The main risk of cerebral arteriovenous malformations (AVMs) is spontaneous hemorrhage, so treatment should be chosen with the lowest treatment complication rate in exchange for minimizing the risk of hemorrhage. Gamma Knife is an important treatment for AVMs, especially for vascular malformations in the deep brain (basal ganglia, internal capsule, thalamus, and brainstem), sensorimotor areas, or visual-center areas, and its benefits are increasingly recognized.
Efficacy of Gamma Knife for AVM.
Compared with surgical treatment of AVM, the occlusion of malformed vessels after gamma knife treatment of AVM. It is a slowly progressive process that occurs. The vessel wall of the aberrant vessel nest appears to be hyperplastic, the lumen is progressively narrowed, the blood flow rate becomes slower, and eventually the aberrant vessel nest is occluded by intravascular thrombosis. This process can occur 6 months to 3 years after gamma knife treatment. The rate of complete occlusion of AVMs is 80% to 90% 2 years after gamma knife treatment.
Prasad retrospectively summarized the efficacy of 2067 gamma-knife treated AVMs compared with 2722 surgically treated AVMs. The results showed that AVMs that can rely on surgical resection naturally have a high cure rate, but surgical treatment is inevitably associated with higher complications and surgical mortality; in contrast, after gamma knife treatment, although the rate of complete occlusion of AVMs is lower than that of the surgical treatment group, the greatest advantage is the low complications and the absence of fatal cases (Table 1).
Table 1 Comparison of the efficacy of AVM treatment
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Treatment method Number of cases Complete occlusion rate % Disability rate % Mortality rate
Gamma knife 2067 78.4 3.6 0
Microsurgery 2722 94.7 11.7 4.4
Vascular embolization 1085 3.3 8.8 1.5
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In addition to this, there is a protective effect on rebleeding in AVMs that are not completely occluded after gamma knife treatment: the Karlsson study found that for AVMs of small to medium volume, the risk of bleeding was significantly reduced after gamma knife treatment, even though the malformed vascular nest was not completely occluded.
The mechanisms underlying the protective effect of gamma knife treatment on bleeding in AVMs with incomplete occlusion are.
(i) Progressive thickening of the vessel wall, which decreases the pressure on the vessel wall and thus reduces the risk of bleeding.
(ii) Since the risk of bleeding is related to the volume of the AVM, partial occlusion of the AVM results in a natural reduction in volume, which has a protective effect against bleeding.
(iii) The formation of thrombus in the AVM reduces the number of recanalized vessels in the nest of the malformation and, according to the principle of randomization, the chance of bleeding.
(iv) The combined effect of the above factors reduces the blood flow through the AVM, thus reducing the risk of bleeding.
A large number of case follow-ups have confirmed that Gamma Knife treatment does not lead to an increase in the annual rebleeding rate after treatment.
Control of epilepsy: In patients with cerebral arteriovenous malformations in which epilepsy is the main clinical symptom, the rate of remission and control of epilepsy after Gamma Knife treatment varies from 19% to 85%. The rate of remission and control of epilepsy after treatment with Gamma Knife alone has been reported to be 62% to 80%.
Evaluation of vascular malformations prior to gamma knife treatment.
Size of the AVM: The size of the AVM can be described very visually in terms of maximum or mean diameter prior to surgery. Those with a mean diameter ≤ 2-2.5 cm or less are considered small AVMs; those with a mean diameter ≥ 5-6 cm or more are considered large or very large AVMs; and those in between are medium-sized AVMs. volume can be calculated precisely in the gamma knife treatment plan, and studies have found that the volume of the lesion is precisely the most important factor affecting the efficacy of gamma knife and the incidence of complications. Therefore, the size of the AVM is described by the volume of the target area, which is more suitable for pre-gamma knife assessment. AVMs with a volume of ≤2cm3 are defined as small AVMs, while AVMs with a volume of ≥2cm3 (2-50cm3, mean 5.8cm3 ) are considered medium-sized AVMs.
The site of AVM: The site of AVM directly affects the efficacy and complications. It can be divided into three major categories.
(i) Central type: AVMs located in the brainstem, thalamus, hypothalamus, basal ganglia, intraventricular or paraventricular, and corpus callosum.
(ii) Cerebellar and cerebellar earth type AVMs.
(iii) Peripheral type: AVMs at sites other than the above two types. the chance of complications is significantly higher in the central type than in the peripheral type.
Classification of AVM: For the purpose of gamma knife prognosis analysis, AVM is classified into cloudy, straight-through and mixed types on angiographic images. Cloudy AVM: supplied by fine arteries, the nests of malformed vessels are homogeneous and finely granular, and the draining veins do not appear on early angiography films. Straight-through AVM: Blood is supplied by thick arteries and enters the draining veins through the thicker straight-through malformation vessels, so the early draining veins are visible on the angiographic images. Hybrid AVM: usually larger in size, with features of both cloudy and straight-through AVMs. In MRI and CT images, AVMs can be divided into homogeneous and non-homogeneous types. Homogeneous AVMs appear as homogeneous streams of empty signals with clear boundaries on MRI, and 3D CT imaging shows that the vascular nests are composed of fine granular structures with clear boundaries. On the other hand, non-homogeneous AVM appears on MRI as a malformed vascular mass with irregular shape and inhomogeneous flow-space signal, which may be mixed with brain tissue and often with unclear borders.
The therapeutic effect after gamma knife treatment is much better for cloudy, homogeneous AVM than for straight-through and non-homogeneous AVM.
Timing of gamma knife treatment
Generally speaking, AVM should be treated as early as possible once it is detected, but patients with bleeding as the first symptom (about 67.8%) should take gamma knife treatment 1-3 months after bleeding. For AVM cases that remain after surgery or after hematoma removal only, gamma knife treatment should usually be considered after the complete disappearance of cerebral edema, normal structure reset, and systemic status stabilization. In cases of AVM that have been treated with embolization without complete occlusion, combined treatment with gamma knife should be arranged within 3 months after embolization treatment if possible to avoid the possibility of potential aberrant vessel recanalization.
Specific implementation of Gamma Knife treatment
Positioning method: The key to gamma knife treatment for AVM is the precise positioning of the entire vascular nest after the implementation of the appropriate dose of treatment. Determining the extent of the target area can be difficult because AVMs are usually irregular in shape, with the blood supplying arteries, malformed vascular nests and draining veins often mixed together and difficult to distinguish. Combining two or more localization methods can be of significant help. Localization methods include general angiography, digital subtraction angiography (DSA), CT and magnetic resonance angiography (MRA). However, the most commonly used is MRI localization. MRI has obvious superiority in determining the AVM site, size and relationship with adjacent important structures.
Treatment target area: Gamma knife treatment target area should be limited to the malformed vascular nest itself, and should not include the blood supply artery and drainage vein. On the one hand, the volume of the treatment target area is reduced, which is conducive to increasing the marginal treatment dose and accelerating the occlusion of the AVM vascular nest; on the other hand, since the blood supply artery and the draining vein are not completely included in the high-dose treatment range, less damage or premature occlusion is produced, reducing the incidence of complications.
Treatment complications: Complications following Gamma Knife treatment are mainly neurological signs and symptoms that newly appear or worsen due to radiation exposure of brain tissue. The incidence of gamma knife complications is relatively low and can range from 0% to 5%, with an average of 3.6%.
Prevention of complications: The occurrence of complications after Gamma Knife treatment is closely related to the site of AVM, previous history of radiation therapy and the dose used during treatment, and these factors should be fully considered and the following points should be noted: ① Strictly control the indications for treatment. In particular, for AVMs of central type or located in a large volume of functional area, a one-time full dose of irradiation should not be forced. A more prudent method is to choose the dose splitting or volume splitting method for treatment; it can also be treated by partial embolization first, and then combined with gamma knife treatment after the volume of AVM is reduced. ②Precise dose planning: good localization images with multi-target and small collimator combined irradiation techniques to minimize the amount of radiation to the surrounding brain tissue. ③Personalized and individualized treatment dose with the aim of achieving a complete occlusion rate of AVM of about 80% within 2 years after treatment; while keeping the incidence of radiation brain necrosis to less than 3%. ④ Regular review, early detection of complications, timely management.
Gamma knife efficacy-related factors.
1, edge dose dependence: the average treatment dose and the minimum edge treatment dose are directly related to whether the AVM is occluded after treatment, and the higher the average treatment dose and the average edge dose used, the higher the proportion of AVM occlusion. Flickinger found that marginal doses of 16 Gy, 18 Gy, and 20 Gy corresponded to occlusion rates of 70%, 80%, and 90%, respectively. Marginal doses higher than 12Gy and AVMs located deeper were significantly more likely to show irradiation-related imaging changes.
The larger the AVM, the longer the occlusion interval required. Even after 3 years or more after treatment, there is still a possibility of occlusion in treated AVMs.
The relationship between AVM volume and occlusion rate and marginal dose: The volume of AVM is inversely proportional to the occlusion rate and the minimum therapeutic marginal dose required after AVM treatment, that is, the larger the volume of AVM, the lower the occlusion rate and the lower the minimum therapeutic marginal dose required. Among these variables, the volume of the AVM is the determining factor for the treatment outcome.
4. K-factor related to AVM occlusion: Karlsson found that the minimum marginal dose required for treatment decreased as the volume of AVM increased in a study of occluded AVM cases. Further studies suggested that the volume of the AVM and the minimum marginal dose directly influenced the rate of occlusion. This effect is achieved by the variation of the K-factor: K-factor di minimum marginal dose x (AVM volume)1/3 . It can be seen that when the K-factor is ≥27, the occlusion rate of AVM can reach 80%; while when the K-factor is <27, the smaller the K-value is, the lower the occlusion rate is. Therefore, the appropriate minimum marginal treatment dose can be selected according to the volume of AVM before treatment in order to obtain a satisfactory treatment result.
5, AVM prognosis assessment score table: MayoClinic and Pittsburgh University established a score table for the assessment of radiosurgery treatment of AVM. The formula is: scoring value: 0.1*AVM volume size (cm3 ) + 0.02*patient age (years) + 0.3*AVM site (0 for frontal and temporal lobes; 1 for parietal and occipital lobes, ventricles, corpus callosum and cerebellum; 2 for basal ganglia, thalamus and brainstem). It was found that AVMs in patients with a scoring value ≤1.0 were completely occluded after treatment. In contrast, only 39% of AVMs with a score higher than 2 were completely occluded after radiosurgery.
6. Dose planning method for complex AVM: For small and medium-sized AVM, most of the radiosurgery treatment can obtain satisfactory results by one-time irradiation. However, for larger complex AVMs or AVMs located in important functional areas, a one-time high dose treatment may cause serious complications. Therefore, treatment can be performed by dose fractionation or volume fractionation.
(1) Dose splitting method: The so-called dose splitting method involves irradiating the entire AVM vascular nest during radiosurgery treatment, but the single marginal dose used is lower. The treatment is ultimately achieved by superimposing 2 or more doses. This method is mostly used for AVMs with a single group of vessels supplying blood, less voluminous AVMs, or AVMs surrounded by important structures that cannot tolerate larger doses of radiation. e.g., treatment of AVMs located in the brainstem, hypothalamus, basal ganglia region, and adjacent to the visual access road. There is no unanimous opinion on the interval between dose fractionation treatments, but most scholars believe that the interval between treatments should preferably be 6 to 12 months or more.
(2) Volume-splitting method: The so-called volume-splitting method is to divide AVM into several parts for fractional treatment, and each part is treated by selecting the corresponding marginal treatment dose according to the actual volume. This method is mostly used for the treatment of multiple groups of vascular blood supply, large volume or irregular morphology, and multiple AVMs. For larger AVMs with multiple vascular supply, the extent of target segmentation can be determined based on selective supply arteriography. In contrast, for AVMs with a single group of vascular supply, volume segmentation is more often performed according to morphological features. When volumetric segmentation is used, the interval period between two treatments should preferably be more than 3 to 6 months.
Efficacy assessment and follow-up.
1. Criteria for AVM occlusion:Whether AVM is completely occluded after radiosurgery treatment should be assessed based on follow-up cerebral angiography. The requirements for achieving complete occlusion should meet the following conditions: complete disappearance of AVM malformation vascular nests, retraction of dilated blood supply arteries and draining veins to normal diameter, and restoration of normal blood circulation time.
2. The status of DSA, CT and MRI in the follow-up after AVM treatment. Although DSA is an important tool to assess the efficacy of AVM after radiosurgery treatment, there are still treatment centers that have not used DSA as a routine follow-up examination method because it is an invasive examination method. Usually, DSA is used more often to screen for AVMs using other screening methods, and then DSA is used to finally confirm the treatment results after estimating that the AVM is completely occluded. For AVMs that are still suspected to be residual more than 2-3 years after treatment, DSA is still an important reference value for confirming the site, size, source of the blood supplying artery, direction of the draining venous return and relationship with adjacent important structures of the residual malformed vascular nest.
CT and MRI still play an important role in the post-treatment follow-up of AVM. On the one hand, this is because CT and MRI are non-invasive and can be performed repeatedly; on the other hand, after years of comparative studies, scholars now believe that it is possible to rely on CT and MRI findings to determine whether the AVM is completely occluded without further confirmation by DSA. On the other hand, after years of comparative studies, it is now believed that we can rely on CT and MRI to determine whether AVM is completely occluded, without the need for DSA. The distended blood supply arteries and draining veins also returned to normal diameter.