ESOC 2023 | Recanalization in cerebral venous thrombosis

Yes. So during this lecture we were discussing the possible relevance of recanalization in cerebral venous thrombosis. So we know that recanalization is important in arterial stroke, but actually that is not so clear in venous stroke. We know that we have the current standard treatment in cerebral venous thrombosis, which is anticoagulation and that improves outcomes. But indeed there are still some patients that have severe disability in the long term. These are usually young patients, mostly women and some patients die both in the acute phase and in the long term. So there is an unmet need for better treatments in cerebral venous thrombosis.

Also, we know that from the pathophysiological point of view it makes sense that venous recanalization is important. We know that there is evidence from basic science models, animal models, and also from patients that increased venous pressure is associated with more probability of having brain lesion and more severe brain lesion according to the increased venous pressure. So it does make sense that reducing venous pressure by producing early recanalization may be relevant.

Also it was published in 2020, we had a single trial assessing the role of a therapeutic venous recanalization, so endovascular treatment in cerebral venous thrombosis on top of the standard treatment. This was the TO-ACT trial. It was published in 2020 and this trial was neutral and it was stopped prematurely for futility. So at this point, although there was indeed some rationale to believe that venous recanalization was relevant, there was some doubt about the relevance of this outcome since the trial was neutral and there was no specific evidence on the role of venous recanalization.

So we have been interested in this topic for the last years. We started by doing a systematic review on venous recanalization in patients treated with anticoagulation. Indeed, most patients achieve venous recanalization during follow up, but we understood in this systematic review that there was absolutely no evidence on early time points after starting treatment, which would be probably the crucial time window for venous recanalization to happen and to have a critical impact on the outcomes. Still, we could see in the systematic review that there was an association between having a more favorable outcome according to the Rankin scale and the in the follow up and achieving venous recanalization. However, there was still at the time no good evidence on the association with recurrence of cerebral venous thrombosis and headache. So we started by that time a prospective study with very standardized MR assessments at several time points, including early time points, to assess the role of venous recanalization in patients treated with anticoagulation to see how often it happened and also if it was associated with some blood biomarkers that could be a marker of disruption of the blood brain barrier and other markers of brain damage and also with the evolution of the brain lesions in the MRI. So the evolution of the brain damage as well on imaging. And in that study, actually it was surprising to find that most patients actually about three quarters already have at least partial recanalization even after treatment only with anticoagulation after eight days. And in these patients, indeed they were much more likely to have recovery of the non hemorrhagic brain lesions and also that patients that have persistent venous occlusion were much more likely to have new brain lesions, non-hemorrhagic brain lesions by day eight after the assessment. Also we found that these patients had an increased levels of MMP-9 which is a marker of blood-brain-barrier disruption in patients with brain damage with lesions on the imaging assessment and that there was a correlation between the evolution of the MMP-9 marker and the venous recanalization status. So patients that achieved venous recanalization by day eight, they have a fast decline of the levels of MMP-9, suggesting that the process is evolving in the favorable way and patients with persistent venous occlusion have persistent high levels of MMP-9 by day eight. And this difference was significantly different between the two groups. So again, this suggests that there is a possible role for the evolution of brain damage in patients with cerebral venous thrombosis.

And also we have an update of our first systematic review recently now including this data we collected in the prospective study and other studies published since 2017. And indeed now there is an evidence of course, just using meta-analysis, different methodologies and so on, several limitations, but there is evidence suggesting that it is also associated with recurrence. So patients achieving recanalization have less recurrent CVT and also with headache, they are less likely to have headache in the follow up. So of course, we need more evidence. We especially need markers that allow us to understand better which patients may benefit from more invasive treatments to promote venous recanalization. So we assessed that in the TO-ACT trial, but indeed it was a very pragmatic trial, several patients selected for the treatment. So we do need probably better markers to select these patients for the treatment and for that we need more collaborative studies and better evidence on what could be the predictors for better outcome with more invasive treatments in this less common form of stroke.