Vertebral Artery Dissection

Background: Vertebral artery dissection (VAD) is an increasingly recognized cause of stroke in patients younger than 45 years. Although its pathophysiology and treatment closely resemble that of its sister condition, carotid artery dissection (CAD), the clinical presentation, etiology, and epidemiological profile of VADs are unique.

Pathophysiology: An expanding hematoma in the vessel wall is the root lesion in 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.

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 brain stem, 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 4 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.

Frequency:

• In the US: Dissections of the extracranial cervical arteries are relatively rare. The combined incidence of both VAD and 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.

Mortality/Morbidity:

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

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

Age: 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.

History: The typical presentation of VAD is a young person with severe occipital headache and posterior nuchal pain following a recent, relatively minor, head or neck injury. 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 brain stem 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 CNS sequelae is not uncommon. Delays of weeks and years also have been reported. Many patients present only at the onset of neurologic symptoms.

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) - Most common symptom
• Dysarthria or hoarseness (cranial nerves [CN] IX and X)
• Ipsilateral limb or trunk numbness (cuneate and gracile nuclei)
• Ipsilateral loss of taste (nucleus and tractus solitarius)
• Hiccups
• Vertigo
• Nausea and vomiting
• Diplopia or oscillopsia (image movement experienced with head motion)
• Dysphagia (CN IX and X)
• Disequilibrium
• Rarely, patients may manifest the following symptoms of a medial medullary syndrome:
• Contralateral weakness or paralysis (pyramidal tract)
• Contralateral numbness (medial lemniscus)

Physical: The physical examination of patients who have not yet manifested neurologic dysfunction may be misleading. The occipital and nuchal pain associated with 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
• Ipsilateral Horner syndrome in as many as one third of patients with VAD (ie, impairment of descending sympathetic tract)
• 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
• 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)

Causes: Spontaneous 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:
• Judo
• Yoga
• Ceiling painting
• Nose blowing
• Minor neck trauma
• Chiropractic manipulation
• Medical risk factors
• Hypertension (48% in one series)
• Oral contraceptive use
• Chronic headache syndromes
• Intrinsic vascular pathology
• Fibromuscular dysplasia
• Cystic medial necrosis
• Female sex
• 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

WORKUP

Lab Studies:

• 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.

Imaging Studies:

• CT scanning
• CT scan is useful in identifying patients with the complication of subarachnoid hemorrhage.
• Absence of hemorrhage, as demonstrated by CT scan, is a prerequisite for instituting anticoagulant therapy.
• Four-vessel cerebral angiography
• Prior to development of noninvasive techniques such as MRI and Doppler ultrasound, cerebral angiography was the criterion standard in diagnosing VAD. These noninvasive techniques are supplanting angiography as the imaging techniques of choice for patients in whom VAD is suspected.
• The characteristic angiographic finding in a dissected vertebral artery is the string or "string and pearl" appearance of the stenotic vessel lumen.
• 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 CAD or VAD.
• Magnetic resonance imaging
• MRI detects both the intramural thrombus and intimal flap that are characteristic of VAD.
• Hyperintensity of the vessel wall seen on T1-weighted axial images is considered by some to be pathognomonic of VAD.
• Magnetic resonance angiography
• 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.
• MRI and MRA are less sensitive than cerebral angiography for the detection of VAD, although they probably have equivalent specificity.
• Cerebral angiography is indicated when clinical suspicion is high but MRI/MRA has failed to isolate the lesion.
• Vascular duplex scanning
• Duplex sonography of the vertebral arteries demonstrates abnormal flow in 95% of patients with VAD.
• Ultrasonographic signs specific to VAD (eg, segmental dilation of the vessel, eccentric channel) are detectable in only 20% of patients.
• 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.

Procedures:

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

Emergency Department Care:

• The accepted management of proven spontaneous VAD consists of anticoagulant therapy in those patients not also affected by the complication of subarachnoid hemorrhage.
• 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.
• This management strategy is adhered to despite the fact that no controlled studies support this approach.
• Furthermore, the pathophysiologic mechanism underlying VAD includes hemorrhage into the arterial wall and subarachnoid hemorrhage as a devastating complication of the condition.
• Evidence in favor of anticoagulation is suggested by a number of published series that demonstrate an encouraging prognosis for those patients who survive their initial presentation and subsequently undergo anticoagulation.
• All of these patients underwent CT scan of the head to exclude frank subarachnoid hemorrhage before beginning anticoagulant therapy.
• Anticoagulation therapy is supported further by the fact that no published cases have documented brainstem hemorrhage or clinical deterioration as a result of this therapy.

Consultations:

• Neurosurgery

Further Inpatient Care:

• Patients with VAD warrant admission and close neurologic monitoring until anticoagulation with warfarin is complete and patient’s clinical condition is stable.
• Transcranial Doppler may be used to monitor the intracranial vertebral artery both for patency and for the abnormal flow associated with embolic phenomena.

Further Outpatient Care:

• 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, either by MRI or follow-up angiography.
• Rarely, patients experience reocclusion when removed from anticoagulant therapy, which subjects them to longer regimens.
• 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.

Complications:

• Brainstem infarction
• Cerebellar infarction
• Subarachnoid hemorrhage
• Vertebral artery pseudoaneurysm causing compressive cranial neuropathy

Prognosis:

• Extracranial dissection
• Most patients do remarkably well if they survive the initial crisis. As many as 88% of these patients demonstrate a complete clinical recovery at follow-up.
• 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 VAD.
• 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.

Medical/Legal Pitfalls:

• Failure to consider diagnosis of VAD. The routine ED evaluation of headache (CT scan and LP) fails to identify patients with VAD. Most patients are evaluated by one other physician before the diagnosis of VAD is established.

• Failure to differentiate between the pain associated with VAD and musculoskeletal pain in the absence of a significant mechanism of injury

• Failure to consider occipital headache as a sign of VAD. Occipital headache lacks features that traditionally indicate a serious etiology. Headaches associated with VAD lack a thunderclap onset, are not associated with meningismus or fever, and are not associated with a history of significant head trauma.

• Failure to consider etiologies of the stroke syndrome, other than atherosclerosis, if the patient presents with brainstem or cerebellar dysfunction. This is especially true in the context of a negative CT scan and/or LP.