The Current State of Stroke and Stroke Treatment

David Holmes really set the stage with his discussion, but let me also summarize what stroke means today. After suffering a major stroke, one-third of patients will recover, one-third will die, and one-third will be wrecked; it’s the latter group that makes life so difficult for us. A normal brain occupies 2% of body mass, consumes nearly 20% of cardiac output, and extracts the largest percentage of oxygen of any organ in the body (A-V difference). Ischemic penumbra (the area peripheral to the core infarct with brain cells at risk, but not yet dead) is the tissue we need to save. There will almost always be a dead area in the middle (as is probably the case with myocardial infarction too). But the space around the edge of the stroke is not functioning because the blood flow is abnormally low, approximately 10–20 cc/100 gm/minute, a level below which most brain tissue is irreversibly damaged. I don’t want to say much about the National Institutes of Health Stroke Scale (NIHSS) because it’s something one has to develop a feel for. The cutoff is about 7. If the patient’s score is much greater than 7, to the stroke will cause him damage. If the score is greater than 10, to the patient will likely spend the rest of his or her life in a nursing home. What strategies are available for treating stroke today? Two primary FDA-approved strategies are currently available. One is intravenous (IV) tissue plasminogen activator (tPA). There are many limitations with tPA, which is toxic to neurons and neurovascular cells. The bottom line is that when IV tPA is used in stroke, the result will be the following: nearly 60% of the patients are dead or disabled at 60 days. Sounds like a great therapy, doesn’t it? The Standard Treatment with Alteplase to Reverse Stroke (STARS) post-market study, which looks carefully at this whole NIHSS issue, documented a 22% decrease in recovery after IV tPA for every 5-point increase in NIHSS score. And a NIHSS greater than 10 results in a 75% decrease in the odds of recovery. The other FDA-approved strategy is the Merci retriever, which is not so red-hot overall either, with a 46% recanalization rate. And if a lytic cocktail such as tPA is added, the recanalization rate reaches 64%, but more hemorrhages occur. Let me discuss where I think the field is heading by using an example. A 26-year-old female patient with 3 young children presented to us with right-sided hemiparesis and a mixed aphasia. She was a smoker. She was not taking birth control pills. The patient had an NIHSS score of 11, which is a pretty bad stroke, and one that if left alone, would cause her a lot of trouble for the rest of her life. Her initial CT scan was basically normal. Her CT perfusion scan, which we are using now as a gating diagnostic study, showed increased time-to-peak (delayed or reduced flow) throughout most of the left hemisphere and a small black hole (indicating minimal or no flow). If we saw a large black hole, we might as well quit because that brain would be dead. Her angiogram showed complete occlusion of the M1 segment of the middle cerebral artery. We decided to use a small dose of IA reteplase in the patient’s middle cerebral artery, and then used a clot retrieval device and balloon angioplasty, but were unable to achieve any revascularization, which is so often the case with patients like this. If you think about it, stroke is usually embolic, and MI is usually a plaque complication or rupture that causes thrombosis. So why is it so difficult to open a clot-occluded vessel in the brain? You would think one could just reach in and grab the clot and be done, but it just doesn’t work that way. I think the clot becomes very adherent. We then decided to place a coronary stent in the inferior division, and then proceeded to try to open the superior division; the patient was given a little more reteplase and underwent angioplasty again — but none of this worked. We went ahead and stented the superior division as well using a second coronary stent. At that point, we saw a little kink in the vessel. We thought, flow is good so we’re done. On the table, she was NIHSS 1, which is essentially normal, with a little bit of neglect of her right side, but otherwise resolved. At 3 months, the patient was readmitted with two stereotypical spells of right-sided numbness and word-finding difficulty reminiscent of her previous stroke. Her angiogram showed slight narrowing still where the first stent was crimped by the second stent. Thus we did what cardiologists normally do — we used kissing balloons and went ahead and fixed that. That was 1 year ago, so the patient has done well. This type of strategy, I think, is where we are headed. The following are some of the data from our study that was presented at the Annual Meeting of the American Association of Neurological Surgeons in 2006, and a follow-up article will be published in the May 2007 issue of the American Journal of Neuroradiology. We took our first 19 patients where everything else failed — the artery was unable to be opened, and stents were placed. The median baseline NIHSS score was 16, obviously very bad strokes. In 79% of patients (15 of 19), Thrombolysis in Myocardial Infarction (TIMI) 2 or 3 flow was achieved. At discharge, the median NIHSS score was 5, which means that the patients were independent, needing some help, but able to live at home and take care of themselves, which is a heck of a lot better than what we started with. Positive predictors of favorable discharge outcome were younger age, lower baseline NIHSS score, and location other than internal carotid artery terminus, which is a big clot — clot burden, I think, more than anything else. So for the future, the strategy will likely involve rapid clot removal, stenting as necessary — moving toward what cardiologists have been doing to treat acute MI over the last couple of decades. What are the market needs? Approximately 600,000 to 650,000 ischemic strokes occur every year, and about half of those are in patients in whom the lesion might be amenable to intervention. What’s the supply of interventionists? There are currently about 200+ card-carrying neurointerventionists, but only about 50 of them actually treat stroke. In fact, a poll we conducted last year revealed that only half of those 50 specialists indicated that they would like to treat stroke. Thus, there’s not a large pool of physicians wanting to get out there and do it. As for neurosurgeons, there are currently about 65 trained, and they’re raring to go, but there aren’t enough of them. There are only about 6 neurologists trained in the United States, which won’t get us very far. And for the most part, neurologists don’t have the desire to deal with something like acute stroke, in an interventional sense, anyway. Finally, only about 5 cardiologists have started to treat acute stroke. So which kind of practitioners do we really need? The ideal practitioners will have catheter skills, access to the lab, a knowledge base, the appropriate mindset — that is, the “procedural” mindset, which involves wanting to fix a problem when it arises. Most of us gathered here have that mindset, as we are used to handling emergencies. Consider interventional neuroradiologists, who certainly have the catheter skills, but who primarily work in major academic centers, so their access to cath labs is not widespread. And as for the necessary mindset, interventional neuroradiologists are used to emergencies in some sense, but it’s the neurointerventionists who are trained as surgeons and who are the leaders in the field in terms of treating stroke. Many interventional neuroradiologists, however, are more used to a diagnostic mindset. As for neurosurgeons, some have the requisite catheter skills, cath lab access, knowledge base, and mindset. But more neurosurgeons with catheter skills are needed if they’re going to participate in this specialty. Most neurologists have the required knowledge base, but lack the catheter skills as far as acute stroke intervention is concerned. Finally, there are the cardiologists. They’ve got the catheter skills, the access to cath labs, the knowledge base — they certainly understand the clinical aspects of treating patients. They lack end-organ skills, however. Cardiologists possess the mindset since they’re used to dealing with emergencies. Also, there are plenty of them: 6,500 interventional cardiologists in the United States today. You can see where I’m going with this. They’re already involved in stroke prevention, management of atrial fibrillation, hypertension, lipids diseases, and so on. Furthermore, cardiologists have the ability to manage cardiac morbidity, acute MI skills (which I think are increasingly the same skills required for stroke management), catheter management, and endopharmacological management and understanding. Thus cardiologists are “almost there”. The ability to perform a neurologic exam is not rocket science, but the ability to recognize subtle findings on exam is important. It’s for this reason that I continue to emphasize that collaboration is key, because a team of trained individuals who can cover everything is the solution. Overall, I think there is a huge opportunity for interventional cardiology in the field of stroke treatment. There will always be naysayer, but working together, we can beat stroke.