Introduction

Posterior circulation strokes account for 30% to 40% of all ischemic strokes, and are particularly prone to devastating consequences due to the concentrated “eloquence” of brain tissue supplied by the posterior circulation.¹ Atherosclerotic occlusive disease of the vertebrobasilar system is a major etiology of posterior circulation ischemia,² and carries a high stroke risk despite medical therapy. Extracranial-intracranial (EC-IC) bypass for augmentation of flow to the posterior circulation is a treatment option for selected patients with hemodynamic compromise and recurrent ischemia.

Etiology

Posterior circulation ischemia can be attributable to a variety of etiologies. Similar to those encountered in anterior circulation stroke, these include atherosclerotic large vessel disease, small penetrating artery disease, embolism (cardiac origin or artery-to-artery), thrombosis, and dissection. In contrast with anterior circulation stroke, large- or small-vessel occlusive disease occurs more commonly in the posterior circulation than thromboembolism.^3,4 Large vessel atherosclerotic vertebrobasilar disease itself accounted for one-third of the strokes reported in the New England Medical Center Posterior Circulation Registry, consisting of 407 prospectively identified patients with posterior circulation ischemia.^2,5 Although thrombotically active plaques are a prominent feature of carotid disease, this mechanism appears less prominent as a cause of ischemia related to vertebrobasilar occlusive disease. The stroke mechanism for patients with posterior circulation atherostenosis is often related directly, or indirectly, to hemodynamic failure with regional hypoperfusion.⁶ Beyond the direct mechanism of hypoperfusion, thrombus formation as a sequelae of low flow must also be considered,² in addition to an underlying low-flow state worsening the consequences of a given thromboembolic event. The potential synergy between thromboembolism and hemodynamic insufficiency can combine to confer higher risk.⁷ Current medical therapies for cerebrovascular occlusive disease are directed primarily at decreasing the risk of in situ thrombosis and thromboembolism, but do not address the underlying low-flow state.

Although flow-limiting disease in the vertebrobasilar system may be well compensated hemodynamically by other collaterals, such as a contralateral vertebral artery, or flow through the posterior communicating arteries, the existence and flow capacity of such collaterals vary widely from individual to individual. Anatomic variants with the potential to affect collateral supply include hypoplastic vertebral arteries, absent posterior communicating arteries, and fetal origin of the posterior cerebral artery, all of which could limit compensatory flow to the vertebrobasilar territory in the setting of vertebrobasilar occlusive disease.

Clinical presentation

Patients with posterior circulation ischemia typically present with a range of symptoms, often referred to as vertebrobasilar insufficiency (VBI). Symptoms can potentially arise from any region of the distal territory of the vertebrobasilar system, including the occipital or temporal lobes, cerebellum, and brainstem with its cranial nerves. Dizziness, vertigo, headaches, diplopia, loss of vision, ataxia, numbness, and weakness involving structures on both sides of the body are frequent symptoms.⁸ The most common neurologic signs are limb weakness, gait and limb ataxia, oculomotor palsies, and oropharyngeal dysfunction. Posterior circulation ischemia generally produces a collection of symptoms and signs dependent upon the area affected, rather than causing an isolated symptom. Neurological impairment can be devastating due to the dense collection of neurological functions harbored in the brainstem and posterior circulation structures at risk.

Patients presenting with VBI symptoms in the setting of vertebrobasilar occlusive disease may be suffering from hemodynamic compromise, thrombo-embolic phenomenon, microvascular disease or a combination of these factors.⁵ As noted earlier, the predominant stroke mechanism for patients with atherosclerotic occlusive disease, however, appears to involve regional hypoperfusion.

Natural history

Symptomatic vertebrobasilar disease, particularly if it affects intracranial vessels, carries a high stroke risk averaging 10% to 15% per year despite medical therapy.^9,10 These rates approach those seen with symptomatic high-grade extracranial carotid stenosis.¹¹ In a retrospective study of 44 patients with symptomatic distal vertebral or basilar artery stenosis of ≥50%, Moufarrij et al. reported a 27% overall incidence of vertebrobasilar ischemic events,¹² with an 80% stroke-free survival at 2 years. In another study of symptomatic vertebrobasilar disease (>50% stenosis), Qureshi et al. demonstrated that 14% of 102 patients experienced recurrent stroke, with a stroke-free survival of 72% at 2 years.¹⁰ Retrospective analysis from the Warfarin Aspirin Symptomatic Intracranial Disease (WASID) study group of 68 patients with symptomatic intracranial vertebrobasilar 50% to 99% stenosis treated with antithrombotic therapy over a median follow-up of 13.8 months, showed stroke recurrence in 15 (22%) patients, of which four (27%) were fatal.⁹ Territorial stroke risks were 7.8 and 10.7 per 100 patient-years for vertebral and basilar artery stenosis, respectively.

The prospective WASID trial of warfarin versus aspirin treatment for patients with >50% intracranial stenosis, demonstrated recurrent stroke within the territory of the stenotic artery in 15% of 569 patients with both anterior and posterior circulation disease over 2 years.¹³ The incidence of stroke at 1 year was 12%, with similar stroke rates for posterior versus anterior circulation disease. Another prospective study of patients with intracranial stenosis ≥50%, GESICA (Groupe d’Etude des Stenoses Intra-Craniennes Atheromateuse symptomatiques), reported recurrent ischemic events in 42.8% of patients with vertebrobasilar disease during a mean follow-up of 23.4 months.¹⁴ Additionally, several studies suggest that recurrent ischemic events occur predominantly within the early months following initial presentation. In Qureshi’s study of 102 patients with symptomatic vertebrobasilar disease, stroke-free survival was 76% at 12 months, and 72% at 24 months, demonstrating that most events occur within 1 year.¹⁰ Similarly, the probability of territory specific stroke from the WASID trial increased little from 12% at 1 year to 15% at 2 years in the aspirin group and 11% to 13% in the warfarin group.¹³

Ischemic stroke in general has been linked with a variety of epidemiological and clinical risk factors including age, hypertension, diabetes, smoking, dyslipidemia, coronary artery disease, peripheral vascular disease, oral contraceptive use, prior stroke, alcohol consumption, and hypercoagulable states. Specific risk factors for stroke in vertebrobasilar disease have not been extensively studied. However, some inferences can be made from data examining risk factors for stroke in both anterior and posterior circulation atherosclerotic intracranial stenosis. Retrospective data suggest that severe stenosis (≥70%)¹⁵ and antithrombotic therapy failure¹⁶ may indicate a higher stroke risk. In the prospective WASID trial, however, use of antithrombotic agents at the time of the qualifying event was not predictive of stroke,¹⁷ despite retrospective data suggesting an elevated risk of recurrent events (45%/year) among such patients.¹⁶ On multivariate analysis, severe stenosis (≥70%) and time from qualifying event were significant stroke predictors.

Given the likelihood that a hemodynamic mechanism plays a key role in vertebrobasilar stroke, determining the extent of flow compromise associated with vertebrobasilar disease is likely to be an important aspect of stroke risk prediction. Stenosis severity likely represents a surrogate marker for flow compromise, which may account for its association with stroke risk in previous studies.^15,17 However, when collateral pathways are considered, the mere presence of a severe stenosis or occlusion, in the absence of demonstrable distal territory flow reduction, may not be the most accurate stroke risk predictor. Without direct hemodynamic measurements, clinical indicators of flow compromise can be considered. In the prospective GESICA study of 102 patients with intracranial stenosis ≥50%, of which 48% were vertebrobasilar, hemodynamically significant stenosis was clinically defined as symptoms precipitated by a change in position or antihypertensive medication.¹⁴ Overall, 27.4% of patients met the clinical criteria for hemodynamically significant disease, and had a 60.7% incidence of recurrent TIA or stroke compared to 31.7% over a mean 23.4 month follow-up. These data support the role of hemodynamic status as an important predictor for recurrent ischemia.

Evaluation

Standard evaluation for patients presenting with VBI, as with other stroke syndromes, includes parenchymal brain imaging and cerebrovascular imaging, typically performed with a combination of magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). If vertebrobasilar occlusive disease is evident, imaging and clinical presentation can ascertain the etiology as atherosclerotic (vs. dissection or extrinsic compression). For athero-occlusive disease, given that a hemodynamic mechanism for stroke appears to be a significant factor, determining the extent of flow compromise within the vertebrobasilar system and distal arterial tree is an important element of patient assessment.

Unlike the anterior circulation, modalities for hemodynamic assessment in the posterior circulation are limited. Validated and precise techniques for assessing blood flow in the posterior circulation are lacking, especially at the tissue perfusion level. The modalities of imaging frequently employed in the anterior circulation to determine flow, by assessing vessel velocities (using transcranial Doppler [TCD]), or tissue perfusion (using positron emission tomography [PET], xenon compute tomography [CT], single-photon emission computed tomography [SPECT], MR/CT perfusion), have been less effective in evaluating the posterior circulation.¹⁸ Regional imaging resolution with these techniques is generally inadequate to reliably demonstrate perfusion deficits in the compact brain territories at risk with posterior circulation disease, and TCD is operator dependent and can be limited by anatomical variation, such as vascular tortuosity or skull density, for intracranial measurements.

Although the traditional methods of hemodynamic assessment have been difficult to apply to the vertebrobasilar system, a technique using phase contrast MR has become available in recent years, which provides the ability to quantify flow rates through individual craniocervical vessels, adding a new dimension to the conventional imaging modalities.^19,20 This technique of quantitative MR angiography (QMRA) allows flow measurement in cubic centimeters per minute in vessels of interest; this technology is now commercially available in a validated software called NOVA (Non-invasive Optimal Vessel Analysis, VasSol, Inc., Chicago, IL).²¹ By direct measurement of volumetric blood flow through the major vessels of the posterior circulation (vertebral, basilar, and posterior cerebral arteries) QMRA can provide an assessment of local and distal flow compromise. In a retrospective study of 47 patients, such vessel flow measurements were highly predictive of recurrent stroke risk in symptomatic vertebrobasilar disease (vertebrobasilar stenosis [≥50%] or occlusion).²² The patients underwent QMRA using NOVA, and flow compromise was defined as >20% reduction below the normative lower limits of blood flow in the vessel measured. Given the potential for collateral to the posterior circulation, through routes such as the posterior communicating artery, the flows of interest in determining the overall hemodynamic status of the posterior circulation were flows in the distal downstream vessels, namely, the basilar artery and its largest terminal branches, the posterior cerebral arteries (PCA). Patients were designated as “low flow” if both the basilar and PCAs were reduced below the flow threshold: <120 cc/min for the basilar and <40 cc/min for the PCAs. Over an average of 28 months follow-up, a significantly higher risk of recurrent symptoms was evident in patients with low flow, 19% per person-year, compared to those with normal flow at 0% per person-year. The stroke-free survival was 100% at 24 months in the normal-flow group compared with 71% in the low-flow group. The utility of QMRA in evaluating patients with vertebrobasilar athero-occlusive disease is currently being investigated through a prospective multicenter National Institutes of Health–funded study, VERiTAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke, NCT 00590980). If predictive, QMRA flow evaluation could help to distinguish patients with flow compromise and at highest risk of recurrent symptoms. Such patients would be the most appropriate candidates for intervention to augment flow to the posterior circulation.

Treatment options

At present, medical management consisting of antithrombotic therapy and risk factor modification aimed at factors such as blood pressure, cholesterol, and smoking cessation are the first line of treatment for patients with symptomatic vertebrobasilar disease. However, recurrent ischemic events can occur despite medical therapy.

Recent advances in angioplasty and stent technology offer a potential endovascular treatment strategy for vertebrobasilar lesions. Early reports indicated high mortality and morbidity rates, especially for intracranial disease. Gress et al. reported a 28% overall stroke and death risk, and 16% risk of disabling stroke and death from angioplasty for symptomatic intracranial vertebrobasilar stenosis in 25 patients treated between 1986 and 1999.²³ Levy et al. reported a 36% complication rate in 11 patients with intracranial vertebrobasilar disease undergoing stent assisted angioplasty, with two of four events being fatalities.²⁴ Fiorella et al. found a 26.1% periprocedural risk associated with stenting 44 patients with intracranial vertebrobasilar disease.²⁵ Other series, however, indicate that endovascular intervention has become less morbid and increasingly feasible in the posterior circulation. Such reports demonstrate reduced complication rates and fatalities with periprocedural event rates ranging from 8% to 18%.^26–29

The efficacy and risks of stenting were prospectively evaluated in the Stenting of Symptomatic Atherosclerotic Lesions in the Vertebral or Intracranial Arteries (SSYLVIA) Study,³⁰