQR]). The number of antiseizure medications was significantly reduced (median 2 drugs, 1-3 IQR, p

OBJECTIVE The aim of this study was to investigate seizure outcomes after resective epilepsy surgery following stereoelectroencephalography (SEEG), including group characteristics, comparing surgical and nonsurgical groups and assess predictors of time to seizure recurrence. METHODS Clinical and EEG data of 536 consecutive patients who underwent SEEG at Cleveland Clinic Epilepsy Center between 2009 and 2017 were reviewed. The primary outcome was defined as complete seizure freedom since the resective surgery, discounting any auras or seizures that occurred within the 1st postoperative week. In addition, the rate of seizure freedom based on Engel classification was determined in patients with follow-up of ≥ 1 year. Presumably significant outcome variables were first identified using univariate analysis, and Cox proportional hazards modeling was used to identify outcome predictors. RESULTS Of 527 patients satisfying study criteria, 341 underwent resective surgery. Complete and continuous seizure freedom after surgery was achieved in 55.5% of patients at 1 year postoperatively, 44% of patients at 3 years, and 39% of patients at 5 years. As a secondary outcome point, 58% of patients achieved Engel class I seizure outcome for at least 1 year at last follow-up. Among surgical outcome predictors, in multivariate model analysis, the seizure recurrence rate by type of resection (p = 0.039) remained statistically significant, with the lowest risk of recurrence occurring after frontal and temporal lobe resections compared with multilobar and posterior quadrant surgeries. Patients with a history of previous resection (p = 0.006) and bilateral implantations (p = 0.023) were more likely to have seizure recurrence. The absence of an MRI abnormality prior to resective surgery did not significantly affect seizure outcome in this cohort. CONCLUSIONS This large, single-center series shows that resective surgery leads to continuous seizure freedom in a group of patients with complex and severe pharmacoresistant epilepsy after SEEG evaluation. In addition, up to 58% of patients achieved seizure freedom at last follow-up. The authors’ results suggest that SEEG is equally effective in patients with frontal and temporal lobe epilepsy with or without MRI identified lesions.

Background Stereoelectroencephalography (SEEG) is used to identify the epileptogenic zone (EZ) in patients with epilepsy for potential surgical intervention. Occasionally, the EZ is difficult to localize even after an SEEG implantation. Objective To demonstrate a safe technique for placing additional electrodes in ongoing SEEG evaluations. Describe efficacy, complications, and surgical outcomes. Methods An operative technique which involves maintaining previously placed electrodes and sterilely placing new electrodes was developed and implemented. All patients who underwent placement of additional SEEG electrodes during the same admission were retrospectively reviewed. Results A total of 14 patients met criteria and had undergone SEEG evaluation with 198 electrodes implanted. A total 93% of patients (13/14) had nonlesional epilepsy. After unsuccessful localization of the EZ after a mean of 9.6 d of monitoring, each patient underwent additional placement of electrodes (5.5 average electrodes per patient) to augment the original implantation. At no point did any patients develop new hemorrhage, infection, wound breakdown, or require any kind of additional antimicrobial treatment. A total 64% (9/14) of patients were able to undergo surgery aimed at removing the EZ guided by the additional SEEG electrodes. A total 44% (4/9) of surgical patients had Engel class I outcomes at an average follow-up time of 11 mo. Conclusion Placing additional SEEG electrodes, while maintaining the previously placed electrodes, appears to be safe, effective, and had no infectious complications. When confronted with difficult-to-localize epilepsy even after invasive monitoring, it appears to be safe and potentially clinically effective to place additional electrodes during the same admission.

Pharmacoresistance in epilepsy is a major challenge to successful clinical therapy. Glucocorticoid receptor (GR) dysregulation can affect the underlying disease pathogenesis. We recently reported that local drug biotransformation at the blood-brain barrier is upregulated by GR, which controls drug-metabolizing enzymes (e.g., cytochrome P450s, CYPs) and efflux drug transporters (MDR1) in human epileptic brain endothelial cells (EPI-ECs). Here, we establish that this mechanism is influenced upstream by GR and its association with heat shock proteins/co-chaperones (Hsps) during maturation, which differentially affect human epileptic (EPI) tissue and brain endothelial cells. Overexpressed GR, Hsp90, Hsp70, and Hsp40 were found in EPI vs. NON-EPI brain regions. Elevated neurovascular GR expression and co-localization with Hsps was evident in the EPI regions with cortical dysplasia, predominantly in the brain micro-capillaries and neurons. A corresponding increase in ATPase activity (*p

OBJECTIVE: We aimed to determine the rates and predictors of resection and seizure freedom after bilateral stereo-electroencephalography (SEEG) implantation. METHODS: We reviewed 184 patients who underwent bilateral SEEG implantation (2009-2015). Noninvasive and invasive evaluation findings were collected. Outcomes of interest included subsequent resection and seizure freedom. Statistical analyses employed multivariable logistic regression and proportional hazard modeling. Preoperative and postoperative seizure frequency, severity, and quality of life scales were also compared. RESULTS: Following bilateral SEEG implantation, 106 of 184 patients (58%) underwent resection. Single seizure type (P = 0.007), a family history of epilepsy (P = 0.003), 10 or more seizures per month (P = 0.004), lower number of electrodes (P = 0.02), or sentinel electrode placement (P = 0.04) was predictive of undergoing a resection, as were lack of nonlocalized (P < 0.0001) or bilateral (P < 0.0001) ictal-onset zones on SEEG. Twenty-six of 81 patients (32% with follow-up greater than 1 year) remained seizure-free. Predictors of seizure freedom were single seizure type (P = 0.01), short epilepsy duration (P = 0.008), use of 2 or fewer antiepileptic drugs (AEDs) at the time of surgery (P = 0.0006), primary localization hypothesis involving the frontal lobe (P = 0.002), sentinel electrode placement only (P = 0.02), and lack of overlap between ictal-onset zone and eloquent cortex (P = 0.04), along with epilepsy substrate histopathology (P = 0.007). Complete resection of a suspected focal cortical dysplasia showed a trend to increased likelihood of seizure freedom (P = 0.09). The 44 of 55 patients (80%) who underwent resection and experienced seizure recurrence had >50% seizure reduction, as opposed to 26 of 45 patients (58%) who continued medical therapy alone (P = 0.003). Seventy-two percent of patients had a clinically meaningful quality of life improvement (>10% decrease in the Quality of Life in Epilepsy [QOLIE-10] score) at 1 year. SIGNIFICANCE: A strong preimplantation hypothesis of a suspected unifocal epilepsy increases the odds of resection and seizure freedom. We discuss a tailored approach, taking into account localization hypothesis and suspected epilepsy etiology in guiding implantation and subsequent surgical strategy.

ObjectiveTo develop and externally validate models to predict the probability of postoperative naming decline in adults following temporal lobe epilepsy surgery using easily accessible preoperative clinical predictors.MethodsIn this retrospective, prediction model development study, multivariable models were developed in a cohort of 719 patients who underwent temporal lobe epilepsy surgery at Cleveland Clinic and externally validated in a cohort of 138 patients who underwent temporal lobe surgery at one of 3 epilepsy surgery centers in the United States (Columbia University Medical Center, Emory University School of Medicine, University of Washington School of Medicine).ResultsThe development cohort was 54% female with an average age at surgery of 36 years (SD 12). Twenty-six percent of this cohort experienced clinically relevant postoperative naming decline. The model included 5 variables: side of surgery, age at epilepsy onset, age at surgery, sex, and education. When applied to the external validation cohort, the model performed very well, with excellent calibration and a c statistic (reflecting discriminatory ability) of 0.81. A second model predicting moderate to severe postoperative naming decline included 3 variables: side of surgery, age at epilepsy onset, and preoperative naming score. This model generated a c statistic of 0.84 in the external validation cohort and showed good calibration.ConclusionExternally validated nomograms are provided in 2 easy-to-use formats (paper version and online calculator) clinicians can use to estimate the probability of naming decline in patients considering epilepsy surgery for treatment of pharmacoresistant temporal lobe epilepsy.

Objective Nuclear receptors and cytochrome P450 (CYP) regulate hepatic metabolism of several drugs. Nuclear receptors are expressed at the neurovascular unit of patients with drug-resistant epilepsy. We studied whether glucocorticoid receptor (GR) silencing or inhibition in human epileptic brain endothelial cells (EPI-ECs) functionally impacts drug bioavailability across an in vitro model of the blood-brain barrier (BBB) by CYP-multidrug transporter (multidrug resistance protein 1, MDR1) mechanisms. Methods Surgically resected brain specimens from patients with drug-resistant epilepsy, primary EPI-ECs, and control human brain microvascular endothelial cells (HBMECs) were used. Expression of GR, pregnane X receptor, CYP3A4, and MDR1 was analyzed pre- and post-GR silencing in EPI-ECs. Endothelial cells were co-cultured with astrocytes and seeded in an in vitro flow-based BBB model (DIV-BBB). Alternatively, the GR inhibitor mifepristone was added to the EPI-EC DIV-BBB. Integrity of the BBB was monitored by measuring transendothelial electrical resistance. Cell viability was assessed by glucose-lactate levels. Permeability of [3 H]sucrose and [14 C]phenytoin was quantified. CYP function was determined by measuring resorufin formation and oxcarbazepine (OXC) metabolism. Results Silencing and inhibition of GR in EPI-ECs resulted in decreased pregnane X receptor, CYP3A4, and MDR1 expression. GR silencing or inhibition did not affect BBB properties in vitro, as transendothelial electrical resistance and Psucrose were unaltered, and glucose metabolism was maintained. GR EPI-EC silencing or inhibition led to (1) increased Pphenytoin BBB permeability as compared to control; (2) decreased CYP function, indirectly evaluated by resorufin formation; (3) improved OXC bioavailability with increased abluminal (brain-side) OXC levels as compared to control. Significance Our results suggest that modulating GR expression in EPI-ECs at the BBB modifies drug metabolism and penetration by a mechanism encompassing P450 and efflux transporters. The latter could be exploited for future drug design and to overcome pharmacoresistance.

Background The management of medically refractory epilepsy patients who are not surgical candidates has remained challenging. Closed loop-or responsive-neurostimulation (RNS) is now an established therapy for the treatment of epilepsy with specific indications. The RNS® system (NeuroPace Inc, Mountainview, California) has recently been shown to be effective in reducing the seizure frequency of partial onset seizures. The electrode design consists of either intracerebral depth electrodes or subdural strip electrodes, and stereotaxis is typically used to guide placement into the EZ. Details on the operative techniques used to place these electrodes have been lacking. Objective To address the advantage of using a robotic-assisted technique to place depth electrodes for RNS® system placement compared to the typical frame-based or frameless stereotactic systems. Methods We retrospectively reviewed our single center, technical operative experience with RNS® system placement using robotic assistance from 2014 to 2016 via chart review. Results Twelve patients underwent RNS® system placement using robotic assistance. Mean operative time was 121 min for a median of 2 depth electrodes with mean deviation from intended target of ∼3 mm in x, y, and z planes. Two patients developed wound infections, 1 of whom was reimplanted. Seizures were reduced by ∼40% at 2 yr, similar to the results seen in the open label portion of the pivotal RNS trial. Conclusion Robotic-assisted stereotaxis can be used to provide a stable and accurate stereotactic platform for insertion of intracerebral RNS electrodes, representing a safe, efficient and accurate procedure.

Summary We recently proposed that the maturation of a new epileptic focus (epileptogenesis) may explain late seizure recurrences, starting months to years after resective epilepsy surgery. We explore here the hypothesis that inherent transcriptomic changes may distinguish such “late relapsers.” An in‐depth clinical review of 2 patients with recurrent seizures starting years after surgery is contrasted to 4 controls who remained seizure‐free postoperatively. This clinical analysis is combined with RNA sequencing from the resected brain tissue, followed by unsupervised hierarchical clustering, independent pathway analysis, and multidimensional scaling analysis. Late‐recurrence patients clustered apart from seizure‐free patients, with late recurrence patients clustering together in the central space, whereas the seizure‐free patients clustered together in the periphery. We utilized RNA‐seq to identify differentially expressed genes between late‐recurrence and seizure‐free samples. We found 29 annotated genes with statistically significant differential expression (q < 0.05). The top canonical pathways identified as distinctly separating the late‐recurrence patients from the seizure‐free patients included the intrinsic prothrombin activation pathway (p = 1.55E‐06), the complement system (p = 4.57E‐05), and the atherosclerosis signaling pathway (p = 4.57E‐05). Our observations suggest that late recurrences after epilepsy surgery may be influenced partly by differences in gene expression in neuroinflammatory and brain healing/remodeling pathways. Such a hypothesis needs to be validated in the future.

Summary Objective To summarize the existing literature on resective epilepsy surgery (RES) in older adults (≥60 years old) and examine seizure and neuropsychological outcomes in a single‐center large cohort of older adults undergoing RES and their comparison to a consecutive, younger (25‐ to45‐year‐old) adult population who underwent RES in routine clinical practice. Methods First, a comprehensive literature review was performed. Then, we identified older adults who underwent RES at our center (2000–2015). Outcome analysis was performed on patients who had ≥1 year of clinical follow‐up. A younger cohort of patients who underwent RES during the same period was selected for comparison. The 2 groups were compared with respect to demographic and disease variables as well as key clinical outcomes. Results Seizure outcomes on 58 older patients were reported in existing literature; 72% achieved Engel class I outcome ≥1 year postoperatively. Sixty‐four older adults underwent RES at our center, accounting for 2.8% of all RES during the study period. A total of 51 older adults (Mage = 65) among them had ≥1‐year clinical follow‐up; 80% achieved Engel I outcome after a mean follow‐up of 3.2 years. This was comparable to the 68% Engel class I outcome among 50 consecutive younger adults, despite later age of onset, longer epilepsy duration, and more comorbidities (all p

Object The objective of the study is to investigate and report our experience with extra operative intracranial EEG monitoring for evaluation of epilepsy surgery among elderly (≥ 60 years) patients. Methods After IRB approval, we searched our prospectively maintained epilepsy surgery database to find patients who underwent eiEEG at the age of 60 years or older. Electronic medical records were reviewed to extract clinical and surgery-related information. Patients who underwent resective epilepsy surgery after eiEEG and had at least 1 year of clinical follow-up were assessed for seizure outcome. Categorical and continuous variables were compared using Pearson chi-square and Student's t-test, respectively. Results A total of 21 patients, with 13 (62%) women, underwent eiEEG in our center at the age of 60 years or older. The mean age at time of implantation was 63.8 ± 2.7 years. Sub-dural grids (SDG) were implanted in five (24%) patients, whereas sixteen (76%) patients underwent stereo-EEG (SEEG) implantation. Median number of contacts in SDG were 106 (56–136) and depth electrodes in SEEG were 12 (9–14). There were 2 complications, including one mortality due to intracerebral hemorrhage. Sixteen (76%) patients underwent respective epilepsy surgery after eiEEG and eleven (69%) achieved Engel class I outcome on the last follow-up [mean follow-up duration of 2.7 (± 1.8) years]. Conclusion We noticed an increased utilization of eiEEG in elderly patients after the introduction of SEEG at our center. Overall, we found that eiEEG can help achieve good seizure outcomes in the elderly population. However, the one eiEEG-related mortality serves a word of caution about the potential risks in this population., Highlights • First report on extra operative intracranial EEG (eiEEG) monitoring use in the elderly • Twenty-one elderly patients underwent eiEEG at the mean age of 63.8 ± 2.7 years. • Sixteen (76%) underwent surgery after eiEEG and 11 (69%) achieved Engel class I outcome. • Utilization of eiEEG increased after the introduction of stereo EEG (SEEG) at our center.

Invasive neuromonitoring is an important component of presurgical workup and seizure onset zone localization in patients with epilepsy being considered for surgical resection. In the United States, intraparenchymal stereoelectroencephalography (SEEG) electrodes have been replacing subdural grid electrodes for most cases, following a trend that has already matured in Europe. The use of robotic assistance has been shown to improve operative times and accuracy in SEEG electrode placement, as users benefit from the embedded planning software as well as the efficiency and accuracy of the robotic arm. The greatest barriers to implementation of this technology are the upfront cost and learning curve. This case-based surgeon's perspective operative video could benefit those considering incorporating robotic assistance for SEEG electrode placement. Those considering robotic assistance for pedicle screw placement and other budding applications may also benefit, as well as innovators looking for new applications. The patient consented for the procedure, video recording, and inclusion in subsequent publications.

Objective To use reliable change indices (RCIs) developed specifically for pediatric patients with epilepsy to examine cognitive outcomes after frontal lobe resection for pharmacoresistant epilepsy. Methods Forty-one pediatric patients (25 male, Mage = 10 years) completed comprehensive neuropsychological evaluations before and an average of 6.5 months after frontal lobe resections for treatment of epilepsy. Evaluations included tests of intelligence, attention/working memory, processing speed, language, visuospatial skills, executive function, and episodic memory. Practice effect-adjusted RCIs were used to determine clinically significant postoperative cognitive change. Demographic, disease, and surgical variables were examined to identify factors associated with postoperative cognitive decline or improvement. Results Within each cognitive domain, there was a large proportion of patients (51–84%) who did not exhibit significant cognitive change. In terms of overall cognitive profile, 44% demonstrated improvement in at least one domain and 69% declined in at least one domain. Postoperative cognitive improvement occurred most commonly in the domain of processing speed, whereas postoperative cognitive decline occurred most frequently in the domain of visuospatial skills. Younger age at surgery was associated with cognitive improvement. Older age at seizure onset and higher baseline cognitive performance were associated with cognitive decline. Significance Approximately 6.5 months after frontal lobe resection, only 15% of our sample showed stable performance across all cognitive domains. Seventeen percent of patients showed improvements without declines, 42% showed declines without improvements, and 27% showed a mix of improvements and declines across different cognitive domains. Age and baseline abilities were associated with postoperative cognitive change on multiple measures. With 1 in 8 children demonstrating postoperative decline across three or more domains, further research is needed to identify factors associated with cognitive decline in order to inform clinical decision-making and patient/family counseling.

OBJECTIVE To analyze longitudinal seizure outcomes following epilepsy surgery, including reoperations, in patients with intractable focal epilepsy. METHODS Clinicoradiological characteristics of patients who underwent epilepsy surgery from 1995 to 2016 with follow-up of ≥1 year were reviewed. In patients undergoing reoperations, the latest resection was considered the index surgery. The primary outcome was complete seizure freedom (Engel I) at last follow-up. Potentially significant outcome variables were first identified using univariate analyses and then fit in multivariate Cox proportional hazards models. RESULTS Of 898 patients fulfilling study criteria, 110 had reoperations; 92 had one resection prior to the index surgery and 18 patients had two or more prior resective surgeries. Two years after the index surgery, 69% of patients with no prior surgeries had an Engel score of I, as opposed to only 42% of those with one prior surgery, and 33% of those with two or more prior resections (P

OBJECTIVE Previous work has suggested that seizure outcome is the most important predictor of quality of life (QoL) after epilepsy surgery, but it is unknown which specific seizure outcome measure should be used in judging surgical success. We assess three different seizure outcome measures (relative seizure reduction, absolute seizure reduction, and seizure freedom [yes/no]) to investigate which measure best predicts postoperative QoL. METHODS We prospectively surveyed patients at outpatient visits before and after epilepsy surgery (n = 550). The QoL measure was the Quality of Life in Epilepsy (QOLIE-10) score at the patient's most recent office visit. We created multivariate regression models to predict postoperative QOLIE-10, with a different seizure outcome measure in each model. We compared models using adjusted R2 values and Akaike information criteria (AIC). RESULTS Our cohort had a high level of disease severity and complexity (17% repeat surgery, 39% extratemporal, and 18% nonlesional). For the cohort as a whole, mean absolute seizure frequency decreased from 1 per day to 0.1 per day (P

We comprehensively studied the clinical presentation, stereo-EEG and MRI findings, histopathological diagnosis, and brain somatic mutations in a retrospective series of drug-resistant patients with difficult-to-localize epilepsy due to focal cortical dysplasia at the bottom of a sulcus (BOS-FCD). We identified 10 patients with BOS-FCD from the Cleveland Clinic epilepsy surgery database submitted for intracranial video-EEG monitoring. Brain MRI, including voxel-based morphometric analysis and surgical tissue submitted for histopathology, was reviewed. Paraffin tissue samples from five patients were made available for targeted next-generation sequencing. Postsurgical follow-up was available in nine patients. BOS-FCD was identified in the superior frontal sulcus in six patients, inferior frontal sulcus in one patient, central sulcus in one patient, and intraparietal sulcus in two patients. All patients had stereotyped seizures. Intracranial EEG recordings identified ictal onset at the BOS-FCD in all 10 patients, whereas ictal scalp EEG had a localizing value in only six patients. Complete resection was achieved by lesionectomy or focal corticectomy in nine patients. Histopathologically, six patients had FCD type IIb and three had FCD type IIa. Next-generation sequencing analysis of DNA extracted from lesion-enriched (micro-dissected) tissue from five patients with FCD type II led to the identification of a germline frameshift insertion in DEPDC5, introducing a premature stop in one patient. Eight out of nine patients with available follow-up were completely seizure-free (Engel Class IA) after a mean follow-up period of six years. Our results confirm previous studies classifying difficult-to-localize BOS-FCD into the emerging spectrum of FCD ILAE type II mTORopathies. Further studies with large patient numbers and ultra-deep genetic testing may help to bridge the current knowledge gap in genetic aetiologies of FCD.

The optimal treatment for medically refractory epilepsy in Aicardi syndrome (AS) is still unclear. Palliative surgical treatment, including vagus nerve stimulation and corpus callosotomy, has therefore been used. There is limited data on the role of resective epilepsy surgery as a treatment choice in patients with AS. Here, we describe the seizures, anatomo-pathological findings, and neurodevelopmental outcome of palliative epilepsy surgery in two children with AS who had resective epilepsy surgery at the Cleveland Clinic. The related literature is also reviewed. Case 1 had a left functional hemispherectomy and was free of seizures and hypsarrhythmia for six months after surgery. Her gross motor skills improved after surgery. Outcome at 43 months was 1-3 isolated spasms per day. Case 2 had a right fronto-parietal lobectomy. Her seizures improved in frequency and severity, but remained daily after epilepsy surgery. Neurodevelopment changes included improved alertness and recognition of caregivers. This patient died 21 months after epilepsy surgery of unclear causes. Surgical pathology in both cases showed focal cortical dysplasia associated with other findings, such as nodular heterotopia and polymicrogyria. Epilepsy surgery could be an alternative palliative treatment choice in selective cases of AS, but studies on a larger patient cohort are needed to identify the possible role of surgery in children with AS. The complexity of the pathological findings may offer an explanation for the severity of seizures in AS.

Objective:This retrospective, observational study examined the frequency and magnitude of change in naming ability as a function of side/site of epilepsy surgery and identified predictive factors to assist clinicians in identifying patients at low, moderate, or high risk of postoperative naming decline.Methods:A total of 875 adults with pharmacoresistant epilepsy (454 left/421 right; 763 temporal/87 frontal/25 posterior quadrant) met inclusion criteria and completed the Boston Naming Test before and after surgery. Clinically meaningful change in naming ability was assessed using reliable change indices for epilepsy. Demographic, cognitive, and seizure variables were examined to determine factors most predictive of naming decline and to develop a decision tree to assist with clinical decision-making.Results:Naming decline was rare in right-sided resections and did not exceed the level expected by chance (5% overall; 90% confidence interval [CI] ± 2%). Naming decline occurred in 41% (CI ± 5%) of patients after left temporal resection (TLR) compared to 10%–12% (CI ± 10%–19%) in other left-sided surgical groups. A sizable proportion of left TLR patients (17%; CI ± 4%) showed substantial declines in naming (>11 points). Decline following left TLR was related to later age at seizure onset, older age at surgery, and higher preoperative naming ability. These factors correctly predicted naming decline in 68% of patients and were associated with degree of decline following left TLR. A decision tree is provided to assist clinicians in identifying patients at low, moderate, or high risk for postoperative naming declines.Conclusions:In addition to discussions regarding risk for memory decline following left TLR, patients should be counseled about potential decline in word-finding ability.