American Heart Association

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Article Commentary: “Treatment and Outcomes of Patients With Ischemic Stroke During COVID-19”

Ericka Teleg, MD

Srivastava PK, Zhang S, Xian Y, Xu H, Rutan C, Alger HM, Walchok JG, Williams JH, de Lemos JA, Decker-Palmer MR, et al. Treatment and Outcomes of Patients With Ischemic Stroke During COVID-19: An Analysis From Get With The Guidelines-Stroke. Stroke. 2021.

The COVID-19 pandemic has caused a shift in stroke systems and has changed the way stroke approach and management are put in place. The impact of this is that time is still brain. Time and stroke outcomes still matter more so during this time. From a patient’s perspective in experiencing and reporting symptoms to the way emergency room systems tackle stroke during the pandemic, remain a challenge.

The objective of this study was to analyze characteristics, evaluation, treatment, and in-hospital outcomes of patients presenting with acute ischemic stroke pre-COVID-19 and during COVID-19 time. This study is important as it allows us to be able to navigate the time-sensitive nature of stroke during COVID-19. With the COVID-19 restrictions and concern for infection and transmission, several studies have demonstrated no difference in diagnostic and treatment times pre-COVID 19 versus the COVID-19 era. On the other hand, some studies showed a decline in stroke presentations. One reason emphasized in this article is underreporting of symptoms due to fear of COVID-19 exposure in-hospital.

The Reversibly Stunned Brain After Successful Endovascular Reperfusion in Acute Anterior Circulation Ischemic Stroke

Tolga D. Dittrich, MD

Talavera B, Gómez-Vicente B, Martínez-Galdámez M, López-Cancio E, García-Cabo C, Castellanos M, Roel A, Tejada-Meza H, Marta-Moreno J, Pérez-Lázaro C, et al. Delayed Neurological Improvement After Full Endovascular Reperfusion in Acute Anterior Circulation Ischemic Stroke. Stroke. 2021;52:2210-2217.

Endovascular thrombectomy (EVT) is an essential part of acute therapy for ischemic stroke due to large vessel occlusion. As early clinical improvement after successful reperfusion therapy is a reliable predictor of long-term independence, the absence of such clinical progress can discourage the treating stroke team. But does this necessarily mean that the long-term prognosis in such patients is unfavorable? This is one of the questions addressed by Talavera et al. in their paper.

A total of 628 patients with proximal occlusions of the anterior circulation, all of whom received successful EVT (i.e., mTICI 3), were included in the study. After EVT, 142 (22.6%) showed no early neurological improvement. However, 32 (22.5%) still had a favorable long-term outcome. In contrast, 323 (66.5%) of a total of 486 patients with early neurological improvement demonstrated a favorable long-term outcome. Baseline predictors of delayed neurological improvement were male sex (OR 6.4 [95% CI, 2.1-22.3] p=.002), lower baseline NIHSS score (OR 1.4 [95% CI, 1.2-1.5]. p=<.001) and treatment with rtPA (OR 9.1, [95% CI, 2.7-30.9], p=<.001).

Plaque Instability Under the Microscope

Aurora Semerano, MD
@semerano_aurora

Ganji M, Nardi V, Prasad M, Jordan KL, Bois MC, Franchi F, Zhu XY, Tang H, Young MD, Lerman LO, Lerman A. Carotid Plaques From Symptomatic Patients Are Characterized by Local Increase in Xanthine Oxidase Expression. Stroke. 2021.

Investigating mechanisms of plaque instability is needed to better treat patients with carotid atherosclerosis. In parallel, the search for reliable biomarkers, including blood parameters and imaging features, is required to identify patients with carotid plaques at the highest risk of embolism. Within this effort of providing new knowledge in the field, this study1 recently published in Stroke aimed at investigating the histological characteristics of plaque instability. The authors were specifically interested in exploring the role of xanthine oxidase, the enzyme that catalyzes the synthesis of uric acid, which acts as an indicator of oxidative homeostasis and has been previously associated with atherosclerosis and increased cardiovascular risk.2

The study examined 88 randomly selected carotid artery specimens from symptomatic (within the previous 6 months) and asymptomatic patients. No difference was observed in the relative percentage of traditional histological components of atherosclerosis (such as fibrosis, plaque hemorrhage, calcium, and lipid core). The amount of macrophage infiltration was also comparable between specimens from symptomatic and asymptomatic patients. Interestingly, the authors found significantly higher expression of xanthine oxidase in symptomatic carotid plaques. Further, in a subset of 27 samples, they observed that percentage of macrophages expressing xanthine oxidase was increased in symptomatic plaques. Moreover, xanthine oxidase expression in the plaques positively correlated with uric acid levels in the blood.

Spoiler Alert in ACA Strokes: It’s All About Collaterals

Elena Zapata-Arriaza, MD PhD
@ElenaZaps

Thirugnanachandran T, Beare R, Mitchell M, Wong C, Vuong J, Singhal S, Slater LA, Hilton J, Sinnott M, Srikanth V, et al. Anterior Cerebral Artery Stroke: Role of Collateral Systems on Infarct Topography. Stroke. 2021.

Anterior cerebral artery (ACA) stroke is less frequent when compared with middle cerebral artery (MCA) occlusion, and consequently, mechanical thrombectomies, perfusion studies, pial collateral system or clinical consequences based on the topography of the lesion are less known. With the aim of evaluating the role of the circle of Willis (CoW) and leptomeningeal anastomoses (LA) in modifying regional variation in infarct topography following occlusion of the anterior cerebral artery and its branches, Thirugnanachandran and colleagues employed voxel-based imaging in conjunction with computer model of cerebral circulation to understand the temporal and spatial evolution of the topography of ACA stroke following vessel occlusion. The experiments included occlusion of successive branches of the anterior cerebral artery while the configurations of the CoW were varied.

The Intense Association of Statins and Post-Stroke Mortality

Melanie R. F. Greenway, MD
@MRFGreenwayMD

Dearborn-Tomazos JL, Hu X, Bravata DM, Phadke MA, Baye FM, Myers LJ, Concato J, Zillich AJ, Reeves MJ, Sico JJ. Deintensification or No Statin Treatment Is Associated with Higher Mortality in Patients With Ischemic Stroke or Transient Ischemic Attack. Stroke. 2021.

Optimizing statin therapy in patients after stroke or TIA is an important component of secondary stroke prevention. High-intensity statin and LDL-C goal <70 mg/dL are the two main targets for secondary stroke prevention based on SPARCL1 and TST.2 The recent “2021 Guideline for the Prevention of Stroke in Patients with Stroke and Transient Ischemic Attack”3 recommends atorvastatin 80mg daily in patients with ischemic stroke, no known coronary artery disease, no major cardiac source of embolism, and LDL-C > 100mg/dL. In those with ischemic stroke or TIA who have evidence of atherosclerotic disease, LDL-C lowering to <70mg/dL is recommended with statin and, if needed, ezetimibe, though a specific dose or intensity of statin is not specified. 

This study looked at 10,871 patients with a primary diagnosis of acute ischemic stroke or TIA who presented to the ER or were admitted during the fiscal year of 2011 at 134 VA centers across the United States. After excluding those who were transferred out of the VA system, died during hospitalization, left against medical advice, were discharged to hospice, or allergic to statins, 9,380 patients were left for review. Their cohort of patients was 96.3% male, 71.1% White, and 34.9% smokers. The mean age was 68.7.

Age at Menopause and Stroke

Ericka Teleg, MD

Welten SJGC, Onland-Moret NC, Boer JMA, Verschuren WMM, van der Schouw YT. Age at Menopause and Risk of Ischemic and Hemorrhagic Stroke. Stroke. 2021.

Stroke risk in women and increasing its knowledge globally will help contribute to understanding specific risk factors to improve stroke prevention and treatment in women. Studies in women are not straightforward due to the presence of heterogeneity among variables and outcome measures, which the article emphasizes in its introduction. This remains a challenge in epidemiological studies in women.

The objective of this prospective cohort study investigates whether the age at menopause is a risk factor for total, ischemic and hemorrhagic stroke. The authors explore if this association is present in natural and surgical menopause.

Back to BASICS

Juan Carlos Martinez Gutierrez, MD
@JCMartinezMD

Langezaal LCM, van der Hoeven EJRJ, Mont’Alverne FJA, de Carvalho JJF, Lima FO, Dippel DWJ, van der Lugt A, Lo RTH, Boiten J, Lycklama À Nijeholt GJ, et al. Endovascular Therapy for Stroke Due to Basilar-Artery Occlusion. N Engl J Med. 2021:384:1910-1920.

Langezaal et al. published results on the BASICS study in the NEJM. This study was an international randomized open-label blinded outcome trial comparing standard medical management (MM) versus Endovascular Thrombectomy (EVT) for Basilar Artery Occlusions (BAO).

They recruited patients aged <85 years with BAO within 6 hours of symptoms onset, National Institutes of Health Stroke Scale score (NIHSS) >10, and no large established infarct (i.e., bilateral brainstem, cerebellar infarct with mass effect or hydrocephalus). The trial was initially powered to detect a 10% difference between arms based on available evidence from the BASICS registry, which showed favorable functional outcome (modified Rankin Score [mRS] 0-3) in 40% of participants treated with EVT and in 30% of those treated with MM. This initial design required 750 patients; however, after 4 years of slow recruitment and new evidence of EVT benefit in the anterior circulation, the trial was redesigned. The new assumption was that treatment effect may be higher based on the positive 2015 EVT trials, so the expected mRS 0-3 rate was increased to 46% for the EVT arm. The 16% risk reduction resulted in a smaller sample size estimation of 300. In addition, to increase potential recruitment, the eligibility criteria was expanded to include patients aged >85 years, those with NIHSS <10 and those with contraindications for intravenous thrombolysis.

Article Commentary: “Obstructive Sleep Apnea as a Risk Factor for Intracerebral Hemorrhage”

Wern Yew Ding, MBChB

Geer JH, Falcone GJ, Vanent KN, Leasure AC, Woo D, Molano JR, Sansing LH, Langefeld CD, Pisani MA, Yaggi HK, Sheth KN. Obstructive Sleep Apnea as a Risk Factor for Intracerebral Hemorrhage. Stroke. 2021;52:1835–1838.

Intracerebral hemorrhage (ICH) is a life-threatening condition associated with poor prognosis. About one in three patients die within the first month of an event. Among those who survive, severe functional disability often ensues. Concerningly, there is no definitive medical treatment for ICH, and the role of surgery remains debatable despite its use in various forms. Hence, the best treatment for ICH may ultimately be prevention. For the prevention of ICH, it is important that the relevant risk factors are identified and managed accordingly.

In this brief report from Geer et al., the authors evaluated the effects of obstructive sleep apnea (OSA) as an independent risk factor for non-traumatic ICH. This was predicated on the premise that OSA causes a cycle of abnormal physiology including hypoxaemia, sympathetic activation, and hemodynamic disturbance, and shares common pathophysiology with ICH. For this analysis, 5808 patients were enrolled as part of the multicenter, case-controlled ERICH (Ethnic/Racial Variations of Intracerebral Hemorrhage) study. Controls were selected at random, independent of exposure, to balance cases by age, sex, race/ethnicity, and metropolitan area. The risk of OSA was determined using the Berlin Questionnaire (BQ), which has previously been validated for this purpose and classifies patients as high or low risk. Patients with non-traumatic ICH had significantly higher rates of OSA compared to controls (OR 2.28 [95% CI, 2.05 – 2.55]). Furthermore, OSA was an independent risk factor for ICH in this patient cohort after controlling for potential confounders.

Baseline CT-Perfusion Deficit Performs Well in Basilar Artery Stroke Prognostication

Csilla Manoczki, MD

Fabritius MP, Tiedt S, Puhr-Westerheide D, Grosu S, Maurus S, Schwarze V, Rübenthaler J, Stueckelschweiger L, Ricke J, Liebig T, et al. Computed Tomography Perfusion Deficit Volumes Predict Functional Outcome in Patients With Basilar Artery Occlusion. Stroke. 2021;52:2016–2023.

Automated CT/MRI perfusion imaging has become the gold standard for therapeutic decision-making of anterior circulation ischemic strokes presenting in the extended time window. However, there is no validated imaging selection criteria available for the less frequent, but more challenging cases of posterior circulation infarcts.

In this study, Fabritius et al. investigated the predictive value of various CT imaging parameters in a cohort of patients who had presented with acute ischemic stroke secondary to basilar artery occlusion and received modern endovascular treatment (with or without prior intravenous thrombolysis). Forty-nine eligible patients were identified retrospectively in the German Stroke Registry between June 2015 and December 2019. The standardized imaging protocol consisted of non-contrast CT, single phase CT-angiogram and whole-brain CT perfusion studies.

Focal Cerebral Arteriopathy and Pediatric Stroke

Kevin O’Connor, MD

Oesch G, Perez FA, Wainwright MS, Shaw DWW, Amlie-Lefond C. Focal Cerebral Arteriopathy of Childhood: Clinical and Imaging Correlates. Stroke. 2021.

Focal cerebral arteriopathy (FCA) is the cause of up to a quarter of strokes in children. FCA involves a focal and unilateral stenosis or irregularity of the distal internal carotid artery and its proximal branches. The suspected underlying pathophysiology is arterial inflammation resulting in vessel narrowing and thrombus formation on damaged endothelium. Post-varicella FCA is a common etiology and may occur within a year of infection. Imaging mimics of FCA include dissection, moyamoya, and embolus. Children with FCA may have progression of symptoms over several days/weeks, and up to a quarter have another stroke within a year.

Oesch et al. identified 15 cases (8%) of FCA among 179 children with strokes at a single center between 2009-2019. The median age was 6.8 years (range 0.5-16.3 years) and 8 were boys. Common presenting symptoms included hemiparesis (n=14), headache (n=7), and a concomitant infectious process (n=6). Two of thirteen tested children (15%) were positive for VZV antibodies and VZV DNA. The lower incidence of FCA with recent VZV infection compared to prior studies may be related to increased VZV vaccination. Six children had stuttering symptoms over 1-4 days prior to stroke. Three children (20%) had progression of stroke symptoms after the initial event. All 15 children received antithrombotic therapy following the stroke and over the course of follow-up (at least one year in 14 of 15 children). Data on the safety and efficacy of steroid use in FCA is unclear.