American Heart Association

Monthly Archives: July 2013

SIS validation

For those who have seen patients who have suffered a stroke, it is very clear that stroke is a life-changing disabling disease. Its high prevalence makes stroke the leading cause of disability in adults from the industrialized world. Measuring the degree of disability after a stroke is, however, less clear. In this paper, researcher from England tested the American-born, 8-dimension Stroke Impact Scale (SIS) and applied to the British population. The goals of the investigators were to evaluate the SIS applicability in the UK and to propose a shortcut of the SIS that might increase the response rate without. Participants were recruited from several mainly urban general practices and health questionnaires were sent (which included the SIS and the generic health questionnaire EuroQoL EQ-5D).   
Only a third of all mailed surveys were retuned (N=151) to the investigators. The final sample consisted of predominantly men (58 %), British (81 %), 75 years or older (39 %) fully retired from works (56 %) that have had their stroke on average 7.3 prior to the survey.  The mead disability score for the physical domain was 73.5/100, with internal consistency reliability > 85, but only half of the patients surveyed responded to all 8 dimensions items. The investigators added on all eight dimensions and created an index reflective of all items. Also, they chose individual components of each domain based on the highest correlation with the total score for that domain to create a short form SIS index. They found a high correlation among the original and shorten version of the indexes. Furthermore, the total disability scores were highly correlated.
Intuitively, one might think that this shorten version of the SIS might improve response rates without sacrificing the quality of what it portends to measure. Would it be the case? Is response rate directly related to the complexity and/or length of the questionnaire? It might be, but further validation might be required.    

High resolution MRI findings of MCA plaques and subcortical infarcts

Jiaying (Jayne) Zhang, MD

Yoon Y, Lee DH, Kang DW, Kwon SU, and Kim JS. Single Subcortical Infarction and Atherosclerotic Plaques in the Middle Cerebral Artery: High-Resolution Magnetic Resonance Imaging Findings. Stroke. 2013


Subcortical stroke is often erroneously equated to lacunar stroke with similar pathophysiology. It is perhaps more accurate to use subcortical stroke as an entity that encompass two disease mechanisms – small perforating artery infarcts caused by native vessel lipohyalinosis/atherosclerosis, and infarction associated with parental artery disease. Given the distinction, it is important to study their differences to aid the understanding of potential distinguishable clinical characteristics that could impact treatment strategies. 

In this interesting study by Yoon et. al, the authors classified single subcortical infarctions (SSI) in the MCA territory into proximal SSI (pSSI) or distal SSI (dSSI) by their radiological appearance on MRI. pSSI extends to the surface of the MCA whereas dSSI does not. They enrolled 39 patients in total, half with pSSI and the other half with dSSI. Patients with pSSI had more number of large infarcts with higher NIHSS but less microbleeds compared to patients with dSSI. Using high resolution MRI (3T), main trunk MCA plaques were detected in 20 patients. In terms of plaque location, superiorly located plaques were more frequently seen in pSSI patients, which the authors speculate could be important in determining the type of SSI.

It must be noted that this study is too small to make any general conclusions about the clinical characteristics of subcortical strokes. Moreover, the high resolution MRI protocol only assessed the main trunk of MCA, so M2 branches and distal MCA vessels are not accounted for. This speaks to the need for more sensitive and accurate radiological methods in the future in studying the cerebrovasculature.

Recanalization and Outcome after IV tPA

Tareq Kass-Hout, MD

Kharitonova T, Melo TP, Andersen G, Egido JA, Castillo J, Wahlgren N. Importance of cerebral artery recanalization in stroke patients with and without neurological improvement after intravenous thrombolysis. Stroke. 2013

Kharitonova et al. conducted a study to evaluate the association of restoration of blood flow and early neurologic improvement (NI) after inyravenous thrombolysis (IVT) on 3-month outcome. This is an important question because many stroke centers are adopting protocols that use recanalization status after IVT to identify patients for rescue reperfusion intervention.

Patients in this retrospective study were enrolled in the Safe Implementation of Treatment in Stroke International Stroke Thrombolysis Register (SITS-ISTR). All 5324 patients had documented baseline vessel occlusion and follow-up vessel imaging 22-36h after IVT. Patients with NI and vessel recanalization were more likely to be independent at 3 months than patients with  persistent occlusion despite NI and and those without NI despite recanalization (OR 15.9; 95% CI 12.5-20.0 vs. OR 4.7; 95% CI 3.6-6.1 and OR 2.7; 95% CI 2.2 -3.3, respectively).

In short, recanalization of an occluded artery in an acute stroke setting was associated with favorable functional outcome regardless of rapid NI after IVT. This concludes that recanalization with rescue therapy should be considered in patients with persisting occlusion after thrombolysis even after significant neurological improvement.

tPA Patients with SIRS have Worse Short-term Functional Outcomes

Shruti Sonni, MD

Boehme AK, Kapoor N, Albright KC, Lyerly MJ, Rawal PV, Shahripour RB. Systemic Inflammatory Response Syndrome in Tissue-Type Plasminogen Activator–Treated Patients is Associated With Worse Short-termFunctional Outcome. Stroke. 2013

Research has shown that successful thrombolytic therapy with tPA attenuates Systemic Inflammatory Response Syndrome (SIRS) in acute stroke patients. The primary goal of this retrospective study was to determine if patients who received IV tPA and developed SIRS had a difference in functional outcomes compared to those who did not. These patients included those without diagnosed infection who had two of the following criteria: temperature <36 or >38 degrees, HR>90, RR>20, WBC <4000 or >12000/mm. Eighteen percent of patients were found to have SIRS, around 1 in 5, and it was a predictor of poor functional outcome at discharge, even after adjusting for confounders such as NIHSS, age, race and prior stroke. Interestingly, Black patients and those with lower total cholesterol at baseline were more likely to have SIRS. 

This study has an interesting result in that, despite adjusting for the known factors contributing to poor outcome in acute ischemic stroke patients, SIRS stands out as an independent predictor. One theory is that despite receiving thrombolysis, which may or may not have ultimately been “successful”, the individual components constituting SIRS have a detrimental effect on functional outcomes. However, future studies should measure inflammatory markers in patients labeled with SIRS and then correlate those levels with outcomes. The ultimate goal, of course, is to identify these patients early to try and abate poor functional outcomes. 

The ULTRA-Stroke Clinical Trial

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  • Van Delden et al did an interesting study looking at three different versions of post-stroke motor rehabilitation therapies for arm paresis: unilateral (modified constraint induced movement therapy), bilateral (modified bilateral arm training with rhythmic auditory cueing) and dose-matched conventional treatment.

    They randomized 60 patients who were 1-6 months after their stroke into the three treatment arms treated for six weeks for 3 hours a week (60minute sessions, 3 times a week) and encouraged to do exercises at home. The results showed no demonstrably different outcomes in arm paresis after the intervention period using a standardized assessment tool Action Research Arm Test (ARAT).

    While much has said about constraint induced movement therapy, few randomized studies have sought out to answer this specific question. I’m glad to see there is work in the stroke rehab community to evaluate the effectiveness of certain therapies compared with others. For now, I will still recommend my patients to seek as much rehab and exercise as they will tolerate, as only maximal effort and maximal time has demonstrated results.

    Predicting Hospital Depression

    Vasileios-Arsenios Lioutas, MD


    de Man-van Ginkel JM, Hafsteinsdóttir TB, Lindeman E, Ettema RGA, Grobbee DE, and Schuurmans MJ. In-Hospital Risk Prediction for Post -stroke Depression: Developmentand Validation of the Post-stroke Depression Prediction Scale. Stroke. 2013

    Depression is a well known post-stroke complication. What predicts development of depression in an individual patient is less well understood. In this interesting study, Dr. van Ginkel et al. attempt to develop a predictive model that will allow in-hospital identification of patients that will later develop depression. 

    To briefly describe the study methodology, a number of clinical (mainly stroke-related) and socio-demographic factors were recorded within the first post-stroke week and before patient’s discharge. Sociodemogrpahic factors included marital status and perceived level of social support. Subsequently, diagnosis of depression was made in the 6th-8th post stroke week. The prediction model was then internally validated.
    As one would perhaps intuitively expect, past history of depression was strongly associated with post-stroke depression (OR 7.22). Angina pectoris showed a positive and hypertension an inverse association, although clearly no causative implications can be made on the basis of this study only. One interesting fact that emerged was the strong association of the “Dressing” element of Barthel Index with subsequent development of depression: Patients completely dependent on others’ help were more likely to be depressed in follow up (OR 1.57 but with CI 0.80-3.09) and more importantly, those needing only partial help were much less likely to develop depression (OR 0.26, CI 0.08-0.82). Although it is difficult to know whether there is a neurobiologic underpinning, it seems plausible from a purely psychologic standpoint that the subjective feeling of “helplessness” in performing such a rudimentary daily task plays a significant role in developing post-stroke depression.
    The study has several limitations: Only communicative patients were included, therefore the sample is not accurately representative of the whole spectrum of a stroke patient population. Although internally validated, rigorous external validation is necessary to further assess its utility and explore its generelizability. It would be interesting to include the stroke location in the model, as it is very likely that certain brain areas are more strongly associated with post-stroke than others. Lastly, it would be interesting to alter the time-point at which diagnosis was made – perhaps choosing a later time (eg 10-12 weeks or later) would yield different results.

    Ischemic Stroke in Sweden

    Nandakumar Nagaraja, MD

    Previous studies have reported a decrease in the incidence of stroke in high income countries and doubling of stroke incidence in the low to middle income countries. Rosengre and colleagues conducted a study to evaluate the trends in the incidence of ischemic stroke in Sweden over a period of 24 years from 1987 – 2010. 
    The authors found that there has been a continuous increase in the incidence of stroke in younger patients aged 18-44 years at a rate of 1.3% for men and 1.6% for women. However, the stroke incidence was declining in patients aged 45-64 years and it was more pronounced in the 65-84 years age group. Mortality from ischemic strokes decreased markedly in all age groups.
    The decline in the incidence of ischemic stroke in patients ≥ 45 years were attributed to the better control of stroke risk factors such as hypertension and smoking cessation. The steady increase in the incidence of stroke in the younger population is concerning. The authors attribute this to the increase in the incidence of obesity, sedentary life style, smoking and heavy drinking in patients aged 18-44 years. 
    Stroke in young adults is less common and many of these patients are evaluated for uncommon causes of stroke such as hypercoaguable conditions, certain genetic disorders etc. However, with the changing life style and increasing incidence of stroke risk factors such as diabetes, obesity, hypercholesterolemia and hypertention at a younger age it is important to recognize these modifiable conditions early and treat appropriately to prevent strokes. Awareness among the younger population about the risk factors of stroke and their early detection and management may help in reducing the incidence of stroke in this age group. 
    Based on recent reports about 14% of strokes are missed in younger patients presenting to the emergency department with acute neurological symptoms of stroke. Because stroke is considered to be a disease of the older age group it is less commonly suspected when younger patients present to the ER with acute neurological symptoms. Similarly there may be some neglect among the younger population and also physicians caring for them not to recognize the importance of controlling the risk factors as they do so in the older age groups. 

                 

    24hr BP in Elderly

    Jose Gutierrez, MD, MPH

  • Weiss A
  • Beloosesky Y
  • Kenett RS
  • and Grossman, E. S
  • ystolic Blood Pressure During Acute Stroke is Associated With Functional Status and Long-term Mortality in the Elderly. Stroke. 2013

    “Let the blood pressure rise”…might be a frequent say among specialists treating patients with an acute stroke. The AHA guidelines for treatment of acute stroke advices caution on treating high blood pressure in this setting. Some clinical trials and observational studies have even suggested that a rapid decline or aggressive lowering of blood pressure might be associated with worse outcomes. In this issue of Stroke, Grossman et al. present data in regards to predictors of short and long term functional status and mortality in an elderly population with acute stroke that challenges the notion that high blood pressure might be protective in the acute stroke context.

    The investigators recruited 177 patients > 70 years old with acute stroke and hypertension (excluding those with DBP/SBP > 120/220). They obtained baseline characteristics, mRs at 7 days and mortality at 5 years. Two key features of this study are original: the continuous blood pressure measurement over the first 24 hrs of the stroke and the long term follow.

    The investigators found that in the short term; average continuously-measured SBP > 160 (compared to manually obtain) predicted a worse outcome, and average SBP > 160 conferred greater odds of mortality compared to those with SBP < 160 after adjusting for covariates included in the model. 

    Although this study doesn’t answer whether blood pressure should be let to freely rise in the setting of acute stroke or if it should be maintained within certain parameters, it brings up some additional interesting questions. For example, is elevated SBP in this elderly population an indicator of stroke severity or could it represent a marker of more advanced cardiovascular disease? Are the effects of increased SBP on functional outcome and mortality the same across different stroke mechanisms? what could be the mechanisms explaining the worse outcome 7 days after the index event vs. the 5-year mortality increment? 

    ASCOD phenotyping of ischemic stroke and overlap of underlying conditions

    Waimei Tai, MD
    Sirimarco et. al. published an interesting paper recently looking at the overlap of associated conditions (A-atherothrombosis, S-small vessel disease, C-cardiac pathology, O-other uncommon causes) in a cohort series of 403 patients. They categorized how each of the these potential factors may have contribured to cause of stroke by 1-potential cause of stroke, 2-causality is uncertain, and 3-disease is present but unlikely to be a direct cause, 0-disease is not present, and 9-when workup is insufficient to determine relationship. They discovered (not surprisingly) that atherothrombosis was the most prevalent (90% having either A1-3 scores) and identified as the most frequent potentially causal underlying condition. Small vessel disease was also highly prevalent (66% S1-3) but the vast majority, it was of uncertain or not directly related to the stroke. Cardiac pathology sat somewhere in the middle. The overlap between atherothrombosis and cardiac pathology was the highest (25 patients had A1 and C1 scores). In long term follow up, those with cardiac pathology had the highest risk of any major vascular event (C1 having a hazard ratio of 5.3!)

    While this is a novel categorization that helps identify the potential overlap of underlying premorbid conditions that may contribute to stroke mechanism, I am not certain how it would change our management. Certainly atherothrombosis, small vessel disease, and cardiac disease are all related to each other and have significant overlap in underlying vascular risk factors.  Likewise, we would be treating patients with small vessel disease and atherothrombosis quite similarly. Cardiac pathology may alter our management, but previous guidelines and framework for evaluating patients would have addressed that already.

    As the authors suggest, perhaps ASCOD grading would be more useful for studying genetics of stroke where overlap in contributing conditions maybe more important. Similarly, this classification scheme may be helpful in finding patients who may benefit from therapeutic trials who may otherwise be missed when using TOAST criteria.

    CKD and cerebral microbleeds

    Claude Nguyen, MD


  • Ovbiagele B,

  •  Wing JJ
  • Menon RS
  • Burgess RE
  • Gibbons MC
  • Sobotka I. 
  • Association of Chronic Kidney Disease With Cerebral Microbleeds in Patients With Primary Intracerebral Hemorrhage. Stroke. 2013

    Chronic kidney disease (CKD) has been traditionally linked to a higher risk of ischemic stroke, though biologically, one would expect intracerebral hemorrhage (ICH) to be more plausible. To further explore the relationship between CKD and ICH, Ovbiagele et al. performed a retrospective review of data from the ongoing DECIPHER trial, a longitudinal trial looking at differences in race and ICH in the Washington, DC area. Three investigators reviewed imaging, focusing on the admission MRI; GRE sequences were assessed for hematoma volume, location, and number of microbleeds, presence of chronic bleeds, and IVH. Using a multivariate model that adjusted for age, sex, average BP, and history of hypertension or white matter disease, these bleeding characteristics were compared to renal function (eGFR) and use of medications affecting the kidneys (mainly ACE inhibitors).

    Through its 197 patients, the group found an association between baseline CKD and both the presence and number of cerebral microbleeds, even after adjusting for admission BP. The authors point out that this was a cross-sectional cohort, and that the inclusion criteria excluded more severe ICH’s. Nevertheless, this study may add weight to the biologically plausible theory that CKD leads to microangiopathy, which increases risk for ICH.  Although the study, by design, could not produce risk ratios for those with CKD enduring ICH later on in life, the study further implicates CKD in ICH, emphasizes the importance of treating those with CKD, and using CKD as a potential therapeutic targets. 

    The study found the association between CKD and microbleeds to be true in black patients but not in non-Hispanic whites. The implications of race and its role in CKD and microbleeds, however, should be taken with caution. Although this further emphasizes the importance of treating HTN and CKD in blacks, the lack of this association in other groups may cause CKD to be taken less seriously in other groups. The group does cite the DECIPHER study’s predominantly African American population and lack of statistical power in other ethnic groups for lack of this association. This study should speak solely to the notion that the cause and prevalence of CKD may be different between groups. Clinicians should be as aggressive at the diagnosis and treatment of such chronic conditions as CKD regardless of background.