Cerebral Venous Thrombosis

Cerebral Venous Thrombosis, Cerebral Venous Sinus Thrombosis, Thrombosis of Cerebral Vein, Thrombophlebitis of Cerebral Vein, Cerebral Vein Thrombophlebitis, Cerebral Infarction due to Cerebral Venous Thrombosis, Lateral Sinus Thrombosis, Transverse Sinus Thrombosis, Superior Sagittal Sinus Thrombosis, Sagittal Sinus Thrombosis ( C0338575), Sigmoid Sinus Thrombosis, Deep Venous Cerebral Thrombosis, Great Cerebral Vein Thrombosis, Cortical Vein Thrombosis, Superficial Cerebral Vein Thrombosis, Cerebral Sinus Thrombosis, CVST

See Also

Epidemiology

Accounts for 0.5 to 1% of all Cerebrovascular Accidents
Female gender in two thirds of cases
Younger patients (mean age 33 years old)

Pathophysiology

See Cerebral Sinus
Images
As with other Venous Thromboembolism, virchow's triad applies to pathogenesis (stasis, vessel wall, Coagulopathy)
Venous obstruction causes increased venous pressure and decreased capillary perfusion
1. Initial compensation with venous dilation including collateral veins
2. Blood brain barrier is disrupted
  1. Results in vasogenic edema and possible cerebral Hemorrhage
3. Cerebrospinal fluid absorption may also be blocked, increasing Intracranial Pressure
  1. Results in decreased Cerebral Perfusion Pressure, cerebral ischemia and cytotoxic edema
  2. Hydrocephalus may develop, with increasing Intracranial Pressure and risk of Cerebral Herniation

Risk Factors

Precautions
1. More than 85% of Cerebral Venous Thrombosis patients have at least one risk factor for thrombosis
Hormonal
1. Oral Contraceptives
2. Tamoxifen
3. Hormone Replacement Therapy
4. Pregnancy or Postpartum State (up to 6 weeks after delivery)
  1. Most common cause in developed countries
  2. Accounted for >10% of cases in one study
    1. Bajko (2021) Brain Sci 11(3): 327 [PubMed]
Medications
1. Asparaginase
2. Corticosteroids
3. Methotrexate
4. Cytotoxic drugs
Hypercoagulable Conditions (Thrombophilia, present in 30% of CVT patients)
1. See Thrombophilia
2. Malignancy (esp. Hematologic Malignancy, myeloproliferative disorder)
3. Vasculitis or Inflammation (e.g. Systemic Lupus Erythematosus, Inflammatory Bowel Disease, Behcet's Disease)
4. Antiphospholipid Antibody Syndrome
5. Hyperhomocysteinaemia (MTHFR gene mutation)
6. Factor V Leiden Mutation
7. Antithrombin Deficiency
8. Protein C Deficiency
9. Protein S Deficiency
10. G20210A Mutation
Hematologic Conditions
Head and Neck Disorders
1. Head and Neck Infections (e.g. paramenigeal infections of the ear, sinus or oropharynx)
  1. Most common cause in developing countries
2. Central Nervous System Infections
3. Recent neurosurgery
4. Closed Head Injury
5. Dural AV Fistula or Arteriovenous Malformation
Miscellaneous Conditions
1. Dehydration
2. Hyperthyroidism

Precautions

Early diagnosis is key to good prognosis
Frequently missed diagnosis
1. Mimics other acute neurologic conditions
2. Requires specific testing in most cases (venogram)
Consider in atypical Cerebrovascular Accident (CVA)
1. Young patients
2. Pregnancy or recent postpartum
3. Infarcts that cross typical arterial distributions
4. Multiple infarcts
5. Associated atypical features (Altered Mental Status, Seizures, Headache)

Findings
General

Findings are specific to venous sinus involved
Headache (90% of cases, and only symptom in 25% of cases)
1. New or different Headache
2. Acute to insidious onset progressive over hours to days (contrast with Thunderclap Headache in SAH)
3. Provoked when Increased Intracranial Pressure (e.g. valsalva, coughing)
Increased Intracranial Pressure
1. Papilledema
2. Visual changes
3. Nausea or Vomiting
Focal Findings
1. Motor deficits
2. Seizure (up to 30% of cases present with Seizure)
  1. More common in postpartum patients
Encephalopathy (esp. deep sinus involvement)
1. Altered Mental Status (esp. in elderly)
Intracranial Hemorrhage
1. Present in up to 40% of CVT patients (secondary to Increased Intracranial Pressure)
2. Bilateral parenchymal hemorrhagic lesions or Hemorrhages across multiple arterial territories

Findings
Transverse Sinus Thrombosis

Accounts for 44 to 73% of cases
Isolated, noninfectious unilateral thrombosis
1. Symptoms may be mild (e.g. Headache) if no infarction
2. Seizures
3. Contralateral Hemiparesis, hyperreflexia, or spasticity (pyramidal symptoms) may be present
Left Transverse Sinus (with venous infarction, occluded vein of Labbe)
1. Aphasia
Contiguous Sinus extension (e.g. Superior Sagittal Sinus)
1. Increased Intracranial Pressure (Intracranial Hypertension)
2. Altered Level of Consciousness
3. Cranial Nerve Palsy (CN 9-12)
Cerebral Vein Extension
1. Headache
2. Vomiting
3. Ataxia
4. Limb Incoordination

Findings
Superior Sagittal Sinus Thrombosis

Accounts for 39-62% of cases
Increased Intracranial Pressure (Intracranial Hypertension)
1. Isolated in many cases
Focal venous infarction related symptoms
1. Headache
2. Blurred Vision, Vision Loss or Hemianopsia (Visual Field Deficit)
3. Nausea or Vomiting
4. Cranial Nerve Palsy
5. Aphasia
6. Hemiparesis or hemi-sensory loss
7. Seizures

Findings
Sigmoid Sinus Thrombosis

Accounts for 40-47% of cases
Mastoid region pain
Cranial Nerve Deficit (CBN 6-8)

Findings
Deep Venous Cerebral Thrombosis (e.g. Great Cerebral Vein of Galen)

Accounts for 10-11% of cases
Altered Mental Status (encephalopathy to coma)
Motor deficits
1. Fluctuating or alternating paresis (or bilateral)

Findings
Cortical Vein Thrombosis (Superficial Cerebral Vein Thrombosis)

Accounts for 3-17% of cases
Thrombosis involving superficial veins (superficial middle and anastomotic cerebral veins)
Seizures
Focal neurologic deficits depending on distribution of thrombosis

Findings
Cavernous Sinus Thrombosis

See Cavernous Sinus Thrombosis
Accounts for 1-2% of cases
Headache
Eye Pain
Chemosis
Proptosis
Cranial Nerve Palsy (CN 3, 4, and 6, as well as opthalmic branch CN 5)
Fever (if septic Thrombophlebitis)

Labs

See Cerebrovascular Accident
Bedside Serum Glucose
Complete Blood Count
Basic Metabolic Panel
Coagulation studies (INR, aPTT)
Erythrocyte Sedimentation Rate or C-Reactive Protein
Serum Troponin
Thrombophilia labs
1. Obtain before Anticoagulation initiated (consult neurology, hematology)
Other testing
1. Evaluate for other triggering events (systemic or CNS Infection)
2. D-Dimer does not exclude Cerebral Venous Sinus Thrombosis

Diagnostics

Electrocardiogram
Optic Nerve Sheath Diameter
1. Increased diameter is a marker of Increased Intracranial Pressure (Papilledema)
Lumbar Puncture
1. Consider in suspected Meningitis or Encephalitis

Differential Diagnosis

Imaging

Non-Contrast Head CT
1. Low Test Sensitivity for Cerebral Venous Thrombosis (~33%)
2. Findings consistent with Cerebral Venous Thrombosis
  1. Delta Sign
    1. Posterior Superior Sagittal Sinus hyperdensity
  2. Venous Cerebral Infarction
    1. Infarct spans more than one arterial perfusion regions
  3. Diffuse cerebral edema
  4. Hydrocephalus
  5. Subarachnoid Hemorrhage (secondary)
CT Venogram (with CT Head)
1. Gold standard study for venous cerebral thrombosis
2. CTV identifies filling defects
3. Similar efficacy to MRV except in Altered Level of Consciousness or encephalopathy (parenchymal lesions)
Magnetic Resonance Venogram (MRI/MRV)
1. As with CT Venogram, gold standard for Cerebral Venous Thrombosis diagnosis
2. MRV is preferred over CT venogram for patients with Altered Level of Consciousness or encephalopathy
  1. Suggests possible deep cerebral vein thrombosis (better visualized on MRV)
3. General Findings
  1. DWI hyperintense
  2. Cerebral venous wall enhancement
  3. Thrombosed sinuses with decreased or absent flow
4. Findings vary by timing from onset
  1. Week 1: T1W/T2W isointense to hypointense
  2. Week 2: T1W/T2W hyperintense

Management

Consult Neurosurgery and Stroke Neurology
Consult hematology in suspected Thrombophilia
Initiate Low Molecular Heparin (e.g. Lovenox) which is preferred over Unfractionated Heparin
1. Use Unfractionated Heparin in Unstable Patients who may require invasive procedure
2. Initiate Anticoagulation with Warfarin with INR target 2-3 for 3-12 months
  1. Limited evidence for DOACs in CVT as of 2020, and therefore Warfarin is preferred
  2. Dabigatran (Pradaxa) also has some evidence for use
3. First episode of CVT: 3-6 months (6-12 months if no known risk factor)
4. Continue Anticoagulation lifelong for recurrent CVT
Endovascular intervention considered in decompensating or refractory cases
Manage Increased Intracranial Pressure
1. See Acute Severe Intracranial Pressure Management
2. Acute monitoring by neurosurgery if risk of Increased Intracranial Pressure
3. Cerebral Herniation is the most common cause of death in acute Cerebral Venous Thrombosis
Manage Seizures
1. Antiepileptic drugs are indicated for clinical evidence of Seizures and are continued for >=1 year

Complications

Persistent Focal Neurologic Deficits
Hydrocephalus and Increased Intracranial Pressure
Cerebral Herniation
Seizures
1. Seen in up to 44% of cases in early Cerebral Venous Thrombosis (up to 30% present with Seizure)
2. Seizure does not predict prognosis or mortality
3. Kalita (2012) Seizure 21(8): 639-42 +PMID:22840965 [PubMed]

Prognosis

Mortality: 4.3% in 2004
1. Decreased from 50% in 1967, likely due to early recognition and improved diagnostics
Recurrent Venous Thrombosis risk off of Anticoagulation
1. Recurrent Cerebral Venous Thrombosis (>50% who recurr, do so in first year)
  1. Within first year: Up to 15% recurrence rate
  2. After first year: 2-7% recurrence per year
2. Recurrent Venous Thromboembolism (e.g. DVT, PE): 4-7% per year
Poor prognostic factors
1. Age >35 years old
2. Fever
3. Altered Level of Consciousness or Coma
4. Increased inracranial pressure or Papilledema
5. Focal Neurologic deficits
6. Banakar (2017) J Neurosci Rural Pract 8(2):204-8 +PMID:28479793 [PubMed]

References

Alfalasi (2022) Crit Dec Emerg Med 36(3): 3-6
Lively and Clare (2022) Crit Dec Emerg Med 36(5): 4-10
Marcolini and Swaminathan in Herbert (2021) EM:Rap 21(2): 5-7
Ulivi (2020) Pract Neurol 20:356-67 [PubMed]