American Heart Association

ANS 2019 Sessions: “Injury to the Nervous System” and “Pathway to Success: Paving the Way for Translational Stroke Research”

The Annual Scientific Meeting of the Australasian Neuroscience Society
December 2–5, 2019

Lin Kooi Ong, PhD

Rebecca Hood, PhD*

The Annual Scientific Meeting of the Australasian Neuroscience Society was held December 2 to 5 in Adelaide. There were many high-quality and exciting sessions. We would like to highlight two key sessions that focused on stroke and brain injury.

The first session, “Injury to the Nervous System,” provided the audience a sample of the insights gleaned from various studies on injury to the nervous system. Dr. Shenpeng Zhang (La Trobe University) kicked off the session with a retrospective analysis of 5 years’ experimental stroke data from 716 mice to identify interrelationships between measures such as infarct volume, brain edema, functional outcomes and leukocytes.

Blood Pressure Control Improves Outcome in Spontaneous Intracerebral Hemorrhage

Ravinder-Jeet Singh, MBBS, DM

Moullaali TJ, Wang X, Martin RH, Shipes VB, Robinson TG, Chalmers J, et al. Blood pressure control and clinical outcomes in acute intracerebral haemorrhage: a preplanned pooled analysis of individual participant data. Lancet Neurol. 2019;18:857-864.

Approach to management of blood pressure during early hours after the onset of intracerebral hemorrhage (ICH) is heterogenous due to potential benefits vs. perceived risks of acute blood pressure lowering. The main rationale of acute blood pressure lowering is to reduce hematoma expansion, thereby, limiting early neurological deterioration and poor long-term outcome associated with hematoma expansion.1 Smaller hematoma expansion also leads to smaller final hematoma volume, therefore, lesser increase in absolute perihematomal edema and better outcomes.2 Conversely, acute blood pressure lowering might cause more cerebral insult by compromising perihematomal penumbra, a concept now widely debated.3 Aggressive blood pressure lowering is associated with systemic complications, especially remote ischemic cerebral lesions, which are associated with neurological deterioration4 and non-cerebral ischemia (especially cardiac ischemia and acute renal injury), worsening outcomes. Therefore, clinicians often face the questions “Where lies the right balance?” and “What’s the sweet spot of blood pressure target?” in an individual patient.

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

Article Commentary: “Stroke Incidence and Case Fatality According to Rural or Urban Residence: Results From the French Brest Stroke Registry”

Kristina Shkirkova, BSc

Grimaud O, Lachkhem Y, Gao F, Padilla C, Bertin M, Nowak E, et al. Stroke Incidence and Case Fatality According to Rural or Urban Residence: Results From the French Brest Stroke Registry. Stroke. 2019;50:2661–2667.

In this entry, I discuss a recent publication by Olivier Grimaud and colleagues regarding the stroke incidence and case fatality according to rural or urban residence. Although rural-urban disparities in stroke epidemiology research have received modest attention in recent years, localization of most stroke registries in large urban areas confounds exploration of stroke mortality as a function of urban/rural area.

There has been conflicting evidence regarding the association between stroke incidence and rural or urban residence status. Recent data in the United States suggests that rural residence location is associated with higher incidence of stroke than urban location of residence. Similarly, results from other high-income countries also report conflicting data. The authors of this study sought to examine the relationship between stroke incidence, case fatality, and residence location using the French Brest Stroke Registry.

Article Commentary: “Contributions of Stepping Intensity and Variability to Mobility in Individuals Poststroke: A Randomized Clinical Trial”

Tamaya Van Criekinge, PT

Hornby TG, Henderson CE, Plawecki A, Lucas E, Lotter J, Holthus M, et al. Contributions of Stepping Intensity and Variability to Mobility in Individuals Poststroke: A Randomized Clinical Trial. Stroke. 2019;50:2492–2499.

Recovery of gait after stroke is considered one of the most important therapy goals for both patients and therapists, to assure independency and the ability to ambulate in the community. However, over 20% of stroke survivors do not reach independent walking, which necessitates the implementation of more intensive gait rehabilitation strategies. As Hornby et al. correctly state, rehabilitation staff are often too reserved, as they are scared of potential adverse effects, such as cardiovascular events and abnormal kinematic movements strategies.

In this study, Hornby and colleagues questioned if the benefits after high-intensity training in motor recovery outweigh the possible adverse events. In total, 97 chronic stroke patients were randomized in three groups: 1) High-intensity in high variable contexts (speed-dependent and skill-dependent multiple direction treadmill training, overground training and stair climbing at 70-80% of the heart rate reserve); 2) High-intensity with minimal variability (forward stepping treadmill and overground training at 70-80% of heart rate reserve); and 3) Low-intensity in high variable contexts (similar variable contexts as group one, yet performing exercises at 30-40% of heart rate reserve). Primary walking outcomes assessed were self-selected and fasted speed, single-limb stance and step-length asymmetry at self-selected and fasted speed, and six-minute walking test at fasted speed.

Tenecteplase: Making its Way to the Guidelines

Victor J. Del Brutto, MD

Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2019

Since the National Institute of Neurological Disorders and Stroke trial results were published in 1995, recombinant tissue plasminogen activator (rtPA) alteplase has been the mainstay of thrombolytic therapy for acute ischemic stroke. Nevertheless, alteplase has a non-negligible risk of symptomatic intracranial hemorrhage, as well as limited efficacy in regards to the rate of vessel recanalization, especially in the setting of large vessel occlusion. For this reason, several studies have aimed to find an alternative thrombolytic agent with superior efficacy, safer profile, and simpler mode of administration. Tenecteplase, a genetically engineered mutant tPA, has several pharmacological advantages over alteplase, including higher fibrin specificity, less disruption of hemostasis, and longer half-life. This suggests that tenecteplase is a potentially better agent with higher rate of recanalization and lesser hemorrhagic complications. In addition, tenecteplase has a more practical way of administration (single bolus) in comparison to alteplase (bolus plus one-hour infusion).

In light of two recent large randomized controlled trials, tenecteplase has made its way into the American Heart Association guidelines. Initially, in the 2018 decree, tenecteplase debuted as a weak recommendation indicating that a 0.4 mg/kg single intravenous bolus might be considered as an alternative to alteplase in patients with minor deficits and no large vessel occlusion. The caveats of the aforementioned recommendation strictly adhered, in terms of dosing and selection criteria, to the NOR-TEST trial. This large (N=1100) phase III, randomized, open-label, double blind, superiority study compared tenecteplase to alteplase within 4.5 hours of symptoms onset using only CT for imaging selection. The authors reported no difference in functional outcome at 3 months and similar rate of hemorrhagic complications in both treatment groups. However, results were significantly affected by a high percentage of minor strokes and stroke mimics.

By |December 3rd, 2019|clinical|0 Comments

Which Medical Treatment After Ischemic Stroke and Patent Foramen Ovale? The Answer (and Questions) of a Meta-Analysis

Raffaele Ornello, MD

Sagris D, Georgiopoulos G, Perlepe K, Pateras K, Korompoki E, Makaritsis K, et al. Antithrombotic Treatment in Cryptogenic Stroke Patients With Patent Foramen Ovale: Systematic Review and Meta-Analysis. Stroke. 2019;50:3135–3140.

Patent foramen ovale (PFO) is a relevant potential cause of cryptogenic ischemic stroke, especially in young people. After a cryptogenic ischemic stroke in patients with PFO, it is unclear whether to start an antiplatelet or an anticoagulant agent.

In this article, the authors performed a systematic review and meta-analysis of randomized controlled trials to summarize the available evidence in the field and help orienting treatment. The authors found that anticoagulants were not superior to antiplatelets in the prevention of recurrent stroke in patients with cryptogenic stroke and PFO in the absence of different bleeding risk. However, the absolute effect sizes suggest a potentially larger preventive effect of anticoagulants over antiplatelets, warranting the feasibility of a large randomized controlled trial of non-vitamin K antagonist oral anticoagulants versus aspirin.

It should be noted that the trials included in the meta-analysis did not consider the effect of some clinical characteristics, such as the size of PFO and the risk of venous thrombosis and, consequently, paradoxical emboli. Before finding answers to the right medical therapy after cryptogenic stroke in the presence of PFO, we might have some further questions to ask ourselves.

By |December 2nd, 2019|clinical|0 Comments

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

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.