American Heart Association

Monthly Archives: December 2020

Balancing Risk-Benefit for Non-Acute Vertebral Artery Occlusion Revascularization

María Gutiérrez, MD

Gao F, Sun X, Zhang H, Ma N, Mo D, Miao Z. Endovascular Recanalization for Nonacute Intracranial Vertebral Artery Occlusion According to a New Classification. Stroke. 2020;51:3340–3343.

Large vessel occlusion of the posterior circulation has devastating effects and carries high morbidity and mortality. One of the main causes for this stroke subtype is vertebral atherosclerosis. The optimal treatment for the non-acute intracranial vertebral artery occlusion (NA-ICVAO) in patients at high risk of stroke despite the best medical treatment remains unclear. Some case-report studies showed that endovascular recanalization (ER) is feasible. However, a large heterogeneity of perioperative outcomes and a high incidence of complications makes critical to identify which patients would benefit from intervention.

In this study, the authors aimed to define an angiographic classification to explore the feasibility and safety of endovascular recanalization for symptomatic atherosclerotic NA-ICVAO that might become a reference for patient selection and risk stratification in future trials. They retrospectively analyzed 50 patients with atherosclerotic NA-ICVAO that were treated with angioplasty and stenting. Patients were divided into 4 groups according to the following angiographic classification: type I (Figure 1A), the occlusion length is ≤15 mm; type II (Figure 1B), the occlusion length is >15 mm; type III (Figure 1C and 2), the occlusion length is >15 mm, and the tortuosity angle of the occluded segment is ≥45°; and type IV (Figure 1D), the occlusion extends to the epidural segment.

Illustration of the angiographic classification of nonacute intracranial vertebral artery occlusion.
Figure 1. Illustration of the angiographic classification of nonacute intracranial vertebral artery occlusion. A, Type I, the occlusion length is ≤15 mm. B, Type II, the occlusion length is >15 mm. C, Type III, the occlusion length is >15 mm, and the tortuosity angle of the occluded segment is ≥45°. D, Type IV, the occlusion extends to the epidural segment.

The median duration of occlusion was 45 days, and the median time from last symptom onset to endovascular treatment was 15 days. The overall technical success rate was 76%. The perioperative complication rate was 16% (8/50); vascular dissection occurred in 5 cases (4 asymptomatic and 1 mild stroke). One patient died of vascular perforation. Stroke or death beyond 30 days was 10.2% (5/49), 2 patients died (one for cerebral hemorrhage and another from ischemic stroke), 1 patient experienced severe ischemic stroke, and 2 patients had mild ischemic stroke. In angiographic follow-up, 4 patients developed in-stent restenosis and 3 developed reclusions.

ELVO and COVID-19: Lessons from New York

Mei Yan Ngun, MBBS

Majidi S, Fifi JT, Ladner TR, Lara-Reyna J, Yaeger KA, Ymir B, Dangayach N, Oxley TJ, Shigematsu T, Kummer BR, et al. Emergent Large Vessel Occlusion Stroke During New York City’s COVID-19 Outbreak: Clinical Characteristics and Paraclinical Findings. Stroke. 2020;51:2656–2663.

The battle against the COVID-19 pandemic continues worldwide. As our understanding of COVID-19 evolves, so does our understanding of its neurological complications. Available evidence shows COVID-19 induces a hypercoagulable state and increases risk of thrombosis, especially in severe disease.

Early data has suggested a higher rate of ischemic stroke in severe COVID-19 infection. Majidi et al. have reported on the clinical and paraclinical findings in emergent large vessel occlusion (ELVO) stroke during New York’s COVID-19 outbreak. This retrospective observational study included data from all patients presenting with an ELVO during the peak 3-week period of hospitalizations and deaths from COVID-19. Data was collected from eight New York hospitals from March 21 to April 12, 2020. Data regarding demographics, comorbidities, risk factors, clinical presentation, treatment received, clinical outcome, and COVID-19 disease status were collected.

By |December 11th, 2020|clinical|0 Comments

Decreased Ischemic Stroke Incidence During the COVID-19 Pandemic — Fact or Fiction?

Lukas Mayer, MD

Jasne AS, Chojecka P, Maran I, Mageid R, Eldokmak M, Zhang Q, Nystrom K, Vlieks K, Askenase M, Petersen N, er al. Stroke Code Presentations, Interventions, and Outcomes Before and During the COVID-19 Pandemic. Stroke. 2020;51:2664–2673.

Due to the rapid worldwide spread of SARS-CoV-2, the World Health Organization declared COVID-19 as a public health emergency on January 30, 2020. Measures to contain the pandemic have not only halted day-to-day living, but have shifted key health and societal priorities, as the pandemic posed an unprecedented situation.

Some recent evidence suggests a decrease in ischemic stroke incidence with some European stroke centers reporting a reduction in acute stroke admissions by as much as 50-80% during the initial phase of the COVID-19 crisis. Furthermore, stroke centers in China highlighted a drop in thrombectomy rates by about 25-50% in large cities and that a majority of stroke patients did not find access to dedicated stroke units. It is important to scrutinize whether these changes are indeed true.

In the September 2020 issue of Stroke, Jasne and co-authors present important data on stroke incidence, interventions, and outcomes before and during the COVID-19 crisis. The authors recorded stroke code calls in 3 major hospitals in Connecticut during the initial peak of SARS-CoV-2 infections from January to April 2020 and compared the stroke code activity with corresponding dates of previous years. Additionally, differences in patient characteristics (i.e., demographics, clinical presentation, pre-existing conditions, socioeconomic status, age), acute stroke management (door-to-needle/door-to-reperfusion time), and outcome were assessed to identify changes during the pandemic.

By |December 10th, 2020|clinical|0 Comments

A Clogged Drain in the Neonatal Brain: Blood Product Breakdown and Hydrocephalus After Preterm Intraventricular Hemorrhage

Jeff Russ, MD, PhD

Mahaney KB, Buddhala C, Paturu M, Morales D, Limbrick Jr DD, Strahle JM. Intraventricular Hemorrhage Clearance in Human Neonatal Cerebrospinal Fluid: Associations With Hydrocephalus. Stroke. 2020;51:1712–1719.

Premature infants are already at high risk of neurodevelopmental delay from prematurity alone, but additional injury from intraventricular hemorrhage (IVH) is all too common, occurring in up to a fifth of premature infants.1 Infants with IVH clearly cannot afford further brain injury, so providers have to remain vigilant for the delayed co-morbidity of post-hemorrhagic hydrocephalus (PHH), which can occur in a quarter of those with severe IVH.2 Red blood cell breakdown and the release of hemoglobin is proinflammatory and damages the choroid plexus and periventricular white matter. The products of cellular destruction are thought to clog cerebrospinal fluid (CSF) reabsorption and lead to hydrocephalus.1

Understanding the detailed pathophysiology of PHH could help neonatal providers determine which infants are most at risk and could also suggest future therapeutic strategies. A study by Mahaney et al. in the June 2020 issue of Stroke3 sets out to shed light on the relationship between the clearance of blood products from the CSF after IVH and the development of PHH.

By |December 9th, 2020|clinical|0 Comments

Infarct Distribution Following Endovascular Therapy in Large Vessel Occlusion Stroke

Christopher Wilkins, MD

Al-Dasuqi K, Payabvash S, Torres-Flores GA, Strander SM, Nguyen CK, Peshwe KU, Kodali S, Silverman A, Malhotra A, Johnson MH, et al. Effects of Collateral Status on Infarct Distribution Following Endovascular Therapy in Large Vessel Occlusion Stroke. Stroke. 2020;51:e193–e202.

Endovascular therapy has become an invaluable tool in the treatment of acute ischemic stroke as it can provide significant improvement in the functional outcome of selected patients. Since its reception, studies have broadened the time window for endovascular therapy by using perfusion imaging during acute ischemic strokes to determine how much cerebral tissue is, or close to be, infarcted (i.e., the core) and comparing it to tissue which has reduced blood flow but is likely salvageable with reperfusion (i.e., the penumbra). The volume of the core, as well as ratio between core and penumbra, ultimately determines which patients are appropriate for endovascular therapy. Studies have shown that cerebral collateral circulation can be a major determinant of final infarct volume and can thus impact who would be deemed appropriate for thrombectomy. However, data on whether the status of collateral circulation impacts final clinical outcome in those undergoing thrombectomy remains discrepant.

In this retrospective study, Al-Dasuqi et al. investigated how collateral status impacts final infarct size, as well as functional outcomes, in those with successful and unsuccessful recanalization following endovascular therapy with either mechanical thrombectomy or intra-arterial thrombolytic drug delivery.  The authors selected patients who: had evidence of large vessel occlusion on CTA in the ICA or MCA at the M1 or proximal M2 segment; underwent mechanical thrombectomy or intraarterial thrombolysis, with or without IV-tPA before intervention; had follow up MRI obtained within 24 hours to 7 days post endovascular treatment.  The collateral status of patients was defined using a grading system designed by Miteff et al.1 There are 3 grades which include: “good,” where the entire MCA distal to the occluded segment reconstitutes with contrast; “moderate,” where some MCA branches distal to the occluded segment reconstituted in the sylvian fissure; and “poor,” where only distal superficial MCA branches reconstituted distal to the occlusion. Though many different grading systems for collateralization have been created, Al-Dasuqi et al. used the grading system by Miteff et al. because this grading system showed to be reliable in predicting favorable and poor outcomes in patients treated with IV-tPA while other collateral grading systems were of limited value. Successful recanalization was defined by mTICI score of 2b-3. A summation map of all infarct lesions detected on MRI was created to identify regions of infarct associated with mTICI scores and collateral grading. Early functional outcome was measured using the modified Rankin Scale (mRS) at discharge with a favorable outcome defined as mRS score of 0 to 2.

Author Interview: Dr. Masafumi Ihara on “Oral Carriage of Streptococcus mutans Harboring the cnm Gene Relates to an Increased Incidence of Cerebral Microbleeds”

Dr. Masafumi Ihara, left, and Dr. Saurav Das

An  interview with Dr. Masafumi Ihara, MD, PhD; Head, Department of Neurology, National Cerebral and Cardiovascular Center, Osaka, Japan.

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

They will be discussing the article “Oral Carriage of Streptococcus mutans Harboring the cnm Gene Relates to an Increased Incidence of Cerebral Microbleeds,” published in the December 2020 issue of Stroke.

Dr. Das: Dr. Ihara, on behalf of the Blogging Stroke team, it is my pleasure to welcome you to this author interview about your publication in Stroke regarding the association between CNM gene-positive Streptococcus mutans and increased incidence of cerebral microbleeds. Given Streptococcus mutans is a common pathogen associated with dental caries, it is a potential treatment target to prevent increase in cerebral microbleeds.

Many of our readers come from a stroke background and may not be as familiar with oral pathology. It will be of interest to start by discussing some common oral pathogens implicated in cerebrovascular disease. Also, what is specific about Streptococcus mutans, and particularly the ones positive for CNM gene?

Dr. Ihara: More than 500 bacterial species have been estimated to exist in the oral cavity, and many remain to be identified and characterized. Of all the known pathogenic oral bacteria, a few have been linked to cerebrovascular diseases. Our co-investigator Prof. Nakano reported that certain strains of Streptococcus mutans (S. mutans) are potential risk factors for intracerebral hemorrhage in stroke-prone spontaneously hypertensive rats and mice with photochemically induced middle cerebral artery occlusion.1 This corresponds with findings showing periodontal infections to be risk factors for stroke, and that S. mutans is detected in 100% of samples of atherosclerotic plaques. S. mutans is a major pathogen in dental caries that can cause bacteremia by dental procedures, such as tooth extraction and periodontal surgery, or even tooth brushing in daily life. S. mutans is well known to be responsible for infective endocarditis. The hemorrhage-causing S. mutans strains express collagen-binding protein Cnm on their cell surface, enabling them to attach to exposed collagen fibers on the surface of damaged blood vessels and prevent platelet activation, thereby, leading to hemorrhages. Another dental bacterium, Porphyromonas gingivalis (P. gingivalis), is also found in atherosclerotic plaques and has been linked to the increased risk of ischemic stroke. P. gingivalis adheres to and infects endothelial cells not only to increase the expression of endothelial adhesion molecules and promote monocyte/macrophage infiltration, but also to produce cysteine proteinase gingipains, which activate protease-activated receptors-1 and -4 on platelets to induce platelet aggregation. Thus, infection from P. gingivalis could cause small vessel disease pathology through thrombotic occlusion and BBB disruption through inflammation.

Article Commentary: “Tenecteplase Thrombolysis for Acute Ischemic Stroke”

Burton J. Tabaac, MD
@burtontabaac

Warach SJ, Dula AN, Milling Jr TJ. Tenecteplase Thrombolysis for Acute Ischemic Stroke. Stroke. 2020;51:3440–3451.

This topical review takes a deep dive analysis into the literature as it pertains to Tenecteplase (tNK), a type of IV thrombolysis, in the treatment of acute ischemic stroke. A qualitative synthesis of published stroke trials is presented. Most interestingly is the argument, using meta-analysis, that tNK is superior in recanalizing large vessel occlusions (LVO) compared to Alteplase (tPA). This resonates with the vascular neurology world because the original prospective studies were unable to demonstrate superiority or non-inferiority of tNK on clinical outcome. As detailed, the current body of clinical trial evidence evaluating tNK relative to tPA points in the direction of superior early recanalization in LVO and non-inferior disability-free outcome at 3 months in favor of tNK.

In regards to dosing, current clinical practice guidelines for stroke include IV tNK 0.25mg/kg recommended for LVO, based on phase 2 trial data with improved 3-month outcome relative to tPA. We have known, at least since 2012, that reperfusion and clinical outcomes with the use of tNK appear improved, and intracranial hemorrhage risk is not increased, as compared to alteplase.1 The paper cites a network meta-analysis of five randomized trials on tNK versus tPA that found better efficacy on clinical and imaging endpoints. The authors elaborate, there has been no evidence to support an advantage of the 0.4mg/kg dose relative to 0.25mg/kg in the treatment of ischemic stroke, adding, “Trials that directly compared the two doses tended to favor the 0.25mg/kg dose.” The National Institute of Neurological Disorders and Stroke Tenecteplase trial has since eliminated the 0.4mg/kg as being inferior, and EXTEND-IA-TNK (part 2) reported a higher number of symptomatic intracranial hemorrhage events in the 0.4mg/kg group relative to the 0.25mg/kg dosed patients.2 The ongoing NOR-TEST 2 trial may confirm whether there is any disadvantage of the 0.4mg/kg dose relative to standard dose tPA. Current randomized phase 3 trials are ongoing in an aim to answer the question of if tNK has decreased hemorrhagic risk, and if tNK can establish efficacy beyond the 4.5 hour time window.

ESO-WSO 2020: Prognosis After Acute Stroke Interventions

Aurora Semerano, MD
@semerano_aurora

European Stroke Organisation-World Stroke Organization 2020 Virtual Conference
November 7-9, 2020
Session: Scientific Communications 16: Prognosis After Acute Stroke Interventions

Revascularization therapies, including intravenous thrombolysis and endovascular thrombectomy, have shown to reduce mortality and disability after stroke in randomized clinical trials, as well as in the real world. However, even when the revascularization treatment is effective, a significant amount of patients experiences poor outcome. Investigating the mechanisms and the predictors of poor prognosis despite acute stroke interventions was the goal of the 8 lectures of this interesting session, chaired by Prof. Mike Charma from Canada and Prof. Else C. Sandset from Norway.

Dr. Chen Chen, from China, illustrated her work aimed at determining patient characteristics of Asian and non-Asian patients with acute ischemic stroke included in the ENCHANTED study: Compared to non-Asian patients, Asian patients were at increased risk of hemorrhagic transformation and neurologic deterioration during hospitalization after thrombolysis treatment, potentially suggesting that distinctive monitoring for complications is needed in subgroups of patients after acute stroke intervention.

ESO-WSO 2020: Vagus Nerve Stimulation Paired With Rehabilitation for Upper Limb Motor Recovery After Stroke

Kate Hayward, PhD PT
@kate_hayward_

European Stroke Organisation-World Stroke Organization 2020 Virtual Conference
November 7-9, 2020

ESO-WSO 2020 Large Clinical Trials & Awards
Presenter: Professor Jesse Dawson
Presentation title: Vagus nerve stimulation paired with rehabilitation for upper limb motor function after ischaemic stroke (VNS-Rehab): A randomised, blinded, pivotal, Phase III device trial

There is much work occurring to identify adjuvants that may boost post-stroke motor recovery — particularly upper limb recovery, which often remains an unmet need for many stroke survivors long-term. The current work focused on vagus nerve stimulation (VNS) as an adjunct to motor rehabilitation and built upon two prior pilot randomized controlled trials of this intervention.1,2 The pilot trials suggested potential for a functional benefit of VNS when combined with intensive motor rehabilitation. The mechanistic rationale put forward to underpin this intervention was that VNS activates release of neuromodulators, which may facilitate behavioral and physiological changes that support motor recovery.

In this randomised, blinded, Phase III trial,3 eligible participants had to have experienced a unilateral ischemic stroke 9 months to 10 years prior to enrolment and demonstrated a Fugl Meyer Assessment Upper Extremity (FMA-UE) score of 20 to 50 points (out of 66 points). This is consistent with moderate to moderately-severe impairment as all participants would be expected to demonstrate some movement if scoring within this range. All enrolled participants had a VNS device implanted and were randomized to receive an active or sham stimulation protocol. Of note, all participants received 5 active stimulations (varying intensities) at the commencement of each in-clinic session, which was designed to expose everyone to a very small volume of VNS and to maintain blinding. All participants received 6 weeks of in-clinic rehabilitation (3 session per week for 2 hours aiming for >300 repetitions) followed by 90 days of at home-rehabilitation (daily therapist prescribed home exercises). Follow up occurred at 1, 30, and 90 days post completion of in-clinic rehabilitation.

ESO-WSO 2020: Three Rounds of Controversies in Recovery and Brain Repair After Stroke

Aurora Semerano, MD
@semerano_aurora

European Stroke Organisation-World Stroke Organization 2020 Virtual Conference
November 7-9, 2020

The Controversies sessions during the ESO-WSO 2020 Conference are intriguing live Q&A sessions focused on grey zones in stroke care, with stroke experts defending their points of view and facing each other in interesting rounds of discussion. On the second day of the conference, the session addressed the following topics about recovery and brain repair after stroke.

Round 1:

Brain Repair is the Right Target to Improve Outcome — John Krakauer (United States of America)
Basing on primate experimental stroke, Dr. Krakauer showed that a certain rate of spontaneous recovery exists after stroke; however, training helps to amplify, rescue, and maintain spontaneous recovery. The main question remains: How does it happen? According to Dr. Krakauer, training-induced recovery in monkeys is not driven by cortical reorganization. Conversely, brain repair occurs via training-induced strengthening of pre-existing alternative cortico-subcortical connections. The recipe for brain repair after stroke is traced: an integrated interaction between behavior, residual architecture, and plasticity.

Brain Repair Does Not Work, Reorganisation is Key — Belen R. Ballester (Spain)
Dr. Ballester dismantled in 15 minutes three common pessimistic beliefs about recovery after stroke. Behavior drives functional and structural reorganization and can meaningfully interact with spontaneous recovery. For this purpose, high repetitive task-oriented and task-specific training is needed. Possibilities for recovery extend well beyond the classical time window of 3-6 month, and plasticity by means of structural and connectivity changes is still present beyond 1 year after stroke. Finally, it is not an invariable destiny of stroke patients to deteriorate in the chronic phase; learning and training can prevent deterioration.