Dural Venous Sinuses

• Superior Sagittal Sinus (SSS): Runs along the superior margin of the falx cerebri from the crista galli to the confluence of sinuses (torcular Herophili) → receives drainage from superficial cortical veins and arachnoid granulations (site of CSF absorption)
• Inferior Sagittal Sinus (ISS): Runs along the inferior free edge of the falx cerebri → joins the vein of Galen to form the straight sinus
• Straight Sinus: Formed by the junction of the ISS and the vein of Galen → runs posteriorly along the junction of the falx and tentorium → drains into the confluence of sinuses
• Transverse Sinuses: Paired sinuses running laterally from the confluence along the attachment of the tentorium → the right transverse sinus is typically dominant (receives most SSS flow); the left receives most straight sinus flow
• Sigmoid Sinuses: S-shaped continuation of the transverse sinuses → course inferiorly along the posterior petrous bone → drain into the internal jugular veins at the jugular foramen
• Cavernous Sinuses: Paired sinuses flanking the sella turcica → contain the internal carotid artery and CN VI within the sinus; CN III, IV, V1, V2 course through the lateral wall → receive drainage from the superior and inferior ophthalmic veins, superficial middle cerebral vein, and sphenoparietal sinus → drain posteriorly into the superior and inferior petrosal sinuses
• Confluence of Sinuses (Torcular Herophili): Junction of SSS, straight sinus, and occipital sinus near the internal occipital protuberance → highly variable anatomy; true symmetric confluence occurs in only ~25% of individuals

Superficial Cortical Veins

• Superficial middle cerebral vein (vein of Sylvius): Runs along the Sylvian fissure → drains into the cavernous sinus or sphenoparietal sinus
• Vein of Trolard (superior anastomotic vein): Connects the superficial middle cerebral vein to the SSS → runs over the parietal convexity — largest of the anastomotic veins
• Vein of Labbé (inferior anastomotic vein): Connects the superficial middle cerebral vein to the transverse sinus → runs over the temporal lobe
• Superficial cortical veins drain the cortical surface and empty into the SSS, transverse sinus, or cavernous sinus — variable anatomy with extensive anastomoses explains why isolated cortical vein thrombosis may be clinically silent

Deep Venous System

• Internal cerebral veins (paired): Run in the roof of the third ventricle → drain the deep white matter, basal ganglia, and thalami
• Basal vein of Rosenthal (paired): Courses around the midbrain from anteromedial (near the anterior perforated substance) to posterosuperior → drains the medial temporal lobe, basal ganglia, and midbrain
• Vein of Galen (great cerebral vein): Formed by the union of the two internal cerebral veins (and receives the basal veins of Rosenthal) beneath the splenium of the corpus callosum → drains into the straight sinus
• Deep venous system thrombosis produces bilateral thalamic involvement — a critical imaging and clinical clue

Demographics

• Incidence: ~1.3–1.6 per 100,000 per year; likely underdiagnosed
• Age: Median age ~30–40 years — much younger than arterial stroke
• Sex: Female predominance (~3:1) due to hormonal risk factors (OCPs, pregnancy)
• Accounts for 0.5–1% of all strokes
• In neonates and children, CVT is a recognized cause of stroke — often related to dehydration, infection, or perinatal complications

Prothrombotic States

Acquired

• Oral contraceptive pills (OCPs): Most common identifiable risk factor in young women — risk increases 5–6-fold; synergistic with inherited thrombophilias (e.g., Factor V Leiden + OCPs → 30-fold increased risk)
• Pregnancy and postpartum period: Risk highest in the third trimester and first 6 weeks postpartum; ~12 per 100,000 deliveries
• Antiphospholipid syndrome: Lupus anticoagulant, anticardiolipin antibodies, anti-β2 glycoprotein I — screen all CVT patients
• Malignancy: Especially hematologic (polycythemia vera, essential thrombocythemia, leukemia) and solid tumors (brain tumors, adenocarcinomas)
• Inflammatory bowel disease (IBD): Ulcerative colitis and Crohn’s disease — both arterial and venous thrombosis risk
• Nephrotic syndrome: Loss of antithrombin III in urine → hypercoagulable state
• Heparin-induced thrombocytopenia (HIT): Paradoxical thrombosis with falling platelets
• Myeloproliferative neoplasms: JAK2 V617F mutation — consider even without overt hematologic abnormalities
• Paroxysmal nocturnal hemoglobinuria (PNH): Rare but associated with unusual site thrombosis including CVT

Inherited

• Factor V Leiden mutation: Most common inherited thrombophilia (~5% of Caucasians); activated protein C resistance
• Prothrombin gene mutation (G20210A): Second most common; elevated prothrombin levels
• Protein C deficiency: Autosomal dominant; homozygous → neonatal purpura fulminans
• Protein S deficiency: Cofactor for protein C
• Antithrombin III deficiency: Highest thrombotic risk among inherited thrombophilias
• Hyperhomocysteinemia: MTHFR mutations; treat with folate, B6, B12

Local & Infectious Causes

• Mastoiditis/otitis media: Classic cause of transverse/sigmoid sinus thrombosis — direct spread from infected mastoid air cells
• Sinusitis (especially sphenoid, ethmoid): Risk factor for cavernous sinus thrombosis
• Meningitis: Bacterial meningitis can cause secondary sinus thrombosis
• Facial/periorbital infections: “Danger triangle of the face” (nose/upper lip) → venous drainage via angular/ophthalmic veins into cavernous sinus
• Head trauma and neurosurgery: Direct injury to sinuses or compression
• Lumbar puncture: Rare but reported, especially with low-pressure states

Medications

• OCPs and hormone replacement therapy — estrogen-containing formulations carry highest risk
• L-asparaginase: Used in ALL chemotherapy → depletes antithrombin III, protein C, protein S
• Tamoxifen: Estrogen receptor modulator with prothrombotic effects
• Erythropoiesis-stimulating agents
• Immune checkpoint inhibitors: Emerging association

Two Mechanisms of Injury

Mechanism 1: Venous Outflow Obstruction

• Thrombosis of a dural sinus or cortical vein → increased venous pressure in upstream veins and capillaries
• Elevated capillary pressure → vasogenic edema (disruption of the blood-brain barrier)
• If venous pressure exceeds capillary wall integrity → diapedesis of red blood cells → petechial hemorrhage → frank hemorrhagic infarction
• Venous infarcts are fundamentally different from arterial infarcts:
  • More likely to be hemorrhagic (~40% present with hemorrhage)
  • Do NOT follow arterial territories — this is a critical imaging clue
  • May be bilateral or parasagittal (e.g., bilateral parasagittal hemorrhages in SSS thrombosis)
  • Surrounding vasogenic edema may be reversible with treatment (unlike cytotoxic edema in arterial stroke)

Mechanism 2: Impaired CSF Absorption

• CSF is absorbed through arachnoid granulations that protrude into the SSS and lateral lacunae
• SSS thrombosis → elevated venous pressure in the sinus → impaired pressure gradient for CSF absorption → raised intracranial pressure (ICP)
• This mechanism explains the “pseudotumor cerebri” presentation — headache, papilledema, visual obscurations, CN VI palsy — WITHOUT focal parenchymal lesions
• All patients presenting with “idiopathic intracranial hypertension” should have CVT excluded with MRV/CTV before the diagnosis of IIH is made

General Features

• CVT is the “great mimicker” — highly variable presentation; must maintain a high index of suspicion
• Onset is typically subacute (days to weeks) — unlike arterial stroke which is hyperacute (seconds to minutes)
• Acute onset in ~30%, subacute in ~50%, chronic (>30 days) in ~20% of cases

Most Common Symptoms

• Headache: ~90% — the most common symptom; often severe, progressive, and unlike the patient’s usual headaches; may worsen with Valsalva or recumbency
• Seizures: ~40% — much higher than arterial stroke (~5%); focal or generalized; may be the presenting symptom
• Focal neurological deficits: ~40–50% — hemiparesis, aphasia, hemianopia; depends on location of venous infarction
• Papilledema: ~30–40% — due to raised ICP; bilateral disc edema on fundoscopy
• Visual obscurations: Transient visual blurring lasting seconds, precipitated by position change or Valsalva
• Altered consciousness: ~15–20% — ranges from lethargy to coma; suggests extensive thrombosis or deep venous involvement
• CN VI palsy: False localizing sign of raised ICP — long intracranial course makes it vulnerable to stretch

Non-Contrast CT (NCCT)

• Dense triangle sign: Hyperdense (bright white) SSS on axial CT — represents acute thrombus within the sinus; seen in ~25% of cases
• Cord sign: Hyperdense cortical vein — linear hyperdensity along the cortical surface representing thrombosed cortical vein
• Hemorrhagic infarct NOT in an arterial territory: Parasagittal, bilateral, or temporal lobe hemorrhage in an atypical distribution
• NCCT is normal in up to 30% of CVT cases — a normal CT does NOT rule out CVT
• Sensitivity of NCCT alone is only ~30–40%

Contrast-Enhanced CT

• Empty delta sign: On contrast CT, the thrombus within the SSS does NOT enhance, but the surrounding dural walls enhance → creates a triangular filling defect (the “delta”) with enhancing rim — seen in ~25–30% of cases
• Best visualized on coronal images through the posterior SSS

CT Venography (CTV) & MR Venography (MRV)

• CTV and MRV are the definitive diagnostic studies — sensitivity and specificity >95%
• CTV: Fast, widely available; shows filling defects within sinuses; excellent for acute diagnosis
• MRV: Can use time-of-flight (TOF) or contrast-enhanced techniques; absence of normal flow signal within a sinus = thrombosis
• Pitfalls of TOF MRV: Slow flow, flow gaps, and arachnoid granulations can mimic thrombosis → correlate with MRI parenchymal sequences
• Contrast-enhanced MRV is more reliable than TOF for equivocal cases

MRI Brain

• Shows both the thrombus itself and parenchymal consequences (edema, infarction, hemorrhage)
• MRI signal of thrombus varies with age:
  • Acute (<5 days): Thrombus is isointense on T1, hypointense on T2 (deoxyhemoglobin) — may be difficult to identify
  • Subacute (5–15 days): Thrombus becomes hyperintense on T1 (methemoglobin) — most easily recognized
  • Chronic (>15 days): Variable signal; thrombus becomes isointense on T1 and variable on T2 as it organizes
• Loss of normal flow void within the sinus on T2-weighted images
• SWI (Susceptibility-Weighted Imaging): Very sensitive for thrombus detection — shows hypointense thrombus due to deoxyhemoglobin/hemosiderin
• Parenchymal changes: Vasogenic edema (T2/FLAIR hyperintensity), hemorrhagic infarction, subcortical white matter edema

D-dimer

• Sensitivity ~97% (using age-adjusted cutoffs); specificity is low (~50–60%)
• Negative D-dimer (<500 ng/mL) makes CVT very unlikely — useful for ruling out CVT in low-probability cases
• May be falsely negative in: isolated headache without parenchymal lesion, chronic/subacute thrombosis, isolated cortical vein thrombosis, small thrombus
• Should NOT be used as a standalone diagnostic test — imaging confirmation always required

Anticoagulation

• Heparin anticoagulation is the cornerstone of CVT treatment — both UFH and LMWH are effective
• Critical board point: Anticoagulate EVEN with hemorrhagic infarction. The hemorrhage is a consequence of venous congestion, not the cause of the problem. Restoring venous outflow (by preventing thrombus propagation) reduces further hemorrhage
• ISCVT (International Study on Cerebral Vein and Dural Sinus Thrombosis, Ferro et al., 2004):
  • Largest prospective observational cohort (n = 624)
  • Established safety profile of heparin anticoagulation in CVT, including cases with hemorrhagic infarction
  • Supported use of LMWH or UFH as initial treatment
• LMWH (e.g., enoxaparin) is generally preferred over UFH for:
  • More predictable pharmacokinetics
  • Lower risk of HIT
  • Ease of dosing (weight-based, subcutaneous)
• UFH preferred when: patient may need surgery (e.g., decompressive craniectomy), severe renal insufficiency, or need for rapid reversibility

Duration of Anticoagulation

Transition to Oral Anticoagulation

• Warfarin: Traditional agent; target INR 2.0–3.0; well-established in CVT
• DOACs (Direct Oral Anticoagulants): Emerging evidence supports their use
  • RE-SPECT CVT trial (Ferro et al., Lancet Haematol, 2019): Randomized, open-label trial of dabigatran 150 mg BID vs. warfarin after acute CVT treatment; dabigatran was non-inferior with no recurrent VTE in either arm; numerically fewer major bleeding events with dabigatran
  • EINSTEIN-Jr CVT (2022): Rivaroxaban in pediatric CVT — supportive evidence
  • DOACs are increasingly used in practice; AHA/ASA 2024 guidelines consider DOACs a reasonable alternative to warfarin
  • Limitations: DOACs should be avoided in antiphospholipid syndrome (TRAPS trial showed worse outcomes with rivaroxaban vs. warfarin in APS)

Endovascular Therapy

• Includes catheter-directed thrombolysis (local tPA infusion) and mechanical thrombectomy
• TO-ACT trial (Coutinho et al., JAMA Neurol, 2020):
  • Randomized trial of endovascular treatment + anticoagulation vs. anticoagulation alone in severe CVT
  • Showed no benefit of routine endovascular treatment
  • Trial was stopped early for futility
• Current role: Reserved for patients with clinical deterioration despite adequate anticoagulation — not for routine use
• No Class I evidence supporting endovascular therapy for CVT

ICP Management

• Acetazolamide: Reduces CSF production; used for headache and papilledema — same approach as IIH
• Serial lumbar punctures: For refractory elevated ICP with threatened vision
• VP shunt or optic nerve sheath fenestration: For refractory cases with progressive visual loss
• Avoid corticosteroids: No proven benefit in CVT and may worsen prothrombotic state; exception: underlying inflammatory or infectious condition
• Elevate head of bed to 30°

Decompressive Craniectomy

• Consider in patients with malignant edema, large hemorrhagic infarction, or transtentorial herniation despite maximal medical therapy
• Unlike arterial stroke, outcomes after decompressive surgery for CVT can be surprisingly good — because venous infarcts have greater potential for reversibility
• No RCT data; evidence from case series and retrospective studies

Seizure Management

• Treat acute seizures with standard antiseizure medications (levetiracetam, benzodiazepines for status)
• Primary prophylaxis (no prior seizures): Not routinely recommended; consider if supratentorial lesion with cortical involvement (higher seizure risk)
• Secondary prophylaxis (after acute seizure): Reasonable to continue antiseizure medication for the acute phase
• Duration of antiseizure therapy: typically 3–12 months; guided by EEG and clinical course

CVT in Pregnancy & Postpartum

• LMWH is the treatment of choice for CVT during pregnancy — does NOT cross the placenta
• Warfarin is contraindicated in the first trimester (teratogenic — warfarin embryopathy: nasal hypoplasia, stippled epiphyses, chondrodysplasia punctata)
• Warfarin is also avoided near term due to fetal hemorrhage risk
• DOACs are contraindicated in pregnancy (no safety data, presumed to cross placenta)
• LMWH may be transitioned to warfarin postpartum — both warfarin and LMWH are safe during breastfeeding
• Future pregnancies: LMWH prophylaxis throughout pregnancy and 6 weeks postpartum is recommended for women with prior CVT

Cavernous Sinus Thrombosis (CST)

Infectious (Septic) CST

• Most commonly from sphenoid sinusitis, ethmoid sinusitis, or dental/facial infections
• Organisms: Staphylococcus aureus (most common), Streptococcus, anaerobes, Mucor/Aspergillus (in immunocompromised/diabetic patients)
• Presents with: fever, orbital pain, proptosis, chemosis, ophthalmoplegia, rapidly progressive
• Bilateral involvement is common due to intercavernous connections
• Treatment: IV antibiotics (broad-spectrum, including anti-staphylococcal coverage) + anticoagulation (controversial but generally recommended) + source control (e.g., sinus drainage)
• Consider antifungal coverage (amphotericin B) in diabetic or immunocompromised patients — mucormycosis can rapidly invade the cavernous sinus

Non-Infectious (Aseptic) CST

• Associated with prothrombotic states, malignancy, or inflammatory conditions
• Treatment: anticoagulation as with other CVT locations

Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT)

• Rare syndrome associated with adenoviral vector COVID-19 vaccines (AstraZeneca/ChAdOx1, Johnson & Johnson/Ad26.COV2.S)
• Mechanism: Antibodies against platelet factor 4 (PF4) → massive platelet activation and consumption → thrombosis + thrombocytopenia (similar to HIT but WITHOUT prior heparin exposure)
• Onset: typically 5–30 days after vaccination
• Diagnosis:
  • Thrombocytopenia (platelets often <150,000, frequently <50,000)
  • Markedly elevated D-dimer (often >4× upper limit of normal)
  • Positive anti-PF4 antibodies (ELISA assay — same test used for HIT)
  • Low fibrinogen (consumptive coagulopathy)
• Treatment:
  • AVOID HEPARIN (anti-PF4 antibodies may be potentiated by heparin, similar to HIT)
  • Use non-heparin anticoagulants: argatroban, bivalirudin, fondaparinux, or DOACs
  • IV immunoglobulin (IVIG) 1 g/kg × 2 days — blocks Fc-mediated platelet activation
  • Avoid platelet transfusions (may worsen thrombosis)
  • Consider plasma exchange for refractory cases

Overall Outcomes

• Mortality: ~5–10% in recent series (historically higher before modern anticoagulation)
• Good functional outcome (mRS 0–2): ~80% — significantly better than arterial stroke
• Complete recovery is possible even after extensive thrombosis — venous infarcts are more reversible than arterial infarcts
• Recanalization: Occurs in ~85% by 12 months; most recanalization occurs within the first 3–6 months

Poor Prognostic Factors

• Deep venous system involvement (internal cerebral veins, vein of Galen, straight sinus) — strongest predictor of poor outcome
• Coma/altered consciousness at presentation
• Hemorrhagic infarction (especially large)
• Underlying malignancy
• CNS infection as the cause
• Male sex, older age (>37)
• Posterior fossa involvement (cerebellar vein thrombosis)
• Mental status changes

Recurrence & Long-Term Complications

• CVT recurrence rate: ~2–5% per year
• Recurrence more likely with persistent prothrombotic risk factors or inadequate anticoagulation duration
• Other VTE events (DVT, PE): ~4–7% per year — higher than CVT recurrence alone
• Chronic headache: Reported in up to 50–75% of CVT survivors; may persist for months to years
• Post-CVT seizures: ~10–15% develop epilepsy; risk highest with cortical involvement and presenting seizures
• Visual impairment: Persistent papilledema or optic atrophy from prolonged raised ICP
• Dural arteriovenous fistula: Rare late complication; results from neovascularization during thrombus organization