18 Cerebral Venous Sinus Thrombosis

Michael C. Brandel, Christian Lopez Ramos, Robert C Rennert, Peter Abraham, Kevin Porras, Arvin R. Wall, Jeffrey A. Steinberg, David R. Santiago-Dieppa.j. Scott Pannell, and Alexander A. Khalessi

Abstract

Cerebral venous sinus thrombosis (CVST) is the acute occlusion of the brain’s dural venous sinuses by a thrombus. CVST is a rare cause of stroke that primarily affects children and young adults. Diagnosis of CVST is often delayed due to variable clinical manifestations, and mortality ranges from 5 to 30%. While systemic anticoagulation is the primary initial treatment for CVST, endovascular therapies including local thrombolysis or mechanical thrombectomy can be considered in refractory cases, although efficacy data remain mixed. Decompressive hemicraniectomy may be performed in patients presenting with severely increased intracranial pressures and impending herniation, despite an increased risk for poor outcomes that is independent of endovascular recanalization. Understanding the scope and quality of evidence regarding neurosurgical and neurointerventional procedures for refractory cases of CVST is critical.

Key words

cerebral venous sinus thrombosis – anticoagulation – thrombolysis – mechanical thrombectomy

18 Cerebral Venous Sinus Thrombosis

18.1 Goals

Review the literature that describes the risk factors and prognosis for cerebral venous sinus thrombosis.
Review the diagnostic methods used to distinguish cerebral venous sinus thrombosis from other neurological conditions.
Review the literature that describes the traditional treatments for cerebral venous sinus thrombosis.
Critically analyze endovascular treatments for cerebral venous sinus thrombosis.

18.2 Case Example

18.2.1 History of Present Illness

A 25-year-old woman presented to the emergency room with altered mental status. As per her family, she had been complaining of a progressively worsening headache and nausea for 3 days. On the morning of presentation, she was found to be poorly responsive with slurred speech. She had no sick contacts, fever, or neck stiffness, and no recent trauma or travel.

Past medical history: Ovarian cysts managed with oral contraceptives (OCPs) started 3 months prior to presentation.

Past surgical history: None.

Family history: Maternal history of migraines.

Social history: No tobacco, alcohol, or substance use. Review of systems: As per the above.

Neurological examination: On examination, the patient attempted to vocalize with moaning but was unable to answer any questions. She opened her eyes to noxious stimuli, flexor postured to pain in the upper extremities bilaterally, and triple flexed in the lower extremities bilaterally.

She had no spontaneous movement of the extremities. Pupils were equal in size and reactive to light. Ophthalmological examination was notable for mild papilledema.

Imaging studies: See Fig. 18.1.

18.2.2 Treatment Plan

The patient was started on anticoagulation with intravenous heparin for treatment of a cerebral venous thrombosis of the straight and transverse sinuses. Despite therapeutic anticoagulation, the patient’s clinical status continued to deteriorate, and she was taken to the neurointerventional suite for a diagnostic angiogram and embolectomy.

During the procedure, a 4-Fr diagnostic catheter and guide-wire were introduced into a right common femoral artery sheath for catheterization of the right internal carotid artery. Angiograms of the anterior circulation demonstrated no opacification of the straight and left transverse sinus and a large thrombus in the right transverse sinus (Fig. 18.2a). An aspiration catheter and guidewire were then advanced through a right internal jugular vein guide sheath to catheterize the straight and transverse sinuses. Venograms demonstrated a large thrombus burden of the straight sinus (Fig. 18.2b). Mechanical aspiration of thrombus resulted in adequate recanalization of the straight and transverse sinuses.

18.2.3 Follow-up

The patient responded well to the treatment and was transitioned to oral anticoagulation with warfarin for 6 months. OCPs were discontinued and thrombophilia work-up was negative. Subsequent imaging demonstrated recanalization of the straight and transverse sinuses. At follow-up, the patient denied any complaints and had an unremarkable neurological examination.

18.3 Case Summary

When is intervention indicated for a patient with cerebral venous sinus thrombosis (CVST)?

Anticoagulation therapy with either dose-adjusted unfractio-nated heparin or weight-based low-molecular-weight heparin (LMWH) is recommended for patients with CVST even in the presence of hemorrhagic lesions. ¹ This recommendation is based on limited evidence from randomized controlled trials (RCTs) ² ^, ³ ^, ⁴ ^, ⁵ and several observational stud-ies ³ ^, ⁶ ^, ⁷ ^, ⁸ ^, ⁹ ^, ¹⁰ ^, ¹¹ ^, ¹² ^, ¹³ ^, ¹⁴ ^, ¹⁵ the largest of which was the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). ⁶ While limited nonrandomized studies suggest that LMWH is more effective compared to unfractionated heparin, no definitive evidence exists. ¹⁶

Endovascular intervention for CVST is generally indicated for patients with progressive neurological deterioration or poor prognosis despite adequate anticoagulation therapy. ¹ Endovascular methods include direct catheter chemical thrombolysis or direct mechanical thrombectomy (balloon-assisted or aspiration catheter) with or without thrombolysis. In a systematic review of 169 patients who received local thrombolysis, more than 80% were independent at follow-up. ¹⁷ Another systematic review of 185 patients treated with mechanical thrombectomy demonstrated that 84% and 74% of patients had a good outcome and near-to-complete or complete recanalization after the procedure, respectively. ¹⁸ However, no RCTs have evaluated the efficacy and safety of endovascular intervention for the treatment of CVST. A decompressive craniectomy is considered for critically ill CVST patients with impending herniation secondary to a large venous hemorrhage and parenchymal infarctions. In a review of 69 patients with ischemic or hemorrhagic parenchymal lesions that underwent decompressive surgery, only 17% had unfavorable outcomes (modified Rankin scale [mRS] score of 5-6), whereas 59% were independent (mRS 0-2) at the end of follow-up. ¹⁹
What is the long-term management of CVST?

Patients are transitioned to oral anticoagulation for 3 to 12 months with an international normalized ratio (INR) goal of 2-3. ¹ Treatment duration depends on the presence of risk factors for recurrent CVST or other venous thromboembolisms (VTE). Patients with idiopathic CVST and a mild thrombophilia may be treated for 6 to 12 months, compared to 3 to 6 months in patients with provoked CVST. ¹ Long-term or indefinite anticoagulation may be considered for patients with a severe inherited thrombophilia, recurrent CVST, or VTE after CVST.
What is the clinical presentation of CVST?

Clinical presentation of CVST is highly variable and dependent on acuity, site, number of occluded vessels, presence of cerebral lesions (edema, venous infarction, hemorrhage), and patient age. The mean age for women and men is 34 and 42 years, respectively. ²⁰ Patients may present with an isolated intracranial hypertension (ICH) syndrome (headache, papilledema), neurological deficits (motor weakness, aphasias, focal or generalized seizures), or signs of encephalopathy (mental status changes). ¹ ^, ²¹

The most common symptom of CVST is severe headache, occurring in 90% of patients. ²¹ Headaches are typically slow in onset, with increasing severity over multiple days. Patients with parenchymal lesions are more likely to have diminished mental status or neurological deficits such as motor weakness, aphasia, and seizures. ²¹ In the ISCVT, 39% of patients presented with seizures, which were associated with supra-tentorial lesions, motor deficits, and sagittal sinus and cortical vein thrombosis. ²²
What are the most commonly involved sites in CVST and their associated clinical characteristics?

In the ISCVT cohort, the most common cerebral venous sites involved were the transverse (86%), superior sagittal (62%), and straight sinuses (18%). ⁶ Sagittal sinus thrombosis commonly manifests with motor deficits and seizures. Transverse sinus thromboses may present with isolated signs and symptoms of ICH. Aphasia is generally associated with thrombus in the left transverse sinus. Involvement of the straight sinus results in more severe signs and symptoms, including coma or altered mental status, and is typically associated with bilateral thalamic lesions, as in the case example patient. ²³
What risk factors should you consider for the development of cerebral venous sinus thrombosis (CVST)?

A genetic or acquired prothrombotic state is the most common risk factor for the development of CVST, identified in 85% of patients. ⁶ Genetic hypercoagulable states include deficiencies in antithrombin, protein C, and protein S, or mutations in factor V Leiden and prothrombin genes. ²⁴ Acquired prothrombotic conditions include antiphospholid syndrome, polycythemia, homocysteinemia, inflammatory diseases, malignancies, and severe systemic infections. ¹ ^, ²¹ Patients with CVST should be evaluated for underlying hypercoagulable states. Head trauma, pregnancy, obstetric delivery, and surgery may precipitate CVST in patients with risk factors for a hypercoagulable state.

CVST commonly affects people in their third decade of life. Of note, 80% of newly diagnosed cases occur in women of childbearing age. ⁶ Increased incidence of CVST among women is likely related to the prothrombotic effects of OCPs.

In the prospective International Study on Cerebral Vein and Dural Sinuses Thrombosis (ISCVT), two-thirds of women with CVST were either on OCPs, hormone replacement therapy, or were pregnant. ²⁰
What imaging modalities are used for diagnosing CVST and what findings are suggestive of the diagnosis?
1. Computed tomography (CT) and CT venography Given the wide variability in clinical presentation, the diagnosis of CVST is often challenging. A head CT is the first investigation to rule out other neurological conditions, yet it is normal in about 70% of CVST cases. ²⁵ Direct signs of CVST include the “dense triangle sign,” characterized by a triangular-shaped hyperdensity caused by the thrombus. ²⁶ On contrast CT, the “empty delta sign” is a triangular pattern of contrast enhancement surrounding a central region lacking contrast enhancement in the sinus due to the thrombus. ²⁶ Another is the “cord sign,” typically observed with a contrast CT as a linear patchy hyperdensity of the occluded vein. ²⁷ Dilated or tortuous cerebral veins, edema, and hemorrhagic venous infarctions can also be seen. About 30 to 40% of patients with CVST present with an intracerebral hemorrhage. ⁶
  
  Per AHA/ASA guidelines, venography (either CT venography or magnetic resonance [MR] venography) should be performed in suspected CVST following a negative CTor magnetic resonance imaging (MRI), or to characterize the extent of thrombosis after a suggestive CTor MRI. ¹ CT venography increases the accuracy of diagnosis of CVST to 90 to 100%. ²⁵ CT venography provides visualization of the major dural sinuses and may demonstrate filling defects, sinus wall enhancement, and increased collateral venous drainage secondary to the presence of a thrombus. ²⁵
2. MRI and MR venography
  
  MR venography in combination with MRI (particularly T2 susceptibility weighted sequences) is also highly sensitive for diagnosing CVST. ²⁶ In the acute phase, thrombosed sinuses appear isointense and hypointense onTl-weighted and T2-weighted images, respectively. ²⁵ Sub-acutely, the signal increases on both Tl- and T2-weighted MRI images. Other lesions, including edema or venous infarction, appear hypointense or isointense onTl-weighted MRI and hyperintense on T2-weighted images. Hemorrhagic venous infarcts can also be seen on MRI, and appear as hyperintense lesions on both Tl and T2 sequences. It is nonetheless important to be aware of normal anatomic variants that may mimic findings of CVST, such as sinus hypoplasia or atresia and asymmetric sinus drainage. ²⁵
3. Angiography
  
  In the event of inconclusive results from CT or MRI, catheter angiography may be used to diagnose CVST ²⁵ Findings on angiography include lack of or delayed opacification of the affected vein or sinus, indicative of a thrombus. Similar to MRI, normal asymmetric angiographic venous anatomy may potentially result in a misdiagnosis of CVST. ²⁷
What is the prognosis of patients with CVST?

The overall ISCVT cohort mortality rate was 8.3% (approximately half of which occurred acutely), with other studies reporting mortality rates up to 21%. ⁶ ^, ²⁸ Nonetheless, nearly 25% of patients experience neurologic deterioration after admission, and acute herniation secondary to hemorrhage is the most common cause of death in the acute period. ¹ Thirty-day mortality predictors include mental status changes, hemorrhage of the right hemisphere, and thrombosis of deep venous structures. ⁶ ^, ⁷ Patients with ICH as their only presentation of CVST have favorable outcomes. Poor long-term prognosis is associated with infection, hemorrhage, Glasgow Coma Scale (GCS)<9 on admission, mental status abnormalities, and male sex. ⁶ ^, ⁷ Complete recovery at the end of follow-up (mean 18.6 months) was observed in 80% of patients in the ISCVT cohort. ⁶ Risk of recurrent CVST and VTE in other sites is 2 to 4% and 4 to 7%, respectively. ⁶ Male patients and those with severe thrombophilias are at higher risk for developing thromboembolic events. ⁶