Long-term Outcomes After Different Management Strategies for High-level Cerebral Arteriovenous Malformation (OHAVM)

Study on the Long-term Outcomes of High-level Cerebral Arteriovenous Malformation

Arteriovenous malformations (AVMs) are complex and rare cerebral vascular dysplasia. The main purpose of treatment is to avoid the neurological impairment caused by hemorrhagic stroke. The Spetzler-Martin (SM) grading system is widely used to estimate the risk of postoperative complication based on maximum AVM nidus diameter, pattern of venous drainage, and eloquence of location. Generally, grade I and II are amenable to surgical resection alone. Grade III is typically treated via a multimodal approach, including microsurgical resection, embolization, and radiosurgery (SRS). Grade IV and V are generally observed unless ruptured. However, some previous studies indicated that despite the high rate of poor outcomes for high-level unruptured AVMs, the mortality for high-level unruptured AVMs are likely lower than untreated patients. With the development of new embolic materials and new intervention strategies, patients with high-level AVMs may have more opportunities to underwent more aggressive interventions. The OHAVM study aims to clarify the clinical outcomes for patients with SM grade IV and V AVMs after different management strategies.

Study Overview

• Status: Recruiting
• Conditions: Arteriovenous Malformation of Brain

Detailed Description

Follow-up: In our neurosurgical center, follow-up was conducted for all patients at the first 3-6 months and annually after discharge by clinical visit and telephone interview.

Study overview: The population in the OHAVM study will be divided into two parts. Clinical and imaging data of high-level AVM patients from 2012/04 to 2019/09 were retrospectively collected. And the high-level AVM patients from 2019/09 to 2019/12 were prospectively collected. The intervention strategies in our institution for high-level AVMs are of four categories: microsurgical resection, embolization, embolization+radiosurgery, and single-stage hybrid surgery (embolization-resection). Each participants will be followed at least for 5 year since enrollment. Finally, we will clarify the clinical outcomes and prognostic predictors for patients with SM grade IV and V AVMs after different management strategies.

Sample size: About 1000 patients will be enrolled in this study, and half of them were unruptured. The population distribution of different management strategies is expected as follows: conservative:100 cases, microsurgical resection: 300 cases, embolization:250 cases, embolization+radiosurgery: 250 cases, single-stage hybrid surgery: 100 cases.

Study endpoints: The neurological function prognosis, occlusion rate and complications were evaluated at 2 weeks, 1 year, 3 years, 5 years after the treatment and the last follow-up, respectively.

• Study Type: Observational
• Enrollment (Anticipated): 1000

Contacts and Locations

• Study Contact: Name: Yuanli Zhao, MD; Phone Number: 86-010-59978478; Email: zhaoyuanli@126.com
• Study Contact Backup: Name: Yu Chen, MD; Phone Number: 8618801239327; Email: chenyu_tiantan@126.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 101100
      • Recruiting
      • Capital Medical University Affiliated Beijing Tiantan Hospital
      • Contact: Yu Chen, MD; Phone Number: +8618801239327; Email: chenyu_tiantan@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 76 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with Spetzler-Martin (SM) grade IV and V brain arteriovenous malformation.

Description

Inclusion Criteria:

1. The diagnosis of AVM was confirmed with digital subtraction angiography (DSA) and/or magnetic resonance imaging(MRI).
2. The SM grade was IV and V.

Exclusion Criteria:

1. Patients with multiple AVMs.
2. Patients with hereditary hemorrhagic telangiectasia (HHT).
3. Patients with missing clinical and imaging data.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort
Conservative management; Patients refused to accept any interventional treatment or patients were not suitable for any interventional treatment.
Microsurgical resection; All microsurgical procedures were performed with intraoperative neuronavigation, ultrasonography, indocyanine fluorescence angiography (ICG), continuous monitoring of electroencephalogram and somatosensory evoked potential.
Embolization; Embolization or radiosurgery was recommended as a priority for lesions located in deep functional locations such as brainstem and basal ganglia. Multi-stage embolization and target embolization were widely used within the embolization. Onyx was the main embolization material.
Embolization+Radiosurgery; Embolization or radiosurgery was recommended as a priority for lesions located in deep functional locations such as brainstem and basal ganglia. Radiosurgery management was recommended for the residual lesions about 3 months after the embolization if necessary.
Single-stage hybrid surgery; Hybrid surgery is a new surgical strategy defined as single-stage combined microsurgical resection and embolization in which embolization is performed firstly on the deep feeding artery, aneurysm, AVF, and meningeal arteries involved in blood supply of the nidus, and then, the microsurgical resection was performed immediately. Intraoperative angiography was performed repeatedly before the skull was closed, confirming complete occlusion of the malformation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
modified Ranking Scale score at 2 weeks after the operation	The scale runs from 0-6, running from perfect health without symptoms to death. 0 - No symptoms.; No significant disability. Able to carry out all usual activities, despite some symptoms.; Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.; Moderate disability. Requires some help, but able to walk unassisted.; Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.; Severe disability. Requires constant nursing care and attention, bedridden, incontinent.; Dead	2 weeks after operation
modified Ranking Scale score at 1 year after the operation	The scale runs from 0-6, running from perfect health without symptoms to death. 0 - No symptoms.; No significant disability. Able to carry out all usual activities, despite some symptoms.; Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.; Moderate disability. Requires some help, but able to walk unassisted.; Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.; Severe disability. Requires constant nursing care and attention, bedridden, incontinent.; Dead	1 year after operation
modified Ranking Scale score at 3 years after the operation	The scale runs from 0-6, running from perfect health without symptoms to death. 0 - No symptoms.; No significant disability. Able to carry out all usual activities, despite some symptoms.; Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.; Moderate disability. Requires some help, but able to walk unassisted.; Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.; Severe disability. Requires constant nursing care and attention, bedridden, incontinent.; Dead	3 years after operation
modified Ranking Scale score at 5 years after the operation	The scale runs from 0-6, running from perfect health without symptoms to death. 0 - No symptoms.; No significant disability. Able to carry out all usual activities, despite some symptoms.; Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.; Moderate disability. Requires some help, but able to walk unassisted.; Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.; Severe disability. Requires constant nursing care and attention, bedridden, incontinent.; Dead	5 years after the operation
modified Ranking Scale score at the last follow-up	The scale runs from 0-6, running from perfect health without symptoms to death. 0 - No symptoms.; No significant disability. Able to carry out all usual activities, despite some symptoms.; Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.; Moderate disability. Requires some help, but able to walk unassisted.; Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.; Severe disability. Requires constant nursing care and attention, bedridden, incontinent.; Dead	up to 10 years after the operation
Long-term hemorrhagic rate	For conservative group, the observation period was from the diagnosis to the last follow-up. For the intervention group, to rule out the influence of transient unstable blood flow in the perioperative period, the observation period was defined as from 2 weeks after the operation to the last follow-up.	Conservative group: from the diagnosis to the last follow-up (up to 10 years); Intervention group: from 2 weeks after the operation to the last follow-up (up to 10 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Obliteration rate	Confirmed by postoperative DSA or MRI/MRA	At least 3 years, up to 10 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of postoperative epilepsy	It can only be diagnosed as postoperative epilepsy with the evidence of typical convulsions and other systemic seizures or EEG evidence.	2 weeks and 1 years after the operation and the last follow-up (up to 10 years)
Incidence of perioperative hemorrhage	Bleeding within two weeks after the operation may be related to the redistribution of cerebral blood flow. The diagnosis of perioperative hemorrhage requires CT confirmation.	2 weeks after the operation
Incidence of perioperative infarction	Perioperative infarction within two weeks after the operation may be related to the redistribution of cerebral blood flow. The diagnosis of perioperative infarction requires CT confirmation or MRI confirmation.	2 weeks after the operation
Incidence of endovascular embolization injury	Endovascular embolization injuries include arterial dissection, catheter failure, etc.	2 weeks after the operation
Incidence of radiation necrosis	Radiation necrosis usually starts to appear within half a year after gamma knife operation. MRI evidence is needed to diagnose radiation necrosis.	Half a year and 1 years after the operation and the last follow-up (up to 10 years)

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Collaborators: Peking University International Hospital
• Investigators: Principal Investigator: Yu Chen, MD, Beijing Tiantan Hospital

Publications and helpful links

General Publications

• Chen Y, Li R, Ma L, Meng X, Yan D, Wang H, Ye X, Jin H, Li Y, Gao D, Sun S, Liu A, Wang S, Chen X, Zhao Y. Long-term outcomes of brainstem arteriovenous malformations after different management modalities: a single-centre experience. Stroke Vasc Neurol. 2021 Mar;6(1):65-73. doi: 10.1136/svn-2020-000407. Epub 2020 Sep 14.
• Chen Y, Li R, Ma L, Zhao Y, Yu T, Wang H, Ye X, Wang R, Chen X, Zhao Y. Single-Stage Combined Embolization and Resection for Spetzler-Martin Grade III/IV/V Arteriovenous Malformations: A Single-Center Experience and Literature Review. Front Neurol. 2020 Oct 29;11:570198. doi: 10.3389/fneur.2020.570198. eCollection 2020.
• Chen Y, Yan D, Li Z, Ma L, Zhao Y, Wang H, Ye X, Meng X, Jin H, Li Y, Gao D, Sun S, Liu A, Wang S, Chen X, Zhao Y. Long-Term Outcomes of Elderly Brain Arteriovenous Malformations After Different Management Modalities: A Multicenter Retrospective Study. Front Aging Neurosci. 2021 Feb 18;13:609588. doi: 10.3389/fnagi.2021.609588. eCollection 2021.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2012
• Primary Completion (Anticipated): November 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: September 15, 2019
• First Submitted That Met QC Criteria: October 21, 2019
• First Posted (Actual): October 23, 2019

Study Record Updates

• Last Update Posted (Actual): November 30, 2020
• Last Update Submitted That Met QC Criteria: November 26, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Cardiovascular Abnormalities; Neoplasms, Vascular Tissue; Nervous System Malformations; Vascular Malformations; Intracranial Arterial Diseases; Central Nervous System Vascular Malformations; Congenital Abnormalities; Hemangioma; Arteriovenous Malformations; Intracranial Arteriovenous Malformations
• Other Study ID Numbers: KY 2019-09-15

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No