scholarly journals Pathogenesis and radiobiology of brain arteriovenous malformations: implications for risk stratification in natural history and posttreatment course

2009 ◽  
Vol 26 (5) ◽  
pp. E9 ◽  
Author(s):  
Achal S. Achrol ◽  
Raphael Guzman ◽  
Monika Varga ◽  
John R. Adler ◽  
Gary K. Steinberg ◽  
...  

Brain arteriovenous malformations (BAVMs) are an important cause of intracerebral hemorrhage (ICH) in young adults. Biological predictors of future ICH risk are lacking, and controversy exists over previous studies of natural history risk among predominantly ruptured BAVM cohorts. Recent studies have suggested that the majority of BAVMs are now diagnosed as unruptured lesions, and that the risk according to natural history among these lesions may be less than previously assumed. In the first part of this review, the authors discuss available data on the natural history of BAVMs and highlight the need for future studies that aim to develop surrogate biomarkers of disease progression that accurately predict future risk of ICH in BAVMs. The etiology of BAVM remains unknown. Recent studies have suggested a role for genetic factors in the pathogenesis of sporadic BAVM, which is further supported by reports of familial occurrence of BAVM and association with known systemic genetic disorders (such as Osler-Weber-Rendu disease, Sturge-Weber disease, and Wyburn-Mason syndrome). Molecular characterization of BAVM tissue demonstrates a highly angiogenic milieu with evidence of increased endothelial cell turnover. Taken together with a number of reports of de novo BAVM formation, radiographic growth after initial BAVM diagnosis, and regrowth after successful treatment of BAVM, these findings challenge the long-held assumption that BAVMs are static lesions of congenital origin. In the second part of this review, the authors discuss available data on the origins of BAVM and offer insights into future investigations into genetics and endothelial progenitor cell involvement in the pathogenesis of BAVM. Current treatment options for BAVM focus on removal or obliteration of the lesion in an attempt to protect against future ICH risk, including microsurgical resection, endovascular embolization, and stereotactic radiosurgery (SRS). In the third part of this review, the authors discuss available data on SRS in BAVMs and highlight the need for future studies on the radiobiology of BAVMs, especially in regard to biomarker detection for tracking SRS response during the latency period. Insights from future investigations in BAVM may not only prove important for the development of novel therapies and relevant biomarkers for BAVM, but could also potentially benefit a variety of other disorders involving new vessel formation in the CNS, including stroke, tumors, moyamoya disease, and other cerebrovascular malformations.

Neurology ◽  
2020 ◽  
Vol 95 (20) ◽  
pp. 917-927 ◽  
Author(s):  
Ching-Jen Chen ◽  
Dale Ding ◽  
Colin P. Derdeyn ◽  
Giuseppe Lanzino ◽  
Robert M. Friedlander ◽  
...  

Brain arteriovenous malformations (AVMs) are anomalous direct shunts between cerebral arteries and veins that convalesce into a vascular nidus. The treatment strategies for AVMs are challenging and variable. Intracranial hemorrhage and seizures comprise the most common presentations of AVMs. However, incidental AVMs are being diagnosed with increasing frequency due to widespread use of noninvasive neuroimaging. The balance between the estimated cumulative lifetime hemorrhage risk vs the risk of intervention is often the major determinant for treatment. Current management options include surgical resection, embolization, stereotactic radiosurgery (SRS), and observation. Complete nidal obliteration is the goal of AVM intervention. The risks and benefits of interventions vary and can be used in a combinatorial fashion. Resection of the AVM nidus affords high rates of immediate obliteration, but it is invasive and carries a moderate risk of neurologic morbidity. AVM embolization is minimally invasive, but cure can only be achieved in a minority of lesions. SRS is also minimally invasive and has little immediate morbidity, but AVM obliteration occurs in a delayed fashion, so the patient remains at risk of hemorrhage during the latency period. Whether obliteration can be achieved in unruptured AVMs with a lower risk of stroke or death compared with the natural history of AVMs remains controversial. Over the past 5 years, multicenter prospective and retrospective studies describing AVM natural history and treatment outcomes have been published. This review provides a contemporary and comprehensive discussion of the natural history, pathobiology, and interventions for brain AVMs.


2021 ◽  
pp. 1-8
Author(s):  
Rajeev D. Sen ◽  
Isaac Josh Abecassis ◽  
Jason Barber ◽  
Michael R. Levitt ◽  
Louis J. Kim ◽  
...  

OBJECTIVE Brain arteriovenous malformations (bAVMs) most commonly present with rupture and intraparenchymal hemorrhage. In rare cases, the hemorrhage is large enough to cause clinical herniation or intractable intracranial hypertension. Patients in these cases require emergent surgical decompression as a life-saving measure. The surgeon must decide whether to perform concurrent or delayed resection of the bAVM. Theoretical benefits to concurrent resection include a favorable operative corridor created by the hematoma, avoiding a second surgery, and more rapid recovery and rehabilitation. The objective of this study was to compare the clinical and surgical outcomes of patients who had undergone concurrent emergent decompression and bAVM resection with those of patients who had undergone delayed bAVM resection. METHODS The authors conducted a 15-year retrospective review of consecutive patients who had undergone microsurgical resection of a ruptured bAVM at their institution. Patients presenting in clinical herniation or with intractable intracranial hypertension were included and grouped according to the timing of bAVM resection: concurrent with decompression (hyperacute group) or separate resection surgery after decompression (delayed group). Demographic and clinical characteristics were recorded. Groups were compared in terms of the primary outcomes of hospital and intensive care unit (ICU) lengths of stay (LOSs). Secondary outcomes included complete obliteration (CO), Glasgow Coma Scale score, and modified Rankin Scale score at discharge and at the most recent follow-up. RESULTS A total of 35/269 reviewed patients met study inclusion criteria; 18 underwent concurrent decompression and resection (hyperacute group) and 17 patients underwent emergent decompression only with later resection of the bAVM (delayed group). Hyperacute and delayed groups differed only in the proportion that underwent preresection endovascular embolization (16.7% vs 76.5%, respectively; p < 0.05). There was no significant difference between the hyperacute and delayed groups in hospital LOS (26.1 vs 33.2 days, respectively; p = 0.93) or ICU LOS (10.6 vs 16.1 days, respectively; p = 0.69). Rates of CO were also comparable (78% vs 88%, respectively; p > 0.99). Medical complications were similar in the two groups (33% hyperacute vs 41% delayed, p > 0.99). Short-term clinical outcomes were better for the delayed group based on mRS score at discharge (4.2 vs 3.2, p < 0.05); however, long-term outcomes were similar between the groups. CONCLUSIONS Ruptured bAVM rarely presents in clinical herniation requiring surgical decompression and hematoma evacuation. Concurrent surgical decompression and resection of a ruptured bAVM can be performed on low-grade lesions without compromising LOS or long-term functional outcome; however, the surgeon may encounter a more challenging surgical environment.


Neurosurgery ◽  
2014 ◽  
Vol 74 (suppl_1) ◽  
pp. S74-S82 ◽  
Author(s):  
R. Webster Crowley ◽  
Andrew F. Ducruet ◽  
Cameron G. McDougall ◽  
Felipe C. Albuquerque

Abstract Arteriovenous malformations (AVMs) of the brain represent unique challenges for treating physicians. Although these lesions have traditionally been treated with surgical resection alone, advancements in endovascular and radiosurgical therapies have greatly expanded the treatment options for patients harboring brain AVMs. Perhaps no subspecialty within neurosurgery has seen as many advancements over a relatively short period of time as the endovascular field. A number of these endovascular innovations have been designed primarily for cerebral AVMs, and even those advancements that are not particular to AVMs have resulted in substantial changes to the way cerebral AVMs are treated. These advancements have enabled the embolization of cerebral AVMs to be performed either as a stand-alone treatment, or in conjunction with surgery or radiosurgery. Perhaps nothing has impacted the treatment of brain AVMs as substantially as the development of liquid embolics, most notably Onyx and n-butyl cyanoacrylate. However, of near-equal impact has been the innovations seen in the catheters that help deliver the liquid embolics to the AVMs. These developments include flow-directed catheters, balloon-tipped catheters, detachable-tipped catheters, and distal access catheters. This article aims to review some of the more substantial advancements in the endovascular treatment of brain AVMs and to discuss the literature surrounding the expanding indications for endovascular treatment of these lesions.


Neurosurgery ◽  
2020 ◽  
Vol 87 (5) ◽  
pp. 871-878
Author(s):  
Daniel M S Raper ◽  
Ethan A Winkler ◽  
W Caleb Rutledge ◽  
Daniel L Cooke ◽  
Adib A Abla

Abstract Despite a variety of treatment options for brain arteriovenous malformations (bAVMs), many lesions remain challenging to treat and present significant ongoing risk for hemorrhage. In Vitro investigations have recently led to a greater understanding of the formation, growth, and rupture of bAVMs. This has, in turn, led to the development of therapeutic targets for medications for bAVMs, some of which have begun testing in clinical trials in humans. These include bevacizumab, targeting the vascular endothelial growth factor driven angiogenic pathway; thalidomide or lenalidomide, targeting blood-brain barrier impairment; and doxycycline, targeting matrix metalloproteinase overexpression. A variety of other medications appear promising but either requires adaptation from other disease states or development from early bench studies into the clinical realm. This review aims to provide an overview of the current state of development of medications targeting bAVMs and to highlight their likely applications in the future.


2018 ◽  
Vol 16 (2) ◽  
pp. E44-E44
Author(s):  
M Neil Woodall ◽  
Robert F Spetzler

Abstract Arteriovenous malformations (AVMs) involving the conus medullaris have a unique angioarchitecture due to their involvement of the arterial basket of the conus medullaris, which represents an arterial anastomotic network between the anterior spinal artery (ASA) and posterior spinal arteries (PSAs) at the level of the conus medullaris.1 These lesions consist of a combination of a true AVM nidus, which is usually extramedullary, and direct shunts between the ASA, PSAs, and the venous system. Patients may present with radiculopathy, myelopathy, or subarachnoid hemorrhage.2 A 40-yr-old woman status post T11-L1 laminoplasty for resection of a ruptured conus AVM 6 yr prior presented with routine follow-up angiography suggestive of an arteriovenous fistula. She was counseled regarding treatment options including endovascular embolization and microsurgical ligation or resection, and she elected to proceed with surgical treatment. At the time of surgery, a recurrent AVM was noted. A 2-dimensional intraoperative video illustrates the microsurgical treatment of her recurrent conus AVM. The patient recovered well postoperatively. Spinal angiography demonstrated complete obliteration of the lesion. The patient experienced transient urinary retention that was self-limited but otherwise was without any new neurological deficit. Due to the retrospective nature of this report, informed consent was not required. Video used with permission from Barrow Neurological Institute, all rights reserved.


Neurosurgery ◽  
2008 ◽  
Vol 62 (6) ◽  
pp. 1402
Author(s):  
Aki Laakso ◽  
Reza Dashti ◽  
Seppo Juvela ◽  
Kristjan Väärt ◽  
Mika Niemela ◽  
...  

Neurosurgery ◽  
2007 ◽  
Vol 60 (3) ◽  
pp. 453-459 ◽  
Author(s):  
Keisuke Maruyama ◽  
Masahiro Shin ◽  
Masao Tago ◽  
Junji Kishimoto ◽  
Akio Morita ◽  
...  

Abstract OBJECTIVE It remains unclear whether or not and to what extent stereotactic radiosurgery can reduce the risk of first intracranial hemorrhage from brain arteriovenous malformations. METHODS We performed a retrospective observational investigation of 500 patients with arteriovenous malformations who were treated with gamma knife radiosurgery. The risk of first hemorrhage was analyzed using the Cox proportional-hazards model with age at radiosurgery and angiographic obliteration included as time-dependent covariates. Three periods were defined: from birth to radiosurgery (before radiosurgery); from radiosurgery to angiographic obliteration (latency period); and from angiographic obliteration to end of the follow-up period (after obliteration). RESULTS Hemorrhage was documented before radiosurgery in 318 patients (median observation period, 30.0 yr), during the latency period in 11 patients (median observation period, 2.2 yr), and after obliteration in two patients (median observation period, 5.5 yr). Compared with the period before radiosurgery, the risk of hemorrhage decreased by 86% after obliteration (hazard ratio, 0.14; 95% confidence interval, 0.03–0.55; P = 0.005), whereas the reduction observed during the latency period was not statistically significant (hazard ratio, 0.56; 95% confidence interval, 0.31–1.04; P = 0.07). Irrespective of obliteration, the risk of hemorrhage decreased by 62% after radiosurgery (hazard ratio, 0.38; 95% confidence interval, 0.22–0.67; P = 0.001). Similar results were observed when the 33 patients who had undergone previous therapy were excluded from the analysis. CONCLUSION Stereotactic radiosurgery significantly reduces the risk of first hemorrhage from brain arteriovenous malformations. The extent of the decrease might be greater if angiography indicates the evidence of obliteration.


2005 ◽  
Vol 11 (2) ◽  
pp. 141-148 ◽  
Author(s):  
T. L. Li ◽  
B. Fang ◽  
X. Y. He ◽  
C. Z. Duan ◽  
Q. J. Wang ◽  
...  

We independently assessed the frequency, severity and determinants of neurological deficits after endovascular embolization with NBCA of brain arteriovenous malformations (BAVMs) to have a better basis for making treatment decisions. All the charts of 469 BAVMs patients who underwent embolization with NBCA were reviewed. We analyzed the complications and their relation to angiographic features. The 469 patients were treated with 1108 endovascular procedures. Each met one to eight times, average 2.3 times. Eleven patients showed treatment-related complications, including four haemorrhagic and seven ischemic complications. Of these 11 cases, two died, two had persistent disabling deficits, and another seven suffered transient neurological deficits. Our finding suggests a low rate of disabling treatment complications for embolization of brain AVMs with NBCA in this center. The management of AVM patients who have high risk of embolization therapy should be treated by special strategy.


2018 ◽  
Vol 128 (5) ◽  
pp. 1354-1363 ◽  
Author(s):  
Adeel Ilyas ◽  
Ching-Jen Chen ◽  
Dale Ding ◽  
Panagiotis Mastorakos ◽  
Davis G. Taylor ◽  
...  

OBJECTIVECyst formation can occasionally occur after stereotactic radiosurgery (SRS) for brain arteriovenous malformations (AVMs). Given the limited data regarding post-SRS cyst formation in patients with AVM, the time course, natural history, and management of this delayed complication are poorly defined. The aim of this systematic review was to determine the incidence, time course, and optimal management of cyst formation after SRS for AVMs.METHODSA literature review was performed using PubMed to identify studies reporting cyst formation in AVM patients treated with SRS. Baseline and outcomes data, including the incidence and management of post-SRS cysts, were extracted from each study that reported follow-up duration. The mean time to cyst formation was calculated from the subset of studies that reported individual patient data.RESULTSBased on pooled data from 22 studies comprising the incidence analysis, the overall rate of post-SRS cyst formation was 3.0% (78/2619 patients). Among the 26 post-SRS cyst patients with available AVM obliteration data, nidal obliteration was achieved in 20 (76.9%). Of the 64 cyst patients with available symptomatology and management data, 21 (32.8%) were symptomatic; 21 cysts (32.8%) were treated with surgical intervention, whereas the remaining 43 (67.2%) were managed conservatively. Based on a subset of 19 studies reporting individual time-to-cyst-formation data from 63 patients, the mean latency period to post-SRS cyst formation was 78 months (6.5 years).CONCLUSIONSCyst formation is an uncommon complication after SRS for AVMs, with a relatively long latency period. The majority of post-SRS cysts are asymptomatic and can be managed conservatively, although enlarging or symptomatic cysts may require surgical intervention. Long-term follow-up of AVM patients is crucial to the appropriate diagnosis and management of post-SRS cysts.


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