American Heart Association

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.

Effect of HRV on the Association Between Obstructive Sleep Apnea and Small Vessel Disease

Kristina Shkirkova, BSc
@KShkirkova

Del Brutto OH, Mera RM, Costa AF, Castillo PR. Effect of Heart Rate Variability on the Association Between the Apnea-Hypopnea Index and Cerebral Small Vessel Disease. Stroke. 2019;50:2486–2491.

Obstructive Sleep Apnea (OSA) is a form of sleep-disordered breathing that has been increasingly implicated in the pathogenesis of cerebral small vessel disease (cSVD). OSA is associated with recurrent episodes of hypoxia, altered cerebral autoregulation, and sympathetic overactivity, which may be contributing triggers for pathophysiology of cSVD. A recent study by Del Brutto et al. used nighttime Heart Rate Variability (HRV) as a measure of sympathetic upregulation to study the association between OSA and cSVD. HRV measures variation in the intervals between heartbeats and is used as a reflection of the balance between sympathetic and parasympathetic tone. Apnea-Hypopnea Index was used to access the degree of OSA and the total cSVD score was chosen to quantify cSVD burden. The study used data from the Atahualpa Project, which included elderly (age above 60) residents of the Atahualpa rural village on the coast of Ecuador. A total of 176 participants who underwent clinical assessment, magnetic resonance imaging (MRI), single-night polysomnography, and 24-hour Holter monitoring were selected for the analysis.

Among study participants, the mean age was 71.8, and 64% were women. The univariate analysis showed that daytime HRV below the 50th percentile was associated with female gender and lower mean percentage of O2 saturation. The nighttime HRV below the 50th percentile was associated with body mass index (BMI) higher than 30 kg/m2. In the generalized linear model analysis, with and without confounding variables, there was a significant association between the cSVD score and AHI (p=0.026). Furthermore, a negative association was observed between sCVD and nighttime HRV, but not daytime HRV (p=0.001). Interaction model analysis showed a significant interaction of nighttime HRV on the relationship between AHI and the cSVD score (P=0.001). The total effect between AHI and the cSVD score mediated by HRV was 30.8%. Additionally, contour plots showed the effect of nighttime HRV on the association between AHI and the cSVD score.

Anxiety Common After Stroke or TIA, Especially in the Young

Elizabeth M. Aradine, DO

Kapoor A, Si K, Yu AYX, Lanctot KL, Herrmann N, Murray BJ, et al. Younger Age and Depressive Symptoms Predict High Risk of Generalized Anxiety After Stroke and Transient Ischemic Attack. Stroke. 2019;50:2359-2363.

Poststroke anxiety is not uncommon and can negatively affect quality of life. The relationship between stroke and anxiety has been demonstrated, but few studies have included young patients. Furthermore, the presence of premorbid depression is a predictor of poststroke anxiety; however, it is unknown if the absence of depression is a protector against poststroke anxiety. The authors of this study sought to elucidate the effect of age and depression on poststroke or TIA anxiety.  

This study was conducted using registry data from the DOC Feasibility Study, a prospective longitudinal cohort of stroke, TIA, and non-stroke patients. Only those with a diagnosis of stroke or TIA were included for analysis in this study. Aphasic patients were excluded. Anxiety was assessed using the Generalized Anxiety Disorder 7-item (GAD-7) scale with a score ≥10 indicating moderate to severe symptoms. Depression was assessed using the Epidemiological Studies Depression Scale (CES-D) with ≥16 indicating moderate to severe symptoms.

257 patients were included, 125 with stroke and 133 with a TIA. 21.7% of patients had a GAD-7 score of ≥10. 25.2% had CES-D scores ≥16. Young patients (<50 years old) and those with CES-D scores ≥16 were more likely to have anxiety after a TIA or stroke. See Figure.

Figure. Frequency of high-risk anxiety and depressive symptoms in younger and older stroke patients.

Figure. Frequency of high-risk anxiety and depressive symptoms in younger and older stroke patients. Frequency of high-risk anxiety and depression symptoms includes patients with and without comorbid symptoms; frequency of high-risk anxiety+depression includes patients with comorbid symptoms.
By |November 4th, 2019|clinical|0 Comments

Collaterals Aid in Predicting Rate of Infarct Growth: Value in Transfer Decisions

Ravinder-Jeet Singh, MBBS, DM

Puhr-Westerheide D, Tiedt S, Rotkopf LT, Herzberg M, Reidler P, Fabritius MP, et al. Clinical and Imaging Parameters Associated With Hyperacute Infarction Growth in Large Vessel Occlusion Stroke. Stroke. 2019;50:2799–2804.

Infarct growth among patients with large vessel occlusion (LVO) is highly variable. In some patients, infarct progresses very quickly (rapid progressor) and they have no or small penumbra even during early hours after their stroke onset, while others progress more slowly (slow progressor) and have large penumbral tissue at later time windows. Therefore, size of pre-treatment penumbra and response to reperfusion therapies, especially endovascular thrombectomy, would vary depending on time from symptom onset and rate of infarct growth, resulting in patient-specific time-windows to intervene. While rapid progressors could benefit from reperfusion therapy during very early time-window, the slow progressors can potentially benefit from treatment in either early- or late-windows This concept has been tested in the recent early- and late-window thrombolysis and thrombectomy trials. Therefore, early distinction between rapid vs slow progressor might prove particularly useful in making time-sensitive decisions, especially interfacility transfer decisions, typically between more peripheral primary stroke centers to larger endovascular therapy capable centers.

The variability in infarct growth is determined by multiple demographic, clinical, and imaging factors, such as age, blood pressure, blood glucose, stroke severity, initial infarct size, and time from ictus; these factors can influence “final” infarct volume and determine functional outcomes. Collateral blood flow status plays an especially major role in providing residual flow, and infarct size. Whether these same factors also underlie “early” infarct growth is less well studied. In the present study, the authors investigated clinical and imaging factors associated with early (hyperacute) infarct growth.

By |November 1st, 2019|clinical|0 Comments

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|0 Comments

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.