Epilepsy Surgery Patients Research Articles

Somatic variant analysis of resected brain tissue in epilepsy surgery patients.

We studied the distribution of germline and somatic variants in epilepsy surgery patients with (suspected) malformations of cortical development (MCD) who underwent surgery between 2015 and 2020 at University Medical Center Utrecht (the Netherlands) and pooled our data with four previously published cohort studies. Tissue analysis yielded a pathogenic variant in 203 of 663 (31%) combined cases. In 126 of 379 (33%) focal cortical dysplasia (FCD) type II cases and 23 of 37 (62%) hemimegalencephaly cases, a pathogenic variant was identified, mostly involving the mTOR signaling pathway. Pathogenic variants in 10 focal epilepsy genes were found in 48 of 178 (27%) FCDI/mild MCD/mMCD with oligodendroglial hyperplasia and epilepsy cases; 36 of these (75%) were SLC35A2 variants. Six of 69 (9%) patients without a histopathological lesion had a pathogenic variant in SLC35A2 (n = 5) or DEPDC5 (n = 1). A germline variant in blood DNA was confirmed in all cases with a pathogenic variant in tissue, with a variant allele frequency (VAF) of ~50%. In seven of 114 patients (6%) with a somatic variant in tissue, mosaicism in blood was detected. More than half of pathogenic somatic variants had a VAF < 5%. Further analysis of the correlation between genetic variants and surgical outcomes will improve patient counseling and may guide postoperative treatment decisions.

Machine learning for (non–)epileptic tissue detection from the intraoperative electrocorticogram

ObjectiveClinical visual intraoperative electrocorticography (ioECoG) reading intends to localize epileptic tissue and improve epilepsy surgery outcome. We aimed to understand whether machine learning (ML) could complement ioECoG reading, how subgroups affected performance, and which ioECoG features were most important. MethodsWe included 91 ioECoG-guided epilepsy surgery patients with Engel 1A outcome. We allocated 71 training and 20 test set patients. We trained an extra trees classifier (ETC) with 14 spectral features to classify ioECoG channels as covering resected or non-resected tissue. We compared the ETC’s performance with clinical ioECoG reading and assessed whether patient subgroups affected performance. Explainable artificial intelligence (xAI) unveiled the most important ioECoG features learnt by the ETC. ResultsThe ETC outperformed clinical reading in five test set patients, was inferior in six, and both were inconclusive in nine. The ETC performed best in the tumor subgroup (area under ROC curve: 0.84 [95%CI 0.79–0.89]). xAI revealed predictors of resected (relative theta, alpha, and fast ripple power) and non-resected tissue (relative beta and gamma power). ConclusionsCombinations of subtle spectral ioECoG changes, imperceptible by the human eye, can aid healthy and pathological tissue discrimination. SignificanceML with spectral ioECoG features can support, rather than replace, clinical ioECoG reading, particularly in tumors.

Outcomes of epilepsy surgery in patients with diffuse gliomas of the brain

Outcomes of epilepsy surgery in patients with diffuse gliomas of the brain

Seizure freedom but not epilepsy surgery is associated with fewer neuropsychiatric difficulties in patients with tuberous sclerosis

BackgroundDrug-resistant epilepsy (DRE) in selected individuals with the rare tuberous sclerosis complex (TSC) may benefit from resective epilepsy surgery. Furthermore, associated neuropsychiatric disorders (TAND) are common in patients with TSC; however, long-term data on how surgery affects neuropsychiatric comorbidities are sparse. Materials and methodsTwo retrospective approaches were used to identify children with TSC and DRE with onset at < 18 years of age. The study group (surgical) was identified through the Swedish National Epilepsy Surgery Registry (n = 17), a registry with complete national coverage since 1990 and prospective patient enrolment since 1995. The reference group (non-surgical) was identified by searching medical records retrieved from the tertiary hospital of Southern Sweden (n = 52). Eligible participants were invited to complete the validated TAND lifetime checklist. Those who did not complete the checklist, never had DRE, or were aged < 7 years old were excluded from the study. The reference group was balanced with the study group for putative confounders, in the following hierarchical order: DRE at the survey, age at seizure onset, age at follow-up, and sex. ResultsAfter the balancing procedure, both groups comprised 13 participants. The median time from epilepsy onset to the survey was 18.5 (range: 7.75–40.25) and 16.0 (7.33–33.5) years in the study and reference groups, respectively. The median time from surgery to the survey was 13 years (range: 4–22). No significant differences were found in behavioural problems, autism spectrum disorder diagnosis or symptoms, or intellectual disability between the groups, regardless of surgery. Seizure-free individuals (n = 11) performed better in social skills (p = 0.016), intellectual skills (p = 0.029), and overall TAND scores (p = 0.005) than the non-seizure-free group (n = 15). ConclusionThis is the first study to evaluate TAND comorbidities during the long-term follow-up after epilepsy surgery in patients with TSC. We found no evidence of the adverse effects of TAND comorbidities after tuberectomy. However, a larger study that allows for a better adjustment for confounders is needed. Following previous studies, seizure-free individuals had fewer symptoms within most TAND domains compared with the group with uncontrolled epilepsy, indicating less severe symptomatology.

Association of Localizing 18F-FDG-PET Hypometabolism and Outcome Following Epilepsy Surgery: Systematic Review and Meta-Analysis.

Although commonly used in the evaluation of patients for epilepsy surgery, the association between the detection of localizing 18fluorine fluorodeoxyglucose PET (18F-FDG-PET) hypometabolism and epilepsy surgery outcome is uncertain. We conducted a systematic review and meta-analysis to determine whether localizing 18F-FDG-PET hypometabolism is associated with favorable outcome after epilepsy surgery. A systematic literature search was undertaken. Eligible publications included evaluation with 18F-FDG-PET before epilepsy surgery, with ≥10 participants, and those that reported surgical outcome at ≥12 months. Random-effects meta-analysis was used to calculate the odds of achieving a favorable outcome, defined as Engel class I, International League Against Epilepsy class 1-2, or seizure-free, with localizing 18F-FDG-PET hypometabolism, defined as concordant with the epilepsy surgery resection zone. Meta-regression was used to characterize sources of heterogeneity. The database search identified 8,916 studies, of which 98 were included (total patients n = 4,104). Localizing 18F-FDG-PET hypometabolism was associated with favorable outcome after epilepsy surgery for all patients with odds ratio (OR) 2.68 (95% CI 2.08-3.45). Subgroup analysis yielded similar findings for those with (OR 2.64, 95% CI 1.54-4.52) and without epileptogenic lesion detected on MRI (OR 2.49, 95% CI 1.80-3.44). Concordance with EEG (OR 2.34, 95% CI 1.43-3.83), MRI (OR 1.69, 95% CI 1.19-2.40), and triple concordance with both (OR 2.20, 95% CI 1.32-3.64) was associated with higher odds of favorable outcome. By contrast, diffuse 18F-FDG-PET hypometabolism was associated with worse outcomes compared with focal hypometabolism (OR 0.34, 95% CI 0.22-0.54). Localizing 18F-FDG-PET hypometabolism is associated with favorable outcome after epilepsy surgery, irrespective of the presence of an epileptogenic lesion on MRI. The extent of 18F-FDG-PET hypometabolism provides additional information, with diffuse hypometabolism associated with worse surgical outcome than focal 18F-FDG-PET hypometabolism. These findings support the incorporation of 18F-FDG-PET into routine noninvasive investigations for patients being evaluated for epilepsy surgery to improve epileptogenic zone localization and to aid patient selection for surgery.

Successful epilepsy surgery in two cases with multiple sclerosis.

Brain surgery is the only curative treatment for people with focal epilepsy, but it is unclear whether this induces active disease in multiple sclerosis (MS). This creates a barrier to evaluate MS patients for epilepsy surgery. We present two cases of successful epilepsy surgery in patients with pharmacoresistant epilepsy and stable MS and give an overview of the existing literature. (1) a 28-year-old woman with seizures arising from a right basal temporo-occipital ganglioglioma was seizure-free after surgery, without MS relapse but with one new MS lesion postsurgically. (2) a 46-year-old woman with seizures arising from a natalizumab-associated progressive multifocal leukoencephalopathy (PML) lesion in the right frontal lobe was seizure-free after surgery preceded by extraoperative subdural electrocorticography, with new subclinical MS lesions. We are the first to report brain surgery in a PML survivor. Both patients stabilized radiologically after initiating second-line therapies. Successful epilepsy surgery can substantially increase the quality of life in patients with pharmacoresistant epilepsy and MS. With increasing survival rates of brain tumors and PML, the risk-benefit ratio of epilepsy surgery compared to a potential MS relapse after surgery becomes critically important. Shared decision-making is valuable for balancing the risks related to both diseases.

Intracranial EEG Structure-Function Coupling and Seizure Outcomes After Epilepsy Surgery.

Surgery is an effective treatment for drug-resistant epilepsy, which modifies the brain's structure and networks to regulate seizure activity. Our objective was to examine the relationship between brain structure and function to determine the extent to which this relationship affects the success of the surgery in controlling seizures. We hypothesized that a stronger association between brain structure and function would lead to improved seizure control after surgery. We constructed functional and structural brain networks in patients with drug-resistant focal epilepsy by using presurgery functional data from intracranial EEG (iEEG) recordings, presurgery and postsurgery structural data from T1-weighted MRI, and presurgery diffusion-weighted MRI. We quantified the relationship (coupling) between structural and functional connectivity by using the Spearman rank correlation and analyzed this structure-function coupling at 2 spatial scales: (1) global iEEG network level and (2) individual iEEG electrode contacts using virtual surgeries. We retrospectively predicted postoperative seizure freedom by incorporating the structure-function connectivity coupling metrics and routine clinical variables into a cross-validated predictive model. We conducted a retrospective analysis on data from 39 patients who met our inclusion criteria. Brain areas implanted with iEEG electrodes had stronger structure-function coupling in seizure-free patients compared with those with seizure recurrence (p = 0.002, d = 0.76, area under the receiver operating characteristic curve [AUC] = 0.78 [95% CI 0.62-0.93]). Virtual surgeries on brain areas that resulted in stronger structure-function coupling of the remaining network were associated with seizure-free outcomes (p = 0.007, d = 0.96, AUC = 0.73 [95% CI 0.58-0.89]). The combination of global and local structure-function coupling measures accurately predicted seizure outcomes with a cross-validated AUC of 0.81 (95% CI 0.67-0.94). These measures were complementary to other clinical variables and, when included for prediction, resulted in a cross-validated AUC of 0.91 (95% CI 0.82-1.0), accuracy of 92%, sensitivity of 93%, and specificity of 91%. Our study showed that the strength of structure-function connectivity coupling may play a crucial role in determining the success of epilepsy surgery. By quantitatively incorporating structure-function coupling measures and standard-of-care clinical variables into presurgical evaluations, we may be able to better localize epileptogenic tissue and select patients for epilepsy surgery. This is a Class IV retrospective case series showing that structure-function mapping may help determine the outcome from surgical resection for treatment-resistant focal epilepsy.

Interictal High-Frequency Oscillations, Spikes, and Connectivity Profiles: a Fingerprint of Epileptogenic Brain Pathologies.

Focal cortical dysplasia (FCD), hippocampal sclerosis (HS), nonspecific gliosis (NG), and normal tissue (NT) comprise the majority of histopathological results of surgically treated drug-resistant epilepsy patients. Epileptic spikes, high-frequency oscillations (HFOs), and connectivity measures are valuable biomarkers of epileptogenicity. The question remains whether they could also be utilized for pre-resective differentiation of the underlying brain pathology. This study explored spikes and HFOs together with functional connectivity in various epileptogenic pathologies. Interictal awake SEEG recordings of 33 patients with focal drug-resistant epilepsy with seizure-free postoperative outcomes were analyzed (15 FCD, 8 HS, 6 NT, and 4 NG). Interictal spikes and HFOs were automatically identified in the channels contained in the overlap of seizure onset zone (SOZ) and resected tissue. Functional connectivity measures (relative entropy, linear correlation, cross-correlation, and phase consistency) were computed for neighboring electrode pairs. Statistically significant differences were found between the individual pathologies in HFO rates, spikes, and their characteristics, together with functional connectivity measures with the highest values in the case of HS and NG/NT. A model to predict brain pathology based on all interictal measures achieved up to 84.0% prediction accuracy. The electrophysiological profile of the various epileptogenic lesions in epilepsy surgery patients was analyzed. Based on this profile, a predictive model was developed. This model offers excellent potential to identify the nature of the underlying lesion prior to resection. If validated, this model may be particularly valuable for counseling patients, as depending on the lesion type, different outcomes are achieved after epilepsy surgery.

Epilepsy surgery in patients with hypothalamic hamartomas - Population-based two-year and long-term outcomes.

Hypothalamic hamartomas are benign lesions associated with drug resistant epilepsy. Surgical treatment has become an increasingly utilised approach with promising results. This study aims to evaluate seizure outcome and complications after surgery in a population-based series of patients with intractable epilepsy and hypothalamic hamartoma. All patients with hypothalamic hamartoma treated with epilepsy surgery in Sweden since 1995 with at least two years of follow-up were included. Preoperative, two-, five- and ten-year prospective longitudinal data were collected from The Swedish National Epilepsy Surgery Register. Data included seizure types and frequency, duration of epilepsy, clinical characteristics, neurological deficits, cognitive level and complications. In a subgroup from Gothenburg, we also analysed data not included in the register such as classification of hamartomas, surgical procedures and gelastic seizures. Eighteen patients were operated on during the period 1995-2020. The median age at epilepsy onset was 6 months and age at surgery 13 years. Four were seizure free and another four had ≥75% reduction in seizure frequency at the two-year follow-up. Two of the 13 patients with a long-term follow-up (five or ten years) were seizure-free and four had ≥75% reduction in seizure frequency. Three had an increased seizure frequency. No major complications were seen. Five had minor complications. In the Gothenburg subgroup all had open pterional disconnection or intraventricular endoscopic disconnection. Six of 12 were free from gelastic seizures at the two-year follow-up and six of eight at the long-term follow-up. This study supports surgical treatment of hypothalamic hamartomas as a safe method with a low risk of permanent complications. The seizure reduction seems to be persistent over time.

Expressional Study of Permeability Glycoprotein and Multidrug Resistance Protein 1 in Drug-resistant Mesial Temporal Lobe Epilepsy.

About 30% of patients with epilepsy do not respond to anti-epileptic drugs, leading to refractory seizures. The pathogenesis of drug-resistance in mesial temporal lobe epilepsy (MTLE) is not completely understood. Increased activity of drug-efflux transporters might be involved, resulting in subclinical concentrations of the drug at the target site. The major drug-efflux transporters are permeability glycoprotein (P-gp) and multidrug-resistance associated protein-1 (MRP-1). The major drawback so far is the expressional analysis of transporters in equal numbers of drug-resistant epileptic tissue and age-matched non-epileptic tissue. We have studied P-gp and MRP-1 drug-efflux transporters in the sclerotic hippocampal tissues resected from the epilepsy surgery patients (n=15) and compared their expression profile with the tissues resected from non-epileptic autopsy cases (n=15). Statistically significant over expression of both P-gp (P<0.0001) and MRP-1 (P=0.01) at gene and protein levels were found in the MTLE cases. The fold change of P-gp was more pronounced than MRP-1. Immunohistochemistry of the patient group showed increased immunoreactivity of P-gp at blood-brain barrier and increased reactivity of MRP-1 in the parenchyma. The results were confirmed by confocal immunofluorescence microscopy. Our results suggested that P-gp in association with MRP-1 might be responsible for the multi-drug resistance in epilepsy. P-gp and MRP-1 could be important determinants of bio availability and tissue distribution of anti-epileptic drugs in the brain which can pharmacologically inhibited to achieve optimal drug penetration to target site.

Comparing vagus nerve stimulation and resective surgery outcomes in patients with co-occurring autism and epilepsy to patients with epilepsy alone: A population-based study.

Autism and epilepsy commonly co-occur. Understanding trends in healthcare utilization and in-hospital outcomes amongst patients with autism and epilepsy can help optimize care and reduce costs. We compared hospital outcomes amongst patients with autism and epilepsy to those with epilepsy alone undergoing vagus nerve stimulation (VNS) and resective/disconnective surgery. Differences in discharge status, in-hospital mortality, mean length of stay (LOS), cost and surgical/medical complications were examined. Elective surgical admissions amongst patients with epilepsy alone and co-occurring autism and epilepsy were identified in the 2003-14 National Inpatient Sample (NIS) using previously validated ICD-9-CM case definitions. One patient with co-occurring epilepsy and autism was matched to three epilepsy patients for age, sex and (1) VNS and (2) resective/disconnective surgery. Multinomial logistic regressions were performed to examine the outcomes of interest. Data were collected on: (1) VNS-52 (mean age: 12.79 ± 1.03; 19.27% female) hospital admissions in persons with comorbid autism and epilepsy, 156 (mean age: 12.84 ± 0.71; 19.31% female) matched controls with epilepsy alone; (2) resective/disconnective surgery-113 (mean age: 12.99 ± 0.84; 24.55% female) with comorbid autism and epilepsy, 339 (mean age: 13.37 ± 0.68; 23.86% female) matched controls with epilepsy alone. Compared to patients with epilepsy alone, patients with autism and epilepsy who underwent either surgery showed no differences for in-hospital mortality, discharge status, mean LOS, hospitalization cost, and surgical/medical complications. Our study shows the feasibility and safety of epilepsy VNS and resective surgery in those with ASD do not differ with those with epilepsy alone, contrary to the prevalent safety concerns of epilepsy surgery in patients with ASD.

Electrical Source Imaging of Somatosensory Evoked Potentials from Intracranial EEG Signals.

Stereoelectroencephalography (SEEG) records electrical brain activity with intracerebral electrodes. However, it has an inherently limited spatial coverage. Electrical source imaging (ESI) infers the position of the neural generators from the recorded electric potentials, and thus, could overcome this spatial undersampling problem. Here, we aimed to quantify the accuracy of SEEG ESI under clinical conditions.We measured the somatosensory evoked potential (SEP) in SEEG and in high-density EEG (HD-EEG) in 20 epilepsy surgery patients. To localize the source of the SEP, we employed standardized low resolution brain electromagnetic tomography (sLORETA) and equivalent current dipole (ECD) algorithms.Both sLORETA and ECD converged to similar solutions. Reflecting the large differences in the SEEG implantations, the localization error also varied in a wide range from 0.4 to 10cm. The SEEG ESI localization error was linearly correlated with the distance from the putative neural source to the most activated contact.We show that it is possible to obtain reliable source reconstructions from SEEG under realistic clinical conditions, provided that the high signal fidelity recording contacts are sufficiently close to the source of the brain activity.

Contralateral hippocampal sclerosis following functional hemispherectomy in children: A report of three cases

PurposeHippocampal Sclerosis (HS) may co-exist with temporal or extratemporal lesions (dual pathology) in children and is usually ipsilateral to the radiological lesion. Here were report three cases with extensive hemispheric cortical malformation and drug resistant epilepsy who had persistent seizures after functional hemispherectomy (FH) and developed contralateral HS after the surgery. MethodsThis retrospective study enrolled children who underwent FH and developed contralateral HS after surgery. Their clinical, EEG, radiological and pathological data were reviewed and summarized. ResultsNinety-five children underwent FH during the study period; Three cases (3.2%) were eligible. They all had unilateral extensive hemispheric cortical malformation who underwent FH between 3 and 5 months of age with no clinical, EEG or radiological suggestion for involvement of contralateral hemisphere prior to FH. All three patients had persisting seizures after FH. Contralateral HS was detected between 2.2 to 3.7 years after FH in all three cases. Two of the patients showed pathogenic variants in GATOR1 pathway genes. ConclusionsThe genesis of contralateral HS in the reported patients remains unexplained. The presence and distribution of “second-hit” somatic mutations may play an important role in governing the seizure outcomes of epilepsy surgery in patients with apparently unilateral malformations of cortical development.

The prevalence and risk factors of coagulopathy in pediatric patients undergoing surgery for epilepsy.

Hematological consequences of novel antiseizure medications (ASMs) or combined therapies are rarely reported, especially in pediatric patients undergoing surgery for epilepsy. This study aimed to assess the prevalence and risk factors of coagulation dysfunction in this population and evaluate their relationship with intra- and postoperative bleeding. Three hundred ninety children who underwent surgery for epilepsy and 104 children without epilepsy who underwent nonepilepsy surgery at the authors' center were included in the study. The authors retrospectively collected and analyzed the following clinical data: sex, age, weight, course of epilepsy, antiseizure therapy, first laboratory data after admission, and transfusion-related data. ASMs were responsible for the higher incidence of coagulation dysfunction in pediatric epilepsy surgery patients. Low body weight (OR 0.95, 95% CI 0.92-0.98) and valproic acid (VPA) therapy (OR 5.13, 95% CI 3.25-8.22) were the most relevant factors leading to coagulation dysfunction. The most common hematological side effects of VPA were thrombocytopenia and hypofibrinogenemia, whereas low body weight was only associated with hypofibrinogenemia. Both VPA and low body weight increased the need for intra- or postoperative transfusion (p < 0.001). Pediatric epilepsy surgery patients often take multiple ASMs, resulting in an increased incidence of coagulopathy. VPA levels and low body weight were found to be the main influential factors associated with an increased risk of coagulation dysfunction. Platelet and fibrinogen levels were the main indices that were affected. Both VPA and low body weight were relevant to additional surgery-related transfusion, necessitating the need for increased awareness of preoperative coagulopathy before pediatric epilepsy surgery. Clinical trial registration no.: NCT05675254 (ClinicalTrials.gov).

Pediatric epilepsy surgery from 2000 to 2018: Changes in referral and surgical volumes, patient characteristics, genetic testing, and postsurgical outcomes.

Neurosurgery is a safe and effective form of treatment for select children with drug-resistant epilepsy. Still, there is concern that it remains underutilized, and that seizure freedom rates have not improved over time. We investigated referral and surgical practices, patient characteristics, and postoperative outcomes over the past two decades. We performed a retrospective cohort study of children referred for epilepsy surgery at a tertiary center between 2000 and 2018. We extracted information from medical records and analyzed temporal trends using regression analyses. A total of 1443 children were evaluated for surgery. Of these, 859 (402 females) underwent surgical resection or disconnection at a median age of 8.5 years (interquartile range [IQR] = 4.6-13.4). Excluding palliative procedures, 67% of patients were seizure-free and 15% were on no antiseizure medication (ASM) at 1-year follow-up. There was an annual increase in the number of referrals (7%, 95% confidence interval [CI] = 5.3-8.6; p < .001) and surgeries (4% [95% CI = 2.9-5.6], p < .001) over time. Duration of epilepsy and total number of different ASMs trialed from epilepsy onset to surgery were, however, unchanged, and continued to exceed guidelines. Seizure freedom rates were also unchanged overall but showed improvement (odds ratio [OR] 1.09, 95% CI = 1.01-1.18; p = .027) after adjustment for an observed increase in complex cases. Children who underwent surgery more recently were more likely to be off ASMs postoperatively (OR 1.04, 95% CI = 1.01-1.08; p = .013). There was a 17% annual increase (95% CI = 8.4-28.4, p < .001) in children identified to have a genetic cause of epilepsy, which was associated with poor outcome. Children with drug-resistant epilepsy continue to be put forward for surgery late, despite national and international guidelines urging prompt referral. Seizure freedom rates have improved over the past decades, but only after adjustment for a concurrent increase in complex cases. Finally, genetic testing in epilepsy surgery patients has expanded considerably over time and shows promise in identifying patients in whom surgery is less likely to be successful.

Baseline frailty status, not advanced patient age, predicts epilepsy surgery outcomes: An analysis of 696 patients from the NSQIP database

ObjectivePreoperative risk stratification of patients undergoing epilepsy surgery remains challenging. Recently, the efforts to look beyond age alone as an outcomes predictor has resulted in the development of measures of physiological reserve, or ‘frailty indices.’ The most frequently cited index in neurosurgery is the 11-item or 5-item modified frailty index (mFI11 or mFI-5). The present study aimed to use a large national registry to evaluate the effect of frailty (as measured by mFI-5 versus age on postoperative outcomes of patients undergoing epilepsy surgery. MethodsThe National Surgical Quality Improvement Program (NSQIP) database, overseen by the American College of Surgeons (ACS), was used to extract data for patients undergoing epilepsy surgery from 2015 to 2019. Univariate and multivariate analyses for age and mFI-5 were performed for the following 30-day outcomes of extended length of hospital stay (eLOS) and non-home discharge (NHD). The effect sizes were summarized by odds ratio and associated 95 % confidence intervals. Receiver operating characteristic (ROC) curve analysis, including area under the curve (AUC), was used to quantify the discrimination. ResultsUnivariate and multivariate analyses demonstrated that frailty statuses from mFI-5, not age, were significantly predictive of eLOS and NHD. On ROC curve analysis, mFI-5 was a stronger predictor of eLOS (C = 0.59, 95 % CI 0.54–0.64, p < 0.001) and NHD (C = 0.69, 95 % CI 0.64–0.76, p < 0.001) than age (C = 0.53, 95 % CI 0.48–0.58, p = 0.21 and C = 0.53, 95 % CI 0.46–0.59, p = 0.44, respectively). ConclusionFrailty, not age, is an independent risk factor for poor postoperative outcomes, particularly eLOS and NHD, in patients undergoing epilepsy surgery. Usage of mFI-5 for preoperative risk stratification of epilepsy surgery patients can help in prognostication.

Increased number and domain of interlaminar astrocytes in layer I of the temporal cortex in epilepsy.

The functions of the interlaminar astrocytes in layer I of the human cortex are currently unknown. Here, we aimed to explore whether there is any morphological remodelling of interlaminar astrocytes in layer I of the temporal cortex in epilepsy. Tissues were obtained from 17 epilepsy surgery patients and 17 post-mortem age-matched controls. In addition, 10 Alzheimer's disease (AD) patients and 10 age-matched controls were used as the disease control group. Paraffin sections (6μm) and frozen sections (35 or 150 μm) of inferior temporal gyrus tissue were used for immunohistochemistry. With the use of tissue transparency, 3D reconstruction and hierarchical clustering, we performed a quantitative morphological analysis of astrocytes. Upper and lower zones were identified in layer I of the human cortex. Compared with the astrocytes in layers IV-V, layer I interlaminar astrocytes occupied a significantly smaller volume and exhibited shorter and fewer process intersections. Increased Chaslin's gliosis (consisting of types I and II subpial interlaminar astrocytes) and number of glial fibrillary acidic protein (GFAP)-immunoreactive interlaminar astrocytes in layer I of the temporal cortex were confirmed in patients with epilepsy. There was no difference in the number of interlaminar astrocytes in layer I between AD and age-matched control groups. Using tissue transparency and 3D reconstruction technology, the astrocyte domain in the human temporal cortex was classified into four clusters, among which the interlaminar astrocytes in cluster II were more abundant in epilepsy, showing specific topological structures in patients with epilepsy. Furthermore, there was a significant increase in the astrocyte domain of interlaminar cells in layer I of the temporal cortex in patients with epilepsy. The observed significant astrocytic structural remodelling in the temporal cortex of epilepsy patients showed that the astrocyte domain in layer I may play an important role in temporal lobe epilepsy.

Postprocessing of MRIs Using FreeSurfer in Epilepsy Surgery Patients Provides an Excellent Imaging Marker of Hippocampal Sclerosis but Fails to Separate Subtypes

Objective. Histopathological examinations will diminish as minimally invasive epilepsy surgery increasingly replaces open surgery. The objective of this study was to test if visual and computer-aided quantitative analyses of presurgical high-quality 3 Tesla MRIs complying with the International League Against Epilepsy (ILAE) Neuroimaging Task Force recommendations can inform on histopathological diagnosis. Methods. Ninety-two patients from Copenhagen and Oslo University Hospitals fulfilled patient-, imaging-, and histopathological inclusion criteria: 69 patients were diagnosed with hippocampal sclerosis (HS) ILAE type 1 or 2, and 23 patients had normal appearing hippocampi or other histopathology than HS (no-HS). MRIs from 52 healthy controls (HC) were included. Image processing was performed in FreeSurfer v.6.0 with the built-in cross-sectional hippocampal subfield segmentation tool and multimodal MRI input. Volume outputs were used to calculate volume asymmetry ratios (VARs) for whole hippocampus (WH) and subfields. Results. HS patients had significantly larger WH VARs compared to no-HS patients and HC, with a sensitivity = 0.93 and specificity = 1.0 for histopathological HS diagnosis. Visual MRI assessment yielded a sensitivity = 0.90 and specificity = 0.96 for histopathological HS diagnosis. CA1 and CA4 VARs and the number of seizure-free patients were not significantly different in HS ILAE type 1 compared to type 2 patients. Significance. FreeSurfer analyses of presurgical MRIs are excellent at separating patients histopathologically diagnosed with HS from patients with other pathology or normal appearing hippocampi. Using the FreeSurfer hippocampal subfield segmentation tool did not allow for separating HS ILAE subtypes.

An individual data-driven virtual resection model based on epileptic network dynamics in children with intractable epilepsy: a magnetoencephalography interictal activity application.

Epilepsy surgery continues to be a recommended treatment for intractable (medication-resistant) epilepsy; however, 30-70% of epilepsy surgery patients can continue to have seizures. Surgical failures are often associated with incomplete resection or inaccurate localization of the epileptogenic zone. This retrospective study aims to improve surgical outcome through in silico testing of surgical hypotheses through a personalized computational neurosurgery model created from individualized patient's magnetoencephalography recording and MRI. The framework assesses the extent of the epileptic network and evaluates underlying spike dynamics, resulting in identification of one single brain volume as a candidate for resection. Dynamic-locked networks were utilized for virtual cortical resection. This in silico protocol was tested in a cohort of 24 paediatric patients with focal drug-resistant epilepsy who underwent epilepsy surgery. Of 24 patients who were included in the analysis, 79% (19 of 24) of the models agreed with the patient's clinical surgery outcome and 21% (5 of 24) were considered as model failures (accuracy 0.79, sensitivity 0.77, specificity 0.82). Patients with unsuccessful surgery outcome typically showed a model cluster outside of the resected cavity, while those with successful surgery showed the cluster model within the cavity. Two of the model failures showed the cluster in the vicinity of the resected tissue and either a functional disconnection or lack of precision of the magnetoencephalography-MRI overlapping could explain the results. Two other cases were seizure free for 1 year but developed late recurrence. This is the first study that provides in silico personalized protocol for epilepsy surgery planning using magnetoencephalography spike network analysis. This model could provide complementary information to the traditional pre-surgical assessment methods and increase the proportion of patients achieving seizure-free outcome from surgery.

Leveraging expertise and optimizing clinical research: Initial success of a pediatric epilepsy surgery collaborative.

Improve data-driven research to inform clinical decision-making with pediatric epilepsy surgery patients by expanding the Pediatric Epilepsy Research Consortium Epilepsy Surgery (PERC-Surgery) Workgroup to include neuropsychological data. This article reports on the process and initial success of this effort and characterizes the cognitive functioning of the largest multi-site pediatric epilepsy surgery cohort in the United States. Pediatric neuropsychologists from 18 institutions completed surveys regarding neuropsychological practice and the impact of involvement in the collaborative. Neuropsychological data were entered through an online database. Descriptive analyses examined the survey responses and cognitive functioning of the cohort. Statistical analyses examined which patients were evaluated and if composite scores differed by domain, demographics, measures used, or epilepsy characteristics. Positive impact of participation was evident by attendance, survey responses, and the neuropsychological data entry of 534 presurgical epilepsy patients. This cohort, ages 6months to 21 years, were majority White and non-Hispanic, and more likely to have private insurance. Mean intelligence quotient (IQ) scores were below to low average, with weaknesses in working memory and processing speed. Full-scale IQ (FSIQ) was lowest for patients with younger age at seizure onset, daily seizures, and magnetic resonance imaging (MRI) abnormalities. We established a collaborative network and fundamental infrastructure to address questions outlined by the Epilepsy Research Benchmarks. There is a wide range in the age and IQ of patients considered for pediatric epilepsy surgery, yet it appears that social determinants of health impact access to care. Consistent with other national cohorts, this US cohort has a downward shift in IQ associated with seizure severity.