Brain Arteriovenous Malformations (bAVM) Research

The UCSF Department of Radiology and Biomedical Imaging is proud to launch a new pilot research project for patients with brain arteriovenous malformations (bAVM) for whom conventional therapy has failed, who have elected to forego invasive treatment, and/or those patients whose bAVM have been deemed unsuitable for invasive treatment.

The study will administer bevacizumab, which is also used to fight cancer, by IV infusion over the course of 12 weeks using the dose of 5mg/kg every 2 weeks (2.5 mg/wk). This is a one-arm, open-label study.

All treatment appointments will take place at UCSF. Our primary outcome will be change in bAVM volume from pre-treatment MRI. For more information, please see the description of the study on the clinic trials site here. If you have patients who could benefit from this study, please contact Dr. Daniel Cooke at [email protected] or at (415) 353-1869.

Brain Arteriovenous Malformations (bAVM)

These images are taken from a brain AVM animal model, whereby the vessels shown are to represent an AVM. The top row (A) shows Lectin-stained (green color) vessels in trastuzamab and bevacizumab-treated mice (Scale bar: 50 μm). Note the relative decrease in the number of green vessels in the bevacizumab-treated group. The bottom row (B) shows the number of vessels and vessel dysplasia score. Again, note that there were fewer vessels and a lower vessel dysplasia score in the bevacizumab-treated animals. This is in keeping with the trial’s premise that bevacizumab will reduce brain AVM size by limiting the growth of its vessels.

This image shows three MR images taken of a brain AVM. The leftmost image shows the tangle of enlarged blood vessels (wavy black structures in the bottom right part of the image). The middle image shows the same information this time with the addition of contrast that now makes the wavy structures appear white. The rightmost image is a special MR sequence sensitive for small areas of bleeding. Note the larger wavy black structure that corresponds to a large vein draining the AVM.

This image shows the same AVM as seen on the MR above as detailed using an angiogram. The top row of images show the AVM as seen looking straight at the patient (rightmost image) and from the side (leftmost image). The bottom row shows these same images now in color such that blood vessels that fill early (arteries) are predominately red and yellow while the veins more green and blue. Information from images such as these help clinicians understand not just the anatomy of the AVM, but how blood moves through it.

The movie shows a brain AVM and the surrounding skull. Note the more compact collection of very wavy vessels (AVM nidus) and the larger single vessel (vein) close the midline at the start of the clip.

Glue embolization of a ruptured AVM.

Daniel Cooke, MD - AVM Radiologist

Highlights

Brain arteriovenous malformations (AVM) are collection of malformed vessels abnormally connecting arteries and veins.
Untreated brain AVM can result in serious problems such as brain damage or stroke.
Please contact us at 415-353-1853 so that we can learn more about your needs.

Our Commitment

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Use of newest and safest technologies
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UCSF AVM Treatment Advantages

Providing the world’s highest standards with our dedicated team of experts, evidence-based practice, and leading technology
Global leader in ongoing research to discover non-invasive solutions to AVM
This project is a collaboration of the departments of Radiology, Neurosurgery, Neurology, and Anesthesiology
The study is sponsored by the American Heart Association and the UCSF Department of Radiology & Biomedical Imaging.
The genesis of this projecdt was rooted in the UCSF Center for Cerebrovascular Research

bAVM deemed unsuitable for invasive treatment OR patient has elected to defer invasive treatment OR failed conventional therapy
Age greater than 18 years at time of first study drug administration
Unruptured bAVM
Spetzler-Martin grade III-V lesion
Progressive or disabling signs and symptoms as determined by the study investigators. These include, though not limited to, are headache, seizure, neuropathy, or paresis.
Patients must have adequate bone marrow function (WBC > 3,000/μl, ANC > 1,500/mm3, platelet count of > 100,000/mm3, and hemoglobin > 10 mg/dl), adequate liver function (SGOT and bilirubin < 1.5 times ULN), and adequate renal function (creatinine < 1.5 mg/dL) within 14 days before starting therapy.

Diffuse lesion that cannot be assessed in terms of volume by cross-sectional imaging on MRI
Inability to undergo MRI scans
Urine protein > 100 mg/dl or > 2+ protein (depending on units used in assay)
History of stroke or transient ischemic attack within 6 months
History of abdominal fistula or gastrointestinal perforation
Prior bAVM therapy (radiosurgery, embolization, microsurgical)
Coagulation disorders, e.g., thrombocytopenia, coagulopathy or anticoagulant therapy (Plavix and ASA is not excluded)
Unstable medical or psychiatric illness
bAVM presenting with evidence of recent or prior hemorrhagic
Atrial fibrillation
Clinically significant thrombotic episode within the last 24 weeks
Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or diastolic blood pressure > 100 mmHg) on antihypertensive medications, hypertensive crisis or hypertensive encephalopathy
Major cardiovascular or peripheral vascular disease¹
Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks of beginning Avastin or the anticipation of need for major surgical procedure during the course of the study
Core biopsy or other minor surgical procedure, within 7 days prior to bevacizumab
Serious, non-healing wound, ulcer, or bone fracture in the past 6 months
History of hemoptysis
Evidence of bleeding diathesis
Pregnant or breast-feeding. Women of childbearing potential are required to obtain a negative pregnancy test within 14 days of starting treatment. Effective contraception (men and women) must be used in subjects of child-bearing potential.
On any other experimental agents/clinical trials

¹New York Heart Association Grade II or greater congestive heart failure, Myocardial infarction or unstable angina within 12 months prior to study enrollment, symptomatic peripheral vascular disease