American Heart Association


In Quest to Enhance Stroke Recovery, Does Daily Fluoxetine Alone Get Us Closer?

Kate Hayward, PhD, PT

ESO-WSO 2020 Large Clinical Trials Webinar
Presentation: Assessment of fluoxetine in stroke recovery (AFFINITY): A randomised double-blind, placebo-controlled trial
Presenter: Prof. Graeme Hankey

There is much interest in identifying a drug to boost post-stroke recovery. Fluoxetine has received considerable attention since the FLAME trial,1 which demonstrated an improvement in motor recovery (Fugl Meyer Assessment) and functional independence (modified Rankin Scale) in acute stroke patients with moderate to severe hemiparesis.

To address uncertainty that existed concerning the use of fluoxetine,2 a family of investigator-led, multicentre, parallel group, randomised, placebo-controlled trials were established: EFFECTS (also presented on the ESO-WSO large clinical trials webinar, Sweden), FOCUS (published in 2019,3 United Kingdom), and AFFINITY, which is the focus of this blog post. These international trials collectively aimed to determine whether the routine administration of fluoxetine (20mg daily) for six months after an acute stroke improves patients’ functional outcome.4

Have We EFFECTively Put an End to the Use of SSRIs in Motor Recovery After Acute Stroke?

Abbas Kharal, MD, MPH

ESO-WSO 2020 Large Clinical Trials Webinar
EFFECTS Trial – Efficacy of Fluoxetine: A Randomized Controlled Trial in Stroke
May 13, 2020

Over the past decade, there has been much controversy regarding the potential benefit of selective serotonin reuptake inhibitors (SSRIs) in neuro-recovery and functional independence after stroke. After data from animal stroke studies showed that SSRIs may have potential neuroprotective properties,1 this concept was further analyzed in humans through a Cochrane review2 of 52 studies of a total of 4059 stroke patients, which suggested that SSRIs may improve disability after stroke; however, given the heterogeneity of data, solid conclusions could not be drawn. Furthermore, a randomized controlled clinical trial published in 2011 in Lancet on fluoxetine for motor recovery after acute ischemic stroke (FLAME trial) that enrolled 118 stroke patients showed improved motor recovery after stroke and functional independence (up to 17%) in those treated with fluoxetine versus placebo.3

Pooled evidence from these studies suggested that there was possibly some promising evidence to suggest that the use of SSRIs after acute stroke may lead to neurogenesis, improved motor recovery after stroke and functional independence; however, given the heterogeneity of the data, small sample sizes and methodological limitations, larger well-designed randomized controlled clinical trials were needed to better test this hypothesis in humans.2,4 This led to further development of three large randomized controlled clinical trials, namely FOCUS, EFFECTS ad AFFINITY, which planned to collectively enroll nearly 6000 patients.5,6

Endovascular Thrombectomy With or Without Intravenous Alteplase: ESO-WSO Large Clinical Trials Webinar

Parneet Grewal, MD

ESO-WSO 2020 Large Clinical Trials Webinar
Presenter: Dr. Jianmin Liu (China)
Article: Yang P, Zhang Y, Zhang L, Zhang Y, Treurniet KM, Chen W, et al, for the DIRECT-MT Investigators. Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke. NEJM. 2020.

The goal of current therapeutic strategies for acute ischemic stroke with large vessel occlusion (LVO) is recanalization of the occlusion before irreversible damage has occurred. In this large multicenter, prospective, randomized, open-label trial with blinded outcome assessment, Dr. Jianmin Liu and his team aimed to answer the question of whether mechanical thrombectomy (MT) alone (thrombectomy alone group) would be non-inferior to combined treatment of IV-tPA and MT (combined group) in patients with LVO.  

This trial included patients ³ 18 years of age who presented to 41 pre-selected academic medical centers in China within 4.5 hours of symptom onset, had National Institutes of Health Stroke Scale (NIHSS) ³ 2 with imaging showing an LVO (intracranial segment of ICA, M1 or proximal M2 only). Any patients who did not meet American Heart Association/American Stroke Association guidelines for alteplase or MT were not included in the trial. The standard dose of tPA at 0.9 mg/kg was used, and the first-line strategy for MT was stent-retriever. Statistically, the trial was designed to provide 80% power (at a two-sided alpha level of 0.05) to determine a non-inferiority margin of 0.8. 656 patients were randomized in 1:1 fashion by a web-based system with 327 patients in the thrombectomy alone group and 329 patients in the combined group. The patient enrollment period was 17 months (February 23, 2018, to July 2, 2019). The baseline characteristics of patients were similar in both the groups with a median age of 69 years, median NIHSS score of 17, and median ASPECTS value of 9. The median duration from stroke onset to randomization was 167 minutes in the thrombectomy alone group and 177 minutes in combined group with time from randomization to groin puncture being 31 minutes and 36 minutes, respectively.

ESO-WSO Large Clinical Trials Webinar: BASICS

Rachel Forman, MD

I was happy to see that although the ESO-WSO 2020 annual meeting was postponed, we still had the opportunity to virtually hear the results of some recent large clinical trials. One of the five trials presented was the Basilar Artery International Collaboration Study (BASICS) presented by Dr. Wouter Schonewille from The Netherlands. Posterior circulation occlusions have been largely excluded from the main endovascular randomized control trials, so these results were highly anticipated. 

Many of us are familiar with the devastating effects of a basilar artery occlusion (BAO), and from a personal experience, some of these cases have been very challenging without having the guidance of large trials as we do with anterior circulation occlusions. The clinical presentations, stroke severity, and collateral patterns are inherently different. This trial was an international, multicenter, controlled trial with randomized treatment-group assignments investigating the efficacy and safety of endovascular therapy (EVT) plus best medical management (BMM) versus BMM alone <6 hours of estimated time of BAO. Patients were randomly assigned (1:1 ratio) to EVT+BMM or BMM alone and stratified according to: randomizing center, use of IVT, and NIHSS (<20 vs >20). The enrollment period was from 2011 through 2019. Patients were excluded with intracranial hemorrhage, extensive brainstem ischemia, or cerebellar mass effect/acute hydrocephalus. The calculated sample size was 300 patients assuming favorable outcome in 46% with EVT+BMM and 30% with BMM. Primary outcome was mRS <3 at 90 days. Secondary outcome measures included clinical outcomes (mRS 0-2 at 90 days and mRS distribution) and imaging outcomes (posterior circulation ASPECTS score at 24 hours and basilar artery patency at 24 hours). 

ISC 2020 Session: “Transradial Approaches for Stroke and Cerebrovascular Disease: The End of Femoral Artery Complications?”

International Stroke Conference
February 19–21, 2020

Kat Dakay, DO

Use of the transradial technique as an alternative to traditional femoral access in neuroendovascular procedures has increased substantially over the last few years after studies have demonstrated its advantages and lower risk of access site complications.[1]   

However, there is a learning curve that one must traverse when adopting the transradial approach. This year, the International Stroke Conference dedicated a symposium to a multifaceted discussion about the benefits, challenges, and potential complications unique to transradial access. 

The session was moderated by Dr. Tudor Jovin and Dr. Nathan Manning, and speakers included Dr. Michael Levitt, Dr. Eric Peterson, Dr. Marios Psychogios, and Dr. Brian Snelling. Some major topics discussed:

1. Why go radial?

There are several reasons to consider utilizing the transradial approach. Dr. Peterson discussed one major reason, patient preference — with a transradial approach, there is no need for patients to lay flat postoperatively, which can make even small tasks like using the restroom awkward and cumbersome. Increased awareness of the transradial method by the general public has led to increasing patient requests to use this approach. Anecdotally, as a fellow explaining and obtaining consent for diagnostic angiograms, many patients have said to me, “I really hope you can use my hand instead of the leg.” As the popularity of transradial access in both cardiology and neuroendovascular procedures grows, this is likely to become more common. Objectively, one study demonstrated that 24/25 patients who underwent prior transfemoral cerebral angiography and subsequently underwent transradial angiography preferred the radial method.[2] Another reason Dr. Peterson discussed is that in patients with obesity or significant arch tortuosity, transfemoral access can prove challenging and the radial approach may be easier in selected cases. Lastly, and probably the most compelling and important reason, which both Dr. Peterson and Dr. Levitt discussed, is that it is safer. Multiple cardiology trials have demonstrated that transradial procedures are safer than transfemoral procedures with an overall lower risk of major complications and mortality.[1, 3] 

ISC 2020 Session: “Screening for Cognition and Factors Related to Brain Health”

International Stroke Conference
February 19–21, 2020

Session: “Screening for Cognition and Factors Related to Brain Health,” Thursday, February 20, 2020

Moderators: Dr. Ronald M. Lazar, Birmingham, AL; and Dr. Rebecca F. Gottesman, Baltimore, MD

Abstract: It is increasingly recognized that vascular risk factors promote cognitive decline, both independently and interactively with neurodegenerative disease. Because these risk factors are modifiable, evaluation in the setting of primary care represents a unique opportunity for early detection and treatment.

Shashank Shekhar, MD, MS

The session had four presentations. Dr. Walter N. Kernan Jr. from New Haven, CT, led the first talk on “Evaluating cognition in elderly at primary care.” He explained why primary care is important in recognizing cognitive issues. He went on to explain the spectrum of cognitive impairment, which ranges from subjective, mild cognitive impairment (annual risk of progression?), dementia (annual risk of progression 7%). He then laid out a simple flow chart of evaluating cognition in the primary setting: identifying the 1) signal, 2) case finding, 3) Classification and management. The signal could be in the form of reporting by patient or family, the observation by a physician, or casual inquiry. Case finding refers to using assessment tools such as Memory Impairment screen, MMSE, MOCA, etc., to screen for cognition. The final step is to confirm the diagnosis, identify any treatable causes, identify functional impairment, classify etiology, and further neuropsychiatric assessment.

The speakers address audience questions during the session “Screening for Cognition and Factors Related to Brain Health” on February 20, 2020, during the International Stroke Conference. From left, Dr. Sudha Seshadri, Dr. Walter N. Kernan, Dr. Virginia J. Howard, Dr Philip B. Gorelick, Dr Ronald M. Lazar, and Dr. Rebecca F. Gottesman.
The speakers address audience questions during the session “Screening for Cognition and Factors Related to Brain Health” on February 20, 2020, during the International Stroke Conference. From left, Dr. Sudha Seshadri, Dr. Walter N. Kernan, Dr. Virginia J. Howard, Dr. Philip B. Gorelick, Dr. Ronald M. Lazar, and Dr. Rebecca F. Gottesman.

Dr. Virginia J. Howard from Birmingham, AL, gave the second presentation on “Considerations in cognitive assessment in disparate populations.” Her talk focused on disparities related to sex, age, disability, socioeconomic status, and geographic locations. She identified barriers to recruitment and retention at different levels, i.e., individual to research institutions. She suggested engaging community leaders in the research process and using community outreach programs, and that preparing a realistic budget would greatly help achieve the goal. Changes are also required in the study design, i.e., in-home evaluations, and identifying all levels of influences and barriers at the institution and community would help with more recruitment and higher retention.

ISC 2020 Session: “Contemporary Management of Unruptured Intracranial Aneurysms: What to Counsel Patients”

International Stroke Conference
February 19–21, 2020

Kat Dakay, DO

Deciding how to manage unruptured intracranial aneurysms is a common challenge in neuroendovascular surgery, as many of these aneurysms are incidentally found on imaging performed for other reasons. The classic dogma of the ISUIA study stratifies rupture risk based on size and location; however, this is an oversimplified picture. In this ISC session, the speakers discussed complex anatomical features, neuroimaging findings, and lifestyle counseling for patients with unruptured intracranial aneurysms.

Dr. Juhana Frösen discussed the influence of wall structure on rupture risk; the wall structure of aneurysms is very heterogenous. This may explain why some small aneurysms can rupture. Macrophages and inflammation can lead to aneurysm wall growth, which increases the stress on the aneurysm and can increase the risk of rupture. Future targets for drug research may include reducing inflammation and reducing wall growth.

ISC 2020 Session: “Widening the Lens of Telestroke: From the ED Across the Stroke Continuum”

International Stroke Conference
February 19–21, 2020

Session: “Widening the Lens of Telestroke: From the ED Across the Stroke Continuum,” Thursday, February 20, 2020

Jennifer Majersik, MD: Physician at the University of Utah – Expansion of Telestroke Networks
Matthew Koenig, MD: Physician at Queens Medical Center – Tele-ICU
Steven Cramer, MD: UCLA, University of California Irvine – Tele-rehabilitation
Christine Holmstedt, DO: Medical University of South Carolina – Outpatient Telestroke Follow-up

Stephanie Lyden, MD, BS

This talk provided multiple examples of varied practice settings that use telemedicine to provide patient care. The talk started with Dr. Jennifer Majersik discussing the Expansion of Telestroke Networks. She initially explained the process of consulting a neurologist via telestroke. This is often being utilized by community hospitals that do not have a local neurologist to consult. She explained that there are different levels of acuity (hyper-acute with telestroke vs acute with emergent teleneurology vs non-urgent with scheduled teleneurology) within teleneurology consults. She noted that with a telestroke consult, the main questions addressed include whether the patient is eligible for tPA or thrombectomy, both of which are time sensitive, and the goal of these consults is for them to be completed within 10-30 minutes.

ISC 2020: “Paola de Rango Memorial Session. Sex Differences in Stroke (a Go Red for Women Session)”

International Stroke Conference
February 19–21, 2020

Charlotte Zerna, MD, MSc

Go Red For Women was created in 2004 and is a comprehensive platform designed to increase women’s health awareness and focus on research into women’s cardiovascular health, and it is meant to empower female patients to take charge of their own heart and brain health to improve outcomes. This year’s International Stroke Conference featured multiple sessions under the Go Red For Women track. The inaugural Paolo de Rango Memorial Session about sex differences in stroke was moderated by Nada El Husseini (Durham, NC) and Amytis Towfighi (Los Angeles, CA).

Salvador Cruz-Flores (El Paso, TX) emphasized that differences have to be avoidable, unjust, and unfair to constitute a disparity and can occur in any one group when compared to the most advantaged group. These differences systematically place socially disadvantaged groups at further disadvantage in regards to their health. Such disparities or social determinants of health are, for example, the adoption of health-promoting behavior and exposure to unhealthy/stressful living and working conditions, as well as access to health care and other public services. Measuring health disparity necessitates an indicator variable for one’s health, an indicator variable for one’s social position, and the ability to compare the health indicators across social position strata. A recent study by Rinaldo and colleagues was able to show the racial and ethnic disparities in the utilization of acute treatment for ischemic stroke in the United States.1 Intravenous alteplase was offered to 4.3% more white patients compared to black/Hispanic patients. About 10% more were also admitted to an endovascular-capable center, and 2.8% more received endovascular treatment.

ISC 2020 Session: “The New Frontiers in Thrombolysis of Patients with Acute Ischemic Stroke (25th Anniversary of NINDS Trial)”

International Stroke Conference
February 19–21, 2020

Mausaminben Hathidara, MD

This session was divided in topics as below, each discussing different aspects associated with making decisions for tPA for extended window, proper patient selection for mild strokes and the dilemma for patients with relative contraindication, as well as thrombolysis in women with ischemic stroke.

The story from bench to bedside by Patrick Lyden

In 1995, the NINIDS trial proved the efficacy of tPA and reasonable safety. Per pilot study analysis, the dose 0.9 mg/Kg demonstrated the best efficacy, therefore, was chosen for the NINDS trial up to 3 hours from symptoms onset, which showed that patients in the treatment arm were 30% more likely to have minimal or no disability at 3 months with reasonable safety (symptomatic ICH 6.4%) for intra-cerebral. Before the NINDS trial, there were several studies that looked into tPA for acute ischemic strokes, including ECASS I and ECASS II, which did not show successful results due to different time window and dosing selection.