Spontaneous Dissection of the Carotid and Vertebral Arteries: the 10-year UCSD Experience

Article Outline

• Abstract
• Introduction
• Methods
• Results
  • Demographics
  • Presentation
  • Diagnosis and treatment
  • Outcomes
• Discussion
• References
• Copyright

The etiology of spontaneous dissection of the carotid and vertebral arteries without antecedent trauma remains unclear. The goal of this 10-year review was to examine factors regarding presentation, diagnosis, treatment, and outcome for all patients at our institution who were diagnosed with spontaneous carotid dissections (SCD) or spontaneous vertebral dissections (SVD) with no prior trauma history. A retrospective chart analysis was performed involving all discharges from UCSD Medical Center from 1995 to 2005. Patients were selected for inclusion based on the diagnosis of carotid or vertebral dissection with no associated traumatic or iatrogenic cause for their presentation. Characteristics of these patients' medical risk factors, presenting symptoms, diagnostic method and time, treatment, and outcomes were analyzed. A total of 20 patients (10 male, age 44.8 +/− 12.9 yrs; 10 female, age 39.6 +/− 14.9 yrs) were included for study. These patients represented 12 cases of SCD and nine SVD. On presentation, a majority of patients with both SVD and SCD reported headache as their primary complaint while a significantly higher rate of nausea (25% vs. 67%, p < 0.01) was reported in SVD. SVD was associated with a significantly longer diagnostic time (11 hr vs. 16 hr, p < 0.01). The most commonly performed diagnostic exam in both SCD and SVD was magnetic resonance angiography (MRA). Anticoagulation was the primary treatment in 11 of 12 SCD and all nine SVD. One patient with persistent, symptomatic bilateral carotid dissection after anticoagulation was treated with stent placement resulting in unilateral intracranial hemorrhage (ICH). Length of stay was significantly longer in SVD (5 d vs. 7 d, p < 0.02). A significantly higher incidence of persistent neurologic deficits on discharge was seen in SCD (71% vs. 33%, p < 0.02). Radiographic evidence of cerebral infarction on discharge had a stronger correlation with clinical deficits in SCD. Although there were only two cases, those treated with endovascular therapy in the setting of SCD suffered complications related to the intervention. On discharge, there did not seem to be a correlation between persistent neurologic deficits and radiographic evidence of infarction in SVD reflecting that recovery after these episodes may not be predictable based on the appearance of the infarction.

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Introduction 

Dissection of an artery involves an intimal laceration allowing the intraluminal flow of blood to separate the layers of the arterial wall resulting in luminal stenosis, thrombosis, and increased potential for aneurysm formation. These dissections, first described in the aortic system by Jean Fernelius in 1542, were not associated with the cervico-cerebral circulation until the mid twentieth century.¹ While reports of the association of carotid dissection with extension of an aortic dissection as well as a complication after cerebral angiography were made in the 1930s-1950s, the recognition of spontaneous dissection of this artery did not occur until much later.², ³ Reports by Mokri et al.⁴ and Fisher et al.⁵ in the late 1970s of spontaneous dissections of the carotid (SCD) and vertebral (SVD) arteries were considered to be the first modern reports alerting physicians to this diagnosis in the ante-mortem setting.

Since the relatively recent recognition of this uncommon diagnostic entity, several studies have analyzed its epidemiology. The overall incidence of spontaneous dissection of the cervical arteries across all age groups has been estimated at 2.5-3/100,000.⁶ These dissections occurred most commonly in the fifth decade of life, although all age groups have been reported to be affected.⁷, ⁸ While only accounting for approximately 2% of all strokes, these spontaneous dissections account for the most common cause of ischemic stroke in the young and middle-aged patient populations.⁹

In an attempt at elucidating an underlying pathology contributing to the development of these lesions, many hereditary and environmental factors have been studied. While connective tissue disorders such as Ehlers-Danlos type IV, Marfan's syndrome, and autosomal dominant polycystic kidney disease have been associated with an increased incidence of SCD, studies have only identified these disorders in 1%-5% of all patients diagnosed with SCD or SVD.¹⁰, ¹¹ Family history of SCD or SVD was only associated with a minority of patients diagnosed, although these patients were found to have a fivefold higher risk of recurrent dissection.¹² A weak association between dissection of the carotid and renal arteries and fibromuscular dysplasia has been reported.¹³ A history of a respiratory infection has been shown to be an independent risk factor for both SCD and SVD corresponding to the reported seasonal variation in patterns of this disease.¹⁴ Despite these well-described associations, however, difficulty in their application as predictors of disease occurrence has allowed SCD and SVD to remain elusive diagnostic entities.

In recent history, the diagnoses of SCD and SVD have employed relatively standardized diagnostic and treatment protocols. Despite the improvement in magnetic resonance resolution, conventional angiography has been considered the gold standard for diagnosis. Once the diagnosis has been established, anticoagulation with heparin and warfarin continues to be the treatment of choice at most medical centers.¹⁵ Given the new technology available for the diagnosis of arterial pathology and myriad endovascular techniques toward their treatment, our goal was to perform a review of all patients with SCD or SVD presenting to our institution over the last 10 years. The goal of this study was to analyze the presentation, diagnosis, treatment, and outcome of this patient cohort at our institution with a specific focus on the application of endovascular interventions.

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Methods 

A retrospective review with prior IRB approval was conducted of all patients discharged from UCSD Medical Center from January 1, 1995, to January 1, 2005, with a diagnosis of carotid and/or vertebral artery dissection. Patients were included based on an established diagnosis of either carotid or vertebral artery dissection with no antecedent trauma history. Any patient who was admitted as a trauma or reported a recent traumatic mechanism associated with the head or neck (e.g., chiropractic manipulation, unusual neck extension, heavy lifting) was excluded. This resulted in the inclusion of 20 patients representing 12 SCD and nine SVD (one patient with bilateral SCD).

All parametric variables are presented as mean +/− standard deviation (SD). All nonparametric variables are presented as median [range]. Prophet 6.0 statistical software was used to perform all summary and comparative statistics. All univariate, nonparametric comparisons were performed using the Mann-Whitney Rank Sum test and multivariate analysis performed with multifactor ANOVA tables. A value of p < 0.05 was considered statistically significant.

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Results 

Demographics 

A total of 20 patients were included in the study representing 11 patients with SCD (57%) and nine with SVD (43%). Of the 20 total patients, there were an equal number of males (six SCD, four SVD) and females (five SCD, five SVD). The mean age of diagnosis was 42.6 +/− 13.8 yrs. (44.8 +/− 12.9 yrs in males, 39.6 +/− 14.9 in females). Smoking (36%) and alcohol use (36%) were the risk factors most commonly associated with SCD, whereas hypertension (44%), smoking (44%), and hyperlipidemia (44%) were those most commonly associated with SVD. There was a fairly equal distribution between right- and left-sided lesions in both groups (57% R and 43% L overall) (Table I).

Table I. Demographics

Presentation 

The most common symptom on presentation in both SCD and SVD patients was headache (83% SCD, 78% SVD). A significantly higher incidence of nausea was reported in the SVD group (67% SVD vs. 33% SCD, p < 0.01). Vertebrobasilar symptoms (vertigo, dysarthria, loss of consciousness, or diplopia) occurred in a majority of patients in each group (67% SCD, 56% SVD) with a relatively higher rate of hemispheric symptoms occurring in the SCD group (33% SCD vs. 25% SVD). Other associated symptoms such as amaurosis, anisocoria, ipsilateral facial droop, partial ipsilateral Horner's syndrome, and neck pain were seen to occur in one-third or fewer patients in each group (Table II).

Table II. Presenting symptoms

Diagnosis and treatment 

The total number of hours from patient presentation to the hospital until the definitive diagnostic test was performed was defined as total diagnostic time. The more relevant time is the time from onset of symptoms to the diagnosis but this time was difficult to ascertain because, not uncommonly, many of these patients had been seen at an outside physician's office where either the diagnosis was delayed or missed, or alternatively the patient was scheduled for an elective appointment with a physician at UCSD. Because this time point could not be obtained with fidelity, the total diagnostic time is as described above. There was a significantly longer total diagnostic time for patients with SVD (16[3-190] hr SVD vs. 11[1-138] hr SCD, p < 0.01), and on multivariate analysis, this increase was associated with nausea on admission, use of MRI, and radiographic evidence of cerebral infarction on discharge (p < 0.03). Magnetic resonance angiography was the definitive diagnostic test in a majority of patients in both groups (67% SCD, 78% SVD) with few requiring conventional angiography for definitive diagnosis and only patients with SCD imaged with duplex ultrasound. Most carotid dissections occurred in the internal carotid artery (ICA) from the bifurcation to the skull base (58%) with three patients (25%) experiencing dissection of only the intracranial portion of the ICA. Two patients (17%) were noted to have both intra- and extracranial ICA involvement.

All patients in the SVD group and all but one patient in the SCD group were treated with primary anticoagulation with heparin and warfarin. Two patients received catheter-directed thrombolysis: one patient in the SCD group as primary treatment and one SVD patient with persistent symptoms. One patient with bilateral carotid artery dissections underwent bilateral stent placement as definitive treatment due to persistent symptoms (Table III).

Table III. Diagnosis and treatment

	Carotid dissection	Vertebral dissection	Total
Time until diagnosisa	11 hr [1-138]	16 hr [3-190]	13 hr [1-190]
Imaging Modality:
Duplex	2/12 (17%)	0/9	2/21 (10%)
CT angio	0/12	0/9	0/21
MRA	8/12 (67%)	7/9 (78%)	15/21 (71%)
Angiography	2/12 (17%)	2/9 (22%)	4/21 (19%)
Location of lesion:
Origin to carotid bifurcation	0/12	-	-
Bifurcation to skull base	7/12 (58%)	-	-
Intracranial	3/12 (25%)	-	-
Both intra- and extracranial	2/12 (17%)	-	-
Treatment:
Primary Heparin/Warfarin	11/12 (92%)	9/9	20/21 (95%)
Catheter-directed thrombolysis	1/12 (8%)	1/9 (11%)	2/21 (10%)
Stent placement and plavix	2/12 (17%)	0/9	2/21 (10%)

Outcomes 

Episodes of SCD were associated with a significantly shorter length of stay (5[3-14] days SCD vs. 7[3-11] days SVD, p < 0.02) but, on discharge, were associated with significantly higher rate of persistent neurologic deficits (58% SCD vs. 33% SVD, p < 0.02). Overall, episodes of SVD had a relatively higher incidence of cerebral infarction on discharge imaging studies (78% SVD vs. 42% SCD). However, there was a significantly higher rate of asymptomatic infarcts in SVD (29% SCD vs. 67% SVD, p < 0.02). There was one death in the series representing a SCD treated with primary thrombolysis (overall death rate 4%). One readmission within a 30-day period after discharge occurred in each group due to persistent symptoms, which resolved (SCD) and stable ICH after anticoagulation (SVD) (Table IV).

Table IV. Outcomes

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Discussion 

Spontaneous dissection of the carotid and vertebral arteries remains an uncommon entity with an unclear etiology. Given the relatively recent recognition of this phenomenon, many aspects of the presentation, diagnosis, treatment, and outcome of these patients are continually evolving. In this patient series representing 12 SCD and nine SVD, in our experience, management aspects are both in agreement with and contradictory to previously published reports. Specifically, these findings include the continued diagnostic challenges posed by patients presenting with SVD versus SCD and the application of different imaging modalities toward diagnosis. The application of endovascular therapy in dissection of the carotid and vertebral arteries appears to be of limited use. Also notable was the interesting correlation between the presence of a radiographic infarction and clinical neurologic deficits in these patients.

Despite heightened awareness regarding the manifestation of cervical artery dissection, SVD required both a longer diagnostic time and hospital stay compared to SCD. As seen in several prior series, headache was the most common presenting symptom for both SCD and SVD.¹⁶ Unlike these previously published results, however, this series did not identify neck pain as a common coexistent complaint on presentation but rather nausea was a common symptom, particularly in the SVD group. Furthermore, this significantly higher incidence of nausea was found to be a significant cofactor in the longer diagnostic time associated with SVD. It is not possible to determine if the relationship between increased diagnostic time and nausea was due to symptomatic treatment of the nausea or confusion of this entity with a migraine headache. The recognition of this subtle symptom associated with SVD may, however, aid in earlier diagnosis. Given that the natural progression of both SCD and SVD commonly involves a “sentinel” headache followed by the appearance of other symptoms including neurologic deficits, over a 4-14-day course, the importance of diagnosing the process prior to symptomatic progression cannot be overemphasized.¹⁶ In fact, the additional association of a longer diagnostic time in SVD with radiographic evidence of cerebral infarction on discharge may provide further support to the notion that early diagnosis may avert late complications. The association of MR scanning in this series with increased SVD diagnostic time is likely related to the fact that, during this time period, the MR scanner at our institution was physically separated from the main hospital. This required EMS transport each time a patient required imaging and this coupled with the increased use of MR in the SVD group likely contributed to this finding.

With dramatic improvements in MR as well as duplex imaging, a majority of both SCD and SVD patients in this series did not undergo conventional angiography as their definitive diagnostic test. In the SCD group, there was equivalent yield of duplex versus angiography in obtaining a final diagnosis. Recent reports have suggested that the presence of staccato flow on duplex exam of the extracranial ICA was strongly associated with the presence of a spontaneous ICA dissection.¹⁷ MRA was found to be the most reliable diagnostic test in both SCD and SVD. The reported increase in MR applicability has been attributed to both improvement in resolution as well as its ability to show the intramural hematoma associated with dissections.¹⁸ Interestingly, one patient in the series with SVD underwent cerebral angiography on admission which was nondiagnostic requiring MRA to confirm the diagnosis (Fig. 1). The MRA in this case revealed the classic crescent-shaped intramural hematoma spiraling along the length of the left vertebral artery while the angiogram only revealed a luminal narrowing.

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• Fig. 1 

  Forty-five-year-old male who presented with headache and partial Horner's syndrome underwent conventional angiography (above left) revealing a narrowing of the left vertebral artery, which was interpreted as nondiagnostic for dissection. Subsequent MR angiography revealed the classic crescent-shaped hematoma spiraling along the length of the left vertebral artery confirming the diagnosis of dissection.

As the use of endovascular therapies for various arterial pathology increases, its applicability to the treatment of spontaneous carotid and vertebral dissections with persistent symptoms after anticoagulation must be systematically evaluated. This series included three patients who underwent endovascular therapies involving stent placement and catheter-directed thrombolysis. Several case reports and single patient series suggest that carotid stenting may be safe in the setting of SCD.¹⁹, ²⁰, ²¹ The patient in this series who underwent carotid stent placement suffered from recurrent symptomatic bilateral carotid dissection while on anticoagulation. (Fig. 2A, B) Prior to stent placement, an early left-sided infarct was noted on brain MRI and it was this infarcted area that underwent subsequent hemorrhagic transformation. (Fig. 2C) No adverse effects were noted after stent placement on the right side, therefore making it difficult to determine whether the anticoagulation associated with stent placement or reperfusion injury to an acutely ischemic area was responsible for the undesired outcome. Consideration must be given, however, to the differing nature of the underlying pathology present in the setting of atherosclerotic disease compared to acute dissections. Thus, results obtained from the study of carotid stent placement for occlusive disease must be interpreted with caution in the setting of arterial dissections. The only death in our group represented a patient who underwent primary thrombolysis after an acute stroke resulting from left ICA dissection with thrombosis of the left MCA M1 distribution. After successful thrombolysis, this patient experienced severe ICH, increased intracranial pressure, and subsequent herniation. Derex et al.²² in 2000 reported a series of 11 patients who underwent systemic tPA administration for the treatment of acute ischemic stroke resulting from ICA dissection. They reported only one occurrence of stable ICH and no deaths; however, they emphasized that this therapy must be instituted within a 7-hour window from onset of ischemia. The patient in this series underwent lysis greater than 10 hours from presentation, which potentially contributed to the adverse outcome. In light of these results, a well-designed prospective study is still needed to more accurately determine the role of these interventions in the setting of SCD and SVD.

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• Fig. 2 

  This 50-year-old female experienced spontaneous, bilateral carotid artery dissections with persistent symptoms after anticoagulation. A She underwent placement of two uncoated, self-expanding Wallstents (6 mm × 21 mm, 8 mm × 21 mm) in the left carotid system and, B one uncoated nitinol stent (6 mm × 56 mm) in the right carotid system. C After stent placement and anticoagulation, she experienced hemorrhagic transformation of a left-sided cerebral infarct seen prior to stent placement.

Patients with SCD in this series had a strong correlation between radiographic evidence of infarct on discharge and clinically evident neurologic deficits. Although all five SCD patients (100%) who had evidence of infarct on discharge also had persistent neurologic deficits, only one of seven (17%) SVD patients had a similar correlation. This suggests that in the setting of SVD, evidence of infarction on computed tomography or MRI may not accurately reflect or predict the patient's level of function after the episode. Although the SCD group had a significantly higher rate of persistent deficits on discharge, this is likely related to the involved distribution of SCD vs. SVD and that small areas of hemispheric ischemia may result in a higher incidence of focal deficits than those occurring in the vertebrobasilar system.

In summary, spontaneous dissection of the carotid and vertebral arteries is an uncommon but important clinical entity. Although improvements in the early recognition of this process should improve outcomes, several aspects of the diagnostic and treatment options require further study. With the difficulty in establishing prospective studies in the settings of rare disease entities, this series serves as a single center experience aimed at furthering the understanding of SCD and SVD in terms of modern medical technology.

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