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Cerebral venous sinus thrombosis

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CONTENTS

pathophysiology

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anatomy
  • The superior sagittal and transverse sinuses are most frequently involved (in 60% of patients).  The internal jugular and cortical veins are involved less often.
  • Venous thrombosis may cause involvement of multiple areas of the brain which extend across numerous different arterial circulations.  This may help differentiate a venous thrombosis from an arterial occlusion.
physiology
  • Dural venous sinuses lack valves, allowing the flow of blood in various directions.  Along with some anastomotic venous connections, this may allow for re-routing of venous blood to overcome thromboses (to a certain extent).
  • If blood backs up enough, the following consequences may occur:
    • (a) Cerebral edema due to elevated capillary pressures.  This may impair brain function, but it is reversible (e.g., if the occlusion can resolve).
    • (b) Blood stasis in the tissues may lead to ischemic infarction.  The combination of infarcted tissue plus elevated venous pressure may lead to hemorrhagic transformation of the infarction.
  • Normally, the venous sinuses play a role in draining cerebrospinal fluid (especially through arachnoid granulations which drain into the superior sagittal sinus).  Sinus thrombosis may therefore lead to excess CSF, leading to communicating hydrocephalus (excessive CSF causes dilation of the ventricles and elevated intracranial pressure).
    • Communicating hydrocephalus is most problematic if the superior sagittal sinus is thrombosed.

epidemiology

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overall epidemiology
  • This typically affects young patients (most commonly between 20-50YO)(29752489)
  • There is a 2-3 fold female predominance.
  • Venous thrombosis accounts for ~1% of all strokes.
  • Its overall incidence is comparable to that of bacterial meningitis.  Although this disease is uncommon, it will be encountered on a regular basis.(29752489)
risk factors
  • Thrombophilia (suggested by prior venous thromboembolic disease)
    • Inherited thrombophilias
    • Oral contraceptive use (Increases risk six-fold, or 30-fold when combined with obesity)(29923367)
    • Pregnancy (especially in the first months following delivery)
    • Antiphospholipid syndrome
    • Sickle cell disease
    • Autoimmune disorders (e.g., lupus, vasculitis, inflammatory bowel disease)
    • Nephrotic syndrome
    • Severe dehydration
    • Malignancy (especially chemotherapy with L-asparaginase, intrathecal methotrexate)
  • Head and neck infections
    • Mastoiditis, sinusitis, otitis media
    • Meningitis, cerebral abscess
  • Mechanical causes
    • Head trauma, neurosurgical procedures
    • Jugular vein catheterization

signs and symptoms

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diagnosis is difficult
  • The manifestations are variable and nonspecific.  This reflects the varying location of thrombosis and its evolution over time (e.g., clots may extend or recanalize).
  • There is a median of one week's delay between initial presentation and diagnosis.  Evolution may occur acutely, subacutely (over several days), or chronically (over more than a month).
  • Different patients can present with a variety of chief complaints, including:
    • Headache
    • Focal neurologic findings
    • Seizure
    • Encephalopathy
findings
  • Headache due to elevated intracranial pressure (90%)(31440838)
    • This is often the first symptom.  If untreated, the thrombus may extend and patients will accrue additional symptoms.
    • Pain may be exacerbated by lying down or by performing the Valsava maneuver.
    • Pain may start gradually or abruptly (causing a “thunderclap” headache).
    • There may be associated features of intracranial pressure elevation:
      • Vision changes, diplopia
      • Nausea, vomiting
      • Papilledema (30%)
      • Cranial nerve 6 palsy (inability to abduct the eye)
  • Focal neurological deficits
    • Paresis (37% of patients)
    • Dysarthria, aphasia
    • Thrombosis of the cavernous sinus may cause dysfunction of CN3, CN4, or CN6 (leading to ocular motor palsies).
  • Seizures (10-40%)
    • May be focal, generalized, or focal with secondary generalization.
  • Mental status changes (22%)
  • Occipital or neck pain may associate with sigmoid sinus involvement.

anatomic basis of symptomatology
  • Thomboses in various vessels may cause specific clinical symptoms (table below).
  • However, reality may be a bit more confusing than this, because patients can have multiple sites of thrombosis simultaneously.

laboratory studies

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D-dimer
  • Sensitivity varies between 82-94%.  The sensitivity is higher for more acute and extensive thrombosis, and lower with more subacute or focal thromboses.
  • Specificity will vary depending on clinical context.  For example:
    • In a population of outpatients presenting with isolated headache, D-dimer may be more specific for venous thrombosis.
    • In a population of patients with meningitis, D-dimer will be wholly nonspecific.
  • The utility of D-dimer will depend on clinical context.  For example:  if there is a moderate or high suspicion for cerebral vein thrombosis, then imaging will be required regardless of the D-dimer value.
lumbar puncture
  • This isn't indicated as part of the evaluation for suspected cerebral vein thrombosis.  However, lumbar puncture may be performed as part of a broader evaluation to exclude infection.
  • The opening pressure will be elevated in patients with elevated intracranial pressure.
  • Cerebrospinal fluid may reveal nonspecific abnormalities (elevated lymphocytes, erythrocytes, and/or elevated protein).
    • ⚠️ Mild abnormalities in the cerebrospinal fluid shouldn't lead to premature diagnostic closure with a diagnosis of “lymphocytic meningitis.”

imaging

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Imaging findings may be divided between direct signs (visualizing the clot itself) and indirect signs (hemorrhage or edema as a consequence of the clot).  Indirect signs may be more dramatic, ideally leading to further evaluation for an underlying clot.  

noncontrast CT scan
  • This is mostly useful for excluding other pathologies.  The sensitivity for cerebral venous thrombosis isn't terrific.
  • Direct signs of venous thrombosis: 
    • May see a hyperdense signal in vessel lumen (which becomes isodense and later hypodense after the first week).
    • This is visible in only about a third of cases.
    • Dense triangle sign, when thrombosis is within the superior sagittal sinus.
    • Dense cord sign, when thrombosis is in a cortical or deep vein.
  • Indirect signs:
    • These are usually more notable than direct signs.
    • Hemorrhage (about 1/3 of patients):  This is typically parenchymal, but less often may be subarachnoid or even subdural in location.
    • Cerebral edema may be seen, if present.  It is often diffuse.
    • Venous infarction:  hypodense tissue may reflect ischemia.  This may be differentiated from arterial occlusion if it spans multiple different arterial territories, or if it spares the cortex.

CT venogram (CT-V)
  • CT venogram increases performance to sensitivity of ~99% and specificity of 88%.  It is considered as accurate as MR venography to detect cerebral venous thrombosis.(28833980)
    • Contrasted head CT has only ~70% sensitivity, so a dedicated CT-venogram is needed.(29752489)
  • A filling defect can be seen (e.g., empty delta sign in a dural sinus).
  • Acute clot can appear dense (similar to contrast material).  Comparison of pre- versus post-contrast images may be needed to detect this.

MRI 

  • MRI is superior to noncontrast CT scan.
  • Direct signs:
    • Normally, dural sinus can be seen as flow voids.  Absence of these flow voids may suggest thrombosis.  Flow voids are best visualized in an imaging plane perpendicular to the vessel.  The appearance of the thrombus will vary over time, however, as shown below.
  • Indirect signs:
    • Vasogenic edema may manifest as hyperintensity on T2 sequences.
    • Hemorrhagic infarction is hyperintense on both T1 and T2 sequences.
MR venography
  • Gadolinium allows for direct visualization of luminal filling, similar to a CT venogram.  Thus, contrast MR venography is highly accurate, on par with CT venogram.
  • In patients unable to receive gadolinium, certain MRI sequences can be used to improve visualization of the venous system (e.g., TOF or phase contrast).  However, these sequences alone remain inferior to gadolinium-enhanced MR venography or to CT venography.
invasive catheter angiography
  • This is rarely used for diagnostic purposes currently.
  • Invasive angiography could be considered if CT and MRI are equivocal.

treatment

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anticoagulation
  • Heparin anticoagulation is the mainstay of therapy.
  • Cerebral venous thrombosis may cause hemorrhagic venous infarction.  This isn't a contraindication to heparin anticoagulation.
    • An observational study found that hemorrhage extension was rare (11% of patients) and not associated with anticoagulation.(29923367)  On the contrary, extension of untreated thrombus due to a lack of anticoagulation seems to be the main risk for worsening hemorrhage.
    • Current guidelines strongly indicate that intracranial hemorrhage isn't a contraindication to anticoagulation. (28833980)
  • Either unfractionated or low molecular-weight heparin may be used.
    • European guidelines weakly recommend low molecular weight heparin, based on one RCT with some methodological limitations.(28833980)  This is consistent with literature regarding DVT and PE, where low molecular-weight heparin may improve outcomes when compared to unfractionated heparin infusion.  
    • Low molecular-weight heparin might be preferable for patients with mild cerebral venous thrombosis who are unlikely to require an emergent procedure (e.g., an external ventricular drain or decompressive craniectomy).  Alternatively, unfractionated heparin is probably preferable for patients who are critically ill and more likely to require a procedure.
    • If unfractionated heparin is used, particular care should be taken to avoid either supratherapeutic or subtherapeutic drug levels.
seizure management
  • Epidemiology of seizures
    • Occur in 10-40% of patients.
    • Risk factors include:  involvement of the brain cortex, hemorrhagic transformation.
  • Seizure prophylaxis is generally not recommended.
  • If seizures do occur, these should be treated aggressively.
communicating hydrocephalus
  • Impaired drainage of CSF into the venous sinuses may lead to elevated intracranial pressure, due to communicating hydrocephalus.
  • Drainage of CSF may be necessary:
    • External ventricular drain placement may rarely be necessary.
    • Lumbar puncture may also be used to reduce intracranial pressure.(29923367)  However, to be effective this probably requires serial lumbar puncture, which is difficult to balance with the need for ongoing anticoagulation.
  • Acetazolamide could be considered to reduce CSF production, but there is no evidence to support this.
    • European guidelines state: “In isolated intracranial hypertension secondary to cerebral vein thrombosis, causing severe headaches or threatening vision, acetazolamide may be considered if its safety profile is acceptable.” (28833980)
focal cerebral edema
  • Focal tissue infarction with subsequent edema may compress adjacent tissue, in extreme cases leading to herniation and death.
  • General supportive measures for cerebral edema may be utilized (e.g., bed elevation and osmotherapy).
  • Decompressive craniectomy may occasionally be necessary to prevent herniation.
    • Decompressive craniectomy is strongly recommended in the European guidelines, albeit in the absence of RCT-level evidence.(28833980)
    •  Among all patients with stroke, younger patients with venous thrombosis may be among the best candidates for decompressive craniectomy.
  • Steroid does not appear to be useful.
catheter-directed endovascular therapy
  • This may include local administration of thrombolytics into the cerebral veins, and/or mechanical clot disruption.
  • Available RCT-level evidence has not shown benefit from interventional therapy.

neurologic deterioration despite treatment

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potential causes (differential diagnosis)
  1. Clot propagation, causing an increased amount of infarcted tissue.
  2. Intracranial hemorrhage (or extension of hemorrhage).
  3. Seizure (either convulsive or non-convulsive).
  4. Enlarging hematoma or edema may cause compression of adjacent tissue, including herniation.
  5. Communicating hydrocephalus due to impaired CSF reabsorption.
evaluation may include:
  • (1) CT scan with CT venogram (to look for #1 & #2 above).
  • (2) EEG if seizure is a concern
  • (3) Evaluation of intracranial pressure (e.g., with ultrasonography to evaluate for papilledema)

prognosis

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overall prognosis
  • Mortality is ~5%.
  • Risk of permanent disability or death is ~15-20%.
poor prognostic factors
  • The most important factors appear to be:
    • Coma or mental status disturbance
    • Thrombosis of the deep venous system
    • Intracerebral hemorrhage (i.e., hemorrhagic venous transformation)
  • Patients without these factors are at very low risk of poor outcome.(28833980)
cerebral venous thrombosis risk score
  • This may be used as a rough tool to determine functional prognosis (see figure below). (19420921)
  • Interestingly, some patients will do well even if they accrue multiple indicators of poor prognosis:

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questions & discussion

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To keep this page small and fast, questions & discussion about this post can be found on another page here.

  • Failure to consider the diagnosis of cerebral venous thrombosis, leading to a failure to perform adequate imaging and thereby missing the diagnosis.
  • Incorrect belief that patients with cerebral venous thrombosis and hemorrhagic transformation cannot be anticoagulated.  In fact, most patients with controlled hemorrhagic transformation should be anticoagulated.
Going further:
References:  
  • 19420921  Ferro JM, Bacelar-Nicolau H, Rodrigues T, et al. Risk score to predict the outcome of patients with cerebral vein and dural sinus thrombosis. Cerebrovasc Dis. 2009;28(1):39-44. doi:10.1159/000215942  [PubMed]
  • 28833980  Ferro JM, Bousser MG, Canhão P, 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):1203-1213. doi:10.1111/ene.13381  [PubMed]
  • 29752489  Dmytriw AA, Song JSA, Yu E, Poon CS. Cerebral venous thrombosis: state of the art diagnosis and management. Neuroradiology. 2018;60(7):669-685. doi:10.1007/s00234-018-2032-2  [PubMed]
  • 29923367  Capecchi M, Abbattista M, Martinelli I. Cerebral venous sinus thrombosis. J Thromb Haemost. 2018;16(10):1918-1931. doi:10.1111/jth.14210  [PubMed]
  • 31440838  Ferro JM, Aguiar de Sousa D. Cerebral Venous Thrombosis: an Update. Curr Neurol Neurosci Rep. 2019;19(10):74. Published 2019 Aug 23. doi:10.1007/s11910-019-0988-x  [PubMed]
  • 31980184  Ghoneim A, Straiton J, Pollard C, Macdonald K, Jampana R. Imaging of cerebral venous thrombosis. Clin Radiol. 2020;75(4):254-264. doi:10.1016/j.crad.2019.12.009  [PubMed]

The Internet Book of Critical Care is an online textbook written by Josh Farkas (@PulmCrit), an associate professor of Pulmonary and Critical Care Medicine at the University of Vermont.


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