Robert L. Grubb Jr., M.D.

DEPARTMENT OF Neurological Surgery
Keywords: stroke, arterial disease, hemodynamic failure, arterial bypass surgery

The importance of hemodynamic factors in the pathogenesis of stroke in patients with carotid occlusion remains controversial. We carried out a blinded, prospective study to test the hypothesis that Stage II hemodynamic failure (increased oxygen extraction) distal to a symptomatic occluded artery is an independent risk factor for subsequent stroke. One hundred and seventeen patients underwent positron emission tomography (PET) measurements of oxygen extraction fraction (OEF) and were evaluated for 17 baseline clinical, epidemiological and arteriographic risk factors. Eighty-one of the patients had symptoms referable to the occluded carotid artery and 36 were asymptomatic. Every six-month telephone follow-up recorded interval medical treatment and the subsequent occurence of stroke. Patients, treating physicians and endpoint adjudicator were unaware of the PET results.

Mean follow-up was 31.5 months. Stroke occured in 12/39 symptomatic patients with Stage II hemodynamic failure and in 3/42 symptomatic patients without [log rank p=.004]. Only 5/36 asymptomatic patients had Stage II hemodynamic failure. Only 2/36 asymptomatic patients had a stroke. Both of these patients did not have Stage II hemodynamic failure and neither stroke was in the territory of the occluded cerebral artery. Only younger age and Stage II hemodynamic failures were significant predictors of subsequent stroke. The age adjusted relative risk conferred by Stage II hemodynamic failure was 6.0 (95% CI 1.7 - 21.6) for all stroke and 7/3 (95% CI 1.6 - 33.4) for ipsilateral ischemic stroke. Stage II hemodynamic failure defines a subgroup of patients with symptomatic carotid occlusion who are at high risk for subsequent stroke.

Surgical revascularization to improve cerebral hemodynamics is the logical treatment for these patients, but its efficacy is unproven. We are organizing a multicenter randomized trial of extracranial-intracranial arterial bypass surgery vs. medical treatment in symptomatic patients with Stage II hemodynamic failure. We also are trying to develop a method to measure cerebral OEF using BOLD MR scanning. Patients with occluded carotid arteries are having both a PET scan and a BOLD MR scan carried out so that the two methods can be compared.