Cell Biochem Biophys DOI 10.1007/s12013-014-9839-1
ORIGINAL PAPER
Digital Subtraction Angiography Imaging Characteristics of Patients with Extra–Intracranial Atherosclerosis and Its Relationship to Stroke Juan Liu • Xiao-Jun Jia • Yan-Jiang Wang • Meng Zhang • Tao Zhang • Hua-Dong Zhou
Ó Springer Science+Business Media New York 2014
Abstract To investigate the angiographic characteristics and clinical features in patients with suspected extra– intracranial atherosclerosis in a large cohort of Chinese population. On the basis of digital subtraction angiography characteristics, pathological morphology of extra–intracranial atherosclerosis was divided into tortuosity, kinking, coiling, and stenosis in 2,218 individuals aged 45–89 years. The degree of stenosis was further divided into low-grade (\30 %), intermediate-grade (30–69 %), and high-grade stenosis (C70 %). Clinical manifestations were divided into transient ischemic attack, cerebral infarction and cerebral hemorrhage. The prevalence of tortuosity and stenosis were significantly higher in the extracranial arterial system than that of intracranial arterial system. The prevalence of tortuosity and kinking were significantly higher on the left side than the right side. The prevalence of mild and moderate stenosis in the internal carotid artery was significantly higher in the left side than the right side. The incidence of cerebral infarction was significantly higher in the internal carotid arterial (ICA) system than the vertebrobasilar arterial (VBA) system. Tortuosity is a common carotid abnormality in the Chinese population. The prevalence of ICA tortuosity is higher than that of VBA. The incidence of cerebral infarction in each atherosclerosis group was significantly higher in ICA than that of VBA. The prevalence of stroke is higher in the ICA system than the VBA system.
Juan Liu and Xiao-Jun Jia have contributed equally. J. Liu X.-J. Jia Y.-J. Wang M. Zhang T. Zhang H.-D. Zhou (&) Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing, China e-mail: [email protected]
Kinkings and coilings may not have a clinical significance if these lesions are not associated with atheromatous plaques or carotid stenosis. Keywords Extra–intracranial atherosclerosis Digital subtraction angiography Stroke
Introduction Cerebrovascular disease is the leading cause of disability in the adult population worldwide. Extra–intracranial atherosclerosis is an important underlying pathological basis for cerebrovascular accidents [1, 2]. Arterial tortuosity, kinking, coiling, and stenosis are the most common lesions of the extra and intracranial vessels. Previous studies suggested that variations of the internal carotid artery occur in approximately 10–40 % of the population. In early angiography and postmortem reports, arterial variations have been classified as coiling, kinking, and tortuosity. Although the exact cause and natural history of kinking, coiling, and tortuosities of cerebral vessels are not clear, atherosclerosis is believed to be the underlying cause of tortuosity and kinking. Currently, digital subtraction angiography (DSA) is the gold standard for the evaluation of cerebral vasculatures. DSA provides essential information regarding hemodynamic status and collateral circulation in patients with stroke. It is an ideal imaging method of choice for diagnosis of cerebrovascular disorders. Imaging study of extra- and intracranial atherosclerosis with DSA is important for understanding of the pathophysiology of cerebrovascular diseases. It also helps with therapeutic decision making in triage patients for medical treatment and surgical/interventional therapy. Investigation of extra- and intracranial arterial coiling,
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Cell Biochem Biophys
kinking, tortuosity, and stenosis may contribute to the diagnosis and treatment of extra–intracranial atherosclerosis [3, 4]. The purpose of our study was to determine the prevalence of extra–intracranial atherosclerosis by using DSA. The clinical profiles of the patients were correlated with angiographic findings in our case cohort.
Materials and Methods
vascular imaging) who were blinded to the clinical information independently assessed all the DSA images. If the interpreters had disagreement, they discussed until a consensus was reached. The reviewers had to assess DSA images for the presence of intra- and extracranial elongation (tortuosity, kinking, coiling) and the degree of stenosis. The degree of stenosis was measured by the internal digital caliber and documented. In evaluation of the vascular lesions, the internal carotid artery system and vertebrobasilar artery (VBA) system were independently assessed and recorded.
Subjects Statistical Analysis The present study was approved by the Ethics Committee of the Third Military Medical University. We retrospectively examined the DSA images of patients with suspected stroke, who underwent cerebral angiography in the department of neurology at Da Ping Hospital between January 2006 and December 2008. Patients underwent DSA if they had signs or symptoms suggestive of stroke. All patients had CT or MRI scan before DSA examination. DSA was performed in those with the diagnosis of stroke based on CT or MRI findings. Patients were excluded from the study if they were diagnosed of stroke mimics. DSA Analysis and Interpretation Three- or four-vessel DSA was performed via a transfemoral approach under local anesthesia. DSA was performed by selective injection of 8–10-mL contrast material in the internal carotid and vertebral arteries. A standard projection format, including anteroposterior, lateral and oblique views, was routinely obtained. DSA images were sent through picture archiving and communication systems (PACS) and viewed on the neurology workstation. The extra- and intracranial atherosclerosis lesions were classified into four categories: tortuosity, kinking, coiling, and stenosis. Tortuosity was characterized by a C-shaped elongation and generalized tortuosity of the cerebral vessels. Kinking was defined as elongation and angulation of blood vessels. Coiling was defined as elongation of blood vessels in a S-shaped circular configuration [5]. Arterial stenosis was documented according to the North American Symptomatic Carotid Endarterectomy (NASCET) trial measurements [6]. The narrowest diameter (N) of the stenosis lumen is compared with the patent luminal diameter (D) of the internal carotid artery. The percentage of stenosis was calculated by using the formula: Stenosis = (1 – N/D) 100. Stenoses were classified as mild (0–29 %), moderate (30–69 %), or severe (70–99 %) according to the NASCET criteria. Two experienced neurologists (Juan Liu and Xiao-Jun Jia, with 10 and 15 years experience in
123
Statistical data were analyzed using the SPSS package (Version 10.0; SPSS Inc., 2010). Group comparisons were made by using Student’s t test. For differences in categorical variables, Chi square tests were performed. A P value of \0.05 was considered statistically significant.
Results Baseline Clinical Profiles A total of 2,218 patients (1,475 male; 743 female) were included in our study. The average patient age was 66.9 ± 7.4 years. Of the 2,218 patients; 1,816 (81.9 %) patients (1,213 male; 603 female) had arterial atherosclerosis on DSA exam. DSA Characteristics of Patients with Atherosclerosis Of the 1,816 patients with intra- and extracranial atherosclerosis, tortuosity is the most common type of vascular abnormalities, which accounted for 59.3 % of cases. The highest prevalence of atherosclerosis was observed in the 60–4 years age group. In the internal carotid arterial (ICA) system, the prevalence of extracranial arterial tortuosity was significantly higher than intracranial tortuosity (P \ 0.01). All kinking and coiling were located at the extracranial arterial segments. The prevalence of tortuosity and kinking were significantly higher in the left side than the right side (P \ 0.01). There is no significant difference in the prevalence of coiling on both sides. In the vertebrabasilar arterial system, the prevalence of extracranial arterial tortuosity was significantly higher than intracranial tortuosity (P \ 0.01). The prevalence of tortuosity and kinking were significantly higher in the left side than the right side (P \ 0.01). Similarly, all kinking and coiling were located at the extracranial arterial segments. The imaging characteristics of the extra- and intracranial lesions are illustrated in Figure 1. The distribution of the
Cell Biochem Biophys
Fig. 1 Diagram of different cerebral vascular elongation. a tortuosity, b coiling, c kinking
Table 1 Distribution of extra- and intracranial arterial system Tortuosity, kinking and coiling in 1,382 patients Tortuosity
Kinking
Coiling
ICA
VBA
ICA
VBA
ICA
VBA
n
687
513
135
139
48
24
%
63.8
47.6
57.7
59.4
67.6
33.8
Extracranial
343 (49.9)a
296 (57.7)a
135 (100.0)
139 (100.0)
48 (100.0)
24 (100.0)
Intracranial
203 (29.5)
125 (24.4)
0
0
0
0
Extra–intra
141 (20.6)
0
0
23 (47.9)
17 (70.8)b
Left
287 (41.8)
92 (17.9) b
233 (45.4)
0 b
0
69 (51.1)
b
96 (69.1)
b
Right
241 (35.1)
183 (35.7)
57 (42.2)
36 (25.9)
21 (43.8)
5 (20.8)
Left–right
159 (23.1)
97 (18.9)
9 (6.7)
7 (5.0)
4 (8.3)
2 (8.4)
a
Extracranial versus intracranial, P \ 0.01
b
Left versus right, P \ 0.01
Table 2 Distribution of extra- and intracranial stenosis in 434 patients Low-grade stenosis
Intermediate-grade stenosis
High-grade stenosis
ICA
VBA
ICA
VBA
ICA
VBA
n
104
138
64
72
53
62
%
50.2
66.7
53.8
60.5
49.1
57.7
Extracranial
81 (77.9)a
101 (73.2)a
48 (75.0)a
62 (86.1)a
41 (77.4)a
51 (82.2)a
Intracranial
14 (13.5)
26 (18.8)
11 (17.2)
8 (11.1)
9 (16.9)
10 (16.1)
Extra–intra
9 (8.6)
11 (8.0)
5 (7.8)
2 (2.8)
3 (5.7)
1 (1.7)
Left
49 (47.1)b
75 (54.3)b
32 (50.0)b
37 (51.4)
25 (47.2)
33 (53.2)b
Right
39 (37.5)
45 (32.6)
26 (40.6)
31 (43.1)
23 (43.4)
27 (43.5)
Left–right
16 (15.4)
18 (13.1)
6 (9.4)
4 (5.5)
5 (9.4)
2 (2.3)
a
Extracranial versus intracranial, P \ 0.01
b
Left versus right, P \ 0.01
lesions is listed in Table 1. In the ICA system, the prevalence of extracranial arterial stenosis was significantly higher than intracranial stenosis (P \ 0.01). The prevalence of mild and moderate were significantly higher in the
left side than the right side (P \ 0.01). The prevalence of severe stenosis was similar on both sides. In the VBA system, the prevalence of extracranial arterial stenosis was significantly higher than intracranial
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Cell Biochem Biophys Table 3 Clinical characteristics in 1,382 patients with extra- and intracranial artery atherosclerosis Clinical manifestations
Tortuosity ICA
Kinking VBA
P
ICA
Coiling VBA
P
ICA
VBA
P
Asymptomatic
282 (41.0)
181 (35.3)
[0.05
30 (22.2)
40 (28.7)
[0.05
13 (27.1)
14 (58.3)
\0.05
TIA
232 (33.8)
287 (55.9)
\0.05
46 (34.1)
80 (57.6)
\0.05
11 (22.9)
6 (25.0)
[0.05
Cerebral infarction
166 (24.2)
37 (7.2)
\0.01
54 (40.0)
14 (10.1)
\0.01
23 (47.9)
4 (16.7)
\0.01
Cerebral hemorrhage
7 (1.0)
8 (1.6)
[0.05
5 (3.7)
5 (3.6)
[0.05
1 (2.1)
0
[0.05
TIA transient ischemic attack
Fig. 2 Diagram of stenosis of ICA and VBA. a, b refers to stenosis of ICA. a high-grade stenosis of left carotid sinus. b high-grade stenosis of left MCA. c, d stenosis of VBA. c high-grade stenosis of V1
segments of right vertebral artery. d high-grade stenosis of V4 segments of right vertebral artery
stenosis (P \ 0.01). The prevalence of mild and severe stenosis was significantly higher in the left side than the right side (P \ 0.01). The prevalence of moderate stenosis was similar on both sides. The distribution of extra- and intracranial stenosis is listed in Table 2.
Clinical Characteristics of Extra- and Intracranial Artery Atherosclerosis
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The clinical characteristics of extra- and intracranial tortuosity, kinking, and coiling were listed in Table 3. In
Cell Biochem Biophys Table 4 Clinical characteristics of 434 patients with extra- and intracranial stenosis Clinical manifestations
Low-grade stenosis
Intermediate-grade stenosis
High-grade stenosis
ICA
VBA
P
ICA
VBA
P
ICA
VBA
P
Asymptomatic
50 (48.0)
59 (42.8)
[0.05
18 (29.8)
27 (37.5)
\0.05
10 (18.9)
23 (37.1)
\0.01
TIA
34 (32.7)
68 (49.3)
\0.01
24 (37.5)
35 (48.6)
\0.01
24 (45.3)
30 (48.4)
[0.05
Cerebral infarction
19 (18.3)
9 (6.5)
\0.01
19 (29.7)
8 (11.1)
\0.01
19 (35.8)
9 (14.5)
\0.01
Cerebral hemorrhage
1 (1.0)
2 (1.4)
[0.05
3 (4.7)
2 (2.8)
[0.05
0
0
0
TIA transient ischemic attack
patients with transient ischemic attack (TIA), the prevalence of tortuosity and kinking were significantly lower in the ICA system than the VBA system (P \ 0.05). In the coiling group, there was no significant difference between the ICA system and the VBA system (Figure 2). In patients with ischemic stroke, the prevalence of tortuosity, kinking, and coiling were significantly higher in the ICA system than the VBA system (P \ 0.01). The clinical characteristics of extra- and intracranial stenosis are listed in Table 4. In asymptomatic patients, the prevalence of moderate stenosis was significantly lower in the ICA system than the VBA system (P \ 0.05) (Fig. 2). In the severe stenosis group, there was no significant difference between the ICA system and the VBA system (P [ 0.05). In patients with ischemic stroke, the prevalence of tortuosity, kinking, and coiling were significantly higher in the ICA system than the VBA system (P \ 0.01).
Discussion Technical innovations in modern imaging have greatly advanced the role of DSA in the diagnosis and treatment of extra- and intracranial atherosclerosis. DSA is the current golden standard in cerebrovascular imaging. It not only allows accurate depiction of vascular structures with high spatial resolution, but also provides additional hemodynamic information [6–8]. Angiographic classification of extra- and intracranial atherosclerosis is of great importance for further cerebrovascular intervention. In previous reports [9, 10], a variety of terms were used to define a carotid artery abnormality. Coiling, elongation, and kinking are some of the terms most commonly used to define these variants. In our present study, we have classified extra- and intracranial vascular lesions into four categories. According to our criteria, extra- and intracranial vascular lesions were further categorized as tortuosity, kinking, coiling, and stenosis. In 1965, Weibel [11, 12] and colleagues described the angiographic characteristics of internal carotid artery in 1,438 patients. They classified the lesions as tortuosity, kinking, and coiling. According to
their classification, tortuosity was defined as an S-or C-shaped elongation in the course of the ICA. Coiling was defined as an exaggerated S-shaped elongation or redundancy of the ICA. Kinking was described as an acute angulation of the ICA. They found that kinking was the most frequently reported type of carotid abnormalities. In the present study, the classification was partly based on Weibel’s definitions. In our study, we have extended Weibel’s classification to the posterior circulation. In addition, we also investigated the prevalence and characteristics of stenosis in patients with extra- and intracranial atherosclerosis. In our present study, we have classified stenosis as mild (0–29 %), moderate (30–69 %), or severe (70–99 %) according to the NASCET trial criteria (Fig. 2). The NASCET trial classification was well-established for identifying the degree of stenosis worldwide and it is also useful in clinical practice for treatment decision-making. In our study, we have examined 1,816 patients with atherosclerosis by using DSA. Consistent with previous reports, we found the most common lesion was tortuosity, which accounted for 59.6 % of cases. According to our study, the prevalence of tortuosity was 63.8 % in the internal arterial system, 47.6 % in the vertebrobasilar system. We found the prevalence of tortuosity was significantly higher in the ICA system than the vertebrobasilar system. In previous autopsy studies, Paulsen [13] and colleagues investigated 282 patients and they found the prevalence of tortuosity was 26–28 % in the internal carotid artery. In another study of 100 healthy subjects by echocolor Doppler, Macchi et al. [14] reported that carotid kinkings were present in 38 % of the individuals. The reported prevalence of tortuosity in our study was significantly higher than the previous reports. Extra- and intracranial atherosclerosis is the underlying pathological basis for a variety of cerebrovascular disease including TIA, ischemic, and hemorrhagic stroke [15, 16]. Kinking and coiling were common lesions in patients with TIA and ischemic stroke. The possible explanations were kinking and coiling may lead to a series of hemodynamic changes, which are responsible for TIA and ischemic stroke. In our present study, the incidence of stroke was significantly higher in the ICA system than the VBA system. In previous
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Cell Biochem Biophys
reports [11, 12], cerebrovascular insufficiency was reported in 4-16 % of patients with internal carotid artery turtuosity. In patients with kinking, 51 % had cerebrovascular insufficiency. Of those with kinking, 93 % patients with cerebrovascular insufficiency were older than 50 years old. In patients with coiling, 59 % had cerebrovascular insufficiency. Of those with coiling, 80 % patients with cerebrovascular insufficiency were older than 50 years old. In our study, we have investigated the prevalence of extra- and intracranial atherosclerosis in patients with suspected stroke and correlated the atherosclerosis with clinical features of TIA and stroke in the internal carotid and VBA system. We found that the prevalence of stroke is significantly higher in the ICA system than the VBA system. However, the prevalence of TIA was lower in the ICA system than the VBA system. We proposed that kinkings and coilings may not have a clinical significance if these lesions were not associated with atheromatous plaques or carotid stenosis. In clinical practice, we also noticed that the degree of stenosis was not in proportion with the severity of clinical symptoms. One possible explanation for a patient with severe MCA stenosis remains asymptomatic could be the good collateral compensation. The exact etiology of carotid abnormality remains unclear. In previous reports, Paulsen, and colleagues consider these variations as congenital anomalies [17], while most authors consider artery elongation a consequence of atherosclerotic vessel remodeling [18]. Recently, Beigelman et al. [19] proposed that carotid dolichoarteriopathies are a result of developmental abnormalities rather than vascular remodeling secondary to aging and/or atherosclerosis. This controversy remains an unsolved issue. Future studies are needed to establish a more detailed classification of intraand extracranial atherosclerosis.
Conclusions Our studies suggest that the incidence of cerebral infarction and stroke in each atherosclerosis group was significantly higher in patients with ICA tortuosity, which has a higher prevalence rate, than in patients with VBA tortuosity. We also suggest that the lesions of kinkings and coilings become clinically significant when they are associated with atheromatous plaques or carotid stenosis.
References 1. The EC/IC Bypass Study Group. (1985). Failure of extracranial– intracranial arterial bypass to reduce the risk of ischemic stroke. Results of an international randomized trial. New England Journal of Medicine, 19, 1191–1200.
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2. Yoon, W. K., Kim, Y. W., Kim, S. D., Park, I. S., Baik, M. W., & Kim, S. R. (2008). Intravascular ultrasonography-guided stent angioplasty of an extracranial vertebral artery dissection. Journal of Neurosurgery, 109, 1113–1118. 3. Donnan, G. A., Fisher, M., Macleod, M., & Davis, S. M. (2008). Stroke. Lancet, 371, 1612–1623. 4. Lam, R. C., Lin, S. C., DeRubertis, B., Hynecek, R., Kent, K. C., & Faries, P. L. (2007). The impact of increasing age on anatomic factors affecting carotid angioplasty and stenting. Journal of Vascular Surgery, 45, 875–880. 5. Nguyen-Huynh, M. N., Wintermark, M., English, J., Lam, J., Vittinghoff, E., & Smith, W. S. (2008). How accurate is CT angiography in evaluating intracranial atherosclerotic disease? Stroke, 39, 1184–1188. 6. North American Symptomatic Carotid Endarterectomy Trial Collaborators. (1991). Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. New England Journal of Medicine, 325, 445–453. 7. Kwon, B. J., Jung, C., Sheen, S. H., Cho, J. H., & Han, M. H. (2007). CT angiography of stented carotid arteries: comparison with Doppler ultrasonography. Journal of Endovascular Therapy, 14, 489–497. 8. Key, H., Jackson, P. C., Thomas, E. A., Jeans, W. D., & Davies, E. R. (1987). The accuracy of digital subtraction angiography for the quantification of atherosclerosis. British Journal of Radiology, 60, 1083–1088. 9. La Barbera, G., La Marca, G., Martino, A., Lo Verde, R., Valentino, F., Lipari, D., et al. (2006). Kinking, coiling, and tortuosity of extracranial internal carotid artery: is it the effect of a metaplasia? Surgical and Radiologic Anatomy, 28, 573–580. 10. Togay-Is¸ ikay, C., Kim, J., Betterman, K., Andrews, C., Meads, D., Tesh, P., et al. (2005). Carotid artery tortuosity, kinking, coiling: stroke risk factor, marker, or curiosity? Acta Neurologica Belgica, 105, 68–72. 11. Weibel, J., & Fields, W. S. (1965). Tortuosity, coiling, and kinking of the internal carotid artery. I. Etiology and radiographic anatomy. Neurology, 15, 7–18. 12. Weibel, J., & Fields, W. S. (1965). Tortuosity, coiling, and kinking of the internal carotid artery. II. Relationship of morphological variation to cerebrovascular insufficiency. Neurology, 15, 462–468. 13. Paulsen, F., Tillmann, B., Christofides, C., Richter, W., & Koebke, J. (2000). Curving and looping of the internal carotid artery in relation to the pharynx: frequency, embryology and clinical implications. Journal of Anatomy, 197(Pt 3), 373–381. 14. Macchi, C., Gulisano, M., Giannelli, F., Catini, C., Pratesi, C., & Pacini, P. (1997). Kinking of the human ICA: a statistical study in 100 healthy subjects by echo color Doppler. Journal of Cardiovascular Surgery, 38, 629–637. 15. Adams, H. P, Jr. (2009). Secondary prevention of atherothrombotic events after ischemic stroke. Mayo Clinic Proceedings, 84, 43–51. 16. Mazighi, M., Labreuche, J., Gongora-Rivera, F., Duyckaerts, C., Hauw, J. J., & Amarenco, P. (2009). Autopsy prevalence of proximal extracranial atherosclerosis in patients with fatal stroke. Stroke, 40, 713–718. 17. Paulsen, F., Tillmann, B., Christofides, C., Richter, W., & Koebke, J. (2000). Curving and looping of the internal carotid artery in relation to the pharynx: frequency, embryology and clinical implications. Journal of Anatomy, 197, 373–381. 18. Gutierrez, J., Sacco, R. L., & Wright, C. B. (2011). Dolichoectasia—an evolving arterial disease. Nature Reviews Neurology, 7, 41–50. 19. Beigelman, R., Izaguirre, A. M., Robles, M., Grana, D. R., Ambrosio, G., & Milei, J. (2010). Are kinking and coiling of carotid artery congenital or acquired? Angiology, 61, 107–112.
ORIGINAL PAPER
Digital Subtraction Angiography Imaging Characteristics of Patients with Extra–Intracranial Atherosclerosis and Its Relationship to Stroke Juan Liu • Xiao-Jun Jia • Yan-Jiang Wang • Meng Zhang • Tao Zhang • Hua-Dong Zhou
Ó Springer Science+Business Media New York 2014
Abstract To investigate the angiographic characteristics and clinical features in patients with suspected extra– intracranial atherosclerosis in a large cohort of Chinese population. On the basis of digital subtraction angiography characteristics, pathological morphology of extra–intracranial atherosclerosis was divided into tortuosity, kinking, coiling, and stenosis in 2,218 individuals aged 45–89 years. The degree of stenosis was further divided into low-grade (\30 %), intermediate-grade (30–69 %), and high-grade stenosis (C70 %). Clinical manifestations were divided into transient ischemic attack, cerebral infarction and cerebral hemorrhage. The prevalence of tortuosity and stenosis were significantly higher in the extracranial arterial system than that of intracranial arterial system. The prevalence of tortuosity and kinking were significantly higher on the left side than the right side. The prevalence of mild and moderate stenosis in the internal carotid artery was significantly higher in the left side than the right side. The incidence of cerebral infarction was significantly higher in the internal carotid arterial (ICA) system than the vertebrobasilar arterial (VBA) system. Tortuosity is a common carotid abnormality in the Chinese population. The prevalence of ICA tortuosity is higher than that of VBA. The incidence of cerebral infarction in each atherosclerosis group was significantly higher in ICA than that of VBA. The prevalence of stroke is higher in the ICA system than the VBA system.
Juan Liu and Xiao-Jun Jia have contributed equally. J. Liu X.-J. Jia Y.-J. Wang M. Zhang T. Zhang H.-D. Zhou (&) Department of Neurology, Daping Hospital, Third Military Medical University, Chongqing, China e-mail: [email protected]
Kinkings and coilings may not have a clinical significance if these lesions are not associated with atheromatous plaques or carotid stenosis. Keywords Extra–intracranial atherosclerosis Digital subtraction angiography Stroke
Introduction Cerebrovascular disease is the leading cause of disability in the adult population worldwide. Extra–intracranial atherosclerosis is an important underlying pathological basis for cerebrovascular accidents [1, 2]. Arterial tortuosity, kinking, coiling, and stenosis are the most common lesions of the extra and intracranial vessels. Previous studies suggested that variations of the internal carotid artery occur in approximately 10–40 % of the population. In early angiography and postmortem reports, arterial variations have been classified as coiling, kinking, and tortuosity. Although the exact cause and natural history of kinking, coiling, and tortuosities of cerebral vessels are not clear, atherosclerosis is believed to be the underlying cause of tortuosity and kinking. Currently, digital subtraction angiography (DSA) is the gold standard for the evaluation of cerebral vasculatures. DSA provides essential information regarding hemodynamic status and collateral circulation in patients with stroke. It is an ideal imaging method of choice for diagnosis of cerebrovascular disorders. Imaging study of extra- and intracranial atherosclerosis with DSA is important for understanding of the pathophysiology of cerebrovascular diseases. It also helps with therapeutic decision making in triage patients for medical treatment and surgical/interventional therapy. Investigation of extra- and intracranial arterial coiling,
123
Cell Biochem Biophys
kinking, tortuosity, and stenosis may contribute to the diagnosis and treatment of extra–intracranial atherosclerosis [3, 4]. The purpose of our study was to determine the prevalence of extra–intracranial atherosclerosis by using DSA. The clinical profiles of the patients were correlated with angiographic findings in our case cohort.
Materials and Methods
vascular imaging) who were blinded to the clinical information independently assessed all the DSA images. If the interpreters had disagreement, they discussed until a consensus was reached. The reviewers had to assess DSA images for the presence of intra- and extracranial elongation (tortuosity, kinking, coiling) and the degree of stenosis. The degree of stenosis was measured by the internal digital caliber and documented. In evaluation of the vascular lesions, the internal carotid artery system and vertebrobasilar artery (VBA) system were independently assessed and recorded.
Subjects Statistical Analysis The present study was approved by the Ethics Committee of the Third Military Medical University. We retrospectively examined the DSA images of patients with suspected stroke, who underwent cerebral angiography in the department of neurology at Da Ping Hospital between January 2006 and December 2008. Patients underwent DSA if they had signs or symptoms suggestive of stroke. All patients had CT or MRI scan before DSA examination. DSA was performed in those with the diagnosis of stroke based on CT or MRI findings. Patients were excluded from the study if they were diagnosed of stroke mimics. DSA Analysis and Interpretation Three- or four-vessel DSA was performed via a transfemoral approach under local anesthesia. DSA was performed by selective injection of 8–10-mL contrast material in the internal carotid and vertebral arteries. A standard projection format, including anteroposterior, lateral and oblique views, was routinely obtained. DSA images were sent through picture archiving and communication systems (PACS) and viewed on the neurology workstation. The extra- and intracranial atherosclerosis lesions were classified into four categories: tortuosity, kinking, coiling, and stenosis. Tortuosity was characterized by a C-shaped elongation and generalized tortuosity of the cerebral vessels. Kinking was defined as elongation and angulation of blood vessels. Coiling was defined as elongation of blood vessels in a S-shaped circular configuration [5]. Arterial stenosis was documented according to the North American Symptomatic Carotid Endarterectomy (NASCET) trial measurements [6]. The narrowest diameter (N) of the stenosis lumen is compared with the patent luminal diameter (D) of the internal carotid artery. The percentage of stenosis was calculated by using the formula: Stenosis = (1 – N/D) 100. Stenoses were classified as mild (0–29 %), moderate (30–69 %), or severe (70–99 %) according to the NASCET criteria. Two experienced neurologists (Juan Liu and Xiao-Jun Jia, with 10 and 15 years experience in
123
Statistical data were analyzed using the SPSS package (Version 10.0; SPSS Inc., 2010). Group comparisons were made by using Student’s t test. For differences in categorical variables, Chi square tests were performed. A P value of \0.05 was considered statistically significant.
Results Baseline Clinical Profiles A total of 2,218 patients (1,475 male; 743 female) were included in our study. The average patient age was 66.9 ± 7.4 years. Of the 2,218 patients; 1,816 (81.9 %) patients (1,213 male; 603 female) had arterial atherosclerosis on DSA exam. DSA Characteristics of Patients with Atherosclerosis Of the 1,816 patients with intra- and extracranial atherosclerosis, tortuosity is the most common type of vascular abnormalities, which accounted for 59.3 % of cases. The highest prevalence of atherosclerosis was observed in the 60–4 years age group. In the internal carotid arterial (ICA) system, the prevalence of extracranial arterial tortuosity was significantly higher than intracranial tortuosity (P \ 0.01). All kinking and coiling were located at the extracranial arterial segments. The prevalence of tortuosity and kinking were significantly higher in the left side than the right side (P \ 0.01). There is no significant difference in the prevalence of coiling on both sides. In the vertebrabasilar arterial system, the prevalence of extracranial arterial tortuosity was significantly higher than intracranial tortuosity (P \ 0.01). The prevalence of tortuosity and kinking were significantly higher in the left side than the right side (P \ 0.01). Similarly, all kinking and coiling were located at the extracranial arterial segments. The imaging characteristics of the extra- and intracranial lesions are illustrated in Figure 1. The distribution of the
Cell Biochem Biophys
Fig. 1 Diagram of different cerebral vascular elongation. a tortuosity, b coiling, c kinking
Table 1 Distribution of extra- and intracranial arterial system Tortuosity, kinking and coiling in 1,382 patients Tortuosity
Kinking
Coiling
ICA
VBA
ICA
VBA
ICA
VBA
n
687
513
135
139
48
24
%
63.8
47.6
57.7
59.4
67.6
33.8
Extracranial
343 (49.9)a
296 (57.7)a
135 (100.0)
139 (100.0)
48 (100.0)
24 (100.0)
Intracranial
203 (29.5)
125 (24.4)
0
0
0
0
Extra–intra
141 (20.6)
0
0
23 (47.9)
17 (70.8)b
Left
287 (41.8)
92 (17.9) b
233 (45.4)
0 b
0
69 (51.1)
b
96 (69.1)
b
Right
241 (35.1)
183 (35.7)
57 (42.2)
36 (25.9)
21 (43.8)
5 (20.8)
Left–right
159 (23.1)
97 (18.9)
9 (6.7)
7 (5.0)
4 (8.3)
2 (8.4)
a
Extracranial versus intracranial, P \ 0.01
b
Left versus right, P \ 0.01
Table 2 Distribution of extra- and intracranial stenosis in 434 patients Low-grade stenosis
Intermediate-grade stenosis
High-grade stenosis
ICA
VBA
ICA
VBA
ICA
VBA
n
104
138
64
72
53
62
%
50.2
66.7
53.8
60.5
49.1
57.7
Extracranial
81 (77.9)a
101 (73.2)a
48 (75.0)a
62 (86.1)a
41 (77.4)a
51 (82.2)a
Intracranial
14 (13.5)
26 (18.8)
11 (17.2)
8 (11.1)
9 (16.9)
10 (16.1)
Extra–intra
9 (8.6)
11 (8.0)
5 (7.8)
2 (2.8)
3 (5.7)
1 (1.7)
Left
49 (47.1)b
75 (54.3)b
32 (50.0)b
37 (51.4)
25 (47.2)
33 (53.2)b
Right
39 (37.5)
45 (32.6)
26 (40.6)
31 (43.1)
23 (43.4)
27 (43.5)
Left–right
16 (15.4)
18 (13.1)
6 (9.4)
4 (5.5)
5 (9.4)
2 (2.3)
a
Extracranial versus intracranial, P \ 0.01
b
Left versus right, P \ 0.01
lesions is listed in Table 1. In the ICA system, the prevalence of extracranial arterial stenosis was significantly higher than intracranial stenosis (P \ 0.01). The prevalence of mild and moderate were significantly higher in the
left side than the right side (P \ 0.01). The prevalence of severe stenosis was similar on both sides. In the VBA system, the prevalence of extracranial arterial stenosis was significantly higher than intracranial
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Cell Biochem Biophys Table 3 Clinical characteristics in 1,382 patients with extra- and intracranial artery atherosclerosis Clinical manifestations
Tortuosity ICA
Kinking VBA
P
ICA
Coiling VBA
P
ICA
VBA
P
Asymptomatic
282 (41.0)
181 (35.3)
[0.05
30 (22.2)
40 (28.7)
[0.05
13 (27.1)
14 (58.3)
\0.05
TIA
232 (33.8)
287 (55.9)
\0.05
46 (34.1)
80 (57.6)
\0.05
11 (22.9)
6 (25.0)
[0.05
Cerebral infarction
166 (24.2)
37 (7.2)
\0.01
54 (40.0)
14 (10.1)
\0.01
23 (47.9)
4 (16.7)
\0.01
Cerebral hemorrhage
7 (1.0)
8 (1.6)
[0.05
5 (3.7)
5 (3.6)
[0.05
1 (2.1)
0
[0.05
TIA transient ischemic attack
Fig. 2 Diagram of stenosis of ICA and VBA. a, b refers to stenosis of ICA. a high-grade stenosis of left carotid sinus. b high-grade stenosis of left MCA. c, d stenosis of VBA. c high-grade stenosis of V1
segments of right vertebral artery. d high-grade stenosis of V4 segments of right vertebral artery
stenosis (P \ 0.01). The prevalence of mild and severe stenosis was significantly higher in the left side than the right side (P \ 0.01). The prevalence of moderate stenosis was similar on both sides. The distribution of extra- and intracranial stenosis is listed in Table 2.
Clinical Characteristics of Extra- and Intracranial Artery Atherosclerosis
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The clinical characteristics of extra- and intracranial tortuosity, kinking, and coiling were listed in Table 3. In
Cell Biochem Biophys Table 4 Clinical characteristics of 434 patients with extra- and intracranial stenosis Clinical manifestations
Low-grade stenosis
Intermediate-grade stenosis
High-grade stenosis
ICA
VBA
P
ICA
VBA
P
ICA
VBA
P
Asymptomatic
50 (48.0)
59 (42.8)
[0.05
18 (29.8)
27 (37.5)
\0.05
10 (18.9)
23 (37.1)
\0.01
TIA
34 (32.7)
68 (49.3)
\0.01
24 (37.5)
35 (48.6)
\0.01
24 (45.3)
30 (48.4)
[0.05
Cerebral infarction
19 (18.3)
9 (6.5)
\0.01
19 (29.7)
8 (11.1)
\0.01
19 (35.8)
9 (14.5)
\0.01
Cerebral hemorrhage
1 (1.0)
2 (1.4)
[0.05
3 (4.7)
2 (2.8)
[0.05
0
0
0
TIA transient ischemic attack
patients with transient ischemic attack (TIA), the prevalence of tortuosity and kinking were significantly lower in the ICA system than the VBA system (P \ 0.05). In the coiling group, there was no significant difference between the ICA system and the VBA system (Figure 2). In patients with ischemic stroke, the prevalence of tortuosity, kinking, and coiling were significantly higher in the ICA system than the VBA system (P \ 0.01). The clinical characteristics of extra- and intracranial stenosis are listed in Table 4. In asymptomatic patients, the prevalence of moderate stenosis was significantly lower in the ICA system than the VBA system (P \ 0.05) (Fig. 2). In the severe stenosis group, there was no significant difference between the ICA system and the VBA system (P [ 0.05). In patients with ischemic stroke, the prevalence of tortuosity, kinking, and coiling were significantly higher in the ICA system than the VBA system (P \ 0.01).
Discussion Technical innovations in modern imaging have greatly advanced the role of DSA in the diagnosis and treatment of extra- and intracranial atherosclerosis. DSA is the current golden standard in cerebrovascular imaging. It not only allows accurate depiction of vascular structures with high spatial resolution, but also provides additional hemodynamic information [6–8]. Angiographic classification of extra- and intracranial atherosclerosis is of great importance for further cerebrovascular intervention. In previous reports [9, 10], a variety of terms were used to define a carotid artery abnormality. Coiling, elongation, and kinking are some of the terms most commonly used to define these variants. In our present study, we have classified extra- and intracranial vascular lesions into four categories. According to our criteria, extra- and intracranial vascular lesions were further categorized as tortuosity, kinking, coiling, and stenosis. In 1965, Weibel [11, 12] and colleagues described the angiographic characteristics of internal carotid artery in 1,438 patients. They classified the lesions as tortuosity, kinking, and coiling. According to
their classification, tortuosity was defined as an S-or C-shaped elongation in the course of the ICA. Coiling was defined as an exaggerated S-shaped elongation or redundancy of the ICA. Kinking was described as an acute angulation of the ICA. They found that kinking was the most frequently reported type of carotid abnormalities. In the present study, the classification was partly based on Weibel’s definitions. In our study, we have extended Weibel’s classification to the posterior circulation. In addition, we also investigated the prevalence and characteristics of stenosis in patients with extra- and intracranial atherosclerosis. In our present study, we have classified stenosis as mild (0–29 %), moderate (30–69 %), or severe (70–99 %) according to the NASCET trial criteria (Fig. 2). The NASCET trial classification was well-established for identifying the degree of stenosis worldwide and it is also useful in clinical practice for treatment decision-making. In our study, we have examined 1,816 patients with atherosclerosis by using DSA. Consistent with previous reports, we found the most common lesion was tortuosity, which accounted for 59.6 % of cases. According to our study, the prevalence of tortuosity was 63.8 % in the internal arterial system, 47.6 % in the vertebrobasilar system. We found the prevalence of tortuosity was significantly higher in the ICA system than the vertebrobasilar system. In previous autopsy studies, Paulsen [13] and colleagues investigated 282 patients and they found the prevalence of tortuosity was 26–28 % in the internal carotid artery. In another study of 100 healthy subjects by echocolor Doppler, Macchi et al. [14] reported that carotid kinkings were present in 38 % of the individuals. The reported prevalence of tortuosity in our study was significantly higher than the previous reports. Extra- and intracranial atherosclerosis is the underlying pathological basis for a variety of cerebrovascular disease including TIA, ischemic, and hemorrhagic stroke [15, 16]. Kinking and coiling were common lesions in patients with TIA and ischemic stroke. The possible explanations were kinking and coiling may lead to a series of hemodynamic changes, which are responsible for TIA and ischemic stroke. In our present study, the incidence of stroke was significantly higher in the ICA system than the VBA system. In previous
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Cell Biochem Biophys
reports [11, 12], cerebrovascular insufficiency was reported in 4-16 % of patients with internal carotid artery turtuosity. In patients with kinking, 51 % had cerebrovascular insufficiency. Of those with kinking, 93 % patients with cerebrovascular insufficiency were older than 50 years old. In patients with coiling, 59 % had cerebrovascular insufficiency. Of those with coiling, 80 % patients with cerebrovascular insufficiency were older than 50 years old. In our study, we have investigated the prevalence of extra- and intracranial atherosclerosis in patients with suspected stroke and correlated the atherosclerosis with clinical features of TIA and stroke in the internal carotid and VBA system. We found that the prevalence of stroke is significantly higher in the ICA system than the VBA system. However, the prevalence of TIA was lower in the ICA system than the VBA system. We proposed that kinkings and coilings may not have a clinical significance if these lesions were not associated with atheromatous plaques or carotid stenosis. In clinical practice, we also noticed that the degree of stenosis was not in proportion with the severity of clinical symptoms. One possible explanation for a patient with severe MCA stenosis remains asymptomatic could be the good collateral compensation. The exact etiology of carotid abnormality remains unclear. In previous reports, Paulsen, and colleagues consider these variations as congenital anomalies [17], while most authors consider artery elongation a consequence of atherosclerotic vessel remodeling [18]. Recently, Beigelman et al. [19] proposed that carotid dolichoarteriopathies are a result of developmental abnormalities rather than vascular remodeling secondary to aging and/or atherosclerosis. This controversy remains an unsolved issue. Future studies are needed to establish a more detailed classification of intraand extracranial atherosclerosis.
Conclusions Our studies suggest that the incidence of cerebral infarction and stroke in each atherosclerosis group was significantly higher in patients with ICA tortuosity, which has a higher prevalence rate, than in patients with VBA tortuosity. We also suggest that the lesions of kinkings and coilings become clinically significant when they are associated with atheromatous plaques or carotid stenosis.
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