Single-cell atlas of the human brain vasculature across development, adulthood and disease.

A broad range of brain pathologies critically relies on the vasculature, and cerebrovascular disease is a leading cause of death worldwide. However, the cellular and molecular architecture of the human brain vasculature remains incompletely understood1. Here we performed single-cell RNA sequencing analysis of 606,380 freshly isolated endothelial cells, perivascular cells and other tissue-derived cells from 117 samples, from 68 human fetuses and adult patients to construct a molecular atlas of the developing fetal, adult control and diseased human brain vasculature. We identify extensive molecular heterogeneity of the vasculature of healthy fetal and adult human brains and across five vascular-dependent central nervous system (CNS) pathologies, including brain tumours and brain vascular malformations. We identify alteration of arteriovenous differentiation and reactivated fetal as well as conserved dysregulated genes and pathways in the diseased vasculature. Pathological endothelial cells display a loss of CNS-specific properties and reveal an upregulation of MHC class II molecules, indicating atypical features of CNS endothelial cells. Cell-cell interaction analyses predict substantial endothelial-to-perivascular cell ligand-receptor cross-talk, including immune-related and angiogenic pathways, thereby revealing a central role for the endothelium within brain neurovascular unit signalling networks. Our single-cell brain atlas provides insights into the molecular architecture and heterogeneity of the developing, adult/control and diseased human brain vasculature and serves as a powerful reference for future studies.

Defining the Role of Oral Pathway Inhibitors as Targeted Therapeutics in Arteriovenous Malformation Care.

Arteriovenous malformations (AVMs) are vascular malformations that are prone to rupturing and can cause significant morbidity and mortality in relatively young patients. Conventional treatment options such as surgery and endovascular therapy often are insufficient for cure. There is a growing body of knowledge on the genetic and molecular underpinnings of AVM development and maintenance, making the future of precision medicine a real possibility for AVM management. Here, we review the pathophysiology of AVM development across various cell types, with a focus on current and potential druggable targets and their therapeutic potentials in both sporadic and familial AVM populations.

Embolization techniques of spontaneous direct carotid-cavernous fistulae: a single-center experience.

PURPOSE: Spontaneous direct carotid-cavernous fistula (CCF) are usually caused by a ruptured carotid cavernous aneurysm. We studied treatment of spontaneous direct CCFs in a single-center cohort of a high-volume tertiary referral center, reporting anatomical details, technical approaches of treatment, and outcomes. METHODS: Adult patients with a spontaneous direct CCF treated between 2010-2022 with follow-up MRI and/or DSA imaging available were retrospectively analyzed. We studied age, sex, clinical presentation, angiographic findings, treatment techniques, outcomes, and complications. RESULTS: Out of 80 patients with CCFs, twelve patients were treated for a non-traumatic direct CCF (15%) in 13 sessions. Median age was 65 years. Two patients had an underlying connective tissue disorder. In 10 cases, the direct CCF was caused by a ruptured cavernous carotid aneurysm. The direct CCFs were treated by endovascular transarterial embolization (10 cases), transvenous embolization (1 case), or surgery (1 case). Selective closure of the shunt was possible in 10 patients. Two patients were treated with parent vessel occlusion (PVO; one endovascular; one surgical, with bypass). Complications occurred in 2 / 12 patients (17%), with permanent morbidity in two patients (17%): trigeminal neuralgia after PVO and new infarct after surgical PVO and bypass. Selective closure of CCF resulted in no morbidity. There was no mortality in our series. CONCLUSION: Spontaneous direct CCFs are caused by rupture of a cavernous carotid aneurysm in most cases. Selective closure of the shunt, usually feasible transarterially with coils, achieves good results. Reconstructive endovascular techniques are preferred to minimize treatment related neurological complications.

The expansion of liquid biopsies to vascular care: an overview of existing principles, techniques and potential applications to vascular malformation diagnostics.

Vascular malformations are congenital lesions that occur due to mutations in major cellular signalling pathways which govern angiogenesis, cell proliferation, motility, and cell death. These pathways have been widely studied in oncology and are substrates for various small molecule inhibitors. Given their common molecular biology, there is now a potential to repurpose these cancer drugs for vascular malformation care; however, a molecular diagnosis is required in order to tailour specific drugs to the individual patient's mutational profile. Liquid biopsies (LBs), emerging as a transformative tool in the field of oncology, hold significant promise in this feat. This paper explores the principles and technologies underlying LBs and evaluates their potential to revolutionize the management of vascular malformations. The review begins by delineating the fundamental principles of LBs, focusing on the detection and analysis of circulating biomarkers such as cell-free DNA, circulating tumor cells, and extracellular vesicles. Subsequently, an in-depth analysis of the technological advancements driving LB platforms is presented. Lastly, the paper highlights the current state of research in applying LBs to various vascular malformations, and uses the aforementioned principles and techniques to conceptualize a liquid biopsy framework that is unique to vascular malformation research and clinical care.

Effect of Cobalt-60 Treatment Dose Rate on Arteriovenous Malformation Obliteration After Stereotactic Radiosurgery With Gamma Knife.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) marginal dose is associated with successful obliteration of cerebral arteriovenous malformations (AVM). SRS dose rate-how old the cobalt-60 sources are-is known to influence outcomes for some neurological conditions and benign tumors. The objective of this study was to determine the association between cobalt-60 treatment dose rate and cerebral AVM obliteration in patients treated with SRS. METHODS: We performed a retrospective cohort study of 361 patients undergoing 411 AVM-directed SRS treatments between 2005 and 2019 at a single institution. Lesion characteristics, SRS details, obliteration dates, and post-treatment toxicities were recorded. Univariate and multivariate regression analyses of AVM outcomes regarding SRS dose rate (range 1.3-3.7 Gy, mean = 2.4 Gy, median = 2.5 Gy) were performed. RESULTS: At 10 years post-SRS, 68% of AVMs were obliterated on follow-up imaging. Dose rates >2.9 Gy/min were found to be significantly associated with AVM obliteration compared with those <2.1 Gy/min ( P = .034). AVM size, biologically effective dose, and SRS marginal dose were also associated with obliteration, with obliteration more likely for smaller lesions, higher biologically effective dose, and higher marginal dose. Higher dose rates were not associated with the development of post-SRS radiological or symptomatic edema, although larger AVM volume was associated with both types of edema. CONCLUSION: Patients with cerebral AVMs treated with higher SRS dose rates (from newer cobalt-60 sources) experience higher incidences of obliteration without a significant change in the risk of post-treatment edema.

Utilisation of the Scepter Mini dual-lumen balloon - An illustrative series.

BACKGROUND: Dual-lumen balloon microcatheters can aid in the safety and efficacy of endovascular embolisation of cerebrospinal vascular malformations. The Scepter Mini dual-lumen balloon is a novel device with a smaller profile than previous balloon microcatheters, opening up new indications not only in the treatment of cerebrospinal malformations but in various other neurovascular therapeutic and diagnostic scenarios. METHODS: Following institutional ethics review board approval, a retrospective review of our prospectively maintained database of cases employing the Scepter Mini dual-lumen microballoon catheter was conducted. Five cases in particular were highlighted, demonstrating utilisation of this device, which may be of interest to the Neurointerventionalist. Patient demographics, procedure details, complications and clinical outcome data were reviewed. RESULTS: Five cases employing the Scepter Mini dual-lumen microballoon catheter are presented; trans-arterial embolisation of cerebral AVM, pre-operative tumour embolisation, diagnostic angiography, trans-venous embolisation of cerebral AVM and trans-arterial embolisation of DAVF. No intraprocedural complications were recorded, one patient had a delayed haemorrhage. CONCLUSION: Potential utilisation of the Scepter Mini lies not only in the trans-arterial embolisation of cerebrospinal vascular malformations, but in a range of other diagnostic and therapeutic indications as demonstrated.

Complication of Middle Cerebral Artery Aneurysm Surgery: An M2 Tear at the Neck, Managed with a Salvage M2-to-M2 In Situ Bypass.

An unexpected rupture at the aneurysm neck, with or without adjacent arterial injury or compromise of distal branches during microsurgical clipping, can be a challenging surgical problem to resolve. In this presented case of a neurologically intact 65-year-old woman, elective clipping of an unruptured right middle cerebral artery bifurcation aneurysm was complicated by an unexpected M2 tear at the neck, involving the origin of the frontal M2. Attempts to seal the tear directly, using various techniques, failed; therefore, it was ultimately managed with sacrifice of the vessel and a salvage side-to-side M2-to-M2 in situ bypass. Six months after surgery, the patient demonstrated moderate disability but was able to ambulate with a cane.

A dual-center validation of the PIRAMD scoring system for assessing the severity of ischemic Moyamoya disease.

Background: Prior Infarcts, Reactivity, and Angiography in Moyamoya Disease (PIRAMD) is a recently proposed imaging-based scoring system that incorporates the severity of disease and its impact on parenchymal hemodynamics in order to better support clinical management and evaluate response to intervention. In particular, PIRAMD may have merit in identifying symptomatic patients that may benefit most from revascularization. Our aim was to validate the PIRAMD scoring system. Methods: Patients with ischemic Moyamoya disease, who underwent catheter angiographic [modified Suzuki Score (mSS) and collateralization status], morphological MRI and a parenchymal hemodynamic evaluation with blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) at two transatlantic centers, were retrospectively included. The primary outcome was the presence of neurological symptoms. The diagnostic capacity of each PIRAMD feature alone was evaluated, as well as combined and the inter-institutional differences of each parameter were evaluated. Results: Seventy-two hemispheres of 38 patients were considered for analysis, of which 39 (54%) were classified as symptomatic. The presence of a prior infarct had the highest odds ratio [odds ratio (OR) =24; 95% CI: 6.7-87.2] for having neurological symptoms, followed by impaired CVR (OR =17; 95% CI: 5-62). No inter-institutional differences in the odds ratios or area under the curve (AUC) were found for any study parameter. The PIRAMD score had an AUC of 0.88 (95% CI: 0.80-0.96) with a similar AUC for the PIRAMD grading score. Conclusions: Our multicentric validation of the recently published PIRAMD scoring system was highly effective in rating the severity of ischemic Moyamoya disease with excellent inter-institutional agreement. Future studies should investigate the prognostic value of this novel imaging-based score in symptomatic patients with Moyamoya disease.

Shaping the brain vasculature in development and disease in the single-cell era.

The CNS critically relies on the formation and proper function of its vasculature during development, adult homeostasis and disease. Angiogenesis - the formation of new blood vessels - is highly active during brain development, enters almost complete quiescence in the healthy adult brain and is reactivated in vascular-dependent brain pathologies such as brain vascular malformations and brain tumours. Despite major advances in the understanding of the cellular and molecular mechanisms driving angiogenesis in peripheral tissues, developmental signalling pathways orchestrating angiogenic processes in the healthy and the diseased CNS remain incompletely understood. Molecular signalling pathways of the 'neurovascular link' defining common mechanisms of nerve and vessel wiring have emerged as crucial regulators of peripheral vascular growth, but their relevance for angiogenesis in brain development and disease remains largely unexplored. Here we review the current knowledge of general and CNS-specific mechanisms of angiogenesis during brain development and in brain vascular malformations and brain tumours, including how key molecular signalling pathways are reactivated in vascular-dependent diseases. We also discuss how these topics can be studied in the single-cell multi-omics era.

Nucleolin promotes angiogenesis and endothelial metabolism along the oncofetal axis in the human brain vasculature.

Glioblastomas are among the deadliest human cancers and are highly vascularized. Angiogenesis is dynamic during brain development, almost quiescent in the adult brain but reactivated in vascular-dependent CNS pathologies, including brain tumors. The oncofetal axis describes the reactivation of fetal programs in tumors, but its relevance in endothelial and perivascular cells of the human brain vasculature in glial brain tumors is unexplored. Nucleolin is a regulator of cell proliferation and angiogenesis, but its roles in the brain vasculature remain unknown. Here, we studied the expression of Nucleolin in the neurovascular unit in human fetal brains, adult brains, and human gliomas in vivo as well as its effects on sprouting angiogenesis and endothelial metabolism in vitro. Nucleolin is highly expressed in endothelial and perivascular cells during brain development, downregulated in the adult brain, and upregulated in glioma. Moreover, Nucleolin expression correlated with glioma malignancy in vivo. In culture, siRNA-mediated Nucleolin knockdown reduced human brain endothelial cell (HCMEC) and HUVEC sprouting angiogenesis, proliferation, filopodia extension, and glucose metabolism. Furthermore, inhibition of Nucleolin with the aptamer AS1411 decreased brain endothelial cell proliferation in vitro. Mechanistically, Nucleolin knockdown in HCMECs and HUVECs uncovered regulation of angiogenesis involving VEGFR2 and of endothelial glycolysis. These findings identify Nucleolin as a neurodevelopmental factor reactivated in glioma that promotes sprouting angiogenesis and endothelial metabolism, characterizing Nucleolin as an oncofetal protein. Our findings have potential implications in the therapeutic targeting of glioma.

Vascular malformations: An overview of their molecular pathways, detection of mutational profiles and subsequent targets for drug therapy.

Vascular malformations are anomalies in vascular development that portend a significant risk of hemorrhage, morbidity and mortality. Conventional treatments with surgery, radiosurgery and/or endovascular approaches are often insufficient for cure, thereby presenting an ongoing challenge for physicians and their patients. In the last two decades, we have learned that each type of vascular malformation harbors inherited germline and somatic mutations in two well-known cellular pathways that are also implicated in cancer biology: the PI3K/AKT/mTOR and RAS/RAF/MEK pathways. This knowledge has led to recent efforts in: (1) identifying reliable mechanisms to detect a patient's mutational burden in a minimally-invasive manner, and then (2) understand how cancer drugs that target these mutations can be repurposed for vascular malformation care. The idea of precision medicine for vascular pathologies is growing in potential and will be critical in expanding the clinician's therapeutic armamentarium.

Minimally Invasive and Outpatient Aneurysm Surgery: New Concepts.

Anterior circulation aneurysms have classically been treated using the pterional (PT) craniotomy. Minimally invasive alternatives to the PT craniotomy have been successfully used to treat vascular pathologies of the anterior circulation. These approaches offer smaller incisions and reduced tissue dissection, resulting in shorter hospital stay, improved cosmetic results, and comparable outcomes for aneurysm treatment compared with classic open approaches. The supraorbital, lateral supraorbital (LSO), mini-PT, minimal interhemispheric, and endoscopic transpterional port approach (ETPA) are each best suited for different aneurysm targets. Outpatient aneurysm surgery has been possible with the use of minimally invasive approaches.

Alpha-Synuclein RT-QuIC in Idiopathic Normal Pressure Hydrocephalus.

This study quantified the occurrence of an underlying synucleinopathy in 50 patients with idiopathic normal pressure hydrocephalus by means of real-time quaking-induced conversion, a highly sensitive and specific technique capable of detecting and amplifying misfolded aggregated forms of α-synuclein in the cerebrospinal fluid. Seven patients were positive and they did not differ from negative cases, except for a more frequent L-dopa responsiveness and gait characterized by a wider base. The two groups did not differ in terms of response rate to tap test or shunt surgery, although step length and gait velocity improved by a lesser extent in positive cases. ANN NEUROL 2022;92:985-991.

Repeat Flow Diversion for Cerebral Aneurysms Failing Prior Flow Diversion: Safety and Feasibility From Multicenter Experience.

BACKGROUND: Aneurysmal persistence after flow diversion (FD) occurs in 5% to 25% of aneurysms, which may necessitate retreatment. There are limited data on safety/efficacy of repeat FD-a frequently utilized strategy in such cases. METHODS: A series of consecutive patients undergoing FD retreatment from 15 centers were reviewed (2011-2019), with inclusion criteria of repeat FD for the same aneurysm at least 6 months after initial treatment, with minimum of 6 months post-retreatment imaging. The primary outcome was aneurysmal occlusion, and secondary outcome was safety. A multivariable logistic regression model was constructed to identify predictors of incomplete occlusion (90%-99% and <90% occlusion) versus complete occlusion (100%) after retreatment. RESULTS: Ninety-five patients (median age, 57 years; 81% women) harboring 95 aneurysms underwent 198 treatment procedures. Majority of aneurysms were unruptured (87.4%), saccular (74.7%), and located in the internal carotid artery (79%; median size, 9 mm). Median elapsed time between the first and second treatment was 12.2 months. Last available follow-up was at median 12.8 months after retreatment, and median 30.6 months after the initial treatment, showing complete occlusion in 46.2% and near-complete occlusion (90%-99%) in 20.4% of aneurysms. There was no difference in ischemic complications following initial treatment and retreatment (4.2% versus 4.2%; P>0.99). On multivariable regression, fusiform morphology had higher nonocclusion odds after retreatment (odds ratio [OR], 7.2 [95% CI, 1.97-20.8]). Family history of aneurysms was associated with lower odds of nonocclusion (OR, 0.18 [95% CI, 0.04-0.78]). Likewise, positive smoking history was associated with lower odds of nonocclusion (OR, 0.29 [95% CI, 0.1-0.86]). History of hypertension trended toward incomplete occlusion (OR, 3.10 [95% CI, 0.98-6.3]), similar to incorporated branch into aneurysms (OR, 2.78 [95% CI, 0.98-6.8]). CONCLUSIONS: Repeat FD for persistent aneurysms carries a reasonable success/safety profile. Satisfactory occlusion (100% and 90%-99% occlusion) was encountered in two-thirds of patients, with similar complications between the initial and subsequent retreatments. Fusiform morphology was the strongest predictor of retreatment failure.

Feasibility of robot-assisted neuroendovascular procedures.

OBJECTIVE: Geographic factors prevent equitable access to urgent advanced neuroendovascular treatments. Robotic technologies may enable remote endovascular procedures in the future. The authors performed a translational, benchtop-to-clinical study to evaluate the in vitro and clinical feasibility of the CorPath GRX Robotic System for robot-assisted endovascular neurointerventional procedures. METHODS: A series of bench studies was conducted using patient-specific 3D-printed models to test the system's compatibility with standard neurointerventional devices, including microcatheters, microwires, coils, intrasaccular devices, and stents. Optimal baseline setups for various procedures were determined. The models were further used to rehearse clinical cases. Subsequent to these investigations, a prospective series of 6 patients was treated using robotic assistance for complex, wide-necked intracranial saccular aneurysms between November 2019 and February 2020. The technical success, incidence of periprocedural complications, and need for conversion to manual procedures were evaluated. RESULTS: The ideal robotic setup for treatment of both anterior and posterior circulation aneurysms was determined to consist of an 80-cm guide catheter with a 115-cm-long intermediate catheter, a microcatheter between 150 and 170 cm in length, and a microwire with a minimum length of 300 cm. All coils, intrasaccular devices, and stents tested were compatible with the system and could be advanced or retracted safely and placed accurately. All 6 clinical procedures were technically successful, with all intracranial steps being performed robotically with no conversions to manual intervention or failures of the robotic system. There were no procedure-related complications or adverse clinical outcomes. CONCLUSIONS: This study demonstrates the feasibility of robot-assisted neurointerventional procedures. The authors' results represent an important step toward enabling remote neuroendovascular care and geographic equalization of advanced endovascular treatments through so-called telestroke intervention.

Embolization strategies for intracranial dural arteriovenous fistulas with an isolated sinus: a single-center experience in 20 patients.

BACKGROUND: Intracranial dural arteriovenous fistulas (DAVFs) draining into an isolated sinus segment constitute a specific entity within the spectrum of cranial dural AV shunts, with under-reporting of their optimal treatment. OBJECTIVE: To describe the multimodal treatment approach to isolated sinus DAVFs in a large single-center cohort. METHODS: Retrospective analysis of adult patients with an isolated sinus DAVF treated at our institution between 2004 and 2020 was performed. Cases were analyzed for demographics, clinical presentation, angiographic findings, treatment techniques, angiographic and clinical outcomes, and complications. RESULTS: Of 317 patients with DAVFs, 20 (6.3%) with an isolated sinus DAVF underwent treatment. Transarterial embolization was performed through the middle meningeal artery in 9 of 12 procedures, with a success rate of 66.7%. Transarterial glue embolization proved successful in two of five procedures (40%) and Onyx in six of seven procedures (85.7%). Transvenous embolization (TVE) with navigation via the occlusion into the isolated sinus was successful in seven out of nine procedures (77.8%). All three open TVE and one pure open surgical procedure gained complete closure of the fistula. There were two major complications. Complete occlusion of the fistula was eventually obtained in all cases (100%). CONCLUSIONS: Isolated sinus DAVFs are always aggressive and require a multimodal approach to guarantee closure of the shunt. Transarterial treatment with Onyx achieves good results. Transvenous treatment appears equally successful, navigating into the occluded segment across the occlusion or via burr hole as backup.

From Above and Below: The Microsurgical Anatomy of Endoscopic Endonasal and Transcranial Microsurgical Approaches to the Parasellar Region.

INTRODUCTION: The parasellar region is one of the most complex of the skull base. In this study, we review the anatomy and approaches to this region through a 360° perspective, correlating microsurgical and endoscopic anatomic nuances of this area. METHODS: An endoscopic endonasal approach (EEA) and microsurgical dissections were performed. The parasellar anatomy is reviewed and common areas of tumor extensions are assessed. Surgical approaches are discussed based on the anatomic nuances of those regions. RESULTS: The cavernous sinus (CS) can be divided into 2 spaces: posterosuperior, above and behind the internal carotid artery (ICA); and anterior, in front of the cavernous ICA. Those spaces can be approached through the CS walls: anterior and/or medial wall via EEA; or superior and/or lateral wall via transcranial approaches. The relationship of the Meckel cave, adjacent to the lateral and posterior wall of the CS, is relevant for surgical planning. Areas often affected by tumor extension can be divided into 6 regions: superior (cisternal), superolateral (parapeduncular), posterolateral (Meckel cave and petrous bone), medial (sella), anterior (superior orbital fissure), and anterior inferior (pterygopalatine fossa). Anatomic and technical nuances of each of those regions should be taken into consideration when dealing with tumors in the parasellar space. CONCLUSIONS: A transcranial approach and EEA provide effective access to the parasellar region. Management of cavernous sinus and Meckel cave tumors requires familiarity with those approaches. Understanding of the surgical anatomy of the parasellar region, from above and below, is therefore necessary for adequate surgical planning and execution.

Robotic-assisted intracranial aneurysm treatment: 1 year follow-up imaging and clinical outcomes.

BACKGROUND: The use of robotics in medicine may enable increased technical accuracy, reduced procedural time and radiation exposure, and remote completion of procedures. We have previously described the first-in-human, robotic-assisted cerebral aneurysm treatment using the CorPath GRX Robotic System. In this report we discuss our early experiences and outcomes using this robotic device for endovascular treatment of intracranial aneurysms using stent-assisted coil embolization and flow diversion. METHODS: The patient and disease characteristics, procedural details, and follow-up imaging and clinical outcomes of consecutive patients undergoing robotically-assisted intracranial aneurysm embolization between November 2019 and February 2020 are presented. RESULTS: Six patients underwent robotically-assisted embolization of intracranial aneurysms. Four of the patients were treated with a neck-bridging stent (with or without coiling) and two patients were treated with a flow-diverting stent. Two patients were treated in the subacute period of subarachnoid hemorrhage and four patients were treated electively. All of the procedures could be completed robotically and there was no need for unplanned manual intervention. The technical success rate of the procedures was 100%. There was no morbidity or mortality associated with the procedures. One year follow-up imaging showed that four aneurysms were completely obliterated (Raymond-Roy Occlusion Classification (RROC) class I) and the remaining two were occluded with a residual neck (RROC class II). CONCLUSIONS: The Corpath GRX Robotic System demonstrated a precise control over the microcatheter, wire and stent during aneurysm treatment. Robotic neuro-procedures seem to be safe and effective and demonstrate stable occlusion results in the midterm follow-up.

Malignant Melanoma within a Cellular Blue Nevi Presenting as a Vascular Malformation and the Connection to Sporadic KRAS Mutations.

We present a case of malignant melanoma (MM) developing within a vascular malformation showing features of cellular blue nevi. A 47-year-old male presented with acute symptoms of a temporal and zygomatic mass, which were both previously asymptomatic upon development 30 years ago. These masses were diagnosed as vascular malformations upon imaging and were treated with sclerotherapy. Embolization and surgical excision were performed 3 years later due to symptomatic growth. Final pathology reports showed MM with congenital blue nevi. We hypothesize a possible linkage to a sporadic KRAS mutation, linking both presentations of vascular malformation, MM, and cellular blue nevi. A literature search for similar cases is also reported.

Cyclo-oxygenase 2, a putative mediator of vessel remodeling, is expressed in the brain AVM vessels and associates with inflammation.

BACKGROUND: Brain arteriovenous malformations (bAVM) may rupture causing disability or death. BAVM vessels are characterized by abnormally high flow that in general triggers expansive vessel remodeling mediated by cyclo-oxygenase-2 (COX2), the target of non-steroidal anti-inflammatory drugs. We investigated whether COX2 is expressed in bAVMs and whether it associates with inflammation and haemorrhage in these lesions. METHODS: Tissue was obtained from surgery of 139 bAVMs and 21 normal Circle of Willis samples. The samples were studied with immunohistochemistry and real-time quantitative polymerase chain reaction (RT-PCR). Clinical data was collected from patient records. RESULTS: COX2 expression was found in 78% (109/139) of the bAVMs and localized to the vessels' lumen or medial layer in 70% (95/135) of the bAVMs. Receptors for prostaglandin E2, a COX2-derived mediator of vascular remodeling, were found in the endothelial and smooth muscle cells and perivascular inflammatory cells of bAVMs. COX2 was expressed by infiltrating inflammatory cells and correlated with the extent of inflammation (r = .231, p = .007, Spearman rank correlation). COX2 expression did not associate with haemorrhage. CONCLUSION: COX2 is induced in bAVMs, and possibly participates in the regulation of vessel wall remodelling and ongoing inflammation. Role of COX2 signalling in the pathobiology and clinical course of bAVMs merits further studies.