Vertebrobasilar arterial disease has a heterogeneous, clinical presentation that depends on the underlying pathophysiology of the lesion. Regardless of etiology, however, vertebrobasilar arterial strokes can be devastating and have, until recently, been associated with a high rate of death and disability. With technical advances in neuroimaging and endovascular procedures, as well as data from randomized, clinical trials on stroke prevention and management of acute stroke, we have gained a better understanding of the pathophysiology and treatment options for vertebrobasilar disease. Although currently there is not always definitive data to guide the treatment of choice, immediate expert evaluation by a stroke neurologist may help in selecting the appropriate imaging modality and treatment plan that can often be lifesaving.

Vertebral Artery

The anatomic course of the vertebral artery (VA) is divided into four segments. The first segment (V1) lies between the origin of VA from the subclavian artery (SA) and the transverse foramen of C5 or C6. The second segment (V2) is located within the transverse foramina from C5 or C6 to C2. The third segment (V3), also known as the vertebral siphon, courses posteriorly and laterally between the atlas and occiput. The fourth segment (V4) is the intracranial portion of the VA; the vessel pierces the dura mater and enters the cranium through the foramen magnum, then courses medially and superiorly to merge with the opposite VA at the level of pontomedullary junction giving rise to the basilar artery (BA).

The left VA originates directly from the aortic arch in approximately 8% of cases. Asymmetry between the vertebral arteries is found in 66% of cases with the left VA being dominant in 45% cases.¹ The VA has three major intracranial branches: anterior spinal artery, posterior spinal artery, and posterior inferior cerebellar artery (PICA).

The anterior spinal artery is a midline unpaired vessel formed by anastamosis of two branches from each VA. It originates at the level of the olivary nucleus to the conus medullaris and descends caudally to supply to the ventral surface of the medulla and the anterior two-thirds of the spinal cord.

The posterior spinal artery is a branch of either the VA or PICA and supplies the posterior third of the spinal cord.

The PICA is usually the largest branch of the distal intracranial portion of the VA, branching in close proximity to the BA origin. Fifteen percent of individuals lack one PICA and 5% have a hypoplastic PICA. Additionally, a PICA originating from the proximal BA directly or from a common trunk with AICA can be occasionally seen.¹ The lateral medulla, inferior cerebellar vermis, and inferior surface of the cerebellum are supplied by the PICA.

Basilar Artery

The BA lies ventral to the pons and extends from the pontomedullary junction to the pontomesencephalic junction where it bifurcates into its terminal branches, the posterior cerebral arteries (PCAs). It is responsible for the vascular supply of the pons, midbrain, cerebellum, labyrinth, cochlea, thalamus, subthalamus, and temporo-occipital lobes. The branches of BA can be divided into three groups: paramedian, long circumferential, and short circumferential branches.

Paramedian arteries branch perpendicular to the BA and penetrate the pons feeding a paramedian wedge of the pontine parenchyma. In the distal part of the BA, close to the bifurcation, there are paramedian vessels, also known as interpeduncular vessels that supply the midbrain and the subthalamus.

Short circumferential arteries enter the brachium pontis and are responsible for the vascular supply of ventrolateral part of the pons. Long circumferential arteries ensure the blood supply to the pontine tegmentum and to the cerebellum. Anterior inferior cerebellar artery (AICA) and superior cerebellar artery (SCA) are also considered long circumferential vessels in addition to unnamed smaller branch vessels.

The AICA is a branch of the proximal BA and supplies the lateral, caudal pons (facial, trigeminal, vestibular and cochlear nuclei, spinothalamic tract, root of seven and eighth cranial nerves), brachium pontis, floculonodular lobe, and the ventral part of cerebellar hemispheres. The internal auditory artery typically branches off of AICA and only occasionally derives directly from the BA. Its vascular territory includes the auditory, vestibular, and facial nerve.

The SCA is a branch of the distal BA, just below the bifurcation into the PCAs. It has a close anatomic relation with the oculomotor nerve in the subarachnoid space, which passes superior to the SCA and inferior to the PCA. The vascular territory of the SCA includes the rostral pontine tegmentum, brachium conjunctivum, superior vermis, and cerebellar hemispheres.

The PCAs are “terminal branches” of the BA. The course of each PCA can be divided in four segments: P1 to P4. More than 25% of humans have a persistent, primitive, and vascular pattern in which the PCA arises from the ICA and where the connection between BA and PCA remains vestigial.

P1, also known as the interpeduncular segment, extends from the bifurcation to the junction of posterior communicating artery. It provides paramedian branches to the midbrain and thalamoperforating branches to the medial thalamus. Percheron’s artery is an anatomic variant in which the two thalamoperforating pedicles arise from a common trunk from one PCA. P2, the ambient segment of the PCA, extends from the posterior communicating artery, in the ambient cistern, to the quadrigeminal cistern. The main branches of P2 are the medial and lateral posterior choroidal arteries that supply the choroid plexus of lateral ventricle. These branches also supply the pretectal region, pulvinar and posterolateral thalamus, as well as the thalamogeniculate pedicle for the posterolateral thalamus. P3, the quadrigeminal segment, courses in the quadrigeminal cistern to the anterior part of the calcarine fissure. P4 is the part of PCA above the tentorial edge, entering the anterior part of the calcarine fissure. Cortical branches of the PCA, which usually arise from P3 or P4, include anterior temporal, posterior temporal, parieto-occipital, and calcarine arteries. The dorsal callosal artery is a branch of the parieto-occipital artery and supplies the splenium of corpus callosum.

Common causes of posterior circulation ischemic stroke can be divided into large-vessel disease, small-vessel disease, and cardioembolism.

Large-Vessel Disease

Atherosclerosis is the leading cause of vertebrobasilar disease and its distribution varies, depending on race and sex. White men have predominantly extracranial large artery atherosclerosis; blacks, Asians, and women have predominantly intracranial large-vessel disease.² The origin of the VA is a frequent site of atherosclerotic lesions. These lesions are commonly associated with atherosclerotic plaques at the level of carotid and coronary arteries, as well as peripheral vascular disease, hypertension, hypercholesterolemia, and smoking.¹ Common intracranial locations of plaques are at the level where the VA pierces the dura and the proximal and middle BA. Pathology of the plaques consists of fatty streaks and fibrous tissue with often superimposed calcifications. Macroscopically the vessel will appear stenosed or occluded. As in coronary arterial disease, a complicated plaque, with hemorrhage, ulceration, or in situ thrombosis, is often responsible for the stroke mechanism either from in situ thrombosis with secondary vessel occlusion or artery-to-artery thrombembolic material propagated to downstream branches. Aortic arch atheroma that is also associated with artery-to-artery embolism may also sometimes be a cause of posterior circulation cerebral ischemia.¹ BA atherosclerotic plaque, located in the proximal or middle portion of the BA, often can occlude the origin of paramedian perforators producing a particular pattern of paramedian pontine or midbrain infarction.³ BA atherothrombosis can be either isolated or occur in the context of widespread posterior circulation atherosclerosis, with intracranial VA stenosis or occlusion being most common. In the context of multiple vessel stenosis or occlusion, an infarct in the territory of the affected posterior circulation vessels more likely is a result of hypoperfusion as opposed to in situ thrombosis.⁴

Dissection of the VA, spontaneous or traumatic, usually occurs in the extracranial segments, with V1 and V3 being predominantly affected because of increased mobility of the vessels within the vertebral canals of the cervical spine.⁵ Intimal tear and accumulation of blood between the layers of arterial wall can result in stenosis caused by subintimal dissection, or aneurismal dilatation of the vessel wall, with possible superimposed thrombosis, caused by subadventitial dissection. Subsequently, strokes may be related to hemodynamic mechanisms associated with stenosis or thromboembolic mechanism in the context of a thrombosed aneurysm.⁵ Dissections may be posttraumatic or may occur in relation with precipitating factors such as neck hyperextension or rotation. Attribubeted causes of cervicocerebral dissection have included minor sports or motor vehicle trauma chiropractic manipulations, and even simply coughing, sneezing, or vomiting. An underlying structural defect of the arterial wall, causing an arteriopathy, can sometimes be identified in association with cervicocephalic dissections. Among such conditions are fibromuscular dysplasia, cystic medial necrosis, Ehlers-Danlos syndrome type IV, Marfan’s syndrome, autosomal dominant polycystic kidney disease, osteogenesis imperfecta type I, and α₁-antitrypsin deficiency.

Dolichoectatic VA or BA is reported as a rare cause of posterior circulation stroke in the absence of atherosclerosis or vascular risk factors.³ Posterior circulation aneurysms can sometimes be associated with ischemic strokes resulting from several mechanisms. These include artery-artery embolism, in situ thrombosis, ischemia caused by compression and traction of posterior fossa structures, or vasospasm secondary to aneurismal leak¹ (Figure 25-1).

Small-Vessel Disease

Lipohyalinosis is the most common pathologic lesion associated with small-vessel disease. Small penetrating arteries are occluded with hyaline material, subsequently resulting in lacunar infarcts. These lesions are usually seen in the context of hypertension.

Cardioembolism

Fifteen to twenty percent of all ischemic strokes occur as a result of cardiac emboli to the brain. Cardioembolism in the posterior circulation is often associated with distal BA occlusion or distal PCA branch occlusions. Common cardiac sources with a high embolic potential include atrial fibrillation, acute myocardial infarction, infective endocarditis, rheumatic mitral stenosis, mechanical prosthetic heart valves, and dilated cardiomyopathy. Interatrial septal aneurysm, patent foramen ovale (PFO), bioprosthetic valves, and atrial flutter are associated with a lower risk of cardioembolic stroke. Congenital heart disease a common cause of cardioembolic stroke in children is being seen more frequently in young adults as children with congenital heart disease survive longer.³

Rare Causes

There are rare causes responsible for strokes in both the anterior and posterior circulation such as hypercoagulable states, septic arteritis, aspergillosis, sickle-cell disease, systemic lupus erythematous, and granulomatous angiitis. Among rare conditions causing strokes with a predilection for the posterior circulation are Behcet syndrome, Fabry disease, syphilitic arteritis, and neurofibromatosis.¹

The mechanisms responsible for ischemia are in situ thrombosis, embolic occlusion, hemodynamic hypoperfusion, and vasospasm. Normal cerebral blood flow (CBF) at rest is 50 to 55 mL/100 g/min. When CBF is less than 18 mL/100 g/min, neuronal electrical activity is disturbed; when CBF is less than 8 mL/100 g/min, membrane failure and cell death ensues. The brain region surrounding the infarct, also known as the ischemic penumbra, has reduced blood flow though above the threshold for absolute cell death and that tissue is therefore potentially salvageable. Ischemia triggers endothelial activation at the level of microvessels, with secondary accumulation of inflammatory mediators. Hypoxia in the precapillary arteries stimulates expression of vascular endothelial growth factors (VEGF) that is involved in angiogenesis and neovascularization.

At the level of the posterior circulation, there are multiple collaterals that can maintain blood flow via both extracranial and intracranial vessels. Intracranially, the long circumferential arteries AICA, PICA, and SCA establish an important collateral network that can compensate for cerebellar or brainstem ischemia. The brainstem tegmentum, caused by multiple collaterals, is usually resistant to ischemia whereas the lateral medullary region, caused by poor collaterals, is usually vulnerable to ischemia.¹ Development of collateral vessels and recanalization of the occluded vessels are important factors that influence the prognosis of vertebrobasilar disease.

Posterior circulation stroke has a variety of clinical presentations depending on the affected region and the underlying pathology.⁶ The most common symptoms and signs suggestive of vertebrobasilar disease are listed in Table 25-1. Patients may have transitory symptoms completely resolving in less then 24 hours, clinically defined as transient ischemic attacks (TIAs) or may have permanent deficits reflecting infarction of the brain parenchyma, clinically defined as ischemic strokes. TIAs usually last 15 to 60 minutes and present with at least two symptoms or signs. Isolated recurrent dizziness or vertigo has traditionally been thought to be a sign of peripheral vestibular dysfunction rather than a manifestation of vertebrobasilar ischemia.⁶ The true frequency of isolated dizziness associated with vertebrobasilar ischemia may be found to be more common in the future with increased frequency of MR imaging of patients with these symptoms, however.

Posterior circulation ischemic strokes can present with different syndromes depending on the occluded vessel that are discussed in the etiopathologic context.

Extracranial VA Disease

Atherosclerotic stenosis or occlusion of the extracranial VA can be asymptomatic or can present with TIAs or strokes secondary to embolic occlusion of distal branches. Lesions limited to the extracranial VA often develop slowly, so extensive collaterals from the external carotid artery, occipital branches, the subclavian artery, or thyrocervical trunk, may develop. Vertebrobasilar TIAs are seen in approximately 50% of patients with extracranial VA atherosclerotic disease, and the most common symptoms associated with this clinical scenario include dizziness, blurred vision, and gait ataxia.⁷ Strokes are usually embolic to the distal branches of posterior circulation but these strokes are rare, however, compared with the otherwise high incidence of cardiac embolic lesions.¹

VA dissection presents with neck pain or occipital headache followed in approximately 90% cases by ischemic manifestations in the brainstem, cerebellum, thalamus, or cerebral hemispheric regions supplied by the posterior circulation. Cervical spinal cord ischemia is a rare complication associated with VA dissection.⁵

Intracranial VA Disease

Intracranial VA occlusion may be asymptomatic, or may present with TIAs or infarcts in the medulla or cerebellum. These syndromes have well known clinical characteristics and will be discussed separately.

Lateral Medullary Syndrome (Wallenberg)

The characteristic clinical presentation is nausea, vomiting, vertigo, gait ataxia, ipsilateral cerebellar signs and symptoms, dysarthria, dysphagia, crossed sensory pattern with decreased sensation in the ipsilateral face and contralateral body, ipsilateral Horner syndrome, and occasionally hiccups (singultus). Clinicoanatomic correlations of Wallenberg syndrome are detailed in Table 25-2. Because of destruction of vestibular nuclei and their connections with the cerebellum as well as with the labyrinth, abnormalities of eye movements such as skew deviation, nystagmus, smooth pursuit, or saccades difficulties may occur. Mild ipsilateral facial paresis is reported with this syndrome, and is probably related to either rostral extension of the infarct or destruction of cortico-bulbar fibers after decussation that loop inferiorly and then ascend to the facial nucleus. Caudal extension of the infarct may affect the corticospinal tract after the pyramidal decussation and may produce an ipsilateral motor deficit. This latter syndrome is known as the submedullary syndrome of Opalski.⁸

Medial Medullary Syndrome (Dejerine’s Anterior Bulbar Syndrome)

This syndrome results from destruction of medially medullary structures: the hypoglossal nucleus and nerve, medial lemniscus, and medullary pyramid. Clinically, it presents with ipsilateral tongue paresis, atrophy and fasciculations, contralateral loss of position and vibration, and contralateral motor deficit with face spring, respectively (Figure 25-2).

Hemimedullary Syndrome (Babinski-Nageote)

This syndrome is the result of a combination of the medial and lateral medullary syndromes.

PICA Infarcts

The PICA vascular distribution can be divided into medial PICA (mPICA) supplying the lateral medulla and the dorsomedial caudal cerebellum, and lateral PICA (l-PICA) supplying the lateral caudal cerebellum. Isolated complete PICA territory infarcts are rarely reported. These infarcts are usually associated with AICA or SCA ischemia, and clinically present with a high tendency for edema, brainstem compression, and tonsillar herniation.⁹ The medial PICA syndrome presents with a complete or incomplete Wallenberg syndrome. Lateral PICA infarcts presents with either isolated vertigo or vertigo associated with ipsilateral cerebellar syndrome.

BA Disease

BA occlusions can be thrombotic or embolic. Thrombotic BA occlusion usually affects the proximal or midportion of the BA and is clinically characterized by the gradual progression of symptoms over variable intervals of time reported from a few hours to more than 2 weeks.¹ Signs and symptoms of pontine ischemia with gradual progression without improvement is a poor, prognostic sign. Alternating transient hemiparesis or inappropriate laugh (“fou rire prodromique”) is classically described as heralding BA occlusion. Coma or a “locked-in syndrome” follows. BA embolism that usually presents with sudden onset is clinically related to “top of the basilar syndrome,” because of anatomic narrowing of the distal BA and lodging of embolic material at this level.

Coma is secondary to destruction of the ascending activating reticular formation in the pontine tegmentum. Apneustic breathing pattern, pinpoint but reactive pupils, and decerebrate postures are often present and may suggest the pontine localization of coma.

Locked-in syndrome is anatomically correlated with bilateral, ventral, and pontine lesions. Clinically, it presents with quadriplegia caused by bilateral corticospinal tract involvement, mutism, bilateral facial paresis, and horizontal eye movements caused byinvolvement of bilateral corticobulbar fibers. Consciousness is preserved because the dorsal pontine tegmentum is spared. Vertical eye movements are also preserved because of sparing of the ri-MLF which is located in the midbrain.

Neuro-ophthalmologic signs described in association with BA occlusion and their anatomic correlation are presented in Table 25-3.