International Stroke Conference 2020: 5 Key Developments That Will Shape the Field

By A. Blake Buletko, MD

Despite COVID-19-related travel restrictions that kept many usual attendees away, the American Heart Association’s International Stroke Conference (ISC) attracted its largest attendance to date last week, drawing over 5,700 registrants to ISC 2020 in Los Angeles from February 19 to 21. Though this meeting always yields a wealth of takeaways that depend in part on one’s subspecialty interests within vascular neurology, there’s usually a handful of presentations that stand out across the field as a whole. Below are five presentations and developments from the meeting that struck me most as an ISC 2020 attendee.

1) B-PROUD shows that mobile stroke units (MSUs) improve clinical outcomes

When the pioneering MSU group from Berlin reported results of their B-PROUD trial, they presented the best evidence to date that MSUs do more than accelerate care delivery for acute ischemic stroke but actually improve patients’ functional outcomes as well. This investigation is the first reported randomized trial showing improved outcomes for patients treated on an MSU compared with those receiving conventional care from EMS and emergency departments. B-PROUD’s findings of improved functional outcomes at three months, as reflected by modified Rankin Scale score, may have been a result of increased rates of tPA use on the MSU as well as faster tPA administration times from stroke onset.

These results are consistent with findings from a nonrandomized study that our team from Cleveland Clinic reported last year at ISC 2019. We have been excited to be at the forefront of MSU implementation in the United States dating back to 2014. These results from B-PROUD support further growth of MSUs worldwide when they can be deployed in judiciously chosen geographic locations.

2) Part 2 of EXTEND-IA TNK reveals optimal dosing for tenecteplase

When results from the EXTEND-IA TNK trial were published in 2018 in the New England Journal of Medicine, they showed that IV tenecteplase (TNK) before endovascular thrombectomy (EVT) was associated with a higher incidence of reperfusion and better functional outcome than IV alteplase when given within 4.5 hours of acute ischemic stroke onset. Tenecteplase was studied because of its increased fibrin specificity, longer half-life and cost-effectiveness relative to alteplase as well as its administration as a single bolus. The study also found no differences in symptomatic intracerebral hemorrhage.

Part 2 of this trial sought to determine optimal dosing for tenecteplase by randomizing patients with large vessel occlusion to either 0.4 or 0.25 mg/kg intravenously. Presentation of part 2 results showed that both groups had the same pre-EVT rates of recanalization (19.3%) and no change in functional outcomes. There was a higher rate of symptomatic intracerebral hemorrhage in the 0.4 mg/kg dosing group, which was largely explained by wire perforation during EVT. Based on these results, the investigators recommend that 0.25 mg/kg be the standard dose for tenecteplase. In view of findings from EXTEND-IA TNK, it is possible that tenecteplase may overtake alteplase as the preferred thrombolytic agent for acute ischemic stroke.

3) Endovascular therapy: How accessible is it, and how can we improve?

Only one-fifth of the U.S. population has access to a stroke center with EVT capabilities (i.e., Comprehensive Stroke Center [CSC] or Thrombectomy-Capable Stroke Center [TSC]) within 15 minutes, according to a study by Sarraj and colleagues presented at ISC 2020 and published in Stroke. These researchers used 2017 Centers for Medicare and Medicaid Services data to determine access to EVT-capable centers and identify ways to optimize access. They found that bypassing non-EVT centers in favor of the closest EVT-capable center within 15 minutes led to overall increased access to EVT, with results being state-dependent due to differing population densities. This remained the most effective way to maximize EVT access even when compared with a separate model where the researchers flipped 10% and 20% of all current non-EVT centers to EVT centers.

Bypassing Primary Stroke Centers (PSCs) has been previously supported by a study published in Circulation: Cardiovascular Quality and Outcomes in 2018. Using Get with The Guidelines–Stroke data from 2013-2015, researchers from Cleveland Clinic and other institutions showed that CSCs had higher rates of tPA administration and faster tPA administration times compared with PSCs.

4) Promising wearable TMS device for post-stroke hemiparesis

A notable presentation in the realm of stroke rehabilitation centered on the use of a novel wearable transcranial magnetic stimulation (TMS) device for post-stroke hemiparesis called a transcranial, rotating, permanent magnetic stimulator (TRPMS). Researchers from Houston Methodist Hospital used the device to stimulate six sites in the brain (four in the lesional hemisphere, two contralesional) in hopes of improving hemiparesis.

The randomized, double-blind, sham-controlled trial enrolled 30 patients at a median of three years post-stroke. All had at least three months of persistent hemiparesis. Patients received 20 sessions of 40-minute treatments over four weeks. The primary endpoint was an increase in active voxels on functional MRI after treatment and at one month. Other outcomes included safety and hemiparesis based on clinical measurement scales at three months. The study found that the treatment was safe and there was a significant change in functional cortical activation of the injured brain regardless of stroke location (cortical vs. subcortical). Clinical scales suggested possible improvement of motor function at three months after treatment. While further studies in larger samples will be required before the TRPMS can be considered for wider use, the device shows promise for patients with long-term hemiparesis.

5) Two notable anniversaries

This year’s ISC meeting celebrated 2020 as the 25th anniversary of the landmark NINDS alteplase (tPA) trial as well as the five-year anniversary of support for EVT in acute ischemic stroke. When the NINDS tPA trial began in 1988, the average time from stroke onset to stroke evaluation at a hospital was 2 days and 160/90 was the standard definition used for hypertension. This trial was the foundation for acute ischemic stroke treatment — specifically for the ability to effectively treat patients within 3 hours of symptom onset. This trial not only changed treatment and outcomes for patients; it changed the landscape of systems of care for acute ischemic stroke. We still use tPA today as a mainstay for acute thrombolysis in eligible patients suffering from disabling stroke symptoms. The fact that ISC has surged from 500 attendees in 1995, the year of the NINDS tPA trial’s publication, to 5,700+ in 2020 is a testament to how much this study has helped expand vascular neurology as a discipline.

One of the first devices developed for EVT (Merci) was approved in 2004. Stent retrievers became more popular around 2012 with technological advances, yet three negative trials were published that year in the New England Journal of Medicine (NEJM). These reports cited slow workflow and poor revascularization rates among the major culprits for a lack of change in patient outcomes. With careful attention to these lessons from the negative studies, four trials were published in NEJM in 2015, all showing improved functional independence and decreased disability if patients were treated within about 7.3 hours from acute ischemic stroke onset. These landmark trials were then expanded on by the DAWN and DEFUSE-3 trials in 2018, which showed that this treatment window could be extended up to 24 hours in carefully selected patients. Thanks to these trials, use of EVT increased by 110% from 2015 to 2018 and by another 40% since 2018. EVT remains one of the most effective treatments we have for acute ischemic stroke due to large vessel occlusion.

Dr. Buletko is a staff physician in Cleveland Clinic’s Cerebrovascular Center.