Temporal change of DNA methylation subclasses between matched newly diagnosed and recurrent glioblastoma.

The longitudinal transition of phenotypes is pivotal in glioblastoma treatment resistance and DNA methylation emerged as an important tool for classifying glioblastoma phenotypes. We aimed to characterize DNA methylation subclass heterogeneity during progression and assess its clinical impact. Matched tissues from 47 glioblastoma patients were subjected to DNA methylation profiling, including CpG-site alterations, tissue and serum deconvolution, mass spectrometry, and immunoassay. Effects of clinical characteristics on temporal changes and outcomes were studied. Among 47 patients, 8 (17.0%) had non-matching classifications at recurrence. In the remaining 39 cases, 28.2% showed dominant DNA methylation subclass transitions, with 72.7% being a mesenchymal subclass. In general, glioblastomas with a subclass transition showed upregulated metabolic processes. Newly diagnosed glioblastomas with mesenchymal transition displayed increased stem cell-like states and decreased immune components at diagnosis and exhibited elevated immune signatures and cytokine levels in serum. In contrast, tissue of recurrent glioblastomas with mesenchymal transition showed increased immune components but decreased stem cell-like states. Survival analyses revealed comparable outcomes for patients with and without subclass transitions. This study demonstrates a temporal heterogeneity of DNA methylation subclasses in 28.2% of glioblastomas, not impacting patient survival. Changes in cell state composition associated with subclass transition may be crucial for recurrent glioblastoma targeted therapies.

Multiple craniotomies in a single surgery - the resection of scattered brain metastases.

Patients with brain metastases (BM), who can benefit from resection of multiple scattered lesions, often will not be offered a procedure involving multiple craniotomies in one session due to the overall poor prognosis. However, carefully selected candidates may well benefit from the resection of multiple lesions using multiple craniotomies through a significantly shortened hospital stay, aggressive decompression, and rapid eligibility for adjuvant therapies. In this retrospective analysis, the records of patients, who were treated for multiple BM using one surgical session involving multiple craniotomies, were reviewed. A group of patients with multiple BM, whose surgery only involved one craniotomy, were assigned to a control group. Clinical and surgical characteristics, preoperative and postoperative Karnofsky Performance Scale (KPS), complication rate, preoperative tumor size, number of lesions, number of craniotomies, skin incisions, and intraoperative repositioning of patients were recorded. Thirty-three patients were included in the multiple-craniotomy group. Thirty patients underwent two craniotomies, while three cases involved three craniotomies. Seven patients (21%) were intraoperatively repositioned from a prone to a supine position, which required an average of 23.3 ± 9.3 min from wound closure to the following skin incision. Thirty-six patients with multiple BM and matching characteristics, who received only one craniotomy for the dominant lesion, served as the control group. No difference was detected in postoperative KPS (p = 0.269), complication rate (p = 0.612), rate of new postoperative neurological deficits (p = 0.278), length of intensive care unit (ICU) (p = 0.991), and hospital stay (p = 0.913). There was a significant difference in average preoperative tumor size (p = 0.002), duration of surgery (p < 0.001), and extent of resection (p = 0.002). In the age of personalized medicine, selected patient may benefit from a single surgery for BM using multiple craniotomies. This study shows no significant increase of the perioperative complication rate for surgeries with multiple craniotomies.

Terson Syndrome in Patients with Aneurysmal Subarachnoid Hemorrhage: A 10-Year Single-Center Experience.

BACKGROUND: Terson syndrome (TS), an intraocular hemorrhage associated with aneurysmal subarachnoid hemorrhage (aSAH), occurs in up to 46% of all patients with subarachnoid hemorrhage. Despite its high incidence, TS is underrepresented in the literature, and patients with aSAH are sometimes not systematically evaluated for the presence of TS in clinical practice. This work aims to raise awareness of TS, reevaluate previous scientific findings, describe risk factors associated with the occurrence of TS, and present our local diagnostic and treatment concept. METHODS: All patients with aSAH treated at our institution between October 2010 and May 2020 were included in this retrospective study. The frequency of ophthalmological screening by indirect funduscopy, as well as the results, was investigated. In addition, the collection and statistical analysis of epidemiological and clinical data was performed using χ2, Kruskal-Wallis, and analysis of variance testing; multivariate regression; and receiver operating characteristic analysis. The significance level was set at p < 0.05. RESULTS: A total of 617 patients were treated for aSAH in our institution. Of these, 367 patients (59.5%) were ophthalmologically examined for the presence of TS. The rate of TS in the examined patients was 21.3% (n = 78). Patients with TS had significantly higher Fisher and World Federation of Neurosurgical Societies (WFNS) scores (p < 0.0001). Regression analyses showed WFNS grade (p = 0.003) and the occurrence of seizures (p = 0.002) as independent predictors of TS, as did receiver operating characteristic analyses, which had a significant area under the curve of 0.66 for the combination of WFNS grade and seizures. For 12 (15.4%) patients, the TS had to be surgically treated by pars plana vitrectomy in a total of 14 eyes, which resulted in significant improvement of visual function in all patients: mean preoperative best-corrected visual acuity was 0.03 (± 0.08) versus 0.76 (± 0.21) postoperatively (p < 0.001). CONCLUSIONS: TS is a common complication in patients with aSAH, affecting approximately one in five patients. A higher WFNS grade and the occurrence of seizures are associated with TS; therefore, screening for TS should be performed in these patients.

Diffusion tensor imaging changes in patients with glioma-associated seizures.

INTRODUCTION: Structural white matter changes associated with certain epilepsy subtypes have been demonstrated using diffusion tensor imaging (DTI). This observational study aims to identify potential water diffusion abnormalities in glioma patients with associated seizures. METHODS: Two cohorts from two centers were analyzed independently: (A) Prospectively recruited patients diagnosed with glioma who received preoperative DTI to measure mean diffusivity (MD) and fractional anisotropy (FA) in regions-of-interest (ROIs) including the marginal tumor zone (TU), adjacent peritumoral white matter as well as distant ipsilateral and contralateral white matter and cortex. Data were compared between patients with and without seizures and tested for statistical significance. (B) A retrospective cohort using an alternative technical approach sampling ROIs in contrast enhancement, necrosis, non-enhancing tumor, marginal non-enhancing tumor zone, peritumoral tissue, edema and non-tumorous tissue. RESULTS: (A) The prospective study cohort consisted of 23 patients with 12 (52.2%) presenting with a history of seizures. There were no significant seizure-associated differences in MD or FA for non-tumor white matter or cortical areas. MD-TU was significantly lower in patients with seizures (p = 0.005). (B) In the retrospective cohort consisting of 46 patients with a seizure incidence of 50.0%, significantly decreased normalized values of MD were observed for non-enhancing tumor regions of non-glioblastoma multiforme (GBM) cases in patients with seizures (p = 0.022). CONCLUSION: DTI analyses in glioma patients demonstrated seizure-associated diffusion restrictions in certain tumor-related areas. No other structural abnormalities in adjacent or distant white matter or cortical regions were detected.

Resective epilepsy surgery in patients aged 50years and older - a retrospective study regarding seizure outcome, memory performance, and psychopathology.

PURPOSE: To assess clinical and demographic characteristics in two cohorts of elderly patients with drug-resistant focal epilepsy, undergoing resective epilepsy surgery (RES). Further, to determine seizure, neuropsychological, and mental health outcomes after RES and evaluate possible influencing factors. METHODS: Consecutive patients aged ≥50 years with temporal lobe epilepsy (TLE) who underwent curative RES in the Hamburg epilepsy surgery program (2004-2017) were identified. Data were retrospectively analyzed. Seizure outcome was classified according to ILAE and Engel outcome scales in patients with first-time surgeries and with reoperations. Previously reported predictors of the seizure outcome were evaluated using regression analyses. Changes in verbal memory were assessed for patients with complete pre- and postoperative datasets (n=30) using repeated-measures analysis of variance. For evaluation of possible predictors of psychopathologic changes after RES a regression analysis was conducted. RESULTS: Fifty-one elderly patients underwent RES of the temporal lobe, including twelve aged ≥60 years, and five with reoperations. After one year, 65% of the patients with first-time surgeries were seizure free and 91% had a favorable outcome. At last follow-up, 49% were seizure free since surgery. Three reoperated patients had an Engel I outcome. Seizure outcome was not dependent on age at surgery, duration of epilepsy, or other evaluated variables. There was no significant decline in the memory performance after surgery. Significant improvements in mental health were found. CONCLUSION: RES for drug-resistant TLE is safe, effective, and improves mental health also in patients aged ≥ 50 years. Thus, it should be evaluated as the treatment of choice also in this age group.

Cranial bone flap resorption-pathological features and their implications for clinical treatment.

Cranioplasty following decompressive craniectomy (DC) has a primary complication when using the autologous bone: aseptic bone resorption (ABR). So far, risk factors such as age, number of fragments, and hydrocephalus have been identified but a thorough understanding of the underlying pathophysiology is still missing. The aim of this osteopathological investigation was to gain a better understanding of the underlying processes. Clinical data of patients who underwent surgical revision due to ABR was collected. Demographics, the time interval between craniectomy and cranioplasty, and endocrine serum parameters affecting bone metabolism were collected. Removed specimens underwent qualitative and quantitative histological examination. Two grafts without ABR were examined as controls. Compared to the controls, the typical layering of the cortical and cancellous bone was largely eliminated in the grafts. Histological investigations revealed the coexistence of osteolytic and osteoblastic activity within the necrosis. Bone appositions were distributed over the entire graft area. Remaining marrow spaces were predominantly fibrotic or necrotic. In areas with marrow cavity fibrosis, hardly any new bone tissue was found in the adjacent bone, while there were increased signs of osteoclastic resorption. Insufficient reintegration of the flap may be due to residual fatty bone marrow contained in the bone flap which seems to act as a barrier for osteogenesis. This may obstruct the reorganization of the bone structure, inducing aseptic bone necrosis. Following a path already taken in orthopedic surgery, thorough lavage of the implant to remove the bone marrow may be a possibility, but will need further investigation.

Decision-making in temporal lobe epilepsy surgery based on invasive stereo-electroencephalography (sEEG).

In medical refractory temporal lobe epilepsy (TLE), the epileptogenic zone can be difficult to identify and therefore difficult to treat, especially in the absence of clear MRI pathologies and specific results from presurgical evaluation. Invasive monitoring with stereo-electroencephalography (sEEG) is a tool for a better determination of the epileptogenic zone. Here, we investigate the impact of sEEG on decision-making in temporal lobe epilepsy surgery. We reviewed patients with TLE who underwent further investigation with sEEG in our epilepsy unit. We examined specifically how sEEG findings influenced our decision regarding indication for a surgical procedure and resection volume. From 2013 to 2017, we performed 152 temporal resections in epilepsy patients. Twenty-one of these patients were designated for further preoperative investigation with sEEG due to incongruent findings in presurgical evaluation. Six patients were implanted bitemporally. In five cases, the hypothesis for the epileptogenic zone and localization had to be changed due to sEEG findings and resulted in a different tailored resection than intended. In three cases, sEEG findings led to the cancelation of the originally intended temporal resection as the epileptogenic zone was not definable or bilateral. In another three cases, the prognosis for reduction of seizures postoperatively had to be reduced due to the sEEG findings. However, the resection was performed after interdisciplinary discussion and informed consent of the patient. The examination by sEEG led to a change of plan for further treatment in 13 patients (61.9%) suffering TLE in total. Invasive monitoring with sEEG electrodes had a strong impact on decision-making for further treatment in patients suffering from temporal lobe epilepsy with incongruent findings in presurgical examination designated for epilepsy surgery. This applies to resection volumes as well as to prediction of seizure outcome.

FASN Is a Biomarker Enriched in Malignant Glioma-Derived Extracellular Vesicles.

Extracellular vesicles (EVs) are known for their important role in cancer progression and hold considerable potential as a source for tumor biomarkers. However, purification of tumor-specific EVs from patient plasma is still an urgent unmet need due to contamination by normal host cell-derived EVs, that results in compromised analytical sensitivity. Here we identified fatty acid synthase (FASN), a key lipogenic enzyme which is highly expressed in malignant glioma cells, to be elevated in CD63- and CD81-positive EVs in glioma patient plasma samples, opening vital opportunities to sort brain tumor-specific EVs.

Seizures as presenting symptom in patients with glioblastoma.

OBJECTIVE: The clinical course and underlying molecular causes in patients with glioblastoma presenting with seizures are poorly understood. Here we investigated clinical features and carrier systems as well as a transaminase relevant in glutamate homeostasis in patients with glioblastoma. METHODS: We performed a retrospective analysis of our clinical glioma database for clinical data during a 2-year period. Patients with glioblastoma were divided into 2 groups: symptomatic and asymptomatic for seizures. Magnetic resonance imaging (MRI) scans and tissue samples from both groups were investigated. A Cox regression analysis was performed for survival and clinical and molecular features. RESULTS: One hundred three patients diagnosed with glioblastoma in this period were identified. Twenty-three patients were symptomatic with seizures (22.3%). All were IDH-1/2 wild-type. We found no significant difference in the tumor localization between the groups. Patients with seizures from glioblastoma had significantly smaller tumors, which caused less edema compared to nonepileptogenic tumors. A significantly increased up-regulation of glutamate carrier systems was evident in symptomatic tumors compared to asymptomatic tumors. Moreover, there seems to be an oversupply of glutamate in symptomatic tumors due to dysregulation in glutamate synthesis. SIGNIFICANCE: Glioblastoma presenting with seizures is morphologically different from asymptomatic tumors. Furthermore, we were able to show that the molecular profile of these tumors, particularly glutamate homeostasis controlling systems, is significantly different.

Rate and risk factors for a hyperactivity delirium in patients with aneurysmal subarachnoid haemorrhage.

Hyperactive delirium (agitation) is a common complication in patients on intensive care units and can be assessed by the Richmond Agitation and Sedation Scale (RASS) in principle. However, the role of agitation in patients with aneurysmal subarachnoid haemorrhage (SAH) is poorly understood. We performed a retrospective analysis to identify risk factors for the development of a hyperactive delirium and its functional consequences for neurological outcome. Three hundred thirty-eight patients with SAH were screened in this study resulting in 212 patients which reached at least once a RASS of 0 and were eligible for further analysis. Clinical characteristics were analysed towards the occurrence of a hyperactive delirium. Neurological outcome at discharge and follow-up was assessed using the Glasgow Outcome Scale. Seventy-eight of 212 patients (36.8%) developed a hyperactive delirium; the duration ranged from 1 to 11 days. Multivariate regression revealed initial hydrocephalus (odds ratio (OR) 3.21 95% confidence interval (CI) [1.33-7.70]; p = 0.01), microsurgical clipping (OR 3.70 95%CI 1.71-8.01]; p = 0.001), male gender (OR 1.97 95%CI [1.05-3.85]; p = 0.047) and a higher Graeb score (OR 1.11 95%CI [1.00-1.22]; p = 0.043) to be significantly associated with the development of agitation. Medical history of psychiatric disorders, alcohol or nicotine abuse showed no correlation with agitation. Cox regression analysis revealed no significant influence of agitation towards unfavourable outcome at discharge or follow-up. We provide four independent risk factors for the development of agitation in SAH patients. Our study emphasizes the specific entity of agitation in patients with SAH and underscores its relevance in neurological patients.

Early clinical course after aneurysmal subarachnoid hemorrhage: comparison of patients treated with Woven EndoBridge, microsurgical clipping, or endovascular coiling.

BACKGROUND: The Woven EndoBridge (WEB) device has been increasingly used for the treatment of intracranial aneurysms after aneurysmal subarachnoid hemorrhage (SAH). Still, recent major clinical trials on patient management after SAH have defined WEB embolization as an exclusion criterion. In an analysis of an unselected patient cohort, we evaluate the early clinical course of SAH patients after WEB treatment compared to those treated with endovascular coiling or surgical clipping. METHODS: Data of all patients with proven SAH who were either treated with a WEB device, coil embolization, or neurosurgical clipping between March 2015 and August 2018 was systematically reviewed. Clinical parameters on intensive care unit (ICU), medical history and mortality rates were evaluated and compared between the different treatment approaches. RESULTS: Of all 201 patients included, 107 patients received endovascular coil embolization, 56 patients were treated with clipping and in 38 cases a WEB device was placed. The overall mortality was 17.9%. Thirteen patients (34.2%) in the WEB group had a Hunt and Hess grade > 3. Essential medical factors showed no clinically relevant differences between the treatment groups, and the analyzed blood parameters were predominantly within physiological limits without any relevant outliers. The Hunt and Hess grade but not the treatment modality was identified as independent risk-factor associated with ICU-mortality in the overall cohort (p < 0.001). CONCLUSION: In this study, there was no difference in the early clinical course between those treated with WEB embolization, coil embolization, or neurosurgical clipping. Since WEB embolization is a valuable treatment alternative to coiling, it seems not justified to exclude this procedure from upcoming clinical SAH trials, yet the clinical long-term outcome, aneurysm occlusion, and retreatment rates have to be analyzed in further studies. CLINICAL TRIAL REGISTRATION NUMBER: not applicable.

Neuropsychological performance and seizure control after subsequent anteromesial temporal lobe resection following selective amygdalohippocampectomy.

OBJECTIVE: Selective amygdalohippocampectomy (sAHE) is a well-established treatment for temporal lobe epilepsy, commonly with favorable neuropsychological outcome. Yet, it is still unknown if subsequent resection of the anteromesial temporal lobe (AMTLR), when necessary, deteriorates neuropsychological performance in this selected group of patients. Thus, we evaluated the clinical and neuropsychological data of patients who, due to insufficient seizure control after sAHE, received a subsequent ipsilateral AMTLR and compared these findings with patients who did not receive a second resection (control group). METHODS: Patients' characteristics and neuropsychological data were assessed and analyzed in the reoperated as well as in the control group at each step of treatment. Experienced neuropsychologists conducted the standardized examination focusing on verbal, figural and working memory, speech fluency and attention. Preoperative diagnostics included further continuous video-electroencephalography monitoring, high-resolution magnetic resonance imaging and functional transcranial Doppler sonography. RESULTS: Eighty patients having received sAHE in our center from 11/2007 to 02/2013 were included in this study. Seventeen of these patients underwent subsequent AMTLR. Thirteen of these were available for follow-up after the second surgery and twelve had a comprehensive neuropsychological testing at all three steps. Analyzing the neuropsychological data revealed no significant differences compared with controls. On the individual level, the data demonstrated that improvement in a subdomain was more frequent than decline, if the performance had already deteriorated after the first procedure. Seizure control improved significantly (p < 0.001) in all patients after subsequent AMTLR resulting in seven patients being seizure-free at follow-up. SIGNIFICANCE: Subsequent AMTLR following sAHE can be a safe procedure to improve seizure outcome in selected patients. In our series the risk for further neuropsychological deterioration after the second procedure was low. The neuropsychological performance after the sAHE can be a valuable criterion to advise patients who are eligible for a second surgery on their risk of further cognitive decline.

The simplified acute physiology score II to predict hospital mortality in aneurysmal subarachnoid hemorrhage.

BACKGROUND: Early prediction of increased morbidity and mortality in aneurysmal subarachnoid hemorrhage (aSAH) remains crucial to improving patient management. Most prediction models lack external validation and focus on disease-specific items without considering physiological parameters and the past medical history. The aim was to assess the validity of the established Simplified Acute Physiology Score II (SAPS-II) in an aSAH cohort for the prediction of hospital mortality and to identify additional physiological and clinical predictors. METHODS: The predictive value of SAPS-II for hospital mortality was assessed in a retrospective analysis of 263 consecutive patients with aSAH. Additional physiological and clinical parameters including the past medical history were analyzed by forward selection multivariate analysis to identify independent predictors of hospital mortality and to improve the prediction model. RESULTS: The SAPS-II predicted hospital mortality with an area under the curve (AUC) of 0.834 with an odds ratio (OR) of 1.097 [95 % confidence interval 1.067-1.128) for each additional point. Forward selection multivariate analysis identified the Glasgow Coma Scale score (P < 0.001), history of chronic headache (P = 0.01) and medication with anticoagulants (P = 0.04) as independent predictors of hospital mortality. Adding these parameters to the SAPS-II, the AUC increased to 0.86. CONCLUSION: This study validates the predictive accuracy of SAPS-II for hospital mortality in aSAH patients. Additional parameters from the past medical history increase its predictive power. From a practical viewpoint, SAPS-II alone already represents a sufficient and powerful score to predict hospital mortality at an early time point and may help to improve patient management.

Development and prospective clinical validation of a convolutional neural network for automated detection and segmentation of focal cortical dysplasias.

PURPOSE: Focal cortical dysplasias (FCDs) are a leading cause of drug-resistant epilepsy. Early detection and resection of FCDs have favorable prognostic implications for postoperative seizure freedom. Despite advancements in imaging methods, FCD detection remains challenging. House et al. (2021) introduced a convolutional neural network (CNN) for automated FCD detection and segmentation, achieving a sensitivity of 77.8%. However, its clinical applicability was limited due to a low specificity of 5.5%. The objective of this study was to improve the CNN's performance through data-driven training and algorithm optimization, followed by a prospective validation on daily-routine MRIs. MATERIAL AND METHODS: A dataset of 300 3 T MRIs from daily clinical practice, including 3D T1 and FLAIR sequences, was prospectively compiled. The MRIs were visually evaluated by two neuroradiologists and underwent morphometric assessment by two epileptologists. The dataset included 30 FCD cases (11 female, mean age: 28.1 ± 10.1 years) and a control group of 150 normal cases (97 female, mean age: 32.8 ± 14.9 years), along with 120 non-FCD pathological cases (64 female, mean age: 38.4 ± 18.4 years). The dataset was divided into three subsets, each analyzed by the CNN. Subsequently, the CNN underwent a two-phase-training process, incorporating subset MRIs and expert-labeled FCD maps. This training employed both classical and continual learning techniques. The CNN's performance was validated by comparing the baseline model with the trained models at two training levels. RESULTS: In prospective validation, the best model trained using continual learning achieved a sensitivity of 90.0%, specificity of 70.0%, and accuracy of 72.0%, with an average of 0.41 false positive clusters detected per MRI. For FCD segmentation, an average Dice coefficient of 0.56 was attained. The model's performance improved in each training phase while maintaining a high level of sensitivity. Continual learning outperformed classical learning in this regard. CONCLUSIONS: Our study presents a promising CNN for FCD detection and segmentation, exhibiting both high sensitivity and specificity. Furthermore, the model demonstrates continuous improvement with the inclusion of more clinical MRI data. We consider our CNN a valuable tool for automated, examiner-independent FCD detection in daily clinical practice, potentially addressing the underutilization of epilepsy surgery in drug-resistant focal epilepsy and thereby improving patient outcomes.

Short post-injection seizure duration is associated with reduced power of ictal brain perfusion SPECT to lateralize the seizure onset zone.

BACKGROUND: The aim of this study was to assess the impact of the post-injection electrical seizure duration on the identification of the seizure onset zone (SOZ) in ictal brain perfusion SPECT in presurgical evaluation of drug-resistant epilepsy. METHODS: 176 ictal SPECT performed with 99mTc-HMPAO (n = 140) or -ECD (n = 36) were included retrospectively. Visual interpretation of the SPECT images (together with individual MRI and statistical hyperperfusion maps) with respect to lateralization (right, left, none) and localization (temporal, frontal, parietal, occipital) of the SOZ was performed by 3 independent readers. Between-readers agreement was characterized by Fleiss' κ. An ictal SPECT was considered "lateralizing" if all readers agreed on right or left hemisphere. It was considered "localizing" if it was lateralizing and all readers agreed on the same lobe within the same hemisphere. The impact of injection latency and post-injection seizure duration on the proportion of lateralizing/localizing SPECT was tested by ANOVA with dichotomized (by the median) injection latency and post-injection seizure duration as between-subjects factors. RESULTS: Median [interquartile range] (full range) of injection latency and post-injection seizure duration were 30 [24, 40] (3-120) s and 50 [27, 70] (-20-660) s, respectively. Fleiss' κ for lateralization of the SOZ was largest for the combination of early (< 30 s) injection and long (> 50 s) post-injection seizure duration (κ = 0.894, all other combinations κ = 0.659-0.734). Regarding Fleiss' κ for localization of the SOZ in the 141 (80.1%) lateralizing SPECT, it was largest for early injection and short post-injection seizure duration (κ = 0.575, all other combinations κ = 0.329-0.368). The proportion of lateralizing SPECT was lower with short compared to long post-injection seizure duration (estimated marginal means 74.3% versus 86.3%, p = 0.047). The effect was mainly driven by cases with very short post-injection seizure duration ≤ 10 s (53.8% lateralizing). Injection latency in the considered range had no significant impact on the proportion of lateralizing SPECT (p = 0.390). The proportion of localizing SPECT among the lateralizing cases did not depend on injection latency or post-injection seizure duration (p ≥ 0.603). CONCLUSIONS: Short post-injection seizure duration is associated with a lower proportion of lateralizing cases in ictal brain perfusion SPECT.

Grade 3 meningioma survival and recurrence outcomes in an international multicenter cohort.

OBJECTIVE: Grade 3 meningioma represents a rare meningioma subtype, for which limited natural history data are available. The objective of this study was to identify demographics and pathologic characteristics, clinical and functional status outcomes, and prognostic factors in an international cohort of grade 3 meningioma patients. METHODS: Clinical and histopathological data were collected for patients treated at 7 sites across North America and Europe between 1991 and 2022. RESULTS: A total of 103 patients (54% female, median age 65 [IQR 52, 72] years) were included. Sixty-seven (65%) patients had de novo grade 3 lesions, whereas 29 (28%) had malignant transformations of lower-grade meningiomas. All patients underwent initial resection of their tumor. Patients were followed for a median of 46 (IQR 24, 108) months, during which time there were 65 (73%) recurrences and 50 (49%) deaths. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 66% (95% CI 56%-77%) and 37% (95% CI 28%-48%), respectively. Age ≥ 65 years and male sex were independent predictors of worse OS and PFS in multivariate regression analysis, while postoperative radiotherapy was independently associated with improved OS. Karnofsky Performance Status (KPS) remained stable relative to baseline over 5 years postdiagnosis among participants who were alive at the end of the follow-up period. CONCLUSIONS: This large multicenter study provides insight into the longitudinal outcomes of grade 3 meningioma, with respect to recurrence, survival, and functional status. This study affirms the survival benefit conferred by radiotherapy in this population and suggests good functional status outcomes for patients surviving to 5 years postoperatively.

Corrigendum: Grade 3 Meningioma Survival and Recurrence Outcomes in an International Multicenter Cohort.

[This corrects the article DOI: 10.1055/s-0044-1779888.].

Functional hemispheric disconnection procedures for chronic epilepsy: history, indications, techniques, complications and current practice in Europe. A consensus statement on behalf of the EANS functional neurosurgery section.

Introduction: The surgical procedure for severe, drug-resistant, unilateral hemispheric epilepsy is challenging. Over the last decades the surgical landscape for hemispheric disconnection procedures changed from anatomical hemispherectomy to functional hemispherotomy with a reduction of complications and stable good seizure outcome. Here, a task force of European epilepsy surgeons prepared, on behalf of the EANS Section for Functional Neurosurgery, a consensus statement on different aspects of the hemispheric disconnection procedure. Research question: To determine history, indication, timing, techniques, complications and current practice in Europe for hemispheric disconnection procedures in drug-resistant epilepsy. Material and methods: Relevant literature on the topic was collected by a literature search based on the PRISMA 2020 guidelines. Results: A comprehensive overview on the historical development of hemispheric disconnection procedures for epilepsy is presented, while discussing indications, timing, surgical techniques and complications. Current practice for this procedure in European epilepsy surgery centers is provided. At present, our knowledge of long-term seizure outcomes primarily stems from open surgical disconnection procedures. Although minimal invasive surgical techniques in epilepsy are rapidly developing and reported in case reports or small case series, long-term seizure outcome remain uncertain and needs to be reported. Discussion and conclusion: This is the first paper presenting a European consensus statement regarding history, indications, techniques and complications of hemispheric disconnection procedures for different causes of chronic, drug-resistant epilepsy. Furthermore, it serves as the pioneering document to report a comprehensive overview of the current surgical practices regarding this type of surgery employed in renowned epilepsy surgery centers across Europe.

Consensus-based recommendations for diagnosis and surgical management of cranioplasty and post-traumatic hydrocephalus from a European panel.

Introduction: Planning cranioplasty (CPL) in patients with suspected or proven post-traumatic hydrocephalus (PTH) poses a significant management challenge due to a lack of clear guidance. Research question: This project aims to create a European document to improve adherence and adapt to local protocols based on available resources and national health systems. Methods: After a thorough non-systematic review, a steering committee (SC) formed a European expert panel (EP) for a two-round questionnaire using the Delphi method. The questionnaire employed a 9-point Likert scale to assess the appropriateness of statements inherent to two sections: "Diagnostic criteria for PTH" and "Surgical strategies for PTH and cranial reconstruction." Results: The panel reached a consensus on 29 statements. In the "Diagnostic criteria for PTH" section, five statements were deemed "appropriate" (consensus 74.2-90.3 %), two were labeled "inappropriate," and seven were marked as "uncertain."In the "Surgical strategies for PTH and cranial reconstruction" section, four statements were considered "appropriate" (consensus 74.2-90.4 %), six were "inappropriate," and five were "uncertain." Discussion and conclusion: Planning a cranioplasty alongside hydrocephalus remains a significant challenge in neurosurgery. Our consensus conference suggests that, in patients with cranial decompression and suspected hydrocephalus, the most suitable diagnostic approach involves a combination of evolving clinical conditions and neuroradiological imaging. The recommended management sequence prioritizes cranial reconstruction, with the option of a ventriculoperitoneal shunt when needed, preferably with a programmable valve. We strongly recommend to adopt local protocols based on expert consensus, such as this, to guide patient care.

Global Outcomes for Microsurgical Clipping of Unruptured Intracranial Aneurysms: A Benchmark Analysis of 2245 Cases.

BACKGROUND AND OBJECTIVES: Benchmarks represent the best possible outcome and help to improve outcomes for surgical procedures. However, global thresholds mirroring an optimal and reachable outcome for microsurgical clipping of unruptured intracranial aneurysms (UIA) are not available. This study aimed to define standardized outcome benchmarks in patients who underwent clipping of UIA. METHODS: A total of 2245 microsurgically treated UIA from 15 centers were analyzed. Patients were categorized into low- ("benchmark") and high-risk ("nonbenchmark") patients based on known factors affecting outcome. The benchmark was defined as the 75th percentile of all centers' median scores for a given outcome. Benchmark outcomes included intraoperative (eg, duration of surgery, blood transfusion), postoperative (eg, reoperation, neurological status), and aneurysm-related factors (eg, aneurysm occlusion). Benchmark cutoffs for aneurysms of the anterior communicating/anterior cerebral artery, middle cerebral artery, and posterior communicating artery were determined separately. RESULTS: Of the 2245 cases, 852 (37.9%) patients formed the benchmark cohort. Most operations were performed for middle cerebral artery aneurysms (53.6%), followed by anterior communicating and anterior cerebral artery aneurysms (25.2%). Based on the results of the benchmark cohort, the following benchmark cutoffs were established: favorable neurological outcome (modified Rankin scale ≤2) ≥95.9%, postoperative complication rate ≤20.7%, length of postoperative stay ≤7.7 days, asymptomatic stroke ≤3.6%, surgical site infection ≤2.7%, cerebral vasospasm ≤2.5%, new motor deficit ≤5.9%, aneurysm closure rate ≥97.1%, and at 1-year follow-up: aneurysm closure rate ≥98.0%. At 24 months, benchmark patients had a better score on the modified Rankin scale than nonbenchmark patients. CONCLUSION: This study presents internationally applicable benchmarks for clinically relevant outcomes after microsurgical clipping of UIA. These benchmark cutoffs can serve as reference values for other centers, patient registries, and for comparing the benefit of other interventions or novel surgical techniques.