Multiple Burrhole Therapy With Erythropoietin for Unstable Moyamoya

Study Overview
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Brief Summary
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In this study, the investigators aim to evaluate the indirect revascularization outcomes of a new combination therapy of multiple burrhole procedure with promotion of arteriogenesis by intravenous (IV) erythropoietin (EPO) pretreatment on Moyamoya patients with acute neurological presentation, and outline the clinical and vascular factors associated with revascularization through the burrholes.

Detailed Description
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This is a investigator led, single-center, single arm, interventional trial in prospective Moyamoya disease (MMD) and Moyamoya syndrome (MMS) registry. MMD or MMS patients with acute neurological presentation such as ischemic stroke or transient ischemic attack are eligible. After inclusion, initial evaluation including transfemoral angiography is performed. A 3 day pre-procedure IV erythropoietin (120000 international units[IU] #3) is given for promotion of arteriogenesis, than multiple burrhole procedure is performed. Arteriogenesis is evaluated by 6 month transfemoral angiography.

Official Title
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Feasibility Study of Multiple Burrhole Therapy Combined With Intravenous Erythropoietin Pretreatment for Unstable Moyamoya

Conditions
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Ischemic Attack, Ischemic Stroke, Moyamoya Disease, Burr Hole, Angiogenesis

Intervention / Treatment
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* Drug: erythropoietin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥16 years Acute neurological presentation with recurrent transient ischemic attacks (TIA) or cerebral infarction within 30 days of symptom onset Angiographic findings compatible with the diagnostic criteria for MMD or MMS (unilateral findings, bilateral distal internal carotid artery involvement without Moyamoya vessels, or presence of other causative factors) Significant decrease in basal perfusion and reservoir capacity on brain perfusion CT or Brain single photon emission computed tomography with acetazolamide (Diamox®) challenge (D-SPECT) Exclusion Criteria: Definite presence of transdural collateral flow on cerebral angiography. Sufficient perfusion status via Willisian, leptomeningeal, or other collateral systems, as evaluated by multimodal imaging methods. > 30 days after symptom onset

Ages Eligible for Study
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Minimum Age: 16 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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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: multiple burrhole therapy and erythropoietin<br>pretreatment with IV erythropoietin for 3 days, 120000IU#3 then multiple burrhole procedure on the hemisphere effected is performed | Drug: erythropoietin<br>* Epokine®, CJ healthcare, South Korea is used preprocedurally to promote revascularization. Total 120,000 units of EPO is injected for three consecutive days, 40,000 units mixed in IV saline 100 ml over 1 hour. The multiple burrhole procedure is performed in area of hemodynamic insufficiency by D-SPECT. It is performed under local anesthesia.<br>* Other names: multiple burrhole procedure;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional status of the participants after 6 months of procedure assessed by modified Rankin Scale. | The functional status of participants will be assessed based on modified Rankin Scale for evaluation of feasibility of procedure. | 6 month post-procedure | 
| transdural arteriogenesis | the extent of collateral flow that has developed from external carotid artery to internal carotid artery through the burrholes | 6 month post-procedural cerebral angiography | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | periprocedural and post-procedural complications | Any complications occuring within <14 days of burrhole procedure + erythropoietin is classified as periprocedural complications. Any complications occuring or detected after 14 days of procedure up to 6 months will be classified as post-procedural. |