Vertebral artery dissection from etiopathogenesis to management therapy: a narrative review with neuroimaging’s case illustration

Abstract

Vertebral artery dissection is one of the causes of stroke and transient ischemic attack in young adults, with an incidence rate of 1.0–1.1 per 100,000 people. Vertebral artery dissection occurs due to a tear in the vertebral artery wall, which results in blood flow entering the blood vessel wall. The etiology of vertebral artery dissection is very diverse, which can be classified as intrinsic (such as anatomical abnormalities of the blood vessels) or extrinsic (such as trauma), and there are several rarer causes. The most frequent clinical manifestations include stroke, transient ischemic attack, neck pain, headaches, and vertigo. Management in this case comprises treatment according to symptoms in the form of intravenous thrombolysis, administering antithrombotic drugs, and endovascular therapy.

Introduction

Vertebral Artery Dissection (VAD) is a condition in the arteriopathy category that does not have the same pathophysiology as other arteriopathies but does have one feature: the occurrence of intramural haemorrhage. VAD is a tear in the wall of the vertebral artery that results in the entry of blood flow into the layers of the vessel wall. VAD usually occurs at an average age of 46.5 years and is one of the causes of stroke and transient ischemic attack (TIA) in young adults. Most patients with VAD have no symptoms and do not seek medical help until they experience symptoms of a stroke or TIA [1].

According to population-based studies conducted in the United States and France, the overall incidence rate of cervical artery disease was 2.6–3.0 per 100,000 population, whereas VAD contributed around 1.0–1.1 per 100,000 population. The typical VAD patient generally experiences delays in obtaining medical treatment because they are often young, have comorbidities, and have ill-defined symptoms. Patients with symptoms of neck pain, and headaches seek medical attention on average for a period ranging from 9 days to 3 months [2]. Diagnosing VAD can be challenging due to the wide variety of symptoms, which include neck pain and clinical manifestations of ischemic stroke. Cerebral Digital Subtraction Angiography (C-DSA) is the gold standard for VAD. Examinations with Magnetic Resonance Angiography (MRA) and Computed Tomography Angiography (CTA) can also be carried out with lower sensitivity [3].

Etiology

The etiology of VAD can be extrinsic or intrinsic factors. Some case reports describe trauma or extreme movement as the primary cause of VAD. The role of these extreme movements cannot be explained in causing VAD, so the actual etiology of VAD is currently unexplained. Extrinsic causes include trauma such as neck manipulation, car accidents, surgical trauma, and sports injuries. Meanwhile, anatomical defects in blood artery walls are considered intrinsic factors. Among them are connective tissue disorders, vasculitis and atherosclerosis, which can cause weakness in the walls of blood vessels [4]. Several case studies by several authors also report some rarer causes of VAD. Some of them can be seen in Table 1.

Table 1 Some etiologies or conditions associated with VAD are based on case reports

Pathogenesis

The walls of blood vessels consist of five layers, namely the tunica intima (endothelium), internal elastic lamina, tunica media (muscular layer), external elastic lamina, and tunica adventitia. A tear in the tunica intima is the most common precipitating event in arterial dissection. After the tear in the blood vessel wall occurs, blood flows into the subintimal space called the false lumen or pseudo lumen, causing an intimal tear. Other factors, such as shear injury from extreme neck motions, direct injury to blood vessels, intraoral trauma, or direct laceration of bone fractures, are also involved in the pathophysiology of cases with traumatic causes. Following the formation of an intramural hematoma, bleeding of the vasa vasorum in the tunica media could lead to swelling of the hematoma. A subintimal hematoma will cause arterial stenosis or occlusion, while a sub adventitial hematoma will cause the formation of pseudoaneurysms [10]. The pathogenesis illustration of VAD is shown Fig. in 1A, B.

Fig. 1

A Image of the vertebral artery and the layers of the blood vessel walls. A. Vertebral artery; A. Inset 1: Layers of the blood vessel wall (horizontal section); A. Inset 2: Cross section of the layers of the vertebral artery, (1.a. Tunica intima; 1.b. Tunica media; 1.c. Tunica adventitia; 1. Endothelium; 2. Connective tissue; 3. Internal elastic membrane (IEM); 4. Muscle fiber; 5. External elastic membrane (EEM); 6. Connective tissue); 1B. Illustration of several types of vertebral artery dissection. B.1. Normal vertebral artery; B.2. A tear in the tunica intima, causing blood to enter the subintimal layer and form a false lumen, resulting in thromboembolism and stenosis/occlusion of blood vessels; B.3. A tear in the tunica adventitia that appears to be the result of trauma, causing the formation of a hematoma due to the tearing of the vasa vasorum in the tunica media layer, leading to the formation of a pseudoaneurysm; B.4. A tear from the tunica intima to the tunica adventitia, causing stenosis/occlusion in blood vessel lumen, thromboembolism and the formation of a pseudoaneurysm

No single mechanism is thought to cause VAD. Various influencing factors include predisposing factors, susceptibility and trigger events, which together exceed the capacity of the blood vessels. A person who does not have predisposing factors can experience VAD in a major event, while a minor event or minor accident can cause VAD in individuals with predisposing factors. The severity of the injury experienced occurs on a spectrum of these factors [11].

Predisposing factors include connective tissue disorders, blood vessel elasticity, and the presence of infection or inflammation. Meanwhile, factors that determine vulnerability are extreme neck positions, contact during sports, use of protective equipment, weather, and playing areas. The trigger event that can cause VAD is an impact or movement, which can be in the form of pulling, compression, tearing, torque, pinching, pressure, or a combination of several mechanisms and the rate of impact at a certain time [11]. Several previous studies have also revealed that numerous chiropractic patients who develop VAD following neck manipulation also experience damage, occlusion and vasospasm or thrombosis in the artery walls [1].

Clinical manifestation

Clinical manifestations of VAD vary widely, ranging from symptoms of ischemic stroke to non-specific symptoms such as dizziness. Gottesman et al. in a systematic review of 75 case reports, discovered remarkably varied symptoms. The most commonly reported symptoms are non-specific ones, such as headache, vertigo, and neck pain; nevertheless, no symptom is sufficiently precise to rule out VAD (e.g., the absence of neck pain does not exclude the diagnosis of VAD). Pain is the most common clinical symptom resulting from dissection. This is due to the presence of pain nerve fibers (PNF) in the cerebral blood vessels, particularly the main cerebral arteries. This PNF is derived from the Trigeminal nerve, of which the most important division is the V1 division, which comprises the Ophthalmic nerve and the cervical nerves C1, C2, and C3. Therefore, any kind of pressure, stretching, or even a little contact will hurt. If left untreated over a prolonged period, this type of pain is one of the so-called local warning indicators that might lead to ischemia symptoms. Although they can also occur in vertebral dissections, local warning symptoms are most frequently seen when the dissection happens in the carotid artery. The average age of patients suffering from VAD is 45 years old, which is 20 years behind the average age in the population of patients with stroke. This study suggests the possibility of VAD as a differential diagnosis in the presence of the above symptoms, even in the absence of obvious stroke symptoms such as hemiparesis or cranial nerve palsies. This is particularly valid for young patients, who frequently receive diagnoses for milder illnesses such as vestibular migraine [12]. A meta-analysis by Trager et al., of VAD patients who had visited a chiropractor's practice showed that neck pain and headache were the primary clinical symptoms in this group of patients, where this group had a middle-adult age range with a sudden onset and course of the disease [1].

Several differences in symptoms are also found between unilateral VAD and bilateral VAD. In a review of 83 patients by Rojas et al., the most common symptoms in patients who did not experience decreased consciousness were unilateral or bilateral headaches in 60 cases, neck pain in 41 cases, and vertigo in 20 cases. Meanwhile, in 23 patients with bilateral VAD, the majority of patients, namely 20 patients, reported having headaches or neck pain in 20 of the cases. However, in other cases, additional blood vessels, including the bilateral internal carotid, and basilar arteries, were also involved. This resulted in additional symptoms like vertigo, dysphagia, and Horner syndrome, which predominate clinical symptoms [13].

VAD can also cause symptoms with topical lesions in the spinal cord, although this is very rare. Spinal cord ischemia occurs in 1% of stroke sufferers and occurs in 4–10% of VAD cases. Montalvo et al. reported a case of spinal cord infarction in the cervical segment at the C3–C4 level caused by right vertebral artery dissection. Clinical symptoms in patients include anterior cord syndrome, quadriplegia, areflexia, and urinary incontinence, accompanied by loss of sensation up to the cervical level [13]. Another clinical symptom that is less frequently reported is spinal cord infarction with Brown-Sequard syndrome. Meng et al. reported a 40-year-old man with symptoms of acute right extremity weakness accompanied by loss of ipsilateral joint position sense and contralateral loss of pain and temperature sensation caused by dissection of the vertebral artery segment at the level of C1-C3 [15].

Diagnosis

Supporting examinations for VAD can be carried out using several non-invasive modalities, such as MRA, CTA, Doppler ultrasonography, and C-DSA as the gold standard. Ultrasonography is restricted to initial screening and is only able to identify proximal dissections; it is not able to detect distant dissections. Some typical findings on imaging in diagnosing VAD are vertebral artery stenosis, string and pearl signs, arterial dilation, arterial occlusion, pseudoaneurysm, double lumen, and intimal flap. CTA has the highest sensitivity (100%) compared to MRA (77%) and Doppler ultrasonography (71%) [16].

Previous studies have also suggested several clinical features in patients as predictors of the presence of VAD, especially in trauma patients. These features are a prerequisite for using imaging examinations such as CTA to verify the existence of VAD. These features are specified in the Denver criteria for screening VAD patients in the form of a Glasgow Coma Scale (GCS) score < 6, Le Fort fracture type II or III, petrosal bone fracture, and diffuse axonal injury [17]. Meanwhile, a study conducted by Gupta et al. revealed that the presence of vertebral fractures, especially the C1–C3 cervical segment, fracture extension to the transverse foramen, and subluxation are very significant indicators of the occurrence of VAD [18]. The typical finding based on MRA and C-DSA neuroimaging of VAD is shown in Fig. 2.

Fig. 2

A Case of Vertebral Artery Dissection. A 26-year-old man suddenly feels pain in his left nuchal while lifting a weight. From 3D-MRA and C-DSA Neuroimaging shown: A. 3D-MRA showed a dissecting aneurysm at the Left VA, segment V4; B. C-DSA showed a dissecting aneurysm from lateral view (inset at the upper right also showed a dissecting aneurysm from the lateral view of C-DSA Roadmap, and C. 3D-MRA showed the resolution of the dissecting aneurysm after conservative therapy with antiplatelet for 3 months (The yellow arrow shows the left vertebral artery dissecting aneurysm)

Management

VAD management therapy has remained controversial to this day. The treatment strategy encompasses a combination of conservative therapies, particularly antithrombotic (AT), anticoagulant (AC) and antiplatelet (AP). The management of patients with VAD is generally adjusted to the accompanying symptoms. In patients with acute ischemic stroke within 4.5 h of onset caused by VAD in the extracranial segment, ESO (European Stroke Organization) recommends intravenous thrombolysis (IVT) using alteplase if it meets the inclusion criteria for thrombolytic administration. Meanwhile, in patients with acute ischemic stroke caused by VAD in the intracranial segment, insufficient data were obtained to provide recommendations. In this case, the expert consensus recommends administering IVT for intracranial artery dissection by ruling out several contraindications, such as brain imaging evidence of subarachnoid haemorrhage [19].

Direct anticoagulant (DOAC) administration is advised in stroke or transient ischemic attack cases instead of vitamin K antagonists. A study conducted by Engelter et al., on 194 patients with CAD failed to show non-inferiority of aspirin to anticoagulants where the primary endpoint in the form of a composite clinical outcome (stroke, bleeding, and death) occurred in 21 (23%) patients in the aspirin group compared to 12 (15%) of 82 patients in the anticoagulation group in patients with cervical artery dissection (CAD) (absolute difference 8% [95% CI –4 to 21] [20]. However, in cases of extracranial dissection, dual antiplatelet administration with aspirin and clopidogrel is recommended for several weeks. As a comparison, according to the AHA/ASA guideline for secondary prevention of acute stroke, patients with acute stroke or TIA within 3 months after the acute event can be given antiplatelets (aspirin) or anticoagulants (warfarin) [21]. Figure 3 shows the management therapy for VAD with fusiform dilatation aneurysm with double antiplatelet therapy (DAPT).

Fig. 3

A Case of Vertebral Artery Dissection with fusiform dilatation aneurysm treated with DAPT. A 69-year-old man, with severe headaches and a history of hypertension ( +). As seen by C-DSA neuroimaging: A. A fusiform dilatation aneurysm of VAD at the Rt-VA, segment V4 from AP View of C-DSA; B. A fusiform dilatation aneurysm of VAD at the Rt-VA, segment V4 from AP View of C-DSA Roadmap; C. A fusiform dilatation aneurysm of VAD at the Rt-VA, segment V4 from Lateral View of C-DSA; D. A fusiform dilatation aneurysm of VAD at the Rt-VA, segment V4 from Lateral View of C-DSA Roadmap. (The red arrow shows the dissecting fusiform dilatation aneurysm of the right vertebral artery.)

Recently, endovascular treatment (EVT) has emerged as a choice for VAD management due to its good efficacy, and low periprocedural morbidity. Endovascular procedures are performed when an ischemic stroke caused by VAD does not respond to AT medical treatment, there is stenosis or occlusion, or there is subarachnoid haemorrhage. Endovascular procedures such as stent angioplasty, double stent, stent-assisted coil and microvascular brain surgery (bypass) must be carried out promptly. According to a research study, the technique used to perform an EVT procedure for a VAD is determined by every fundamental condition of the case to be treated, as well as factors such as the patient's clinical symptoms, hemodynamic status, collateralization of the cerebral blood vessels, particularly the posterior circulation area, and significant features of the anatomy of blood vessels and perforators. If a VAD ruptures, the EVT procedure aims to close the ruptured area either by completely closing the VA or by performing stent-assist coiling. Meanwhile, for VADs that have not ruptured, the main aim of EVT is to ensure that the hemodynamic flow of cerebral blood is maintained using stenting. The choice of EVT treatment depends on the patency of the contralateral vertebral artery (VA) and the relationship between the dissection segment and the location of the origin of the posterior inferior cerebellar artery (PICA). Complete occlusion of the dissection segment is the best option. If the dissection is proximal or distal to the PICA without hypoplasia of the contralateral VA, treatment can be carried out with total occlusion of the dissection segment with a coil, where the PICA will obtain flow from the contralateral VA. If the VAD is present at the PICA branch, isolation of the dissected segment can be done by coil trapping with PICA revascularization via bypass surgery or PICA stenting [22, 23, 24]. The management therapy of EVT with stenting, and coil embolization or double stenting is shown in Figs. 4 and 5.

Fig. 4

A Case of Vertebral artery Dissection treated with EVT (Stenting + Coil embolization). A 60-year-old woman has severe nuchal on the right side and a history of hypertension ( +). From 3D-MRA and C-DSA Neuroimaging shown: A. 3D-MRA showed a dissecting aneurysm with fusiform dilatation at the right vertebra artery, segment V4; B. C-DSA showed a dissecting aneurysm with fusiform dilatation at the right vertebra artery from anterior–posterior (AP) view; C. C-DSA showed a dissecting aneurysm with fusiform dilatation at the right vertebra artery from lateral view; D. C-DSA showed a dissecting aneurysm with fusiform dilatation at the right vertebra artery from AP view of C-DSA Roadmap; E/F. Post-EVT procedures showed that a stent was inserted inside the lumen of the right VA with coil embolization. (The red arrow shows the dissecting aneurysm of the right vertebral artery.)

Fig. 5

A Case of Vertebral Artery Dissection treated with EVT (Double Stent). An asymptomatic 62-year-old man, smoker ( +), history of hypertension ( +) and history of SAH. From 3D-MRA and C-DSA Neuroimaging shown: A. 3D-MRA showed a dissecting aneurysm with fusiform dilatation at the right vertebra artery, segment V4; B. C-DSA showed a dissecting aneurysm with fusiform dilatation at the right vertebra artery from AP view; C. C-DSA showed a dissecting aneurysm with fusiform dilatation at the right vertebra artery from Lateral view of C-DSA Roadmap; D/E. Post-EVT procedures showed that a double stent was inserted inside the lumen of the right VA (The yellow arrow shows the placement of a double stent inside the VAD fusiform dilatation aneurysm)

Conclusion

VAD is an infrequent cause of stroke, but it should be considered a differential diagnosis when young patients present with stroke-like symptoms. VAD can be caused by external factors such as moderate trauma around the neck as well as constitutional variables in our bodies such as vascular disease, which has been shown to cause VAD, such as connective tissue diseases directly, and elastin insufficiency indirectly. A neuroimaging assessment is essential to diagnose VAD properly. The most significant modalities are CTA and MRI/MRA, with C-DSA acting as the gold standard. Thrombosis between the arteries is the most common cause of stroke-like symptoms in VAD, followed by hypoperfusion due to stenosis. Current treatment consists of combination therapy, including anti-thrombolytic, anticoagulant, antiplatelet, endovascular therapy, and cerebral vascular microsurgery (bypass). However, VAD treatment management is highly personalized. Overall, the prognosis for VAD is excellent, although it can be fatal if not adequately managed. Even if patients suffer local symptoms such as neck discomfort, the result is often favourable, as opposed to patients who encounter symptoms such as stroke, which tend to be worse.