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| EDITORIAL |
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| Year : 2022 | Volume
: 70
| Issue : 6 | Page : 2340-2342 |
Management of Arteriovenous Malformations – A Sisyphean Task?
Dwarakanath Srinivas
Professor and Head, Department of Neurosurgery, NIMHANS, Bengaluru, Karnataka, India
| Date of Submission | 09-Dec-2022 |
| Date of Decision | 09-Dec-2022 |
| Date of Acceptance | 09-Dec-2022 |
| Date of Web Publication | 19-Dec-2022 |
Correspondence Address:
Dwarakanath Srinivas
Professor and Head, Department of Neurosurgery, NIMHANS, Bengaluru - 560 011, Karnataka
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0028-3886.364081
How to cite this article:
Srinivas D. Management of Arteriovenous Malformations – A Sisyphean Task?. Neurol India 2022;70:2340-2 |
There is scarcely any passion without struggle: Albert Camus (The myth of Sisyphus and other essays).
There has been a myriad of possibilities in the management strategies for arteriovenous malformations (AVMs) of the brain. The ideal management has remained a matter of debate over the years, partly because of the variable natural history and the risk of rupture being around 2%–4% per annum. The therapeutic options range from microsurgical resection to embolization and radiosurgery. However, the risk of curse of the Maslow's hammer looms large over the management options offered to the patient.
There has been a general agreement on the management of a ruptured Arteriovenous malformations of Brain (BAVM), with all clinicians agreeing that some form of intervention is needed as the rebleed rate is high. However, when it comes to the management of unruptured BAVMs (uBAVMs), the value of intervention is not so well accepted. The publication of a randomized trial of unruptured brain arteriovenous malformations (ARUBA) and The Scottish Intracranial Vascular Malformation Study (SIVMS) has reignited the debate about the relative value of conservative therapy and any form of intervention for uBAVMs. Although conservative management has always been a management option for selected group of uBAVMs, such as Spetzler–Martin (SM) grade IV and V AVMs, the above-mentioned studies suggest that the value of masterly inactivity (with the philosophy of “primum non nocere”)[1],[2] may also be appropriate for patients with better grade uBAVMs (namely, SM grades I, II, and III). They have forced neurosurgeons to rethink strategies which were considered to have been fairly well accepted for the management of an uBAVM. Moreover, the burden of proof now lies with the neurosurgeons to convince patients that the risks of intervention do not outweigh the risks of conservative therapy for uBAVMs.[3]
Natural history of AVMs
The risk of bleeding from intracranial AVM ranges from 2% to 4% per year.[4] The rehemorrhage rates are highest in the first year (15.4%), falling to 5.3% in the following 4 years and remaining at 1.7% after 5 years. Other risk factors for rupture of AVMs[4] include age, sex, deep location with exclusive deep venous drainage, evidence of microhemorrhage in the lesions, and large size of AVMs.
Overview of management
Historically, the rationale of management has been based on the Spencer Martin (SM) classification of AVMs. While there has been criticism over the management and classification, it still remains the basis of surgical management algorithms. The brunt of the criticism and much of the debate centered upon the status of grade III AVMs, which again were lumped together in spite of having different characteristics.[5]
ARUBA: Setting the cat among pigeons?
ARUBA was a prospective, multicenter, parallel design, nonblinded, randomized controlled trial.[1] The trial was prematurely stopped since the trial had shown an overwhelming superiority for the medical management arm over the outcome of any intervention in uBAVMs when looking at outcomes at 5 years. Since its publication, there have been multiple critiques and series highlighting the flaws of the ARUBA study. The European consensus conference on uBAVMs, in 2017, published a balanced set of recommendations in the light of current evidence.[6]
| » Current Management Options | |  |
Currently, the management of intracranial AVMs ranges from watchful conservative follow-up to using the various intervention modalities mentioned above, either alone or in combination.
Microsurgery
Microsurgical outcomes of SM grade I, grade II, and various grade III AVMs show high cure rates with low complications and immediate elimination of risk of bleed.[7] The radiological cure rate with microsurgery is 94%–100%. Surgery alone can achieve 100% angiographic obliteration in cases of unruptured surface AVMs of a diameter smaller than 3 cm and having superficial venous drainage. The AVMs of grades I, II, and III have combined surgical morbidity and mortality of less than 10%. A study reported that grade I–III AVMs had a good outcome in 89.9% of cases and significant disability occurred in 9.5% of cases with early postoperative mortality in 0.5% cases, whereas 60.7% of good functional outcome, 37.5% of significant disability, and 1.8% of postoperative mortality were reported in grade IV and V AVMs. A recent systematic review revealed the seizure-free outcomes following microsurgical resection, endovascular embolization, and stereotactic radiosurgery (SRS) were 78.3%, 62.8% and 49.3%, respectively.[8]
Radiosurgery in AVMs
AVMs with recent hemorrhage in a surgically inaccessible site are considered good candidates for SRS. For individualized decisions, the Pollock–Flickinger score[9] and SM grade[10] can be used to estimate the efficacy of radiosurgery and surgical resection.
- AVM response following radiosurgery
Obliteration of AVM following Gamma knife radiosurgery (GKRS) occurs between 1 and 5 years. Factors associated with failure of AVM obliteration include low radiation dose, targeting errors, re-expansion of the nidus after hemorrhage, partial recanalization of the previously embolized AVM, diffuse nidus, neovascularization, high blood flow, and complex geometric shape.[11] - Radiosurgery of large AVMs
Existing literature on the dose–volume relationship of AVM radiation-related complications shows a high rate of complications for large AVMs following radiosurgery (15%–22%).[12] Various strategies have been incorporated to circumvent this problem, which include embolization followed by SRS, fractionated radiation techniques, and volume-staged stereotactic radiosurgery (VS-SRS). However, the safest and most effective hypofractionated dosing schedule remains unclear. VS-SRS is an effective treatment strategy in large AVMs. The rate of AVM obliteration has been reported as 14%, 54%, and 75% at 3, 5, and 7 years, respectively.[13]
Embolization in AVM management
The current role of endovascular embolization in the treatment of these lesions includes its use (1) as an adjunctive procedure (before micro- or radiosurgery), (2) as a palliative procedure to partially embolize the weak areas of the AVM angioarchitecture, decreasing the risk of bleeding and improving symptoms, and (3) to produce curative occlusion in selected cases.[14] High-grade AVMs (grade IV–V) with a high flow may become symptomatic due to the vascular steal phenomenon. When these AVMs are deemed incurable, partial palliative embolization has a role in symptomatic management. It is important to remember that while radiosurgery downregulates vascular endothelial growth factor (VEGF), embolization upregulates it. This seemingly antagonistic effect has been proposed as the reason why partially embolized AVMs do worse than nonembolized AVMs in patients undergoing radiosurgery.
- Factors associated with favorable outcomes
When AVMs are associated with intranidal aneurysms, the annual hemorrhage increases to 7% from 4%.[15] The favorable predictors for successful endovascular obliteration are nidus size <30 mm, located in the noneloquent cortex, deep location, nontortuous and superficial large feeders with a single arterial pedicle, angioarchitecture allowing for embolic material reflux of 2–3 cm, unobstructed views of major proximal draining veins, and nonsmoker status. - Embolization before microsurgery
The goals for endovascular embolization of AVMs before surgery are occlusion of the nidus and perinidal feeders with preservation of the venous outflow, elimination of high-risk features (i.e., arterial aneurysms), and occlusion of the deep arterial feeders which would otherwise require more dissection of the brain parenchyma to tackle the nidus. - Embolization before radiosurgery
The main treatment goal is to reduce the volume of AVM and the latency period risk of hemorrhage and to eliminate the radio-resistant features (aneurysms, high-flow fistulas). Pretreatment embolization of large AVMs before SRS helps in achieving obliteration rates of more than 60%. Recanalization of embolized vessels (more common with Polyvinyl alcohol (PVA) embolization) with obscured nidal margins due to proximal feeder embolization, shielding effects prompted by the radiopaque embolic materials, resultant local ischemia promoting angiogenesis, and alteration of AVM geometry interfering with conformal dose planning are the main limitations of pre-SRS embolization.[16] - Outcomes
With the advent of new embolic technology, the morbidity with AVM embolization has significantly reduced (2.4%–2.7%). The overall complication rate of embolization ranges from 5% to 15%. Permanent neurological deficit or death is seen in less than 10% of cases.
| » The Conundrum of the Maslow's Hammer and Current Management Paradigm | | |
Many AVMs are managed in centers where all the three modalities are not available together and the tendency to use whatever resource or modality available becomes the norm. This, in fact actually leads to suboptimal treatment and outcomes. It is better if these patients are referred to a multidisciplinary center for optimal management. Based on available literature, we suggest a simplified management algorithm [Figure 1]. | Figure 1: Simplified suggested management algorithm for management of arteriovenous malformations
Click here to view |
| » Conclusion | | |
Despite the glaring fallacies in the ARUBA trial, it points toward the fact that the treatment of unruptured AVMs is a treacherous adversary and comes with a cost.[17] Continued medical therapy and observation are certainly not universal management for all unruptured AVMs. Appropriate patient selection in high-volume, multidisciplinary centers is key to successful treatment in these extremely complex groups of lesions.
| » References | | |
| 1. | Mohr JP, Parides MK, Stapf C, Moquete E, Moy CS, Overbey JR, et al. Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): A multicentre, non-blinded, randomised trial. Lancet 2014;383:614-21.  |
| 2. | Al-Shahi R, Bhattacharya JJ, Currie DG, Papanastassiou V, Ritchie V, Roberts RC, et al. Prospective, population-based detection of intracranial vascular malformations in adults: The Scottish Intracranial Vascular Malformation Study (SIVMS). Stroke 2003;34:1163-9. |
| 3. | Meling TR, Proust F, Gruber A, Niemela M, Regli L, Roche PR, et al. On apples, oranges, and ARUBA. Acta Neurochir 2014;156:1775-9. |
| 4. | Stapf C, Mast H, Sciacca RR, Choi JH, Khaw AV, Connolly ES, et al. Predictors of hemorrhage in patients with untreated brain arteriovenous malformation. Neurology 2006;66:1350–5. |
| 5. | Lawton MT. Spetzler-Martin Grade III arteriovenous malformations: Surgical results and a modification of the grading scale. Neurosurgery 2003;52:740-9. |
| 6. | Cenzato M, Boccardi E, Beghi E, Vajkoczy P, Szikora I, Motti E, et al. European consensus conference on unruptured brain AVMs treatment (Supported by EANS, ESMINT, EGKS, and SINCH). Acta Neurochir (Wien) 2017;159:1059-64. |
| 7. | Heros RC, Korosue K, Diebold PM. Surgical excision of cerebral arteriovenous malformations: Late results. Neurosurgery 1990;26:570–8. |
| 8. | Baranoski JF, Grant RA, Hirsch LJ, Visintainer P, Gerrard JL, Günel M, et al. Seizure control for intracranial arteriovenous malformations is directly related to treatment modality: A meta-analysis. J Neurointerv Surg 2014;6:684–90. |
| 9. | Pollock BE, Flickinger JC. Modification of the radiosurgery-based arteriovenous malformation grading system. Neurosurgery 2008;63:239–43; discussion 243. |
| 10. | Spetzler RF, Martin NA. A proposed grading system for arteriovenous malformations. J Neurosurg 1986;65:476–83. |
| 11. | Zipfel GJ, Bradshaw P, Bova FJ, Friedman WA. Do the morphological characteristics of arteriovenous malformations affect the results of radiosurgery? J Neurosurg 2004;101:393–401. |
| 12. | Nagy G, Rowe JG, Radatz MWR, Hodgson TJ, Coley SC, Kemeny AA. A historical analysis of single-stage γ knife radiosurgical treatment for large arteriovenous malformations: Evolution and outcomes. Acta Neurochir (Wien) 2012;154:383–94. |
| 13. | Kano H, Kondziolka D, Flickinger JC, Park K-J, Parry P V, Yang H, et al. Stereotactic radiosurgery for arteriovenous malformations, Part 6: Multistaged volumetric management of large arteriovenous malformations. J Neurosurg 2012;116:54–65. |
| 14. | Valavanis A, Pangalu A, Tanaka M. Endovascular treatment of cerebral arteriovenous malformations with emphasis on the curative role of embolisation. Interv Neuroradiol 2005;11(Suppl 1):37–43. |
| 15. | Elhammady MS, Aziz-Sultan MA, Heros RC. The management of cerebral arteriovenous malformations associated with aneurysms. World Neurosurg 2013;80:e123-9. |
| 16. | Sirin S, Kondziolka D, Niranjan A, Flickinger JC, Maitz AH, Lunsford LD. Prospective staged volume radiosurgery for large arteriovenous malformations: Indications and outcomes in otherwise untreatable patients. Neurosurgery 2006;58:17–27. |
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[Figure 1]
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