Journal of Clinical Neuroscience 21 (2014) 769–772
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Clinical Study
Risk factors for dural arteriovenous fistula intracranial hemorrhage Tangming Peng, Aihua Liu ⇑, Jianwen Jia, Chuhan Jiang, Youxiang Li, Zhongxue Wu, Xinjian Yang Department of Interventional Neuroradiology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Tiantan Xili 6, Dongcheng District, Beijing 100050, China
a r t i c l e
i n f o
Article history: Received 28 February 2013 Accepted 12 July 2013
Keywords: Dural arteriovenous fistula Hemorrhage risk Intracranial hemorrhage Risk factors
a b s t r a c t To our knowledge, the risk factors for intracranial hemorrhage from dural arteriovenous fistula (DAVF) have not been systematically described, due to the complexity of their anatomy and low incidence. We performed this retrospective study to investigate the DAVF factors predicting intracranial hemorrhage. A 10 year database of 144 consecutive patients with DAVF was reviewed. Data collected and analyzed were demographics, morphologic features of DAVF, sex, age, fistula flow rate, arterial supply, lesion location, and venous drainage pattern. Linear univariate and multivariate logistic regression analyses were used to evaluate the association between influencing factors and hemorrhage. A first linear univariate analysis was performed for all influencing factors, and showed that sex, lesion location, and venous drainage pattern were statistically significant in predicting intracranial hemorrhage (p < 0.05). Secondary multivariate logistic regression analysis with sex, lesion location, and venous drainage pattern showed that only venous drainage pattern was statistically significant in predicting intracranial hemorrhage (p < 0.05). Therefore, venous drainage pattern, particularly the cortical venous drainage, significantly predicts intracranial hemorrhage from DAVF. Both sex and lesion location may be confounding factors in predicting intracranial hemorrhage from DAVF, while the other factors may not be associated with hemorrhage. Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction Dural arteriovenous fistula (DAVF) is a rare neurovascular abnormality, which accounts for approximately 10–15% of all intracranial arteriovenous lesions. The DAVF shunts blood from the dural arteries to the dural venous sinuses, the meningeal veins, or the cortical veins [1–3]. The etiology of DAVF is incompletely understood, but they are considered to be acquired. The primary symptoms of DAVF are intracranial hemorrhage and non-hemorrhagic neurological dysfunction, which may be related to numerous factors including age, sex, fistula flow rate, arterial supply, lesion location, and venous drainage pattern. Among these, sex, lesion location, and venous drainage pattern have attracted increasing attention. The most significant influencing factor may be the venous drainage pattern, particularly cortical venous reflux (CVR), which is strongly associated with aggressive clinical manifestations, especially intracranial hemorrhage [4,5]. Previously published reports have shown that the annual mortality for DAVF with CVR may be as high as 10.4%, with an annual risk of intracranial hemorrhage of 10.9% [6]. The re-hemorrhage rate of patients with DAVF is estimated to be up to 35% in the first 2 weeks following an initial hemorrhage. In some studies, the re-hemorrhage rate ⇑ Corresponding author. Tel.: +86 10 6709 8852. E-mail address: [email protected] (A. Liu). 0967-5868/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jocn.2013.07.024
is as high as 43% in the first few days [7]. We undertook a retrospective study to assess features of DAVF associated with intracranial hemorrhage, and consequently, to determine treatment for those DAVF high risk to reduce the incidence of aggressive clinical manifestations. The clinical presentation of DAVF is closely related to the venous drainage pattern. The widely used Borden classification [27] of DAVF is based on the venous drainage pattern [8] as is the Cognard classification [28], but with greater detail [9,10], including CVR and the pattern of venous sinus drainage. 2. Materials and methods 2.1. Patient selection A retrospective 10 year clinical database in Beijing Tiantan Hospital, Capital Medical University, of 144 consecutive patients was reviewed for all patients with DAVF. The clinical records and imaging studies, including CT scans, CT angiography, MRI, magnetic resonance angiography and digital subtraction angiography (DSA), were reviewed in detail. Patients with complete clinical and imaging information were entered into a database created for this study. All included patients had available imaging with CT scan and conventional DSA, including bilateral external carotid arteries, bilateral internal carotid arteries, and bilateral vertebral
770
T. Peng et al. / Journal of Clinical Neuroscience 21 (2014) 769–772
arteries to assess the arterial supply, lesion location, fistula flow rate and the venous drainage pattern. Patients without complete clinical and imaging information were excluded from the study. 2.2. Definition of fistula flow rate and classification of DAVF The fistula flow rate was grouped into two types according to the initial contrast agent filling time of the fistula/venous drainage compared to the initial contrast agent filling time of the M1 internal carotid artery segment on DSA. A high fistula flow rate was defined as an initial contrast agent filling time of the fistula/venous drainage earlier than that of the M1 internal carotid artery segment. In contrast, low fistula flow rate was defined as an initial contrast agent filling time of the fistula/venous drainage later than that of M1 internal carotid artery segment. The DAVF were classified into three types based on the Borden classification, with reference to Cognard type [8,9,11–13]: Type I: Direct anterograde flow into the dural sinus/meningeal vein without CVR. Type II: Drainage into the sinus with CVR and without significant ectasia of the leptomeningeal veins. Type III: Direct CVR (drainage into the sinus with CVR, with veins/venous lakes >5 mm or three times larger than the diameter of the draining vein).
Table 1 Presentation and clinical symptoms of patients with dural arteriovenous fistula
Headache Intracranial murmur/bruit Cavernous sinus hyperemia (conjunctival congestion, chemosis) Unilateral Bilateral Visual deterioration Blindness Seizure Exophthalmos Disorders of consciousness Other neurological deficit
n
%
80 77 75 60 15 16 2 8 35 5 6
55.6 53.4 52.1 41.7 10.4 11.1 1.4 5.6 24.3 3.8 4.2
Table 2 Correlation of dural arteriovenous fistula classification with risk of intracranial hemorrhage Current study Type I Type II Type III
Borden [27] 0% 43.3% 76%
Type I Type II Type III
Cognard [28] 2% 39% 79%
Type Type Type Type Type Type Type
I IIa IIb IIa + b III IV V
0% 7% 38% 40% 69% 83% 100%
2.3. Statistical analysis The Statistical Package for the Social Sciences (SPSS, Chicago, IL, USA) was used to analyze the association between DAVF features and hemorrhage risk. All factors were expressed in the form of mean ± standard deviation or number including sex, age, fistula flow rate, artery supply, lesion location and venous drainage pattern, and continuous variables were analyzed using the t-test, and categorical variables using Pearson’s chi-squared test. To identify independent predictive factors and confounding factors for intracranial hemorrhage from DAVF, univariate analyses and multivariate logistic regression analysis (forward stepwise conditional) were performed for clinical and angiographic parameters. A p value 0.05), with non-significant odds ratio values. Only the venous drainage pattern was an independent and significant factor in predicting hemorrhage from DAVF. Consequently, patients with CVR had a higher risk of intracranial hemorrhage than those without CVR; and the risk of hemorrhage in Type II patients was lower than the risk in Type III patients. In addition, the odds ratio value was as high as 11.950 for venous drainage pattern in logistic regression analyses, indicating venous drainage pattern was a significant predictor of hemorrhage.
3.1. Patient demographics and angiographic characteristics Baseline characteristics and presentation of the 144 patients are shown in Table 1. The most common presentations were headache (55.6%) and intracranial murmur/bruit (53.4%). The average age was 43.0 ± 13.4 years in the non-hemorrhage group versus 40.7 ± 13.3 years in the hemorrhage group, with no significant difference (p = 0.745), similar to many other previous studies. The arterial supply of DAVF was divided into two groups by unilateral or bilateral arterial supply. Hemorrhage occurred in 14 out of 80 patients (17.5%) with unilateral arterial supply, and in 18 out of 64 (28.1%) patients with bilateral arterial supply. However, arterial supply was not significantly different (p = 0.128). According to the fistula flow rate defined above, 89 patients had a high flow fistula with a 20.2% risk of hemorrhage, while 55 patients had a low flow fistula, with a 25.5% risk of hemorrhage. However, the risk of intracranial hemorrhage with respect to the fistula flow rate was not significantly different (p = 0.463). There was a female dominance (1.5:1), with 87 females and 57 males. The incidence of hemorrhage was 18 out of 57 (31.6%) males, and only 14 out of 87 (16.1%) females (p = .029). Lesions were located at the cavernous sinus (49.3%), transverse and sigmoid sinus (33.3%), superior sagittal sinus (4.9%), anterior
3.2. Significant factors related to intracranial hemorrhage
T. Peng et al. / Journal of Clinical Neuroscience 21 (2014) 769–772 Table 3 Univariate analysis of factors related to the risk of intracranial hemorrhage in dural arteriovenous fistula
Sex Male Female Age, mean ± SD Fistula flow rate Low High Arterial supply Unilateral feeding Bilateral feeding Lesion location Cavernous sinus Non-cavernous sinus Venous drainage Type I Type II Type III
Group A
Group B
Statistical test
p value
39 73 43.0 ± 13.40
18 14 40.7 ± 13.27
v2 = 4.779
0.029
t = 0.106
0.745
71 41
18 14
v2 = 0.538
0.463
66 46
14 18
v2 = 2.322
0.128
70 42
1 31
v2 = 35.10
0.000
89 17 6
0 13 19
v2 = 74.99
0.000
Group A = patients with dural arteriovenous fistula presenting with hemorrhage, Group B = patients with dural arteriovenous fistula presenting without hemorrhage, SD = standard deviation.
Table 4 Multivariate logistic regression analysis of factors related to the risk of intracranial hemorrhage in dural arteriovenous fistula Coefficient Venous drainage pattern Sex Lesion location
2.481 0.218 1.689
Wald value
p value
Odds ratio
14.525 0.132 2.139
0.000 0.716 0.144
11.950 0.087 0.348
4. Discussion DAVF can be defined as an abnormal shunt inside the dura. Patients may have benign or aggressive symptoms depending on the venous drainage pattern and the anatomic location of DAVF [14]. Aggressive symptoms include intracranial hemorrhage, a life-threatening event. In our series, 144 patients with mild to aggressive symptoms were analyzed and 32 (22.2%) patients had experienced at least once hemorrhage during the 10 year study period. Previous reports have suggested that sex, age, lesion location, fistula flow rate, arterial supply and venous drainage pattern may have a strong relationship with hemorrhage [5,15–17]. In the present study, patients with DAVF were analysed for the risk of hemorrhage with regard to the above factors via univariate analysis. Most published reports suggest that hemorrhage risk is related to gender, but several reports show no sex preponderance [15,16]. In this study, male sex was associated with hemorrhage (p = 0.029). This may be because our patients with cavernous sinus DAVF were primarily female; the cavernous sinus is generally a benign lesion location with a low risk of intracranial hemorrhage (1–2%) [15]. Furthermore, the sample size may have been too small to evaluate sex preponderance objectively. Chung et al. also reported DAVF over a period of 10 years, and male patients had a higher risk of hemorrhage [15]. However, sex was not an independent predictor of hemorrhage from DAVF on logistic regression analysis (p = 0.716). Therefore, sex may be a confounding factor in predicting intracranial hemorrhage and the underlying mechanism may be more associated with the anatomical location of DAVF. Similarly, lesion location was also a confounding factor in predicting intracranial hemorrhage. In our study, 71 (49.3%) patients
771
had DAVF located in the cavernous sinus, with an extremely low risk of hemorrhage, and only one (1.4%) patient suffered an intracranial hemorrhage in this territory. Meanwhile the risk of hemorrhage in the non-cavernous sinus group was as high as 42.5%, showing a significant difference between lesion locations. This is similar to the results of Lucas et al. who reported 26% of DAVF were located in the cavernous sinus and 74% in non-cavernous sinus locations in a meta-analysis of 258 patients [18]. Suh et al. reported that cavernous sinus DAVF have a low risk of hemorrhage because they lack CVR and have abundant venous drainage routes, including anterior, posterior and lateral drainage as well as drainage to the contralateral side [19]. In addition, Jung et al. reported that the high risk of hemorrhage in non-cavernous sinus DAVF relates to the presence of CVR, drainage via the leptomeningeal veins and insufficient venous drainage routes [5]. In our study, nearly half of DAVF were located in the cavernous sinus with many venous drainage routes, and few had CVR, leading to a low risk of hemorrhage. However, the majority of patients with hemorrhage had DAVF located in non-cavernous sinus locations, with insufficient venous drainage and the presence of CVR [20]. Consequently, the location of DAVF may be another confounding factor in predicting intracranial hemorrhage risk (p = 0.144). At present, the most widely used classifications of DAVF are those proposed by Cognard et al. and Borden et al. based on venous drainage pattern [14,15,17–20,27,28]. Davies et al. studied these two classifications in a large group of patients in clinical practice [11]. The Borden type was judged to be more concise and effective, with the three grades predicting risk of hemorrhage [21]; however, CVR was not considered in the Borden classification. So to investigate the relationship between venous drainage pattern and hemorrhage, a modified Borden classification was used in our study with reference to Cognard type in CVR and leptomeningeal venous drainage. It is generally accepted that the venous drainage pattern of DAVF is the most important factor in predicting the risk of hemorrhage [22]. DAVF with CVR or drainage into the leptomeningeal venous frequently cause intracranial hemorrhage. Classified using DSA, none of the 89 Type I patients had an intracranial hemorrhage. However, the bleeding was as high as 43.3% (13/30) in Type II patients, and increased to 76% (19/25) in Type III patients. Thus, the incidence of hemorrhage was 58.2% (32/55) in DAVF with CVR or drainage into leptomeningeal veins (Type II and III). These results are similar to many previous reports using Borden type, with hemorrhage incidence ranging from 2% to 6% in Borden Type I, from 31% to 40% in Borden Type II, and from 77% to 80% in Borden Type III [23]. Van Dijk and his colleagues reported that 25% of DAVF with CVR suffered intracranial hemorrhage over an average 4.3 year follow-up period, and the annual risk of intracranial hemorrhage was 8.1% in Borden Type II and III patients [22]. Huffmann et al. reported that the presence of long draining vein ectasia may increase the hemorrhage risk in DAVF with CVR [24]. However, Bink et al. reported that no patient experienced a hemorrhage accompanied by CVR in their series of 21 patients with transverse and sigmoid sinus DAVF (non-cavernous sinus) [9,12]. The underlying mechanisms of venous drainage pattern leading to intracranial hemorrhage from DAVF include the following hypotheses [25,26]. First, diversion of venous drainage may cause the symptoms of DAVF and reflux of the venous drainage into cortical veins carries a risk of hemorrhage. Second, hemorrhage in these patients may be due to venous congestion related to venous hypertension. In addition, sinus outflow thrombosis or venous outlet obstruction may lead to progressive obstruction of drainage veins. Lastly, a venous aneurysm may rupture, particularly as they are characterized by a thin aneurysmal wall, absence of elastic tissue in media and poor connective tissue between the intima and media [10–15].
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5. Conclusion Venous drainage pattern, especially CVR, is a significant factor predicting intracranial hemorrhage from DAVF. Both sex and lesion location may be confounding factors in predicting intracranial hemorrhage of DAVF, while age, fistula flow rate and arterial supply may be not associated with hemorrhage.
Conflicts of interest/disclosures The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication. Acknowledgements This article was supported by the National Natural Science Foundation of China (No. 30901557, 81220108007), The High Level Health Technique Talent Training Plan of Beijing Health System (No. 2011-3-036), and the Nova Plan of Beijing Municipal Science and Technology (2007A043), Disciplines Backbone of Beijing Tiantan Hospital (No. DLB2011-09). References [1] Murphy M, Van Gompel JJ. Medullary venous hypertension secondary to a petrous apex dural arteriovenous fistula: a case report. Case Rep Neurol 2012;4:187–93. [2] Liu JK, Choudhry OJ, Barnwell SL, et al. Single stage transcranial exposure of large dural venous sinuses for surgically-assisted direct transvenous embolization of high-grade dural arteriovenous fistulas: technical note. Acta Neurochir (Wien) 2012;154:1855–9. [3] Jung KH, Kwon BJ, Chu K, et al. Clinical and angiographic factors related to the prognosis of cavernous sinus dural arteriovenous fistula. Neuroradiology 2011;53:983–92. [4] Dutzmann S, Beck J, Gerlach R, et al. Management risk factors and outcome of cranial dural arteriovenous fistulae: a single-center experience. Acta Neurochir (Wien) 2011;153:1273–81. [5] Oh JT, Chung SY, Lanzino G, et al. Intracranial dural arteriovenous fistulas clinical characteristics and management based on location and hemodynamics. J Cerebrovasc Endovasc Neurosurg 2012;14:192–202. [6] van Dijk JM, TerBrugge KG, Willinsky RA, et al. Clinical course of cranial dural arteriovenous fistulas with long-term persistent cortical venous reflux. Stroke 2002;33:1233–6. [7] Byun JS, Hwang SN, Park SW, et al. Dural arteriovenous fistula of jugular foramen. J Korean Neurosurg Soc 2009;45:199–202. [8] Celik O, Piippo A, Romani R, et al. Management of dural arteriovenous fistulas – Helsinki and Kuopio experience. Acta Neurochir 2010;107(Suppl.):77–82.
[9] Abe E, Tashima A, Nakano T, et al. Postoperative hyperperfusion in a patient with a dural arteriovenous fistula associated with intracerebral hemorrhage: a case report. No Shinkei Geka Neurol Surg 2012;40:887–94. [10] Campero A, Campero AA, Martins C, et al. Surgical anatomy of the dural walls of the cavernous sinus. J Clin Neurosci 2010;17:746–50. [11] Davies MA, TerBrugge K, Willinsky R, et al. The validity of classification for the clinical presentation of intracranial dural arteriovenous fistulas. J Neurosurg 1996;85:830–7. [12] Bink A, Berkefeld J, Luchtenberg M, et al. Coil embolization of cavernous sinus in patients with direct and dural arteriovenous fistula. Eur Radiol 2009;19:1443–9. [13] Cohen SD, Goins JL, Butler SG, et al. Dural arteriovenous fistula: diagnosis, treatment, and outcomes. Laryngoscope 2009;119:293–7. [14] Rath SA, Derakshani S. Concepts of combined endovascular and surgical treatment for dural arteriovenous fistulae: concepts derived from experience in treating three unusual lesions. Acta Neurochir (Wien) 2004;146:229–35. [15] Chung SJ, Kim JS, Kim JC, et al. Intracranial dural arteriovenous fistulas: analysis of 60 patients. Cerebrovasc Dis 2002;13:79–88. [16] Kirsch M, Liebig T, Kuhne D, et al. Endovascular management of dural arteriovenous fistulas of the transverse and sigmoid sinus in 150 patients. Neuroradiology 2009;51:477–83. [17] Burger IM, Murphy KJ, Jordan LC, et al. Analysis in 241 consecutive diagnostic angiograms. Stroke 2006;37:2535–9. [18] Lucas CP, Zabramski JM, Spetzler RF, et al. Treatment for intracranial dural arteriovenous malformations: a meta-analysis from the English language literature. Neurosurgery 1997;40:1119–30. discussion 1130–1112. [19] Suh DC, Lee JH, Kim SJ, et al. New concept in cavernous sinus dural arteriovenous fistula: correlation with presenting symptom and venous drainage patterns. Stroke 2005;36:1134–9. [20] Geibprasert S, Pereira V, Krings T, et al. Dural arteriovenous shunts: a new classification of craniospinal epidural venous anatomical bases and clinical correlations. Stroke 2008;39:2783–94. [21] Aihara N, Mase M, Nishikawa Y, et al. Lumbar peritoneal shunt containing a programmable valve for intracranial hypertension caused by Borden type 1 dural arteriovenous fistulas. Acta Neurochir (Wien) 2011;153:2219–23. [22] van Dijk JM, TerBrugge KG, Willinsky RA, et al. Clinical course of cranial dural arteriovenous fistulas with long-term persistent cortical venous reflux. Stroke 2002;33:1233–6. [23] Ihn YK, Kim MJ, Shin YS, et al. Dural arteriovenous fistula involving an isolated sinus treated using transarterial onyx embolization. J Korean Neurosurg Soc 2012;52:480–3. [24] Huffmann AH, Mayfrank L, Laborde G, et al. A clinical presentation of dural arteriovenous fistulas of the anterior cranial fossa diagnosis and microneurosurgical treatment. Adv Neurosurg 1993;21:22–8. [25] Choi HS, Kim DI, Kim BM, et al. Endovascular treatment of dural arteriovenous fistula involving marginal sinus with emphasis on the routes of transvenous embolization. Neuroradiology 2012;54:163–9. [26] Wang Q, Song D, Chen G, et al. Endovascular treatment of high-flow cervical direct vertebro-vertebral arteriovenous fistula with detachable coils and Onyx liquid embolic agent. Acta Neurochir (Wien) 2011;153:347–52. [27] Borden JA, Wu JK, Shucart WA. A proposed classification for spinal and cranial dural arteriovenous fistulous malformations and implications for treatment. J Neurosurg 1995;82:166–79. [28] Cognard C, Gobin YP, Pierot L, et al. Cerebral dural arteriovenous fistulas: clinical and angiographic correlation with a revised classification of venous drainage. Radiology 1995;194:671–80.
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Clinical Study
Risk factors for dural arteriovenous fistula intracranial hemorrhage Tangming Peng, Aihua Liu ⇑, Jianwen Jia, Chuhan Jiang, Youxiang Li, Zhongxue Wu, Xinjian Yang Department of Interventional Neuroradiology, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Tiantan Xili 6, Dongcheng District, Beijing 100050, China
a r t i c l e
i n f o
Article history: Received 28 February 2013 Accepted 12 July 2013
Keywords: Dural arteriovenous fistula Hemorrhage risk Intracranial hemorrhage Risk factors
a b s t r a c t To our knowledge, the risk factors for intracranial hemorrhage from dural arteriovenous fistula (DAVF) have not been systematically described, due to the complexity of their anatomy and low incidence. We performed this retrospective study to investigate the DAVF factors predicting intracranial hemorrhage. A 10 year database of 144 consecutive patients with DAVF was reviewed. Data collected and analyzed were demographics, morphologic features of DAVF, sex, age, fistula flow rate, arterial supply, lesion location, and venous drainage pattern. Linear univariate and multivariate logistic regression analyses were used to evaluate the association between influencing factors and hemorrhage. A first linear univariate analysis was performed for all influencing factors, and showed that sex, lesion location, and venous drainage pattern were statistically significant in predicting intracranial hemorrhage (p < 0.05). Secondary multivariate logistic regression analysis with sex, lesion location, and venous drainage pattern showed that only venous drainage pattern was statistically significant in predicting intracranial hemorrhage (p < 0.05). Therefore, venous drainage pattern, particularly the cortical venous drainage, significantly predicts intracranial hemorrhage from DAVF. Both sex and lesion location may be confounding factors in predicting intracranial hemorrhage from DAVF, while the other factors may not be associated with hemorrhage. Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction Dural arteriovenous fistula (DAVF) is a rare neurovascular abnormality, which accounts for approximately 10–15% of all intracranial arteriovenous lesions. The DAVF shunts blood from the dural arteries to the dural venous sinuses, the meningeal veins, or the cortical veins [1–3]. The etiology of DAVF is incompletely understood, but they are considered to be acquired. The primary symptoms of DAVF are intracranial hemorrhage and non-hemorrhagic neurological dysfunction, which may be related to numerous factors including age, sex, fistula flow rate, arterial supply, lesion location, and venous drainage pattern. Among these, sex, lesion location, and venous drainage pattern have attracted increasing attention. The most significant influencing factor may be the venous drainage pattern, particularly cortical venous reflux (CVR), which is strongly associated with aggressive clinical manifestations, especially intracranial hemorrhage [4,5]. Previously published reports have shown that the annual mortality for DAVF with CVR may be as high as 10.4%, with an annual risk of intracranial hemorrhage of 10.9% [6]. The re-hemorrhage rate of patients with DAVF is estimated to be up to 35% in the first 2 weeks following an initial hemorrhage. In some studies, the re-hemorrhage rate ⇑ Corresponding author. Tel.: +86 10 6709 8852. E-mail address: [email protected] (A. Liu). 0967-5868/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jocn.2013.07.024
is as high as 43% in the first few days [7]. We undertook a retrospective study to assess features of DAVF associated with intracranial hemorrhage, and consequently, to determine treatment for those DAVF high risk to reduce the incidence of aggressive clinical manifestations. The clinical presentation of DAVF is closely related to the venous drainage pattern. The widely used Borden classification [27] of DAVF is based on the venous drainage pattern [8] as is the Cognard classification [28], but with greater detail [9,10], including CVR and the pattern of venous sinus drainage. 2. Materials and methods 2.1. Patient selection A retrospective 10 year clinical database in Beijing Tiantan Hospital, Capital Medical University, of 144 consecutive patients was reviewed for all patients with DAVF. The clinical records and imaging studies, including CT scans, CT angiography, MRI, magnetic resonance angiography and digital subtraction angiography (DSA), were reviewed in detail. Patients with complete clinical and imaging information were entered into a database created for this study. All included patients had available imaging with CT scan and conventional DSA, including bilateral external carotid arteries, bilateral internal carotid arteries, and bilateral vertebral
770
T. Peng et al. / Journal of Clinical Neuroscience 21 (2014) 769–772
arteries to assess the arterial supply, lesion location, fistula flow rate and the venous drainage pattern. Patients without complete clinical and imaging information were excluded from the study. 2.2. Definition of fistula flow rate and classification of DAVF The fistula flow rate was grouped into two types according to the initial contrast agent filling time of the fistula/venous drainage compared to the initial contrast agent filling time of the M1 internal carotid artery segment on DSA. A high fistula flow rate was defined as an initial contrast agent filling time of the fistula/venous drainage earlier than that of the M1 internal carotid artery segment. In contrast, low fistula flow rate was defined as an initial contrast agent filling time of the fistula/venous drainage later than that of M1 internal carotid artery segment. The DAVF were classified into three types based on the Borden classification, with reference to Cognard type [8,9,11–13]: Type I: Direct anterograde flow into the dural sinus/meningeal vein without CVR. Type II: Drainage into the sinus with CVR and without significant ectasia of the leptomeningeal veins. Type III: Direct CVR (drainage into the sinus with CVR, with veins/venous lakes >5 mm or three times larger than the diameter of the draining vein).
Table 1 Presentation and clinical symptoms of patients with dural arteriovenous fistula
Headache Intracranial murmur/bruit Cavernous sinus hyperemia (conjunctival congestion, chemosis) Unilateral Bilateral Visual deterioration Blindness Seizure Exophthalmos Disorders of consciousness Other neurological deficit
n
%
80 77 75 60 15 16 2 8 35 5 6
55.6 53.4 52.1 41.7 10.4 11.1 1.4 5.6 24.3 3.8 4.2
Table 2 Correlation of dural arteriovenous fistula classification with risk of intracranial hemorrhage Current study Type I Type II Type III
Borden [27] 0% 43.3% 76%
Type I Type II Type III
Cognard [28] 2% 39% 79%
Type Type Type Type Type Type Type
I IIa IIb IIa + b III IV V
0% 7% 38% 40% 69% 83% 100%
2.3. Statistical analysis The Statistical Package for the Social Sciences (SPSS, Chicago, IL, USA) was used to analyze the association between DAVF features and hemorrhage risk. All factors were expressed in the form of mean ± standard deviation or number including sex, age, fistula flow rate, artery supply, lesion location and venous drainage pattern, and continuous variables were analyzed using the t-test, and categorical variables using Pearson’s chi-squared test. To identify independent predictive factors and confounding factors for intracranial hemorrhage from DAVF, univariate analyses and multivariate logistic regression analysis (forward stepwise conditional) were performed for clinical and angiographic parameters. A p value 0.05), with non-significant odds ratio values. Only the venous drainage pattern was an independent and significant factor in predicting hemorrhage from DAVF. Consequently, patients with CVR had a higher risk of intracranial hemorrhage than those without CVR; and the risk of hemorrhage in Type II patients was lower than the risk in Type III patients. In addition, the odds ratio value was as high as 11.950 for venous drainage pattern in logistic regression analyses, indicating venous drainage pattern was a significant predictor of hemorrhage.
3.1. Patient demographics and angiographic characteristics Baseline characteristics and presentation of the 144 patients are shown in Table 1. The most common presentations were headache (55.6%) and intracranial murmur/bruit (53.4%). The average age was 43.0 ± 13.4 years in the non-hemorrhage group versus 40.7 ± 13.3 years in the hemorrhage group, with no significant difference (p = 0.745), similar to many other previous studies. The arterial supply of DAVF was divided into two groups by unilateral or bilateral arterial supply. Hemorrhage occurred in 14 out of 80 patients (17.5%) with unilateral arterial supply, and in 18 out of 64 (28.1%) patients with bilateral arterial supply. However, arterial supply was not significantly different (p = 0.128). According to the fistula flow rate defined above, 89 patients had a high flow fistula with a 20.2% risk of hemorrhage, while 55 patients had a low flow fistula, with a 25.5% risk of hemorrhage. However, the risk of intracranial hemorrhage with respect to the fistula flow rate was not significantly different (p = 0.463). There was a female dominance (1.5:1), with 87 females and 57 males. The incidence of hemorrhage was 18 out of 57 (31.6%) males, and only 14 out of 87 (16.1%) females (p = .029). Lesions were located at the cavernous sinus (49.3%), transverse and sigmoid sinus (33.3%), superior sagittal sinus (4.9%), anterior
3.2. Significant factors related to intracranial hemorrhage
T. Peng et al. / Journal of Clinical Neuroscience 21 (2014) 769–772 Table 3 Univariate analysis of factors related to the risk of intracranial hemorrhage in dural arteriovenous fistula
Sex Male Female Age, mean ± SD Fistula flow rate Low High Arterial supply Unilateral feeding Bilateral feeding Lesion location Cavernous sinus Non-cavernous sinus Venous drainage Type I Type II Type III
Group A
Group B
Statistical test
p value
39 73 43.0 ± 13.40
18 14 40.7 ± 13.27
v2 = 4.779
0.029
t = 0.106
0.745
71 41
18 14
v2 = 0.538
0.463
66 46
14 18
v2 = 2.322
0.128
70 42
1 31
v2 = 35.10
0.000
89 17 6
0 13 19
v2 = 74.99
0.000
Group A = patients with dural arteriovenous fistula presenting with hemorrhage, Group B = patients with dural arteriovenous fistula presenting without hemorrhage, SD = standard deviation.
Table 4 Multivariate logistic regression analysis of factors related to the risk of intracranial hemorrhage in dural arteriovenous fistula Coefficient Venous drainage pattern Sex Lesion location
2.481 0.218 1.689
Wald value
p value
Odds ratio
14.525 0.132 2.139
0.000 0.716 0.144
11.950 0.087 0.348
4. Discussion DAVF can be defined as an abnormal shunt inside the dura. Patients may have benign or aggressive symptoms depending on the venous drainage pattern and the anatomic location of DAVF [14]. Aggressive symptoms include intracranial hemorrhage, a life-threatening event. In our series, 144 patients with mild to aggressive symptoms were analyzed and 32 (22.2%) patients had experienced at least once hemorrhage during the 10 year study period. Previous reports have suggested that sex, age, lesion location, fistula flow rate, arterial supply and venous drainage pattern may have a strong relationship with hemorrhage [5,15–17]. In the present study, patients with DAVF were analysed for the risk of hemorrhage with regard to the above factors via univariate analysis. Most published reports suggest that hemorrhage risk is related to gender, but several reports show no sex preponderance [15,16]. In this study, male sex was associated with hemorrhage (p = 0.029). This may be because our patients with cavernous sinus DAVF were primarily female; the cavernous sinus is generally a benign lesion location with a low risk of intracranial hemorrhage (1–2%) [15]. Furthermore, the sample size may have been too small to evaluate sex preponderance objectively. Chung et al. also reported DAVF over a period of 10 years, and male patients had a higher risk of hemorrhage [15]. However, sex was not an independent predictor of hemorrhage from DAVF on logistic regression analysis (p = 0.716). Therefore, sex may be a confounding factor in predicting intracranial hemorrhage and the underlying mechanism may be more associated with the anatomical location of DAVF. Similarly, lesion location was also a confounding factor in predicting intracranial hemorrhage. In our study, 71 (49.3%) patients
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had DAVF located in the cavernous sinus, with an extremely low risk of hemorrhage, and only one (1.4%) patient suffered an intracranial hemorrhage in this territory. Meanwhile the risk of hemorrhage in the non-cavernous sinus group was as high as 42.5%, showing a significant difference between lesion locations. This is similar to the results of Lucas et al. who reported 26% of DAVF were located in the cavernous sinus and 74% in non-cavernous sinus locations in a meta-analysis of 258 patients [18]. Suh et al. reported that cavernous sinus DAVF have a low risk of hemorrhage because they lack CVR and have abundant venous drainage routes, including anterior, posterior and lateral drainage as well as drainage to the contralateral side [19]. In addition, Jung et al. reported that the high risk of hemorrhage in non-cavernous sinus DAVF relates to the presence of CVR, drainage via the leptomeningeal veins and insufficient venous drainage routes [5]. In our study, nearly half of DAVF were located in the cavernous sinus with many venous drainage routes, and few had CVR, leading to a low risk of hemorrhage. However, the majority of patients with hemorrhage had DAVF located in non-cavernous sinus locations, with insufficient venous drainage and the presence of CVR [20]. Consequently, the location of DAVF may be another confounding factor in predicting intracranial hemorrhage risk (p = 0.144). At present, the most widely used classifications of DAVF are those proposed by Cognard et al. and Borden et al. based on venous drainage pattern [14,15,17–20,27,28]. Davies et al. studied these two classifications in a large group of patients in clinical practice [11]. The Borden type was judged to be more concise and effective, with the three grades predicting risk of hemorrhage [21]; however, CVR was not considered in the Borden classification. So to investigate the relationship between venous drainage pattern and hemorrhage, a modified Borden classification was used in our study with reference to Cognard type in CVR and leptomeningeal venous drainage. It is generally accepted that the venous drainage pattern of DAVF is the most important factor in predicting the risk of hemorrhage [22]. DAVF with CVR or drainage into the leptomeningeal venous frequently cause intracranial hemorrhage. Classified using DSA, none of the 89 Type I patients had an intracranial hemorrhage. However, the bleeding was as high as 43.3% (13/30) in Type II patients, and increased to 76% (19/25) in Type III patients. Thus, the incidence of hemorrhage was 58.2% (32/55) in DAVF with CVR or drainage into leptomeningeal veins (Type II and III). These results are similar to many previous reports using Borden type, with hemorrhage incidence ranging from 2% to 6% in Borden Type I, from 31% to 40% in Borden Type II, and from 77% to 80% in Borden Type III [23]. Van Dijk and his colleagues reported that 25% of DAVF with CVR suffered intracranial hemorrhage over an average 4.3 year follow-up period, and the annual risk of intracranial hemorrhage was 8.1% in Borden Type II and III patients [22]. Huffmann et al. reported that the presence of long draining vein ectasia may increase the hemorrhage risk in DAVF with CVR [24]. However, Bink et al. reported that no patient experienced a hemorrhage accompanied by CVR in their series of 21 patients with transverse and sigmoid sinus DAVF (non-cavernous sinus) [9,12]. The underlying mechanisms of venous drainage pattern leading to intracranial hemorrhage from DAVF include the following hypotheses [25,26]. First, diversion of venous drainage may cause the symptoms of DAVF and reflux of the venous drainage into cortical veins carries a risk of hemorrhage. Second, hemorrhage in these patients may be due to venous congestion related to venous hypertension. In addition, sinus outflow thrombosis or venous outlet obstruction may lead to progressive obstruction of drainage veins. Lastly, a venous aneurysm may rupture, particularly as they are characterized by a thin aneurysmal wall, absence of elastic tissue in media and poor connective tissue between the intima and media [10–15].
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5. Conclusion Venous drainage pattern, especially CVR, is a significant factor predicting intracranial hemorrhage from DAVF. Both sex and lesion location may be confounding factors in predicting intracranial hemorrhage of DAVF, while age, fistula flow rate and arterial supply may be not associated with hemorrhage.
Conflicts of interest/disclosures The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication. Acknowledgements This article was supported by the National Natural Science Foundation of China (No. 30901557, 81220108007), The High Level Health Technique Talent Training Plan of Beijing Health System (No. 2011-3-036), and the Nova Plan of Beijing Municipal Science and Technology (2007A043), Disciplines Backbone of Beijing Tiantan Hospital (No. DLB2011-09). References [1] Murphy M, Van Gompel JJ. Medullary venous hypertension secondary to a petrous apex dural arteriovenous fistula: a case report. Case Rep Neurol 2012;4:187–93. [2] Liu JK, Choudhry OJ, Barnwell SL, et al. Single stage transcranial exposure of large dural venous sinuses for surgically-assisted direct transvenous embolization of high-grade dural arteriovenous fistulas: technical note. Acta Neurochir (Wien) 2012;154:1855–9. [3] Jung KH, Kwon BJ, Chu K, et al. Clinical and angiographic factors related to the prognosis of cavernous sinus dural arteriovenous fistula. Neuroradiology 2011;53:983–92. [4] Dutzmann S, Beck J, Gerlach R, et al. Management risk factors and outcome of cranial dural arteriovenous fistulae: a single-center experience. Acta Neurochir (Wien) 2011;153:1273–81. [5] Oh JT, Chung SY, Lanzino G, et al. Intracranial dural arteriovenous fistulas clinical characteristics and management based on location and hemodynamics. J Cerebrovasc Endovasc Neurosurg 2012;14:192–202. [6] van Dijk JM, TerBrugge KG, Willinsky RA, et al. Clinical course of cranial dural arteriovenous fistulas with long-term persistent cortical venous reflux. Stroke 2002;33:1233–6. [7] Byun JS, Hwang SN, Park SW, et al. Dural arteriovenous fistula of jugular foramen. J Korean Neurosurg Soc 2009;45:199–202. [8] Celik O, Piippo A, Romani R, et al. Management of dural arteriovenous fistulas – Helsinki and Kuopio experience. Acta Neurochir 2010;107(Suppl.):77–82.
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