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Examining evidence for EVT in MeVO stroke · VJNeurology Podcast

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  Hello, and welcome to today's VJ Sounds podcast, presented by the Video Journal of Neurology.
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  We are an open access video journal showcasing the latest breakthroughs in all
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  major neurology disciplines.
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  Join us for exclusive insights from leading experts as we explore endovascular
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  therapy use in small and medium vessel occlusions.
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  Medium vessel occlusion, also known as MEVO, MEVO refers to the blockage of
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  medium-sized intracranial arteries, leading to acute ischemic strokes.
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  While endovascular thrombectomy is the gold standard for large vessel occlusions,
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  there's a lack of robust randomized control data supporting its routine use in MEVO strokes.
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  During this episode, we will meet with Professors Joanna Ospel,
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  Nishita Singh, and Jan Grala to discuss recent updates in this field.
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  By discussing ongoing trials looking at how effective endovascular thrombectomy
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  is in treating acute ischemic strokes caused by MEVO, we'll provide you with
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  a comprehensive overview of the latest research findings.
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  Professor Joanna Ospel from the University of Calgary will kick off the conversation,
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  explaining the uncertainties surrounding the application of endovascular thrombectomy.
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  Stay tuned for an engaging discussion with experts at the forefront of neurology research.
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  Medium vessel occlusions are occlusions that are a little bit smaller than kind
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  of the very large vessel occlusions that we're used to see frequently and treat frequently.
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  And we currently, there are a few uncertainties. So one of them is how to detect them.
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  And that's the topic of my debate because they're relatively hard to see.
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  It's kind of a small little vessel that then suddenly stops.
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  The other, also very interesting question, is how to treat them,
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  because currently we don't have very high-level evidence to suggest that endovascular
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  treatment, meaning catheter-based removal of clots, is beneficial for these vessel occlusions.
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  That's currently investigated in several randomized trials.
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  It's kind of a chicken and egg problem. If you can't detect them,
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  then you can't treat them, because you're not aware of them.
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  That's why these two things are tightly tied together.
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  Yeah, and kind of closely related. There are different imaging techniques to,
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  we call them advanced imaging techniques, to kind of visualize the brain parenchyma a little bit better.
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  And CT perfusion is one of them. It's probably the most widely used one,
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  where intravenous contrast is detected, and then the brain is scanned many,
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  many times, 45 or even 50 or 60 times.
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  And then those beautiful colored brain maps are generated.
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  And medium vessel inclusions are really easy to detect on CT perfusion,
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  just because there's a wedge-shaped red or orange defect, and that kind of is
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  the area that's affected by the medium vessel occlusion.
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  So they're really easy to find because they point directly towards the site of occlusion.
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  But that being said, not every hospital has possibility to perform CT perfusion.
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  It requires kind of a special software, special post-processing,
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  and there are other imaging techniques that are also very well suited to detect
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  medium vessel occlusions.
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  One of them is multiphase CTA, for example, where where it's kind of an abbreviated
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  version of CT perfusion.
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  So instead of 45 or 50 times, the brain is just scanned three times.
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  And then those three kind of maps are put next to each other.
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  And the area where the vessels kind of fill later and wash out later,
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  that's the area that's affected by the occlusion.
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  And you can see it's black and white, but you can see occlusions just as well on multi-phase CTA.
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  And then there's even the option to kind of overlay all three phases and generate
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  maps that are similar to CT perfusion. They're a little bit more noisy because
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  there are less data points than with CT perfusion, but it's good enough to detect vessel occlusions.
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  And my argument would be, you don't need to have beautiful maps that look awesome.
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  You just need them to be good enough to detect vessel occlusions.
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  And I think we should kind of do imaging that's just good enough to answer our
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  questions, but we shouldn't attempt to make it beautiful and perfect because time is brain.
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  And we get to treat the patient faster if we kind of acquire only the images that are,
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  that are necessary and not more than that. We haven't paid much attention until
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  recently to those occlusions because they were just treated with the intravenous
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  thrombosis with drugs that dissolve the clot.
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  But now that we have those ongoing thrombectomy trials for medium vessel occlusions,
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  people are starting to pay more attention.
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  And I think that those trials will basically answer the question which imaging
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  paradigm should be used. Some of them use CT perfusion.
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  Some of them use multi-phase CTA. Some sites that in our trial,
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  ESCAPE-MUVO for instance, instance, they only use single-phase CTA.
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  So that's another option, just a very, very basic imaging protocol.
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  And I hope that by kind of pooling all those trials together in one or two years
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  from now, we'll be able to find out which imaging paradigm is the best one.
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  There is evidence to suggest now that either multiphase or CT perfusion kind
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  of helped over and beyond single-phase CTA to detect medium-less occlusion.
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  So some form of advanced imaging is kind of beneficial, but which form is just
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  enough and which one is better than the other is not sure at this point, I think.
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  It's always a balance between risk and benefit in any treatment in medicine,
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  and Mevo thrombectomy is no exception.
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  And the kind of challenge with medium vessel occlusions is that the occluded
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  vessel is smaller, meaning that the brain damage is also smaller compared to
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  larger vessel occlusions.
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  So patients do generally better, even without kind of any invasive treatment.
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  And the other problem is that invasive treatment is harder in those distal occlusions,
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  because they're smaller vessels, tinier and fragile, and it's harder to get
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  to those kind of more peripherally located vessels.
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  So the risk of accidentally perforating a vessel or dissecting a vessel with
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  a wire or a catheter is higher.
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  So the benefits are lower, the risks is higher. And the question is where the
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  tipping point is, so to speak. And that's what we're trying to find out with those trials.
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  And then there are just technical challenges. For instance, catheters are kind
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  of, they have a certain length and the more peripheral you go in the brain,
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  the longer your catheter has to be in the current catheters.
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  They're mostly designed for large vessel occlusions that are more central.
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  So sometimes you actually run out of catheter length and your catheter is just that long enough.
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  So that problem hopefully will get solved because companies kind of will design longer catheters.
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  But at the time being, we have to kind of deal with those kinds of issues as well.
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  There's the trial that we're running that's Escape Mevo run from within Calgary,
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  but there are sites in Canada, the US, Germany and Hungary and the UK.
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  Then there's Distil, That's the Swiss trial, which is running in Europe,
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  mainly. There is this count, which is a French trial.
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  Then there is Frontier AP, I think. That's an Australian trial.
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  Then there's another US trial that has a technical outcome, meaning reperfusion
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  instead of a clinical outcome.
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  And I think that's all for now. I hope I didn't forget any. But I think this
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  little Swiss trial and Escape Mevo, the Canadian one, are kind of...
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  They have enrolled most patients, so Distel has enrolled around 350 or so, I think.
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  This gave me around 330, and then the French trial is kind of the next one.
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  And I think they will all finish within one to two years from now,
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  and hopefully give us some answers.
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  Next, Nishita Singh, MD, University of Calgary, provides insights into the current
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  guidelines for treating acute ischemic strokes caused by medium vessel occlusion.
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  This is the data from the Quaker Registry, which is a quality improvement initiative
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  of registry data, which we collect for all patients who receive somatosis as
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  well as under vascular treatment within Alberta.
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  The current analysis that I'll be presenting on is restricted to Southern Alberta,
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  so Calgary and the area around.
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  Yeah, so we collected data for patients who underwent endovascular treatment
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  between January 2015 to December 2020.
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  And imaging data was re-read by physicians with the two physician consensus.
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  And we included patients who had medium vessel occlusion, which was defined
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  as occlusion beyond M2MCA, A2AC, and P2PCA. And these were compared with large
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  vessel occlusion patients.
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  So because this is registry-linked data, which we further linked with administrative
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  data, so the study actually has a very, again, a pragmatic administrative outcome,
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  which is 90-day home time.
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  And a 90-day home time is basically the number of nights a patient is back to
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  their pre-morbid living situation without increasing the level of care within 90 days of stroke.
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  So unlike conventional trials or conventional studies which use MRSS and outcome
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  measure, we've used 90-day home time here.
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  And one drawback of 90-day home time is it has a very skewed distribution,
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  so with an inflated zero.
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  So we had to do some random forest regression modeling to account for that. that.
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  So in the end, we had 806 cases in the registry out of which 139 were MEVO and
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  524 were non-MEVO or LVO cases and we compared the two groups.
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  So on baseline characteristics, we really did not find anything surprising.
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  We didn't find anything different except that the large vessel occlusion patients
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  were slightly older as compared to those with medium vessel occlusion and the
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  the patients with large vessel occlusion had a higher percentage of poor collateral
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  scores compared to the medium vessel occlusion, but otherwise,
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  their baseline characteristics were pretty much similar.
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  And we also, in our results, did not
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  find that home time was significantly different between the two groups.
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  And on further doing random forest regression, we found that there was not much
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  difference between the home time in patients with MEVO as compared to LVO after
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  adjusting for all other covariates.
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  And yeah, so, but, you know, having said that, there are certain limitations to the study.
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  Big case this is non-branded data we've collected it
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  from provincial registry and the primary
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  outcome of 90-day home time although has it has been validated
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  against MRS and multiple studies it is not something that is routinely collected
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  in clinical times trials so date direct comparison with other data is is difficult
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  only patients who underwent EVT were included in the study so we don't really
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  know what happened to the MIMO patients who actually did not undergo EVT as a competitor.
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  And overall, the numbers are small. There are a lot of ongoing large randomized
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  studies which will help us answer this question.
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  Current guidelines only recommend endovascular treatment for the artrosis occlusion.
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  Having said that, you know, amongst the physicians and the interventionists,
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  there is not much echo poise for proximal M2 occlusions.
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  And there is enough data published in literature that we do end up treating
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  proximal M2 occlusions endovascularly, especially if they have disabling deficits.
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  Apart from that, the guidelines do not recommend endovascular treatment for
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  distal M2s, A2s, or P2s or M2 occlusions.
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  We have the ESCAPE-NEVO trial, which is ongoing as well as the DISTAL trial.
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  So ESCAPE-NEVO is out of Calgary with multiple sites across the world.
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  Similarly, DISTAL is a trial out of Switzerland with multiple sites across the
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  world, and they're They're trying to randomize patients with medium vessel occlusion
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  into standard of care or endovascular treatment arm.
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  And, you know, this is the data from this is potentially going to help change guideline.
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  I think the biggest challenge for treating medium vessel occlusions is or randomizing
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  patients in trials with medium vessel occlusion is if you have tape for poison or not.
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  So these trials do include proximal M2 occlusions. And I said,
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  as before, that, you know, many people just go and treat these proximal M2s.
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  So it might be a challenge to enroll these patients in a clinical trial where
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  there is a 50-50 chance that they might be in the control arm.
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  So that is one big challenge.
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  Having said that, there is also this concept of primary MEWOs versus secondary MEWOs.
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  And primary MEWOs is, you know, when we see that the occlusion on a CTA is in
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  one of the medium vessel occlusions and secondary MEVOS are something which
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  can be out of because of the intervention or it could just be that the clot migrated.
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  One challenge in medium vessel occlusion is also because these patients have
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  relatively minor deficits. So what would be a good
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  primary outcome, is it MR0 to 1, is it MR0 to 2, and how much difference or
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  what effect size would be sufficient to call it significant enough to change guidelines.
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  So those are the challenges that are anticipated.
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  Finally, we will be hearing from Jan Gweller from Insul Spital Adversity Hospital,
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  Bern, who discusses the efficacy of endovascular interventions in small strokes,
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  specifically exploring endovascular mechanical thrombectomy.
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  It's a very interesting topic because since we have the large randomized controlled trials in 2014.
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  The large vessel effusions are, I wouldn't say sore, but at least there has
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  been shown lots of potential for mechanical thrombectomy in endovascular interventions.
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  For peripheral strokes, small vessel stroke, this is a bit more complicated
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  because patients present with with few neurological deficits because of the smaller territory.
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  The vessels themselves are smaller as well, and they're in a torturous anatomy.
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  So it's much more interesting to see whether endovascular treatment is successful there as well.
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  But definitely it's an important topic because some patients don't have any
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  other possibility than endovascular treatment.
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  So far, there are a couple of randomized control trials on their way.
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  Basically, we can distinguish between two different categories of small vessel stroke.
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  One is the primary occlusion. So patients present with this particular occlusion
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  from the beginning, and they are either non-eligible for IV therolitics.
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  So again, we don't have any other treatment possibility.
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  Or they have dislodged the thrombus or the larger thrombus from the proximal
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  vessel to this distal vessel under IV treatment.
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  Nevertheless, they present with an occlusion distally to the large vessel, so a small vessel.
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  The other group are those in which the large vessel occlusion has been recanalized
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  by using endovascular thromectomy, for example, and there's a remaining occlusion
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  In both categories so far, single arm prospective or retrospective studies have
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  shown that endovascular treatment or more general recalibration is helpful.
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  But this has not been shown on a randomized patrol level for each group yet.
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  I think the techniques are pretty similar to what we use in large vessel occlusions.
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  So the endovascular techniques are either stent shiever thrombectomy with all
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  its pros and cons, in combination with local aspiration or in combination with
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  the Ruhlgaard catheter.
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  Then diuretic aspiration, which from my point of view has some potential there
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  because the mechanical force that we apply to this vessel territory might be less.
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  And then the third option, which I think might be very, very interesting,
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  is intra-arthrofomalysis, either on the basis of RTPA as standard or formally
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  with urokinase or with new approaches such as synaptoplace.
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  So three different approaches, two mechanically and one pharmaceutical intervention.
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  Well, I think the most tricky part is we know that IV thrombolytics are very
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  effective there. So, from my feeling, this might not be the group in which we're
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  going to investigate mechanical sumpectomy first.
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  So, the patient is eligible for audiopharmaceutics. I think that's a very,
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  very good target to go for these small vessel diseases or small vessel strokes.
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  As we have learned from previous stroke studies,
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  the imaging, especially the imaging of the remaining vital tissue,
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  issue, meaning the pin number, will be crucial to determine what kind of technique is successful.
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  So I think if we go into studies, you have to be sure that the overall population
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  is not blurred by patients who cannot gain any benefit from recalibration at all.
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  So I think the imaging will be a crucial point here. I think in the end,
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  we have seen so many surprises in randomized controlled trials in the recent
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  years and basically weeks, there has to be a randomized controlled trial on
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  these different topics.
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  So primary, small vessel occlusions, secondary, small vessel occlusions,
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  and they're on their way.
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  So we look at two randomized controlled
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  trials on medium and small vessel occlusions in the primary setting.
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  And there is a new trial which has recently been supported by the Swiss National
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  Foundation called TECNO, which took place in the secondary occlusions after
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  the mechanical thrombectomy. I think this is what we have to look at.
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  What we have seen so far is the
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  mechanical thrombectomy, or let's say the endovascular treatment of OSTOC,
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  can be very, very successful if conducted in a clear setting with a clear procedural
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  pathway and a clear way of doing it, which device to use when.
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