Intracranial artery stenosis is an important cause of ischemic stroke and is approximately twice as common as extracranial artery stenosis in Asian patients with ischemic stroke. Current pharmacological treatment of intracranial artery stenosis has failed to achieve the desired outcome. With the advancement of technology, angioplasty and stenting have become an effective treatment for intracranial artery stenosis because of their safety, reliability, minimal injury and positive efficacy.
Intracranial artery stenosis is an important cause of ischemic stroke and is less likely to present with warning symptoms. Most patients do not present with TIA but directly cause a complete stroke, especially in vessels located distally with little and incomplete collateral circulation and a higher incidence of stroke. According to a large sample demographic survey, about 10-29% of cerebral ischemic events are caused by intracranial atherosclerosis.
Marzewski et al. reported a 27.3% rate of cerebral ischemic events in patients with intracranial segment stenosis of the internal carotid artery during a mean follow-up of 3.9 years, including a 15.2% rate of stroke and a 12.1% rate of transient ischemic attack (TIA), and concluded that intracranial artery stenosis predicts extensive cerebrovascular and systemic atherosclerotic lesions with a higher risk of stroke or even The risk of stroke and even death is higher.
Wong et al. examined 705 consecutive ischemic stroke patients admitted to Prince of Wales Hospital in Hong Kong and found that 49% had large artery occlusions, 37% of which had only intracranial artery lesions. Of these, 37% had only intracranial arterial lesions and 2.3% had only extracranial arterial lesions.
Tan et al. reported that the incidence of intracranial vascular lesions was twice as high as that of extracranial vascular lesions in patients with atherosclerotic stroke in Taiwan according to TOAST staging. Although recent studies have shown that the incidence of atherosclerotic stenosis in the extracranial segment of the carotid artery in China has improved compared with the past and is approaching the level in Europe and the United States, intracranial arterial stenosis is still an important cause of ischemic stroke in China that should not be ignored. Therefore, active and effective treatment of intracranial artery stenosis is of great importance for stroke prevention and treatment.
I. Current status of intracranial artery stenosis treatment
The current primary and secondary prevention of cerebral atherosclerotic lesions (control of vascular risk factors, antiplatelet, anticoagulation and antihypertensive therapy) has not achieved satisfactory results in the treatment of intracranial arterial lesions, and even with the above-mentioned regular treatment, a significant proportion of patients still have recurrent cerebral ischemic events.
The results of the Warfarin-Aspirin Clinical Study of Symptomatic Intracranial Artery Stenosis (WASID) showed that with strict antiplatelet aggregation drugs or anticoagulant therapy, the annual stroke rate in the stenotic vascular supply area of the basilar and intracranial segment of the vertebral artery was 10.7% and 7.8%, respectively. With the continuous development of endovascular interventions for extracranial artery stenosis, attempts to apply interventional techniques for intracranial artery stenosis were also made, but they were not successful in the early stages.
It was not until the continuous development of balloon catheter and stent technology in recent years, the flexibility and compression ability of new catheters and stents were improved, and the number of cases of intracranial artery stenosis treated by endovascular interventional techniques gradually increased and attracted people’s attention. In 1980, Kerber et al. reported the first case of percutaneous transluminal angioplasty (PTA) of the carotid artery, and in the same year Sundt et al. reported two cases of PTA of the basilar artery, both of which were successful.
In 1999, Mori et al. reported the first case of successful stenting of the basilar artery.
In 2000, Gomez et al. reported the first case of successful stenting of the middle cerebral artery. Studies over the years have shown that intracranial angioplasty and stenting are significantly more effective than PTA alone, and that stenting can limit the extent of vascular retraction and medically induced arterial dissection and can cover the broken intima, reducing the technical complications of PTA alone.
II. Indications
Interventional treatment of intracranial artery stenosis is still at a preliminary stage, and there are no unified, standardized and systematic operational guidelines and indications. Because the structure and anatomical characteristics of intracranial arteries are obviously different from those of extracranial and coronary arteries, intracranial artery stenosis cannot be completely referred to the interventional treatment of extracranial or coronary arteries.
At this stage, the recommended indications for interventional treatment of intracranial arteries are
1. 350% stenosis in patients with corresponding symptoms and 380% stenosis in patients without corresponding symptoms.
After relevant examinations, such as digital subtraction angiography (DSA), xenon-CT, single photon emission computed tomography (SPECT), positron emission tomography (PET), transcranial DopplerTCD, and MRI perfusion weighted imaging (PWI) demonstrated significant hemodynamic changes at the stenosis, and no effective collateral circulation was established distal to the stenosis.
2. The reference diameter of the treated vessel is >2mm.
III. Technical points
Compared with the extracranial arteries, the intracranial arteries have their own structural and morphological peculiarities: they are tortuous, especially those with severe atherosclerosis; they have thin walls and lack elasticity; they are located in the cerebrospinal fluid of the subarachnoid space and are not surrounded and supported by soft tissues; they send out many perforating arteries to supply the deep brain parenchyma, and most of them are terminal arteries, and the collateral circulation is not perfect. These characteristics of intracranial arteries make endovascular treatment of intracranial arterial stenosis more difficult and increase the risk of complications, so that extracranial arterial endovascular intervention techniques cannot be applied to intracranial arteries.
Compared with extracranial arterial interventions, intracranial angioplasty and stenting have the following characteristics.
1. Anesthesia: Most scholars recommend general anesthesia for intracranial arterial interventions. General anesthesia can ensure the maximum safety of the procedure, reduce the motion artifacts of contrast, and shorten the procedure time. However, general anesthesia may cause further reduction of cerebral blood flow and cause cerebral ischemia, especially when the treatment device is placed at the lesion. Therefore, it is especially important to pay attention to the lesions with severe stenosis and when the blood flow may be blocked due to too much distortion of blood vessels, so as to ensure the safety and shorten the time of blood flow blockage.
2. Choice of delivery system: Compared with the extracranial arteries, the intracranial arteries are obviously tortuous and have many branches, making the large intracranial arteries float relatively fixed in the cerebrospinal fluid. Some of the small penetrating arteries are only 250um in diameter or even smaller, and they penetrate deep into the brain parenchyma.
These arteries are invisible under DSA, so delivery of catheters, guidewires and stents can easily lead to vessel avulsion and intracranial hemorrhage. Therefore, it is required that the delivery system has good flexibility and can pass through tortuous vessels. If the vessel is excessively tortuous (especially the siphon section of the internal carotid artery), it is difficult for the delivery system to pass, and it should be done with caution and not reluctantly [14].
3, stent selection: due to the special anatomical structure of the intracranial artery, high precision of stent release is required; the required release pressure is low (generally not more than 8 atm); good flexibility (can pass through the tortuous intracranial artery and reach the target vessel), so balloon-expandable stents are generally chosen. The appropriate stent diameter should be equal to or slightly smaller than the normal vessel diameter of the distal proximal segment of the stenosis, so that the stent can maintain sufficient tension to maintain the patency of the vessel lumen; and the stent can be embedded in the vessel wall to prevent stent displacement; at the same time, the stent diameter is not too large to cause arterial endothelial stripping or arterial rupture.
Application of vascular protection device: Because the minimum diameter of vascular protection device is generally around 4mm, which is larger than the diameter of most intracranial arteries. Moreover, for a vascular protection device to be effective, it needs to fit tightly against the vessel wall or even slightly dilate the vessel wall.
Even for intracranial arteries larger than 4 mm in diameter (e.g., the intracranial segment of the internal carotid artery), the placement of a vascular protection device is sufficient, but because of the thin wall of the intracranial artery and the lack of surrounding support tissue, the vascular protection device can easily move when the vascular protection device is released or the catheter is moved during other operations, resulting in arterial entrapment or even rupture. Therefore, the use of vascular protection devices is generally not recommended in intracranial artery stenting.
4. The degree of residual stenosis: The success criteria for stenting of intracranial artery stenosis is that the review of the angiogram shows residual stenosis ≤ 20% and good antegrade flow. The aim of interventional treatment is to reduce the degree of stenosis and increase blood flow. The cerebral blood flow is exponentially related to the lumen radius, i.e., a small lumen change can cause a large blood flow change. Therefore, in practice, it is not necessary to pursue perfect imaging results; a residual stenosis of 20% or slightly higher is acceptable, otherwise it is very easy to rupture a weak intracranial artery, resulting in serious consequences.
IV. Complications
In recent years, a number of retrospective studies have demonstrated the efficacy of intracranial angioplasty and stenting in the treatment of intracranial artery stenosis. Studies have shown that the technical success rate of intracranial angioplasty and stenting is 85.7%-97.6%, with failure mostly due to vessel distortion and abandonment of the stent in place. de Rochemornt et al. reported 18 cases of intracranial stenting, and the postoperative stenosis rate decreased from 82% (72%-97%) to 16% (5%-40%).
It can be seen that intracranial angioplasty and stenting are effective in reducing the degree of stenosis. However, a prospective multicenter study found that the incidence of stroke 30 days and 1 year after intracranial angioplasty and stenting was still quite high, 6.6% and 13.2%, respectively, and Kim et al. reported that the incidence of complications and mortality of middle cerebral artery stenting were 33.3% and 8.3%, respectively. This suggests that the risks of intracranial angioplasty and stenting should still be taken seriously.
The common complications of intracranial angioplasty and stent placement are as follows.
1. Restenosis: It is an important concern of intracranial angioplasty and stenting. In extracranial arteries, due to the large diameter, even if in-stent stenosis occurs, the stenosis rate is generally low and the hemodynamic impact is small and negligible. Unlike intracranial arteries, even minor changes in diameter can cause significant hemodynamic changes. To a greater or lesser extent, the stenting process can damage the vessel, causing smooth muscle proliferation, neointimalization, endothelial hyperplasia, and revascularization, leading to restenosis.
Other possible mechanisms of restenosis include thrombosis and vascular retraction. Risk factors for restenosis include diabetes mellitus, small diameter of the stented vessel, and postoperative residual stenosis greater than 30%. The incidence of restenosis varies among studies and is generally similar to the incidence of restenosis after coronary stenting, with Suh et al. reporting symptomatic restenosis in approximately 6% of patients and asymptomatic restenosis in approximately 9% of patients with intracranial artery stenting during a 22-month follow-up period.
The majority of restenoses were asymptomatic, which may be related to improved cerebral blood supply due to vasodilation after stenting. In addition, the slow rate of restenosis allows sufficient time for the body to establish a better collateral circulation; at the same time, despite the hyperplasia of the intima, the re-formed intima is smoother than the original atherosclerotic plaque, so the hemodynamic impact is not significant and the symptoms are not obvious.
2.Occlusion of penetrating arteries: There are many penetrating arteries in the intracranial arteries, especially the middle cerebral artery, supplying blood to the basal ganglia and brainstem, and these arteries are mostly terminal arteries, which may cause serious cerebral infarction once they are occluded. Since intracranial atherosclerosis often occurs at the bifurcation of vessels or in the immediate vicinity of branch vessel openings, the mesh structure of the stent itself will inevitably compress or cover the openings of the penetrating arteries after stent placement.
However, because the mesh of the currently used balloon-expandable stents is larger and the mesh filaments of the woven stents are finer, they have little effect on the more important branch arteries (e.g., ductus arteriosus). In a retrospective analysis of 10 patients, Lopes et al. compared the pre and post stent placement imaging results and clinical features and found no significant effect of stents on some important branch arteries.
In addition, the “snow plowing effect” is a factor that causes the occlusion of the penetrating artery, that is, the atherosclerotic plaque is displaced by the stent, balloon cutting, squeezing and expansion, and enters and blocks the penetrating artery.
3.Vascular rupture: It is one of the most serious intraoperative complications of intracranial angioplasty and stenting.
Intraoperative vascular rupture may be caused by.
① Over-selection of stent;
② The balloon expansion pressure of the balloon expansion stent is too large and too fast;
(3) All intracranial vessels are located in the subarachnoid space without any surrounding support tissue and small diameter, which, together with long-term atherosclerosis, leads to poor structure and increased brittleness of the vessel itself, and there is a potential risk of vessel rupture when the stent is placed in the stenotic segment and released by dilation.
Suh et al. reported a 3% incidence of catheter puncture during endovascular treatment of symptomatic intracranial artery stenosis, manifesting as subarachnoid hemorrhage and severe headache in the patient.
4. Distal embolism: Intracranial arterial interventions generally cannot be performed with vascular protection devices, increasing the risk of distal embolism. Distal embolism can occur at all stages of the procedure and is an important cause of intraoperative and postoperative acute ischemic stroke. Distal embolism can cause severe neurological deficits or can be asymptomatic, depending on the ability of collateral circulation to compensate. Other common complications are thrombosis, vasospasm, cerebral hyperperfusion syndrome, stent displacement, and puncture site hematoma, similar to extracranial arterial interventions.
In summary, angioplasty and stenting of intracranial artery stenosis are safe, reliable, less invasive, and have positive efficacy, and are gradually gaining recognition as an important treatment for intracranial artery stenosis. However, this technique is still in its infancy, and there are still many problems to be solved in terms of technique, materials, indications, perioperative management, long-term prognosis, and further reduction of complications, which depend on the conduct of multicenter randomized controlled studies with large samples, as well as the progress and experience of neurointerventionalists.