Endovascular treatment as the first-line approach for cure of low-grade brain arteriovenous malformation

Seyed Ali Shariat Razavi Section of Neurovascular Intervention, Neurosurgical Department, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran; and

Search for other papers by Seyed Ali Shariat Razavi in
jns
Google Scholar
PubMed
Close
 MD
,
Mohammad Hossein Mirbolouk Section of Neurovascular Intervention, Neurosurgical Department, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran; and

Search for other papers by Mohammad Hossein Mirbolouk in
jns
Google Scholar
PubMed
Close
 MD
,
Reza Gorji Section of Neurovascular Intervention, Neurosurgical Department, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran; and

Search for other papers by Reza Gorji in
jns
Google Scholar
PubMed
Close
 MD
,
Feizollah Ebrahimnia Section of Neurovascular Intervention, Neurosurgical Department, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran; and

Search for other papers by Feizollah Ebrahimnia in
jns
Google Scholar
PubMed
Close
 MD
,
Payam Sasannejad Section of Neurovascular Intervention, Neurosurgical Department, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran; and

Search for other papers by Payam Sasannejad in
jns
Google Scholar
PubMed
Close
 MD
,
Samira Zabihyan Section of Neurovascular Intervention, Neurosurgical Department, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran; and

Search for other papers by Samira Zabihyan in
jns
Google Scholar
PubMed
Close
 MD
,
Farid Qoorchi Moheb Seraj Section of Neurovascular Intervention, Neurosurgical Department, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran; and

Search for other papers by Farid Qoorchi Moheb Seraj in
jns
Google Scholar
PubMed
Close
 MD
,
Hamid Etemadrezaie Section of Neurovascular Intervention, Neurosurgical Department, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran; and

Search for other papers by Hamid Etemadrezaie in
jns
Google Scholar
PubMed
Close
 MD
,
Mahla Esmaeilzadeh Section of Neurovascular Intervention, Neurosurgical Department, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran; and

Search for other papers by Mahla Esmaeilzadeh in
jns
Google Scholar
PubMed
Close
 MD
,
Raphaël Blanc Department of Interventional Neuroradiology, Rothschild Foundation Hospital, Paris, France

Search for other papers by Raphaël Blanc in
jns
Google Scholar
PubMed
Close
 MD, MSc
,
Michel Piotin Department of Interventional Neuroradiology, Rothschild Foundation Hospital, Paris, France

Search for other papers by Michel Piotin in
jns
Google Scholar
PubMed
Close
 MD, PhD
, and
Humain Baharvahdat Section of Neurovascular Intervention, Neurosurgical Department, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran; and
Department of Interventional Neuroradiology, Rothschild Foundation Hospital, Paris, France

Search for other papers by Humain Baharvahdat in
jns
Google Scholar
PubMed
Close
 MD
Free access

OBJECTIVE

While microsurgery has been proposed as the first-line treatment for patients with low-grade (Spetzler-Martin grade I or II) brain arteriovenous malformations (bAVMs), recent studies have shown promising results for endovascular treatment (EVT) as a single proper choice for the management of this group of bAVMs. In this study, the authors evaluated the safety and efficacy of EVT as a first-line strategy for curing low-grade bAVMs at their center.

METHODS

All patients with low-grade bAVMs managed primarily by EVT between 2015 and 2021 were enrolled in this study. Patients were evaluated and treated by the same team and followed with the same protocol. The primary endpoint was the efficacy of EVT on the cure of low-grade bAVMs. The second endpoint was the safety of EVT for the treatment of low-grade bAVMs, including procedural complications and long-term clinical outcomes.

RESULTS

A total of 109 patients were enrolled and represented in the study population. The mean patient age was 31.6 ± 14.8 years. Forty-eight AVMs (44%) were Spetzler-Martin grade I and 61 (56%) were grade II. Of 99 patients who completed their EVT sessions, complete exclusion was achieved in 89 patients (89.9%). Overall, complete exclusion was achieved in 59.6% of patients after a single EVT session. At the 6-month follow-up, 106 patients (97.2%) had a favorable outcome. Four patients (4.6%) experienced transient neurological deficits, and 1 patient (0.9%) had a permanent neurological deficit.

CONCLUSIONS

EVT can be offered as the first choice of treatment for select patients with low-grade bAVMs, with a high cure rate and low morbidity.

ABBREVIATIONS

ARUBA = A Randomized Trial of Unruptured Brain Arteriovenous Malformations; bAVM = brain arteriovenous malformation; EVT = endovascular treatment; ICH = intracerebral hemorrhage; IVH = intraventricular hemorrhage; mRS = modified Rankin Scale; ND = neurological deficit; SAH = subarachnoid hemorrhage; SRS = stereotactic radiosurgery.

OBJECTIVE

While microsurgery has been proposed as the first-line treatment for patients with low-grade (Spetzler-Martin grade I or II) brain arteriovenous malformations (bAVMs), recent studies have shown promising results for endovascular treatment (EVT) as a single proper choice for the management of this group of bAVMs. In this study, the authors evaluated the safety and efficacy of EVT as a first-line strategy for curing low-grade bAVMs at their center.

METHODS

All patients with low-grade bAVMs managed primarily by EVT between 2015 and 2021 were enrolled in this study. Patients were evaluated and treated by the same team and followed with the same protocol. The primary endpoint was the efficacy of EVT on the cure of low-grade bAVMs. The second endpoint was the safety of EVT for the treatment of low-grade bAVMs, including procedural complications and long-term clinical outcomes.

RESULTS

A total of 109 patients were enrolled and represented in the study population. The mean patient age was 31.6 ± 14.8 years. Forty-eight AVMs (44%) were Spetzler-Martin grade I and 61 (56%) were grade II. Of 99 patients who completed their EVT sessions, complete exclusion was achieved in 89 patients (89.9%). Overall, complete exclusion was achieved in 59.6% of patients after a single EVT session. At the 6-month follow-up, 106 patients (97.2%) had a favorable outcome. Four patients (4.6%) experienced transient neurological deficits, and 1 patient (0.9%) had a permanent neurological deficit.

CONCLUSIONS

EVT can be offered as the first choice of treatment for select patients with low-grade bAVMs, with a high cure rate and low morbidity.

While ruptured brain arteriovenous malformations (bAVMs) should be treated to eliminate the risk of hemorrhage, management of unruptured bAVMs is controversial after the publication of A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA).1 The results of the ARUBA study were in favor of conservative management of all graded unruptured bAVMs compared with any intervention. Because of its short-term follow-up and the study method, this conclusion raised much criticism about the natural history of unruptured bAVMs and their management. Following ARUBA, many studies were published to address the shortages of this study and clarify the efficacy and safety of the intervention, including surgery, radiosurgery, and endovascular treatment (EVT). Surgery has been established as the first-line treatment for the management of low-grade (Spetzler-Martin grade I or II) bAVMs, with a high cure rate and very low complication rate.2,3 Recently, several studies were published and showed that EVT has a comparable high cure rate with low side effects as surgery for treatment of low-grade bAVMs.4,5 With the same concept and confirming the results of these studies, we assessed the efficacy and safety of our experience with EVT for the cure of low-grade bAVMs in the department of neurovascular intervention at Mashhad University of Medical Sciences, Mashhad, Iran.

Methods

Study Design

This observational retrospective study enrolled all patients with low-grade (Spetzler-Martin grade I or II6) bAVMs, treated with EVT as the first approach between 2015 and 2021 at our center. All patients were evaluated and treated by the same team that followed the same protocol and had 6 months of clinical and imaging follow-up. All endovascular procedures were performed by our senior endovascular neurosurgeon (H.B.). The study was approved by the ethics committee board of Mashhad University of Medical Sciences.

This study aimed to evaluate the efficacy and safety of EVT as the first approach for managing and curing low-grade bAVMs. The primary endpoint was the efficacy of EVT in the treatment of low-grade bAVMs, which was defined by complete occlusion of the bAVM at 6 months of angiographic follow-up. The second endpoint was the safety of EVT for treatment of low-grade bAVMs, which was defined as any complication during or after the operation and 6-month clinical follow-up assessed using the modified Rankin Scale (mRS).

Patient Selection

Before the decision for management, patients were assessed by clinical examination and appropriate imaging, including MRI and cerebral angiography, to define the bAVM’s precise location, size, and architecture. Angioarchitecture of the bAVM was further evaluated by a 3D rotational cerebral angiogram. The patient’s management was decided by a multidisciplinary committee. The majority of low-grade bAVMs have been treated with EVT at our center since 2010. Less than 10% have been surgically treated. All ruptured low-grade bAVMs were allocated to EVT at least 1–2 weeks after the hemorrhagic event. Unruptured low-grade bAVMs were treated with EVT if feasible and safe, if there was a higher risk of rupture than its natural history, if the nidus was compact and small, and if the patient requested intervention. Unruptured bAVMs located in the motor or language cortex were excluded for EVT.

Brain AVMs were classified according to the Spetzler-Martin grading system. The location of the bAVMs was defined as cortical (cortical-subcortical), deep, and infratentorial. The clinical status of patients was evaluated and reported according to the mRS score at admission, discharge, and follow-up. For ruptured bAVMs, the consciousness of patients was reported according to the World Federation of Neurosurgical Societies at admission. Procedural complication events were classified as ischemic or hemorrhagic. Ischemic events were defined as any ischemic sign on postoperative brain MRI. Hemorrhagic events were defined as any sign of hemorrhage (subarachnoid hemorrhage [SAH], intracerebral hemorrhage [ICH], or intraventricular hemorrhage [IVH]) on postoperative brain CT or MRI. Significant hemorrhagic complications were considered if the patient experienced a new neurological deficit (ND) or if he/she required surgery. NDs were classified as transient if they were resolved within 3 months and permanent if they were persistent for more than 3 months. The outcome was considered favorable if the mRS score was 0–2 at 6 months of follow-up and poor if the mRS score was 3–6.

Endovascular Procedure

Informed consent was obtained from all patients or their next of kin. The goal of the procedure was to cure low-grade bAVMs in one session, if possible, or in multiple sessions. All procedures were performed under general anesthesia using a biplane flat-panel angiographic suite (Artis zee with PURE, Siemens). Patients were heparinized with 2500–5000 U after the femoral or radial puncture. Depending on the accessibility and angioarchitecture of the bAVM, an arterial or venous approach was considered and undertaken. The most common arterial access was femoral before 2019, and it was changed to radial access for most cases after 2019. A direct puncture of the internal jugular vein was used for the venous approach. A transvenous approach was considered if we did not find a safe transarterial approach for EVT. All bAVMs were embolized by injection of liquid embolic agents, including Onyx-18 (Medtronic), Squid-18 (Emboflu), and Glubran 2 (GEN). All patients were transferred to the ICU after the procedure, and systolic blood pressure was maintained at less than 90 mm Hg for 24 hours. In patients who underwent multiple sessions, the interval between sessions was 6–12 weeks.

Statistical Analysis

Numerical data are reported as mean ± SD or median and IQR (25th and 75th percentile) depending on their distribution. Categorical data are registered as the number of patients and their percentage. Patients were categorized into ruptured and unruptured groups, and the basic characteristics and clinical and imaging outcomes were compared between two groups. Statistical comparisons were performed using the Student t-test for normally distributed data and the Mann-Whitney U-test for data with a skewed distribution. Statistical analysis was performed using the chi-square and Fisher exact tests for categorical data. Univariate analysis was carried out to find predictive factors for the exclusion of AVM, hemorrhagic complications, NDs, and poor outcomes; p < 0.05 was considered significant. Statistical analysis was performed using SPSS (version 16.0, SPSS Inc.).

Results

Basic Demographic of Patients

A total of 109 patients with low-grade bAVMs were enrolled in the study and treated exclusively with EVT between 2015 and 2021. The mean patient age was 31.6 ± 14.8 years (Table 1). Forty-eight AVMs (44%) were Spetzler-Martin grade I, and 61 (56%) were Spetzler-Martin grade II. Sixty-nine patients (63.3%) presented with hemorrhage and 22 patients (20.2%) with seizures. There was no statistically significant difference between patients with a ruptured bAVM and those with an unruptured bAVM for the majority of baseline characteristics (Table 1), except for the nidus diameter and venous ectasia, which were significantly larger in the unruptured group (p < 0.0001).

TABLE 1.

Patient demographics

VariableTotal (n = 109)Ruptured (n = 69)Unruptured (n = 40)p Value
Mean age, yrs31.6 ± 14.829.8 ± 15.134.8 ± 13.90.091
Female sex55 (50.5)32 (46.4)23 (57.5)0.263
Presentation
 Hemorrhage69 (63.3)69 (100)0 (0.0)
 Seizure22 (20.2)0 (0.0)22 (55.0)
 Focal symptoms8 (7.3)0 (0.0)8 (20.0)
 Incidental10 (9.2)0 (0.0)10 (25.0)
Preop good consciousness status (WFNS 0–II)100 (91.7)62 (89.9)38 (95.0)0.481
Preop condition0.213*
 mRS score 0–288 (80.7)53 (76.8)35 (87.5)
 mRS score 3–521 (19.3)16 (23.2)5 (12.5)
Spetzler-Martin grade0.877
 I48 (44.0)30 (43.5)18 (45.0)
 II61 (56.0)39 (56.5)22 (55.0)
Mean nidus diameter, mm18.4 ± 9.915.9 ± 8.922.8 ± 10.1<0.0001
Compact nidus72 (66.1)43 (62.3)29 (72.5)0.297
Location
 Eloquent20 (18.3)14 (20.3)6 (15.0)0.492
 Cortical-subcortical93 (85.3)55 (79.7)38 (95.0)0.079
 Deep12 (11.0)11 (15.9)1 (2.5)
 Infratentorial4 (3.7)3 (4.3)1 (2.5)
Intranidal aneurysm26 (23.9)16 (23.1)10 (25.0)
Arterial aneurysm2 (1.8)2 (2.9)0 (0.0)0.531*
Single venous drainage28 (25.7)20 (29.0)8 (20.0)0.301
Deep venous drainage27 (24.8)21 (30.4)6 (15.0 )0.072
Venous ectasia32 (29.4)9 (13.0)23 (57.5)<0.0001

WFNS = World Federation of Neurosurgical Societies.

Values represent the number of patients (%) or mean ± SD unless stated otherwise.

Fisher’s exact test.

Treatment and Endovascular Procedures

Seventy-five patients (68.8%) were treated in one session, 20 patients (18.3%) had two sessions, and 14 patients needed three or more sessions (Table 2). In 10 patients, EVT was ongoing or was interrupted because the patient was unwilling to continue. Ninety-nine patients had finished their EVTs. Femoral access was used in 98 patients (89.9%), and radial access was used in 11 patients (10.1%). The technical approach was arterial in 102 bAVMs (93.6%), venous in 7 bAVMs (6.4%), and simultaneously arterial and venous in 2 bAVMs (1.8%). In 2 bAVMs, the venous approach was used to exclude the remnant of a previously embolized nidus from the last session. Detachable microcatheters were used in 74 patients (67.9%) and balloon microcatheters in 5 patients (4.6%). In addition to Onyx-18, we injected Squid-18 in at least one session for embolization of 15 AVMs and Glubran for embolization of 4 AVMs. The median volume of embolic agents injected in each patient was 2 ml (IQR 1–4.75 ml). We did not find any significant difference between the ruptured bAVM group and the unruptured bAVM group in terms of technical approach. There was a tendency to inject a larger amount of the embolic agent in patients with unruptured bAVMs, but this did not reach statistical significance.

TABLE 2.

EVT characteristics and surgical management of patients

Total (n = 109)Ruptured (n = 69)Unruptured (n = 40)p Value
Median no. of EVT sessions1 (1–2)1 (1–2)1 (1–2)0.803*
Radial access11 (10.1)8 (11.6)3 (7.5)0.494
Technical approach0.576
 Exclusively arterial100 (91.7)62 (89.9)38 (95.0)
 Exclusively venous5 (4.6)4 (5.8)1 (2.5)
 Venous in last session2 (1.8)2 (2.9)0 (0.0)
 Both arterial-venous in 1 session2 (1.8)1 (1.4)1 (2.5)
Detachable microcatheter74 (67.9)45 (65.2)29 (72.5)0.433
Balloon microcatheter5 (4.6)4 (5.8)1 (2.5)0.392
Median vol of embolic agent, ml2 (1–4.75)1.7 (0.90–3.65)3.6 (1.73–6.98)0.803*
Surgery before EVT12 (11.0)12 (17.4)0 (0.0)0.050
Decompressive craniectomy6 (5.5)6 (8.7)0 (0.0)
ICH evacuation2 (1.8)2 (2.9)0 (0.0)
External ventricular drainage4 (3.7)4 (5.8)0 (0.0)

Values represent the number of patients (%) or median (IQR) unless stated otherwise.

Mann-Whitney U-test.

Fisher’s exact test.

Of the 69 patients who presented with hemorrhage, 12 patients (17.4%) were managed with surgery before EVT. Decompressive craniectomy was performed in 6 patients (8.7%) during the acute phase of hemorrhage. In 2 patients (1.8%), an ICH was evacuated without any attempt to remove the bAVM; the bAVM was later treated with EVT. Four patients received external ventricular drainage to reduce intracranial pressure immediately after their presentation with IVH.

EVT-Related Complications

Hemorrhagic events were observed on postoperative CT scans in 12 patients (11%), including 7 ICHs (6.4%), 3 SAHs (2.8%), and 2 IVHs (1.8%). Of these hemorrhagic events, only 50% (6 hemorrhagic complications) were significant (Table 3). Seven hemorrhagic events originated from arterial ruptures that were benign, leading to no NDs except for 1 patient who experienced transient foot paresis. Five hemorrhagic complications were due to venous rupture, including 4 ICHs and 1 IVH. The majority of venous ICHs (3 of 4, 75%) occurred with delay (8 hours and 72 hours). In 1 patient, ICH occurred at the end of the operation, and immediate ICH evacuation was necessary. The patient had no ND at the 6-month follow-up. Three other patients experienced transient NDs, including visual problems and hemiparesis. In 1 patient, despite her recovery from hemiparesis, her seizures worsened and were poorly controlled. No new hemorrhagic events were reported between the sessions of EVT.

TABLE 3.

Procedural complications and clinical and imaging outcomes

No. of Patients (%)p Value
Total (n = 109)Ruptured (n = 69)Unruptured (n = 40)
bAVM exclusion*89 (89.9)58 (90.6)31 (88.6)0.739
bAVM exclusion in 1 session65 (59.6)42 (60.9)23 (57.5)0.730
Hemorrhagic events12 (11.0)7 (10.1)5 (12.5)0.756
 Significant hemorrhagic complications6 (5.5)1 (1.4)5 (12.5)0.150
 ICH7 (6.4)3 (4.3)4 (10.0)
 IVH2 (1.8)1 (1.4)1 (2.5)
 SAH3 (2.8)3 (4.3)0 (0.0)
 Arterial rupture7 (6.4)5 (7.2)2 (5.0)0.501
 Venous rupture5 (4.6)2 (2.9)3 (7.5)
Ischemia3 (2.8)2 (2.9)1 (2.5)>0.99
ND6 (5.5)1 (1.4)5 (12.5)0.015
 Transient5 (4.6)1 (1.4)4 (10.0)
 Permanent1 (0.9)0 (0.0)1 (2.5)
Clinical outcome>0.99
 Favorable (mRS score 0–2)106 (97.2)67 (97.1)39 (97.5)
 Poor (mRS score 3–6)3 (2.8)2 (2.9)1 (2.5)
 mRS score worsened1 (0.9)0 (0.0)1 (2.5)0.365

In patients who finished their EVT sessions.

Fisher’s exact test.

Three patients had ischemic complications found on postoperative MRI. Two patients were asymptomatic, and 1 experienced permanent visual and memory problems.

Interpreting the significant covariate (hemorrhagic presentation, nidus diameter, deep venous drainage, arterial rupture, and Onyx volume), we found venous rupture as the only significant predictive factor of significant hemorrhagic complication using multivariate analysis (OR 204.0 [95% CI 15.2–2746.7], p < 0.0001).

Clinical and Imaging Outcome

Complete obliteration of the bAVM was achieved in 89 patients (81.7%), including 58 (84.1%) in the ruptured bAVM group and 31 (77.5%) in the unruptured bAVM group. When we excluded 10 patients who had not finished their sessions of EVT, the exclusion rate was as high as 89.9% in total and 90.6% (58 of 64) in the ruptured bAVM group and 88.6% (31 of 35) in the unruptured bAVM group (Table 3). Using the venous approach, the rate of complete obliteration increased to 100%. In 65 patients (59.6%), we excluded the nidus in one session. After controlling for covariates, including age, hemorrhagic presentation, eloquent location, nidus type, single venous drainage, and injected embolic agent volume, we found that smaller nidus diameter, Spetzler-Martin grade I, and exclusively deep venous drainage were the significant predictive factors of bAVM exclusion in one session (OR 0.860 [95% CI 0791–0935], p < 0.0001; OR 5.904 [95% CI 1.509–23.210], p = 0.011; and OR 5.474 [95% CI 1.197–25.036], p = 0028, respectively).

One hundred six patients (97.2%) had favorable outcomes at long-term follow-up of more than 6 months, including 97.1% in the ruptured bAVM group and 97.5% in the unruptured bAVM group (Table 3). Four patients experienced transient NDs in the unruptured bAVM group, and 1 patient had permanent NDs (recent memory problem and visual deficit). In the ruptured bAVM group, 1 patient had transient ND. In general, the majority of patients either had the same preoperative mRS score at long-term follow-up or had improved (Table 4).

TABLE 4.

Follow-up clinical status change after EVT

mRS ScoreAdmission mRS Score (n = 109)Follow-Up mRS Score
012345
0262510000
1540540000
28062000
39080100
45031100
57051001

With interpreting covariates, including hemorrhagic presentation, eloquent location, nidus diameter, number of embolization, and technical approach, we found that significant ICH was the significant predictive factor of new ND (OR 510.0 [95% CI 27.7–9395.4], p < 0.0001). After controlling for covariates, including age, hemorrhagic presentation, Spetzler-Martin grade, eloquent location, technical approach, hemorrhagic complications, and ischemic complications, the only significant predictive factor of poor outcome was preoperative disability (OR 5.889 [95% CI 3.866–8.971], p = 0.006).

Discussion

In this study, we found that EVT of low-grade bAVMs with the intent to cure is safe with acceptable efficacy. Following EVT, the ND was as low as 5.5%, with no deaths. In the majority of cases, the NDs improved over time, and permanent NDs occurred in less than 1% of patients. In our study, the favorable outcome was approximately 97% at the 6-month follow-up, with a cure rate of 90%. In 60% of patients, complete obliteration of low-grade bAVMs was achieved in only one session. The results of our study are consistent with other published studies that reported a high success rate of EVT with a low complication rate for the cure of low-grade bAVMs.4,5

The publication of the ARUBA study1 in 2014 has changed the practice for the treatment of bAVMs in many centers. The study results showed that during 33 months of follow-up of unruptured bAVMs, the conservatively treated group had a significantly lower risk of stroke and death compared with the intervention group (10.1% vs 30.7%) and conservative management was superior to any intervention. Consequently, much criticism has been made of the ARUBA study. A mean of 33 months of follow-up seems to be too short to evaluate the true natural history and rupture risk of bAVMs, especially in young individuals. While low-grade bAVMs could be suitable for intervention, especially microsurgery, a small number of patients had low-grade bAVMs. Furthermore, microsurgery was used in fewer cases than other modalities of intervention.7 Therefore, many studies have been published to challenge the results of the ARUBA study and to justify the treatment of bAVMs when patients are appropriately selected and the proper intervention is chosen.

The goal of low-grade bAVM treatment is exclusion of the nidus and occlusion of venous drainage to achieve a complete cure and to eliminate the risk of its rupture. Microsurgery has been considered ideal for achieving this purpose because of the smaller size and more straightforward structure of low-grade bAVMs than higher grades.8 The cure rate of surgery for low-grade bAVMs has been reported to be as high as 94%–100%, with a rate of permanent ND of 0%–6%.2,3,9 While classic low-grade bAVMs are mostly suitable for surgery, those located in eloquent/deep areas and those that have deep venous drainage could be associated with high ND rates after operation.2,3,7,10 Stereotactic radiosurgery (SRS) is another approach for the treatment of low-grade bAVMs because a majority of these bAVMs are small and would respond significantly to SRS. Graffeo et al. recently published a review article on low-grade bAVMs, including 8 studies with 1102 patients.11 SRS reached a complete obliteration rate of 80% (63%–93%) within a median time of 37 months. There was a low post-SRS hemorrhagic rate of 6% (4%–10%), with a 3% rate of radiation-induced complications and less than 1% mortality.

With a better understanding of the angioarchitecture of bAVMs and the development of new tools and techniques, EVT has extended its role as the first line of treatment for low-grade bAVMs at several centers. The nonadhesive nature of new embolic agents permitted prolonged and controlled injection of these agents, leading to better penetration into the nidus and draining veins that are essential for bAVM exclusion.5,12,13 Using detachable microcatheters and double microcatheter injection increased the rate of nidus obliteration.5,14,15 The venous approach is another method that can lead to complete obliteration of low-grade AVMs.5,16,17 By using the venous approach in 34% of patients, Iosif et al. completely obliterated the nidus in 85% of low-grade bAVMs in one session, while in the study by Baharvahdat et al., the venous approach was not applied, and the authors were able to obliterate the nidus in only 62% of cases in the first session.4,5 With the same concept, we achieved complete obliteration of the nidus in all low-grade bAVMs using the venous approach. After EVT in the study by Iosif et al., the clinical condition was stable or improved in 93.2% of patients and deteriorated in 6.4%.5 In the other study, Baharvahdat et al. also showed that the patients’ clinical conditions either did not change or improved after EVT in 94% of cases, and deteriorated in 6%, with 0.4% mortality.4 We had somewhat slightly better clinical results after EVT with a stable or improving condition in 99% of patients and deterioration in 1%, as we were less aggressive and therefore we had a lower exclusion rate than the other two studies (90% vs 99%5 and 92%4). Pooling the results from recent publications,4,5,18 including our results, demonstrated that EVT could achieve a high cure rate of 93%, with very low morbidity of 3.6% and mortality of 0.2% (Table 5). These results are encouraging for EVT as a suitable approach in parallel to microsurgery for the treatment of low-grade bAVMs, especially for bAVMs in eloquent/deep locations or with deep venous drainage.

TABLE 5.

EVT clinical outcomes and exclusion rates after treatment of low-grade AVMs in studies over the last 10 years

Authors & YearNo. of Patients (%)
TotalPermanent NDMortality RateExclusion Rate
van Rooij et al., 201218200 (0.0)0 (0.0)19 (95)
Iosif et al., 20195732 (2.7)0 (0.0)72 (99)
Baharvahdat et al., 2019422412 (5.4)1 (0.4)206 (92)
Present study*991 (1.0)0 (0.0)89 (90)
Total41615 (3.6)1 (0.2)386 (93)

Includes only the patients who finished their EVT sessions.

Our study showed that the majority of NDs (83%) after EVT were transient and improved on long-term follow-up. These results are consistent with those of other studies on EVT for the cure of low-grade bAVMs.4,5 Baharvahdat et al. showed that of 32 patients who developed new NDs after EVT, 20 patients (62.5%) improved within 30 days.4 The same experiences were reported in the surgical studies: many NDs following surgery of bAVMs improved over time and were transient.8,19

Exclusion of the nidus in one session of EVT is an ideal strategy for the cure of low-grade bAVMs. This approach has been followed by several centers, and exclusion was achieved in 60%–85% of patients with low-grade bAVMs in recent studies, including ours,4,5 whereas the majority of surgical studies had the benefit of preoperative embolization in 8%–64% of patients to simplify the surgery of low-grade bAVMs.2,3,8 In our study, we demonstrated that low-grade bAVMs with smaller diameters, especially Spetzler-Martin grade I bAVMs and/or those with exclusive deep venous drainage, are good candidates for exclusion of nidus in one session by EVT. Therefore, EVT could be considered as the first approach in this subgroup instead of microsurgery.

Limitations

Our study faced a number of limitations. This is an observational retrospective study reported from a single institution, which may impose sample biases and may limit generalization of the results. Few cases (8.5%) were managed by the venous approach, and other approaches such as double microcatheter embolization were not used, which may affect the cure rate and safety results in our series. Patients’ clinical outcomes were assessed by mRS scores, which did not precisely evaluate higher cortical function. The psychoneurological tests could be better options. Finally, 10% of our patients could not finish their EVT sessions, which may have an important impact on the result.

Conclusions

In addition to microsurgery, EVT can be a suitable approach as a first-line treatment for low-grade bAVMs, offering a high cure rate with very low morbidity and mortality. Patient selection with an appropriate EVT technical approach is the key factor for achieving optimal results. Further studies are needed to verify the encouraging results of our series and those of other authors.

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: Baharvahdat, Etemadrezaie, Esmaeilzadeh, Blanc, Piotin. Acquisition of data: Shariat Razavi, Mirbolouk, Ebrahimnia, Sasannejad, Qoorchi Moheb Seraj, Esmaeilzadeh. Analysis and interpretation of data: Baharvahdat, Qoorchi Moheb Seraj. Drafting the article: Baharvahdat. Critically revising the article: Mirbolouk, Gorji. Reviewed submitted version of manuscript: Baharvahdat, Mirbolouk, Gorji. Approved the final version of the manuscript on behalf of all authors: Baharvahdat. Statistical analysis: Baharvahdat. Administrative/technical/material support: Ebrahimnia. Study supervision: Baharvahdat, Zabihyan, Etemadrezaie, Blanc, Piotin.

References

  • 1

    Mohr JP, Parides MK, Stapf C, et al. Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial. Lancet. 2014;383(9917):614621.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Potts MB, Lau D, Abla AA, Kim H, Young WL, Lawton MT. Current surgical results with low-grade brain arteriovenous malformations. J Neurosurg. 2015;122(4):912920.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Morgan MK, Rochford AM, Tsahtsarlis A, Little N, Faulder KC. Surgical risks associated with the management of Grade I and II brain arteriovenous malformations. Neurosurgery. 2007;61(1 suppl):417424.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Baharvahdat H, Blanc R, Fahed R, et al. Endovascular treatment for low-grade (Spetzler-Martin I-II) brain arteriovenous malformations. AJNR Am J Neuroradiol. 2019;40(4):668672.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Iosif C, de Lucena AF, Abreu-Mattos LG, et al. Curative endovascular treatment for low-grade Spetzler-Martin brain arteriovenous malformations: a single-center prospective study. J Neurointerv Surg. 2019;11(7):699705.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Spetzler RF, Martin NA. A proposed grading system for arteriovenous malformations. J Neurosurg. 1986;65(4):476483.

  • 7

    Javadpour M, Al-Mahfoudh R, Mitchell PS, Kirollos R. Outcome of microsurgical excision of unruptured brain arteriovenous malformations in ARUBA-eligible patients. Br J Neurosurg. 2016;30(6):619622.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Wang A, Mandigo GK, Feldstein NA, et al. Curative treatment for low-grade arteriovenous malformations. J Neurointerv Surg. 2020;12(1):4854.

  • 9

    Moon K, Levitt MR, Almefty RO, et al. Safety and efficacy of surgical resection of unruptured low-grade arteriovenous malformations from the modern decade. Neurosurgery. 2015;77(6):948953.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Hung AL, Yang W, Westbroek EM, et al. Differences in functional outcome across subtypes with Spetzler-Martin Grade II arteriovenous malformations. Neurosurgery. 2017;81(3):441449.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Graffeo CS, Sahgal A, De Salles A, et al. Stereotactic radiosurgery for Spetzler-Martin Grade I and II arteriovenous malformations: International Society of Stereotactic Radiosurgery (ISRS) practice guideline. Neurosurgery. 2020;87(3):442452.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Saatci I, Geyik S, Yavuz K, Cekirge HS. Endovascular treatment of brain arteriovenous malformations with prolonged intranidal Onyx injection technique: long-term results in 350 consecutive patients with completed endovascular treatment course. J Neurosurg. 2011;115(1):7888.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Derdeyn CP, Zipfel GJ, Albuquerque FC, et al. Management of brain arteriovenous malformations: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2017;48(8):e200e224.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Abud DG, Riva R, Nakiri GS, Padovani F, Khawaldeh M, Mounayer C. Treatment of brain arteriovenous malformations by double arterial catheterization with simultaneous injection of Onyx: retrospective series of 17 patients. AJNR Am J Neuroradiol. 2011;32(1):152158.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Renieri L, Consoli A, Scarpini G, Grazzini G, Nappini S, Mangiafico S. Double arterial catheterization technique for embolization of brain arteriovenous malformations with onyx. Neurosurgery. 2013;72(1):9298.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Chen CJ, Norat P, Ding D, et al. Transvenous embolization of brain arteriovenous malformations: a review of techniques, indications, and outcomes. Neurosurg Focus. 2018;45(1):E13.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Mendes GAC, Kalani MYS, Iosif C, et al. Transvenous curative embolization of cerebral arteriovenous malformations: a prospective cohort study. Neurosurgery. 2018;83(5):957964.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    van Rooij WJ, Jacobs S, Sluzewski M, van der Pol B, Beute GN, Sprengers ME. Curative embolization of brain arteriovenous malformations with Onyx: patient selection, embolization technique, and results. AJNR Am J Neuroradiol. 2012;33(7):12991304.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Schramm J, Schaller K, Esche J, Boström A. Microsurgery for cerebral arteriovenous malformations: subgroup outcomes in a consecutive series of 288 cases. J Neurosurg. 2017;126(4):10561063.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • Collapse
  • Expand

Illustration from Agosti et al. (E5). Used with permission of Mayo Foundation for Medical Education and Research. All rights reserved.

  • 1

    Mohr JP, Parides MK, Stapf C, et al. Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial. Lancet. 2014;383(9917):614621.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Potts MB, Lau D, Abla AA, Kim H, Young WL, Lawton MT. Current surgical results with low-grade brain arteriovenous malformations. J Neurosurg. 2015;122(4):912920.

  • 3

    Morgan MK, Rochford AM, Tsahtsarlis A, Little N, Faulder KC. Surgical risks associated with the management of Grade I and II brain arteriovenous malformations. Neurosurgery. 2007;61(1 suppl):417424.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Baharvahdat H, Blanc R, Fahed R, et al. Endovascular treatment for low-grade (Spetzler-Martin I-II) brain arteriovenous malformations. AJNR Am J Neuroradiol. 2019;40(4):668672.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Iosif C, de Lucena AF, Abreu-Mattos LG, et al. Curative endovascular treatment for low-grade Spetzler-Martin brain arteriovenous malformations: a single-center prospective study. J Neurointerv Surg. 2019;11(7):699705.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Spetzler RF, Martin NA. A proposed grading system for arteriovenous malformations. J Neurosurg. 1986;65(4):476483.

  • 7

    Javadpour M, Al-Mahfoudh R, Mitchell PS, Kirollos R. Outcome of microsurgical excision of unruptured brain arteriovenous malformations in ARUBA-eligible patients. Br J Neurosurg. 2016;30(6):619622.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Wang A, Mandigo GK, Feldstein NA, et al. Curative treatment for low-grade arteriovenous malformations. J Neurointerv Surg. 2020;12(1):4854.

  • 9

    Moon K, Levitt MR, Almefty RO, et al. Safety and efficacy of surgical resection of unruptured low-grade arteriovenous malformations from the modern decade. Neurosurgery. 2015;77(6):948953.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Hung AL, Yang W, Westbroek EM, et al. Differences in functional outcome across subtypes with Spetzler-Martin Grade II arteriovenous malformations. Neurosurgery. 2017;81(3):441449.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Graffeo CS, Sahgal A, De Salles A, et al. Stereotactic radiosurgery for Spetzler-Martin Grade I and II arteriovenous malformations: International Society of Stereotactic Radiosurgery (ISRS) practice guideline. Neurosurgery. 2020;87(3):442452.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Saatci I, Geyik S, Yavuz K, Cekirge HS. Endovascular treatment of brain arteriovenous malformations with prolonged intranidal Onyx injection technique: long-term results in 350 consecutive patients with completed endovascular treatment course. J Neurosurg. 2011;115(1):7888.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Derdeyn CP, Zipfel GJ, Albuquerque FC, et al. Management of brain arteriovenous malformations: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2017;48(8):e200e224.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Abud DG, Riva R, Nakiri GS, Padovani F, Khawaldeh M, Mounayer C. Treatment of brain arteriovenous malformations by double arterial catheterization with simultaneous injection of Onyx: retrospective series of 17 patients. AJNR Am J Neuroradiol. 2011;32(1):152158.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Renieri L, Consoli A, Scarpini G, Grazzini G, Nappini S, Mangiafico S. Double arterial catheterization technique for embolization of brain arteriovenous malformations with onyx. Neurosurgery. 2013;72(1):9298.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Chen CJ, Norat P, Ding D, et al. Transvenous embolization of brain arteriovenous malformations: a review of techniques, indications, and outcomes. Neurosurg Focus. 2018;45(1):E13.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Mendes GAC, Kalani MYS, Iosif C, et al. Transvenous curative embolization of cerebral arteriovenous malformations: a prospective cohort study. Neurosurgery. 2018;83(5):957964.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    van Rooij WJ, Jacobs S, Sluzewski M, van der Pol B, Beute GN, Sprengers ME. Curative embolization of brain arteriovenous malformations with Onyx: patient selection, embolization technique, and results. AJNR Am J Neuroradiol. 2012;33(7):12991304.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Schramm J, Schaller K, Esche J, Boström A. Microsurgery for cerebral arteriovenous malformations: subgroup outcomes in a consecutive series of 288 cases. J Neurosurg. 2017;126(4):10561063.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 2549 757 159
PDF Downloads 2061 750 136
EPUB Downloads 0 0 0