American Heart Association


Article Commentary: “One-Year Home-Time and Mortality After Thrombolysis Compared With Nontreated Patients in a Propensity-Matched Analysis”

Jennifer Harris, MD

Yu AYX, Fang J, Kapral MK. One-Year Home-Time and Mortality After Thrombolysis Compared With Nontreated Patients in a Propensity-Matched Analysis. Stroke. 2019;50:3488–3493.

Thrombolytic therapy with intravenous recombinant tissue plasminogen activator (r-tPA) is an effective treatment in acute ischemic stroke. Several studies have examined functional outcome and mortality at 3 months after intravenous r-tPA treatment. However, data on long-term outcome are limited. Two randomized controlled stroke trials, the National Institute of Neurological Disorders and Stroke trial (NINDS) and the third International Stroke Trial (IST-3), have examined long-term mortality after intravenous r-tPA and revealed no differences in mortality rates among treated and nontreated patients at 12- and 18-months follow-up, respectively.

To explore long-term clinical outcome after intravenous r-tPA, Yu et al. conducted a nationwide register-based follow up study using a propensity score matching method. Using the Ontario Stroke Registry, they identified 29,036 patients with ischemic stroke and used propensity score methods to match the 4,449 patients treated with intravenous r-tPA to nontreated patients. The primary outcome was 1-year home-time, which was defined as the number of days spent outside of any healthcare institutions, and showed that compared with nontreated patients, those treated with intravenous r-tPA experienced a mean of 9.5 additional days at home in the first year. Now, while looking at these results from an individual patient perspective, this might seem like a rather small improvement; however, looking at the larger picture, it can mean significant cost savings for the healthcare system at large. With roughly 700,000 ischemic strokes occurring annually in the United States, and associated stroke care costs estimated at $34 billion each year, even a small increase in the rate of thrombolysis could potentially lead to reduced hospital stays and large costs savings.

Article Commentary: “Advances and Innovations in Aphasia Treatment Trials”

Burton J. Tabaac, MD

Berube S, Hillis AE. Advances and Innovations in Aphasia Treatment Trials. Stroke. 2019;50:2977–2984.

Aphasia is a disorder that results from damage to portions of the brain that are responsible for language. For most people, these areas reside in the left hemisphere of the brain. Aphasia usually occurs suddenly, often following a stroke or head injury, but it may also develop slowly, as the result of a brain tumor or a progressive neurological disease. The disorder impairs the expression and understanding of language, as well as reading and writing. Aphasia may co-occur with speech disorders, such as dysarthria or apraxia of speech, which also result from brain damage.1 This Stroke article summarizes advances in clinical trials of aphasia, secondary to stroke, and the treatment studied from clinical trials over the past 5 years. The authors discuss noninvasive brain stimulation, transcranial direct current stimulation, and transcranial magnetic stimulation, as well as pharmacological and medical interventions.

Drs. Berube and Hillis noted, “methodological weaknesses in many of the aphasia treatment studies compromise strong conclusions about efficacy.” Interestingly, the authors added, “The distribution of aphasia subtypes might influence efficacy … it is possible that individuals with Broca’s aphasia respond more to certain types of treatment, while those with Wernicke’s aphasia respond more to other types. However, none of the studies have been adequately powered to identify differential efficacy across subtypes.” Drs. Berube and Hillis concluded in their review that the most effective or efficient interventions currently available combine novel Speech-Language Therapy (SLT) with noninvasive brain stimulation (NIBS) or medications.

FLAIR-rSI is Time, and Time is Brain, so FLAIR-rSI is Brain?

Lina Palaiodimou, MD

Cheng B, Boutitie F, Nickel A, Wouters A, Cho T-H, Ebinger M, et al. Quantitative Signal Intensity in Fluid-Attenuated Inversion Recovery and Treatment Effect in the WAKE-UP Trial. Stroke. 2019.

Advanced neuroimaging has already changed the scene in acute stroke treatment, allowing patients with unknown or extended time windows to receive recanalization therapies (intravenous thrombolysis, mechanical thrombectomy). The cornerstone of this recent breakthrough is the demonstration of viable brain tissue regardless of time elapsed since stroke onset. That was also the case in the WAKE-UP trial, which proved clinical benefit in alteplase-treated acute stroke patients with unknown time of onset, but clearly presenting salvageable brain tissue, as was demonstrated by diffusion-weighted imaging (DWI) – fluid-attenuated inversion recovery (FLAIR) mismatch.   

The study by Cheng et al. presents a post-hoc analysis of the WAKE-UP trial with the aim to associate quantitatively measured relative signal intensity in FLAIR (rSI-FLAIR) with the clinical outcomes of the treated patients. The objective of this study was rationalized by previous studies, which correlated rSI-FLAIR with time elapsed since stroke onset. That correlation was linear; higher rSI-FLAIR corresponded to longer time since stroke onset and, actually, when the clock was ticking, FLAIR was glowing. Consequently, Cheng et al. moved to the next logical reasoning that, since rSI-FLAIR is associated with time and time is associated with clinical outcomes, rSI-FLAIR may relate to clinical outcomes of alteplase-treated patients. 

Glowing Stem Cells May Shine A Light on Stroke Recovery Research

Lin Kooi Ong, PhD

Yu SP, Tung JK, Wei ZZ, Chen D, Berglund K, Zhong W, et al. Optochemogenetic Stimulation of Transplanted iPS-NPCs Enhances Neuronal Repair and Functional Recovery after Ischemic Stroke. J Neurosci. 2019; 39:6571-6594.

Stem cell-based therapies certainly do hold potential as therapeutic tools for promoting brain repair and functional recovery after stroke. However, there are several fundamental issues to be considered, such as whether the transplanted stem cells can survive, differentiate and form meaningful connections with the host brain. This recent article by Yu and colleagues described an innovative method called “optochemogenetic” to promote the integration of transplanted stem cells into a stroked (or injured) brain that could lead to neuronal restoration and functional recovery. The team genetically introduced luminopsin 3 into neural progenitor cells that have been derived from induced pluripotent stem cells, which they called LMO3-iPS-NPCs. Luminopsin 3 is a bioluminescent protein that can be simulated by either a physical light source or light-emitting molecule such as coelenterazine.

By |November 19th, 2019|clinical|0 Comments

Article Commentary: “Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial”

Pamela Cheng, DO

RESTART Collaboration. Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial. Lancet. 2019;393:2613-2623.

What to do after having a spontaneous intracerebral hemorrhage while on blood thinners? Prior to RESTART, there were no published randomized controlled trials testing the safety or benefit of resuming long-term antithrombotic therapy in survivors of intracerebral hemorrhage. Previous secondary stroke prevention trials showed a favorable benefit of antithrombotic therapy, but these trials excluded patients with history of intracerebral hemorrhage. RESTART was thus initiated with the aim of establishing whether starting versus avoiding antiplatelet therapy had any effect on recurrent symptomatic intracerebral hemorrhage and whether this risk of bleeding would exceed the benefit of reduction of vascular events.

RESTART was an investigator-led, pragmatic, multi-center, prospective, randomized, open-label, blinded endpoint, parallel-group trial in 122 hospitals in the United Kingdom. Inclusion criteria were adults older than 18 years of age who had survived at least 24 hours of spontaneous intracerebral hemorrhage while on either anticoagulant or antiplatelet therapy. Exclusion criteria included hemorrhage related to trauma, hemorrhagic transformation of an ischemic stroke, intracranial hemorrhage without intracerebral hemorrhage, or if they were pregnant, breastfeeding, or of childbearing age. Intervention arm was restricted to use of either oral aspirin, dipyridamole, or clopidogrel, begun within 24 hours of randomization.

By |November 18th, 2019|clinical|0 Comments

Cerebral Venous Thrombosis: Beyond Usual Therapies

Elena Zapata-Arriaza, MD

Ferro JM, Coutinho JM, Dentali F, Kobayashi A, Alasheev A, Canhão P, et al. Safety and Efficacy of Dabigatran Etexilate vs Dose-Adjusted Warfarin in Patients With Cerebral Venous Thrombosis: A Randomized Clinical Trial. JAMA Neurol. 2019.

Cerebral venous thrombosis (CVT) survivors are exposed to an increased risk of recurrent venous thrombotic events (VTEs) in cerebral venous sinuses, limbs, and splanchnic veins, or pulmonary embolism. Current practice recommendations for preventing VTE recurrence after CVT is anticoagulation using vitamin K antagonists for variable periods. Direct non–vitamin K oral anticoagulants, like dabigatran, as an alternative to warfarin treatment, have shown increased but insufficient evidence for CVT management. In order to evaluate the efficacy and safety of dabigatran compared with dose-adjusted warfarin in the prevention of recurrent VTE and CVT, the authors performed an exploratory, multicenter PROBE design clinical trial (the RE-SPECT CVT trial).

By |November 12th, 2019|clinical|0 Comments

Blood Pressure and Non-Recanalized Large Vessel Occlusion

Parneet Grewal, MD

Jeong H-G, Kim BJ, Kim H, Jung C, Han M-K, Liebeskind DS, et al. Blood Pressure Drop and Penumbral Tissue Loss in Nonrecanalized Emergent Large Vessel Occlusion. Stroke. 2019;50:2677–2684.

Despite recent advances in acute stroke care, many patients with large vessel occlusion (LVO) are not eligible for, or remain non-recanalized after, endovascular treatment. Ischemic penumbra, which is the target of recanalization treatment strategies, is an area that stands on a fragile balance between viability of the ischemic brain tissue and cerebral perfusion, and fluctuations in blood pressure may disrupt this balance. Patients with persistent LVO can easily have regional blood flow fall below the lower limit of cerebral autoregulation in the acute phase and, hence, accumulate recurrent ischemic insults. In this retrospective analysis, the authors investigated whether increased blood pressure (BP) variability or a transient but severe drop in BP within 24 hours of onset significantly contributed to penumbral tissue loss in persistent LVO patients. They also aimed to determine whether the relationships are modified by Hypoperfusion Intensity Ratio (HIR) on baseline perfusion imaging.

This retrospective study included 80 participants with acute ischemic stroke admitted to a single center between January 2010 and March 2018 with symptomatic occlusion of middle cerebral artery or internal carotid artery in whom no intravenous or endovascular recanalization was attempted. All the participants were admitted within 24 hours of symptom onset and had National Institute of Health Stroke scale (NIHSS) ³ 4 with serial blood pressure measurements. Follow up CT or MR scans were performed on days 3-5 of admission to evaluate for hemorrhage conversion or extent of final infarct.

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

Effect of HRV on the Association Between Obstructive Sleep Apnea and Small Vessel Disease

Kristina Shkirkova, BSc

Del Brutto OH, Mera RM, Costa AF, Castillo PR. Effect of Heart Rate Variability on the Association Between the Apnea-Hypopnea Index and Cerebral Small Vessel Disease. Stroke. 2019;50:2486–2491.

Obstructive Sleep Apnea (OSA) is a form of sleep-disordered breathing that has been increasingly implicated in the pathogenesis of cerebral small vessel disease (cSVD). OSA is associated with recurrent episodes of hypoxia, altered cerebral autoregulation, and sympathetic overactivity, which may be contributing triggers for pathophysiology of cSVD. A recent study by Del Brutto et al. used nighttime Heart Rate Variability (HRV) as a measure of sympathetic upregulation to study the association between OSA and cSVD. HRV measures variation in the intervals between heartbeats and is used as a reflection of the balance between sympathetic and parasympathetic tone. Apnea-Hypopnea Index was used to access the degree of OSA and the total cSVD score was chosen to quantify cSVD burden. The study used data from the Atahualpa Project, which included elderly (age above 60) residents of the Atahualpa rural village on the coast of Ecuador. A total of 176 participants who underwent clinical assessment, magnetic resonance imaging (MRI), single-night polysomnography, and 24-hour Holter monitoring were selected for the analysis.

Among study participants, the mean age was 71.8, and 64% were women. The univariate analysis showed that daytime HRV below the 50th percentile was associated with female gender and lower mean percentage of O2 saturation. The nighttime HRV below the 50th percentile was associated with body mass index (BMI) higher than 30 kg/m2. In the generalized linear model analysis, with and without confounding variables, there was a significant association between the cSVD score and AHI (p=0.026). Furthermore, a negative association was observed between sCVD and nighttime HRV, but not daytime HRV (p=0.001). Interaction model analysis showed a significant interaction of nighttime HRV on the relationship between AHI and the cSVD score (P=0.001). The total effect between AHI and the cSVD score mediated by HRV was 30.8%. Additionally, contour plots showed the effect of nighttime HRV on the association between AHI and the cSVD score.

Anxiety Common After Stroke or TIA, Especially in the Young

Elizabeth M. Aradine, DO

Kapoor A, Si K, Yu AYX, Lanctot KL, Herrmann N, Murray BJ, et al. Younger Age and Depressive Symptoms Predict High Risk of Generalized Anxiety After Stroke and Transient Ischemic Attack. Stroke. 2019;50:2359-2363.

Poststroke anxiety is not uncommon and can negatively affect quality of life. The relationship between stroke and anxiety has been demonstrated, but few studies have included young patients. Furthermore, the presence of premorbid depression is a predictor of poststroke anxiety; however, it is unknown if the absence of depression is a protector against poststroke anxiety. The authors of this study sought to elucidate the effect of age and depression on poststroke or TIA anxiety.  

This study was conducted using registry data from the DOC Feasibility Study, a prospective longitudinal cohort of stroke, TIA, and non-stroke patients. Only those with a diagnosis of stroke or TIA were included for analysis in this study. Aphasic patients were excluded. Anxiety was assessed using the Generalized Anxiety Disorder 7-item (GAD-7) scale with a score ≥10 indicating moderate to severe symptoms. Depression was assessed using the Epidemiological Studies Depression Scale (CES-D) with ≥16 indicating moderate to severe symptoms.

257 patients were included, 125 with stroke and 133 with a TIA. 21.7% of patients had a GAD-7 score of ≥10. 25.2% had CES-D scores ≥16. Young patients (<50 years old) and those with CES-D scores ≥16 were more likely to have anxiety after a TIA or stroke. See Figure.

Figure. Frequency of high-risk anxiety and depressive symptoms in younger and older stroke patients.

Figure. Frequency of high-risk anxiety and depressive symptoms in younger and older stroke patients. Frequency of high-risk anxiety and depression symptoms includes patients with and without comorbid symptoms; frequency of high-risk anxiety+depression includes patients with comorbid symptoms.
By |November 4th, 2019|clinical|0 Comments

Collaterals Aid in Predicting Rate of Infarct Growth: Value in Transfer Decisions

Ravinder-Jeet Singh, MBBS, DM

Puhr-Westerheide D, Tiedt S, Rotkopf LT, Herzberg M, Reidler P, Fabritius MP, et al. Clinical and Imaging Parameters Associated With Hyperacute Infarction Growth in Large Vessel Occlusion Stroke. Stroke. 2019;50:2799–2804.

Infarct growth among patients with large vessel occlusion (LVO) is highly variable. In some patients, infarct progresses very quickly (rapid progressor) and they have no or small penumbra even during early hours after their stroke onset, while others progress more slowly (slow progressor) and have large penumbral tissue at later time windows. Therefore, size of pre-treatment penumbra and response to reperfusion therapies, especially endovascular thrombectomy, would vary depending on time from symptom onset and rate of infarct growth, resulting in patient-specific time-windows to intervene. While rapid progressors could benefit from reperfusion therapy during very early time-window, the slow progressors can potentially benefit from treatment in either early- or late-windows This concept has been tested in the recent early- and late-window thrombolysis and thrombectomy trials. Therefore, early distinction between rapid vs slow progressor might prove particularly useful in making time-sensitive decisions, especially interfacility transfer decisions, typically between more peripheral primary stroke centers to larger endovascular therapy capable centers.

The variability in infarct growth is determined by multiple demographic, clinical, and imaging factors, such as age, blood pressure, blood glucose, stroke severity, initial infarct size, and time from ictus; these factors can influence “final” infarct volume and determine functional outcomes. Collateral blood flow status plays an especially major role in providing residual flow, and infarct size. Whether these same factors also underlie “early” infarct growth is less well studied. In the present study, the authors investigated clinical and imaging factors associated with early (hyperacute) infarct growth.

By |November 1st, 2019|clinical|0 Comments