The New England Journal of Medicine
e-mail icon  FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |    Advanced Search
Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe
 
Original Article
PreviousPrevious
Volume 330:393-397 February 10, 1994 Number 6
NextNext

Recurrent Spontaneous Cervical-Artery Dissection
Wouter I. Schievink, Bahram Mokri, and W. Michael O'Fallon

 

This Article
-Abstract

Tools and Services
-Add to Personal Archive
-Add to Citation Manager
-Notify a Friend
-E-mail When Cited

More Information
-PubMed Citation
ABSTRACT

Background Spontaneous dissection of the internal carotid and vertebral arteries is increasingly recognized as a cause of ischemic stroke in young people. An underlying arteriopathy is often suspected in the pathogenesis of such dissection, but the frequency of recurrent dissection is unknown.

Methods We describe the long-term follow-up of 200 consecutive patients (104 women and 96 men) with spontaneous cervical-artery dissections evaluated at the Mayo Clinic between 1970 and 1990. All diagnoses were confirmed by angiography.

Results The mean age of the patients was 44.9 years (range, 16 to 76). Internal carotid arteries were affected in 150 patients, vertebral arteries in 37, and both in 13. Multivessel dissections were present in 28 percent of the patients. The mean follow-up was 7.4 years. Recurrent dissection occurred only in arteries not previously involved by dissection. A recurrent arterial dissection developed in 16 patients (8 percent) -- within a month after the initial dissection in 4 patients (2 percent) and between 1.4 and 8.6 years later in 12 patients (a rate of 1 percent per year). The cumulative rate of recurrent dissection among patients followed for 10 years was 11.9 percent. Younger patients had a greater risk of recurrent dissection.

Conclusions Although dissections in multiple cervical vessels are common at presentation, after the first month the risk of recurrent dissection is only about 1 percent per year.

In dissections of the extracranial internal carotid or vertebral arteries, blood penetrates through an intimal tear, splits off the media, and extends along the artery, usually distally1. Spontaneous cervical-artery dissection typically occurs in young and middle-aged persons, with a slight preponderance among women. The cause and pathogenesis of such dissection are not clear in most cases. Extrinsic factors, such as trauma or even hypertension, and intrinsic factors, such as a primary disease of the arterial wall, or a combination of both may lead to the development of dissection1,2,3. The role of trivial trauma is disputable because there is a clear difference in course and outcome between dissection caused by definite severe trauma and dissection occurring spontaneously or caused by minor trauma3,4. Angiographic evidence of fibromuscular dysplasia has been noted in 10 to 15 percent of patients1,2,3,5. Marfan syndrome,6,7,8 type IV Ehlers-Danlos syndrome,9,10 and cystic medial necrosis11,12 have been reported in several patients. The occurrence of multivessel dissections,13,14 the increased incidence of intracranial aneurysms among patients with spontaneous cervical-artery dissection,15 the familial association of intracranial aneurysms and cervical-artery dissection,16 and the familial occurrence of cervical-artery dissection17 all suggest the presence of arterial disease that predisposes cervical arteries to dissection. However, an underlying arteriopathy can be demonstrated in only a minority of patients.

Although it is not a common disorder, spontaneous cervical-artery dissection has been diagnosed in approximately 10 to 20 percent of young adults with ischemic stroke,18,19 often in association with unilateral headache or neck pain. Besides the manifestations of cerebral ischemia and pain, internal carotid-artery dissection may cause oculosympathetic palsy, cranial-nerve dysfunction, and pulsatile tinnitus,1,2,3,5,20,21 whereas vertebral-artery dissection may extend intracranially and cause subarachnoid hemorrhage1,3,22.

Several studies have addressed the clinical manifestations of cervical-artery dissection, their features on angiography and other methods of imaging, management options, and prognosis1,2,3,5,19,22,23,24,25. We undertook a study to determine the risk of recurrent arterial dissection.

Methods

Patients

Using a computer-based indexing system, we identified 200 consecutive patients evaluated for spontaneous cervical-artery dissection at the Mayo Clinic between 1970 and 1990. All were evaluated by at least one staff neurologist, and most were also evaluated by a staff neurosurgeon; medical and radiographic records were available for all these patients. The diagnosis of dissection was confirmed by angiography in all cases. Forty-one additional patients with cervical-artery dissection related to obvious trauma (including one patient with Marfan syndrome)8 were not included in this study.

All patients were first contacted by letter, and subsequently they or their relatives were contacted by telephone. Follow-up clinical information was gathered by examination of the patients at our institution or by telephone or correspondence with them (in some cases, relatives were contacted), or from communications with personal physicians, hospital records, autopsy records, or death certificates. When applicable, angiograms obtained during follow-up were reviewed. Some form of follow-up information was gathered for all patients.

A recurrent dissection was defined on the basis of angiographic evidence of dissection in a previously visualized but unaffected artery or angiographic evidence of multiple arterial dissections with a clear clinical correlation for each separate dissection; patients were excluded if they were believed to have had dissections in two or more arteries within 24 hours of each other. Hypertension was indicated by a history of treatment of elevated blood pressure or by a blood pressure of more than 160/95 mm Hg on at least two occasions. A diagnosis of fibromuscular dysplasia was based on angiographic criteria.

Statistical Analysis

The relation between recurrent arterial dissection and several risk factors was assessed with proportional-hazards models26. Variables were tested in univariate and multivariate models. Kaplan-Meier survival estimation27 was used to describe and examine the period from the first dissection to either recurrent dissection or last contact. Associations between recurrence-free survival and the patients' characteristics were evaluated with the log-rank test28. The threshold of significance was set at 0.05. All calculated P values were two-tailed.

Results

Characteristics of Patients

The demographic and clinical characteristics of the study population at presentation are shown in Table 1, as are some of the presumed risk factors. One patient had type IV Ehlers-Danlos syndrome, one had dermatomyositis, and one had retinal angioid streaks but not the dermatologic manifestations of pseudoxanthoma elasticum. Of the 200 patients, 104 were women (52 percent) and 96 were men (48 percent). At the time of the initial dissection, their mean age was 44.9 years (range, 16 to 76); their distribution according to age and sex is shown in Figure 1. The internal carotid artery was involved in 150 patients, the vertebral artery in 37 patients, and both arteries in the remaining 13 patients. The male:female ratio was approximately equal among the patients with dissection of the internal carotid artery or vertebral artery, but most of the patients with dissections of both arteries were women (11 of 13 [85 percent], P=0.05). A total of 269 cervical arteries were affected (198 internal carotid and 71 vertebral) (Table 2). In addition, renal arteries were affected by dissections in two patients, the subclavian artery in one patient, and multiple visceral arteries in one patient. Intradural extension of the dissection occurred in two patients with affected internal carotid arteries and six patients with affected vertebral arteries.

View this table:
[in this window]
[in a new window]
  		Table 1. Clinical Characteristics of 200 Patients with Spontaneous Cervical-Artery Dissection.

 

View larger version (11K):
[in this window]
[in a new window]
  		Figure 1. Distribution of 200 Patients with Spontaneous Cervical-Artery Dissection, According to Age and Sex.

 
View this table:
[in this window]
[in a new window]
  		Table 2. Distribution of Arterial Involvement in 200 Patients with Spontaneous Cervical-Artery Dissection.

 
Clinical Manifestations

Of 163 patients with dissection of the internal carotid artery (including 13 with associated vertebral-artery dissection), 117 (72 percent) had headaches, 103 (63 percent) had symptoms of cerebral ischemia, and 60 (37 percent) had oculosympathetic palsy. The dissection was asymptomatic in eight patients (5 percent) and was detected during the evaluation of clinically evident vertebral-artery dissections. Of 50 patients with vertebral-artery dissection (including 13 with associated dissection of the internal carotid artery), 35 (70 percent) had headaches and 32 (64 percent) had symptoms of cerebral ischemia. Asymptomatic vertebral-artery dissection was detected in 10 patients (20 percent) during the evaluation of symptomatic dissection of the internal carotid artery.

Follow-up

The mean duration of follow-up was 7.4 years; the total follow-up time was 1472 patient-years. When the one patient who died of cervical-artery dissection (see below) was excluded from the analysis of follow-up, the duration of follow-up ranged from 1 to 21.3 years. One hundred ninety-nine patients (99.5 percent) were thus followed for at least 1 year, 136 (68 percent) for at least 5 years, and 48 (24 percent) for at least 10 years. The average length of follow-up was similar irrespective of sex, age group (<45 vs. >= 45 years), and site of dissection (internal carotid artery vs. vertebral artery).

To date, six patients have died two days to seven years after the initial dissection. One of these deaths was directly related to the dissection; a 35-year-old man died of a massive ischemic stroke two days after dissection of the internal carotid artery. Another death was related to an undetermined underlying arteriopathy; a 37-year-old man with multiple visceral-artery dissections and aneurysms died of a ruptured brachiocephalic-artery aneurysm four years after bilateral dissections of the internal carotid artery. The remaining four patients died of unrelated causes three to seven years after the initial dissection; these deaths were due to myocardial infarction, renal failure, colon cancer, and respiratory failure related to emphysema. On an actuarial basis, the 10-year survival rate for the study population was 95.5 percent, with an expected survival rate of 91.9 percent in an age- and sex-matched white population derived from U.S. 1980 census life tables (P>0.05).

Recurrent Dissection

The clinical characteristics of the 16 patients (8 percent) with recurrent dissection are shown in Table 3. The dissection recurred 2 days to 8.6 years after the initial event. The mean age of the 12 women and 4 men was 39.3 years at the time of the initial dissection and 42.9 years at the time of the recurrent dissection. The dissection recurred within 1 month after initial dissection in 4 patients and after 1.4 to 8.6 years in the other 12 patients (mean time to recurrence, 4.8 years). The rate of recurrent dissection was 2 percent per month during the first month and then decreased to 1 percent per year between one and nine years after the initial dissection. The cumulative rate of recurrent dissection was 2.0 percent after 1 month, 3.7 percent over the first 2 years, 5.0 percent over 5 years, and 11.9 percent over 10 years (Figure 2). When the patients who had a recurrent dissection within a month after the initial dissection were excluded from analysis, the cumulative risks were 1.7 percent, 3.8 percent, and 10.1 percent at 2, 5, and 10 years, respectively.

View this table:
[in this window]
[in a new window]
  		Table 3. Clinical Characteristics of 16 Patients with Recurrent Arterial Dissection.

 

View larger version (13K):
[in this window]
[in a new window]
  		Figure 2. Cumulative Rate of Recurrent Arterial Dissection in All Patients (Upper Panel) and According to Age (Lower Panel).

The numbers below each panel are the numbers of patients at risk for recurrent dissection at each point.

 
The recurrent dissection affected the internal carotid arteries in nine patients (bilateral involvement in one patient), vertebral arteries in four, renal arteries in two, and the common carotid artery in one. The initial dissection had involved the internal carotid arteries in nine patients, the vertebral arteries in five, and both internal carotid and vertebral arteries in two. Recurrence was symptomatic in all patients except one, in whom it was detected during angiography for follow-up of a dissecting aneurysm. Recurrent dissection in four patients was diagnosed and treated elsewhere; we reviewed these patients' angiograms.

Multivariate analysis revealed that age was the only significant variable associated with recurrent dissection. Increasing age was found to be inversely related to the risk of recurrence (P = 0.03). Actuarial analysis showed that the cumulative rate of recurrent dissection during the 10 years after the initial event was 16.8 percent among patients who were younger than the mean age (45 years) and 6.1 percent among patients who were of the mean age or older (Figure 2). In the multivariate model, there was no relation between recurrent arterial dissection and any of the following variables: sex, site of dissection, multivessel dissection, hypertension, cigarette smoking, use of oral contraceptives, or fibromuscular dysplasia.

Discussion

Before the widespread use of angiography, cervical-artery dissection was rarely diagnosed before postmortem examination. When it was diagnosed earlier, the prognosis was considered to be grave12,29,30. More recent studies reveal that spontaneous cervical-artery dissection is associated with a high rate of recovery1,2,3,31. Although the low mortality rate in our cohort may have been partly related to referral bias, the generally favorable prognosis was also noted in a recent community-based study32. We did not detect any change in the clinical characteristics of dissection or the referral pattern during the two decades of the study. The diagnosis was confirmed by angiography in all patients. In only the past few years have we relied on magnetic resonance imaging and magnetic resonance angiography to confirm the diagnosis. It will be some years before we know whether the use of these procedures changes the pattern of diagnosis or referral among patients with this disease.

Recurrent arterial dissection has only rarely been reported,6,13,22,23,33 and the risk of recurrence, a major concern to patient and physician, has been unclear. Our study demonstrates that recurrent arterial dissection, although uncommon, is not rare. The distribution of recurrences seemed to be bimodal; some dissections recurred within the first month (early recurrence, with a rate of 2 percent per month), but most did not recur until a year or more after the initial dissection (late recurrence, with a rate of 1 percent per year). Some recurrences developed as late as the ninth year after the initial dissection. The discrepancy between the relatively low frequency of recurrent arterial dissection and the common occurrence of multivessel dissection at first presentation may be due in part to the fact that some dissections are asymptomatic or cause trivial or nonspecific transient symptoms that do not lead to the diagnosis. More important, however, is the fact that spontaneous cervical-artery dissections may occur virtually simultaneously, as evidenced by the large number of patients with multivessel dissections at first presentation. On angiography, many of these dissections appear to be in a similar stage of evolution and therefore of a similar age. The frequent simultaneous dissections and the fairly high rate of recurrent dissection within the first four to six weeks may be related to a transient arteriopathy. In contrast, dissection that recurs later (at least one year after the initial dissection) and at a much lower rate may be more commonly related to underlying conditions, such as fibromuscular dysplasia, cystic medial degeneration, or other disorders affecting the extracellular matrix.

Younger patients were more likely to have a recurrent dissection than older patients. Aside from age, we were unable to identify any factors associated with an increased risk of a recurrent dissection, but the relatively small number of events precludes definite conclusions.

All recurrences were symptomatic except in one patient. If other asymptomatic dissections occurred in patients who did not undergo follow-up angiography or if they occurred after follow-up angiography, they have been missed. However, dissection without any symptoms is very uncommon, and even mild symptoms are rarely ignored by patients with previous dissection. Overall, it is difficult to address the incidence of asymptomatic dissection because the lesions are angiographically dynamic, in that after the initial period of evolution, they begin to resolve, and most resolve completely31. This issue requires a reliable, noninvasive, and inexpensive method of detection that can be carried out repeatedly over many years.

There were no recurrences of dissection within the same vessel. In one patient, we observed a thrombus extending from a persistent subcranial aneurysmal dilatation caused by the dissection, mimicking a local recurrence. If dissection does recur within the same artery, as reported by others,23 it must be rare. Once a dissection has resolved, the intramural healing and changes in connective tissue may tend to prevent local recurrence.


Source Information

From the Departments of Neurologic Surgery (W.I.S.), Neurology (B.M.), and Health Sciences Research (W.M.O.), Mayo Clinic and Mayo Foundation, Rochester, Minn.

Address reprint requests to Dr. Mokri at the Mayo Clinic, 200 First St. SW, Rochester, MN 55905.

References

  1. Mokri B. Dissections of cervical and cephalic arteries. In: Sundt TM Jr, ed. Occlusive cerebrovascular disease: diagnosis and surgical management. Philadelphia: W.B. Saunders, 1987:38-59. 
  2. Fisher CM, Ojemann RG, Roberson GH. Spontaneous dissection of cervico-cerebral arteries. Can J Neurol Sci 1978;5:9-19. [Medline]
  3. Hart RG, Easton JD. Dissections of cervical and cerebral arteries. Neurol Clin 1983;1:155-182. [Medline]
  4. Mokri B. Traumatic and spontaneous extracranial internal carotid artery dissections. J Neurol 1990;237:356-361. [CrossRef][Medline]
  5. Mokri B, Sundt TM Jr, Houser OW, Piepgras DG. Spontaneous dissection of the cervical internal carotid artery. Ann Neurol 1986;19:126-138. [CrossRef][Medline]
  6. Youl BD, Coutellier A, Dubois B, Leger JM, Bousser MG. Three cases of spontaneous extracranial vertebral artery dissection. Stroke 1990;21:618-625. [Free Full Text]
  7. Austin MG, Schaefer RF. Marfan's syndrome, with unusual blood vessel manifestations: primary medionecrosis dissection of right innominate, right carotid, and left carotid arteries. Arch Pathol 1957;64:205-209. 
  8. Mokri B, Okazaki H. Cystic medial necrosis and internal carotid artery dissection in a Marfan sibling: partial expression of Marfan syndrome. J Stroke Cerebrovasc Dis 1992;2:100-5.
  9. Schievink WI, Limburg M, Oorthuys JWE, Fleury P, Pope FM. Cerebrovascular disease in Ehlers-Danlos syndrome type IV. Stroke 1990;21:626-632. [Free Full Text]
  10. Schievink WI, Piepgras DG, Earnest F IV, Gordon H. Spontaneous carotid-cavernous fistulae in Ehlers-Danlos syndrome Type IV: case report. J Neurosurg 1991;74:991-998. [Medline]
  11. Bostrom K, Liliequist B. Primary dissecting aneurysm of the extracranial part of the internal carotid and vertebral arteries: a report of three cases. Neurology 1967;17:179-186. [Free Full Text]
  12. Brice JG, Crompton MR. Spontaneous dissecting aneurysms of the cervical internal carotid artery. BMJ 1964;2:790-792.
  13. Mokri B, Stanson AW, Houser OW. Spontaneous dissections of the renal arteries in a patient with previous spontaneous dissections of the internal carotid arteries. Stroke 1985;16:959-963. [Free Full Text]
  14. Mokri B, Houser OW, Stanson AW. Multivessel cervicocephalic and visceral arterial dissections: pathogenic role of primary arterial disease in cervicocephalic arterial dissections. J Stroke Cerebrovasc Dis 1991;1:117-23.
  15. Schievink WI, Mokri B, Piepgras DG. Angiographic frequency of saccular intracranial aneurysms in patients with spontaneous cervical artery dissection. J Neurosurg 1992;76:62-66. [Medline]
  16. Schievink WI, Mokri B, Michels VV, Piepgras DG. Familial association of intracranial aneurysms and cervical artery dissections. Stroke 1991;22:1426-1430. [Free Full Text]
  17. Mokri B, Piepgras DG, Wiebers DO, Houser OW. Familial occurrence of spontaneous dissection of the internal carotid artery. Stroke 1987;18:246-251. [Free Full Text]
  18. Cronqvist SE, Norrving B, Nilsson B. Young stroke patients: an angiographic study. Acta Radiol Suppl (Stockh) 1986;369:34-7.
  19. Bogousslavsky J, Regli F. Ischemic stroke in adults younger than 30 years of age: cause and prognosis. Arch Neurol 1987;44:479-482. [Erratum, Arch Neurol 1987;44:817.] [Free Full Text]
  20. Mokri B, Schievink WI, Olsen KD, Piepgras DG. Spontaneous dissection of the cervical internal carotid artery: presentation with lower cranial nerve palsies. Arch Otolaryngol Head Neck Surg 1992;118:431-435.
  21. Schievink WI, Mokri B, Garrity JA, Nichols DA, Piepgras DG. Ocular motor nerve palsies in spontaneous dissections of the cervical internal carotid artery. Neurology 1993;43:1938-1941. [Free Full Text]
  22. Mokri B, Houser OW, Sandok BA, Piepgras DG. Spontaneous dissections of the vertebral arteries. Neurology 1988;38:880-885. [Free Full Text]
  23. Bogousslavsky J, Despland P-A, Regli F. Spontaneous carotid dissection with acute stroke. Arch Neurol 1987;44:137-140. [Free Full Text]
  24. Mas J-L, Bousser M-G, Hasboun D, Laplane D. Extracranial vertebral artery dissections: a review of 13 cases. Stroke 1987;18:1037-1047. [Free Full Text]
  25. d'Anglejan Chatillon J, Ribeiro V, Mas JL, Bousser MG, Laplane D. Dissection de l'artere carotide interne extracranienne: soixante-deux observations. Presse Med 1990;19:661-667.
  26. Cox DR. Regression models and life-tables. J R Stat Soc [B] 1972;34:187-220.
  27. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-81.
  28. Mantel N. Ranking procedures for arbitrarily restricted observation. Biometrics 1967;23:65-78. [CrossRef][Medline]
  29. Anderson RMD, Schechter MM. A case of spontaneous dissecting aneurysm of the internal carotid artery. J Neurol Neurosurg Psychiatry 1959;22:195-201.
  30. Brown OL, Armitage JL. Spontaneous dissecting aneurysms of the cervical internal carotid artery: two case reports and a survey of the literature. Am J Roentgenol Radium Ther Nucl Med 1973;118:648-653. [Medline]
  31. Houser OW, Mokri B, Sundt TM Jr, Baker HL Jr, Reese DF. Spontaneous cervical cephalic arterial dissection and its residuum: angiographic spectrum. AJNR Am J Neuroradiol 1984;5:27-34. [Abstract]
  32. Schievink WI, Mokri B, Whisnant JP. Internal carotid artery dissection in a community: Rochester, Minnesota, 1987-1992. Stroke 1993;24:1678-1680. [Free Full Text]
  33. Rohr J, Gauthier G. Hematomes dissequants spontanes successifs a 3 ans et demi d'intervalle des deux arteres carotides internes. Rev Neurol (Paris) 1987;143:115-120. [Medline]

 

This Article
-Abstract

Tools and Services
-Add to Personal Archive
-Add to Citation Manager
-Notify a Friend
-E-mail When Cited

More Information
-PubMed Citation

This article has been cited by other articles:


HOME  |  SUBSCRIBE  |  SEARCH  |  CURRENT ISSUE  |  PAST ISSUES  |  COLLECTIONS  |  PRIVACY  |  TERMS OF USE  |  HELP  |  beta.nejm.org

Comments and questions? Please contact us.

The New England Journal of Medicine is owned, published, and copyrighted © 2009 Massachusetts Medical Society. All rights reserved.