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OBJECTIVE The role of endovascular treatment in the management of patients with brain arteriovenous malformations (AVMs) remains uncertain. AVM embolization can be offered as stand-alone curative therapy or prior to surgery or stereotactic radiosurgery (SRS) (pre-embolization). The Treatment of Brain AVMs Study (TOBAS) is an all-inclusive pragmatic study that comprises two randomized trials and multiple registries. METHODS Results from the TOBAS curative and pre-embolization registries are reported. The primary outcome for this report is death or dependency (modified Rankin Scale [mRS] score > 2) at last follow-up. Secondary outcomes include angiographic results, perioperative serious adverse events (SAEs), and permanent treatment-related complications leading to an mRS score > 2. RESULTS From June 2014 to May 2021, 1010 patients were recruited in TOBAS. Embolization was chosen as the primary curative treatment for 116 patients and pre-embolization prior to surgery or SRS for 92 patients. Clinical and angiographic outcomes were available in 106 (91%) of 116 and 77 (84%) of 92 patients, respectively. In the curative embolization registry, 70% of AVMs were ruptured, and 62% were low-grade AVMs (Spetzler-Martin grade I or II), while the pre-embolization registry had 70% ruptured AVMs and 58% low-grade AVMs. The primary outcome of death or disability (mRS score > 2) occurred in 15 (14%, 95% CI 8%–22%) of the 106 patients in the curative embolization registry (4 [12%, 95% CI 5%–28%] of 32 unruptured AVMs and 11 [15%, 95% CI 8%–25%] of 74 ruptured AVMs) and 9 (12%, 95% CI 6%–21%) of the 77 patients in the pre-embolization registry (4 [17%, 95% CI 7%–37%] of 23 unruptured AVMs and 5 [9%, 95% CI 4%–20%] of 54 ruptured AVMs) at 2 years. Embolization alone was confirmed to occlude the AVM in 32 (30%, 95% CI 21%–40%) of the 106 curative attempts and in 9 (12%, 95% CI 6%–21%) of 77 patients in the pre-embolization registry. SAEs occurred in 28 of the 106 attempted curative patients (26%, 95% CI 18%–35%, including 21 new symptomatic hemorrhages [20%, 95% CI 13%–29%]). Five of the new hemorrhages were in previously unruptured AVMs (n = 32; 16%, 95% CI 5%–33%). Of the 77 pre-embolization patients, 18 had SAEs (23%, 95% CI 15%–34%), including 12 new symptomatic hemorrhages [16%, 95% CI 9%–26%]). Three of the hemorrhages were in previously unruptured AVMs (3/23; 13%, 95% CI 3%–34%). CONCLUSIONS Embolization as a curative treatment for brain AVMs was often incomplete. Hemorrhagic complications were frequent, even when the specified intent was pre-embolization before surgery or SRS. Because the role of endovascular treatment remains uncertain, it should preferably, when possible, be offered in the context of a randomized trial.

OBJECTIVE The Treatment of Brain Arteriovenous Malformations Study (TOBAS) is a pragmatic study that includes 2 randomized trials and registries of treated or conservatively managed patients. The authors report the results of the surgical registry. METHODS TOBAS patients are managed according to an algorithm that combines clinical judgment and randomized allocation. For patients considered for curative treatment, clinicians selected from surgery, endovascular therapy, or radiation therapy as the primary curative method, and whether observation was a reasonable alternative. When surgery was selected and observation was deemed unreasonable, the patient was not included in the randomized controlled trial but placed in the surgical registry. The primary outcome of the trial was mRS score > 2 at 10 years (at last follow-up for the current report). Secondary outcomes include angiographic results, perioperative serious adverse events, and permanent treatment-related complications leading to mRS score > 2. RESULTS From June 2014 to May 2021, 1010 patients were recruited at 30 TOBAS centers. Surgery was selected for 229/512 patients (44%) considered for curative treatment; 77 (34%) were included in the surgery versus observation randomized trial and 152 (66%) were placed in the surgical registry. Surgical registry patients had 124/152 (82%) ruptured and 28/152 (18%) unruptured arteriovenous malformations (AVMs), with the majority categorized as low-grade Spetzler-Martin grade I–II AVM (118/152 [78%]). Thirteen patients were excluded, leaving 139 patients for analysis. Embolization was performed prior to surgery in 78/139 (56%) patients. Surgical angiographic cure was obtained in 123/139 all-grade (89%, 95% CI 82%–93%) and 105/110 low-grade (95%, 95% CI 90%–98%) AVM patients. At the mean follow-up of 18.1 months, 16 patients (12%, 95% CI 7%–18%) had reached the primary safety outcome of mRS score > 2, including 11/16 who had a baseline mRS score ≥ 3 due to previous AVM rupture. Serious adverse events occurred in 29 patients (21%, 95% CI 15%–28%). Permanent treatment-related complications leading to mRS score > 2 occurred in 6/139 patients (4%, 95% CI 2%–9%), 5 (83%) of whom had complications due to preoperative embolization. CONCLUSIONS The surgical treatment of brain AVMs in the TOBAS registry was curative in 88% of patients. The participation of more patients, surgeons, and centers in randomized trials is needed to definitively establish the role of surgery in the treatment of unruptured brain AVMs. Clinical trial registration no.: NCT02098252 (ClinicalTrials.gov)

To assess the accuracy of intraoperative neurophysiological monitoring (IONM) in predicting immediate and 3-month postoperative neurological new deficit (or deterioration) in patients benefiting from spinal cord (SC) surgery; and to identify factors associated with a higher risk of postoperative clinical worsening.Consecutive patients who underwent SC surgery with IONM were included. Pre and postoperative clinical (modified McCormick scale), radiological (lesion-occupying area ratio), and electrophysiological features were collected.A total of 99 patients were included: 14 (14.1%) underwent extradural surgery, 50 (50.5%) intradural extramedullary surgery, and 35 (35.4%) intramedullary surgery. Cumulatively, multimodal IONM (motor and somatosensory evoked potentials, D-wave whenever possible) significantly predicted postoperative deficits (p0.001), with a sensitivity, specificity, positive predictive value, and negative predictive value of 0.81, 0.93, 0.83, and 0.92, respectively. Sixty (60.6%) patients displayed no IONM change, whereas 39 (39.4%) displayed IONM worsening. In multivariate analysis, predictors for postoperative clinical worsening were: abnormal preoperative electrophysiological assessment (p=0.03), intramedullary tumor (p0.001), lesion-occupying area ratio ≥0.7 (p0.001), and IONM alterations (p0.001). Three months after the surgical procedure, in patients presenting at least one of the risk factors described above, 45/81 (55.6%) and 19/81 (23.5%) were clinically and electrophysiologically improved, respectively; while 13/81 (16.0%) and 10/81 (12.3%) were clinically and electrophysiologically worsened.Multimodal IONM is an essential tool to guide SC surgery, and enables the accurate prediction of postoperative neurological outcome. Specific attention should be given to patients presenting with preoperative electrophysiological abnormalities, large tumor volume, and intramedullary tumor location.

Brain invasion has not been recognized as a standalone criterion for atypical meningioma by the WHO classification until 2016. Since the 2007 edition suggested that meningiomas harboring brain invasion could be classified as grade 2, brain invasion study was progressively strengthened in our center, based on a strong collaboration between neurosurgeons and neuropathologists regarding sample orientation and examination. Practice changes were considered homogeneous enough in 2011. The aim of the present study was to evaluate the impact of gross practice change on the clinical and pathological characteristics of intracranial meningiomas classified as grade 2.The characteristics of consecutive patients with a grade 2 meningioma surgically managed before (1998-2005, n = 125, group A) and after (2011-2014, n = 166, group B) practices changed were retrospectively reviewed.Sociodemographical and clinical parameters were comparable in groups A and B, and the median age was 62 years in both groups (p = 0.18). The 5-year recurrence rates (23.2% vs 29.5%, p = 0.23) were similar. In group A, brain invasion was present in 48/125 (38.4%) cases and was more frequent than in group B (14/166, 8.4%, p 0.001). In group A, 33 (26.4%) meningiomas were classified as grade 2 solely based on brain invasion (group A

Molecular glioblastomas (i.e. without the histological but with the molecular characteristics of IDH-wild-type glioblastoma) frequently lack contrast enhancement, which can wrongly lead to suspect a lower-grade glioma. Herein, we aimed to assess the diagnostic value of gyriform infiltration as an imaging marker for molecular glioblastomas.Two independent investigators reviewed the MRI scans from patients with newly diagnosed gliomas for the presence of a gyriform infiltration defined as an elective cortical hypersignal on MRI FLAIR sequence. Diagnostic test performance of this sign for the diagnosis of molecular glioblastoma were calculated.A total of 426 patients were included, corresponding to 31 molecular glioblastoma, 294 IDH-wild-type glioblastoma, 50 IDH-mutant astrocytoma, and 51 IDH-mutant 1p19q-codeleted oligodendroglioma. A gyriform infiltration was observed in 16/31 (52%) molecular glioblastoma, 40/294 (14%) IDH-wild-type glioblastoma, and none of the IDH-mutant glioma. All the 56 gyriform-infiltration-positive tumors were IDH-wild-type and all but two had a TERT promoter mutation. The inter-rater agreement was good (κ = 0.69, p 0.001). The sensitivity, specificity, positive predictive value and negative predictive value of the presence of a gyriform infiltration for the diagnosis of molecular glioblastoma were 52%, 90%, 29%, 96%, respectively. The median overall survival was better for gyriform-infiltration-negative patients compared to gyriform-infiltration-positive patients in the whole series and in patients with non-enhancing lesions (n = 95) (25.6 vs 16.9 months, p = 0.005 and 20.2 months vs not reached, p 0.001).Gyriform infiltration is a specific imaging marker of molecular glioblastomas that can help distinguishing these tumors from IDH-mutant lower-grade gliomas.

Background Incidence and characteristics of pseudoprogression in isocitrate dehydrogenase-mutant high-grade gliomas (IDHmt HGG) remain to be specifically described. Methods We analyzed pseudoprogression characteristics and explored the possibility of pseudoprogression misdiagnosis in IDHmt HGG patients, treated with radiotherapy (RT) (with or without chemotherapy [CT]), included in the French POLA network. Pseudoprogression was analyzed in patients with MRI available for review (reference cohort, n = 200). Pseudoprogression misdiagnosis was estimated in this cohort and in an independent cohort (control cohort, n = 543) based on progression-free survival before and after first progression. Results In the reference cohort, 38 patients (19%) presented a pseudoprogression after a median time of 10.5 months after RT. Pseudoprogression characteristics were similar across IDHmt HGG subtypes. In most patients, it consisted of the appearance of one or several infracentimetric, asymptomatic, contrast-enhanced lesions occurring within 2 years after RT. The only factor associated with pseudoprogression occurrence was adjuvant PCV CT. Among patients considered as having a first true progression, 7 out of 41 (17%) in the reference cohort and 35 out of 203 (17%) in the control cohort were retrospectively suspected to have a misdiagnosed pseudoprogression. Patients with a misdiagnosed pseudoprogression were characterized by a time to event and an outcome similar to that of patients with a pseudoprogression but presented with larger and more symptomatic lesions. Conclusion In patients with an IDHmt HGG, pseudoprogression occurs later than in IDH-wildtype glioblastomas and seems not only frequent but also frequently misdiagnosed. Within the first 2 years after RT, the possibility of a pseudoprogression should be carefully considered.

International audience; Background: Intracranial solitary fibrous tumour (iSFT) is an exceptional mesenchymal tumour with high recurrence rates. We aimed to analyse the clinical outcomes of newly diagnosed and recurrent iSFTs.Methods: We carried out a French retrospective multicentre (n = 16) study of histologically proven iSFT cases. Univariate and multivariate Cox models were used to estimate the prognosis value of the age, location, size, WHO grade, and surgical extent on overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS).Results: Eighty-eight patients were included with a median age of 54.5 years. New iSFT cases were treated with gross tumour resection (GTR) (n = 75) or subtotal resection (STR) (n = 9) and postoperative radiotherapy (PORT) (n = 32, 57%). The median follow-up time was 7 years. The median OS, PFS, and LRFS were 13 years, 7 years, and 7 years, respectively. Forty-two patients experienced recurrence. Extracranial metastasis occurred in 16 patients. Median OS and PFS after the first recurrence were 6 years and 15.4 months, respectively. A higher histological grade was a prognosis factor for PFS (p = 0.04) and LRFS (p = 0.03). GTR influenced LRFS (p = 0.03).Conclusion: GTR provided benefits as a first treatment for iSFTs. However, approximately 40% of patients experienced relapse, which remains a challenging state.

International audience; Adult tumors diagnosed as cerebellar glioblastoma (cGBM) are rare and their optimal classification remains to be determined. The aim of this study was to identify subgroups of cGBM based on targeted molecular analysis. cGBM diagnosed between 2003 and 2017 were identified from the French Brain Tumor Database and reviewed according to the WHO 2021 classification. The following molecular alterations were studied: IDH1/2, H3F3A, FGFR1, BRAF, TERT promoter mutations, EGFR amplification, MGMT promoter methylation, and alternative lengthening of telomere status. DNA methylation profile was assessed in a subset of cases. Eighty-three cGBM were included and could be classified into 6 mutually exclusive subgroups associated with median age at diagnosis (MA) and prognosis: TERT-mutant and/or EGFR-amplified tumors (n=22, 26.5%, MA=62 y, median overall survival [OS]=4 mo), H3K27M-mutant tumors (n=15, 18.1%, MA=48 y, median OS=8 mo), mitogen-activated protein kinases (MAPK) pathway-activated tumors (FGFR1, BRAF mutation, or occurring in neurofibromatosis type I patients, n=15, 18.1%, MA=48 y, median OS=57 mo), radiation-associated tumors (n=5, 6%, MA=47 y, median OS=5 mo), IDH-mutant tumors (n=1), and unclassified tumors (n=25, 30.1%, MA=63 y, median OS=17 mo). Most MAPK pathway-activated tumors corresponded to high-grade astrocytomas with piloid features based on DNA methylation profiling. In multivariate analysis, MAPK pathway-activating alterations, ATRX loss of expression, and alternative lengthening of telomere positivity were independently associated with a better outcome and TERT/EGFR alterations with a worse outcome. cGBM display an important intertumoral heterogeneity. Targeted molecular analysis enables to classify the majority of tumors diagnosed as cGBM into mutually exclusive and clinically relevant subgroups. The presence of MAPK pathway alterations is associated with a much better prognosis.

Intraoperative optical imaging is a localization technique for the functional areas of the human brain cortex during neurosurgical procedures. However, it still lacks robustness to be used as a clinical standard. In particular new biomarkers of brain functionality with improved sensitivity and specificity are needed. We present a method for the real time identification of the activated cortical areas based on the analysis of the cortical hemodynamic using a RGB camera and a white light source. We measure the quantitative oxy and deoxy-hemoglobin concentration changes in the human brain cortex with the modified Beer-Lambert law and Monte Carlo simulations. A functional model has been implemented to define in real time a binary biomarker of the cortical activation following neuronal activation by physiological stimuli. The results show a good correlation between the computed activation maps and the brain areas localized by electrical brain stimulation. We demonstrate that a RGB camera combined with a quantitative modeling of brain hemodynamics biomarkers can evaluate in real time the functional areas during neurosurgery and serve as a tool of choice to complement electrical brain stimulation.

Treatment of an unruptured brain arteriovenous malformation (bAVM) is a matter of debate, especially for low-grade bAVM (Spetzler-Martin grade I and II). The aim is to compare the outcomes of patients with low-grade unruptured bAVM after interventional or medical management in a pragmatic manner.Adults with unruptured low-grade bAVM diagnosed between 2006 and 2016 were included. The primary end points were death from all causes and disabling stroke that resulted in a modified Rankin Scale (mRS) score2 at last follow-up.Eighty-four patients presented with an unruptured Spetzler-Martin low-grade bAVM. Among these patients, 55 (65.5%) were treated and 29 (34.5%) were untreated, with no differences regarding clinical and radiologic characteristics. The modality of treatment was embolization in 25.5%, radiosurgery (alone, 30.9%; with embolization, 18.2%), and surgery (alone, 5.5%; with embolization, 20%). The rupture rate was 6.7% person-year in the untreated group; 12.7% (n = 7) of treated and 16.7% (n = 5) of untreated patients achieved the primary evaluation criteria (P = 0.744). Using a Kaplan-Meier curve, the probability of reaching this criterion at 5 years was not different between groups (P = 0.07). Complications resulting in an mRS score2 at last follow-up occurred in 9.1%, in 80% of cases after embolization.This study shows no differences between treated and untreated low-grade bAVM. Embolization seems to carry a high risk of complication and should be used with caution. The small number of cases must encourage cautious interpretations especially because of the spontaneous high-rupture rate. One major interest is to investigate center habits in pathology when treatment standards are limited.

OBJECTIVE The role of surgery in the treatment of malignant gliomas in the elderly is not settled. The authors conducted a randomized trial that compared tumor resection with biopsy only—both followed by standard therapy—in such patients. METHODS Patients ≥ 70 years of age with a Karnofsky Performance Scale (KPS) score ≥ 50 and presenting with a radiological suspicion of operable glioblastoma (GBM) were randomly assigned between tumor resection and biopsy groups. Subsequently, they underwent standard radiotherapy during the first years of the trial (2008–2017), with the addition of adjunct therapy with temozolomide when this regimen became standard (2017–2019). The primary endpoint was survival, and secondary endpoints were progression-free survival (PFS), cognitive status (Mini-Mental State Examination), autonomy (KPS), quality of life (European Organisation for Research and Treatment of Cancer [EORTC] QLQ-C30 and QLQ-BN20), and perioperative morbidity and mortality. RESULTS Between 2008 and 2019, 107 patients from 9 centers were enrolled in the study; 101 were evaluable for analysis because a GBM was histologically confirmed (50 in the surgery arm and 51 in the biopsy arm). There was no statistically significant difference in median survival between the surgery (9.37 months) and the biopsy (8.96 months, p = 0.36) arms (adjusted HR 0.79, 95% CI 0.52–1.21, p = 0.28). However, the surgery group had an increased PFS (5.06 vs 4.02 months; p = 0.034) (adjusted HR 0.50, 95% CI 0.32–0.78, p = 0.002). Less deterioration of quality of life and KPS score evolution than in the biopsy group was observed. Surgery was not associated with increased mortality or morbidity. CONCLUSIONS This study suggests that debulking surgery is safe, and—compared to biopsy—is associated with a less severe deterioration of quality of life and autonomy, as well as a significant although modest improvement of PFS in elderly patients suffering from newly diagnosed malignant glioma. Although resection does not provide a significant survival benefit in the elderly, the authors believe that the risk/benefit analysis favors an attempt at optimal tumor resection in this population, provided there is careful preoperative geriatric evaluation. Clinical trial registration no.: NCT02892708 (ClinicalTrials.gov)

Meningiomas are the most common benign intracranial tumors. They are generally asymptomatic, and discovered incidentally during cerebral imaging. The vast majority of meningiomas are solid, highly cellular and well-vascularized neoplasms. However, in several cases, they can be partially or, even rarely, almost completely cystic making their differential diagnosis and management challenging. In this paper, we present the rare case of a 59-year-old female patient, presenting with persistent headaches, who was diagnosed with a left parieto-occipital purely cystic lesion. The patient underwent a complete resection of this cystic lesion because of increasing headaches and volumetric progression. Interestingly, the histological assessment confirmed a cystic WHO grade I meningioma. The evolution was favorable and there was no recurrence after 3 years of follow-up. We also perform a systematic review of the literature concerning purely cystic meningiomas and we discuss the particular histological features of cystic meningiomas as well as the possible pathogenesis. This challenging clinical entity can easily be misdiagnosed as hemangioblastoma or glial/metastatic tumor with cystic component.

Background Pituitary stalk hemangioblastomas (PSHBLs) are rare vascular tumors and their surgical removal is challenging due to the proximity with several fundamental anatomic structures including the pituitary stalk, third ventricle, hypothalamus, and optic pathways. To date, only few descriptions of transcranial and transsphenoidal approaches for PSHBLs have been reported in the literature and none in video, with suboptimal outcomes in terms of pituitary function preservation. Here, we describe the use of orbitozygomatic (OZ) craniotomy with extradural anterior clinoidectomy (EAC) for the removal of a PSHBL with preservation of the pituitary stalk. Case Description A 60-year-old woman with a sporadic symptomatic HBL of the pituitary stalk, with the typical features of avid contrast enhancement on T1- and flow voids on T2-weighted magnetic resonance imaging (MRI) images, underwent a right OZ craniotomy with EAC. The choice of the approach was guided by the necessity of exposing the floor of the 3rd ventricle and infundibulum, where the origin of the pituitary stalk is better appreciated and preserved, without brain retraction. EAC was deemed important due to the necessity of widening the right carotico-oculomotor and opticocarotid triangles and gaining access to the ophthalmic segment of the internal carotid artery, origin of the superior hypophyseal artery, and the tumor supply. The postoperative MRI confirmed gross tumor removal with preservation of the pituitary stalk and no tumor recurrence after 2 years of follow-up. Conclusion OZ craniotomy coupled with EAC facilitates surgical removal of PSHBLs thus augmenting the chances of pituitary function preservation.The link to the video can be found at https://youtu.be/hH65W937RGY.

BACKGROUND Biopsies in patients with a suspected glioma are occasionally nondiagnostic. OBJECTIVE To explore the utility of molecular testing in this setting by determining whether IDH1 and TERT promoter (pTERT) mutations could be detected in nondiagnostic biopsies from glioma patients. METHODS Using SNaPshot polymerase chain reaction, we retrospectively assessed IDH1 and pTERT mutation status in nondiagnostic biopsies from 28 glioma patients. RESULTS The nondiagnostic biopsy (needle biopsy n = 25, open or endoscopic biopsy n = 3) consisted of slight glial cell hypercellularity, hemorrhage, and/or necrosis. After another biopsy (n = 23) or a subsequent surgical resection (n = 5) the diagnosis was an IDH1-wildtype (WT) pTERT-mutant glioma (glioblastoma n = 16, astrocytoma n = 4), an IDH1-mutant pTERT-mutant oligodendroglioma (n = 1), an IDH1-mutant pTERT-WT astrocytoma (n = 1), and an IDH1-WT pTERT-WT glioblastoma (n = 6). An IDH1 mutation was identified in the nondiagnostic biopsies of the 2 IDH-mutant gliomas, and a pTERT mutation in the nondiagnostic biopsies of 16 out of the 21 of pTERT mutant-gliomas (76%). Overall, an IDH1 and/or a pTERT mutation were detected in 17 out of 28 (61%) of nondiagnostic biopsies. Retrospective analysis of the nondiagnostic biopsies based on these results and on imaging characteristics suggested that a new biopsy could have been avoided in 6 patients in whom a diagnosis of "molecular glioblastoma" could have been done with a high level of confidence. CONCLUSION In the present series, IDH1 and pTERT mutations could be detected in a high proportion of nondiagnostic biopsies from glioma patients. Molecular testing may facilitate the interpretation of nondiagnostic biopsies in patients with a suspected glioma.

International audience; Purpose To analyze the outcomes and predictors in a large series of cerebellar glioblastomas in order to guide patient management. Methods The French brain tumor database and the Club de Neuro-Oncologie of the Societe Francaise de Neurochirurgie retrospectively identified adult patients with cerebellar glioblastoma diagnosed between 2003 and 2017. Diagnosis was confirmed by a centralized neuropathological review. Results Data from 118 cerebellar glioblastoma patients were analyzed (mean age 55.9 years, 55.1% males). The clinical presentation associated raised intracranial pressure (50.8%), static cerebellar syndrome (68.6%), kinetic cerebellar syndrome (49.2%) and/or cranial nerve disorders (17.8%). Glioblastomas were hemispheric (55.9%), vermian (14.4%) or both (29.7%). Hydrocephalus was present in 49 patients (41.5%). Histologically, tumors corresponded either to IDH-wild-type or to K27-mutant glioblastomas. Surgery consisted of total (12.7%), subtotal (35.6%), partial resection (33.9%) or biopsy (17.8%). The postoperative Karnofsky performance status was improved, stable and worsened in 22.4%, 43.9% and 33.7% of patients, respectively. Progression-free and overall survivals reached 5.1 months and 9.1 months, respectively. Compared to other surgical strategies, total or subtotal resection improved the Karnofsky performance status (33.3% vs 12.5%, p < 0.001), prolonged progression-free and overall survivals (6.5 vs 4.3 months, p = 0.015 and 16.7 vs 6.2 months, p < 0.001, respectively) and had a comparable complication rate (40.4% vs 31.1%, p = 0.29). After total or subtotal resection, the functional outcomes were correlated with age (p = 0.004) and cerebellar hemispheric tumor location (p < 0.001) but not brainstem infiltration (p = 0.16). Conclusion In selected patients, maximal resection of cerebellar glioblastoma is associated with improved onco-functional outcomes, compared with less invasive procedures.

International audience; The characteristics of hydrocephalus associated with cerebellar glioblastoma (cGB) remain poorly known. The objectives were to describe the occurence of hydrocephalus in a French nationwide series of adult patients with cGB, to identify the characteristics associated with hydrocephalus and to analyze the outcomes associated with the different surgical strategies, in order to propose practical guidelines. Consecutive cases of adult cGB patients prospectively recorded into the French Brain Tumor Database between 2003 and 2017 were screened. Diagnosis was confirmed by a centralized neuropathological review. Among 118 patients with cGB (mean age 55.9 years), 49 patients (41.5%) presented with pre-operative hydrocephalus. Thirteen patients (11.0%) developed acute (n=7) or delayed (n=6) hydrocephalus postoperatively. Compared to patients without hydrocephalus at admission, patients with hydrocephalus were younger (52.0 years vs 58.6 years, p=0.03) and underwent more frequently tumor resection (93.9% vs 73.9%, p=0.006). A total of 40 cerebrospinal-fluid diversion procedures were performed, including 18 endoscopic third ventriculostomies, 12 ventriculoperitoneal shunts and 10 external ventricular drains. The different cerebrospinal-fluid diversion options had comparable functional results and complication rates. Among the 89 patients surgically managed for cGB without prior cerebrospinal-fluid diversion, 7 (7.9%) were long-term shunt-dependant. Hydrocephalus is frequent in patients with cGB and has to be carefully managed in order not to interfere with adjuvant oncological treatments. In case of symptomatic hydrocephalus, a cerebrospinal-fluid diversion is mandatory, especially if surgical resection is not feasible. In case of asymptomatic hydrocephalus, a cerebrospinal-fluid diversion has to be discussed only if surgical resection is not feasible.

Introduction Although the association of developmental venous anomalies (DVAs) with cavernous malformations is well documented, the association with arteriovenous malformations (AVM) is unusual. The aim is herein to report an additional case and to review the concepts associated to these mixed malformations in order to guide patient management. Methods A case of AVM associated with a DVA was identified and a literature review was performed according to PRISMA guidelines. Case report In an 18-year-old man presenting with sub-acute headache but with a normal neurological examination, the MRI-scan showed a right occipital DVA associated with hemosiderin spots evocative of earlier asymptomatic bleedings. The Digital Subtraction Angiography revealed a right parieto-occipital Spetzler-Martin Grade III AVM, fed by branches from the right middle and posterior cerebral arteries, with a superficial drainage flowing into a DVA that then joined the superior sagittal sinus. Multistep embolization was performed, leading to a partial reduction of the nidus, but preserving the DVA permeability. After a six-year follow-up. bleeding did not recur and the MRI aspect of the malformation was perfectly stable. Conclusion The co-occurrence of a DVA and an AVM is rare but has a higher bleeding risk than AVM alone (69% vs 38%) and must consequently be suspected when a DVA is revealed by a haemorrhage, in the absence of associated cavernoma. These mixed malformations represent a therapeutic challenge which has to be tailored to the venous anatomy and to the malformation Spetzler-Martin grade. DVA permeability should be preserved to avoid deleterious venous infarction.

BACKGROUND Pulse pressure variation (PPV) and plethysmographic variability index (PVI), dynamic indicators of preload dependence based on heart-lung interactions, are used to predict fluid responsiveness in mechanically ventilated patients in the supine position. The sitting position for neurosurgery, by changing intrathoracic blood volume, could affect the capacity of PPV and PVI to predict fluid responsiveness. The aim of the study was to assess the ability of PPV and PVI to predict fluid responsiveness during general anesthesia in the sitting position. METHODS In total, 31 patients were included after settling in the sitting position but before surgery began. PPV, PVI with a finger sensor (PVI finger), and PVI with an ear sensor (PVI ear) were recorded before and after a fluid challenge of hydroxylethylstarch 250 mL over 10 minute. Esophageal Doppler was used to record stroke volume. Patients were defined as fluid responders if stroke volume increased by more than 10% after the fluid challenge. RESULTS In total, 13 (42%) patients were fluid responders. PPV and PVI ear were higher in responders than in nonresponders before the fluid challenge (12±5 vs. 7±3; P=0.0005 and 14±5 vs. 8±3; P=0.001, respectively). Areas under the receiver-operating curves to predict fluid responsiveness were 0.87 for PPV (P

Adult IDH-wildtype astrocytomas with TERT promoter mutations (TERTp) are associated with a poor prognosis.To analyze the radiological presentation and natural history of adult IDH-wildtype astrocytomas with TERTp.We retrospectively reviewed the characteristics of 40 IDH-wildtype TERTp-mutant astrocytomas (grade II n = 19, grade III n = 21) and compared them to those of 114 IDH-mutant lower grade gliomas (LGG), of 92 IDH-wildtype TERTp-mutant glioblastomas, and of 15 IDH-wildtype TERTp-wildtype astrocytomas.Most cases of IDH-wildtype TERTp-mutant astrocytomas occurred in patients aged50 yr (88%) and presented as infiltrative lesions without contrast enhancement (73%) that were localized in the temporal and/or insular lobes (37.5%) or corresponded to a gliomatosis cerebri (43%). Thalamic involvement (33%) and extension to the brainstem (27%) were frequently observed, as was gyriform infiltration (33%). This radiological presentation was different from that of IDH-mutant LGG, IDH-wildtype TERTp-mutant glioblastomas, and IDH-wildtype TERTp-wildtype astrocytomas. Tumor evolution before treatment initiation was assessable in 17 cases. Ten cases demonstrated a rapid growth characterized by the apparition of a ring-like contrast enhancement and/or a median velocity of diametric expansion (VDE) ≥8 mm/yr but 7 cases displayed a slow growth (VDE8 mm/yr) that could last several years before anaplastic transformation. Median overall survival of IDH-wildtype TERTp-mutant astrocytomas was 27 mo.IDH-wildtype TERTp-mutant astrocytomas typically present as nonenhancing temporo-insular infiltrative lesions or as gliomatosis cerebri in patients aged50 yr. In the absence of treatment, although rapid tumor growth is frequent, an initial falsely reassuring, slow growth can be observed.

BACKGROUND The role of surgery for the treatment of malignant gliomas in patients 70 years of age or older is unsettled. We conducted a randomized trial that compared surgical resection of the tumor and biopsy only, both followed by standard therapy, in such patients. MATERIAL AND METHODS Patients aged 70 years and older, with a KPS of at least 50, presenting with a radiological suspicion of an operable glioblastoma (GBM) were randomly assigned between tumor resection and biopsy. Subsequently, they underwent standard radiotherapy during the first years of the trial (2008–2017), with the adjunction of concomitant and adjuvant temozolomide when this regimen became standard (2017–2019). The primary end point was survival; secondary endpoints were progression free survival (PFS), cognitive status (MMS), autonomy (KPS), quality of life (EORTC QLQ C30 and BN20), and perioperative morbidity/ mortality. RESULTS From 2008 to 2019, 107 patients from 9 centers were enrolled in the study, of whom 101 were evaluable for analysis because the diagnosis of GBM was histologically confirmed (50 patients in the “surgery” arm and 51 patients in the “biopsy” arm). There was no statistically significant difference of median survival between the “surgery” arm (9.37 mo) and the “biopsy” arms (8.96 mo, p=0.36). However, the surgery group had increased PFS (5.06 mo vs 4.02 mo; p=0.034; p=0.002 on multivariate analysis) and better QOL (e.g. physical and cognitive functioning, motor dysfunction, fatigue) and KPS score evolution as compared to the “biopsy” group. Surgery was not associated with increased mortality or morbidity. CONCLUSION This study suggests that optimal debulking surgery does not provide a significant survival benefit in elderly patients suffering from newly diagnosed malignant glioma, but resection improves QOL and autonomy with a significant though modest improvement of PFS.

A growing literature supports maximal safe resection followed by standard combined chemoradiotherapy (i.e. maximal first-line therapy) for selected elderly glioblastoma patients. To assess the prognostic factors from recurrence in elderly glioblastoma patients treated by maximal safe resection followed by standard combined chemoradiotherapy as first-line therapy. Multicentric retrospective analysis comparing the prognosis and optimal oncological management of recurrent glioblastomas between 660 adult patients aged of

International audience; Gliomas are diffuse brain tumors still hardly curable due to the difficulties to identify margins. 5-ALA induced PpIX fluorescence measurements enable to gain in sensitivity but are still limited to discriminate margin from healthy tissue. In this fluorescence spectroscopic study, we compare an expert-based model assuming that two states of PpIX contribute to total fluorescence and machine learning-based models. We show that machine learning retrieves the main features identified by the expert approach. We also show that machine learning approach slightly overpasses expert-based model for the identification of healthy tissues. These results might help to improve fluorescence-guided resection of gliomas by discriminating healthy tissues from tumor margins.

Gliomas are infiltrative brain tumors with a margin difficult to identify. 5-ALA induced PpIX fluorescence measurements are a clinical standard, but expert-based classification models still lack sensitivity and specificity. Here a fully automatic clustering method is proposed to discriminate glioma margin. This is obtained from spectroscopic fluorescent measurements acquired with a recently introduced intraoperative set up. We describe a data-driven selection of best spectral features and show how this improves results of margin prediction from healthy tissue by comparison with the standard biomarker-based prediction. This pilot study based on 10 patients and 50 samples shows promising results with a best performance of 77% of accuracy in healthy tissue prediction from margin tissue.

Background Intracranial meningiomas display a variable amount of peritumoral brain edema (PTBE), which can significantly impact perioperative morbidity. The role of microcirculatory disturbances in the pathogenesis of PTBE is still debated. The aim of this study was to microscopically demonstrate and intraoperatively quantify, for the first time, the alterations to microcirculation in PTBE using sidestream dark-field (SDF) imaging. Methods Adult patients with WHO grade I meningiomas were recruited over a 9-month period and divided into 2 groups depending on the absence (NE group) or the presence (E group) of PTBE. In vivo intraoperative microcirculation imaging was performed in the peritumoral area before and after microsurgical resection. Results Six patients were included in the NE group and 6 in the E group. At the baseline in the NE group, there was a minor decrease in microcirculatory parameters compared to normal reference values, which was probably due to the mass effect. In contrast, microcirculatory parameters in the E group were significantly altered, affecting both vessel density and blood flow values, with a drop of approximately 50% of normal values. Surgical resection resulted in a quasi-normalization of microcirculation parameters in the NE group, whereas in the E group, even if all parameters statistically significantly improved, post-resection values remained considerably inferior to those of the normal reference pattern. Conclusion Our study confirmed significant alterations of microcirculatory parameters in PTBE in meningiomas. Further in vivo SDF imaging studies may explore the possible correlation between the severity of these microcirculatory alterations and the postoperative neurological outcome.

International audience; Intraoperative optical imaging is a localization technique for the functional areas of the human brain cortex during neurosurgical procedures. However, it still lacks robustness to be used as a clinical standard. In particular, new biomarkers of brain functionality with improved sensitivity and specificity are needed. We present a method for the computation of hemodynamics-based functional brain maps using an RGB camera and a white light source. We measure the quantitative oxy and deoxyhemoglobin concentration changes in the human brain cortex with the modified Beer-Lambert law and Monte Carlo simulations. A functional model has been implemented to evaluate the functional brain areas following neuronal activation by physiological stimuli. The results show a good correlation between the computed quantitative functional maps and the brain areas localized by electrical brain stimulation (EBS). We demonstrate that an RGB camera combined with a quantitative modeling of brain hemodynamics biomarkers can evaluate in a robust way the functional areas during neurosurgery and serve as a tool of choice to complement EBS. © The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

A RGB camera and a continuous wave white light illumination is a suitable approach to intraoperatively localize the sensory and motor areas of the patient brain. The analysis of the reflectance spectra through the modified Beer-Lambert law enables us to measure the concentration changes of oxygenated and deoxygenated hemoglobin during the video acquisition. However these concentration changes depend on the wavelength dependent optical mean path length. A manual image segmentation and Monte-Carlo simulations allow us to precisely choose the mean path length in a pixel-wise manner.

We demonstrate that a RGB camera and a continuous wave white light illumination is a suitable approach to intraoperatively localize in real time the sensory and motor areas of the patient brain. The analysis of the reflectance spectra of the acquired light and Monte Carlo simulations allow us to measure the concentration changes of oxygenated and deoxygenated hemoglobin during the video acquisition. These measures are compared to the expected hemodynamic response to precisely localize the functional areas of the patient brain.

Background Diffuse H3 K27M-mutant gliomas occur primarily in children but can also be encountered in adults. The aim of this study was to describe the characteristics of H3 K27M-mutant gliomas in adults. Methods We analyzed the characteristics of 21 adult H3 K27M-mutant gliomas and compared them with those of 135 adult diffuse gliomas without histone H3 and without isocitrate dehydrogenase (IDH) mutation (IDH/H3 wild type). Results The median age at diagnosis in H3 K27M-mutant gliomas was 32 years (range: 18-82 y). All tumors had a midline location (spinal cord n = 6, thalamus n = 5, brainstem n = 5, cerebellum n = 3, hypothalamus n = 1, and pineal region n = 1) and were IDH and BRAF-V600E wild type. The identification of an H3 K27M mutation significantly impacted the diagnosis in 3 patients (14%) for whom the histological aspect initially suggested a diffuse low-grade glioma and in 7 patients (33%) for whom pathological analysis hesitated between a diffuse glioma, ganglioglioma, or pilocytic astrocytoma. Compared with IDH/H3 wild-type gliomas, H3 K27M-mutant gliomas were diagnosed at an earlier age (32 vs 64 y, P < .001), always had a midline location (21/21 vs 21/130, P < .001), less frequently had a methylated MGMT promoter (1/21 vs 52/129, P = .002), and lacked EGFR amplification (0/21 vs 26/128, P = .02). The median survival was 19.6 months in H3 K27M-mutant gliomas and 17 months in IDH/H3 wild-type gliomas (P = .3). Conclusion In adults, as in children, H3 K27M mutations define a distinct subgroup of IDH wild-type gliomas characterized by a constant midline location, low rate of MGMT promoter methylation, and poor prognosis.

Background The management of gliomas is based on precise histologic diagnosis. The tumor tissue can be obtained during open surgery or via stereotactic biopsy. Intraoperative tissue imaging could substantially improve biopsy precision and, ultimately, the extent of resection. Objective To show the feasibility of intraoperative in vivo probe-based confocal laser endomicroscopy (pCLE) in surgery and biopsy of gliomas. Methods In our prospective observational study, 9 adult patients were enrolled between September 2014 and January 2015. Two contrast agents were used: 5-aminolevulinic acid (3 cases) or intravenous fluorescein (6 cases). Intraoperative imaging was performed with the Cellvizio system (Mauna Kea Technologies, Paris). A 0.85-mm probe was used for stereotactic procedures, with the biopsy needle modified to have a distal opening. During open brain surgery, a 2.36-mm probe was used. Each series corresponds to a separate histologic fragment. Results The diagnoses of the lesions were glioblastoma (4 cases), low-grade glioma (2), grade III oligoastrocytoma (2), and lymphoma (1). Autofluorescence of neurons in cortex was observed. Cellvizio images enabled differentiation of healthy "normal" tissue from pathological tissue in open surgery and stereotactic biopsy using fluorescein. 5-Aminolevulinic acid confocal patterns were difficult to establish. No intraoperative complications related to pCLE or to use of either contrast agent were observed. Conclusion We report the initial feasibility and safety of intraoperative pCLE during primary brain tumor resection and stereotactic biopsy procedures. Pending further investigation, pCLE of brain tissue could be utilized for intraoperative surgical guidance, improvement in brain biopsy yield, and optimization of glioma resection via analysis of tumor margins. Abbreviations 5-ALA, 5-aminolevulinic acidpCLE, probe-based confocal laser endomicroscopyPpIX, protoporphyrin IX.

cited By 0; International audience; Background: When feasible, the surgical resection is the standard first step of the management of high-grade gliomas. 5-ALA fluorescence-guided-surgery (5-ALA-FGS) was developed to ease the intra-operative delineation of tumor borders in order to maximize the extent of resection. Methods: A Medline electronic database search was conducted. English language studies from January 1998 until July 2018 were included, following the PRISMA guidelines. Results: 5-ALA can be considered as a specific tool for the detection of tumor remnant but has a weaker sensibility (level 2). 5-ALA-FGS is associated with a significant increase in the rate of gross total resection reaching more than 90% in some series (level 1). Consistently, 5-ALAFGS improves progression-free survival (level 1). However, the gain in overall survival is more debated. The use of 5-ALA-FGS in eloquent areas is feasible but requires simultaneous intraoperative electrophysiologic functional brain monitoring to precisely locate and preserve eloquent areas (level 2). 5-ALA is usable during the first resection of a glioma but also at recurrence (level 2). From a practical standpoint, 5-ALA is orally administered 3 hours before the induction of anesthesia, the recommended dose being 20 mg/kg. Intra-operatively, the procedure is performed as usually with a central debulking and a peripheral dissection during which the surgeon switches from white to blue light. Provided that some precautions are observed, the technique does not expose the patient to particular complications. Conclusion: Although 5-ALA-FGS contributes to improve gliomas management, there are still some limitations. Future methods will be developed to improve the sensibility of 5-ALA-FGS. © 2019 Elsevier Masson SAS

cited By 0; Purpose: A first cost-effectiveness analysis has raised a strong concern regarding the cost of tumor treatment fields (TTF) added to maintenance temozolomide for patients with glioblastoma. This evaluation was based on effectiveness outcomes from an interim analysis of the pivotal trial, moreover it used a “standard” Markov model. Our objective was to update the cost-effectiveness evaluation using the more flexible potential of the “partitioned survival” model design and using the latest effectiveness data. Methods: We developed the model with three mutually exclusive health states: stable disease, progressive disease, and dead. Good fit parametric models were developed for overall survival and progression free survival and these generated clinically plausible extrapolations beyond the observed data. We adopted the perspective of the French national health insurance and used a 20-year time horizon. Results were expressed as cost/life-years (LY) gained (LYG). Results: The base case model generated incremental benefit of 0.604 LY at a cost of €453,848 which, after 4% annual discounting of benefits and costs, yielded an incremental cost effectiveness ratio (ICER) of €510,273/LYG. Using sensitivity analyses and bootstrapping methods results were found to be relatively robust and were only sensitive to TTF device costs and the modelling of overall survival. To achieve an ICER below €100,000/LYG would require a reduction in TTF device cost of approximately 85%. Conclusions: Using a different type of model and updated survival outcomes, our results show TTF remains an intervention that is not cost-effective, which greatly restrains its diffusion to potentially eligible patients. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.

Gliomas are diffuse and hard to cure brain tumors. A major reason for their aggressive behavior is their property to infiltrate the brain. The gross appearance of the infiltrative component is comparable to normal brain, constituting an obstacle to extended surgical resection. 5-ALA induced PpIX fluorescence measurements enable gains in sensitivity to detect infiltrated cells, but still lack sensitivity to get accurate discrimination between the tumor margin and healthy tissue. In this fluorescence spectroscopic study, we assume that two states of PpIX contribute to total fluorescence to get better discrimination of healthy tissues against tumor margins. We reveal that fluorescence in low-density margins of high-grade gliomas or in low-grade gliomas is mainly influenced by the second state of PpIX centered at 620 nm. We thus conclude that consideration of the contributions of both states to total fluorescence can help to improve fluorescence-guided resection of gliomas by discriminating healthy tissues from tumor margins.

International audience; In this paper, we present a motion compensation algorithm dedicated to video processing during neurosurgery. After craniotomy, the brain surface undergoes a repetitive motion due to the cardiac pulsation. This motion as well as potential video camera motion prevent accurate video analysis. We propose a dedicated motion model where the brain deformation is described using a linear basis learned from a few initial frames of the video. As opposed to other works using linear basis for the flow, the camera motion is explicitly accounted in the transformation model. Despite the nonlinear nature of our model, all the motion parameters are robustly estimated all at once, using only one singular value decomposition (SVD), making our procedure computationally efficient. A Lagrangian specification of the flow field ensures the stability of the method. Experiments on in vivo data are presented to evaluate the capacity of the method to cope with occlusion or camera motion. The method we propose satisfies the intraoperative constraints: it is robust to surgical tools occlusions, it works in real time, and it is able to handle large camera viewpoint changes.

International audience; ObjectiveAneurysm wall biomechanics are not yet an integral part of aneurysm rupture risk evaluation. We aimed to develop a new technique describing the biomechanical properties of aneurysm wall and correlating them to rupture status.MethodsAneurysm wall samples collected during surgery were submitted before and after freezing to tensile tests or as fresh samples to indentation tests. The lateral stiffness or the Young's modulus of the different samples was determined as a function of the mechanical test used. The impact of freezing on biomechanical properties was evaluated. The correlation of clinical and radiologic data with the biomechanical profile of the aneurysm samples was investigated. Two-photon microscopy was used to study collagen fiber organization.ResultsSixteen aneurysm samples (11 unruptured and 5 ruptured) were included. Freezing decreased tissue stiffness. No significant difference was found between ruptured and unruptured aneurysm wall samples regarding demographic characteristics, ethnicity, smoking status, arterial hypertension, site, size and shape of the aneurysm, PHASES score, mechanical profile, or overall Young's modulus. Indentation tests found that the rupture occurred in a restricted area of increased elastic capacity and unruptured areas had increased stiffness. Two-photon microscopy found disruption of the collagen fiber network in rupture zones.ConclusionsThe indentation test of fresh aneurysm wall samples described the heterogeneity of biomechanical properties of the tissue and found increased elastic capacity in the rupture zone and increased stiffness in the remainder of the aneurysm. This study could be a basis for further research aimed at building a biomechanical-based model of aneurysm rupture risk.

BACKGROUND: Adult IDH-wildtype astrocytomas with TERT promoter mutations (TERTp) are associated with a poor prognosis. The aim of the present study was to analyze their radiological presentation and natural history. MATERIAL AND METHODS: We retrospectively reviewed the characteristics of 40 IDH-wildtype TERTp-mutant astrocytomas (grade II n=19, grade III n=21) and compared them to those of 114 IDH-mutant lower grade gliomas (LGG), of 92 IDH-wildtype TERTp-mutant glioblastomas and of 15 IDH-wildtype TERTp-wildtype astrocytomas. RESULTS: Most cases of IDH-wildtype TERTp-mutant astrocytomas occurred in patients aged >50 years (88%) and presented as infiltrative lesions without contrast enhancement (73%) that were localized in the temporal and/or insular lobes (37.5%) or corresponded to a gliomatosis cerebri (43%). Thalamic involvement (33%) and extension to the brainstem (27%) were frequently observed, as was gyriform infiltration (33%). This radiological presentation was different from that of IDH-mutant LGG, IDH-wildtype TERTp-mutant glioblastomas, and IDH-wildtype TERTp-wildtype astrocytomas. Tumor evolution before treatment initiation was assessable in 17 cases. Ten cases demonstrated a rapid growth characterized by the apparition of a ring-like contrast enhancement and/or a median velocity of diametric expansion (VDE) ≥ 8 mm/year but 7 cases displayed a slow growth (VDE < 8 mm/year) that could last several years before anaplastic transformation. Median overall survival of IDH-wildtype TERTp-mutant astrocytomas was 27 months. CONCLUSION: IDH-wildtype TERTp-mutant astrocytomas typically present as non-enhancing temporo-insular infiltrative lesions or as gliomatosis cerebri in patients aged >50 years. In the absence of treatment, although rapid tumor growth is frequent, an initial falsely reassuring, slow growth can be observed.