Selection of indications for endovascular treatment of cerebral arteriovenous malformations
1.The lesion is extensive and deep, which is not suitable for direct surgery.
2.The lesion is located in important functional areas, such as brain motor area, language area, brain stem, etc., which will produce serious complications and sequelae after surgery.
3.For those who have high blood flow lesions, serious blood theft, and bleeding from surgical resection or over-perfusion syndrome may occur after surgery, partial embolization of the malformed vascular mass or blood supply artery can be performed first, and then surgical resection can be performed.
The basic objectives of treatment for cerebral arteriovenous malformation
1.Removal of the lesion; therefore microsurgical resection is still the best option, especially with the application of temporary embolization techniques, which makes the procedure easier, but difficult to achieve in most patients.
2. reduction of spontaneous bleeding and prevention of the risk of rebleeding.
(1) Clinical factors, history of hypertension, and history of bleeding. A history of bleeding, small AVM or volume, high blood pressure in the supply artery, paraventricular and intraventricular AVM, deep venous drainage, with aneurysm and poorly draining veins, and diffuse type are all associated with a higher risk of bleeding.
(2) Vascular constructive factors: flow-associated aneurysm/malformed intracluster aneurysm/deep venous drainage/deep or paraventricular AVM/stagnant flow type/stenosis of the draining vein. Smaller AVMs, higher pressure ones with aneurysms, or AVMs with venous occlusions have a higher risk of hemorrhage. However, the management of large AVMs is still very tricky. The most experienced surgeons and radiologists also consider asymptomatic large AVMs that are difficult to cure and recommend conservative treatment. Palliative embolization should be performed with caution, and some investigators have even concluded that partial embolization causes a higher bleeding rate than untreated patients and that only large AVMs with a high risk of bleeding should be treated; Miyamoto et al. reported that palliative treatment resulted in an increased annual bleeding rate of 17%, treatment-related complications of 23%, and a mortality rate of 9.3%.
(3) Age factor, regarding age: If the annual bleeding rate is calculated at 2-3%, the risk of bleeding in a patient with unruptured AVM can be calculated with the following formula: lifetime risk rate (%) = 105 – patient’s current age. The rebleeding rate in the first year after the initial bleeding is 6 to 17.9%.
(4) Other factors are: it has been suggested that epilepsy has a higher risk of bleeding, and although the Spetzler-Martin scale is used to predict surgical outcome, it is now also used to predict outcome of combined treatment, so improvements are still needed, such as functional magnetic resonance imaging (fMRI) is increasingly being used to map brain function when developing AVM treatment plans. Prior to embolization, radiation therapy, or surgery for AVM, fMRI can be used to localize important functional brain areas, such as speech, memory, visual, motor, or sensory functional areas, located in or around the AVM lesion. Functional areas need to be redefined or vary from patient to patient. Palliative care may be used as part of a stepwise treatment or to improve certain symptoms. However, there is no evidence to reduce the risk of long-term bleeding
Treatment strategies for cerebral AVM are established
There are currently three basic modalities for the treatment of cerebral AVM: endovascular embolization, radiosurgery, and surgical resection. Treatment strategies, especially for complex lesions, often employ more than one modality. Although in a few cases, the goal of neurointerventional treatment is complete embolization of AVM, in most cases embolization is a preparation for or surgical resection, and radiosurgery. Total surgical resection of the lesion is considered the most desirable radical approach, but it is difficult to remove the lesion if it is extensive and deep or located in a vital functional area. In recent years, the development of endovascular microcatheterization techniques has opened new avenues for the treatment of this disease. As a preparation before surgical resection, embolization is performed to facilitate surgical resection, resulting in less bleeding and better prognosis. In particular, embolization of deep blood supplying arteries can make surgical procedures easier and also reduce the risk of surgery. Thus preoperative embolization can reduce surgical risk. In order to reduce the risk of bleeding during treatment, the intra-focal aneurysm should be embolized first during embolization. Brain AVMs that cannot be cured by endovascular embolization or surgical resection are most often treated with radiosurgery.
Pre-surgical embolization
For some AVMs, microsurgical resection is a safe and effective treatment method; Spetzler-Martin scoring can help select the right patient for surgery; functional MRI can be used to establish the functional localization of the adjacent AVM to help plan treatment; as an adjunct, preoperative embolization can reduce bleeding and can first treat surgically difficult or dangerous arteries such as striatal artery, and treating associated aneurysms with glue or spring coils. It can simplify the surgical access and avoid reoperation. Large high-flow AVMs cause bleeding due to postoperative breakthrough of normal perfusion pressure. Preoperative embolization in stages over several weeks or months can reduce bleeding by adapting the brain tissue around the AVM to the hemodynamic changes.
Pre-radiotherapy embolization
For small AVMs, radiotherapy is a relatively safe and effective treatment measure, especially for deep AVMs. such as thalamic and basal ganglia regions, where surgical risks are high. AVMs smaller than 10 ml have a 78-88% clearance rate after 3 years of radiotherapy. It is because of these limitations of radiotherapy and the effectiveness of embolization in reducing AVM volume that embolization combined with radiotherapy has been developed and many successes have been reported in this area. However, embolization combined with radiotherapy requires permanent embolization agents such as NBCA and ONYX as well as attention to dynamic follow-up of cerebral angiography.
Techniques in embolization.
How much to embolize and which part to embolize?
Embolization decisions serve treatment goals and when embolization is part of the treatment plan, the strategy is determined by predetermined goals with few exceptions, the ultimate goal for cerebral AVM being complete clearance of the lesion. In the management of acute bleeding in AVMs, it is common to wait until the hematoma and cerebral edema have subsided. The exception is when the hemorrhage is caused by an aneurysm and surgical or interventional intervention is warranted; the risk of rebleeding is much higher in these patients than from a malformed vascular mass.
In embolization, we follow several principles to reduce complications and improve the efficiency of treatment.
1. Less than 50% at a time, typically 1-3 supplying arteries are embolized at a time to minimize intra-sinus hemodynamic changes and shorten the operation time, the latter being associated with the risk of thromboembolism. If there is an aneurysm, deal with the aneurysm first.
2. Once the microcatheter is inserted into the blood supply artery, two or more angles are angiographed to check for regurgitation. In summary, the closer the microcatheter is to the aberrant mass, the safer the embolization will be. Avoid injecting embolic agents by placing the microcatheter only at the normal vessel end. Our goal is to place the catheter into a vessel that is intended for AVMs only. In case of preoperative embolization, we do not only reduce the volume of the lesion, but we mainly embolize the deep blood supply artery which is not easily accessible during surgery. Sometimes the deep blood supply artery is small and not easily accessible by microcatheter, we can embolize the superficial vessels, and after a period of time, the deep blood supply artery is dilated and then the microcatheter is placed to embolize it. In case of embolization before radiotherapy, we do not distinguish between superficial and deep vessels and try to embolize them.
Embolization agents
Liquid embolic agents: such as NBCA and ONYX. NBCA has been the most widely used since 90 years, while the effectiveness and safety of onyx is being evaluated.
NBCA embolization technique
Due to the thin wall of the floating catheter, which is easily damaged, it is usually used once. Its suitable for high-flow AVMs, and for slow-flow AVMs, the catheter is usually guided by a guidewire, but it is important to avoid the guidewire entering the AVM. We approach the catheter as close and safely as possible to the AVM under the roadway. If the floating catheter is appropriate and the lesion is in the anterior circulation, the microcatheter is placed into the distal internal carotid artery with a 0.010 or 0.008-inch guidewire and then the microcatheter is withdrawn in the posterior circulation, once it reaches the distal vertebral artery the microcatheter should be withdrawn.
When the microcatheter reaches the lesion, superselective angiography is performed to assess the vascular architecture of the arteriovenous malformation, and the microcatheter is injected intravenously with amytal test to determine the absence of neurological deficit, and then the microcatheter is flushed with sugar water. To prolong the polymerization time even more, we can even add glacial acetic acid to obtain better dispersion. For patients with high flow rate fistula, spring coils can be applied to slow down the flow rate. When injecting glue, it is important to find a working angle that allows observation of the draining vein and best reflects the vascular reflux. Observation of reflux and draining vein is the most critical when injecting, once the glue reaches the catheter tip, the injection speed slows down, faster for dilute glue and slower for concentrated glue, and the assistant holds the microcatheter during injection for quick withdrawal. When there is reflux or gum enters the vein, the assistant is ordered to withdraw the tube quickly.
NBCA is attractive because of permanent embolization, recanalization of NBCA is low, and many authors report low complications. Complications include catheter adhesions, occlusion of the draining vein, and bleeding from AVM rupture. the ratio of NBCA to iodobenzylate determines the polymerization time of the glue, which can be prolonged by adding glacial acetic acid if necessary. Multicenter studies have confirmed the safety and efficacy of NBCA, with most embolizations reducing AVM volume by more than 50%, and many surgeons have reported that embolization can make surgery easier. Embolization combined with Gamma Knife for cerebral arteriovenous malformations has a clearance rate of 46%, with complications ranging from 3% to 25%.
ONYX is nonadhesive, has no risk of adhering to the catheter, allows for more force volume push time variation, acts as a preoperative embolic agent, and after embolization the malformed vascular mass remains elastic and intact, making it easy to separate surgically. These features theoretically make embolization more controllable and enable the interventionalist to discontinue the injection in time before embolization of the draining vein. In animal studies, the solvent dimethyl maple in ONYX is the chemical component that causes severe vasospasm and vascular necrosis, and the vascular toxicity is related to the amount and rate of injection of the solvent. It was reported that 12 patients underwent radiotherapy and 11 underwent surgery after ONYX embolization in 23 patients, and the surgery was able to completely excise the lesion, and the excisional histopathological examination revealed a mild inflammatory response one day after embolization and a chronic inflammatory response 4 days after embolization, and necrosis of the embolized vessels could be observed in 2 patients. Based on the experience of those authors, they recommend to push slowly when embolizing and to mix the tantalum powder thoroughly to ensure a good intraoperative observation. Based on their experience and ours with the use of ONYX, it is felt that it is very useful.
Microcatheters and Microguidewires
Microcatheters are divided into guidewire-guided catheters and floating catheters, floating catheters are easier and faster to reach the malformed vascular mass, their ultra-soft characteristics and small outer diameter are relatively less likely to damage the fragile blood supply arteries, the disadvantage is the lack of support, if the injection is not careful, the soft and thin wall is easy to break, so you need to avoid a great pushing force when injecting, this force experience only comes from the clinic, there is no good animal model for practice, guidewire The guidewire catheter can reach the blood supply artery which is not easily reached by the floating catheter, but the risk of breakage is greater than the floating catheter, when the guidewire or larger catheter enters. Therefore, we recommend using a guide wire with the smallest possible catheter and soft tip.
Embolization under consciousness and general anesthesia?
Cerebral AVM embolization can be performed either awake with sedative pain medication or under general anesthesia. In the former case, intraoperative monitoring is facilitated by intraoperative microcatheter injection of barbiturates or lidocaine for neurological assessment to avoid embolization of the vessels supplying the normal cortex. For the latter, immobilization of the patient’s head after general anesthesia and control of the ventilator frequency during imaging can result in high image quality, but the amytal test cannot be performed and requires a good knowledge of neurovascular anatomy on the part of the operator. Therefore, it is generally safer to try to keep the patient awake under embolization, but for children and more irritable patients who cannot cooperate, general anesthesia is still necessary when applying ONYX.
Complication prevention and management
Acute complications during embolization include intracerebral hemorrhage or intraventricular hemorrhage, adhesion of the microcatheter to the malformed vascular mass, occlusion of the draining vein, and perforation of the vessel. Intracerebral hemorrhage or intraventricular hemorrhage can be seen as contrast spillage or changes in symptoms and vital signs of neurological deficits during imaging. If hemorrhage is suspected, discontinue the procedure and anticoagulation and perform an immediate CT scan. If the conscious patient is declining, immediately intubate the airway to establish airway ventilation, place extraventricular drainage to monitor and control intracranial pressure, and occlude the bleeding vessel if possible, if it can be identified. If the tube is adherent, it can be buried. It can be removed at the time of surgery; otherwise, anticoagulant medication is required to prevent thrombosis on the catheter. Drainage vein occlusion is the most dreaded complication that will lead to bleeding in the brain parenchyma. Once the drainage vein is found to be occluded and the embolization procedure is completed, CT is reviewed immediately to assess whether to operate if there is bleeding. If there is no bleeding, the management is more controversial. If the vein is significantly occluded or easily reached by AVM surgery, some advocate immediate surgery, a concept derived from the intraoperative observation that the lesion is prone to bleeding after treatment of the vein before separating the malformed mass. Another option is to occlude all the blood supplying arteries.
In conclusion, embolization is a powerful tool in the treatment of AVMs, and its safety and effectiveness will be further improved with the continuous improvement of microcatheters, microguidewires, and embolization materials. Safe and effective embolization requires operational skills and a holistic understanding of cerebral AVM and the rational application of multiple therapeutic tools to develop an appropriate treatment strategy. Close cooperation and communication between specialists in various disciplines of cerebrovascular disease, radiotherapy, and neurointervention is the guarantee of the best treatment outcome.