preferred for patients with brain AVMs associated with a low risk of poor treatment outcomes, correlating with Spetzler-Martin ( table 1) grade 1 or grade 2 lesions [38], with radiosurgery as an alternative for small lesions based upon location or other vascular or anatomic features. Stereotactic radiosurgery is also preferred for small grade 3 lesions. Large grade 3 lesions that involve eloquent cortex have a high surgical morbidity and available evidence suggests that treatment is no better than observational medical management. Conservative medical management is usually preferred for grade 4 or 5 lesions, although some may benefit from partial obliteration with endovascular treatment for high-risk features such as associated aneurysms located within the nidus or on feeding arteries. Microsurgical resection appears to have the highest success rate for seizure control among treatment options for brain AVMs. When analyzed by type of intervention in systematic reviews https://www.uptodate.com/contents/brain-arteriovenous-malformations/print 12/33 7/5/23, 12:18 PM Brain arteriovenous malformations - UpToDate and meta-analyses, the median rate of seizure freedom was highest for resective surgery (73 to 78 percent), followed stereotactic radiosurgery (52 to 63 percent) and embolization (49 to 54 percent) [44,52]. However, as previously noted, observational data suggest that interventional management of brain AVMs may not reduce the risk of subsequent seizures or epilepsy. (See 'Other factors influencing treatment' above.) Particular advantages and disadvantages of the interventional modalities for brain AVMs are discussed in the sections that follow. Microsurgical excision Open microsurgical excision has the longest history of use for the definitive treatment of selected patients with AVMs and offers the best chance immediate cure in patients considered to be at high risk of hemorrhage [37]. The surgery is complicated and often requires detailed planning with review of imaging studies. The main advantages of microsurgical excision compared with other interventions (radiosurgery and endovascular embolization) include a high success rate of complete nidus obliteration, the immediate elimination of hemorrhage risk, and long-term durability [19]. Disadvantages include the invasive nature of the treatment with a risk of neurologic impairments related to dissection of normal adjacent brain parenchyma and neurovascular structures needed to reach the AVM, and a longer recovery period. Postoperative complications include arterial or venous infarction or hemorrhage from the resection cavity. Typically, an arteriogram is performed after the surgery to document complete resection of the lesion. There have been isolated cases of hemorrhage into a resection bed despite obliteration on angiography. The mechanism of such bleeding is uncertain, but may be venous in nature. In addition to cortical injury, deep fiber tract injury can cause transient or permanent morbidity. Pre-operative assessment utilizing functional MRI studies with tractography may help minimize such complications. An important factor in recommending therapy is an assessment of surgical risk. Multiple or large lesions, those in eloquent brain areas, and those with deep venous drainage are more difficult to safely resect. Many surgeons use the Spetzler-Martin grading scale ( table 1) to assess the surgical risk [19]. Several studies have correlated surgical risk with higher Spetzler-Martin grading scale score [53,54]. Female sex may also increase surgical risk [55]. Stereotactic radiosurgery Stereotactic radiosurgery is most successful when used to treat small brain AVMs eg, <3 cm in diameter [2]. Latency period Stereotactically focused high energy beams of photons or protons to a defined volume containing the brain AVM nidus induces progressive thrombosis of properly selected lesions via fibrointimal hyperplasia and subsequent luminal obliteration. The time course of these changes is usually one to three years, sometimes longer, and the https://www.uptodate.com/contents/brain-arteriovenous-malformations/print 13/33 7/5/23, 12:18 PM Brain arteriovenous malformations - UpToDate time between treatment and obliteration is referred to as the latency period. During this latency period, the patient remains at risk for hemorrhage [2]. (See "Stereotactic cranial radiosurgery".) The magnitude of brain AVM hemorrhage risk during the latency period between treatment and obliteration is uncertain; however, the best evidence suggests that it gradually declines during this interval [56]. This is an important consideration, particularly for lesions at higher bleeding risk. Existing studies are generally limited by retrospective and observational design. Earlier studies reported conflicting results, including increased [57-59], decreased [60,61], and unchanged [62,63] bleeding rates during the latency period. One of the largest studies including 500 patients found that the risk of hemorrhage declined by 54 percent during the latency period and by 88 percent after obliteration. The risk reduction was greater among patients who presented with hemorrhage than those who presented without hemorrhage. Another study including 657 patients had similar findings [64]. An untreated cerebral aneurysm was found to be a risk factor for hemorrhage in the latency period in another consecutive case series; the hemorrhage rate was 6.4 percent per year for untreated aneurysms versus 0.8 percent per year for clipped or embolized aneurysms [65]. Once the lesion is completely obliterated, the hemorrhage risk from the brain AVM is very low [66-68], but not totally eliminated [67,69-71]. Incomplete lesion obliteration, hypertension, and prior hemorrhage are risk factors for late bleeding [71]. Success rate Successful brain AVM obliteration with radiosurgery depends upon lesion size and dose of radiation [70]. Complete cure is considerably higher with smaller lesions; an overall 80 percent obliteration rate by three years occurs with lesions that are 3 cm or smaller [59,72-75]. Larger lesions have reported obliteration rates of 30 to 70 percent at three years [72,74,76]. Brain AVMs with a diffuse nidus or associated neovascularity were less likely to achieve a radiographic cure in one clinical series of 248 patients [77]. Despite the lower initial success rates for angiographic obliteration seen with larger brain AVMs (>3 cm), some amount of lesion volume reduction (mean 66 percent) typically occurs [78,79]. The success rate of radiographic brain AVM obliteration also varies with the amount of radiation delivered to the margin of the lesion. Doses of 16, 18, and 20 Gray (Gy) are associated with obliteration rates of about 70, 80, and 90 percent, respectively [79-81]. In one series, brainstem lesions were associated with lower obliteration rates, perhaps because of more conservative radiation dosing [82]. Radiation dose is generally selected according to a protocol which takes in account the size and location of the lesion. https://www.uptodate.com/contents/brain-arteriovenous-malformations/print 14/33 7/5/23, 12:18 PM Brain arteriovenous malformations - UpToDate Retreatment with radiosurgery is effective for complete obliteration in about 60 to 80 percent of patients with residual brain AVMs, depending on the size and other factors [78,83]. Complications Complications after radiosurgery include radiation necrosis, which can produce new neurologic deficits and seizures. In a multinational study that included 1255 patients undergoing radiosurgery for cerebral AVMs, therapy-related complications developed in 102 (8 percent) and included radiographic parenchymal lesions, cranial nerve deficits, seizures, headaches, and cyst formation [84]. Symptoms were disabling in 21, fatal in two, and resolved completely in 42 (41 percent). The risk of radiation necrosis with permanent neurologic deficit is 1 to 3 percent in most reports [72,74,79,85]. In another case series, 10 of 75 patients who had not had seizures and were not on antiseizure medications before radiosurgery had provoked seizures after radiosurgery [86]. The risk of hemorrhage following angiographically confirmed AVM obliteration appears low. In a retrospective cohort of 1607 patients treated with radiosurgery, hemorrhage occurred in 16 patients (1 percent) [87]. Only two of these 16 patients had developed a recurrent AVM, suggesting that hemorrhagic recurrence may also be due to other factors such as dysregulated neovascular proliferation following treatment. The incidence of complications are related to the brain AVM location and the volume treated [75,88]. Thalamic, basal ganglionic, and brainstem locations are particularly prone to development of deficits after radiosurgery [82,88,89]. The risk of complications is also related to the radiation dose directed to the surrounding tissue. The risk of complications is also increased in large brain AVMs that require larger treatment volumes. In a series of 73 patients, in whom one-half of the brain AVMs were >3 cm in diameter, the incidence of post-treatment imaging abnormalities and clinical complications rose with increasing treatment volume [90]. In patients whose treatment volumes were >14 mL and who received a dose 16 Gy, the incidence of post-treatment MRI abnormalities was 72 percent, and 22 percent required resection for radiation necrosis. The rate of post- treatment hemorrhage was also higher for treatment volumes 14 mL (7.5 versus 2.7 percent per person-year). Repeated radiosurgery is also associated with increased complications; but the rate is not clearly prohibitive [83,91]. In one series of 15 patients who underwent two radiosurgeries with a mean dose per session of 18 Gy and 21 Gy, three (20 percent) had permanent radiation-induced complications [91]. No rebleeding occurred over 137 patient-years of follow-up. https://www.uptodate.com/contents/brain-arteriovenous-malformations/print 15/33 7/5/23, 12:18 PM Brain arteriovenous malformations - UpToDate In contrast to standard fractionation cranial irradiation, radiosurgery does not appear to impact cognitive function. One study of 10 patients found no effect of radiosurgical treatment of brain AVMs upon neuropsychological performance 11 months after treatment [92]. Endovascular embolization Despite initial optimism that embolic agents such as microparticles and cyanoacrylates could cure brain AVMs, less than 25 percent of lesions are cured by this approach alone [93]. Typically, AVMs successfully treated with endovascular embolization are small and have a single draining vein [2]. Some experts suggest that embolization can be an effective adjunct to surgery and radiosurgery [94]. Embolization prior to surgery is employed to reduce blood loss and to occlude vessels that may be difficult to control during surgery [95]. Embolization prior to radiosurgery is 3 controversial; it has been used to reduce the nidus size of large brain AVMs to less than 10 cm , as these large AVMs have a lower cure rate with radiosurgery alone. Embolization may also reduce overall flow to the AVM. However, there is some evidence suggesting that embolization may reduce the obliteration rate and the rate of favorable outcomes after radiosurgery [96-100]; this drawback may be caused be embolic material in the AVM that can make it difficult to accurately target the nidus and can shield the AVM from the effects of radiation [19,38]. Endovascular therapy may also be used as primary treatment for intranidal aneurysms. (See "Treatment of cerebral aneurysms", section on 'Endovascular therapy'.) A meticulous analysis of angiographic information (size, eloquent location, deep versus superficial venous drainage, vascular anatomy/number of feeders) determines the suitability for embolization [94,101]. Generally, only afferent pedicles to the nidus are embolized in an attempt to avoid occlusion of branches irrigating normal brain. The risk of new neurologic deficits following endovascular treatment ranges from 8 to 20 percent [93,101,102]. Disabling treatment complications appear to be uncommon [101,102]. The most feared complications are ischemic stroke from embolic material occluding vessels to healthy cerebral adjacent tissue, and periprocedural hemorrhage. Hemorrhage with AVM embolization is usually the result of venous occlusion from the embolic material. Follow-up Long-term follow-up is recommended after AVM treatment with brain MRI, magnetic resonance angiography (MRA), and in some cases with DSA [103]. For adult patients treated with embolization and microsurgical excision, DSA is obtained immediately after the procedures to document complete obliteration of the AVM. https://www.uptodate.com/contents/brain-arteriovenous-malformations/print 16/33 7/5/23, 12:18 PM Brain arteriovenous malformations - UpToDate For adult patients treated with radiosurgery, interval MRI and MRA studies can be obtained at six months and one year. The regression of the AVM nidal volume can be accurately measured and followed with MRI, and the patient can be monitored for white matter change consistent with small vessel occlusion, post-therapy edema, or radiation necrosis [104]. Once an AVM is no longer visualized on an MRI and MRA, DSA can be performed to confirm complete obliteration. For adult patients treated with microsurgical excision, radiosurgery, and/or embolization, no further studies are needed if complete obliteration is documented, unless new symptoms occur. For children treated with microsurgical excision, radiosurgery, and/or embolization, DSA is obtained after both treatment and in a delayed fashion, typically at six months and at five years [103]. For patients who are managed conservatively, we defer follow-up imaging unless new symptoms develop. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Stroke in adults" and "Society guideline links: Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a https://www.uptodate.com/contents/brain-arteriovenous-malformations/print 17/33 7/5/23, 12:18 PM Brain arteriovenous malformations - UpToDate variety of subjects by searching on "patient info" and the keyword(s) of interest.) Basics topics (see "Patient education: Arteriovenous malformations in the brain (The Basics)") SUMMARY AND RECOMMENDATIONS Definition and epidemiology Brain arteriovenous malformations (AVMs) are cerebrovascular malformations characterized by direct arterial to venous connections without an intervening capillary network. They occur in about 0.1 percent of the population but may be the cause of an estimated 1 to 2 percent of all strokes, 3 percent of strokes in young adults, and 9 percent of subarachnoid hemorrhages. (See 'Pathogenesis and pathology' above and 'Epidemiology' above.) Clinical presentation Brain AVMs usually present between the ages of 10 and 40 years with intracranial hemorrhage, seizure, focal neurologic deficit, or headache; a substantial number are asymptomatic and are found incidentally. Hemorrhage is the most common presentation, particularly in children. (See 'Clinical presentation' above.) Risk of hemorrhage Overall, annual hemorrhage rates from brain AVMs are between 2 and 3 percent. After an initial hemorrhage, annual hemorrhage rates are approximately 5 percent. Combinations of risk factors (eg, hemorrhage at initial AVM presentation, deep venous drainage, and deep brain location) may identify patients at particularly low or high risk. Patients with none of these risk factors have an estimated annual hemorrhage rate of approximately 1 percent, while those with all three risk factors may have an annual hemorrhage rate of >30 percent. (See 'Hemorrhage risk' above.) Imaging diagnosis Brain AVMs can be detected on computed tomography, magnetic resonance imaging, and/or noninvasive angiography with computed tomography angiography or magnetic resonance angiography. Digital subtraction angiography is essential for treatment planning and follow-up after treatment of brain AVMs. (See 'Neuroimaging' above.) Management The management of AVMs in any given patient is individualized based on risk factors such as patient age, medical comorbidities, and the anatomic and vascular features of the AVM ( table 1) as well as the risks of morbidity with intervention (see 'Natural history' above and 'Who should be treated?' above): https://www.uptodate.com/contents/brain-arteriovenous-malformations/print 18/33 7/5/23, 12:18 PM Brain arteriovenous malformations - UpToDate For most patients with a ruptured AVM, we suggest intervention (Grade 2C). In some cases, intervention may not be technically feasible or safe or desired by the patient. (See 'Ruptured AVMs' above.) For patients with an unruptured AVM who are not at high risk of rupture, we suggest conservative management (Grade 2C). However, interventional treatment of unruptured AVMs may be performed in select patients at low treatment-related risks, with symptoms (eg, seizures) refractory to medical treatment, or with AVM features posing high risk for rupture. (See 'Unruptured AVMs' above.) For patients selected for intervention, microsurgical excision is often preferred for patients with brain AVMs associated with a low risk of poor treatment outcomes, with radiosurgery as an alternative. Conservative medical management is usually preferred for patients with brain AVMs associated with a high risk of poor treatment outcomes, although some may benefit from partial obliteration with endovascular treatment. (See 'Choice of treatment' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Dalton A, Dobson G, Prasad M, Mukerji N. De novo intracerebral arteriovenous malformations and a review of the theories of their formation. Br J Neurosurg 2018; 32:305. 2. Flemming KD, Lanzino G. 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Assessment of cerebral arteriovenous malformations with high temporal and spatial resolution contrast-enhanced magnetic resonance https://www.uptodate.com/contents/brain-arteriovenous-malformations/print 26/33 7/5/23, 12:18 PM Brain arteriovenous malformations - UpToDate angiography: a review from protocol to clinical application. Top Magn Reson Imaging 2008; 19:251. Topic 1087 Version 37.0 https://www.uptodate.com/contents/brain-arteriovenous-malformations/print 27/33 7/5/23, 12:18 PM Brain arteriovenous malformations - UpToDate GRAPHICS Cerebellar hematoma due to ruptured AVM (A) Noncontrast head CT showing acute right cerebellar ICH with smaller adjacent focus of hemorrhage (black arrow). (B) Subsequent FLAIR sequence on brain MRI after decompressive craniectomy showing flow void (white arrow) adjacent to ICH (white dashed arrow). (C) Digital subtraction angiogram subsequently identified an AVM with a nidus (white arrowhead), feeding artery (white thick arrow), and draining vein (white short arrow). CT: computed tomography; ICH: intracerebral hemorrhage; FLAIR: fluid-attenuated inversion recovery; MRI: magnetic resonance imaging; AVM: arteriovenous malformation. Courtesy of Glenn A Tung, MD, FACR. Graphic 132273 Version 1.0 https://www.uptodate.com/contents/brain-arteriovenous-malformations/print 28/33 7/5/23, 12:18 PM Brain arteriovenous malformations - UpToDate MRI of brain arteriovenous malformation T2-weighted MRI of the brain demonstrates multiple flow voids in the right hemisphere, suggestive of a large arteriovenous malformation. MRI: magnetic resonance imaging. From: Flemming KD, Lanzino G. Management of Unruptured Intracranial Aneurysms