Brain arteriovenous malformations are rare vascular lesions with the presentation of hemorrhagic stroke, seizure, headache, and focal neurological deficit [6]. Despite the incidence was scarcity, bAVMs account for the majority of spontaneous intracranial hemorrhage in children and young adults [7]. The SM grading system is widely used to estimate the risk of postoperative complications [8]. Generally, for ruptured bAVMs, intervention was recommended regardless of grade. However, the management of unruptured bAVMs was still controversial. To summarize the current status and experiences of the treatment of bAVMs in mainland China, we conducted a web-based nationwide questionnaire survey among 49 tertiary neurosurgical institutions (63 participants) including microsurgery, embolization, and radiosurgery.
Although ARUBA indicated negative outcomes of intervention than conservative management in unruptured bAVMs [2], all participants in this study still support intervention for specific selected bAVMs. The main criticisms of the ARUBA trial included insufficient follow-up period (33 months), heterogeneity and uneven distribution between treatment modalities, low obliteration rate, small sample size, and unusual high incidence of post-interventional complication [9]. These deficiencies make ARUBA’s findings cannot be recognized as the first-line evidence to select conservative management or intervention of all unruptured bAVMs. Previous studies proposed that elevations of vascular endothelial growth factor (VEGF) or alterations in the vascular wall [10] and many hemodynamic changes, such as flow-related aneurysms [11], abnormally high blood flow through shunting [12], smaller bAVMs, a single and/or stenosed draining vein, and so on [13], may contribute to bAVMs rupture. In this study, the hemorrhagic hemodynamic factors were similar to previous studies, which means that most of the participants in mainland China share the same view on the hemorrhagic risk factors.
Interventional indications and contraindications
Two recent completed randomized clinical trials or prospective registries (ARUBA and SAIVM) suggested that the risk of intervention may outweigh the risk of future rupture for unruptured bAVMs [2, 14]. Therefore, the selection of interventional indications has become more cautious clinically, especially in unruptured patients. Generally, SM grades IV–V bAVMs are recommended to observed unless ruptured [15]. However, previous studies calculated an average rate of 15% for persisting disability and a risk of 15% death after bAVMs hemorrhage [16]. The outcomes of the hemorrhage were a permanent downgrade in function to an mRS score > 1 in 88% and an mRS score > 2 in 69% [3]. Therefore, for patients with hemorrhagic risk factors and younger age, more aggressive treatment might be recommended because of the high cumulative subsequent rupture risk [3, 16].
The ARUBA trial did not include giant bAVMs, and it is still controversial whether the intervention can benefit giant bAVMs in other previous studies [2]. Yang et al. indicated that interventions for giant bAVMs should be considered cautiously because the hemorrhagic risk is similar and functional outcomes may be better in the conservatively managed population [17]. In contrast, Chang et al. proposed that selected symptomatic patients with giant bAVMs can be treated successfully with good outcomes and acceptable risk [18]. Recently, Reinard et al. found that good outcomes are attainable with a multimodal treatment approach in carefully selected patients with giant bAVMs [19]. Besides, further study indicated that radiosurgery after microsurgery or embolization might be the most advantageous strategy [20]. In this study, most participants considered that intervention for giant bAVMs was desirable, and multi-modality strategy was more preferred, especially in patients with hemorrhagic risk factors.
Only adult bAVMs were included in the ARUBA trial [2]. However, due to the long life expectancy, the high cumulative lifelong hemorrhagic risk and better neural plasticity of pediatric bAVMs, the ARUBA conclusion that medical management alone has a better prognosis may not apply to pediatric bAVMs. In fact, pediatric bAVMs were often treated more aggressively than adults [21]. Minimum trauma and maximum occlusion were the intervention principle for pediatric bAVMs [22]. Similar to giant bAVMs, multi-modality strategy was more preferred for pediatric bAVMs in this study. On the other hand, another special population corresponding to pediatric bAVMs is elderly bAVMs (> 65). Nowadays, whether elderly bAVMs should undergo intervention treatment is still controversial. Many previous studies proposed that elderly bAVMs were interventional contraindication, because only a life expectancy over 20 years could be a prerequisite for treatment [20], and the risk of treatment can outweigh the risk of bleeding. However, Pabaney et al. proposed surgical management of elderly bAVMs can result in complete obliteration and acceptable clinical outcomes, with an overall mortality rate of 3.6% and an obliteration rate of 87% [23]. In this study, most participants agreed that elderly patients should receive intervention management, but more minimally invasive and lower risk strategies were recommended, such as partial occlusion of hemorrhagic risk factors.
Eloquence has always been considered to be closely related to the postoperative neurological outcomes. No matter in the SM Grade Scale [8], or the Lawton-Young Grade Scale [24], or the new prediction scale of postoperative neurofunctional deficit-HDVL Grade Scale [25], eloquence is the key evaluation criteria. Generally, limited visual deficit and mild aphasia were acceptable because of the small impact on the quality of life [20], and bAVMs in the deep location or central motor cortex were considered as surgical contraindication [26, 27]. Lesion-to-eloquence distance (LED) < 4.95 mm was indicated as an independent predictor for postoperative neurofunctional deficits [25]. Target embolization for hemorrhagic risk factors was considered feasible in eloquent bAVMs by neurointerventists because of the less risk of postoperative neurofunctional deficits and effective reduction of subsequent hemorrhagic risk [28]. Besides, most previous studies suggested that radiosurgery has unique advantages for eloquent bAVMs, especially in small to moderate-sized and compact nidus [29].
Giant bAVMs, pediatric bAVMs, elderly bAVMs, and eloquent bAVMs are relatively rare in the overall bAVMs population. The current studies are all retrospective studies based on a small sample size, which cannot provide high-level management evidence for such patients. Further multi-center randomized controlled trials with larger sample size are needed for this particular bAVMs.
Current single-modality and multi-modality strategies
Available treatment strategies for bAVMs currently include medical management, microsurgical resection, endovascular embolization, stereotactic radiosurgery, or combination thereof. However, there is still no consensus on the timing of intervention for ruptured bAVMs. Ahmad et al. found that the time interval between AVM bleeding and surgery did not influence early or late outcomes [30]. Martinez et al. recommended a delayed intervention for at least 4 weeks after the initial hemorrhage. In contrast, Deng et al. proposed that short-term outcomes of the early intervention were better, though the long-term outcomes were similar [31]. In this study, most of the neurosurgeons and neurointerventionists recommended early intervention (< 30 days) for ruptured bAVMs; however, the radiosurgeons suggested intervention in the chronic phase or recovery phase and preferably 3 months after bleeding. Therefore, we speculated that different intervention strategies may have different optimal intervention window periods for ruptured bAVMs.
Microsurgical resection is currently considered as the first-line strategy for low-level (SM grades I–II) and superficial lesions because of the highest rates of complete cure with an acceptable safety profile [32], especially in emergency patients [33]. However, previous studies reported that the risk of a serious neurologic deficit increases dramatically for SM grades III and IV/V bAVMs to 17% and 45% [3, 32], respectively. Curative embolization of bAVMs is difficult to achieved, and previous studies have suggested that > 25% embolization in a single session might be associated with an increased risk of perioperative complications [34]. Recently, target embolization of discrete hemorrhagic risk factors was indicated that embolization of nidal or perinidal aneurysms can reduce recurrent hemorrhage within the first year following initial hemorrhage [28, 35], and transvenous embolization of selected bAVMs could achieve high angiographic obliteration rate [36]. Radiosurgery causes denaturation of endothelial cells and proliferation of vascular smooth muscle by radiation, which blocks or compresses the vascular lumen [37]. But the increased hemorrhagic risk between treatment-occlusion interval and radiation-induced complications (RICs) may limit the application of radiosurgery [38].
Multi-modality strategies are often recommended for complex bAVMs. Generally, embolization is usually used as an adjunct therapy to reduce a bAVM’s volume before radiosurgery or reduce the nidus blood flow before resection at present [39, 40]. However, the increased hemodynamic stress in the remain lesions after invasive treatment for partial nidus may induce an increased hemorrhagic risk in the treatment interval [41], and pre-radiosurgery embolization has been demonstrated that may cause the lesions divided into distinct compartments, finally inducing a negative impact on obliteration [42]. Single-stage combined embolization and microsurgery in the hybrid angio-surgical operating room might an efficient strategy for complex bAVMs to reduce the complications in the treatment interval and detect the residual lesions in time [43, 44]. In this study, we found that for the same type of bAVMs, the optimal intervention strategy proposed by different subspecialty departments often differ. Therefore, further studies are required to organize multicenter international trials to explore the most optimal and individualized intervention strategies for bAVMs.
Several potential limitations of this study should be noted. Firstly, this is a web-based questionnaire survey that prevents all participants from having in-depth discussions face-to-face. Secondly, the uneven proportion of doctors in the three departments may lead to deviations in the conclusions. Thirdly, there may be inconsistent opinions due to different economic conditions and technological capabilities in each region. However, this study still reflects the current experience and diagnosis and treatment of bAVMs in most parts of mainland China.
