Unraveling Cryptogenic Stroke

Dr. Johanna Seiden joins us to talk about a challenging topic, cryptogenic stroke. What do you do when you need to look beyond the obvious causes? Dr. Seiden gives some useful recommendations and idea for further investigation in some of the toughest stroke cases.

Find her online at @JohannaSeidenMD

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The views expressed do not necessarily represent those of any associated organizations. The information in this podcast is for educational and informational purposes only and does not represent specific medical/health advice. Please consult with an appropriate health care professional for any medical/health advice.

Chapters

• 0:00 Defining Cryptogenic Stroke And ESUS
• 2:15 Why Anticoagulation Isn’t The Default
• 3:40 When To Hunt For Rare Causes
• 6:50 Smarter History Taking For Clotting Risk
• 9:50 Stop The Scattershot Thrombophilia Panel
• 13:05 APLS: Tests, Risk Tiers, And Treatment
• 20:05 AdamTS13, TTP, And Atypical Presentations
• 27:00 JAK2, MPNs, And Stroke Patterns
• 31:40 Cancer-Associated Stroke And Workup
• 37:20 Drug Effects, Anticoagulants, And Tradeoffs
• 41:30 PFO: Who To Image And Who To Close
• 48:45 TEE vs TTE And Practical Logistics
• 53:20 The Judgment Calls That Keep Us Up
• 57:35 Sickle Cell Disease And Stroke Pathways
• 1:07:30 Teaming With Hematology And Follow-Up
• 1:08:20 Closing Remarks And Where To Find Us

Transcript

Michael Kentris: 0:01

Hello and welcome back to the Neurotransmitters, your podcast about everything related to clinical neurology. I'm your host, Dr. Michael Kentris, and today I am pleased to introduce our guest, Dr. Joanna Siden, a vascular neurologist at Montefiore Medical Center in the Bronx. And I'm really happy that she's coming to talk to us today, because this is a topic that I struggle with a lot as someone who has to frequently cover the inpatient neurology service, and that is the evaluation of stroke, in particular cryptogenic stroke, in particular thrombophilia coagulability type issues. So, Joanna, thank you so much for coming in, and I am really looking forward to some knowledge to drop on us today.

Johanna Seiden: 0:41

Thanks for having me. Yeah, I'm excited to be here and kind of yeah, talk about what to do in these tricky, tricky stroke workups.

Michael Kentris: 0:50

So cryptogenic stroke, right? It's a very mysterious sounding name. But what do we mean when we say cryptogenic?

Johanna Seiden: 0:59

Yeah, so cryptogenic stroke kind of means that it is any sort of stroke that we don't have a clear cause for. So a stroke that could be small vessel disease, could be large vessel disease, but we haven't figured out the clear etiology of it, despite a rather complete workup, which typically includes like an MRI of the brain, vessel imaging, an echo, some sort of cardiac monitoring, looking for stroke risk factors like hypertension, hyperlipdemia, diabetes, and all of that done without a clear etiology. And that's somewhat related to this concept that you might have heard of of Aesis or embolic stroke of undetermined source, which has a lot of overlap with cryptogenic stroke, but just means that the only difference is that it clearly looks embolic, but we haven't found where that stroke originates from, whether it's like atheroembolic or cardioembolic or embolic from some other source in the body.

Michael Kentris: 2:07

And you know, I know there's been tons of trials, in particular about the ESUS phenomenon. Like, should we just anticoagulate these people and call it a day? And it seems like time after time the answer is kind of like probably not.

Johanna Seiden: 2:21

Yeah, it's it's really tricky. And I think I think the trials so far have been a little bit disappointing, the results of them anyway. But at this point, we're kind of still left with treating them for the most part with aspirin until we find that clear source.

Michael Kentris: 2:40

Gotcha. Now, cryptogenic stroke in particular is it's one of these very frustrating things, especially if we have someone maybe on the younger side, like late 40s, early 40s, maybe even younger in some of these very unusual cases. And like you said, they don't have the classic cerebrovascular risk factors. And we're like, well, why did this person have a stroke? And like you said, the cardiac monitoring that's been going on and all that jazz, everything's come back unremarkable, no etiology found. When do we dive deep into some of these more esoteric, unusual type entities?

Johanna Seiden: 3:14

Yeah, yeah. So, you know, I think when something in the story just doesn't really make sense for an ischemic stroke in someone who, again, doesn't have those typical vascular risk factors isn't the normal typical age. So, as you said, like someone who's a little bit younger. So Yeah, I think we start to look for these more esoteric diagnoses when certainly like an embolic appearing stroke has occurred in someone without these typical vascular risk factors, without um not being the typical age. So, as you said, like someone who's a little bit younger. Um and a lot of it is in the history, other medical problems, history of sort of like clotting in other areas. And that kind of you know gets us into some of these specific etiologies. But we're yeah, we're kind of taking a very uh detailed sort of clotting hypercoagulability history, finding if there's any like family history of this, and kind of going from there.

Michael Kentris: 4:17

So a lot of times, I'm just thinking back to kind of my own practice to an extent, for better or worse. And a lot of the questions I'll ask, like history of different clotting events, so kind of like unprovoked clotting like DBTs or pulmonary emboli, things like that. And then in particular in women, if there is a history of spontaneous miscarriages or other kinds of difficulty getting pregnant, things like that. And then kind of broadly speaking, symptoms of usually I'm asking kind of symptoms of like autoimmune conditions like lupus, is that is that enough? Or what else should I be asking about?

Johanna Seiden: 4:52

Yeah, um I think I think that's that's right. Right. So we're asking like, uh, does anyone in your family or have you had any history of clotting either in the extremities or in the brain, in other parts of the body, asking about those history of like miscarriages? Sorry, I'm just looking at this really fast. So um from what I remember about about the APLS like obs obstetric criteria, it's like recurrent miscarriages. And I I heard actually like this this great podcast by Curbsiders interviewing Dr. Ariel Linger, who's a hematologist who specializes who does a lot with APLS, and and she did a they did a whole podcast on this. And and she was saying, you know, in someone who has had a lot of pregnancies, you want to kind of understand the work up um and have have they had pregnancy loss in a row? I can't sorry, I can't hear you.

Michael Kentris: 5:54

So an isolated miscarriage in and of itself, probably not enough to be a red flag, but like you were saying, the serial events or these recurrent events certainly raises a little more suspicion.

Johanna Seiden: 6:06

Early miscarriages before like 10 weeks, and then I think also having three sequential spontaneous abortions or prematurity due to vascular disease. Those are kind of the obstetric concerns. So it's not really like I had two healthy births and then I had one miscarriage, and then I went on to have multiple other ones. It's more like these continuous ones are very early.

Michael Kentris: 6:30

The vascular events, would that be like like help syndrome or eclampsia, pre-eclampsia, that kind of thing?

Johanna Seiden: 6:36

Yeah, yeah, exactly.

Michael Kentris: 6:38

Okay. That makes sense. So, you know, one of the things, especially when I don't find anything in the history, which I feel like is all too often, is we send all these hypercoagulity labs. And there's a lot of them. And I've I've heard a lot of commentary on them in the past where basically they were criticizing neurologists for ordering too many labs and not knowing what they're looking for, and probably guilty as charged. So how do we tailor this in? Should we be ordering kind of a a panel, quote unquote, versus like kind of trying to be a little more surgically selective with single labs?

Johanna Seiden: 7:15

Yeah, yeah, it's a great question. And I feel like this is a product of like the dot phrase. And I think, you know, as a resident and trainee, I, you know, I had a dot phrase for hypercoagulal workup and it had everything in it. And as I've kind of gotten more advanced in training, I've kind of realized that a lot of the workup that I was sending was really not appropriate for arterial stroke. So again, we're talking about arterial stroke. Um the if there's a PFO that kind of changes things a little bit, maybe. I mean, there's not great evidence for that, but in an arterial stroke for this sort of hypercoagulable workup, we're we're sending very few labs. So we're sending APLS, we're sending Jack 2, we're sending Adam TS13, and that's pretty much it. Those are, you know, the ones in in our institution that that um that we routinely send. These other ones that you know used to be in my dot phrase of like protein C and S and factor V Liden and anti-thrombin, the pro thrombin like G20210, all of that, um homocysteine, those are really for venous infarcs. And I think those, even for venous infarcs, it's the evidence is pretty poor. So this goes back to like the fact that these inherited thrombophilias are present um in the general population up to like 5% for factor five Leiden. And they really don't end up changing management even if they're positive. So I think that's like kind of what this all boils down to is are we sending things that, if positive, would really change management? And if the answer is no, then you know, I don't think that they're worth sending. So, like right now, the American Heart Association, American Stroke Association doesn't support routine thrombophilia testing in patients. And there was a study by a group in Colorado that showed that two of five patients who underwent this thrombophilia testing had at least one positive test, but only one in 12 ended up having a change in management related to that test. This was mostly in young patients, and most of the patients who ended up having some sort of change in management, it was because of APLS. These tests also cost a huge amount of money, up to like two or three thousand dollars. They're not always covered by insurance. And they're, they're they're not recommended. They like, there is some data that these sort of venous-related thrombophilic states are associated with higher stroke risk, but stroke recurrence itself is not higher in those patients with thrombophilic states versus the general population. And it's not really shown to make a difference. These patients would be on aspirin, kind of regardless of whether the test is positive or not. So it's not going to change management. And I think, you know, the caveat of all of this is that if there is like a paradoxical emboli from a venous thrombosist, some of these may become more appropriate. But even that is not clearly guided by by evidence at this point. So, you know, I think for for me, when there is a venous, venous, thrombosis, venous event, I'm more likely to send these these tests, but whether it ends up really changing things is, you know, not entirely clear because the PFO will probably be end up being treated or kind of fixed whether or not these tests are positive.

Michael Kentris: 11:00

Yeah, I make sure. And we might come back around to uh PFOs in a little bit, because I certainly have some questions on that one as well. Uh but as far as anecdotally, again, I I definitely have had people who come back like heterozygous for some of these gene mutations, and I'll send them to hematology for a second opinion. And I'm like, yeah, aspirin's fine. And I'll be like, okay.

Johanna Seiden: 11:25

Yeah. Yeah.

Michael Kentris: 11:26

And it it does, it happens all the time. Especially when I, like you said, I get like those PA PAI uh mutations and things like that. I'm just like, I don't know what the heck this is. Um it's like there's a like a mildly increased risk, like you said, of venous usually. But I'm just like, well Does that change anything? Probably not that much.

Johanna Seiden: 11:46

Right, right. Uh uh, it's like fixing it's our curiosity, but it doesn't really make a difference for the patient.

Michael Kentris: 11:52

Uh no. And that's that's always the frustrating thing. Uh-huh. Especially when you do have these younger people who have a stroke for for no apparent reason. Um And again, it's one of those things where like sometimes they maybe have like pre-diabetes and mild hypertension, it's well controlled in meds. They're in their mid to late 40s. Is that enough? Like, do I need to keep looking? I don't know. Just painting that broad picture. What are your thoughts?

Johanna Seiden: 12:17

Yeah. Um I think in a young person with stroke, if we're gonna blame it on vascular risk factors, they gotta be like pretty severe. Um, I think mild hypertension, mild hyperlipidemia, pre-diabetes, it's not a slam dunk for kind of athero as the as the cause to not look at least look for these other these other etiologies. The frustrating thing is I think even at the end of all of this, there, you know, we have to recognize that there are going to be like a third to a quarter of patients who end up still being cryptogenic. And if we look back at these patients 20, 30 years from now, I think you know, we're gonna have answers to why these many of these patients had strokes. This is still such an evolving field, but there are this proportion of patients who end up um, you know, with we don't know sort of sort of situation. But but they do deserve like a as complete and appropriate a workup as we can do before we label them like that.

Michael Kentris: 13:26

If it is kind of an easeless-looking picture, I know insurance can be tricky for some people. So you end up doing like a two-week or however many weeks insurance will grant you, like a xyopatch or holter monitor or some sort of cardiac event monitor. Do you always send them back for like an implantable loop recorder?

Johanna Seiden: 13:44

Um if they I you know, I I think the implantable loop recorder is obviously so much more sensitive than a two-week monitor, especially if that two-week monitor is being done not directly after the event, but you know, a month later, two months later when you see them in clinic. So if someone is is willing and my suspicion is high enough for it being being embolic appearing, then I would rather go for the loop recorder. But that's obviously not uh totally my decision. So, you know, uh want to make a a good case for it.

Michael Kentris: 14:21

No, that's that's totally reasonable. And I know I've drifted off our primary topic here.

Johanna Seiden: 14:26

No, it's fine.

Michael Kentris: 14:28

Getting back to kind of our our coagability, so you mentioned the antiphossolipid antibodies. So walk me through these. I know that they're kind of associated with things like lupus and so forth, but what uh what is our their significance and why why should I, as a neurologist, care about them?

Johanna Seiden: 14:50

Yeah, it's a yeah. It's a good question. And I think I think APLS, these labs can be like really confusing, and interpreting them can also be really confusing. And um, luckily we're not always doing this in isolation. We are lucky enough to usually have hematology colleagues um helping us out. But basically, these these antibodies and and um serologic tests that we're we're using are testing whether the patient's body has these antibodies that recognize clotting and kind of overactivate it. So um, you know, a lot of people have these inherent antibodies. Let me sorry, I don't like the way that I'm saying that. Um the antibodies are recognizing these bodies wanting to sorry, it's really hard to explain this. Yeah, so I I think that these that the antibodies are are being activated in patients who have this kind of clotting system that's being overactivated in the in the setting of of a lot of inflammation. So there are three tests that we send: lupus anticoagulant, cardiolipine, and beta-2 glycoprotein. The lupus anticoagulant is really like when PTT is elevated and doesn't correct with the addition of fresh frozen plasma. This one is the most um the most high risk for thrombosis, both arterial and venous, compared to the other two antiphospholipid antibodies. And we should keep in mind that this one is also affected by anticoagulation. So if a patient's already on AC, this um this can certainly be um influenced by that. And you know, this is why we end up needing to recheck this lab about 12 weeks later to confirm that, um, to confirm the finding. Cardiolipin and beta-2 glycoprotein are both um are both ELISA-based. The elevated cardiolipin is either an IgG or an IgM, um, antibeta two glycoprotein as well, an IgG or an IgM, and they're both affected by inflammation. And we're looking at titers for these. So we're looking at a titer, I think the lower limit is 40, so greater than 40. And again, the like the the titers mean something. So the higher the titer, the more the body is is being overactivated by this. So we need two positive assays that are separated by six to 12 weeks. And the amount and which which test is positive gives us kind of a spectrum of risk. So a high risk um APLS binding would be a positive lupus anticoagulant plus either anticardiolipin or antibeta two glycoprotein being positive or neither. So having a positive lupus anticoagulant is the most most concerning, and that would be a high risk. So you could also have double or triple positive. The low risk would be an isolated anti-cardiolipin antibody, an isolated beta-2 glycoprotein at like low to medium titers, and then uh, you know, having one just one of these very, very low titers is probably less likely to be to be APLS. So that these are the lab findings, but in you know, we also have to have a clinical finding. So the Sapporo criteria requires the presence of both, um, both clinical and lab related. So the clinical findings, we kind of talked about this already, but it's the presence of some sort of thromboembolic event. So stroke obviously fits into that, or a pregnancy-related complication. So those are the clinical ones. Yeah. So management-wise, we want to treat these aggressively. So the data suggests using warfarin, um, warfarin rather than doax. Multiple studies have shown that warfarin um does better than doax. Um so usually we're doing warfarin with an you know a typical INR goal of of two to three. There have been some studies asking whether like a higher INR goal is is more um is better and it it hasn't they haven't shown um positivity. Some people end up adding aspirin as well. I don't think there's really good evidence for that, although evidence of downsides of that are also like not um not super clear. So I think if someone is having like severe clotting events or clotting through anticoagulation, I think at that point um that's what we're adding.

Michael Kentris: 19:53

Gotcha.

Johanna Seiden: 19:54

But we're again, we're doing this like with hematology. Usually they're they're kind of helping guide the treatment. Based on how the uh the degree of of positivity of these tests and and the clinical story.

Michael Kentris: 20:08

That makes sense. Thank thank God for hematology.

Johanna Seiden: 20:11

Yeah.

Michael Kentris: 20:13

I know uh because I only get these labs on maybe one patient every two or three months, and every time I have to like go back and flip open some resource to read about like what does this mean, what does that mean? And be like, is this should I be worried about this or not? Like you said, uh a lot of times I will get like like a weekly positive anti beta two, and I'm just like, is that enough? Like, oh, I guess not. Um and it it does it's very frustrating sometimes just because like you were saying, with these criteria, the clinical criteria is like, well, a thermometer embolic event, obviously, if we're on the case, it's because they've had a stroke. Is that enough to meet the criteria in the presence of, let's say, medium tighter antibodies?

Johanna Seiden: 20:55

Yeah, yeah, it's a great question. So I I think one of these things is like is the pretest probability. So if this is a patient who doesn't have these classic vascular risk factors, um, is young, you know, our pretest probability is already pretty high to for these tests to be appropriate to send, where if you end up with a positive result, it's real. So I think that that's why we're we're not sending these on every patient. We're not sending these on patients who have like a really good reason to be having be having strokes. So I think if it's a young patient who doesn't have any other clear reason for strokes, and we get these kind of middle of the road titers, sometimes we'll end up treating at that point, and sometimes we'll end up repeating the test, wait, you know, waiting to treat until we repeat the test. So how this has been explained to me is those the tests are confirmatory, but if you're concerned that this patient is, you know, in a like florid APLS crisis, that we're not gonna wait until 12 weeks to start treating them. So it depends on the story. But I think those repeating the test a 12 week kind of tries to weed out a lot of this. And sometimes the test can be positive initially because of, you know, the reason that the patient's in the hospital anyway. So both the cardiolipin and the beta 2 are affected by like inflammation in the body. So again, like a lot of patients in the hospital have some sort of inflammation going on. So if those are positive and then you repeat it and then it's normal, then probably that wasn't that wasn't the cause in the first place.

Michael Kentris: 22:39

Gotcha. And I don't know if you know the answer to this or not, but sometimes I wonder if we have one of these patients and they receive like IB thrombolytics, you know, on initial presentation. Again, it's one of those things where like how valid if we draw it during like even like a a day or two later, is that going to affect any of these markers? And I don't know if that's something that's ever been studied. I imagine a data set, if it exists, is small.

Johanna Seiden: 23:04

Yeah, I'm yeah, I'm not sure of any specific studies about it, but the the lupus anticoagulant, I think, would be the one that could be affected by this. Um I think it's still worthwhile to have that have that initial draw after the patient is on some sort of blood thinning medication or received some sort of blood thinning medication. And then when you get your repeat, you have something to compare it to. But yeah, it's it's a good question, and and I'm sure you know we'll we'll have data that that supports that moving forward.

Michael Kentris: 23:35

That makes sense. Now the other two tests that you said that you routinely check for are the um the Jack 2 and the was it the Adams T.

Johanna Seiden: 23:43

Yeah, yeah, yeah, exactly. The you know, the Adam TS13, which if you don't routinely send this, it can be like, wait, I remember hearing about this lab like back in med school and I don't remember what this is.

Michael Kentris: 23:56

So that that is me, yes.

Johanna Seiden: 23:58

Just some background on that. So that is a uh is a test that we send when we're looking for TTP. So that remember that's like a microangiopathy that results from some deficiency in this metalloprotease atom TS-13 that regulates von Willebrand factor, another blast from the past, and it it cleaves the like really large von Willebrand factor and prevents spontaneous coagulation. So if you have um an atom TS-13 deficiency, then you're not able to prevent spontaneous coagulation, you end up being hypercoagulable. So this is this is characterized by hypercoagulity, acute hemolytic anemia, thrombocytopenia, end organ damage, super high mortality, like up to 90% if it's not treated properly. And we all kind of learn this like pentad of symptoms of thrombocytopenia, hemolytic anemia, fever, neurologic, renal complications in patients, but you know, all five are present together only in like less than 10% of cases. There can be small and large artery infarcts in these patients. And I think what's the most interesting development in TTP research is that there's evidence of atom TS-13 deficiency even when platelets are normal or not so abnormal. So that's super scary. And you can also have uh, yeah, so platelets and hemoglobin really being being normal. So they're they can have like atypical neurosymptoms, they can have like some sort of cytopenia, they might not need to, but no, they're this again, going back to like does the test being positive change management? Absolutely, because these patients need plasma exchange, and uh, you know, we're avoiding this really high mortality rate. We tend to send this in in patients who have sort of this cryptogenic stroke of unclear radiology, certainly if there's low platelet levels or anemia, but even even if there isn't. So, for example, I recently had a case of this 80-year-old woman who presented multiple times with these bilateral embolic showers. She kept having kept having more events despite being on the typical stroke medications of aspirin, lipitor. She had like a complete workup. She had vascular risk factors too, which made it really difficult. And we ended up placing a loop recorder, which wasn't showing any events. She kept stroking, kept stroking. They looked very embolic. And ultimately, after this sort of risk-benefit discussion with family, we ended up starting empiric um anticoagulation, which, as we talked about, is not evidence-based, but you know, I didn't know what else to do. She kept having these strokes. She had normal platelets. Um, and then she presented like a fourth time, again, with this like with altered mental status, had this teeny little cerebowler infarct, super small, and she had platelets of 148,000. We checked Adam T, which is you know, 150,000 is like the lower. Yeah. So we check and we checked and it was positive. And you know, the mistake, I think, was that we had I hadn't checked after her third stroke, after her fourth stroke. Um we, you know, I we h we weren't routinely doing this in in our practice. Um, but there have been, you know, a bunch of at least two case series um that have come out about TTP kind of presenting in the in this sort of atypical way. Um and, you know, because of this, we now are are are checking more routinely. So this patient, you know, we stopped the eloquist, she's just on aspirin, she's getting these therapeutic plasma exchanges. And you know, hopefully this is the end of of her stroke journey with us. But it was just one of these cases where uh the that positive result totally changes the course of her treatment. So it's it's worth sending.

Michael Kentris: 28:07

No, that's fascinating. Yeah, it's it's definitely not one that I think of as often as I probably should. So I'll have to keep that in mind.

Johanna Seiden: 28:16

You know, it's it's and it's not it's not in the guidelines. This is like not recommended by the Stroke Association, but it's uh I think I think there's gonna be more coming out about it, and um, you know, it's something to consider um in in some of these Aesus sort of patients.

Michael Kentris: 28:34

That's the the challenging thing because sometimes you think like someone comes in little platelets, well, I imagine she was bent on some anti-platelet medication for a period of time at this point, and so you do start to like kind of second guess yourself, I would almost imagine, like, is this a side effect of the medications I've been giving her? Is this something her body is doing? And yeah, it can be a real conundrum.

Johanna Seiden: 28:56

Yeah, totally. Yeah, I went back um through her her platelet levels through the years because she started having strokes like two years ago. And for the most part, when she would come in, they were normal. But then during the course, they would dip, they would dip down and then come back up. And I, you know, I think we when we see that in our inpatients, we kind of come up with lots of reasons why that could be happening. Right. Oh, it's dilutional or yeah, yeah. All you know, all sorts of things. But I think that's also something to be aware of when you don't you don't initially send it on a patient, it looks fine, and then someone starts to get thrombocytopenic. I think um, you know, that's it's also something that that we can send later later on during their course.

Michael Kentris: 29:42

This is probably my own ignorance speaking, but I tend to think of with like TTP, like the papura, right? Like the big skin manifestations are uh the thing that come to mind. Do these patients tend to have those typical skin manifestations or are they a little atypical on that front?

Johanna Seiden: 29:58

I think they tend to be um, you know, I think there's mixed, mixed findings, but I I you know I think the lack of that shouldn't make us not not check it. I haven't seen any TTP stroke patients who have had that, but I but I really don't know like how often that is is present.

Michael Kentris: 30:16

I mean, yeah, you see someone with a big honk and bruise somewhere on their body that's not traumatic, like that's gonna raise some red flags. But yeah, if it's not there, it's hard to harder to say.

Johanna Seiden: 30:26

Right. And if it is if it is there, these patients are getting like daily heparin injections, like sort of you know, other reasons.

Michael Kentris: 30:34

Explain it away, yeah.

Johanna Seiden: 30:35

Yeah, yeah, exactly. Exactly. Yeah, so that's so that's that's the story of of Adam TS13. And I, you know, I I'm excited about these cases. I think you know, we've we've at our institution are kind of going through back through our data to see how often we're getting these cases, and hopefully we'll we'll you know write up some write up like a case series about this. But but I know that there has been one that's come out uh a couple years ago, and and it really is our hematologists who are who have this in their uh in their hypercoagulable workup for the past couple years based on some of this data.

Michael Kentris: 31:12

Excellent.

Johanna Seiden: 31:13

Yeah.

Michael Kentris: 31:14

So what other entities should we be thinking about as we as we go through this clotting landscape?

Johanna Seiden: 31:22

Yeah, yeah. So um the other one that we that we often will send is JAC2. So it's like a one of these myeloproliferative neoplasms, and it's it can be found in like three percent of the general population, but patients who have ischemic strokes are about two and a half times more likely to have JAC2 positive. And the prevalence of it in like TIA and strokes, at least in one study, is about 11.4%, which is eightfold higher than those who don't have um TIA or stroke. And remember, smokers have a higher risk of having this positive. So it, you know, it seems to induce a prothrombotic state. We don't have like clearly elucidated pathogenesis for it. Um most common presentation for for strokes related to JAC2 are large artery occlusion, but we can also get strokes that that look more embolic in nature. So um we tend to to send this certainly in the setting of like thrombocytosis above 450,000 or hemoglobin levels that are elevated. Again, and this is this is not recommended. Um, this is not you know guideline based, but but we're also sending these in in patients who do don't have those those specific findings because again, it really will um change management, these patients will have um will get uh get treatments that'll kind of thin out their blood. And um, you know, it that ends up being their their course of stroke prevention. Oh this one I don't think there's much as much uh clear data on, but you know, we've seen this in cases, and so like to be on the lookout, especially if they have these these abnormal lab findings, and if they're smokers.

Michael Kentris: 33:19

Right, right, right. And I tend to think, and again, my my hematology is rusty, as we were saying before uh before we started recording. Uh I tend to sometimes think, is Jack 2 also sort of things like like polycythemia vera? Am I remembering that correctly?

Johanna Seiden: 33:34

Yes, yes, okay, exactly. Yeah. So yeah, you're checking like the EPO level and and whether or not the EPO level is is is positive or elevated or or low, then it's polycythemia or it's primary. So um so yeah, we recently had a case of someone who like a 60-year-old smoker came in with cryptogenic sort of stroke and ended up he actually came in with this like erythrocytosis of unclear radiology. It turns out he wasn't his JAC 2 was negative, but he had he had very high hemoglobin levels and ended up getting these treatments throughout his course and was a smoker. So higher risk uh, you know, did did end up needing needing these treatments as a result.

Michael Kentris: 34:24

Gotcha. I tend to think of this perhaps overly simplified as the case where the medieval bloodletting is still applicable.

Johanna Seiden: 34:32

But uh it is, it yeah, it totally is. That's so true. That's so true. Yeah. And I guess the other, like the other big umbrella of of this sort of hypercoagulable workup that we do is is assessing for any sort of malignancy in in anyone with a cryptogenic stroke or an embolic stroke um where we haven't yet found AFib, which is majority of the embolic stroke sort of patients, is I, you know, I always like to ask first, are they up to date with cancer screening? So in females, have they gotten recent mammograms? They got and in everyone about colonoscopies. So I always ask that. I ask about like constitutional symptoms, so any recent weight loss, um uh you know, like hot flashes, unexplained fatigue, which I feel like everybody says yes to. But yeah, because like similar to this sort of atom TS13 where stroke can be the first presentation of TTP, stroke can also be the first presentation of malignancy. So the risk of malignancy, or the risk of stroke rather, peaks about one month before the diagnosis of malignancy in many cases. 15% of patients with malignancy will suffer from stroke. That's like two times higher risk than patients without malignancy. Um, and you it's not really clear whether the mechanism of this is is directly from the tumor itself or coagulopathy or iatrogenic, but things that kind of clue us into this potentially being related to an underlying malignancy. We hear about this T sign or three territory signs, so seeing embolic appearing strokes in three different vascular territories or both posterior and anterior, seeing unexplained weight loss, an elevated D-dimer, which again is a is a lab that can often be elevated in our in our stroke patients, but being very elevated is is something that clues us in an increased CRP, also nonspecific, anemia, low albumin. So if there's any sort of atypical features of the case, something that's that's you know making us think that perhaps this could be, and of course, a history of smoking is another one too. But um, we do end up like checking a CT, chest, abdomen, pelvis just to make sure we're not missing any any like very clear lymphatinopathy or any solid tumor. Um, because we have certainly seen that um, you know, these tests end up showing something, and then we, you know, we know the reason for the stroke in a lot of cases. Management-wise, you know, there is a lot of there is a lot of or some evidence that anticoagulation is better than aspirin for these patients. Initially it was like kind of modest evidence of parental AC, so heparin or lovenox being the being the treatment of choice. There was some concern of increased bleeding risk, and there's, you know, some obviously it's inconvenient for patients. There's some decent evidence that do Ax are appropriate for preventing venous thromboembolism in patients with cancer. There's more of an evidence gap for arterial clots. So um I think a lot of us have have shifted from saying Lovinox to using DOAX now, but you know, the caveat is that there is not clear evidence from an arterial standpoint, but it it you know it it has been supported from a venous standpoint.

Michael Kentris: 38:08

Gotcha. And I tend to think, uh just to clarify, in my mind, I tend to associate the hypercoagulable state more with people who are with like kind of more diffuse metastatic cancer rather than someone with like a focally invasive cancer. Is that typical, or can you still see that hypercoagulability creeping up with someone who maybe has like say a grade one or grade two kind of like lung cancer or something like that?

Johanna Seiden: 38:33

Yeah, yeah. That um I I think you know obviously the more active, metabolically active cancers, I think, have a higher risk of of hypercoagulability and and stroke, but I think we can see them in in just like solid tumors too. So yeah, so so so worth worth checking. You know, again, this is kind of like looking for the like uncovering the reason for stroke, but but certainly we see a lot of patients who have underlying cancer um that is being treated coming in with it with stroke too. So you know, we're not always uncovering, unmasking this. Sometimes you know it's it's being given as the clear. Yeah, exactly.

Michael Kentris: 39:18

Now, just to add a wrinkle there, if I may. Because as you were mentioning, right, is it the cancer, is it a result of the treatments? And especially with the way that a lot of chemotherapy is evolving these days with some of the checkpoint inhibitors and the CAR T modulating and all that kind of jazz. We're starting to see a lot of these unusual neurologic uh symptoms. Uh has that been showing up? I know on the general neurology side of thing, you know, I've been seeing cases like autoimmune induced, or I should say uh like uh checkpoint inhibitor induced like myasthenia, guy and barray, stuff like that. Are we seeing similar entities evolving in the stroke field as well?

Johanna Seiden: 39:56

So I I definitely haven't seen as many of these cases. As I did when, you know, as a resident. I think there are like one or two cases where someone's on a particular um agent and we end up finding a few case reports that are that are supporting that, you know, strokes can be due to these medications. I think more frequently it we end up kind of attributing it to just a general hypercoagulability and not not the treatment specifically. But but I don't think we know.

Michael Kentris: 40:26

Yeah. I I mean, unless you said, I think I've seen maybe one or two cases in the last handful of years where someone was on like bebysisiumab for I forget what kind of cancer they were getting treatment for, but right, one of those vascular endothelial growth factor inhibitors, which we know can do like, you know, vascular injury, like with heart attack, stroke, things like that. So in that particular case, I'd recommended maybe not using that for future treatments if possible, but it does become a little bit of a rock in a hard place in terms of someone with usually if they're using something like that, a fairly aggressive cancer versus the risk of further vascular injury.

Johanna Seiden: 41:03

Yeah, yeah, it can be really challenging. We usually try to speak to the oncologist and kind of asking them in their experience have they seen other patients who've had this sort of event on this medication and you know, we're kind of coming from two different places, but I agree that that taking someone off of a medication, especially if it's helping because of the this question of maybe it being the cause, um, I would say we don't often feel that that is the best way forward. I think we, you know, more often we tend to just recommend some sort of blood thinning medication to try to to try to help decrease the coagulability in the patient.

Michael Kentris: 41:45

Right. Definitely a risk versus benefit. Uh no, no clear answers in those situations, usually I'd say.

Johanna Seiden: 41:50

Yes. And you know, that also to add even another wrinkle onto this, definitely had patients come in who are already on a blood thinning medication for the cancer, come in with another, another embolic appearing stroke. And, you know, there's quite the the team will ask, well, should we switch the blood thinner to another another blood thinning medication? Maybe they're stroking through Lovinox, but should we do, you know, eloquence? And we don't have the answer for that. I I I don't think we don't think the suspicion is high enough that it's the problem is the specific anticoagulant. I think it's that, you know, perhaps the underlying coagulability is just is just too high at that point. So yeah, they can be really, really sad, tough cases on for patients who are already dealing with with so much.

Michael Kentris: 42:40

I don't know uh if you're a Star Trek nerd like I am, but I remember this one one line from Captain Picard where he was saying, like, you can still do everything right and still lose. Yeah. Which, you know, it's on the one part, you know, you can you can be proud of what you have done, the work you have done, and not be ashamed of anything, but know that the outcome may still not be optimal. So totally.

Johanna Seiden: 43:06

I feel like I I don't know that quote directly, but I feel like that sentiment I like am constantly saying to myself. I think, you know, all of us are are are trying to help patients who are coming to us already with some some issue, and we're trying to do the best that we can to take that issue away. Um and and you know, especially in I think in stroke where patients are coming in, you know, very sick and very far gone at times from from stroke, and you know, we're trying to give them a chance at getting those symptoms reversed. And I think the most most painful thing that I I deal with is is when I decide, you know, uh, that a patient is not a good thrombectomy candidate for for whatever reason. I think that's like the most painful part of of of the job, you know, because the stroke is too is too far gone at that point. They have, you know, other reasons why they're not a good candidate. I think, you know, I think that's where that I end up doing a lot of self-talk that we're trying to, you know, we're trying to do what's best for the patient, but it can be really painful when you feel like you know, you you couldn't do everything.

Michael Kentris: 44:19

Right. Yeah. Sometimes certain options just aren't on the table. I think we've all been in that situation where it's just like, if only they'd been here a few hours earlier. Right. Exactly. And you're just like, yeah, it uh it really frustrates everybody involved. I think that's I don't know, just an unfortunate nature of our current treatment paradigms. Right.

Johanna Seiden: 44:40

That's what we've got. We all came into this profession like trying to do the most to help people. And I think it's such an unnatural and bad position when we feel like we all the tools that we have are like not enough to help that person.

Michael Kentris: 44:54

I think in that situation it's sometimes good. I think back, I think a great example of this is like multiple sclerosis, where in the 90s, you know, before the early to mid-90s, there was nothing, right? And so it was just a question of like how long how long is it going to be until this person is in a wheelchair or disabled in some fashion. And you know, I think stroke in a lot of ways is also mirroring that. Like just in the last decade, there have been so many advancements in terms of interventions available and things like that. I mean, uh still obviously very front-loaded on the acute side, but as we've been talking about today, still looking very much into the back end of things and trying to write prevention always of the utmost importance.

Johanna Seiden: 45:39

Yeah, definitely. Definitely. Yeah. Stroke used to be they used to say it was diagnose and adios. Right. And now, and now there's a lot, uh, you know, a lot we can do, not you know, not everything, but a lot we can do to try to reverse the symptoms, which is I think, you know, why it's so so rewarding is because you can see someone with a with a huge infarct or huge potential for infarct that um have uh come in with a lot of a lot of symptoms and then and then that clot is taken out and they and they end up walking out of the hospital the next day or the day after. So, you know, that's like the most those are the best cases.

Michael Kentris: 46:17

Um I wish those were a little bit more often, but so what other entities do we need to think about in these cases in terms of you know clotting disorders or things that might prompt us down a different treatment pathway for some of these people without the typical risk factor profile?

Johanna Seiden: 46:36

Yeah. So um, I think these are most of the this is most of like the hypercoagulable sort of workup. Um I you know, another area which which isn't really what we what we're focusing on today, but I think is worth mentioning is is this always comes up of like when to look further in the heart with a TEE rather than a T T. You know, when are we gonna, when is that gonna be helpful? And I think in many of, especially in these young patients with embolic appearing infarcts, we do end up wanting to look for like a cardiac tumor. We do want to, you know, make sure that we're ruling out a large PFO. So, and then, you know, if there's any concern for infection, fever, we want to make sure that we're ruling out endocarditis too. So a lot of these like cardiac tumors, like cardiac myxoma, fibroelastoma, those are better visualized using a TEE. In general, the TEE is better than the TTE for looking at like the ascending aorta, for looking at the aortic arch, the left atrium, um, an atrial septal aneurysm, endocarditis, we can often see more clearly evidence of um evidence of clots in uh using a TEE. And then for PFO, a TEE gives us a better view of the septum. So that can be a that's a better test. So um, so you know, if the suspicion is high enough and the patient is is young enough, doesn't have those other vascular risk factors, then I think it is worth it to to try to get our cardiology colleagues to okay a TEE, which can vary by institution in in how easy it is to do that off, you know, often if we end up saying like PFO or endocarditis. Those are the magic words.

Michael Kentris: 48:30

Mm-hmm. Yeah, I know that's the getting that TEE, especially like in the hospital in the acute stages, can be challenging logistically. Uh, you know, they may only do it on certain days of the week, so you're waiting. Like, do I keep this patient who's otherwise like ambulatory and ready to go in the hospital for another five plus days if they come in just after the window for when they do the procedure or what have you, you know, especially at a smaller hospital. That can be a hard sell, uh at least from a financial standpoint to everyone involved. Yeah. So I know that, like you said, sometimes you have to coordinate uh with your colleagues in the other departments and get something expedited on the outpatient side sometimes.

Johanna Seiden: 49:11

Right. Right.

Michael Kentris: 49:13

But yes.

Johanna Seiden: 49:13

And I guess just you know, while we're talking while we're mentioning PFO, because I feel like it's it's a hot topic. It is a hot topic. So when we're concerned about PFO, as you know, like PFOs are present in like a quarter of the population. So the question is not really if a PFO exists in this patient, but is the PFO itself the cause of the stroke? So there are a couple like scoring systems that have been developed that kind of help us answer this question. One is the rope score, and so that's sort of asking the question does this patient have another like better reason to have stroke than a potential PFO if we were to find it? So it's taking into account patient's age, um, the presence of these vascular risk factors, the presence of the stroke, which you know everyone would have a point for that. Um and but even then that might not be uh specific enough. So the Pascal score or criteria um adds in this this added uh these added um factors of how are there high risk features of the PFO? So is the PFO itself large? Is there um presence of like an atrial septal aneurysm? Those increase the the risk of the PFO being pathogenic and and being uh being the cause of that stroke. So, you know, a lot of the time we'll get an echo report that says like small PFO. Some if that's on a TTE, then sometimes we'll, you know, that's enough indication to move forward with a TEE to better evaluate it. If it again, you know, rates the the PFO as small, just like a couple bubbles, no atrial septal aneurysm, you know, that patient, the likelihood that that patient has a stroke related to that go down, go down a bit. So in someone who doesn't have other reasons to have a stroke, um, doesn't have hypertension, hyperlipidemia, diabetes, doesn't have like carotid disease, has a large PFO with high-risk features, that is the sort of patient that we think about closing the PFO in. So typically we don't even look for a PFO in patients who are generally older than 60 or 65, because if we were to find it, it generally won't change management. Um the reason why why the PFO why it's it's not as easy a question of, oh, just just close the PFO is is because closing the PFO itself is very is a very risky procedure and actually like has a pretty large um risk of of causing atrial fibrillation and potentially causing another stroke. So you know this this whole this whole risk-benefit um balance becomes very, very important in these PFO conversations.

Michael Kentris: 52:17

Yeah, I know we have uh a structural cardiologist in the area. And I say that because there aren't that many in our area. Uh and I'll get you know referrals from him where someone maybe had a small stroke, they found an incidental PFO, and they send it to me like, do you think this was causative? And like you said, you kind of have to go through uh you know calculating the rope score of like, nah, it's like or you know, like the MRI characteristics is a small thalamic lacuna infarct. Probably not. Um, in the 20-year smoker with high blood pressure and diabetes. But uh but it is one of those things where I I certainly appreciate the thought that goes into asking that question as opposed to, as you said, just kind of closing the PFO.

Johanna Seiden: 52:59

Yeah, for sure. That's very uh considerate of the cardiologist to reach out, because I also feel like um many don't. Many don't.

Michael Kentris: 53:09

Yeah. Yeah, it's yeah. Sometimes you you have colleagues that don't communicate as well as you would like, and I'm fortunate at having the ones that I do who do.

Johanna Seiden: 53:18

Yeah.

Michael Kentris: 53:20

But I do wonder. So let's say if I if I can hypotheticalize for a moment. If we have let's say a younger person late forties, early fifties, again, kind of similar to the earlier one, like kind of mild hypertension, maybe sleep apnea that's untreated, and a little bit of prediabetes has what looks like, you know, in an ESUS category, embolic stroke of some kind. Initial echo was negative, and initial, like the transthoracic and then the two-week monitor was also negative for AFib. Are you gonna be these patients probably should be going for both a TEE and a loop recorder? Would that be accurate?

Johanna Seiden: 54:04

Yeah, yeah. I I mean I would I would definitely do the TEE on that on that patient. The loop recorder, I mean, I think the likelihood of like a 40-year-old having having AFib is pretty low. Um, so I, you know, I I think that would probably be the last test I would like really talk to the patient and and see if that's something that they want. You know, some patients really want to have all of their I's dotted and all their T's crossed and are not comfortable unless we do that. Right. I think other people are are also very put off by something going under their skin and kind of staying there. And the truth is that many people end up getting an ILR and then it's never removed. Um so but I think the TEE is is much more, much more potentially, yeah, much more of an important test for that sort of patient.

Michael Kentris: 54:52

No, I that makes a lot of sense. And certainly I think this conversation today is it was very beneficial for me and hopefully for our listeners as well. We tend to, for us nonvascular neurologists, you think, oh, stroke boring. But it is, right? As you were saying, this is a significant minority of patients presenting with stroke, probably the most common inpatient neurologic entity that we deal with. And you know, it's not always just plug and chug as far as we follow the algorithm and aspirin plavics, statin, see in a month in the clinic.

Johanna Seiden: 55:27

Yeah, right, right.

Michael Kentris: 55:28

So there are a lot of these cases where it does require that critical thinking to say, does this make sense? Do I have an explanation? And when I'm working with residents, a lot of times I'm asked, I'm asking that question, does that make sense? And that's that's really, I think, the problem is that it's easy for us to take the easy way out so that we don't have to think as hard about things. We're like, oh, well, they got a little bit of hypertension, a little bit of diabetes, and they come with this, you know, like you know, branch M2 occlusion or something like that. Like, wow, well, is that enough? I don't know. And so you always wonder, right? You're trying to strike that balance between you know, cost to the patient, testing the patient has to go through, versus do I have a sufficient explanation to make sure that they aren't at high risk of a recurrent event. And that is always a challenge in some of those cases where you don't have the smoking gun, as it were.

Johanna Seiden: 56:23

Totally. Yeah, absolutely. This uh this brings up this a case that has been really making me lose sleep the past couple weeks of this of the again, like 40-something year old has very, very mild hypertension, she's not overweight, there's no like evidence of metabolic syndrome, and she came in with this these very bad headaches. She has a history of psoriatic arthritis, she's on methotrexate and laflunamide, and yeah, came in with this very bad headache. She has a right M stenosis, luckily no stroke, and ended up having like a very, very extensive stroke sort of workup to figure out why she had this M1 stenosis. She ended up having a diagnostic angiogram that showed multifocal vasculopathy versus vasculitis. This this also like a dreaded conundrum of like, is it vasculitis? You know, this could be a whole podcast for for another day. They'll probably end up being multiple days long. But but, you know, I I saw intracranial stenosis in different vascular territories. She has like a little bit of hypertension, her LDL was like a hundred. So, you know, my first my first thought was, oh yeah, she probably has ICAD. Let's just do aspirin plavics for three months and we'll see her in clinic. And then, and then, you know, something doesn't feel right. Something doesn't feel right. Can I, can I really just say this this 40-year-old with really no clear vascular risk factors has has ICAD? She has this sort of like rheumatologic kind of background. You know, we had room involved to try to see is it methotrexate be the be the cause? Does this patient have like other indication of of of uh like increased inflammation in the body? Kind of all of those labs were were negative, like the ANA, the ENA, the LP was fine. And so, you know, now we're going down this whole rabbit hole of like a primary CNS vasculitis because you know, it doesn't make sense. When we when we really think about it, this patient having ICAD doesn't make sense. She doesn't, she's not the typical patient for it. So I think um, you know, as as exhaustive and extensive of oh, you know, of a of a medication course for possible vasculitis is, it's because that thing doesn't really fit. Um it doesn't make sense to say to chalk it up to something that is just not typical in that sort of patient.

Michael Kentris: 59:04

So did you did you pull the trigger?

Johanna Seiden: 59:06

Yep. Steroids, reduction. Steroid course, cell sept.

Michael Kentris: 59:10

Nice.

Johanna Seiden: 59:11

The whole the whole thing. It feels, you know, even though it's it's way more for the patient, it feels like that's that's what needs to be done.

Michael Kentris: 59:19

Mm-hmm. Yeah. I know I had an attending, you know, she was a retired military person, and I would ask her, like, you know, how did you because she would, you know, she was a a little more bold than some of my other attendings. And she would just say, like, sometimes, Mike, you just need to put on your big boy pants and do it. And and uh, she's pretty much right. Uh it's true, you know, uh this is uh something that I observe a lot in medicine at large, where you get people saying they're not quote unquote comfortable doing something. I'm like, guess what? I'm not comfortable doing a lot of things, but sometimes it's The right thing to do, you know, like being the one to make a decision, you know, on a potentially life-altering medication like thrombolytics day after day. Some days might feel a little uncomfortable. But that is the decision. That is a role we have signed up for, and we have to own that responsibility. So yes, unfortunately, being a physician in medicine means you have to make decisions that will make you uncomfortable. And so that's just one of my pet peeves in medicine. No, and people saying they're not comfortable with things.

Johanna Seiden: 1:00:29

Yeah, no, it's true. It's it's true. And I think I think like we have all seen cases that made decisions on on cases that and then we sit with that decision and it feels like, ooh, I don't know, like, you know, not getting that extra imaging, not getting vessel imaging up front, something like that. And then often it kind of sits with you and and you're questioning, you're questioning. You can always, you know, modify your plan. This this this comes up a lot, at least with our with our with our stroke fellows, that you know, they'll make a decision, they'll say, I don't think we need X or Y, we don't need vessel imaging, I don't think this is a you know, a potential treatment case doesn't sound like a large vessel occlusion, and then and then we you know we change it and we say, you know what, let's get the vessel imaging, and it ends up being being something that we that we need to treat. So I think it's also, you know, don't be afraid to kind of trust the your gut telling you that something doesn't feel right about the decision you made. Usually there's there's time to to go back and change course.

Michael Kentris: 1:01:35

Yes. No, absolutely true. Any final thoughts that you have on on this particular topic for our listeners today?

Johanna Seiden: 1:01:46

Yeah, I mean, I think kind of piecing it all together when we're thinking about hypercoagulable conditions and stroke, you know, we're thinking about those tests that would really like change our management. So we talked about APLS, we talked about JAC2, we talked about ADM TS-13, we talked about talked about potential malignancy. I think, you know, one more area that we didn't really discuss, which is maybe worth mentioning, is sickle cell disease. Yeah. Especially, you know, this is more for like pediatric population because for adults, majority of the time, a patient knows that they have sickle cell disease, comes in with a stroke, and you know, we we can kind of figure out that that stroke is due to due to sickle cell disease. But in pediatrics, I think, you know, they haven't always presented yeah with symptoms. And most of patients are screened, have like some sort of hemoglobinopathy, screening at when they're newborns or or you know, as as in their routine anemia screening. But especially if if you work at an institution where you get a lot of patients coming from other countries or may have not been, you know, not gotten proper care, something might have fallen through the cracks. We do tend to think about that in in pediatric strokes because as we know, sickle cell disease is a very common cause of stroke. A quarter of patients with it will have a stroke by age 45. And so at least in the PEDS population, there's there's clear guidelines about screening kids from two to 16 with um with late, uh, sorry, with yearly transcranial Dopplers, planning for transfusion therapies to get the hemoglobin S down to less than 30%. That reduces, that's been shown with trials to reduce the risk of of stroke in those with elevated risks. It's not really clear whether adults have the same untreated risk or whether they would benefit from that treatment. So there is this gap where patients are, you know, are no longer with a pediatric hematologist with sickle cell disease and don't, you know, don't continue to get this sort of screening. Sometimes we'll end up seeing patients who have stroke related to sickle cell disease and so they haven't gotten that sort of you know yearly TCDs. But I think these these patients are very you know high risk for stroke from from this kind of atypical mechanism. So I think it's reasonable to screen for sickle cell in patient, any patient, um adult patient with like anemia, any who have stroke, especially if there's like evidence of moya moya disease, we see we see that a lot. And then certainly in pediatric population, we want to we wanna consider that because there's clear there's clear management decisions that come after patients with sickle cell have have stroke. So if they if they present with stroke, we're like immediately doing mixed change transfusions. Um the question about using TNK or thrombectomy, there are evidence for using TNK or TPA, but um the recommendation class is is A, and there's not great evidence. So it can be beneficial, but we don't have great evidence for it. And then there really aren't clear guidelines on thrombectomy. Um, but you know, we especially like in the Bronx, we see, we see sort of patient a lot. And even last year we ended up doing a thrombectomy. I was we were talking before on a patient who was a a three-year-old who came in with like a left ACA and an M1 occlusion and sickle cell disease. So she ended up getting um getting prompt exchange transfusion and going for for thrombectomy and having a you know a pretty good recovery, all things considered. So these these do um these patients do do come up and you know it's it's just important to be aware of the link between sickle cell disease and stroke, especially if you're in practicing in an area where where you have a pretty uh sizable sickle cell population.

Michael Kentris: 1:05:55

Great point. Great point. Very challenging when we get into some of these disease entities where we just don't have the the data to guide us as as robustly as we would like, especially when we have more aggressive treatments for the general kind of population, as it were. But yeah, just kind of kind of cross-apply and do the best you can.

Johanna Seiden: 1:06:16

Definitely. And another another area where having open communication with the hematology team is is super important because as quickly as as we want to get these patients um in the scanner, give them these these potential treatments, you know, they need to get the exchange transfusion as soon as possible on their end too. So we're kind of juggling multiple things. And then you know, once they leave the the hospital, they obviously are continuing to follow with their with the hematologist. If they're kids, they're getting um these these regularly scheduled transfusion therapies. Sometimes they're getting hydroxyorrhea, they're getting these yearly TCDs. So, you know, they're they're they need to be really hooked up into the into the system.

Michael Kentris: 1:07:00

Yeah, yeah. It can be it can be a lot to take on, especially for a child.

Johanna Seiden: 1:07:04

Yeah, definitely.

Michael Kentris: 1:07:06

Well, I've certainly learned a lot. I've been jotting down notes for things I need to institute into my own practice as we've been talking today. And I hope others will be doing the same as they listen. So uh thank you again to Dr. Joanna Siden. If people want to find you or contact you, if you want them to, where should they look for you online?

Johanna Seiden: 1:07:27

Yeah, um, that would be great. Um so I am on X slash Twitter, at least for the time being, at JoannaSiden MD. So yeah, reach out to me via that. I try to post some little schematics to try to make stroke education a little bit um a little bit more clear. So yeah, if there's any questions anyone has or any any any clarification from this, I'm I'm more than happy to chat.

Michael Kentris: 1:07:58

Yes, though those have been some great infographics that I've been enjoying as well. Thank you. And you can of course find me also on Twix as well. I'm at Dr. Kentris, D-R-K-En-T-R-I-S. And you can, of course, find the rest of our stuff at theneurotransmitters.com. Joanna, thank you again so much. I really appreciate you taking the time today.

Johanna Seiden: 1:08:18

Thanks, Michael. Such a pleasure.

Michael Kentris: 1:08:20

Take care.

Johanna Seiden: 1:08:21

Bye.