Extracranial-Intracranial Bypass Surgery for Stroke Prevention in Hemodynamic Cerebral Ischemia

Abstract

Context Patients with symptomatic atherosclerotic internal carotid artery occlusion (AICAO) and hemodynamic cerebral ischemia are at high risk for subsequent stroke when treated medically. Objective Test the hypothesis that extracranial-intracranial (EC-IC) bypass surgery, added to best medical therapy, reduces subsequent ipsilateral ischemic stroke in patients with recently symptomatic AICAO and hemodynamic cerebral ischemia. Design Parallel group, randomized, open-label, blinded-adjudication clinical treatment trial conducted from 2002–2010. Setting 49 clinical centers and 18 positron emission tomography (PET) centers in the United States and Canada. The majority were academic medical centers. Participants Arteriographically-confirmed AICAO causing hemispheric symptoms within 120 days and hemodynamic cerebral ischemia identified by ipsilateral increased oxygen extraction fraction measured by PET. 195 were randomized: 97 to surgery and 98 to no surgery. Follow-up for the primary endpoint until occurrence, 2 years, or end of trial was 99% complete. No participant withdrew because of adverse events. Interventions Anastomosis of superficial temporal artery branch to a middle cerebral artery cortical branch for the surgical group. Anti-thrombotic therapy and risk factor intervention were recommended for all. Main Outcome Measure For all participants who were assigned to surgery and received surgery, the combination of (1) all stroke and death from surgery through 30 days post surgery and (2) ipsilateral ischemic stroke within 2 years of randomization. For the nonsurgical group and participants assigned to surgery who did not receive surgery was the combination of (1) all stroke and death from randomization to randomization plus 30 days and (2) ipsilateral ischemic stroke within two years of randomization. Results The trial was terminated early for futility. Two-year rates for the primary endpoint were 21.0% (95% CI, 12.8% to 29.2%; 20 events) for the surgical group and 22.7% (95% CI, 13.9% to 31.6%; 20 events) for the nonsurgical group (p=0.78, z-test); difference = 1.7% (95% CI, −10.4% to 13.8%). Thirty-day rates for ipsilateral ischemic stroke were 14.3% (14/97) in the surgical group and 2.0% (2/98) in the nonsurgical group; difference = (95% CI, 4.9% to 19.9%) Conclusions Among participants with recently symptomatic AICAO and hemodynamic cerebral ischemia, EC-IC bypass surgery plus medical therapy compared to medical therapy alone did not reduce the risk of recurrent ipsilateral ischemic stroke at 2 years.

Improvement in cerebral hemodynamic parameters and outcomes after superficial temporal artery-middle cerebral artery bypass in patients with severe stenoocclusive disease of the intracranial internal carotid or middle cerebral arteries

“…12,17,29 Although the EC-IC bypass trials were conducted for patients with symptomatic ICA stenoocclusive disease, they failed to show the benefit of surgery over the "best medical therapy." 24,35 Similar failures were noted in a recent clinical trial of intracranial stent placement for patients with severe (70%-99%) intracranial stenosis. 3 This trial failed due to unacceptably high rates of periprocedural complications and "lower than expected" rates of primary end points with "aggressive medical therapy."…”

“…The current status of STA-MCA bypass surgery, especially in view of the recent clinical trial results, 3,24 was explicitly explained to the patients and their relatives.…”

“…3 Although both the older as well as the recent extracranialintracranial (EC-IC) bypass trials were conducted for patients with symptomatic occlusive disease of the cervical segment of the internal carotid artery (ICA), there were no significant benefits of surgery compared with "best medical therapy." 7,24 Artery-to-artery embolization and cerebral hemodynamic insufficiency are the 2 main mechanisms of cerebral ischemic events in patients with intracranial stenosis. 9,16,25,30 Transcranial Doppler (TCD) ultrasonography monitoring can demonstrate a cerebral embolization by identifying the spontaneous microembolic signals in appropriate arterial branches distal to the stenoocclusive lesion 19,22,28 and help in planning the appropriate antithrombotic treatment.…”

Endothelial Progenitor Cells Augment Collateralization and Hemodynamic Rescue in a Model of Chronic Cerebral Ischemia

“…According to the literature, bypass grafting remains controversial and does not appear to be the way to effectively improve hemodynamic reserve in patients with typical arteriosclerotic symptomatic ICA occlusion. 17,18 Thus, there is a need to develop safe and technically robust revascularization techniques. The cerebrovascular system underlies permanent vascular remodeling to maintain adequate tissue perfusion under physiologic and pathologic conditions but the development of new blood vessels in the chronically hypoperfused brain is poorly understood.…”

Snapshot MR Technique to Measure OEF Using Rapid Frequency Mapping

“…The OEF increase would be much more (450%) for severe cases, 29 a threshold of 13% increase OEF was used for patient selection in the COSS (Carotid Occlusion Surgery Study) study. 30 It is known that the offset frequencies in the range shown (10 to 45 Hz) can be estimated using PARSE. 23 Also, PARSE is more well suited to estimate frequency as the inherent bias errors and random errors are the smallest for frequency estimates.…”