American Heart Association

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ISC 2021 Session: Treatment of Acute Stroke in Childhood and Young Adults (Debate)

Sishir Mannava, MD
@sishmannMD

International Stroke Conference 2021
March 17–19, 2021
Session: Treatment of Acute Stroke in Childhood and Young Adults (Debate) (179, On Demand)

This session began with Dr. Lisa Sun from Johns Hopkins School of Medicine presenting on brain attacks in teenagers, and that “we can best care for adolescents with stroke by organizing existing adult stroke centers to be able to treat teenagers.” Dr. Sun discussed how adult stroke centers and dedicated stroke units have better outcomes with organized stroke teams and stroke protocols. This leads to faster stroke recognition and treatment times. Dr. Sun presented data from time to imaging/diagnosis in major pediatric stroke centers after stroke protocol initiation, and, at best, the times appear to be between 1.3-1.6 hours, which is slower than the DTN times median of about 1 hour in adult stroke programs. Although primary pediatric stroke center development has been proven by the TIPS trial, Dr. Sun argued that it may not be feasible or resourceful to develop the needed amount of pediatric stroke centers to provide adequate coverage to all pediatric stroke populations.

“Endovascular therapy can be more safely and effectively administered to adolescents at an adult stroke center.” Dr. Sun discussed how thrombectomy in adolescents is technically like adult thrombectomy, and that by 5 years of age, head and neck arteries approach adult size. The common femoral artery (FA) sheaths used in adults can even be used in smaller adolescents as long as the ratio of FA size to catheter size is maintained, to avoid vasospasm. Adult stroke centers also have greater procedural experience, larger stock of devices, and higher volume of thrombectomies than pediatric thrombectomy centers. Data from the TRACK registry showed a significant difference in mRS ≥ 2 and final mTICI ≥2c-3 amongst higher volume centers as opposed to lower volume centers.

By |March 26th, 2021|clinical, Conference, treatment|Comments Off on ISC 2021 Session: Treatment of Acute Stroke in Childhood and Young Adults (Debate)

ISC 2021 Session: Tenecteplase Is Ready for Clinical Practice (Debate)

Saurav Das, MD
@sauravmed

International Stroke Conference 2021
March 17–19, 2021
Session: Tenecteplase Is Ready for Clinical Practice (Debate) (183)

Whether tenecteplase (TNK) is ready for clinical practice is certainly one of the crucial questions faced by the stroke community today, especially in the changing landscape with emerging evidence for non-inferiority of direct thrombectomy compared to bridging recanalization treatment, the success of mobile stroke units (MSU), and our ability for pre-hospital treatment of patients within the golden hour of last known well. TNK is not a new drug. It is successfully used in treatment of myocardial infarction, and we have evidence from five randomized controlled trials (alluded to several times in the following debate) for non-inferiority compared to alteplase (tPA) in treatment of stroke. The nay-sayers do point to inherent issues with these trials and argue that we need more data. But the question is, how much longer is this wait going to be?

This debate was in 5 segments. In the first segment, Dr. Jeffrey Saver from the University of California, Los Angeles (UCLA) argued in favor of the motion. In the second segment, Dr. Patrick Lyden from Keck School of Medicine, University of South California, argued against the motion. In the third segment, both the speakers had an opportunity for rebuttal. In the fourth segment, Dr. Shelagh Coutts from the University of Calgary provided her balancing view. And in the final segment, Dr. Steven Warach from Dell School of Medicine, UT Austin, shared his practical experience with use of TNK for the past 15 months. The session was moderated by Dr. E. Clarke Haley Jr. from the University of Virginia, Charlottesville.

By |March 22nd, 2021|clinical, Conference, treatment|Comments Off on ISC 2021 Session: Tenecteplase Is Ready for Clinical Practice (Debate)

ISC 2021 Session: Challenging EVT Decision Making: When, Where, and Who to Treat (Debate)

Robert W. Regenhardt, MD, PhD
@rwregen

International Stroke Conference 2021
March 17–19, 2021
Session: Challenging EVT Decision Making: When, Where, and Who to Treat (Debate) (33, On Demand)

The session “Challenging EVT Decision Making: When, Where, and Who to Treat” (Debate) highlights some of the most difficult management decisions regarding EVT.

Dr. Sandra Narayanan built the case “Low NIHSS proximal occlusions should undergo thrombectomy.” She started by reviewing the magnitude of the question. An LVO is present in 18% of patients with NIHSS 0-4 and 39% of those with NIHSS 5-8. Furthermore, 15% of LVO stroke patients have minor symptoms. Deterioration can happen in early or delayed fashion; about 40% deteriorate early. Current guidelines suggest that treating patients with low NIHSS is reasonable. Indeed, several studies show a benefit. The Grady experience (JNIS 2017; 9:917-921) described 32 patients with NIHSS<6. Analyses of this cohort, while small, suggested a benefit of EVT. 22 were treated with medical management, of which 9 declined requiring EVT. The median time from arrival to deterioration was 5.2 hours. Subsequently, a larger study of 6 CSCs (Stroke 2018;49: 2391-2397) described 300 patients with NIHSS<6; 11.3% of those treated with medical management later declined. At 90 days, mRS 0-2 was observed in 84% of those treated with EVT, 70% of those with medical management, and 55% of those who underwent rescue EVT. Those who are allowed to deteriorate tend to have worse outcomes. The risks versus benefits should be carefully weighed up front because waiting more than 3 hours appears to impact outcomes. There is growing data that patients at risk for decline can be selected by collaterals, orthostatic challenges, perfusion imaging, and NIHSS eloquence/disability. Three randomized controlled trials are forthcoming: ENDOLOW, IN EXTREMIS, and TEMPO 2.

By |March 22nd, 2021|clinical, Conference, treatment|Comments Off on ISC 2021 Session: Challenging EVT Decision Making: When, Where, and Who to Treat (Debate)

ISC 2021 Session: Mismatch Misalignments for Extended-window IV-thrombolysis for Non-Large Vessel Occlusion Strokes (Debate)

Yasmin Aziz, MD

International Stroke Conference 2021
March 17–19, 2021
Session: Mismatch Misalignments for Extended-window IV-thrombolysis for Non-Large Vessel Occlusion Strokes (Debate)
Moderator: Dr. Gotz Thomalla

Can thrombolytics be given safely and efficaciously beyond 4.5 hours? That was the debate topic for one of ISC’s first live debates to kick off Wednesday morning. 

Dr. Shlee Song: DWI-FLAIR Mismatch Rules!

The arguments began with Dr. Song, who focused on DWI-FLAIR mismatch. After a brief introduction with the MR WITNESS trial results, she then discussed how patients with DWI-FLAIR mismatch treated with alteplase had better outcomes at 90 days in the WAKE UP study. She also made the point that while efficient MRI scanning of acute stroke patients can be cumbersome, in addition to treating more patients, we can also avoid potential side effects of treating with conventional CT/CTA methods (i.e., contrast nephropathy and ICH in the event of unseen microhemorrhages only visible on MR).

By |March 20th, 2021|clinical, Conference, treatment|Comments Off on ISC 2021 Session: Mismatch Misalignments for Extended-window IV-thrombolysis for Non-Large Vessel Occlusion Strokes (Debate)

Low-Dose Intravenous Alteplase in Stroke with Unknown Time Onset

Sohei Yoshimura, MD, PhD

Koga M, Yamamoto H, Inoue M, Asakura K, Aoki J, Hamasaki T, Kanzawa T, Kondo R, Ohtaki M, Itabashi R, et al. Thrombolysis With Alteplase at 0.6 mg/kg for Stroke With Unknown Time of Onset: A Randomized Controlled Trial. Stroke. 2020;51:1530–1538.

The guidelines of the American Heart Association/American Stroke Association recommend MRI to identify diffusion-positive FLAIR-negative lesions (DWI-FLAIR mismatch) for selecting patients who can benefit from IV alteplase in acute ischemic stroke (AIS) patients who awake with stroke symptoms or have unclear time of onset > 4.5 hours from last known well.1 The efficacy and safety of IV alteplase for these patients was revealed by the WAKE-UP trial.2

In the WAKE-UP trial, a favorable outcome defined by mRS 0 to 1 at 90 days was achieved in 53.3% in the alteplase group and 41.8% in the placebo group (adjusted odds ratio, 1.61; 95% confidence interval [CI], 1.09 to 2.36; P = 0.02). The trial was stopped early for lack of funding, and there was numerically more death (4.1% vs 1.2%, P=0.07) and significantly more symptomatic intracranial hemorrhage (sICH) (2.0% vs. 0.4%, P= 0.15). So, there still have been some concerns about safety of the therapy.

By |January 12th, 2021|clinical, treatment|Comments Off on Low-Dose Intravenous Alteplase in Stroke with Unknown Time Onset

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.

By |December 16th, 2020|clinical, treatment|Comments Off on Balancing Risk-Benefit for Non-Acute Vertebral Artery Occlusion Revascularization

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.

By |December 7th, 2020|clinical, treatment|Comments Off on Article Commentary: “Tenecteplase Thrombolysis for Acute Ischemic Stroke”

Dual Antiplatelet Therapy: Shotgun or Aiming at Precision Targets?

Thomas Raphael Meinel, MD
@TotoMynell

Amarenco P, Denison H, Evans SR, Himmelmann A, James S, Knutsson M, Ladenvall P, Molina CA, Wang Y, Johnston SC, on behalf of the THALES Steering Committee and Investigators. Ticagrelor Added to Aspirin in Acute Nonsevere Ischemic Stroke or Transient Ischemic Attack of Atherosclerotic Origin. Stroke. 2020.

Short-term dual antiplatelet therapy (DAPT) has emerged as a powerful treatment option in patients with non-severe ischemic stroke or high-risk TIA.1 However, the efficacy of antithrombotic therapy might vary according to etiology of the ischemic event.2 Amarenco et al. aimed to investigate whether the efficacy and safety of DAPT with Aspirin plus Ticagrelor as compared to Aspirin differed in the subgroup of patients with minor stroke or TIA due to atherosclerotic vascular disease.

For this purpose, the authors conducted a substudy of the THALES trial including patients aged 40 years or older with non-severe non-cardioembolic ischemic stroke (NIHSS ≤5) or high-risk TIA (ABCD2-Score ≥6 or vascular stenosis ≥50% in the suspected vascular territory). Main exclusion criteria were atrial fibrillation, suspicion of cardioembolic cause, high bleeding risk and — importantly — planned carotid revascularization that required halting study medication within 3 days of randomization. or the main prespecified analysis, atherosclerotic ipsilateral stenosis was defined as presence of narrowing of the lumen of ≥30% ipsilateral to the ischemic event as assessed by CT- or MR-angiography or neurovascular ultrasound. The primary efficacy endpoint was time from randomization to the first subsequent event of stroke or death. The primary safety endpoint was occurrence of a severe bleeding event according to the GUSTO definition. 11,016 patients underwent randomization (roughly 50% representing a European and 40% Asian population).

By |November 17th, 2020|clinical, Conference, treatment|Comments Off on Dual Antiplatelet Therapy: Shotgun or Aiming at Precision Targets?

World Stroke Day: The Long Journey of Revascularization Treatments for Ischemic Stroke: From Strict Patient Selection to Extending Time Windows

Raffaele Ornello, MD

Until the early 1990s, stroke was regarded as a disabling event with no cure. The NINDS trial of intravenous thrombolysis, published in 1995, changed the minds of stroke physicians and marked the rise of revascularization treatments for acute ischemic stroke. The initial criteria for patient selection were very strict. After that, more and more refined protocols were established, allowing the progressive extension of the therapeutic window and the loosening of selection criteria.

The last decade saw the rise of endovascular treatments. After the first unsuccessful trials, adequate protocols for the selection of patients with salvageable brain ischemic tissue led to success in recanalization treatments. Better use of brain neuroimaging led to refinements in patient selection, allowing the extension of time windows for treatments in eligible patients. Over the years, revascularization treatments for ischemic stroke spread over most hospitals in the world, allowing widespread access to treatments.

By |October 29th, 2020|clinical, treatment, World Stroke Day|Comments Off on World Stroke Day: The Long Journey of Revascularization Treatments for Ischemic Stroke: From Strict Patient Selection to Extending Time Windows

World Stroke Day: Interview with Dr. Anna Bersano on the Impact of the COVID-19 Pandemic on Stroke Care in Italy

Dr. Anna Bersano
Dr. Anna Bersano

An interview with Dr. Anna Bersano, MD, PhD, at the Cerebrovascular Unit of Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy, about the impact of the COVID-19 pandemic on stroke care in Italy.

Interviewed by Francesca Tinelli, MCs, rare cerebrovascular disease fellow at Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.

Dr. Tinelli: First of all, I present you Dr. Anna Bersano, the neurologist I work with, and I would like to thank Anna for agreeing to do this interview. 

Anna is a stroke neurologist with long-term expertise in cerebrovascular diseases, particularly in genetics of monogenic and complex stroke diseases, combining research with an active practice as a vascular care neurologist. She coordinated several studies on genetics of stroke, such as the Lombardia GENS study on stroke monogenic disease and the SVE-LA study on genetics of small vessel disease and lacunar stroke. Recently, she implemented an Italian network for the study of Moyamoya disease named GE-NO-MA (Genetics of Moyamoya Disease) and an Italian network for the study of Cerebral Amyloid Angiopathy (SENECA project). 

Dr. Bersano: Thank you for discussing this relevant and critical topic in the current situation.

Dr. Tinelli: What is the correlation between SARS-CoV2 and cerebrovascular diseases?

Dr. Bersano: It is well known that SARS-CoV2 invades human respiratory epithelial cells through its S-protein and ACE2 receptor on human cell surface. Then, the virus can spread from the respiratory tract to the central nervous system, causing possible neurological complications. A recent study on 214 Chinese COVID-19 patients reported acute cerebrovascular events in 5.7% of COVID-19 patients. However, the exact relationship between SARS-CoV2 and stroke is unclear. Patients affected by COVID-19 have been observed to have a higher risk of cerebrovascular events, probably due to the activation of coagulation and inflammatory pathways, which lead to cardiovascular and thrombotic complications, or to cardioembolic causes.

By |October 29th, 2020|author interview, clinical, treatment, World Stroke Day|Comments Off on World Stroke Day: Interview with Dr. Anna Bersano on the Impact of the COVID-19 Pandemic on Stroke Care in Italy