Malignant venous thrombosis - Ep.1/2 - SLICE Worldwide 2022

Is there a role for endovascular treatment in cerebral sinus thrombosis?

Introduction:

Cerebral venous sinus thrombosis (CVT) accounts for 0.5% of all stroke cases and is a relatively uncommon cause of cerebral hemorrhage and edema. Due to the rarity of the disease and the overall outcome that is more favorable than for ischemic stroke or spontaneous ICH, evidence still lacks for the efficacy of endovascular treatment in cerebral sinus thrombosis. Different techniques have been described, but endovascular treatment (EVT) practice varies widely between centers. Some allegedly report as many as 20 cases annually, while other high-volume centers perform less than 1. This is a quick review of the literature focusing on currently available results for EVT in CVT and potential selection criteria for individualized treatment decisions.

TO-ACT trial(1):

• Investigator initiated randomized trial, included severe CVT (def: coma/mental status disorder/intracerebral hemorrhagic lesion/thrombosis of the deep venous system), which were randomized between standard treatment and endovascular treatment + standard treatment, primary endpoint was mRS at 12 months, and the trial was stopped after the first interim analysis due to futility;
• The trial randomized 67 patients during 2011-2016 and showed no clinical benefit (mRS 0-1, 67% in the EVT arm vs. 68% in the standard care arm). Most importantly, despite selecting severe patients, mRS 0-2 at 12 months was achieved in 85% in the EVT arm vs. 82% in the standard treatment arm.
• Criticism of the trial relates to using predominately older generations’ devices. Nowadays, due to the development of the ischemic stroke armamentarium, there are better options available on the market to perform EVT in CVT. Also, selecting only very severe patients might have led to an interventional treatment that comes too late after the fate of the tissue at risk has already been decided (proponents of EVT in CVT tend to select patients early on and to rush them to the angiosuite as early as possible). 
• The median patient age in the trial was consistent with CVT cohorts of approximately 40 years. Given that these are young adults, two important discussions arise: 1) the better long-term outcomes in young adults after cerebral insults (which is consistent with 80% mRS 0-2 in this cohort); 2) is an mRS 0-1 at 12 months an ideal discriminant? Would we be able to accelerate the recovery to an mRS of 0, faster in patients in whom we perform EVT? Thus, helping patients to regain social work-related inclusion faster.
• However, despite these criticisms, real-world prospective observational data corroborates the TO-ACT trial results and shows a potential benefit in patients with successful recanalization.(2)

Experts-recommendations for patient selection for EVT in CVT:

• EVT for CVT is a reasonably safe procedure with a very low complication rate – care should be taken not to perforate cortical veins while navigating through thrombosed sinuses.
• EVT for CVT should be performed on selective patients with radiologically confirmed CVT that are either severe or at a high risk of deterioration, judged by the local multi-disciplinary team.
• EVT for CVT is not a substitute for intravenous anticoagulation but should always accompany a form of anticoagulation. 
• The scope of EVT for CVT is not to perform a full recanalization of the sinus but to create a channel inside the thrombosed sinus that may facilitate endogenous tPA and systemic anticoagulation to act faster and better. 
• The role of tPA during EVT for CVT is uncertain. Some case series and small studies claim benefits for either arterial or venous infusions of tPA coupled with the fragmentation of the thrombus. However, this strategy is heterogenous and may be associated with the additional risk of ICH and thus should be reserved for severe cases.

Conclusion

There is still reasonable debate about the benefit of EVT in CVT patients. Currently, available experience with endovascular treatments suggests that it should be reserved for selected patients, and most importantly, the treatment decision should not wait for the initial outcome of anticoagulation therapy. The main scope of the treatment may be to create a channel inside the thrombosed sinus, to establish flow, and to augment the effects of local endogenous tPA and systemic anticoagulation.

Bibliography:

1.           Coutinho JM, Zuurbier SM, Bousser MG, Ji X, Canhão P, Roos YB, et al. Effect of Endovascular Treatment With Medical Management vs Standard Care on Severe Cerebral Venous Thrombosis: The TO-ACT Randomized Clinical Trial. JAMA Neurol. 2020 Aug 1;77(8):966–73. 

2.           Siegler JE, Shu L, Yaghi S, Salehi Omran S, Elnazeir M, Bakradze E, et al. Endovascular Therapy for Cerebral Vein Thrombosis: A Propensity-Matched Analysis of Anticoagulation in the Treatment of Cerebral Venous Thrombosis. Neurosurgery. 2022;91(5).