Hereditary cervical and cerebral artery dissection

Arterial dissections result from a split in the vascular wall caused by a hematoma. There are two types of dissection, sub intimal (on the inner surface of the wall) and sub adventitial (on the outer surface of the wall). The hematoma on the wall may be the result of a break in the   lumen of the vessel or a haemorrhage within the wall supplied by microscopic vessels (vasa-vasorum).

The dissections responsible for ICHs occur in a cephalic artery, usually a carotid artery or a vertebral artery in the neck, more rarely an intracranial artery. In most groups of patients, the dissections occur in several arteries in 10 to 20% of cases.

Spontaneous dissections (with no trauma) of the carotid or vertebral arteries are usually sporadic. They are rarely detected in several members of the same family.

Familial types of dissections are rare. They are defined as the occurrence of a spontaneous arterial dissection in at least two members of the same family.

Definition

Arterial dissections result from the splitting of the vascular wall by a hematoma. There are two types of dissections, subintimal (on the inner surface of the wall) and subadventitial (on the outer surface of the wall). The hematoma on the wall may be the result of a break in the lumen of the vessel or a haemorrhage within the wall supplied by microscopic vessels (vasa-vasorum).

The dissections responsible for ICHs occur in a cephalic artery, usually a carotid artery or a vertebral artery in the neck and more rarely in an intracranial artery. In most series of patients, the dissections occur in several arteries in 10 to 20% of cases.

Spontaneous dissections (with no trauma) of the carotid or vertebral arteries are usually sporadic. They are rarely found in several members of the same family.

Familial types of dissections are rare. They are defined as the occurrence of a spontaneous arterial dissection in at least two members of the same family.

Epidemiology

In the general population, the incidence (number of new cases per year) of dissections varies from 1 to 3 cases per 100,000 people per year. Dissections of the carotid arteries are twice as common as dissections of vertebral arteries. Dissections of intracranial arteries are extremely rare.

In a single epidemiological study of familial types, 5% of patients with a dissection of the cervical arteries followed for more than 10 years had a relative with a dissection of another artery (cervical, renal or aortic).

Clinical Description

Dissections of internal carotid arteries are responsible for the following:

• local signs (headache (often one-sided), neck pain, Horner’s sign, rarely tinnitus, paralysis of the cranial nerves IX, X, XI, XII),
• cerebral or retinal ischemic attacks (transitory or permanent)

Dissections of the vertebral arteries are responsible for:

• local signs (headache (usually occipital) and posterior cervical pain)
• cerebral ischemic attacks
• subarachnoid haemorrhages (when the dissection involves the end of a vertebral artery in the skull)

Familial types of dissection have not yet been widely reported in the literature. The observations available suggest:

• that they occur, on average, earlier than the so-called “sporadic” non-familial types (most often at around 30 years on average for familial types and 40 years for sporadic types)
• that they reoccur more frequently (on average, 7% of patients suffer a further dissection 10 years later, with this figure rising to 55% for familial types)
• that they are more often multiple (dissection of several arteries is 2 to 3 times more frequent in non-familial types)

Some familial cases of dissection seem to be connected with a hereditary disease of conjunctive tissue which is usually responsible for other symptoms (Cf. Etiology – Pathophysiology).

Etiology – Pathophysiology

The thickening of the arterial wall by the hematoma often leads to stenosis or narrowing of the vessel lumen, and sometimes to complete occlusion of the artery with subsequent decrease in blood flow.

The reduction in blood flow can lead directly to a reduction in cerebral blood flow throughout the corresponding supplied area (in the hemisphere supplied by the carotid artery, for example). In some cases, this cannot be compensated for by the other vessels supplying that region (circle of Willis). This drop in cerebral blood flow can lead to transient neurological symptoms (transient retinal or cerebral ischemic attacks) or an extensive cerebral infarction.

Because of the abnormalities in blood flow affecting the vessel wall at the site of the stenosis, dissection can be further complicated by a more or less extensive thrombosis within the lumen of the vessel which produces emboli in the area supplied by this artery. These emboli (fragments of blood clots) can also be responsible for temporary or ongoing ischemic attacks in the retina or brain). Anticoagulant or ant-platelet drugs are sometimes prescribed to prevent these problems.

The thickening of the wall can lead to compression of structures in contact with the vessel wall (in particular the sympathetic nerves and certain cranial nerves) that cause local signs such as neck pain, Horner’s sign or the paralysis of certain cranial nerves around the vessel (cranial nerve IX, X, XI, XII).

In a few exceptional cases, when the dissection is subadventitial (external section of the vessel wall) in an intracranial artery, it may lead to a subarachnoid haemorrhage.

The familial types of arterial dissections may be observed as part of a known hereditary disease causing increased fragility of the arterial wall.

It may be vascular Ehlers Danlos Syndrome due to mutations in the COL3A1 gene on chromosome 2 (which encodes for Type III collagen, a large protein that ensures the solidity of the collagen in the walls of blood vessels and various organs). This autosomal dominant disease is rare (prevalence: 1 case in 10,000 to 20,000 people).
It causes fragility of arterial walls leading to aneurysms, dissections, arterio-venous fistulas and, sometimes, the complete rupture of the wall of the vessel producing haemorrhages of varying degrees of severity. Other signs or symptoms may be observed e.g. hyperelasticity of the skin, fragility and transparency of the skin, bruising, acrogeria, intestinal perforation, pneumothorax, rupture of the uterine wall during childbirth and, more rarely, joint subluxation. The clinical signs of the disease appear in 25% of cases before the age of 20 and in 80% of cases before the age of 40. For further information on this disease, contact the benchmark centre for rare vascular diseases at Hôpital Européen Georges Pompidou.

Marfan’s disease is caused by mutations in the Type 1 fibrillin gene on chromosome 15 (a major component of microfibrils within the connective tissue of many organs, muscles, skin and blood vessels). It is an autosomal dominant disease affecting approximately 15,000 people in France (1/5,000). The disease can lead to cardiac complications (dilatation or rupture of the aorta, mitral valve prolapse), skeletal defects (scoliosis, arachnodactyla, pectus carinatum or excavatum and excessively long limbs), ophthalmological disorders (crystalline ectopia and myopia, possibly leading to blindness), skin disorders (stretch marks) and lung problems (pneumothorax). The risk of death with this disease is mainly related to the occurrence of aortic dissection (without treatment, 80% of patients die before the age of 45). Diagnosis is based on a combination of major or minor clinical criteria and is established by specialists. Specific medical and, in some cases, surgical treatment at the early stages increases patients life expectancy by 30 years. The benchmark centre for Marfan’s Disease is the cardiology department under Professor Jondeau at Hospital Ambroise Paré.

In a single observation of 3 families with arterial dissections (aorta or cervico-cephalic arteries), association with bicuspid aortic valve was observed in 3 cases (the normal aortic valve has 3 leaflets; bicuspid valves have two leaflets and this is often associated with other cardiac malformations).

An association with cutaneous lentigines was reported in one family with two cases of dissection of the cervical arteries and in another family with one case of carotid dissection and one case of aortic dissection.

A dissection of the cervical arteries was observed in a brother and sister with brittle bones (ontogenesis imperfecta). This disease can be secondary to mutations of the collagen gene (Col1A1, col1A2).

Fibromuscular dysplasia is associated with sporadic arterial dissection of the cervical arteries in approximately 15% of cases. The disease affects medium-sized arteries and causes a succession of stenosis (narrowing) and dilatations (ectasia, aneurysms). Fibromuscular dysplasia affects mainly the renal arteries but can also affect the cervical arteries. Only 5% of cases of fibromuscular dysplasia are familial. Arterial dissection is exceptional in the familial types of fibromuscular dysplasia.

Screening for one of these hereditary diseases which render the walls of blood vessels fragile may be totally negative.

Diagnosis (criteria – methods)

A diagnosis of arterial dissection is initially confirmed, in most cases, by ultrasound investigations of the vessels in the neck and the intracranial vessels. This investigation will reveal any increase in the size of the artery and it allows for an assessment of the effect of the dissection on local blood supply or cerebral blood flow. Sometimes it also reveals hematoma in the vessel wall.

Magnetic resonance imaging with cross-sections of the neck (sequence with saturation of the fatty signal: Fat Sat sequence) confirms the diagnosis by showing the hyperintense signal of the hematoma in the vessel wall. Magnetic resonance angiography with injection of a dye may show the stenosis or occlusion of the artery and it provides a means of assessing the extent of the dissection. Cross-sections of the brain performed during the same investigation enable specialists to study the areas of the brain that may be affected (infarctions).

When combined with an angioscanner, a brain scan can provide the same information.

Conventional angiography (injection of a dye into an artery to highlight the arteries in the neck and brain, and sometimes in other organs) may be necessary particularly in difficult cases. The need for this investigation should be assessed in an environment dedicated for familial types of dissection because of the high risk of serious complications that may occur with rare familial diseases sometimes associated with arterial dissection, such as Ehlers-Danlos syndrome. In familial cases, screening for hereditary disease of the connective tissue in the vessel walls is a particularly important part of the specialist consultation. A detailed study of family history will be carried out. In addition to neurological and full cardiovascular examination, clinical examination will include a general physical examination and detailed examination of the skin, joints and eyes. Depending on the findings of this examination, additional tests may be requested to study certain organs (heart, aorta and arteries, kidneys, lungs and GI tract). The presence of signs suggestive of a known hereditary disease of the connective tissue may lead to the carrying out of a genetic test.

Treatment

At the onset of dissection, and in the case of non-familial arterial dissection, anticoagulant or anti-platelet drugs may be suggested to prevent ischemic complications (stroke) that may arise at the onset of dissection (especially during the first month). Anti-platelet treatment is usually continued for several months or years depending on the degree of repair of the vessel wall.

Prognosis

The seriousness of the disease is mainly related to the extent of the ischemic lesions (infarctions) in the brain. These lesions can leave permanent damage, of varying degrees of severity.

For familial dissections, the risk is the same as the risk observed in non-familial dissections unless the dissection occurs in several arteries (dissections of several arteries are thought to be 2 to 3 times more frequent in familial dissections).

Data which remains limited at the present time also suggests that relapse is more common with familial dissections (on average, 7% of patients with a non-familial dissection experience a further dissection ten years later but this figure rises to more than 50% for familial types).