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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Arteriovenous Malformation of Brain

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The diagnosis of AVM was confirmed with digital subtraction angiography (DSA) and/or magnetic resonance imaging(MRI). The SM grade was IV and V. Exclusion Criteria: Patients with multiple AVMs. Patients with hereditary hemorrhagic telangiectasia (HHT). Patients with missing clinical and imaging data.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Conservative management<br>Patients refused to accept any interventional treatment or patients were not suitable for any interventional treatment. | |
| Microsurgical resection<br>All microsurgical procedures were performed with intraoperative neuronavigation, ultrasonography, indocyanine fluorescence angiography (ICG), continuous monitoring of electroencephalogram and somatosensory evoked potential. | |
| Embolization<br>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<br>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<br>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?
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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 |