In the Company of Angels

WSO Announces Launch of WSO Angels Awards

The World Stroke Organization is proud and happy to strengthen the partnership with the ANGELS Initiative with the launch of a WSO Angels Award. This will see the extension of the Boehringer Ingelheim founded initiative, to include institutions providing stroke care worldwide and will help to extend and provide WSO with real time, quality data that will help to shape the resources and the support we provide to our members.

The partnership builds on WSO’s and the Angels Initiative’s ongoing work to drive improvement of stroke treatment and care across the world. The programme consolidates our respective efforts to improve stroke outcomes worldwide, complements the WSO roadmap to delivering quality stroke care stroke care and will provide key data to inform the development and delivery of WSO educational activities.

WSO Angels Awards will be given to hospitals who provide data and evidence of delivery of care and treatment against a set of seven criteria. In this way Angels Awards encourage continuous data capturing, enabling analysis of that data to identify and act to address areas for improvement.  

Hospitals submitting data in either the RES-Q or SITS QR Registry using the WSO Awards Protocol, will be eligible for an award. Based on their performance against various measures, participating hospitals can be recognised with either Gold, Platinum or Diamond level award. 

In addition to the Award, participating professionals and institutions in the Angels community will be supported to convene and connect, to identify good practices and to share learning that will help them to implement and accelerate improvements for patients. The Awards will also provide another platform for WSO to acknowledge excellent stroke care and honour the teams and organizations who go above and beyond in the care for their patients.

The first deadline for WSO Angels Award applications will be June 30, 2019. More information about the requirements and the application process will be posted on the WSO website in due course. 

Thrombolysis, Thrombectomy and Acute Stroke Therapy. Series. Part 3

In series 3, our panel of experts, reporting from the 14^th International Symposium on Thrombolysis, Thrombectomy and Acute Stroke Therapy has a very interesting and in-depth look into the drip and ship model of treating with thrombolytics, the treatment landscape in Finland  and performance and training standards set by a multi-society consensus (CAST) for neurointerventional training recommendations.

A summary of this meeting, and an extended report are available in the International Journal of Stroke, the flagship publication of the World Stroke Organization.  

Structuring Stroke Systems of Care

Drip and ship—safety, what is an acceptable time delay, what imaging should be done and where?

Atte Meretoja, Sheryl Martin-Schild, Heinrich Audebert 

The drip-and-ship model of treating with thrombolytics facilitates access to time-sensitive proven intervention to more patients with suspected stroke.  One consequence of this model is that patients treated with thrombolytics are vulnerable to complications while in transit via ground or air ambulance. While remote guidance provides access to otherwise unavailable neurological expertise for decision making on ischemic stroke thrombolysis, the dripping sites usually have lower volume of acute strokes and may be less efficient in treating with thrombolytic than the hubs.  This complicates the analysis of whether there is advantage for patients with suspected stroke stopping at a thrombolytic capable spoke versus bypassing in favor of access to the hub, where definitive care can be provided, particularly for patients who are candidates for thrombectomy. Reducing the door-in-door- out times for sites who do not keep post-thrombolytic patients and for those patients who have emergent large vessel occlusion is a major opportunity for process improvement.  In most ischemic stroke patients, the only imaging test necessary for decision-making is the non-contrast head CT. In our new world of treatment for stroke due to large vessel occlusion, access to and appropriate utilization of endovascular resources is critical.  Vascular and penumbral imaging may evolve, particularly when thrombolytic is given.  The “want to know” must be balanced with the “need to know” and is most relevant for sites who keep post-thrombolytic patients who do not require thrombectomy for a large vessel occlusion. Depending on hub priorities and tolerance of limitations, clinical tools for identifying patients with large vessel occlusion may substitute vascular imaging and reduce the need for repeating studies upon arrival at the hub.

Successful networks in resource rich and poor, urban and rural regions

Lee Schwamm, Markku Kaste, Tsong-Hai Lee 

Finland is presented as an example of a successful European network. After organizing acute stroke care and stroke unit care in Helsinki University Hospital, Dr. Kaste and the leadership team in Helsinki encouraged other Finnish university hospitals to follow their example. To ensure equal access to high-quality acute stroke care including thrombolysis for the entire population of Finland, the Helsinki team developed a telestroke program to support rural hospitals with low resources. These hospitals now have equally good results from thrombolysis as those observed in Helsinki University Hospital. Through telestroke, assistance to rural hospitals in recognizing thrombectomy candidates is given, and when appropriate, patients are transferred to the nearest university hospital applying the drip-and-ship method.  The ways in which other European countries have done the same differ by country, but high-quality stroke care is ensured over much of Western Europe.

In Asia, the resource-rich areas, mainly high-income countries, have sufficient support for acute stroke treatment networks in urban areas. However, in some rural areas where resources are limited, there are still problems of lack of public awareness of stroke and limited access to mechanical thrombectomy. The establishment of stroke centers should be helpful in public and provider education, and the diagnosis and treatment of stroke.

Key components to implementing an effective Stroke System of Care include the need to factor in the nature of the First Responders (e.g., fire/police/volunteer, BLS, ALS, Paramedic, Flight Nurse) and how they can bring to bear various levels of education and training into a more standard approach to prehospital diagnosis (Figure 2). This includes incorporating EMS assets effectively, taking into account EMS by ground and air, and Mobile Stroke Units as available to provide the greatest coverage without depleting critical resources from a community for too long. It also means creating regionalized point of entry routing plans for suspected stroke destination so that the region fairly allocates suspected stroke patients to a level of capability that fits the resources. It will be important to maintain a strong PSC network while developing a broader plan for rapid access to EVT at TSC and CSC facilities, and to standardize stroke alert pre-arrival notification and severity scale use so that each community or state becomes comfortable in the use of a single scale and can thereby communicate more effectively. Also needed is a tiered accreditation or designation of stroke centers that includes the recommended levels of Basic, Acute Stroke Ready, Primary and Comprehensive centers. All these activities should ideally be done by national organizations, since national organizations provide greater transparency and uniformity, and potentially better outcomes. These systems should encourage high levels of participation in National QI programs with recognition for performance to ensure that systems are based on infrastructure and performance. 

Discussion Panel

George Tsvigoulis, Michael Lerario, Nate Bornstein, Claude Nguyen  

Traditional hub and spoke networks for acute stroke treatment were developed to balance resource allocation in urbanized, resource rich regions and improve access to care in rural, resource poor regions.  However, as the need for thrombectomy services expands and technology is increasingly used to improve triaging decisions, newer stroke systems have developed and compete with hub and spoke networks utilizing drip and ship protocols in both resource rich and poor regions.  

Examples of stroke system innovations disrupting current drip-and-ship networks include those where field triage is performed to bypass suspected LVO patients directly to a hospital with thrombectomy services.  Field triage can be accomplished through standard emergency medical services staffing,(1) through telehealth,(2) or through the use of mobile applications (3) and may improve time efficiency and outcomes in time-sensitive stroke care.  Mobile stroke units offer comparable services to PSCs and can assist in the triaging of suspected LVO patients directly to endovascular centers without delaying thrombolysis times.(4) Prospective studies are underway to ascertain if these newer methods of stroke triaging will continue to supplement or even replace drip and ship networks.

Drip-and-ship networks alone cannot optimize resource utilization since false positive screens may occur up to 40-50% of the time if only clinical scores are used for LVO assessment,(5)and recanalization of an identified LVO may occur in 10-20% of patients during transport to the hub facility as a result of intravenous thrombolysis. (6,7) These factors generate confusion as to whether vessel imaging should occur at the hub or spoke facility and may result in overtriage of stoke patients to endovascular centers, when a primary stroke center may have been sufficient. Overtriage to advanced stroke centers could theoretically burden hub hospitals with unnecessary transfers and decrease volumes at spoke centers where competencies may be more difficult to maintain if patient numbers diminish.  

Key Points:

1. Stroke systems of care will need to be restructured to improve patient access to EVT. Key elements include reducing door-in-door-out times, determining whether clinical tools for evaluating for LVO may substitute for imaging, and improving access to subspecialty care with technology including telemedicine and mobile stroke units.
2. Standardization of pre-hospital notifications and pre-hospital routing changes to avoid over-triage to comprehensive centers will be important.

Who is carrying out thrombolysis and who should do it in the future?

Andrew Demchuk, Steven R. Levine, Elizabeth Jones  

Thrombolysis is carried out in hospitals, emergency departments and in the field with the help of mobile stroke units. Intravenous alteplase can be administered by non-vascular and vascular neurologists, emergency medicine physicians, residents and fellows in the training programs, physician assistants and advanced nurse practitioners. Telemedicine has allowed for more patients, especially in the rural networks, to get access to thrombolysis and for neurology expertise to become readily available for decision-making. In controlled trials, telemedicine stroke consultations within an organized system of care have demonstrated improved and safe intravenous alteplase use and better patient outcomes than without telemedicine coverage. Many networks, including hub and spokes, have developed telestroke coverage for their patients, including some rural networks. 

Data from a recent study (8)show that approximately 40% of emergency department physicians are uncomfortable treating acute stroke patients. The lack of expertise in interpreting CT imaging and the limited follow up of the patient after a code stroke is activated leaves the physician uncertain and unprepared to treat future stroke patients. On the other hand, physicians tend to exclude patients from receiving thrombolysis, as they often overestimate the risks of administering intravenous alteplase, especially the risk of hemorrhagic transformation. There is a higher number of emergency medicine doctors than neurologists in the US, and despite the clear advance in stroke care systems, emergency physicians need to be qualified and equipped to determine whether a patient is a candidate for thrombolysis. Implementation of pathways for stroke care and neurology training in emergency medicine residency programs will help physicians to be familiar with thrombolytic therapy.

In the near future, proper support for health providers from vascular neurologists should allow expanding and improvement of stroke patient care, empowering the autonomy of providers in the decision-making of thrombolysis. Guidance by a vascular neurologist, either on the field or through telemedicine, will lead to more patients getting the proper treatment, at the right time and the right place.   

Who is carrying out thrombectomy and who should do it in the future?

Arthur Day, Marc Ribo, Reza Jahan

Almost all stroke programs across the United States are now led by neurologically-trained subspecialist practitioners being either neuroradiologists, neurologists, or neurosurgeons who are doing intracranial thrombectomy, with only a small number of non-neurologic subspecialists with catheter skills due to their training and routine practice that are now venturing into the intracranial circuit, which may include vascular surgeons, cardiologists and interventional radiologists. (Table 1) The existing dichotomy on who should be doing thrombectomy in the future has on one side the scenario where more subspecialties should be able to deliver intracranial thrombectomy as the number of practitioners does not meet the needs of stroke care, while on the other hand, it is not a matter of available providers but a lack of an equally distributed and available expertise in small or rural communities.

The reason of a more restricted delivery of thrombectomy between providers is the complex access to the delicate intracranial vasculature which has a higher risk of perforation or distal embolization than the extracranial circulation, the need of a more comprehensive knowledge of the anatomical variants and functional anatomy of the collateral circulation, as well as the awareness of the physiology and pathophysiology of the disease which is entirely different from other organ systems suffering from infarction. This organ-specific expertise is what limits, to say, a neurosurgeon or radiologist from performing an arteriography and stenting in the management of a myocardial infarction. Future safe practice of intracranial thrombectomy requires a practitioner highly skilled with intracranial catheter-based vascular techniques, with a firm knowledge base of the anatomy, pathophysiology, and treatment alternatives of the various cerebrovascular conditions that may arise during the evolution of a thrombotic stroke. (Figure 3) Further research will be needed to ascertain the number of trained physicians to meet the demands of stroke intervention, distribution of these physicians across the nation and better understanding of access of populations to stroke centers to help on planning regional stroke programs.

Current guidelines for training for thrombolysis and thrombectomy; appropriateness of current guidelines

Sunil Sheth, Don Heck, Diogo Hausen, James Grotta 

Performance and training standards set by a multi-society consensus (CAST) for neurointerventional training demands a proper 1-year minimum training under direction of multiple neurointerventionists at a high-volume center. Pre-requisites to training include neuroscience-based residency training. A distribution of diagnostic and interventional procedures, covering the breadth of neurointerventional diseases including cerebral aneurysms, cerebral arteriovenous malformations as well as spinal diseases is required. Final certification is obtained following the completion of such a training program as well as a review of two years of subsequent practice data, to ensure high quality outcomes after training.

Should the standards for stroke thrombectomy be different? On the one hand, there is a clear and present need to expand patient access to the therapy. This treatment is highly time sensitive – perhaps one of the most time sensitive in medicine – and as such delays in treatment such as those created by prolonged pre-hospital transports or inter-hospital transfers are costly. On the other hand, all the data supporting the efficacy of EVT at improving clinical outcomes after LVO stroke were derived from high volume hospitals and high volume neurointerventionalists. As such, treatment outside these specialized centers could be considered unproven.

Would it be beneficial then to train a group of neurointerventionalists for EVT alone, and forgo the remainder of neurointerventional training? Insisting that all providers to treat stroke also be proficient in aneurysm treatments, for example, would likely be mathematically impossible. But would a model in which some providers perform only EVT be even possible, whereby one can learn to effectively perform delicate and intricate intra-cranial thrombectomy without exposure to other cerebrovascular disorders? 

Ultimately, these discussions should be framed in the context of what is best for patients, and not along specialty or “turf” considerations. As such, this topic is one that will need to be addressed with data, particularly from lower volume centers and lower volume physician practices, which are notoriously absent from traditional data generating mechanisms including clinical trials and clinical registries.

Discussion Panel

Mike Frankel, Gary Spiegel, Hen Hallevi, Jonathan Zhang 

Since the FDA approval of alteplase (recombinant tissue plasminogen activator - rtPA) for acute ischemic stroke in 1996 and the publication of consensus guidelines, the acceptance by the medical community has been mixed. Although vascular neurologists have fully embraced the robust nature of the data supporting the benefit of alteplase there has been reluctance to treat by general neurologists and emergency medicine physicians in large part due to fear of causing harm. As such, it is imperative that vascular neurologists work together to create more opportunities for clinical coverage through telestroke and education of general neurologists and emergency medicine physicians. 

In the case of thrombectomy, adoption of the procedure has not been a problem. However, a strategy to equally distribute neurological expertise for thrombolysis and thrombectomy in both urban and rural areas may lead to certification of centers and physicians not fully competent to be involved in stroke care. Expanding certification of centers to deliver treatment to all population is only part of the solution, as more expertise from first responders and ways to reduce onset-to-door time play an important role in patient care. On the other hand, certifying non-neuroscience-based physicians, such as cardiologists or interventional radiologists, to perform thrombectomy requires a thorough review of training requirements and experience. It is clear that extracranial vessels differ enormously from intracranial vessels. Hence a singular set of technical and cognitive expertise, as well as catheter-based skills and knowledge is necessary to better perform the thrombectomy procedure. 

Key Points:

1. There is a need for an expansion of providers able to oversee thrombolysis treatments. Advanced practice providers including nurse practitioners, telemedicine, and MSUs may help address this issue.
2. With the magnitude of benefit EVT confers on patients with AIS, and the resulting increase in need for proficient providers and suitable hospitals, there is a need to rethink hospital certification and training standards for Neurointervention. These standards, however, must be determined with the patients’ best interest in mind.

1. Schlemm L, Ebinger M, Nolte CH, Endres M. Impact of Prehospital Triage Scales to Detect Large Vessel Occlusion on Resource Utilization and Time to Treatment. Stroke. 2018;49:439–446. 

2. Belt GH, Felberg RA, Rubin J, Halperin JJ. In-Transit Telemedicine Speeds Ischemic Stroke Treatment: Preliminary Results. Stroke. 2016;47:2413–2415. 

3. Nogueira RG, Silva GS, Lima FO, Yeh Y-C, Fleming C, Branco D, Yancey AH, Ratcliff JJ, Wages RK, Doss E, Bouslama M, Grossberg JA, Haussen DC, Sakano T, Frankel MR. The FAST-ED App: A Smartphone Platform for the Field Triage of Patients With Stroke. Stroke. 2017;48:1278–1284. 

4. Kettner M, Helwig SA, Ragoschke-Schumm A, Schwindling L, Roumia S, Keller I, Martens D, Kulikovski J, Manitz M, Lesmeister M, Walter S, Grunwald IQ, Schlechtriemen T, Reith W, Fassbender K. Prehospital Computed Tomography Angiography in Acute Stroke Management. Cerebrovasc Dis. 2017;44:338–343. 

5. Smith EE, Kent DM, Bulsara KR, Leung LY, Lichtman JH, Reeves MJ, Towfighi A, Whiteley WN, Zahuranec DB, American Heart Association Stroke Council. Accuracy of Prediction Instruments for Diagnosing Large Vessel Occlusion in Individuals With Suspected Stroke: A Systematic Review for the 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke. Stroke. 2018;49:e111–e122. 

6. Campbell BCV, Mitchell PJ, Churilov L, Yassi N, Kleinig TJ, Dowling RJ, Yan B, Bush SJ, Dewey HM, Thijs V, Scroop R, Simpson M, Brooks M, Asadi H, Wu TY, Shah DG, Wijeratne T, Ang T, Miteff F, Levi CR, Rodrigues E, Zhao H, Salvaris P, Garcia-Esperon C, Bailey P, Rice H, de Villiers L, Brown H, Redmond K, Leggett D, Fink JN, Collecutt W, Wong AA, Muller C, Coulthard A, Mitchell K, Clouston J, Mahady K, Field D, Ma H, Phan TG, Chong W, Chandra RV, Slater L-A, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Bladin CF, Sharma G, Desmond PM, Parsons MW, Donnan GA, Davis SM. Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke. N Engl J Med. 2018;378:1573–1582. 

7. Tsivgoulis G, Katsanos AH, Schellinger PD, Köhrmann M, Varelas P, Magoufis G, Paciaroni M, Caso V, Alexandrov AW, Gurol E, Alexandrov AV. Successful Reperfusion With Intravenous Thrombolysis Preceding Mechanical Thrombectomy in Large-Vessel Occlusions. Stroke. 2018;49:232–235. 

8. Scott PA, Xu Z, Meurer WJ, Frederiksen SM, Haan MN, Westfall MW, Kothari SU, Morgenstern LB, Kalbfleisch JD. Attitudes and Beliefs of Michigan Emergency Physicians Toward Tissue Plasminogen Activator Use in Stroke. Stroke. 2010;41:2026–2032.

About: International symposium on Thrombolysis, Thrombectomy and Acute Stroke Therapy 

The 14^thInternational Symposium on Thrombolysis, Thrombectomy and Acute Stroke Therapy (TTST) took place in Houston, Texas on October 21^stand 22^nd, 2018. TTST meetings began in 1990 during the initial simultaneous clinical investigations into thrombolysis taking place in the United States, Europe, and Japan. Since then, TTST has brought together invited experts on reperfusion therapy for acute stroke every two years, and rotates among venues in Europe, North America, and Asia. TTST has provided opportunities for stimulating controversial discussions on data from recent clinical trials, the status of major ongoing studies, and priorities for future research. Initially focused on thrombolytic therapy, recent TTST conferences have helped lay the groundwork for the success of thrombectomy clinical research. 

Leading the way in home based care for stroke survivors in Zambia

New stroke support organisation (SSO), National Stroke Aid, Zambia leads the way in home based care for stroke survivors.

National Stroke Aid, Zambia has become the latest member of WSO. The SSO was founded at the beginning of 2019 by Mr. Phanuel Mabbola, a physiotherapist working in rehabilitation with stroke survivors. Phanuel recognised the extent to which stroke survivors are neglected or ignored in the city of Lusaka and he decided to establish a home based physiotherapy service. As well as physiotherapy, the service will also include healthy lifestyle education.

In Zambia, stroke is a leading cause of death and disability and is increasingly affecting a younger population, with hypertension the most common risk factor.

Although in the course of his work Phanuel observed that people in the community know that stroke is sudden and can happen to anyone at any time, prevention and managing risk factors is less well understood. In addition, many stroke survivors have little or no access to rehabilitation and recovery services.

Addressing these needs is the primary focus of the newly established National Stroke Aid, which will provide stroke awareness, healthy life style education and facilitate or provide home based care to stroke survivors. The objectives of the SSO are:

·        To help reduce the incidence rates of stroke through sensitisation of the community on causes of stroke and educating society on the need for healthy life styles

·        To restore stroke survivors’ body functions through physiotherapy and provide occupational and home based care

·        To advocate for policy that includes stroke survivors’ empowerment, and involvement in decision making institutions

·        To organise workshops or seminars and hold social gatherings for capacity building among the stroke survivors and the membership of organisation

National Stroke Aid will draw its membership from the community, in particular those that have been affected by stroke.  

In January, the Permanent Secretary of the Zambian Ministry of Health recommended National Stroke Aid for registration as an NGO; recognising its role in complementing government efforts to provide home based care to stroke survivors, and that the organisation’s activities are in line with the National Health Strategic Plan.

We are excited to welcome National Stroke Aid to the global SSO network and commend Phanuel on his commitment to providing home based care.

Thrombolysis, Thrombectomy and Acute Stroke Therapy. Series. Part 2

Last week we published the first in a series of excerpts from experts on Thrombolysis, Thrombectomy and Acute Stroke Therapy, expert commentary which came out of the 14^th International Symposium on Thrombolysis, Thrombectomy and Acute Stroke Therapy.

In last weeks blog session some of the most dynamic researchers in stroke explored strokes changing demographics, global rates of thrombectomy, and how current treatments have changed the stroke landscape in this area.

This week the question is pondered Thrombolysis and thrombectomy—where, when, and who? Jeyaraj Pandian and Pooja Khatri will highlight the existing and projected distribution of thrombolysis centers worldwide, while others will tackle where and for who thrombolysis should be done?

A summary of this meeting, and an extended report are available in the International Journal of Stroke, the flagship publication of the World Stroke Organization.  

Thrombolysis and thrombectomy—where, when, and who? 

Existing and projected distribution of thrombolysis centers worldwide

Jeyaraj Pandian, Pooja Khatri

In the US, the most recent analysis of the geographic distribution of thrombolysis centers from administrative data described access of the US population to all facilities that provided at least one case of intravenous alteplase for acute ischemic stroke (AIS). (1) The 2011 US Medicare Provider and Analysis Review (MEDPAR) data set was used, although it was limited by excluding patients younger than 65 years of age, except transplant and permanently disabled patients. Based on this analysis, 81% of US population may have access to intravenous-capable hospitals within 60 minutes by ground and 97% by air. These projections may be an overestimate, since provision of one dose of alteplase may not guarantee an appropriate level of thrombolysis readiness.  Similar good penetration of thrombolysis centers is likely in Canada, based on even older numbers from a 1998 publication using 1996 interim census numbers by Scott et al (2). They used Geographic Information System (GIS) just like the US study, but identified hospitals capable of delivering intravenous alteplase as those with a Computed Tomography (CT) scanner and a neurologist and EM specialist on staff, as opposed to the actual administration of at least one dose of intravenous alteplase. 67.3%, 78.2%, and 85.3% of the total Canadian population were within 32, 64, and 105 kilometers, respectively, of an identified hospital.

Among the South Asian countries, India and Thailand have organized stroke programs with thrombolysis and thrombectomy capable centers. The intravenous thrombolysis rates in India (1.25 to 4.58%) and Thailand (4.78%) are growing every year. There are 75 centers in India currently offering mechanical thrombectomy with an overall of 1,000 procedures a year, and the government has approved the use of tenecteplase, a generic biosimilar which is cheaper than alteplase for acute stroke treatment. Over 4,800 patients have received tenecteplase in the country. In Thailand, 25 hospitals offer endovascular treatment for stroke. In Pakistan and Srilanka, intravenous thrombolysis is being used but only a few centers may provide EVT. For South Korea, government nationwide initiated 11 Regional Comprehensive Stroke Centers (CSCs) since 2008. After the initiation, door-to-needle time for the intravenous thrombolysis was shortened to less than 30 minutes in the CSCs and the chance of intraarterial thrombectomy was increased from 30% to 47% in 2016 after the initiation of the CSCs. However, the quality of acute stroke management including thrombolytic therapy has not been clearly known in the provincial area of South Korea.(3) 

Where and for whom should thrombolysis be done 

Phil Scott, Henry Ma, Didier Leys

Use of thrombolytic therapy in patients with acute ischemic stroke requires an initial recognition of stroke symptoms, confirmation of diagnosis and eligibility for therapy, proper delivery of thrombolytic agent, and a follow-up period post treatment. A prompt recognition of signs or symptoms associated with stroke in the prehospital setting is crucial in reducing delays to stroke identification and time from onset to hospital arrival, thus increasing the number of patients that may be eligible for thrombolytic therapy. Utilization of a single emergency number may speed healthcare access, along targeted education programs for physicians, hospital, and Emergency Medical Services (EMS) personnel have demonstrated utility in increasing thrombolytic treatment rates. 

Confirmation of diagnosis requires a focused history and a through neurological examination to rule out other causes of acute neurological deficits. Minimal neuroimaging requirements include a noncontrast head CT, with a CT angiogram (CTA) as a tool to identify patients with a large vessel occlusion who would benefit from mechanical thrombectomy. New emerging technologies such as machine learning and biomarkers may aid in the near future to accurately identify a positive stroke. As evidence from clinical trials becomes available and the experience in thrombolytic administration increases, some of the exclusion criteria are changing from absolute to relative, allowing more patients to benefit from medical management. Therefore, the physician should evaluate on an individual case basis the benefits and risks of thrombolysis. 

Delivery of thrombolytic therapy may occur in the field through Mobile Stroke Units (MSUs) or in the emergency department/hospital. European systems of stroke care have demonstrated that the prehospital intravenous administration of alteplase can be accomplished effectively and increases the proportion of patients receiving thrombolysis within 60 minutes of onset. Prehospital administration of alteplase may translate into better outcomes in patients with pre-stroke dependency compared to in-hospital administration.(4) Generalization of pre-hospital delivery of thrombolytics faces challenges in non-densely populated regions and in non-resource rich communities. 

Expanding Thrombolytic Use Safely

Minimal resources needed to confirm eligibility for thrombolytic treatment are currently based on either a checklist approach identifying evidence-based inclusion and exclusion criteria or utilizing physicians with stroke thrombolytic expertise, again, provided either at the bedside or remotely via telemedicine. Further minimal requirements include initial selection of a specific thrombolytic agent to be used which includes cost, actual drug availability, physical drug stability, and physical drug delivery (availability of intravenous infusion pumps, etc.) which are important considerations in limited resource environments globally. Finally, minimal resource requirements for the management of post thrombolytic treated patients require cardiac and blood pressure monitoring and management capability.  This can be implemented using, again, either a checklist approach by local post-thrombolytic care providers or accessing physicians with thrombolytic expertise either at the bedside or remotely via telemedicine and includes management of treatment complications.

Numerous points in the stroke chain of survival exist in which to improve and expand thrombolytic use safely. Improved prehospital systems reduce delays to stroke identification and treatment. Data indicate that public education to identify stroke symptoms and recognition of stroke as an emergency and that is sustained over time reduces delays. Utilization of a single emergency number (911 in the United States and 112 in the European Union) also speeds healthcare access. Targeted education programs for physicians, hospital personnel and EMS personnel have demonstrated utility in increasing thrombolytic treatment rates. Finally, consistent utilization of prehospital notification by EMS personnel has been demonstrated to reduce in-hospital delays to stroke treatment.

In communities where thrombolytics are administered only within a stroke unit, opportunities to safely expand its use include starting treatment prior to stroke unit admission through remote neurologic expertise either in person or by telemedicine. Interactive and multifaceted training programs for emergency physicians have demonstrated increased access to thrombolytics in the community setting. These programs frequently include an organized protocol for emergency evaluation.

The existing paradigm of excluding patients from thrombolytic use on the basis of time has the potential to lead to a future paradigm where patients are excluded on the basis of perfusion imaging. This reflects prominent advances in the fields of neuroimaging to provide meaningful information on local tissue viability in stroke. If ultimately proven efficacious, such a shift will remove the single most common barrier to thrombolytic treatment–time from symptom onset.

As experience with thrombolytic delivery increases and further data on thrombolytic use becomes available, some prior exclusion criteria are migrating from absolute to relative. Note should be made by the practicing clinician that the level of evidence for this migration frequently comes from non-randomized trials. 

Discussion Panel

Chris Lewandowski, Wade Smith, Nerses Sanossian, Martin Ebinger  

The use of intravenous thrombolysis in the Emergency Department (ED) is hindered by the limited clinical experience and teachings of the average emergency department physician. Neurologic complaints represent 8 percent of the total consults for ED physicians, with acute stroke representing 1-2%.It is estimated the ED doctor treats 2 acute ischemic stroke patients per decade with thrombolysis. The lack of experience and the low availability of neurologists on site doesn’t allow for physicians in the front line to take a more active role in the care of stroke patients. It is thought that by simplifying the review of eligibility and providing support for the use of thrombolysis more physicians may feel comfortable delivering thrombolytics to patients. Telemedicine has proven to be an essential tool in this process along with the active role of nurses and advanced nurse practitioners in acute stroke care. 

In addition, further development of pre-hospital triage is needed. Progress has been made in education of the lay public about the importance of activating EMS as soon as stroke is suspected, prehospital stroke identification, and routing of stroke patients to designated acute stroke center hospitals. Areas of active investigation in prehospital stroke include in-ambulance therapy (i.e. neuroprotective agents), mobile stroke unit ambulances with imaging capabilities, and multi-tiered routing protocols. The goal of any prehospital system of stroke care is to deliver patients quickly and safely to the most capable hospital.

Any prehospital LVO triage instrument is likely to have significant rates of over-triage/false positive and under-triage/false negative. Over-triage may delay intravenous thrombolysis in patients without LVO through longer transport times and bypass of closer hospitals, leading to later thrombolytic treatment, as well as over-crowding of specialized centers. (5)

On the other hand, an under-triage screen may route a patient to a hospital without endovascular capabilities (under-triage), leading to later thrombectomy.  

The goal of EMS triage is to get to the right hospital in the right amount of time. When done correctly this improves outcomes.(6-9) Proper EMS triage is more cost-effective than creating additional specialty receiving facilities.(10) In the setting of stroke, almost all published experience with existing EMS triage tools focuses on identifying patients with LVO, which conflicts with the purpose of triage itself which is to get the right patient to the right place in the right amount of time, regardless of diagnosis. We need to refine prehospital assessment of stroke patients to focus not only on LVO but on how to best get patients the care they need to improve outcomes and increase disability. This may require a regional approach, but making thrombectomy available to the greatest numbers of individuals in the shortest time will require development of new prehospital tools.  

Key Points:

1. Earlier identification of stroke syndromes, particularly in pre-hospital settings, is crucial to ensure the right patient is treated in the right place.
2. Minimal requirements for thrombolysis are being and should continue to be rethought, as treatments are moving out of specialized centers and closer to patients, particularly through MSUs.
3. As thrombolysis becomes a viable treatment options for greater numbers of patients through increasingly complicated imaging and decision-making pathways, the need for additional availability of Neurology expertise, or training of ED physicians, gains heightened relevance. Options include telemedicine, checklists, and consistent messaging to ED providers. 

Existing and projected distribution of thrombectomy centers worldwide

Raul Nogueira, May Nour, Olvert Berkhemer

The mismatch between lower resources and the increased stroke incidence is a devastating challenge that demands a timely solution. Despite the increased number of centers capable of carrying out mechanical thrombectomy, long travel times and delay in identification of patients with LVO who should be transferred to comprehensive stroke centers limit stroke care. In the United States, the two most prevalent certifying bodies are the Joint Commission (JC) and the DNV-GL. There are 194 CSCs accredited by the JC as a facility with Neurointerventional coverage with a neurologist on site and a backup physician, with coverage for stroke neurology, neurosurgery, and neurocritical care coverage available 24/7. 67 current CSCs accredited by the DVN-GL are required to provide only neurointerventional coverage 24/7 and have the ability to either accommodate or transfer out neurosurgical emergencies. In March 16, 2018, the JC in collaboration with the American Heart Association/American Stroke Association certified the first Thrombectomy-capable Stroke Center (TSC) defined as a facility with EVT capability 24/7, have at least 15 patients with ischemic stroke in the past 12 months or at least 30 patients over the past 24 months, and was required to collect data for 13 standardized performance measures, and meet expectations of neurological expertise availability aligned with that of a CSC. These certifications served the goal of improving patient outcomes by facilitating access to care for stroke patients, so patients with a suspected LVO would get re-routed to the nearest CSC or TSC center rather than to a Primary Stroke Center (PSC).

In Canada, thrombectomy access is evolving with a projected creation of 6 centers across the country. Latin America has a very limited distribution of thrombectomy centers when compared with the increased morbidity and mortality associated with acute stroke. In Europe, 32% of the countries have overall EVT coverage with the rest not providing EVT due to high costs and lack of trained personnel and facilities. 29% of eligible EVT patients were treated in 2016, and around 52% of centers are available 24/7. (11)

Where should thrombectomy be done—centralized vs distributed model; what do the guidelines say and how do they square with reality?

Tudor Jovin, Bernard Yan, Diogo Haussen 

The American Stroke Association 2018 guidelines regarding the provision of thrombectomy services to acute ischemic stroke clearly recognizes that patients should be treated at experienced thrombectomy centers with rapid access, qualified neurointerventionists, and comprehensive periprocedural care team.(12) Evidence for other neurological diseases, such as subarachnoid hemorrhage and carotid endarterectomy, prove a worse clinical course in patients treated by lower volume operators at low-volume centers. (13-22) This is buttressed by similar experiences in the field of coronary percutaneous intervention and trauma. (23) Importantly, both operator and center volumes metrics are to be considered together, since one affects the other when evaluating for quality of care.(24) The data on mechanical thrombectomy has accrued and uniformly point towards improved outcomes in patients treated in higher volume centers.(25,26)  

Significant concerns and unease were voiced by the presenters and the audience of the low volume (fewer than 15 thrombectomies per annum) required by the Joint Commission to qualify as a thrombectomy center, especially since most centers performing thrombectomies appear to have volume <10 a="" also="" and="" care="" center="" decentralized="" different="" expected="" high="" including="" lower="" model="" models="" nbsp="" neurointerventionists="" of="" outlined="" p="" per="" presenters="" provide="" quality="" services.="" spoke="" the="" therefore="" thrombectomies="" thrombectomy="" to="" travel="" volume="" whereby="" year="">

Discussion Panel

Carlos Molina, Ed Jauch, Albert Yoo 

The question of who should be performing EVT, both in terms of physician qualifications as well as hospital qualifications, was a central question during this meeting, and one that pervaded nearly all the discussions of the first day. In this discussion section, the speakers noted that there is an ongoing debate regarding manpower needs for mechanical thrombectomy and more broadly for neurointerventional procedures, which include treatments such as aneurysm coiling and arteriovenous malformation embolization. However, this debate ignores the fact that most neurointerventionists coming out of training do not move to underserved communities. They move to metropolitan areas where established practices already exist. Healthcare systems shoulder some of the blame. Despite the presence of nearby comprehensive stroke centers, in the United States hospitals are incentivized to become comprehensive or thrombectomy-capable centers to capture EMS traffic and the higher reimbursements associated with thrombectomy care. As a result, neurointerventional practices are competing for smaller and smaller case volumes, and the debate has naturally shifted to focus on the better outcomes at high-volume centers as an argument to stem this tide.  

Meanwhile, populations residing in rural markets are being neglected. Patients who suffer a large vessel stroke in these communities must be transported to the closest major city. Unfortunately, transport can take several hours even with air transport. Despite publications projecting adequate neurointerventional availability to much of the US population, there is a clear need to better distribute thrombectomy expertise to underserved areas, given the highly time sensitive nature of large vessel stroke. If there are not enough aneurysms or arteriovenous malformations to support a full-time neurointerventionist in a rural market, then other interventional disciplines (peripheral radiologists or when necessary even interventional cardiologists) may be trained to provide thrombectomy care. Alternatively, neurointerventional training and certification guidelines may need to be altered to accommodate this shift in modern neurointerventional practice, in which the largest need is for acute ischemic stroke, and as such requirements mandating high numbers of aneurysm and arteriovenous malformation treatments may be outdated. In such a system, additional thrombectomy-capable interventionists would be credentialed to treat large vessel strokes in regions where there is demonstrated need. Although thrombectomy care in the rural setting is likely to be less optimal than at high-volume centers in major cities, it may be better than the alternative which is to delay treatment by hours or to have a high proportion of cases that do not meet treatment criteria due to a combination of late arrival and large infarct volume (i.e., futile transfers).(27,28) The neurointerventional community along with other professional organizations should propose criteria for defining areas in need of local thrombectomy expertise and decide what constitutes adequate thrombectomy training and long-term quality assurance in these areas. Hybrid models including tele-neurointerventional expertise for intra-procedural decision making may help to bridge the quality gap. As technology continues to advance, remote robotic intervention may also be possible.

Key Points:

1. At present, there is a palpable shortage of access to high quality EVT care. This shortage is present in developed as well as developing nations globally. This is an issue for both hospitals/stroke systems of care as well as physicians, and in particular, thrombectomy providers. 
2. Alternative models of stroke systems of care have developed to improve patient access. These models include improved pre-hospital routing paradigms, improved intra-hospital transfer paradigms, and models in which thrombectomy providers travel to outlying hospitals. All these systems however remain imperfect and limited, and ultimately, increased numbers of thrombectomy-capable physicians and provider teams are needed.
3. There is a clear need for additional data examining outcomes data in low volume centers, and by low volume practitioners. The outcomes are likely to be poorer, but how much so? And is that decrement in outcome outweighed by the time delays associated with transfers? 

Summary of new data from clinical trials of thrombolysis since International Stroke Conference (ISC) or European Stroke Organization Conference (ESOC)

WAKE UP and ECASS 4 primary results and secondary analyses

Werner Hacke

The primary results of two trials testing the efficacy of alteplase in patients with longer or unknown time window using advanced imaging selection were presented at ESOC 2018 in Gothenburg. The WAKE-UP trial was terminated early for lack of funding. It selected wake up stroke patients on the basis of the DWI-FLAIR Mismatch concept. Despite the early termination, the study showed a highly significant advantage in reaching modified Rankin Scale (mRS) 0,1 for alteplase in patients with a positive DWI-FLAIR mismatch (OR 1.63 95% CI 1.09-2.36, p=.02,).(29)

ECASS 4 used the classic DWI-Perfusion mismatch in patients between 4.5-9 hours or in wake-up strokes. It was also terminated prematurely because of futile recruitment because of massively increasing use of thrombectomy in this patient group. The OR point estimates were likely anticipated in favor of alteplase treatment (OR 1.23 for the categorical shift, OR 1.38 for mRS 0,1), but the confidence intervals were wide and clearly overlapped unity because of the small sample size.(30)

Further ECASS 4 secondary analyses presented in Montreal (WSC 2018) indicated that this type of selection is more useful in known, late time window than in unknown time window. Using the FLAIR-DWI Mismatch paradigm in a non-predefined sub analysis of ECASS 4 showed also a clear trend towards better results in the DWI-FLAIR Mismatch cohort, but with the caveat of increased late (stroke unrelated) mortality signal in the alteplase treated group. Again, due to the small sample size the CIs overlapped the unity line.

EXTEND

Henry Ma, Bruce Campbell, Mark Parsons, Stephen Davis, Geoffrey Donnan 

EXTEND is a multicenter randomized, double-blind, placebo-controlled trial of alteplase in ischemic stroke patients presenting within 4.5-9 hours from onset or those with wake-up stroke (WUS). Selection was based on automated perfusion imaging software showing salvageable brain tissue. Primary outcome was excellent functional outcome (modified Rankin Scale, mRS 0-1) adjusted for age and baseline NIHSS at 3 months.(31) Other prespecified outcomes included independent functional outcome (mRS 0-2), early reperfusion, clinical improvement with NIHSS reduction of 8 points or reaching 0-1 at 24 hours, death and symptomatic intracerebral hemorrhage (sICH). After 225 of the planned 310 patients had been randomized, the study was terminated early after the publication of WAKE UP study and loss of clinical equipoise.  Patients who received alteplase achieved significantly better functional outcomes at three months. Secondary end points, including reperfusion and early neurological improvement, were superior in the alteplase group while mortality was not significantly different. EXTEND is the first positive thrombolytic trial in the extended time window using automated penumbral selection software

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About: International symposium on Thrombolysis, Thrombectomy and Acute Stroke Therapy 

The 14^thInternational Symposium on Thrombolysis, Thrombectomy and Acute Stroke Therapy (TTST) took place in Houston, Texas on October 21^stand 22^nd, 2018. TTST meetings began in 1990 during the initial simultaneous clinical investigations into thrombolysis taking place in the United States, Europe, and Japan. Since then, TTST has brought together invited experts on reperfusion therapy for acute stroke every two years, and rotates among venues in Europe, North America, and Asia. TTST has provided opportunities for stimulating controversial discussions on data from recent clinical trials, the status of major ongoing studies, and priorities for future research. Initially focused on thrombolytic therapy, recent TTST conferences have helped lay the groundwork for the success of thrombectomy clinical research.