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Article Commentary: “Advances in Acute Ischemic Stroke Therapy”
Ayush Agarwal, MD, DM, DNB
@drayushagarwal
The management of acute ischemic stroke continues to progress, and there is a shift towards ‘tissue window’ from the traditional ‘time window.’ Recent trials have demonstrated that thrombolysis can safely be done out of the traditional time window based on careful patient selection using advanced imaging techniques including brain MRI and CT-perfusion (1,2). Although, traditionally, alteplase has been the mainstay of treatment, tenecteplase usage is rapidly gaining ground based on ease of administration and higher fibrin specificity. It has not only been proven non-inferior, but also better at lysing large vessel clots (when compared to alteplase) (3). The advent of mobile stroke units with CT scanners and point-of-care laboratory support has further reduced door-to-needle times and led to even better stroke outcomes (4,5).
Article Commentary: “Association of Intraventricular Fibrinolysis With Clinical Outcomes in ICH”
Ericka Samantha Teleg, MD
This meta-analysis examines the utilization of intraventricular fibrinolysis (IVF) and its impact on clinical outcomes in intracerebral hemorrhage. Despite several studies showing intraventricular clot resolution and safety among an intracerebral hemorrhage (ICH) population with a small hematoma volume but larger intraventricular hemorrhage volumes, the primary efficacy analyses for functional outcomes were neutral. Thus, tailoring clinical selection of patients that may benefit from IVF may determine functional benefit.
The statistical method that the authors have utilized to summarize data from several trials and observational data is crucial, as this kind of method used in meta-analysis preserves the clustering of the cohorts of patients from the different studies. This method also allows a large sample to be studied. This is the strength of the data and its results. The Individual Participant Data meta-analysis included 9 studies. The IPD set was compiled and analyzed in an academic center, University Hospital Erlangen in Germany. The eligibility for IPD inclusion included the following: (1) supratentorial primary ICH or IVH with IVH causing acute hydrocephalus treated with an external ventricular drainage (EVD); (2) patients aged >18 years; (3) pre-morbid modified Rankin Scale (mRS) < 3; (4) >10 patients treated with IVF within each study framework; (5) no evidence of early care limitations or death within 48 hours after admission; (6) no evidence of secondary ICH-etiologies; (7) no other competing treatment intervention; (8) use of validated imaging methods; (9) standardized scoring of neurological status; (10) availability of standardized functional outcome assessed by the mRS.
Article Commentary: “Recurrent Ischemic Stroke and Bleeding in Patients With Atrial Fibrillation Who Suffered an Acute Stroke While on Treatment With Nonvitamin K Antagonist Oral Anticoagulants”
Dixon Yang, MD
Though non-vitamin K antagonist oral anticoagulants (NOACs) are the gold standard for stroke prevention in atrial fibrillation (AF) in absence of significant mitral stenosis or mechanical heart valve, a small proportion (1.4% per year) of residual risk for ischemic stroke remains based on pooled statistics from randomized control trials. Some observation studies report a residual annual risk as high as 10%. Therefore, Dr. Maurizio Paciaroni and authors sought to estimate the rates of ischemic and bleeding events after an acute ischemic stroke in patient with AF while on NOAC treatment and investigate predictive factors in those events, especially in the context of antiplatelet/anticoagulation strategies.
The study involved a multicenter observational cohort, which included consecutive acute ischemic stroke patients with AF who were taking NOAC at the time of event and adherent to NOAC therapy. Patients were enrolled and data collected prospectively from 43 centers across the United States and Europe. Investigators recorded NOAC doses and any reasons for reduced dosing. The study considered reduced NOAC dosing off-label in the absence of the recommended clinical and laboratory criteria for dose reduction. Participants were followed for at least 1 year. The study’s primary outcome was composite recurrent ischemic stroke, systemic embolism, intracranial bleeding, and major extracranial bleeding. The authors compared risk of outcome event between those who had their anticoagulant changed versus those who kept the same anticoagulation after index event.
Author Interview: Prof. Dr. Matthias Endres on “Immune Pathways in Etiology, Acute Phase, and Chronic Sequelae of Ischemic Stroke”
A conversation with Prof. Dr. Matthias Endres, MD, Director of the Department of Neurology, Charité-Universitätsmedizin, Berlin, Germany, on neuro-immune crosstalk in ischemic stroke.
Interviewed by Dr. Aurora Semerano, MD, Stroke Neurologist, San Raffaele Hospital, Milan, Italy (@semerano_aurora).
They will be discussing the article “Immune Pathways in Etiology, Acute Phase, and Chronic Sequelae of Ischemic Stroke,” published in the April 15, 2022 issue of Circulation Research.
Dr. Semerano: Your article is part of a Compendium on Stroke and Neurocognitive Impairment published in Circulation Research, which includes several contributions about the advances made over the past five years in different fields of stroke research that were not addressed in the previous compendium. Which are, in your opinion, the most relevant advances in stroke immunology in these last five years?
Prof. Dr. Endres: First of all, thanks for including me in your blog, and thank you for very elaborate questions. Many of them would require a long answer, but I will try to be brief and refer interested readers to our review article instead.
Regarding the most important advances of the last five years — this is not an easy question. With regard to etiology and stroke risk, I think that recent large-scale genetic studies have led to a huge step forward to identify novel loci associated with stroke risk that can also be targeted pharmacologically. Personally, I find the work on clonal hematopoeisis and association with vascular and stroke risk very interesting. Regarding the acute phase of stroke, there are quite a number of high-quality publications on the complex role of the different players (i.e., neutrophils, monocytes, microglia, as well as T and B cells) in the ischemic cascade in the brain. Lastly, there is now a strong link between immune pathways following stroke and the development of post-stroke dementia (and also depression).
Interview: Dr. Lesli Skolarus, MD, MS, on Community Partnerships in Stroke Care
Dr. Lesli Skolarus, MD, MS, is a professor of neurology and co-chief of the vascular neurology division at the University of Michigan. She is well-renowned for her work on community partnerships to improve stroke outcomes and stroke equity. She has used several innovative concepts in improving outreach and engaging and empowering underserved communities in stroke care, such as providing stroke education in Black churches, using wearable devices and mobile apps, decentralizing stroke care by improved focus on Federally Qualified Health Centers, and emphasizing the importance of preventive stroke care in the community. She is on several diversity committees, including that of the American Heart Association and American Neurological Association, and has received several prestigious awards, including the 2017 Derek Denny-Brown Young Neurological Scholar Award from the American Neurological Association.
She is interviewed by Dr. Saurav Das, MD, Assistant Professor, Department of Neurology, University of Kentucky College of Medicine.
Dr. Das: Dr. Skolarus, I want to thank you on behalf of the Blogging Stroke team for joining us for an interview for National Stroke Awareness Month. You have tremendous experience working to reduce stroke disparities using novel strategies like stroke education in Black churches, strengthening the role of Federally Qualified Health Centers in stroke care, extending advanced care planning to the Black community, etc. Can you outline for us a few of your favorite initiatives and insights you have gained regarding what strategies work and what do not?
Dr. Skolarus: I have learned the power of broad-based community partnerships. From our hospital and clinic operational partners to our community partners, everyone has something to add to our shared goals of promoting health equity. Every type of partner has been vested in the stroke care initiatives. By leveraging collaborators’ interests and strengths, we have been able to develop and test health behavior theory-based interventions that may make significant strides toward improving the lives of stroke survivors and reducing the risk of stroke. In addition, I have learned the importance of cultural humility, which is a process of lifelong learning and self-reflection, acknowledging one’s own biases, desire to fix power imbalances, and accountability. It is a commitment to respecting all viewpoints and engaging authentically from a place of learning. That being said, from the beginning, we have always approached our community partners as true and equal partners — experts to learn with, challenge us, and help us grow. You cannot expect to make a difference by coming in with hubris; our process has always been about building a relationship and trust and letting the community partners lead us in ways we can help improve the health of the community.
Differences Between Real World and Clinical Trials After Left Atrial Appendage Occlusion in Atrial Fibrillation
Wern Yew Ding, MBChB
Patients with atrial fibrillation are at an increased risk of thromboembolic complications, particularly from clot arising in the left atrial appendage. Therefore, percutaneous left atrial appendage occlusion (LAAO) lowers the risk of stroke by mechanically excluding the left atrial appendage from the systemic circulation. Nonetheless, the optimal antithrombotic regime post-device implantation remains ill-defined.
In this study, Freeman and colleagues studied the deviations from full post-procedure treatment protocols in clinical practice compared to pivotal LAAO trials, and evaluated the impact of different antithrombotic treatment patterns on the risk of adverse events. The authors utilized data from the National Cardiovascular Data Registry LAAO Registry, which serves as a formal post-market surveillance vehicle required by the U.S. Food and Drug Administration for the Watchman device. As of April 2016, U.S. hospitals were required to submit data for all Watchman procedures to the LAAO Registry to qualify for Medicare reimbursement.
“Seeking Glocal Solutions to Cerebrovascular Health Inequities”: 2021 William Feinberg Award Lecture from Dr. Bruce Ovbiagele
Dixon Yang, MD
No, ”glocal” isn’t a typo. In the 2021 William Feinberg Award Lecture given at the International Stroke Conference of the same year, Dr. Bruce Ovbiagele discussed inequities in stroke burden among Black individuals in the United States and sub-Saharan Africa, opening with the term “glocal.” A portmanteau of global and local, glocal is an encompassing term that refers to consideration of issues on both a global and local scale in a highly interconnected manner. Often used in political or business realms, Dr. Ovbiagele brought the term to the forefront in thinking about how to best address stroke disparities.
Locally in the United States, it is well known that Black individuals experience higher stroke incidence and mortality than other race and ethnic groups. While stroke mortality in the United States has been improving, including among Black individuals, the mortality inequities have not objectively diminished. Conversely, projections suggest a further widening of the Black-White stroke prevalence gap in the next decade despite better risk factor control. A more nuanced approach to assessing vascular risk factors (i.e., differential impact by race and ethnic group, or temporal factors like duration and fluctuations of risk factors) may be needed. Furthermore, psychosocial, socioeconomic, and neighborhood level factors are increasingly recognized as potential risk factors in stroke disparity. In addition to studying risk factors, Dr. Ovbiagele urged identification of strategies in reducing stroke disparities, discussing his own local randomized trial testing efficacy of Bluetooth-enabled pill trays with reminders and BP monitoring among stroke survivors, half of whom are Black individuals.
ESOC 2022: ESMINT-ESO Joint Symposium: Persistent Frontiers Facing Acute Reperfusion Therapies
Ammad Mahmood, MBChB, BMedSci
@AMahmoodNeuro
A joint symposium between ESO and ESMINT discussed the challenges faced in acute reperfusion therapies, including patient selection and therapeutic targets.
Endovascular thrombectomy for mid-sized artery occlusions – Raul Nogueira
The importance of IV thrombolysis (IVT) therapy in this patient population was highlighted, and what constitutes mid-sized arteries considered. The anatomical variation of the M2 segment of the MCA makes this definition critical — there is generally agreement on EVT for clots in the proximal portion of larger M2 vessels. The terminology of DMVO — distal medium vessel occlusions — separates proximal dominant M2 occlusions from non-dominant M2 occlusions, as well as M3, ACA, and PCA territories. The literature suggests DMVOs cause 25-40% of acute ischemic stroke either as the primary finding or a secondary embolization complicating mechanical thrombectomy. Although IVT for this population is advocated, only half achieve reperfusion and around 25-33% have functional independence after DMVO stroke, highlighting the room for improvement potentially with EVT. Registry data showed DMVO stroke had moderately high baseline NIHSS with similar rates of reperfusion and complication with EVT compared with more proximal occlusions and up to two-thirds of patients achieving functional independence at 90 days. Patient selection in DMVO stroke needs to take into consideration many factors, including correlation of imaging and clinical findings to determine the eloquence of the area of brain involved, as well as technical considerations of the EVT procedure, such as tortuosity of the vessel, which can making procedures higher risk.
ESOC 2022: “Stroke, Thrombosis and Cancer”
Aurora Semerano, MD
@semerano_aurora
European Stroke Organisation Conference
May 4-6, 2022
Among other themes, this year ESOC has represented a unique opportunity to discuss cancer-related stroke in a dedicated Scientific Session titled “Stroke, thrombosis and cancer,” chaired by Blanca Fuentes (Spain) and Leo Bonati (Switzerland).
Indeed, cancer is recently emerging as a risk factor for arterial thromboembolism, including stroke. Among ischemic stroke patients, comorbid cancer is a devastating condition associated with increased stroke severity, disability, and mortality. Importantly, the optimal strategies to prevent and acutely treat stroke in cancer patients are yet to be established, with high recurrence rates despite antithrombotic therapies, and there are currently limited resources to assist stroke clinicians in the specific management of cancer patients.
