Radiosurgery as a microsurgical adjunct: outcomes after microsurgical resection of intracranial arteriovenous malformations previously treated with stereotactic radiosurgery

OBJECTIVE Microsurgical resection of arteriovenous malformations (AVMs) can be aided by staged treatment consisting of stereotactic radiosurgery followed by resection in a delayed fashion. This approach is particularly useful for high Spetzler-Martin (SM) grade lesions because radiosurgery can reduce flow through the AVM, downgrade the SM rating, and induce histopathological changes that additively render the AVM more manageable for resection. The authors present their 28-year experience in managing AVMs with adjunctive radiosurgery followed by resection. METHODS The authors retrospectively reviewed records of patients treated for cerebral AVMs at their institution between January 1990 and August 2019. All patients who underwent stereotactic radiosurgery (with or without embolization), followed by resection, were included in the study. Of 1245 patients, 95 met the eligibility criteria. Univariate and multivariate regression analyses were performed to assess relationships between key variables and clinical outcomes. RESULTS The majority of lesions treated (53.9%) were high grade (SM grade IV–V), 31.5% were intermediate (SM grade III), and 16.6% were low grade (SM grade I–II). Hemorrhage was the initial presenting sign in half of all patients (49.5%). Complete resection was achieved among 84% of patients, whereas 16% had partial resection, the majority of whom received additional radiosurgery. Modified Rankin Scale (mRS) scores of 0–2 were achieved in 79.8% of patients, and 20.2% had poor (mRS scores 3–6) outcomes. Improved (44.8%) or stable (19%) mRS scores were observed among 63.8% of patients, whereas 36.2% had a decline in mRS scores. This includes 22 patients (23.4%) with AVM hemorrhage and 6 deaths (6.7%) outside the perioperative period but prior to AVM obliteration. CONCLUSIONS Stereotactic radiosurgery is a useful adjunct in the presurgical management of cerebral AVMs. Multimodal therapy allowed for high rates of AVM obliteration and acceptable morbidity rates, despite the predominance of high-grade lesions in this series of patients.

Magnetic Resonance Imaging-Based Robotic Radiosurgery of Arteriovenous Malformations

ObjectiveCyberKnife offers CT- and MRI-based treatment planning without the need for stereotactically acquired DSA. The literature on CyberKnife treatment of cerebral AVMs is sparse. Here, a large series focusing on cerebral AVMs treated by the frameless CyberKnife stereotactic radiosurgery (SRS) system was analyzed.MethodsIn this retrospective study, patients with cerebral AVMs treated by CyberKnife SRS between 2005 and 2019 were included. Planning was MRI- and CT-based. Conventional DSA was not coregistered to the MRI and CT scans used for treatment planning and was only used as an adjunct. Obliteration dynamics and clinical outcome were analyzed.Results215 patients were included. 53.0% received SRS as first treatment; the rest underwent previous surgery, embolization, SRS, or a combination. Most AVMs were classified as Spetzler-Martin grade I to III (54.9%). Hemorrhage before treatment occurred in 46.0%. Patients suffered from headache (28.8%), and seizures (14.0%) in the majority of cases. The median SRS dose was 18 Gy and the median target volume was 2.4 cm³. New neurological deficits occurred in 5.1% after SRS, with all but one patient recovering. The yearly post-SRS hemorrhage incidence was 1.3%. In 152 patients who were followed-up for at least three years, 47.4% showed complete AVM obliteration within this period. Cox regression analysis revealed Spetzler-Martin grade (P = 0.006) to be the only independent predictor of complete obliteration.ConclusionsAlthough data on radiotherapy of AVMs is available, this is one of the largest series, focusing exclusively on CyberKnife treatment. Safety and efficacy compared favorably to frame-based systems. Non-invasive treatment planning, with a frameless SRS robotic system might provide higher patient comfort, a less invasive treatment option, and lower radiation exposure.

Somatic Mosaicism in the Pathogenesis of de novo Cerebral Arteriovenous Malformations: A Paradigm Shift Implicating the RAS-MAPK Signaling Cascade

Cerebral arteriovenous malformations (AVMs) are leading causes of lesional hemorrhagic stroke in both the pediatric and young adult population, with sporadic AVMs accounting for the majority of cases. Recent evidence has identified somatic mosaicism in key proximal components of the RAS-MAPK signaling cascade within endothelial cells collected from human sporadic cerebral AVMs, with early preclinical models supporting a potential causal role for these mutations in the pathogenesis of these malformations. Germline mutations that predispose to deregulation of the RAS-MAPK signaling axis have also been identified in hereditary vascular malformation syndromes, highlighting the key role of this signaling axis in global AVM development. Herein, we review the most recent genomic and preclinical evidence implicating somatic mosaicism in the RAS-MAPK signaling pathway in the pathogenesis of sporadic cerebral AVMs. Also, we review evidence for RAS-MAPK dysregulation in hereditary vascular malformation syndromes and present a hypothesis suggesting that this pathway is central for the development of both sporadic and syndrome-associated AVMs. Finally, we examine the clinical implications of these recent discoveries and highlight potential therapeutic targets within this signaling pathway.

Combined strategies on the treatment of cerebellar arteriovenous malformation

Cerebellar arteriovenous malformations (AVMs) comprise 10%–15% of all intracranial AVMs and have a higher risk for morbidity and mortality than supratentorial AVMs. Patients with cerebellar AVMs present with hemorrhage more often than patients with cerebral AVMs, justifying an interventional treatment. Patient outcome can be predicted with specific grade systems, guiding vascular neurosurgeons in decision-making. The authors present the case of a 42-year-old man incidentally diagnosed with an unruptured cerebellar inferior vermian AVM, which was managed through a combined strategy of preoperative endovascular embolization of the main arterial feeders followed by microsurgical resection via midline suboccipital craniotomy, with a favorable outcome.The video can be found here: https://youtu.be/3WESejZbk90