Sinus Venous Thrombosis Joseph J Gemmete, MD FACR, FSIR, FAHA Professor Departments of Radiology and Neurosurgery University of Michigan Hospitals Ann Arbor, MI
Outline Introduction Medical Treatment Options Predictors of Outcome Techniques Literature Review Randomized Controlled Trial Conclusion
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Introduction Sinus Venous Thrombosis (SVT/CVT) Incidence 1.3 per 100, 000 A rare cause of stroke (0.5 1%) Median age / peak incidence 30-40 yrs. Affects women > men
Introduction Symptoms and Findings headache (90%) Visual disturbances Papilledema (28 47%) Seizures (40 %) Focal neurological deficits Impaired consciousness Coma Hemorrhage to some degree (40%) Nature Reviews Neurology
Medical Treatment Options Intra-venous heparin or LWH is considered the standard therapy for patients with SVT Anticoagulation is generally accepted as the principal therapy based on data from 3 small randomized trials Notable: Both don t possess thrombolytic properties Rationale for treatment is to prevent appositional thrombus growth and recurrent thrombosis
Medical Treatment Results Despite anticoagulant treatment 20% do not respond to medical therapy Ischemic and hemorrhagic stroke, cerebral edema and mass effect, death International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) Largest prospective cohort study, 624 pts., 80% treated with heparin 21% poor outcome (8% death, 13% mrs>2)
Predictors of outcome Main predictors for poor outcome Age, male gender Infection of the CNS and malignancy ICH Deep SVT Mental status disorder Coma
Predictors of Outcome Main predictors for good outcome Collateral venous drainage
Role of Venous Collaterals in CVT Intracranial Venous Hemodynamics is a Factor Related to Favorable Outcome in Cerebral Venous Thrombosis 26 pts with CVT evaluated prospectively by trans-cranial colorcoded sonography (TCCS), initial TCCS pathological in 69% (18/26) 5 major drainage patterns Cavernous sinus drainage: -FV spheno-parietal sinus/ superior petrosal sinus Sigmoid sinus thrombosis Deep cerebral venous drainage: -FV deep cerebral veins Superior sagittal sinus thrombosis Basal cerebral venous drainage: -Reversal of flow direction in basal veins straight sinus thrombosis Transverse sinus drainage: -compensatory FV in contralateral TS in case of proximally occluded ipsilateral TS TS thrombosis Transverse sinus drainage: -ipsilateral reversed flow in proximal TS in case of distally occluded TS TS thrombosis
Predictors of Outcome Less clear Influence of recanalization in SVT on outcome is not well established
Rationale for EVT Anticoagulant treatment is slow / less likely to recanalize large vessels/high thrombus burden fast EVT may facilitate rapid recanalization of major sinuses EVT in combination with anticoagulant treatment is possible Enable the anticoagulant treatment to reach small vessels
Indications for EVT (so far) Patients presenting with predictors for poor outcome Progressive thrombosis despite anticoagulation Neurological deterioration despite anticoagulation Development of new or worsening of hemorrhage/edema despite anticoagulation Contraindication to anticoagulation
Techniques Endovascular treatment for CVT first reported in the 1908s
Techniques Various endovascular treatment techniques and approaches have been applied Intra-sinus thrombolysis Urokinase and tpa As bolus or continuous infusion over several hours to days PTA/Stent Rheolytic thrombectomy (Angiojet) Direct manual or continuous aspiration Snare/Merci retriever Stent Retriever
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Literature Review EVT Endovascular mechanical thrombectomy for cerebral sinus thrombosis: a systemic review Adeel Ilyas, Ching-Jen Chen, Damiel M Raper, Dael Ding, Thomas Buell, Panogiotis Mastorakos, Kenneth C Liu, JNIS 2017; 9:1086-1092 -Literature review -identified 17 studies -235 patients
Literature Review EVT
Literature Review Uncontrolled studies have shown in parts promising results for the use of endovascular treatment in severely affected patients Data based almost exclusively on small retrospective studies without control group, subject to high risk of publication bias Time for a randomized controlled trial
Randomized Controlled Trial TO-ACT Trial (Thrombolysis Or Anticoagulation for Cerebral Venous Thrombosis) Jonathan Coutinho, MD PhD et al., Results presented at the ESO Congress 2017 RCT-great scientific achievement in a rare disease
TO-ACT Trial Question Does endovascular treatment improve the clinical outcome of patients with severe CVT? Study Design Investigator-initiated, international multi-center RCT Open-label clinical trial with blinded endpoint measurement (PROBE)
TO-ACT Trial Inclusion criteria Radiographically proven CVT Severe CVT Coma Mental status disorder Intracerebral hemorrhage Thrombosis deep cerebral venous system Uncertainty by the treating physician about the optimal treatment Coutinho et al. Int J Stroke 2013
TO-ACT Trial Endpoints: Primary endpoint: mrs 12 months (0-1 vs 2) Secondary endpoints: mrs 6 months Recanalization rate 6 months All-cause mortality Surgical interventions Safety endpoint major bleeding complications
TO-ACT Trial Randomization (1:1) Standard treatment (anticoagulation) Standard treatment + endovascular treatment Endovascular procedure Local intra-sinus thrombolysis (urokinase or rtpa) Mechanical thrombectomy combination
TO-ACT Trial Primary Endpoint (12 months) Endovascular Treatment (n=31) Standard Treatment (n=32) Odds Ratio (95% CI) mrs 0-1 22 (65%) 22 (66%) 0.95
TO-ACT Trial Complications Perforation sinus/cortical vein Symptomatic intracranial hemorrhage Endovascular treatment (n=33) Standard treatment (n=34) 3 (9%) 0 (0%) NA Odds ratio (95% CI) 1 (3%) 3 (9%) 0.3 (0.3 3.3) Mortality 6 months 4 (12%) 1 (3%) 4.5 (0.5 43.1)
TO-ACT Trial Conclusion TO-ACT: Endovascular treatment did not improve clinical outcome in patients with severe cerebral venous thrombosis The end of the story for EVT?
Conclusion Despite standard of care anticoagulation therapy poor outcome in CVT is as high as 20% Room for therapeutic improvement In the TO-ACT trial endovascular treatment did not improve clinical outcome in patients with severe cerebral venous thrombosis
Conclusion From my point of view Parts of the pathophysiology not explained (recanalization, collaterals) Patient selection so far not clear Endovascular treatment approaches need to be standardized and this may include the development of dedicated devices Future protocols or local protocols need to address these aspects