7/6/23, 12:24 PM Cerebral and cervical artery dissection: Clinical features and diagnosis - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Cerebral and cervical artery dissection: Clinical features and diagnosis : David S Liebeskind, MD : Scott E Kasner, MD : John F Dashe, MD, PhD All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Mar 13, 2023. INTRODUCTION Arterial dissections are a common cause of stroke in the young but may occur at any age. Dissection occurs when structural integrity of the arterial wall is compromised, allowing blood to collect between layers as an intramural hematoma. Dissections that occur without overt trauma are often labeled as "spontaneous" even though there is often a triggering event or underlying predisposition contributing to the pathogenesis. This topic will review the pathophysiology, etiology, clinical features, and diagnosis of cerebral and cervical artery dissection. The treatment and prognosis of cervicocephalic dissection is reviewed in detail separately. (See "Cerebral and cervical artery dissection: Treatment and prognosis".) Other mechanisms of ischemic stroke and subarachnoid hemorrhage are discussed elsewhere. (See "Ischemic stroke in children and young adults: Epidemiology, etiology, and risk factors" and "Stroke: Etiology, classification, and epidemiology" and "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis" and "Nonaneurysmal subarachnoid hemorrhage".) ANATOMY AND PATHOLOGY Separation of the arterial wall layers results in dissection. A false lumen arises in the space where blood seeps into the vessel wall ( figure 1). Hemorrhage may be due to an intimal tear https://www.uptodate.com/contents/cerebral-and-cervical-artery-dissection-clinical-features-and-diagnosis/print 1/39 7/6/23, 12:24 PM Cerebral and cervical artery dissection: Clinical features and diagnosis - UpToDate or result from rupture or other pathology in the vasa vasorum [1,2]. Subintimal dissections cause luminal stenosis or occlusion, whereas subadventitial dissections largely result in dissecting aneurysm formation ( figure 2). False lumen extension back into the true lumen can form a double channel for blood flow in the artery. [3,4] Extracranial carotid dissections typically occur 2 cm or more beyond the carotid bifurcation, near or adjacent to the level of the skull base [3]. Intracranial carotid dissections are most frequent in the supraclinoid segment [4]. Vertebral artery dissection most often occurs in the cervical transverse processes of C6 to C2 (V2 segment) or the extracranial segment between the transverse process of C2 and the foramen magnum at the base of the skull (V3 segment) ( figure 3) [5]. Multiple simultaneous cervicocephalic dissections are found in 13 to 22 percent of cases [6-9] and may occur more often in females than males [7,8,10]. Three or more dissections occur in approximately 2 percent of cases [10]. Although evidence is limited to observations in small numbers of patients, multiple simultaneous dissections are not typically associated with a known underlying predisposition to dissection [10]. Rather, most cases may be due to a transient vasculopathy following minor trauma or infection. Ischemia may manifest in only one of the downstream arterial territories, if at all. Histopathologic specimens of dissected arteries are rarely obtained; when done, examination may reveal intramural hemorrhage, disruption of the subintimal plane, and less frequently separation of the media and adventitia ( picture 1) [11]. In a case-control study, superficial temporal artery specimens obtained by biopsy or autopsy from 14 patients with cervical artery dissection showed pathologic changes involving mainly the adventitial and medial layers, with vacuolar degeneration and fissuring, along with capillary neoangiogenesis and microscopic erythrocyte extravasation into connective tissue [2]. In contrast, only one of nine control arteries obtained from accident victims showed pathologic changes in the outer arterial walls. There is a high prevalence of ultrastructural connective tissue abnormalities in patients with apparently sporadic cervicocephalic artery dissection [12-14]. These abnormalities consist primarily of composite fibrils within collagen bundles and fragmented elastic fibers. PATHOPHYSIOLOGY The development of intramural hematoma with subintimal dissections causes luminal stenosis or occlusion. This may result in cerebral ischemia due to thromboembolism, hypoperfusion, or a https://www.uptodate.com/contents/cerebral-and-cervical-artery-dissection-clinical-features-and-diagnosis/print 2/39 7/6/23, 12:24 PM Cerebral and cervical artery dissection: Clinical features and diagnosis - UpToDate combination of both. Thromboembolism rather than hypoperfusion is considered the major cause of ischemic symptoms [15,16]. (See 'Ischemic stroke or TIA' below.) Subadventitial dissections with aneurysm or hematoma formation and vessel dilatation ( figure 2) may cause local symptoms from compression of adjacent nerves and their feeding vessels, resulting in pain, partial oculosympathetic paresis (Horner syndrome), lower cranial neuropathies, or cervical nerve root involvement. (See 'Local symptoms' below.) In a minority of cases, dissection of intracranial arteries, which lack an external elastic lamina and have only a thin adventitial layer, can lead to vessel rupture with subarachnoid hemorrhage. (See 'Subarachnoid hemorrhage' below.) Head, neck, or facial pain is thought to be caused by activation of nociceptors from distension of the vessel wall due to the intimal tear and/or intramural hematoma formation [17,18]. ETIOLOGY Arterial dissections are generally caused by various degrees of trauma or triggering events, with or without an underlying predisposition. While major head and neck trauma can cause dissection, most dissections occur after a mechanical trigger, which may not always be remembered [19]. Dissections that occur without overt trauma are often labeled as "spontaneous" even though there is often a triggering event or underlying predisposition contributing to the pathogenesis. Minor trauma and other triggers Observational data suggest that trauma, typically mild or trivial in nature, or other mechanical events are triggers for cervical artery dissection in up to 40 percent of cases [20]. The list of physical activities associated with dissection is long and includes the following: Basketball [21] Childbirth [22] Cervical manipulation therapy [23-28] Coughing or sneezing [29] Dancing [30,31] Minor sports injuries [32,33] Roller coaster or amusement park rides [34-39] Scuba diving [40,41] Sexual intercourse [42] Skating [43] https://www.uptodate.com/contents/cerebral-and-cervical-artery-dissection-clinical-features-and-diagnosis/print 3/39 7/6/23, 12:24 PM Cerebral and cervical artery dissection: Clinical features and diagnosis - UpToDate Swimming [44] Tennis [45,46] Trampoline use [47] Vigorous exercise [29] Volleyball [48] Weightlifting [49] Yoga [29] While cervical manipulation therapy may trigger dissection, causality is difficult to establish, and the absolute incidence of dissection caused by spinal manipulation is unknown [28,50-52]. Associated conditions and risk factors Connective tissue disorders, vascular abnormalities, and other conditions have been associated with dissection. Connective tissue or vascular disorders The proportion of patients with cervical artery dissection who are affected by a known connective tissue or vascular disorder is low [53- 56]. Nevertheless, various connective tissue and vascular disorders have been associated with dissection, including the following [13,57,58]: Fibromuscular dysplasia [59-63] Ehlers-Danlos syndrome type IV (vascular Ehlers-Danlos) Marfan syndrome Osteogenesis imperfecta [64] Cystic medial necrosis [65] Reticular fiber deficiency [66] Homocystinuria [67] Autosomal dominant polycystic kidney disease [68] Alpha-1 antitrypsin deficiency [69] Segmental mediolytic arteriopathy [70] Reversible cerebral vasoconstriction syndromes [71] Aortic root diameter >34 mm [72] Carotid artery redundancy [73] Cervical artery tortuosity [74] Cerebral aneurysms [75] The most common association is with fibromuscular dysplasia, a nonspecific arteriopathy, which accounts for 15 to 40 percent of cases of cervicocephalic dissection in some reports [61,63,76]. Ehlers-Danlos syndrome type IV is found in <2 percent of all cases of cervical or cerebral artery dissection [53,54]. The prevalence of dissection among all patients with https://www.uptodate.com/contents/cerebral-and-cervical-artery-dissection-clinical-features-and-diagnosis/print 4/39 7/6/23, 12:24 PM Cerebral and cervical artery dissection: Clinical features and diagnosis - UpToDate Ehlers-Danlos is similarly infrequent. In one cohort of over 400 patients with Ehlers Danlos type IV, carotid artery dissection was observed in 2 percent [77]. For the remaining connective tissue and vascular disorders listed above, all of which are rare diseases, it remains uncertain whether the association with dissection is greater than would be expected by chance alone [58]. As an example, a series of 1934 patients with cervical artery dissection identified only 6 (<1 percent) with an inherited connective tissue disease [55]. There were two patients with genetically confirmed vascular Ehlers-Danlos and one patient each (diagnosed by clinical criteria) with Marfan syndrome, classic Ehlers- Danlos, hypermobile Ehlers-Danlos, and osteogenesis imperfecta. Although Marfan syndrome is a known cause of aortic dissection, only a few cases of isolated cervicocephalic dissection have been reported in patients with Marfan syndrome [78,79], and several large series of patients with Marfan syndrome have reported no occurrences of cervicocephalic dissection [80,81]. In contrast to the rare association of connective tissue disease with cervicocephalic artery dissection, one case-control study involving 84 patients with cervical artery dissection compared with 84 matched controls who had ischemic stroke without dissection found that the individuals with cervical artery dissection were significantly more likely to have clinical signs suggestive of connective tissue abnormalities [56]. These signs involved mainly skeletal (eg, scoliosis, pectus excavatum), skin (eg, mild skin hyperextension), and ocular abnormalities as well as craniofacial dysmorphisms. However, none of the patients with cervical artery dissection had an established hereditary connective tissue disease. Other conditions A number of other conditions have been associated with cervicocephalic dissection, including: Recent infection [58,72,82-84] Hypertension [85,86] Migraine [72,87-91] Elevated homocysteine levels [58,72,92] Oral contraceptive use [63,93] Smoking [87] Higher body height and lower body weight [94] Elongated styloid process compressing the cervical internal carotid artery (sometimes referred to as the stylocarotid artery syndrome or the vascular variant of the Eagle syndrome) [95,96] Pregnancy, mainly in the postpartum period [97] https://www.uptodate.com/contents/cerebral-and-cervical-artery-dissection-clinical-features-and-diagnosis/print 5/39 7/6/23, 12:24 PM Cerebral and cervical artery dissection: Clinical features and diagnosis - UpToDate Genetics There are no established genetic markers for cervicocephalic dissection. Studies using whole exome sequencing of candidate genes associated with arterial dissection or aneurysm have identified probable pathogenic variants in genes associated with connective tissue disorders, including Marfan syndrome, vascular Ehlers-Danlos syndrome, classic Ehlers Danlos syndrome, digenic Alport syndrome, and hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC) syndrome [98,99]. In addition, a genome-wide association study suggested that the rs9349379[G] allele of the PHACTR1 gene was associated with a lower risk of cervical artery dissection [100]. However, further confirmation in larger studies is needed to confirm these findings. In addition to the monogenic connective tissue disorders, polygenetic factors may be involved in the etiology and pathophysiology of dissection as part a multifactorial predisposition [53]. In theory, such factors could cause an inherited weakness of the vessel wall, thereby increasing susceptibility to dissection from minor trauma, inflammation, thrombosis, or other environmental triggers. Despite the paucity of evidence, there are valid reasons to suspect that genetic factors are related to the pathophysiology of cervicocephalic dissection. As an example, patients with a family history of arterial dissections involving cervicocephalic arteries, renal arteries or the aorta appear to be at increased risk for recurrent arterial dissection [101,102]. Furthermore, patients with apparently sporadic cervicocephalic artery dissection have a high prevalence of ultrastructural connective tissue abnormalities (see 'Anatomy and pathology' above) that are not associated with any defined collagen vascular disease. In some families, these connective tissue alterations appear to be transmitted in an autosomal dominant pattern [103,104]. EPIDEMIOLOGY Dissection is a common cause of stroke, particularly in young adults (see "Ischemic stroke in children and young adults: Epidemiology, etiology, and risk factors", section on 'Extracranial dissection'). In studies from North America and Europe, the mean age of individuals affected by dissection was 44 to 53 years [6-8,105]. While the prevalence of dissection as a cause of ischemic stroke is higher in younger adults, evidence from national registry data in the United States indicates that the prevalence of hospitalization for dissection-related stroke is evident across the lifespan [105]. A population-based study from Minnesota reported that the average annual incidence rate for internal carotid artery dissection was 1.72 per 100,000 individuals, while that for vertebral artery dissection was 0.97 per 100,000; the combined annual incidence of dissection was 2.6 per https://www.uptodate.com/contents/cerebral-and-cervical-artery-dissection-clinical-features-and-diagnosis/print 6/39 7/6/23, 12:24 PM Cerebral and cervical artery dissection: Clinical features and diagnosis - UpToDate 100,000 [6]. The true incidence is probably even higher, since many cases of dissection may escape detection because they have minor or no clinical signs [58]. There is no clear sex or ethnic predilection [6-8,58,106,107]. Dissection may be more common in winter, although the cause of seasonal variation remains unclear [108]. Extracranial dissection is far more frequent than intracranial dissection in reports from North America and Europe. However, evidence from several case series suggests that intracranial dissection is more common in Asian populations and in children [109,110]. CLINICAL MANIFESTATIONS Evidence from population- and hospital-based reports suggests that dissection most often results in ischemic stroke or transient ischemic attack, usually associated with local symptoms such as neck pain or headache [6-8,111]. However, these studies may underestimate the proportion of cases that are asymptomatic or associated with local symptoms only [58]. For patients without ischemia at the time of diagnosis, retrospective data suggest that the risk of ischemic stroke is highest in the first two weeks after the diagnosis of cervical artery dissection [112]. Local symptoms Local symptoms caused by cervical or cerebral artery dissection can include pain, Horner syndrome, cranial and cervical neuropathies, and pulsatile tinnitus. Head and neck pain The most frequent initial symptom of cervicocephalic dissection is head and/or neck pain, found in 57 to 90 percent of cases [6,111,113-116]. The pain is often severe, continuous, and of recent onset; in a study of 49 patients with cervical artery dissection, patients with head or neck pain presented within one to five days after the onset of pain [116]. Neck pain may be more frequent with vertebral artery dissection compared with carotid artery dissection [111]. The headache is typically ipsilateral to the dissection and often localizes to the temple, eye, cheek, or teeth with carotid artery dissection, and to the occipital region with vertebral artery dissection [117]. Headaches from dissection may also mimic migraine or cluster headache [118], or have a sudden and severe ("thunderclap") onset [119]. (See "Overview of thunderclap headache".) Isolated orbital or monocular pain is a rare presentation of carotid artery dissection [120,121] Horner syndrome Horner syndrome ( figure 4) occurs in approximately 25 percent of cases [6] and is due most often to distension of sympathetic fibers spanning the external surface https://www.uptodate.com/contents/cerebral-and-cervical-artery-dissection-clinical-features-and-diagnosis/print 7/39 7/6/23, 12:24 PM Cerebral and cervical artery dissection: Clinical features and diagnosis - UpToDate of the internal carotid artery [6,122,123]. The Horner syndrome seen with internal carotid artery dissection is usually partial, involving ptosis and miosis but not anhidrosis. This occurs because the sympathetic fibers responsible for facial sweating and vasodilation branch off at the superior cervical ganglion from the remainder of the oculosympathetic pathway and travel with the external carotid artery. (See "Horner syndrome", section on 'Third-order syndrome'.) Cranial or cervical neuropathies Carotid dissection may cause single or multiple compressive cranial neuropathies in up to 12 percent of cases [7,124,125]. Cranial nerve XII is most commonly affected ( figure 5), followed by IX; involvement of cranial nerves III, V, and VI is less common [124-127]. Cervical nerve root involvement is a rare complication of vertebral artery dissection [128-131]. Cranial or cervical neuropathies due to arterial dissection may occur without associated ischemia. Pulsatile tinnitus Pulsatile tinnitus can occur in isolation or in combination with other manifestations of cervical artery dissection [132-134]. In the Cervical Artery Dissection and Ischemic Stroke Patients (CADISP) study of 778 patients with cervical artery dissection, pulsatile tinnitus was present in 8 percent [134]. Ischemic stroke or TIA Ischemic symptoms are a common manifestation of cerebral and cervical artery dissection. In a population-based report of 48 patients with dissection of the internal carotid and vertebral arteries, cerebral ischemia was noted in 67 percent, with transient ischemic attack (TIA) and cerebral infarction in 23 and 56 percent, respectively [6]. Neurologic symptoms and signs of ischemic stroke or TIA due to carotid or vertebral artery dissection are not specific to dissection but are related to the different vascular territories involved. Carotid artery dissection may cause anterior circulation stroke syndrome, transient monocular blindness, retinal artery occlusion, or ischemic optic neuropathy [7,111,135,136]. Vertebral artery dissection may lead to lateral medullary infarction (Wallenberg syndrome), other posterior circulation stroke syndromes, or cervical spinal cord ischemia [128]. In a 2012 systematic review of 75 studies that described over 1900 patients with vertebral artery dissection, dizziness/vertigo was the most common symptom, although it is not certain that ischemia was the cause [137]. Subarachnoid hemorrhage Intracranial artery dissection may result in subarachnoid hemorrhage. In a 2015 systematic review of retrospective case series, subarachnoid https://www.uptodate.com/contents/cerebral-and-cervical-artery-dissection-clinical-features-and-diagnosis/print 8/39 7/6/23, 12:24 PM Cerebral and cervical artery dissection: Clinical features and diagnosis - UpToDate hemorrhage was associated with intracranial artery dissection in 8 to 69 percent of cases [110]. In rare cases, subarachnoid hemorrhage is found in combination with ischemic stroke [5]. EVALUATION AND DIAGNOSIS When to suspect dissection The diagnosis of cervical or intracranial artery dissection should be suspected in patients presenting with acute or subacute headache, neck pain, and/or stroke symptoms, particularly in following settings [138]: History of recent potential triggering events: Trauma, even if minor or trivial Participation in sports or physical activities Intense sneezing or coughing Peripartum Valsalva Personal or family history of connective tissue or vascular disorders or migraine Acute or subacute symptoms: Neurologic symptoms suggestive of ischemic stroke involving the anterior or posterior circulation stroke or suggestive of subarachnoid hemorrhage Horner syndrome Cranial or cervical neuropathies Pulsatile tinnitus Tooth pain without a dental cause Headache or neck pain at or prior to stroke onset may suggest underlying dissection, especially as a cause of stroke in the young. The acute onset of Horner syndrome in association with neck pain and an ischemic stroke or transient ischemic attack (TIA) in the territory of the ipsilateral internal carotid artery is suggestive of carotid artery dissection [58]. However, patients age 60 years with cervical artery dissection may be less likely to present with neck pain, headache, preceding trauma, or a mechanical triggering event [139]. Therefore, the possibility of dissection should not be disregarded when these features are absent in older individuals with unexplained TIA or acute ischemic stroke. Confirming the diagnosis We obtain urgent noninvasive multimodal imaging with brain and neck magnetic resonance imaging (MRI) and head and neck magnetic resonance angiography (MRA), or head computed tomography (CT) and computed tomography angiography (CTA) of the head and neck to confirm an initial diagnosis of cervicocephalic dissection and to guide serial https://www.uptodate.com/contents/cerebral-and-cervical-artery-dissection-clinical-features-and-diagnosis/print 9/39 7/6/23, 12:24 PM Cerebral and cervical artery dissection: Clinical features and diagnosis - UpToDate treatment decisions. While clinical features may raise suspicion for dissection, the diagnosis is confirmed by neuroimaging findings, particularly the demonstration of a long tapered arterial stenosis, a tapered occlusion, a dissecting aneurysm (pseudoaneurysm), an intimal flap, a double lumen, or an intramural hematoma. (See 'Choice of neuroimaging study' below.) Choice of neuroimaging study MRI should be ordered with standard axial T1-weighted, T2- weighted, fluid attenuation inversion recovery (FLAIR), and diffusion-weighted sequences. Cervical and cranial T1 fat-saturation imaging is useful for identifying small intramural hemorrhages [140]. MRA of the head and neck should be obtained with contrast-enhanced and time-of-flight MRA. Alternatively, a noncontrast head CT with CTA (which requires injection of contrast media) of the head and neck can be ordered. Axial source images and three- dimensional reconstructions are useful for detecting dissection, intimal tears, and medial or subendothelial hemorrhage [140]. The choice between these modalities is based primarily on availability and experience at local hospitals. There is no "gold standard," and the diagnosis often requires complementary imaging modalities, which may need repeating over time. These imaging studies should be performed urgently as part of a comprehensive stroke evaluation for patients who present with a clinical diagnosis of acute ischemic or hemorrhagic stroke, particularly for patients with ischemic stroke who may be candidates for reperfusion therapy using intravenous thrombolysis or mechanical thrombectomy. In addition, we obtain multimodal MRI/MRA or CT/CTA if dissection is suspected on the basis of local symptoms in the absence of ischemic stroke or subarachnoid hemorrhage. We reserve the use of conventional angiography for younger patients when clinical suspicion for dissection remains high despite negative noninvasive imaging. There is no need for conventional angiography if the diagnosis of cerebral or cervical artery dissection is clear using CTA or MRA. In most centers, conventional angiography has been supplanted by noninvasive approaches, particularly brain MRI with MRA and cranial CT with CTA [141-143]. A systematic review published in 2009 found that the sensitivity and specificity of MR techniques and CTA for the diagnosis of cervicocephalic arterial dissection were relatively similar [141]. Carotid duplex and transcranial Doppler ultrasonography (TCD) may be used to screen for suspected dissection, or to monitor therapy [144-147]. However, carotid duplex detects abnormalities in only 68 to 95 percent of cases [144,148]. Duplex and transcranial Doppler have a suboptimal yield for identifying arterial dissection near the skull base and vertebral artery dissection within the transverse foramina [58,143]. In addition, ultrasound is unreliable for detecting carotid artery dissection in patients with an isolated Horner syndrome [149]. Therefore, confirmation with MRA or CTA should be pursued in ultrasound-negative cases when the clinical history is suggestive of dissection [150]. https://www.uptodate.com/contents/cerebral-and-cervical-artery-dissection-clinical-features-and-diagnosis/print 10/39 7/6/23, 12:24 PM Cerebral and cervical artery dissection: Clinical features and diagnosis - UpToDate Characteristic imaging findings Angiographic findings of dissection include: String sign ( image 1) Tapered stenosis or occlusion or flame-shaped occlusion ( image 2) Intimal flap ( image 3) Dissecting aneurysm ( image 4) Intramural hematoma crescent sign ( image 5) Distal pouch In a population-based study of 48 consecutive patients with cervical artery dissection, the diagnostic neuroimaging patterns were an elongated tapered stenosis, a tapered occlusion, and a dissecting aneurysm in 48, 35, and 17 percent, respectively [6]. In a prospective European study of patients with vertebral artery dissection, the most frequent diagnostic neuroimaging finding on MRI was intramural hematoma, which was observed in 91 percent of 157 vertebral artery dissections [5]. The pathognomonic crescent sign of intramural hematoma is formed by an eccentric rim of hyperintensity surrounding a hypointense arterial lumen on MRI ( image 5). This crescent sign has traditionally been described on T1-weighted fat-saturation MRI sequences but may be apparent on other sequences such as diffusion-weighted imaging [151] or CTA. The degree of MRI hyperintensity and the methemoglobin content of the intramural hematoma varies with age of the lesion. Dissections of the horizontal vertebral artery segment may be difficult to diagnose as the classic crescent may be missing due to orientation of the vessel and the vertebral venous plexus may also appear hyperintense. The orientation of the vertebral artery may also limit delineation of a crescent, as the lumen may be patent yet surrounded by a more irregular "suboccipital rind" sign [152]. Assessment of multimodal CT or MRI source images is crucial to define vessel wall abnormalities. The pattern of brain ischemia on diffusion-weighted MRI may be influenced by the patency of the dissected artery, with territorial rather than borderzone infarcts apparent when there is complete occlusion of the vessel [153]. The advent of high-resolution 3 Tesla MRI has made it possible to detail interval recanalization, degree of stenosis, formation of dissecting aneurysms and the appearance of new dissections as part of serial imaging evaluations [154]. Periarterial inflammation associated with dissection may also be visualized with such high-resolution MRI techniques [155]. Evaluation for connective tissue disorders As noted previously (see 'Associated conditions and risk factors' above), the proportion of patients with dissection who are affected by a known connective tissue or vascular disorder is low. Therefore, we generally do not pursue additional https://www.uptodate.com/contents/cerebral-and-cervical-artery-dissection-clinical-features-and-diagnosis/print 11/39 7/6/23, 12:24 PM Cerebral and cervical artery dissection: Clinical features and diagnosis - UpToDate testing for such disorders unless there is heightened clinical suspicion because of suggestive symptoms, signs or family history (eg, joint hypermobility, multiple joint dislocations, translucent skin, poor wound healing, easy bruising, and unusual scars consistent with Ehlers-Danlos syndrome). (See "Clinical manifestations and diagnosis of Ehlers-Danlos syndromes".) The diagnosis of fibromuscular dysplasia (FMD) is made from angiography, so typically no additional testing is needed if extracranial arteries show no signs of FMD on MRA or CTA. An exception might be patients with clinical manifestations suggestive of renal FMD, where evaluation of renal arteries could prove diagnostic. (See "Clinical manifestations and diagnosis of fibromuscular dysplasia".) DIFFERENTIAL DIAGNOSIS The differential diagnosis of cervicocephalic dissection is broad, given that the manifestations may include local symptoms (primarily head and neck pain, Horner syndrome, lower cranial nerve palsy), brain ischemia, or subarachnoid hemorrhage, either in isolation or in combination. (See 'Clinical manifestations' above.) Head and neck pain Entities to be considered in the differential diagnosis of head and neck pain include various types of headache, particularly those with unilateral head pain and those accompanied by autonomic symptoms such as ptosis and miosis. The list includes migraine, cluster headache and other trigeminal autonomic cephalalgias (eg, paroxysmal hemicrania and short-lasting unilateral neuralgiform headache with conjunctival injection and tearing [SUNCT] syndrome), and Raeder paratrigeminal neuralgia [114]. Migraine should be suspected when there is a characteristic march of transient neurological deficits, although this pattern has been reported as well in rare patients with internal carotid artery dissection [156]. Cluster headache typically occurs without focal deficits. (See "Pathophysiology, clinical manifestations, and diagnosis of migraine in adults" and "Pathophysiology, clinical features, and diagnosis of migraine in children" and "Cluster headache: Epidemiology, clinical features, and diagnosis" and "Paroxysmal hemicrania: Clinical features and diagnosis" and "Overview of craniofacial pain", section on 'Paratrigeminal oculosympathetic syndrome'.) Thunderclap headache Thunderclap headache, a severe headache of sudden onset, occurs in a minority of patients with cervicocephalic dissection. In addition, thunderclap headache is characteristic of the pain associated with the onset of subarachnoid hemorrhage and can be associated with multiple other causes as listed in the table ( table 1). (See "Overview of thunderclap headache".) https://www.uptodate.com/contents/cerebral-and-cervical-artery-dissection-clinical-features-and-diagnosis/print 12/39 7/6/23, 12:24 PM Cerebral and cervical artery dissection: Clinical features and diagnosis - UpToDate Ischemic stroke and TIA The differential diagnosis for the cause of brain ischemia includes cardiogenic embolism, large artery atherosclerosis, small vessel disease, and a host of less common mechanisms such as a vasculopathy other than dissection. Intracranial vertebral artery occlusive disease due to atherosclerosis is a more common cause of lateral medullary ischemia than is vertebral dissection. (See "Differential diagnosis of transient ischemic attack and acute stroke" and "Stroke: Etiology, classification, and epidemiology" and "Ischemic stroke in children and young adults: Epidemiology, etiology, and risk factors" and "Posterior circulation cerebrovascular syndromes", section on 'Lateral medullary infarction'.) Subarachnoid hemorrhage The differential diagnosis of subarachnoid hemorrhage includes saccular aneurysm rupture, bleeding from a vascular malformation, perimesencephalic nonaneurysmal subarachnoid hemorrhage, and a number of less common causes. Angiography is the key to determining whether subarachnoid hemorrhage is caused by intracranial dissection or another vascular abnormality. (See "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis" and "Nonaneurysmal subarachnoid hemorrhage" and "Perimesencephalic nonaneurysmal subarachnoid hemorrhage".) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Stroke in adults" and "Society guideline links: Stroke in children" and "Society guideline links: Fibromuscular dysplasia".) SUMMARY AND RECOMMENDATIONS Location Extracranial carotid dissections typically occur 2 cm or more beyond the carotid bifurcation, near or adjacent to the level of the skull base. Intracranial carotid dissections are most frequent in the supraclinoid segment. Vertebral artery dissection most often occurs in the cervical transverse processes of C6 to C2 (V2 segment) or the extracranial segment between the transverse process of C2 and the foramen magnum at the base of the skull (V3 segment) ( figure 3). (See 'Anatomy and pathology' above.) Pathophysiology Separation of the arterial wall layers results in dissection. A false lumen arises in the space where blood seeps into the vessel wall ( figure 1). Hemorrhage may https://www.uptodate.com/contents/cerebral-and-cervical-artery-dissection-clinical-features-and-diagnosis/print 13/39 7/6/23, 12:24 PM Cerebral and cervical artery dissection: Clinical features and diagnosis - UpToDate be due to an intimal tear or result from rupture or other pathology in the vasa vasorum. Subintimal dissections cause luminal stenosis or occlusion whereas subadventitial dissections largely result in dissecting aneurysm formation ( figure 2). (See 'Pathophysiology' above.) Etiology Dissection may result from a combination of intrinsic deficiencies of vessel wall integrity and extrinsic factors, including minor trauma. Numerous proposed risk factors and inciting activities have been associated with dissection. (See 'Etiology' above.) Epidemiology Dissection of the cervical and cerebral arteries occurs in about 3 cases per 100,000 individuals across all ages yet accounts for up to one quarter of all strokes in the young. (See 'Epidemiology' above.) Clinical manifestations Evidence from population and hospital-based reports suggests that dissection most often results in ischemic stroke or transient ischemic attack, usually preceded or accompanied by local symptoms such as neck pain, headache, Horner syndrome ( figure 4), and/or cranial neuropathies ( figure 5). However, these studies may underestimate the proportion of cases that are asymptomatic or associated with local symptoms only. Uncommonly, intracranial dissection results in subarachnoid hemorrhage. (See 'Clinical manifestations' above.) Evaluation and diagnosis We obtain urgent noninvasive multimodal imaging with magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) of the head and neck, or computed tomography (CT) and computed tomography angiography (CTA) of the head and neck to confirm an initial diagnosis of cervicocephalic dissection and to guide serial treatment decisions. While clinical features may raise suspicion for dissection, the diagnosis is confirmed by neuroimaging findings, particularly the demonstration of a long tapered arterial stenosis, a tapered occlusion, a dissecting aneurysm (pseudoaneurysm), an intimal flap, a double lumen, or an intramural hematoma. (See 'Evaluation and diagnosis' above.) Treatment and prognosis The treatment and prognosis of cervicocephalic dissection is reviewed in detail separately. (See "Cerebral and cervical artery dissection: Treatment and prognosis".) Use of UpToDate is subject to the Terms of Use. REFERENCES https://www.uptodate.com/contents/cerebral-and-cervical-artery-dissection-clinical-features-and-diagnosis/print 14/39 7/6/23, 12:24 PM Cerebral and cervical artery dissection: Clinical features and diagnosis - UpToDate 1. Pannone A, Lucchetti G, Stazi G, et al. Internal carotid artery dissection in a patient with Beh et's syndrome. Ann Vasc Surg 1998; 12:463. 2. V lker W, Dittrich R, Grewe S, et al. The outer arterial wall layers are primarily affected in spontaneous cervical artery dissection. Neurology 2011; 76:1463. 3. Downer J, Nadarajah M, Briggs E, et al. The location of origin of spontaneous extracranial internal carotid artery dissection is adjacent to the skull base. J Med Imaging Radiat Oncol 2014; 58:408. 4. Chaves C, Estol C, Esnaola MM, et al. Spontaneous intracranial internal carotid artery dissection: report of 10 patients. Arch Neurol 2002; 59:977. 5. Arnold M, Bousser MG, Fahrni G, et al. Vertebral artery dissection: presenting findings and predictors of outcome. Stroke 2006; 37:2499. 6. Lee VH, Brown RD Jr, Mandrekar JN, Mokri B. Incidence and outcome of cervical artery dissection: a population-based study. Neurology 2006; 67:1809. 7. Arnold M, Kappeler L, Georgiadis D, et al. Gender differences in spontaneous cervical artery dissection. Neurology 2006; 67:1050. 8. Touz E, Gauvrit JY, Moulin T, et al. Risk of stroke and recurrent dissection after a cervical artery dissection: a multicenter study. Neurology 2003; 61:1347. 9. Hassan AE, Zacharatos H, Mohammad YM, et al. Comparison of single versus multiple spontaneous extra- and/or intracranial arterial dissection. J Stroke Cerebrovasc Dis 2013; 22:42. 10. Arnold M, De Marchis GM, Stapf C, et al. Triple and quadruple spontaneous cervical artery dissection: presenting characteristics and long-term outcome. J Neurol Neurosurg Psychiatry 2009; 80:171. 11. Besselmann M, Vennemann B, Lowens S, et al. Internal carotid artery dissection. Neurology 2000; 54:442. 12. Ulbricht D, Diederich NJ, Hermanns-L T, et al. Cervical artery dissection: An atypical presentation with Ehlers-Danlos-like collagen pathology? Neurology 2004; 63:1708. 13. Brandt T, Morcher M, Hausser I. Association of cervical artery dissection with connective tissue abnormalities in skin and arteries. Front Neurol Neurosci 2005; 20:16. 14. Brandt T, Orberk E, Weber R, et al. Pathogenesis of cervical artery dissections: association with connective tissue abnormalities. Neurology 2001; 57:24. 15. Lucas C, Moulin T, Deplanque D, et al. Stroke patterns of internal carotid artery dissection in 40 patients. Stroke 1998; 29:2646. https://www.uptodate.com/contents/cerebral-and-cervical-artery-dissection-clinical-features-and-diagnosis/print 15/39 7/6/23, 12:24 PM Cerebral and cervical artery dissection: Clinical features and diagnosis - UpToDate 16. Morel A, Naggara O, Touz E, et al. Mechanism of ischemic infarct in spontaneous cervical artery dissection. Stroke 2012; 43:1354. 17. Arnold M, Cumurciuc R, Stapf C, et al. Pain as the only symptom of cervical artery dissection. J Neurol Neurosurg Psychiatry 2006; 77:1021.