Blood flow velocity in the arteries of the anterior cerebral artery complex in patients with an azygos anterior cerebral artery aneurysm: A transcranial color-coded sonography study

1. Introduction 

The azygos anterior cerebral artery (Az) was first described in 1888 by Windle [1]. It represents a rare anomaly of the anterior cerebral artery (ACA) complex. There are three types of anomalies of the distal segment of the anterior cerebral artery: (1) the Az—a single artery is present, which supplies both hemispheres; (2) the bihemispheric ACA—both ACAs are present, but one of them, called the bihemispheric ACA, is clearly dominant and distributed to both hemispheres; (3) the accessory ACA—in addition to the right and left ACAs, a third, middle or median artery is present, distributed either to one or both hemispheres [2]. It is presumed that the Az results from abnormal fusion of the paired A2 vessels from the medial branch of the primitive olfactory artery at the 16-mm stage of the embryo, at about the 40th day of embryonic development, prolonging cranially the process accomplished with the basilar artery and anterior spinal axis [3], [4]. This anomaly is closely associated with cerebral aneurysms. Huber at al. [5] reported 17 cases of unpaired pericallosal trunks among 7782 patients in whom bilateral angiographies were performed for various indications, 4 of which were of the azygos type, while 13 belonged to the bihemispheric pericallosal type. Among these 17 patients, 7 (41%) had an aneurysm at the bifurcation of the unpaired trunk close to the genu corporis callosi; 2 of these were found on the Az, and 5 were located on the bihemispheric pericallosal artery. It is believed that increased blood flow through the single Az trunk, instead of the normal paired A2, contributes to an increased hemodynamic stress across Az distal end bifurcation, which results in the development of the aneurysm [6]. Therefore, we performed transcranial color-coded sonography (TCCS) to assess the blood flow velocity in the Az and A1 segment of the ACA in three consecutive patients with Az aneurysm. To our knowledge, this is the first report on the blood flow characteristics of the human Az.

2. Clinical material and methods 

Between January 1989 and August 2007 we treated 1788 patients with cerebral aneurysm. Among them, 31 (1.7%) patients had pericallosal artery aneurysm, including 3 patients with aneurysm of the Az. We did not find the Az in the remaining patients diagnosed with cerebral aneurysm. The demographic data of the 3 patients with aneurysm of the distal segment of the Az are shown in Table 1.

Table 1. Demographic and radiological data of the study group.

	No	Sex	Age (years)	Clinical presentation	Past medical history	Location of aneurysm on the distal portion of the azygos artery	Additional abnormalities at angiography
	1	Female	65	SAH	Hypertension, coronary heart disease	At the origin of the callosomarginal artery at the level of the genu of the corpus callosum	Aneurysm of the left middle cerebral artery
	2	Male	52	Non-SAH, vertigo	Irrelevant	At the origin of the callosomarginal artery at the level of the genu of the corpus callosum	None
	3	Male	41	Non-SAH, headache	Epilepsy	At the trifurcation formed by the callosomarginal artery and pericallosal arteries at the level of the genu of the corpus callosum	Aneurysm of the left middle cerebral artery agenesis of A1 segment of the right anterior cerebral artery

The first patient was admitted to our department after a subarachnoid hemorrhage from a ruptured aneurysm of the Az; the remaining two patients had undergone an angio-MR prior to admission, which showed nonbleeding intracranial aneurysms. A selective digital subtraction cerebral panangiography using a femoral artery approach was performed in each patient (Fig. 1, Fig. 2, Fig. 3). Patients #1 and #2 underwent a right frontal craniotomy and interhemispheric approach with subsequent clipping of the aneurysm. In the first patient the postoperative course was complicated by transient left hemiparesis. In patient #3 an uncomplicated endovascular embolization was performed. MDS platinum coils (Balt Extrusion, Montmorency, France) were used. A near-complete aneurysm occlusion with a neck remnant was achieved. The stent was not applied.

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Fig. 1. Patient #1—oblique angiographic views of bilateral ICAs [(A) right ICA; (B) left ICA)] and lateral projection of the right ICA (C) revealing an anomaly of the ACA complex, with the azygos anterior cerebral artery (Az) (black arrowheads). An aneurysm is visible at a distal portion of the Az, where it branches into the callosomarginal artery and branches of the middle internal frontal artery (black arrows). The distal portion of the Az divides into two segments (white arrowheads), which branch into the middle internal frontal artery (black arrows) and posterior internal frontal artery (white arrow). (D) Transcranial color-coded sonography through the frontal bone window showing the Az. Mean blood flow velocity in the Az was 42cm/s. cc, corpus callosum; sb, skull bone.

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Fig. 2. Patient #2—oblique angiographic views of the right ICA (A and B) and lateral projection of the left ICA (C). The azygos anterior cerebral artery (Az) (black arrowheads) divides into two distal branches of pericallosal artery (white arrowheads). An aneurysm is visible at a distal portion of the Az, where it branches into two callosomarginal arteries (short black arrows), dividing into two internal frontal arteries: anterior and middle (long black arrows). The posterior internal frontal arteries arise from distal portions of the Az (white arrow). (D) Transcranial color-coded sonography through the frontal bone window showing the Az. Mean blood flow velocity in the Az was 58cm/s. cc, corpus callosum; sb, skull bone.

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Fig. 3. Patient #3—anteroposterior angiographic view of the right ICA (A). Agenesis of the A1 segment of the right ACA. Anteroposterior (B) and lateral (C and D) angiographic view of the left ICA before and after aneurysm coil embolization. Aneurysms are visible at a distal portion of the Az and at the middle cerebral artery (short white arrow). The single trunk of the Az (black arrowheads) divides into two callosomarginal arteries (white arrowheads) which branch into frontal internal cerebral arteries (long black arrows). One of the callosomarginal arteries and two distal portions of the pericallosal artery (short black arrow) arise from the distal end of the Az, where an aneurysm is visible. E. Transcranial color-coded sonography through the frontal bone window showing the Az. Mean blood flow velocity in the Az was 50cm/s. cc, corpus callosum; sb, skull bone.

3. Results 

Table 1 presents the results of a cerebral angiography with respect to localization of the aneurysm on the Az, and the presence of other vascular abnormalities. Table 2 shows the Doppler examination results in patients from both the study and control group. There was a trend toward decreased Vm in the Az compared with velocities in the A2 segment of the ACA of the control group (the raw uncorrected p-value=0.06). The remaining Doppler examination results did not differ between patients with Az aneurym and control group (Table 2).

Table 2. Doppler examination results in patients with azygos anterior cerebral artery and in the control group.

		Parameter	Study group	Control group	p-value
	Azygos (A2)	Vs±S.D. (cm/s)	76±16	94±18	NS
		Ved±S.D. (cm/s)	35±9	44±9	NS
		Vm±S.D. (cm/s)	48±10	63±12	NSa
		PI±S.D.	0.86±0.05	0.81±0.16	NS
		RI±S.D.	0.54±0.02	0.53±0.06	NS
	A1b	Vs±S.D. (cm/s)	78±6	81±16	NS
		Ved±S.D. (cm/s)	33±4	39±8	NS
		Vm±S.D. (cm/s)	46±2	54±10	NS
	Azygos (A2)/A1	Vs±S.D. (cm/s)	1.10±0.08	1.17±0.17	NS
		Ved±S.D. (cm/s)	1.25±0.17	1.14±0.14	NS
		Vm±S.D. (cm/s)	1.18±0.09	1.18±0.15	NS

a Trend toward statistical significance, the raw uncorrected p-value=0.06. b In Case #1 no signal was obtained from A1 segments of the anterior cerebral artery due to lack of acoustic penetration of the ultrasound beam through a temporal bone window. In Case #3 a sonographic signal could not be obtained from the right A1 due to agenesis of this segment confirmed in arteriography; NS, non significant; PI, pulsatility index; RI, resistance index; Ved, end-diastolic velocity; Vm, mean velocity; Vs, peak systolic velocity.

For patients #2 and #3, who underwent their first TCCS study before clipping and embolization, the consecutive Doppler examinations provided similar results, with a coefficient of variation ranging from 0.7% for PI in the Az to 9.7% for PI in the A1 segment for patient #2, and from 1.4% for RI in the Az to 9.8% for Ved in the A1 segment for patient #3.

4. Discussion 

The anatomical anomalies or variants of the circle of Willis may play some role in the development of cerebral aneurysms [12], [13], [14], [15]. For example, aneurysms of the AComA occur frequently in cases of inequality in size of the proximal segments of ACAs [14], [15], [16], [17], [18]. In such cases aneurysms are more common at the junction of the larger A1 segment and the AComA. Stehbens explains that where there is a sizeable shunt from one ACA to the contralateral vessel, the aneurysm arising has been attributed to augmented hemodynamic stress [15].

The occurrence of a large unpaired pericallosal trunk may increase the risk of cerebral aneurysm formation. Huber et al. [5] found berry aneurysms at a bifurcation in 41% of cases with a large unpaired pericallosal trunk. Among all the aneurysms observed at the pericallosal artery, 25% were located at the bifurcation of a wide unpaired pericallosal artery.

In the majority of cases described so far, the aneurysms of the Az were located at the distal end of the artery where it branches into the callosomarginal and pericallosal arteries. Such localization suggests the role of hemodynamic stress related to increased blood flow through the single Az trunk in the development of the aneurysm [6].

Impingements of the central stream on the apex of the intracranial bifurcations generate hemodynamic forces, which could be an important factor contributing to aneurysm formation [19], [20]. These forces are directly proportional to the blood flow velocity and depend on the geometry of bifurcation. Our findings showed that the blood flow velocities in the Az, Az/A1 velocity ratios, PI and RI values in the Az did not differ from those in control patients. Therefore, neither an absolute nor a relative increase in blood flow velocity has been observed in the Az. These findings closely resemble the conclusions from our earlier studies on intracranial aneurysms coexistent with the occlusion of extracranial feeding vessels. These results showed that aneurysm development on vessels forming the collateral pathways of the circle of Willis is not necessarily related to increased blood flow velocity in these vessels [21].

Experiments with glass models of vessels demonstrated that disturbances of flow near the apex of the bifurcation, so crucial in initiating the formation of aneurysm, depend on the shape of the flow divider and increase with the flow rate, bifurcation angle, and pulsatile flow [19], [22]. In the glass AComA model, the hemodynamic stress generated in the AComA increases with changes from symmetrical to asymmetrical geometry of the AComA complex [23]. These experimental observations were confirmed in patients with AComA aneurysms using a 3D-computed tomographic angiography, which showed that not only the size of the A1 segment, but also the size of the angle between the A1 and A2 were associated with AComA aneurysms [16].

Aneurysms of the Az are typically located at the distal portion of this artery, where the Az divides into pericallosal and callosomarginal arteries. The anatomy at this branch point is variable, with bifurcation, trifurcation and even quadrifurcation being possible [13], [24]. A variable geometry of the bifurcation of the distal end of the Az and the presence of an enlarged single vessel instead of a normal paired A2 may lead to an abnormal blood flow pattern, induce higher shear stress and favor aneurysm formation. The hemodynamic forces released at the bend of the Az at the level of the genu of the corpus callosum may contribute to aneurysm formation in addition to the above-mentioned factors. At a vessel bend, the laminae of the blood flow are rearranged, secondary vortices generated and the threshold of transition to turbulence is lowered [20].

A complex ontogenesis of ACA suggests an increased risk of Az wall developmental abnormalities, which may play an additional role in aneurysm formation. A post-mortem examination, available in a single case of Az aneurysm, showed only degenerative changes, attributed to abnormal flow pattern [25]. A more extensive histological examination is needed to elucidate the significance of putative congenital Az abnormalities.

Apart from the increased risk of aneurysm formation, anomalies of the distal ACA have another clinical significance; an occlusion of the single vascular trunk may lead to a bilateral cerebral ischemia in the territory of the ACA, with severe neurological and neuropsychological sequelae [26].

The main limitation of our study was the small number of cases examined, which results from the rarity of Az. We did not observe any Az patient without the Az aneurysm; therefore a comparison of hemodynamic parameters in Az patients with the aneurysm with data from Az patients with no aneurysm was not feasible.

In conclusion, aneurysms of the Az in our patients were not associated with increased flow velocity in the Az. It is likely that an important role in their development is played by hemodynamic stress related to the bifurcation morphology of the distal end of the Az.