Intracranial dural arteriovenous fistulas: association with cerebral venous thrombosis, baseline aggressiveness, and clinical outcomes. A retrospective multicenter study on 263 consecutive patients and literature review.

OBJECTIVE: The pathogenesis of intracranial dural arteriovenous fistulas (icDAVFs) is controversial. Cerebral vein thrombosis (CVT) and venous hypertension are recognized predisposing factors. This study aimed to evaluate the incidence of association between icDAVF and CVT and describe baseline aggressiveness and clinical outcomes for icDAVFs associated with CVT. The authors also performed a literature review of studies reporting icDAVF associated with CVT. METHODS: Two hundred sixty-three consecutive patients in two university hospitals with confirmed icDAVFs were included. A double-blind imaging review was performed to determine the presence or absence of CVT close or distant to the icDAVF. Location, type (using the Cognard classification), aggressiveness of the icDAVF, clinical presentation, treatment modality, and clinical and/or angiographic outcomes at 6 months were also collected. All prior brain imaging was analyzed to determine the natural history of onset of the icDAVF. RESULTS: Among the 263 included patients, 75 (28.5%) presented with a CVT concomitant to their icDAVF. For 18 (78.3%) of 23 patients with previous brain imaging available, CVT preceding the icDAVF was proven (6.8% of the overall population). Former/active smoking (OR 2.0, 95% CI 1.079-3.682, p = 0.022) and prothrombogenic status (active inflammation or cancer/coagulation trouble) were risk factors for CVT associated with icDAVF (OR 3.135, 95% CI 1.391-7.108, p = 0.003). One hundred eighty-seven patients (71.1%) had a baseline aggressive icDAVF, not linked to the presence of a CVT (p = 0.546). Of the overall population, 11 patients (4.2%) presented with spontaneous occlusion of their icDAVF at follow-up. Seven patients (2.7%) died during the follow-up period. Intracranial DAVF + CVT was not associated with a worse prognosis (modified Rankin Scale score at 3-6 months: 0 [interquartile range {IQR} 0-1] for icDAVF + CVT vs 0 [IQR 0-0] for icDAVF alone; p = 0.055). CONCLUSIONS: This was one of the largest studies focused on the incidence of CVT associated with icDAVF. For 6.8% of the patients, a natural history of CVT leading to icDAVF was proven, corresponding to 78.3% of patients with previous imaging available. This work offers further insights into icDAVF pathophysiology, aiding in identifying high-risk CVT patients for long-term follow-up imaging. Annual imaging follow-up using noninvasive vascular imaging (CT or MR angiography) for a minimum of 3 years after the diagnosis of CVT should be considered in high-risk patients, i.e., smokers and those with prothrombogenic status.

KDM1A genotyping and expression in 146 sporadic somatotroph pituitary adenomas.

IMPORTANCE: A paradoxical increase of growth hormone (GH) following oral glucose load has been described in ∼30% of patients with acromegaly and has been related to the ectopic expression of the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) in somatotropinomas. Recently, we identified germline pathogenic variants and somatic loss of heterozygosity of lysine demethylase 1A (KDM1A) in patients with GIP-dependent primary bilateral macronodular adrenal hyperplasia with Cushing's syndrome. The ectopic expression of GIPR in both adrenal and pituitary lesions suggests a common molecular mechanism. OBJECTIVE: We aimed to analyze KDM1A gene sequence and KDM1A and GIPR expressions in somatotroph pituitary adenomas. SETTINGS: We conducted a cohort study at university hospitals in France and in Italy. We collected pituitary adenoma specimens from acromegalic patients who had undergone pituitary surgery. We performed targeted exome sequencing (gene panel analysis) and array-comparative genomic hybridization on somatic DNA derived from adenomas and performed droplet digital PCR on adenoma samples to quantify KDM1A and GIPR expressions. RESULTS: One hundred and forty-six patients with sporadic acromegaly were studied; 72.6% presented unsuppressed classical GH response, whereas 27.4% displayed a paradoxical rise in GH after oral glucose load. We did not identify any pathogenic variant in the KDM1A gene in the adenomas of these patients. However, we identified a recurrent 1p deletion encompassing the KDM1A locus in 29 adenomas and observed a higher prevalence of paradoxical GH rise (P = .0166), lower KDM1A expression (4.47 ± 2.49 vs 8.56 ± 5.62, P < .0001), and higher GIPR expression (1.09 ± 0.92 vs 0.43 ± 0.51, P = .0012) in adenomas from patients with KDM1A haploinsufficiency compared with those with 2 KDM1A copies. CONCLUSIONS AND RELEVANCE: Unlike in GIP-dependent primary bilateral macronodular adrenal hyperplasia, KDM1A genetic variations are not the cause of GIPR expression in somatotroph pituitary adenomas. Recurrent KDM1A haploinsufficiency, more frequently observed in GIPR-expressing adenomas, could be responsible for decreased KDM1A function resulting in transcriptional derepression on the GIPR locus.

Nidus Compacity Determined by Semi-Automated Segmentation is a Strong Quantitative Predictor of Brain Arterio-Venous Malformation Cure.

BACKGROUND AND OBJECTIVE: A compact nidus is a well-known feature of good outcome after treatment in brain arteriovenous malformations (bAVM). This item, included in the "Supplementary AVM grading system" by Lawton, is subjectively evaluated on DSA. The present study aimed to assess whether quantitative nidus compacity along with other angio-architectural bAVM features were predictive of angiographic cure or the occurrence of procedure-related complications. MATERIALS AND METHODS: Retrospective analysis of 83 patients prospectively collected data base between 2003 to 2018 having underwent digital subtraction 3D rotation angiography (3D-RA) for pre-therapeutic assessment of bAVM. Angio-architectural features were analyzed. Nidus compacity was measured with a dedicated segmentation tool. Univariate and multivariate analyses were performed to test the association between these factors and complete obliteration or complication. RESULTS: Compacity was the only significant factor associated with complete obliteration in our predictive model using logistic multivariate regression; the area under the curve for compacity predicting complete obliteration was excellent (0.82; 95% CI 0.71-0.90; p < 0.0001). The threshold value maximizing the Youden index was a compacity > 23% (sensitivity 97%; specificity 52%; 95% CI 85.1-99.9; p = 0.055). No angio-architectural factor was associated with the occurrence of a complication. CONCLUSION: Nidus high compacity quantitatively measured on 3D-RA, using a dedicated segmentation tool is predictive of bAVM cure. Further investigation and prospective studies are warranted to confirm these preliminary results.

Endovascular treatment as first-line therapy in Spetzler-Martin grade III brain arteriovenous malformations: a multicenter retrospective study.

OBJECTIVE: The management of Spetzler-Martin grade (SMG) III brain arteriovenous malformations (bAVMs) may be challenging, whatever the exclusion treatment modality chosen. The purpose of this study was to evaluate the safety and effectiveness of endovascular treatment (EVT) as a first-line treatment of SMG III bAVMs. METHODS: The authors performed a retrospective, two-center, observational cohort study. Cases recorded in institutional databases between January 1998 and June 2021 were reviewed. Patients who were ≥ 18 years of age, had ruptured or unruptured SMG III bAVMs, and received EVT as first-line therapy were included. Baseline characteristics of patients and bAVMs, procedure-related complications, clinical outcome according to the modified Rankin Scale, and angiographic follow-up were assessed. The independent risk factors of procedure-related complications and poor clinical outcome were assessed using binary logistic regression. RESULTS: One hundred sixteen patients with 116 SMG III bAVMs were included. The mean age of the patients was 41.9 ± 14.0 years. The most common presentation was hemorrhage (66.4%). Forty-nine (42.2%) bAVMs were found to be completely obliterated by EVT alone at follow-up. Complications occurred in 39 patients (33.6%), including 5 (4.3%) major procedure-related complications. There was no independent predictor of procedure-related complication. Age > 40 years and poor preoperative modified Rankin Scale score were the independent predictors of poor clinical outcome. CONCLUSIONS: EVT of SMG III bAVMs provides encouraging results but needs further improvement. When the embolization procedure performed with intent to cure appears difficult and/or risky, a combined technique (with microsurgery or radiosurgery) may be a safer and more effective strategy. In terms of safety and effectiveness, the benefit of EVT (alone or included in a multimodal management strategy) for SMG III bAVMs needs to be confirmed by randomized controlled trials.

Corticosteroid treatment for refractory intracranial hypertension: a rescue therapy in patients with severe traumatic brain injury with contusional lesions-a feedback.

INTRODUCTION: Refractory intracranial hypertension (rICH) is a severe complication among patients with severe traumatic brain injury (sTBI). Medical treatment may be insufficient, and in some cases, the only viable treatment option is decompressive hemicraniectomy. The assessment of a corticosteroid therapy against vasogenic edema secondary to severe brain injuries seems interesting to prevent this surgery in sTBI patients with rICH caused by contusional areas. METHODS: This is a monocentric retrospective observational study including all consecutive sTBI patients with contusion injuries and a rICH requiring cerebrospinal fluid drainage with external ventricular drainage between November 2013 and January 2018. Patient inclusion criterium was a therapeutic index load (TIL; an indirect measure of TBI severity) > 7. Intracranial pressure (ICP) and TIL were assessed before and 48 h after corticosteroid therapy (CTC). Then, we divided the population into two groups according to the evolution of the TIL: responders and non-responders to corticosteroid therapy. RESULTS: During the study period, 512 patients were hospitalized for sTBI, and among them, 44 (8.6%) with rICH were included. They received 240 mg per day [120 mg, 240 mg] of Solu-Medrol for 2 days [1; 3], 3 days after the sTBI. The average ICP in patients with rICH before the CTC bolus was 21 mmHg [19; 23]. After the CTC bolus, the ICP fell significantly to less than 15 mmHg (p < 0.0001) for at least 7 days. The TIL decreased significantly the day after the CTC bolus and until day 2. Among these 44 patients, 68% were included in the responder group (n = 30). DISCUSSION: Short and systemic corticosteroid therapy in patients with refractory intracranial hypertension secondary to severe traumatic brain injury seems to be a potentially useful and efficient treatment for lowering intracranial pressure and decreasing the need for more invasive surgeries.

'Balloon pressure technique' for endovascular treatment of spinal cord arteriovenous fistulas: preliminary results in 10 cases.

BACKGROUND: Spinal arteriovenous fistulas (SAVFs) are challenging lesions to treat by endovascular means. Our purpose was to report our early experience with dual lumen balloons (DLBs) for embolization of SAVFs using ethylene vinyl alcohol (EVOH) (the so-called 'balloon pressure technique' (BPT)). MATERIALS AND METHODS: During the inclusion period, 10 consecutive patients (nine men, mean age 61.6 years) underwent endovascular treatment of a SAVF (seven dural SAVFs and three epidural SAVFs) at a single institution using the BPT. DLBs were used in all cases. In seven cases (70%), a regular DLB was used, while in three cases (30%), low profile DLBs were used. EVOH was used as the liquid embolic agent in all cases. Technical and clinical complications were systematically recorded. Clinical and angiographic outcomes were systematically evaluated more than 3 months after the procedure. RESULTS: Complete cure of the SAVF by endovascular means alone was obtained in 80% of cases (8/10). For the two patients with incomplete SAVF occlusion, surgery was successfully performed secondarily. No recurrence was found at the 3 month follow-up in the eight patients for whom complete occlusion was obtained at the end of the embolization procedure. No permanent clinical complication was recorded using the BPT. Clinical improvement was observed in 6/10 (60%) cases. CONCLUSION: BPT was a feasible technique, with regular or low profile DLBs, for embolization of SAVFs. Our preliminary results suggest the safety and effectiveness of this technique.

Safety and Effectiveness of First-line Endovascular Management of Low-Grade Brain Arteriovenous Malformations : Single Center Experience in 145 Patients.

PURPOSE: Spetzler-Martin grade (SMG) I-II (low-grade) brain arteriovenous malformations (BAVMs) are often considered safe for microsurgical resection; however, the role of endovascular treatment (EVT) remains to be clarified in this indication, especially for unruptured BAVMs. The purpose of our study was to assess the safety and effectiveness of endovascular treatment as the first-line treatment for low-grade BAVMs. METHODS: From our local database, we retrospectively retrieved patients with low-grade BAVMs, either ruptured or unruptured, treated by embolization as first-line treatment in our department between January 2005 and January 2020. The primary endpoint was the total obliteration rate of BAVMs, and secondary endpoints were hemorrhagic complications and final clinical outcome, assessed through shift of the modified Rankin scale, and mortality rate secondary to BAVM embolization. RESULTS: A total of 145 patients meeting inclusion criteria and treated by EVT as first-line therapy were included in the study (82 ruptured and 63 unruptured BAVMs). Overall, complete exclusion of BAVMs was achieved in 110 patients (75.9%); 58 patients (70.7%) with ruptured and 52 (82.5%) unruptured BAVMs, including 37.9% BAVMs excluded by EVT alone (35.5% among ruptured and 44.4% among unruptured BAVMs) and 38% by combined treatment (EVT and surgery or EVT and SRS). There was no BAVM volume cut-off predictive for total obliteration by embolization alone. Early minor hemorrhagic complications were reported in 14 patients (9.6%) and early major hemorrhagic complications were reported in 5 patients (3.4%). No late hemorrhagic complications (0%) occurred; mortality rate was 0.7% (1/145 patients). Improved/unchanged mRS was reported in 137 patients (94.5%). CONCLUSION: Endovascular treatment alone or associated with others exclusion techniques, might be safe and effective for complete exclusion of low-grade brain arteriovenous malformations regardless of the volume.

Brain Biopsy for Neurological Diseases of Unknown Etiology in Critically Ill Patients: Feasibility, Safety, and Diagnostic Yield.

OBJECTIVES: Brain biopsy is a useful surgical procedure in the management of patients with suspected neoplastic lesions. Its role in neurologic diseases of unknown etiology remains controversial, especially in ICU patients. This study was undertaken to determine the feasibility, safety, and the diagnostic yield of brain biopsy in critically ill patients with neurologic diseases of unknown etiology. We also aimed to compare these endpoints to those of non-ICU patients who underwent a brain biopsy in the same clinical context. DESIGN: Monocenter, retrospective, observational cohort study. SETTING: A French tertiary center. PATIENTS: All adult patients with neurologic diseases of unknown etiology under mechanical ventilation undergoing in-ICU brain biopsy between January 2008 and October 2020 were compared with a cohort of non-ICU patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 2,207 brain-biopsied patients during the study period, 234 biopsies were performed for neurologic diseases of unknown etiology, including 29 who were mechanically ventilated and 205 who were not ICU patients. Specific histological diagnosis and final diagnosis rates were 62.1% and 75.9%, respectively, leading to therapeutic management modification in 62.1% of cases. Meningitis on prebiopsy cerebrospinal fluid analysis was the sole predictor of obtaining a final diagnosis (2.3 [1.4-3.8]; p = 0.02). ICU patients who experienced therapeutic management modification after the biopsy had longer survival (p = 0.03). The grade 1 to 4 (mild to severe) complication rates were: 24.1%, 3.5%, 0%, and 6.9%, respectively. Biopsy-related mortality was significantly higher in ICU patients compared with non-ICU patients (6.9% vs 0%; p = 0.02). Hematological malignancy was associated with biopsy-related mortality (1.5 [1.01-2.6]; p = 0.04). CONCLUSIONS: Brain biopsy in critically ill patients with neurologic disease of unknown etiology is associated with high diagnostic yield, therapeutic modifications and postbiopsy survival advantage. Safety profile seems acceptable in most patients. The benefit/risk ratio of brain biopsy in this population should be carefully weighted.

Exclusion treatment of ruptured and unruptured low-grade brain arteriovenous malformations: a systematic review.

PURPOSE: To assess the obliteration rate, functional outcome, hemorrhagic complication, and mortality rates of exclusion treatment of low-grade brain arteriovenous malformations (BAVMs) (Spetzler and Martin grades (SMGs) 1 and 2), either ruptured or unruptured. METHODS: Electronic databases-Ovid MEDLINE and PubMed-were searched for studies in which there was evidence of exclusion treatment of low-grade BAVMs treated either by endovascular, surgical, radiosurgical, or multimodality treatment. The primary outcome of interest was angiographic obliteration post-treatment and at follow-up. The secondary outcomes of interest were functional outcome (mRS), mortality rate, and hemorrhagic complication. Descriptive statistics were used to calculate rates and means. RESULTS: Eleven studies involving 1809 patients with low-grade BAVMs were included. Among these, 1790 patients treated by either endovascular, surgical, radiosurgical, or multimodality treatment were included in this analysis. Seventy-two percent of BAVMs were Spetzler-Martin grade II. The overall (i.e., including all exclusion treatment modalities) complete obliteration rate ranged from 36.5 to 100%. The overall symptomatic hemorrhagic complication rate ranged from 0 to 7.3%; procedure-related mortality ranged from 0 to 4.7%. CONCLUSION: Our systematic review of the literature reveals a high overall obliteration rate for low-grade BAVMs, either ruptured or unruptured, with low mortality rate and an acceptable post-treatment hemorrhagic complication rate. These results suggest that exclusion treatment of low-grade BAVMs may be safe and effective, regardless of the treatment modality chosen.

Benefits from Exclusion Treatment of Unruptured Brain Arteriovenous Malformations on Epilepsy in Adults.

PURPOSE: In approximately 30% of the patients, brain arteriovenous malformations (bAVMs) are revealed by seizures, which may alter the patients' quality of life. Our objective was to evaluate the benefits of exclusion treatment (radiosurgery, embolization and/or surgery) on posttherapeutic epilepsy in bAVM patients without intracranial hemorrhage prior to treatment. METHODS: Our retrospective observational single-center study included all consecutive adult patients with an unruptured bAVM and epilepsy, treated at our institution from 1995 to 2019 and who were followed for at least 1 year. Data on angioarchitectural characteristics of bAVMs, on epilepsy and posttreatment modified Rankin Scale (mRS) were collected. The primary endpoint was a seizure-free status (defined as Engel class IA) after exclusion treatment versus conservative management. RESULTS: In this study one hundred and one consecutive adult patients with bAVMs, epilepsy and without bAVM rupture before any treatment were included; 21 (21%) in the conservative management group vs. 80 (79%) in the exclusion treatment group. After exclusion treatment, 55% of the patients from the group were Engel IA after treatment vs. 10% of the conservative management group (odds ratio [OR] 11.37, 95% confidence interval [CI] 2.48-107.24, p < 0.001). CONCLUSION: Our results suggest that exclusion treatment in unruptured bAVMs with epilepsy is associated with a higher seizure-free rate in comparison with conservative management. Data from randomized controlled studies are necessary to confirm these findings.

Clinical Characteristics, Angioarchitecture and Management of Tectum Mesencephali Arteriovenous Malformations : A Retrospective Case Series.

PURPOSE: Tectum mesencephali arteriovenous malformations (TM-AVMs) are rare lesions deeply located close to eloquent structures making them challenging to treat. We aimed to present clinical presentation, angiographic features and treatment strategies of TM-AVMs through a single center retrospective case series. METHODS: A TM-AVMs is defined as a nidus located in the parenchyma or on the pia mater of the posterior midbrain. Records of consecutive patients admitted with TM-AVMs over a 21-year period were retrospectively analyzed. Vascular anatomy of the region is also reviewed. RESULTS: In this study 13 patients (1.63% of the complete cohort; 10 males), mean age 48 years, were included. All patients presented with intracranial hemorrhage and two patients (15%) died after an early recurrent bleeding. Mean size of the TM-AVMs was 10.1 ± 5 mm. Multiple arterial feeders were noted in every cases. Of the patients 11 underwent an exclusion treatment, 8 via embolization (6 via arterial access and 2 via venous access) and 4 via stereotactic radiosurgery (SRS) (1 patient received both). Overall success treatment rate was 7/11 patients (64% overall; 63% in the embolization group, 25% in the SRS group). Two hemorrhagic events led to a worsened outcome, one during embolization and one several years after SRS. All other patients remained clinically stable or improved. CONCLUSION: The TM-AVMs are rare but stereotypic lesions found in a hemorrhagic context. Multiple arterial feeders are always present. Endovascular treatment seems to be an effective technique with relatively low morbidity; SRS had a low success rate but was only use in a limited number of patients.

Anterior interhemispheric approach for anterior fossa dural arteriovenous fistulas.

Anterior fossa dural arteriovenous fistulas (AF-DAVF) usually display a cortical venous drainage and are therefore at risk for rupture. Microsurgery is traditionally considered in many centers as the first-line treatment since endovascular treatment (EVT) entails a lower cure rate and significant ophthalmic risks. The anterior interhemispheric approach (AIA), originally described by Mayfrank in 1996, seems to offer the effectiveness of microsurgery while limiting the risks related to subfrontal craniotomy. The objective of this study was to analyze the surgical outcomes of patients who underwent this surgical approach for the treatment of AF-DAVF. We hereby describe our 10 years' experience of patients treated for an AF-DAVF with this technique in our institution and retrospectively analyzed our results. In addition, we describe our operative technique and its specificities. Eleven patients with AF-DAVF were included in our study. The definitive cure of the fistula was confirmed in all cases with postoperative cerebral angiography. All patients had a good neurological outcome and no major complication occurred. Brain retractors were never used during surgery, the frontal sinus was never opened neither, and anosmia was never observed after surgery. Anterior interhemispheric approach seems to be safe and effective to treat AF-DAVF with lower risks than other surgical approaches. This technique could be more widely considered when facing such midline vascular lesion.

Somatic PIK3CA Mutations in Sporadic Cerebral Cavernous Malformations.

BACKGROUND: Cerebral cavernous malformations (CCMs) are common sporadic and inherited vascular malformations of the central nervous system. Although familial CCMs are linked to loss-of-function mutations in KRIT1 (CCM1), CCM2, or PDCD10 (CCM3), the genetic cause of sporadic CCMs, representing 80% of cases, remains incompletely understood. METHODS: We developed two mouse models harboring mutations identified in human meningiomas with the use of the prostaglandin D2 synthase (PGDS) promoter. We performed targeted DNA sequencing of surgically resected CCMs from patients and confirmed our findings by droplet digital polymerase-chain-reaction analysis. RESULTS: We found that in mice expressing one of two common genetic drivers of meningioma - Pik3ca H1047R or AKT1 E17K - in PGDS-positive cells, a spectrum of typical CCMs develops (in 22% and 11% of the mice, respectively) instead of meningiomas, which prompted us to analyze tissue samples from sporadic CCMs from 88 patients. We detected somatic activating PIK3CA and AKT1 mutations in 39% and 1%, respectively, of lesion tissue from the patients. Only 10% of lesions harbored mutations in the CCM genes. We analyzed lesions induced by the activating mutations Pik3ca H1074R and AKT1 E17K in mice and identified the PGDS-expressing pericyte as the probable cell of origin. CONCLUSIONS: In tissue samples from sporadic CCMs, mutations in PIK3CA were represented to a greater extent than mutations in any other gene. The contribution of somatic mutations in the genes that cause familial CCMs was comparatively small. (Funded by the Fondation ARC pour la Recherche contre le Cancer and others.).

Strategies for embolization of direct arteriovenous shunts in brain arteriovenous malformations.

Intranidal direct arteriovenous (AV) shunts are rarely observed in brain arteriovenous malformations (bAVMs).1 The endovascular treatment of such direct AV shunts may be challenging. Indeed, there is a significant risk of venous migration of the embolic agent used to occlude the AV shunt, leading to a subsequent risk of nidus bleeding due to impairment (slowdown or even occlusion) of the bAVM's venous drainage.2 Various endovascular techniques have been developed to avoid the risk of such inopportune impairment of the venous drainage during attempts to occlude a direct intranidal AV shunt.3-5 We present in this Technical Video (video 1) different endovascular strategies to occlude such direct AV shunts using dual-lumen balloons with various liquid embolic agents, or using occlusion plugs. neurintsurg;13/11/1064/V1F1V1Video 1.

Multimodal management of surgery- and radiation-refractory meningiomas: an analysis of the French national tumor board meeting on meningiomas cohort.

PURPOSE: Meningiomas represent the most frequent tumor of the central nervous system in adults. While most meningiomas are efficiently treated by surgery and radiotherapy/radiosurgery, there is a small portion of radiation- and surgery-refractory tumors for which there is no clear recommendation for optimal management. The French National Tumor Board Meeting on Meningiomas (NTBM) offers a glimpse on the current management of such patients. METHODS: We retrospectively reviewed the charts of patients presented to the multidisciplinary Meeting between 2016 and 2019. We selected patients with a progressive disease after at least two treatments, including surgery and radiotherapy. RESULTS: In this multicentric cohort of 86 cases, patients harbored 17 (19.8%) WHO Grade I, 48 (55.8%) WHO Grade II and 21 (24.4%) WHO Grade III tumors. The median number of treatments received before inclusion was 3 (range: 2 - 11). Following the Board Meeting, 32 patients (37.2%) received chemotherapy, 11 (12.8%) surgery, 17 (19.8%) radiotherapy, 14 (16.3%) watchful observation and 12 (13.9%) palliative care. After a mean follow-up of 13 months post-inclusion, 32 patients (37.2%) had died from their disease. The mean progression free survival was 27 months after radiotherapy, 10 months after surgery, 8.5 months after chemotherapy (Bevacizumab: 9 months - Octreotide/Everolimus: 8 months). CONCLUSIONS: Surgery- and radiation-refractory meningiomas represent a heterogeneous group of tumors with a majority of WHO Grade II cases. If re-irradiation and redo-surgery are not possible, bevacizumab and octreotide-everolimus appear as a valuable option in heavily pre-treated patients considering the current EANO guidelines.

Four-dimensional digital subtraction angiography for exploration of spinal cord vascular malformations: preliminary experience.

BACKGROUND: The precise understanding of the angioarchitecture of spinal vascular malformations (SVMs) is often difficult to reach with conventional digital subtraction angiography (DSA). The purpose of our study was to evaluate the potential of four-dimensional DSA (4D-DSA) (Siemens Healthcare) in the exploration of SVMs. METHODS: We retrospectively studied all patients who underwent spinal DSA, including 4D-DSA acquisition, from July 2018 to June 2019 at a single institution. All spinal DSA acquisitions were performed under general anesthesia. 4D-DSA acquisitions were acquired with the protocol '12 s DSA Dyna4D Neuro'. 12 mL of iodixanol 320 mg iodine/mL were injected via a 5 F catheter (1 mL/s during the 12 s 4D-DSA acquisition). Inter-rater (three independent reviewers) and intermodality agreements were assessed. RESULTS: Nine consecutive patients (six men, three women, mean age 55.3±19.8 years) with 10 SVMs (spinal dural arteriovenous fistulas n=3, spinal epidural arteriovenous fistulas n=2, spinal pial arteriovenous fistulas n=2, and spinal arteriovenous malformations n=2; one patient had two synchronous pial fistulas) had spinal DSA, including 4D-DSA acquisition. Inter-rater agreement was good and moderate for the venous drainage pattern and the SVM subtype, respectively. In 9 of 10 cases, the quality of the acquisition was graded as good. Satisfactory concordance between 4D-DSA and the selective microcatheterization was observed in 90% of cases for the location of the shunt point. CONCLUSION: 4D-DSA acquisition may be helpful for a better understanding of the angioarchitecture of SVMs. Larger series are warranted to confirm these preliminary results.

Idiopathic Intracranial Hypertension: Glymphedema of the Brain.

BACKGROUND: During the last decade, our understanding of cerebrospinal fluid (CSF) physiology has dramatically improved, thanks to the discoveries of both the glymphatic system and lymphatic vessels lining the dura mater in human brains. EVIDENCE ACQUISITION: We detail the recent basic science findings in the field of CSF physiology and connect them with our current understanding of the pathophysiology of idiopathic intracranial hypertension (IIH). RESULTS: Transverse sinus (TS) stenoses seem to play a major causative role in the symptoms of IIH, as a result of a decrease in the pressure gradient between the venous system and the subarachnoid space. However, the intracranial pressure can be highly variable among different patients, depending on the efficiency of the lymphatic system to resorb the CSF and on the severity of TS stenoses. It is likely that there is a subclinical form of IIH and that IIH without papilledema is probably under-diagnosed among patients with chronic migraines or isolated tinnitus. CONCLUSIONS: IIH can be summarized in the following pathological triad: restriction of the venous CSF outflow pathway-overflow of the lymphatic CSF outflow pathway-congestion of the glymphatic system. To better encompass all the stages of IIH, it is likely that the Dandy criteria need to be updated and that perhaps renaming IIH should be considered.

Neurological diseases of unknown etiology: Brain-biopsy diagnostic yields and safety.

BACKGROUND: For nonneoplastic neurological diseases, no recommendation exists regarding the place or appropriate timing of brain biopsy. The aim of this study was to evaluate the diagnostic yield and safety of brain biopsies from patients with neurological diseases of unknown etiology. METHODS: We performed a retrospective cohort study from January 1, 2008 to December 31, 2018. We analyzed 1847 brain-biopsied patients, including 178 biopsies indicated for neurological diseases of unknown etiology. Specific histological and final diagnosis rates, positive diagnosis-associated factors, complication rate and complication-associated factors were assessed. RESULTS: Specific histological diagnosis and final diagnosis rates were 71.3% and 83.1%, respectively, leading to therapeutic management change(s) for 75.3% of patients. Brain- biopsy-related mortality and permanent neurological morbidity occurred in 1.1% and 0.6% of the patients, respectively. The multivariable logistic-regression model retained (odds ratio [95% CI] only immunodepression (2.2 [1.1-4.7]; P=.04) as being independently associated with specific histological diagnosis, while supratentorial biopsy-targeted lesions (4.1 [1.1-15.2]; P=.04) were independently associated with a final diagnosis. Biopsies obtained from comatose patients were less contributive to the diagnosis (0.2 [0.05-0.7]; P=.01). Prebiopsy platelet count <100 G/L (28.5 [1.8-447]; P=.02), hydrocephalus (6.3 [1.2-15.3]; P=.02) and targeted lesions <1 cm (4.3 [1.2-15.3]; P=.03) were independently associated with brain biopsy-related complications. CONCLUSION: For highly selected patients with neurological diseases of unknown etiology, brain biopsy has a high diagnostic yield and low frequency of severe complications. We advocate that this procedure be considered early in the diagnosis algorithm of these patients.

Middle meningeal artery embolization reduces the post-operative recurrence rate of at-risk chronic subdural hematoma.

BACKGROUND: Embolization of the middle meningeal artery (MMA) has emerged as a potential treatment of chronic subdural hematomas (CSDHs). OBJECTIVE: To evaluate the impact on recurrence rate of postsurgical embolization of CSDH in patients with a higher than average risk of recurrence. METHODS: A monocentric retrospective study was performed on retrospectively collected data. From March 2018 to December 2019, embolization of the MMA was proposed as an adjunct postoperative treatment after burr-hole surgery in patients operated for a recurrent CSDH or a CSDH with an independent recurrence risk factor, including antiplatelet therapy, full anticoagulation therapy, coagulation disorder, hepatopathy, or chronic alcoholism. Patients who had undergone postoperative embolization were compared with a historic group of patients operated between March 2016 and March 2018, selected based on the same inclusion criteria. RESULTS: During the study period, 89 patients (with 74 unilateral and 15 bilateral CSDHs) were included and underwent an embolization procedure, leading to 91 out of a total of 104 MMA being embolized (88%). These were compared with 174 patients (138 unilateral and 36 bilateral CSDH) in the historic control group. One major procedure-related adverse event was registered. Four of the 89 patients (4%) required surgery for a CSDH recurrence in the embolization group, significantly less than the 24 of 174 patients (14%) in the control group (OR=0.28, 95% CI 0.07 to 0.86, p=0.02). CONCLUSIONS: Postsurgical embolization of the MMA may reduce the recurrence rate of CSDHs with a risk factor of recurrence.

Retinal microvasculature in pituitary adenoma patients: is optical coherence tomography angiography useful?

PURPOSE: To examine retinal vascular changes in the peripapillary and macular areas in patients with pituitary adenoma (PA) using optical coherence tomography angiography (OCTA). METHODS: Cross-sectional, retrospective study of 17 consecutive PA patients and 16 healthy subjects. All patients underwent a neuro-ophthalmological examination to assess the presence of optic neuropathy (ON). Static automated perimetry (SAP), macular and optic disc structural OCT [retinal nerve fibre layer (RNFL) and ganglion cell complex (GCC) thicknesses] and OCTA were performed. Pituitary adenoma (PA) patients with ON were compared to those without ON and to healthy subjects. RESULTS: Optic neuropathy (ON) was found in 16 eyes of nine PA patients. Peripapillary vessel density (ppVD) and macular vessel density (VD) in the superficial vascular plexus were significantly decreased in PA eyes with ON, compared to healthy eyes (45.21 ± 5.69 versus 50.52 ± 2.14% and 43.79 ± 5.03% versus 48.96 ± 2.94%, respectively). No significant difference in VD was observed in the macular deep vascular complex (DVC) between groups. Pituitary adenoma (PA) patients with ON had a mean ppVD reduction by 10.51% compared to healthy subjects. RNFL and GCC thicknesses were significantly reduced in PA eyes with ON compared to the other groups. Peripapillary VD (ppVD) significantly correlated with RNFL thickness and SAP mean deviation. CONCLUSIONS: Optical coherence tomography angiography showed a significant decrease in ppVD and superficial macular VD in PA eyes with ON compared to healthy eyes, according to RNFL and GCC thinning. Together with the absence of DVC alterations, it may provide further insights into neurovascular coupling.