The director of UCSF’s stroke clinic, neurologist Karl Meisel, MD, presents the latest evidence-based strategies for evaluating and treating ischemic stroke and TIA, including new thoughts on medical management and post-event monitoring. Plus: what to know about young patients with stroke.
It's my pleasure to talk to you today about scheming stroke. I'm going to use case based discussions on, but I will be happy to answer your questions later on in the presentation. I have some disclosures. Uh, some of the studies that I'll be talking about today I've been participating in particularly current Arcadia trial from the N I H. The point trial. Our reference in this discussion, uh, the respect uses trial the implants, er, post marketing study for P fo closure in the stroke, a f trial of Medtronic uh, implantable loop recorders. I did not receive financial reimbursement from these trials, but served as site P ice. Today's outline. I will be talking to you about various roles of Tia's stroke management, uh, as an outpatient clinic, and we're gonna start off with our first case case. One is a 71 year old man who has a prior history of hypertension. Hyper lipid EMEA. He comes to the emergency department or your clinic with right sided face, arm and leg weakness. Describes it as having been sudden a non set. He has no other signs or symptoms, and he's already taking an aspirin. 81 mg daily Now, in neurology, we love to focus on localization. Localization helps us, uh, in many ways to figure out what is the cause of stroke. Uh, where the stroke is in the brain. Eso stroke, as you know, is a problem of blood flow, uh, to a particular part of the brain. And this gives you the localizing features. The symptoms obviously are sudden in onset and had these localized findings. So here is his memory at someone what I've had ordered, um, and you see this increased signal here. Hyper intensity in the left basil ganglia. Uh, this, uh, symptoms of right face, arm and leg weakness all appearing together without speech deficits would place the lesion in this what we call sub cortical location or in the basil ganglia. Um, yeah. In this particular case, this is important to us because it focuses our attention on small vessel risk factors. Um, and we're going to go into greater detail about what those small vessel risk factors are. But some I'm sure you're all very familiar with the reason is that the blood vessels going to this particular part of the brain are coming off a larger blood vessel on a 90 degree angle to this location. Thes air small penetrating arteries rather than large branches of the Middle Cerebral Artery or anterior cerebral artery. So I'll go through the small vessel risk factors in some detail. But I thought this slide was helpful to focus our attention on them. Here in this column and here we can kind of see a nice bar graph of aggregate risk as we had one risk factor on top of another. Another way that I like to talk about it is in terms of a pie chart, and you want to eat as much of the pious possible to reduce your risk factors. So, for example, um, blood pressure elevated hyper hypertension will get you TOE column be here then this is men and women, women being read and diabetes adding diabetes. Get you column c. Cigarette smoking, obviously is bad for blood vessels and gets you two column D. Atrial fibrillation in is a huge risk factor. You can see this jump. Some people would say a four full risk increased with atrial fib, relation and cardiovascular disease. So we're gonna go into each of these a little bit more detail. Um, small vessel risk factors in particular. Hyperloop Adamia eyes unknown modifiable risk factor. Our guideline statements say that the l D l should be less than 100 after a t I or stroke and people who have diabetes uh, they're LDL goal should be left in 70. This is quite aggressive. Sometimes people feel limited in achieving this LDL goal. Uh, because of Staten reactions, this trial of called a Sparkle Trial came out in the New England Journal and it including both T I and Stroke and showed that it was quite a bit of ah hazard ratio of improvement with a high dose of atorvastatin of 80 mg overall, each 10% LDL reduction reduces the risk of stroke by 15%. Andi, I think this is a, uh, important thing that I like to tell patients about terms of how much of the pie that they're eating by taking their statin medication. Now there are new classes of agents coming out or have come out already The PCSK nine inhibitors on e Think those air also important alternatives to patients with statins, uh, intolerance, hypertension. So when patients come into the hospital, they are allowed to have permission. Hypertension. But after they leave the hospital, we really try to reduce their blood pressure, Uh, to less than 130 over 80. So really, um, this would be the kind of the newer update. The guidelines have been staying less than 1 40/90 in the past, but many of us are moving to a more aggressive blood pressure control less than 1. 30/80. And I talked about this as the biggest part of the pie that people are eating so, uh, 37% stroke reduction by controlling blood pressure to the ideal level. Um, and I think that the blood pressure I recommend is people take their home blood pressure with Cuff and asked them to call me in a week or two. Give me their home readings. We talked about in great detail. And I think that back and forth and communication allows quicker detraction to medications to get it to where they ought to be the best. Prevent them from a future stroke. The tip. The agent's air preferred our ace inhibitors. The Hope trial showed us this, but diuretics are also first line agents azi. You know, I think blood pressure is being highly stressed these days and for many different reasons, but also in neurology, we found that blood pressure is probably the number one risk factor we can modify in terms of dementia development. So mild cognitive impairment, uh, was shown to be reduced by having a very strict blood pressure goal at this lower level of lesson 1 30/80 even closer to 1 20/80 is ah, being done in the memory clinic here at UCSF. So that was based on the sprint trial in terms of anti platelets. This I won't really shocked people too much, but aspirin is our medication of choice. It's about a 15% risk reduction. We start off with 325 mg in the hospital, but we feel that 81 mg is all that's needed to keep this effect going in the outpatient center. Uh, setting. Now you will see us discharging patients from the hospital on aspirin, plus Plavix clopidogrel. Uh, this is based off the point trial that I mentioned earlier that I was involved with, and that was led by investigators here at UCSF. It started off in the chance trial in Asia and China in particular. And they used for PETA girl on aspirin for 21 days and showed a benefit. Even people who may not be Plavix responders for some reason. And then this was reconfirmed in the U. S. Population and, uh, inclusion criteria. I'll go into a bit detail, but it was a t I a, uh, with a particular score, which I'll mention later, and NH stroke scale of less than four. So you'll see many of us start patients on both clopidogrel and aspirin. The hospital important thing for you to know take away from the side is that we only want to continue for 21 days after 21 days. Both of these trials suggest that, um, there's an increased risk of bleeding on less risk of less chance of benefit. And no older times. We have been giving Agra knocks occasionally, and it's fortunately dose twice daily, and it hasn't really been shown to be superior to clopidogrel. Um, in fact, they were compared head to head and they're non inferior to each other. And there was more discontinuation with Agron OCS Group because of side effects. Um, so I think most of us have moved toward clopidogrel or aspirin. The number needed to treat to benefit one patient of switching from aspirin and clopidogrel over 200. So, in general, aspirin is our education of choice. There may be a future. Uh, medications like Sloss was all came out as a new medication to use for, ah, stroke prevention. Again, this was done in a duel anti platelet type of analyzation trial. And it showed significant benefit to duel dual therapy. And this they did over a long period of time. This needs to be replicated, but it wasn't exciting, um, finding that was published, uh, over a year ago. So we'll move on to case, too. Keep your attention. Rolling thistles. A 57 year old man is healthy, athletic. He had a sudden onset of inability to speak. He had this artery a and right arm weakness. The symptoms lasted only 14 minutes. Andi came to the emergency department to get that checked out. Um, in the emergency department, he got a normal head. C T and his a c T angiogram of his crowds were done on git showed this severe stenosis and inclusion near occlusion. So his diagnosis is a T I A. Because his symptoms have resolved within 24 hours. However, many of us would encourage people to get a Marie with these symptoms to see if there is actually in Fort Tissue. Eso If there is infarction, we call it a stroke, despite the symptoms having resolved within 24 hours. So we've moved to a tissue based definition of TIA versus stroke. People who have tedious need to be quickly evaluated. Uh, 20% of patients with a stroke have had a proceeding t a leading up to it in the United States that you can see it quite a large variety of admission rates for people with Tia's. And it's not clear, um, what is the best strategy? However, we do know that the best strategy based on expressed trial is to, uh, rapidly address their risk factors. Um, and part of that would be to make sure that they have created imaging T. A s are also harbinger of long term risk. There's increased risk of death. I mentioned already increased risk of stroke, but also heart attack. Overall, 10% per year increased risk of the vascular event of some type and then, um, overall risk of dementia. So e think this dementia and vascular risk I'll come together and are re occurring. Theme that we're developing a stronger appreciation for I promised to talk to you about the A B c D to score, which was part of the point trial. This is a way to evaluate a patient's risk over two days, seven days, 30 days and 90 days. I typically use it for a two day risk, but it's based on this a b c D d, to score eso that's age for a that's greater than unequal to 60. Blood pressure of greater than 140 speech impairment like this patient had weakness, get you two points and then the first D is duration, so you needed to have symptoms for more than 10 minutes, but up less than an hour. If you get over an hour or equal to an hour, you get two points as well, and then diabetes is your second D. And then based on your scoring, you have this type of risk over the next two days. So the maximum you know, there's about 8% risk of having a stroke if your score is high at 67. So promise to talk a bit more about crowd stenosis. We are basing a lot of our trials on old literature before even, uh, statin medications are available. But patients who have greater than 70% stenosis on the side of their stroke symptoms. Uh, so for this gentleman, there would be a left sided um, crowded stenosis. We recommend surgical intervention. Uh, typically crowd ultrasound is a good screening technique to detect significant stenosis, But many surgeons would require or request a C T angiogram or an m R angiogram to follow it up. I personally prefer C t angiogram, because I feel an M r angiogram, uh, sometimes over calls the greatest stenosis. Now, in this case, where there's a near occlusion of the carotid that sometimes needs to be confirmed by actually doing a catheter based angiogram, Uh, the elder alternative that we've developed is a C T angiogram with delayed profusion. Uh, so they take a kind of a delayed picture off the contrast, and they kind of wait a longer period of time to see if there's a trickle of flow through it. This means like it's a near occlusion rather than a total inclusion. The differences ifit's totally included. We don't offer surgery andare director me, but if it's nearly included, then it's a Nim. Urgent issue and the best outcomes are within the first two weeks of finding this, So it's really important to find it and treat it early. How to treat it as also, uh, informed by the Crest Trial Crest trial was comparing stenting versus endarterectomy Uh, and we've come down to the idea that they're pretty much equal. However, we favor crowd and directed me more on the cute setting. That's where it's been tried and true. In addition, patients who are greater than seventies seemed to benefit more from crowd and director me, uh, meaning they have less strokes. Onda better outcomes. People who are less than seventies seemed to favor stenting. Uh, stenting group had more strokes where the crowd and direct Me group had more myocardial functions as complications. All right onto Case three Thistle is an 84 year old woman with mild hypertension. She had a sudden inability to see the right half of words. She is reading the exam showed a right. Hm. Ominous Hemi an option. And, uh, she came to the emergency department for evaluation. Um, sorry. So we would typically wanna localize this. This is gonna be a cortical lesion similar to the last patients stroke. Or Tia was left cortical lesion because he had aphasia. This is in comparison to the first case I talked about which had a low Kunar or small vessel or sub cortical location in the emergency department. They got a head C T and C T A or C T angiogram of Kuroda's, and the blood vessels were normal. However, she had, uh, us, um, intracranial stenosis. So when what was found was that she had very small post your community cerebral artery, um, and show significant intracranial stenosis. So this is a high risk group. These patients who have Afro sclerosis off medium vessels in the brain, um, have a higher risk of the occurrence. And the best way to treat them has been somewhat debated and tried out. So the first was wasin. They compared warfarin versus aspirin, and there was no benefit to anti coagulation over aspirin alone. Sampras was a trial of using ah, Wingspan stent device in these intracranial vessels to prop them open and actually had ah, significant adverse events that led Thio superiority of the medications And this trial. It's very important to know that medication therapy was quite aggressive. They included aspirin plus clopidogrel for 90 days, plus atorvastatin, 80 mg intensive blood pressure monitoring with nursing calls to do lifestyle, uh, check ins and modifications, uh, in terms of diet and exercise. Um, In addition, this stenting was again tried in the visit study that showed again medical management was a very superior to stenting. Now, the you see, the medical arm still has a higher rate of re occurrence. There's 12 to 15% risk of recurrence. And then in the way past, they tried, um, external, created to internal carotid bypass surgery for patients compared to aspirin and again, aspirin, a medical therapy were superior. So I've talked to you about various types of stroke ideologies, and the reason is that three cause of the stroke is very important to directing how to prevent the next stroke from happening. So this pie graph helps you understand the causes of stroke from ischemic ideology, so scheming stroke is 85 to 88% of all strokes. So we didn't talk. We're not talking today about hemorrhagic stroke, but in general, hemorrhagic stroke is typically also can be related to small muscle risk factors, in particular hypertension. So after a Socratic disease, we talked about small vessel disease. We talked about cardio genic and m bolic stroke. People talk about next. Aziz. Well, is the crypto genic group, which kind of overlaps a little bit and you'll see why I say that in the second and we'll finish off with other causes. A stroke so cryptic genic stroke has been tried Thio redefined as symbolic stroke of undetermined source. Or I'm gonna say, use this from now. Yes, you ask. Um, so stroke is detected and confirmed by an Emory, uh, or C t scan. And again, it's gonna be unlike pattern one that we saw in case one. It's gonna be mawr cortical based out on the surface of this other brain. Um, and that's going to be confirmed by imaging. Second, we need tohave the blood vessels image so similar to the prior case where they had a CT angiogram, had a neck. This will tell us whether there is any stenosis of blood vessels that are greater than 50% in the proximal artery. Then the patient does not have atrial fib relation or other thrombosis in the heart valve agitations that would be a source of embolism. And then there's no arterial dissections. Drug abuse our rightists that couldn't explain this. There's a high impact of thesis, Uh, because there's a per year risk of 3 to 4%. Despite anti platelet therapy patients, uh, groups have tried to figure out what's best in terms of doing something more than aspirin, and that was tried out in the wars study, and they looked at the subgroup of patients there. The head, crypto, genic strokes and warfarin seemed to be trending toward benefit versus aspirin, um, but was not significant, and authors and commentary suggested maybe that was due toa hemorrhagic risk washing out the benefit. So that led to the respect uses trial, which I mentioned I was involved with. That was compared to bigotry and 150 mg versus aspirin, Uh, and there was no benefit to using the bigger trail over aspirin. Second, there was another trial called Navigate Thesis that looked at River Rock, Saban versus Aspirin. And again, there was no benefit. Currently, as I mentioned, we're involved in Arcadia Trial, which is looking at a subgroup of patients with thesis who have left atrial enlargement or L a Onda. Again, we're comparing a pixel band versus aspirin. Um, so in the script Agenda group, before it was really well established to use the term thesis, there was a study called the Crystal A F in New England Journal that looked at implantable loop recorders. Um, and that showed that patients who were greater than 40 years of age, um, would have higher prevalence of stroke, Uh, in the future. Uh, sorry. Higher prevalence of atrial fibrillation in the future. So at 36 months, there was a 30% discovery of atrial fibrillation versus 3% at standard of care. Um, and this led to change the medical management. So instead of anti platelets, the patients now have a reason to be an anti coagulation. The Embrace trial looked at 30 day cardiac monitors. They included the older group of patients a greater than 55 years of age and then compared 30 days versus typical e k g, or telemetry in house, uh, in the hospital. And they found a rate of 16.1% of atrial fibrillation at 30 days, and therefore they came up with the number need to screen of eight. So this is now our standard approach for patients who have had a crypto genic stroke. Uh, our thesis stroke now is toe have a 30 day cardiac monitor at the time of discharge. So this would be something that you'll see the patient having been discharged with cardiac monitor that needs follow up if it hasn't been done. Thanet needs to be done. Is now patient if the cardiac monitor is negative for atrial fib relation. But again, there's a strong suspicion that this that the patient might have a tribulation, especially if they're elderly, talked about palpitations, may have coronary disease. Uh, cabbage are in the past, Then I typically will go on to suggested implantable loop recorder toe provide the three year monitoring. The reason is that treating atrial fib relation is one of the most effective things you could do to help prevent future stroke. So, um, now that we have, uh, direct Orel anticoagulant type of therapy like a pixie band or rocks, even or dig a trend. Those medications are reasonable alternatives toe warfarin, and I think they offer patients benefit for future stroke prevention. As I said earlier in the slides, uh, atrial fib relation can increase your risk of stroke by four. Full case for talked about a young woman. She was a 34 year old gymnasts. She was healthy. She suddenly developed the right side of neck pain and transient nausea, vertigo and hearing loss on the right. On exam, she has nystagmus of her eyes and various directions, and you perform a finger to nose testing that shows her right hand is not functioning well with some dismay. Tria this presentation with localized to post your circulation of material vascular system and in particular cerebellum. So here you see a right cerebellum infarct. That's a hemispheric Here. This is a kind of a large. This is a large stroke and this is concerning for herniation. You can already see the brain stem kind of being compressed here. Fortunately, she does well, but you see kind of attenuation of her vertebral artery here and this was likely a dissection. However, she, um, was treated just with anti platelet medications due to recent studies and particularly scatters trial. Comparing anti platelets versus anti coagulation uh, there showed no benefit. Thio anti coagulation again, Uh, anti platelets was sufficient and preventing future stroke at three months. So that is the highest risk period of time for dissection. Typically, I may re image the patient who has a dissection on bond. I can see a fair amount of times a healing of the dissection. Oftentimes it stays the same, and very rarely does it get worse. But in those rare situations, especially if there is worsening symptoms, um, or severe stenosis, then we could talk more about intervention potentially. But, um, anti platelets have become our treatment of choice. In the past, when I was training, you know, we would place people on heparin drips and an anti coagulate them, but no longer. In addition, this patient, you know young patients should be evaluated for PF. Oh, so if you didn't find the dissection, um, and this patient had this type of stroke playing a kind of changing the scenario a little bit. So let's say she didn't have a dissection. Let's say she just had p fo found on her trans Jurassic echocardiogram. Um, then we were going into that topic now, which is something that you should be aware of The trials only mentioning really included patients who are less than 60. And here at UCSF, we have talked to our cardiologists and they're willing to do straight to the transits Often do echocardiogram For patients who have a high probability of having a p f o is their cause. P F O s, as you know, are quite common The general population So we always had a hard time attributing pf os is the cause of stroke. But we've learned that large P. F O s, um uh are more risky than small PF Oh, so we like Thio obtain a size, uh, from our cardiology colleagues. So the large sizes to find this greater than six micro bubbles. However, we also want to know of this small sh p f o has an atrial septal aneurysm. Both of these scenarios monitor large hunting and atrial septal aneurysms are considered higher risk for am bolic stroke mechanisms. We think that young adults are more common toe have CFOs who are in the symbolic stroke category. And, uh, I find that if you have a hard time measuring the size of the shunt well, or uh huh transcranial Doppler counter CFO Thio to maybe an easier way than the trans Thor ASIC echocardiogram. So the first trial that I'll talk about is called reduce came out in the New England Journal showed that there was benefit, uh, in the P f O closure group compared to the anti platelet group, Um, there was a adverse effects, uh, causing atrial fibrillation. And 6.6% of the patients in the PFL closure group, the closed try Ally also had this atrial fibrillation risk and also confirmed this benefit at five years between anti platelets compared to P f o closure. This is a nice summery slide about prior trials. Didn't really show any benefit of closing P f o s. Uh, you should be aware that their inclusion criteria included any shunt size. Um, and this will be shown here where you see this kind of increasing percentage of the study population having large moderate size shuns, um, which I think explains why there was a scene of benefit in these later trials, and they were seen in the earlier trials here. You can see this benefit in large shunts that air present. Uh, when you put together this meta analysis, you see a clear benefit risk reduction. When you look at small Shawn's present, you don't see a school benefit and a tribulation. This is what you patients need to be aware of, and us physicians need to be aware of. The patients who have had P fo closures can have atrial fibrillation as a side effect. Typically, it's thought to be transitory atrial fib relation, but again because we would change our medical management. If the patient does develop atrial fib relation, especially if it's persistent, then there's a strong argument. Tow anti coagulate thumb. I have a high degree of suspicion that once you have h the atrial fibrillation, you're at risk of having it again. So I would be aggressive with a patient who has had atrial fibrillation after p fo with the implantable loop recorder, or at least a 30 day cardiac monitor. Lastly, I talked about others eso prior to P f o closure. Other causes a stroke so prior to p f O closure I check anti fossil lipid antibody panel, especially in young patients again under 50. The definitely would be a high prevalence. But you know, in the P F O closure group that includes less than 60 years of age. You know, we asked things about miscarriage rate. Uh, and there's an increased risk of stroke patients who are Lupus, Lupus. Positive. So I think that anti fossil lipid syndrome is something that can cause material strokes, Um, and should be checked in patients with crypto genic stroke ideology. In addition, uh, patients who have p fos on did have a prior history of DVT s or particular family history of traumatic events. I will check. In addition, tow anti fossil open antibody. I'll check. Hype required will risk factors like factor five line program gene mutation. So this ends my talk today. I hope that was informative to you in terms of running down the landscape of secondary stroke prevention based on cause