**1. Introduction**

Arteriovenous malformations (AVM) are vascular malformations composed of a network of abnormal vessels connecting directly between the artery and vein without an intervening capillary bed. AVMs are thought to be congenital lesions originated from persistence of primitive arteriovenous connections [1].

#### **1.1 Epidemiology**

According to epidemiological studies, including Netherland Antilles [2], Olmsted county Minnesota [3], and New York islands [4], incidence of cerebral arteriovenous malformations is between 0.8 and 1.3 per 100.000 person years. In addition to sporadic cases, brain AVMs can be associated with syndromes including hereditary hemorrhagic telangiectasia, Wyburn-Mason syndrome, and Sturge-Weber syndrome [5, 6].

#### **1.2 Clinical presentation**

Symptomatic brain AVMs may present with intracranial hemorrhage (50%), seizure (33%), headache (16%), or focal neurologic deficit (6%) [7]. Annual risk of bleeding of due to brain AVMs is approximately 2–4%. Risk factors increasing the odds of bleeding include prior history of intracranial bleeding due to AVM, deep location, exclusive deep venous drainage and single draining vein, intranidal aneurysm, and high intranidal pressure [7–9]. When there are three factors, risk may increase up to 34%. In patients presenting with hemorrhage, rebleeding risk in the first year is approximately 32% that decrease to 11% in subsequent years [10]. Annual mortality rate is approximately 1.5% and 10–30% of survivors have long-term disability. Neurological disability is more common in ruptured AVMs compared to aneurysm rupture due to higher likelihood of a lobar hematoma [11]. Although there is conflictive data, smaller AVMs have a higher tendency to present with hemorrhage. Spetzler et al. [12] found that 82% of smaller AVMs (<3 cm) present with hemorrhage compared to 21% of hemorrhage seen in larger AVMs (>6 cm). Ondra et al. [13] published a series of 160 symptomatic untreated AVM cases and found that 23% of the patients died during a mean follow-up of 23.7 years.

#### **1.3 Therapeutic strategies**

AVM treatment includes medical management, surgical, endovascular, and radiosurgical modalities. ARUBA, largest multicenter randomized trial to date, showed that medical management alone is superior to interventional therapy for the prevention of death and stroke in patients with unruptured AVMs [14, 15]. However, the follow-up period in this study was only 33 months, and 5-year follow-up results that will prove whether these results are persistent are yet to be published. Nevertheless, ruptured AVMs, unruptured AVMs with significant risk factors, and some symptomatic AVMs in young patients must be treated. These treatment modalities can be used as stand-alone treatment for cure, or a combination of different techniques can be used to increase the efficiency and minimize the risks associated with treatment. Although there is still no consensus on the ideal treatment, every case is evaluated specifically for its rupture risk and risks associated with its treatment. The most common grading system used to stratify the risks of surgical treatment of AVMs is the Spetzler-Martin system [16]. This system classifies the AVMs according to size, location, and venous drainage. Larger lesions, AVMs with deep venous drainage, and lesions in eloquent locations have higher surgical risk. Eloquent locations include sensorimotor cortex, visual cortex, thalamus, internal capsule, brainstem, cerebellar peduncles, and deep cerebellar nuclei. Deep venous drainage sites are straight sinus, internal cerebral veins, basal veins of Rosenthal, and precentral cerebellar veins. Spetzler and Ponce proposed a modified version of the grading system in 2011 [17].

AVMs larger than 3 cm in a non-eloquent and superficial location can be safely treated with embolization followed by surgery. AVMs larger than 3 cm with a deep or eloquent location can be embolized and then radiosurgery can be used for the ultimate cure. Smaller lesions (<3 cm) can be safely treated with surgery alone or

radiosurgery can be used as stand-alone treatment in case of eloquent or deep location. For ruptured small deeply located surgically inaccessible AVMs, embolization can be used as a stand-alone treatment for cure.
