|Year : 2021 | Volume
| Issue : 3 | Page : 158-165
The relationship between early neurological deterioration, poor clinical outcome, and venous collateral score in cerebral venous sinus thrombosis
Yasemin Dinc1, Rıfat Özpar2, Bahattin Hakyemez2, Mustafa Bakar1
1 Department of Neurology, Faculty of Medicine, Uludağ University, Nilüfer, Bursa, Turkey
2 Department of Radiology, Faculty of Medicine, Uludağ University, Nilüfer, Bursa, Turkey
|Date of Submission||16-Dec-2020|
|Date of Decision||25-Mar-2021|
|Date of Acceptance||10-Apr-2021|
|Date of Web Publication||20-Sep-2021|
Department of Neurology, Uludag University Faculty of Medicine, Nilüfer, Bursa
Source of Support: None, Conflict of Interest: None
Background and Purpose: Cerebral venous sinus thrombosis (CVST) is one of the rare causes of cerebrovascular disease and has an extremely heterogeneous prognosis. The aim of this study was to investigate the potential relationship between early neurological deterioration, poor clinical outcome in CVST and the venous collateral score. Materials and Methods: A total of 121 patients diagnosed with CVST between 2010 and 2020 were retrospectively included. The demographic, clinical, and radiological findings related to venous sinus thrombosis and early neurological deterioration were investigated in relation to the clinical outcome. Results: The factors associated with early neurological deterioration were superior sagittal sinus thrombosis (P < 0.001), sinus rectus thrombosis (P = 0.031), parenchymal lesions (P < 0.001), and venous collateral score (P < 0.001). The factors associated with poor clinical outcome were superior sagittal sinus thrombosis (P < 0.001), cortical vein thrombosis (P < 0.001), venous collateral score (P < 0.001), and initial clinical symptoms. Binary logistic regression analyses revealed poor clinical outcome as a significant variable, with a venous collateral scale of 0 or 1 as a risk factor for a poor outcome (significance of the model P < 0.001). Conclusion: Early neurologic deterioration and poor clinical outcome may occur due to poor collateralization in CVST. Identifying the subgroup of CVST patients at risk of clinical deterioration is therefore important. This study highlights the clinical importance of venous collaterals; however, larger prospective multicenter studies are required to confirm the relationship with venous collaterals in patients with CVST.
Keywords: Cerebral venous sinus thrombosis, early neurological deterioration, venous collateral score
|How to cite this article:|
Dinc Y, Özpar R, Hakyemez B, Bakar M. The relationship between early neurological deterioration, poor clinical outcome, and venous collateral score in cerebral venous sinus thrombosis. Neurol Sci Neurophysiol 2021;38:158-65
|How to cite this URL:|
Dinc Y, Özpar R, Hakyemez B, Bakar M. The relationship between early neurological deterioration, poor clinical outcome, and venous collateral score in cerebral venous sinus thrombosis. Neurol Sci Neurophysiol [serial online] 2021 [cited 2021 Oct 18];38:158-65. Available from: http://www.nsnjournal.org/text.asp?2021/38/3/158/326289
| Introduction|| |
Cerebral venous sinus thrombosis (CVST) is a rare form of venous thromboembolism and one of the rare causes of ischemic cerebrovascular disease, with an incidence of 2–12 cases per million people per year.,, CVST has a highly variable clinical spectrum, but diagnosis is possible with high clinical suspicion and additional radiological examinations. Various etiologies occur, and the prognosis is extremely heterogeneous. The clinical presentation and prognosis of CVST vary according to the involvement of the deep or superficial systems, the formation of parenchymal lesions and the grade of the venous collateral scale (VCS).,,,,
The management of CVST focuses on timely diagnosis and treatment, with treatment consisting of anticoagulation to prevent the thrombus from spreading.,, In some cases, the patient's condition may worsen despite treatment; for example, 9%–13% of patients with CVST have poor results despite anticoagulation. In those cases, mechanical thrombectomy or endovascular thrombolysis may be an option.
The importance of collaterals in CVST is now increasingly recognized, as evidenced by the development of several collateral scales; however, knowledge about the VCS remains insufficient.,, Early neurological deterioration is a frequent complication of CVST and is defined as a clinical worsening or recurrence within the first 72 h after ischemic cerebrovascular disease. This neurological deterioration is associated with poor clinical outcomes; therefore, the consequences can be serious. For this reason, knowing which factors will lead to early neurological deterioration and poor clinical outcomes is important to ensure that appropriate precautions are taken. The aim of the present study was to determine the rates of early neurological deterioration and poor clinical outcomes in patients with CVST in our tertiary center and to analyze the relationship between these rates and the extent of venous collaterals.
| Materials and Methods|| |
This was a retrospective study of 121 patients who were followed up with a diagnosis of CVST between 2010 and 2020 at Uludağ University Faculty of Medicine, Department of Neurology. The inclusion criteria were a diagnosis of CVST by contrast-enhanced (CE) cranial magnetic resonance (MR) venography, patient follow-up by the neurology clinic, and regular follow-up by the Department of Neurology of Uludağ University for 3 months following the CVST. The exclusion criteria were leaving the neurology clinical follow-up and not completing the necessary examinations to clarify the etiology of CVST.
Approval for the study was obtained from the Uludağ University Faculty of Medicine. The Clinical Research Ethics Committee approved the study with a letter dated September 2, 2020, and approval number 2020-15/7. Since this was a retrospective study, patient approval was not required.
In our center, all medical records are stored electronically; therefore, the patients diagnosed with CVST were identified by retrospective screening of all patients who had undergone brain MR venography. The records of the patients with CVST were examined to extract the patients' demographic data, the underlying factors, and history of their disease, the signs and symptoms at presentation, the neuroimaging examinations, and any factors that could have caused coagulation disorders, as well as their laboratory examination results, including thyroid hormones, the presence of early neurological deterioration, treatment methods, and neurological functions at the time of discharge. In this study, we defined early neurological deterioration, according to a previously recommended definition, as a 2-point increase in the National Institutes of Health Stroke Scale score over a period of 72 h after hospitalization; only deterioration due to seizure was excluded from this definition. Patients were followed up in the stroke outpatient clinic of Uludağ University Faculty of Medicine, Department of Neurology and the clinical outcomes of the patients were evaluated in the 3rd month. The Modified Rankin Scale scores of 0, 1, and 2 were evaluated as good clinical outcomes, whereas scores of 3, 4, 5, or 6 were ranked as poor clinical outcomes.
Magnetic resonance venography technique
MR venography examinations were performed with an Achieva 3T® MR scanner (Philips, Best, Netherlands). Both phase-contrast (PC) MR venography and CE MR venography were used. The parameters for PC MR venography were as follows: Repetition time (TR), 19.1 msec; echo time (TE), 7.0 ms; number of excitations (NEX), 2; voxel size, 0.8 mm × 1.1 mm × 1.6 mm; encoding velocity, 15 cm/s; and duration, 4 min 27 s. The CE MR venography was performed using a fast and saturated three-dimensional gradient-recalled echo sequence (TR: 3.98 ms, TE: 1.42 ms, VS: 0.7 mm × 0.9 mm × 1 mm, SENSE factor: 3, duration: 24 s) for precontrast and postcontrast imaging. When all images were obtained, the precontrast image series of the CE MR venography was subtracted from the postcontrast series. The contrast medium was 0.5 mmol gadoterate meglumine and was applied from the antecubital venous system with an automatic injection device at a dose of 0.2 ml/kg.
The diagnosis of CVST was made in all patients based on the initial 3 T CE cranial MR venography results and collateral classification was obtained using initial contrast cranial MR venography. All radiologic examinations were reviewed by two radiologists. The first observer had 18 years of neuroradiology experience, and the second observer had a 6 years of radiology experience. All reviewers were blinded to the results. In cases of interobserver discordance, the evaluation result of the first observer was considered. Venous collaterals were examined in three categories, where a VCS 0 indicated no significant venous drainage that could be visualized from the brain area affected by sinus obstruction and VCS 1 indicated observation of a vein flowing from the affected area but not connected to an open sinus. By contrast, VCS 2 indicated visualization of a vein flowing from the affected area; that vein then connected to an open sinus and could thereby function as a suitable venous collateral [Figure 1]. All images were evaluated in terms of the number of thrombosed venous sinuses, the VCS score from MR venography and the presence of hematoma and brain damage associated with venous congestion visible on noncontrast computed tomography and/or on T2W sequences from MR imaging (MRI) performed on the same day as the MR venography.
|Figure 1: Venous collateral scale 0 case (a); Thrombosis in the left transverse sigmoid sinus, no collatetal appearance providing drainage of the affected area. venous collateral scale 1 case (b); Partially recanalized thrombus in the anterior and distal of the superior sagittal sinus, cortical vein (arrow) that provides drainage from the location of the thrombus to other collatetal venous structures. Venous collateral scale 2 case (c and d); thrombus in the superior sagittal sinus, collateral (arrowhead) providing drainage to the inferior sagittal sinus, and collateral (arrow mark) providing drainage to the left sphenoparietal sinus|
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The radiological, demographic, and clinical data of the patients were compared. Statistical analysis was conducted using the IBM SPSS Statistics 25.0 package (IBM Corp., Armonk, New York, USA). The Shapiro–Wilk test, a histogram, and a Q-Q plot were implemented to determine the data normality. The means and standard deviations or medians (25%–75% quartiles) were then used for the analysis of continuous variables. Frequencies and percentages were given for categorical variables. Levene's test was applied to determine the variance homogeneity. A two-sided independent sample t-test or a two-sided Mann–Whitney U test was used to analyze the differences between groups for continuous variables. A two-sided Fisher's Exact, Pearson, Chi-square, and Continuity Correction test for (2 × 2) or (r × c) tables were used to analyze the differences between the groups for categorical variables. Logistic regression analysis was applied to determine the risk factors for a poor clinical outcome for CVST. A P < 0.05 was considered statistically significant.
| Results|| |
A total of 121 patients (35 males [28.9%] and 86 females [71.1%]) were included in this study. The mean age of the patients was 40.83 ± 15.6 years (range 16–80); the mean age of the women was 40.46 ± 13.89 years and the mean age of the men was 41.74 ± 18.11 years. No statistically significant difference was noted between gender and age. The initial clinical symptoms of CVST were examined in four categories. The initial symptom was isolated intracranial hypertension in 79 (65.3%) patients, focal neurological deficit in 19 (15.7%), epileptic seizures in 22 (18.2%) and encephalopathy in 1 (0.8%) patient. The VCS was examined in three categories. 24 (19.8%) patients had VCS scores of 0, 41 (33.9%) had VCS scores of 1 and 56 (46.3%) had VCS scores of 2. Early neurological deterioration occurred in 41 (33.9%) patients, and 30 (24.8%) patients had poor clinical outcomes. Intracranial herniation occurred in 17 (14%) patients. Decompressive craniectomy was performed in 14 (9.7%) patients. Death due to CVST occurred in 7 (5.8%) patients. In total, 47 (38.8%) patients had parenchymal lesions, and 29 (23.9%) of those patients had intracranial hemorrhage. Among those 29 patients, 13 (10.7%) had an intraparenchymal hematoma, 11 (9%) had juxtacortical hemorrhages, 3 (2.4%) patients had subarachnoid hemorrhages and 2 (1.6%) patients had subdural hematomas.
Statistically significant relationships were detected between patients with CSVT with and without early neurological deterioration in terms of parenchymal lesions (P < 0.001), clinical outcome (P < 0.001), venous collateral score (P < 0.001), thrombosis of the superior sagittal sinus (P < 0.001), cortical vein involvement (P < 0.001), thrombosis of sinus rectus (P = 0.031), intracranial herniation (P < 0.001), death (P < 0.001), and the initial clinical symptoms (P < 0.001). By contrast, no relationships were found between the groups in terms of age, gender, thrombosis of the inferior sagittal sinus, thrombosis of the transverse sinus, thrombosis of the jugular vein, thrombosis of the sigmoid vein, the number of thrombosed sinuses, and the etiology of CVST [Table 1].
|Table 1: The comparison of patients having early neurological detoriation and not, and clinical, radiologic and demographic properties|
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Logistic regression analysis identified the presence of a parenchymal lesion, a VCS score of 0 or 1 and involvement of the superior sagittal sinus as significant risk factors for early neurological deterioration in patients with CVST (significance of the model P < 0.001) [Table 2]. Patients with CSVT with and without a poor clinical outcome showed statistically significant relationships in terms of parenchymal lesions (P < 0.001), clinical outcome (P < 0.001), venous collateral score (P < 0.001), thrombosis of the superior sagittal sinus (P < 0.001), cortical vein involvement (P < 0.001), intracranial herniation (P < 0.001), death (P < 0.001), and the initial clinical symptoms (P < 0.001). By contrast, no relationships were detected between the groups in terms of age, gender, thrombosis of inferior sagittal sinus, thrombosis of the transverse sinus, thrombosis of the jugular vein, thrombosis of the sinus rectus, thrombosis of the sigmoid vein, the number of thrombosed sinuses and the etiology of CVST [Table 3].
|Table 2: Significant variables of early neurological deteriotion of patients with cerebral venous sinus thrombosis using binary logistic regression analysis|
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|Table 3: The comparison of patients having poor clinical outcome and not, and clinical, radiologic and demographic properties|
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Binary logistic regression analysis identified the presence of a parenchymal lesion, a VCS score of 0 or 1, and involvement of the superior sagittal sinus as statistically significant risk factors for poor clinical outcomes in patients with CVST (significance of the model P < 0.001) [Table 4].
|Table 4: Significant variables of poor clinical outcome of patients with cerebral venous sinus thrombosis using binary logistic regression analysis|
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| Discussion|| |
This study of 10 years of data from our tertiary referral center revealed that the VCS score is associated with early neurological deterioration and poor clinical outcome in patients with CVST. Fifty years ago, CVST progressed with very high mortality; however, the introduction of modern neuroimaging has since minimized CVST mortality. In previous studies, the mortality rate had been reported to range from 3% to 27%;,,,,,, whereas the mortality rate in our study was 5.5%. The reason for this difference may be that we diagnosed our patients early and started anticoagulation treatment early at our referral center.
Cerebral venous drainage consists of two systems: The superficial and the deep venous systems. The clinical picture of CVST varies due to differences in the impaired drainage of these two systems. When cerebral veins are occluded, venous congestion occurs due to obstruction of the outflowing blood, with a resulting increase in the capillary hydrostatic pressure. The consequences can include vasogenic edema, enlarged vessels, petechial hematoma, ischemic neuronal damage, and intraparenchymal hematoma., By contrast, occlusion of the venous sinuses can result in intracranial hypertension, as the cerebrospinal fluid (CSF) normally drains into the superior sagittal sinus through the Pacchioni or arachnoid granulation.
The occurrence of CVST causes an increase in the venous pressure due to the delay of venous discharge from the impaired CSF absorption and the subsequent increase in intracranial pressure., Therefore, the adequacy of collateral blood drainage determines the symptoms. When the collaterals are sufficient, the symptoms are associated with increased intracranial pressure, but when they are insufficient, parenchymal lesions may be observed.
Many studies have been conducted on the clinical worsening in patients with CVST, and the reported clinical deterioration determinants have included parenchymal lesions, age above 37 years, Glasgow coma score below 9, seizures, posterior fossa lesions, intracranial hemorrhages, and the presence of any malignancy in the patient., A retrospective study investigating the imaging markers of clinical deterioration in CVST patients found that patients with venous infarction and hyperintensity on diffusion-weighted imaging MRI showed an increased risk of clinical deterioration. In the present study, the group with early neurologıcal deterioration were patients with parenchymal lesions, with the involvement of the superior sagittal sinus, and with VCS scores of 0 and 1.
The superior sagittal sinus is the main vein into which the CSF drains when occluded, so its collaterals are very important. This is because an increase in severe intracranial pressure will be accompanied by increases in the venous pressure, as well as by an increased likelihood of parenchymal lesions and a poor clinical outcome. Previous studies have also shown that superior sagittal sinus thrombosis is a predictor of poor prognosis. By contrast, jugular vein and transverse sinus thrombosis, which are distal thromboses, showed no significant statistical association with poor clinical outcomes in our study.
The proportion of poor clinical outcomes reported previously also differs depending on the study. For example, the RENEMEVASC study showed that 23.7% of the patients with CVST had poor outcomes (continued dependency) at 1 month, whereas the International Study on Cerebral Venous Thrombosis study found that only 5.1% of the patients had a poor clinical outcome.,, In our study, the clinical outcome was evaluated at 3 months, and the poor clinical outcome rate was 23%. Our high rate of poor clinical outcomes may reflect that our center is a referral center.
Poor clinical outcomes in our patients included the development of intracranial herniation in 17 of our patients. Subfalcine herniation occurred in 12 patients with parenchymal lesions, while uncal herniation due to increased intracranial pressure occurred in 5 patients without parenchymal lesions. The mortality was higher for uncal herniation due to CVST than for subfalcine herniation, and all patients with uncal herniation in our study died, although the overall CVST mortality in our study was 5.5%. One point that should be kept in mind is that patients with CVST may develop intracranial herniation and require decompressive craniectomy. The CVST guidelines recommend anticoagulation for all patients, and patients with clinical worsening under adequate anticoagulation may be candidates for mechanical thrombectomy. Therefore, identifying the subgroup of CVST patients at risk of clinical deterioration is important.
Complications arising from CVST may be avoided by taking some precautions. The VCS used in this study was developed by Sheth et al. and it differs somewhat from the VCS developed by Qureshi, as the scale developed by Qureshi does not take into account which sinus the collateral drains into, but considers all patent sinuses that can receive flow and reduce pressure from tissue that would have otherwise drained to occluded sinus equivalent. The scale introduced by Sheth et al. successfully indicated clinical worsening; however, the insufficient number of patients and the evaluation of venous collaterals with different imaging methods (BT venography, MR venography, and venous diagnostic cerebral angiography) are the limitations of that study. For this reason, as suggested by Sheth et al., all the venous collaterals in our study were evaluated using the same imaging method (CE cranial venography).
The greatest limitation of the present study is that the data were based on a retrospective single-center cohort study with a limited number of patients. The majority (65%) had isolated intracranial hypertension, but these patients only very rarely show early neurologic deterioration. For this reason, our data reflect the general population in only a limited way.
| Conclusion|| |
Early neurologic deterioration and poor clinical outcomes may be observed due to poor collateralization in CVST. Identifying the subgroup of CVST patients at risk of clinical deterioration is therefore important. This study highlights the clinical importance of venous collaterals; however, larger prospective multicenter studies are required to confirm the relationship with venous collaterals in patients with CVST.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Bousser MG, Crassard I. Cerebral venous thrombosis, pregnancy and oral contraceptives. Thromb Res 2012;130 Suppl 1:S19-22.
Stam J. Thrombosis of the cerebral veins and sinuses. N Engl J Med 2005;352:1791-8.
Bousser MG, Ferro JM. Cerebral venous thrombosis: An update. Lancet Neurol 2007;6:162-70.
Coutinho JM, Zuurbier SM, Aramideh M, Stam J. The incidence of cerebral venous thrombosis: A cross-sectional study. Stroke 2012;43:3375-7.
Dlamini N, Billinghurst L, Kirkham FJ. Cerebral venous sinus (sinovenous) thrombosis in children. Neurosurg Clin N Am 2010;21:511-27.
Corvol JC, Oppenheim C, Manaï R, Logak M, Dormont D, Samson Y, et al
. Diffusion-weighted magnetic resonance imaging in a case of cerebral venous thrombosis. Stroke 1998;29:2649-52.
Yoshikawa T, Abe O, Tsuchiya K, Okubo T, Tobe K, Masumoto T, et al
. Diffusion-weighted magnetic resonance imaging of dural sinus thrombosis. Neuroradiology 2002;44:481-8.
Guenther G, Arauz A. Cerebral venous thrombosis: A diagnostic and treatment update. Neurologia 2011;26:488-98.
de Bruijn SF, Stam J. Randomized, placebo-controlled trial of anticoagulant treatment with low-molecular-weight heparin for cerebral sinus thrombosis. Stroke 1999;30:484-8.
Coutinho JM, Stam J. How to treat cerebral venous and sinus thrombosis. J Thromb Haemost 2010;8:877-83.
Coutinho J, de Bruijn SF, Deveber G, Stam J. Anticoagulation for cerebral venous sinus thrombosis. Cochrane Database Syst Rev 2011;2011:CD002005.
Saposnik G, Barinagarrementeria F, Brown RD Jr., Bushnell CD, Cucchiara B, Cushman M, et al
. Diagnosis and management of cerebral venous thrombosis: A statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011;42:1158-92.
Qureshi AI. A classification scheme for assessing recanalization and collateral formation following cerebral venous thrombosis. J Vasc Interv Neurol 2010;3:1-2.
Barboza MA, Mejías C, Colin-Luna J, Quiroz-Compean A, Arauz A. Intracranial venous collaterals in cerebral venous thrombosis: Clinical and imaging impact. J Neurol Neurosurg Psychiatry 2015;86:1314-8.
Sheth SA, Trieu H, Liebeskind DS, Saver JL, Szeder V, Jahan R, et al
. Venous collateral drainage patterns predict clinical worsening in dural venous sinus thrombosis. J Neurointerv Surg 2018;10:171-5.
Cuadrado-Godia E. Early neurological deterioration, easy methods to detect it. Indian J Med Res 2015;141:266-8.
] [Full text]
Ruiz-Sandoval JL, Chiquete E, Bañuelos-Becerra LJ, Torres-Anguiano C, González-Padilla C, Arauz A, et al
. Cerebral venous thrombosis in a Mexican multicenter registry of acute cerebrovascular disease: The RENAMEVASC study. J Stroke Cerebrovasc Dis 2012;21:395-400.
Ferro JM, Canhão P, Stam J, Bousser MG, Barinagarrementeria F. Prognosis of cerebral vein and dural sinus thrombosis: Results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke 2004;35:664-70.
Dentali F, Gianni M, Crowther MA, Ageno W. Natural history of cerebral vein thrombosis: A systematic review. Blood 2006;108:1129-34.
Daif A, Awada A, al-Rajeh S, Abduljabbar M, al Tahan AR, Obeid T, et al
. Cerebral venous thrombosis in adults. A study of 40 cases from Saudi Arabia. Stroke 1995;26:1193-5.
Ferro JM, Canhão P, Bousser MG, Stam J, Barinagarrementeria F; ISCVT Investigators. Cerebral vein and dural sinus thrombosis in elderly patients. Stroke 2005;36:1927-32.
Khealani BA, Wasay M, Saadah M, Sultana E, Mustafa S, Khan FS, et al
. Cerebral venous thrombosis: A descriptive multicenter study of patients in Pakistan and Middle East. Stroke 2008;39:2707-11.
Koopman K, Uyttenboogaart M, Vroomen PC, van der Meer J, De Keyser J, Luijckx GJ. Long-term sequelae after cerebral venous thrombosis in functionally independent patients. J Stroke Cerebrovasc Dis 2009;18:198-202.
Canhão P, Ferro JM, Lindgren AG, Bousser MG, Stam J, Barinagarrementeria F, et al
. Causes and predictors of death in cerebral venous thrombosis. Stroke 2005;36:1720-5.
Yii IY, Mitchell PJ, Dowling RJ, Yan B. Imaging predictors of clinical deterioration in cerebral venous thrombosis. J Clin Neurosci 2012;19:1525-9.
Krajíčková D, Klzo L, Krajina A, Vyšata O, Herzig R, Vališ M. Cerebral venous sinus thrombosis: Clinical characteristics and factors influencing clinical outcome. Clin Appl Thromb Hemost 2016;22:665-72.
de Bruijn SF, de Haan RJ, Stam J. Clinical features and prognostic factors of cerebral venous sinus thrombosis in a prospective series of 59 patients. For The Cerebral Venous Sinus Thrombosis Study Group. J Neurol Neurosurg Psychiatry 2001;70:105-8.
Kenet G, Kirkham F, Niederstadt T, Heinecke A, Saunders D, Stoll M, et al
. Risk factors for recurrent venous thromboembolism in the European collaborative paediatric database on cerebral venous thrombosis: A multicentre cohort study. Lancet Neurol 2007;6:595-603.
[Table 1], [Table 2], [Table 3], [Table 4]