American Heart Association

Monthly Archives: October 2019

Analyzing Effect of Antiplatelets on Stroke After Intracerebral Hemorrhage in High-Risk Recurrence Group

Mausaminben Hathidara, MD

Al-Shahi Salman R, Minks DP, Rodrigues MA, Bhatnagar P, du Plessis JC, Joshi Y, et al. Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial. Lancet Neurol. 2019;18:643-652.

Due to high prevalence of vascular diseases, almost one-third of adults in high-income countries are taking antithrombotic (antiplatelet or anticoagulation). Whether it is beneficial to restart antiplatelet after spontaneous intracerebral hemorrhage (ICH) to prevent another vascular occlusive disease such as stroke, myocardial infarction, or peripheral arterial disease is a dilemma to clinicians due to fear of recurrence of ICH. To date, our knowledge to weigh risk and benefits in this situation is derived from observational and retrospective studies. Recently published, RESTART1 was the first prospective, randomized, open-label and blinded end point trial showing evidence that the risk of recurrent intracerebral hemorrhage was very small against the benefit of antiplatelets for secondary prevention. However, some of the sub-groups such as lobar hemorrhage and presence of cerebral microbleed have higher risk of recurrence intracerebral hemorrhage per observational studies,2,3,4 and whether the benefit still exceeds the risk amongst them is unclear.

The sub-group analysis performed by Dr. Al-Shahi Salman et al. recruited patients >18 years with spontaneous intracerebral hemorrhage who were already on antiplatelet or anticoagulation at the time of hemorrhage and after which therapy was discontinued. 537 participants were enrolled, of whom 525 (98%) had intracerebral hemorrhage: 507 (97%) were diagnosed on CT (252 assigned to start antiplatelet therapy and 255 assigned to avoid antiplatelet therapy), and 254 (48%) underwent the required brain MRI protocol (122 in the start antiplatelet therapy group and 132 in the avoid antiplatelet therapy group). Participants were followed for a median of 2 years to look for primary outcome as recurrence of intracerebral hemorrhage and secondary outcome of vascular occlusive events.

By |October 30th, 2019|clinical|Comments Off on Analyzing Effect of Antiplatelets on Stroke After Intracerebral Hemorrhage in High-Risk Recurrence Group
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World Stroke Day: Stroke Care Advances in Armenia

David Sahakyan, MD
General and Endovascular Neurosurgeon, Head of Cerebrovascular Neurosurgery Service, Erebouni Medical Center, Yerevan, Republic of Armenia

Stroke is the primary worldwide healthcare problem, especially for developing countries. Armenia was one of those countries, where the implementation of modern, time-sensitive stroke treatment modalities like intravenous thrombolysis and mechanical thrombectomy was insufficient and sometimes impossible due to the high cost and underdeveloped stroke care system. For years, neurologists and neurosurgeons willing to provide state-of-the-art treatment to stroke patients were unable to do so because patients and their families had to pay for the procedures and medications out of their pocket before the treatment could be delivered. 

Everything changed in 2019. A collective effort of stroke specialists from Armenia and abroad, combined with the willingness of the new government to recognize the disability burden imposed by this devastating disease, led to amazing transformations in stroke care for the entire country. A national stroke program developed by a group of stroke specialists from the United States, Canada, France, and Armenia and supported by governmental funding made modern acute stroke care accessible for everyone in need in Armenia. In a small country with a population of 3 million, out of 5000 annual ischemic stroke patients, more than 300 patients have received acute stroke treatment for free since the beginning of 2019. More than 240 intravenous rTPA and 120 endovascular thrombectomies have already been performed at two stroke centers. In patients who received treatment, marked reduction of morbidity and mortality was achieved. It is worth mentioning that the budget of the program is around $1 million US dollars. And this is just the beginning. Further development of the stroke network is on the way.

Armenia is an excellent example of how a small developing country with limited financial resources can develop a world-class stroke care system with the help of experienced specialists from developed countries, motivated local physicians, and a supportive government.   

By |October 29th, 2019|clinical, World Stroke Day|Comments Off on World Stroke Day: Stroke Care Advances in Armenia
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World Stroke Day: October 29

Richard Jackson, MD

This is an exciting time for the acute treatment of ischemic strokes with innovations in thrombectomy and advancements in imaging-based tissue evaluation for thrombolysis. Yet the percentage of patients being treated with these advancements remains low at around 15%. The treatment of ischemic cerebral disease is following in the footsteps of ischemic cardiac disease with the creation of hospital-led evidence-based programs and regional treatment programs involving primary and comprehensive stroke centers collaborating with local EMS providers. 

However, as the director of a primary stroke center, I am continually surprised by the delays in presentation to the hospital for care. I remember, as an intern on the telemetry rotation, admitting what seemed like a never-ending amount of chest pain patients for evaluation. Every night on call for stroke, I, like all neurologists, face questions regarding the disposition of patients with resolved symptoms, patients with delayed presentation to the emergency room, patients not wanting to come into the hospital for treatment, and the questions surrounding acute treatment. These nights, I am always left wondering, what has cardiology done better than neurology? Why don’t people in the community present for evaluation at the slightest possible acute cerebral insult? Is it that our treatments and programs need time to create the system they have, or do we need to do more on the community education programs?

By |October 29th, 2019|clinical, World Stroke Day|Comments Off on World Stroke Day: October 29
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NASAM Stroke Games 2019 and Stroke in Malaysia

Lin Kooi Ong, PhD
@DrLinOng

The National Stroke Association of Malaysia (NASAM) Stroke Games 2019, an amazing event showcasing remarkable possibilities of #LifeAfterStroke, kicked off with an inspiring start at the Panasonic National Sports Complex in Malaysia on October 19. This event is in conjunction with the World Stroke Organisation – World Stroke Day, Southeast Asia Route. Over 800 participants from different states, including Penang, Sabah and Johor, as well as Singapore, participated in 25 events. The youngest athlete was 16 years old, and the oldest was 81 years old. The games kicked off with seated volleyball and hand cycle. The event closed on October 20 with Janet Yeo, stroke survivor and founder chairman of NASAM, putting out the flame.

The NASAM Stroke Games 2019 was declared open.
The NASAM Stroke Games 2019 was declared open. Left to right are: Dato’ Wan Hashimi Albakri, Acting Group CEO, Sime Property Berhad; Tun Jeanne Abdullah, Patron of the Malaysian Paralympic Council; Janet Yeo, NASAM Founder Chairman; Hannah Yeoh, Deputy Minister, Ministry of Women, Family and Community Development; Stuart Milne, CEO, HSBC Bank Malaysia Berhad; Toh Puan Dato’ Seri Hajjah Dr Aishah Ong, Patron of NASAM; and Ruchira Gupta, NASAM Senior Advisor. Photo provided by Frankie Goh, NASAM, with permission.

“The Games is NASAM’s contribution to the stroke community around the world,” said Yeo. “We wish that this fighting spirit of a stroke champion is ignited into every person affected by a stroke no matter where they are.”

By |October 29th, 2019|clinical, World Stroke Day|Comments Off on NASAM Stroke Games 2019 and Stroke in Malaysia
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World Stroke Day: Staying Above the Fray

Burton J. Tabaac, MD

Join the fight against stroke!

In 2015, the World Stroke Campaign focused on raising awareness of stroke prevention and risk among women using the tagline “I am Woman – Stroke Affects Me, Stroke Affects Everyone.” In 2016, World Stroke Day was marked by recognizing that although stroke is a complex medical issue, there are ways to significantly reduce its impact. The World Stroke Organization built a campaign to underscore that “Stroke is Treatable.” The World Stroke Day 2017 campaign focused on risk awareness and prevention. Last year, World Stroke Day 2018 emphasized that there are resources and a network to assist those who have suffered from stroke, underscoring that you are not in it alone. #UpAgainAfterStroke was used as a rallying cry to inform the public about the well-developed network for caregivers, families, and friends affected by stroke who can help their loved ones.

This year, 2019, calls attention to prevention.

By |October 29th, 2019|clinical, World Stroke Day|Comments Off on World Stroke Day: Staying Above the Fray
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Article Commentary: “Phase I/II Study of Safety and Preliminary Efficacy of Intravenous Allogeneic Mesenchymal Stem Cells in Chronic Stroke”

Yan Hou, MD, PhD

Levy ML, Crawford JR, Dib N, Verkh L, Tankovich N, Cramer SC. Phase I/II Study of Safety and Preliminary Efficacy of Intravenous Allogeneic Mesenchymal Stem Cells in Chronic Stroke. Stroke. 2019;50:2835–2841.

Substantial preclinical data support the safety and efficacy of mesenchymal stem cells (MSC) to improve outcomes during the chronic phase of stroke. Initial human studies of MSC after stroke focused on autologous cell therapies, whereby bone marrow is taken from each patient to produce his/her own MSC batch, and found MSC infusion to be safe. Compared to autologous cells, allogeneic MSC can be manufactured to enables broad clinical application, and it have been found to be safe without use of concomitant immunosuppression, because MSC are relatively immunoprivileged given their very low levels of human leukocyte antigen molecule expression. Studies of allogeneic MSC poststroke have focused on using an invasive procedure to implant cells intracerebrally. An intravenous method of introducing MSC if comparably efficacious might facilitate widespread implementation and also avoid adverse events attributable to invasive procedures.

The authors performed a phase I/II multi-center, open-labeled, dose-escalation trial that examined effects of a single intravenous infusion of allogeneic ischemia-tolerant MSC in patients with chronic ischemic stroke (>6 month from onset) and substantial functional deficits. MSC were grown from the bone marrow of a single human donor and are from the same batch used in prior preclinical and clinical studies. Thirty-six patients were enrolled (75% were males, 86% were Caucasians, at age 61.1 ± 10.8, time from stroke to infusion was 4.2 ± 4.6 years). Part 1 of the study consisted of 3 cohorts (n=5 per cohort) in a dose-escalation manner, with subjects receiving one of 3 doses based on body weight (0.5, 1, and 1.5 million cells/kg). The target dose of 1.5 million cells/kg corresponds to allometric scaling from animal studies using the intravenous route in the post-acute period. In Part 2 of the study, 21 patients received a single dose of 1.5 million cells/kg. The primary outcome was safety, and preliminary estimates of treatment efficacy were also examined. Patients were followed for one year after MSC infusion without any restriction of other medications.

By |October 28th, 2019|clinical|Comments Off on Article Commentary: “Phase I/II Study of Safety and Preliminary Efficacy of Intravenous Allogeneic Mesenchymal Stem Cells in Chronic Stroke”
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Transradial Access in Neurointerventional Procedures: Advances and Challenges

Gurmeen Kaur, MBBS, and Kat Dakay, DO
@kaurgurmeen; @katarinadakay

Conventional cerebral angiography has been trans-femoral and has a consistent 2-3% rate of femoral arterial complications, including pseudo-aneurysms, retroperitoneal hematomas, and access site bleeding.

Interventional cardiology has promoted and adopted the trans-radial approach, significantly reducing access site complications. Large-scale cardiology trials (RIVAL, RIFLE) have even demonstrated the increased safety of percutaneous coronary interventions using the radial approach.1

Over the last two years, the use of the radial approach for neuro-interventional procedures has dramatically increased. Multiple studies have demonstrated improved patient experience and a reduction in access site complications using the radial approach. Another major advancement has been the use of distal radial access.2 The distal radial artery, located in the anatomical snuff box, is distal to the origin of the superficial palmer branch, which supplies numerous palmar collaterals to the deep palmar arch. This further reduces the incidence of ischemic hand from radial artery occlusion and is more ergonomic for the operators.3 Additionally, in a patient undergoing a diagnostic angiogram as part of treatment planning, the proximal radial artery, which has a bigger caliber, can be preserved for the interventional procedure.

By |October 25th, 2019|clinical|Comments Off on Transradial Access in Neurointerventional Procedures: Advances and Challenges
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Microstimulation Guidance Results in Accurate and Reproducible Preclinical Lacunar Infarcts, Modeled in the Rat

Melissa Trotman-Lucas, PhD
@TrolucaM

Wen TC, Sindhurakar A, Contreras Ramirez V, Park H, Gupta D, Carmel JB. Targeted Infarction of the Internal Capsule in the Rat Using Microstimulation Guidance. Stroke. 2019;50:2531-2538.

Lacunar stroke occurs when a penetrating arteriole becomes blocked, leading to ischemic damage to deep brain structures such as subcortical white matter or deep grey matter. Lacunes are small areas of cell damage that can cause significant disability to the sufferer. This type of cerebral ischemic occurrence accounts for a fifth of all strokes, resulting in varied clinical presentations. Lacunar stroke of the internal capsule, or IC, is associated with lasting motor deficits and poor recovery. It is critical to develop a reliable preclinical model, focusing on corticospinal tract (CST) damage located within the IC, as this damage is a reliable predictor of stroke severity and clinical outcome.

In this article commentary, the recent publication by Tong-Chun Wen and colleagues reporting lacunar infarction induction using microstimulation guidance is discussed. Microstimulation was used by the group as a guide as the IC is a small subcortical structure, within already limited rat white matter, with an elongated irregular shape that can vary with age, sex and strain. Wen et al. set out to develop a reliable preclinical IC stroke model that could produce tightly focused lesions to improve upon the various preclinical methods currently used, including chemical, physical and photo induced models. Chemical induction can result in off target injuries due to unpredictable diffusion of the inducting solution and physical induction, although closely imitating the mechanism of human lacunar stroke induction, requires significant surgical expertise. The group utilized photothrombolysis, where a photosensitive dye is first injected into the blood stream and then target vessels are illuminated by a laser light source inducing thrombus formation. The group enhanced this method with the addition of micro-electrical stimulation to guide placement of the illuminating optical fibre. This was achieved through the use of an optrode, a combined electrode and optical-fibre probe.

By |October 23rd, 2019|basic sciences|Comments Off on Microstimulation Guidance Results in Accurate and Reproducible Preclinical Lacunar Infarcts, Modeled in the Rat
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Clinical and Radiographic Predictors of Mortality After Intracerebral Hemorrhage

Elizabeth M. Aradine, DO

Fallenius M, Skrifvars MB, Reinikainen M, Bendel S, Curtze S, Sibolt G, et al. Spontaneous Intracerebral Hemorrhage: Factors Predicting Long-Term Mortality After Intensive Care. Stroke. 2019;50:2336-2343.

High mortality from a large spontaneous intracerebral hemorrhage (ICH) is somewhat intuitive, but whether this holds true months after the event is not well known. The authors sought to better elucidate this in “Spontaneous Intracerebral Hemorrhage: Factors Predicting Long-Term Mortality After Intensive Care.” This multicenter retrospective study included all adults admitted to the ICU in Finland from 2003 to 2013 with spontaneous ICH. Demographics and clinical data including age, admission GCS, anticoagulation use, and chronic medical comorbidities were recorded. A CT scan was required to evaluate the hemorrhage location and were categorized as supratentorial superficial, supratentorial deep, brainstem, and cerebellum. The volume of hemorrhage was calculated using the ABC/2 formula, which incorporates length, width, and shape of hemorrhage, as well as CT slice thickness and number of slices where hemorrhage is present. Three models (clinical, radiographic, and combined clinical and radiographic) were used to evaluate the predictability of mortality from ICH. Patients were followed for 12 months.

By |October 22nd, 2019|clinical, prognosis|Comments Off on Clinical and Radiographic Predictors of Mortality After Intracerebral Hemorrhage
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Article Commentary: “Leveraging Human Genetics to Estimate Clinical Risk Reductions Achievable by Inhibiting Factor XI”

Alan C. Cameron, MB ChB, BSc (Hons), MRCP

Georgi B, Mielke J, Chaffin M, Khera AV, Gelis L, Mundl H, et al. Leveraging Human Genetics to Estimate Clinical Risk Reductions Achievable by Inhibiting Factor XI. Stroke. 2019.

In this recent article, Georgi and colleagues highlight coagulation factor XI (FXI) as a promising new target for antithrombotic therapy to prevent ischemic stroke without an increased risk of major bleeding. The authors analyzed data from the UK Biobank and two large genome wide association studies to formulate a genetic score standardized to a 30% increase in relative activated partial thromboplastin time, which is equivalent to effects achieved by pharmacological FXI inhibition compared to enoxaparin for the prevention of venous thromboembolism after total knee arthroplasty. 

The results herald what could potentially be a game-changer in antithrombotic therapy for stroke prevention. The authors demonstrate that genetic predisposition to lower FXI levels is associated with a 53% reduction in risk of ischemic stroke (OR 0.47, 95% CI 0.36–0.61; p=1.5×10−8) and a 90% reduction in risk of venous thrombosis (OR 0.1, 95% CI 0.07–0.14; p=3.03×10−43) without an increase in major bleeding (OR 0.69, 95% CI 0.45–1.04; p=0.0739). The reductions in risk of ischemic stroke are similar in patients with or without a history of atrial fibrillation (AF), suggesting that absolute risk reductions are higher in patients with AF. The authors went on to apply a calibration factor to estimate the effects of genetically lower FXI levels compared to placebo and demonstrate an estimated risk reduction of 56% (OR 0.44, 95% CI 0.31–0.62); this is broadly comparable to relative risk reductions observed with warfarin compared to placebo.

By |October 21st, 2019|clinical, epidemiology and genetics|Comments Off on Article Commentary: “Leveraging Human Genetics to Estimate Clinical Risk Reductions Achievable by Inhibiting Factor XI”
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