American Heart Association


Outcomes of Anticoagulation for Venous Thrombosis, a Meta-Analysis

Gurmeen Kaur, MBBS

Aguiar de Souza D, Neto LL, Canhão P, Ferro JM. Recanalization in Cerebral Venous Thrombosis: A Systematic Review and Meta-Analysis. Stroke. 2018

With the advent of the endovascular era for ischemic strokes, the role for endovascular therapy for cerebral venous thrombosis (CVT) has been approached with growing interest. However, anticoagulation continues to be the mainstay of treatment for CVT.

In this interesting meta-analysis, de Sousa et al reviewed recanalization rates, clinical outcomes and recurrence rates in patients with CVT.

A total of 468 studies were screened, of which 19 were identified after excluding those studies which had pediatric patients, in which >10% of individuals had endovascular treatment and in whom anticoagulation was not used as part of the post-operative treatment plan.

By |October 1st, 2018|clinical, prognosis|0 Comments

IV-tPA and Mechanical Thrombectomy – A Winning Team

Kevin S. Attenhofer, MD

Ferrigno M, Bricout N, Leys D, Estrade L, Cordonnier C, Personnic T, et al. Intravenous Recombinant Tissue-Type Plasminogen Activator: Influence on Outcome in Anterior Circulation Ischemic Stroke Treated by Mechanical Thrombectomy. Stroke. 2018

2015 was a big year for stroke. For the first time in 20 years, stroke practitioners demonstrated an effective tool in the treatment of acute ischemic stroke. Mechanical thrombectomy (MT) quickly became standard practice. While MT was proposed as an adjunctive therapy for stroke in addition to IV-rtPA (IVT), many of the 2015 trials, as well as the subsequent imaging based trials (DAWN, DEFUSE 3), included patients who did not receive IVT.

The benefit of MT was similar in patients who received IVT and MT compared to MT alone in some trials. This has led some to suggest that MT alone could be a treatment option which maximizes potential benefit while minimizing some of the risks associated with IVT (such as hemorrhage). In fact, I’ve seen non-neurology physicians advocate for MT to replace IVT entirely. Still, others argue that IVT facilitates MT (higher rate of successful recanalization, shorter procedures, and shorter time to recanalization) as well as dissolving distal clots. To date, no randomized controlled trial has compared combination IVT/MT versus MT alone. A recent meta-analysis of the 2015 thrombectomy trials seems to support the latter view: that IVT and MT are complimentary.

Does tPA Really Save Lives?

Kevin S. Attenhofer, MD

Muruet W, Rudd A, Wolfe C, and Douiri A. Long-Term Survival After Intravenous Thrombolysis for Ischemic Stoke: A Propensity Score-Matched Cohort with up to 10-Year Follow-Up. Stroke. 2018

Although tissue plasminogen activator (tPA) has been approved in the United States for treatment of acute ischemic stroke since the mid-90s, there persists a sharp divide between neurologists and the emergency medicine community regarding the safety and efficacy of tPA. Imbalances between the treatment and control groups in the NINDS tPA study, criticisms of the subjective nature of functional outcome scores, and allegations of conflicts of interest have all contributed to the lingering controversy surrounding tPA. I have personally encountered significant resistance and hostility to IV tPA from other providers over 20 years after its approval. In this article, Muruet et al. add to a growing volume of literature that should help the community neurologist assuage the concerns of fellow providers.

Predicting Blood in the Real World

Kevin S. Attenhofer, MD

Hilkens NA, Li L, Rothwell PM, Algra A, Greving JP. External Validation of Risk Scores for Major Bleeding in a Population-Based Cohort of Transient Ischemic Attack and Ischemic Stroke Patients. Stroke. 2018

You can’t discuss stroke prevention without talking about antiplatelet drugs. Drugs like Aspirin and Clopidigrel are frequently used by stroke neurologists as the secondary prevention treatment of choice for patients with TIA and non-cardioembolic ischemic strokes. However, we must remember that bleeding is a clinically important and potentially life-threatening side effect of these agents. Reliably predicting who is most likely to bleed would dramatically inform the clinician’s decision-making process and likely result in improved patient outcomes.

To that end, the S2TOP-BLEED score was derived from patient data from six randomized trials (CAPRIE, ESPS-2, MATCH, CHARISMA, ESPRIT, and PRoFESS). It is a 28-point score that incorporates readily available patient characteristics: Sex, Smoking history, Type of antiplatelet, Outcome (mRS), Prior stroke, Blood pressure, Low BMI, Elderly, Ethnicity, Diabetes. It was validated in the PERFORM trial (Prevention of Cerebrovascular and Cardiovascular Events of Ischemic Origin Terutroban in Patients with a History of Ischemic Stroke or Transient Ischemic Attack Study). In this paper, Hilkens et al. externally validate the S2TOP-BLEED score in observational data from a real-world setting.

Stressing Over Sugar: Prognostic Implications of Stress Hyperglycemia After Stroke

Kevin S. Attenhofer, MD

Pan Y, Cai X, Jing J, Meng X, Li H, Wang Y, et al. Stress Hyperglycemia and Prognosis of Minor Ischemic Stroke and Transient Ischemic Attack: The CHANCE Study (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events). Stroke. 2017

Diabetes is becoming increasingly prevalent worldwide, with over 30 million people diagnosed in the United States as of 2015. It is no secret that diabetes is an independent risk factor for stroke. In fact, mortality is higher and post-stroke outcomes are poorer in patients with stroke and uncontrolled glucose levels.

In some patients, a phenomenon of stress hyperglycemia is observed at the time of stroke. This is a relative increase in glucose during an acute critical illness. It is an ill-defined metric with no consistent definition in the literature. Previous studies have shown that stress hyperglycemia is a better predictive biomarker of critical illness than absolute hyperglycemia. The authors of this paper sought to determine an association between stress hyperglycemia and incidence of new stroke or TIA following index ischemic stroke.

Serum Gamma-Glutamyl Transferase at Time of Stroke is Associated With Post-Stroke Mortality and Recurrent, Fatal Stroke

Neal S. Parikh, MD 

Tu W, Liu Q, Cao J, Zhao S, Zeng X, Deng A. γ-Glutamyl Transferase as a Risk Factor for All-Cause or Cardiovascular Disease Mortality Among 5912 Ischemic Stroke. Stroke. 2017

In light of an increasing interest in and understanding of the association between liver disease and cerebrovascular disease, Wen-Jun Tu and colleagues sought to explore the association between serum γ-glutamyl transferase (GGT) and post-stroke mortality.

In their well-designed and well-powered prospective, multicenter cohort observational study, the authors enrolled 5,912 patients within 24 hours of acute ischemic stroke. The study was conducted in China. They excluded patients with known hepatobiliary disease and alcohol abuse. Serum GGT level at baseline was the exposure of interest, and patients were followed for a median of 1 year with regular telephone interviews and review of death certificates. The primary outcome was all-cause mortality, and cardiovascular death (including fatal stroke) was separately adjudicated. Men and women were analyzed differently because normative values for GGT are sex-specific.

Predicting Stroke Outcome with Multimodality CT

Kevin S. Attenhofer, MD

Dankbaar JW, Horsch AD, van den Hoven AF, Kappelle LJ, van der Schaaf IC, van Seeters T, et al. Prediction of Clinical Outcome After Acute Ischemic Stroke: The Value of Repeated Noncontrast Computed Tomography, Computed Tomographic Angiography, and Computed Tomographic Perfusion. Stroke. 2017

A significant aspect of stroke care is the long-term ramifications with respect to a patient’s ability to manage their activities of daily living. Part of the physician’s role is to help the patient navigate this challenge to maintain as much independence as possible. Understanding likely outcomes helps set the stage for realistic expectations and goals. Today, the most commonly used metric to score outcomes is the modified Rankin scale (mRS) performed well after the index event (often 90 days).

In stroke research, follow-up imaging markers such as computed tomographic angiography (CTA) recanalization and computed tomographic perfusion (CTP) reperfusion are sometimes used as proxy measurements for clinical outcomes. In this study, Dankbaar et al. used multimodality commuted tomography to predict mRS at 90 days.

By |September 11th, 2017|clinical, prognosis|0 Comments

Stroke Risk Stratification in Non-Valvular Atrial Fibrillation — Validating CHA2DS2-VASc in an Asian Cohort

Gurmeen Kaur, MBBS

Kim T, Yang P, Uhm J, Kim J, Pak H, Lee M, et al. CHA2DS2-VASc Score (Congestive Heart Failure, Hypertension, Age ≥75 [Doubled], Diabetes Mellitus, Prior Stroke or Transient Ischemic Attack [Doubled], Vascular Disease, Age 65–74, Female) for Stroke in Asian Patients With Atrial Fibrillation: A Korean Nationwide Sample Cohort Study. Stroke. 2017

Non-valvular atrial fibrillation (AF) is a cause of at least 15-20% of strokes in the U.S., with a 5-times increased risk when compared to patients with no atrial fibrillation. The safety, efficacy and availability of oral anticoagulants, in addition to Vitamin K antagonists like warfarin, have made strokes secondary to atrial fibrillation virtually preventable. This has created a need for accurate Stroke Risk Assessment and Stratification.

Various stroke risk schemas over the years have included AFI/ SPAF (1994), CHADS2 (2001), Framingham (2003), NICE (2006) and the relatively recent CHA2DS2-VASc Score, also referred to as Birmingham 2009, that accounts for congestive heart failure, hypertension, 75 years of age and older (2 points), diabetes mellitus, previous stroke or transient ischemic attack (2 points), vascular disease, 65 to 74 years of age, female sex.

Kim et al study a total of 5855 oral anticoagulant (OAC) naïve patients with AF to determine whether the CHA2DS2-VASc score could be reliably used for the Asian population, because the validation studies were performed in an all-Caucasian cohort and various Asian studies have previously reported ethnic differences in the conventional stroke risk factors.

By |August 14th, 2017|clinical, prognosis|0 Comments

As in adults, TIA heralds stroke in Children

Alexander E. Merkler, MD

Lehman LL, Watson CG, Kapur K, Danehy AR, and Rivkin MJ. Predictors of Stroke After Transient Ischemic Attack in Children. Stroke. 2015

Pediatric stroke is a leading cause of death and disability in children. In adults, stroke occurs in 10-15% of adults within 3 months of transient ischemic attack (TIA), but little is known about risk of stroke after TIA in children. In this manuscript, Dr. Lehman et al evaluate predictors of stroke after TIA in children.

63 children were identified as having a TIA at Boston Children’s Hospital. TIA was defined using the time-based definition: a focal neurological deficit that resolved within 24 hours. All patients were required to have an MRI within 3 months of TIA. Similar to adults, almost 80% of patients had motor symptoms. Headache accompanied TIA in 54% of children, but only 10% of patients carried a diagnosis of migraine.

After a median follow-up of 4.5 years, 10/63 children (16%) developed MRI evidence of stroke, 4 (6%) of whom had imaging evidence of stroke at the time of TIA, and 8 (13%) of whom developed new imaging evidence of ischemic injury not seen on the MRI done at the time of TIA.

Independent predictors for stroke after TIA included female sex (OR 11.3, 95% CI, 1.3-98.7), cerebral arteriopathy (OR 24.5, 95% CI, 4.0-149.8), and presence of autoimmune disorders (OR 26.5, 95% CI, 3.6-191.6).

Limitations included 1) small number of patients and therefore wide confidence intervals; 2) retrospective design; 3) use of a time-based definition of TIA thereby likely included cerebrovascular mimics such as migraine.

Overall, similar to adults, children with TIA seem to have a significant risk of developing a stroke. Risk factors for stroke after TIA include female sex, cerebral arteriopathy, and presence of an autoimmune disorder. Further research will be necessary to confirm these findings and help prevent the development of stroke in the pediatric population.

By |December 23rd, 2015|prognosis|0 Comments

Copeptin: a promising marker in risk stratification after ischemic stroke and TIA

Luciana Catanese, MD

Griesenegger S, Segal HC, Burgess AI, Poole DL, Mehta Z, Rothwell PM. Copeptin and Long-Term Risk of Recurrent Vascular Events after TIA and Ischemic Stroke: Population-Based Study. Stroke. 2015.

Copeptin is a stress hormone released in an equal proportion to vasopressin (AVP), and serves a surrogate marker for the hypothalamo-pituitary-adrenal axis. Prior literature has suggested that Copeptin is a promising prognostic biomarker in vascular diseases such as MI, CHF and ischemic stroke/TIA. However, the prognostic value of Copeptin in regard to long-term risk of vascular events after TIA and stroke remains uncertain.

In this issue of Stroke, Griesenegger et al. present a longitudinal population-based study with a mean follow–up of 5.7 years, to determine whether Copeptin levels could predict the long-term risk of vascular events in patients with TIA or ischemic stroke. The authors also contrasted Copeptin level amongst different etiological subtypes of stroke/TIA.

Of 92,728 individuals in the Oxford Vascular Study, 1076 eligible patients (mean age 75) with TIA, minor and major ischemic stroke recruited from 2002-2007, were included. Copeptin level was obtained at baseline (median time to sampling 5 days) and repeated in 384 patients after one year.

After about 6000 patient-years of follow-up, the cox regression analysis including age, sex, hypertension, diabetes, previous MI, stroke, peripheral vascular disease, smoking, CHF, atrial fibrillation, and treatment with antiplatelets, statins or antihypertensive agents, showed that Copeptin significantly predicted subsequent vascular events (HR 1.47), recurrent ischemic stroke (HR 1.22), vascular death (HR 1.85) and all cause death (HR 1.75). The predictive value of Copeptin was greatest following a cardioembolic cerebrovascular event. Moreover, Copeptin outperformed other circulating biomarkers of thrombosis, inflammation and neuronal/myocardial injury within this population.

Inclusion of Copeptin into a model containing the aforementioned vascular risk factors improved the model’s predictive ability for recurrent vascular events, vascular death, death and recurrent stroke by 32%, 55%, 66% and 16%, respectively.

Overall, Copeptin seems to be a promising biomarker in risk stratification after ischemic stroke and TIA, particularly in patients with cardiogenic strokes/TIA. One of the main limitations of the study is the lack of adjustment for other possible confounding factors, such as indices of cardiac function. Therefore, further validation of these findings with the inclusion of cardiac markers is warranted.

By |November 10th, 2015|prognosis|0 Comments