American Heart Association


Blood pressure variability and acute stroke.

Russell Mitesh Cerejo, MD 

Manning LS, Rothwell PM, Potter JF, and Robinson TG. Prognostic Significance of Short-Term Blood Pressure Variability in Acute Stroke: Systematic Review. Stroke. 2015 

Appropriate management of blood pressure in acute stroke has always a moving target. In a meta-analysis of 18 studies, Dr. Manning and her group evaluated the effect of blood pressure variability within the first seven days after a stoke on short and long term outcomes. None of the studies were randomized controlled trials (RCT) but seven studies were of a prospective observational nature, five were observational analyses of prospective stroke registry data and six were observational analyses of previous RCT data. Seven studies were deemed suitable for the final meta-analysis of blood pressure variability on functional outcome. 

The group found that greater variability in blood pressure early after acute stroke might be associated with an increased risk of death and disability. Early on, systolic blood pressure variation was also associated with hemorrhagic complications after thrombolysis. However no effect was seen on short-term functional or neurological outcomes.

There was considerable heterogeneity in the studies that were reviewed by the group. The authors stress the importance of standardized practice for reporting of blood pressure measurements, blood pressure medications and timing with respect to the stroke onset. This will help draw robust conclusion in the future with regards to blood pressure management in acute stroke care.

By |August 28th, 2015|prognosis|Comments Off on Blood pressure variability and acute stroke.

CHA2DS2VASc score as a predictor of recurrent stroke in non-AF patients.

Jay Shah, MD 

Andersen SD, Gorst-Rasmussen A, Lip GYH, Bach FW, and Bjerregaard Larsen TB. Recurrent Stroke: The Value of the CHA2DS2VASc Score and the Essen Stroke Risk Score in a Nationwide Stroke Cohort. Stroke. 2015  

There is great interest in developing clinical scoring systems that stratify patients based upon ischemic stroke risk profiles. CHA2DS2VASc score is one such system where congestive heart failure, hypertension, age 65-74 years, diabetes, peripheral artery disease, and female gender earn a point while history of stroke or TIA and age >75 register 2 points. This score has been validated in patients with atrial fibrillation (AF) and is utilized to determine anticoagulation candidacy. It has also been shown to predict recurrent stroke in non-AF population but has not been adequately replicated. In this observational cohort study, the authors assessed the ability of CHA2DS2VASc score to predict recurrent stroke, death, and cardiovascular event using registry-based data of adults without AF and first-time stroke across a 10-year span. Essen Stroke Risk Score, a risk score specifically developed for the stroke population, was also calculated as a comparison. It allocates one point for age 65-75 years (2 for >75), hypertension, diabetes, myocardial infarction, other cardiovascular disease, peripheral arterial disease, smoking and previous stroke or TIA.

The cohort consisted of 42,182 patients. Patients were followed-up for an average of 3.5 years. Mean CHA2DS2VASc score was 4.3 and mean Essen Stroke Risk Score was 2.4. Increasing values of both scoring systems were associated with an increased risk of all three outcomes. One and five-year hazard ratios for CHA2DS2VASc score of > 7 were 1.56 and 1.90, respectively. Essen Stroke Risk Score had marginally better discriminatory performance in relation to stroke recurrence.

The difference in stroke recurrence rates between the lowest and highest risk scores were fairly modest, as reflected in the low hazard ratios (hazard ratio of 1.2 in CHA2DS2VASc score of 4 versus 1.56 in CHA2DS2VASc score of > 7). This implies that incremental addition of stroke risk factors only minimally increased stroke risk and prior ischemic infarct results in much higher baseline risk outweighing the impact of other risk factors. Overall, the CHA2DS2VASc score did correlate with increased risk of stroke, death, and cardiovascular events but further refinement is needed and clinical application and decision making based upon the score in this population may be premature. An area of further interest would be to determine mechanism of stroke recurrence and evaluate if there is correlation with clinical scoring systems. Finding such an association would help guide tailored therapy thereby decreasing stroke risk.

By |August 11th, 2015|prognosis|Comments Off on CHA2DS2VASc score as a predictor of recurrent stroke in non-AF patients.

Seizures After Stroke in Young Adults Are Associated with Mortality

Mark N. Rubin, MD
Arntz RM, Rutten-Jacobs LCA, Maaijwee NAM, Schoonderwaldt HC, Dorresteijn LDA, van Dijk EJ, and de Leeuw FE. Poststroke Epilepsy Is Associated With a High Mortality After a Stroke at Young Age: Follow-Up of Transient Ischemic Attack and Stroke Patients and Unelucidated Risk Factor Evaluation Study. Stroke. 2015 

As if decades of disability or premature death is not enough for young adults who suffer an ischemic stroke, the development of post-stroke epilepsy – which is not entirely rare – is associated with a dramatic climb in short- and long-term post-stroke mortality. 

The authors of this study bring us the results of a large Dutch cohort (631 patients) recruited over a 30 year period (1980-2010) with substantial follow up (mean 12.5 years) scrutinizing the association between post-stroke epilepsy and mortality in young adults (age 18-50 years). Overall 76 of the patients (~12%) developed epilepsy in their post-stroke course. The cumulative 30-day case fatality difference was astounding: 27.4% vs 2.1% in those with and without post-stroke epilepsy, respectively. After adjusting for confounders, the development of epilepsy remained independently associated with mortality (HR 4.8, 95% CI 1.7-14), with the index stroke being the major cause of death in these patients.

There are other data that provide nuance to the consideration of post-stroke epilepsy as a reason to raise the hairs on the back of a provider’s neck, but the punchline is thus: a stroke severe enough to cause a seizure is also severe enough to take a life. It’s a Biomarker of Badness, although not quite so bad being singled out by Oscar!

By |July 23rd, 2015|prognosis|Comments Off on Seizures After Stroke in Young Adults Are Associated with Mortality

White Matter Lesions Increase the Risk of Intracerebral Hemorrhage after Thrombolysis

Cerebral white matter lesions (WML), a manifestation of small vessel disease, has been associated with intracerebral hemorrhage (ICH). In this report, Curtze et al evaluated the risk of spontaneous ICH conferred by WML in ischemic stroke patients treated with intravenous thrombolysis (IVT). 

2485 consecutive patients treated with IVT over a 14 year period at the Helsinki University Central Hospital were evaluated. In addition to the baseline CT completed prior to IVT administration, a 24-hour post-IVT head CT scan was routinely done in this cohort (as well as when ICH was suspected). Symptomatic ICH (sICH) was defined per the ECASS-2 criteria; remote parenchymal hemorrhage was also assessed. WML grading (by four visual rating scales – Gorter scale, van Swieten scale, Blennow rating scale, and Wahlund rating scale) was completed from baseline CT scans by stroke neurologists blinded to patient data and outcomes.

124 patients developed sICH (5%). All of the rating scales (tested as continuous variables and dichotomized with different cut-off points) were associated with an increased risk of sICH (in univariate and multivariate models). A Wahlund scale score >1 (at least moderate focal WML) conferred a 2.7 (95% CI 1.87-3.90) higher odds of developing sICH in univariate analysis. This association remained (OR 2.64, 95% CI 1.71-4.02) even after adjusting for confounding variables. A Blennow score of 5 had the highest association with sICH (OR 3.59, 95% CI 1.72-7.5) in multivariate analysis. A Blennow score >4 (high burden of WML) also was associated with remote parenchymal hemorrhage (multivariable adjusted OR 4.11, 95% CI 2.38-7.1).

This study suggests that IVT-eligible patients with moderate-to-severe WML on baseline CT could have over two-fold higher risk of sICH. It the largest study on this topic; prior reports have evaluated smaller cohorts and demonstrated conflicting results. The notable limitations to this study are that it did not include a non-IVT treated stroke patient cohort and that it was a retrospective analysis. Though multiple factors contribute to sICH risk after IVT, this association should be kept in mind when discussing IVT with patients.

By |July 13th, 2015|prognosis, treatment|Comments Off on White Matter Lesions Increase the Risk of Intracerebral Hemorrhage after Thrombolysis

Early recurrence and cerebral bleeding in patients with acute ischemic stroke and AF

Rajbeer Singh Sangha, MD

Paciaroni M, Agnelli G, Falocci N, Caso V, Becattini C, Marcheselli S, et al. Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation: Effect of Anticoagulation and Its Timing: The RAF Study. Stroke. 2015 

The authors of this study tackled an important question and one that has always been a grey area for stroke neurologists. They looked to answer the question of when anticoagulation should be initiated following a cardioembolic stroke. This international prospective multicenter study looked at three main questions which included the risk of recurrent ischemic events and bleeding following a cardioembolic stroke, the risk factors which are associated with these events and finally what is the rate of recurrence and bleeding when anticoagulation has been initiated.

The study looked at 1029 patients out of which 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or TIA or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding and 14 (1.4%) major extracranial bleeding. Primary study outcome looked at recurrent ischemic cerebrovascular events (stroke or TIA) and symptomatic systemic Embolisms and also symptomatic cerebral bleedings and major extra-cerebral bleeding at 90 days. At 90 days, 50% of the patients were either deceased or disabled (mRS≥3), and 10.9% were deceased. Factors predictive of the primary study outcomes included CHA2DS2-VASc score, high NIHSS, large ischemic lesion and type of anticoagulant. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared to initiating treatment before the aforementioned time period. About 7% of the patients treated with oral anticoagulants alone had an outcome event compared to 16.8% and 12.3% of the patients treated with low molecular weight heparins (LMWHs) alone or followed by oral anticoagulants, respectively (p=0.003).

Patients who received a direct oral anticoagulant were found to have low risks for both
symptomatic intracranial bleeding (2.1%) and ischemic event (4.3%), suggesting the need for further testing the new class of novel anticoagulant drugs in the acute phase of ischemic stroke in patients with AF. The advent of the novel anticoagulants has allowed for a reduction not only in ischemic events secondary to AF but also reduced bleed rates and thus I ask how far can we push the boundaries of starting these medications before we run into greater risks than benefits. This topic continues to be one of contention as the point in time to start anticoagulation is likely to be stratified secondary to multiple factors; perhaps a composite score should be created and tested in future studies.

A circulating soluble blood molecule (sCD40L) a marker for recurrent stroke?

Prachi Mehndiratta, MD

Li J, Wang Y, Lin J, Wang D, Wang A, Zhao X, et al. Soluble CD40L Is a Useful Marker to Predict Future Strokes in Patients With Minor Stroke and Transient Ischemic Attack. Stroke. 2015   

Soluble CD40 ligand (sCD40L) has been associated with ischemic cardiovascular events. The authors of this study sought an association of sCD40L with recurrent stroke. A total of 5170 participants in the CHANCE study (Clopidogrel in High Risk patients with Acute Non Disabling Cerebrovascular Events) were studied. Serum samples for sCD40L were collected within 24+/- 12 hours of initial event and the primary outcome was recurrent stroke within 90 days. In addition high sensitivity C Reactive Protein (hs-CRP) was also measured.

Cox proportional hazards model was utilized to determine the association between ligand levels and stroke. Seventy-three centers participated in the biomarker study and a total of 3044 patients were enrolled. Patients with high sCD40L levels were categorized into tertiles and the highest tertile of patients were younger, with a history of hypercholesterolemia, higher baseline cholesterol and leukocyte counts. These patients had the highest risk of recurrent stroke. An interaction was noted between hs-CRP and sCD40L and increased recurrent stroke (HR 1.81, 95% CI 1.23-2.68, p = 0.003).

So is measurement of sCD40L warranted in all our stroke patients? Is it ready for prime time? I don’t think so. While the findings are certainly intriguing, we need to sort out the etiologic role of this ligand. Is it just another inflammatory molecule or is it really predictive of recurrent events? What happens to these levels further out from the acute event? Is it elevated in other stroke types? What about non atherosclerotic vasculopathies that result in ischemic events? Is testing cost effective? There are too many questions at this point that need to be answered before we translate this test to real life

By |June 9th, 2015|prognosis|Comments Off on A circulating soluble blood molecule (sCD40L) a marker for recurrent stroke?

Does Stroke Contribute to Racial Differences in Cognitive Decline?

Rajbeer Singh Sangha, MD

Levine DA, Kabeto M, Langa KM, Lisabeth LD, Rogers MAM, and Galecki AT. Does Stroke Contribute to Racial Differences in Cognitive Decline? Stroke. 2015

The authors of this study tackle the interesting topic of racial disparities in dementia due to the fact that older non-Hispanic blacks have greater risk (approximately 2x) of having cognitive decline, including Alzheimer’s disease and vascular dementia, than older non-Hispanic whites. They investigated whether racial differences in cognitive decline are explained by differences in the frequency or impact of incident stroke between blacks and whites, controlling for baseline cognition. 

The study analyzed 4,908 black and white participants aged 65 and above free of stroke and cognitive impairment. They examined longitudinal changes in global cognition by race, before and after adjusting for time-dependent incident stroke followed by a race-by-incident strokes. They identified 34 of 453 (7.5%) blacks and 300 of 4,455 (6.7%) whites with incident stroke over a mean (SD) of 4.1 (1.9) years of follow-up (P=0.53). Blacks had greater cognitive decline than whites and even with further adjustment for cumulative incidence of stroke, the black-white difference in cognitive decline persisted. While incident stroke was associated with a decrease in global cognition corresponding to approximately 7.9 years of cognitive aging it did not statistically differ by race (P=0.52).

The authors conduct a study which addresses an important issue of whether strokes disproportionately affect cognitive decline in the non-Hispanic black population. The racial disparities that exist in cognitive decline for the two populations would be difficult to discern as the contribution of multiple factors plays a role in the process. Contributions from genetics, socio-economic status and education levels, as well as multiple other factors play a significant role in cognitive decline in racial groups. One of the questions I have for the authors is whether they looked at varying types of cognitive declines (i.e. MCI vs vascular dementia vs Alzheimers) to see if incident stroke played a more significant role in the varying subtypes of dementia. They also acknowledge the limitation that strokes in certain areas were not analyzed as this may predispose an individual to develop more severe deficits in cognition than strokes in other regions. As imaging modalities improve and our understanding of dementia as well as the effect strokes in certain regions of the cerebrum have on functioning, we may be able to better discern the effect of vascular disease on cognitive decline.

By |June 5th, 2015|prognosis|Comments Off on Does Stroke Contribute to Racial Differences in Cognitive Decline?

Left Atrial Enlargement and Recurrent Stroke

Rizwan Kalani, MD

Yaghi S, P. Moon YP, Mora-McLaughlin C, Willey JZ, Cheung K, Di Tullio MR, et al. Left Atrial Enlargement and Stroke Recurrence: The Northern Manhattan Stroke Study
. Stroke. 2015 

Left atrial enlargement (LAE) is associated with paroxysmal atrial fibrillation (AF), first-ever ischemic stroke, and detection of AF after cryptogenic stroke. In this report, Yaghi et al evaluated the association of LAE and recurrent stroke.

The authors identified first-ever ischemic stroke patients from the Northern Manhattan Stroke Study (NOMASS). 95% of the enrolled patients completed an electrocardiogram and cardiac telemetry monitoring with their first stroke. Transthoracic echocardiogram (TTE) was completed within three months of the initial infarct and the size of the left atrium (LA) was measured by its anteroposterior diameter. In cases where accurate measurement was not possible, a qualitative assessment was completed – there was excellent agreement between the two methods in the patients that had both done. Normal LA size was categorized into four groups – normal, mild LAE, moderate LAE, and severe LAE. Over a five year follow-up period, stroke occurrence and etiologic subtype (based on the TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria) was tracked. The primary outcome for this study was total recurrent ischemic stroke and the secondary outcome was combined recurrent cardioembolic or cryptogenic infarct. 


529 patients with a first stroke had LA size data available. The mean age was 69 years and average LA diameter was 40.6 mm (standard deviation 6.3 mm). 279 (53%) had normal LA size, 167 (32%) had mild LAE, and 83 (16%) had moderate-severe LAE. Over a median of 4 year follow-up period, 80 patients (15%) had recurrent stroke; 65 were ischemic, of which 13 were cardioembolic and 16 were cryptogenic. LA diameter and moderate-severe LAE were not associated with the risk of total recurrent ischemic stroke. However, those with moderate-severe LAE had a greater risk of recurrent (combined) cardioembolic or cryptogenic stroke (unadjusted model HR 4.35, 95% CI 1.81-10.48). When adjusting for baseline demographics and risk factors (including AF, heart failure) the association was still present (adjusted HR 2.83, 95% CI 1.03-7.81). Mild LAE was not associated with recurrent cryptogenic or cardioembolic stroke. LA diameter (assessed as a continuous variable) was also associated with a higher risk – adjusted HR 1.55 per SD change in LA diameter (95% CI 1.01-2.37). Finally, none of the patients with moderate-severe LAE were found to have AF at time of recurrent infarct.

This study demonstrates that, in patients with ischemic stroke, moderate-severe LAE is an independent risk factor for recurrent cryptogenic or cardioembolic infarct. Evaluation for LAE, along with other clinical markers of atrial dysfunction – N-terminal pro-brain natriuretic peptide, p-wave terminal force in lead V1 on EKG, and paroxysmal supraventricular tachycardia – may identify a population with elevated risk of stroke even in the absence of paroxysmal AF. This may allow for development of improved risk prediction models for risk of stroke and systemic embolism in patients with an “atrial cardiopathy” (of which paroxysmal AF may only be one manifestation). Additionally, this could identify a group of cryptogenic stroke patients who benefit from anticoagulation over antiplatelet therapy. An important limitation to this study was that prolonged AF monitoring was not routinely conducted, and thus occult AF may not have been detected in some of these patients. Also, LA volume was not assessed in this study, which is a better reflection of LA size than its diameter.

By |May 26th, 2015|prognosis|Comments Off on Left Atrial Enlargement and Recurrent Stroke

To treat, or not to treat? That’s the question

Chirantan Banerjee, MD

Backes D, Rinkel GJE, van der Schaaf IC, Nij Bijvank JA, Verweij BH, Visser-Meily JMA, et al. Recovery to Preinterventional Functioning, Return-to-Work, and Life Satisfaction After Treatment of Unruptured Aneurysms. Stroke. 2015

The cerebral vasculature, as well as unruptured intracranial aneurysms (UIAs) are complex biologic entities. Their behavior cannot be ascribed to just their location and size. A multidisciplinary international research group published a consensus statement in Stroke (Stroke. 2014;45:1523-1530) in 2014 which echoed this sentiment. We do not have a prospective randomized double blind clinical trial to base decisions on whether and how to treat UIAs. The TEAM trial aimed at assessing the role of prophylactic vascular intervention of UIAs, but never materialized due to poor recruitment. 

In order to advance the science of treating UIAs, we need risk prediction models of rupture. PHASES score was proposed in 2013 by Greving et al where pooled data from 8382 participants in six prospective cohort studies was used, and age, hypertension, history of SAH, aneurysm size, aneurysm location, and geographical region were the predictors of 5 year rupture risk. In addition, risk prediction models for complications of interventions (surgical vs endovascular) are also needed in order to carry out an informed decision analysis on a patient with UIA. In the current study, Backes et al carried out a cross-sectional survey of functional status, working capacity and life satisfaction in 159 patients treated with microsurgery or endovascular intervention for UIA between Jan 1st 2000 and Jan 1st 2013. The questionnaire was sent out in June 2014, and 69% (110) patients responded. 81% patients reported complete recovery after treatment. With regards to life satisfaction (measured using validated LiSat score), patients with high life satisfaction decreased from 76% before treatment to 52% during recovery, and 67% in the long term.

 These findings underlie the important concept that in addition to aneurysm and patient characteristics, treatment effects also should play an integral role in the decision analysis of whether and how to treat a UIA in a patient. An unnecessary intervention may end up doing more harm that good.

By |May 20th, 2015|prognosis|Comments Off on To treat, or not to treat? That’s the question

Four Year Follow up of Transient Ischemic Attacks, Strokes and Mimics: A Retrospective TIA Clinic Cohort Study

Daniel Korya, MD

Frequently, patients who have transient neurologic symptoms are referred to the emergency department where they may receive further work-up. The usual TIA work-up may ensue after more precise questioning and examination are performed to rule out TIA mimics.

Several studies have been conducted to evaluate the prognosis and outcome of patients after TIA is diagnosed in the hospital or emergency department. The study by Dr. Dutta and colleagues is different because it aimed to determine the prognosis and outcome of patients who were evaluated for TIA at designated daily TIA clinics, based on the EXPRESS study model. 

Although the great majority of patients referred to TIA clinics by non-specialists end up being TIA mimics, there may be a difference in the way they are managed as compared with the ED or hospital. This may be due to the fact that several studies have shown that the TIA mimics are often the result of posterior circulation insufficiency, coronary events or dementia. Therefor a more specialized work-up may be necessary to distinguish these cases.

This study was conducted in the UK and derived data from the TIA clinics of Gloucestershire Royal Hospital (GRH) between April 2010 and May 2012. The majority of practitioners that referred to the GRH were EDs, GPs and paramedics. After a patient was referred to the TIA clinic, they would have their risk factors evaluated, a history and exam would be done along with same-day investigations of CT head, carotid duplex ultrasounds, EKGs as well serum studies. If patients needed MRIs, echocardiograms, Holter monitoring or angiograms, these were done subsequently as required. Patients received treatment the same day as well, with statins, anti-platelet agents or oral anti-coagulants (if AF was diagnosed).

The outcome measures were pre-defined as stroke, MI, any vascular event (TIA, stroke or MI) and all-cause mortality. These were assessed by reviewing hospital records electronically and not by direct patient contact. The investigators looked at subsequent hospital admissions, discharge summaries, outpatient referrals and death. There were no patients lost to follow up and statistical analysis was done by univariate comparison of the TIAs, stokes and mimics with the chi-squared and Kruskal-Wallis tests.

In all, there were 1067 patients that were included in the study who presented to the TIA clinic within the time period of April 2010 and May 2012. Of these patients, 337 were diagnosed with TIA, while 189 were actually strokes and 538 were mimics. The median follow-up period was for 34.9 months. At 90 days, 0.9% of TIAs had a stroke, 2.1% of patients with strokes had a subsequent stroke and 0.2% of mimics had suffered a stroke. Subsequent strokes occurred in 7.1% of patients with TIA, 10.9% of patients with stroke and 2.0% of mimics by the 50-month period of follow up.

Overall, the 90-day risk of subsequent stroke for patients receiving services at these daily TIA clinics was 1.3%. This rate is much lower than that demonstrated by prior studies conducted on TIA patients in the mid-2000s that ranged from 7.5%-9.4%. If these numbers are actually representative of reality, then they imply a reduction of stroke in TIA patients by over 80%!

Why was this number so low compared to historical rates? The investigators believed that this was due to the earlier and more focused treatment of stroke risk factors. These patients received their prescriptions in-hand after their evaluation and were quickly and appropriately assessed in these specialized clinics.

These results sound encouraging and are hinting toward the potential benefit of developing more daily TIA clinics. However, this study should be reproduced in a prospective manner with actual patient assessment and evaluation as opposed to a review of electronic medical records. At any rate, the dramatic reduction of subsequent stroke or MI after TIA as compared to historical controls is promising!
By |March 26th, 2015|prognosis|Comments Off on Four Year Follow up of Transient Ischemic Attacks, Strokes and Mimics: A Retrospective TIA Clinic Cohort Study