Vertebral Artery Dissection

Vertebral artery dissection (VAD) is an increasingly recognized cause of stroke in patients younger than 45 years.[4, 14, 15, 16, 17] Although its pathophysiology and treatment closely resemble that of its sister condition, carotid artery dissection (CAD), the clinical presentation, etiology, and epidemiologic profile of VADs are unique. In particular, advances in imaging have contributed to growing awareness of this entity.[8]

An expanding hematoma in the vessel wall is the root lesion in vertebral artery dissection (VAD). This intramural hematoma can arise spontaneously or as a secondary result of minor trauma, through hemorrhage of the vasa vasorum within the media of the vessel. It also can be introduced through an intimal flap that develops at the level of the inner lumen of the vessel. Major trauma is also an increasingly recognized cause of VAD.[18]

This intramural hemorrhage can evolve in a variety of ways, resulting in any of the following consequences:

• The hematoma may seal off and, if sufficiently small, remain largely asymptomatic.

• If the dissection is subintimal, the expanding hematoma may partially or completely occlude the vertebral artery or one of its branches. Extensive dissections (those that extend intracranially and involve the basilar artery) result in infarctions of the brainstem, cerebellum or, rarely, the spinal cord. Subintimal dissections also may rupture back into the vertebral artery, thus creating a false lumen (pseudolumen).

• Subadventitial dissections tend to cause pseudoaneurysmal dilation of the vertebral artery, which may compress adjacent neurologic structures. These subadventitial dissections are prone to rupture through the adventitia, resulting in subarachnoid hemorrhage. In an autopsy series of more than 100 patients with subarachnoid hemorrhage, 5% of the hemorrhages were deemed the result of VAD.

• The intimal disruption and low flow states that arise in VAD create a thrombogenic milieu in which emboli may form and propagate distally. This results in transient ischemia or infarction.

An understanding of the anatomy of the vertebral artery is helpful. The course of the vertebral artery usually is divided into four sections as follows:

• Segment I runs from its takeoff at the first branch of the subclavian artery to the transverse foramina of cervical vertebra C5 or C6.

• Segment II runs entirely within the transverse foramina of C5/C6 to C2.

• Segment III, a tortuous segment, begins at the transverse foramen of C2, runs posterolaterally to loop around the posterior arch of C1, and passes subsequently between the atlas and the occiput. This segment is encased in muscles, nerves, and the atlanto-occipital membrane.

• Segment IV, the intracranial segment, begins as it pierces the dura at the foramen magnum and continues until the junction of the pons and medulla, where the vertebral arteries merge to join the larger proximal basilar trunk.

Spontaneous dissection of the vertebral artery usually occurs in the tortuous distal extracranial segment (segment III) but may extend into the intracranial portion or segment IV.

Spontaneous vertebral artery dissection (VAD) is the term used to describe all cases that do not involve blunt or penetrating trauma as a precipitating factor. However, a history of trivial or minor injury is elicited frequently from patients with so-called spontaneous VAD. The diagnosis of traumatic VAD is reserved for those patients with a history of significant trauma, including motor vehicle accidents (MVAs), falls, or penetrating injuries. Despite the severity of the injury mechanism, dissections of the vertebral artery are exceedingly rare in these contexts.

Several risk factors have been associated with the development of VAD. These include the following:

• Spinal manipulation[6, 15, 16, 19, 20, 21, 22] : Has one of the best studied and strongest demonstrated associations with VAD (The Canadian Chiropractic Association, Canadian Federation of Chiropractic Regulatory Boards, Clinical Practice Guidelines Development Initiative, Guidelines Development Committee have specific recommendations on assessment of signs of impaired vertebral artery flow and recommendations for treating or not treating patients with suspected impaired flow.[23] )

• Vertebral artery hypoplasia[24]

• Yoga

• Ceiling painting

• Nose blowing

• Minor neck trauma

• Judo

• Medical risk factors

• Hypertension[25] (48% in one series)

• Oral contraceptive use

• Chronic headache syndromes/migraines[6, 9, 16]

• Intrinsic vascular pathology

• Fibromuscular dysplasia

• Cystic medial necrosis

• Female sex

• Postpartum (rare)[26]

• Recent infection[12]

When patients with serious cervical trauma, such as cord injuries or cervical spine fractures, are screened for vertebral artery injury, 20-40% may demonstrate traumatic occlusion. This traumatic vertebral artery occlusion (as opposed to dissection) is asymptomatic, and its management is controversial.

United States statistics

Dissections of the extracranial cervical arteries are relatively rare. The combined incidence of both verterbral artery dissection (VAD) and carotid artery dissection (CAD) is estimated to be 2.6 per 100,000. However, cervical dissections are the underlying etiology in as many as 20% of the ischemic strokes presenting in younger patients aged 30-45 years. Among all extracranial cervical artery dissections, CAD is 3-5 times more common than VAD.[1]

Sex- and age-related demographics

The female-to-male ratio is 3:1.

In contrast to atherothrombotic disease of the vertebrobasilar circulation, VAD occurs in a much younger population. The average age is 40 years; the average age of a patient with CAD is closer to 47 years.[9]

Extracranial dissection

Most patients with extracranial dissection do remarkably well if they survive the initial crisis. As many as 88% of these patients demonstrate a complete clinical recovery at follow-up. However, this suggests an overall risk of death, recurrent transient ischemic attacks, or stroke of approximately 10%.

One series suggests that the severity of neurologic deficits at the time of presentation is related directly to the functional outcome.

Follow-up angiography demonstrates spontaneous healing in as many as two thirds of these patients.

Intracranial dissection

Patients with intracranial vertebrobasilar dissection constitute a more severely affected subgroup of all patients with verterbral artery dissection (VAD).[13]

The presentation of a dissection involving the intracranial portion of the vertebral artery (segment IV) is characterized by rapidly progressive neurologic deficits, including depressed consciousness.

VAD is associated with subarachnoid hemorrhage, brainstem infarctions, and high mortality rate.[13]

Morbidity/mortality

VAD has been associated with a 10% mortality rate in the acute phase. Death is the result of extensive intracranial dissection, brainstem infarction, or subarachnoid hemorrhage.[6]

Those who survive the initial crisis do remarkably well, with long-term sequelae rare.

Complications

Complications include the following:

• Brainstem infarction

• Cerebellar infarction

• Subarachnoid hemorrhage

• Vertebral artery pseudoaneurysm causing compressive cranial neuropathy

Major complications of vertebral artery dissection include stroke and death. Previous observational studies have yielded stroke rates between 0.3% and 8.5% after vertebral or carotid artery dissection. However, one randomized clinical trial observed a much lower stroke rate of 1.2% at 3 month follow-up and no deaths were reported in this time.[27, 28] As recurrences are rare, any definitive study examining complications following dissection will require large sample sizes.

The typical presentation of vertebral artery dissection (VAD) is a young person with severe occipital headache and posterior nuchal pain[29, 30] following a recent, relatively minor, head or neck injury.[3, 31] The trauma is generally from a trivial mechanism but is associated with some degree of cervical distortion.

Focal neurologic signs attributable to ischemia of the brainstem or cerebellum ultimately develop in 85% of patients; however, a latent period as long as 3 days between the onset of pain and the development of central nervous system (CNS) sequelae is not uncommon. Delays of weeks and years also have been reported. Many patients present only at the onset of neurologic symptoms. Thus, when VAD is suspected, clinicians should evaluate patients for the presence of a unilateral headache and/or neck pain and vertigo, with or without objective neurologic signs.[29]

When neurologic dysfunction does occur, patients most commonly report symptoms attributable to lateral medullary dysfunction (ie, Wallenberg syndrome).

Patient history may include the following:

• Ipsilateral facial dysesthesia (pain and numbness)[6] : Most common symptom

• Dysarthria or hoarseness (cranial nerves [CN] IX and X)

• Contralateral loss of pain and temperature sensation in the trunk and limbs

• Ipsilateral loss of taste (nucleus and tractus solitarius)

• Hiccups

• Vertigo[1]

• Nausea and vomiting

• Diplopia or oscillopsia (image movement experienced with head motion)

• Dysphagia (CN IX and X)

• Disequilibrium

• Unilateral hearing loss[2]

Rarely, patients may manifest the following symptoms of a medial medullary syndrome:

• Contralateral weakness or paralysis (pyramidal tract)

• Contralateral numbness (medial lemniscus)

The physical examination of patients who have not yet manifested neurologic dysfunction may be misleading. The occipital and nuchal pain associated with vertebral artery dissection (VAD) mimics musculoskeletal pain and often is attributed to the mechanical strain that precipitated the dissection.

Depending upon which areas of the brain stem or cerebellum are experiencing ischemia, the following signs may be present:

• Limb or truncal ataxia

• Nystagmus[3]

• Ipsilateral Horner syndrome in as many as one third of patients with VAD (ie, impairment of descending sympathetic tract)[4]

• Ipsilateral hypogeusia or ageusia (ie, diminished or absent sense of taste)

• Ipsilateral impairment of fine touch and proprioception

• Contralateral impairment of pain and thermal sensation in the extremities (ie, spinothalamic tract)

• Lateral medullary syndrome[6]

Cerebellar findings may include the following:

• Nystagmus

• Medial medullary syndrome

• Tongue deviation to the side of the lesion (impairment of CN XII)

• Contralateral hemiparesis

• Ipsilateral impairment of fine touch and proprioception (nucleus gracilis)

• Internuclear ophthalmoplegia (lesion of the medial longitudinal fasciculus)

Vertebral artery dissection (VAD) is a disease of young, generally healthy individuals. Laboratory evaluation is directed toward establishing baseline parameters in anticipation of anticoagulant therapy.

Prothrombin time (PT), activated partial thromboplastin time (aPTT), and international normalized ratio (INR) are the usual monitoring parameters for patients on anticoagulant medication.

Erythrocyte sedimentation rate (ESR), if elevated, may suggest vasculitis involving the cerebrovascular circulation.

Procedures

Patients with suspected subarachnoid hemorrhage and a normal computed tomography (CT) scan may undergo lumbar puncture (LP) if VAD is not pursued by other imaging modalities.

Diagnosis of vertebral artery dissection (VAD) is usually made by neuroimaging, which has largely replaced conventional angiography in most centers.[32] The 2011 combined ASA/ACCF/AHA guidelines gave a class I recommendation to noninvasive computed tomography angiography (CTA) or magnetic resonance angiography (MRA) as the initial diagnostic study for suspected VAD.[33] These studies were favored over ultrasonography, but there was no specific guidance on CTA over MRA provided. If these imaging modalities are inconclusive for VAD but the clinical suspicion remains high, the guidelines gave a class IIa recommendation to either serial noninvasive imaging or invasive contrast angiography (if the patients would be candidates for revascularization).[33]

Computed tomography scanning

Data examining CTA versus magnetic resonance imaging-angiography (MRI-A)/MRA for VAD are limited, but there may be a slight preference for CTA for identifying VAD given the smaller arterial diameters compared to internal carotid dissections.[34] However, CTA is less accurate if heavy calcifications are present. CTA studies have a reported 90%-99% specificity and 40%-100% sensitivity for VAD.

CT scanning is useful in identifying patients with the complication of subarachnoid hemorrhage.[3]

Absence of hemorrhage, as demonstrated by CT scan, is a prerequisite for instituting anticoagulant therapy. Ease of access to CT scanners may provide the impetus for using CTA over MRA as the inital diagnostic study.

Magnetic resonance imaging

MRI detects both the intramural thrombus and intimal flap that are characteristic of VAD.[7]

Hyperintensity of the vessel wall seen on T1-weighted axial images is considered by some to be pathognomonic of VAD.[7, 8, 9, 10, 11]

Park et al conducted a retrospective study of 41 vertebral arteries to evaluate radiologic findings according to the stages in spontaneous and unruptured, intracranial VAD (IVAD) on 3T high-resolution MRI (HR-MRI).[35] The 3T HR-MRI revealed the vessel wall characteristics as well as provided distinguishing findings between earlier stages and the chronic stage in spontaneous and unruptured IVAD. The investigators concluded that the characterization of these radiologic findings according to stages may help with the age estimation of the dissection.[35]

In a review of VAD cases registered between April 2008 and October 2014 that compared radiologic findings between patients with extracranial VAD (EVAD) and intracranial VAD (IVAD), Kobayashi et al found that intramural hematomas were more commonly revealed by MRI in patients with EVAD.[36] By contrast, in patients with IVAD, MRI and CT scanning more frequently revealed aneurysm formation.

Magnetic resonance angiography

MRA can identify abnormalities that are characteristic of the disturbed arterial flow seen in VAD. These include the presence of a pseudolumen and aneurysmal dilation of the artery.[7]

New generation MRI and MRA appear to be as sensitive as cerebral angiography for the detection of VAD, although they probably have equivalent specificity.[8, 9, 10, 11, 12, 37]

Cerebral angiography may still have a role when clinical suspicion is high but MRI/MRA has failed to isolate the lesion. In these situations, the choice can be made between serial noninvasive imaging (if symptoms are suggestive of VAD) or invasive angiography (if the patient is a candidate for revascularization and might benefit from simultaneous diagnosis and therapy).

Prior to the development of noninvasive techniques such as magnetic resonance imaging (MRI) and Doppler ultrasonography, cerebral angiography was the criterion standard in diagnosing vertebral artery dissection (VAD). These noninvasive techniques are supplanting angiography as the imaging techniques of choice for patients in whom VAD is suspected.[7]

A French retrospective study that evaluated clinical and imaging features with outcomes in 20 pediatric patients with extracranial VAD over 14 years indicated that the initial imaging studies should include the posterior fossa vessels and the craniocervical region with V2-V3 segments.[38] In the presence of inconclusive findings on nonivasive imaging studies, the investigators suggested use of conventional angiography for definitive diagnosis.[38]

The characteristic angiographic finding in a dissected vertebral artery is the string or "string and pearl" appearance of the stenotic vessel lumen.[10] Angiograms are shown in the images below.

A, Dissection of the left vertebral artery secondary to guidewire injury. B, Complete resolution occurred in 6 months with only aspirin and clopidogrel (Plavix) therapy.

Gunshot wound to the right side of the neck. A, The angiogram shows transections of the right vertebral artery (RVA) and the right internal maxillary artery (RIMAX), with partial transection and pseudoaneurysm formation of the midcervical right internal carotid artery (RICA). The transected segments of the RVA and RIMAX were embolized with coils. B and C, The RICA pseudoaneurysm was successfully treated with a 7 x 40-mm covered stent (Wallgraft).

Because of the high incidence (up to 40% in some series) of multiple extracranial cervical artery dissections occurring simultaneously in the same patient, 4-vessel angiography is the angiographic technique of choice in all patients with potential carotid artery dissection (CAD) or VAD.[10]

Vascular duplex scanning

Duplex ultrasonography of the vertebral arteries demonstrates abnormal flow in 95% of patients with vertebral artery dissection (VAD).[8]

Ultrasonographic signs specific to VAD (eg, segmental dilation of the vessel, eccentric channel) are detectable in only 20% of patients. Thus, ultrasonography may be useful as an initial test only if computed tomography angiography (CTA) or magnetic resonance angiography (MRA) are not readily available.

Transcranial Doppler

Transcranial Doppler is approximately 75% sensitive to the flow abnormalities seen in VAD. It is useful also in detecting high-intensity signals (HITS), which are characteristic of microemboli propagating distally as a result of the dissection. HITS are associated with symptomatic ischemic symptoms both in VAD and in other types of cerebrovascular disease.

Patients who demonstrate significant neurologic deficits merit transport to stroke centers or other health care institutions able to offer appropriate care of either spontaneous or traumatic vertebral artery dissection (VAD).

Immediate management for dissections leading to acute ischemia includes the initiation of thrombolytic agents provided there are no contraindications to their administration. This therapy is best reserved for patients presenting within 4.5 hours of symptom onset. Beyond this phase, treatment with either anticoagulation or antiplatelet agents are the treatments of choice.

The accepted management of proven or suspected spontaneous VAD consists of antithrombotic therapy (with either antiplatelet or anticoagulant agents) in those patients who are not also affected by the complication of subarachnoid hemorrhage.[13, 39] This approach is intended to prevent thrombogenic or embolic occlusion of the vertebrobasilar network and subsequent infarction of posterior CNS structures, brain stem, and cerebellum.

Data guiding this management strategy comes from the 2015 Cervical Artery Dissection in Stroke Study (CADISS) trial discussed in the Medical Care section.[40] The pathophysiologic mechanism underlying VAD includes hemorrhage into the arterial wall and subarachnoid hemorrhage as a devastating complication of the condition.

Consultations

Consult with a neurosurgeon.

Hospitalization

Patients with vertebral artery dissection (VAD) warrant admission and close neurologic monitoring until anticoagulation with warfarin is complete and patient's clinical condition is stable.

Findings from the Cervical Artery Dissection in Stroke Study (CADISS) trial, the only randomized trial to examine antiplatelets versus anticoagulants in the treatment of extracranial carotid and vertebral artery dissections (VADs) were published in 2015, in which no differences in outcomes between groups receiving antiplatelets versus anticoagulants were found.[40] Two hundred and fifty patients (118 with carotid artery dissection [CAD]; 132 with VAD) were randomized to either antiplatelet therapy or anticoagulant therapy and followed out to a 3 month period. Recurrent stroke was rare within this time frame (2%).[40] There was a very low incidence of postdissection adverse effects in both groups, meaning randomized studies examining treatment effects on secondary outcomes will be lacking.

Similar findings to those discussed above have been reported in previous meta-analyses examining antithrombotic treatments for CAD and VADs.[41, 42]

At this time, therefore, it would be reasonable to treat patients who are not candidates for surgical therapy, to receive either antiplatelet therapy (aspirin, with or without clopidogrel) or anticoagulant therapy (warfarin, with or without heparin).

New technological advancements in endovascular procedures indicate the growing popularity of endovascular recanalization of dissections. These procedures are viable, effective, and tolerable treatment alternatives with impressive radiographic results.[43] However, endovascular treatments are controversial, as most of the related mortality and morbidity is secondary to emboli formation in the vessel, which is amenable to antiplatelet or anticoagulation therapy. Furthermore, most dissections heal spontaneously. Surgical or endovascular repair of dissections is best reserved for patients who experience recurrent ischemic episodes despite antithrombotic therapy. It may also have a role for patients with intracranial dissections who present with subarachnoid hemorrhage.[44]

A 2014 meta-analysis of vertebral artery dissections (VADs) treated endovascularly found that 86.3% of procedures were associated with good or excellent outcomes.[45] Postoperative complications occurred in 10.5% (complications included vasospasm, postoperative rebleeding, and ischemia) with an overall mortality of 8.7%. The authors suggested that reduced operating time, minimal invasiveness, and comparative safety make endovascular procedures suitable options for intervention-amenable dissections.[45]

Surgical treatment is reserved for those patients in whom symptoms are persistent and refractory to maximal medical therapy and who are not candidates for endovascular procedures. Surgical options for vertebral artery dissections include in situ interposition grafting or extracranial-intracranial bypasses.[46]

Medications

No clear guidelines exist on the duration of anticoagulation in patients with VAD. Consider treatment regimens of 3-6 months or until radiographic resolution is established by either MRI or follow-up angiography.

Rarely, patients experience reocclusion when removed from anticoagulant therapy, which subjects them to longer regimens.

Other considerations

Most authors support follow-up imaging at 3 months after diagnosis, preferably with a noninvasive technique such as MRI.

As with all patients on warfarin therapy, monitor INR at regular intervals.

Therapy recommendations for patients with stroke and arterial dissection are available from the American Heart Association/American Stroke Association.[47, 48]

For patient education resources, see the Brain and Nervous System Center, as well as Stroke.

Anticoagulant and antiplatelet agents are the drugs of choice (DOCs) to prevent thromboembolic disorders associated with vertebral artery dissection (VAD). More potent agents (eg, intra-arterial thrombolytics) have also been described in treating selective cases.

In a randomized controlled trial of 250 patients with vertebral artery (n = 132) or extracranial carotid (n = 118) dissections who were randomly assigned to antiplatelet therapy versus anticoagulation therapy within 7 days of symptom onset, the investigators found no difference between either agent in preventing stroke and death after 3 months.[27] Indeed, there were only 4 strokes in the entire cohort and no deaths, far lower than reported in other observational studies.[27] These results were similar to a previous meta-analysis.[28]

Studies in recent years suggest that novel oral anticoagulants (NOACs) such as dabigatran, rivaroxaban, and apixaban may be viable alternatives with similar efficacy and safety outcomes to vitamin K antagonists.[49] NOACs may be associated with similar rates of stroke at follow-up, but they have fewer hemorrhagic complications.[50] Nonetheless, further research is required.

Class Summary

These agents are indicated in patients with VAD to prevent recurrent or ongoing thromboembolic occlusion of vertebrobasilar circulation.

Heparin

Potentiates antithrombin III activity. Does not actively lyse, but blocks further thrombogenesis. Prevents reaccumulation of a clot after spontaneous fibrinolysis. aPTT value 1.5-2 times control (50-80 s) is considered therapeutic.

Warfarin (Coumadin)

For prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders. Interferes with hepatic vitamin K-dependent carboxylation. Usually prolongs PT in 48 h.

Class Summary

Antiplatelet agents have been used effectively in treating VAD but are reserved for those patients who cannot tolerate or have contraindications to anticoagulants.

Aspirin (Zorprin, Bayer Buffered Aspirin)

Inhibits cyclooxygenase, which produces thromboxane A2, a potent platelet activator.

Ticlopidine (Ticlid)

Second-line antiplatelet therapy for patients who are intolerant to aspirin or in whom aspirin therapy fails.

Class Summary

Lysis of the occluding embolus may be considered by localized intra-arterial injection of alteplase (ie, tissue plasminogen activator [TPA]).

Alteplase (Activase, TPA)

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.

Intra-arterial dose: 0.3 mg/kg; not to exceed 10-20 mg