Management of Arteriovenous Malformations – A Sisyphean Task?
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.364081
Source of Support: None, Conflict of Interest: None
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”), 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.
Natural history of AVMs
The risk of bleeding from intracranial AVM ranges from 2% to 4% per year. 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 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.
ARUBA: Setting the cat among pigeons?
ARUBA was a prospective, multicenter, parallel design, nonblinded, randomized controlled trial. 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.
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.
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. 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.
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 and SM grade can be used to estimate the efficacy of radiosurgery and surgical resection.
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. 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.
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].
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. 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.