Unraveling Cryptogenic Stroke

Send us a text

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

• Check out our website at www.theneurotransmitters.com to sign up for emails, classes, and quizzes!
• Would you like to be a guest or suggest a topic? Email us at [e-mail]
• Follow our podcast channel on 𝕏 @neuro_podcast for future news!
• Find me on 𝕏 @DrKentris

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.

Episode Transcript

Michael Kentris (00:01):
Hello and welcome back to the
Neurotransmitters, your podcastabout everything related to
clinical neurology.
I'm your host, Dr.
Michael Kentris, and today I ampleased to introduce our guest,
Dr.
Joanna Siden, a vascularneurologist at Montefiore
Medical Center in the Bronx.
And I'm really happy that she'scoming to talk to us today,
because this is a topic that Istruggle with a lot as someone

(00:22):
who has to frequently cover theinpatient neurology service, and
that is the evaluation ofstroke, in particular
cryptogenic stroke, inparticular thrombophilia
coagulability type issues.
So, Joanna, thank you so muchfor coming in, and I am really
looking forward to someknowledge to drop on us today.

Johanna Seiden (00:41):
Thanks for having me.
Yeah, I'm excited to be hereand kind of yeah, talk about
what to do in these tricky,tricky stroke workups.

Michael Kentris (00:50):
So cryptogenic stroke, right?
It's a very mysterious soundingname.
But what do we mean when we saycryptogenic?

Johanna Seiden (00:59):
Yeah, so cryptogenic stroke kind of means
that it is any sort of strokethat we don't have a clear cause
for.
So a stroke that could be smallvessel disease, could be large
vessel disease, but we haven'tfigured out the clear etiology
of it, despite a rather completeworkup, which typically

(01:22):
includes like an MRI of thebrain, 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 clearetiology.
And that's somewhat related tothis concept that you might have
heard of of Aesis or embolicstroke of undetermined source,

(01:47):
which has a lot of overlap withcryptogenic stroke, but just
means that the only differenceis that it clearly looks
embolic, but we haven't foundwhere that stroke originates
from, whether it's likeatheroembolic or cardioembolic
or embolic from some othersource in the body.

Michael Kentris (02:07):
And you know, I know there's been tons of
trials, in particular about theESUS phenomenon.
Like, should we justanticoagulate these people and
call it a day?
And it seems like time aftertime the answer is kind of like
probably not.

Johanna Seiden (02:21):
Yeah, it's it's really tricky.
And I think I think the trialsso far have been a little bit
disappointing, the results ofthem anyway.
But at this point, we're kindof still left with treating them
for the most part with aspirinuntil we find that clear source.

Michael Kentris (02:40):
Gotcha.
Now, cryptogenic stroke inparticular is it's one of these
very frustrating things,especially if we have someone
maybe on the younger side, likelate 40s, early 40s, maybe even
younger in some of these veryunusual cases.
And like you said, they don'thave the classic cerebrovascular
risk factors.
And we're like, well, why didthis person have a stroke?
And like you said, the cardiacmonitoring that's been going on

(03:03):
and all that jazz, everything'scome back unremarkable, no
etiology found.
When do we dive deep into someof these more esoteric, unusual
type entities?

Johanna Seiden (03:14):
Yeah, yeah.
So, you know, I think whensomething in the story just
doesn't really make sense for anischemic stroke in someone who,
again, doesn't have thosetypical vascular risk factors
isn't the normal typical age.
So, as you said, like someonewho's a little bit younger.
So Yeah, I think we start tolook for these more esoteric

(03:37):
diagnoses when certainly like anembolic appearing stroke has
occurred in someone withoutthese typical vascular risk
factors, without um not beingthe typical age.
So, as you said, like someonewho's a little bit younger.
Um and a lot of it is in thehistory, other medical problems,
history of sort of likeclotting in other areas.

(03:59):
And that kind of you know getsus into some of these specific
etiologies.
But we're yeah, we're kind oftaking a very uh detailed sort
of clotting hypercoagulabilityhistory, finding if there's any
like family history of this, andkind of going from there.

Michael Kentris (04:17):
So a lot of times, I'm just thinking back to
kind of my own practice to anextent, for better or worse.
And a lot of the questions I'llask, like history of different
clotting events, so kind of likeunprovoked clotting like DBTs
or pulmonary emboli, things likethat.
And then in particular inwomen, if there is a history of
spontaneous miscarriages orother kinds of difficulty

(04:39):
getting pregnant, things likethat.
And then kind of broadlyspeaking, symptoms of usually
I'm asking kind of symptoms oflike autoimmune conditions like
lupus, is that is that enough?
Or what else should I be askingabout?

Johanna Seiden (04:52):
Yeah, um I think I think that's that's right.
Right.
So we're asking like, uh, doesanyone in your family or have
you had any history of clottingeither in the extremities or in
the brain, in other parts of thebody, asking about those
history of like miscarriages?
Sorry, I'm just looking at thisreally fast.

(05:13):
So um from what I rememberabout about the APLS like obs
obstetric criteria, it's likerecurrent miscarriages.
And I I heard actually likethis this great podcast by
Curbsiders interviewing Dr.
Ariel Linger, who's ahematologist who specializes who

(05:37):
does a lot with APLS, and andshe did a they did a whole
podcast on this.
And and she was saying, youknow, in someone who has had a
lot of pregnancies, you want tokind of understand the work up
um and have have they hadpregnancy loss in a row?
I can't sorry, I can't hearyou.

Michael Kentris (05:54):
So an isolated miscarriage in and of itself,
probably not enough to be a redflag, but like you were saying,
the serial events or theserecurrent events certainly
raises a little more suspicion.

Johanna Seiden (06:06):
Early miscarriages before like 10
weeks, and then I think alsohaving three sequential
spontaneous abortions orprematurity due to vascular
disease.
Those are kind of the obstetricconcerns.
So it's not really like I hadtwo healthy births and then I
had one miscarriage, and then Iwent on to have multiple other
ones.
It's more like these continuousones are very early.

Michael Kentris (06:30):
The vascular events, would that be like like
help syndrome or eclampsia,pre-eclampsia, that kind of
thing?

Johanna Seiden (06:36):
Yeah, yeah, exactly.

Michael Kentris (06:38):
Okay.
That makes sense.
So, you know, one of thethings, especially when I don't
find anything in the history,which I feel like is all too
often, is we send all thesehypercoagulity labs.
And there's a lot of them.
And I've I've heard a lot ofcommentary on them in the past
where basically they werecriticizing neurologists for

(06:58):
ordering too many labs and notknowing what they're looking
for, and probably guilty ascharged.
So how do we tailor this in?
Should we be ordering kind of aa panel, quote unquote, versus
like kind of trying to be alittle more surgically selective
with single labs?

Johanna Seiden (07:15):
Yeah, yeah, it's a great question.
And I feel like this is aproduct of like the dot phrase.
And I think, you know, as aresident and trainee, I, you
know, I had a dot phrase forhypercoagulal workup and it had
everything in it.
And as I've kind of gotten moreadvanced in training, I've kind
of realized that a lot of theworkup that I was sending was

(07:37):
really not appropriate forarterial stroke.
So again, we're talking aboutarterial stroke.
Um the if there's a PFO thatkind of changes things a little
bit, maybe.
I mean, there's not greatevidence for that, but in an
arterial stroke for this sort ofhypercoagulable workup, we're
we're sending very few labs.

(07:58):
So we're sending APLS, we'resending Jack 2, we're sending
Adam TS13, and that's prettymuch it.
Those are, you know, the onesin in our institution that that
um that we routinely send.
These other ones that you knowused to be in my dot phrase of

(08:23):
like protein C and S and factorV Liden and anti-thrombin, the
pro thrombin like G20210, all ofthat, um homocysteine, those
are really for venous infarcs.
And I think those, even forvenous infarcs, it's the
evidence is pretty poor.

(08:43):
So this goes back to like thefact that these inherited
thrombophilias are present um inthe general population up to
like 5% for factor five Leiden.
And they really don't end upchanging management even if
they're positive.
So I think that's like kind ofwhat this all boils down to is

(09:04):
are we sending things that, ifpositive, would really change
management?
And if the answer is no, thenyou know, I don't think that
they're worth sending.
So, like right now, theAmerican Heart Association,
American Stroke Associationdoesn't support routine
thrombophilia testing inpatients.
And there was a study by agroup in Colorado that showed

(09:28):
that two of five patients whounderwent this thrombophilia
testing had at least onepositive test, but only one in
12 ended up having a change inmanagement related to that test.
This was mostly in youngpatients, and most of the
patients who ended up havingsome sort of change in
management, it was because ofAPLS.
These tests also cost a hugeamount of money, up to like two

(09:50):
or three thousand dollars.
They're not always covered byinsurance.
And they're, they're they'renot recommended.
They like, there is some datathat these sort of
venous-related thrombophilicstates are associated with
higher stroke risk, but strokerecurrence itself is not higher
in those patients withthrombophilic states versus the

(10:11):
general population.
And it's not really shown tomake a difference.
These patients would be onaspirin, kind of regardless of
whether the test is positive ornot.
So it's not going to changemanagement.
And I think, you know, thecaveat of all of this is that if
there is like a paradoxicalemboli from a venous
thrombosist, some of these maybecome more appropriate.

(10:31):
But even that is not clearlyguided by by evidence at this
point.
So, you know, I think for forme, when there is a venous,
venous, thrombosis, venousevent, I'm more likely to send
these these tests, but whetherit ends up really changing
things is, you know, notentirely clear because the PFO

(10:53):
will probably be end up beingtreated or kind of fixed whether
or not these tests arepositive.

Michael Kentris (11:00):
Yeah, I make sure.
And we might come back aroundto uh PFOs in a little bit,
because I certainly have somequestions on that one as well.
Uh but as far as anecdotally,again, I I definitely have had
people who come back likeheterozygous for some of these
gene mutations, and I'll sendthem to hematology for a second

(11:21):
opinion.
And I'm like, yeah, aspirin'sfine.
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 yousaid, I get like those PA PAI uh
mutations and things like that.
I'm just like, I don't knowwhat the heck this is.
Um it's like there's a like amildly increased risk, like you
said, of venous usually.
But I'm just like, well Doesthat change anything?
Probably not that much.

Johanna Seiden (11:46):
Right, right.
Uh uh, it's like fixing it'sour curiosity, but it doesn't
really make a difference for thepatient.

Michael Kentris (11:52):
Uh no.
And that's that's always thefrustrating thing.
Uh-huh.
Especially when you do havethese younger people who have a
stroke for for no apparentreason.
Um And again, it's one of thosethings where like sometimes
they maybe have likepre-diabetes and mild
hypertension, it's wellcontrolled in meds.
They're in their mid to late40s.
Is that enough?

(12:12):
Like, do I need to keeplooking?
I don't know.
Just painting that broadpicture.
What are your thoughts?

Johanna Seiden (12:17):
Yeah.
Um I think in a young personwith stroke, if we're gonna
blame it on vascular riskfactors, they gotta be like
pretty severe.
Um, I think mild hypertension,mild hyperlipidemia,
pre-diabetes, it's not a slamdunk for kind of athero as the

(12:43):
as the cause to not look atleast look for these other these
other etiologies.
The frustrating thing is Ithink even at the end of all of
this, there, you know, we haveto recognize that there are
going to be like a third to aquarter of patients who end up
still being cryptogenic.
And if we look back at thesepatients 20, 30 years from now,

(13:04):
I think you know, we're gonnahave answers to why these many
of these patients had strokes.
This is still such an evolvingfield, but there are this
proportion of patients who endup um, you know, with we don't
know sort of sort of situation.
But but they do deserve like aas complete and appropriate a
workup as we can do before welabel them like that.

Michael Kentris (13:26):
If it is kind of an easeless-looking picture,
I know insurance can be trickyfor some people.
So you end up doing like atwo-week or however many weeks
insurance will grant you, like axyopatch or holter monitor or
some sort of cardiac eventmonitor.
Do you always send them backfor like an implantable loop
recorder?

Johanna Seiden (13:44):
Um if they I you know, I I think the implantable
loop recorder is obviously somuch more sensitive than a
two-week monitor, especially ifthat two-week monitor is being
done not directly after theevent, but you know, a month
later, two months later when yousee them in clinic.
So if someone is is willing andmy suspicion is high enough for

(14:06):
it being being embolicappearing, then I would rather
go for the loop recorder.
But that's obviously not uhtotally my decision.
So, you know, uh want to make aa good case for it.

Michael Kentris (14:21):
No, that's that's totally reasonable.
And I know I've drifted off ourprimary 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 theantiphossolipid antibodies.
So walk me through these.
I know that they're kind ofassociated with things like
lupus and so forth, but what uhwhat is our their significance
and why why should I, as aneurologist, care about them?

Johanna Seiden (14:50):
Yeah, it's a yeah.
It's a good question.
And I think I think APLS, theselabs can be like really
confusing, and interpreting themcan also be really confusing.
And um, luckily we're notalways doing this in isolation.
We are lucky enough to usuallyhave hematology colleagues um
helping us out.
But basically, these theseantibodies and and um serologic

(15:15):
tests that we're we're using aretesting whether the patient's
body has these antibodies thatrecognize clotting and kind of
overactivate it.
So um, you know, a lot ofpeople have these inherent
antibodies.
Let me sorry, I don't like theway that I'm saying that.

(15:37):
Um the antibodies arerecognizing these bodies wanting
to sorry, it's really hard toexplain this.
Yeah, so I I think that thesethat the antibodies are are
being activated in patients whohave this kind of clotting

(15:58):
system that's beingoveractivated in the in the
setting of of a lot ofinflammation.
So there are three tests thatwe send: lupus anticoagulant,
cardiolipine, and beta-2glycoprotein.
The lupus anticoagulant isreally like when PTT is elevated

(16:19):
and doesn't correct with theaddition of fresh frozen plasma.
This one is the most um themost high risk for thrombosis,
both arterial and venous,compared to the other two
antiphospholipid antibodies.
And we should keep in mind thatthis one is also affected by
anticoagulation.
So if a patient's already onAC, this um this can certainly

(16:45):
be um influenced by that.
And you know, this is why weend up needing to recheck this
lab about 12 weeks later toconfirm that, um, to confirm the
finding.
Cardiolipin and beta-2glycoprotein are both um are
both ELISA-based.
The elevated cardiolipin iseither an IgG or an IgM, um,

(17:08):
antibeta two glycoprotein aswell, an IgG or an IgM, and
they're both affected byinflammation.
And we're looking at titers forthese.
So we're looking at a titer, Ithink the lower limit is 40, so
greater than 40.
And again, the like the thetiters mean something.
So the higher the titer, themore the body is is being

(17:29):
overactivated by this.
So we need two positive assaysthat are separated by six to 12
weeks.
And the amount and which whichtest is positive gives us kind
of a spectrum of risk.
So a high risk um APLS bindingwould be a positive lupus

(17:49):
anticoagulant plus eitheranticardiolipin or antibeta two
glycoprotein being positive orneither.
So having a positive lupusanticoagulant is the most most
concerning, and that would be ahigh risk.
So you could also have doubleor triple positive.
The low risk would be anisolated anti-cardiolipin

(18:13):
antibody, an isolated beta-2glycoprotein at like low to
medium titers, and then uh, youknow, having one just one of
these very, very low titers isprobably less likely to be to be
APLS.
So that these are the labfindings, but in you know, we
also have to have a clinicalfinding.

(18:35):
So the Sapporo criteriarequires the presence of both,
um, both clinical and labrelated.
So the clinical findings, wekind of talked about this
already, but it's the presenceof some sort of thromboembolic
event.
So stroke obviously fits intothat, or a pregnancy-related
complication.
So those are the clinical ones.
Yeah.
So management-wise, we want totreat these aggressively.

(19:00):
So the data suggests usingwarfarin, um, warfarin rather
than doax.
Multiple studies have shownthat warfarin um does better
than doax.
Um so usually we're doingwarfarin with an you know a
typical INR goal of of two tothree.
There have been some studiesasking whether like a higher INR

(19:22):
goal is is more um is betterand it it hasn't they haven't
shown um positivity.
Some people end up addingaspirin as well.
I don't think there's reallygood evidence for that, although
evidence of downsides of thatare also like not um not super

(19:42):
clear.
So I think if someone is havinglike severe clotting events or
clotting throughanticoagulation, I think at that
point um that's what we'readding.

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 ofhelping guide the treatment.
Based on how the uh the degreeof 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 orthree months, and every time I
have to like go back and flipopen some resource to read about
like what does this mean, whatdoes that mean?
And be like, is this should Ibe worried about this or not?
Like you said, uh a lot oftimes I will get like like a
weekly positive anti beta two,and I'm just like, is that

(20:34):
enough?
Like, oh, I guess not.
Um and it it does it's veryfrustrating 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 thecriteria in the presence of,
let's say, medium tighterantibodies?

Johanna Seiden (20:55):
Yeah, yeah, it's a great question.
So I I think one of thesethings is like is the pretest
probability.
So if this is a patient whodoesn't have these classic
vascular risk factors, um, isyoung, you know, our pretest
probability is already prettyhigh to for these tests to be

(21:15):
appropriate to send, where ifyou end up with a positive
result, it's real.
So I think that that's whywe're we're not sending these on
every patient.
We're not sending these onpatients who have like a really
good reason to be having behaving strokes.
So I think if it's a youngpatient who doesn't have any
other clear reason for strokes,and we get these kind of middle

(21:38):
of the road titers, sometimeswe'll end up treating at that
point, and sometimes we'll endup repeating the test, wait, you
know, waiting to treat until werepeat the test.
So how this has been explainedto me is those the tests are
confirmatory, but if you'reconcerned that this patient is,
you know, in a like florid APLScrisis, that we're not gonna

(22:02):
wait until 12 weeks to starttreating them.
So it depends on the story.
But I think those repeating thetest a 12 week kind of tries to
weed out a lot of this.
And sometimes the test can bepositive initially because of,
you know, the reason that thepatient's in the hospital
anyway.
So both the cardiolipin and thebeta 2 are affected by like

(22:25):
inflammation in the body.
So again, like a lot ofpatients in the hospital have
some sort of inflammation goingon.
So if those are positive andthen you repeat it and then it's
normal, then probably thatwasn't that wasn't the cause in
the first place.

Michael Kentris (22:39):
Gotcha.
And I don't know if you knowthe answer to this or not, but
sometimes I wonder if we haveone of these patients and they
receive like IB thrombolytics,you know, on initial
presentation.
Again, it's one of those thingswhere like how valid if we draw
it during like even like a aday or two later, is that going
to affect any of these markers?
And I don't know if that'ssomething that's ever been

(23:00):
studied.
I imagine a data set, if itexists, is small.

Johanna Seiden (23:04):
Yeah, I'm yeah, I'm not sure of any specific
studies about it, but the thelupus anticoagulant, I think,
would be the one that could beaffected by this.
Um I think it's stillworthwhile to have that have
that initial draw after thepatient is on some sort of blood
thinning medication or receivedsome sort of blood thinning
medication.
And then when you get yourrepeat, you have something to

(23:26):
compare it to.
But yeah, it's it's a goodquestion, and and I'm sure you
know we'll we'll have data thatthat supports that moving
forward.

Michael Kentris (23:35):
That makes sense.
Now the other two tests thatyou said that you routinely
check for are the um the Jack 2and 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 andI 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 thatwe send when we're looking for
TTP.
So that remember that's like amicroangiopathy that results
from some deficiency in thismetalloprotease atom TS-13 that
regulates von Willebrand factor,another blast from the past,

(24:19):
and it it cleaves the likereally large von Willebrand
factor and prevents spontaneouscoagulation.
So if you have um an atom TS-13deficiency, then you're not
able to prevent spontaneouscoagulation, you end up being
hypercoagulable.
So this is this ischaracterized by hypercoagulity,
acute hemolytic anemia,thrombocytopenia, end organ

(24:42):
damage, super high mortality,like up to 90% if it's not
treated properly.
And we all kind of learn thislike pentad of symptoms of
thrombocytopenia, hemolyticanemia, fever, neurologic, renal
complications in patients, butyou know, all five are present
together only in like less than10% of cases.

(25:03):
There can be small and largeartery infarcts in these
patients.
And I think what's the mostinteresting development in TTP
research is that there'sevidence of atom TS-13
deficiency even when plateletsare normal or not so abnormal.

(25:25):
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 likeatypical neurosymptoms, they can
have like some sort ofcytopenia, they might not need
to, but no, they're this again,going back to like does the test
being positive changemanagement?

(25:45):
Absolutely, because thesepatients need plasma exchange,
and uh, you know, we're avoidingthis really high mortality
rate.
We tend to send this in inpatients who have sort of this
cryptogenic stroke of unclearradiology, certainly if there's
low platelet levels or anemia,but even even if there isn't.

(26:06):
So, for example, I recently hada case of this 80-year-old
woman who presented multipletimes with these bilateral
embolic showers.
She kept having kept havingmore events despite being on the
typical stroke medications ofaspirin, lipitor.
She had like a complete workup.
She had vascular risk factorstoo, which made it really

(26:29):
difficult.
And we ended up placing a looprecorder, which wasn't showing
any events.
She kept stroking, keptstroking.
They looked very embolic.
And ultimately, after this sortof risk-benefit discussion with
family, we ended up startingempiric um anticoagulation,
which, as we talked about, isnot evidence-based, but you
know, I didn't know what else todo.

(26:50):
She kept having these strokes.
She had normal platelets.
Um, and then she presented likea fourth time, again, with this
like with altered mentalstatus, had this teeny little
cerebowler infarct, super small,and she had platelets of
148,000.
We checked Adam T, which is youknow, 150,000 is like the

(27:12):
lower.
Yeah.
So we check and we checked andit was positive.
And you know, the mistake, Ithink, was that we had I hadn't
checked after her third stroke,after her fourth stroke.
Um we, you know, I we h weweren't routinely doing this in
in our practice.
Um, but there have been, youknow, a bunch of at least two
case series um that have comeout about TTP kind of presenting

(27:37):
in the in this sort of atypicalway.
Um and, you know, because ofthis, we now are are are
checking more routinely.
So this patient, you know, westopped the eloquist, she's just
on aspirin, she's getting thesetherapeutic plasma exchanges.
And you know, hopefully this isthe end of of her stroke
journey with us.
But it was just one of thesecases where uh the that positive

(28:02):
result totally changes thecourse of her treatment.
So it's it's worth sending.

Michael Kentris (28:07):
No, that's fascinating.
Yeah, it's it's definitely notone that I think of as often as
I probably should.
So I'll have to keep that inmind.

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 bythe Stroke Association, but
it's uh I think I think there'sgonna be more coming out about
it, and um, you know, it'ssomething to consider um in in
some of these Aesus sort ofpatients.

Michael Kentris (28:34):
That's the the challenging thing because
sometimes you think like someonecomes in little platelets,
well, I imagine she was bent onsome anti-platelet medication
for a period of time at thispoint, and so you do start to
like kind of second guessyourself, I would almost
imagine, like, is this a sideeffect of the medications I've
been giving her?
Is this something her body isdoing?
And yeah, it can be a realconundrum.

Johanna Seiden (28:56):
Yeah, totally.
Yeah, I went back um throughher her platelet levels through
the years because she startedhaving strokes like two years
ago.
And for the most part, when shewould 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 wewhen we see that in our

(29:17):
inpatients, we kind of come upwith lots of reasons why that
could be happening.
Right.
Oh, it's dilutional or yeah,yeah.
All you know, all sorts ofthings.
But I think that's alsosomething to be aware of when
you don't you don't initiallysend it on a patient, it looks
fine, and then someone starts toget thrombocytopenic.
I think um, you know, that'sit's also something that that we

(29:38):
can send later later on duringtheir course.

Michael Kentris (29:42):
This is probably my own ignorance
speaking, but I tend to think ofwith like TTP, like the papura,
right?
Like the big skinmanifestations are uh the thing
that come to mind.
Do these patients tend to havethose typical skin
manifestations or are they alittle 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 usnot not check it.
I haven't seen any TTP strokepatients who have had that, but
I but I really don't know likehow often that is is present.

Michael Kentris (30:16):
I mean, yeah, you see someone with a big honk
and bruise somewhere on theirbody that's not traumatic, like
that's gonna raise some redflags.
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, likesort 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'sthat's the story of of Adam
TS13.
And I, you know, I I'm excitedabout these cases.
I think you know, we've we'veat our institution are kind of
going through back through ourdata to see how often we're
getting these cases, andhopefully we'll we'll you know
write up some write up like acase series about this.

(30:57):
But but I know that there hasbeen one that's come out uh a
couple years ago, and and itreally is our hematologists who
are who have this in their uh intheir hypercoagulable workup
for the past couple years basedon 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 throughthis clotting landscape?

Johanna Seiden (31:22):
Yeah, yeah.
So um the other one that wethat we often will send is JAC2.
So it's like a one of thesemyeloproliferative neoplasms,
and it's it can be found in likethree percent of the general
population, but patients whohave ischemic strokes are about
two and a half times more likelyto have JAC2 positive.

(31:44):
And the prevalence of it inlike TIA and strokes, at least
in one study, is about 11.4%,which is eightfold higher than
those who don't have um TIA orstroke.
And remember, smokers have ahigher risk of having this
positive.
So it, you know, it seems toinduce a prothrombotic state.

(32:04):
We don't have like clearlyelucidated pathogenesis for it.
Um most common presentation forfor strokes related to JAC2 are
large artery occlusion, but wecan also get strokes that that
look more embolic in nature.
So um we tend to to send thiscertainly in the setting of like

(32:28):
thrombocytosis above 450,000 orhemoglobin levels that are
elevated.
Again, and this is this is notrecommended.
Um, this is not you knowguideline based, but but we're
also sending these in inpatients who do don't have those
those specific findings becauseagain, it really will um change

(32:49):
management, these patients willhave um will get uh get
treatments that'll kind of thinout their blood.
And um, you know, it that endsup being their their course of
stroke prevention.
Oh this one I don't thinkthere's much as much uh clear
data on, but you know, we'veseen this in cases, and so like

(33:10):
to be on the lookout, especiallyif they have these these
abnormal lab findings, and ifthey'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 beforewe started recording.
Uh I tend to sometimes think,is Jack 2 also sort of things
like like polycythemia vera?
Am I remembering thatcorrectly?

Johanna Seiden (33:34):
Yes, yes, okay, exactly.
Yeah.
So yeah, you're checking likethe EPO level and and whether or
not the EPO level is is ispositive or elevated or or low,
then it's polycythemia or it'sprimary.
So um so yeah, we recently hada case of someone who like a

(33:54):
60-year-old smoker came in withcryptogenic sort of stroke and
ended up he actually came inwith this like erythrocytosis of
unclear radiology.
It turns out he wasn't his JAC2 was negative, but he had he
had very high hemoglobin levelsand ended up getting these

(34:15):
treatments throughout his courseand 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 perhapsoverly simplified as the case
where the medieval bloodlettingis 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 theother big umbrella of of this
sort of hypercoagulable workupthat we do is is assessing for
any sort of malignancy in inanyone with a cryptogenic stroke

(34:52):
or an embolic stroke um wherewe haven't yet found AFib, which
is majority of the embolicstroke sort of patients, is I,
you know, I always like to askfirst, are they up to date with
cancer screening?
So in females, have they gottenrecent mammograms?
They got and in everyone aboutcolonoscopies.
So I always ask that.
I ask about like constitutionalsymptoms, so any recent weight

(35:14):
loss, um uh you know, like hotflashes, unexplained fatigue,
which I feel like everybody saysyes to.
But yeah, because like similarto this sort of atom TS13 where
stroke can be the firstpresentation of TTP, stroke can

(35:35):
also be the first presentationof malignancy.
So the risk of malignancy, orthe risk of stroke rather, peaks
about one month before thediagnosis of malignancy in many
cases.
15% of patients with malignancywill suffer from stroke.
That's like two times higherrisk than patients without

(35:56):
malignancy.
Um, and you it's not reallyclear whether the mechanism of
this is is directly from thetumor itself or coagulopathy or
iatrogenic, but things that kindof clue us into this
potentially being related to anunderlying malignancy.
We hear about this T sign orthree territory signs, so seeing

(36:18):
embolic appearing strokes inthree different vascular
territories or both posteriorand anterior, seeing unexplained
weight loss, an elevatedD-dimer, which again is a is a
lab that can often be elevatedin our in our stroke patients,
but being very elevated is issomething that clues us in an

(36:38):
increased CRP, also nonspecific,anemia, low albumin.
So if there's any sort ofatypical features of the case,
something that's that's you knowmaking us think that perhaps
this could be, and of course, ahistory of smoking is another
one too.
But um, we do end up likechecking a CT, chest, abdomen,
pelvis just to make sure we'renot missing any any like very

(37:02):
clear lymphatinopathy or anysolid tumor.
Um, because we have certainlyseen that um, you know, these
tests end up showing something,and then we, you know, we know
the reason for the stroke in alot of cases.
Management-wise, you know,there is a lot of there is a lot
of or some evidence thatanticoagulation is better than

(37:24):
aspirin for these patients.
Initially it was like kind ofmodest evidence of parental AC,
so heparin or lovenox being thebeing the treatment of choice.
There was some concern ofincreased bleeding risk, and
there's, you know, someobviously it's inconvenient for
patients.
There's some decent evidencethat do Ax are appropriate for

(37:44):
preventing venousthromboembolism in patients with
cancer.
There's more of an evidence gapfor arterial clots.
So um I think a lot of us havehave shifted from saying Lovinox
to using DOAX now, but youknow, the caveat is that there
is not clear evidence from anarterial standpoint, but it it
you know it it has beensupported from a venous

(38:07):
standpoint.

Michael Kentris (38:08):
Gotcha.
And I tend to think, uh just toclarify, in my mind, I tend to
associate the hypercoagulablestate more with people who are
with like kind of more diffusemetastatic cancer rather than
someone with like a focallyinvasive cancer.
Is that typical, or can youstill see that
hypercoagulability creeping upwith someone who maybe has like

(38:28):
say a grade one or grade twokind of like lung cancer or
something like that?

Johanna Seiden (38:33):
Yeah, yeah.
That um I I think you knowobviously the more active,
metabolically active cancers, Ithink, have a higher risk of of
hypercoagulability and andstroke, but I think we can see
them in in just like solidtumors too.
So yeah, so so so worth worthchecking.
You know, again, this is kindof like looking for the like

(38:56):
uncovering the reason forstroke, but but certainly we see
a lot of patients who haveunderlying cancer um that is
being treated coming in with itwith stroke too.
So you know, we're not alwaysuncovering, unmasking this.
Sometimes you know it's it'sbeing 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 waythat a lot of chemotherapy is
evolving these days with some ofthe checkpoint inhibitors and
the CAR T modulating and allthat kind of jazz.
We're starting to see a lot ofthese unusual neurologic uh
symptoms.

(39:38):
Uh has that been showing up?
I know on the general neurologyside of thing, you know, I've
been seeing cases likeautoimmune induced, or I should
say uh like uh checkpointinhibitor induced like
myasthenia, guy and barray,stuff like that.
Are we seeing similar entitiesevolving 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 aresident.
I think there are like one ortwo cases where someone's on a
particular um agent and we endup finding a few case reports
that are that are supportingthat, you know, strokes can be
due to these medications.
I think more frequently it weend up kind of attributing it to

(40:19):
just a generalhypercoagulability 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, Ithink I've seen maybe one or two
cases in the last handful ofyears where someone was on like
bebysisiumab for I forget whatkind of cancer they were getting
treatment for, but right, oneof those vascular endothelial
growth factor inhibitors, whichwe know can do like, you know,
vascular injury, like with heartattack, stroke, things like
that.
So in that particular case, I'drecommended maybe not using

(40:50):
that for future treatments ifpossible, but it does become a
little bit of a rock in a hardplace in terms of someone with
usually if they're usingsomething like that, a fairly
aggressive cancer versus therisk of further vascular injury.

Johanna Seiden (41:03):
Yeah, yeah, it can be really challenging.
We usually try to speak to theoncologist and kind of asking
them in their experience havethey seen other patients who've
had this sort of event on thismedication and you know, we're
kind of coming from twodifferent places, but I agree
that that taking someone off ofa medication, especially if it's
helping because of the thisquestion of maybe it being the

(41:26):
cause, um, I would say we don'toften feel that that is the best
way forward.
I think we, you know, moreoften we tend to just recommend
some sort of blood thinningmedication to try to to try to
help decrease the coagulabilityin the patient.

Michael Kentris (41:45):
Right.
Definitely a risk versusbenefit.
Uh no, no clear answers inthose situations, usually I'd
say.

Johanna Seiden (41:50):
Yes.
And you know, that also to addeven another wrinkle onto this,
definitely had patients come inwho are already on a blood
thinning medication for thecancer, come in with another,
another embolic appearingstroke.
And, you know, there's quitethe the team will ask, well,
should we switch the bloodthinner to another another blood
thinning medication?

(42:10):
Maybe they're stroking throughLovinox, but should we do, you
know, eloquence?
And we don't have the answerfor that.
I I I don't think we don'tthink the suspicion is high
enough that it's the problem isthe specific anticoagulant.
I think it's that, you know,perhaps the underlying
coagulability is just is justtoo high at that point.

(42:31):
So yeah, they can be really,really sad, tough cases on for
patients who are already dealingwith 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 oneone line from Captain Picard
where he was saying, like, youcan still do everything right
and still lose.
Yeah.
Which, you know, it's on the onepart, you know, you can you can
be proud of what you have done,the work you have done, and not
be ashamed of anything, butknow that the outcome may still

(43:04):
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 Ilike am constantly saying to
myself.
I think, you know, all of usare are are trying to help
patients who are coming to usalready with some some issue,
and we're trying to do the bestthat we can to take that issue
away.
Um and and you know, especiallyin I think in stroke where

(43:30):
patients are coming in, youknow, very sick and very far
gone at times from from stroke,and you know, we're trying to
give them a chance at gettingthose symptoms reversed.
And I think the most mostpainful thing that I I deal with
is is when I decide, you know,uh, that a patient is not a good

(43:52):
thrombectomy candidate for forwhatever reason.
I think that's like the mostpainful part of of of the job,
you know, because the stroke istoo is too far gone at that
point.
They have, you know, otherreasons why they're not a good
candidate.
I think, you know, I thinkthat's where that I end up doing
a lot of self-talk that we'retrying to, you know, we're
trying to do what's best for thepatient, but it can be really

(44:14):
painful when you feel like youknow, you you couldn't do
everything.

Michael Kentris (44:19):
Right.
Yeah.
Sometimes certain options justaren't on the table.
I think we've all been in thatsituation where it's just like,
if only they'd been here a fewhours earlier.
Right.
Exactly.
And you're just like, yeah, ituh it really frustrates
everybody involved.
I think that's I don't know,just an unfortunate nature of
our current treatment paradigms.

(44:40):
Right.

Johanna Seiden (44:40):
That's what we've got.
We all came into thisprofession like trying to do the
most to help people.
And I think it's such anunnatural and bad position when
we feel like we all the toolsthat 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 greatexample 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 questionof like how long how long is it
going to be until this person isin a wheelchair or disabled in
some fashion.

(45:15):
And you know, I think stroke ina lot of ways is also mirroring
that.
Like just in the last decade,there have been so many
advancements in terms ofinterventions available and
things like that.
I mean, uh still obviously veryfront-loaded on the acute side,
but as we've been talking abouttoday, still looking very much
into the back end of things andtrying to write prevention

(45:36):
always of the utmost importance.

Johanna Seiden (45:39):
Yeah, definitely.
Definitely.
Yeah.
Stroke used to be they used tosay 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 Ithink, you know, why it's so so
rewarding is because you cansee someone with a with a huge

(46:00):
infarct or huge potential forinfarct that um have uh come in
with a lot of a lot of symptomsand then and then that clot is
taken out and they and they endup walking out of the hospital
the next day or the day after.
So, you know, that's like themost 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 weneed to think about in these
cases in terms of you knowclotting disorders or things
that might prompt us down adifferent treatment pathway for
some of these people without thetypical risk factor profile?

Johanna Seiden (46:36):
Yeah.
So um, I think these are mostof the this is most of like the
hypercoagulable sort of workup.
Um I you know, another areawhich which isn't really what we
what we're focusing on today,but I think is worth mentioning
is is this always comes up oflike when to look further in the

(46:57):
heart with a TEE rather than aT 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 appearinginfarcts, we do end up wanting
to look for like a cardiactumor.
We do want to, you know, makesure that we're ruling out a

(47:18):
large PFO.
So, and then, you know, ifthere's any concern for
infection, fever, we want tomake sure that we're ruling out
endocarditis too.
So a lot of these like cardiactumors, like cardiac myxoma,
fibroelastoma, those are bettervisualized using a TEE.
In general, the TEE is betterthan the TTE for looking at like

(47:40):
the ascending aorta, forlooking at the aortic arch, the
left atrium, um, an atrialseptal aneurysm, endocarditis,
we can often see more clearlyevidence of um evidence of clots
in uh using a TEE.
And then for PFO, a TEE givesus a better view of the septum.

(48:03):
So that can be a that's abetter test.
So um, so you know, if thesuspicion is high enough and the
patient is is young enough,doesn't have those other
vascular risk factors, then Ithink it is worth it to to try
to get our cardiology colleaguesto okay a TEE, which can vary
by institution in in how easy itis to do that off, you know,

(48:25):
often if we end up saying likePFO or endocarditis.
Those are the magic words.

Michael Kentris (48:30):
Mm-hmm.
Yeah, I know that's the gettingthat TEE, especially like in
the hospital in the acutestages, can be challenging
logistically.
Uh, you know, they may only doit on certain days of the week,
so you're waiting.
Like, do I keep this patientwho's otherwise like ambulatory
and ready to go in the hospitalfor another five plus days if

(48:51):
they come in just after thewindow for when they do the
procedure or what have you, youknow, especially at a smaller
hospital.
That can be a hard sell, uh atleast 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 theother departments and get
something expedited on theoutpatient 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 aboutPFO, as you know, like PFOs are
present in like a quarter of thepopulation.
So the question is not reallyif a PFO exists in this patient,

(49:36):
but is the PFO itself the causeof the stroke?
So there are a couple likescoring systems that have been
developed that kind of help usanswer this question.
One is the rope score, and sothat's sort of asking the
question does this patient haveanother like better reason to
have stroke than a potential PFOif we were to find it?

(49:58):
So it's taking into accountpatient's age, um, the presence
of these vascular risk factors,the presence of the stroke,
which you know everyone wouldhave a point for that.
Um and but even then that mightnot be uh specific enough.
So the Pascal score or criteriaum adds in this this added uh

(50:22):
these added um factors of howare there high risk features of
the PFO?
So is the PFO itself large?
Is there um presence of like anatrial septal aneurysm?
Those increase the the risk ofthe PFO being pathogenic and and
being uh being the cause ofthat stroke.

(50:44):
So, you know, a lot of the timewe'll get an echo report that
says like small PFO.
Some if that's on a TTE, thensometimes we'll, you know,
that's enough indication to moveforward with a TEE to better
evaluate it.
If it again, you know, ratesthe the PFO as small, just like
a couple bubbles, no atrialseptal aneurysm, you know, that

(51:05):
patient, the likelihood thatthat patient has a stroke
related to that go down, go downa bit.
So in someone who doesn't haveother reasons to have a stroke,
um, doesn't have hypertension,hyperlipidemia, diabetes,
doesn't have like carotiddisease, has a large PFO with
high-risk features, that is thesort of patient that we think

(51:29):
about closing the PFO in.
So typically we don't even lookfor a PFO in patients who are
generally older than 60 or 65,because if we were to find it,
it generally won't changemanagement.
Um the reason why why the PFOwhy it's it's not as easy a

(51:50):
question of, oh, just just closethe PFO is is because closing
the PFO itself is very is a veryrisky procedure and actually
like has a pretty large um riskof of causing atrial
fibrillation and potentiallycausing another stroke.
So you know this this wholethis whole risk-benefit um

(52:11):
balance becomes very, veryimportant 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 therearen't that many in our area.
Uh and I'll get you knowreferrals from him where someone
maybe had a small stroke, theyfound an incidental PFO, and
they send it to me like, do youthink this was causative?
And like you said, you kind ofhave to go through uh you know
calculating the rope score oflike, nah, it's like or you

(52:39):
know, like the MRIcharacteristics is a small
thalamic lacuna infarct.
Probably not.
Um, in the 20-year smoker withhigh blood pressure and
diabetes.
But uh but it is one of thosethings where I I certainly
appreciate the thought that goesinto asking that question as
opposed to, as you said, justkind of closing the PFO.

Johanna Seiden (52:59):
Yeah, for sure.
That's very uh considerate ofthe cardiologist to reach out,
because I also feel like um manydon't.
Many don't.

Michael Kentris (53:09):
Yeah.
Yeah, it's yeah.
Sometimes you you havecolleagues that don't
communicate as well as you wouldlike, and I'm fortunate at
having the ones that I do whodo.

Johanna Seiden (53:18):
Yeah.

Michael Kentris (53:20):
But I do wonder.
So let's say if I if I canhypotheticalize for a moment.
If we have let's say a youngerperson late forties, early
fifties, again, kind of similarto the earlier one, like kind of
mild hypertension, maybe sleepapnea that's untreated, and a

(53:40):
little bit of prediabetes haswhat looks like, you know, in an
ESUS category, embolic strokeof some kind.
Initial echo was negative, andinitial, like the transthoracic
and then the two-week monitorwas also negative for AFib.
Are you gonna be these patientsprobably should be going for
both a TEE and a loop recorder?

(54:02):
Would that be accurate?

Johanna Seiden (54:04):
Yeah, yeah.
I I mean I would I woulddefinitely do the TEE on that on
that patient.
The loop recorder, I mean, Ithink the likelihood of like a
40-year-old having having AFibis pretty low.
Um, so I, you know, I I thinkthat would probably be the last
test I would like really talk tothe patient and and see if
that's something that they want.
You know, some patients reallywant to have all of their I's

(54:26):
dotted and all their T's crossedand are not comfortable unless
we do that.
Right.
I think other people are arealso very put off by something
going under their skin and kindof staying there.
And the truth is that manypeople end up getting an ILR and
then it's never removed.
Um so but I think the TEE is ismuch more, much more

(54:47):
potentially, yeah, much more ofan important test for that sort
of patient.

Michael Kentris (54:52):
No, I that makes a lot of sense.
And certainly I think thisconversation today is it was
very beneficial for me andhopefully for our listeners as
well.
We tend to, for us nonvascularneurologists, you think, oh,
stroke boring.
But it is, right?
As you were saying, this is asignificant minority of patients
presenting with stroke,probably the most common

(55:14):
inpatient neurologic entity thatwe deal with.
And you know, it's not alwaysjust plug and chug as far as we
follow the algorithm and aspirinplavics, 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 thinkingto say, does this make sense?
Do I have an explanation?
And when I'm working withresidents, a lot of times I'm
asked, I'm asking that question,does that make sense?
And that's that's really, Ithink, the problem is that it's
easy for us to take the easy wayout so that we don't have to
think as hard about things.

(55:49):
We're like, oh, well, they gota little bit of hypertension, a
little bit of diabetes, and theycome with this, you know, like
you know, branch M2 occlusion orsomething like that.
Like, wow, well, is thatenough?
I don't know.
And so you always wonder,right?
You're trying to strike thatbalance between you know, cost
to the patient, testing thepatient has to go through,

(56:11):
versus do I have a sufficientexplanation to make sure that
they aren't at high risk of arecurrent event.
And that is always a challengein some of those cases where you
don't have the smoking gun, asit were.

Johanna Seiden (56:23):
Totally.
Yeah, absolutely.
This uh this brings up this acase that has been really making
me lose sleep the past coupleweeks of this of the again, like
40-something year old has very,very mild hypertension, she's
not overweight, there's no likeevidence of metabolic syndrome,
and she came in with this thesevery bad headaches.

(56:46):
She has a history of psoriaticarthritis, she's on methotrexate
and laflunamide, and yeah, camein with this very bad headache.
She has a right M stenosis,luckily no stroke, and ended up
having like a very, veryextensive stroke sort of workup

(57:07):
to figure out why she had thisM1 stenosis.
She ended up having adiagnostic angiogram that showed
multifocal vasculopathy versusvasculitis.
This this also like a dreadedconundrum of like, is it
vasculitis?
You know, this could be a wholepodcast for for another day.

(57:28):
They'll probably end up beingmultiple days long.
But but, you know, I I sawintracranial stenosis in
different vascular territories.
She has like a little bit ofhypertension, her LDL was like a
hundred.
So, you know, my first my firstthought was, oh yeah, she
probably has ICAD.
Let's just do aspirin plavicsfor three months and we'll see

(57:50):
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 saythis this 40-year-old with
really no clear vascular riskfactors has has ICAD?
She has this sort of likerheumatologic kind of
background.
You know, we had room involvedto try to see is it methotrexate

(58:13):
be the be the cause?
Does this patient have likeother indication of of of uh
like increased inflammation inthe body?
Kind of all of those labs werewere negative, like the ANA, the
ENA, the LP was fine.
And so, you know, now we'regoing down this whole rabbit
hole of like a primary CNSvasculitis because you know, it

(58:35):
doesn't make sense.
When we when we really thinkabout it, this patient having
ICAD doesn't make sense.
She doesn't, she's not thetypical patient for it.
So I think um, you know, as asexhaustive and extensive of oh,
you know, of a of a medicationcourse for possible vasculitis
is, it's because that thingdoesn't really fit.

(58:57):
Um it doesn't make sense to sayto chalk it up to something
that is just not typical in thatsort 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 thoughit's it's way more for the
patient, it feels like that'sthat's what needs to be done.

Michael Kentris (59:19):
Mm-hmm.
Yeah.
I know I had an attending, youknow, she was a retired military
person, and I would ask her,like, you know, how did you
because she would, you know, shewas 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 anddo it.
And and uh, she's pretty muchright.

(59:41):
Uh it's true, you know, uh thisis uh something that I observe
a lot in medicine at large,where you get people saying
they're not quote unquotecomfortable doing something.
I'm like, guess what?
I'm not comfortable doing a lotof things, but sometimes it's
The right thing to do, you know,like being the one to make a

(01:00:03):
decision, you know, on apotentially life-altering
medication like thrombolyticsday after day.
Some days might feel a littleuncomfortable.
But that is the decision.
That is a role we have signedup for, and we have to own that
responsibility.
So yes, unfortunately, being aphysician in medicine means you
have to make decisions that willmake you uncomfortable.

(01:00:23):
And so that's just one of mypet peeves in medicine.
No, and people saying they'renot comfortable with things.

Johanna Seiden (01:00:29):
Yeah, no, it's true.
It's it's true.
And I think I think like wehave all seen cases that made
decisions on on cases that andthen we sit with that decision
and it feels like, ooh, I don'tknow, like, you know, not
getting that extra imaging, notgetting vessel imaging up front,
something like that.
And then often it kind of sitswith you and and you're

(01:00:54):
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 youknow, they'll make a decision,
they'll say, I don't think weneed X or Y, we don't need
vessel imaging, I don't thinkthis is a you know, a potential
treatment case doesn't soundlike a large vessel occlusion,

(01:01:14):
and then and then we you know wechange it and we say, you know
what, let's get the vesselimaging, and it ends up being
being something that we that weneed to treat.
So I think it's also, you know,don't be afraid to kind of
trust the your gut telling youthat something doesn't feel
right about the decision youmade.
Usually there's there's time toto go back and change course.

Michael Kentris (01:01:35):
Yes.
No, absolutely true.
Any final thoughts that youhave on on this particular topic
for our listeners today?

Johanna Seiden (01:01:46):
Yeah, I mean, I think kind of piecing it all
together when we're thinkingabout hypercoagulable conditions
and stroke, you know, we'rethinking about those tests that
would really like change ourmanagement.
So we talked about APLS, wetalked about JAC2, we talked
about ADM TS-13, we talked abouttalked about potential
malignancy.

(01:02:06):
I think, you know, one morearea that we didn't really
discuss, which is maybe worthmentioning, is sickle cell
disease.
Yeah.
Especially, you know, this ismore for like pediatric
population because for adults,majority of the time, a patient
knows that they have sickle celldisease, comes in with a
stroke, and you know, we we cankind of figure out that that

(01:02:28):
stroke is due to due to sicklecell disease.
But in pediatrics, I think, youknow, they haven't always
presented yeah with symptoms.
And most of patients arescreened, have like some sort of
hemoglobinopathy, screening atwhen they're newborns or or you
know, as as in their routineanemia screening.
But especially if if you workat an institution where you get

(01:02:51):
a lot of patients coming fromother countries or may have not
been, you know, not gottenproper care, something might
have fallen through the cracks.
We do tend to think about thatin in pediatric strokes because
as we know, sickle cell diseaseis a very common cause of
stroke.
A quarter of patients with itwill have a stroke by age 45.

(01:03:12):
And so at least in the PEDSpopulation, there's there's
clear guidelines about screeningkids from two to 16 with um
with late, uh, sorry, withyearly transcranial Dopplers,
planning for transfusiontherapies to get the hemoglobin
S down to less than 30%.
That reduces, that's been shownwith trials to reduce the risk

(01:03:35):
of of stroke in those withelevated risks.
It's not really clear whetheradults have the same untreated
risk or whether they wouldbenefit from that treatment.
So there is this gap wherepatients are, you know, are no
longer with a pediatrichematologist with sickle cell
disease and don't, you know,don't continue to get this sort

(01:03:56):
of screening.
Sometimes we'll end up seeingpatients who have stroke related
to sickle cell disease and sothey haven't gotten that sort of
you know yearly TCDs.
But I think these thesepatients are very you know high
risk for stroke from from thiskind of atypical mechanism.

(01:04:18):
So I think it's reasonable toscreen for sickle cell in
patient, any patient, um adultpatient with like anemia, any
who have stroke, especially ifthere's like evidence of moya
moya disease, we see we see thata lot.
And then certainly in pediatricpopulation, we want to we wanna
consider that because there'sclear there's clear management

(01:04:38):
decisions that come afterpatients with sickle cell have
have stroke.
So if they if they present withstroke, we're like immediately
doing mixed change transfusions.
Um the question about using TNKor thrombectomy, there are
evidence for using TNK or TPA,but um the recommendation class

(01:04:58):
is is A, and there's not greatevidence.
So it can be beneficial, but wedon't have great evidence for
it.
And then there really aren'tclear guidelines on
thrombectomy.
Um, but you know, we especiallylike in the Bronx, we see, we
see sort of patient a lot.
And even last year we ended updoing a thrombectomy.
I was we were talking before ona patient who was a a

(01:05:20):
three-year-old who came in withlike a left ACA and an M1
occlusion and sickle celldisease.
So she ended up getting umgetting prompt exchange
transfusion and going for forthrombectomy and having a you
know a pretty good recovery, allthings considered.
So these these do um thesepatients do do come up and you

(01:05:43):
know it's it's just important tobe aware of the link between
sickle cell disease and stroke,especially if you're in
practicing in an area wherewhere you have a pretty uh
sizable sickle cell population.

Michael Kentris (01:05:55):
Great point.
Great point.
Very challenging when we getinto some of these disease
entities where we just don'thave the the data to guide us as
as robustly as we would like,especially when we have more
aggressive treatments for thegeneral kind of population, as
it were.
But yeah, just kind of kind ofcross-apply and do the best you

(01:06:16):
can.

Johanna Seiden (01:06:16):
Definitely.
And another another area wherehaving open communication with
the hematology team is is superimportant because as quickly as
as we want to get these patientsum in the scanner, give them
these these potentialtreatments, you know, they need
to get the exchange transfusionas soon as possible on their end
too.
So we're kind of jugglingmultiple things.

(01:06:37):
And then you know, once theyleave the the hospital, they
obviously are continuing tofollow with their with the
hematologist.
If they're kids, they'regetting um these these regularly
scheduled transfusiontherapies.
Sometimes they're gettinghydroxyorrhea, they're getting
these yearly TCDs.
So, you know, they're they'rethey need to be really hooked up

(01:06:58):
into the into the system.

Michael Kentris (01:07:00):
Yeah, yeah.
It can be it can be a lot totake on, especially for a child.

Johanna Seiden (01:07:04):
Yeah, definitely.

Michael Kentris (01:07:06):
Well, I've certainly learned a lot.
I've been jotting down notesfor things I need to institute
into my own practice as we'vebeen talking today.
And I hope others will be doingthe same as they listen.
So uh thank you again to Dr.
Joanna Siden.
If people want to find you orcontact you, if you want them
to, where should they look foryou online?

Johanna Seiden (01:07:27):
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 viathat.
I try to post some littleschematics to try to make stroke
education a little bit um alittle bit more clear.

(01:07:49):
So yeah, if there's anyquestions anyone has or any any
any clarification from this, I'mI'm more than happy to chat.

Michael Kentris (01:07:58):
Yes, though those have been some great
infographics that I've beenenjoying as well.
Thank you.
And you can of course find mealso on Twix as well.
I'm at Dr.
Kentris, D-R-K-En-T-R-I-S.
And you can, of course, findthe rest of our stuff at
theneurotransmitters.com.
Joanna, thank you again somuch.
I really appreciate you takingthe time today.

Johanna Seiden (01:08:18):
Thanks, Michael.
Such a pleasure.

Michael Kentris (01:08:20):
Take care.

Johanna Seiden (01:08:21):
Bye.