The target of brain AVM treatment is to eliminate the risk of bleeding. This target could be achieved by complete occlusion of AVM. Various options are available (embolization, surgery, and radiosurgery) either alone or in combination. Embolization usually used as the first step in treatment plan, but in two different strategies. In the first strategy, the target is to achieve occlusion as much as possible before thinking in other options. The second strategy is to use embolization to prepare the patient to other modality of treatment. In the current study, we used the first strategy whenever possible.
A recent meta-analysis showed that the average cure rate for all NBCA-used studies was 13.7%. The cure rate increased to 24% in a subgroup analysis (387 patients) for studies conducted after the year 2000 (Elsenousi et al. 2016). Valavanis and Yaşargil (1998) embolized 7.7 feeders per AVM using NBCA with a cure rate of 40%. On the other hand, ethylene-vinyl alcohol copolymer (EVOH) (Onyx; eV3-Covedien, Irvine, California, USA) average cure rate was 30.5% in all studies, and 30.1% in the studies that did not use detachable microcatheters (Elsenousi et al. 2016a). The BRAVO trial was a European prospective multicenter trial to assess the safety and efficacy of Onyx. It showed 23.5% complete occlusion rate using onyx (Pierot et al. 2013b). Meanwhile, the range of complete occlusion rates in published case series was 8.3–53.9% (Pierot et al. 2013b). In the current study, complete occlusion was achieved in 9 patients (42.9%), this cure rate is similar to the previously quieted figures, and this high cure rate could be explained by the prior intention to completely occlude the lesion whenever possible, the use of Oynx with detachable tip catheters which permit longer injection time, and the use of staged approach. With case selection, van Rooij et al. (2012) reported achievement of cure for all the selected patient (24 patients) using Onyx without morbidity or mortality; also, de Castro-Afonso et al. (2016) reported (91.3%) cure rate in their selected AVM pediatric patients (23 patients) with (13%, 3 patients) procedure-related complications, yet without significant morbidity or mortality.
A new trend of embolization of brain AVMs with intent to angiographic cure was noticed. In some centers, curative embolization is offered to selected patients (van Rooij et al. 2012; de Castro-Afonso et al. 2016). This trend was encouraged by the expansion of the use of Onyx. This was reflected by higher cure rates of onyx compared with glue, but this was claimed to be associated with worse neurological outcomes. On the other hand, NBCA showed higher cure rates with time also, but without increase in poor neurological outcome. The assumption that the introduction of detachable microcatheter was associated with better neurological outcome was not supported by the results of meta-analysis. This may be explained by the fact that the use of the detachable microcatheters was associated with more aggressive Onyx embolization that may lead to venous occlusion and hemorrhagic complications (Elsenousi et al. 2016). It seems that the results of meta-analysis in this area should not be generalized, as it depends on operator experience which is variable, and cautious slow controlled injections that avoid the draining veins can minimize the procedural risk even in eloquent locations with longer injection time especially with the use of detachable tip microcatheters.
A meta-analysis showed that poor neurological outcomes for glue and Onyx embolization were 5.2 and 6.8%, respectively. When the results for patients embolized with Onyx using detachable catheters were excluded, poor outcome associated with Onyx embolization increased to 7.1% (Elsenousi et al. 2016). The BRAVO trial showed that Onyx embolization is associated with 4.3% mortality and 5.1% morbidity (Pierot et al. 2013b). The range of hemorrhagic complication in published case series was 4.0–12.2% while the range of mortality and morbidity was 0.0–3.2 and 3.5–15.5%, respectively (Pierot et al. 2013b). In the current study, early hemorrhage occurred in 3 sessions out of 43 sessions (7.0%) for 2 patients (9.5%). Only 2 patients (9.5%) were at grade 3 mRS at discharge (one of them was already on grade 3 on admission) which goes in line with the previously published data.
In our series, 17 AVMs (80.9%) were classified as high bleeding risk lesions. Thirteen AVMs (61.9%) were < 3 cm in size, 5 AVMs (23.8%) had deep venous drainage (not-exclusive), and 4 AVMs (19.0%) were associated with venous aneurysms. Crawford et al. (1986) described that 7% of the AVMs were associated with aneurysms and 75% of these aneurysms located on the major feeder vessels. AVM-associated aneurysms tend to present 10 years later than AVMs (Ondra et al. 1990). D’Aliberti et al. in their series found that the different types of AVM-associated aneurysms had different bleeding risk. The bleeding risk of the unrelated type and the remote flow-related type should be considered almost the same as any else unruptured aneurysm, where the INSUIA parameters were applicable. On the other hand, the adjacent flow-related type and the venous type carried higher bleeding risk (D’Aliberti et al. 2015). Choi et al. (2005) had suggested that AVMs with deep or infratentorial location, single or few draining veins, venous stenosis, and intranidal aneurysms may had increased risk of bleeding. Guo et al. (1995) found that small AVMs (< 3 cm) carried higher risk of bleeding. Meanwhile, deep venous drainage was found to be independent risk factor for AVM bleeding (Stapf et al. 2006). Although infratentorial AVM in adults account for only 7 to 15% of all brain AVMs, it was found to be an independent risk factor for bleeding; the bleeding rates were high up to 92% (Arnaout et al. 2009; Khaw et al. 2004; Westphal and Grzyska 2000).
The average age at presentation in this study was 34 years, which was in keeping with the previously quoted figure of 33 years (Ondra et al. 1990). In a recent meta-analysis for the outcome of embolization of cerebral AVMs, the mean for patients’ age was 35.8 and 35 years in the glue and Onyx groups, respectively (Elsenousi et al. 2016). AVMs were known to show male predominance, which went in the same direction with the current study findings [13 patients (61.9%) were males] (Ondra et al. 1990).
In the current series, 15 patients (71.4%) had a history of intracranial hemorrhage, 10 patients (47.6%) had a history of seizures, and 4 patients (19.0%) were complaining of chronic headache. In a meta-analysis, hemorrhage was the presenting symptom in 47% of patients in the glue and 41.5% of patients in the Onyx group. Epileptic seizures were the presenting symptom in 28% of the glue group and in 33% of the Onyx group (Elsenousi et al. 2016). Hemorrhagic presentation accounted for 50–61% of cases (Drake 1979; Perret and Nishioka 1966). AVM bleeding was associated with neurological deficit in 30–50% of cases only (Hetts et al. 2014). The high rate of bleeding as a presenting event in our series could be explained by the fact that 17 AVMs (80.9%) were classified as high bleeding risk lesions or due to small size of the sample. An association between age and the incidence of seizures was described by Crawford et al. (1986), with a seizure risk 44% in patients aged 10–19 years, 31% in patients aged 20–29 years, and 6% risk in patients aged 30–60 years.
Interventional treatment of AVMs is generally accepted; the annual risk of bleeding is 2–4%, which occurs over time, with high lifetime risk of bleeding that can result in morbidity or mortality (Young et al. 2015). The ARUBA (a randomized trial for unruptured brain arteriovenous malformation) has challenged this concept. The study concluded that medical treatment alone is better than interventional options, for prevention of stroke or death in patients with unruptured brain AVMs (Mohr et al. 2014). Despite the importance of the study, criticism to its design and follow-up duration undermined the value of its conclusion (Russin and Spetzler 2014). The poor outcome in the intervention arm of ARUBA trial is 30%, which is much higher than what was reported in a meta-analysis (5.2% for NBCA and 6.8% for EVOH) (Elsenousi et al. 2016); on the other hand, this poor outcome is also higher than the published rates of poor outcome for surgical resection of AVMs (0.34–2.2% in grades I–II) (Spetzler and Martin 1986; 2013). It was not clear how much of the poor outcome was related to surgical resection, embolization, or delayed hemorrhage from partially embolized AVM. On the other hand, a curative embolization with Onyx with high cure rates as recently published (van Rooij et al. 2012; de Castro-Afonso et al. 2016) that was associated with low morbidity and mortality (< 10%) may serve as a good treatment option. A low complication rate (< 10%) is lower than the complication rate of the medical arm of the ARUBA trial (Mohr et al. 2014). Six patients (28.57%) in our case series had unruptured AVM. Embolization treatment was considered for these cases due to the presence of high bleeding risk criteria of these AVMs.
In the current study, we used the staged approach in AVMs with multiple feeders. Despite that the value of this approach was debated, we thought it was associated with less hemorrhagic complications (Mounayer et al. 2007). This approach allowed smooth normalization of hemodynamics and prevented extensive venous thrombosis. The use of NBCA (glue) was limited to high flow fistulas in 4 patients (19.0%), where we thought it was more simple and effective method.
We compared between patients who achieved angiographic cure and patients who had partial occlusion. The comparison included the site, the total number of feeders, the size, the presence in eloquent site, and the presence of deep venous drainage. Only the presence of AVM in eloquent site was significantly associated with partial occlusion. This finding was logic, but we thought that larger sample size of study was needed to identify more factors that were associated with angiographic cure.
We think that curative embolization should be offered for selected cases based on certain criteria that need further research. For the cases that are not fulfilling these criteria, embolization should be offered as preparing step for other modality of treatment. For curative embolization, the AVM should be small sized (< 3 cm), supplied by one vascular territory, with feeders that can tolerate reflux up to 2–3 cm, with clear proximal parts of the draining veins, and not located in deep structure or brain stem (van Rooij et al. 2012).
