American Heart Association

Deferoxamine and Outcomes in Mid-Volume Intracerebral Hemorrhage

Vignan Yogendrakumar, MD MSc

Wei C, Wang J, Foster LD, Yeatts SD, Moy C, Mocco J, Selim M. Effect of Deferoxamine on Outcome According to Baseline Hematoma Volume: A Post Hoc Analysis of the i-DEF Trial. Stroke. 2021.

Intracerebral hemorrhage is a complex disease because, truly, no two bleeds are ever the same. Hemorrhages can differ in size, location, or compartment, and the varying combinations of these elements can lead to dramatic differences in clinical severity and long-term outcome. A small but well-placed hemorrhage in the internal capsule can lead to contralateral hemiplegia, whilst a moderately sized lobar hemorrhage can sometimes present with minimal clinical symptoms. This heterogeneity has been a point of frustration in treatment trials that aim to improve clinical outcomes because a candidate therapy may have a significant effect on a portion of the trial population, but the treatment effect may be diluted when the whole population is assessed. Past trials have informed subsequent studies regarding patient selection, but even with the numerous lessons learned, identifying patients that are most likely to benefit from a candidate therapy remains a difficult task.

By |April 8th, 2022|clinical|Comments Off on Deferoxamine and Outcomes in Mid-Volume Intracerebral Hemorrhage

Microvascular Circadian Rhythmicity and Subarachnoid Hemorrhage-Induced Injury

Kristina Shkirkova, BSc

Lidington D, Wan H, Dinh DD, Ng C, Bolz SS. Circadian Rhythmicity in Cerebral Microvascular Tone Influences Subarachnoid Hemorrhage–Induced Injury. Stroke. 2022;53:249–259.

Clinical and epidemiological evidence suggests that cerebrovascular events are influenced by circadian rhythms. Due to changes in coagulative balance and vascular tone during a 24-hour period, strokes are observed to occur more often in the mornings followed by evenings, the second most prevalent time.1 Similarly, it was previously reported that variations in circadian blood pressure and microvascular perfusion influenced the incidence of subarachnoid hemorrhage (SAH).2

SAH neuronal damage and poor outcomes have been associated with changes to tissue perfusion. Since cellular mechanisms controlling circadian rhythms play an important role in cerebral blood flow autoregulation, circadian oscillation of microcirculation following SAH drive the cerebral perfusion rhythm. However, the evidence of circadian influence on neuronal injury after SAH remains elusive. The authors of the study by Lidington et al., recently published in Stroke, looked at cerebral resistance artery myogenic reactivity, a mechanism of cerebral blood flow autoregulation, which is strongly correlated with cerebral perfusion and neuronal injury after SAH. 

By |April 6th, 2022|basic sciences|Comments Off on Microvascular Circadian Rhythmicity and Subarachnoid Hemorrhage-Induced Injury

POST-NIHSS and Posterior Circulation Strokes

Kevin O’Connor, MD

Alemseged F, Rocco A, Arba F, Schwabova JP, Wu T, Cavicchia L, Ng F, Ng JL, Zhao H, Williams C, et al. Posterior National Institutes of Health Stroke Scale Improves Prognostic Accuracy in Posterior Circulation Stroke. Stroke. 2021.

The NIH Stroke Scale (NIHSS) is an indispensable part of acute stroke evaluations, but its components focus more on anterior circulation deficits than posterior circulation deficits. Alemseged et al. developed the POST-NIHSS to augment the NIHSS with additional posterior circulation deficits based on retrospective analysis of 202 patients with clinical and radiographic evidence of posterior circulation stroke and NIHSS score <10 who did not undergo mechanical thrombectomy from the Basilar Artery Treatment and Management registry. They then validated their POST-NIHSS with 65 prospectively recruited patients.

Clinical features of posterior circulation strokes may include gait/truncal ataxia, diplopia, ptosis, nystagmus, internuclear ophthalmoplegia, vertical gaze impairment, Horner syndrome, palatal palsy, tongue deviation, and abnormal cough. The retrospective analysis identified gait/truncal ataxia (OR, 3.14 [95% CI, 1.24–7.92], P=0.02), dysphagia (OR, 5.22 [95% CI, 1.63–16.7], P=0.005), and abnormal cough (OR, 8.17 [95% CI, 1.49–44.8], P=0.02) as significantly associated with poor outcome. To the standard NIHSS, the POST-NIHSS adds 3 points for gait/truncal ataxia when assessing item 7 and a new item 12 to assess for abnormal cough (5 points) and dysphagia (4 points). In a ROC analysis for age-adjusted poor outcome, POST-NIHSS performed better than NIHSS (POST-NIHSS AUC, 0.80 [95% CI, 0.73–0.87] versus NIHSS AUC, 0.73 [95% CI, 0.64–0.83]). In a subgroup sensitivity analysis of 156 of the 202 patients with NIHSS 0-5 (77%), POST-NIHSS remained associated with age-adjusted poor outcome (OR, 1.40 [95% CI, 1.14–1.70], P=0.01) while NIHSS was not (OR, 1.12 [95% CI, 0.82–1.56], P=0.46).

By |April 4th, 2022|clinical, outcomes, prognosis|Comments Off on POST-NIHSS and Posterior Circulation Strokes

Article Commentary: “Endovascular Treatment for Posterior Circulation Stroke in Routine Clinical Practice”

Tolga D. Dittrich, MD

Pirson FAV, Boodt N, Brouwer J, Bruggeman AAE, den Hartog SJ, Goldhoorn R-JB, Langezaal LCM, Staals J, van Zwam WH, van der Leij C, et al., and on behalf of the MR CLEAN Registry Investigators. Endovascular Treatment for Posterior Circulation Stroke in Routine Clinical Practice: Results of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands Registry. Stroke. 2021.

In contrast to anterior circulation stroke, the evidence for endovascular treatment (EVT) of posterior circulation stroke remains low. In practice, this means that clinicians still face uncertainties regarding the benefit of EVT, with the decision often based on the individual assessment of the treating physician.

In their observational study, Pirson and colleagues compared outcomes of patients who received EVT outside of the BASICS trial at study centers with those from non-study centers. Of 264 patients included, the majority (77%) had basilar artery involvement, with 51% receiving intravenous thrombolysis. A modified Rankin Scale score of 0 to 3 was achieved by 46% (115/252), and 43% (109/252) of patients died. Successful reperfusion was established in 75% (178/238), and symptomatic intracranial hemorrhage was rare, totaling 3% (9/264). Functional outcome was comparable between BASICS study centers and non-study centers (cOR: 0.77 [95%CI, 0.5-1.2]).

By |April 1st, 2022|clinical|Comments Off on Article Commentary: “Endovascular Treatment for Posterior Circulation Stroke in Routine Clinical Practice”

Target: Stroke: A Quality Improvement Measure That Successfully Reduced IV tPA Door-To-Needle Times

Mona Al Banna, MB BCh, Msc(Res)

Xian Y, Xu H, Smith EE, Saver JL, Reeves MJ, Bhatt DL, Hernandez AF, Peterson ED, Schwamm LH, Fonarow GC. Achieving More Rapid Door-to-Needle Times and Improved Outcomes in Acute Ischemic Stroke in a Nationwide Quality Improvement Intervention. Stroke. 2021.

Thrombolysis trials have shown that the benefits of tPA are time dependent, with the number needed to treat increasing from 4.5 when treated in the first 90 minutes to 14.9 when treated in the 3 to 4.5 hour window.1 National guidelines have established target goals for door-to-needle (DTN) times. However, rapid delivery thrombolytic therapy occurs infrequently in hospitals in the United States, and often these target goals are not met.

The authors of this study set out to evaluate DTN times and clinical outcomes in patients pre- and post- two successive nationwide quality improvement intervention initiatives between April 2003 and September 2018. The intervention was Target: Stroke, which is a QI initiative sponsored by the American Heart Association/American Stroke Association (AHA/ASA) to assist hospitals in improving DTN times. Target Stroke I provided participating hospitals with best practice strategies, supporting tools, and educational resources. An expert working group performed a systematic review and identified 10 best practice strategies that could be rapidly, feasibly, and cost-effectively adopted. These strategies included things such as EMS pre-notification, rapid acquisition of brain imaging and premixing tPA. In addition, an annual honor roll recognition program for hospitals achieving the DTN goal was also implemented to incentivize institutions. For Target: Stroke phase II, best practice strategies of direct EMS transfer of patients to imaging, updated comprehensive educational materials, customizable clinical decision support tools and performance feedback were made available to the participating institutions. The goal of Target: Stroke Phase I was to achieve DTN times within 60 minutes in at least 50% of ischemic stroke patients treated with tPA. Target: Stroke Phase II set the goal of achieving DTN times ≤60 minutes in 75% and ≤45 minutes in 50% of patients treated with tPA. The authors also evaluated clinical outcomes, including mortality, symptomatic ICH, discharge destination and functional outcomes at discharge and analyzed these trends before and after the initiation of Target: Stroke Phase I and Phase II programs.

By |March 31st, 2022|clinical|Comments Off on Target: Stroke: A Quality Improvement Measure That Successfully Reduced IV tPA Door-To-Needle Times

Stroke Risk Factors in Young Black and White Patients

Kevin O’Connor, MD

Aradine EM, Ryan KA, Cronin CA, Wozniak MA, Cole JW, Chaturvedi S, Dutta TLM, Hou Y, Mehndiratta P, Motta M, et al. Black-White Differences in Ischemic Stroke Risk Factor Burden in Young Adults. Stroke. 2022;53:e66–e69.

Aradine et al. explore differences in diabetes, hypertension, and smoking in Black patients and White patients as risk factors for ischemic stroke using data from the Stroke Prevention in Young Adults Study. The study population (1044 cases and 1099 controls, aged 15-49 years) was recruited from first-time ischemic stroke patients in the Baltimore, Maryland, and Washington, DC, area between 1992 and 2008.

Black patients, regardless of gender, had a higher prevalence of diabetes, hypertension, and smoking than White patients. There was no significant difference in odds ratio (OR) for diabetes among men (Black OR 3.2, versus White OR, 3.6; P=0.77) or women (Black OR, 2.7 versus OR, 5.2; P=0.71). Although Black men had a higher OR for hypertension than White men (OR, 3.9 versus OR, 1.8; P=0.0008), there was no significant difference among women (Black OR, 2.4 versus White OR, 3.8; P=0.93). The OR for smoking, however, was higher among White men (OR, 2.2 versus OR, 1.5; P=0.03) and White women (OR, 2.9 versus OR, 1.7; P=0.007).

By |March 30th, 2022|clinical|Comments Off on Stroke Risk Factors in Young Black and White Patients

ISC 2022 Session: Effect of Marijuana on Brain Health

Fransisca Indraswari, MD

International Stroke Conference 2022
February 9–11, 2022
Session: Effect of Marijuana on Brain Health

Marijuana is perceived as a harmless drug, and its recreational use has gained popularity among young individuals. The concentration of active ingredients in recreational formulations has gradually increased over time, and high-potency illicit cannabinomimetics have become available. Marijuana use in the United States is increasing, particularly among adolescents and young adults, with about one-third of 12th graders and nearly half of college students reporting marijuana use in 2018. In addition, the use of marijuana medicinally and/or recreationally has been legalized or decriminalized in many states across the U.S. in the past 2 decades, and the concentration of tetrahydrocannabinol (THC, the psychoactive component in marijuana) in cannabis products has increased significantly, from about 4% in 1995 to 15% in 2018.1

By |March 29th, 2022|clinical, Conference|Comments Off on ISC 2022 Session: Effect of Marijuana on Brain Health

Is Atrial Fibrillation an Independent Risk Factor for Venous Thromboembolism?

Wern Yew Ding, MBChB

Hornestam B, Adiels M, Wai Giang K, Hansson PO, Björck L, Rosengren A. Atrial fibrillation and risk of venous thromboembolism: a Swedish Nationwide Registry Study. Europace. 2021;23:1913-1921.

Thromboembolism is a major cause of global mortality. The risk of thromboembolism with atrial fibrillation (AF) is well established. However, most studies on this topic have focused on the risk of stroke and systemic arterial embolism. The risk of venous thromboembolism (VTE) in association with AF is less studied or even recognized in clinical practice.

In this study, Hornestam and colleagues investigated the relationship between AF and total VTE, including pulmonary embolism (PE) and deep venous thrombosis (DVT). The authors utilized the Swedish National Inpatient Register to identify patients with a first diagnosis of AF and no prior history of stroke, PE, DVT, or pulmonary hypertension along with matched controls by sex, age, and county from 1987 to 2013. The final cohort consisted of 463,244 patients with AF and 887,336 controls without AF. The main findings of the study were that patients with AF had a significantly greater risk of PE, DVT, and VTE compared to matched controls, particularly in younger patients and females, after accounting for other risk factors. Moreover, patients were at greatest risk of VTE (and DVT and PE) during the initial 1 month (male: HR 6.64 [95% CI, 5.74 – 7.69]; female: HR 7.56 [95% CI, 6.47 – 8.83]), but this risk declined over time and did not persist beyond the first year.

By |March 28th, 2022|clinical|Comments Off on Is Atrial Fibrillation an Independent Risk Factor for Venous Thromboembolism?

Role of Ferric Ions in Formation of Arteriolar Microvasospasms After Subarachnoid Hemorrhage

Kristina Shkirkova, BSc

Liu H, Schwarting J, Terpolilli NA, Nehrkorn K, Plesnila N. Scavenging Free Iron Reduces Arteriolar Microvasospasms After Experimental Subarachnoid Hemorrhage. Stroke. 2021;52:4033–4042.

This study investigated the role of Ferric ions (Fe3+) in the mechanism of microvasospasms secondary to subarachnoid hemorrhage (SAH). Unlike a rapid spike and decrease in intracranial pressure immediately after subarachnoid hematoma, prolonged reduction in cerebral blood flow due to microvasospasms produces a global state of cerebral ischemia that lasts beyond the acute phase of SAH. The acute nature of SAH hematoma damage coupled with prolonged and often delayed states of vasospasm contributes to tissue ischemia and subsequent posthemorrhagic brain damage in SAH.

Previous studies have implicated the role of nitric oxide (NO) in the regulation of cerebral blood flow in the brain and observed a significant decrease in NO levels after SAH. A reduction in microvasospasms was observed when exogenous NO was supplied after SAH.

By |March 25th, 2022|basic sciences|Comments Off on Role of Ferric Ions in Formation of Arteriolar Microvasospasms After Subarachnoid Hemorrhage

Neuroprotective Effects of Small Extracellular Vesicles in Stroke of the Aged: A Further Step Toward Clinically Relevant Stroke Research

Aurora Semerano, MD

Wang C, Börger V, Mohamud Yusuf A, Tertel T, Stambouli O, Murke F, Freund N, Kleinschnitz C, Herz J, Gunzer M, et al. Postischemic Neuroprotection Associated With Anti-Inflammatory Effects by Mesenchymal Stromal Cell-Derived Small Extracellular Vesicles in Aged Mice. Stroke. 2022;53:e14–e18.

Age is the most important non-modifiable stroke risk factor. Over 80% of ischemic strokes occur in people aged 65 years and older. Elderly patients with stroke have higher mortality, greater disability, and longer hospitalizations, they receive less evidence-based care, and they are less likely to be discharged to their original place of residence.1 Understanding the mechanisms of increased vulnerability that occurs with age is pivotal to reveal new therapeutic opportunities for stroke.

A profound dysregulation of the immune system is observed in elderly people, and it is commonly referred to with the term “inflamm-ageing”,2 characterized by a persistent subtle increase of inflammatory stress accompanied by a blunted inflammatory response to immunogenic triggers. “Inflamm-ageing” likely contributes to the pathophysiology of different age-dependent conditions, including stroke. Patients with ischemic stroke showed increased plasma levels of the pro-inflammatory cytokine TNF-α with age.3 A transcriptomic analysis of peripheral blood RNA in patients with acute ischemic stroke revealed differential expression in aged and young patients, mostly in genes associated with altered B-cell receptor signaling, lymphocyte proliferation, and leukocyte homeostasis.4 In human postmortem brain tissue, age positively correlates with neutrophil infiltration, MMP-9 expression, and hemorrhagic transformation.5 However, studying ageing and its consequences in humans is tricky as other cerebrovascular risk factors can operate as confounders. In this context, experimental stroke in rodents offers the advantage to isolate the effects of ageing. TNF-α inhibition restored the volume of cerebral infarct, neuromotor performance, and survival rates in aged stroke mice to the levels observed in young ones.3 After middle cerebral artery occlusion (MCAO), aged animals reconstituted with young bone marrow showed reduced behavioral deficits and significantly fewer brain-infiltrating neutrophils compared to younger controls.5

By |March 24th, 2022|basic sciences|Comments Off on Neuroprotective Effects of Small Extracellular Vesicles in Stroke of the Aged: A Further Step Toward Clinically Relevant Stroke Research