American Heart Association

Monthly Archives: February 2021

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

Sishir Mannava, MD

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

The goal for neurologists is ultimately to find ways to treat all stroke patients to some extent such that these patients are able to suffer less significant disability and have an opportunity to lead a full life. Patients who present with markers of early ischemic changes on initial CT brain often are unable to receive acute therapies if they present outside the 4.5-hour window for IV-tPA, or have a low ASPECTS score.

In an attempt to demonstrate benefit of acute endovascular reperfusion therapy in patients presenting with ASPECTS 0-5, Kaesmacher et al. studied the value of mechanical thrombectomy with SOLITAIRE FR device on functional outcomes, mortality, and symptomatic intracranial hemorrhage (sICH). Among patients included in the BEYOND-SWIFT registry, 237 patients had ASPECTS 0-5 and were included in the analysis. Patients presented with severe neurological deficits (median NIHSS 18), and successful reperfusion (TICI 2b or greater) was achieved in 69.9%. Patients who achieved successful reperfusion had significantly superior outcome than the patients who did not achieve successful reperfusion in all outcome variables. However, favorable outcome was defined as mRS 0-3 which is a deviation from traditional definitions of favorable outcome as mRS 0-2. This outcome was more often observed in those selected by MRI DWI-ASPECTS than patients selected by CT. When comparing those with low ASPECTS 0-5 to those with more favorable ASPECTS 6-10, the low ASPECTS patients had significantly lower rates of favorable outcome (mRS score, 0–3; 40.1% versus 61.2%; P<0.001) and a doubled mortality (40.9% versus 21.2%; P<0.001). Rates of symptomatic ICH were comparable between the two groups.

By |February 26th, 2021|clinical|0 Comments

Article Commentary: “Association Between the Onset Pattern of Adult Moyamoya Disease and Risk Factors for Stroke”

Francesca Tinelli, MSc

Hirano Y, Miyawaki S, Imai H, Hongo H, Ohara K, Dofuku S, Teranishi Y, Nakatomi H, Saito N. Association Between the Onset Pattern of Adult Moyamoya Disease and Risk Factors for Stroke. Stroke. 2020;51:3124–3128.

Moyamoya angiopathy (MA) is a rare cerebrovascular disease characterized by chronic and progressive stenosis of the terminal part of the internal carotid arteries, associated with the compensatory development of an unstable vascular network (MA vessels).

Despite MA pathogenesis being unknown, an increasing number of studies propose alterations in angiogenesis and vasculogenesis as potential disease mechanisms. Moreover, the strong association with variants of Ring Finger Protein 213 (RNF213) gene in East Asian patients strengthens the role of genetic factors in MA pathogenesis.

By |February 25th, 2021|clinical|0 Comments

Monogenic Causes of Cerebral Small Vessel Disease Reveal Themselves Beyond the Brain

Aurora Semerano, MD

Rannikmäe K, Henshall DE, Thrippleton S, Ginj Kong Q, Chong M, Grami N, Kuan I, Wilkinson T, Wilson B, Wilson K. Beyond the Brain: Systematic Review of Extracerebral Phenotypes Associated With Monogenic Cerebral Small Vessel Disease. Stroke. 2020;51:3007–3017.

Significant progress has been recently achieved in the field of cerebral small vessel disease (cSVD), and increasing efforts are ongoing to shed light on the underlying pathogenetic mechanisms. Whereas the vast majority of cases are multifactorial, a number of monogenic disorders with cSVD as dominant phenotype have been recognized, demonstrating that different molecular defects can ultimately result in similar brain involvement. A deeper knowledge of monogenic cSVD, and the identification of some unifying pathways, may also help in the comprehension of sporadic cSVD.

Since genes involved in cSVD are frequently expressed more broadly than in the brain, extracerebral manifestations are not surprising. The recent paper presented here by Rannikmäe et al. illustrates the results of a systematic literature review, aimed at summarizing the spectrum of extracerebral phenotypes of individuals with a pathogenic variant in a monogenic cSVD gene. Genes which have been taken into consideration are COL4A1, COL4A2, TREX1, HTRA1, ADA2, and CTSA. Information about extracerebral manifestations, as well as demographics, clinical characteristics, and stroke details, has been collected from any publication in literature reporting at least one patient carrying a pathogenic variant of the above-mentioned genes.

By |February 24th, 2021|clinical|0 Comments

Antiplatelets for Transient Ischemic Attack and Minor Stroke: This is the Way Forward


Xiong Y, Bath PM. Antiplatelet Therapy for Transient Ischemic Attack and Minor Stroke. Stroke. 2020;51:3472–3474.

Another landmark has been reached to inform the early management of transient ischemic attack (TIA) and minor stroke. If you have not heard already, the THALES (Acute STroke or Transient IscHaemic Attack Treated With TicAgreLor and ASA for PrEvention of Stroke and Death) trial has recently hit the stroke scene. THALES was an international randomized controlled trial that found that early dual antiplatelet therapy (DAPT) for TIA and minor stroke (aspirin + ticagrelor) was superior to aspirin alone in the prevention of recurrent stroke or death.

Xiong and Bath pave the way forward in their recent review article in this field. The authors have pointed out three important points that have not remained answered, and therefore, directions for future research. First, exclusion of patients eligible for reperfusion therapy makes these findings less generalizable to this subgroup. Second, the optimal duration of aspirin + ticagrelor has not yet been established, and more information is required regarding bleeding rates as a function of time. Third, using aspirin as a control arm may no longer be the most relevant comparator, and aspirin + ticagrelor and aspirin + clopidogrel are yet to be compared.

By |February 23rd, 2021|clinical|0 Comments

Endovascular Treatment in Ischemic Stroke: The Controversy About the Relevance of the Image-Defined Infarct Core

Tolga D. Dittrich, MD

Goyal M, Ospel JM, Menon B, Almekhlafi M, Jayaraman M, Fiehler J, Psychogios M, Chapot R, van der Lugt A, Liu J, et al. Challenging the Ischemic Core Concept in Acute Ischemic Stroke Imaging. Stroke. 2020;51:3147–3155.

Endovascular treatment (EVT) is a fundamental component of acute therapy for ischemic stroke due to large vessel occlusion. Although the clinical decision for or against EVT is individual and multifactorial, it is mainly based on radiological parameters, especially the ischemic core’s visualization on neuroimaging. In their review, Goyal et al. address the practical difficulties in attributing image-defined core significance to EVT.

Clinically, the term “core” is commonly used as a synonym for infarcted brain tissue that can no longer be saved. However, the concept of a homogeneous infarction core is increasingly being challenged. The reality seems to be much more complicated, since the susceptibility of different cell and tissue types is variable, and, depending on the speed of reperfusion, there may be no, partial, or complete necrosis of the core area.

In-Hospital Delays Reduce Likelihood of Successful Reperfusion

Ammad Mahmood, MBChB

Kaesmacher J, Maamari B, Meinel TR, Piechowiak EI, Mosimann PJ, Mordasini P, Goeldlin M, Arnold M, Dobrocky T, Boeckh-Behrens T, et al. Effect of Pre- and In-Hospital Delay on Reperfusion in Acute Ischemic Stroke Mechanical Thrombectomy. Stroke. 2020;51:2934–2942.

Following the onset of vessel occlusion, the progressive detriment in the effectiveness of therapy is known and the mantra of “time is brain” is imbedded in the delivery of stroke pathways. Reducing door-to-needle, admission-to-groin (ATG), and symptom-to-admission (STA) times requires robust public health messaging, efficient pre-hospital care, and streamlined inpatient pathways. Analysis of the HERMES data suggested that prolonged ATG times were associated with reduced chances of achieving reperfusion. However, symptom-onset-to-groin (STG) times were not found to have a significant effect on reperfusion, though this was attributed to strict inclusion criteria for the HERMES trials.

In this study, real-world data from the BEYOND-SWIFT registry studied the effect of ATG, STA and STG on the likelihood of reperfusion in 2386 patients, of whom 2008 (84%) had successful reperfusion (TICI 2b-3). There was a small reduction in chance of successful reperfusion with increasing STA (aOR 0.97 [0.94–0.99] per hour). There was a stronger relationship between increasing ATG with reduced chance of successful reperfusion, aOR, 0.87 [0.79–0.96] per hour, meaning a 13% reduced chance of successful reperfusion with each hour of increase in ATG time. STG time was also significantly related, but this effect was attributed to the ATG time period.

By |February 22nd, 2021|clinical|0 Comments

Author Interview: Dr. Rajat Dhar on “Automated Quantification of Reduced Sulcal Volume Identifies Early Brain Injury After Aneurysmal Subarachnoid Hemorrhage”

Dr. Rajat Dhar, left, and Dr. Saurav Das
Dr. Rajat Dhar, left, and Dr. Saurav Das

A conversation with Dr. Rajat Dhar, MD, Associate Professor of Neurology and Neuro-critical care, Washington University School of Medicine, St. Louis, MO.

Interviewed by Dr. Saurav Das, MD, Fellow in Vascular Neurology, Washington University School of Medicine, St. Louis, MO.

They will be discussing the article “Automated Quantification of Reduced Sulcal Volume Identifies Early Brain Injury After Aneurysmal Subarachnoid Hemorrhage,” published in Stroke.

Dr. Das: Dr. Dhar, on behalf of the Blogging Stroke team, we welcome you to this author interview.  I read with great interest your paper pertaining to the automated estimation of selective sulcal volume (SSV) to quantify global cerebral edema (GCE) from early brain injury (EBI) in aneurysmal subarachnoid hemorrhage (aSAH). This is an important paper as our understanding of clinical outcomes following aSAH is shifting from vasospasm induced delayed cerebral ischemia (DCI) towards GCE from EBI. Also, we currently do not have the tools to measure GCE accurately.

This research uses a “deep learning-based approach” for the analysis of serial CT scans to measure SSV. Many of our readers may not be familiar with the use of artificial intelligence (AI) in image analysis. I will begin by requesting you to explain what deep learning is.

Dr. Dhar: Applications of artificial intelligence, specifically machine learning, to the realm of biomedical image analysis have been growing exponentially over the past few years. AI is well-suited to image analysis because, at its core, machine learning seeks to find patterns in data, and images are just patterns of intensity and location data. Machine learning algorithms can be trained to learn from labeled data. For example, to determine what regions of a scan represent blood vs. brain vs. CSF is called a segmentation task. We can use machine learning to perform a segmentation task on new imaging data. AI algorithms can perform image analysis in a fast and reproducible way, eliminating the need for time-intensive human input. They can measure volumes of similar brain structures over serial time points more objectively and accurately than one or more humans may be able to.

Considering Mechanical Thrombectomy in Pediatric Acute Ischemic Stroke

Kevin O’Connor, MD

Sun LR, Harrar D, Drocton G, Castillo-Pinto C, Felling R, Carpenter JL, Wernovsky G, McDougall CG, Gailloud P, Pearl MS. Mechanical Thrombectomy for Acute Ischemic Stroke: Considerations in Children. Stroke. 2020;51:3174–3181.

Although there are no evidence-based guidelines for the use of mechanical thrombectomy (MT) in children with acute ischemic stroke, trials in adult and limited pediatric studies currently guide decision making. Several unique aspects of the pediatric stroke population warrant attention when considering MT.

There is no randomized controlled trial (RCT) comparing intravenous tPA plus MT to MT alone in children. Additionally, dosing for IV tPA in children is based on adult data and the Thrombolysis in Pediatric Stroke (TIPS) study, which was stopped before the needed number of patients was enrolled due to slow recruitment. Various analyses of data from adults shows no significant difference between MT alone and IV tPA plus MT, although one meta-analysis found a tendency toward lower modified Rankin Scale scores (0-2) at 90 days with IV tPA plus MT. Administration of IV tPA to children prior to MT can be considered if they are otherwise candidates for a thrombolytic.

By |February 19th, 2021|clinical|0 Comments

Personalizing ESUS: Using DNA Content of Thrombi to Identify Cardioembolic Stroke

Melanie R. F. Greenway, MD

Di Meglio L, Desilles J-P, Solonomenjanahary M, Labreuche J, Ollivier V, Dupont S, Deschildre C, Maacha MB, Consoli A, Lapergue B, et al. DNA Content in Ischemic Stroke Thrombi Can Help Identify Cardioembolic Strokes Among Strokes of Undetermined Cause. Stroke. 2020;51:2810–2816.

With cryptogenic stroke comprising 20-30% of all ischemic stroke, many researchers are investigating a variety of methods to de-mystify cryptogenic stroke. In this article, potential biomarkers of the clot retrieved from mechanical thrombectomy were compared to the known stroke cause to evaluate potential clot characteristics that may predict stroke cause.

Glycoprotein VI (GPVI), heme, and DNA content were used to evaluate platelet, red blood cell, and leukocyte content of a random sample of 250 thrombi from 1209 consecutive acute ischemic stroke patients who underwent mechanical thrombectomy. 

The thrombus specimens were grinded through a tissue lyser, and thrombus homogenates were recovered after centrifugation. RBC content was estimated using heme concentration. GPVI levels were used to estimate platelet concentration. DNA content was quantified as an estimation of leukocyte count.

Would a Longer Life Expectancy Be a Negative Prognostic Factor?

Isabella Canavero, MD

Fukuda-Doi M, Yamamoto H, Koga M, Palesch YY, Durkalski-Mauldin VL, Qureshi AI, Yoshimura S, Okazaki S, Miwa K, Okada Y, et al. Sex Differences in Blood Pressure–Lowering Therapy and Outcomes Following Intracerebral Hemorrhage: Results From ATACH-2. Stroke. 2020;51:2282–2286.

Previous data from large stroke cohorts highlighted a globally poorer functional outcome for women than men, although in terms of the major rough outcome measures (mortality, disability, recurrences), no relevant disparities were observed. In fact, the perceived quality of life and the frequent occurrence of post stroke depression seemed to play a major role in determining women’s disadvantage.

Fukuda-Doi et al. further explored sex differences in affecting post ICH outcome, and the response to BP-lowering therapy, by evaluating data from the Antihypertensive Treatment in Intracerebral Hemorrhage-2 (ATACH-2) trial (comparing standard versus intensive BP-lowering strategies). Demographics pointed out heterogeneity between men and women, whom were older and more frequently on antihypertensive before onset. Of note, women more frequently suffered from lobar ICH, while hematoma expansion and perihematomal edema were less common than in men. At 3 month-follow up, women had higher death and disability rate than men, being sex independently associated after multivariate adjustment. The worse outcome despite the favorably lower rate of hematoma expansion and perihematomal edema suggested, again, the existence of additional underlying mechanisms, pointing to psychological, social, and environmental, rather than pathophysiological, factors.

By |February 17th, 2021|clinical|0 Comments