Stroke Alert May 2021

05/20/21 • 21 min

On Episode 4 of the Stroke Alert Podcast, host Dr. Negar Asdaghi highlights two featured articles from the May 2021 issue of Stroke: “Association of Serum IL-6 With Functional Outcome After Intracerebral Hemorrhage” and “SARS-CoV-2 and Stroke Characteristics: A Report from the Multinational COVID-19 Stroke Study Group.” This episode also features a conversation with Dr. Alvaro Garcia-Tornel Garcia-Camba to discuss his article “Ischemic Core Overestimation on Computed Tomography Perfusion.”

Dr. Negar Asdaghi:

1) Can a pro inflammatory marker predict the hematoma size and clinical outcomes in patients with intracerebral hemorrhage?

2) What are the characteristics of stroke patients infected with coronavirus?

3) Is ischemic core reliably represented by the current established cerebral blood flow thresholds on CT perfusion imaging? Or are we underestimating the importance of perfusion overestimating the ischemic core?

We will discuss these topics in today's podcast. You're listening to Stroke Alert Podcast. Stay with us.

Dr. Negar Asdaghi: From the Editorial Board of Stroke, welcome to the Stroke Alert Podcast. My name is Negar Asdaghi. I'm an Associate Professor of Neurology at the University of Miami Miller School of Medicine and your host for the monthly Stroke Alert Podcast. For the May 2021 issue of Stroke, we have an exciting program today, as we cover topics from the predictive role of inflammatory markers in intracerebral hemorrhage to characteristics of stroke patients infected with SARS-CoV-2 virus. Later in the podcast, I have the privilege of interviewing Dr. Alvaro Garcia-Tornel Garcia-Camba from Autonomous University of Barcelona on the topic of ischemic core overestimation by CT perfusion imaging. I hope you enjoy our podcast.

Dr. Negar Asdaghi: Intracerebral hemorrhage is an aggressive form of stroke with high morbidity and mortality rates. Increased systemic inflammation may be correlated with more severe neurological presentation, larger hematoma volume, and worse clinical outcome in these patients. Elevated levels of interleukin 6, or IL-6, have been found in the experimental models of ICH and may represent a therapeutic target to reduce the inflammatory response in ICH if similar findings were replicated in clinical studies of patients with ICH.

Dr. Negar Asdaghi: In the May issue of the journal, in the study titled “Association of Serum IL-6 With Functional Outcome After Intracerebral Hemorrhage,” Dr. Kevin Sheth from Department of Neurosurgery at Yale University and colleagues performed a pre-specified exploratory analysis of the patients enrolled in the FAST trial, testing the association of admission levels of serum IL-6 with baseline neuroimaging and functional outcome at 90 days.

Dr. Negar Asdaghi: But just a reminder for our listeners that FAST trial was a multicenter randomized trial of the recombinant factor VIIa administered in two doses versus placebo in patients with spontaneous nontraumatic intracerebral hemorrhage presenting within three hours of symptom onset.

Dr. Negar Asdaghi: So, in the current analysis, amongst 841 patients enrolled in the trial, 66% were included who had both baseline IL-6 measurements and the follow-up modified Rankin Scale on day 90. Patients were stratified into four quartiles based on their admission IL-6 serum levels from low/normal in quartile one to very high levels in quartile four. And their ...

Dr. Negar Asdaghi:

1) Can a pro inflammatory marker predict the hematoma size and clinical outcomes in patients with intracerebral hemorrhage?

2) What are the characteristics of stroke patients infected with coronavirus?

We will discuss these topics in today's podcast. You're listening to Stroke Alert Podcast. Stay with us.

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Stroke Alert April 2021

On Episode 3 of the Stroke Alert Podcast, host Dr. Negar Asdaghi highlights two featured articles from the April 2021 issue of Stroke. This episode also features a conversation with Dr. Simon Nagel, from Heidelberg University in Germany, to discuss his article “Predictors for Failure of Early Neurological Improvement After Successful Thrombectomy in the Anterior Circulation.”

Dr. Negar Asdaghi:

1) Is Andexanet a cost-effective treatment for the reversal of coagulopathy in factor Xa-associated intracranial hemorrhage?

2) Are statins safe and efficacious in secondary prevention of stroke in the elderly population?

3) What are the predictors of futile recanalization amongst successfully treated patients with endovascular therapy?

We have the answers to the above and much more in today's podcast. You're listening to Stroke Alert Podcast. Stay with us.

Dr. Negar Asdaghi: Factor Xa inhibitors, such as apixaban, edoxaban and rivaroxaban, are commonly used for prevention of ischemic stroke and systemic embolism in patients with non-valvular atrial fibrillation. Bleeding is a serious adverse consequence of treatment with anticoagulants, including factor Xa inhibitors, with intracranial hemorrhage representing the most devastating form of such adverse events.

Dr. Negar Asdaghi: Anticoagulant-associated intracranial hemorrhage typically results in larger hematoma volumes, higher risk of expansion, and worst clinical outcomes as compared to their spontaneous counterparts and requires immediate reversal of coagulopathy. Andexanet alfa is a recombinant modified factor Xa protein which is an effective antidote to reverse this coagulopathy, though it comes with an increased risk of thromboembolic events, either from Andexanet itself or delayed or lack of resumption of anticoagulation in the setting of intracranial hemorrhage.

Dr. Negar Asdaghi: It is important to note that the estimated cost of Andexanet is between $25-50,000 US dollars, depending on the standard versus high dose used, and this medication is currently not available in many countries, including in Canada, and even in the United States, it's still not accessible in many centers mainly due to its high cost. Now, when Andexanet is not available, the non-specific antidote of prothrombin complex concentrate, or PCC, is used, carrying an approximate cost of $4-8,000 US dollars, depending on the dosage used.

Dr. Negar Asdaghi: PCC, which is a combination of various clotting factors, together with protein C and protein S, have a limited efficacy and reversal of Xa inhibitors coagulopathy. In the absence of randomized control trials to directly compare Andexanet to PCC, there remains a significant gap in knowledge with regards to comparative efficacy, adverse events, and cost-effectiveness of these therapies for life-threatening bleeding, specifically intracranial hemorrhage, in the setting of Xa inhibitor use.

Dr. Negar Asdaghi: In the current issue of the journal, Dr. Andrew Micieli and colleagues from the Division of Neurology, Department of Medicine, Universities of Toronto and Calgary, in Canada, did a comparative analysis between Andexanet and PCC in a study titled “Economic Evaluation of Andexanet Versus Prothrombin Complex Concentrate for Factor Xa-Associated Intracranial Hemorrhage.” Using a patient population on chronic factor Xa inhibitor treatment, when presenting with an intracranial hemorrhage, the authors applied a probabilistic Markov model over a lifetime horizon for each patient to evaluate the cost and benefits if either Andexanet or PCC was administered to reverse the coagulopathy.

Dr. Negar Asdaghi: Estimates of outcomes, dosing, and administration protocols for Andexanet were derived from the ANNEXA-4 study and from the UPRATE study for the PCC. These are two previously published large cohorts of treatment for these agents, respectively.

Dr. Negar Asdaghi: So, what they found was an overall reduction in the occurrence of fatal intracranial hemorrhage with Andexanet therapy, estimated around 18%, as compared to PCC, estimated at 34%, specifically if the antidote was administered in...

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Stroke Alert June 2021

On Episode 5 of the Stroke Alert Podcast, host Dr. Negar Asdaghi highlights two articles from the June 2021 issue of Stroke: "Preexisting Mild Cognitive Impairment, Dementia, and Receipt of Treatments for Acute Ischemic Stroke” and “Body Mass Index in 1.9 Million Adolescents and Stroke in Young Adulthood.” She also interviews Dr. Shyam Prabhakaran, from the University of Chicago, about his article "Predictors of Early Infarct Recurrence in Patients With Symptomatic Intracranial Atherosclerotic Disease."

Dr. Negar Asdaghi:

1) Do people with mild cognitive impairment receive the same quality of stroke care as their cognitively normal counterparts?

2) Is there a causative relationship between the alarming rise in adolescent obesity and the rise in the incidence of stroke under the age of 50?

3) What are the independent predictors of radiographic recurrence in patients with symptomatic intracranial atherosclerotic disease?

These are the topics that we will cover in today's podcast. You're listening to the Stroke Alert Podcast. Stay with us.

Dr. Negar Asdaghi: From the Editorial Board of Stroke, welcome to the Stroke Alert Podcast. My name is Negar Asdaghi. I'm an Associate Professor of Neurology at the University of Miami Miller School of Medicine and your host for the monthly Stroke Alert Podcast. For the June 2021 issue of Stroke, we have a range of publications that cover a variety of topics from activation of neuroinflammatory pathways and intracerebral hemorrhage to predictors of outcome in patients with mild and rapidly improving ischemic stroke, which I encourage you to review, in addition to our podcast. Later in today's podcast, I have the privilege of interviewing Dr. Shyam Prabhakaran from University of Chicago on his work with various radiographic biomarkers as predictors of outcome in patients with symptomatic intercranial atherosclerotic disease. But first, with these two papers.

Dr. Negar Asdaghi: In the United States, one in five adults over the age of 65 have mild cognitive impairment, and one in seven have a formal diagnosis of dementia. With our aging population, these numbers are estimated to triple by year 2050. Prior studies suggest that patients with dementia are less likely to receive evidence-based stroke care as compared to those with normal cognition. Less is known about the quality of stroke care amongst patients with mild cognitive impairment. In their paper titled "Preexisting Mild Cognitive Impairment, Dementia, and Receipt of Treatments for Acute Ischemic Stroke," Dr. Deborah Levine from Departments of Neurology and Internal Medicine at the University of Michigan and colleagues studied the quality of care in acute ischemic stroke patients with mild cognitive impairment, or MCI, and preexisting dementia as compared to patients with normal cognition.

Dr. Negar Asdaghi: This was a cross-sectional analysis of prospectively obtained data on adults with acute ischemic stroke included in the Brain Attack Surveillance in the Corpus Christi project from 2008 to 2013. Primary outcome of the study is a composite quality measure of defect-free care calculated by dividing the number of treatments that a patient received by the number of treatments they were eligible to receive. Defect-free care was defined as receipt of seven stroke performance measures when eligible, and included administration of IV tPA, use of antithrombotic therapy by end of hospital day two, administration of DVT prophylaxis, assessment for rehabilitation, discharge on antithrombotic therapy, discharge on lipid-lowering therapy, and discharge on anticoagulation therapy for atrial fibrillation.

Dr. Negar Asdaghi: Amongst 836 adults included in this study with a median age of 65, 58%, that's over half of the patients in this study, had some degree of cognitive impairment prior to their presenting stroke. 44% of patients with preexisting dementia received defect-free care as compared to 55% with either normal cognition or mild cognitive impairment. The difference, they did not reach statistical significance after adjusting for the sex, vascular comorbidities, and BMI in multivariate analysis. However, preexisting MCI remain an independent factor to be negatively associated with receipt of IV tPA echocardiogram and assessment for rehabilitation. Similarly, after adjusting for all confounders, preexisting dementia remained negatively associated with receipt of antithrombotic therapy by day two, lipid-lowering therapy at discharge, and receiving an echocardiogram. The authors highlighted their find...