Logo: to the web site of Uppsala University

Background: This study aimed to explore the potential association between tumor shape, 1p/19q codeletion, EOR, and new postoperative focal deficits in patients with diffuse low-grade glioma.

Methods: We analyzed data from 225 WHO grade 2 glioma surgeries performed in nine centers in Norway and Sweden. The tumor measurements were based on automatic segmentations of preoperative T2/FLAIR MRI scans by Raidionics. Contact surface area (CSA) was defined as the area between the tumor and brain parenchyma and was estimated by subtracting the surface area covered by the dura from the total surface area. The sphericity index (SI) was defined as the quotient of the tumor surface area and the surface area of a sphere with equal volume. Focal deficits were defined as any new motor, language, or visual deficits postoperatively.

Results: The univariable analyses showed that a larger CSA was associated with higher age (P = .02), lower EOR (P < .0001), and more focal deficits (P = .005) but not with 1p/19q codeletion (P = .54). A higher SI was associated with higher age (P = .02) and lower EOR (P < .0001) but not with focal deficits (P = .08) or 1p/19q codeletion (P = .90). The multivariable linear regression model supported the univariable associations between EOR and CSA (P = .0003) and SI (P = .0013), respectively. Contrarily, the logistic regression model showed that focal deficits were associated with SI (P = .014) but not with CSA (P = .056)

Conclusion: The tumor shape appears to be independently associated with EOR and new focal deficits but not with molecular diagnosis in patients with low-grade glioma.

Background and objectives Maximal safe resection is the cornerstone of diffuse low-grade glioma (dLGG) management, although epidemiological data are limited. We aim to explore surgical selection, techniques, and outcomes in a population-based cohort.Materials and methods This study utilized a multi-center case series (9 out of 10 neurosurgical departments in Norway and Sweden) of all adults (>= 18 years) with histopathologically verified supratentorial dLGG, WHO grade 2, undergoing primary surgery from 2012-2017. Complications within 30 days and neurological outcomes at 3 months were assessed. Pre- and postoperative MRIs were reviewed centrally, blinded to patient outcome and center.Results Of 517 included patients, 217 (41.7%) were female, and the mean (SD) age was 44.5 (15.0) years. Biopsy only was performed in 119 (23.0%) patients (13.8-38.9% across centers), and 398 (77.0%) underwent resection (61.1-86.2%). Intraoperative neurophysiological monitoring (IONM) was used in 142 (35.7%, 0-58.7%) resections. The biopsy-only patients were older (52.7 years vs. 42.1 years, P<.001), had larger tumors (56.6 ml vs. 31.9 ml, P<.001), and these tumors were more often eloquently located (86.6% vs. 56.5%, P<.001). The median (IQR) extent of resection (EOR) was 82.9% (63.3-97.7%), 69.7-100.0% across centers. The median (IQR) residual tumor was 4.6 ml (0.5-19.9 ml), 0.0-14.1 ml across centers. Age and histopathology were the most important predictors of EOR. New/worsened neurological deficits occurred in 165 patients (41.5%), 23.1-66.7% across centers, and persisted in 19 (4.8%, 0-22.7%) at 3 months after surgery. A complication was observed in 87 patients (21.4%, 0-31.7%), with 12 patients (3.1%, 0-9.8%) having grade III-IV complications.Conclusions We found that surgical selection was associated with age, tumor size, and location. The median EOR in a population-based cohort was 83%, with age and tumor biology being significant predictors. EOR did not correlate with higher risks or worse neurological outcomes. We provide an epidemiological perspective demonstrating a variation in surgical selection and techniques reflecting persistent controversy in dLGG management.

Intro: Seizure incidence in diffuse glioma ranges between 60% and 90%. This study aimed to investigate the association between seizures and diffuse glioma in subcortical and cortical brain regions, including white matter tracts.

Methods: Adult patients with diffuse glioma at Uppsala University Hospital from 2005 to 2021 were analysed retrospectively. The relationship between tumour location in specific brain voxels and preoperative seizures was examined concerning white matter tract involvement. Tumour volumes were segmented based on T2-weighted or FLAIR MRI after spatial normalisation to standard space (MNI) and combined to create a location-specific frequency map.

Results: Of the 93 patients meeting the inclusion criteria, 70 (75%) experienced seizures. A significant decreased risk was found in tumours present within the left fronto-mesial and dorsal voxel (A3C1S1). Increased seizure risk was found in tumours located in the left supramarginal and posterior insular voxel (A4C2S3). The voxels differed in terms of type and extent of white matter networks. Additionally, there was a difference in seizure risk and voxel associations between oligodendrogliomas and astrocytoma, with specific voxels associated with seizures identified in both groups.

Conclusion: The study provides new insights into the epileptogenic potential of diffuse gliomas in relation to their spatial distribution, highlighting the need to analyse both cortical and subcortical localisation of tumours. The observed differences in seizure risks across brain regions underscore the need for personalised post-surgery treatment strategies and further research to understand the pathophysiology of brain tumour-related epilepsy, BTRE.

Purpose

Adult patients with diffuse lower-grade gliomas (dLGG) show heterogeneous survival outcomes, complicating postoperative treatment planning. Treating all patients early increases the risk of long-term side effects, while delayed treatment may lead to impaired survival. Refinement of prognostic models could optimize timing of treatment. Conventional radiological features are prognostic in dLGG, but MRI could carry more prognostic information. This study aimed to investigate MRI-based radiomics survival models and compare them with clinical models.

Methods

Two clinical survival models were created: a preoperative model (tumor volume) and a full clinical model (tumor volume, extent of resection, tumor subtype). Radiomics features were extracted from preoperative MRI. The dataset was divided into training set and unseen test set (70:30). Model performance was evaluated on test set with Uno’s concordance index (c-index). Risk groups were created by the best performing model’s predictions.

Results

207 patients with mutated IDH (mIDH) dLGG were included. The preoperative clinical, full clinical and radiomics models showed c-indexes of 0.70, 0.71 and 0.75 respectively on test set for overall survival. The radiomics model included four features of tumor diameter and tumor heterogeneity. The combined full clinical and radiomics model showed best performance with c-index = 0.79. The survival difference between high- and low-risk patients according to the combined model was both statistically significant and clinically relevant.

Conclusion

Radiomics can capture quantitative prognostic information in patients with dLGG. Combined models show promise of synergetic effects and should be studied further in astrocytoma and oligodendroglioma patients separately for optimal modelling of individual risks.

BACKGROUND/OBJECTIVES: Olfaction is in many ways the least understood sensory modality. Its organization and connectivity are still under debate. The aim of this study was to investigate the anatomy of the olfactory system by using a cadaver fiber dissection technique and in vivo tractography to attain a deeper understanding of the subcortical connectivity and organization.

METHODS: Ten cerebral hemispheres were used in this study for white matter dissection according to Klingler's technique. Measurements of different cortical structures and interhemispheric symmetry were compared. Diffusion tensor imaging sequences from twenty-five healthy individuals from the Human Connectome Project dataset were used to explore the connectivity of the olfactory system using DSI Studio. White matter connectivity between the following were reconstructed in vivo: (1) Olfactory bulb to primary olfactory cortices; (2) Olfactory bulb to secondary olfactory cortices; (3) Primary to secondary olfactory cortices. The DTI metrics of the identified major associative, projection and commissural pathways were subsequently correlated with olfactory function and cognition in seventy-five healthy individuals with Spearman's rank correlation and the Benjamini-Hochberg method for false discoveries (CI 95%, p < 0.05) using R.

RESULTS: 1. The dissection showed that the lateral stria was significantly longer on the left side and projected towards the amygdala, the entorhinal and piriform cortex. 2. The medial stria was not evident as a consistent white matter structure. 3. Both dissection and tractography showed that major associative white matter pathways such as the uncinate fasciculus, the inferior fronto-occipital fasciculus and cingulum supported the connectivity between olfactory areas together with the anterior commissure. 4. No significant correlation was found between DTI metrics and sensory or cognition test results.

CONCLUSIONS: We present the first combined fiber dissection analysis and tractography of the olfactory system. We propose a novel definition where the primary olfactory network is defined by the olfactory tract/bulb and primary olfactory cortices through the lateral stria only. The uncinate fasciculus, inferior fronto-occipital fasciculus and cingulum are the associative pathways supporting the connectivity between primary and secondary olfactory areas together with the anterior commissure. We suggest considering these structures as a secondary olfactory network. Further work is needed to attain a deeper understanding of the pathological and physiological implications of the olfactory system.

The natural history of suspected diffuse low-grade gliomas (DLGG) depends heavily upon the molecular status. To fully comprehend this integrated information preoperatively, a clinical phenotype incorporating both clinical and radiological information may be of value. We aimed to analyse this systematically in a large multicentre study to identify clinical/radiological phenotypes of DLGG molecular subgroups at the onset. Patients from nine Scandinavian centres, with confirmed World Health Organization (WHO) grade 2 at the time of diagnosis (according to the WHO 2016/2007 classification), known molecular status [isocitrate dehydrogenase (IDH) status and 1p19q codeletion status] and preoperative images of adequate quality, were analysed. MRI-based tumour volume segmentation was used to create a frequency map of their locations in the Montreal Neurological Institute space. A Brain-Grid (BG) system was also used for tumour invasiveness analysis. Variables were analysed for each subgroup of DLGG with regression analyses. A total of 235 patients were included in the study. The three molecular subgroups differed in age, tumour location, epileptic onset and cognitive status. Seizure onset was linked to the number of BG voxels and the A3C2S2 location in all three molecular subgroups. Cognitive deficits were related to increasing age (IDH-mutated oligodendrogliomas), female gender (IDH-wildtype) and tumour volume (oligodendrogliomas). Patients with IDH-mutated astrocytomas (n = 65) displayed younger age, left-sided fronto-insular preferential location, infiltration of anterior ventral inferior fronto-occipital fasciculus (IFOF) and external capsule, and seizure as the onset symptoms. Oligodendrogliomas (n = 116) were more often found in patients >40 years old, with frontal location, dorsal IFOF, frontal aslant tract and superior longitudinal fasciculus invasion, and seizures as the onset symptoms. IDH-wildtype astrocytomas (n = 54) displayed: age >40 years old, left-sided temporo-insular preferential location, invasion of posterior IFOF and cortico-spinal tract, cognitive deficits at onset and the infiltration of posterior left peri-insular voxel (A3C2S3) as a strong predictor of IDH-wildtype. Using an integrated clinico-radiological approach, we identified differences in age, clinical presentation, preferential location and white matter infiltration among specific molecular subgroups of suspected DLGG. The systematic combination of patient-specific variables (age/clinical onset) and tumour-specific features (sub-lobar preferential location) may be relevant to create future prediction models and to better understand the onco-functional trajectory already at the preoperative stage. Prediction models may benefit from combining information rather than, for instance, analysing images only.

Background: Diffuse astrocytomas preferentially infiltrate eloquent areas affecting the outcome. A preoperative understanding of isocitrate dehydrogenase (IDH) status may offer opportunities for specific targeted therapies impacting treatment management. The aim of this study was to analyze clinical, topographical, radiological in WHO 2 astrocytomas with different IDH status and the long-term patient's outcome.

Methods: A series of confirmed WHO 2 astrocytoma patients (between 2005 and 2015) were retrospectively analyzed. MRI sequences (FLAIR) were used for tumor volume segmentation and to create a frequency map of their locations into the Montreal Neurological Institute (MNI) space. The Brain-Grid (BG) system (standardized radiological tool of intersected lines according to anatomical landmarks) was used as an overlay for infiltration analysis of each tumor. Long-term follow-up was used to perform a survival analysis.

Results: Forty patients with confirmed IDH status (26 IDH-mutant, IDHm/14 IDH-wild type, IDHwt) according to WHO 2021 classification were included with a mean follow-up of 7.8 years. IDHm astrocytomas displayed a lower number of BG-voxels (P < 0.05) and were preferentially located in the anterior insular region. IDHwt group displayed a posterior insular and peritrigonal location. IDHwt group displayed a shorter OS compared with IDHm (P < 0.05), with the infiltration of 7 or more BG-voxels as an independent factor predicting shorter OS.

Conclusions: IDHm and IDHwt astrocytomas differed in preferential location, number of BG-voxels and OS at long follow-up time. The number of BG-voxels affected the OS in IDHwt was possibly reflecting higher tumor invasiveness. We encourage the systematic use of alternative observational tools, such as gradient maps and the Brain-Grid analysis, to better detect differences of tumor invasiveness in diffuse low-grade gliomas subtypes.

Background: Grade 2-3 diffuse gliomas (DGs) show extensive infiltration through white matter (WM) tracts. Along-tract analysis of WM tracts based on diffusion tensor tractography (DTI) can been performed to assess the microstructural integrity of WM tracts. The clinical implication of these DTI-related findings is still under debate, especially in tumor patients. The aim of this study was to analyze and compare diffusion-based parameters along WM tracts and variables specific to WM -tumor interactions in DGs and correlate them with preoperative neuropsychological assessment.

Methods: Fourteen patients with IDH-mutated grade 2-3 DGs were included. Tumor volumes were manually segmented on 3D-FLAIR images after spatial normalisation to MNI space. DTI was acquired using a single-shot echo-planar sequence on a 3T with 48 sampling directions. DTI data were reconstructed within the MNI space using q-space diffeomorphic reconstruction (QSDR) in DSI studio. Five bilateral sets of WM tracts were reconstructed based on the HCP-1065 template. All WM tracts were stretched to the same length of 100 indices, and for each index diffusion-based parameters fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD), mean diffusivity (MD) and quantitative anisotropy (QA) were sampled. Tumor-related parameters (TRP); tumor volume (Tv), maximum tumor presence (MTP) and the number of sequential indices in which a tumor is present (Te) were derived based on the along-tract analysis. Normal data were constructed by calculating the average and standard deviations of contralateral and not-affected WM tracts for each diffusion-based parameter, respectively. Affected WM tracts were individually compared to normal data using a z-test. Preoperative neuropsychological assessment was performed in all subjects and correlated to results from the along-tract analysis using correlation and logistic regression models.

Results: Abnormalities in diffusion-based parameters were detected in WM tracts. Topographical and quantitative information were presented within the same graph. AD and MD displayed the highest linear correlation with the TRPs. Abnormal QA showed a linear correlation with Tv per WM tract. Neuropsychological impairment was correlated with all the TRPs and with abnormal FA (p < 0.05) and abnormal QA (p < 0.01). Abnormal QA was the only independent variable able to predict the presence of neuropsychological impairment in the patients based on the linear regression analysis.

Conclusions: Graphical presentation of the along-tract analysis presented in this study shows that it may be a sensitive and robust method to acquire and display topographical and qualitative information regarding WM tracts in close proximity to DGs. Further studies and refinements to the methods presented herein may advance current clinical methods for evaluating displacement and infiltrations and further aid the efforts of pre-planning surgical interventions with the goal to maximise EOR and tailor oncological treatment.

Introduction: One of the major goals of neurointensive care is to prevent secondary injuries following aSAH. Bed rest and patient immobilization are practiced in order to decrease the risk of DCI.

Research question: To explore the current practices in place concerning the management of patients with aSAH, specifically, protocols and habits regarding restrictions of mobilization and HOB positioning.

Material and methods: A survey was designed, modified, and approved by the panel of the Trauma & Critical Care section of the EANS to cover the practice of restrictions of patient mobilization and HOB positioning in patients with aSAH.

Results: Twenty-nine physicians from 17 countries completed the questionnaire. The majority (79.3%) stated that non-secured aneurysm and the presence of an EVD were the factors related to the establishment of restriction of mobilization. The average duration of the restriction varied widely ranging between 1 and 21 days. The presence of an EVD (13.8%) was found to be the main reason to recommend restriction of HOB elevation. The average duration of restriction of HOB positioning ranged between 3 and 14 days. Rebleeding or complications related to CSF over-drainage were found to be related to these restrictions.

Discussion and conclusion: Restriction of patient mobilization regimens vary widely in Europe. Current limited evidence does not support an increased risk of DCI rather the early mobilization might be beneficial. Large prospective studies and/or the initiative of a RCT are needed to understand the significance of early mobilization on the outcome of patients with aSAH.

PURPOSE: Since the introduction of the molecular definition of oligodendrogliomas based on isocitrate dehydrogenase (IDH)-status and the 1p19q-codeletion, it has become increasingly evident how this glioma entity differs much from other diffuse lower grade gliomas and stands out with longer survival and often better responsiveness to adjuvant therapy. Therefore, apart from using a molecular oligodendroglioma definition, an extended follow-up time is necessary to understand the nature of this slow growing, yet malignant condition. The aim of this study was to describe the long-term course of the oligodendroglioma disease in a population-based setting and to determine which factors affect outcome in terms of survival.

METHODS: All adults with WHO-grade 2 oligodendrogliomas with known 1p19q-codeletion from five Scandinavian neurosurgical centers and with a follow-up time exceeding 5 years, were analyzed regarding survival and factors potentially affecting survival.

RESULTS: 126 patients diagnosed between 1998 and 2016 were identified. The median follow-up was 12.0 years, and the median survival was 17.8 years (95% CI 16.0-19.6). Factors associated with shorter survival in multivariable analysis were age (HR 1.05 per year; CI 1.02-1.08, p < 0.001), tumor diameter (HR 1.05 per millimeter; CI 1.02-1.08, p < 0.001) and poor preoperative functional status (KPS < 80) (HR 4.47; CI 1.70-11.78, p = 0.002). In our material, surgical strategy was not associated with survival.

CONCLUSION: Individuals with molecularly defined oligodendrogliomas demonstrate long survival, also in a population-based setting. This is important to consider for optimal timing of therapies that may cause long-term side effects. Advanced age, large tumors and poor function before surgery are predictors of shorter survival.