Until very recently, the standard of care in acute ischemic stroke was tissue plasminogen activator (tPA). Then, a rare confluence of studies from different parts of the world showed the superior efficacy of mechanical thrombectomy (MT) added to IV tPA in stroke patients with large blood vessel blockage over tPA alone when applied within six hours from start of stroke symptoms. This shifted the treatment spectrum on a global scale, and led to the development of new guidelines and standards of care. Implementation of new stroke networks and protocols for the rapid delivery of care for this very time-sensitive therapy is ongoing but has not been nearly as fast as therapeutic advances. Moreover, the role of neurologists in this new stroke treatment paradigm is also in rapid evolution. Ahead, two neurointerventional specialists offer perspective on the implications of the new standard of care and guidelines and how, exactly, general neurologists will fit in this quickly developing frontier.

A New Standard of Care

When it comes to scientific advances, rarely does the term breakthrough apply better than in the case of stroke care, according to Dileep Yavagal, MD, Chief of Interventional Neurology and Co-Director of Endovascular Neurological Surgery at the University of Miami. The extent of the breakthrough is hard to fully realize at present because it’s such a big change, Dr. Yavagal observes. For the first time, we can in a large percentage of patients with very disabling strokes, treat to achieve about a 70 percent chance of reversing their stroke to the extent that they can be independent again, he says. That’s never been possible in the past.


Revamped guidelines and emerging networks of care are paving the way for a new chapter in stroke management. Despite the size and number of challenges associated with this new direction, the process of ensuring timely care and access to endovascular therapy is moving in the right direction. To that end, neurologists will have an important role to play in directing patients to the appropriate channels for optimal care.

According to Johanna Fifi, MD, Assistant Professor of Neurology, Neurosurgery, and Radiology and Director of the Endovascular Stroke Program at Mount Sinai Health System, it would have been hard to imagine the current status of stroke care as recently as four years ago. In 2013, there were three trials that came out looking at mechanical embolectomy for treating large vessel occlusion, says Dr. Fifi. These trials used old technology and all were negative, further solidifying tPA as the current standard of care, she observes. The initial signs of a breakthrough came in 2015, according to Dr. Fifi. The MR CLEAN study showed the overwhelming efficacy of mechanical embolectomy versus tPA alone, suggesting that patients should be taken directly to the angio suite to have the clot removed in addition to doing standard of care treatment. The procedure was overwhelmingly efficacious, she notes, at returning patients to normal function at three months.

Following the MR CLEAN results, four trials were simultaneously presented and published in The New England Journal of Medicine that were all positive, says Dr. Fifi. These were the EXTEND-IA (Extending the Time for Thrombolysis in Emergency Neurological Deficits–Intra-Arterial) trial in Australia, the ESCAPE (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times) trial in Canada, the SWIFT PRIME (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke) trial in the US and European sites, and REVASCAT (Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within 8 Hours of Symptom Onset) in Spain. The sweep of these findings translated to a need for a complete change in stroke care. These five trials from various parts in the world that have shown significant benefit have left no doubt that this is an immensely effective therapy, says Dr. Yavagal.

Examining the New Guidelines for Management

Later in 2015, the American Heart Association and American Stroke Association updated their joint guidelines for the early management of patients with acute ischemic stroke to reflect the new findings. The guidelines now state that patients over 18 years of age with a NIH Stroke Scale score of six or more presenting within six hours who have been given intravenous tPA must be taken to the angio-suite for endovascular care, says Dr. Yavagal. This is a Class 1, Level A recommendation, the highest level of recommendation for evidence-based medicine, he adds. With such a sweeping change, Dr. Yavagal, observes, neurologists and other practitioners who care for stroke patients cannot ignore endovascular therapy or dismiss it as an experimental therapy.

Another important aspect of the guidelines is the Class 1, Level A recommendation to treat fast and fully, says Dr. Yavagal. Everything requires sources and organization, and the questions always comes to: How fast, exactly, should we be implementing treatment? The scientific proof was not there to say how fast, but, he notes, now we know that every second counts. The proof is now there from all of these trials that if a person is walking with a stick after stroke, they might not have needed it if we had given therapy 30 minutes prior, saving almost 60 million neurons, says Dr. Yavagal. The guidelines clearly state that eligible patients should be treated with mechanical thrombectomy in the angio suite as fast as possible without waiting to see if tPA has worked. The guidelines also offer direction regarding the extent of opening the artery, Dr. Yavagal explains. The correlation between percentage of blood flow returning and the clinical outcome is extremely sensitive, which is why physicians need to be as aggressive as possible. The neurointerventionalist must be highly skilled so that they achieve 60 percent or more reperfusion a majority of the time, he says.

The other major change in the recommendations relates to advanced imaging. Another Class 1, Level A recommendation states that CT and CT angiogram should be done for every patient as quickly as possible in order to meet the criteria, to localize the site of occlusion, says Dr. Yavagal. Moreover, we no longer need advanced perfusion imaging—either CT perfusion or MR perfusion—to select a patient for endovascular therapy, he adds. Importantly, the guidelines do not state that CT perfusion should not be done, rather that it’s not a requirement in order to take a patient to the angiosuite, as the first-line brain imaging is now CT and CTA to select patients for mechanical thrombectomy.

Evolving Systems of Care

The new guidelines effectively rewrite the standard of care for stroke, according to Dr. Fifi. For patients with large vessel occlusion with a large stroke syndrome presenting to your ER, we’ve gone from not only thinking about giving them medication but also having to get them to endovascular therapy, she says. Although there is good evidence to support the changes, implementing these changes on a broad scale comes with many challenges. Availability of timely MT in North America, Dr. Yavagal estimates, is far from optimal, but he observes that it is available in most major urban centers. Just like when anything changes so drastically, it takes time to fully absorb and implement. That’s the stage we are in, he says. That said, much work is underway to ensure that patients everywhere may have access to mechanical thrombectomy.

Ongoing Research in Endovascular Stroke Care

As work continues to solidify logistical structures and clinical protocols for the efficient delivery of endovascular therapy for acute stroke, Dr. Fifi points out that ongoing studies will bring additional clarity to the particulars of care. Right now, the guidelines are for stroke presenting within six hours, but there are three ongoing trials looking at patients beyond that window. There is some evidence that if you use imaging selection to see which patients have salvageable tissue, you can still save people up to 12 or even 16 hours, she explains.

In order for timely treatment to be given, patients need to be rapidly triaged, and the systems to do that are currently evolving, according to Dr. Fifi. Right now, we have a HUB and spoke model, consisting of primary stroke centers and comprehensive stroke centers, she notes. At primary centers, patients can receive tPA, whereas comprehensive stroke centers must have the ability to perform endovascular procedures along with other procedures for hemorrhages, aneurysms, etc. The main concept of the HUB model is that if a patient comes to a primary center (the ‘spokes’) and requires endovascular care, they can be immediately shipped to comprehensive centers (the HUB). Dr. Fifi points out that these systems are already in place in many big cities in the US. If you’re in the ER or stroke center and have a candidate, you should be able to pick up the phone and call a comprehensive stroke center and have them shipped immediately.

Sometimes, however, there is a delay in the process, particularly if patients who are candidates for endovascular therapy are first taken to a primary center. In some cities, for instance, there might be a situation in which the primary stroke center is bypassed completely in favor of the comprehensive center, if they are within a certain proximity and think it’s a large vessel occlusion. The kind of bypass is being worked out on a regional, city-by-city basis, she explains. So much is based on local politics, she adds.

Another significant factor is the impact on population volume and traffic on time to treatment. In New York City, for example, there are several comprehensive stroke centers in Manhattan, and while Queens is geographically close enough that patients from a primary stroke center can be sent to Manhattan, it can be very hard to find a comprehensive stroke center within 30 minutes, Dr. Fifi observes.

Hospital networks can also have an important influence on the treatment process. In New York, Mount Sinai Medical Center is a comprehensive stroke center and is part of a large network of hospitals consisting of several primary centers, she says. We’ve been transporting our team to those centers, because if a patient arrives at a primary center, it can take up to two hours to make a transfer, whereas we can transfer our team to primary centers in less time than that, says Dr. Fifi. Primary stroke centers have a team there that can facilitate diagnosing and getting patient ready for procedure, then we transport ourselves and be ready in procedure room in shorter amount of time, she says.

While this notion might be effective for large hospital networks, it may not translate so easily in all other situations. Moreover, the urban/rural divide is difficult to account for when it comes to the distribution of neurointerventionalists capable of performing mechanical thrombectomy. You can have a stroke interventionalist in almost every city and they would have some amount of cases, but if you put a stroke interventionalist in a small hospital, they may not have enough volume to keep their skills up, Dr. Fifi imparts. No one knows the right answer, but there should be balance somewhere in between where non-urban neurointerventionalists are going to have enough volume to have skills to do the procedure and people have access to procedure.

Despite these challenges, Dr. Fifi believes that the process of ensuring timely care and access to endovascular therapy is moving in the right direction. Right now, smaller hospitals are hiring neurointerventionalists to do procedures and comprehensive stroke centers are developing relationships with other hospitals in creating networks to transfer patients in, she says. It’s being worked out organically, but will probably take about five to 10 years to balance.

According to Dr. Yavagal, the pressure to achieve that balance is incredibly high. For every 30 minute delay, there is a 10 percent chance of the patient not being independent, which is quite high, Dr. Yavagal explains. So not only do we need to devise our stroke systems so that everyone has access to them, but that access needs to be very fast, like in the trauma model of care but even more time-sensitive to an extent.

The Role of the General Neurologist

As new systems of care take shape, Dr. Fifi and Dr. Yavagal agree that general neurologists will have an increasingly significant part to play. Implementation is going to take time to be fully realized at all centers, and neurologists will have an important role in directing patients to the right therapy, says Dr. Yavagal. If directed appropriately, patients have a 70 percent chance of being fully independent, so it’s important for every neurologist to get this therapy rapidly to as many patients as we can, he says.


Watch Dr. Fifi discuss new advances in stroke management— particularly new devices and procedures that will shape the future of care—as part of our video coverage of last year’s Annual Meeting of the American Academy of Neurology in Vancouver. Dr. Fifi also discusses the practical challenges of navigating care networks and facilitating a team-based approach to allow for optimal outcomes.

According to Dr. Fifi, general neurologists will need to help with the rapid triaging of patients. When the patient presents to a local ER, the general neurologist may be called, and they will need to determine if the patient is a candidate for the procedure, and if they should be transferred to a CSC, says Dr. Fifi. Therefore, education will be paramount as stroke care delivery networks continue their evolution. If more general neurologists are attuned to the changing guidelines, they can play a critical role in helping patients get the care they need as well as assist in the development of efficient practices and protocols moving forward.

One of the most important aspects of the general neurologist’s role in care is the diagnosis. For primary stroke centers that are taking care of stroke patients, typically the first test is a CT scan, which rules out bleeding, says Dr. Fifi. Then, the common test that was used to actually identify large vessel occlusion was a CT angiogram. This may be more or less difficult to get depending on the hospital, according to Dr. Fifi. Given the variability of access to CT angiograms, Dr. Fifi recommends building a good line of communication with the radiology department. If you’re a general neurologist or in a small hospital, try to approach the radiology department and see how willing they’d be to do CT angiograms on an emergency basis to look for large vessel occlusion. If the radiology department is not willing or it’s too impractical, it’s possible to over-triage, Dr. Fifi suggests.

Another effective way of ensuring rapid and efficient triaging is to know ahead of time which hospitals can perform the procedures in your community, says Dr. Fifi. A lot of comprehensive stroke centers or places that have this capability are willing to receive patients and are organizing rapid transport systems, she adds. Many of these systems are set up ahead of time, so a comprehensive stroke center may have a telemedicine relationship with a hospital in a rural place.

If these structures aren’t in place, Dr. Fifi recommends contacting the closest comprehensive center ahead of time, as this may expedite the transfer process. Setting up alliances ahead of time is especially beneficial, she observes.


We are at a unique juncture in the realm of stroke care, Dr. Fifi suggests. It’s been a long time in stroke therapy that there’s been this big of an advance in treatment and to show that something actually works, she says. Moreover, the extent of the breakthrough cannot be overstated, according to Dr. Yavagal. Patients no longer have to think about stroke as a life sentence anymore, he says. Though it will undoubtedly take time for the appropriate systems of care to develop, Dr. Fifi and Dr. Yavagal believe that neurologists have a pivotal role to play right now. Neurologists have a huge incentive to become champions of stroke care, says Dr. Yavagal. The gratification of playing a role in reversing paralysis in a stroke patient is unparalleled for anyone.

Johanna Fifi, MD is an Assistant Professor of Neurology, Neurosurgery, and Radiology and Director of the Endovascular Stroke Program at Mount Sinai Health System in New York.

Dileep Yavagal, MD is an Associate Professor of Clinical Neurology and Neurosurgery and Co-Director of Endovascular Neurological Surgery at the University of Miami.