For professionals

Cerebral venous thrombosis

Cerebral Venous Thrombosis (CVT) is an uncommon cause of stroke with an incidence of 1.3-1.6 per 100 000 (1, 2). It affects mostly young and middle-aged adults (median age of 37 years), predominantly women (3).

This skewed sex ratio can be explained by female-specific risk factors such as such as oral contraceptive use, pregnancy, puerperium and hormone replacement therapy (3-6). Other risk factors for CVT include genetic trombophilia, inflammatory diseases, cancer, infection, and head trauma (3, 7, 8).

Thrombosis of cerebral veins and sinuses causes venous drainage obstruction and impeded absorption of the cerebrospinal fluid. While venous drainage obstruction causes increase in venous and capillary pressure, damages the blood-brain barrier and causes ischemia, the inability to drain the cerebrospinal fluid causes increased intracranial pressure (9). Therefore, CVT often manifests itself with signs and symptoms characteristic for intracranial hypertension such as severe headache, papilledema and decreased visual acuity (3, 4, 10). Other common manifestations include epileptic seizures, focal deficits, and coma (3, 11, 12). Depending on the location of the thrombosis, manifestations of CVT can be grossly grouped in four major clinical syndromes: isolated intracranial hypertension, focal syndrome, diffuse encephalopathy, and cavernous sinus syndrome (13). The diagnosis should be confirmed with computerized tomography-venography, magnetic resonance imaging with MR-venography or (rarely) catheter angiography (14).

The acute treatment of CVT consist of unfractionated heparin or low molecular weight heparin (LMWH). This recommendation also applies to patients who present with intracranial haemorrhage (15-17). In patients with threatening transtentorial herniation, decompressive hemicraniectomy can be performed as a life-saving procedure (18-20). Based on results of the TO-ACT trial, endovascular treatment should not be used routinely, but may be considered in special circumstances (21). In the post-acute phase, stable patients should generally be anticoagulated with oral anticoagulation to prevent recurrent thrombosis. The optimal duration of anticoagulation is subject of an ongoing study (EXCOA)(22). Based on results of RESPECT-CVT, direct oral anticoagulants may be considered as an alternative to vitamin K antagonists(23). The efficacy and safety of DOACs for the treatment of CVT are further being assessed in the DOAC-CVT study.  (7, 20).

Prognosis of CVT has improved over the last decades (24). Although around 5-10% of patients die in the acute phase, usually as a result of transtentorial herniation, more than 80% of patients recover without functional disabilities (3, 24, 25). Residual symptoms, however, are common in CVT survivors, and often negatively impact quality of life (26, 27).

For further information on CVT, we refer to the review articles listed below.

Sources:

1. Coutinho JM, Zuurbier SM, Aramideh M, Stam J. The incidence of cerebral venous thrombosis: a cross-sectional study. Stroke. 2012;43(12):3375-7.
2. Devasagayam S, Wyatt B, Leyden J, Kleinig T. Cerebral Venous Sinus Thrombosis Incidence Is Higher Than Previously Thought: A Retrospective Population-Based Study. Stroke. 2016;47(9):2180-2.
3. 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(3):664-70.
4. Stam J. Thrombosis of the cerebral veins and sinuses. N Engl J Med. 2005;352(17):1791-8.
5. Coutinho JM, Ferro JM, Canhão P, Barinagarrementeria F, Cantú C, Bousser MG, et al. Cerebral venous and sinus thrombosis in women. Stroke. 2009;40(7):2356-61.
6. Cantú C, Barinagarrementeria F. Cerebral venous thrombosis associated with pregnancy and puerperium. Review of 67 cases. Stroke. 1993;24(12):1880-4.
7. 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(4):1158-92.
8. Silvis SM, Middeldorp S, Zuurbier SM, Cannegieter SC, Coutinho JM. Risk Factors for Cerebral Venous Thrombosis. Semin Thromb Hemost. 2016;42(6):622-31.
9. Zuurbier SM, Coutinho JM. Cerebral Venous Thrombosis. Adv Exp Med Biol. 2017;906:183-93.
10. Biousse V, Ameri A, Bousser MG. Isolated intracranial hypertension as the only sign of cerebral venous thrombosis. Neurology. 1999;53(7):1537-42.
11. Ferro JM, Canhão P, Bousser MG, Stam J, Barinagarrementeria F. Early seizures in cerebral vein and dural sinus thrombosis: risk factors and role of antiepileptics. Stroke. 2008;39(4):1152-8.
12. Ferro JM, Canhão P, Stam J, Bousser MG, Barinagarrementeria F, Massaro A, et al. Delay in the diagnosis of cerebral vein and dural sinus thrombosis: influence on outcome. Stroke. 2009;40(9):3133-8.
13. Silvis SM, de Sousa DA, Ferro JM, Coutinho JM. Cerebral venous thrombosis. Nat Rev Neurol. 2017;13(9):555-65.
14. Einhäupl K, Stam J, Bousser MG, De Bruijn SF, Ferro JM, Martinelli I, et al. EFNS guideline on the treatment of cerebral venous and sinus thrombosis in adult patients. Eur J Neurol. 2010;17(10):1229-35.
15. Einhäupl KM, Villringer A, Meister W, Mehraein S, Garner C, Pellkofer M, et al. Heparin treatment in sinus venous thrombosis. Lancet. 1991;338(8767):597-600.
16. Stam J, de Bruijn S, deVeber G. Anticoagulation for cerebral sinus thrombosis. Stroke. 2003;34(4):1054-5.
17. Ferro JM, Bousser M-G, Canhão P, Coutinho JM, Crassard I, Dentali F, et al. European Stroke Organization guideline for the diagnosis and treatment of cerebral venous thrombosis – endorsed by the European Academy of Neurology. European Journal of Neurology. 2017;24(10):1203-13.
18. Coutinho JM, Majoie CB, Coert BA, Stam J. Decompressive hemicraniectomy in cerebral sinus thrombosis: consecutive case series and review of the literature. Stroke. 2009;40(6):2233-5.
19. Coutinho JM, Stam J. How to treat cerebral venous and sinus thrombosis. J Thromb Haemost. 2010;8(5):877-83.
20. Ferro JM, Bousser MG, Canhão P, Coutinho JM, Crassard I, Dentali F, et al. European Stroke Organization guideline for the diagnosis and treatment of cerebral venous thrombosis - endorsed by the European Academy of Neurology. Eur J Neurol. 2017;24(10):1203-13.
21. Coutinho JM, Zuurbier SM, Bousser MG, Ji X, Canhão P, Roos YB, et al. Effect of Endovascular Treatment With Medical Management vs Standard Care on Severe Cerebral Venous Thrombosis: The TO-ACT Randomized Clinical Trial. JAMA Neurol. 2020;77(8):966-73.
22. Miranda B, Aaron S, Arauz A, Barinagarrementeria F, Borhani-Haghighi A, Carvalho M, et al. The benefit of EXtending oral antiCOAgulation treatment (EXCOA) after acute cerebral vein thrombosis (CVT): EXCOA-CVT cluster randomized trial protocol. Int J Stroke. 2018;13(7):771-4.
23. Ferro JM, Coutinho JM, Dentali F, Kobayashi A, Alasheev A, Canhão P, et al. Safety and Efficacy of Dabigatran Etexilate vs Dose-Adjusted Warfarin in Patients With Cerebral Venous Thrombosis: A Randomized Clinical Trial. JAMA Neurol. 2019;76(12):1457-65.
24. Coutinho JM, Zuurbier SM, Stam J. Declining mortality in cerebral venous thrombosis: a systematic review. Stroke. 2014;45(5):1338-41.
25. Canhão P, Ferro JM, Lindgren AG, Bousser MG, Stam J, Barinagarrementeria F. Causes and predictors of death in cerebral venous thrombosis. Stroke. 2005;36(8):1720-5.
26. 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(3):198-202.
27. Hiltunen S, Putaala J, Haapaniemi E, Tatlisumak T. Long-term outcome after cerebral venous thrombosis: analysis of functional and vocational outcome, residual symptoms, and adverse events in 161 patients. J Neurol. 2016;263(3):477-84.