Management Of Cerebral Arteriovenous Malformations Research Articles

Impact of COVID-19 pandemic on treatment and outcomes of cerebral arteriovenous malformations

BackgroundThere has been a recent decrease in interventional management of cerebral arteriovenous malformations (AVMs). The objective of our study was to evaluate the changing patterns in management of AVMs in...

A Rational Approach to the Management of Cerebral Arteriovenous Malformations

Cerebral arteriovenous malformations (AVMs) typify the delicate balance cerebrovascular specialists face in weighing the treatment risk against the natural history of a pathologic lesion. The goal of our review was to provide an overview of the current evidence for the treatment of cerebral AVMs and describe a contemporary approach to developing a treatment strategy according to individual AVM characteristics. A review of the contemporary literature on the natural history and treatment of cerebral AVMs was completed through the PubMed and Google Scholar databases. The studies were reviewed for original advances in the characterization and treatment of cerebral AVMs. The overall risk of hemorrhage for cerebral AVMs is 2%-4% per year. Individual AVM characteristics, including small size, exclusive deep venous drainage, deep or posterior fossa location, venous ectasia, and the presence of a flow-associated aneurysm, appear to confer a greater risk of presentation with rupture. A diverse array of modalities have been developed to achieve the goal of complete lesion obliteration, including microsurgery, endovascular therapy, and radiosurgery. Advances in treatment strategies and technology have continued to decrease the morbidity associated with lesion obliteration. Microsurgical or multimodal treatment strategies are often required to achieve complete obliteration; however, it remains critical that each treatment approach is individualized by the specific AVM characteristics.

Clinical–epidemiological characteristics and management of cerebral arteriovenous malformations at the Neurosurgery Service of the Instituto Nacional de Salud del Niño San Borja, 2015–2017

Objetive: To describe the clinical-epidemiological characteristics and the management of Cerebral Arteriovenous Malformations (cAVM) in patients treated at the San Borja National Institute of Child Health (SB – NICH). Materials and methods: Retrospective, descriptive study of patients diagnosed with cAVM at the SB - NICH treated from 2015–2017. Data was processed and analyzed in the version 22 SPSS software. Qualitative variables were expressed in absolute and relative frequencies. Results: 41 cases of cAVM were identified, being more frequent in the group between 6-12 years of age (56.1%) and in the female sex (65.9%). Ruptured cAVM occurred in 56.7% of cases. Headache (92.7%) was the predominant clinical manifestation. The anatomical areas with the highest occurrence of cAMV were the frontal lobe (36.6%) and the left cerebral hemisphere (51.2%). The most common Spetzler-Martín grade was grade III (43.9%). The main treatment modality was embolization (39%). Mortality was 2.4%. Conclusions: The female sex and the 6 to 12-year-old group were the most frequent to suffer from cAVM. A little more than half had a ruptured cAVM. Headache is the predominant clinical manifestation of this disease. The most frequent Spetzler-Martin grade was grade III. Embolization is the most used surgical method. Mortality was low. Key words: Intracranial arteriovenous malformations, pediatrics, neurologic manifestations, neurosurgery, therapeutic embolization.

Bibliometric analysis of the top-100 most cited articles on the radiosurgical management of cerebral arteriovenous malformation

Background: Radiosurgery is an effective, alternative treatment modality in managing patients with cerebral arteriovenous malformations (AVMs). The present study aims to highlight the scholarly impact of the top-100 most cited articles on the radiosurgical management of AVMs.Methods: A title-specific search using the keyword “arteriovenous malformation” was conducted in the Scopus database. The outcome of the search was rearranged based on the citations count. Articles were categorized into four entities; clinical, gamma knife radiosurgery, linear accelerator (LINAC) radiosurgery, and proton beam radiosurgery. The exclusion criteria were applied to spinal or non-intracranial AVM, conference papers, non-English articles predominantly discussing the endovascular or microsurgical management.Results: The top-100 articles on the radiosurgical management of AVM were published between 1972 and 2016. Approximately one-third of the publications were produced between 1995 and 2000. The average citations per year for all papers were seven. The most-studied entity was pertinent to the clinical application of gamma knife radiosurgery in AVM (68%). The United States was the most active country in studying the radiosurgical application in AVM. The Journal of Neurosurgery published approximately one-third of the most-cited articles in the list. The top-3 most contributing authors, publishing 80% of articles in the list, were Lunsford et al.Conclusion: The radiosurgical management of AVMs evolved significantly throughout the years. Identifications of the publication trends facilitate the acquisition of evidence-based articles for authors investigating various radiosurgical techniques in the treatment of AVMs.

Abstract TMP118: Clinical Outcomes of Surgical Resection After Stereotactic Radiosurgery Among Patients With Cerebral Arteriovenous Malformations

Introduction: Surgical treatment of arteriovenous malformations (AVMs), particularly higher grade lesions, can be aided by staged treatment consisting of stereotactic radiosurgery (SRS) followed by surgical resection in a delayed fashion. This strategy can be used to downgrade the AVM S-M grade, reduce blood flow through the AVM and often results in histopathological changes making AVMs more amenable to microsurgical resection. We present our 28-year clinical experience in managing AVMs with pre-operative SRS as a surgical adjunct. Methods: We retrospectively reviewed and analyzed records of all patients treated for cerebral AVMs between February 1991 and July 2019 at our institution. All patients that underwent SRS, with and without embolization, followed by microsurgery were included in the study. Of the 1245 cerebral AVM patients treated at our institution, 62 patients met eligibility criteria. Univariate and multivariate regression analysis was performed where appropriate to examine relationships between key variables and outcomes. Results: The majority of lesions (50%) were high grade (SM 4-5), 28.6% were intermediate (SM 3), while 21.4% were low grade (SM 1-2). Hemorrhage was the presenting sign among 22.6% of patients. Complete resection was achieved among 64.5%, 79% and 82% of patients after first, second and third surgical stages respectively; 16.1% of patients had partial resection requiring further treatment. Radiographic cure was achieved among 53 patients (85.5%), while 8 (12.9%) patients had residual AVM at last follow up. Six of 8 patients without radiographic cure received post-operative SRS. Thirty-seven patients (63.8%) had improved (26, 44.8%) or stable mRS scores (11, 19%), while 21 (36.2%) had a decline in mRS at final follow up compared to mRS at presentation; this includes 4 (6.9%) deaths due to hemorrhage, outside of the perioperative period, but occurring during follow up prior to AVM obliteration. Conclusion: SRS is a useful adjunct in the surgical management of cerebral AVMs. Multimodal therapy allowed for high obliteration rates with acceptable morbidity in this series of patients with predominantly high grade AVMs.

Delayed hemorrhagic complication after complete embolization of a brain arteriovenous malformation

Endovascular embolization is an essential therapeutic approach in the multidisciplinary management of cerebral arteriovenous malformations (AVM). However, it rarely occludes the AVM in its entirety. It is often combined with surgery or stereotactic radiosurgery. The aim of embolization is to reduce the size of the nidus and the intra-nidal flow in order to facilitate the microsurgical or the radiosurgical procedure. We report the case of a 61-year-old patient with a right frontal hemorrhagic AVM treated with complete embolization in a single session. Initially, a surgical procedure for excision of the AVM was scheduled 24hours post-embolization. This surgery was canceled due to a good angiographic result of the embolization. Eight days post-embolization, there was a massive re-bleed of the AVM which justified emergency surgical management. This case illustrates a delayed post-embolization hemorrhagic complication of an occluded AVM and prompts a review of the therapeutic strategy of the cerebral AVM to select the most effective and least morbid procedure or combination of procedures.

Impact of Onyx Embolization on Radiosurgical Management of Cerebral Arteriovenous Malformations: Treatment and Outcome.

Stereotactic radiosurgery (SRS) is a well-established treatment modality for cerebral arteriovenous malformations (AVMs). The main limiting factor in the radiosurgical treatment of AVMs is the volume of the nidus, with high-grade lesions often requiring combined treatment to reduce the SRS target volume. To overcome this limitation, we have been using a combined treatment approach consisting of endovascular embolization with Onyx followed by SRS. To evaluate our clinical experience for safety and feasibility of this multimodality treatment approach. This is a retrospective review of all adult patients with cerebral AVMs who received SRS treatment to their AVM after endovascular embolization with Onyx between June 2007 and June2014. Thirty-five consecutive patients were identified. The mean follow-up period was 52.4 ± 22.6 months (range 18-97 months). We confirmed 18 (51.4%) complete nidus closures at a median time of 49.5 months (range 6.5-81 months) from SRS. High-resolution Magnetic resonance imaging/magnetic resonance angiography was performed routinely in all patients until closure of the nidus. Digital subtraction angiography was performed to confirm complete obliteration in 5 of the patients (28%); 13 patients are either planned for digital subtraction angiography or have refused it. In 6 patients (17%) a significant flow reduction was noted after a mean of 32 ± 16 months. No significant improvement was observed in 9 patients (26%) during the follow-up period. Two patients were lost to follow-up. The multimodality treatment of cerebral AVMs using embolization with Onyx followed by SRS is feasible and safe. The use of Onyx significantly reduced the SRS treatment target volume.

Assessing the Role of Preoperative Embolization in the Surgical Management of Cerebral Arteriovenous Malformations

Preoperative embolization is established as an advantageous adjunct in multimodality treatment of cerebral arteriovenous malformations (AVMs). However, the benefit of preoperative embolization in AVMs with favorable surgical risk profile is debatable, because it has yet to be supported by evidence in comparative studies. In this study, we assessed outcome of surgically treated patients in a comparative setting. Our institutional AVM database of retrospectively and prospectively collected data between 1990 and 2015 was reviewed. Patients with complete clinical data who underwent surgical resection for AVMs were included. We performed a 1:1 ratio propensity score match for baseline variables that differed between patients with or without preoperative embolization. Differences in surgical risk and outcomes were evaluated between these 2groups. AVM size, eloquence, deep drainage, middle cerebral artery feeder, and ruptured presentation differed significantly between the 2 groups. Forty-eight patients without preoperative embolization were matched to 48 with embolization, with no significant differences in baseline variables or AVM characteristics between the 2 groups. We found no significant differences in AVM obliteration and postoperative modified Rankin Scale (mRS) score between embolized and nonembolized patients, respectively. Change in mRS score from preoperative score was also not significant, although more embolized patients had a decline in mRS score. Secondary outcome measures including duration of surgery (P= 0.172), intraoperative bleeding (P= 0.280), duration of hospitalization (P=0.368), and postoperative symptoms were also similar between both groups. Our data do not support substantial benefit of preoperative embolization for patients with a favorable surgical risk profile. Because of risks and costs with this intervention, the prudent use of preoperative embolization should be individually considered.

Multimodality Management of Cerebral Arteriovenous Malformations with Special Reference to AVM-Related Hemorrhages During Ongoing Staged Treatment.

In this study we report and analyze the results of a multimodality management concept for intracranial arteriovenous malformations (AVMs), including microsurgery, embolization, and gamma knife radiosurgery. The study population consists of a consecutive series of 294 patients treated for 304 intracranial AVMs over a 10-year period.

Novel double catheter technique with detachable microcatheter for the treatment of arteriovenous malformations: A technical note.

Background:Onyx has improved the safety and efficacy of endovascular treatment in the management of cerebral arteriovenous malformations (AVMs). However, during injection inadvertent reflux around the delivery microcatheter into important normal arterial branches remains a major challenge.Methods:We describe a new double arterial catheterization technique using a detachable tip microcatheter in conjunction with a second microcatheter to form a proximal antireflux Onyx plug. This novel technique allows for increased amounts of Onyx to be steadily injected while avoiding dangerous backflow in the treatment of AVMs.Results:The patient tolerated the procedure well without changes in hemodynamics. Using the novel double catheter technique, a significant portion of the AVM was embolized and the patient had no complications postoperatively.Conclusions:The novel double catheter technique with a detachable microcatheter is a safe and effective technique to increase the amount of Onyx embolization material into the AVM nidus.

Neurological morbidity and mortality associated with the endovascular treatment of cerebral arteriovenous malformations before and during the Onyx era.

The widespread implementation of the embolic agent Onyx has changed the endovascular management of cerebral arteriovenous malformations (AVMs). Recent data suggest that outcomes following embolization and resection may have worsened in the Onyx era. It has been hypothesized that there may be increased complications with Onyx embolization and increased surgical aggressiveness in patients treated with Onyx. In this study the authors analyzed their institutional experience with the endovascular treatment of cerebral AVMs prior to and after the introduction of Onyx to determine factors associated with periprocedural neurological morbidity and mortality. A retrospective review was performed of all patients with cerebral AVMs undergoing embolization at the Barrow Neurological Institute from 1995 to 2012. Endovascular treatment of 342 cerebral AVMs was performed over 446 treatment sessions (mean age 37.8 years, range 1-83 years). Clinical presentation included hemorrhage in 47.6%, seizures in 21.9%, headaches in 11.1%, and no symptoms in 10% of cases. The endovascular pretreatment strategy was preoperative in 78.9%, preradiosurgery in 9.1%, palliative in 5.3%, targeted in 4.4%, and curative in 2.3%. The median Spetzler-Martin grade was III. The mean number of arteries embolized was 3.5 (range 0-13 arteries), and the mean number of treatment sessions was 1.3 (range 1-4 sessions). Onyx was used in 105 AVMs (30.7%), and N-butyl cyanoacrylate (NBCA) without Onyx was used in 229 AVMs (67%). AVMs treated with Onyx had a higher mean number of arterial pedicles embolized than did NBCA cases (4.3 ± 2.7 vs 3.2 ± 2.4, respectively; p < 0.001) and a greater number of sessions (1.5 ± 0.7 vs 1.2 ± 0.5, respectively; p < 0.05). Unexpected immediate postprocedural permanent neurological deficits were present in 9.6% of AVMs, while transient deficits were present in 1.8%. There was 1 death (0.3%). Spetzler-Martin grade was not associated with differences in outcome, as permanent neurological deficits were observed in 12%, 9%, 13%, 11%, and 13% of AVMs for Spetzler-Martin Grades I-V, respectively (p = 0.91). The use of Onyx compared with NBCA was not associated with differences in periprocedural morbidity (p = 0.23). This lack of a difference persisted even when controlling for number of arteries and sessions (p = 0.14). Sex was not associated with differences in outcome. Permanent and transient postprocedural neurological deficits were noted in 9.6% and 1.8% of all cases, respectively. AVM grade was not associated with endovascular outcome. Despite the greater number of sessions required and arteries embolized for Onyx cases, there was no statistically significant difference in the risk of neurological deficits following cerebral AVM embolization with Onyx and NBCA.

Curing arteriovenous malformations using embolization.

Endovascular embolization is typically reserved as an adjuvant therapy in the management of cerebral arteriovenous malformations (AVMs), either for preoperative devascularization or preradiosurgical volume reduction. Curative embolization plays a limited role in AVM treatment but several studies have shown that it is possible, especially with later-generation liquid embolic agents. Given the complexity of AVM anatomy and the recent controversies over the role of any intervention in AVM management, it is critical that the cerebrovascular community better define the indications of each treatment modality to provide quality AVM management. In this review, the authors evaluate the role of curative AVM embolization. Important considerations in the feasibility of curative AVM embolization include whether it can be performed reliably and safely, and whether it is a durable cure. Studies over the past 20 years have begun to define the anatomical factors that are amenable to complete endovascular occlusion, including size, feeding artery anatomy, AVM morphology, and endovascular accessibility. More recent studies have shown that highly selected patients with AVMs can be treated with curative intent, leading to occlusion rates as high as 100% of such prospectively identified lesions with minimal morbidity. Advances in endovascular technology and techniques that support the efficacy and safety of curative embolization are discussed, as is the importance of superselective diagnostic angiography. Finally, the durability of curative embolization is analyzed. Overall, while still unproven, endovascular embolization has the potential to be a safe, effective, and durable curative treatment for select AVMs, broadening the armamentarium with which one can treat this disease.

Indocyanine Green Angiography in the Surgical Management of Cerebral Arteriovenous Malformations

Indocyanine green (ICG) angiography is commonly used to map the vascular configuration of cerebral arteriovenous malformations (AVMs) during resection. To determine whether ICG improves rates of resection and clinical outcomes. A retrospective chart review was done for all patients undergoing resection of an AVM by the senior author (R.F.S.) between 2007 and 2011. Operative reports, hospital records, and radiographic imaging were used to determine the use of ICG, the incidence of residual disease, and clinical outcomes. A total of 130 cases (56 ICG, 74 non-ICG) were identified. Average AVM grade (2.2 vs 2.4) and size (2.7 vs 2.7 cm) were similar between the ICG and non-ICG groups, respectively. ICG was more often used when the AVM nidus was close to the cortical surface (71.4% vs 17.6%; P = .001) or lobar (82.1% vs 54.1%; P = .008). Eighteen patients (13.8%) were noted to have residual disease. Reoperation rates and change in modified Rankin Scale score were not different between the 2 groups (12.5% vs 14.9%, P = .8; 0.6 vs 0.4, P = .17). There were no ICG-attributable complications. ICG videoangiography is a quick and safe method of intraoperatively mapping the angioarchitecture of superficial AVMs, but it is less helpful for deep-seated lesions. This modality alone does not improve the identification of residual disease or clinical outcomes. Surgeon experience with extensive study of preoperative vascular imaging is paramount to achieving acceptable clinical outcomes. Formal angiography remains the gold standard for the evaluation of AVM obliteration.

Vascular endothelial growth factor blockade: A potential new therapy in the management of cerebral arteriovenous malformations

Abstract Cerebral arteriovenous malformations (AVMs) occur universally in 1.1 per 100,000 people. These malformations are the cause of serious neurological morbidity or even death when they bleed. AVMs are not necessarily static congenital abnormalities. They can undergo internal changes due to angiogenesis resulting in vascular remodelling. They can even regrow after successful therapy. Vascular endothelial growth factors (VEGFs) play an important role in angiogenesis. Drugs that block the action of VEGF on vascular endothelial growth factor receptors (VEGFRs) on the endothelial cell surface are available. This blockade causes an anti-angiogenetic effect. Anti-angiogenic drugs are widely used as adjuvant therapy in the management of cancers because they suppress the formation of new blood vessels required by the tumour for growth. For similar reasons, they are used in the treatment of age-related macular degeneration. The present treatment options for AVMs are surgery, embolisation and irradiation either on their own or in combination. Irradiation with stereotactic radiosurgery (SRS) offers the advantage of being non-invasive, but it relies on the late radiation effects to achieve its therapeutic goal of complete obliteration. This latent time (1–3 years), during which the risk for a bleed remains, is an inherent drawback of SRS. The histopathology of surgical specimens of post-SRS AVMs demonstrates a role of endothelial cells in repairing the radiation damage. Suppressing their activity post SRS by a VEGF blockade has the potential to enhance the radiation damage and hence speed up the obliteration process and reduce the latent time. It is postulated that such a ‘VEGF blockade’ could be useful as an adjuvant therapy to SRS. In addition, there is also the potential for a neo-adjuvant use, whereby a VEGF blockade could cause regression in the size of the AVM, making definite therapy easier. The rationale for the VEGF-blockade concept is presented and discussed.

The Management of Cerebral Arteriovenous Malformations Associated with Aneurysms

n the September/October 2011 issue of WORLD NEUROSURGERY, Lv et al. presented a retrospective analysis of 302 I consecutive cerebral arteriovenous malformations (AVMs) managed at the Beijing Neurosurgical Institute over a 9-year period. They attempted to identify patient andAVM-related factors that correlated with the presence of an associated intracranial aneurysm. Aneurysms were identified by selective and supraselective angiography and subsequently classified as intranidal, proximal flow-related, and unrelated circle of Willis aneurysms. Seventy-four (24.5%) patients were found to have a total of 77 aneurysms (47 intranidal, 26 proximal flow-related , and 10 unrelated aneurysms of the circle of Willis). Presentation with intracranial hemorrhage occurred in 159 (52.6%) patients and was determined to be caused by the aneurysm in 56. Proximal aneurysms were more likely to present with hemorrhage as compared to intranidal aneurysms. On both univariate and multivariate analyses, AVMs coexisting with aneurysms were found to be significantly associated with hemorrhage at initial presentation as well as infratentorial location. Older age also was found to correlate with presence of an aneurysm on multivariate analysis. There was no correlation between the presence of an associated aneurysm and patient sex, AVM size, and pattern of venous drainage.

Endovascular Management of Cerebral Arteriovenous Malformations in Pregnancy: Two Case Reports and a Review of the Literature

Cerebral arteriovenous malformations are rare, congenital lesions that affect the vasculature of the brain and have the possibility of rupturing. The presentation of a cerebral arteriovenous malformations in a pregnant woman warrants an even greater level of concern due to the maternal physiological changes, which may affect the structural integrity of the arteriovenous malformations and lead to hemorrhaging. A proper plan of action should be deployed to successfully treat pregnant women with cerebral arteriovenous malformations. In all cases, both the mother’s and fetus’s well being must be taken into consideration. Two cases and the current management options for cerebral arteriovenous malformations in pregnancy are presented. Online databases, such as PubMed provided by the United States National Library of Medicine at the National Institutes of Health, were searched for references to convey endovascular management options for cerebral arteriovenous malformations in pregnancy. Additional references were obtained from articles that were reviewed by the authors. The first case is of a 27-year-old pregnant woman with a right-sided periventricular intraparenchymal hemorrhage. She was treated with an external ventriculostomy drain. The second case is of a 26-year-old pregnant woman with a prior stage 2 embolization of a left parietal arteriovenous malformation. She did not show evidence of intracranial hemorrhage and was treated with further embolization regimens. A multifaceted approach, tailored to the individual patient may be necessary for cerebral arteriovenous malformations in pregnancy. Successful therapeutic strategies often involve close collaboration with a group of obstetricians, neuroradiologists, anesthesiologists, and neurosurgeons. doi: http://dx.doi.org/10.4021/jnr148w

Management of Arteriovenous Malformations by Stereotactic Radiosurgery: A Single Center Experience

The aim of this monoinstitutional study is to evaluate the efficiency of stereotactic radiosurgery (SRS) in the management of arteriovenous malformations (AVM). Between June 1998 and July 2011, 51 patients with AVM were treated with linear accelerator-based SRS at our department. All patients were preevaluated for AVM size, location, neurological status, previous history of hemorrhage and Spetzler-Martin grading. Treated patients then underwent follow-up to evaluate obliteration and clinical status. Median followup time was 32 months (range; 20-93 months). Spetzler-Martin grade I-II and AVM sizes below 3 cm were associated with increased obliteration rate (p=0.01). The annual hemorrhage risk was 1.9%. No patients experienced deterioration of neurological status at follow-up. LINAC-based SRS is a safe and effective treatment modality in the management of cerebral AVMs. SRS comprises an effective alternative to surgery for the treatment of particularly small AVMs inaccessible with surgery.

A single centre audit into the outcome of transsphenoidal surgery in the treatment of acromegaly

A single centre audit into the outcome of transsphenoidal surgery in the treatment of acromegaly

Endovascular Management of Cerebral Arteriovenous Malformations in Pregnancy: Two Case Reports and a Review of the Literature

Cerebral arteriovenous malformations are rare, congenital lesions that affect the vasculature of the brain and have the possibility of rupturing. The presentation of a cerebral arteriovenous malformations in a pregnant woman warrants an even greater level of concern due to the maternal physiological changes, which may affect the structural integrity of the arteriovenous malformations and lead to hemorrhaging. A proper plan of action should be deployed to successfully treat pregnant women with cerebral arteriovenous malformations. In all cases, both the mother’s and fetus’s well being must be taken into consideration. Two cases and the current management options for cerebral arteriovenous malformations in pregnancy are presented. Online databases, such as PubMed provided by the United States National Library of Medicine at the National Institutes of Health, were searched for references to convey endovascular management options for cerebral arteriovenous malformations in pregnancy. Additional references were obtained from articles that were reviewed by the authors. The first case is of a 27-year-old pregnant woman with a right-sided periventricular intraparenchymal hemorrhage. She was treated with an external ventriculostomy drain. The second case is of a 26-year-old pregnant woman with a prior stage 2 embolization of a left parietal arteriovenous malformation. She did not show evidence of intracranial hemorrhage and was treated with further embolization regimens. A multifaceted approach, tailored to the individual patient may be necessary for cerebral arteriovenous malformations in pregnancy. Successful therapeutic strategies often involve close collaboration with a group of obstetricians, neuroradiologists, anesthesiologists, and neurosurgeons. J Neurol Res. 2012;2(5):215-220 doi: https://doi.org/10.4021/jnr148w

Thrombospondin-1 Modulates the Angiogenic Phenotype of Human Cerebral Arteriovenous Malformation Endothelial Cells

The management of cerebral arteriovenous malformation (AVM) is challenging, and invasive therapies place vital intracranial structures at risk of injury. The development of noninvasive, pharmacologic approaches relies on identifying factors that mediate key angiogenic processes. Previous studies indicate that endothelial cells (ECs) derived from cerebral AVM (AVM-ECs) are distinct from control brain ECs with regard to important angiogenic characteristics. To determine whether thrombospondin-1 (TSP-1), a potent angiostatic factor, regulates critical angiogenic features of AVM-ECs and to identify factors that modulate TSP-1 production in AVM-ECs. EC proliferation, migration, and tubule formation were evaluated with bromodeoxyuridine incorporation, Boyden chamber, and Matrigel studies, respectively. TSP-1 and inhibitor of DNA binding/differentiation 1 (Id1) mRNA levels were quantified with microarray and quantitative real-time polymerase chain reaction analyses. TSP-1 protein expression was measured using Western blotting, immunohistochemical, and enzyme-linked immunosorbent assay techniques. The mechanistic link between Id1 and TSP-1 was established through small interfering RNA-mediated knockdown of Id1 in AVM-ECs followed by Western blot and enzyme-linked immunosorbent assay experiments assessing TSP-1 production. AVM-ECs proliferate faster, migrate more quickly, and form disorganized tubules compared with brain ECs. TSP-1 is significantly down-regulated in AVM-ECs. The addition of TSP-1 to AVM-EC cultures normalizes the rate of proliferation and migration and the efficiency of tubule formation, whereas brain ECs are unaffected. Id1 negatively regulates TSP-1 expression in AVM-ECs. These data highlight a novel role for TSP-1 in the pathobiology of AVM angiogenesis and provide a context for its use in the clinical management of brain AVMs.