Cerebral venous thrombosis G08.-

In cerebral sinus/venous thrombosis, thrombotic occlusion of cerebral veins and their draining large blood vessels (sinuses) occurs. The result is venous outflow disorders with potential stasis bleeding and consecutive neurological symptoms.

Basically, a distinction is made between a

• septic and
• aseptic (bland sinus vein thrombosis)

cerebral sinus/vein thrombosis.

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Further classification and terminology according to location and extent of thrombosis:

• Sinus thrombosis: Isolated occlusion of one or more sinuses (sinus durae matris).
• Cerebral vein thrombosis: isolated occlusion of one or more cerebral veins
• Thrombosis of the superficial cerebral veins (also called "bridging vein thrombosis")
• Thrombosis of the internal cerebral veins
• Thrombosis of cerebellar veins (extremely rare)
• Sinus vein thrombosis: combined thrombosis of veins and sinus

Incidence for aseptic sinus vein thrombosis: 3-5/1,000,000 population per year ; w > m = 3:1

Incidence for septic sinus vein thrombosis: Proportion of all sinus vein thromboses: Approximately 10%.

Etiopathogenesis (according to DGN guideline 2018)

idiopathic (20-35% of cases):

oral contraceptives (sole trigger in 10% of cases), postpartum, rarely in the last trimester of pregnancy.

Coagulation disorders:

• heterozygous or homozygous factor V Leiden mutation (10-25% of cases)
• heterozygous or homozygous prothrombin mutation G20210A
• congenital antithrombin deficiency
• congenital protein C or protein S deficiency
• persistently elevated factor VIII
• Antiphospholipid antibodies (including lupus anticoagulants, anticardiolipin IgG, anticardiolipin IgM, anti-β2-glycoprotein I IgG, anti-β2-glycoprotein I IgM, only clinically relevant, if repeatedly positive, at least 3 months after initial detection - DGN guideline 2018)
• Hyperhomocysteinemia
• Very rarely dysfibrinogenaemia, disseminated intravascular coagulation, heparin-induced thrombocytopenia.
• Note: In children and adolescents with venous thrombosis, including cerebral sinus and venous thrombosis, the association between initial manifestation of thrombosis or thromboembolic recurrence and congenital thrombophilic risk factors is more pronounced than in adults (Kenet et al., 2010; Young et al., 2008).

Malignancies: carcinoma, lymphoma, carcinoid, leukemia.

Hematologic disorders: polycythemia, sickle cell anemia, paroxysmal nocturnal hemoglobinuria, hypochromic or immune hemolytic anemia, thrombocythemia.

Collagenoses: lupus erythematosus, Sjögren's syndrome (Vidailhet M et al. 1990)

Vasculitides: Behçet's disease, Wegener's granulomatosis, sarcoidosis.

Very rare:

• intracranial hypotension (cerebrospinal fluid hypotension syndrome)
• lumbar CSF puncture: CVST may occur with a time delay after CSF puncture. In these cases, unlike CSF hypotension syndrome, the headache increases when the patient is lying down.
• local: traumatic brain injury, neurosurgical operations, mechanical obstruction of outflow by tumours.
• disorders involving venous stasis: central venous catheters, strangulation, dural arteriovenous malformation
• drug toxicity: androgens, chemotherapeutics, corticosteroids, erythropoietin, vitamin A overdose, asparaginase derived from E. coli in combination with prednisone, drugs
• metabolic diseases: diabetes mellitus, thyrotoxicosis, uremia, nephrotic syndrome
• gastrointestinal tract: cirrhosis of the liver, Crohn's disease, ulcerative colitis
• cardiac diseases: heart failure, cardiomyopathy

Locally infectious:

• Midface infections
• mastoiditis, otitis media, tonsillitis, sinusitis
• Stomatitis, dental abscesses
• Brain abscess, empyema, meningitis

Generalized infectious:

• bacterial: septicaemia, endocarditis, typhoid fever, tuberculosis
• viral: measles, hepatitis, encephalitis (HSV, HIV), cytomegalovirus
• parasitic: malaria, trichinosis
• fungal infections: aspergillosis

Possible at any age, especially in the 3rd and 4th decade of life; women are more often affected than men.

Leading symptoms are prolonged or recurrent headaches, often accompanied by neurological precipitates such as paralysis or sensory disturbances like numbness, nausea and vomiting, congestive papules, visual disturbances, qualitative and quantitative disturbances of consciousness.

Diagnosis (according to guidelines): If cerebral sinus/venous thrombosis (CVST) is suspected, imaging diagnostics must be performed immediately.

Computed tomography (CT) and magnetic resonance imaging (MRI), each with venous angiography, are considered equivalent in the diagnosis of sinus thrombosis (Wetzel SG et al 1999). In cortical venous thrombosis, MRI is superior to CT. Due to the lack of radiation exposure, MRI should preferably be used in younger patients and during pregnancy (see also Selim M et al. 2002).

Screening for coagulation disorders to prevent recurrence of venous thrombosis, reduce mortality, and improve functional outcome is recommended (but not generally recommended). D-dimers: The diagnostic value of testing D-dimers is variably assessed. Its predictive reliability depends on the patient population being studied and is generally insufficient to confidently diagnose or, more importantly, confidently rule out CVST without cerebral imaging (Tanislav et al. 2011). For patients with isolated headache, D-dimers have been shown to have a high negative predictive value, i.e., CVST can be excluded with 99.8% certainty when D-dimers are negative. On the other hand, if the D-dimer test is positive, the specificity in this patient population is particularly low at 33% (Alons et al. 2015).

Therapy (according to DGN guideline 2018): Adult patients with CVST should be treated with heparin at a therapeutic dose in the acute phase, whether or not intracranial hemorrhage is already present.

Oral anticoagulation: Oral anticoagulation with a vitamin K antagonist may be given for 3 to 12 months to prevent recurrent CVST and extracerebral venous thrombosis. Currently, there is insufficient data to recommend the use of direct oral anticoagulants (factor Xa inhibitors or thrombin inhibitors) for the treatment of CVST patients, especially in the acute phase.

Thrombolytic therapy: is not recommended in patients with acute CVST who are at low risk for poor clinical outcome.

Surgicaldecompression: Despite the overall paucity of evidence, surgical decompression is recommended in patients with CVST, lesions of the parenchyma (congestive edema and/or hemorrhage), and impending entrapment to prevent death (Raza E et al 2014).

Steroids should not be given due to their prothrombotic effects and lack of efficacy. Exceptions are patients with CVST due to auto-immune inflammatory diseases such as Behçet's disease or systemic lupus erythematosus.

Antiepileptic treatment: Antiepileptic drug treatment should be given to patients with CVST only after an epileptic seizure has occurred to prevent recurrence of epileptic seizures.

Hormonal contraceptives: Women with previous CVST should avoid oral use of combined hormonal contraceptives.

Pregnancy: Previous CVST is unlikely to be a contraindication to repeat pregnancy. Women with previous CVST without contraindications to LMWH use should receive LMWH prophylaxis in a new pregnancy/puerperium.

Note: There is no definite association between the presence of hereditary thrombophilia and the incidence of recurrence in CVST. Results from observational studies and case-control studies showed conflicting findings regarding the severe but rare thrombophilic coagulation disorders(antithrombin deficiency, protein C or prothrombin S deficiency). Detection of one of the common, weak thrombophilias(heterozygous factor V Leiden mutation or prothrombin G20210A mutation) was not associated with the occurrence of a second CVST or venous thromboembolism at another site (Ferro et al. 2017). As with the much more common leg vein thrombosis or pulmonary embolism, there are no prospective randomized trials that investigated the effect of systematic thrombophilia screening on recurrence frequency or even mortality after CVST. In contrast, individual studies have demonstrated a worse long-term functional outcome with evidence of hereditary thrombophilia (Lauw et al. 2013; Dentali et al. 2012).

Patients with sinus vein thrombosis often have a good prognosis; however, severe courses with high lethality also occur.

Recently, individual cases of sinus vein thrombosis as well as disseminated intravascular coagulopathy (DIC) were observed in the course of the Covid vaccination campaign conducted in 2020/2021 (the vector vaccine from Astra Seneca appears to be causally related). The etiopathological links are currently unclear - EMA communication of 18/3/2021).

Patients with cerebral venous or cerebral sinus thrombosis must be treated as inpatients, e.g. in a stroke unit. The mainstay of therapy is the inhibition of blood clotting and, if the cause is inflammatory, the administration of antibiotics. Provided that no complications occur, the prospects of recovery are good.

1. Alons IM et al. (2015) D-dimer for the exclusion of cerebral venous thrombosis: a meta-analysis of low risk patients with isolated headache. BMC Neurol 15:118.
2. AWMF guideline register 003/001. prophylaxis of venous thromboembolism (VTE). As of: 2015-10-15, valid until 2020-10-14. http://www.awmf.org/leitlinien/detail/ll/003-001.html.
3. AWMF guideline register 065/002. diagnosis and therapy of venous thrombosis and pulmonary embolism. Status: 10.10.2015, valid until 09.10.2020. www.awmf.org/leitlinien/detail/ll/065-002.html
4. Dentali Fet al. (2012) D-dimer testing in the diagnosis of cerebral vein thrombosis: a systematic review and a meta-analysis of the literature. J Thromb Haemost 10:582-589.
5. German Society of Neurology (AWMF guideline) Cerebral venous and sinus thrombosis 2018 LL 030 098 Cerebral venous and sinus thrombosis 2018 - Deutsche Gesellschaft für Neurologie e. V.. (dgn.org)
6. Ferro JM et al. (2017) European Stroke Organization guideline for the diagnosis and treatment of cerebral venous thrombosis - endorsed by the European Academy of Neurology. Eur J Neurol 24:1203-1213.
7. Kenet G et al. (2010) Impact of thrombophilia on risk of arterial ischemic stroke or cerebral sinovenous thrombosis in neonates and children: a systematic review and meta-analysis of observational studies. Circulation121:1838-1847.
8. Lauw MN et al (2013) Cerebral venous thrombosis and thrombophilia: a systematic review and meta-analysis. Semin Thromb Hemost 39:913-927.
9. Raza E et al. (2014) Decompressive surgery for malignant cerebral venous sinus thrombosis: a retrospective case series from Pakistan and comparative literature review. J Stroke Cerebrovasc Dis 23:e13-22.
10. Selim M et al.(2002) Diagnosis of cerebral venous thrombosis with echo-planar T2*-weighted magnetic resonance imaging. Arch Neurol 59:1021-1026.
11. Tanislav C et al. (2011) Cerebral vein thrombosis: clinical manifestation and diagnosis. BMC Neurol 11:69.
12. Vidailhet M et al (1990) Cerebral venous thrombosis in systemic lupus erythematosus. Stroke 21:1226-1231.
13. Wetzel SG et al (1999) Cerebral veins: comparative study of CT venography with intraarterial digital subtraction angiography. AJNR Am J Neuroradiol 20:249-255.
14. Young G et al. (2008) Impact of inherited thrombophilia on venous thromboembolism in children: a systematic review and meta-analysis of observational studies. Circulation 118:1373-1382.