Prognostic significance of MRI contrast enhancement in newly diagnosed glioblastoma, IDH-wildtype according to WHO 2021 classification.

BACKGROUND AND OBJECTIVES: Contrast enhancement in glioblastoma, IDH-wildtype is common but not systematic. In the era of the WHO 2021 Classification of CNS Tumors, the prognostic impact of a contrast enhancement and the pattern of contrast enhancement is not clearly elucidated. METHODS: We performed an observational, retrospective, single-centre cohort study at a tertiary neurosurgical oncology centre (January 2006 - December 2022). We screened adult patients with a newly-diagnosed glioblastoma, IDH-wildtype in order to assess the prognosis role of the contrast enhancement and the pattern of contrast enhancement. RESULTS: We included 1149 glioblastomas, IDH-wildtype: 26 (2.3%) had a no contrast enhancement, 45 (4.0%) had a faint and patchy contrast enhancement, 118 (10.5%) had a nodular contrast enhancement, and 960 (85.5%) had a ring-like contrast enhancement. Overall survival was longer in non-contrast enhanced glioblastomas (26.7 months) than in contrast enhanced glioblastomas (10.9 months) (p < 0.001). In contrast enhanced glioblastomas, a ring-like pattern was associated with shorter overall survival than in faint and patchy and nodular patterns (10.0 months versus 13.0 months, respectively) (p = 0.033). Whatever the presence of a contrast enhancement and the pattern of contrast enhancement, surgical resection was an independent predictor of longer overall survival, while age ≥ 70 years, preoperative KPS score < 70, tumour volume ≥ 30cm3, and postoperative residual contrast enhancement were independent predictors of shorter overall survival. CONCLUSION: A contrast enhancement is present in the majority (97.7%) of glioblastomas, IDH-wildtype and, regardless of the pattern, is associated with a shorter overall survival. The ring-like pattern of contrast enhancement is typical in glioblastomas, IDH-wildtype (85.5%) and remains an independent predictor of shorter overall survival compared to other patterns (faint and patchy and nodular).

Impact of frailty on survival glioblastoma, IDH-wildtype patients.

PURPOSE: Frailty increases the risk of mortality among patients. We studied the prognostic significance of frailty using the modified 5-item frailty index (5-mFI) in patients harboring a newly diagnosed supratentorial glioblastoma, IDH-wildtype. METHODS: We retrospectively reviewed records of patients surgical treated at a single neurosurgical institution at the standard radiochemotherapy era (January 2006 - December 2021). Inclusion criteria were: age ≥ 18, newly diagnosed glioblastoma, IDH-wildtype, supratentorial location, available data to assess the 5-mFI index. RESULTS: A total of 694 adult patients were included. The median overall survival was longer in the non-frail subgroup (5-mFI < 2, n = 538 patients; 14.3 months, 95%CI 12.5-16.0) than in the frail subgroup (5-mFI ≥ 2, n = 156 patients; 4.7 months, 95%CI 4.0-6.5 months; p < 0.001). 5-mFI ≥ 2 (adjusted Hazard Ratio (aHR) 1.31; 95%CI 1.07-1.61; p = 0.009) was an independent predictor of a shorter overall survival while age ≤ 60 years (aHR 0.78; 95%CI 0.66-0.93; p = 0.007), KPS score ≥ 70 (aHR 0.71; 95%CI 0.58-0.87; p = 0.001), unilateral location (aHR 0.67; 95%CI 0.52-0.87; p = 0.002), total removal (aHR 0.54; 95%CI 0.44-0.64; p < 0.0001), and standard radiochemotherapy protocol (aHR 0.32; 95%CI 0.26-0.38; p < 0.0001) were independent predictors of a longer overall survival. Frailty remained an independent predictor of overall survival within the subgroup of patients undergoing a first-line oncological treatment after surgery (n = 549) and within the subgroup of patients who benefited from a total removal plus adjuvant standard radiochemotherapy (n = 209). CONCLUSION: In newly diagnosed supratentorial glioblastoma, IDH-wildtype patients treated at the standard combined radiochemotherapy era, frailty, defined using a 5-mFI score ≥ 2 was an independent predictor of overall survival.

Radiographic growth rate as a predictor of aggressiveness of diffuse gliomas without 1p19q codeletion.

OBJECTIVE: The 2021 WHO classification of CNS tumors has refined the definition of adult-type diffuse gliomas without 1p19q codeletion. Nevertheless, the aggressiveness of gliomas is based exclusively on histomolecular criteria performed on a limited sample of the tumor. The authors aimed to assess whether the spontaneous radiographic tumor growth rate is associated with tumor aggressiveness and allows preoperative identification of malignancy grade of adult-type diffuse gliomas without 1p19q codeletion. METHODS: The authors retrospectively reviewed the records of adult patients harboring a newly diagnosed supratentorial diffuse glioma without 1p19q codeletion, with available preoperative MRI follow-up between January 2008 and April 2022. The spontaneous radiographic tumor growth rate was quantified by tumor volume segmentation and regression of the evolution of the mean tumor diameter over time and was compared with clinical, imaging, histomolecular, and survival data. RESULTS: Ninety-six patients were included. The spontaneous radiographic tumor growth rates (mean 17.8 ± 38.8 mm/year, range 0-243.5 mm/year) significantly varied according to IDH1/2 mutation (p < 0.001), grade of malignancy (p < 0.001), and presence of microvascular proliferation (p < 0.001). The spontaneous radiographic tumor growth rate allowed preoperative identification of high-grade cases: 100% of grade 3 and 4 IDH-mutant diffuse astrocytomas had a spontaneous radiographic tumor growth rate ≥ 8.0 mm/year, and 100% of IDH-wild-type glioblastomas had a spontaneous radiographic tumor growth rate ≥ 42.0 mm/year. A spontaneous radiographic growth rate ≥ 8.0 mm/year was an independent predictor of shorter progression-free (p = 0.014) and overall (p = 0.007) survival. A mitotic count threshold ≥ 4 mitoses was the optimal threshold for identifying aggressive IDH-mutant astrocytomas based on spontaneous radiographic tumor growth. CONCLUSIONS: The spontaneous radiographic tumor growth rates could be used as an additional tool to preoperatively screen tumor aggressiveness of adult-type diffuse gliomas without 1p19q codeletion.

Incidence, severity and impact on functional outcome of persistent hypoperfusion despite large-vessel recanalization, a potential marker of impaired microvascular reperfusion: Systematic review of the clinical literature.

The reported incidence of persistent hypoperfusion despite complete recanalization as surrogate for impaired microvascular reperfusion (IMR) has varied widely among clinical studies, possibly due to differences in i) definition of complete recanalization, with only recent Thrombolysis in Cerebral Infarction (TICI) grading schemes allowing distinction between complete (TICI3) and partial recanalization with distal occlusions (TICI2c); ii) operational definition of IMR; and iii) consideration of potential alternative causes for hypoperfusion, notably carotid stenosis, re-occlusion and post-thrombectomy hemorrhage. We performed a systematic review to identify clinical studies that carried out brain perfusion imaging within 72 hrs post-thrombectomy for anterior circulation stroke and reported hypoperfusion rates separately for TICI3 and TICI2c grades. Authors were contacted if this data was missing. We identified eight eligible articles, altogether reporting 636 patients. The incidence of IMR after complete recanalization (i.e., TICI3) tended to decrease with the number of considered alternative causes of hypoperfusion: range 12.5-42.9%, 0-31.6% and 0-9.1% in articles that considered none, two or all three causes, respectively. No study reported the impact of IMR on functional outcome separately for TICI-3 patients. Based on this systematic review, IMR in true complete recanalization appears relatively rare, and reported incidence highly depends on definition used and consideration of confounding factors.

Predictors of functional outcomes following spinal meningioma surgery. A single-center retrospective experience of 59 cases.

BACKGROUND: To better predict the postoperative functional outcomes of patients operated on for a spinal meningioma, we assessed: 1) the prevalence of good and poor postoperative functional outcomes following surgery; 2) the impact of age and frailty on postoperative functional outcomes. METHODS: In this retrospective cohort study, we screened adult patients operated on for a spinal meningioma from 2005 to 2022. Inclusion criteria were: 1) patients ≥18 years; 2) histopathological diagnosis of meningioma; 3) location to the cervical, thoracic or lumbar spine (foramen magnum meningioma excluded); 4) surgery as first-line treatment; and 5) available postoperative follow-up ≥1 year. Clinical outcomes were assessed using the modified McCormick scale preoperatively and at one-year of postoperative follow-up. RESULTS: In this single institution experience of 59 cases, we found that: 1) surgical resection positively impacts patients' functional outcomes, 91.2% either showing an improved or maintained good postoperative neurological status defined by a modified McCormick scale score ≤ II; 2) a good modified McCormick scale status was achieved in 84.2% of patients at one postoperative year; 3) 87.5% of patients who were not improved postoperatively maintained an overall good neurological status defined by a modified McCormick scale score ≤ II; and 4) frail or aged patients were not at a higher risk of poor postoperative functional outcomes. CONCLUSION: Surgical resection positively impacts outcomes of patients operated for a spinal meningioma. Sex, presence of a meningioma-related myelopathy, extent of resection, and occurrence of surgery-related postoperative complications, but not age or frailty, predict postoperative functional outcomes.

Assessing biomarkers of remission in female patients with anorexia nervosa (REMANO): a protocol for a prospective cohort study with a nested case-control study using clinical, neurocognitive, biological, genetic, epigenetic and neuroimaging markers in a French specialised inpatient unit.

BACKGROUND: Anorexia nervosa (AN) is a severe psychiatric disorder associated with frequent relapses and variability in treatment responses. Previous literature suggested that such variability is influenced by premorbid vulnerabilities such as abnormalities of the reward system. Several factors may indicate these vulnerabilities, such as neurocognitive markers (tendency to favour delayed reward, poor cognitive flexibility, abnormal decision process), genetic and epigenetic markers, biological and hormonal markers, and physiological markers.The present study will aim to identify markers that can predict body mass index (BMI) stability 6 months after discharge. The secondary aim of this study will be focused on characterising the biological, genetic, epigenetic and neurocognitive markers of remission in AN. METHODS AND ANALYSIS: One hundred and twenty-five (n=125) female adult inpatients diagnosed with AN will be recruited and evaluated at three different times: at the beginning of hospitalisation, when discharged and 6 months later. Depending on the BMI at the third visit, patients will be split into two groups: stable remission (BMI≥18.5 kg/m²) or unstable remission (BMI<18.5 kg/m²). One hundred (n=100) volunteers will be included as healthy controls.Each visit will consist in self-reported inventories (measuring depression, anxiety, suicidal thoughts and feelings, eating disorders symptoms, exercise addiction and the presence of comorbidities), neurocognitive tasks (Delay Discounting Task, Trail-Making Test, Brixton Test and Slip-of-action Task), the collection of blood samples, the repeated collection of blood samples around a standard meal and MRI scans at rest and while resolving a delay discounting task.Analyses will mainly consist in comparing patients stabilised 6 months later and patients who relapsed during these 6 months. ETHICS AND DISSEMINATION: Investigators will ask all participants to give written informed consent prior to participation, and all data will be recorded anonymously. The study will be conducted according to ethics recommendations from the Helsinki declaration (World Medical Association, 2013). It was registered on clinicaltrials.gov on 25 August 2020 as 'Remission Factors in Anorexia Nervosa (REMANO)', with the identifier NCT04560517 (for more details, see https://clinicaltrials.gov/ct2/show/record/NCT04560517). The present article is based on the latest protocol version from 29 November 2019. The sponsor, Institut National de la Santé Et de la Recherche Médicale (INSERM, https://www.inserm.fr/), is an academic institution responsible for the monitoring of the study, with an audit planned on a yearly basis.The results will be published after final analysis in the form of scientific articles in peer-reviewed journals and may be presented at national and international conferences. TRIAL REGISTRATION NUMBER: clinicaltrials.govNCT04560517.

Characteristics and Prognosis of Tumor-Related Epilepsy During Tumor Evolution in Patients With IDH Wild-Type Glioblastoma.

BACKGROUND AND OBJECTIVES: Tumor-related epilepsy is a well-known symptom of glioblastoma. However, the particular characteristics of epileptic seizures related to glioblastoma, isocitrate dehydrogenase (IDH)-wild-type is almost unexplored longitudinally during the whole course of the disease. We assessed tumor-related epilepsy and seizure control during tumor evolution and the prognostic significance of tumor-related epilepsy. METHODS: We performed an observational, retrospective single-center study at one tertiary referral neuro-oncology surgical center (2000-2020). We included adult patients treated for a newly diagnosed supratentorial glioblastoma, IDH-wild-type with available preoperative and postoperative MRI and with available epileptic seizure status at diagnosis. To determine factors associated with tumor-related epilepsy or seizure control, univariate analyses were performed using the χ2 or Fisher exact tests for categorical variables and the unpaired t test or Mann-Whitney rank-sum test for continuous variables. Predictors associated with tumor-related epilepsy and seizure control in unadjusted analysis were entered into backward stepwise logistic regression models. RESULTS: One thousand six patients were enrolled. The cumulative incidence of tumor-related epilepsy increased during tumor evolution (33.1% at diagnosis, 44.7% after oncologic treatment, 52.4% at progression, and 51.8% at the end-of-life phase) and is related to tumor features (cortex involvement, no necrosis, and small volume). Uncontrolled epileptic seizures increased during tumor evolution (20.1% at diagnosis, 32.0% after oncologic treatment, 46.7% at progression, and 41.1% at the end-of-life phase). Epileptic seizure control after oncologic treatment was related to seizure features (uncontrolled before oncologic treatment and focal-to-bilateral tonic-clonic seizures) and to the extent of resection. Epileptic seizure control at tumor progression was related to seizure features (presence at diagnosis and uncontrolled after oncologic treatment) and to the time to progression. Tumor-related epilepsy at diagnosis was a predictor of a longer overall survival (adjusted hazard ratio, 0.78; 95% CI 0.67-0.90; p < 0.001) independent of age, Karnofsky Performance Status score, tumor location and volume, extent of resection, standard combined chemoradiotherapy, levetiracetam use, and MGMT promoter methylation. DISCUSSION: The progression of tumor-related epilepsy with the evolution of glioblastoma, IDH-wild-type and the effects of surgery on seizure control argue for proper antiseizure medication and maximal safe resection. Tumor-related epilepsy is an independent predictor of a longer survival.

Presentation and Management of Cerebral Venous Sinus Thrombosis After Supratentorial Craniotomy.

BACKGROUND AND OBJECTIVES: Cerebral venous sinus thrombosis (CVST) after supratentorial craniotomy is a poorly studied complication, for which there are no management guidelines. This study assessed the incidence, associated risk factors, and management of postoperative CVST after awake craniotomy. METHODS: This is an observational, retrospective, monocentric analysis of patients who underwent a supratentorial awake craniotomy. Postoperative CVST was defined as a flow defect on the postoperative contrast-enhanced 3D T1-weighted sequence and/or as a T2* hypointensity within the sinus. RESULTS: In 401 supratentorial awake craniotomies (87.3% of diffuse glioma), the incidence of postoperative CVST was 4.0% (95% CI 2.5-6.4): 14/16 thromboses located in the superior sagittal sinus and 12/16 located in the transverse sinus. A venous sinus was exposed during craniotomy in 45.4% of cases, and no intraoperative injury to a cerebral venous sinus was reported. All thromboses were asymptomatic, and only two cases were diagnosed at the time of the first postoperative imaging (0.5%). Postoperative complications, early postoperative Karnofsky Performance Status score, and duration of hospital stay did not significantly differ between patients with and without postoperative CVST. Adjusted independent risk factors of postoperative CVST were female sex (adjusted Odds Ratio 4.00, 95% CI 1.24-12.91, P = .021) and a lesion ≤1 cm to a venous sinus (adjusted Odds Ratio 10.58, 95% CI 2.93-38.20, P < .001). All patients received standard prophylactic-dose anticoagulant therapy, and none received treatment-dose anticoagulant therapy. No thrombosis-related adverse event was reported. All thromboses presented spontaneous sinus recanalization radiologically at a mean of 89 ± 41 days (range, 7-171). CONCLUSION: CVST after supratentorial awake craniotomy is a rare event with satisfactory clinical outcomes and spontaneous sinus recanalization under conservative management without treatment-dose anticoagulant therapy. These findings are comforting to neurosurgeons confronted with postoperative MRI reports suggesting CVST.

Efficacy and Safety of Carmustine Wafer Implantation After Ventricular Opening in Glioblastomas, Isocitrate Dehydrogenase-Wildtype, in Adults.

BACKGROUND AND OBJECTIVES: We assessed the impact of ventricular opening on postoperative complications and survival of carmustine wafer implantation during surgery of newly diagnosed supratentorial glioblastomas, isocitrate dehydrogenase (IDH)-wildtype in adults. METHODS: We performed an observational, retrospective, single-center cohort study at a tertiary surgical neuro-oncological center between January 2006 and December 2021. RESULTS: One hundred ninety-four patients who benefited from a first-line surgical resection with carmustine wafer implantation were included. Seventy patients (36.1%) had a ventricular opening. We showed that ventricular opening (1) did not increase overall postoperative complication rates (P = .201); (2) did not worsen the early postoperative Karnofsky Performance Status score (P = .068); (3) did not increase the time interval from surgery to adjuvant oncological treatment (P = .458); (4) did not affect the completion of the standard radiochemotherapy protocol (P = .164); (5) did not affect progression-free survival (P = .059); and (6) did not affect overall survival (P = .142). CONCLUSION: In this study, ventricular opening during first-line surgical resection did not affect the survival and postoperative complications after use of carmustine wafer implantation in adult patients with a newly diagnosed supratentorial glioblastoma, IDH-wildtype. This warrants a prospective and multicentric study to clearly assess the impact of the ventricular opening after carmustine wafer implantation in glioblastoma, IDH-wildtype.

Multicenter validation of synthetic FLAIR as a substitute for FLAIR sequence in acute ischemic stroke.

PURPOSE: To evaluate performance of synthetic and real FLAIR for identifying early stroke in a multicenter cohort. METHODS: This retrospective study was conducted using DWI and FLAIR extracted from the Endovascular Treatment in Ischemic Stroke image registry (2017-2021). The database was partitioned into subsets according to MRI field strength and manufacturer, and randomly divided into training set (70%) used for model fine-tuning, validation set (15%), and test set (15%). In test set, five readers, blinded to FLAIR sequence type, assessed DWI-FLAIR mismatch using real and synthetic FLAIR. Interobserver agreement for DWI-FLAIR rating and concordance between synthetic and real FLAIR were evaluated with kappa statistics. Sensitivity and specificity for identification of ⩽4.5 h AIS were compared in patients with known onset-to-MRI delay using McNemar's test. RESULTS: 1454 complete MRI sets (1172 patients, median (IQR) age: 73 years (62-82); 762 women) acquired on 125 MRI units were analyzed. In test set (207 MRI), interobserver reproducibility for DWI-FLAIR mismatch labeling was substantial for real and synthetic FLAIR (Fleiss κ = 0.79 (95%CI: 0.73-0.84) and 0.77 (95%CI: 0.71-0.82), respectively). After consensus, concordance between real and synthetic FLAIR was excellent (κ = 0.85 (95%CI: 0.78-0.92)). In 141 MRI sets with known onset-to-MRI delay, diagnostic performances for ⩽4.5 h AIS identification did not differ between real and synthetic FLAIR (sensitivity: 60/71 (85%) vs 59/71 (83%), p = .56; specificity: 65/70 (93%) vs 65/70 (93%), p > 0.99). CONCLUSION: A deep-learning-based FLAIR fine-tuned on multicenter data can provide comparable performances to real FLAIR for early AIS identification. This approach may help reducing MR protocol duration and motion artifacts.

Cerebral microbleeds and risk of symptomatic hemorrhagic transformation following mechanical thrombectomy for large vessel ischemic stroke.

BACKGROUND AND PURPOSE: In patients with acute ischemic stroke (AIS) treated with endovascular therapy (EVT), the association of pre-existing cerebral small vessel disease (cSVD) with symptomatic intracerebral hemorrhage (sICH) remains controversial. We tested the hypothesis that the presence of cerebral microbleeds (CMBs) and their burden would be associated with sICH after EVT of AIS. METHODS: We conducted a retrospective study combining cohorts of patients that underwent EVT between January 1st 2015 and January 1st 2020. CMB presence, burden, and other cSVD markers were assessed on a pre-treatment MRI, evaluated independently by two observers. Primary outcome was the occurrence of sICH. RESULTS: 445 patients with pretreatment MRI were included, of which 70 (15.7%) demonstrated CMBs on baseline MRI. sICH occurred in 36 (7.6%) of all patients. Univariate analysis did not demonstrate an association between CMB and the occurrence of sICH (7.5% in CMB+ group vs 8.6% in CMB group, p = 0.805). In multivariable models, CMBs' presence was not significantly associated with increased odds for sICH (-aOR- 1.19; 95% CI [0.43-3.27], p = 0.73). Only ASPECTs (aOR 0.71 per point increase; 95% CI [0.60-0.85], p < 0.001) and collaterals status (aOR 0.22 for adequate versus poor collaterals; 95% CI [0.06-0.93], p 0.019) were independently associated with sICH. CONCLUSION: CMB presence and burden is not associated with increased occurrence of sICH after EVT. This result incites not to exclude patients with CMBs from EVT. The risk of sICH after EVT in patients with more than10 CMBs will require further investigation. REGISTRATION: Registration-URL: http://www. CLINICALTRIALS: gov ; Unique identifier: NCT01062698.

Supra-tentorial Ependymomas with ZFTA Fusion, YAP1 Fusion, and Astroblastomas, MN1-altered: Characteristic Imaging Features.

PURPOSE: Supratentorial (ST) ependymoma subgroups are defined by two different fusions with different prognoses. Astroblastomas, MN1-altered, have ependymal-like histopathologic features and represent a differential diagnosis in children. We hypothesized that ZFTA-fused ependymoma and YAP1-fused ependymoma on the one hand, and astroblastoma, MN1-altered, on the other hand, show different MRI characteristics. METHODS: We retrospectively analyzed the preoperative imaging of 45 patients with ST ependymoma or astroblastoma between January 2000 and September 2020, blinded to histomolecular grouping. Several characteristics, such as location, tumor volume, calcifications, solid/cystic component, and signal enhancement or diffusion were evaluated. We compared imaging characteristics according to their molecular subtype (ZFTA-fused, YAP1-fused, and astroblastoma, MN1-altered). RESULTS: Thirty-nine patients were classified as having an ependymoma, 35 with a ZFTA fusion and four with a YAP1 fusion, and six as having an astroblastoma, MN1-altered. YAP1-fused ependymomas were more likely to involve at least 3 lobes than ZFTA-fused ependymomas. Astroblastomas were located in the frontal lobe in 100% of the tumors versus 49% of the ependymomas. Cerebral blood flow by arterial spin labeling was higher in astroblastomas than in ependymomas. There were no differences in the other characteristics between the molecular groups. All the tumors showed common features: intra-axial extra-ventricular tumors, very frequent contrast enhancement (39/43, 91%), a cystic/necrotic component (41/45, 91%), restricted diffusion (32/36, 89%), calcifications (15/18, 83%), and peri-tumoral edema (38/44, 86%). CONCLUSION: The distinction between ST ependymoma subtypes and astroblastomas can be guided by several imaging features. These tumors share common imaging features that may help to differentiate ST ependymomas and astroblastomas from other pediatric ST tumors.