Glioblastoma (GBM), an incurable primary brain tumor, typically requires surgical intervention followed by chemoradiation; however, recurrences remain fatal. Our previous work demonstrated that a nanomedicine hydrogel (GemC12-LNC) delays recurrence when administered post-surgery. However, tumor debulking also triggers time-dependent immune reactions that promote recurrence at the resection cavity borders. We hypothesized that combining the hydrogel with an immunomodulatory drug could enhance therapeutic outcomes. A thorough characterization of the post-surgical microenvironment (SMe) is crucial to guide combinatorial approaches.In this study, we performed cellular resolution imaging, flow cytometry and spatial hyperplexed immunofluorescence imaging to characterize the SMe in a syngeneic mouse model of tumor resection. Owing to our dynamic approach, we observed transient opening of the blood-brain barrier (BBB) during the first week after surgery. BBB permeability post-surgery was also confirmed in GBM patients. In our murine model, we also observed changes in immune cell morphology and spatial location post-surgery over time in resected animals as well as the accumulation of reactive microglia and anti-inflammatory macrophages in recurrences compared to unresected tumors since the first steps of recurrence growth. Therefore we investigated whether starting a systemic treatment with the SMAC mimetic small molecule (GDC-0152) directly after surgery would be beneficial for enhancing microglial anti-tumoral activity and decreasing the number of anti-inflammatory macrophages around the GemC12-LNC hydrogel-loaded tumor cavity. The immunomodulatory effects of this drug combination was firstly shown in patient-derived tumoroids. Its efficacy was confirmed in vivo by survival analysis and correlated with reversal of the immune profile as well as delayed tumor recurrence.This comprehensive study identified critical time frames and immune cellular targets within the SMe, aiding in the rational design of combination therapies to delay recurrence onset. Our findings suggest that post-surgical systemic injection of GDC-0152 in combination with GemC12-LNC local treatment is a promising and innovative approach for managing GBM recurrence, with potential for future translation to human patient.

BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease involving rapid motor neuron degeneration leading to brain, primarily precentral, atrophy. Neurofilament light chains are a robust prognostic biomarker highly specific to ALS, yet associations between neurofilament light chains and MR imaging outcomes are not well-understood. We investigated the role of neurofilament light chains as mediators among neuroradiologic assessments, precentral neurodegeneration, and disability in ALS. MATERIALS AND METHODS: We retrospectively analyzed a prospective cohort of 29 patients with ALS (mean age, 56 [SD, 12] years; 18 men) and 36 controls (mean age, 49 [SD, 11]?years; 18 men). Patients underwent 3T (n?=?19) or 7T (n?=?10) MR imaging, serum (n?=?23) and CSF (n?=?15) neurofilament light chains, and clinical (n?=?29) and electrophysiologic (n?=?27) assessments. The control group had equivalent 3T (n?=?25) or 7T (n?=?11) MR imaging. Two trained neuroradiologists performed blinded qualitative assessments of MR imaging anomalies (n?=?29 patients, n?=?36 controls). Associations between precentral cortical thickness and neurofilament light chains and clinical and electrophysiologic data were analyzed. RESULTS: We observed extensive cortical thinning in patients compared with controls. MR imaging analyses showed significant associations between precentral cortical thickness and bulbar or arm impairment following distributions corresponding to the motor homunculus. Finally, uncorrected results showed positive interactions among precentral cortical thickness, serum neurofilament light chains, and electrophysiologic outcomes. Qualitative MR imaging anomalies including global atrophy (P?=?.003) and FLAIR corticospinal tract hypersignal anomalies (P?=?.033), correlated positively with serum neurofilament light chains. CONCLUSIONS: Serum neurofilament light chains may be an important mediator between clinical symptoms and neuronal loss according to cortical thickness. Furthermore, MR imaging anomalies might have underestimated prognostic value because they seem to indicate higher serum neurofilament light chain levels.

Glioblastoma (GBM), an incurable brain tumor, necessitates surgery followed by chemoradiation, but recurrences remain fatal. While regenerative responses post-tumor debulking aid healing, they also trigger time-dependent immune reactions promoting recurrence onset at resection cavity borders. Our prior work demonstrated that a nanomedicine hydrogel (GemC 12 -LNC) delays recurrence onset when administered post-surgery. Combining it with an immunomodulatory drug is hypothesized to enhance therapeutic outcomes. However, the post-surgical microenvironment (SMe) lacks proper characterization, hindering the development of combinatory therapies. In this study, we examined the impact of surgery on the brain and SMe, aiming to identify time frames and therapeutic targets for combinatory approaches. Blood and magnetic resonance images of GBM patients pre- and post-surgery were analyzed to understand the systemic immune response and blood-brain barrier (BBB) permeability changes following tumor debulking. Additionally, a mouse model of tumor resection was utilized for longitudinal SMe characterization through various imaging and analytical techniques. Dynamics of immune cell recruitment and localization from the brain parenchyma or periphery were examined. Transient BBB disruption post-surgery, recovering within a week, provided a systemic treatment window. Differences in immune cell composition, morphology, and spatial localization between unresected and resected tumors were identified, highlighting overexpression of pro-tumoral macrophages, border-associated macrophages and reactive microglia in resected tumors. Combining local GemC 12 -LNC with systemic SMAC-mimetic drug reversed this immune response, delaying post-surgical recurrence onset and increasing overall survival in GBM-bearing mice. This comprehensive study identified SMe time frames and immune cellular targets, facilitating the design of a rational combinatory treatment to delay recurrence onset.

HomeStrokeVol. 55, No. 3Added Value of Ultrahigh-Resolution 7T MRI in Dural Arteriovenous Fistulas No AccessCase ReportRequest AccessFull TextAboutView Full TextView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplemental MaterialNo AccessCase ReportRequest AccessFull TextAdded Value of Ultrahigh-Resolution 7T MRI in Dural Arteriovenous Fistulas Benoit Testud, Xavier Carle, Claire Costes, Jean-François Hak and Maxime Guye Benoit TestudBenoit Testud Correspondence to: Benoit Testud, MD, APHM La Timone, CEMEREM, 264 St-Pierre St, 13385 Marseille, France. Email E-mail Address: [email protected] https://orcid.org/0000-0003-1444-3702 Aix-Marseille University, CNRS, CRMBM, UMR 7339, Marseille, France (B.T., C.C., M.G.). CEMEREM (B.T., M.G.), APHM La Timone, Marseille, France. , Xavier CarleXavier Carle https://orcid.org/0009-0000-5614-1310 Department of Neuroradiology (X.C., J.-F.H.), APHM La Timone, Marseille, France. , Claire CostesClaire Costes https://orcid.org/0009-0009-3536-2128 Aix-Marseille University, CNRS, CRMBM, UMR 7339, Marseille, France (B.T., C.C., M.G.). , Jean-François HakJean-François Hak https://orcid.org/0000-0002-0225-7876 Department of Neuroradiology (X.C., J.-F.H.), APHM La Timone, Marseille, France. and Maxime GuyeMaxime Guye Aix-Marseille University, CNRS, CRMBM, UMR 7339, Marseille, France (B.T., C.C., M.G.). CEMEREM (B.T., M.G.), APHM La Timone, Marseille, France. Originally published25 Jan 2024https://doi.org/10.1161/STROKEAHA.123.045930Stroke. 2024;55:e46–e47"Added Value of Ultrahigh-Resolution 7T MRI in Dural Arteriovenous Fistulas." Stroke, 55(3), pp. e46–e47FootnotesFor Sources of Funding and Disclosures, see page e47.Supplemental Material is available at https://www.ahajournals.org/doi/suppl/10.1161/STROKEAHA.123.045930.Correspondence to: Benoit Testud, MD, APHM La Timone, CEMEREM, 264 St-Pierre St, 13385 Marseille, France. Email benoit.testud@ap-hm.frREFERENCES1. Kumar T, Virador GM, Brahmbhatt P, Bhatt AA, Middlebrooks EH, Desai A, Agarwal A, Vibhute P, Gupta V. High-resolution 7T MR imaging of the trochlear nerve.AJNR Am J Neuroradiol. 2023; 44:186–191. doi: 10.3174/ajnr.A7774CrossrefGoogle Scholar2. Sui B, Sannananja B, Zhu C, Balu N, Eisenmenger L, Baradaran H, Edjlali M, Romero JM, Rajiah PS, Li R, et al. Report from the Society of Magnetic Resonance Angiography: clinical applications of 7T neurovascular MR in the assessment of intracranial vascular disease.J NeuroIntervent Surg. 2023;jnis-2023-020668. doi: 10.1136/jnis-2023-020668CrossrefGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetails March 2024Vol 55, Issue 3 Advertisement Article InformationMetrics © 2024 American Heart Association, Inc.https://doi.org/10.1161/STROKEAHA.123.045930PMID: 38269539 Originally publishedJanuary 25, 2024 Keywordsarteriovenous fistuladiplopiamagnetic resonance imagingtinnitustrochlear nervePDF download Advertisement SubjectsMagnetic Resonance Imaging (MRI)Vascular Disease

Focal epilepsy is characterized by repeated spontaneous seizures that originate from cortical epileptogenic zone networks (EZN). More recently, analysis of intracerebral recordings showed that subcortical structures, and in particular the thalamus, play an important role in facilitating and/or propagating epileptic activity. This supports previously reported structural alterations of these structures. Nonetheless, between-patient differences in EZN (e.g., temporal vs. non-temporal lobe epilepsy) as well as other clinical features (e.g., number of epileptogenic regions) might impact the magnitude as well as spatial distribution of subcortical structural changes. Here we used 7 Tesla MRI T 1 data to provide a comprehensive description of subcortical morphological (volume, tissue deformation, and shape) and longitudinal relaxation (T 1 ) changes in focal epilepsy patients to evaluate the impact of the EZN and patient-specific clinical features. Our results showed widespread morphometric and T 1 changes. Focusing on the thalamus, atrophy varied across nuclei but appeared most prominent for the TLE group and the ipsilateral side, while shortening of T 1 was observed for the lateral thalamus, in particular. Multivariate analyses across thalamic nuclei and basal ganglia showed that volume acted as the dominant discriminator between patients and controls, while (posterolateral) thalamic T 1 measures looked promising to further differentiate patients based on EZN. In particular, the observed differences in T 1 changes between thalamic nuclei indicated differential involvement of thalamic nuclei based on EZN. Finally, the number of epileptogenic regions was found to best explain the observed variability between patients. To conclude, this work revealed multi-scale subcortical alterations in focal epilepsy as well as their dependence on several clinical characteristics. Our results provide a basis for further, in-depth investigations using (quantitative) MRI and SEEG data and warrant further personalization of intervention strategies, such as deep brain stimulation, for treating focal epilepsy patients.

The segmentation of brain substructures is very useful in the characterization of alterations involved in multiple diseases. From 200 7T brain MRI scan including MP2RAGE and MGRE used to generate quantitative T1 maps (qT1), R2* and QSM volumes, a pipeline was developed to create a high-resolution multi-modal template at (400 µm)3 based on these multiple quantitative imaging modalities. Preliminary results show that multi-modality allows for a more precise parcellation of the SN, RN and STH substructures.

In this study, we report our local experience of type A aortic dissections in patients with cerebral malperfusion treated with carotid stenting before or after aortic surgery, and present a systematic literature review on these patients treated either with carotid stenting (CS) before or after aortic surgery (AS) or with aortic and carotid surgery alone (ACS). We report on patients treated in our center with carotid stenting for brain hemodynamic injury of carotid origin caused by type A dissection since 2018, and a systematic review was conducted in PubMed for articles published from 1990 to 2021. Out of 5307 articles, 19 articles could be included with a total of 80 patients analyzed: 9 from our center, 29 patients from case reports, and 51 patients from two retrospective cohorts. In total, 8 patients were treated by stenting first, 72 by surgery first, and 7 by stenting after surgery. The mean age; initial NIHSS score; time from symptom onset to treatment; post-treatment clinical improvement; post-treatment clinical worsening; mortality rate; follow-up duration; and follow-up mRS were, respectively, for each group (local cohort, CS before AS, ACS, CS after AS): 71.2 ± 5.3 yo, 65.5 ± 11.0 yo; 65.3 ± 13.1 yo, 68.7 ± 5.8 yo; 4 ± 8.4, 11.3 ± 8.5, 14.3 ± 8.0, 0; 11.8 ± 14.3 h, 21 ± 39.3 h, 13.6 ± 17.8 h, 13 ± 17.2 h; 56%, 71%, 86%, 57%; 11%, 28%, 0%, 14%; 25%, 12.3%, 14%, 33%; 5.25 ± 2.9 months, 54 months, 6.8 ± 3.8 months, 14 ± 14.4 months; 1 ± 1; 0.25 ± 0.5, 1.3 ± 0.8, 0.68 ± 0.6. Preoperative carotid stenting for hemodynamic cerebral malperfusion by true lumen compression appears to be feasible, and could be effective and safe, although there is still a lack of evidence due to the absence of comparative statistical analysis. The literature, albeit growing, is still limited, and prospective comparative studies are needed.

BACKGROUND AND PURPOSE:The detection of spinal cord lesions in patients with MS is challenging. Recently, the 3D MP2RAGE sequence demonstrated its usefulness at 3T. Benefiting from the high spatial resolution provided by ultra-high-field MR imaging systems, we aimed to evaluate the contribution of the 3D MP2RAGE sequence acquired at 7T for the detection of MS lesions in the cervical spine. MATERIALS AND METHODS:Seventeen patients with MS participated in this study. They were examined at both 3T and 7T. The MR imaging examination included a Magnetic Imaging in MS (MAGNIMS) protocol with an axial T2*-WI gradient recalled-echo sequence ("optimized MAGNIMS protocol") and a 0.9-mm isotropic 3D MP2RAGE sequence at 3T, as well as a 0.7-mm isotropic and 0.3-mm in-plane-resolution anisotropic 3D MP2RAGE sequences at 7T. Each data set was read by a consensus of radiologists, neurologists, and neuroscientists. The number of lesions and their topography, as well as the visibility of the lesions from one set to another, were carefully analyzed. RESULTS:A total of 55 lesions were detected. The absolute number of visible lesions differed among the 4 sequences (linear mixed effect ANOVA, P = .020). The highest detection was observed for the two 7T sequences with 51 lesions each (92.7% of the total). The optimized 3T MAGNIMS protocol and the 3T MP2RAGE isotropic sequence detected 41 (74.5%) and 35 lesions (63.6%), respectively. CONCLUSIONS:The 7T MP2RAGE sequences detected more lesions than the 3T sets. Isotropic and anisotropic acquisitions performed comparably. Ultra-high-resolution sequences obtained at 7T improve the identification and delineation of lesions of the cervical spinal cord in MS.

BackgroundMore than half of infants with complex congenital heart disease (CHD) will have a neurodevelopmental disorder of multifactorial causes. The preoperative period represents a time-window during which neonates with complex CHD are in a state of hypoxia and hemodynamic instability, which fosters the emergence of brain injuries and, thus, affects early brain networks and neurodevelopmental outcomes. Currently, there is no consensus regarding the optimal age for cardiac surgery in terms of neurodevelopmental outcomes, and its definition is a real challenge. Our aim is to determine the relationship between cardiac surgical timing and long-term neurodevelopmental outcomes for various types of complex CHD.MethodsWe hypothesize that earlier surgical timing could represent a neuroprotective strategy that reduces perioperative white matter injuries (WMIs) and postoperative morbidity, leading to improved neurodevelopmental outcomes in infants with complex CHD. Firstly, our prospective study will allow us to determine the correlation between age at the time of surgery (days of life) and neurodevelopmental outcomes at 24 months. We will then analyze the correlation between age at surgery and (i) the incidence of WMIs (through pre- and postoperative MRIs), (ii) postoperative morbidity, and (iii) the duration of the hospital stay.Implications and DisseminationThis research protocol was registered in the Clinical Trial Registry (National Clinical Trial: NCT04733378). This project aims to help launch the first Neurocardiac Investigation Clinic in Marseille — AP-HM — to propose an overall personalized monitoring and treatment program for patients operated on for complex CHD.

BackgroundBalloon-assisted mechanical angioplasty for cerebral vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) has a number of limitations, including transient occlusion of the spastic blood vessel. Comaneci is an FDA-approved device for temporary coil embolization assistance which has recently also been approved for the treatment of distal symptomatic refractory vasospasm. We aimed to report the feasibility, efficacy and safety of our experience with Comaneci angioplasty for refractory distal vasospasm (up to the second segment of the cerebral arteries) following aSAH.MethodsThis is a retrospective analysis of a prospective series of 18 patients included between April 2019 and June 2021 with aSAH and symptomatic vasospasm refractory to medical therapy, who were treated using Comaneci-17-asssisted mechanical distal angioplasty. Immediate angiographic results, procedure-related complications, and clinical outcomes were assessed. Inter-rater reliability of the scores was determined using the intraclass correlation coefficient.ResultsComaneci-assisted distal angioplasty was performed in 18 patients, corresponding to 31 target arteries. All distal anterior segments were easily accessible with the Comaneci-17 device. Vasospasm improvement after Comaneci mechanical angioplasty was seen in 22 distal arteries (71%) (weighted Cohen’s kappa (κw) 0.73, 95% CI 0.69 to 0.93). Vasospasm recurrence occurred in three patients (16.67%) and delayed cerebral infarction in three patients (16.67%), with a mean±SD delay between onset of symptoms and imaging follow-up (MRI/CT) of 32.61±8.93 days (κw0.98, 95% CI 0.88 to 1).ConclusionThis initial experience suggests that distal mechanical angioplasty performed with the Comaneci-17 device for refractory vasospasm following aSAH seems to be safe, with good feasibility and efficacy.

A 45-year-old woman with a history of chronic lymphocytic leukemia treated by ibrutinib presented with progressive-onset left-sided body deficit, diplopia, and fever. A CT of the head showed right pericentral nodular hemorrhagic lesions with perilesional edema. Brain MRI (Figures 1 and 2) revealed nodular hemorrhagic lesions with perilesional edema, ring enhancement, and central diffusion restriction mainly distributed along the right corticospinal tract. Lumbar puncture detected neutrophilic meningitis, and blood cultures revealed Listeria monocytogenes.

BackgroundMost periventricular nodular heterotopias (PNHs) are associated with a mutation in the filamin A (FLNA) gene in Xq28. This condition is associated with cardiovascular malformations, connective tissue abnormalities, epilepsy, and intellectual deficiency of varying severity.Materials and MethodsWe report a new FLNA gene mutation in a male patient associated with PNH and diffuse interstitial lung disease.ResultsA 23-year-old woman was referred at 31 gestational weeks to evaluate a suspected mega cisterna magna and ventricular septal defect with atrioventricular valve alignment in a male fetus. The fetal magnetic resonance imaging showed PNH associated with corpus callosum dysgenesis and a mega cisterna magna. At 2 months of age, the infant was diagnosed with severe respiratory distress with hypoxemia. A chest CT scan demonstrated a diffuse interstitial lung pattern with emphysema, multiple atelectasis foci, and signs of pulmonary hypertension. Rapid worsening led to his death at 4 months. Targeted sequencing of the FLNA gene identified a de novo hemizygous variant in 75% mosaic in lymphocyte cells, resulting in incomplete FLNA function loss.Discussion & ConclusionOn the diagnosis of antenatal PNH, the possibility of such lung involvement should be considered in the prognostic evaluation during prenatal counseling. What is already known about this topic?Most periventricular nodular heterotopias (PNHs) are associated with a X-linked mutation in the filamin A (FLNA) gene.FLNA related PNH in female patients is associated with cardiovascular malformations, connective tissue abnormalities, epilepsy, and intellectual deficiency of varying severity.What does this study add?A mosaic loss-of-function FLNA mutation should be considered in male fetuses with PNH. FLNA related PNH can be associated with severe diffuse interstitial lung disease and pulmonary arterial hypertension.

Purpose: AI brain tumour segmentation and brain extraction algorithms promise better diagnostic and follow-up of brain tumours in adults. The development of such tools for paediatric populations is restricted by limited training data but careful adaption of adult algorithms to paediatric population might be a solution. Here, we aim exploring the transferability of algorithms for brain (HD-BET) and tumour segmentation (HD-GLIOMA) in adults to paediatric imaging studies. Method: In a retrospective cohort, we compared automated segmentation with expert masks. We used the dice coefficient for evaluating the similarity and multivariate regressions for the influence of covariates. We explored the feasibility of automatic tumor classification based on diffusion data. Results: In 42 patients (mean age 7 years, 9 below 2 years, 26 males), segmentation was excellent for brain extraction (mean dice 0.99, range 0.85-1), moderate for segmentation of contrast-enhancing tumours (mean dice 0.67, range 0-1), and weak for non-enhancing T2-signal abnormalities (mean dice 0.41). Precision was better for enhancing tumour parts (p < 0.001) and for malignant histology (p = 0.006 and p = 0.012) but independent from myelinisation as indicated by the age (p = 0.472). Automated tumour grading based on mean diffusivity (MD) values from automated masks was good (AUC = 0.86) but tended to be less accurate than MD values from expert masks (AUC = 1, p = 0.208). Conclusion: HD-BET provides a reliable extraction of the paediatric brain. HD-GLIOMA works moderately for contrast-enhancing tumours parts. Without optimization, brain tumor AI algorithms trained on adults and used on paediatric patients may yield acceptable results depending on the clinical scenario.

Les thalami sont connus pour être impliqués dans la dynamique des crises épileptiques à une échelle structurale1 ou fonctionnelle2,3. Grace à sa résolution l'IRM 7T permet d'accéder à la cytoarchitecture complexe du thalamus4. Notre objectif était d’évaluer la morphométrie et le temps de relaxation T1 des noyaux thalamiques chez des patients avec une épilepsie focale pharmaco-résistante en IRM 7T. Matériels et méthodes Rétrospectivement, 24 patients avec une épilepsie temporale (TLE) et 14 patients avec une épilepsie non temporale (nTLE) ont été comparés à 31 sujets sains. Tous les patients ont reçu une stéréo-électroencéphalographie pour caractériser l’épilepsie et une IRM 7T avec une séquence MP2RAGE5 permettant de mesurer la volumétrie et d'extraire les valeurs de relaxation T1. Les différences de volume et de relaxation T1 des noyaux thalamiques entre les groupes et la latéralisation (ipsi et controlatérale) de l’épilepsie ont été explorées à l'aide des données z-score et d'une analyse de variance univariée et multivariée. Les groupes TLE (p<.001) et nTLE (p<.005) étaient caractérisés par un volume thalamique réduit bilatéralement par rapport aux contrôles sains, (figure1). Un schéma similaire a été observé pour le T1 (p<.005) mais avec un T1 plus faible dans le groupe nTLE (p<.005), figure1.Des différences significatives ont été observées entre les noyaux pour le volume (p<.001) et le T1 (p<.001). Dans les deux cas, le pulvinar était caractérisé par un effet de groupe apparent avec une taille réduite chez les TLE tandis que le T1 était plus faible chez les nTLE, (figure2). La relaxation T1 constitue un biomarqueur pertinent des altérations structurales thalamiques dans l’épilepsie. La spécificité spatiale des différences observées pourrait s'expliquer par des profils de connectivité structurelle et fonctionnelle distincts des noyaux thalamiques impactés différemment en fonction de la zone épileptogène.

Purpose The natural evolution of unruptured intracranial aneurysms (UIA) is indeed difficult to predict at the individual level. Objective In a large prospective multicentric European cohort, we aimed to evaluate whether the PHASES, UCAS, and ELPASS scores in patients with aneurysmal subarachnoid hemorrhage would have predicted a high risk of aneurysmal rupture or growth. Methods Academic centers treating patients with intracranial aneurysms were invited to prospectively collect de-identified data from all patients admitted at their institution for a subarachnoid hemorrhage-related to intracranial aneurysmal rupture between January 1 and March 31, 2021 through a trainee-led research collaborative network. Each responding center was provided with an electronic case record form (CRF) which collected all the elements of the PHASES, ELAPSS, and UCAS scores. Results A total of 319 patients with aneurysmal subarachnoid hemorrhage were included at 17 centers during a 3-month period. One hundred eighty-three aneurysms (57%) were less than 7 mm. The majority of aneurysms were located on the anterior communicating artery (n = 131, 41%). One hundred eighty-four patients (57%), 103 patients (32%), and 58 (18%) were classified as having a low risk of rupture or growth, according to the PHASES, UCAS, and ELAPSS scores, respectively. Conclusion In a prospective study of European patients with aneurysmal subarachnoid hemorrhage, we showed that 3 common risk-assessment tools designed for patients with unruptured intracranial aneurysms would have not identified most patients to be at high or intermediate risk for rupture, questioning their use for decision-making in the setting of unruptured aneurysms.

OBJECTIVE: According to A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA), conservative treatment seems to be superior to any intervention for unruptured brain arteriovenous malformations (AVMs). This study aims to evaluate safety and efficacy of upfront and repeated Gamma-Knife Radiosurgery (GKRS) in patients harboring small AVMs fulfilling the inclusion criteria of ARUBA. METHODS: A retrospective study was conducted to evaluate outcomes of unruptured naive brain AVM with a volume <= 5 ml eligible to ARUBA treated by GKRS with at least 3 years of follow-up. RESULTS: From 1992 to 2014, 249 patients fulfilled the inclusion criteria of this study. The median age was 36 years (range: 18-78 years). The median treated volume of the nidus was 1.3 ml (range: 0.4-5 ml) and 63% of the AVM were in eloquent areas. Radiosurgery-based AVM score was 1-1.8 (76%), the Spetzler-Martin grade was II-III (73%), and the Virginia Radiosurgery AVM scale was <= 1 point (75%). The overall AVM obliteration rate was 77.1% after up to 3 GKRS sessions. The median dose at the margin was 24 Gy (15-25 Gy) and the median follow-up was 45 months (range: 36-205 months). Eight patients (3.2%) experienced hemorrhage after GKRS, corresponding to a post-GKRS hemorrhage annual rate of 1.03%. Permanent symptomatic radio-induced changes rate was 2% (4 increased seizures, 1 neurologic deficit). CONCLUSIONS: The very low toxicity rate and the high occlusion rate suggest in favor of upfront and repeated GKRS for unruptured small AVMs (<= 5 mL).