American Heart Association

Monthly Archives: June 2021

Focal Cerebral Arteriopathy and Pediatric Stroke

Kevin O’Connor, MD

Oesch G, Perez FA, Wainwright MS, Shaw DWW, Amlie-Lefond C. Focal Cerebral Arteriopathy of Childhood: Clinical and Imaging Correlates. Stroke. 2021.

Focal cerebral arteriopathy (FCA) is the cause of up to a quarter of strokes in children. FCA involves a focal and unilateral stenosis or irregularity of the distal internal carotid artery and its proximal branches. The suspected underlying pathophysiology is arterial inflammation resulting in vessel narrowing and thrombus formation on damaged endothelium. Post-varicella FCA is a common etiology and may occur within a year of infection. Imaging mimics of FCA include dissection, moyamoya, and embolus. Children with FCA may have progression of symptoms over several days/weeks, and up to a quarter have another stroke within a year.

Oesch et al. identified 15 cases (8%) of FCA among 179 children with strokes at a single center between 2009-2019. The median age was 6.8 years (range 0.5-16.3 years) and 8 were boys. Common presenting symptoms included hemiparesis (n=14), headache (n=7), and a concomitant infectious process (n=6). Two of thirteen tested children (15%) were positive for VZV antibodies and VZV DNA. The lower incidence of FCA with recent VZV infection compared to prior studies may be related to increased VZV vaccination. Six children had stuttering symptoms over 1-4 days prior to stroke. Three children (20%) had progression of stroke symptoms after the initial event. All 15 children received antithrombotic therapy following the stroke and over the course of follow-up (at least one year in 14 of 15 children). Data on the safety and efficacy of steroid use in FCA is unclear.

Limited Access to Mechanical Thrombectomy for Ischemic Stroke in the United States: A Public Health Problem

Tolga D. Dittrich, MD

Kamel H, Parikh NS, Chatterjee A, Kim LK, Saver JL, Schwamm LH, Zachrison KS, Nogueira RG, Adeoye O, Díaz I, et al. Access to Mechanical Thrombectomy for Ischemic Stroke in the United States. Stroke. 2021.

Mechanical thrombectomy (MT) helps prevent disability in patients with acute ischemic stroke due to large vessel occlusion. However, MT is not offered by every hospital since its performance requires special technical expertise. A key factor for functional outcome in the context of MT is the duration between symptom onset and successful recanalization. Therefore, the goal of acute stroke care is to avoid time loss, whether due to long transport to an MT-capable center or delayed diagnostic workups to detect a stroke whenever possible. Kamel et al. examined whether current systems of stroke care in the United States provide adequate access to MT.

From 2016 to 2018, discharge data from all nonfederal emergency departments and acute care hospitals in 11 U.S. states were examined. Hospitals were categorized according to their ability to provide MT as follows: (a) hubs (if they were able to perform MT); (b) gateways (if they referred patients who ultimately underwent MT); and (c) gaps (otherwise). Of 205,681 patients with ischemic stroke, 48.7% received care in a hub, 35.3% in a gateway, and 16.0% in an MT gap. Rural patients had particularly limited access, with 27.7% of these patients initially receiving care at hubs compared with 69.5% of urban patients. Thrombolysis could be initially performed in 93.8% of patients at gateways compared with 76.3% of patients at gaps. A substantial proportion of ischemic stroke patients in the U.S. did not have access to MT, even after accounting for interhospital transfers.

Disparities to Certified Stroke Care in the United States

Parneet Grewal, MD

Yu CY, Blaine T, Panagos PD, Kansagra AP. Demographic Disparities in Proximity to Certified Stroke Care in the United States. Stroke. 2021.

The impact of time on treatment and clinical outcomes in stroke patients has been well studied. American Heart Association/American Stroke Association guidelines recommend treatment with intravenous alteplase (IV-tPA) within 4.5 hours of last known well in the majority of the cases and endovascular therapy within 24 hours of last known well. This highlights the time-sensitive nature of the acute reperfusion therapies for ischemic stroke patients. Stroke systems of care include certification of centers to optimize acute stroke treatment, patient triage by emergency medical services and patient transportation. There are multiple levels of stroke certifications, which include acute stroke ready hospitals, primary stroke center, thrombectomy-capable stroke centers and comprehensive stroke centers. Variable geographic distribution of certified stroke centers and geographical clustering of demographic groups have created potential disparities in acute stroke care with multiple studies trying to characterize the access to stroke care in the United States.

In this cross-sectional study, the authors try to meticulously quantify these relationships using national and statewide data in order to potentially impact and reduce the inequalities to access. The population data is obtained at census tract level from 2014-2018, and stroke hospital data is curated from both national and statewide data of stroke certification. Certified stroke centers were defined as the centers able to provide IV-tPA as of August 2020 in this study, and road distances from each census tract to the nearest stroke center in 48 states and the District of Columbia were estimated. The authors further classified each census tract by composition of age, race, ethnicity, and insurance status, median annual income, and population density along with additional classification as urban and non-urban.

Article Commentary: “Race Differences in High-Grade Carotid Artery Stenosis”

Nurose Karim, MD

Lal BK, Meschia JF, Brott TG, Jones M, Aronow HD, Lackey A, Howard G. Race Differences in High-Grade Carotid Artery Stenosis. Stroke. 2021.

Why is there less carotid revascularization in African American and Hispanic populations despite them having greater cardiovascular risk factors? Is this due to disparities in the access to care? Or it is truly due to low incidence of severe carotid stenosis (defined as the peak systolic velocity >230 cm/sec on carotid ultrasound)? While American Heart Association and United States Preventive Services Taskforce (USPSTF) recommendations do not support the carotid screening of the general population, Life Line Screening (LLS, Independence, Ohio) is a direct-to-consumer company in which individuals can self-pay for vascular assessments if they choose.

The authors collected data from LLS for all the patients who underwent screening for carotid stenosis from 2005-2019. Data was stratified on the basis of race/ethnicity (White, Black, Hispanic, Asian, Native American or other), sex (men or women), and age (45-54, 55-64, 65-74 or 75-84 years). Patients above age 85 were excluded. This led to a total of 6,130,481 unique participants. The prevalence of high-grade carotid stenosis was significantly lower for Black, Hispanic and Asian individuals compared to White individuals. This is comparable with the data from the 2015 census for population with high-grade stenosis and reported the prevalence as 72% of the White population, with Black and Hispanic populations comprising 11% each, and women comprising 52%.

Early Neurological Recovery in Ischemic Stroke: Time to Consider a Baseline-Adjusted 24-Hour NIHSS

Setareh Salehi Omran, MD

Mistry EA, Yeatts S, de Havenon A, Mehta T, Arora N, De Los Rios La Rosa F, Starosciak AK, Siegler III JE, Mistry AM, Yaghi S, Khatri P. Predicting 90-Day Outcome After Thrombectomy: Baseline-Adjusted 24-Hour NIHSS Is More Powerful Than NIHSS Score Change. Stroke. 2021.

Endovascular therapy (ET) is the recommended treatment for acute ischemic stroke due to a large vessel occlusion. Early neurological improvement and recovery, most commonly measured using the 24-hour National Institutes of Health Stroke Scale score (NIHSS), can occur in some patients undergoing thrombolysis or ET. Early measurements of NIHSS are associated with a favorable long-term functional outcome1-4 and are frequently used as an outcome measure in ET trials. Despite its utility, there appears to be a lack of consensus on the definition of early neurological recovery. An absolute decrease in NIHSS score of 4,5 8,6 or 107 or binary NIHSS outcomes have all been used to reflect early neurological recovery in various trials. However, a change in NIHSS from baseline and an arbitrarily chosen dichotomous outcome both have limitations. A change in NIHSS (from baseline to 24-hour) does not account for the baseline NIHSS and its accompanying deficits. While dichotomization can simplify statistical analyses, it also comes with several major drawbacks. Dichotomization of continuous variables such as NIHSS may lead to the loss of critical clinical information and a reduction in statistical power, underestimation of the degree of variation in outcomes between groups, and a concealment of non-linearity between the variable and outcome. Given the lack of a standardized approach, it is important to identify the best early NIHSS-based outcome measure to predict the 90-day functional outcome in ischemic stroke patients.  

Time is Brain, For Some More Than Others

Elena Zapata-Arriaza, MD

Ospel JM, Hill MD, Kappelhof M, Demchuk AM, Menon BK, Mayank A, Dowlatshahi D, Frei D, Rempel JL, Baxter B, Goyal M. Which Acute Ischemic Stroke Patients Are Fast Progressors? Results From the ESCAPE Trial Control Arm. Stroke. 2021;52:1847-1850.

Time is brain; however, there are patients for whom that time runs faster. Penumbra brain tissue, due to large vessel occlusion, tends to progress to ischemia in the absence of intracranial reperfusion. However, there are a number of conditions that cause a faster progression (rapid progressors) or not, even in those who will receive endovascular treatment. To identify acute ischemic stroke patients with rapid infarct growth, Ospel and colleagues performed a post hoc analysis of the ESCAPE trial (Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke) in order to investigate baseline clinical and imaging characteristics of fast progressors stroke patients.

The authors included control arm patients if they had follow-up imaging at 2-8 hours without substantial recanalization, and if their baseline Alberta Stroke Program Early CT Score was ≥9. Fast infarct progression was defined as Alberta Stroke Program Early CT Score decay ≥3 points from baseline to 2- to 8-hour follow-up imaging.

Article Commentary: “Increased Risk of Stroke in Patients With Obsessive-Compulsive Disorder”

Burton J. Tabaac, MD

Chen M-H, Tsai S-J, Su T-P, Li C-T, Lin W-C, Chen T-J, Pan T-L, Bai Y-M. Increased Risk of Stroke in Patients With Obsessive-Compulsive Disorder: A Nationwide Longitudinal Study. Stroke. 2021.

The World Health Organization has categorized obsessive compulsive disorder (OCD) as one of the top ten disabling conditions worldwide, noting a lifetime prevalence of 1-3%. The authors of this comprehensive study cite mounting evidence supporting an association between OCD and stroke-related risk factors inclusive of obesity and diabetes. Using data collected between 2001 and 2010 by Taiwan’s National Health Insurance Research Database, it was demonstrated that patients with OCD have an elevated risk of suffering an acute ischemic stroke compared to non-OCD controls, with no difference in hazard ratio for hemorrhagic stroke.

Obsessive compulsive disorder secondary to cerebral infarction has been reported in the medical literature, yet the relationship between OCD and subsequent stroke has been minimally investigated. This study included patients aged 20 years and older diagnosed with OCD by psychiatrist expertise between January 2001 and December 2010, and who had no history of stroke prior to enrollment. In a follow up analysis (up to 11 years), the use of OCD medications was assessed, with study cohorts separated into subgroups: nonusers, short-term users (1 month to 1 year), and long-term users (more than 1 year). Medication use included SSRIs, SNRIs, and norepinephrine-dopamine reuptake inhibitors, e.g., bupropion.

Article Commentary: “Dual Antiplatelet Therapy Versus Aspirin in Patients With Stroke or Transient Ischemic Attack”

Wern Yew Ding, MBChB

Bhatia K, Jain V, Aggarwal D, Vaduganathan M, Arora S, Hussain Z, Uberoi G, Tafur A, Zhang C, Ricciardi M, Qamar A. Dual Antiplatelet Therapy Versus Aspirin in Patients With Stroke or Transient Ischemic Attack: Meta-Analysis of Randomized Controlled Trials. Stroke. 2021;52:e217–e223.

Transient ischemic attack (TIA)/cerebral vascular accident (CVA) and acute coronary syndrome share many similarities. An integral element to the management of patients with either condition includes the use of antiplatelet therapy to reduce the risk of recurrent events. In acute coronary syndrome, the administration of dual antiplatelet therapy (DAPT) has been established, while this is less certain in TIA/CVA. Recently, several trials have investigated this issue. In this meta-analysis by Bhatia and colleagues, they sought to compare the safety and efficacy of aspirin plus a P2Y12 inhibitor against aspirin alone for the prevention of recurrent stroke in patients with minor ischemic stroke or high-risk TIA.

The authors performed a thorough literature search to identify a total of 8,211 citations, of which, 4 were eventually included in this article with a total of 21,459 patients. Patients with presumed cardioembolic stroke, who received thrombolysis, were planned for endovascular therapy and had underlying indications for anticoagulation were excluded. Compared to aspirin alone, DAPT was associated with a lower risk of recurrent stroke (ischemic and hemorrhagic), major adverse cardiovascular event and recurrent ischemic event but with greater risk of major bleeding. There was no difference in the risk of hemorrhagic stroke or all-cause death between DAPT vs. aspirin alone. Overall, the authors surmised that current data supports the use of DAPT in patients with minor ischemic stroke or TIA.

Transcranial Doppler-Based Insights on Pathophysiology of COVID-19–Associated Neurological Disorders

Isabella Canavero, MD

Ziai WC, Cho S-M, Johansen MC, Ergin B, Bahouth MN. Transcranial Doppler in Acute COVID-19 Infection: Unexpected Associations. Stroke. 2021.

COVID-19 has been reported to increase the risk of ischemic stroke, especially from large vessel disease, probably due to a combination of hypercoagulability and vascular inflammation. To explore the pathophysiology of COVID-19–related neurological and especially cerebrovascular diseases, Ziai et al. analyzed TCD findings in patients with and without COVID-19 infection, some of which also suffered from acute ischemic stroke. Indeed, differently from other radiological techniques, specific practical advantages make TCD easy to perform in the critical care setting. In cerebrovascular patients, TCD allows the identification of useful information such as detection of circulating microemboli and the assessment of cerebral blood flow velocity (CBV).

Hypercoagulable Testing After Stroke

Kevin O’Connor, MD

Salehi Omran S, Hartman A, Zakai NA, Navi BB. Thrombophilia Testing After Ischemic Stroke: Why, When, and What? Stroke. 2021;52:1874-1884.

What are the indications for a thrombophilia evaluation in a patient who had an ischemic stroke? Salehi Omran et al. explore this in their topical review. They suggest that rather than obtaining thrombophilia studies in unselected patients who had an otherwise cryptogenic ischemic stroke, factors such as patient age, race, sex (i.e., pregnancy, estrogen-containing medication), presence of a patent foramen ovale (PFO), and personal or family history of thrombosis should guide testing. For example, younger patients may benefit from testing more than older patients. It is important to consider concomitant anticoagulant use, as well as the acuteness of the stroke when testing for thrombophilia. Repeat testing after 12 weeks validates positive results found in the acute setting and reduces the likelihood of false positives. Additionally, reference ranges derived from White European populations are important to consider when evaluating results from patients of different racial backgrounds.

Available studies find no association between ischemic stroke and inherited thrombophilias such as factor V Leiden (FVL) and prothrombin gene mutation (G20210A) in older adults. Fewer studies on protein C, protein S, and antithrombin deficiency in patients with ischemic stroke are available, but do not show associations between the respective deficiencies and stroke in older adults. Antiphospholipid syndrome (APLS; an acquired thrombophilia) is a risk factor for ischemic stroke, but the association is stronger in younger adults. Although studies show an association between ischemic stroke and FVL in younger adults, the association between ischemic stroke and prothrombin mutation is less evident. Studies in children who had a stroke find an association with inherited (except protein S and antithrombin deficiency) and acquired thrombophilias.