2002 IAGS Proceedings: Intracranial Interventions (Part I of II)

John Anderson: In the U.S. and in Australia, stroke is the third leading cause of death and the leading cause of disability. Yet despite this, there is an air of therapeutic nihilism about stroke. Patients who present to the emergency room with a stroke are often considered beyond help. Unfortunately, Nick is correct: Where neurologists are with stroke today is essentially where cardiologists were with acute coronary syndromes in 1980, and treatment is not progressing very quickly. General physicians today seem unaware of the fact that things can be done for stroke patients. Unfortunately in the case of stroke, unlike in cardiology, the window of opportunity is considerably smaller for intervention. Several stroke trials have been conducted using systemic fibrinolysis. One such trial conducted in Australia used streptokinase. The neurologists involved in the Australian trial were advised that streptokinase probably would not work and that it may cause more harm than good by precipitating intracranial hemorrhage. Systemic fibrinolysis does not work in the brain; it must be catheter-directed and often must be done all at the one time, requiring someone to actually stand by the patient with a small microcatheter to dissolve the clot by hand infusion or to pulse a thrombolytic agent directly into the lesion. Fortunately, some good quality catheters are available for this application from Target Therapeutics, and more recently from Cordis. However, the peripheral story does not end with occlusion, it includes hemorrhage as well. When basilar angioplasty is performed, particularly by an aggressive operator, perforators can actually be sheared off. In these cases, because the patients are anticoagulated, fatal subarachnoid hemorrhage frequently occurs. My personal experience is limited to the posterior circulation. It may be surprising, but the patients referred to me — a vascular surgeon — usually come from neurologists as opposed to radiologists, because the former are not very aggressive in stroke treatment. I have avoided the use of stents in the intracranial circulation because the arteries are very difficult to get up into and trackability is a problem. When I perform a diagnostic study using the groin approach I sometimes change to the brachial approach in order to get up into the vertical and basilar arteries. It’s often a matter of looking at the angles and choosing the best approach. Since I work in a cardiac catheterization lab, I tend to use cardiac balloons, all of which are Monorail — we don’t use any coaxial cardiac balloons. These balloons have proven fairly effective, especially when combined with an appropriate guiding catheter. Maneuvering these devices, however, is difficult; sometimes you push a little more than necessary and the balloons tend to fly forward and jump around. This procedure is time-consuming and needs to be performed when the patient presents, but the results can be rewarding. Unlike cardiologists, we often don’t have the same degree of evidence-based medicine to work with because we deal with a very fragmented group of physicians: neurologists, general physicians, emergency room physicians, radiologists, and others. Most interventional neuroradiology is probably still handled by radiologists in my country where very few, if any, facilities offer acute stroke services. I congratulate Nick for establishing such a service in Buffalo. Nick Hopkins: I believe we have a terrific opportunity to make a dent in stroke treatment, but neurology cannot do this without cardiology’s help. For one thing, cardiology has the manpower. I don’t see how we can train enough neurosurgeons and neuroradiologists to make significant progress in the treatment of stroke. Many cardiologists have asked me to teach them how to perform neuro interventional procedures and current technology makes it fairly easy to do this. I think there is an opportunity for cardiology to expand its horizons — but I will probably be shot for saying it! Gary Roubin: I had the opportunity to speak at the American Heart Association Stroke Conference two weeks ago in San Antonio where it was very clear that the neurology community is accepting of interventional cardiologists participating in the acute stroke interventional programs throughout the country. In fact, nearly all interventional cardiology meetings where a peripheral vascular component is included offer a segment on intracranial intervention, both acute and elective. I am encouraging the American College of Cardiology to accept a role in this field. We are now seeing a move toward cardiologists treating carotid bifurcations and some intracranial anatomy cases. Interventional cardiologists need to get on board if we are to meet the challenge of treating the 750,000 stroke cases we see each year. At our institution, the interventional cardiologists will be handling some of the stroke cases under the guidance of Jiri Vitek, an experienced and talented neuroradiologist who is with us here today. Other centers may want to have the neurosurgeon offering guidance to the cardiologists. I think this cooperative method between the disciplines is the best way to proceed. Nick Hopkins: Neuroradiologists are very concentrated in major urban centers, whereas cardiologists can be found everywhere. I also agree that it’s crucial for cardiology to get involved. Every year we have a neuro-interventional complications conference attended by many neuro-interventionists from across the country. At this conference three years ago, I asked the question using the polling system: Should we train interventional cardiologists to perform these procedures? One-hundred percent of these physicians responded No! (laughter) The following year, however, two responded affirmatively, and last year, 15–20% were in favor, which is a significant shift in opinion. Paul La Violette: From industry’s perspective, stroke is an enormously important issue and a potentially huge market. Boston Scientific has the largest interventional neuroradiology business in the industry and does a significant amount of cardiology and interventional radiology business as well. I can say for certain that we will never make inroads into stroke intervention with the existing pool of interventional neuroradiologists. Boston Scientific is funding neurosurgery and interventional fellowships, but there are only one to eight fellows a year on average. As was mentioned earlier, the disparity between interventional cardiology programs and interventional neurology programs is 100 to 1. There really are no technology barriers, only technology needs, and we will meet those needs. The overlap between the interventional fields will undoubtedly create those technologies, with neurology actually lending some technologies to the cardiology field. However, it makes no economic sense to invest in those technologies if only a handful of centers can ultimately utilize them. All of the $40 billion spent annually in the U.S. on stroke management goes toward patients who have already had a stroke. This is a total waste of money. We have a massive global budgeting problem, and I think stroke is probably one of the best examples of how not to spend money. We wait until it’s too late, and then throw a bunch of money at the problem. Nick Hopkins: I don’t think you should underestimate the importance of your fellowship program because it’s not so much that you are training neurosurgeons how to technically perform the work; what you are doing, rather, is planting a valuable “seed” in a major center with a major department of neurosurgery. Neurosurgeons and neuroradiologists, who have traditionally had a very negative or almost nihilistic approach to stroke, are suddenly beginning to see the light and are excited about it. Thus, one “enlightened” neurosurgeon in a department can have an enormous impact on the way the others in the department look at stroke. We are very grateful for your fellowship programs. Jim Zidar: Over the past fifteen years at Duke we have developed a team approach to stroke management. Duke has three or four vascular surgeons who did all the carotid endarterectomy work but who were not very interested in the endovascular side of things. We began to make some progress when the interventional cardiology department teamed up with the interventional radiologists. Two of these interventional radiologists in particular have been involved; one has some previous neurology training, and the other is a neuroradiologist. Duke’s program is similar to that of Lenox Hill with Jiri Vitek where a group of people from different specialties work toward one goal. The key to Duke’s success involved situating a cardiology-based peripheral room exactly opposite the radiology suite, in the radiology department, so that we share a control room. Staff members from both disciplines talk to one another every day. When, for example, the radiology staff asked about new wires, we were able to say, “We have this new Whisper wire and the Choice PT — give them a try.” We share ideas and new information on balloons, stents, and so forth. There seems to be considerable difficulty with tortuosity in the brain that requires even more challenging balloon/wire and stent/wire combinations. Duke’s interventional radiologist, Tony Smith, will sometimes hear about a new device that the interventional cardiology department is using experimentally. He will then call the company to find out what he can do with the device up in the head and whether he can get a registry started. I think stroke treatment requires a group effort involving multiple specialties because each discipline has something valuable to offer. At Duke, Mike Alexander, a neurosurgeon with endovascular training, has made the biggest impact. Mike is a young, aggressive physician who came to Duke as the only neurosurgeon with radiology privileges. He performs carotid endarterectomies — which had always been vascular surgery’s territory — as well as carotid stenting and intracranial work. Duke also now holds weekly conferences where we discuss complications with representatives from all of the different specialties. As a result, we will hopefully do well in CREST, ARCHER, and other trials. Nick Hopkins: I agree that it is crucial to bring the different specialties together in order to broaden our perspective. In each institution, local politics will play a role, and every institution plays by different rules. Some institutions, for example, have radiology departments that don’t want to cooperate. The bottom line is that if the different specialties will work cooperatively with one another and offer privileges, then we can begin to actually make some progress and the movement will snowball, as it has at Duke. Max Amor: I have no magic bullet, but I think that politics are an extremely important component of this issue. In France in the past ten years, I have not seen any changes in the approach to treating stroke. There are still efforts to make advances in some centers, but I have realized that it is very difficult to convince neurologists to enter into that domain. It has also been difficult to convince neuroradiologists to involve cardiologists in stroke treatment. I would say that the situation has been quite stagnant in my country over the past four to five years. From my experience with carotid angioplasty and carotid stenting, I think it is extremely important to organize collaborative, multi-disciplinary studies on an international, European, and national basis. These types of studies show local practitioners how to treat stroke. Perhaps the IAGS could have a role in defining a multidisciplinary territory to convince local practitioners to work as a team. If we don’t do this, we will continue holding meeting after meeting while the stroke situation remains unchanged. Likewise, industry will have no incentive to invest money in stroke research. Gary Roubin: I called Richard Stack twelve years ago to ask how I could get our people organized at UAB to improve stroke treatment. Following Richard’s advice, I got interventional radiology and neuroradiology involved. It is important for the group here to understand that it was actually at the IAGS meeting ten years ago, attended by Bob Ferguson and a few other interventional radiologists, where we had discussions like this one today regarding carotid stenting. That meeting ten years ago gave us the confidence to join with Jiri Vitek and get carotid stenting started. There has been a major change over the last decade in the way that carotid disease is treated, and it started with this group. This change is something we should be able to replicate in other areas as well. I would be interested to know what Fayaz Shawl, Howard Cohen, and perhaps some of our South American colleagues think about this. Some of the practical issues we need to address involve finding ways to share information and ideas, overcoming some of the interdisciplinary barriers that we face, and getting major players such as Cordis, Boston Scientific, and Guidant more involved in bringing different disciplines together. For a number of years thought leaders such as yourself, Nick, have acknowledged that there will be no progress in stroke intervention without the help of interventional cardiology. The national bodies of neurology have just recently acknowledged that interventional cardiologists are far ahead in acute myocardial infarction intervention and now have many experienced operators available to help in acute stroke intervention. And yet, we are still struggling. We should perhaps turn this discussion over to those of you who come from some of the largest centers in the country — many of them very influential academic centers such as Mayo Clinic, Montreal Heart Institute, and Duke, which has the largest interventional laboratory in the country. As a society, the IAGS doesn’t quite have the “muscle,” but with companies like Cordis, Guidant, and Boston Scientific behind us, we can get organized. Tom Linnemeier: Medical technology seems to be outpacing the medical subspecialties. There is nothing you showed us, Nick, that can’t be fixed with the devices currently available from the major catheter companies. This is a good place to start, but I think that industry is hoping that medicine will move things forward. You can give example after example of failure for every successful Lenox Hill or Duke. One such example would be at my own institution, St. Vincent Hospital, where we thought we would solve the interventional radiology problem by hiring Don Schwarten. Within a two-week time period, the vascular surgeons hired their own interventional radiologist and Dan sat around for a long time with nothing to do. This is a very complex subject with complex dynamics. It requires someone like Nick Hopkins to stand up and say that interventional cardiology and neurology ought to work together. I am glad to hear that the American Heart Association is encouraging interventional cardiologists to get involved with stroke intervention. Some of our own societies such as the AMA, the ACC, and the AHA have some relatively conservative views on how this ought to be handled. There certainly are some influential people in this room today — so let’s work through the professional societies to help move this technology forward. Nick Hopkins: One of the biggest problems is that we fail sometimes and we will continue to experience failures in some of our cases, with devastating outcomes. The neurology community is tightly focused on clinical research and outcomes, as well they should be. However, a very powerful force against the new technology crops up when a disaster occurs. We experienced a huge battle at our institution following a failed procedure that resulted in committee hearings. It was just awful. Neurology basically said, “You had a hemorrhage here; the patient died.” I told the committee that the patient had an NIH stroke scale of 23 when we started, which is worse than death by almost anyone’s definition. Yes, the patient died. He died because he had a hemorrhage. But frankly, if it were my stroke, I would hope you would intervene on me — I’ll take my chances, thank you. Progress will come only when we train more neurologists who will then go back to their institutions and preach the gospel to their colleagues. As Gary Roubin said, the neurology meeting represented an enormous breakthrough this year because there was finally a recognition that they need the help of cardiology. Neurology still represents a major hurdle, however. They will hold our feet to the fire, as they should, but we must bring them along. Tom Linnemeier: Generally speaking, one doesn’t become a neurologist because one enjoys performing acute interventions. I’ve watched Gary Roubin get shot down so many times over the past fifteen years for performing carotid angioplasty, I don’t know how he’s still standing! The amount of grief Gary has taken is unbelievable. It takes people like Gary, Andreas Gruentzig, Richard Myler, and Eberhard Zeitler, to stand up and say: “Yes, we will have complications, but we need to move this technology forward.” It takes courage, charisma, and perseverance. I guarantee you that Andreas Gruentzig did not back off when a patient died or when a patient had a complication. We simply wouldn’t be gathered here today if not for the courage of these men. Doug Cavaye: I am a vascular surgeon. My intervention work ends in the carotid artery. I have jotted down some comments which all happen to start with the letter “p.” The first “p” represents the concept of a neurological penumbra — an area of ischemic or dying brain cells that are electrically negative and that may or may not be able to be rescued. Thus, the concept of a penumbra implies that time is very important. If a patient has a deficit that lasts for 60 minutes, my understanding of the literature is that he has about a one in four chance of rescue. If the deficit is present at two hours, the patient has a less than 10% chance of the event being a transient ischemic attack. In other words, a stroke is established in more than 90% of patients at two hours post-event. Thus, getting a patient to the hospital — which is the second “p” for protocol — is just as important as the penumbra. The third “p” is for perforators, which are deadly little arteries. You can’t blow up a balloon 2 cm long in intracerebral vessels without getting a perforator, and it is difficult to predict the occlusion’s locality. A perforator occlusion is dramatic and disastrous. The final “p” — for pharmacology — is something we have not yet discussed. Many of the cardiological improvements, or rescues of cardiac interventions, have relied on pharmacology — whether these are anticoagulants, lytic agents, or anti-spasmodics. What is the current situation with intracerebral or neurological pharmacologic rescue? From what I understand, very few agents are effective. Nick Hopkins: You talked about the window of time, the first “p.” In certain circumstances a stroke is indeed likely to be established within two hours. But everything depends on the substrate. For patients with no underlying collateral, there may not be very much penumbra. That’s actually one of the big “bugaboos”: we have difficulty determining which patients will do well and which ones will not. If you see a big infarct on the CT scan, you know the patient is cooked; there’s nothing you can do. But if you don’t see a big infarct on the CT scan, you don’t really know the status of the penumbra. There is no test available yet to quickly assess a patient’s condition. We have all seen patients — particularly cases involving the vertebral-basilar system — who were as long as 12, 14, even 24 hours out, were locked in neuroradiology, and who then made dramatic recoveries when their vessel was opened up. As for the pharmacological aspect, we are trying to inch our way along at our center with small numbers of patients. We’ve been reporting groups of 15 to 20 patients, with 15 patients in thrombolysis alone. There was a high rate of hemorrhage and a relatively low rate of reperfusion in these patients. If we used thrombolysis plus mechanical disruption of the clot, 85–90% were reperfused, but there was still a significant incidence of hemorrhage. Now with a much lower dose of thrombolytics and the addition of abciximab, we are achieving much better reperfusion and many fewer strokes. We still experience a good number of failures, however. We are now looking toward opening the window of time with techniques such as cooling, which a lot of previous work has shown to be the best brain protectant available. Thus, we are inching along with the same pharmacologic agents that are being used in cardiology, but it’s a slow process and it’s difficult to get patients into the centers. Neurology does control most of the strokes and we must keep working to convince them that we should be entering these patients in the experimental trials. Chris Cates: I want to revert back to what we were discussing earlier. I have done carotid work since 1994 after training under Gary Roubin. I am constantly amazed at the visceral response that carotid stenting by cardiologists evokes in colleagues who are on the multi-disciplinary team. It seems that at the early, vestigial phase, there is a lot of camaraderie. However, as soon as success and notoriety come along, a visceral reaction — subtle nastiness —takes over. The quality assurance process is used in every way possible to stifle the program. Given that, I would like to address what Paul and Tom have said about industry’s influence. Paul said that because not many physicians are involved in stroke intervention, it is difficult for industry to justify expenditures in that area. On the other hand, you (Paul) and others have done a lot to try to be politically correct and develop the protocols for the very small group that you were just complaining about. One way to “enlarge the pie” would be to start involving cardiology more in those protocols. In fact, instead of putting the stroke protocol with the typically anti-intervention neurology group, give it to the group you want it to grow with, which is cardiology. Let the others either join in or not. This would be a way to justify from the company’s and the FDA’s point of view that the physicians you involve in this protocol are in fact eligible to perform the procedures it calls for. I think this type of strategy will have a much greater impact on the marketplace than you think. See 2002 IAGS Proceedings: Intracranial Intervention - Part II