ESOC 2024 | Trial updates in CVT: latest data on surgical and endovascular treatment

This was a teaching course dedicated to the topic of severe stroke, including severe cerebral venous thrombosis. We know these patients often do well in terms of Rankin scale, they have a Rankin scale 0-1 in about 80% of cases but still about 15% of patients either die or are dependent during follow-up. Also we know that even these patients that do well, that seem to have a Rankin scale 0-1, they have often cognitive complaints, epilepsy, headaches, and
neuropsychological complaints in general and they are often not able to return to their previous occupational activities. We know that cerebral venous thrombosis patients are often young adults so this is something that we were also discussing during this session and also what we can do for these patients particularly severe patients that present with large brain lesions, with a more severe presentation in terms of neurological complaints and also consciousness, often in a coma. We were focusing more specifically on this group of patients and for these patients we have two main treatments: one is decompressive surgery and the other is endovascular treatment

So, concerning the first, endovascular treatment, we don’t have very good evidence still on who should be the patients to treat because there was only one randomized, controlled trial (the TO-ACT trial) and this trial was neutral so we could not show a benefit of endovascular treatment on top of best medical treatment. Still, this was a pragmatic trial so the criteria for inclusion were very broad, just having one of the main predictors of poor outcome on the previous landmark studies on CVT, and also the technique was up to the treating physician and there was quite a lot of variability also on this on this regard. Still at this point we do need more evidence. We have been looking into observational data to understand better what happens also in patients receiving the standard treatment which is anticoagulation and actually in a recent observational study on patients treated only with anticoagulation but with early assessment for early venus recanalization using standardized protocol and the standardized classification on MRI, we could find that actually these patients on anticoagulation often also show early venus recanalization. So, after one week of treatment, there is already some flow around the thrombus and inside the thrombus. Of course recanalization continues to progress until 90 days which was the last follow-up but this shows that probably these patients often have some degree of early venous recanalization under best medical treatment which is something we should also consider.

Also, we were interested in exploring whether venous recanalization was or not associated with the evolution of the brain lesions because especially after the TO-ACT trial, there was some doubt whether venus recanalization was even important in this group of patients and that will be very important for our conclusions concerning the need for endovascular treatment in these patients and who will be these patients that need this immediate venus recanalization. Actually, we could also see in our observational data that patients that have early venous recanalization often have a recovery of their non-hemorrhagic brain lesions very quickly at this one week follow-up and also that patients that have persistent venous occlusion they often have new brain lesions. This difference, although the numbers were relatively small, was very significant so it’s a proof of concept that maybe this association is relevant.
Also, we collected some more translational data for example markers for blood-brain-barrier disruption. MMP-9 is increased in patients that do not have this early venus recanalization compared with the patients that have the early venous recanalization in whom we see a fast decline of the levels of MMP-9 through the admission until day 8. So this also suggests this is kind of a marker of hemodynamic processes surrounding the early venous recanalization in these patients.

However, we still don’t know exactly who should be the patients treated. We are doing some new studies trying to understand what can be imaging and clinical markers of this early worsening and this worse outcome and also to understand better who are the patients not having early venus recanalization on anticoagulation and then we should probably conduct new trials using this more detailed assessment and also in the meantime we should improve classifications and also the technique for venus recanalization and endovascular treatments. These were the main discussions around this question of endovascular treatment.

Concerning decompressive surgery, we do have news. Just a few weeks ago the results of the DECOMPRESS2 were published. This was a study coordinated by our Lisbon group and it was conducted in 10 countries including large number of centers all across the world and included 118 patients with decompressive surgery after cerebral venous thrombosis. Before that we only had retrospective data and this data was highly suggestive of an effect of decompressive surgery, however there was a high risk of reporting bias and the outcomes could be different in a prospective setting. This was the reason why this study was performed. Indeed, we could confirm that the outcomes are worse than what was described by the retrospective data, but still the conclusion is not very different. We could see that about 1/3rd of patients still die despite decompressive surgery which shows that the mortality is higher than what was described before, but still patients that survive very often have good outcomes during the follow-up. More than 1/3rd are independent by the last follow-up which was 12 months and also only 10% of patients have a Rankin scale 4 or 5 which shows that either patients died despite surgery or most likely they have still a good functional outcome during follow-up despite this very severe presentation of cerebral venous thrombosis with impending brain herniation and the need for decompressive surgery. Indeed, the patients in the cohort, and this is well described in the publication, that were selected for surgery they had very severe presentation, often large midline deviation, dilated pupils, coma, etc.… so this is a severe cohort but still the outcomes are relatively good although worse than what was described by the retrospective data.

So, in conclusion we should perform decompressive surgery in patients with cerebral venous thrombosis and impending brain herniation that’s still the recommendation but we should be aware of this maybe worse prognosis than previously expected.