American Heart Association

Monthly Archives: November 2019

Collateral Adequacy as a Predictor of Eventual DWI Lesion Volume in Patients with Acute Ischemic Stroke Undergoing EVT

Piyush Ojha, MBBS, MD, DM

Yu I, Bang OY, Chung J-W, Kim Y-C, Choi E-H, Seo W-K, et al. Admission Diffusion-Weighted Imaging Lesion Volume in Patients With Large Vessel Occlusion Stroke and Alberta Stroke Program Early CT Score of ≥6 Points: Serial Computed Tomography-Magnetic Resonance Imaging Collateral Measurements. Stroke. 2019;50:3115–3120.

In patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO), infarct grows over time after arterial occlusion, the progression of which may be non-linear across individuals depending on the variations in the collateral blood flow capacity and the cerebral ischemic tolerance.

The pial collateral status, which can be assessed by conventional angiography, single-phase or multiphase CT angiography (mCTA), CT perfusion, and contrast-enhanced MRI, is a key determinant of the infarct volume and progression in patients with AIS due to LVO. In addition to a small core (ASPECTS ≥6 points on NCCT), pial collateral status can be used for guiding patient selection for EVT.

Inwu Yu et al. in this study hypothesized that the pial collateral status at the time of presentation could predict the infarct size on MRI in patients with similar degrees of early ischemic changes on CT and hence tested the association between serial changes in collateral status and infarct volume defined as DWI lesions in patients with LVO and small core. They also tested whether mCTA- and MRI-based collaterals are congruent over time during the hyperacute phase of stroke.

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

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

Jennifer Harris, MD
@JenHarrisMD

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
@burtontabaac

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
@DrLinOng

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

Investigating Stem Cell Treatment in Stroke-Associated Retinal Ischemia

Melissa Trotman-Lucas, PhD
@TrolucaM

Nguyen H, Lee JY, Sanberg PR, Napoli E, Borlongan CV. Eye Opener in Stroke: Mitochondrial Dysfunction and Stem Cell Repair in Retinal Ischemia. Stroke. 2019;50:2197–2206.

Retinal damage is a significant stroke-associated outcome, with 92% of patients suffering visual impairments during the initial recovery phase. Partial, and in some cases complete, recovery can occur; however, 20% of patients will suffer persistent or permanent visual impairment. The anatomic link between the ophthalmic artery and the middle cerebral artery is a potential factor in the reduction of retinal blood flow during middle cerebral artery occlusion (MCAO). The reduced blood flow leads to ischemic retinal damage and subsequent visual impairment. Visual disability is much less evident than other motor or speech deficits following stroke, yet can significantly affect a patient’s rehabilitation, including functional recovery and quality of life. Reduction in rapid eye movements, visual acuity and visual field defects can occur, affecting daily activities and capabilities such as reading, mobility, postural stability, spatial recognition and more. These directly affect a patient’s independence, increasing fear and disorientation, reducing confidence and leading to social withdrawal. Current therapy for stroke-associated visual impairment is neurovisual rehabilitation, involving guiding a patient to learn coping strategies to improve quality of life. Retinal ischemia also shares parallels in pathology to other ocular vascular diseases, such as diabetic retinopathy, glaucoma, retinal vein occlusion and central retinal artery occlusion. There is a need to better understand the similarities and relationship between cerebral ischemia and retinal ischemia, particularly ischemic stroke that incorporates retinal ischemic damage. The lack of current understanding may contribute to the absence of effective treatments for this prevalent post-stroke outcome.

Cerebral Venous Thrombosis: Beyond Usual Therapies

Elena Zapata-Arriaza, MD
@ElenaZaps

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

Burst of Stress Hormone is Necessary for Poststroke Survival

Lin Kooi Ong, PhD
@DrLinOng

Yang J, Kim E, Beltran C, Cho S. Corticosterone-Mediated Body Weight Loss Is an Important Catabolic Process for Poststroke Immunity and Survival. Stroke. 2019;50:2539–2546.

“Stress is bad for you, right? Well, not necessarily. The devil is in the dose, and how you perceive the stress.”1
—Dr. Lila Landowski, University of Tasmania

In response to stroke, the hypothalamic-pituitary-adrenal axis is activated and releases glucocorticoids such as cortisol. Cortisol is involved in stress responses, regulation of energy and immune reactions. Yang et al. aimed to elucidate the acute actions of corticosterone in body weight loss, immunity responses and survival after experimental stroke in mice. Corticosterone is a major catabolic steroid hormone produced from the adrenal gland in rodents (cortisol in humans). The team observed a small burst of corticosterone levels around 1 to 3 hours and decreased back to baseline around 6 hours after stroke. Further, they noted that the degree of weight loss at day 3 estimates the severity of the stroke as well as the infiltration of peripheral immune cells into the brain. As the role of corticosterone during the acute stroke phase is controversial, the team tested the concept by surgically removing the adrenal glands prior to induction of experimental stroke. All mice with intact adrenal glands survived after stroke, and only 1 out of 8 mice following adrenalectomy survived. Interestingly, treating adrenalectomy mice with corticosterone partially rescued the survival rate to 4 out of 10. Based on the findings, the authors suggested that the adrenal corticosterone-mediated catabolic process is necessary for poststroke immunity and survival.