Arteriovenous malformations (AVM)

• Abnormal collection of blood vessels where arterial blood flows directly into draining veins without normal interposed capillary beds.

• No brain parenchyma within nidus

• AVM are not congenital (not present at birth)

• Aggregates of abnormal arteries and veins of variable diameters with direct connections through a nidus or fistula instead of a normal capillary bed.

• AVM have no predilection for specific central nervous system locations and are distributed proportionately within the brain mass.

• Prevalence
• 0.14%
• Adults 10 -100 per 100 000 (Morris et al., 2009).

• Incidence:
• 0.9– 1.5 per 100 000 head of population per year (Al- Shahi et al., 2003; Stapf et al., 2003)

• Congenital origin
• Bonnet- Dechaume Blanc syndrome
• Wyburn- Mason syndrome
• Hereditary haemorrhagic telangiectasia (HHT)
• Autosomal dominant capillary malformation
• Presents with skin capillary malformations
• AVM of the brain, limb, or face (no intra- abdominal or intrathoracic organ involvement) has been described with a RASA1 mutation

• Secondary

graph TD
    subgraph A ["Sporadic causes"]
        subgraph A1 ["Multiple gene involvement"]
	        A11["Upregulation/downregulation<br>of multiple homeobox genes<br>(HoxD4 HoxB3)"]
	        A12["Involve<br>with angiogenesis"]
	        A11 --> A12
        end
        A2["Somatic Kras mutations<br>(85% of AVM)"]
    end
    A --> C

    subgraph B ["Syndromic causes"]
        B1["Cerebrofacial arteriovenous<br>metameric syndrome (CAMS)"]
        B2["Hereditary haemorrhagic<br>telangiectasia (HHT)"]
    end
    B --> C

    subgraph C ["Models of AV shunt formation"]
        C1["Notch4 induced arteriovenous<br>shunt development from capillaries<br>(NOTCH3 gene In CADASIL)"]
        C2["Dilation and a primary<br>disorder of venules"]
        C3["Failure of regression of<br>primitive arteriovenous connections<br>during development"]
    end
    C --> D1
    style C text-align:left

    D1["Formation of a nidus (conglomeration<br>of numerous AV shunts) that shunts bloods"]
    D1 --> E1
    D1 --> D2

    D2["High output Cardiac failure<br>(<1%)with pulmonary hypertension<br>can occur in neonates and infants"]

    E1["Due to lack of capillary bed"]
    E1 --> F1

    F1["High pressure arterial bloods<br>enters venous system with low<br>resistance causes high flow of blood"]
    F1 --> G

    subgraph G ["Remodeling process"]
        subgraph G1 ["One"]
	        G11["The high venous pressure and<br>high flow remodels the vein"] 
	        G12["dilate and walls to thin"]
	        G11 --> G12
        end
        subgraph G2 ["Two"]
	        G21["The lower arterial pressure<br>remodels the artery"] --> G22["dilate"]
        end
        G3["This is why it is not congenitally<br>abnormal it requires time to form)"]
        G4["All these changes are mediated<br>through upregulation of eNOS and<br>down-regulation of endothelin along<br>with the remodelling vasculogenesis<br>factors (e.g. vascular endothelial<br>growth factor, VEGF)."]
        G5["There is usually no sharply<br>identifiable point where AVM can<br>be said to begin or end, rather<br>there is a transition zone reflecting<br>the pathological response to the<br>physiological perturbations."]
    end
    style G text-align:left
    G --> H1
    G --> H2
    G --> H3
    G --> H4
    G --> H5
    G --> H6

    H1["High flow vascular in arteries"]
    H1 --> H1_1

    H1_1["Degeneration of remodelled<br>vessel wall"]
    H1_1 --> H1_2

    subgraph H1_2 ["Aneurysm: (7% of AVM)"]
        H1_2a["Extranidal<br>Arterial aneurysms: located<br>on the wall of feeding arteries"]
        H1_2b["Unrelated aneurysm: arise<br>from vessels that are not<br>AVM feeders"]
        H1_2c["Flow related aneurysm: arise<br>from vessels that play a role in the<br>perfusion of the nidus and<br>(hemodynamically related to the AVM)"]
        H1_2d["Both can be either<br>Prenidal: proximal to the AVM nidus<br>Postnidal: distal to the AVM nidus"]
        H1_2e["Venous varices: located on<br>the wall of draining veins"]
        H1_2f["Intranidal:<br>Located within the boundaries of the nidus<br>Angiographically opacified before substantial<br>venous filling has occurred 75% in major<br>feeding arteries (inc. flow)"]
    end
    style H1_2 text-align:left

    H2["Haemorrhage (50%)"]

    H3["High flow in a low resistant<br>system will cause blood to be<br>stolen through the AVM"]

    H4["pressure is elevated within<br>the venous sinuses"]

    H5["If CPA AVM"]

    H6["Hb extravasation"]

    style A1 text-align:left
    style A2 text-align:left
    style B1 text-align:left
    style B2 text-align:left
    style C1 text-align:left
    style C2 text-align:left
    style C3 text-align:left
    style G1 text-align:left
    style G2 text-align:left
    style G3 text-align:left
    style G4 text-align:left
    style G5 text-align:left

• Proliferative angiopathy
• A response to infarct or ICH
• Particularly in the young
• Should be considered in diffuse vascular lesions that may resemble AVM but lack the very early venous drainage pattern of AVM.
• Do not share the same propensity to haemorrhage