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Article Commentary: “Mechanical Thrombectomy in Ischemic Stroke Patients With Alberta Stroke Program Early Computed Tomography Score 0–5”

Mausaminben Hathidara, MD

Kaesmacher J, Chaloulos-Iakovidis P, Panos L, Mordasini P, Michel P, Hajdu SD, et al. Mechanical Thrombectomy in Ischemic Stroke Patients With Alberta Stroke Program Early Computed Tomography Score 0–5. Stroke. 2019;50:880–888.

Mechanical thrombectomy (MT) for patients with large vessel occlusion of anterior circulation, presenting within 6 hours from symptoms onset and ASPECT score 6-10, is the standard of treatment and recommended by the American Stroke Association. However, very limited data is available regarding safety and efficacy for such treatment modalities for patients with ASPECT score 0-5. This multicenter retrospective non-randomized study analyzed MT outcome for patients with ASPECT score 0-5 at 90 days. Primary outcome of the study was favorable outcome (mRS 0-3) at 90 days and secondary outcome was mRS 0-2 at 90 days, major early neurological improvement (defined as change in NIHSS >8 points, 24 hr NIHSS<1), all-cause mortality at 90 days and symptomatic intracerebral hemorrhage (sICH). 1532 patients who had confirmed anterior circulation LVO including intracranial ICA, ICA T/L, M1, M2, tandem occlusion and ASPECT score available on either CT (910/1532) or MRI (600/1532) were included in the final analysis. TICI score and ASPECT score were determined by an independent research fellow at each site. 90 days mRS was obtained by a physician or trained certified nurse. NIHSS at admission and 24 hours was performed by a stroke neurologist.

By |September 16th, 2019|clinical|0 Comments

Stenting in the Vertebral Artery? Best Extracranial

Elena Zapata-Arriaza, MD

Markus HS, Harshfield EL, Compter A, Kuker W, Kappelle LJ, Clifton A, et al. Stenting for symptomatic vertebral artery stenosis: a preplanned pooled individual patient data analysis. Lancet Neurol. 2019;18:666-673.

Symptomatic vertebral artery stenosis is related to an increased risk of recurrent ischemic stroke. However, the superiority of endovascular treatment over the medical approach in vertebral stenosis is not supported by solid scientific evidence, so it’s difficult to determine which therapeutic option is better. Markus et al. aimed to define whether vertebral stenting is more effective than medical treatment for symptomatic vertebral stenosis, using individual patient data pooled from trials published up to now.

After reviewing randomized controlled trials comparing stenting vs medical treatment for vertebral stenosis, the authors included the VIST, VAST and SAMMPRIS trials in pooled analysis. Data from the intention-to-treat analysis were used for all studies. Primary outcome was any fatal or non-fatal stroke during follow-up. Secondary outcomes were posterior circulation stroke, any stroke or transient ischaemic attack, stroke or death, and periprocedural stroke or death, which was defined as stroke or death within 30 days of randomisation. Analyses were performed for vertebral stenosis at any location and separately for extracranial and intracranial stenoses.

By |September 13th, 2019|clinical|0 Comments

Article Commentary: “Cardiovascular Risk Scores to Predict Perioperative Stroke in Noncardiac Surgery”

Parneet Grewal, MD

Wilcox T, Smilowitz NR, Xia Y, Berger JS. Cardiovascular Risk Scores to Predict Perioperative Stroke in Noncardiac Surgery. Stroke. 2019;50:2002–2006.

Perioperative stroke has been linked to increased mortality and morbidity in patients undergoing surgical procedures. A number of cardiovascular risk assessment tools, such as Revised Cardiac Risk Index (RCRI)1, the myocardial infarction or cardiac arrest (MICA) calculator1, the American College of surgeons surgical risk calculator (ACS-SRC), and Mashour et al. risk score,2 have been published to predict perioperative complications. CHADS2 and CHA2DS2-VASc risk scores have also been shown to improve prediction of postoperative stroke in patients undergoing cardiac procedures even in absence of atrial fibrillation3. In this retrospective study, Wilcox et al. aimed to compare the effectiveness of existing cardiovascular risk stratification scores in predicting risk of perioperative stroke after non-cardiac surgery.

By |September 11th, 2019|clinical|0 Comments

Article Commentary: “Twenty-Four–Hour Reocclusion After Successful Mechanical Thrombectomy”

Wayneho Kam, MD

Marto JP, Strambo D, Hajdu SD, Eskandari A, Nannoni S, Sirimarco G, et al. Twenty-Four–Hour Reocclusion After Successful Mechanical Thrombectomy: Associated Factors and Long-Term Prognosis. Stroke. 2019

Early mechanical thrombectomy (MT) with successful recanalization leads to better outcomes following acute ischemic stroke. However, reocclusion of the treated vessel can occur in certain patients. It is important to identify those patients who are at high risk for such events so that measures can be taken to prevent potential neurological deterioration.

The study by Marto et al. published in Stroke in August 2019 sought to address this very topic. The authors examined data from the Acute Stroke Registry and Analysis of Lausanne cohort and included patients with anterior and posterior circulation strokes who were treated with MT, with resultant TICI 2B-3, and had 24-hour vascular imaging available. Reocclusion was defined as a new intracranial occlusion within an arterial segment that was recanalized at the end of MT.

By |September 10th, 2019|clinical|0 Comments

Article Commentary: “Time Trends in Race-Ethnic Differences in Do-Not-Resuscitate Orders After Stroke”

Anusha Boyanpally, MD

Bailoor K, Shafie-Khorassani F, Lank RJ, Case E, Garcia NM, Lisabeth LD, et al. Time Trends in Race-Ethnic Differences in Do-Not-Resuscitate Orders After Stroke. Stroke. 2019;50:1641–1647.

In-hospital mortality was significantly influenced by Do-not-resuscitate (DNR) orders in patients with intracerebral hemorrhage (ICH) (1). In 2007, the American Heart Association/American Stroke Association updated guidelines to avoid early DNR orders in the first 24 hours after ICH admission (2).

This is a single center study with a large minority population, which assessed calendar time trends of DNR orders after stroke from 2007 through 2016 in the ischemic stroke (IS) and intracerebral hemorrhage (ICH) patients in different race-ethnic groups.

Only the first stroke events (both IS or ICH) were included, and patients with missing DNR status were excluded. Race-ethnicity was obtained both from medical records and from interview if missing from medical records. Time to DNR was calculated as time from stroke presentation to DNR order in hours. DNR orders were considered early if documented at or before 24 hours from the admission, and late if documented > 24 hours after admission. The authors have included neurodegenerative disease, history coronary artery disease, congestive heart failure, myocardial infarction, cancer, chronic obstructive pulmonary disease, end stage renal disease, cholesterol, hypertension, history of stroke, atrial fibrillation, diabetes, insurance status, and stroke severity. The authors initially used two types of 3-way interaction: one was between stroke type, calendar year, and binary DNR timing; another one was between race-ethnicity, calendar year, and DNR timing, but was removed due to lack of significance. So, eventually calculated 2-way interactions. DNR timing (early and late) was represented as dichotomous covariates.

By |September 9th, 2019|clinical|0 Comments

Article Commentary: “Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA”

Pamela Cheng, DO

Johnston SC, Easton JD, Farrant M, Barsan W, Conwit RA, Elm JJ, et al. Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA. N Engl J Med. 2018; 379:215-225.

The CHANCE trial had previously shown that dual antiplatelet therapy reduced the risk of recurrent stroke. However, the trial was conducted in a homogenous population in China; therefore, its applicability on an international population was uncertain. Enter the POINT trial.

A total of 4881 patients were enrolled at 269 international sites. Patients had to be at least 18 years of age and randomized within 12 hours after having an acute ischemic stroke with a score of 3 or less on the NIHSS or a high-risk TIA defined as ABCD2 score of 4 or more. Isolated numbness, isolated dizziness, and isolated visual changes were all excluded. Patients were randomly assigned in a 1:1 ratio to receive either clopidogrel plus aspirin or placebo plus aspirin. Patients receiving clopidogrel were given a 600 mg loading dose on day 1, followed by 75 mg daily from day 2 to day 90. Aspirin dose was determined by treating physician but was given in doses ranging from 50 mg to 325 mg daily. The primary outcome was the risk of composite ischemic stroke, myocardial infarction, or death from ischemic vascular causes. The primary safety outcome was the risk of major hemorrhage or death from hemorrhage.

By |September 6th, 2019|clinical|0 Comments

Clot Histology: A Possible Clue to the Etiology of Ischemic Stroke

Piyush Ojha, MBBS, MD, DM

Fitzgerald S, Dai D, Wang S, Douglas A, Kadirvel R, Layton KF, et al. Platelet-Rich Emboli in Cerebral Large Vessel Occlusion Are Associated With a Large Artery Atherosclerosis Source. Stroke. 2019;50:1907–1910.

Stroke accounts for approximately 10% of all deaths worldwide and leads to substantial long-term disability. The majority of the strokes are ischemic in origin. No identifiable cause is found in up to one-third of the patients after a standard evaluation, which limits the options for secondary stroke prevention. Mechanical thrombectomy has been found to be highly effective in patients with large vessel occlusions (LVO). In addition to the revascularisation, endovascular procedures have also created a unique opportunity to identify the likely stroke pathogenesis by providing thrombus material for further study. Emerging insights on various thrombus characteristics can not only provide valuable information that might be useful for guiding acute therapies, but also in optimizing secondary stroke prevention, as different components in the clot may respond to different pharmacological strategies.

Studies have tried to correlate thrombus histological composition and stroke pathogenesis. Sporns et al.1 observed that clots from a cardioembolic source had a higher proportion of fibrin/platelets and fewer red blood cells than noncardioembolic thrombi.

NLRP3 Inflammasome as a Therapeutic Target for Ischaemic Stroke: Are We Really There Yet?

Melissa Trotman-Lucas, PhD

Lemarchand E, Barrington J, Chenery A, Haley M, Coutts G, Allen JE, et al. Extent of Ischemic Brain Injury After Thrombotic Stroke Is Independent of the NLRP3 (NACHT, LRR and PYD Domains-Containing Protein 3) Inflammasome. Stroke. 2019;50:1232-1239.

Inflammation plays a key role in the fight against infection. However, following ischaemic brain injury, inflammation can play a very different role, exacerbating the severity of damage. Inflammation results in long lasting, ongoing damage from the onset of vessel blockage through to and during reperfusion of the ischaemic brain area. One possible player within the inflammation related post-stroke damage is the NLR family pyrin domain containing 3 (NLRP3) inflammasome. During ischaemic brain injury, NLRP3 senses multiple stroke-induced stimuli leading to the recruitment of the adaptor protein ASC (the apoptosis-associated speck-like pro-caspase-1) resulting in caspase 1 production leading to downstream IL-1β and IL-18 production and release. IL-1β is well-reported to have significant pro-inflammatory and pro-apoptotic effects during acute ischaemic stroke.   

A recent study by Lemarchand et al., published in Stroke, sought to determine the importance of NLRP3 to the damage occurring following ischaemic brain damage. Previous studies have reported associations between NLRP3 and an increase in the severity of ischaemic brain injury, leading to the suggestion that targeting NLRP3 could be a potential therapeutic avenue. These previous studies report NLRP3 inhibition to be protective during ischaemia, alongside data showing that mice deficient in NLRP3 show decreased damage when compared to WT counterparts. However, contrary to this, the group responsible for the paper discussed here have previously reported that ischaemic brain injury develops independent of the NLRP3 inflammasome in a rodent model of stroke, suggesting instead that the NLRC4 (NLR family, CARD containing 4) and AIM2 (absent in melanoma 2) inflammasomes contribute to the resulting brain injury, independent of NLRP3. Lemarchand et al. sought to categorically determine the role of NLRP3 in ischaemic stroke damage, using genetic and pharmacological inhibition of NLRP3. Furthermore, to increase the robustness of the data, the group utilized the FeCl3 (ferric chloride induced thrombosis) model of preclinical ischaemic stroke, where FeCl3 soaked strips are applied to the middle cerebral artery causing localized and immediate thrombus formation, a model that may have considerable clinical relevance.   

Narrowing the ESUS Concept: Left Atrial Volume Index as Indicator of Left Atrial Enlargement and its Relationship with Presence of AF in Stroke Patients

Reyes de Torres Chacon, MD

Jordan K, Yaghi S, Poppas A, Chang AD, Mac Grory B, Cutting S, et al. Left Atrial Volume Index Is Associated With Cardioembolic Stroke and Atrial Fibrillation Detection After Embolic Stroke of Undetermined Source. Stroke. 2019;50:1997–2001.

The concept of ESUS is still a broad field of study that includes multiple etiologies, including hidden atrial fibrillation (AF), among many others. The latest published studies of secondary prevention in patients with ESUS (NAVIGATE-ESUS, RESPECT-ESUS) have not demonstrated superiority of anticoagulation versus aspirin, probably due, among other reasons, to the etiological heterogeneity of the ESUS concept. The latest studies, still in development, such as ARCADIA or ATTICUS, seek to refine and reformulate the concept of ESUS using biomarkers of atrial pathology such as morphological (left atrial enlargement) or electrical changes (atrial high rate episodes, increased P-wave terminal force in V1 on ECG) as indicators of hidden atrial fibrillation in patients with ESUS.

Jordan et al. show that left atrial enlargement measured as left atrial volume indexed (LAVI) is a good biomarker of the presence of atrial fibrillation in stroke patients. The LAVI of 1020 patients admitted to their hospital after an ischemic stroke are prospectively analyzed and correlated with the etiological subtype, divided into three categories: cardioembolic stroke (CES), non-cardioembolic stroke (NCE), and ESUS. In addition, in the ESUS subtype, prolonged cardiac monitoring was performed in 24% of them, with a hidden AF detection rate of 18.2%.

By |August 27th, 2019|clinical|0 Comments

Is Triple Antithrombotic Therapy History?

Victor J. Del Brutto, MD

Knijnik L, Rivera M, Blumer V, Cardoso R, Fernandes A, Fernandes G, et al. Prevention of Stroke in Atrial Fibrillation After Coronary Stenting: Systematic Review and Network Meta-Analysis. Stroke. 2019;50:2125–2132

Approximately one-fourth of patients with atrial fibrillation (AF) have coronary artery disease (CAD), and a significant number of them undergo percutaneous coronary intervention (PCI) and stent placement. This clinical scenario represents a special circumstance in which a combined antithrombotic regimen with platelet anti-aggregation (to prevent stent thrombosis and myocardial ischemia) and anticoagulation (to prevent AF-related cardioembolic stroke) is warranted. Previously, in the absence of randomized controlled trials, guidelines supported the use of a Vitamin K antagonist (VKA) and dual antiplatelet (DAPT), especially when drug eluting stents were used. This regimen known as “triple therapy” has shown to have a fourfold risk of bleeding complications when compared to oral anticoagulation alone.