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.
. A 'Virtual resection' consists of computationally simulating the effect of an actual resection on the brain. We validated two functional connectivity based virtual resection methods with the actual ...connectivity measured using post-resection intraoperative recordings.
. A non-linear association index was applied to pre-resection recordings from 11 extra-temporal focal epilepsy patients. We computed two virtual resection strategies: first, a 'naive' one obtained by simply removing from the connectivity matrix the electrodes that were resected; second, a virtual resection with partialization accounting for the influence of resected electrodes on not-resected electrodes. We validated the virtual resections with two analysis: (1) we tested with a Kolmogorov-Smirnov test if the distributions of connectivity values after the virtual resections differed from the actual post-resection connectivity distribution; (2) we tested if the overall effect of the resection measured by contrasting pre-resection and post-resection connectivity values is detectable with the virtual resection approach using a Kolmogorv-Smirnov test.
. The estimation of post-resection connectivity values did not succeed for both methods. In the second analysis, the naive method failed completely to detect the effect found between pre-resection and post-resection connectivity distributions, while the partialization method agreed with post-resection measurements in detecting a drop connectivity compared to pre-resection recordings. Our findings suggest that the partialization technique is superior to the naive method in detecting the overall effect after the resection.
. We pointed out how a realistic validation based on actual post-resection recordings reveals that virtual resection methods are not yet mature to inform the clinical decision-making.
Signal analysis biomarkers, in an intra-operative setting, may be complementary tools to guide and tailor the resection in drug-resistant focal epilepsy patients. Effective assessment of biomarker ...performances are needed to evaluate their clinical usefulness and translation. We defined a realistic ground-truth scenario and compared the effectiveness of different biomarkers alone and combined to localize epileptogenic tissue during surgery. We investigated the performances of univariate, bivariate and multivariate signal biomarkers applied to 1 min inter-ictal intra-operative electrocorticography to discriminate between epileptogenic and non-epileptogenic locations in 47 drug-resistant people with epilepsy (temporal and extra-temporal) who had been seizure-free one year after the operation. The best result using a single biomarker was obtained using the phase-amplitude coupling measure for which the epileptogenic tissue was localized in 17 out of 47 patients. Combining the whole set of biomarkers provided an improvement of the performances: 27 out of 47 patients. Repeating the analysis only on the temporal-lobe resections we detected the epileptogenic tissue in 29 out of 30 combining all the biomarkers. We suggest that the assessment of biomarker performances on a ground-truth scenario is required to have a proper estimate on how biomarkers translate into clinical use. Phase-amplitude coupling seems the best performing single biomarker and combining biomarkers improves localization of epileptogenic tissue. Performance achieved is not adequate as a tool in the operation theater yet, but it can improve the understanding of pathophysiological process.
Intraoperative electrocorticography is used to tailor epilepsy surgery by analysing interictal spikes or spike patterns that can delineate epileptogenic tissue. High-frequency oscillations (HFOs) on ...intraoperative electrocorticography have been proposed as a new biomarker of epileptogenic tissue, with higher specificity than spikes. We prospectively tested the non-inferiority of HFO-guided tailoring of epilepsy surgery to spike-guided tailoring on seizure freedom at 1 year.
The HFO trial was a randomised, single-blind, adaptive non-inferiority trial at an epilepsy surgery centre (UMC Utrecht) in the Netherlands. We recruited children and adults (no age limits) who had been referred for intraoperative electrocorticography-tailored epilepsy surgery. Participants were randomly allocated (1:1) to either HFO-guided or spike-guided tailoring, using an online randomisation scheme with permuted blocks generated by an independent data manager, stratified by epilepsy type. Treatment allocation was masked to participants and clinicians who documented seizure outcome, but not to the study team or neurosurgeon. Ictiform spike patterns were always considered in surgical decision making. The primary endpoint was seizure outcome after 1 year (dichotomised as seizure freedom defined as Engel 1A–B vs seizure recurrence Engel 1C–4). We predefined a non-inferiority margin of 10% risk difference. Analysis was by intention to treat, with prespecified subgroup analyses by epilepsy type and for confounders. This completed trial is registered with the Dutch Trial Register, Toetsingonline ABR.NL44527.041.13, and ClinicalTrials.gov, NCT02207673.
Between Oct 10, 2014, and Jan 31, 2020, 78 individuals were enrolled to the study and randomly assigned (39 to HFO-guided tailoring and 39 to spike-guided tailoring). There was no loss to follow-up. Seizure freedom at 1 year occurred in 26 (67%) of 39 participants in the HFO-guided group and 35 (90%) of 39 in the spike-guided group (risk difference –23·5%, 90% CI –39·1 to –7·9; for the 48 patients with temporal lobe epilepsy, the risk difference was –25·5%, –45·1 to –6·0, and for the 30 patients with extratemporal lobe epilepsy it was –20·3%, –46·0 to 5·4). Pathology associated with poor prognosis was identified as a confounding factor, with an adjusted risk difference of –7·9% (90% CI –20·7 to 4·9; adjusted risk difference –12·5%, –31·0 to 5·9, for temporal lobe epilepsy and 5·8%, –7·7 to 19·5, for extratemporal lobe epilepsy). We recorded eight serious adverse events (five in the HFO-guided group and three in the spike-guided group) requiring hospitalisation. No patients died.
HFO-guided tailoring of epilepsy surgery was not non-inferior to spike-guided tailoring on intraoperative electrocorticography. After adjustment for confounders, HFOs show non-inferiority in extratemporal lobe epilepsy. This trial challenges the clinical value of HFOs as an epilepsy biomarker, especially in temporal lobe epilepsy. Further research is needed to establish whether HFO-guided intraoperative electrocorticography holds promise in extratemporal lobe epilepsy.
UMCU Alexandre Suerman, EpilepsieNL, RMI Talent Fellowship, European Research Council, and MING Fund.
The 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.
The 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).
Ten 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).
In 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.
Objective
We aimed to evaluate determinants of functional outcome after pediatric hemispherotomy in a large and recent multicenter cohort.
Methods
We retrospectively investigated the functional ...outcomes of 455 children who underwent hemispherotomy at 5 epilepsy centers in 2000–2016. We identified determinants of unaided walking, voluntary grasping with the hemiplegic hand, and speaking through Bayesian multivariable regression modeling using missing data imputation.
Results
Seventy‐five percent of children were seizure‐free, and 44% stopped antiseizure medication at a 5.1‐year mean follow‐up (range = 1–17.1). Seventy‐seven percent of children could walk unaided, 8% could grasp voluntarily, and 68% could speak at the last follow‐up. Children were unlikely to walk when they had contralateral magnetic resonance imaging (MRI) abnormalities (40/73, p = 0.04), recurrent seizures following hemispherotomy (62/109, p = 0.04), and moderately (50/61, p = 0.03) or severely impaired (127/199, p = 0.001) postsurgical intellectual functioning, but were likely to walk when they were older at outcome determination (p = 0.01). Children were unlikely to grasp voluntarily with the hand contralateral to surgery when they had Rasmussen encephalitis (0/61, p = 0.001) or Sturge–Weber syndrome (0/32, p = 0.007). Children were unlikely to speak when they had contralateral MRI abnormalities (30/69, p = 0.002) and longer epilepsy duration (p = 0.01), but likely to speak when they had Sturge–Weber syndrome (29/35, p = 0.01), were older at surgery (p = 0.04), and were older at outcome determination (p < 0.001).
Interpretation
Etiology and bilaterality of structural brain abnormalities were key determinants of functional outcome after hemispherotomy. Longer epilepsy duration affected language outcomes. Not surprisingly, walking and talking ability increased with older age at outcome evaluation. ANN NEUROL 2024;95:377–387
The aim of this study is to determine whether the use of 7 tesla (T) MRI in clinical practice leads to higher detection rates of focal cortical dysplasias in possible candidates for epilepsy surgery.
...In our center patients are referred for 7 T MRI if lesional focal epilepsy is suspected, but no abnormalities are detected at one or more previous, sufficient-quality lower-field MRI scans, acquired with a dedicated epilepsy protocol, or when concealed pathology is suspected in combination with MR-visible mesiotemporal sclerosis-dual pathology. We assessed 40 epilepsy patients who underwent 7 T MRI for presurgical evaluation and whose scans (both 7 T and lower field) were discussed during multidisciplinary epilepsy surgery meetings that included a dedicated epilepsy neuroradiologist. We compared the conclusions of the multidisciplinary visual assessments of 7 T and lower-field MRI scans.
In our series of 40 patients, multidisciplinary evaluation of 7 T MRI identified additional lesions not seen on lower-field MRI in 9 patients (23%). These findings were guiding in surgical planning. So far, 6 patients underwent surgery, with histological confirmation of focal cortical dysplasia or mild malformation of cortical development.
Seven T MRI improves detection of subtle focal cortical dysplasia and mild malformations of cortical development in patients with intractable epilepsy and may therefore contribute to identification of surgical candidates and complete resection of the epileptogenic lesion, and thus to postoperative seizure freedom.
•Increased vascular density in white matter in tubers in TSC vs healthy controls.•Increased vascular density in tubers is linked to neuroinflammation.•No significant change in vascular density in ...mMCD and FCD compared to controls.•Higher vascular density in lesional vs. perilesional tissue in mMCD, FCD and tubers.•Vascular density increased with longer epilepsy duration.
Recent studies suggested a possible association between malformations of cortical development and microvascular density. In this study we aimed to further elucidate the relation between microvascular density and cortical developmental abnormalities in a cohort of 97 patients with epilepsy and histologically proven mild malformation of cortical development (mMCD), focal cortical dysplasia (FCD) or tuberous sclerosis complex (TSC). Surgical tissue samples were analyzed with quantitative measures of vessel density, T-cell response, microglial activation and myelin content. Subsequently, the results were compared to an age- and localization matched control group. We observed an increase in microvasculature in white matter of TSC cortical tubers, which is linked to inflammatory response. No increase was seen in mMCD or FCD subtypes compared to controls. In mMCD/FCD and tubers, lesional cortex and white matter showed increased vascular density compared to perilesional tissues. Moreover, cortical vessel density increased with longer epilepsy duration and older age at surgery while in controls it decreased with age. Our findings suggest for that the increase in white matter vascular density might be pathology-specific rather than a consequence of ongoing epileptic activity. Increased cortical vessel density with age and with longer epilepsy duration in mMCD/FCD’s and tubers, however, could be a consequence of seizures.
Abstract
Background
Glioblastoma (GBM) is the most common primary, malignant brain tumour with a 5-year survival of 5%. If possible, a glioblastoma is resected and further treated with chemoradiation ...therapy (CRT), but resection is not feasible in about 30% of cases. Current standard of care in these cases is a biopsy followed by CRT. Magnetic resonance (MR) imaging-guided laser interstitial thermal therapy (LITT) has been suggested as a minimally invasive alternative when surgery is not feasible. However, high-quality evidence directly comparing LITT with standard of care is lacking, precluding any conclusions on (cost-)effectiveness. We therefore propose a multicenter randomized controlled study to assess the (cost-)effectiveness of MR-guided LITT as compared to current standard of care (EMITT trial).
Methods and analysis
The EMITT trial will be a multicenter pragmatic randomized controlled trial in the Netherlands. Seven Dutch hospitals will participate in this study. In total 238 patients will be randomized with 1:1 allocation to receive either biopsy combined with same-session MR-guided LITT therapy followed by CRT or the current standard of care being biopsy followed by CRT. The primary outcomes will be health-related quality of life (HR-QoL) (non-inferiority) using EORTC QLQ-C30 + BN20 scores at 5 months after randomization and overall survival (superiority). Secondary outcomes comprise cost-effectiveness (healthcare and societal perspective) and HR-QoL of life over an 18-month time horizon, progression free survival, tumour response, disease specific survival, longitudinal effects, effects on adjuvant treatment, ablation percentage and complication rates.
Discussion
The EMITT trial will be the first RCT on the effectiveness of LITT in patients with glioblastoma as compared with current standard of care. Together with the Dutch Brain Tumour Patient association, we hypothesize that LITT may improve overall survival without substantially affecting patients’ quality of life.
Trial registration
This trial is registered at ClinicalTrials.gov (NCT05318612).
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