Vertebrobasilar atherothrombotic disease (VBATD) describes a wide spectrum of clinical entities with a common pathophysiology. Transient ischemic attacks (TIAs) in this vascular territory are also referred to as vertebrobasilar insufficiency (VBI). This more commonly used term was developed in the 1950s when Fisher introduced the term carotid insufficiency to describe TIAs of the anterior circulation. These, in turn, frequently serve as the prodrome to carotid branch infarcts. Although carotid insufficiency has been dropped from common medical jargon, vertebrobasilar insufficiency persists as the term that encompasses all TIA syndromes of the posterior circulation. In this article, vertebrobasilar atherothrombotic disease describes both transient and permanent ischemic deficits as they affect posterior cerebral circulation.
Vertebrobasilar atherothrombotic disease (VBATD) deserves special attention among emergency physicians because it is difficult to diagnose and important not to misdiagnose. Signs and symptoms of VBATD overlap those of other more common benign entities (eg, labyrinthitis, vestibular neuronitis, benign paroxysmal positional vertigo).
Vertebrobasilar (posterior) circulation constitutes the arterial supply to the brainstem, cerebellum, and occipital cortex. The image below shows the vascular territories of the brain.
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Vascular territories of the brain.
Any interruption in blood flow to these areas may manifest in a myriad of symptoms. These symptoms are determined by which particular branch or branches of the vertebrobasilar circulation have been compromised, extent of any collateral circulation, and degree of occlusion.
The brainstem is an intensely concentrated area of neurologic activity, housing cranial nerves, the reticular activating system, and a series of ascending and descending neurosensory tracts. As a result of impaired blood flow, this compact area of neurologic activity malfunctions and results in several different but overlapping clinical syndromes.
Embolic phenomena cause infarction in vertebrobasilar territory in 9-40% of reported cases. The vertebrobasilar bed appears less susceptible than carotid circulation to embolic occlusion.
The vertebral artery is often classified into intracranial and extracranial segments; the atherosclerotic process tends to affect vertebrobasilar circulation at specific intracranial and extracranial sites. The extracranial site is defined as the initial segment of the vertebral artery just proximal to its take-off from the subclavian. The intracranial site is defined as the proximal portion of the basilar artery, just after the joining of the 2 vertebral arteries or just distal to the pontomedullary junction.
Approximately one fourth of strokes and transient ischemic attacks (TIAs) occur in the vertebrobasilar distribution.[1]
Brainstem infarctions have been reported in autopsy series at a rate of 2 per 1000 cases. One clinical study has suggested that the disease occurs 25% as frequently as occlusions of the carotid artery and its branches.
Recent developments in neuroimaging provide new perspectives about the disease's prevalence. Some studies using MRI suggest that 40% of patients with vertebrobasilar TIAs have evidence of brainstem infarction.
Mortality/Morbidity
Vertebrobasilar ischemic disease encompasses a vast spectrum of clinical syndromes, extending from subclinical to lethal brainstem infarctions.
Of patients who suffer infarctions in the vertebrobasilar territory, 50% report TIAs in the days or weeks (rarely months) prior to onset of the permanent deficit. A systematic review suggests that although overall mortality is no different than anterior territory ischemia, the early risk (within 7 d) of recurrent stroke or TIA progression to stroke is higher with VBATD.[1]
Basilar artery syndrome, which presents as a locked-in state, is caused by complete occlusion of the intracranial portion of vertebrobasilar circulation. It is a devastating disease with a mortality rate of 75-85%.
Race
Intracranial atherosclerosis is more common among black African[34] or East Asian ethnicities.[33]
Sex
As with atherosclerosis, this disease affects men twice as often as it does women.
Age
Vertebrobasilar ischemic disease occurs in the late decades of life (eg, 70s and 80s).
Vertebrobasilar TIAs typically have shorter duration than attacks involving the carotid territory, lasting 8 minutes on average compared with 14 minutes for carotid TIAs.
Classic symptoms of posterior region ischemia include the following[29] :
Hemisensory extremity symptoms (eg, contralateral to facial component)
Vertigo is the hallmark symptom of patients experiencing ischemia in the vertebrobasilar distribution. Many patients describe their vertigo as nonviolent or more of a swimming or swaying sensation. Exact incidence of vertigo is unknown, yet as many as one third of patients with VBI may experience vertigo as the sole manifestation of their illness.
Other symptoms specific to regional infarcts and syndromes include the following:
Lateral medullary infarct (Wallenberg syndrome): When VBI progresses to a complete brainstem infarction, a common syndrome is impaired neurologic functioning in the lateral aspect of the medulla, first described by Wallenberg. This is characterized by the following:
Ipsilateral facial pain and numbness
Ipsilateral ataxia (falling to side of lesion)
Vertigo, nausea, vomiting
Contralateral pain and thermal impairment over body and occasionally face
Medial medullary infarct: Occlusion of a vertebral artery or branch of the lower basilar artery may produce the following symptoms:
Contralateral arm and leg weakness (facial sparing)
Diplopia
Basilar artery syndrome: Caused by complete basilar artery occlusion, this is characterized by the following:
Locked-in state (awake quadriplegia)
Paralysis or weakness of all extremities
Horizontal gaze paresis, stupor, coma
Subclavian steal syndrome: This syndrome results from retrograde blood flow down the vertebral artery in response to increased demands from the left upper limb.
One of the earliest descriptions of VBI was reported in patients who suffered from stenotic lesions of their left subclavian arteries, just proximal to the take-off of the vertebral artery. Half of these patients reported vertigo symptoms consistent with posterior circulation ischemia when exercising their left arms.
Some series suggest that arm claudication and headache are the most prominent features in patients with symptomatic subclavian steal syndrome.
Labyrinthine artery occlusion: This artery commonly branches from the anterior inferior cerebellar artery. The resulting ear damage may lead to the following symptoms:
Most patients with early stage VBI have only transient episodes of neurologic dysfunction. As a result, most commonly cited physical symptoms may be minimal or nonexistent. Patients with ongoing symptoms, or those who already have incurred an ischemic deficit, demonstrate physical findings that reflect brainstem and cerebellar dysfunction. Crossed signs (eg, contralateral motor and sensory findings) are hallmarks of many types of brainstem strokes.
Vertebrobasilar insufficiency
Nystagmus
Limb ataxia
Truncal ataxia (falling to side of lesion)
Contralateral deficit in pain and temperature perception
Ipsilateral limb and trunk numbness
Ipsilateral loss of taste
Visual field defects
Ipsilateral hearing loss[29]
Lateral medullary infarct (Wallenberg syndrome)
Contralateral impairment of pain and thermal sensation to the extremities
Atherosclerosis is by far the most common cause of VBI, making VBI most common among patients with cardiovascular risk factors such as age, hypertension, diabetes mellitus, smoking, dyslipidemias, and family history of premature coronary artery disease (men < 55 years old, women < 65). VBI may result from any disease process that has an impact on the arterial supply to the posterior fossa, including the following:
Fibromuscular dysplasia
Rotational occlusion (Bow hunter's stroke) - Mechanical occlusion or stenosis of the vertebral artery at the C1-C2 level caused by lateral flexion
Imaging studies are the primary tools used to confirm a vertebrobasilar atherothrombotic disease (VBATD) diagnosis. They also help exclude differential diagnoses that would preclude such therapies as anticoagulants. Ancillary evaluations, however, are important in the search for other conditions whose signs and symptoms overlap VBATD's complex clinical syndrome. These include the following:
CT scanning helps rule out CNS hemorrhage or mass effect secondary to cerebellar infarction. However, CT is not a good choice for detecting brainstem infarctions because of bony interference.
CT scanning can also demonstrate a hyperdense basilar artery sign, shown in the image below, in the setting of a suspected posterior circulation stroke.[2] This finding is highly specific but only moderately sensitive. It is also associated with a poor prognosis.
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Hyperdense basilar artery (arrow).
MRI is far superior to CT for brainstem and posterior fossa imaging.[29] MRI is more sensitive to small ischemic areas that characterize branch occlusion of the vertebrobasilar circulation. As a result MR is the imaging method of choice for patients with posterior circulation ischemia.
Contrast-enhanced magnetic resonance angiography (CE-MRA) and CTA may be as good as cerebral angiography for detecting occlusions and stenoses of the vertebrobasilar circulation, but may not be as good for quantifying degree of stenosis. When comparing CE-MRA and CTA for detection of vertebrobasilar circulation stenosis, both have a high sensitivity and specificity, although CTA is perhaps slightly less than CE-MRA.[31] MRA and angiography images are shown below.
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Magnetic resonance angiography demonstrating the absence of flow in the vertebrobasilar system.
Doppler ultrasound (duplex ultrasonography) may complement MRA and provide important hemodynamic data on degree of vertebrobasilar stenosis.[3] Specifically, it is widely used to identify carotid stenosis, but is much less sensitive in the detection of vertebral artery stenosis.[27]
Multimodal MRI can provide unique information about the extent and prognosis of smaller infarcts and demonstrate tissue at risk in the ischemic penumbra.
Transcranial Doppler helps assess and monitor vertebrobasilar patency in patients who have received intra-arterial thrombolysis.
Chest radiography may be indicated to rule out conditions whose signs and symptoms are similar to those of VBATD.
A therapeutic gap is recognized.
Diagnostic neuroimaging developments have surpassed therapeutic interventions available for patients with VBATD.
Surgery is not an established treatment option for VBATD, in contrast to its value for treating carotid territory ischemia.
Invasive techniques such as intraarterial thrombolysis and angioplasty generally are investigational at this time.
Specialized neuroimaging (eg, MRI, angiography) has no impact on clinical decision making for the vast majority of patients with VBATD.
For imaging patients with uncomplicated VBATD, the American Heart Association now recommends MR imaging in addition to or instead of CT scanning and duplex ultrasonography of the carotid vessels to search for surgically amenable stenoses.[4]
Vertebrobasilar atherothrombotic disease (VBATD) management in the emergency department (ED) varies on the basis of the patient's symptoms and condition.
For patients with VBATD who have experienced ischemic infarcts, management falls into 2 major categories: supportive measures and interventions to reestablish patency in the infarct-related artery or to prevent occlusion of a vessel at risk for atherothrombotic or embolic occlusion.
Airway issues must be addressed in patients with brainstem infarction resulting from VBATD.
Compromise of ninth and tenth cranial nerves can blunt the gag reflex and inhibit even a conscious or awake patient from handling secretions effectively.
Secure the airway of patient with an unstable course or severe deficits before starting prolonged diagnostic imaging studies.
Patients who present to the ED with ischemic stroke are often hypertensive, even in the absence of premorbid blood pressure elevations.
Given the autoregulatory curve's tendency to shift to the right during hypertension, most authors caution against lowering the blood pressure in the first 24-48 hours after onset of stroke.
A precipitous drop in blood pressure can have a significant impact on cerebral perfusion pressure.
Consider antihypertensive medication only in cases of concomitant hypertensive emergency (ongoing end-organ damage), mean arterial pressure (MAP) greater than 130 mm Hg, or systolic blood pressure greater than 220 mm Hg.
Because most patients with significant neurologic symptoms are denied oral intake until swallowing mechanisms are evaluated, goals of intravenous fluid therapy are to provide isotonic hydration and to avoid hyperglycemia, which appears to exacerbate neuronal injury in stroke.
Treat vomiting with antiemetics; vomiting may be severe in some brainstem infarctions.
If a hemorrhagic lesion has been excluded, patients with VBATD are treated with antiplatelet agents or, in certain circumstances, an anticoagulant such as warfarin (see Medication).[5] Reperfuse the infarct-related artery by intra-arterial thrombolysis or percutaneous transluminal angioplasty (see Consultations).
Neurosurgeon: Consultation with a neurosurgeon is indicated for surgical evacuation of cerebellar hemorrhages and to manage cerebellar infarction complicated by hydrocephalus.
Interventional neuroradiologist
Intra-arterial thrombolysis: The high mortality rate associated with basilar artery occlusion and resulting brainstem infarction has prompted research into reperfusion therapy via intra-arterial infusion of thrombolytic agents (see Medication). Several case series and small randomized controlled trials have shown promise with regards to recanalization and improved clinical outcomes in basilar artery occlusion and vertebrobasilar stroke.[6, 7] Prethrombolysis and postthrombolysis angiograms are shown below.
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Right vertebral artery angiography showing an occlusion with no flow in the basilar artery.
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Angiography performed after intra-arterial thrombolysis and angioplasty showing recanalization and perfusion of the basilar artery and its branches.
Percutaneous transluminal cerebral angioplasty: Increasingly, investigators have described successful dilation of high-grade vertebral artery stenoses in patients with VBATD who did not respond to medical therapy. Although this approach is not without risk (rate of stroke as high as 40% in some series), other studies have described 80% success rates in restoring flow and eliminating symptoms.
Antiplatelet medications constitute first-line treatment for patients with vertebrobasilar atherothrombotic disease (VBATD). This approach is supported by a large body of clinical research in the secondary prevention of strokes, and although benefits are small, its application to posterior circulation events is well established.[8]
Important inferences can be drawn from the European Stroke Prevention Study, which examined the efficacy of a daily regimen of 225 mg of dipyridamole and 990 mg of aspirin in 2500 patients randomized to receive drug therapy or placebo.[9] The overall total incidence of stroke or death (the end points) during the 2-year follow-up in the placebo group was lower in the vertebrobasilar group compared to the carotid group (14% versus 24%, respectively). The combination therapy of dipyridamole and acetylsalicylic acid caused a marked reduction in the incidence of stroke or death in patients with vertebrobasilar (51%) and carotid (30%) events. When only stroke was considered as the end point, dipyridamole and acetylsalicylic acid seemed to be more effective in reducing the risk of transient ischemic attacks than stroke, and more effective in men than in women.
No randomized clinical trials have been conducted to determine antiplatelet therapy's efficacy in treating VBATD. Antiplatelet therapy's widely perceived benefits for cerebrovascular disease may prevent an ethically acceptable trial with a placebo arm.
Data from the International Stroke Trial (IST) revealed a small but real clinical benefit of antiplatelet therapy in patients who experienced a completed stroke.[10] The IST results suggest that only 1% of patients may benefit from aspirin therapy.
Arguments for anticoagulant therapy in VBATD are much more tenuous. A nonrandomized, concurrent, cohort study suggested that anticoagulation provided superior stroke protection for patients with vertebrobasilar TIAs than for patients with carotid TIAs.[11] No randomized clinical trials involving patients with vertebrobasilar TIAs have compared anticoagulants to antiplatelet therapy or to placebos.
A strong argument favoring use of anticoagulants in VBATD includes settings in which the embolic source of thrombi is known or suspected (eg, atrial fibrillation).
Use of low-molecular-weight heparins has shown no significant improvement in outcome over conventional treatments.
Very little evidence from well-powered RCTs supports using intravenous administered thrombolytics to patients with posterior circulation infarcts. A single study of 883 patients comparing anterior circulation strokes (ACS) and posterior circulation strokes (PCS) suggested that PCS had lower symptomatic intracranial hemorrhage frequency following intravenous thrombolysis. Although, favorable outcomes and mortality were both similar between the ACS and PCS patients.[32] All thrombolytics are plasminogen activators and act either directly (urokinase, alteplase) or indirectly (streptokinase).
Use of an intra-arterial thrombolytic is also supported by some experts for those patients within 6 hours of stroke onset who do not qualify for IV thrombolytics.
The incidence of intracerebral hemorrhage as a complication of treatment was apparently 10%, similar to rates seen in stroke trials using systemic thrombolysis.
Clinical Context:
Augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. Does not actively lyse yet is able to inhibit further thrombogenesis. Prevents reaccumulation of clots after spontaneous fibrinolysis.
Clinical Context:
Interferes with hepatic synthesis of vitamin K-dependent coagulation factors. Used for prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders. Tailor dose to maintain INR in range of 2-3.
Clinical Context:
Inhibits prostaglandin synthesis, which prevents formation of platelet-aggregating thromboxane A2. Studies report 300 mg/d dose as effective as larger dose and may be associated with fewer adverse effects.
Clinical Context:
Inhibits platelet aggregation by inhibiting binding of ADP to platelet receptor and subsequent ADP-mediated activation of glycoprotein GPIIb/IIIa complex. Rapidly absorbed from GI tract. Used as second-line therapy for patients with TIA crescendo symptoms who are already taking aspirin.
Clinical Context:
Tissue plasminogen activator exerts effect on fibrinolytic system to convert plasminogen to plasmin. Plasmin degrades fibrin, fibrinogen, and procoagulant factors V and VIII. Serum half-life is 4-6 min but half-life lengthened when bound to fibrin in clot. Used in management of acute myocardial infarction (MI), acute ischemic stroke, and pulmonary embolism (PE). Heparin and aspirin are not given for 24 h after tPA. Must be given within 3 h of stroke onset. Exclude hemorrhage by CT scan. If hypertensive, lower BP with labetalol, 10 mg IV. Safety and efficacy of concomitant administration with aspirin and heparin during first 24 h after onset of symptoms have not been investigated.
Vertebrobasilar TIAs (ie, VBI) generally may have a more favorable prognosis than carotid territory TIAs because the risk of developing a completed stroke is less. Collateral circulation may account for improved outcome in these patients.
Lateral medullary infarction (Wallenberg syndrome) is characterized by persistent symptoms that last for years.
Eddy S Lang, MDCM, CCFP(EM), CSPQ, Associate Professor, Senior Researcher, Division of Emergency Medicine, Department of Family Medicine, University of Calgary Faculty of Medicine; Assistant Professor, Department of Family Medicine, McGill University Faculty of Medicine, Canada
Disclosure: Nothing to disclose.
Coauthor(s)
Marc Afilalo, MD, FACEP, FRCPC, MCFP(EM), CSPQ, Director, Emergency Department, Associate Professor, Faculty of Medicine, Section of Emergency Medicine, The Sir Mortimer B Davis Jewish General Hospital
Disclosure: Nothing to disclose.
Ryan Wilkie, University of Calgary Faculty of Medicine, Canada
Disclosure: Nothing to disclose.
Specialty Editors
Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
J Stephen Huff, MD, FACEP, Professor of Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia School of Medicine
Disclosure: Nothing to disclose.
Chief Editor
Robert E O'Connor, MD, MPH, Professor and Chair, Department of Emergency Medicine, University of Virginia Health System
Disclosure: Nothing to disclose.
Additional Contributors
Richard S Krause, MD, Senior Clinical Faculty/Clinical Assistant Professor, Department of Emergency Medicine, University of Buffalo State University of New York School of Medicine and Biomedical Sciences
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