Levels of α ₁ -Antitrypsin in Plasma and Risk of Spontaneous Cervical Artery Dissections

Abstract

Background and Purpose-Abnormalities of dermal connective tissue have been detected in patients with spontaneous cervical artery dissections (sCAD), suggesting an underlying structural defect of the arterial wall. ␣ 1 -Antitrypsin (A1-AT) is a circulating serine proteinase inhibitor of proteolytic enzymes that helps to maintain the integrity of elastic and collagen fibers. Methods-To test the hypothesis that moderate deficiency of A1-AT may be a risk factor for sCAD, 22 cases with sCAD and 113 controls were included in the study. Key Words: alpha 1-antitrypsin Ⅲ aneurysm, dissecting Ⅲ risk factors G enetic and environmental factors have been proposed in the pathogenesis of spontaneous cervical artery dissections (sCAD). 1 Abnormalities of dermal connective tissue have been detected in most patients with sCAD, suggesting an underlying structural defect of the arterial wall. 2 In such patients, damaged collagen and elastic fibers might predispose to arterial wall rupture in points of weakness after mechanical stress. 1,2 The presence and intensity of vascular risk factors (smoking, homocysteine, hypertension, oral contraceptives, infections, etc) might explain the sCAD cluster at about the middle of life despite the congenital structural defect of the vessel. Genetically determined alterations of the extracellular matrix may be an important field to investigate the genesis of sCAD. 2,3 ␣ 1 -Antitrypsin (A1-AT) is a circulating serine proteinase inhibitor of proteolytic enzymes that contributes to the maintenance of the integrity of connective tissues. Deficiency of A1-AT may result in degradation of the arterial wall through inadequate protection against the proteolytic effect of elastase and collagenase. 4,5 A1-AT deficiency is a genetic and systemic disorder characterized not only by lung and liver disease but also by vascular manifestations, including sCAD, fibromuscular dysplasia, or aneurysms. 4,5 However, A1-AT deficiency ranges from severe forms with very low circulating levels (10% of normal) in homozygous patients to other forms with moderately low concentrations (60% to 70% of normal) in heterozygous patients. 4,5 To evaluate whether moderate deficiency of A1-AT may be a risk factor for sCAD, we performed a prospective case-control study comparing plasma levels of A1-AT in consecutive patients with sCAD and controls. Results-Patients MethodsWe examined 22 consecutive patients with stroke and sCAD confirmed by conventional angiography or MR angiography and cervical MRI. Controls (nϭ113) were stroke patients without sCAD admitted during the same period of time who had complete neurovascular studies (carotid ultrasounds, MR angiography, or conventional arteriography).We recorded demographic data and presence of vascular risk factors. A blood sample was taken at least 2 weeks after stroke onset in cases and controls to avoid the effect of the acute-phase response on plasma protein levels. A1-AT determinations were performed at the hospital laboratory following a standard immune nephelometric technique. Estab...

The Genetics of Cervical Artery Dissection

“…It has been associated with major head and neck trauma 4 as well as with minor trauma secondary to a wide range of insults. 5 Other risk factors proposed include recent infection, 6 hyperhomocysteinemia, 7-9 migraine, 10 low levels of ␣1-antitrypsin, 11 and hypertension [12][13][14] and fibromuscular dysplasia, 15 but most evidence is limited. 16 Several arguments suggest genetic factors may play an important role in the pathophysiology of CAD, in rare cases as part of a single gene disorder and more commonly as part of a multifactorial predisposition (Figure 1).…”

Spontaneous Multiple Arterial Dissections Presenting With Renal Infarction and Subarachnoid Hemorrhage in a Patient Under Treatment for Infertility

“…10,11 Vila et al recently showed that A1-AT plasma concentrations less than 90 mg/dl were associated with spontaneous cervical artery dissections regardless of age, sex, or vascular risk factors. 12 The family history of the present patient does not support this diagnosis, but measurement of her serum concentration of A1-AT and genetic diagnosis may have been helpful. The differential diagnosis includes any abnormalities in the type I collagen molecules, such as the defect of fibrillin in Marfan syndrome, 13 the COL3A1 gene in Ehlers-Danlos syndrome type IV, 14 and lysyl hydroxylase in Ehlers-Danlos syndrome type VI.…”

Bilateral dissecting aneurysms of the internal carotid arteries misdiagnosed as skull base tumors: A case report

“…Previous studies have reported the involvement of various combinations of nerves (6,15), however, at present, there are a limited number of studies that describe ICADs manifesting as space-occupying lesions with skull base erosion (21). The present study suggests that, for patients with single or multiple space-occupying lesions of the skull base and end-group cranial nerve palsy, a differential diagnosis should be established from malignant skull base tumors, schwannoma, soft meningioma, infectious diseases and spontaneous diseases (9).…”