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Effectiveness of Preradiosurgical Embolization with NBCA for Arteriovenous Malformations - Retrospective Outcome Analysis in a Japanese Registry of 73 Patients (J-REAL study)

Article information

Neurointervention. 2017;12(2):100-109
Publication date (electronic) : 2017 September 05
doi : https://doi.org/10.5469/neuroint.2017.12.2.100
1Neuroendovascular Therapy Center, Aichi Medical University, Nagakute, Japan.
2Department of Neurosurgery and Endovascular Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
3Department of Neurosurgery, National Cerebral and Cardiovascular Center, Suita, Japan.
4Department of Neurosurgery, Tokai University Hospital, Isehara, Japan.
5Department of Neuroendovascular Therapy, Kohnan Hospital, Sendai, Japan.
6Department of Neurosurgery, Showa University Fujigaoka Hospital, Yokohama, Japan.
7Department of Neurosurgery, University of Tsukuba Hospital, Tsukuba, Japan.
8Department of Radiology, Oita University Hospital, Oita, Japan.
Correspondence to: Shigeru Miyachi, MD, PhD, Department of Neurosurgery and Neuroendovascular Therapy, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, 480-1195 Aichi, Japan. Tel. +81-561-62-3311, Fax. +81-561-63-2879, miyachi.shigeru.752@mail.aichi-med-u.ac.jp
Received 2017 July 20; Revised 2017 August 02; Accepted 2017 August 10.



Recent reports have posed doubts about the effect of preradiosurgical embolization in brain arteriovenous malformation (AVM) because it makes the planning of stereotactic radiosurgery (SRS) difficult and has the risk of recanalization out of the target. We investigated whether the performance and quality of embolization may influence the success of SRS based on a retrospective case cohort study.

Materials and Methods

Seventy-three patients who underwent embolization followed by SRS between 2003 and 2012 in eight institutes with neurointerventionists were considered. They were divided into the following two groups at 3 years of follow up after the final SRS: “successful occlusion group” (S group), with radiologically complete occlusion of AVM; and “non-successful occlusion group” (N group) with persistent remnant nidus or abnormal vascular networks. Patient background, AVM profile, embolization performance grade and complications were compared in each group. The quality of embolization was evaluated with the new grading system: embolization performance grade (E grade), specializing the achievement of nidus embolization. E grade A was defined as sufficient nidus embolization with more than half of the total number of feeders achieving nidus penetration. E grade B was defined as less than half achievement of nidus embolization, and E grade C was defines as failure to perform nidus embolization.


Forty-three patients were included in the S group, and 29 patients were included in the N group. The size and Spetzler-Martin grade of AVM and the rate of diffuse type was higher in the N group without statistical significance. The embolization performance level according to E grade indicated a significantly higher rate of successful embolization with more than 50% of nidus penetration in the S group (P<0.001). This difference was also confirmed in the subanalysis for limited cases, excluding smaller AVMs with complete occlusion with SRS alone (P=0.001).


The cause of the unsuccessful result of post-embolization SRS might be the large, diffuse angioarchitecture, but proper embolization with a high rate of nidus penetration to avoid recanalization is more important. Effective embolization is essential to contribute to and promote the effect of radiosurgery.

Preradiosurgical embolization of cerebral arteriovenous malformations (AVMs) has been warranted as a signif icant treatment to eliminate the risk of hemorrhage during the latency period after radiosurgical treatment, and to achieve AVM volume reduction to a size amenable to radiosurgical treatment, resulting in earlier obstruction [12]. The treatment of inappropriate factors, such as flow-related aneurysms, is warranted because proximal and pedicular aneurysms and intranidal aneurysms have a 7% to 10% annual risk of hemorrhage [34].

However, embolization has recently been criticized as a useless option for radiosurgery because embolization decreases the obliteration rates after stereotactic radiosurgery (SRS) compared with radiosurgical treatment alone [5]. Recanalization of embolized feeder after RS is seen in 5–7% of patients, and some reports question the efficacy of embolization [67891011121314]. The recanalization or vascular remodeling of remaining feeders tends to occur in cases with incomplete nidus embolization and far proximal feeder occlusion [1516]. For this reason, radiosurgeons may struggle to plan the interested area because the part with pretended obstruction after embolization with a risk of late recanalization is outside the target. By contrast, proper nidus embolization will prevent recanalization [27] and can contribute to achieving a preferable result from SRS.

In Japan, where there are a large number of Gamma Knife centers, the treatment option with SRS following embolization has a comparatively higher rate among the combined therapeutic modalities [17], and this difference affects the rate of favorable results. This multicenter study, J-REAL (Japanese registry of Radiosurgery following Embolization for Arteriovenous maLformations), is a retrospective analysis of the selected AVM cases treated with SRS following embolization that was planned to clarify the efficacy of embolization and address the discrepancy in the results between Japan and western countries.


Outline of the study

A retrospective review of AVMs treated between 2003 and 2012 with embolization followed by SRS was performed. The data were harvested from institutes, enrolling experienced neurointerventionists who had proper and secure strategies for the endovascular treatment of AVM. The clinical materials were AVMs with a maximum diameter of more than 1 cm in patients older than 6 years of age. Patients who underwent SRS or direct surgery before embolization, except for emergency ventricular drainage, were excluded. All AVMs were embolized with NBCA mixture in one or staged sessions, and no cases with Onyx embolization were included. The SRS tool was a Gamma Knife in all cases. Patients treated with other methods, such as LINAC and X knife, were excluded. The timing of SRS was specified as within 6 months after the final embolization, and the decision of the marginal dose and targeting area was based on the guidelines of each Gamma Knife center. The operators of endovascular treatment were senior board experts trained by the Japanese society of neuroendovascular therapy with experience in more than 20 cases of AVM embolization. Similarly, the operators of the Gamma Knife were required to have experience with more than 50 radiosurgery cases for AVM.

The performance of endovascular treatment was impartially judged by multiple neurointerventionists, and the final image judgment was performed by the experienced multiple radiosurgeons 3 years after the final radiosurgery. This study was approved of the local institutional review board.

Clinical data

We investigated patent profile including gender, age, clinical manifestation, undergone initial treatment and general complications, and AVM profile including location, Spetzler-Martin grade[18], maximum diameter; volume, modified radiosurgery-based arteriovenous malformation score (mRBAS)[19] and angioarchitecture including nidus type$, daughter nidus, draining pattern, varix, associated aneurysm, and meningeal feeders. AVM volumes were calculated from a 3-dimensional angiogram after determination of the radius (r) on three orthogonal planes using the formula for an ellipsoid (4πr1×r2×r3/3). mRBAS were determined by the following equation: AVM score = (0.1×volume in cm3) + (0.02×age in years) + (0.5×location). The location values are as follows: frontal/temporal/parietal/occipital/intraventricular/corp us callosum/cerebellar = 0, and basal ganglia/thalamus/brainstem = 1. Nidus type was categorized into compact type and diffuse type. Compact type was defined as AVM with clearly demarcated nidus without daughter ones. While, diffuse type was defined as AVM with abnormal vessel dilatation or a non-shunting abnormal vascular network surrounding the nidus, particularly expressed at the watershed area between different perfusion territories.

Performance of the treatment

A. Performance of embolization

Data were collected for the total number of accessible / inaccessible feeders, successful / incomplete occlusion of f istulous feeders, and successful / unsuccessful nidus penetration as proximal feeder occlusion alone. The achievement level of embolization was defined in the newly provided categorization, embolization performance grade (E-grade), to exclude the operator's subjective preference (Table 1). E grade A was defined as sufficient nidus embolization with more than 50% of total number of feeders achieving nidus penetration. E grade B was defined as less than 50% achievement of nidus embolization, and E grade C was defines as failure to perform nidus embolization due to a lack of access, technical error or fistulous AVM with no nidus components. Grades A and B were subdivided according to the components and treatment of fistulous feeders. The final embolization rate was calculated as the result of the three-dimensional volume reduction of the nidus. The size of the remaining nidus after embolization was expressed as the maximum diameter of the residual nidus. Procedure-related or perioperative complications associated with embolization and the neurological deterioration due to the complications were registered.

Classification of the Grade of Embolization Performance (E Grade)

B. Performance of radiosurgery

The effect of SRS was evaluated at 2 years after the first operation. The post-SRS radiological evaluation was performed using the original grading system (SRS-grade). Patients with complete occlusion of AVM in the f inal angiogram were classif ied as SRS grade A. Patients who had a fine abnormal vascular network without AV shunt remaining in the site of the nidus were classif ied as SRS grade B, and those with a remaining nidus with obvious AV shunt were classified as SRS grade C. Other information concerning the radiosurgery, including the duration between embolization and SRS; major adverse events after the radiosurgery, such as rupture or delayed complications; and the final clinical outcome were registered.

Statistical analysis

Patients with SRS grade A were categorized as the “successful occlusion group” (S group), and the patients in SRS grades B and C were categorized as the “non-successful occlusion group” (N group). These two groups were compared in terms of patient background, AVM profile and embolization performance. As a sub-analysis, SRS grade-B patients were independently studied to determine differences from SRS grade-C patients. The statistical analysis of categorical variables was performed using the χ2 and Fisher exact tests. The comparison of means was performed using Student's t-test, and an analysis of variance (ANOVA) followed by Bonferroni post hoc testing was performed, as appropriate. Predictive factors in the univariate analysis concerning size and embolization specif ication were entered into a multivariate logistic regression analysis using a stepwise method. The percentage of incidence and 95% confidence intervals (CI) were calculated for all considered variables and results. P-values <0.05 were considered to indicate significance.


Patient profile

A total of 73 patients met the inclusion criteria and underwent embolization followed by SRS during the study period (Table 2). There were 40 males and 33 females ranging from 6–78 years old with a mean age of 35.8 years. Of the 30 unruptured AVMs, the clinical manifestations were asymptomatic in 10, convulsion in 10, headache in five, and focal neurological deficits including cognitive and psychological function deficits in five. Of 43 patients with ruptured AVMs, 20 patients had intracerebral hemorrhage, 16 had intraventricular hemorrhage, and seven had subarachnoid hemorrhage. The initial treatments before embolization were medication for seizure, intracranial pressure control, and vital stabilization in 23 patients, as well as ventricular drainage in four patients. Precedent general complications were recognized in 4 patients and neurological deficits before treatment were observed in 18 patients, including mild deficits (mRS 1) in 9 patients, middle (mRS 2) in 3 patients and severe (mRS 4) in 6 patients.

Patient Profile

AVM profile

The AVM profile is summarized in Table 3. Of the AVMs, the location was frontal in 20, temporal in 8, parietal in 10, occipital in 11, cerebellum in 16, thalamostriate in three and brain stem in four. Large AVMs extending over multiple areas were sorted according to the area containing of the largest part. For the Spetzler-Martin grade, there were nine AVMs in grade 1, 17 in grade 2, 32 in grade 4 and one in grade 5. The preoperative mean maximum diameter was 31.6 mm (range 11–72 mm) and the mean volume was 13.8 ml (range 1–46 ml). The distribution of the volume was less than 5 ml in 24 AVMs, 6–10 ml in 15 AVMs, 11–20 ml in 13 AVMs, 21–30 ml in 10 AVMs, 31–40 ml in 9 AVMs and more than 40 ml in 2 AVMs. The median mRBAS before embolization was 2.13, and the distribution of AVMs in mRBASs was as follows: ≤ 1.00 in 14, 1.01–1.50 in 11, 1.51–2.00 in 16 and >2.00 in 31.

AVM Profile

Regarding the angioarchitecture of the AVMs, 52 were classified as compacted types and 21 were classified as diffuse types; a daughter nidus was observed in five AVMs. The draining pattern of the AVMs was as follows: single superficial drainage in 18, single deep drainage in 11, multiple superficial drainage in 32 and multiple deep drainage in 12. The cases with both superficial and deep drainers were classified to the category of the main drainage side. Varices on the drainers were observed in six AVMs. Associated aneurysms were found in 22 AVMs, including 13 proximal feeder aneurysms, 3 flow-related aneurysms and 6 intranidal aneurysms. Of these, 12 aneurysms were treated with embolization in addition to the embolization for AVM. Seventeen AVMs were also supplied by meningeal feeders, and 9 of these were embolized in a manner similar to that use for AVMs supplied by pial feeders.

Performance of embolization

According to our embolization grading system, the AVMs were distributed in grades as follows: 12 in E-Grade A1, 20 in E-Grade A2, 19 in E-Grade B1, 18 in E-Grade B2 and two in E-Grade C (Table 4). The mean final volume reduction rate was 61.2%. The maximum diameter of the remaining nidus was almost zero in 7 AVMs, <1 cm in 22 AVMs, 1–2 cm in 24 AVMs, 2–3 cm in 13 AVMs, and ≥ 3 cm in 7 AVMs. Perioperative complications occurred in 14 patients, including perioperative or delayed hemorrhage in eight patients, postoperative convulsion in two patients, and other minor complications in four patients. Of these, two patients had neurological deterioration with score changes of ≥ 2 on the modified Rankin Scale.

Performance of Embolization

Performance of radiosurgery

The AVMs classified by SRS grade as follows: 44 in SRS-grade A, 18 in SRS-Grade B and 11 in SRS-Grade C (Table 5). The median duration between final embolization and SRS was 1.9 months. Delayed adverse events occurred in 4 patients, including hemorrhage in three patients and cyst formation in one patient. Of these, two patients presented with neurological deterioration and a score change of ≥ 2 on the modified Rankin Scale.

Performance of Radiosurgery

Comparison of profiles by SRS grade

The data of patients and AVM profiles were compared between the S and N groups (Tables 2 and 3). For patient prof iles, there was no difference between the two groups in terms of age distribution, clinical manifestation, and initial treatment methods. While the dominancy of gender is different between S group (female: 16/44 (36%)) and N group (17/29 (59%)) with female dominancy, in particular significantly different between S group and SRS grade C (9/11(82%)) with female dominancy (P=0.015).

For the clinical manifestation, initial treatments and preceding neurological deficits, there were no significant differences between the two groups. The AVM location and Spetzler-Martin Grade showed no deviation and had a similar distribution in both groups. The sizes of the AVMs also had a similar distribution. However, the mean maximum diameter (SRS-grade A: 28.7 mm, B: 32.9 mm, C: 40.7 mm) showed no significant difference between the SRS-grade A and B groups, but they were significantly larger in the SRS-grade C group than group A (P=0.013). The mean initial volume (SRS-grade A: 12.0 ml, B:12.4 ml, C: 23.5 ml) showed similar tendency and signif icant difference between Grade A and C groups (P=0.004). The mean mRBAS (SRS-grade A: 2.01, B: 1.94, C: 2.97) was also significantly higher in SRS-Grade C AVMs (P<0.001)

Regarding angioarchitecture, a diffuse type of nidus was significantly more frequent in the N group (14/29 (48%), P=0.004), particularly in Grade C AVMs (8/11 (73%), P<0.001), than the S group (7/44 (16%)). Multiple drainers were significantly more frequent in the N group (22/29 (76%)) than the S group (22/44 (50%) (P=0.031). The presence of a daughter nidus, associated aneurysm and varix were not different among the groups. The supply from the meningeal feeder (S group: 6/44 (14%), N group:11/29 (38%) ) was significantly frequent in the N group (P=0.023).

Comparison of embolization performance by SRS grade

Table 4 shows the comparison of embolization performance by SRS grade. The E grade groups were divided into two groups by the rate of successful nidus embolization; one was the successful embolization group, including E grades A1 and A2 (n=32); and the other was the unsuccessful group, including E grades B1, B2 and C (n=41). In the former group, SRS grade A was achieved in 30 patients (94%), while in the latter, SRS grade A was achieved in only 14 patients (34%). There was a significant difference between the two groups (P<0.001). Because a small AVM has more potential for complete occlusion after SRS without the aid of embolization, subanalysis was performed to target the relatively larger AVMs (n=43; S group: 21 (49%), N group: 22 (51%)), excluding AVMs less than 3 cm in diameter. These results also showed a significant difference between small and larger AVMs (P<0.001). The size of the remaining nidus, one of the main factors defining the marginal dose of radiosurgery, was compared between the S and N groups. Remaining nidus was observed following embolization in 67 AVMs (S group: 38/44 (86%), N group: 28/29 (97%)). The comparison was performed between two groups that had a maximum remaining nidus diameter of more and less than 2 cm. A smaller remaining nidus (less than 2 cm in maximum residual nidus diameter) was seen in 22 cases (50%) in the S group but was seen in only 7 cases (24%) in the N group. There were signif icant differences in this analysis (P=0.03), and the subanalysis in the 43 cases of larger AVMs excluding AVMs less than 3 cm in maximum diameter also demonstrated a difference (P=0.05).

When we performed another subanalysis with another categorization, SRS-group A +B vs. group C, there was a significant difference in the rate of successful embolization (P<0.002). There was no significant difference in the rate of procedure related complications (S group: 7/44 (16%), N group 7/29 (24%)) and the rate of morbidity between the two groups. Post-radiosurgery complications were not encountered in the S group and signif icantly higher in the N group (4/29(14%) (P=0.022)

Multivariate analysis between the size and embolization specification

We performed a selective multivariate study focusing on AVM size and embolization specif ication. As important factors corresponding to either the S or N group, the mRBAS, nidus type, embolization grade and residual nidus size were selected and analyzed. Of these four factors, a significant difference was obtained in the nidus type (odds ratio 0.261, 95% CI: 0.073–0.938, P=0.04) and embolization grade (odds ratio = 4.397, 95% CI 2.113–9.149, P<0.001).


There have been many reports supporting the usefulness of embolization preceding surgical removal and SRS, which can make the subsequent treatment easier, safer and more successful [1234516]. By contrast, recent reports addressed the negative effect of preradiosurgical embolization. Embolization prior to SRS was associated with a lower rate of total obliteration than radiosurgery alone [1214] and had no sufficient role in reducing the recurrence correlated with deep regions [10]. The main reasons for such a result might include the followings: 1) the embolization blurs the nidus margin and causes a targeting error, 2) a part of the nidus that disappears just after the proximal feeder occlusion due to the temporary flow regression is outside of the radiosurgery target and may later recanalize due to hemodynamic remodeling [111213142021].

For the adverse events secondary to the radiosurgery, the rate of post-radiosurgery hemorrhage is not affected by preceding embolization [2122]. There are conflicting reports on radiation-induced change; one shows no correlation and larger complications with preceding embolization [41423]. Additionally, it is obvious that the larger AVM may result in a lower obliteration rate for SRS. A higher tendency of the larger nidus of the virgin state was observed in the N group in our study. Therefore, we performed a multivariate study to clarify the signif icance of specif ication or quality of the embolization independent of the original AVM size. The result suggested that a successful SRS is expected to increase by more than four times for each increase in embolization grade. Therefore, the embolization grade was a strongly independent factor that influenced the success of SRS, which may suggest that a proper and meticulous embolization strategy, highly skillful microcatheterization, and best performance of injecting liquid embolic materials are essential for achieving good results. The diffuse type of AVM makes it a challenge to perform the ideal embolization. Therefore, we should preoperatively evaluate the type of nidus, and cases without the possibility of suff icient embolization should be omitted from the plan of preradiosurgical embolization. By contrast, cases with high odds of embolization that affect the positive use of embolization will contribute to and complement the desirable result of SRS.

Although we did not compare the results between two groups with and without embolization, we showed that a high quality embolization is essential to achieve ideal radiosurgery results. The embolization of nidus is particularly important for avoiding recanalization and regional vascular remodeling, as mentioned in many previous reports from the past century [2317]. However, when treating cases with a diffuse, large AVM in which effective embolization is difficult, we should consider novel combined treatment options. Yashar et al. [24] recommends that the compartments of an embolized AVM should be contained within the radiosurgery plan. According to this concept, volume-staged radiosurgery [252627] and preembolization radiosurgery [11] may be useful.

This study is a retrospective case cohort study of the limited institutes employing operators with a reliable and proper technique and strategy for AVM embolization. Therefore, larger prospective studies will be needed to confirm the findings.


Embolization before radiosurgery remains a controversial neoadjuvant therapy. It is clear that reducing the size and shunt flow of AVMs improves the effect of SRS. Although sufficient volume reduction should be the most important goal of embolization, false occlusion due to the temporary depression of hemodynamics may disappoint radiosurgeons. This study showed that proper embolization with a high rate of nidus penetration to avoid recanalization is important for complete, cooperative combined treatments. A proper strategy and technique is essential for promoting occlusion following SRS.

This study was supported from the grant of the 2016 Japanese Society of Neuroendovascular Therapy.


We thank Dr. Kenta Murotani (Clinical Research Center, Aichi Medical University) for statistical studies. We also thank Drs. Noriaki Matsubara and Ryo Hiramatsu (Department of Neurosurgery and Neuroendovascular Therapy, Osaka Medical College), Drs. Osamu Masuo and Kenji Kubo (Department of Neurosurgery, Wakayama Medical College), Dr. Rie Aoki (Department of Neurosurgery, Tokai University Hospital), Dr. Shuichi Tanoue (Department of Radiology, Kurume University of Medicine), Dr. Masayuki Sato (Department of Neurosurgery, Mito Medical Center), Dr. Eika Hamano (Department of Neurosurgery, National Cerebral and Cardiovascular Center) and Dr. Yosuke Tamari (Department of Neurosurgery and Endovascular Neurosurgery, Nagoya University Graduate School of Medicine) for assistance of data management.


1. Gobin YP, Laurent A, Merienne L, Schlienger M, Aymard A, Houdart E, et al. Treatment of brain arteriovenous malformations by embolization and radiosurgery. J Neurosurg 1996;85:19–28. 8683274.
2. Miyachi S, Negoro M, Okamoto T, Kobayashi T, Tanaka T, Kida Y, et al. Embolisation of cerebral arteriovenous malformations to assure successful subsequent radiosurgery. J Clin Neurosci 2000;(Suppl 1):82–85. 11013105.
3. Ellis JA, Lavine SD. Role of embolization for cerebral arteriovenous malformations. Methodist Debakey Cardiovasc J 2014;10:234–239. 25624978.
4. Schwyzer L, Yen CP, Evans A, Zavoian S, Steiner L. Long-term results of gamma knife surgery for partially embolized arteriovenous malformations. Neurosurgery 2012;71:1139–1147. 22986603.
5. Blackburn SL, Ashley WW Jr, Rich KM, Simpson JR, Drzymala RE, Ray WZ, et al. Combined endovascular embolization and stereotactic radiosurgery in the treatment of large arteriovenous malformations. J Neurosurg 2011;114:1758–1767. 21332288.
6. Pollock BE, Flickinger JC, Lunsford LD, Maitz A, Kondziolka D. Factors associated with successful arteriovenous malformation radiosurgery. Neurosurgery 1998;42:1239–1244. 9632181.
7. Andrade-Souza YM, Ramani M, Scora D, Tsao MN, terBrugge K, Schwartz ML. Embolization before radiosurgery reduces the obliteration rate of arteriovenous malformations. Neurosurgery 2007;60:443–451. 17327788.
8. Ding D, Yen CP, Xu Z, Starke RM, Sheehan JP. Radiosurgery for primary motor and sensory cortex arteriovenous malformations: outcomes and the effect of eloquent location. Neurosurgery 2013;73:816–824. 23867301.
9. Starke RM, Kano H, Ding D, Lee JY, Mathieu D, Whitesell J, et al. Stereotactic radiosurgery for cerebral arteriovenous malformations: evaluation of long-term outcomes in a multicenter cohort. J Neurosurg 2017;126:36–44. 26943847.
10. Ivanov AA, Alaraj A, Charbel FT, Aletich V, Amin-Hanjani S. Recurrence of Cerebral Arteriovenous Malformations Following Resection in Adults: Does Preoperative Embolization Increase the Risk? Neurosurgery 2016;78:562–571. 26702837.
11. Hodgson TJ, Kemeny AA, Gholkar A, Deasy N. Embolization of residual fistula following stereotactic radiosurgery in cerebral arteriovenous malformations. AJNR Am J Neuroradiol 2009;30:109–110. 18687747.
12. Kano H, Kondziolka D, Flickinger JC, Park KJ, Iyer A, Yang HC, et al. Stereotactic radiosurgery after embolization for arteriovenous malformations. Prog Neurol Surg 2013;27:89–96. 23258513.
13. Ding D, Starke RM, Kano H, Lee JY, Mathieu D, Pierce J, et al. Stereotactic radiosurgery for Spetzler-Martin Grade III arteriovenous malformations: an international multicenter study. J Neurosurg 2017;126:859–871. 27081906.
14. Xu F, Zhong J, Ray A, Manjila S, Bambakidis NC. Stereotactic radiosurgery with and without embolization for intracranial arteriovenous malformations: a systematic review and meta-analysis. Neurosurg Focus 2014;37(3)E16. 10.3171/2014.6.FOCUS14178.
15. Marks MP, Marcellus ML, Santarelli J, Dodd RL, Do HM, Chang SD, et al. Embolization Followed by Radiosurgery for the Treatment of Brain Arteriovenous Malformations (AVMs). World Neurosurg 2017;99:471–476. 28017742.
16. Izawa M, Chemov M, Hayashi M, Iseki H, Hori T, Takakura K. Combined management of intracranial arteriovenous malformations with embolization and gamma knife radiosurgery: comparative evaluation of the long-term results. Surg Neurol 2009;71:43–52. 18291487.
17. Kondo R, Matsumoto Y, Endo H, Miyachi S, Ezura M, Sakai N. Endovascular Embolization of Cerebral Arteriovenous Malformations: Results of the Japanese Registry of Neuroendovascular Therapy (JR-NET) 1 and 2. Neurol Med Chir (Tokyo) 2014;54(Suppl 2):54–62.
18. Spetzler RF, Martin NA. A proposed grading system for arteriovenous malformations. J Neurosurg 1986;65:476–483. 3760956.
19. Wegner RE, Oysul K, Pollock BE, Sirin S, Kondziolka D, Niranjan A, et al. A modified radiosurgery-based arteriovenous malformation grading scale and its correlation with outcomes. Int J Radiat Oncol Biol Phys 2011;79:1147–1150. 20605347.
20. Kano H, Kondziolka D, Flickinger JC, Park KJ, Iyer A, Yang HC, et al. Stereotactic radiosurgery for arteriovenous malformations after embolization: a case-control study. J Neurosurg 2012;117:265–275. 22631689.
21. Cohen-Inbar O, Starke RM, Paisan G, Kano H, Huang PP, Rodriguez-Mercado R, et al. Early versus late arteriovenous malformation responders after stereotactic radiosurgery: an international multicenter study. J Neurosurg 2017;127:503–511. 27662534.
22. Knippen S, Putz F, Semrau S, Lambrecht U, Knippen A, Buchfelder M, et al. Predictors for occlusion of cerebral AVMs following radiation therapy: Radiation dose and prior embolization, but not Spetzler-Martin grade. Strahlenther Onkol 2017;193:185–191. 27757503.
23. Oermann EK, Ding D, Yen CP, Starke RM, Bederson JB, Kondziolka D, et al. Effect of Prior Embolization on Cerebral Arteriovenous Malformation Radiosurgery Outcomes: A Case-Control Study. Neurosurgery 2015;77:406–417. 25875580.
24. Yashar P, Amar AP, Giannotta SL, Yu C, Pagnini PG, Liu CY, Apuzzo ML. Cerebral arteriovenous malformations: issues of the interplay between stereotactic radiosurgery and endovascular surgical therapy. World Neurosurg 2011;75:638–647. 21704930.
25. Seymour ZA, Sneed PK, Gupta N, Lawton MT, Molinaro AM, Young W, et al. Volume-staged radiosurgery for large arteriovenous malformations: an evolving paradigm. J Neurosurg 2016;124:163–174. 26140495.
26. Firlik AD, Levy EI, Kondziolka D, Yonas H. Staged volume radiosurgery followed by microsurgical resection: a novel treatment for giant cerebral arteriovenous malformations: technical case report. Neurosurgery 1998;43:1223–1228. 9802869.
27. Back AG, Vollmer D, Zeck O, Shkedy C, Shedden PM. Retrospective analysis of unstaged and staged Gamma Knife surgery with and without preceding embolization for the treatment of arteriovenous malformations. J Neurosurg 2008;109(Suppl):57–64.

Article information Continued

Funded by : Japanese Society of Neuroendovascular Therapy

Table 1

Classification of the Grade of Embolization Performance (E Grade)

E Grade A1: ≥50% of successful nidus embolization for compact (plexiform) type AVM
E Grade A2: ≥50% of successful nidus embolization and proximal occlusion of fistulous feeders for mixed (plexiform + fistulous) type AVM
E Grade B1: <50% of successful nidus embolization for compact (plexiform) type AVM
E Grade B2: <50% of successful nidus embolization and proximal occlusion of fistulous feeders for mixed (plexiform + fistulous) type
AVM or remaining daughter nidus on diffuse type*
E Grade C: No successful embolization (all proximal occlusion) for all feeders in any types of AVM or failed obvious size reduction (only change of vascular density)

*: Including remnant daughter nidus on diffuse type

Table 2

Patient Profile

Grade of radiosurgical effect (SRS grade) Total A B C B + C
category of group S group N group
total number 73 44 18 11 29 S vs N group
Patient profile
 Gender (M:F) 40 vs. 33 28 vs. 16 10 vs. 8 2 vs. 9 12 vs. 17 NS
 Mean age (range) 38.3 (6~78) 38.5 (6~78) 30.9 (10-58) 33.2 (13-62) 31.8 (10~62) NS
 Clinical Unruptured NS
 Manifestation No symptom 10 6 2 2 4
Convulsion 10 4 4 2 6
Headache 5 4 1 0 1
Focal neurological symptoms 5 2 1 2 3
Ruptured NS
Intracerebral hemorrhage 20 14 4 2 6
Intraventricualr hemorrhage 16 9 4 3 7
Subarachnoid hemorrhage 7 5 2 0 2
 Initial treatment NS
No treatment 42 25 9 8 17
Medical treatment 23 15 7 1 8
Ventricular drainage 4 2 2 0 2
Others 4 2 0 2 2
 Precedent neurological deficits NS
None (mRS 0) 55 32 13 10 23
Mild (mRS 1) 9 5 3 1 4
Medium (mRS 2, 3) 3 2 1 0 1
Severe (mRS ≥4) 6 5 1 0 1

Table 3

AVM Profile

Grade of radiosurgical effect (SRS grade) Total A B C B + C
category of group S group N group
total number 73 44 18 11 29 S vs N group SRS grade A vs C
AVM profile
 location NS NS
Frontal 20 15 4 1 5
Temporal 8 4 2 2 4
Parietal 10 4 3 3 6
Occipital 11 6 2 3 5
Cerebellum 16 11 5 0 5
Thalamostriate 3 2 1 0 1
Brainstem 4 1 2 1 3
 Spetzler-Martin grade NS NS
Grade 1 9 8 1 0 1
Grade 2 17 12 3 2 5
Grade 3 32 18 10 4 14
Grade 4 14 6 3 5 8
Grade 5 1 0 1 0 1
 size maximum diameter (mm) 31.6 (11-72) 28.7 (12-55) 32.9 (11-45) 40.7 (20-72) 35.9 (11-72) NS 0.013
initial volume (ml) 13.8 (1-46) 12.0 (1-45) 12.4 (1-35) 23.5 (2-46) 16.6 (1-46) NS 0.004
≤5 ml 24 18 6 0 6
6-10 ml 15 11 3 1 4
11-20 ml 13 6 3 4 7
21-30 ml 10 4 4 2 6
31-40 ml 9 4 2 3 5
>40 ml 2 1 0 1 1
 mBRAS mean value 2.13 2.01 1.94 2.97 2.33 NS <0.001
≤1.00 15 11 3 0 4
1.01-1.50 11 6 4 1 5
1.51-2.00 16 11 4 1 5
≥2.01 31 16 7 9 15
 Nidus type compact 52 37 12 3 15 0.004 <0.001
diffuse 21 7 6 8 14
 Daughter nidus 5 2 1 2 3 NS NS
 Draining pattern single (superficial) 18 14 3 1 4 0.031 0.0013
single (deep) 11 8 3 0 3
multiple (superficial main) 32 17 8 7 15
multiple (deep main) 12 5 4 3 7
 Associated varix 6 5 1 0 1 NS NS
 Associated aneurysm no aneurysms 52 33 13 6 19 NS NS
proximal (treated) 13(5) 6(2) 3(0) 4(3) 7(3)
flow-related (treated) 3(3) 2(2) 1(1) 0 1(1)
intranidal (treated) 6(4) 3(3) 2(1) 1(0) 3(1)
 Meningeal feeders no 56 38 16 4 18 0.023 0.002
yes (treated) 17(9) 6(4) 4(1) 7(4) 11(5)

mBRAS: modified radiosurgery-based arteriovenous malformation (AVM) score

Table 4

Performance of Embolization

Grade of radiosurgical effect (SRS grade) Total A B C B + C
category of group S group N group
total number 73 44 18 11 29 S vs N group
Performance of embolization
 Embolization grade E grade A1 12 12 0 0 0 <0.001
E grade A2 20 18 2 0 2
E grade B1 19 8 7 4 13
E grade B2 18 6 5 7 12
E grade C 2 0 2 0 2
 Final embolization rate 61.2% 63.6% 60.0% 53.6% 57.6% NS
 Final results of embolization complete occlusion 7 6 1 0 1 NS
 Size of remained nidus (diameter) <1 cm 22 16 5 1 6
 1-2 cm 24 14 8 2 10
2-3 cm 13 3 4 6 10
 ≥3 cm 7 5 0 2 2
Procedure-related complications total 14 7 5 2 7 NS
hemorrhage (inta- & perioperative) 8 6 2 0 2
convulsion 2 0 1 1 2
others 4 1 2 1 3
 Influence of complication on outcome none 11 7 2 2 4 NS
mRS 1 rank down 1 0 1 0 1
mRS 2 rank down 1 0 1 0 1
mRS 3 rank down 1 0 0 1 1

Table 5

Performance of Radiosurgery

Grade of radiosurgical effect (SRS grade) Total A B C B + C
category of group S group N group
total number 73 44 18 11 29 S vs N group
Performance of radiosurgery
 Post-radiosurgery complications total 4 0 1 3 4 0.022
hemorrhage, rebleeding 3 0 1 2 3
delayed cystic formation 1 0 0 1 1
 Influence of complication on outcome none 0 0 0 0 0 0.022
mRS 1 rank down 2 0 0 2 2
mRS 2 rank down 1 0 1 0 1
mRS 3 rank down 1 0 0 1 1