**1.3 Pathogenesis**

AVM is generally considered congenital and/or of developmental origin. Beneš and Bradác describe several genetic pathways associated with AVM pathogenesis, such as hereditary hemorrhagic telangiectasia (HHT, an autosomal dominant genetic disease) [23]. Typically, the genes Endoglin, ALK-1 (ACVRL1, TGF-β related), and SMAD4 are implicated [24]. These genes also participate in angiogenesis and vascular remodeling. The main signaling pathways disrupted are: (i) TGF-β—cellular growth, communication, and inflammatory processes; (ii) NOTCH—angiogenesis, considered critical for arterial fate determination; (iii) MAPK(1/3)—physiological and pathological cell proliferation; and (iv) PI3K/Akt—cell cycle regulation.

#### **1.4 Epidemiology, natural history, and clinical features**

Fast-flow lesions' prevalence is estimated to be 1–2 out of 10,000 people or 1.2–1.3 in 100,000 per person-year [23]. AVMs are found in 0.05% of all brain MRIs [25]. In the USA and Canada, 5000 new cases are detected yearly [26]. Demographic, morphological, and clinical (particularly age-related) characteristics do vary, but many important pathology-related statistics (e.g., rate of incident hemorrhages) remain roughly similar worldwide [17]. In South Africa, male gender and African-black origin were found to be strong indicators for AVM seizure development [27]. Frontal (20.4%), parietal (22.2%), temporal (16.6%), and cerebellar (14.0%) are the most common anatomical brain regions to present AVMs [17, 27]. Supratentorial lesions account for 90% of brain AVMs [28]. Intracranial hemorrhage is the most common clinical presentation (30–82% of lesions) [29]. AVMs account for 1–2% of all strokes and 2–4% of all non-traumatic intracerebral hemorrhages [23]. However, the unique age distribution among stroke etiologies (the median age for an AVM patient is 32 years old [30]) suggests that AVMs are responsible for more than a third of hemorrhagic strokes in young adults [19]. Furthermore, some studies suggest that higher hemorrhage risk values of 4.6% [31] and 30% of lesions are subarachnoid [32]. These are considered highly catastrophic and present the mortality rates of 25–50% [33]. Main factors influencing hemorrhage risk statistics are initial hemorrhagic (7.48%) or seizure (4.16%) presentations, associated aneurysms (6.93%), and deep venous drainage (5.42%) [31]. Other clinical representations are neurological deficits (24%), chronic headaches (19%), and focal or generalized seizures (46%) [17]. The American Association of Neurological Surgeons (AANS) provides a wide symptoms list—seizures, muscle weakness or paralysis, loss of coordination, difficulties carrying out organizational tasks, dizziness, headaches, visual disturbances, language problems, abnormal sensations, memory deficits, mental confusion, hallucinations, and dementia [34]. Annual mortality rates vary between 0.7 and 2.9% [23]. Considering an estimated number of 300,000 US patients, this results in ~2100–8700 annual mortalities in the USA alone.

*Advocating Intraluminal Radiation Therapy in Cerebral Arteriovenous Malformation Treatment DOI: http://dx.doi.org/10.5772/intechopen.89662*

## **1.5 Brief history**

Early AVM descriptions may date back to ~1500 BC, evidenced in the Ebers Papyrus description of hemorrhoids, varicose veins, and aneurysms. Vessel malformations were apparently also familiar throughout the Roman and early Arabic empires. However, the first modern documented AVM procedure was performed by Hunter during the eighteenth century, the first official clinical diagnosis was described in 1895, and the first surgery (a feeding artery ligation) was performed by Giordano in 1889 and was immediately followed by a full AVM resection in Paris [23]. The early era of AVM microsurgery is traditionally attributed to Kunc et al. who suggested the whole AVM obliteration as a standalone fully efficient treatment strategy in 1965 [35]. The interventional radiology approach and radio-surgical techniques emerged during the 1980s and eventually paved the way for present treatment modalities. The 1980s were also pivotal regarding treatment strategies. Up to then, recommendations for AVM treatment were mainly institution/physician based. However, during the 1980s, Spetzler and Martin (based on vast surgical work) developed the first well-established AVM classification and treatment scale. This grading scale is considered the "gold standard" decision-making tool in the field to date [36].
