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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.

Article Commentary: “Repeated Mechanical Endovascular Thrombectomy for Recurrent Large Vessel Occlusion”

Sishir Mannava, MD

Mohamed GA, Aboul Nour H, Nogueira RG, Mohammaden MH, Haussen DC, Al-Bayati AR, Nguyen TN, AbdalkaderM, Kaliaev A, Ma A, et al. Repeated Mechanical Endovascular Thrombectomy for Recurrent Large Vessel Occlusion: A Multicenter Experience. Stroke. 2021.

In this article, Mohamed et al. report on the outcome of repeat mechanical thrombectomy (rMT) for patients who have recurrent LVO in a multicenter retrospective cohort study involving 6 tertiary institutions in the United States over a period of four years. The study collected patients who had MT via various interventional approaches, (e.g., aspiration catheters, stent retriever devices, stents, angioplasty balloons, or combinations thereof) depending on each participating hospital’s protocols. Out of their large cohort of 3,059 patients who underwent MT, 56 patients (1.8%) had at least one rMT. Fifty patients (93%) had one rMT, three (6%) underwent two rMT procedures, and one (2%) had rMT performed three times. Of these patients, 54 of 56 patients (96%) were analyzed. Of note, the interval between index MT (iMT) and rMT was 2 days, and 35 patients (65%) had recurrent LVO (rLVO) during the index hospitalization.

A final modified Thrombolysis in Cerebral Infarction (mTICI) recanalization score of 2b or 3 was achieved in all 54 patients during iMT (100%) and in 51 of 54 patients (94%) of those patients who underwent rMT, mostly with the combination of stent retrieval and aspiration. Mechanism of stroke in rLVO was cardioembolism in 30 patients (56%), intracranial atherosclerosis in four patients (7%), extracranial atherosclerosis in two patients (4%), and other causes in 18 patients (33%).

The COVID-19 Strokes

Juan Carlos Martinez Gutierrez, MD

Shahjouei S, Tsivgoulis G, Farahmand G, Koza E, Mowla A, Vafaei Sadr A, Kia A, Vaghefi Far A, Mondello S, Cernigliaro A, et al. SARS-CoV-2 and Stroke Characteristics: A Report From the Multinational COVID-19 Stroke Study Group. Stroke. 2021;52:e117-e130.

A large 32-country multinational group published an observational study of ischemic and hemorrhagic stroke characteristics in patients with coexisting SARS-CoV-2.

There was a total of 432 patients with ischemic strokes (75%), hemorrhagic strokes (21%) and venous thrombosis (4%). A surprising 38% of patients has asymptomatic infection on admission, 24% were less than 55 years old, and 24% had no vascular risk factors supporting concerns of COVID-19 induced thrombotic/hemorrhagic complications.

When to Call It Quits: Number of EVT Passes is Associated With Increased ICH Risk

Lauren Peruski, DO

Maros ME, Brekenfeld C, Broocks G, Leischner H, McDonough R, Deb-Chatterji M, Alegiani A, Thomalla G, Fiehler J, Flottmann F, for the GSR Investigators. Number of Retrieval Attempts Rather Than Procedure Time Is Associated With Risk of Symptomatic Intracranial Hemorrhage. Stroke. 2021;52:1580–1588.

Endovascular therapies used to treat acute ischemic stroke are becoming increasingly common and effective. As more of these procedures are being conducted, we are becoming aware of the potential risks and complications associated with such treatments. Established adverse events include vessel dissection and/or perforation, cerebral vasospasm, clot migration with distal ischemia, and symptomatic intracerebral hemorrhage (sICH), among others. Of these, sICH in particular has been associated with poor outcomes and high mortality rates. Prior studies have concluded that >3 device passes correlates to increased sICH risk; however, procedure time was not properly adjusted for. Therefore, the data previously presented was confounded by time. This study was designed around the hypothesis that the number of retrieval attempts is positively associated with sICH regardless of procedure time.

The cohort described in this paper was collected from the German Stroke Registry – Endovascular Treatment (GSR-ET); this registry was created between 2015 and 2018. The adult patients included were required to have undergone endovascular therapy to treat an acute ischemic stroke caused by a large vessel occlusion of the anterior circulation. Those selected needed to have pre-specified data points within their chart (for example, Alberta Stroke Program Early CT Score, NIH Stroke Scale, Thrombolysis in Cerebral Infarction [TICI] score, 90-day Modified Rankin Scale [mRS], etc.). Patients were not included if they had an occlusion of the extracranial internal carotid artery (ICA), or an ICA occlusion proximal to the carotid terminus. Patients were also excluded if they required stent placement at the time of endovascular therapy, or if they experienced spontaneous recanalization at the time of angiography.