Arterial Histology and Surrounding Milieu

Differences in arterial histology reflect the pathophysiologic dissimilarities between extracranial and intracranial arterial dissections. Craniocervical artery dissections (CAD) arise from a tear in the vessel lumen. Depending upon the extent of the tear, associated hemodynamic forces, and strength of the various arterial layers, a dissection may result in stenosis or aneurysmal dilatation of the artery. Subintimal dissections tend to cause stenosis of the parent artery, while subadventitial dissections may result in pseudoaneurysm formation and compression of surrounding soft tissue structures. Compared to extracranial arteries, intradural arteries have a thinner tunica media and adventitia with a relative paucity of elastic fibers making them more susceptible to subadventitial dissection resulting in pseudoaneurysm formation and potential subarachnoid hemorrhage.² Extradural arteries are more likely to have subintimal dissections presenting with arterial stenosis or thromboembolic complications.^1,3 The relatively weak milieu consisting of cerebrospinal fluid and brain parenchyma that surrounds the intracranial arteries predisposes patients to hemorrhagic complications in addition to potential thromboembolic phenomena.

Epidemiology

Craniocervical artery dissection accounts for approximately 2% of all ischemic strokes, but 10% to 25% of strokes in young and middle-aged patients.³ Extracranial arterial dissection is more common than intracranial dissection. Specifically, the extracranial carotid artery is the most common site of arterial dissection, with an incidence estimated at 2.5 to 3.0 per 100,000 people.^3–5 Extracranial vertebral artery dissection occurs less frequently with an estimated incidence of 1.0 to 1.5 per 100,000 people.^3–7 Intracranial arterial dissection is relatively rare, with the intradural vertebral artery (V4 segment) being the most commonly affected vessel. In Yamaura’s series of 338 patients with intracranial arterial dissections, 60% involved the intradural vertebral artery while only 9% affected the internal carotid artery.⁸

The etiology of CAD is multifactorial and appears to be linked to both environmental and genetic factors. Trauma has been proposed as an inciting factor of dissections, although in many cases there is no clear antecedent injury. The severity of trauma may range from a seemingly trivial injury (i.e., vigorous nose blowing or chiropractic maneuvers) to severe high-impact motor vehicle collisions resulting in blunt or direct injury to the craniocervical arteries.⁹ Genetic factors have also been associated with CAD. In a population-based study by Schievink etal., approximately 5% of patients with CAD had a positive family history of spontaneous arterial dissections.¹⁰ Patients with heritable connective tissue disorders such as Ehlers-Danlos syndrome type IV, Marfan’s disease, autosomal dominant polycystic kidney disease, osteogenesis imperfecta type I, and α₁-antitrypsin deficiency have an increased risk of spontaneous extra- or intra-cranial artery dissection.^11–13 Recently, hyperhomocysteinemia has been linked to CAD. A significant reduction in methylenetetrahydrofolate reductase (MTHFRT) levels due to a mutation in the coding region of this gene results in increased serum levels of homocysteine.¹⁴ Respiratory infections have also been associated with spontaneous CAD in a case-controlled study.¹⁵

Radiographic Diagnosis

Pathognomonic radiographic features of CAD include intramural hematoma, the presence of a double lumen, and/or intimal flap. Digital subtraction angiography (DSA) is the gold standard method for diagnosing CAD. The “string sign,” a long arterial segment with a narrowed lumen, is the most common angiographic finding diagnostic of an arterial dissection. Intimal flaps and/or double lumens are appreciated in less than 10% of CAD cases diagnosed using DSA.¹⁶ DSA is an invasive test with an estimated iatrogenic stroke rate of 0.5% to 1%.¹⁷ Other risks of DSA include potential contrast-induced nephropathy and symptomatic hemorrhage at the arteriotomy site. Doppler ultrasonography (DUS) is a safe and effective method of diagnosing arterial dissections with reported sensitivity rates estimated at 90% when used in combination with hemodynamic signs and direct ultrasonic findings.¹⁸ However, DUS is limited by bony regions that cannot be accurately insonated (i.e., skull base and/or carotid canal) and may overestimate the degree of stenosis.^19,20

Magnetic resonance (MR) and computed tomographic (CT) angiography have replaced conventional angiography at many institutions as the primary diagnostic modalities for CAD. Advances in MR and CT angiography techniques have improved overall sensitivity and specificity rates at detecting CAD.²¹ Intramural hematomas can be readily identified on T1-weighted MR series as hyperintense signals due to methemoglobin accumulation with a characteristic crescent shape adjacent to the arterial lumen. Fat suppression techniques may accurately differentiate small intramural hematomas from surrounding soft tissues in the acute period. MR angiography can accurately display luminal stenosis and/or occlusion. The temporal relationship between dissection occurrence and MRI/MRA imaging is a potential limitation to this diagnostic modality as the sensitivity is highest within the first 2 days following the dissection.

Multidetector row CT angiography provides improved spatial resolution of less than 1 mm sections with relatively short acquisition times and reduced doses of contrast material.²² CT angiography may be superior to MR angiography at detecting acute intramural hematoma.²³ Complete hyperintense signal in the affected artery may be difficult to distinguish between intramural hematoma and vessel occlusion on MRI. In addition, CT angiography more accurately depicts near complete arterial occlusions and pseudoaneurysms than time-of-flight MR angiography, which is not as sensitive in slow flow arterial segments.²⁴ For these reasons, CT angiography is the primary diagnostic modality used at our institution in the rapid diagnosis of CAD. Recent public and governmental concerns regarding patient and healthcare worker radiation exposure during diagnostic testing have tempered our institutional use of CT angiography for interval follow-up imaging in favor of MRI/MRA especially in young patients.^25,26 Figs. 67-1 to 67-3 illustrate classic radiographic findings associated with extracranial carotid and vertebral artery dissections.

FIGURE 67-1 A, Axial CT angiogram revealing a left internal carotid artery extracranial dissection with intimal flap and associated pseudoaneurysm (arrow). B, Sagittal CT angiogram reconstruction illustrating the left internal carotid artery dissection with associated extracranial pseudoaneurysm.

FIGURE 67-2 A, CT angiogram revealing bilateral extracranial carotid artery dissections following a high-speed motor vehicle collision (arrows). B, Left common carotid artery lateral digital subtraction angiogram revealing segmental narrowing (string sign) of the internal carotid artery with luminal reconstitution proximal to the skull base. C, Right common carotid artery lateral digital subtraction angiogram showing moderate stenosis of the internal carotid artery distal to the arterial dissection.

FIGURE 67-3 A, T1-weighted axial MRI of the neck revealing dissection of the right extracranial vertebral artery with associated isointense intramural hematoma (arrow). B, T2-weighted axial MRI scan of the neck demonstrating loss of flow void in the dissected right extracranial vertebral artery.

Extracranial Carotid Artery Dissection

The extracranial carotid artery is the most common site of CAD, with an estimated incidence of 2.5 to 3.0 cases per 100,000 people.^3–5 Cervical internal carotid artery dissection occurs approximately 2 cm distal to the artery’s origin and usually terminates proximal to its entry into the petrous bone.^1,27,28 The classic clinical triad for presentation of extracranial carotid dissection is ipsilateral pain in the head, face, or neck,¹ post-ganglionic partial Horner’s syndrome characterized by ipsilateral miosis and ptosis without anhidrosis,² and cerebral or retinal ischemic symptoms.³ All three components are found in less than one third of patients with extracranial carotid artery dissection.³ Dissection-induced ischemia may manifest as transient ischemic attacks (TIAs) or cerebral infarctions. Fisher coined the term “carotid allegro” to describe dissection-associated TIAs as they tend to occur more frequently than ischemic episodes due to atherosclerotic disease.¹ Ipsilateral lower cranial nerve palsies may result from extracranial carotid artery dissection. In a retrospective series of 190 consecutive adult patients diagnosed with spontaneous dissection of the internal carotid artery, 23 (12%) presented with cranial nerve palsies.²⁹ The hypoglossal nerve was most frequently affected (5.2% of patients), with or without involvement of cranial nerves IX, X, and XI. Oculomotor and trigeminal nerve palsies were also observed in this series, possibly due to indirect interruption of nutrient vessels supplying the respective cranial nerves. Taste disturbance and tongue weakness are the most common manifestations of hypoglossal nerve compression due to its proximity to the carotid sheath. Pulsatile tinnitus may be experienced in up to one third of patients.³⁰

Treatment of extracranial carotid artery dissections is medical, with neurointerventional and surgical procedures being reserved for dissections refractory to medical therapy and/or symptomatic associated pseudoaneurysms or flow-limiting stenosis. Anticoagulation with intravenous heparin followed by conversion to oral warfarin has been recommended as first-line treatment of patients with extracranial carotid artery dissections to prevent the risk of thromboembolic complications.^3,31,32 After 3 to 6 months of anticoagulation with a goal international normalized ratio of 2.0 to 3.0, patients should undergo reimaging to evaluate for dissection resolution. Arterial recanalization rates range from 50% to 70% with an estimated 10% of patients suffering a delayed thromboembolic event during medical therapy.^33–35 Patients should be reimaged following completion of anticoagulant therapy. No randomized controlled trial has investigated the optimal medical treatment of CAD. A 2003 Cochrane Database Review found no significant differences in mortality or clinical outcomes among 327 patients in 27 studies with carotid artery dissections who were treated with either anticoagulation or antiplatelet therapy.³⁶ A small, non–statistically significant increased incidence of intracranial hemorrhage was observed in patients treated with anticoagulation (0.5%). A prospective multicenter nonrandomized study conducted by the Canadian Stroke Consortium found a non–statistically significant increased risk of recurrent stroke in patients with CAD treated with aspirin (12.4%) versus anticoagulation (8.3%).³⁷ The Cervical Artery Dissection in Stroke Study (CADISS) is an ongoing multicenter, prospective study investigating the medical treatment of extracranial arterial dissections.³⁸ Patients diagnosed with acute extracranial carotid and/or vertebral artery dissection are randomized to antiplatelet or anticoagulation therapy. The primary end points are ipsilateral stroke or death within 3 months of randomization. The results of this trial should be available in the next several years.

Endovascular and surgical treatments are typically reserved for cases of anticoagulation treatment failure defined by persistent luminal irregularities in the setting of recurrent thromboembolic disease and/or enlarging associated pseudoaneurysms. Endoluminal stenting and/or coil embolization of associated dissecting aneurysms are effective therapies for the treatment of extracranial carotid artery dissections.^39–44 Multiple stents may be deployed in a telescoping fashion for treatment of long segment arterial dissections.⁴⁰