Cerebral venous sinus thrombosis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kalsang Dolma, M.B.B.S.[2]

Overview

Pharmacologic therapy is indicated in cerebral venous sinus thrombosis. Medical therapy includes anticoagulants, acetazolamide, and anticonvulsants. Empiric antimicrobial therapy is required and generally includes the combination of Metronidazole, a penicillinase-resistant penicillin, and a third generation cephalosporin.

Medical Therapy

Pharmacotherapy

Anticoagulants

Anticoagulants are the first line treatment of cerebral venous thrombosis with or without intracranial hemorrhage. Intravenous unfractionated heparin or subcutaneous low molecular weight heparin are administered initially followed by oral anticoagulant Warfarin. Usually patients with CVT get treated with anticoagulants for 3 months but patients with prothrombotic risk factors treatment duration can be 6-12 months.

Thrombolysis

Removal of the blood clot with "clot buster" medication has been described, either systemically by injection into a vein or directly into the clot during angiography. The 2006 EFNS guideline recommends that thrombolysis is only used in patients who deteriorate despite adequate treatment, and other causes of deterioration have been eliminated. It is unclear which drug and which mode of administration is the most effective. Bleeding into the brain and in other sites of the body is a major concern in the use of thrombolysis.

Acetazolamide

It may be used to decrease raised intracranial pressure.

Anticonvulsants

It may be used prophylactically (i.e. to prevent seizures); these are focal neurological problems (e.g. inability to move a limb) and/or focal changes of the brain tissue on CT or MRI scan.

Antimicrobial Regimen

• Cavernous sinus thrombosis is considered a medical emergency.
• Duration of therapy is usually a total of 3-4 weeks. More prolonged administration of antimicrobial therapy (total of 6-8 weeks) may be indicated among patients who are suspected to have developed complications (e.g. suppurative intracranial disease).
• ENT surgery must be consulted to evaluate the need of surgical drainage (e.g. sphenoidotomy if sphenoid sinus infection is the primary cause).
• Septic thrombosis of cavernous or dural venous sinus

• 1. Empiric antimicrobial therapy

• Preferred regimen: (Vancomycin 30–45 mg/kg IV q8–12h for 3-4 weeks OR Nafcillin 2 g IV q4h for 3-4 weeks OR Oxacillin 2 g IV q4h for 3-4 weeks) AND (Ceftriaxone 2 g IV q12h for 3-4 weeks OR Cefotaxime 8–12 g/day IV q4–6h for 3-4 weeks) AND Metronidazole 7.5 mg/kg IV q6h 3-4 weeks

Note (1): If risk of MRSA is high, Vancomycin should be administered instead of either nafcillin or oxacillin

Note (2): The optimal duration of therapy remains unclear

• 2. Specific anatomic considerations

• 2.1 Cavernous sinus

• Preferred regimen: Vancomycin 30–45 mg/kg IV q8–12h for 3-4 weeks AND (Ceftriaxone 2 g IV q12h for 3-4 weeks OR Cefotaxime 8–12 g/day IV q4–6h for 3-4 weeks) AND Metronidazole 7.5 mg/kg IV q6h for 3-4 weeks

Note: Daptomycin 8–12 mg/kg IV q24h OR Linezolid 600 mg IV q12h could be considered for patients unable to tolerate vancomycin

• 2.2 Lateral sinus

• Preferred regimen: Cefepime 2 g IV q8h for 3-4 weeks AND Metronidazole 500 mg IV q8h for 3-4 weeks AND Vancomycin 15-20 IV mg/kg for 3-4 weeks
• Alternative regimen: Meropenem 1-2 g IV q8h 3-4 weeks AND Linezolid 600 mg IV q12h 3-4 weeks

• 2.3 Superior sagittal sinus

• Preferred regimen: Ceftriaxone 2 g IV q12h for 3-4 weeks AND Vancomycin 15–20 mg/kg for 3-4 weeks AND Dexamethasone 10 mg IV q6h continued until symptomatic improvement and tailed gradually over several weeks
• Alternative regimen: Meropenem 1–2 g IV q8h for 3-4 weeks AND Vancomycin 15–20 mg/kg for 3-4 weeks AND Dexamethasone 10 mg IV q6h continued until symptomatic improvement and tailed gradually over several weeks

• 3. Pathogen-directed antimicrobial therapy

• Staphylococcus aureus, methicillin-resistant (MRSA)

• Preferred regimen: Vancomycin 15–20 mg/kg/dose IV q8–12h for 4–6 weeks
• Alternative regimen: Linezolid 600 mg PO/IV q12h for 4–6 weeks OR TMP-SMX 5 mg/kg/dose PO/IV q8–12h for 4–6 weeks
• Pediatric dose: Vancomycin 15 mg/kg/dose IV q6h 4–6 weeks OR Linezolid 10 mg/kg/dose PO/IV q8h 4–6 weeks
• Note (1): Surgical evaluation for incision and drainage of contiguous sites of infection or abscess is recommended whenever possible
• Note (2): Consider the addition of Rifampin 600 mg qd or 300–450 mg bid to vancomycin