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(Stroke. 1996;27:622-624.)
© 1996 American Heart Association, Inc.

Articles

Recurrent Spontaneous Arterial Dissections

Risk in Familial Versus Nonfamilial Disease

Wouter I. Schievink, MD; Bahram Mokri, MD; David G. Piepgras, MD James D. Kuiper, BS

From the Departments of Neurologic Surgery (W.I.S., D.G.P.), Neurology (B.M.), and Health Sciences Research (J.D.K.), Mayo Clinic, Rochester, Minn.

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Background and Purpose Among patients with spontaneous cervical artery dissections, the risk of recurrent arterial dissection is relatively low at 1% per year, but this risk may be higher for patients with a family history of arterial dissections. We compared the risk of a recurrent arterial dissection in patients with familial versus nonfamilial disease.

Methods Long-term follow-up was established in 200 patients (104 women and 96 men with a mean age of 44.9 years) with spontaneous cervical artery dissections evaluated at a single institution between 1970 and 1990.

Results Among the 200 patients, 10 (5%) were identified who had a family history of spontaneous arterial dissections. In a multivariate analysis, family history was the only significant variable associated with the risk of recurrent dissection (²=15.51; P=.0001). A recurrent arterial dissection was identified in 5 (50%) of the 10 patients with familial disease compared with 11 (5.8%) of the 190 patients with nonfamilial disease, with an estimated relative risk of 6.3 (95% confidence interval, 2.2 to 18.3; P=.0007).

Conclusions Among patients with spontaneous cervical artery dissections, a family history of arterial dissection is an important risk factor for the development of a recurrent arterial dissection.

Key Words: aneurysm • cerebrovascular disorders • dissection • genetics

	Introduction

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In a long-term follow-up study of 200 patients with spontaneous cervical (internal carotid or vertebral) artery dissections, we identified 16 with a recurrent arterial dissection.¹ Excluding patients with an early recurrence (ie, within 1 month of the initial dissection), the risk of a recurrent arterial dissection was relatively low, at 1% per year.¹ Among this cohort of 200 patients we have now identified 10 patients (belonging to eight families) with a family history of arterial dissections. A disproportionately high number of these patients with familial disease suffered a recurrent arterial dissection. The present study was undertaken to compare the risk of a recurrent arterial dissection in patients with spontaneous cervical artery dissections and familial disease versus those without known familial disease.

	Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
The study population consisted of 200 patients with spontaneous dissections of the extracranial internal carotid or vertebral arteries evaluated at the Mayo Clinic between 1970 and 1990. The mean age of these 104 women and 96 men was 44.9 years (range, 16 to 76 years). Angiographic changes of fibromuscular dysplasia were found in 25 patients (12.5%). The characteristics of this cohort of patients have been described in detail previously.¹

A detailed family history of vascular disease was completed for 189 patients (94.5%). A diagnosis of arterial dissection in a family member was verified by review of imaging studies, hospital and autopsy records, or death certificates.

The relations between recurrent arterial dissection and several variables were assessed with proportional hazard models. The variables included sex, age, location of affected arteries, involvement of multiple arteries, family history of arterial dissection, hypertension, tobacco use, and oral contraceptive use. Variables were tested in univariate and multivariate models. The cumulative incidence of recurrent arterial dissection was analyzed with Kaplan-Meier survival estimation. Values of P<.05 were considered significant.

	Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Of the 200 patients with spontaneous cervical artery dissections, 10 (5%) had one or more family members with spontaneous dissections involving the aorta, renal arteries, or cervicocephalic arteries (Fig 1). Two of the probands were related to the other probands, for a total of eight families. Characteristics of these families are summarized in the Table. Seven of these families have been reported previously,^{2 3 4} at least in part.

View larger version (86K): [in this window] [in a new window]   Figure 1. Carotid angiograms (CA; lateral views) demonstrating recurrent cervical artery dissections. A, Right CA shows a dissection manifested by an elongated stenosis tapering to a virtual occlusion (arrow) in an 18-year-old girl (patient 2). B, Right CA obtained 5 years and 4 months later shows complete resolution of the dissection (arrow). C, Left CA obtained at that time shows a dissection manifested by an area of stenosis and aneurysmal dilatation (arrowhead). D, Left CA obtained 6 months later shows resolution of the stenosis, although some aneurysmal dilatation has persisted (arrowhead).

View this table: [in this window] [in a new window]   Table 1. Clinical Characteristics of 10 Patients With Spontaneous Cervical Artery Dissections and Positive Family History of Arterial Dissections

There were no significant differences between the 10 patients with familial disease compared with the 190 patients without known familial disease in the following variables: sex and age distribution, location of affected arteries, involvement of multiple arteries, mortality rate, or the presence of possible risk factors such as hypertension, tobacco use, and oral contraceptive use. There was a trend toward a lower mean±SD age for patients with familial disease, but the difference (39.8±17.6 versus 45.2±10.0 years) did not quite reach statistical significance (P=.055).

In the multivariate analysis, family history was the only statistically significant variable associated with the risk of recurrent dissection (²=15.51; P=.0001).

A recurrent arterial dissection was identified in 5 (50%) of the 10 patients with familial disease compared with 11 (5.8%) of the 190 without known familial disease, with an estimated relative risk of 6.3 (95% confidence interval, 2.2 to 18.3; P=.0007) (Fig 1). Recurrent dissection occurred only in arteries not previously involved by dissection, and none of the recurrent arterial dissections in the familial cases occurred within 1 month of the initial dissection. The cumulative rate of recurrent dissection for patients with familial disease was 0% after 1 month, 0% over the first 2.5 years, 0% over 5 years, 32.5% over 7.5 years, and 55.0% over 10 years. For patients with no known familial disease, the corresponding values were 2.1%, 4.5%, 5.3%, 7.0%, and 7.0% (Fig 2).

View larger version (16K): [in this window] [in a new window]   Figure 2. Cumulative rate of recurrent arterial dissection according to the presence or absence of a family history of arterial dissection. The numbers below the graph are those of patients at risk for recurrent dissection at each point.

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
This study shows that among patients with spontaneous cervical artery dissections a positive family history of spontaneous arterial dissections is an important risk factor for the development of a recurrent arterial dissection. Patients with familial arterial dissections were about six times more likely to develop a recurrent dissection than those with no known familial disease. The dissections in affected family members involved the aorta, renal arteries, or cervicocephalic arteries, and it is likely that a positive family history reflects the presence of a primary generalized arteriopathy predisposing the arteries to spontaneous dissection. The exact nature of this arteriopathy, however, could not be determined in any of the presently described families, although a neural crest disorder was suspected in five families on the basis of associated abnormalities of the heart or skin,^{3 4} and abnormalities of elastin have been detected in one family.^{2 5}

None of the patients in our study with familial disease suffered an early recurrent arterial dissection. Among previously reported families with spontaneous arterial dissections that have included at least one family member with involvement of the cervical arteries, recurrent arterial dissections have not been identified, but the follow-up in these families has generally been short-term.^{6 7 8 9 10}

An alternative explanation for the high risk of a recurrent arterial dissection in patients with familial disease that was observed in our study might be that the family history was more thoroughly evaluated in patients with recurrent dissections because a heritable systemic disorder was suspected. However, in some patients the presence of a contributory family history was established before the recurrent dissection; moreover, the family history was specifically evaluated at the time of follow-up in almost 95% of the entire cohort of patients by at least one of the authors.

Because of the implications for patient prognosis, this study underscores the importance of obtaining a thorough family history in patients with spontaneous cervical artery dissections. The family history should focus not only on strokes and dissections of the cervicocephalic arteries but also on the presence of dissections involving other arteries.

In conclusion, a family history of arterial dissection is an important risk factor for the development of a recurrent arterial dissection.

	Footnotes

 
Reprint requests to Dr Wouter I. Schievink, Department of Neurologic Surgery, Mayo Clinic, 200 First St SW, Rochester, MN 55905.

Received November 17, 1995; accepted January 4, 1996.

	References

Top Abstract Introduction Subjects and Methods Results Discussion References

 
1. Schievink WI, Mokri B, O'Fallon WM. Spontaneous recurrent cervical-artery dissection. N Engl J Med. 1994;330:393-397. [Abstract/Free Full Text]

2. Mokri B, Piepgras DG, Wiebers DO, Houser OW. Familial occurrence of spontaneous dissection of the internal carotid artery. Stroke. 1987;18:246-251. [Abstract/Free Full Text]

3. Schievink WI, Michels VV, Mokri B, Piepgras DG, Perry HO. A familial syndrome of arterial dissections with lentiginosis. N Engl J Med. 1995;332:576-579. [Free Full Text]

4. Schievink WI, Mokri B. Familial aorto-cervicocephalic arterial dissections and congenitally bicuspid aortic valve. Stroke. 1995;26:1935-1940. [Abstract/Free Full Text]

5. Mokri B, Roche PC, O'Brien JF, Schievink WI, Piepgras DG. Abnormalities of elastin in spontaneous internal carotid and vertebral artery dissections. Ann Neurol. 1994;36:263. Abstract.

6. Petit H, Bouchez B, Destee A, Clarisse J. Familial form of fibromuscular dysplasia of the internal carotid artery. J Neuroradiol. 1983;10:15-22. [Medline] [Order article via Infotrieve]

7. Varani E, Magnani G, Magelli C, Ferretti RM, Agosta R, Craincevich T, Magnani B. Aneurisma dissecante dell'aorta: descrizione di casi familiari. Medicina. 1988;8:293-297.

8. Somlo S, Rutecki G, Giuffra LA, Reeders ST, Cugino A, Whittier FC. A kindred exhibiting cosegregation of an overlap connective tissue disorder and the chromosome 16 linked form of autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 1993;4:1371-1378. [Abstract]

9. Majamaa K, Portimojarvi H, Sotaniemi KA, Myllylä VV. Familial aggregation of cervical artery dissection and cerebral aneurysm. Stroke. 1994;25:1704-1705. [Medline] [Order article via Infotrieve]

10. Neau J-P, Masson C, Vandermarq P, Dumas P, Levillain P, Tantot A-M, Masson M, Gil R. Familial occurrence of dissection of the cervical arteries. Cerebrovasc Dis. 1995;5:310-312.

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