Arterial Dissection, Fibromuscular Dysplasia, and Carotid Webs

Epidemiology

Cervicocerebral arterial dissections account for approximately 2% of all ischemic strokes, but they are among the more common causes of stroke in young and middle-aged patients. Most patients with dissection are between 30 and 50 years of age, with a mean age of approximately 40 years. ^, In patients younger than 45 years, arterial dissection is the second leading cause of stroke, accounting for 10%–25% of ischemic strokes. Although older studies reveal no overall gender predilection in adults, a 2006 study of 696 patients with spontaneous cervicocerebral dissection found a preponderance in males. Females with arterial dissection are approximately 5 years younger at the time of dissection. ^, Childhood arterial dissections are unique in that they occur more commonly in boys. ^,

Population-based studies have reported the incidence of dissection as ranging from 2.6 to 2.9 cases per 100,000 per year. ^, The true incidence of cervicocerebral arterial dissection is likely higher than these estimates, however, because asymptomatic patients and patients with pain but no neurologic symptoms are underdiagnosed. The annual incidence of cervical internal carotid artery (ICA) dissection was 3.5 per 100,000 in those older than 20 years in a Mayo Clinic series. Seventy percent of cervical internal carotid dissections occur in patients between 35 and 50 years of age, with a mean age at presentation of 44 years; there is no sex predilection. Patients with intracranial carotid dissection tend to be younger than those with cervical dissections. In a review of 59 cases of intracranial carotid dissection, the mean age at onset was 30 years and there was a slight male predominance. The annual incidence of spontaneous vertebral artery dissection is one- third of ICA dissections, ^, with estimates of 1–1.5 per 100,000. Extracranial vertebral artery dissection accounts for up to 15% of cervicocerebral dissections, whereas dissection of the intracranial vertebral artery accounts for only 5%. The mean age at onset of intracranial vertebral dissection is the late 40s for isolated and the late 30s for dissection with extension to the basilar artery. In contrast to extracranial dissections, intracranial vertebral artery dissections are more common in men than in women. ^,

Pathology

Arterial dissections usually arise from an intimal tear that allows the development of an intramural hematoma (false lumen) ( Fig. 35.1 ). In some patients, no communication between the true and false lumens can be demonstrated, suggesting that some dissections are the result of a primary intramedial hematoma. Furthermore, intimal disruption could occur as a result of rupture of a primary intramural hematoma into the intima. Although it is likely that the former mechanism is more common, both could occur.

The intramural hematoma is located within the layers of the tunica media but may be eccentric towards the intima (subintimal dissection) or adventitia (subadventitial dissection). Subintimal dissections are more likely to cause luminal stenosis, whereas subadventitial dissections may cause arterial dilatation (aneurysm). These aneurysms are often referred to as “false aneurysms” or “pseudoaneurysms,” but they are true aneurysms because their walls contain blood vessel elements (i.e., media and adventitia) ; they are better termed “dissecting” aneurysms. ^, The absence of an external elastic lamina and a thin adventitia makes intracranial arteries prone to subadventitial dissection and subsequent subarachnoid hemorrhage (SAH). SAH is reported in about one-fifth of intracranial ICA dissections and in more than one-half of intracranial vertebral artery dissections. ^{, , , ,}

Pathogenesis

The pathogenesis of most spontaneous arterial dissections is unknown. Dissections can be iatrogenic or due to severe trauma, in which cases the causes are obvious, but most occur spontaneously or are associated with antecedent trivial trauma. Precipitating events reported to antedate dissection include sudden head movement, coughing, vomiting, sneezing, chiropractic manipulation, performing yoga, painting a ceiling, vigorous nose blowing, sexual activity, anesthesia administration, resuscitation, and many types of sports activity. Such activities may cause arterial injury due to mechanical stretching. A prospective study found that 81% of dissections were associated with some form of sudden neck movement. Estimates of dissection risk following chiropractic manipulation vary widely based on study methodology but range from 1 in 5.85 million manipulations to as many as 1 in 20,000 manipulations. One study found connective tissue disorders in one-fourth of patients with cervical artery dissection after chiropractic manipulation.

An underlying arteriopathy has been postulated to lead to structural instability of the arterial wall. FMD is found in approximately 15%–20% of all patients with cervicocephalic dissection and is seen in more than half of those with bilateral carotid involvement. ^, From 1% to 5% of patients have an identifiable heritable connective tissue disorder, such as Ehlers–Danlos syndrome type IV, Marfan syndrome, ^{, , ,} autosomal dominant polycystic kidney disease, osteogenesis imperfecta type I, pseudoxanthoma elasticum, ^, type I collagen point mutation, or α ₁ -antitrypsin deficiency. Dissection has also been associated with other arteriopathies such as cystic medial necrosis ^, and moyamoya disease. The association with arterial redundancies (e.g., coils, kinks, and loops), ^, increased arterial distensibility, widened aortic root, and intracranial aneurysms ^, provide indirect evidence of an underlying arteriopathy.

Five percent of patients with spontaneous cervicocephalic dissection have at least one family member with a spontaneous dissection of the aorta or its main branches, including the vertebral and carotid arteries. Atherosclerosis does not appear to be a risk factor. Other reported risk factors for dissection include migraine, recent infection, pregnancy, ^, hyperhomocyst(e)inemia, ^, smoking, ^, hypertension, ^, and oral contraceptive use. The possibility of an infectious etiology is supported by the reported seasonal variation of cervical artery dissection, with a 58% increase in frequency in the autumn. Schievink and colleagues ^, have reported familial associations between dissection and multiple cutaneous lentigines and bicuspid aortic valves, suggesting an underlying neural crest defect.

Ultrastructural aberrations of dermal collagen fibrils and elastic fibers have been reported in 54%–68% of patients with spontaneous cervical artery dissection in whom there is no clinical evidence of a known connective tissue disorder, suggesting a molecular defect in the biosynthesis of the extracellular matrix. Evidence of a generalized arteriopathy was reported in an ultrastructural study of superficial temporal artery specimens in patients with spontaneous cervicocephalic dissection. A study of skin biopsies from healthy relatives of patients with dissection indicates a familial occurrence of connective tissue abnormalities. No genetic mutation responsible for the majority of patients with cervical artery dissection has been identified. Results of screening for mutations in the genes for type V procollagen (COL5A1) , type III collagen (COL3A1) , ^, and tropoelastin (ELN) have been negative.

Despite an association with many disorders ( Box 35.1 ), the precise cause of cervicocephalic dissection remains unknown in most cases. The pathogenesis is likely multifactorial with mechanical factors and underlying arteriopathy, possibly genetic or infectious, playing roles.

Sites of Dissection

Dissection of the extracranial carotid and vertebral arteries accounts for approximately 80%–90% of all cervicocephalic dissections. ^, This disparity may be explained by the greater mobility of the extracranial segments and the potential for injury by contact with bony structures such as the transverse processes of the upper cervical vertebrae or the styloid process, either normal or pathologically elongated (Eagle syndrome) ( Fig. 35.2 ). ^, Extracranial ICA dissection typically occurs at least 2 cm distal to the bifurcation, near the C2–C3 vertebral level, and extends superiorly for a variable distance. It usually terminates before the artery enters the petrous bone, where mechanical support appears to limit further dissection in the majority of cases. This location is distinct from that of atherosclerosis, which most commonly affects the ICA origin or the siphon. The vertebral artery is most mobile, and most susceptible to mechanical injury, at the C1–C2 level, as it leaves the transverse foramen of the axis and abruptly turns to enter the intracranial cavity (the V3 segment) ( Fig. 35.3 ). The C1–C2 site is involved in one-half to two-thirds of all vertebral artery dissections and in 80%–90% of rotation-related dissections. ^,

Intracranial arterial dissection is more common in children and adolescents than in adults, although intracranial dissection in children usually affects the anterior circulation, and intracranial posterior circulation dissection is more common in adults. The most commonly involved intracranial sites are the supraclinoid segment of the ICA and the middle cerebral artery stem. ^, The most common site of intracranial vertebral artery dissection is the V4 segment at or near the origin of the posterior inferior cerebellar artery. At this level the artery may be compressed during head maneuvers, the media and adventitia diminish in size and elastic components, and the external elastic lamina terminates. Approximately 20% of vertebral artery dissections involve both the extra- and intracranial segments.

Mechanisms of Ischemia

Cervicocephalic dissection can cause ischemic symptoms due to hemodynamic compromise secondary to luminal narrowing or occlusion, thromboembolism, or both. Several reports investigating the pattern of infarction in patients with carotid dissection indicate that most strokes are the result of distal embolization. A high incidence of middle cerebral artery microemboli correlating with stroke symptoms has been found in patients with carotid artery dissection, further supporting a thromboembolic mechanism.

Clinical Manifestations