Latest Advances in Stroke Treatment

My name’s Jeremy Heit. I’m currently one of the
fellows in neuro-interventional radiology, and I’ll describe
what that is in just a minute. And I’ll be staying on
at Stanford as staff next year, so I’ll be around
for hopefully quite a long time. So a little bit of
background about me. I trained, actually,
here at Stanford. I did an MD and a PhD here
at Stanford, ended in 2008. And then I decided the
weather was too nice. I needed to harden myself up. So I went to Boston. I did an internship
in internal medicine at the Brigham and
Women’s Hospital. And then I did my
radiology residency at Massachusetts
General Hospital. And then my wife was sick
of shoveling all the snow and decided, actually, the
weather is better here, so we came back here,
and we’ve been here for two more years while I’ve
been doing my fellowship. So it’s good to be
back in California. And I want to talk to
you about a topic that’s very important for our field. And by way of introduction to
neuro-interventional radiology, it sounds like a mouthful. My wife still doesn’t
think I have a real job, because it sounds futuristic. And it kind of is. But basically, what
it is as we are the specialists of the blood
vessels of the brain and spine. And most of what
we do is minimally invasive surgery in the
brain through inside of blood vessels. And I’ll show you how that
pertains to stroke as we talk about stroke later today. So I have no financial
conflicts of interest. I’m a fellow. So I don’t have
any money, either. [LAUGHTER] So what we’ll talk
about tonight, a little bit of background about
what an ischemic stroke is. I’ll talk about what it is,
what causes it, and a little bit about the biology of how
we think about stroke, in terms of treating it. And then I want to spend a
little bit of time talking about how we image stroke. That’s become a very
important topic, and very important
in how we decide who we can take for a
procedure that we perform as neuro-interventionalists. Talk about what those
procedures are currently. It’s a very exciting time to
be a neuro-interventionalist. And then talk about, and
speculate a little bit about, what the future might hold for
endovascular stroke treatment. So let’s start off by talking
about what is ischemic stroke? Well, this is a picture many
of you may have seen before. It’s very popular and put out by
the American Heart Association. And I like it because
it’s a very nice summary of what a patient having
a stroke might look like. This is a gentleman
who’s trying to smile. And what you can see is
that his smiles asymmetric. This side looks normal. He’s got a good grin. His cheek is coming up. But this side, he has a droop. This cheek is not moving upward. His eye’s a little bit droopy. And moreover, if this were
a very dramatic stroke, you would find that he
has profound weakness in his right arm, his right leg. His sensation on the right side
of his body may be affected. These are very profound
neurologic symptoms. And just to keep you
straight in going forward, we think about
stroke in opposites. So this patient,
where all the symptoms are on the right
side of his body, has a problem on the
left side of his brain. Now, patients with
these symptoms can be very severe like
that or less severe. But overall in this
country, stroke, every year, affects 800,000 people. So it’s a very big problem
for our medical system. 140,000 of those
people will die. That’s a very high
mortality rate. And it is the leading cause
of disability in this country, so it’s a big financial impact
to our health care system, as well. Expenditures that the US
spends treating and caring for patients with stroke
exceed $73 billion a year. So it’s a big problem. So those are the symptoms
that you might see. There are other
variations of that, but that’s sort of a
good overall picture. But what causes that? Well, a good way to
think about stroke is an analogy to
something most of you are probably familiar with,
which is a heart attack. When you have a
heart attack, you block an artery
going to the heart. Well, similarly, when
you have a stroke, it’s a problem with giving
blood flow to the brain. And we think about
it as something that happens very
rapidly, and it’s usually a blood clot that blocks a
major blood vessel in the brain or on the way up to the brain. And this is a nice schematic
from a recent review in the literature. And what you see here is there
are blood vessels in our neck that run up toward the brain. This is the internal
carotid artery. And then they turn, they
have a very torturous course, and then this right here
represents a small blood clot blocking a major
artery in the brain called the middle cerebral
artery, or MCA. The MCA provides blood
flow to around 80% of the cerebral hemispheres,
and most large strokes affect this blood vessel. So in the patient
I just showed you, he would have a blockage in the
left middle cerebral artery, which would account
for his symptoms, including the
right-sided weakness, right-sided facial droop. So now I want to jump
forward to thinking about– we see what the
blood vessel looks like, but what’s going on in
this patient’s head? And I’ve made some images to
try to schematize what this is. So these are images
just from an MRI, but I’ve kind of
color-coded them to help us think
about, conceptually, what’s going on in the brain. Normally we’re all sitting
here with good blood flow to our brains. If you interrupt
that blood flow, the effects are very immediate. You can think of a stroke
as an immediate symptom. You’re doing fine. Suddenly, you’re very weak. It happens like that. And there’s kind of two things
that can happen to the brain when you don’t get
enough blood flow. One is that the tissue
can die very rapidly. Neurons do not tolerate the lack
of blood flow for very long. And if that happens,
you get dead tissue. But not everything that’s
downstream of the blocked artery dies right away. Kind of like if you’re
driving on a highway and there’s an accident,
if you have the right app, you can get off and kind of
go around the back streets and get back on the
highway and keep going. The brain has a way
to reroute blood to areas that aren’t
getting enough blood flow. But if that route
takes too long, it’s not enough to
keep the tissue alive. But you have another
whole area of tissue that’s at risk of
going on to die if something’s not
done to restore blood flow to the brain. And in the medical
literature, we’ve termed these two areas
core and penumbra. Core refers to the
core infarction that happens in a stroke. That’s dead tissue. We think of it as
irreversibly damaged. It doesn’t get better. It doesn’t come back. By contrast, the penumbra
refers to the tissue that’s at risk of injury,
but it’s not dead yet. It’s not functioning normally. If we can restore the
blood flow to the brain, we think we can
save the penumbra. We spend a lot of time
and appropriate energy in imaging these two
areas, because it makes tremendous impact,
as I’ll tell you later, in how we can treat
patients with stroke. So at Stanford,
we’ve been a leader in some of the advanced imaging
that images core and penumbra, and here’s one example
from a recent patient. This is a patient who’s
coming in with a stroke. This is an MRI sequence
called the diffusion-weighted sequence, and what this assesses
is the movement of water. And when brain tissue
dies, water doesn’t move, and you can take
a picture of that. And right here in the
brain, this is a stroke. It’s a relatively small stroke. And now in this same
patient, we have a way to quantitatively assess the
blood flow up to the brain by injecting a label
that you can see by MRI. And you can see that
although the patient has a relatively small stroke of
core infarction that’s there, there’s a large amount
of territory that’s not getting enough blood flow,
and likely functioning poorly, which is the patient’s penumbra. So let’s go back to an
image that looks like this. This is the patient
that’s having a stroke. And we can see that let’s
say this part is core. It’s infarcted. We’re not going to get
that amount of tissue back. However, this part of the
brain might leave the patients with relatively less
profound symptoms. However, there’s also
this area of penumbra that, if that is not saved,
results in much worse symptoms. If we’re able to
reperfuse the brain, meaning restore the blood flow,
then everything that’s blue is saved. It goes back to normal. And we’re left with the
same size of core infarction that the patient came in with. That’s what we want to do as
physicians, because that’s giving the patient the
best chance at having a good outcome. By contrast, if we aren’t able
to open the blood vessel that’s blocked going to the brain,
and there’s no reperfusion, the tissue that is the
penumbra will eventually go on and infarct, and you’ll
have a larger core infarction. And as the amount
of brain tissue that dies increases in size,
so do the consequences. So in thinking
about that, I think you can probably understand
that reperfusion is really the goal of all stroke therapy. We work very rapidly through
both medical treatments and endovascular treatments
that I’ll describe in a bit to get the blood
vessel open, in order to minimize the amount of
injury that a brain sustains. Let me show you a
few examples, just to illustrate these points. This is from a patient
that I took care of, a 69-year-old woman who
was out with some friends when she very suddenly develop
weakness in her left arm and a droop in her left face. She came right into Stanford. She was brought by her friend. She had a head CT scan that
really looked very normal. There is no evidence of
a large infarction here. There’s no evidence
of overt injury. She got perfusion imaging to
assess what the penumbra is, and you can see she has a very
large amount of tissue that is at risk of infarction. We also were able to image the
blood vessels non-invasively. This is a CT angiogram. And what you can see is the
normal side of the brain, this is the middle
cerebral artery, in white. And if you look on the other
side, it starts off fine, but there’s a hole right there. That’s a blood clot. So that’s the blood clot that’s
partially blocking this artery, and the patient does not have
very many blood vessels going to this part of the brain. Without blood flow in
that part of the brain, she has this large penumbra. So this is a patient
you can help, because she’s not had
a big stroke here yet, of core infarction. But if we don’t get that blood
vessel open, she’s in trouble. So she was given a
medication called tPA, which is tissue
Plasminogen Activator. It’s a clot-busting medication. And literally in
front of your eyes, she started moving the left arm. She regained her strength
quite dramatically. She then got an MRI scan
around an hour later. And an MRI is better at
showing where the actual core infarction is, and she had a
very small core infarction. This is less than a
milliliter in volume. It’s very tiny. Her perfusion had normalized,
except in the area immediately around the stroke,
which we expect to see. And her blood
vessel is now open. The medication worked, and
she made a great outcome. Here’s another patient
I took care of, a 68-year-old gentleman who came
in with right-sided weakness and had a very small
stroke on an MRI scan. You can barely even see it,
it’s happening so quickly. This is a patient that we
took for endovascular stroke therapy, and we were
able to find the blocked artery in the brain. And I’ll describe this later,
but this is an angiogram where we’ve injected a black dye. Looks black by x-ray. And what we see is that
there’s nothing here where there should be
a lot of blood vessels. This is where the middle
cerebral artery should be, and the arrow
denotes the blockage. We were able to get the
blood clot out, restore all this blood flow,
and the patient was left with
basically the same size stroke that he came in with. Again, that’s what
you want to do. Get the blood flow to the
brain back, minimize the damage so it doesn’t get bigger. This gentleman also made
an excellent recovery. Here’s a different patient. This is a little bit bigger
core infarction on an MRI, but you can see it’s still not
that big, relative to the size of the brain. This was another patient that
was brought to our endovascular suite for endovascular
stroke therapy. And this was done
before I arrived here, when some of the
technology was older. And again, you can see, not
a lot of blood vessels here where the middle cerebral
artery should be. And there’s a blockage. This just stops. It should go like that. So the doctors
worked their best. They worked very hard. They could not get this
open, despite everything that they did. And the consequences of
that for this patient was that the patient
went on to have a much larger stroke and a
much worse clinical outcome. So those are three
examples of why you want to have the blood
vessel open, because it really does maximize the
chance of having a good recovery from a stroke. So in going forward,
keep in mind that what we’re going
to be talking about are ways to reperfuse the brain. Get the blood vessel open,
restore the blood flow, minimize the size of the stroke. And again, I’ve been
speaking a lot about we want to do this quickly. This is a widely cited paper in
our literature from Dr. saver at UCLA, where he
calculated, well, how much injury do
you get in the brain on a per-minute basis,
on a per-stroke basis? And a widely quoted
number is this one. Per minute, if you don’t
restore blood flow, you lose around two
million neurons. That’s a lot. So you really want to get
that blood vessel open. And I was alarmed to see
that one stroke accelerates your aging by around 36 years. So these are a little
bit of extrapolation, because he’s doing this
on just some rough math. But the point is that you
want to get blood vessel open, because there are real effects
to not doing so, in terms of how a patient will do. OK, so what can we do to
help patients with a stroke? Well, we have a few options. In 1995, there was
a very large study published in the New
England Journal of Medicine showing that intravenous
administration of the clot-busting
medication tPA was very effective in taking
care of patients with stroke. OK, tPA, again, stands for
tissue Plasminogen Activator. It’s injected through an IV,
and it acts to find a blood clot and actively dissolve it. So patients that got
this drug, compared to a control group of
patients that were just managed medically, 30% of
the patients who got the drug had a favorable outcome and
were functionally independent. That’s very good data. And this was just a landslide,
in terms of stroke therapy. It was a real
game-changer at the time. Because prior to
that, all you could do were sort of measures to try
to increase the blood pressure, make sure you try to get
more blood flow that way. But you weren’t
really doing anything to actively get rid
of the blood clot. Now, the downside of
tPA is that the data shows there’s a very
limited time window in which this is helpful. The original trial said you
need to give the medication within three hours. And follow-up
studies have said you need to get it into the patient
within four and a half hours. Many patients with strokes do
not get to the hospital in time to get treated with tPA. In fact, it’s only
around 7% to 10% of patients now that are
even eligible for tPA. These are very small
numbers in the context of what I showed
you demographically goes on in the country earlier. So that’s a problem. That being said, if you
can get to the hospital, it’s a good thing. So subsequent to
that, in 1999, there was another trial called the
PROACT II trial, from Japan. And this trial showed that
there’s another option. If you’re able to get a
catheter, which is just a hollow plastic tube,
from inside the arteries all the way up into the
arteries in the brain where the blood clot is,
and then directly deliver a similar clot-busting
medication, you can make an improvement
in how the patients will do. And importantly, they extended
the time window to six hours. So this actually increases
the number of patients that you can offer a treatment
to pretty significantly. That being said,
these early studies were also plagued with high
rates of complications. A lot of these
patients developed bleeding in the brain, and
that was a significant concern, in terms of how you
care for people. And it is something that’s still
limited the use of this therapy broadly. Now, more recently, there’s
been a technique called mechanical
thrombectomy, and this is a technique that’s also
an endovascular therapy from inside blood vessels. And the goal of this is to
mechanically remove the clot. And you can do that by
either putting a device up to grab the clot
and pull it out, putting a device
up to grab the clot and suck it out like a vacuum. But these newer
devices have actually begun to be a
game-changer, which I’ll talk about more in a minute. And more importantly,
the recent trials have extended the window in
which these devices can be used from six hours to eight hours. And many people,
including even us, are taking this
beyond eight hours now and getting
very good results. So we’re moving in
the right direction, in terms of being able
to fight this clock and being able to help people. But we’ve got to know who will
really benefit from what we do, and that’s where imaging
has played a big role. And one of the things we’re
likely see going forward is that imaging could be
a way to stop the clock. Wouldn’t it be nice
if a patient woke up with a stroke– we have no
idea what time it started. Maybe it happened five
minutes before they woke up. Maybe it happened two hours
after they went to bed, and it’s done. But what if you had a way
to sort that out and say, you know what? They’re eligible for treatment. Well, people are working on
ways to use advanced imaging, particularly at
places like Stanford, to say, this is a patient
who still can be helped, even though we don’t know
when the stroke started. And I expect that this
will be an exciting area to watch in the years to come. OK, so how do we use imaging
to kind of fight this clock and decide who is a good patient
to take to the cath lab that will benefit from our therapy? Well, again, remember,
what we’re trying to do is reperfuse the brain and
minimize the amount of injury. And in thinking about
who is a good patient to put through a procedure to
try to reperfuse the brain, there are three criteria. You want to have a patient
with a relatively small core, a small amount of infarction. This patient should
also have a large amount of tissue at risk of
infarction if we are not successful in getting
the blood vessel open. It’s that mismatch
that’s really critical. And lastly, there’s got to be a
blood clot that we can get to. There’s a big difference
in a blood clot that’s at the base of the skull,
where the arteries are just coming into the brain, in terms
of being able to access it, to something that’s the way
up near the top of the brain. The technical
difficulties of getting further out, and practicality,
is very different. So we’ve got to have a
way to answer these three questions for every
patient that we’re going to consider taking to
the cath lab for a procedure. And at Stanford, we are
very good at doing this with two different ways
of advanced imaging. We can use MRI
and we can use CT, and there are reasons for each
that I’m happy to talk about with you guys later. But both of these can basically
get at the same points. An MRI is very good
at finding how big is the area of infarction? It’s very good at finding
how big is the penumbra? Again, by injecting a dye that
changes how the MRI senses it, and you can quantitatively
assess blood flow to each side of the brain. And it’s very good at
finding whether there’s a vessel that’s missing. Similarly, CT is
very good at finding early signs of a stroke. Not as good as MRI,
but good enough. It’s equally good at perfusion,
in terms of assessing the size of the penumbra. And it’s excellent
at finding a cut-off in a vessel that represents
the location of the blood clot. So any patient that’s going
to be considered for stroke therapy, by and large, should
have these three questions answered by CT or MRI scan. And that’s really becoming the
standard of care nationally. OK, so now we know how
to pick the patients that we think we can help. We know that we can get them
up and do something about it. So what exactly can we do? Well, endovascular stroke
therapy is very, very exciting right now. And that’s because in
the last five months– almost five months. It’s almost May– there have
now been five randomized control trials, all published in the
New England Journal of Medicine, showing a remarkable benefit
to endovascular stroke therapy, compared to medical
management alone. So I want to put
one data slide up. So I apologize if
it’s too much, but I think this is a really nice
way to illustrate this. This slide’s inspired by Dr.
Albers, one of our stroke neurologists, who gave an
excellent talk about this recently. And what you’re looking
at here, on the y-axis, this is the percentage of
patients with a good outcome after a stroke. The medical literature,
we usually define a good outcome as someone who
is functionally independent and with minimal symptoms. Because that’s a
patient that overall still has a very
good quality of life, and maybe even a
normal quality of life, and is also someone who is
not stuck needing assistance, and so on and so forth. So obviously, that’s
what you want to be. Someone who still has a
very good quality of life. And then on the
x-axis here, these are the names of
the five trials. You can see they give
them kind of goofy names. And in each trial,
there’s both a medical arm and there’s an endovascular arm. All the patients that
got endovascular therapy got equal medical therapy. So this is added benefit to what
we normally do for patients. And you can see, if you
look at the patients who underwent endovascular stroke
therapy, it’s really remarkable how much better
they can do, if you select the patients
properly by the criteria I discussed earlier. 33% good outcome
to 19%– this was the first study that came out. 53% of patients treated have a
good outcome compared to 30%. 44%, 60%, 71%. These are excellent,
excellent numbers. And this makes a
big, big difference for each one of these patients. And even on a bigger scale,
it’s a massive difference to our society, both in
how people are doing, how their health is, the
financial impact of stroke. These are steps in
the right direction. So again, what is
happening to patients that are in this red group that
were brought for a procedure? Well, as I discussed earlier,
there’s three options. We can give tPA, that
clot-busting medication, directly into the clot
to break it apart. We can put a big
catheter up to the clot and try to suck it out. Or we can use a device
that looks like this. This has been termed
a stentriever. These were initially developed
as stents for narrowing in the blood vessels, and they
weren’t very good for that. But what we found by
accident in testing them is that they’re very
good at grabbing blood clots and pulling them back out. So as long as you can leave
the stent attached to something you can pull, you can use
it to get a blood clot out of a vessel. So all these things
I’m talking about now require things to be inside
an artery that’s way up here in your brain. But how do you get it up there? Well, everything
we do has to have a little bit of road-mapping
and driving on the highway. Basically, we put our equipment
into an artery in the leg. Again, these are
largely catheters, which are just long,
hollow plastic tubes. And then we use x-rays
to navigate them from an artery in the
leg, all the way backwards into the neck, up into
the arteries in the brain. So it’s a pretty big distance. I’m a short guy, but you can
imagine a taller person– that’s a long way to go. And it’s really a testament
to material science that we’re able to do this. When I first got
interested in this field, these procedures were not
only extremely difficult, and in many cases not possible,
they took hours to do. These procedures now can
be done in 20 minutes. They can be very, very fast. So there’s been a
remarkable advancement in catheter technology
biomaterials, such that you can have
a wire in your hand, and by turning it
a little bit, you can manipulate a device that’s
all the way up in the brain. That’s really an amazing feat. And it’s really made a big
difference for patients. So what does this look like? Well, here’s a patient
that we took care of, and I thought it would be
interesting to show you guys how we get a
device up there, and sort of the curly-course-Q
that’s required. So this is a short movie. This is a catheter here
that’s all the way up in the internal carotid
artery in the skull. And then there’s
a smaller catheter call a microcatheter that’s
been put through this, that winds its way up into the
artery in the brain right here. Here’s the tip of
the microcatheter. The blood clot that we’re
going after is right here. So if you watch, you can
see, this is the device. This is the stentriever
getting pushed up. And it goes through
the microcatheter. Look at the turns this thing has
to make to get all the way out, up into the brain. Again, that’s really remarkable. It’s navigating 180-degree
turns, 360-degree turns, by pushing something
down in the leg. And once we get the
device all the way up there, we can basically
unsheathe it, expose the stent, and then we’re able
to grip the clot. After we do that, you
can pull the clot out. This is the same patient. I’m going to warn you, this
is a patient who was awake– which we do on purpose. I’m happy to talk about that
later– and very confused. So you’re going to see the
head moving around a lot. He was very comfortable. We don’t let our patients hurt. But it’s going to look funny. This is what happens
when we start to pull the blood clot out. So first thing we do is
we’re moving this big sucking catheter up along this
stentriever right here. And you can see
the patient’s kind of chit-chatting away,
moving around, very confused. And now you’re going
to see that we’re going to start to
pull the stentriever device into the catheter. Here it comes. We’re moving along, moving
along, and almost there. Pop– we got it out. Blood clot’s gone. Patient’s doing OK. So that’s sort of
what this looks like. And you can kind of appreciate
the difficulty of doing it, but also the fact we can do it. And it’s really, I
think, quite remarkable. All right, so I want to show
you a few success stories. These are all patients
that I’ve taken care of during my fellowship. This first one is a
63-year-old surfer girl. You heard both the age and
the description correctly. She was actually running at
the gym on the treadmill, which she still does every day–
extremely active, very fit– when she collapsed. She was brought to
an outside hospital. They thought she
was having a stroke. They gave her tPA to try
to break up the blood clot, and they asked us if there
was anything else we can do. She was put on a helicopter,
flown to Stanford, and as soon as she
landed on the roof, she came right down
to an MRI scanner, where our whole team was
waiting, and she had the scan. Her diffusion-weighted
imaging shows she has a very, very
small core infarction. It’s tiny. Could barely even see it. You might even miss it. There’s an arrow to help. But look at her perfusion. Her penumbra is
unbelievably large. This is her dominant hemisphere. It’s actually on the left side. These are as if you’re looking
at the feet of the patient. But this is a
remarkable penumbra. This is a great patient that
you can take to the cath lab and really help. And we know where
the blood clot is. Here’s the normal side. Look at all these blood vessels. This is the middle
cerebral artery, and look at the lack
of them on this side. And this is actually
the blood clot itself. You can see the blood clot
using a different MRI sequence. So we’ve got a patient with
a small existing stroke, a lot of tissue at risk, and a
blood clot that we can get to. We go straight to the cath lab. So here we are, first
picture we’ve taken. The catheter is now in
the artery in the neck. We’ve injected the contrast
dye, which is black. It winds its way
up, and boom, stops. This is where the blood clot is. There should be blood
vessels all the way up here, and there are not. So we know that we’ve
got to get to there. We go further up into the
arteries in the brain. We’ve got an aspiration
catheter here. We’ve got a stentriever across
the area of the blood clot. We suck, we pull, and we’re able
to open up the blood vessel. This is a great result. Here’s the blood clot. This patient did great. She was in the hospital
for two days, went home. She’s still running every day. This is a different
patient we took care of. This is a triathlete. Not all strokes
happen in patients who are in their 60s or older. He’s 50. He was training for a triathlon,
running, when he collapsed. Again, was brought to
an outside hospital. Was again given tPA. He got to the hospital quickly. Same thing– we were called. Put him on a helicopter,
flew him to Stanford, and he went straight
to the MRI scan. This patient’s also had a
relatively small stroke. Bigger than the last
one I showed you, but this is still quite small. Has a large amount
of brain tissue at risk of infarcting
further if we don’t get the blood vessel open. And again, like the last
patient, the normal side. You can see the middle
cerebral artery, and look– there’s
a complete absence of the middle cerebral
artery on this side. He comes straight
up to the cath lab. This is an image that was
taken 40 minutes after arriving at Stanford, 20 minutes of
which were the MRI scan. So pretty quick. And what you can
see is a little bit of a different picture than
what I showed you last time, and let me kind of show
you what’s going on. This is looking at
the side of the head. This other picture
here is looking at the front of the head. All of the contrast dye
we’ve injected is coming up and instead of going out
to this part of the brain, it’s actually shooting
backwards and going to these blood vessels
in the back of the brain. And that’s because there’s
a blood clot right here, where all of the blood
vessels that are right here are not filling. This is a very bad
stroke to have. This is a blood clot
you want to get out. Here’s another
image, kind outlining the length of this blood clot. This was almost 2
centimeters long. So we were able to go across
it with our equipment, grab it, pull it out, and
look at the difference. Restored the blood flow. This was one pull. This whole procedure
took 32 minutes. Here’s the blood clot. So look what
happened after that. This is how he started. His stroke got a little bit
bigger, but not too much. There are a little
bit of small areas of bleeding in here, which
is something that can happen. Here’s what the perfusion
looked like, completely normal after we opened up
the blood vessel. And here’s what
his blood vessels looked like on the MRI scan. Again, there was nothing
here, and now it’s normal. And I had to put this one in. This is just a great picture. This is a reconstructed image of
the blood vessels from his MRI when he came in. And again, here’s the
blood clot right here. And there it is now. He also did very well. One more example. This is a 64-year-old
gentleman who came in. Kind of subtle symptoms–
nausea, some kind of funny vision changes. And I show this case
to kind of hearken back to earlier, in that
why don’t all patients get to the hospital quickly? Sometimes you don’t know
you’re having a stroke. I mean, these are symptoms
you’ve all probably had– blurry vision. My wife called me today. She said her eyes
were a little blurry. She has bad allergies. Sometimes you don’t feel well. But you could be missing
something that’s a big problem. And that amount of confusion
is to be completely expected, and it’s going to limit some
people getting to the hospital. This patient did
get to the hospital, because the nausea
was quite bad. And there’s a very,
very small stroke in the back part of the brain. This is the pons. This is a very important
part of your brain. This is the part
of the brain that controls your level of arousal,
consciousness, basic functions of breathing and being alive. And this patient, different to
what I’ve showed you before, has a blockage in an artery
in the back of the brain. This is the basilar
artery, arguably the most important
artery in your body. And there’s a blood clot
right at the top of it that’s blocking part of the
posterior cerebral artery, which goes toward the
back of the brain. This patient was brought
right up to the cath lab, and here’s the picture. You kind of see this little
fuzzy interface here? That’s the contrast
flowing around the clot into the normal side here. But there should
be something that looks like this on this
side, and there’s not. So the blood clot
is blocking the top of this artery and the artery
that goes to– in this case, it’s the right side. It’s opposite. So we were able to get the blood
clot out, open the patient up. Here’s the blood clot. And again, the patient
did very, very well. OK. So those are some examples
of what we can do now. And again, this is a
very exciting time. Just to give you some
numbers, I mentioned that the drug tPA, when it was
approved, in 30% of patients was able to open up these type
of clots, and 30% of patients had a good, functionally
independent outcome. We looked at the
numbers that I’ve been shown for the recent
trials for endovascular stroke therapy, showing an
excellent outcome anywhere from 40% to 70% of patients. And in terms of how often
we’re able to get those blood clots out and the
blood vessel open, we’re successful between
80% and 85% of the time, and sometimes even
higher than that. So we’re very good at
getting blood clots out now. So that’s important to keep
in mind, because what does that mean for going forward? Well, I think we’re going
to see a few things. There’s going to be better
neuro-imaging triage of patients. And a large part
of this, I think, is going to be trying
to stop the clock. Again, it’d be great if we
could just have a standard way to scan people,
know whether they’re going to benefit
from what we can do, and also what they’re
likely to benefit from. I expect there’ll be
some further improvements in the devices that
we can use to do the mechanical
thrombectomy procedures. There’s been a very rapid
advancement already, and I think they can still
do better, and they will. And I think there’s
now going to be a lot more emphasis on
timeliness of these procedures. We want to be able to get
patients into a hospital, get the imaging to make sure
that they’re the right patient to help, and get them
up to the procedure room as expeditiously as possible,
in order to try to help them. Those are sort of, I
think, obvious next steps. And then I think,
just it would be fun to speculate for
a minute, about what can a place like Stanford do? And this is what
I hope that we’ll be starting to see in the
coming, probably, 10 years. But we can get catheters
to places very quickly that really is unprecedented. And it’s a really
unique opportunity to start to explore,
well, can we do something to change the
biology of a stroke itself and the after-effects? What about stem cell therapies? What if you could
deliver a stem cell? Maybe not a neuronal
stem cell, maybe a cell that supports the environment
that the neurons need to be nourished, and sort
of change the inflammatory surroundings that those
cells are bathed in, in the setting of a stroke. That could potentially be
a very exciting treatment that might really alter the
course of even a patient that’s already had a larger stroke. What about the delivery
of biologic therapies? What we do right now
is we give medications. It’s very effective. We’ve been doing it for years. But we also are now
in the era where we’ve sequenced the genome–
I was in graduate school when that happened–
and we have a better understanding of the cellular
signaling that goes on in the setting of stroke. Well, what if we can start to
deliver biologic therapies? You can deliver RNA that
can change gene expression. What if you can do that
to calm down inflammation, promote the survival of neurons? Can you deliver these things
through nanoparticles? Can you package different
drugs in nanoparticles to promote neuronal survival? These are all very
interesting questions, and I think we’re likely to
see many of these technologies start to explored and exploited. And I hope that Stanford will
be on the leading edge of it. And with the resources we
have, I think that we will. So just by way of
summary, stroke, it’s a big health problem. It’s caused by blockage of
an artery going in the brain or going up to the brain. We went over some of
the demographic numbers. 800,000 strokes in this
country alone a year. It’s a big public
health problem, and it’s a big problem for many
patients and many families. And we also talked a
little bit about some of the recent emerging
technologies in endovascular stroke therapy and
the differences that they’re making
for patients. And with these changes
that are already happening, I know at Stanford,
we’re certainly going to start taking one
blood clot out at a time. Each patient, we’re
going to do it, we’re going to do our
best to help them. And there are many other
hospitals that are doing this. And if we keep doing
this, this can really chip away at those big
numbers, and that’s what we’re all about. If you have friends, if
you’re near people that you see something like this– this
is put out by the American Heart Association. The acronyms is FAST. Do they have a facial droop? Do they have arm weakness? Do they have speech difficulty? Those can be symptoms of a
stroke that may be overlooked. And if you see them,
time to call 911. So think about that. You may be a person
who spots that. It could happen at a restaurant. Someone may look to be
drunk, and it’s a stroke. So keep these things
in mind, because you may be able to help someone,
just by having heard about it. OK. Thank you. I’m happy to take any questions. [APPLAUSE] Sir? We talk about all these clots. Why do we get the clots
in the first place? A very good question. So my job is to
get the clot out. The question is, where
do the clots come from? So that’s a big part of taking
care of patients with strokes. When you come to a
place like Stanford, you can’t just have a
couple of people involved in the care of the patient. You need a whole host
of expert people. You need neurologists. You need
neuro-interventionalists. You need speech therapists. You need intensivists. You need medical doctors. You need speech therapists. And much of what happens after
we get the blood clot out is getting at your question. Why is it there? The most common cause is
an arrhythmia in the heart. Atrial fibrillation is the
number one cause of strokes that we take care of. When the heart normally
beats like this, atrial fibrillation
is an arrhythmia where it’s irregular. It just beats in an erratic
and unpredictable manner. When that happens,
there are pockets of the heart where blood
is not moving through because it’s getting squished
out in a repeated pattern. As blood pools, it forms a clot. So there can be little blood
clots that hide in the heart, and those can break off
and fly up and block an artery in the brain. That’s the most common cause. Another cause is disease in
the arteries in the neck. It can be atherosclerotic
disease and narrowing that are very inflammatory. You can get a blood
clot that forms on it that can fly up and
block an artery in the brain. A similar process can
happen in the brain itself. Good question. The person with the
basilar artery problem, because it was in the
back of their neck, when they were nauseated, did
they also have vertigo? This patient did not. Many of the patients do. That’s a very
common presentation. And again, you can imagine
how that’s a problem. A lot of patients have vertigo. A lot of patients feel nauseous. Good question. She was asking about
whether there’s vertigo from a basilar stroke. The question is why do these
patients have arrhythmias? The examples I showed
you were, in general, younger healthy people. Many of the patients we
take care of are not. Smoking, high blood pressure,
diabetes, hyperlipidemia, having your cholesterol
be out of whack– these are the major
risk factors for stroke. The vast majority of
patients have that situation, which leads to heart
disease and arrhythmias. You can also have an
arrhythmia just because it’s the way you were born,
or because you’ve had some small damage at
some point in your heart that’s created an
arrhythmia focus. And those can be things
that are just bad luck. Good question. So the question is, well, what
is the blood clot made out of? There’s kind of two
different things. One is that it can be
made up largely fibrin, which is sort of a blood
breakdown type of product. And that’s the type of
clot that you typically get from the heart. Some clots are made
out of platelets, and those are more of the
inflammatory type of clots that come from an atherosclerotic
plaque that’s very irritating, a lot of inflammatory
change, and a platelet plug forms there and flies off. You can even get other,
more goofy types of clots. You can get fat. Patients with trauma can
have injury to bones, and fat can fly through and
block an artery in the vein. So the question is,
if you live far away from a place like
Stanford, how do you get to a place like
Stanford that can help you? How do you get a
helicopter to come here? So we have a few ways. Number one is we
actually have a network. So we have relationship with
hospitals that people know. If the stroke comes into
the emergency department, they can call us. Our doctors will be on the
phone within five minutes. We’ll listen to the story,
understand what’s going on. If it sounds like it’s
someone we can help, we can dispatch the
helicopter and get them here. [INAUDIBLE] That’s a good question. I’ve taken care of two
patients from Eureka that were put on a small
medical transport plane, landed at Moffett
or at San Jose, and then were helicoptered up. It’s a longer transport time. We were able to
help both of them, and they both actually
did very, very well. The unpredictability comes in
that each patient’s physiology is different. That transport
time, the patients we took care of, that
penumbra didn’t shrink, and the core
infarct didn’t grow. You need to be able to make
sure that the brain that’s at risk of dying doesn’t die as
you’re getting a patient here. And that’s another big part
of why we image patients when they get here. And then one more quick
comment about stroke centers. Not all stroke centers
are stroke centers. So there’s comprehensive
stroke centers, and there are stroke centers. So Stanford is a
comprehensive stroke center. It’s actually the first
comprehensive stroke center. And that denotes–
losing my voice. That denotes a very
high level of care. It means there’s a
neuro-interventionalist on call 24/7. There are neuro critical
care doctors 24/7, neurosurgeons 24/7. It takes a lot of resources
to be a comprehensive stroke center, and there are
actually relatively few of those in the area. So the question is
most of what I’ve talked about is the actual
treatment of the clot when patients show up with a stroke. But what about
preventing a stroke? And similar to what
we were talking about for the other
gentleman here, being healthy is the most important thing. Don’t smoke. Get your blood
pressure under control. If you have diabetes, make sure
your glucose is well managed. Make sure your lipids are low. If you have atrial
fibrillation, make sure that you are put
on a medication, if it’s appropriate when
you talk to your doctor, to prevent a blood clot
from forming in your heart. Coumadin– there are now
newer-generation medications that do the same thing. Those are important
discussions to have, because a large amount
of those efforts can prevent something
like a stroke. We take care of
a lot of patients that have atrial fibrillation,
and they actually knew they had it, but for
one reason or another, either they thought, oh, I don’t
need to take the medication, or they’re in financial
hardship and they can’t afford the medication,
and they come in with strokes, just because they
weren’t able to be on the medication they need. How does aspirin work
at helping a stroke? So we like aspirin. It’s a very good drug. So aspirin inhibits
platelets, which is very good for
blood vessel health. It’s an anti-inflammatory. So a lot of stroke patients
will benefit from aspirin. That’s another drug that’s been
tried and true over the years. It’s a very good
preventative medicine. In the actual acute
stroke, once it’s happened, there’s not a large
role for it, in terms of breaking up the blood
clot that caused the stroke. It’s really a
preventative medication, and it’s a very good one. The question is whether you
should be on a baby dose aspirin or a full dose aspirin. Different physicians
have different opinions. I think many people
now would tell you that the amount of
inhibition of your platelets, whether you take a baby
aspirin or a full dose, is very similar. And I would say that. So the question is,
I showed two examples of patients that were exercising
when they had their strokes. And it’s not to discourage
you all from exercising. What’s good for
your blood vessels is good for preventing a stroke. So there is a theoretical
question about when you’re exercising, you get a
catecholamine surge, which is some of the hormones
that help rev your body up for exercise. Those can affect
your heart rate. So there’s a
theoretical possibility that as you’re exercising,
you may trip yourself into an irregular heart rate. Or by pumping the heart
more, it may theoretically cause a blood clot to be
more likely to break off. That being said, there’s
no good evidence for that. It’s all hand-waving
explanations. Most of the patients
that we take care of are not these examples. But I find it neat
to see people who are very active have
bad luck, and that do very well afterwards. So the question is
patients that get tPA. It’s effective in
one type of stroke– and I’ll clarify that in a
minute– 30% of the time. And what are the
risks of using it? So most of the strokes that
I’ve been talking about today are what we call large
vessel occlusion strokes, meaning you’re blocking the
internal carotid artery, the middle cerebral artery,
very close to the skull base. Those are notoriously
tough clots for tPA. And the 30% reflects what are
the chances of tPA breaking up a clot in those locations? Now, if you have
a smaller stroke because the blockage
is further out, meaning you probably have
a small blood clot that blocks something out
here, tPA actually is more likely to help
you in that situation. But it’s really these
big vessel clots that it just is
not that effective. So people have started
to look at this. There are a few ideas out there. If an artery this close
to the skull is blocked, it’s a big clot, which means
there’s a lot more surface area to dissolve. Which means if you give
a drug through an IV, it’s got to coat all that
surface area to break it up, which is the taller order. That’s one explanation. There have been studies to look
at the length of the blood clot and how well it responds to tPA. There are very good
studies showing that if a blood clot is
longer than 8 millimeters, it actually responds
very poorly to tPA. So people are looking at that
as a criteria for selection for stroke therapy. One of the studies I
showed you actually had that as a criteria. And then your second
part of your questions was what is the risk of tPA? So the risk of tPA is
actually the same risk that we tell patients. And the major risk
I would tell you is causing bleeding
in the brain. One of the examples
I showed you, the patient, after we
pulled the blood clot out, had a little bit of
bleeding in the brain. That can certainly happen
for a couple of reasons. One is that you have that whole
area of brain that’s not been getting a lot of blood flow. The blood vessels in that
brain volume are damaged. They’re leaky. So if suddenly, you
open up the blood vessel and get a lot of blood
pressure coming back into it, a little bit of
blood can leak out. And that’s what happened to
the gentleman I showed you. However, you can also be unlucky
and have a massive hemorrhage. So that’s the concern. It’s a small number
of patients, but there is a real risk, both
with tPA and what we do, of causing bleeding in the
brain that can, frankly, be catastrophic. Do you see that
happen sometimes? Very rarely. We’ve been lucky at
Stanford, actually. Our numbers are
very low for that, and we think it’s because of the
imaging selection that we do. But you definitely will see it. Yeah, so the question is if you
are a patient who’s had a TIA, does that in any
way preclude you for being a candidate for
endovascular stroke therapy. Is that correct? What’s a TIA? A TIA is a Transient
Ischemic Attack. And this is something that’s a
precursor, or something that’s a high-risk sign, for a
stroke that could happen. And usually what that means is–
I can’t connect to [? box– ?] is that it’s telling you that
you have a situation where there’s something wrong,
and your body’s giving you a warning sign. TIA can be something
like your arm is weak, and it concerns you. You notice it. But it gets better after
a few seconds, or even a couple of minutes. You may have a hard time
speaking for a few minutes, but then it gets better. That can be many things. That could be a seizure. It could be a TIA. It could even be a small stroke. But if you have those
kind of symptoms, you need to be evaluated
by a physician, because that could be a warning
sign of something bigger come. If you have that, that
doesn’t preclude you for being treated by what we do. So the question is, there
are many things that can cause strokes
that we talked about, and some of the risk factors. What about if you have a problem
in your carotid artery and not just your heart? And what can you do about that? How do you know about it? So there are classic
symptoms that can tip you off that you have a problem
with your carotid artery. A very common one is something
called amaurosis fugax. And that’s described
as you suddenly have a veil that
drops across your eye and you lose vision in one eye. And then it recovers. That’s a very common
sign of a problem with your carotid artery
on the same side where your visual symptoms are. If you have that,
that’s concerning. You need to be evaluated. The way you deal with
narrowing in the neck, there are many things. You do medical management. So aspirin is good. Other antiplatelet
medications are very good to help with that. If the narrowing is too severe
and you’re having symptoms, you need to get it fixed. Two ways to fix the
narrowing are surgery, to kind of go and kind of
Roto-Rooter it out, clean it up, sew it back together. That’s call a carotid
endarterectomy. It’s a very good treatment. Patients that get it tend
to do very, very well. The second thing is you
could put a stent in it. carotid stent. That’s a procedure
that we also do. And that’s where you come
from inside the blood vessels and you basically put a little
strut to open up the narrowing. Those are good treatments
for problems in the neck. Some patients will
have foggy thinking. Some patients will
get light-headed. They’ll get weakness
when they’re dehydrated. There are many
symptoms that you can– Yeah, so the question
is, are there tests you can do to look
for narrowing in the blood vessels in the neck? There are. I would say for in general,
for any medical test, it should be indicated. Because if you go
looking for things and you don’t have
a symptom, it’s not a good use of resources. And honestly, it will
just turn up trouble that you didn’t want
to know about it. But if you are symptomatic,
ultrasound is very good. CT scans are very good. MRI is very good. So talk to your doctor. So she’s talking about
what are the risk factors for having
a stroke that you might identify by blood test? So the main things are in
keeping with the major risk factors of stroke. So what is your–
are you diabetic? What’s your sugar? What’s your hemoglobin A1c? Are those normal range? What is your lipid profile? Also very important. Those are the kind of
tests that most of us will, if we go see our primary
care doctor, will look into. Things about your heart– some
patients will say, you know, I notice I don’t have a
normal heart rhythm when I put my finger on my pulse. Or I have palpitations,
the sense that my heart’s skipping a beat. Those are symptomatic things
that you’re not necessarily going to see by a
blood test, but it’s similar in terms of
identifying a risk factor. [INAUDIBLE] So inflammatory
markers right now, in terms of stroke
risk factors, is not something that has
been widely studied. And it’ll be interesting to
see if that does come out in the future as something
that’s important. Sir? When was TIA developed,
and how much does it cost? tPA? tPA. So 1995 is when it was approved. I’m actually not sure when
it was developed before that. tPA. Yeah. And I actually don’t know
what they charge for it now. I would say that
anything what they charge for, it’s very hard to
know what it actually costs. Yeah, so it’s a good question. So the question is, you know,
there are a lot of delays. If you’re going to be someone
who’s going to get tPA, there are a lot of delays
in getting you to a hospital so that you’re
eligible for the tPA. And calling a paramedic,
an ambulance transport, getting into the ER and
being seen, and understanding what’s going on, those
things can add up, and what if that pushes
you out of the window where you can get the medication? And so why not just
train paramedics to identify stroke and
give tPA in the field? That’s a very good thought. But I would say there’s
a few things that we have to make sure we understand. Number one is not
everything that looks like a stroke is a stroke. So seizures can
look like a stroke. Low blood sugar can
look like a stroke. Intracranial tumors
can look like a stroke. A patient who’s had a
hypertensive hemorrhage in the brain can
look like a stroke. And it is important
to understand what you’re dealing with,
because although the risk of tPA is relatively low,
if you massively expand the number of patients
that you’re going to treat and don’t really understand
what the diagnosis is, you will hurt a lot of
people, particularly patients with tumors that are
causing their symptoms, or who have already hemorrhaged. Because you’re going to
make them bleed more. But people have started
to do what you’re asking. So in Europe, for example,
they have little lands that have a CT scanner in them. And they can drive these
mobile stroke units around, scan the patient in the
field, have a neuroradiologist interpret the image,
give the thumbs up, and they can start to
give the tPA in the field. So you can start to think
about things like that. But that has been tossed around. But there are those
limitations to it. And then just to clarify the
numbers– so fewer than 10% of patients are eligible
for tPA because of the time constraints. And of the patients that get
tPA compared to that do not, 30% will have a good
clinical outcome and be functionally independent. So the question is, what is
sort of the communication between the imaging, the
people looking at the imaging, and the
neuro-interventionalist who’s going to go and try
to get the blood clot? So it’s very highly integrated. The people that do
these procedures now come from a
variety of backgrounds, the most common backgrounds
being neuroradiologists like myself, neurologists
who are trained in stroke, and neurosurgeons
who are trained in stroke through
endovascular techniques. So all of those groups are
very savvy with neuro-imaging. It’s very important
that we understand the anatomy of the brain. And all those
people that do this should have a very
good understanding of the brain anatomy, as well
as of the vasculature anatomy. The way it works
at Stanford, and I don’t know how it
works everywhere, but I think most
places try to do this. When we are made aware of a
patient who’s been flown in, our team is activated
before they arrive. So I’m there at the scanner,
waiting for the patient to show up. We clinically
evaluate the patient. We are there when the patient
goes right into the magnet, and we’re looking at
the images in real time while they’re in the
MRI or the CT scan. So that interpretation
happens by us instantaneously, and we make a
decision, by the time they wheel out of the scanner,
whether we’re taking them with us up to the cath
lab or whether they’re someone that’s not
likely to benefit from what we have to offer. Other places have– they can
look at imaging on their phones or their computers at home. There’s a variety of set-ups. As a stroke preventative,
can you give us your thoughts on blood thinners? If you need one, take it. [LAUGHTER] So the question is, what is
the thought on blood thinners? So if you have an indication
to take a blood thinner and your doctor tells
you it’s a good idea, then I think it’s a good idea. But you’ve got to
remember, everything that we do is not without risk. So should we all
just take an aspirin? Should we all just be on
Coumadin to prevent it? Well, a certain
percentage of us, and it’s not a small
percent, is going to have a complication
from that. And that could even be
bleeding in the brain. And you want to
just make sure you have a reason for the
medication you’re taking, because you are accepting
a little bit of risk any time you put
something in your body. The question is,
is there a benefit to drinking red wine to
clear out the arteries? There are studies
that have shown moderate consumption
of red wine to be good for your
cardiovascular health. I do not know the
literature on that, in terms of stroke prevention. In general, what is good for
your cardiovascular health is good for stroke prevention. But I don’t know the
data as to whether having a glass of red wine a night,
what’s your decrease stroke risk from that. It’s an interesting question. Good question. So there’s two parts to the
question that’s being asked. One is, what are
your options if you get to the hospital outside of
the time windows we discussed, in terms of treating you,
because you didn’t recognize the symptoms, or for
some other reason? And the second part
of the question is, well, what about if
there’s a blood clot that’s very far away,
that’s not something that’s really safe
for us to get to from inside the blood vessels? So first off, if you get to the
hospital outside of that four and a half-hour time
window when you get tPA, we can still offer you
treatment from an endovascular perspective. That right now, there are
good data for going out to six to eight hours. That being said, most major
academic medical centers are now making their
decisions based on the imaging profile that I talked about. So we have taken patients
12-plus hours out, because they get
here, we do a scan, they’ve got a small stroke,
they’ve got a lot of brain at risk, and there’s a
clot that we can get to. And I think
increasingly, we’re going to start to see more of that. So you do have options. Number two, what if
you have a small artery that’s blocked way out here? What can be done? There’s a little
bit of a gray zone. And I would say you
have to be thoughtful. Because which artery is blocked? If you come into me and
your symptoms are you can’t speak because
your angular artery is blocked on your
dominant hemisphere on the left, that’s going
to leave you with a pretty significant neurologic deficit. A patient like that,
we would actually consider taking to
the procedure room and putting a microcatheter into
that artery, as far as we can, and giving tPA to
break up the clot. It’s not safe to put a device
out to pull the clot out, in my opinion, that far out. But there are options. If it’s a smaller blood vessel,
that maybe your symptoms are less profound, it’s
a cost/benefit. The risk of these
procedures is not zero. And maybe the odds of you
recovering some function, or it not really limiting what you
do, you just say, you know what? We’re going to keep your blood
pressure appropriate place, and help you recover. That’s a good question. So the question is among
the patients with stroke that come in, what’s the
breakdown of men and women? So you know, there are many
more patients with stroke that come into Stanford than I see. So the patients that we see are
the ones who are really sick and have a blood vessel
that’s blocked that’s really close to the brain. I’ve got to for us,
it’s pretty 50-50. We took care of a
gentleman today, and yesterday we
took care of a lady. And that kind of pans out. It’s really pretty
close to 50-50 now. One more. That’s it, though,
before I get yelled at. [LAUGHTER] Go ahead. Some hospitals offer
stroke risk assessment. Does Stanford do that? That’s a good question. Nick, are you here? Do you know? I don’t. I don’t know the answer to that. I live in Alameda,
and the hospital there offers that quarterly. So– That’s something that we
should certainly look into. I don’t know that we have
a clinic that does that. We certainly have doctors
that, you know, everyone in our network, if you come
in and see your primary care physician in the
Stanford network, you’re going to get
asked the questions that are going to be pertinent
to your stroke risk. But someone who, you
know, a specific stroke clinic about what
your stroke risk is, I don’t know if we have that. We can find that out for you. So. Thank you, Dr. Heit. My pleasure. Thank you all for coming. [APPLAUSE]