**3. Hypothesis**

Etiologically, DAVF is revealed secondary to causes such as trauma, inflammation, or sinus thrombosis5-8. However, most causes are idiopathic and independent of the preceding hematological and immunological impairments. Therefore, comprehensive factors concerning the initiation of DAVF that covers all of the pathological features should be considered. From this perspective, we focused on the location of emissary veins (EV) and discovered that the distribution of EV definitely corresponds to those of the location of DAVF (Fig. 1). According to this previous consensus and to new information, we propose following hypothesis concerning the development of DAVF which focuses on the emissary vein.

A Postero–anterior view

B Lateral view 1. parietal (parasagittal ) emissary vein (EV), 2. occipital (torcular) EV, 3. mastoid EV, 4. condylar (condyloid) EV, 5. hypogroassal EV, 6. frontal (ethmoidal) emissary vein (EV), 7. petrosquamosal EV, 8. foramen ovale EV, 9. foramen spinosum EV, 10. foramen lacerum EV, 11. Basilar plexus EV and Trolard's inferior petrooccipital vein (venous plexus of Raktzik)

#### Fig. 1. Distribution of emissary veins

Emissary veins connecting the intracranial and extracranial venous system through the bone are distributed in specific parts of the vault or base of the skull9. They are usually accompanied by and penetrate together through the same foramen with emissary arteries (transosseous perforating arteries) (Fig. 2A). Fig. 2 shows the scheme of this process in the DAVF at SSS (a representative of sinus type DAVF). First, some inflammatory reaction occurs at the penetrating site of EV. It may be reasonable to consider the cause of inflammation to the infection of adjacent tissue such as sinusitis and mechanical inflammation after trauma (including catheter intervention). Sinus thrombosis is occasionally observed before the occurrence of DAVF7, however, such thrombosis might be the result of focal inflammation. In most cases with DAVF, inflammation will develop undetected or as an autoimmune allergic reaction. Local inflammation may expand with expression of various cytokines, cause vessel dilatation, and open the physiological AV shunt at the level of capillary vessels (Fig. 2B).

Etiologically, DAVF is revealed secondary to causes such as trauma, inflammation, or sinus thrombosis5-8. However, most causes are idiopathic and independent of the preceding hematological and immunological impairments. Therefore, comprehensive factors concerning the initiation of DAVF that covers all of the pathological features should be considered. From this perspective, we focused on the location of emissary veins (EV) and discovered that the distribution of EV definitely corresponds to those of the location of DAVF (Fig. 1). According to this previous consensus and to new information, we propose following hypothesis

> A B

B Lateral view 1. parietal (parasagittal ) emissary vein (EV), 2. occipital (torcular) EV, 3. mastoid EV, 4.

petrosquamosal EV, 8. foramen ovale EV, 9. foramen spinosum EV, 10. foramen lacerum EV, 11. Basilar

Emissary veins connecting the intracranial and extracranial venous system through the bone are distributed in specific parts of the vault or base of the skull9. They are usually accompanied by and penetrate together through the same foramen with emissary arteries (transosseous perforating arteries) (Fig. 2A). Fig. 2 shows the scheme of this process in the DAVF at SSS (a representative of sinus type DAVF). First, some inflammatory reaction occurs at the penetrating site of EV. It may be reasonable to consider the cause of inflammation to the infection of adjacent tissue such as sinusitis and mechanical inflammation after trauma (including catheter intervention). Sinus thrombosis is occasionally observed before the occurrence of DAVF7, however, such thrombosis might be the result of focal inflammation. In most cases with DAVF, inflammation will develop undetected or as an autoimmune allergic reaction. Local inflammation may expand with expression of various cytokines, cause vessel dilatation, and open the physiological AV

condylar (condyloid) EV, 5. hypogroassal EV, 6. frontal (ethmoidal) emissary vein (EV), 7.

plexus EV and Trolard's inferior petrooccipital vein (venous plexus of Raktzik)

concerning the development of DAVF which focuses on the emissary vein.

**3. Hypothesis** 

A Postero–anterior view

Fig. 1. Distribution of emissary veins

shunt at the level of capillary vessels (Fig. 2B).

A Normal site. Emissary vein (EV) and artery (a) is penetrating through a foramen of the parasagittal skull. EV is connected with the venous lacunae (b). Meningeal arteries (c) have no connection with SSS (d) and cortical vein (e).

B Neovascularization (arrow) and vessel dilatation induced by dural inflammation

C AV shunt formation at the level of dural arteriole and penetration into the sinus (initial stage of DAVF). Note the shunt flow draining into the sinus as well as EV (double arrow).

D. Shunt development with thrombosis of an emissary vein (asterisk) and recruitment of distal arteries from anterior falx artery (f) and posterior meningeal arteries (g).

E. Maturation of DAVF with the reflux to cortical veins (red arrow) due to sinus occlusion (white arrow). Note the further recruitment of feeders from the other side or transosseous branches (h).

Fig. 2. Mechanism of development of the DAVF at the superior sagittal sinus (SSS) as a representative of the sinus type DAVF.

Hypothetical Mechanism of the Formation of Dural Arteriovenous

representative of non-sinus type DAVF.

ethmoidal artery

occlusion of an emissary vein

a representative of the non-sinus type DAVF.

Fistula – The Role and Course of Thrombosis of Emissary Vein and Sinuses 227

of this process. However, this final isolated part of the DAVF will not be always consistent with the first trigger point of a micro AV shunt, because the inflammatory extension and recruitment of many dural arteries will easily cause the movement of the main shunt point. It is quite easy to adopt this mechanistic hypothesis to non-sinus type DAVF. Fig. 4 demonstrates the scheme of the development of ethmoidal (anterior skull base) DAVF as a

A B

C D

Fig. 4. Mechanism of development of the DAVF: an ethmoidal (anterior skull base) DAVF as

A. Normal state. a; frontal cortex, b; frontal emissary vein, c; dural branches from anterior

C. AV shunt formation at the level of dural arteriole and reflux into an EV (initial stage of DAVF) D. Shunt development and increased reflux into the varicose cortical vein (white arrow) following the

B. Neovascularization and dilatation induced with dural inflammation (#)

In sinus type DAVF, a micro AV shunt between the emissary artery and vein will enlarge to the adjacent sinus wall. The increase in shunt flow triggers drainage into the sinus, and subsequently changes the main drainage route from the EV to the sinus. As a result, the sinus will be occupied by the shunt flow more than the normal intracranial venous outflow pathway (Fig. 2C). While this shift in shunt flow direction decreases the role of EV as the drainage pathway, the developed and swollen emissary artery compresses the accompanied EV and impairs the drainage flow. This results in occlusion of the EV (Fig. 2D).

This degeneration of the EV is an important process in the formation of a well-known style of sinus type of DAVF. However, in some cases of DAVF at CS and SSS the EV may remain patent and serve as a drainage route to the pterygoid plexus or parietal vault. Also an EV that connects with diploic veins can form an enlarged intraosseus venous lake, and appear as a new channel of sinus or duplication. The shunt recruits other dural feeders from the distant and contralateral parts due to angiogenetic and hemodynamic factors, and forms the extended vascular network as a new DAVF10. Extracranial arteries on the skull or under the skull base are often mobilized through the bone. Such active recruitment of feeders is considered to be due to angiogenesis enhanced by the expression of vasculogenetic factors at the affected dura (including vascular endothelial growth factor (VEGF)) 11-16.

The next key process in maturation of the DAVF is the occlusive change of the draining system. Although draining pathway may finally occlude due to intrasinus thrombosis associated with hypercoagulopathy, the essence of the occlusive mechanism should be hypertrophy of the sinus wall12. This occlusive process is typical in the DAVF at CS17. Its drainage route gradually occludes from the inferior petrosal sinus and superior ophthalmic vein11, and occasionally causes a paradoxical worsening of visual acuity and chemosis with ocular hypertension following occlusion of the anterior drainage route. During this progression, the thrombophilic abnormalities characteristic of DAVF are also reported18-22. In some cases such thrombotic change of drainage route may occur in the initial stage preceding the development of the shunt.

Next, the same process progresses in the upstream side because the remaining upstream drainage with more hemodynamic stress may yield the hypertrophic change of sinus wall12, 23. As a result, the meeting point of the shunt flow will be isolated, and shunt flow without exit to the sinus may reflux into cortical veins (Fig. 2E). Such a matured and aggressive type of DAVF with an affected isolated sinus or dural vein 24 (Fig. 3), may be the final expression

A. DAVF at cavernous sinus, B. DAVF at transvers-sigmoid sinus Fig. 3. Examples of matured sinus type DAVF

In sinus type DAVF, a micro AV shunt between the emissary artery and vein will enlarge to the adjacent sinus wall. The increase in shunt flow triggers drainage into the sinus, and subsequently changes the main drainage route from the EV to the sinus. As a result, the sinus will be occupied by the shunt flow more than the normal intracranial venous outflow pathway (Fig. 2C). While this shift in shunt flow direction decreases the role of EV as the drainage pathway, the developed and swollen emissary artery compresses the accompanied

This degeneration of the EV is an important process in the formation of a well-known style of sinus type of DAVF. However, in some cases of DAVF at CS and SSS the EV may remain patent and serve as a drainage route to the pterygoid plexus or parietal vault. Also an EV that connects with diploic veins can form an enlarged intraosseus venous lake, and appear as a new channel of sinus or duplication. The shunt recruits other dural feeders from the distant and contralateral parts due to angiogenetic and hemodynamic factors, and forms the extended vascular network as a new DAVF10. Extracranial arteries on the skull or under the skull base are often mobilized through the bone. Such active recruitment of feeders is considered to be due to angiogenesis enhanced by the expression of vasculogenetic factors

The next key process in maturation of the DAVF is the occlusive change of the draining system. Although draining pathway may finally occlude due to intrasinus thrombosis associated with hypercoagulopathy, the essence of the occlusive mechanism should be hypertrophy of the sinus wall12. This occlusive process is typical in the DAVF at CS17. Its drainage route gradually occludes from the inferior petrosal sinus and superior ophthalmic vein11, and occasionally causes a paradoxical worsening of visual acuity and chemosis with ocular hypertension following occlusion of the anterior drainage route. During this progression, the thrombophilic abnormalities characteristic of DAVF are also reported18-22. In some cases such thrombotic change of drainage route may occur in the initial stage

Next, the same process progresses in the upstream side because the remaining upstream drainage with more hemodynamic stress may yield the hypertrophic change of sinus wall12, 23. As a result, the meeting point of the shunt flow will be isolated, and shunt flow without exit to the sinus may reflux into cortical veins (Fig. 2E). Such a matured and aggressive type of DAVF with an affected isolated sinus or dural vein 24 (Fig. 3), may be the final expression

A B

A. DAVF at cavernous sinus, B. DAVF at transvers-sigmoid sinus

Fig. 3. Examples of matured sinus type DAVF

EV and impairs the drainage flow. This results in occlusion of the EV (Fig. 2D).

at the affected dura (including vascular endothelial growth factor (VEGF)) 11-16.

preceding the development of the shunt.

of this process. However, this final isolated part of the DAVF will not be always consistent with the first trigger point of a micro AV shunt, because the inflammatory extension and recruitment of many dural arteries will easily cause the movement of the main shunt point. It is quite easy to adopt this mechanistic hypothesis to non-sinus type DAVF. Fig. 4 demonstrates the scheme of the development of ethmoidal (anterior skull base) DAVF as a representative of non-sinus type DAVF.

A. Normal state. a; frontal cortex, b; frontal emissary vein, c; dural branches from anterior ethmoidal artery

B. Neovascularization and dilatation induced with dural inflammation (#)

C. AV shunt formation at the level of dural arteriole and reflux into an EV (initial stage of DAVF) D. Shunt development and increased reflux into the varicose cortical vein (white arrow) following the occlusion of an emissary vein

Fig. 4. Mechanism of development of the DAVF: an ethmoidal (anterior skull base) DAVF as a representative of the non-sinus type DAVF.

Hypothetical Mechanism of the Formation of Dural Arteriovenous

condylor vein occasionally remains one of the draining veins.

connection between pial and dural veins.

constitutional factors.

**5. Supporting clinical situation** 

(arrows)

Fistula – The Role and Course of Thrombosis of Emissary Vein and Sinuses 229

3. Vault DAVF This rare type of DAVF is located at the temporal or occipital convexity, and is a non-sinus type DAVF. An aggressive feature of this type of DAVF is that it directly drains into cerebral cortical veins. According to our theory, it may be caused by the focal inflammation around the atypically located EV, or due to the congenital focal

4. Multiple, de novo, recurrent DAVF. These clinical features cannot be explained with the single inflammation theory, and spreading or multifocal inflammation should be considered (Fig. 6). Although recurrence of the same lesion can be due to incomplete occlusion of the shunt29, de novo creation of DAVF independent from the previous ones may follow the newly developing process, possibly be promoted with

Fig. 6. Mulitple DAVF Multiple DAVF at superior sagittal, tranevers and sigmoid sinus

This hypothesis is supported by some familiar features encountered in clinical cases. First, in the case of mature SSS-DAVF, shunt flow usually drains into the cortical vein through an isolated sinus with the particular congestion of pial veins. However, in spite of such an aggressive type with reflux to the cortical vein, SSS is still patent in some particular cases. This unusual situation suggests the influence of EV at the initial location of the micro AV shunt. As seen in Fig. 7, the parasagittal (parietal) EV has no direct connection with SSS itself and drains from venous lacunae. The abnormal state mentioned above can be interpreted as

through multiple channels28. As seen in previous nomenclature, one of the important drainage routes is the anterior condylor vein is the EV passing though the hypoglossal canal. However, in most cases, the anterior condylor vein has been already occluded, and other venous systems (including the lateral condylor vein, inferior petroclival vein, and inferior petrosal sinus) may function as a drainage route via ACC. Specific characteristics of this type of DAVF include patients suffering from strong tinnitus just when the DAVF is initially formed. Hypoglossal palsy develops in some cases. DAVF at the ACC tends to be diagnosed in the early stages. Therefore, as the original drainage route, the anterior

EV at the anterior skull base (Fig. 4A) connecting with the cortical vein will create, secondary to the ethmoidal inflammation, a micro AV shunt at the skull base dura (Fig. 4B). Subsequently the EV will occlude according to the same process as described above (Fig. 4C, D). As a result, all the shunt flow supplied from ethmoidal arteries drains into the cortical veins, which is the common style encountered in the clinical setting. The pathological process at the spine or craniocervical junction DAVF can be explained by the same mechanism.
