Application of the Principles of Safe Hemodynamic Rearrangement to Reduce the Risk of Cerebral Arteriovenous Malformation Rupture during Curative Embolization using the Multimodal Approach

Abstract

Introduction

The grading system for arteriovenous malformations (AVMs) and the curative embolization principles for reducing the risks of AVM rupture caused by abrupt hemodynamic rearrangement have been modified using mathematical modeling methods. The objective of the study was to confirm the clinical effectiveness of these principles for reducing the rate of postoperative bleeding according to real-world data.

Methods

A retrospective study employing a pooled database involving 532 patients was performed for groups matched by demographic, anatomical, and clinical characteristics using the PSM method: the group of patients treated with adherence to all the embolization principles (Principles group, n = 92) and the control group of patients treated with violation of at least one principle (Control group, n = 46). Each patient underwent 1–9 embolization stages. If needed, radiosurgery or microsurgery was used at the final stage. The therapy outcomes were assessed according to the rate of achieving 100% AVM obliteration at follow-up angiography, as well as morbidity, mortality, and perioperative complication rate.

Results

Patients in the Principles group had much higher safety parameters after multimodal embolization therapy; the rate of postoperative bleeding episodes was 9 (9.78%) versus 11 (23.91%) in the Control group (p = 0.039). Radicality levels of AVM nidus obliteration at the control visit were comparable in groups (85 (93.41%) versus 42 (95.45%), respectively, p > 0.999), while the rate of neurologic deficit progression (worsening by at least 2 mRS points) in the principles group was significantly lower (5 (5.43%) versus 9 (19.57%), p = 0.015).

Conclusions

Endovascular embolization shows great potential as the main curative option for reducing the risk of postoperative bleeding due to changing the patient management strategy. Occluding a fistula (if it is present) at the first stage and reducing the degree of AVM obliteration per stage to 60% for large-sized malformations improve treatment safety without decreasing its radicality.

 

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Resumo

Introdução

O sistema de classificação para malformações arteriovenosas (MAVs) e os princípios de embolização curativa para reduzir os riscos de ruptura de MAV causada por rearranjo hemodinâmico abrupto foram modificados utilizando métodos de modelagem matemática. O objetivo do estudo foi confirmar a eficácia clínica desses princípios na redução da taxa de sangramento pós-operatório, de acordo com dados do mundo real.

Métodos

Um estudo retrospectivo, utilizando um banco de dados agrupado, envolvendo 532 pacientes, foi realizado para grupos pareados por características demográficas, anatômicas e clínicas, utilizando o método PSM: o grupo de pacientes tratados com adesão a todos os princípios de embolização (grupo Princípios, n = 92) e o grupo controle, composto por pacientes tratados com violação de pelo menos um princípio (grupo Controle, n = 46). Cada paciente foi submetido a 1 a 9 estágios de embolização. Se necessário, radiocirurgia ou microcirurgia foram utilizadas no estágio final. Os desfechos da terapia foram avaliados de acordo com a taxa de obliteração de 100% da MAV na angiografia de acompanhamento, bem como a morbidade, a mortalidade e a taxa de complicações perioperatórias.

Resultados

Os pacientes do grupo Princípios apresentaram parâmetros de segurança muito mais elevados após a terapia de embolização multimodal; a taxa de episódios de sangramento pós-operatório foi de 9 (9,78%) versus 11 (23,91%) no grupo Controle (p = 0,039). Os níveis de radicalidade da obliteração do nicho da MAV na visita de controle foram comparáveis entre os grupos (85 (93,41%) versus 42 (95,45%), respectivamente, p > 0,999), enquanto a taxa de progressão do déficit neurológico (piora em pelo menos 2 pontos de mRS) no grupo Princípios foi significativamente menor (5 (5,43%) versus 9 (19,57%), p = 0,015).

Conclusões

A embolização endovascular apresenta grande potencial como principal opção curativa para reduzir o risco de sangramento pós-operatório devido à mudança na estratégia de manejo do paciente. A oclusão de uma fístula (se presente) no primeiro estágio e a redução do grau de obliteração da MAV por estágio para 60% em malformações de grande porte melhoram a segurança do tratamento sem diminuir sua radicalidade.

 

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Keywords

AVM - brain arteriovenous malformation

Palavras-chave

MAV - malformação arteriovenosa cerebral

Introduction

A brain arteriovenous malformation (AVM) is a developmental abnormality of cerebral vessels characterized by the presence of a tangle of multiple arteriovenous fistulas and lacking the normal intervening capillary network.[1] These abnormalities restrict blood supply to the brain, causing “blood stealing” in certain zones[2] and the development of different clinical presentations, ranging from the asymptomatic course to epilepsy and severe neurologic deficit in patients with the pseudotumoral course of the disease.[3] [4] Spontaneous brain AVM rupture is the most severe form of the disease; it results in patient disability in at least one-third of cases and a death rate of at least 20%.[5] [6] Therefore, preventive obliteration of AVMs with a high rupture risk needs to be performed.

Three independent surgical options (endovascular embolization, microsurgery, and radiosurgery), or a combination thereof, are currently used for AVM obliteration.[7] The continuous advances in technology increase the effectiveness of using monomodal endovascular embolization and endovascular embolization as part of multimodal AVM treatment.[8] [9] Nonetheless, there still remain several AVMs for which entirely safe total obliteration of AVM can be achieved by none of these embolization options.[10] Postoperative AVM rupture is the most serious risk of embolization that is hard to predict.[11] The total perioperative bleeding rate varies significantly across different studies (1–39% per patient) depending on the surgical option used and patients' baseline characteristics.[12] However, postoperative bleeding is the most life-threatening complication, with the disability rate after it being as high as 45%.[13]

It was believed for a long time that the risk of postoperative bleeding primarily depends on baseline characteristics of AVM such as its size, location, and venous drainage type; many studies have focused on searching for specific predictors to create risk grading systems.[11] [13] [14] However, it has been proved in several recent publications, including those employing mathematical modeling methods, that the perioperative patient management strategy is another crucial factor for reducing the risk of complications.[5] [15] Thus, setting the limit of the degree of single-stage AVM occlusion to be no more than 40–60% of the total AVM size or maintaining postoperative hypotension substantially reduces the rate of postoperative complications in the overall patient cohort.[11] [16] [17] However, no specific embolization principles that would take into consideration a combination of the baseline AVM characteristics and indications for endovascular treatment have been proposed and unified thus far.

We have elaborated and implemented the principles of endovascular treatment of AVMs based on a modification of the Spetzler–Martin AVM grading system (grades 1–3)[18] supplemented with such parameters as the presence of high-flow fistula in the AVM. According to these principles, the endovascular treatment strategy should depend on the baseline parameters of AVM to reduce the risk of postoperative bleeding. The objective of the present study was to evaluate how adherence to the proposed embolization principles affects the reduction of postoperative bleeding rate in clinically, demographically, and angioarchitectonically matched groups of patients with AVM selected from a retrospective database by propensity score matching (PSM).

 

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Methods

Study Design and Patient Selection

A retrospective study with a matched groups selected using the PSM method was conducted for a pooled database involving 532 patients with intracranial AVMs who consequently received endovascular treatment at the Neurosurgery Department of the Meshalkin National Medical Research Center in 2009–2017 and at the Medical Center of the Far Eastern Federal University in 2014–2022.

Patients who had undergone at least a single stage of endovascular treatment and completed treatment (n = 430) were selected from the entire database for subanalysis. The exclusion criteria were as follows:

• patients who had previously received endovascular therapy at other medical centers (n = 47), since treatment protocols differ between medical centers.

• patients with grade 4–5 AVMs according to the Spetzler–Martin grading system (n = 73) because of the high frequency of using palliative approaches without aiming at radical obliteration and patients with subtentorial AVMs (n = 19) due to the obvious higher risk of poor outcome in the cases of complications of endovascular therapy.

• patients who had undergone at least a single stage of transvenous embolization (n = 60) because of the baseline anatomical non-matching compared with the overall cohort.

The overall group of patients (n = 231) was retrospectively divided into two subgroups depending on their adherence to the embolization principles and the risk grading system ([Fig. 1]). The principles group consisted of 174 patients who had received treatment in full adherence with the embolization principles; the Control group (violation of at least one embolization principle) involved 57 patients.

Fig. 1 The scheme of adherence to the curative embolization principles depending on the baseline characteristics of AVM and the SVEF grading when using the multimodal approach. Patients with the respective SVEF grades treated in compliance with these scheme were allocated into the Principles group (n = 174); patients treated using any other treatment modality were allocated into the Control group (n = 54).

Patient groups matched according to their demographic, clinical, and anatomical characteristics were selected by PSM to analyze the treatment outcomes; the ratio between patients in the Control and Principles groups was 1: 2 to increase the study power. To eliminate intergroup differences and potential bias in group selection, patients were matched by the following parameters: sex; age; disease duration; Spetzler–Martin AVM grade; AVM size; number of fistulas; number of aneurysms; number, type, and diameter of catheterizable afferents; venous drainage type; number of draining veins; caliber of AVM vessels; type of AVM manifestation; history of AVM rupture; presence and severity of neurologic deficit at treatment initiation. The total reference group consisted of 92 patients in the principles group and 46 patients in the Control group.

 

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The Modified Risk Grading System

Along with the parameter used in the Spetzler–Martin system, our grading system considers the presence of a direct fistula in AVM. Each AVM is assigned a code according to the following SVEF system:

• S – AVM size: 1–up to 3 cm; 2–from 3 to 6 cm; 3–larger than 6 cm.

• V – drainage type: 0–drainage into the superficial venous system.

• E – localization: 0–non-eloquent brain areas; 1–eloquent brain areas.

• F – presence of a direct fistula; 0–no direct fistula; 1–a direct fistula was detected.

 

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Embolization Principles

• – If there is a direct fistula in the AVM, the first stage should involve its embolization. It is not recommended that its racemose portion is embolized during the same session because of the substantial hemodynamic rearrangement after fistula exclusion; it would be safer to divide treatment into several steps.

• – If there are aneurysms hemodynamically associated with the AVM, it is recommended that the first treatment stage involves their embolization, since hemodynamic rearrangement may cause aneurysm rupture.

• – single-stage embolization is acceptable for patients with Spetzler–Martin grades 1–3 malformations sized up to 3 cm; treatment of larger AVMs should be subdivided into several stages. The AVM nidus size (larger or smaller than 3 cm after each stage), presence/absence of a direct fistula or other signs of high flow, and vessel caliber are crucial for embolization staging.

• – if the AVM involves vessels of different caliber, its large-vessel portion needs to be embolized first, and then smaller vessels need to be occluded.

• – when performing stepwise treatment of medium-sized and large AVMs, the size of AVM obliterated during a single session should be ≤ 60%.

 

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Data Collection and Definition of Endpoints

When including a patient in the registry, the information about disease history, AVM characteristics, its manifestation and therapy type, the gross preoperative neurologic status, and angiographic characteristics of AVM based on preoperative examination (CT, MRI, and angiography) were collected, and prospectively submitted to the registry. Technical aspects of the conducted surgery, the emergent complications, and the patient's postoperative status were documented after each treatment stage.

The primary endpoint of the study was the frequency of postoperative bleeding per patient and per treatment stage. The secondary endpoints were 100% AVM obliteration, neurological outcomes in patients (postoperative changes in mRS), development of any perioperative complication and its effect on the patient's overall condition, and early postoperative mortality.

 

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Treatment Protocol and Ethics

Patients underwent 1–9 stages of endovascular treatment. Onyx was conventionally used as the main or the only embolic agent; cyanoacrylates were mostly employed to fill additional AVM compartments (fistulas and fine vascular network). PHIL and coils could also be used at individual steps during the multistage treatment. The individual stepwise treatment approach was determined by performing a dynamic follow-up of the patient's condition after each embolization stage and adding, if needed, radiosurgery or microsurgery methods after one or several embolization stages. For each patient, the total radicality of AVM obliteration was confirmed by intraoperative angiography data at the final treatment stage; the patients underwent additional follow-up examination after 6–12 months to assess the delayed effectiveness of occlusion.

The study was conducted according to the good clinical practice guidelines ensuring that the design, implementation, and communication of data were reliable, patients' rights were protected, and the integrity of subjects was maintained by the confidentiality of their data. The study conducted was approved by the Local Ethics Committee of the Meshalkin National Medical Research Center (Protocol No. 15 dated September 3, 2009). All the patients provided written informed consent in compliance with the Declaration of Helsinki, which included their consent for using their data in analyses and to be presented.

 

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Statistical Analysis

Descriptive statistics were shown as absolute frequencies or medians with interquartile range. The Mann–Whitney U-test, ANOVA, Pearson's χ² test, Fisher's exact test, and non-parametric Kruskal–Wallis test by rank and median multiple comparisons were used depending on the type of the analyzed data. All the reported p-values were based on two-tailed tests of significance; the p-values < 0.05 were considered statistically significant.

To isolate matched groups of patients who had received surgical intervention and minimize the risk of bias, patients were selected using the PSM method. Such parameters as sex, age and type of AVM manifestation, age at treatment initiation, afferent pool, caliber of AVM vessels, afferent size, presence of fistulas and aneurysms, and AVM grade according to the Spetzler–Martin grading system were considered when conducting PSM.

The STATISTICA 7.0 software (StatSoft, USA) and RStudio software version 1.0.136 (Free Software Foundation, Inc., USA) with R packages version 3.3.1 (R Foundation for Statistical Computing, Austria) were used for the analyses.

 

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Results

Patient Characteristics after Propensity Score Matching

Propensity score matching allowed us to isolate reference groups matched by the baseline characteristics but differing in terms of the endovascular treatment strategy employed. [Table 1] summarizes patients' demographic, anamnestic, and clinical characteristics, as well as the angiographic characteristics of AVMs. The number of patients in the principles group (receiving treatment with adherence to the embolization principles) was 92; the Control group (where at least one embolization principle was violated) comprised 46 patients. Men predominated in both groups: 47 (51.09%) in the principles group and 29 (63.04%) in the Control group (p = 0.250).

Table 1 Comparative characteristics of the patients treated with adherence and with violation of the embolization principles after selecting matched groups using the PSM method

Parameter	Principles group (n = 92)	Control group (n = 46)	p-value
sex: females, n (%)	45 (48.91%)	17 (36.96%)	0.25
age at disease onset, years, Me (IQR)	31 (22.75: 40)	33 (23.5: 44.5)	0.385
age at treatment initiation, years, Me (IQR)	36.5 (26: 43.25)	40.5 (29.25: 47.75)	0.14
Spetzler–Martin grade, n (%):
grade 1	5 (5.43%)	2 (4.35%)	0.481
grade 2	38 (41.3%)	24 (52.17%)
grade 3	49 (53.26%)	20 (43.48%)
Maximum AVM size, cm, Me (IQR)	32 (28.75: 38.25)	34 (30: 41)	0.087
Venous drainage, n (%):
superficial	61 (66.3%)	35 (76.09%)
deep	20 (21.74%)	5 (10.87%)	0.294
mixed	11 (11.96%)	6 (13.04%)
Localization in the eloquent area, n (%)	45 (48.91%)	16 (34.78%)	0.163
Presence of fistula in the AVM, n (%)	28 (30.43%)	20 (43.48%)	0.185
Cysts associated with AVM, n (%)	18 (19.57%)	13 (28.26%)	0.349
Presence of an aneurysm associated with AVM, n (%)	22 (23.91%)	14 (30.43%)	0.537
Number of draining veins:
one vein	39 (42.39%)	17 (36.96%)
two veins	28 (30.43%)	16 (34.78%)	0.879
three and more veins	25 (27.17%)	13 (28.26%)
Number of catheterizable afferents, n (%):
one afferent  2–3 afferents  4–5 afferents  ≥ 6 afferents	30 (32.61%) 23 (25%) 12 (13.04%) 27 (29.35%)	14 (30.43%) 19 (41.3%) 5 (10.87%) 8 (17.39%)	0.218
Primary symptom, n (%):
a history of AVM rupture	33 (35.87%)	22 (47.83%)	0.585
pseudotumoral (epileptic seizures, neurologic deficit)	39 (42.39%)	15 (32.61%)
headaches, pulsatile tinnitus	15 (16.30%)	7 (15.22%)
asymptomatic (an MRI finding)	5 (5.43%)	2 (4.35%)
mRS, score, n (%):
score 0: no symptoms	75 (81.52%)	42 (91.3%)	0.273
score 1: no significant impairment of vital activity	15 (16.3%)	3 (6.52%)
score 2: mild impairment of vital activity	2 (2.17%)	1 (2.17%)

Spetzler–Martin grade 1 AVMs were detected in five (5.43%) patients in the principles group and two (4.35%) patients in the Control group; grade 2 AVMs were detected in 38 (41.3%) versus 24 (52.17%) patients, respectively (p = 0.481). AVMs were distributed over localization as follows: the parietal cerebral lobe was affected most frequently (36 (39.13%) versus 13 (28.26%) patients, p = 0.285); then there followed the occipital (22 (23.91%) versus 11 (23.91%), p > 0.999), the frontal (20 (21.74%) versus 11 (23.91%), p = 0.943), and the temporal (18 (19.57%) versus 10 (21.74%), p = 0.94) cerebral lobes.

Approximately 25% of patients in each group were admitted to the medical center for AVM treatment during the first year after the onset of AVM symptoms or finding of AVM in MRI (20 (21.74%) and 13 (28.26%), respectively, p = 0.525). In 24 (26.09%) and 13 (28.26%) patients in the groups, treatment was initiated ≥ 4 years after AVM rupture (p = 0.840). Most patients had no history of AVM rupture (59 (64.13%) versus 24 (52.18%), p = 0.199), but AVM was asymptomatic only in a small percentage of patients (5 (5.43%) versus 2 (4.35%), p > 0.999).

 

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Characterization of the Conducted Treatment

Depending on the patient's baseline condition, as well as AVM size and characteristics, and in compliance with the principles of safe multimodal treatment, each patient underwent one to nine successive stages of surgical treatment. For 20 (21.74%) patients in the Principles group and 25 (54.35%) patients in the Control group, treatment involved a single stage (p < 0.001); at least four treatment stages were conducted for 36 (39.13%) and 8 (17.39%) patients in both groups (p = 0.012); the median number of treatment stages was 3 (2: 4) and 1 (1: 3), respectively (p < 0.001). Endovascular treatment was combined with elective microsurgery and radiosurgery as the final treatment stage because radical AVM occlusion using monomodal embolization as the only technique was either infeasible or unsafe in 19 (20.65%) and 8 (8.70%) patients in the principles group and in 5 (10.87%) and 2 (4.35%) patients in the Control group (p = 0.218). A total of 301 treatment stages with 278 embolizations were conducted for patients in the principles group and 94 treatment stages with 87 embolizations, for patients in the Control group.

During the entire treatment period, Onyx was used at most treatment stages (n = 221 (79.5%) and 64 (73.56%) embolization stages in the Principles and Control groups, respectively, p = 0.239); cyanoacrylates were applied less frequently (68 (24.46%) and 20 stages (22.99%), p = 0.886); PHIL was used at 8 (2.88%) and 6 (6.9%) stages, p = 0.109); coils were additionally used at 20 (7.19%) and 6 (6.9%) stages, p > 0.999. In total, combinations of two embolic agents were applied at 24 (8.63%) and 5 (5.75%) stages, p = 0.498.

 

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Clinical and Angiographic Effectiveness of Treatment

[Table 2] summarizes the results of AVM occlusion and clinical outcomes after the final treatment stage and after the follow-up for 6–12 months. Both treatment strategies made it possible to achieve comparable occlusion effectiveness: 80 (86.96%) in the principles group and 40 (86.96%) in the Control group (p > 0.999) immediately after the final treatment stage had been completed; at the control visit, this parameter was 85 (93.41%) versus 42 (95.45%) (p > 0.999). Adherence to the embolization principles ensured better clinical outcomes: the number of patients having mRS = 0–2 at discharge was 88 (95.65%) versus 38 (82.61%) (p = 0.021). Furthermore, the neurologic deficit was substantially worsened (by ≥ 2 mRS points) in a significantly smaller percentage of patients in the principles group (5 (5.43%) versus 9 (19.57%), p = 0.038).

Table 2 The main clinical and angiographic treatment outcomes in the groups

Outcome	Principles group	Control group	p value
Parameters after treatment completion	92 patients	46 patients
Radicality (total AVM obliteration immediately after treatment)	80 (86.96%)	40 (86.96%)	>0.999
No neurologic deficit (mRS = 0) at discharge	72 (78.26%)	31 (67.39%)	0.213
Good neurologic outcome (mRS = 0–1) at discharge	86 (93.48%)	37 (80.43%)	0.038
No neurologic deficit or any improvement	73 (79.35%)	32 (69.57%)	0.212
Worsening (by at least 1 mRS point)	16 (17.39%)	13 (28.26%)	0.183
Significant worsening (by at least 2 mRS points)	5 (5.43%)	9 (19.57%)	0.015
Attainment of mRS = 2 or higher	6 (6.52%)	9 (19.57%)	0.038
Morbidity (mRS = 3–5)	3 (3.26%)	6 (13.04%)	0.06
In-hospital mortality rate	1 (1.09%)	2 (4.35%)	0.258
Parameters at follow-up examination after 6–12 months	91 patients	44 patients
Radicality	85 (93.41%)	42 (95.45%)	>0.999
No neurologic deficit (mRS = 0)	72 (79.12%)	31 (70.45%)	0.286
No neurologic deficit or any improvement (compared with the baseline condition)	73 (80.22%)	32 (72.73%)	0.379
Morbidity (mRS = 3–5)	3 (3.3%)	6 (13.64%)	0.058

 

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Treatment-related Complications

All the technical complications related to intraoperative bleeding and thromboembolic complications, as well as any postoperative complications, were recorded at each treatment stage. Patients in the Principles groups had significantly better safety parameters concerning the total risk of perioperative complications at each treatment stage (46 (16.55%) versus 24 (27.59%) stages with complications, p = 0.029) and perioperative complications related to the development of persistent neurologic deficit (19 (6.83%) versus 17 (19.54%) stages, p = 0.002). [Table 3] lists the detailed structure of the types of intraoperative technical and postoperative complications.

Table 3 The structure of intra- and postoperative complications in the treatment groups with allowance for the total rates of technical complications and complications related to aggravation of patient's condition by ≥ 1 mRS points

Complication type	Rate per patient			Rate per treatment stage
	Principles group (n = 92)	Control group (n = 46)	p-value	Principles group (n = 278)	Control group (n = 87)	p-value
The total rate of complications, including those unrelated to aggravation of patient's condition
Intraoperative technical complications	16 (17.39%)	6 (13.04%)	0.625	20 (7.19%)	6 (6.9%)	>0.999
Postoperative complications	23 (25%)	16 (34.78%)	0.236	26 (9.35%)	18 (20.69%)	0.008
Hemorrhagic	9 (9.78%)	11 (23.91%)	0.039	9 (3.24%)	11 (12.64%)	0.002
Ischemic	16 (17.39%)	7 (15.22%)	0.813	17 (6.12%)	7 (8.05%)	0.62
Complications related to aggravation of patient's condition
Intraoperative technical complications	3 (3.26%)	2 (4.35%)	>0.999	3 (1.08%)	2 (2.3%)	0.343
Postoperative complications	15 (16.3%)	11 (23.91%)	0.356	16 (5.76%)	15 (17.24%)	0.002
Hemorrhagic	5 (5.43%)	8 (17.39%)	0.032	5 (1.8%)	8 (9.2%)	0.004
Ischemic	11 (11.96%)	7 (15.22%)	0.600	11 (3.96%)	7 (8.05%)	0.154

Adherence to the embolization principles was shown to significantly reduce the risk of postoperative bleeding in patients (both for each patient and during the entire treatment period): (9 (9.78%) patients having complications in the principles group versus 11 (23.91%) patients in the Control group, p = 0.039). This benefit was demonstrated not only for the total number of postoperative bleeding episodes but also for complications associated with persistent aggravation of the patient's condition by at least one mRS point ([Fig. 2]). Longer treatment duration because of the increasing number of stages was not associated with higher risk of disabling postoperative complications if embolization principles were adhered to, while non-adherence to these principles abruptly increased the number of complications when the number of treatment stages was more than four.

Fig. 2 The dynamics of the risk of postoperative bleeding episodes depending on the number of treatment stages in the groups of patients treated with adherence to the embolization principles and those treated with violation of at least one principle. (A) The total number of postoperative bleeding episodes; (B) postoperative bleeding episodes associated with the development of persistent neurologic deficit.

 

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Discussion

A comparison of the two surgical treatment strategies demonstrated that adherence to the outlined curative embolization principles (obliteration of the fistula component at the first individual stage followed by gradual occlusion of large-sized malformations, with no more than 60% of malformation volume being occluded per session) both significantly reduces the risk of postoperative bleeding, while maintaining radicality of AVM treatment, and allows better clinical outcomes to be achieved. In groups matched by their baseline demographic, anatomic, and clinical characteristics, the approach involving adherence to the embolization principles ensured complete AVM obliteration in 93.4% of patients at the follow-up examination; the total rate of postoperative bleeding decreased from 12.64% to 3.24% per stage, and the rate of associated disabilities was reduced to 1.8% per stage.

Performing total AVM nidus occlusion is always the key objective of AVM treatment since only this procedure eliminates the risk of further bleeding from the AVM.[5] However, the surgery per se is also associated with certain risks of hemorrhagic complications that need to be taken into account when planning a surgical intervention and deciding whether or not it is justified for the patient at this very moment.[19] The clinical significance of these complications may substantially vary depending on the bleeding type. A study involving 408 patients with AVM demonstrated that although almost half (48%) of all the hemorrhagic complications were related to periprocedural arterial perforation, they did not aggravate patients' clinical condition, and their sequelae were compensated.[ 20] Contrariwise, more neurologic deficits, and worse prognoses were observed in patients having hemodynamic hemorrhagic complications; premature venous occlusion was among their significant predictors. Therefore, as demonstrated in our study, modification of the endovascular strategy is very promising for mitigating the risks of disabling perioperative bleeding.

The risk of postoperative bleeding is currently being reduced by using different approaches to complication prediction, such as assessment of individual predictors of unfavorable outcomes,[11] [13] application of comprehensive grading systems,[13] [14] [21] and various hemodynamic rearrangement modeling methods.[5] [15] [16] [22] Many studies are currently attempting to identify factors predicting complications of surgical AVM treatment.[12] [23] [24] Indeed, this approach allows one to elucidate the general patterns and identify groups having the highest complication risk. Thus, most researchers agree that the treatment of high-grade deep AVMs is the most challenging since this type of AVM is associated with the worst degree of obliteration radicality and functional outcomes.[23] [24] However, predictors of unfavorable outcomes for low-grade AVMs sometimes cannot be identified.[17] [25] Furthermore, there exists significant variability in data on individual predictors reported in different studies. Thus, several studies consider smaller AVM size a predictor of lower complication rate,[11] [26] while this parameter can be regarded as a factor of greater risk of interventions in other patient samples.[27] Such lack of consistency is attributed to the heterogeneity of the baseline characteristics and the fact that additional patient subgroups need to be singled out for analysis, which is not always feasible within a single study site with group size being retained.[28] [29] In our study, we have demonstrated that combining factors that allow one to identify groups as being more homogeneous from a surgical strategy perspective is an important aspect of risk stratification. Simultaneous consideration of AVM size and the presence of individual compartments responsible for the hemodynamic features of AVMs enables the creation of a more realistic hemodynamic model and allows one to identify the optimal AVM embolization scenarios.[16]

Another method for assessing the complication risk is to preliminarily calculate the likelihood of unfavorable outcomes using different grading systems.[13] [14] [21] The Spetzler–Martin grading system[18] remains the most popular, even though it was not originally intended to be employed during the endovascular treatment of AVMs. This approach has several drawbacks. First, most existing risk grading systems target a certain AVM treatment modality and cannot be used to answer the question of whether there is a more prognostically favorable alternative treatment strategy (e.g., switching from microsurgery to radiosurgery). Second, it has been demonstrated recently that risks need to be additionally stratified depending on patients' baseline characteristics (e.g., the features of AVM manifestation or anatomical characteristics of AVM). Some researchers have attempted to solve these problems by proposing algorithms to decide a certain treatment modality based on modified grading scales or assessment of additional AVM parameters.[15] [21] [30] However, the strategies they proposed did not involve endovascular embolization as the main curative option, which is currently one of the leading trends in AVM treatment.[23] [31] Finally, none of the existing scales addresses the question related to surgical strategy modification within a single modality depending on the baseline characteristics of AVM. It has been shown that individual intra- and postoperative measures such as reduction of the devascularization volume per session,[11] [16] occlusion of individual AVM compartments at the first stage,[32] and controlling postprocedural hypotension[33] can significantly affect the complication rate and severity. Therefore, it is important to assess the risks caused by each type of intervention, and surgical strategies should be modified with allowance for elimination of potential risks which have been undertaken in this work.

A mathematical model was employed in our previous studies to demonstrate that isolated occlusion of the fistula component at the first stage and stepwise occlusion of large-sized AVMs (no more than 60% of AVM volume per stage) are the two key factors minimizing the risk of AVM rupture during treatment.[16] Based on this preliminary modeling of hemodynamic rearrangement during treatment, we have proposed a safer scenario of AVM embolization, where the fistula component was occluded at the first stage, and then the blood flow in large AVMs was gradually reduced. However, the questions related to real-world evidence of the effectiveness of employing these hemodynamic rearrangement principles for reducing the risks of AVM rupture and integrating them with multimodal treatment strategies remain unanswered. We have elaborated our modification of the Spetzler–Martin risk grading system[18] with allowance for the fact whether there was a fistula in the AVM and proposed the principles of endovascular treatment of AVMs considering both the preoperative characteristics of patients and the treatment course. Therefore, the benefits of all three assessment methods have been combined and used, so we proceeded from the isolated risk grading paradigm to using a practical tool to make decisions regarding patient management to minimize risks and choose the optimal surgical strategy.

In some studies, such parameter as rapid AVM occlusion (with the minimal number of stages used) is considered to attest to high treatment effectiveness because of the significant risk of postoperative rupturing of AVM that has not been completely obliterated and the economically driven motivation to decrease the number of expensive endovascular treatment stages.[2] However, most surgeons and professional communities have recently inferred that it is a multistage treatment that enables gradual reduction of blood flow through the nidus and minimization of the risks of hemorrhage and cerebral edema,[34] and cost-effectiveness analysis must take into account the post-treatment disability rate. Our study has demonstrated that the larger number of embolization stages during multistage treatment does not increase the risk of disabling postoperative hemorrhages and even significantly reduces it both per stage (from 9.2% to 1.8%) and per patient (from 17.39% to 5.43%), which is associated with substantial reduction of indirect medical costs, including those for patient rehabilitation.

The present study has several limitations. First, its design is non-randomized. Due to the use of the PSM method, we have achieved good matching between the initial groups concerning the anatomic, demographic, and clinical characteristics. However, further multicenter prospective studies are required to expand the list of indications for using the proposed principles. The sample size is another limitation. Although our total cohort of patients was one of the largest prospective cohorts, with the total number of patients being > 400, implementation of the embolization principles and quick attainment of clinically significant benefits from using them have made it ethically impossible to have a large Control group where these principles would be violated.

 

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Conclusions

Implementing the principles of fistula occlusion at the first stage followed by gradual blood flow reduction in large AVMs and devascularization of no more than 60% of total AVM volume per stage into the scenarios of endovascular AVM embolization allows one to substantially improve the safety of both mono- and multimodal treatment strategies due to minimization of the total risk of perioperative complications per stage and the risk of disabling postoperative bleeding, while the occlusion effectiveness remains high.

 

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Conflict of Interest

None.

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Publication History

Received: 15 November 2023

Accepted: 20 March 2025

Article published online:
16 July 2025