Surgical Indirect Revascularization For Symptomatic Intracranial Arterial Stenosis
Condition: Intracranial Arterial Stenosis; Intracranial Atherosclerosis; Ischemic Stroke; Cerebral Angiogenesis
MeSH terms: Ischemic Stroke; Intracranial Arteriosclerosis; Atherosclerosis; Constriction, Pathologic
Study type: Interventional

Summary: 
      Stroke due to intracranial arterial atherosclerosis is a significant medical problem,
      carrying one of the highest rates of recurrent stroke despite best medical therapy, with
      annual recurrence rates as elevated as 25% in high risk groups.

      The goal of this investigation is to advance a promising surgical treatment for symptomatic
      atherosclerotic intracranial stenosis - encephaloduroarteriosynangiosis (EDAS). The
      investigation will test in a phase II futility trial the potential of EDAS for further
      development before proceeding with the design of a definitive clinical trial of EDAS
      Revascularization in patients with Symptomatic Intracranial Arterial Stenosis (ERSIAS).

      The investigation is a 4-year futility trial to test the hypothesis that EDAS
      revascularization combined with aggressive medical therapy warrants further evaluation in a
      subsequent pivotal trial as an alternative to aggressive medical management alone for
      preventing the primary endpoint of stroke or death in patients with symptomatic intracranial
      arterial stenosis (Specific Aim 1). During the investigation the time course of
      collateralogenesis and perfusion improvement following EDAS will also be evaluated (Specific
      Aim 2.
    

Detailed description: 
      Intracranial arterial atherosclerosis is a significant medical problem, with elevated rates
      of recurrent stroke despite medical therapy, with annual recurrence rates for ischemic stroke
      reported in the SAMMPRIS Trial as high as 12.2% in the intensive medical therapy arm. The
      incidence of recurrence stroke can be even higher in some high-risk groups, as high as 25% in
      African-Americans and females. The ultimate goal of this project is to advance a promising
      surgical treatment for symptomatic atherosclerotic intracranial stenosis -
      encephaloduroarteriosynangiosis (EDAS). Compared with direct revascularization operations
      (bypass), EDAS has the advantages of being less technically demanding, avoiding temporary
      occlusion of cerebral vessels, and allowing gradual development of collateral circulation
      where the brain demands it, deterring early hyperperfusion and hemorrhage. There has been no
      systematic trial exploring the use of EDAS in cases of symptomatic, non-moyamoya intracranial
      arterial stenosis. Based on preliminary positive results, the investigators propose the
      long-term objective of demonstrating that EDAS improves the outcome in patients with
      symptomatic intracranial stenosis compared with aggressive medical therapy. This will require
      future phase III clinical trials. The present proposal has the purpose of testing in a phase
      II futility-design trial the potential of EDAS for further development before proceeding with
      the design of a definitive clinical trial of EDAS Revascularization in patients with
      Symptomatic Intracranial Arterial Stenosis (ERSIAS). The present project will be 4-year
      futility-design trial to determine if EDAS revascularization combined with aggressive medical
      therapy warrants further evaluation in a subsequent pivotal trial as an alternative to
      aggressive medical management alone for preventing the primary endpoint of stroke or death at
      two years in patients with symptomatic intracranial arterial stenosis (Specific Aim 1).
      During the investigation the investigators will systematically evaluate the time course of
      collateralogenesis and perfusion improvement following EDAS by using quantitative and
      semiquantitative perfusion MRI studies (Specific Aim 2). The new knowledge generated by this
      study on understanding the role of collateral circulation in stroke pathophysiology, patient
      selection, and use of non-invasive imaging will be useful not only for EDAS evaluation but
      potentially next generation stents and future novel medical therapies, such as use of
      angiogenic growth factors and/or endothelial stem cells.
    

Intervention name(s): Encephaloduroarteriosynangiosis (EDAS)
Intervention type(s): Procedure
Intervention description(s): The operation is a form of indirect revascularization or EC-IC bypass, performed under general endotracheal anesthesia, with intraoperative electroencephalographic monitoring. The surgery consists in the dissection and relocation of the superficial temporal artery (STA) and middle meningeal artery (MMA) branches, which are separated from their surrounding tissues under microscopic visualization and re-routed through a craniotomy to be placed intracranially in close proximity to the branches of the middle cerebral artery (MCA). The MCA branches are dissected in the arachnoid space and the STA and MMA are kept in position with microsutures to the arachnoid or MMA dural cuffs, maintaining close contact between the EC and MCA branches.
Other intervention name(s): Indirect revascularization; Indirect bypass; EC-IC revascularization; EC-IC indirect bypass; EC-IC indirect revascularization
Intervention model: Single Group Assignment
Intervention model description: EDAS surgery for Intracranial atherosclerosis. Non-futility design
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Intracranial Arterial Stenosis; Atherosclerosis; Stroke; EDAS; Angiogenesis