Chinese Medical Journal 2012;125(20):3671-3674
Correlation analysis of internal jugular vein abnormalities and cerebral venous sinus thrombosis

JIA Ling-yun,  HUA Yang,  JI Xun-ming,  LIU Jiang-tao

JIA Ling-yun (Department of Vascular Ultrasonography, Xuanwu Hospital, Capital Medical University, Beijing 100053, China)

HUA Yang (Department of Vascular Ultrasonography, Xuanwu Hospital, Capital Medical University, Beijing 100053, China)

JI Xun-ming (Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China)

LIU Jiang-tao (Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China)

Correspondence to:HUA Yang,Department of Vascular Ultrasonography, Xuanwu Hospital, Capital Medical University, Beijing 100053, China (Tel: 86-10-83198923. Fax:86-10-83198967. E-mail:dryanghua@sohu.com)
Keywords
cerebral venous sinus thrombosis; risk factor; internal jugular veins; hemodynamics; color Doppler flow imaging
Abstract
Background  Cerebral venous sinus thrombosis (CVST) is a special form of stroke with multiple causes and risk factors. However, there are still a portion of cases with unknown reasons. The aim of this study was to investigate the relationship between internal jugular vein (IJV) abnormalities and the development of CVST.
Methods  A total of 51 CVST patients and 30 healthy controls were enrolled. The diameter, the maximum velocity (Vmax) and the reflux time in bilateral IJVs were measured by color Doppler flow imaging (CDFI). The paired t test was used to compare the numeric values between the bilateral IJVs. The Pearson chi-square test was used to evaluate the relationship between IJV abnormality and CVST, IJV abnormality and IJV reflux, respectively.
Results  Among the 51 CVST patients, 20 (39%) patients were with normal IJV and 31 (61%) patients were with abnormal IJV. The types of IJV abnormality included annulus stenosis 19 cases (61%), hypoplasia 9 cases (29%), thrombosis 2 cases (7%) and anomalous valve 1 case (3%). In patients with unilateral IJV abnormality, the minimum diameter of the IJV on the lesion side was significantly smaller than that of the contralateral side (P <0.0001). When compared with contralateral side, the Vmax of the lesion side with unilateral annulus stenosis was significant higher, however, it was obvious lower in patients with unilateral hypoplasia (P <0.05). Furthermore, among 27 cases with unilateral IJV abnormality, all the CVST occurred on the same side as the IJV lesions.
Conclusion  IJV abnormality closely correlated with the development of CVST, which is a newly identified risk factor for CVST.
Cerebral venous sinus thrombosis (CVST) is a unique and frequently unrecognized form of stroke, with an estimated 5 cases per million annually, and accounts for 0.5%–1.0% of all strokes.1 CVST usually affects young individuals and has a high risk of recurrence, disability and mortality. There is an approximately 6.5% annual risk of recurrence, and the proportion of dependency is 9.7%.2-4 A meta-analysis indicated that 3%–15% CVST patients died in the acute phase, and the overall reported mortality was 9.4%.3 Thus, identifying the underlying etiology and risk factors contributing to CVST would be very helpful in developing strategies for the diagnosis, treatment and prevention of this disorder.
 
The identified risk factors for CVST are numerous. These risk factors can be divided generally into acquired risks (e.g., infection, surgery, trauma, pregnancy, puerperium, cancer, drugs) and genetic risks (e.g., inherited thrombophilia).5-10 However, the largest CVST cohort study (the International Study on Cerebral Venous and Dural Sinuses Thrombosis (ISCVT)) reported that the etiology for 12.5% (78/624 cases) of cases was still unknown.4 According to Virchow’s trial, hemodynamic changes, vessel wall injury and hypercoagulability are the three essential factors for developing thrombosis. Most of the identified risk factors for CVST have been linked to vessel wall injury and hypercoagulability of the blood. It is well known that the internal jugular veins (IJVs) represent the main outflow pathways for the cerebral venous system,11 and we speculated that IJV abnormality may change the cerebral venous outflow hemodynamic, leading to insufficient venous drainage, and subsequently cause CVST.
 
METHODS
 
Subjects  
This study protocol was approved by the Institutional Review Board. Each patient was fully informed and signed a consent form. In total, 51 consecutive CVST cases that were diagnosed at our institution by magnetic resonance venography (MRV) and digital subtraction angiography (DSA) from October 2010 to August 2011 and 30 healthy individuals, who served as normal controls, were enrolled in this study. The inclusion criteria for CVST patients were as follows: (1) patients had CVST (superior sagittal sinus, transverse sinus, sigmoid sinus or straight sinus thrombosis) diagnosed by MRV and DSA; and (2) the etiology of CVST was unidentified using all available methods. The exclusion criteria were as follows: (1) CVST patients with identified causes (including infection, surgery, trauma, pregnancy, puerperium, cancer, drugs, hypercoagulability and other known risk factors5); and (2) patients with pre-existing medical conditions known to be associated with brain pathology, including neurodegenerative disorders, severe cerebrovascular disease, etc.
 
Among the 30 healthy controls, there were 12 (40%) male and 18 (60%) female subjects with a mean age of (34.0±10.6) (15–62) years. Among the 51 CVST cases, there were 20 (39%) male and 31 female (61%) subjects with a mean age of (33.3±14.5) (range: 5–64) years. The median time of CVST process was 2 (range: 1–120) months prior to IJV examination by color Doppler flow imaging (CDFI). All the CVST located at transverse sinus and/or sigmoid sinus. The main recorded clinical symptoms were headaches (39 cases, 76%), visual loss (9 cases, 18%), diplopia (1 case, 2%), dysesthesia (1 case, 2%) and limb paralysis (1 case, 2%).
 
IJV ultrasonography  
The Philips ultrasound system (IU-22, Phillip Inc., the Netherlands) with a 3.0–9.0 MHz linear array probe and a 2.0–5.0 MHz curvilinear array probe were utilized to examine the IJVs. All ultrasound examinations were performed by an experienced (over 20 years) ultrasound physician (HUA Yang). The CDFI examiner was blinded to the clinical diagnosis of the subject. IJV examination was performed using the methods that Menegatti et al11 and Zamboni et al12 had previously described with some modifications. In brief, the subject was in the supine position, and during the examination, the subject was asked to breathe normally and relax his/her neck muscles. The IJV was first scanned in a transverse view in B-mode, and the diameters of three points along the IJV were measured, respectively (defined as J1 point: the level of IJV influx into innominate vein; J2 point: the level at which the superior thyroid vein influx into IJV; J3 point: the IJV level representing for the bifurcation level of common carotid artery). The IJV was then scanned in longitudinal view in B-mode and CDFI mode, and the abnormal morphology of IJV as well as the anomalous valves were recorded. Finally, the maximum velocity (Vmax) and the reflux time of the IJV at the 3 points were measured by Doppler spectrum.
 
MRV and DSA
Whole-brain DSA and MRV were performed using a double C-arm angiography system and a 1.5T MRI system (Siemens Inc., Germany) following the protocol we reported previously.13,14 The 2-dimensional time-of-flight (TOF) MRV imaging and the venous phase imaging of cerebral DSA were used to diagnose CVST and confirmed the IJV abnormality detected by ultrasonography.
 
Statistical analysis
The Statistical Package for Social Sciences (SPSS version 11.5, SPSS Inc., USA) was used for statistical analysis. Numeric values were shown as the mean ± standard deviation (SD). The paired t test was used to compare the numeric values between the bilateral IJVs. The Pearson chi-square test was used to evaluate the relationship between IJV abnormality and CVST, IJV abnormality and IJV reflux, respectively. A P value <0.05 was considered a statistically significant difference.
 
RESULTS
 
Characteristics of IJV abnormality in CVST patients
Among the 51 CVST patients, 20 (39%) patients had a normal IJV, and 31 (61%) patients had an abnormal IJV as evaluated by CDFI. The types of abnormalities included annulus stenosis (significant local circumferential stenosis of vein) in 19 cases (61%), hypoplasia (venous with long segments underdeveloped) in 9 cases (29%), part or complete IJV thrombosis in 2 cases (7%) and anomalous valve (very long valve causing significant flow obstacle at the J1 level) in 1 case (3%). Images of four types of IJV abnormalities detected by CDFI were shown in Figure 1. The IJV abnormality was confirmed by MRV and DSA. As shown in Figure 1B and 1F, in a patient with right transverse sinus thrombosis, CDFI showed hypoplasia of the right IJV, that was confirmed by DSA. Moreover, we found that IJV abnormality commonly occurred on the left side (18/31 cases, 58%) and at the J3 point (27/31 cases, 87%).
 

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Figure 1. The four types of IJV abnormalities identified by CDFI and the MRV, DSA images of CVST. A: CDFI showed an annulus stenosis at the J3 points of the left IJV (red blood flow). B: CDFI showed hypoplasia of the right IJV (red blood flow). C: CDFI showed no blood flow (IJV thrombosis, white arrow) in the right IJV in a cross-sectional view. D: B-mode showed a very long valve (white arrow) at the J1 point of the right IJV. E: MRV image of the same patient as B showed partial thrombosis at the right transverse sinus. F: DSA image of the same patient as B showed partial thrombosis at the right transverse sinus and hypoplasia of the right IJV.
 
Ultrasound characteristics of unilateral IJV abnormality
As demonstrated in Table 1, among the 30 healthy individuals, the diameter and Vmax of bilateral IJVs were symmetrical, and there were no differences between the two sides regarding the mean values of diameter and Vmax at the three points along the IJV.
 

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Table 1. IJV diameter and the maximum velocity (Vmax) in normal controls
 
Among the 31 cases with IJV abnormalities, there were 27 cases with unilateral IJV lesions (with 18 cases on the left side and 9 cases on the right side). In these 27 cases, we compared the diameter and Vmax at the lesion point and at the same point on the contralateral IJV. The minimum diameter of the IJV on the lesion side was significantly smaller than that on the contralateral side ((2.1±1.1) mm vs. (6.2±3.0) mm, t=7.52, P <0.0001).
 
When compared with the contralateral side, the Vmax on the lesion side in a patient with unilateral annulus stenosis was significantly higher; however, it was significantly lower in patients with unilateral hypoplasia (Table 2).
 

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Table 2. The maximum velocity (Vmax) in patients with unilateral IJV abnormality
 
IJV reflux in CVST patients and normal controls
There were 28 cases with IJV reflux among the 30 healthy individuals and 48 cases with IJV reflux among the 51 CVST patients. In both healthy individuals and CVST patients, bilateral IJV reflux was common (Table 3). There was no significant difference in the maximum reflux time between healthy controls and CVST patients ((339.3±118.2) ms vs. (330.7±176.8) ms, t=0.23, P >0.05). Moreover, there was no association between IJV reflux and IJV lesion (χ2=0.046, P=0.830, Table 4).
 

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Table 3. IJV reflux in CVST patients and normal controls (n)
 

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Table 4. Relationship between IJV lesion and reflux
 
Association between IJV abnormality and CVST
In 31 cases with IJV abnormalities, the CVST was located on either unilateral or bilateral transverse sinuses and/or sigmoid sinuses. Among 27 cases with unilateral IJV abnormality, we found that all the CVST occurred on the same side as the IJV lesions. In 4 cases with bilateral IJV abnormalities, 2 cases had bilateral CVST, and the other 2 cases had unilateral CVST. These results strongly suggested the close relationship between IJV abnormality and CVST (χ2=42.95, P <0.0001, Table 5).
 

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Table 5. Relationship between IJV lesion and CVST
 
DISCUSSION
 
CVST is a frequently unrecognized form of stroke with poor acute phase and long-term outcomes. Although a number of risk factors have been identified for CVST, the causes for partial cases are still unclear.4,6 Using CDFI with confirmation by MRV and DSA, we demonstrated in this study that IJV abnormalities changed the hemodynamics of the IJV, causing cerebral venous outflow insufficiency and subsequent CVST.
 
Saponaro et al15 and Gurley et al16 previously reported one case with superior sagittal sinus and two cases with sigmoid sinus thrombosis, respectively, that were in the presence of IJV stenosis or occlusion, which suggested the possibility that IJV abnormality may be associated with CVST. However, as far as we know, there were no studies with a large sample size to illustrate the relationship between IJV abnormality and CVST. In this study, among 51 consecutive CVST cases with unknown etiologies, we found that 61% of the cases (31/51) had an IJV abnormality. More importantly, almost all the CVST occurred on the same side as the IJV lesions (Table 5), which strongly suggests a close association between IJV abnormalities and CVST.
 
As for the mechanism that causes IJV abnormality to be a risk factor for CVST, we believe the hemodynamic changes would be the essential one, since IJVs are the main outflow pathway of the cerebral venous circulation, as demonstrated in our study, the diameter and the Vmax on the lesion side were significantly changed when compared with the contralateral side (Table 2). Thus, differing from most other identified risk factors for CVST,5,6 IJV abnormality is linked to CVST through a change in venous hemodynamics.
 
MRV and DSA are the main modalities used to diagnose CVST.17,18 As a non-invasive, cost-effective and convenient method, CDFI can evaluate morphology as well as hemodynamics of IJV simultaneously. In this study, we identified four types of IJV lesions by CDFI. These were annulus stenosis, hypoplasia, IJV thrombosis and anomalous valve. Furthermore, we found differences in hemodynamic change in two types of lesions, with higher Vmax in the annulus stenosis group and lower Vmax in the hypoplasia group (Table 2). Thus, CDFI is an ideal modality to screen CVST patients for IJV abnormalities and to determine the etiology. It is important to distinguish the types of lesions in IJVs to select the appropriate cases for interventional therapy. In general, percutaneous tansluminal angioplasty is suitable for patients with an annulus stenosis lesion but not for patients with IJV hypoplasia. We need additional follow-up studies to investigate the effects of IJV intervention on recurrence and the long-term outcomes of CVST in patients with IJV abnormalities. IJV reflux is another hemodynamic parameter for IJV evaluation by CDFI.11 However, in this study, we found that in both normal control and CVST patients, most of the patients had reflux and that there was no significant difference in the maximum reflux time between the two groups (Tables 3 and 4), which suggests that IJV reflux is not a valuable parameter for screening of CVST patients.
 
In conclusion, by studying a large number of subjects, we identify IJV abnormality as a novel risk factor for CVST and believe that it should be considered when determining the cause of CVST.
 
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  1. Research Fund for the Doctoral Program of Higher Education of China,No. 20111107120001; National Natural Science Foundation of China, No. 81200912;