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Monthly Archives: June 2015

Visual Vertical Orientation: A tool to guide post-stroke rehab?

Michelle Christina Johansen, MD

Piscicelli C, Barra J, Davoine P, Chrispin A, Nadeau S, and Pérennou D. Inter- and Intra-Rater Reliability of the Visual Vertical in Subacute Stroke. Stroke. 2015

Visual Vertical (VV) testing may be a concept unfamiliar to many neurologists but does this simple assessment hold promise for directing physical therapy regimens after stroke?

Falls are associated with increased morbidity in the elderly and especially are of great concern in a post stroke patient placed on anticoagulation. Prior review of the literature on verticality perception after stroke by Piscicelli, first author on this publication, demonstrates that patients with a hemispheric stroke align their posture tilted to the side opposite the lesion and those with brainstem strokes demonstrate ipsilateral lateropulsion. How should this guide rehabilitation? In order to develop effective therapies, a quantitative technique that characterizes the deficit is first needed. 

In order to establish the veracity of the VV, Piscicelli et al. evaluated the inter and intra-rater reliability in 20 subacute stroke patients in neuro-rehabilitation who had suffered a first and unique hemispheric stroke. The patient population enrolled was mainly male (12), middle aged (64±15years) with an ischemic (13) right sided lesion (12). Brainstem and cerebellar strokes were excluded due to the thought that VV orientation in these patients is different. Notable exclusions also include those with aphasia or dementia.

In testing VV perception, the patients were asked while sitting upright in a dark room to verbally adjust a bright line to the vertical (light bar test) without a time limit or feedback from the examiner. Mean VV orientation and uncertainty was calculated over 10 trials with a 5 minute break between trials. VV was assessed three times: once by a novice to the technique, once by an expert and then again the next day at the same time by the same expert. Reliability was assessed using the intraclass correlation coefficient (ICC), Bland-Altman plots (also called difference plots) and minimal detectable change (MDC).

The investigators found that inter- and intra-rater reliability for VV orientation (direction perceived as vertical) was excellent with ICC way above 0.75 (0.979, 0.982). The Bland-Altman plots and the MDC revealed a difference <2 degrees between the two tests meaning that a change ≥2 degrees can be interpreted with 95% confidence as a real change. There was excellent concordance between the two examiners for diagnosis of abnormal VV orientation.

In contrast, the intra-rater reliability was satisfactory and inter-rater reliability poor when testing for VV uncertainty (robustness of the internal model of verticality).

The conclusion of the authors is that VV orientation is highly reliable and should be used as a tool at the bedside as well as for research. They acknowledge some of the more concerning limitations of the study to include the patient population (subacute hemispheric strokes who are not aphasic) but state that a code could be established for aphasic patients. The study also contains a small sample size (20) and occurred at a single European neuro-rehabilitation center limiting generalizability. In consideration of the results, does the duration of rehabilitation the patient had received prior to testing influence the results? Those with brainstem and cerebellar strokes were excluded but clinically, this patient population suffers the most devastating symptoms concerning vertical perception and thus VV orientation could be most useful in this cohort.

Visual Vertical testing certainly warrants additional investigation and could represent an inexpensive, easily performed method by which to quantify verticality disorders post stroke.

By |June 11th, 2015|clinical|1 Comment

Does staying fit really help prevent strokes?

Ali Saad, MD

Åberg ND, Kuhn HG, Nyberg J, Waern M, Friberg, P Svensson J, et al. Influence of Cardiovascular Fitness and Muscle Strength in Early Adulthood on Long-Term Risk of Stroke in Swedish Men. Stroke. 2015
We always tell our patients to exercise in order to decrease their risk of stroke. But is there really strong data to support it? Most of it is based on data from self-reporting and not really focused on young people followed long term to look at prevention. 

A Swedish group followed a cohort of over 1.6 million young men from the 60s through the early 2000s for 5-42 years. They tested their isometric muscle strength and fitness (cycle ergometric testing to assess cardiovascular fitness) at age 18 when they were drafted for military duty and divided each of these measures into tertiles of intensity. They then looked at their hospital discharge summaries over the years to capture their first stroke. They found a dose responsive and independent relationship between more exercise or muscle strength and less strokes of any type (ischemic, ICH, or SAH). This association remained for each of the 3 subgroups of stroke, but was highest for ICH. Fitness remained an independent association for lower stroke risk when adjusted for muscle strength. This was not the case when muscle strength was adjusted for fitness. So it seems that fitness in young , Swedish men, which typically is associated with increased muscle strength, is inversely proportional to risk of stroke of all kinds. 

For the lowest tertile of fitness, the HR was 1.7 for all strokes and 2.52 for fatal stroke
For the lowest tertile of muscle strength, the HR was 1.39 for all strokes

Limitations of this study include the absence of women, the elderly, and being limited to Swedes. It also assessed patients’ baseline fitness and strength which could be related to their genetic fitness and not necessarily anything they have control over. We don’t’ have data on how fit they were or how other lifestyle demographics changed over the years after their initial assessments. There is also selection bias as patients with certain medical conditions may have been excused from military duty. 
How does this study change my practice? 
I could cite data when counseling patients on exercise for the prevention of stroke, even though it’s common sense. More importantly, I could direct neurology residents and medical students to this data for their education and future research.

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

And Crown Thy Good With Efficient Stroke Care From Sea to Shining Sea! Marked Regional Variation in Acute Stroke Treatment

Mark N. Rubin, MD

Skolarus LE, Meurer WJ, Shanmugasundaram K, Adelman EE, Scott PA, and Burke JF. Marked Regional Variation in Acute Stroke Treatment Among Medicare Beneficiaries. Stroke. 2015

The same sprawling wonder of our beautiful country that inspired the lyrics to America, The Beautiful – and the intensely disparate socioeconomic, ethnic and educational variation that comes part and parcel with it – makes estimation of regional stroke treatment practice patterns in the United States quite difficult. Despite that, however, the question must be asked and answered to the best of our ability as acute ischemic stroke remains a very morbid and mortal disease and we must learn from both the highest and lowest performing regions as regards stroke treatment.

Some University of Michigan stroke researchers have provided us with some insight. They undertook a massive search of administrative data from the U.S. Federal government in the form of stroke diagnostic and procedural codes for Medicare beneficiaries over the four year period of 2007-2010. They then screened for any type of thrombolysis – medical and/or endovascular – according to hospital service area, of which there were ~3500 to review, and categorized each by occurrence of stroke diagnosis and frequency of treatment. They attempted to control for regional differences in socioeconomics and education by controlling for many factors including population density, median income, number of primary stroke centers in the region, presence or absence of emergency services bypass protocols, and educational attainment.

Their results are interesting and important. Not surprisingly, there are marked differences between stroke treatment practice patterns across this country. Thrombolysis of any kind was provided to only 3.9% of all patients in the cohort, with a range of 0-9.3%. Perhaps shockingly, 20% of surveyed regions provided no stroke treatment whatsoever during the four year period. True to the idea that we can learn from how practice has grown organically, the authors ran hypothetical algorithms to calculate the potential gain from bringing “low performers” with below-median stroke treatment rates into the median range or above. They estimate that “[a]n optimistic ceiling for acute thrombolysis treatment in the United States can be estimated by increasing all regional treatment rates to that of the highest performing region which would yield an additional 92,847 patients treated with thrombolysis and 8,078 stroke patients without disability.”

This cohort is limited to the Medicare population and the data are inferential from coding and billing which is notoriously flawed, but this still represents a first and important step in better understanding how acute stroke treatment is provided across the country. With hope, these data can be leveraged to enhance acute ischemic stroke treatment and mitigate disability. 

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.

Underneath the Surface: Sulcal Effacement with Preserved Gray-White Junction may be a sign of Reversible Ischemia

Vikas Pandey, MD

Haussen D, Lima A, Frankel M, Anderson A, Belagaje S, Nahab F, et al. Sulcal Effacement With Preserved Gray–White Junction: A Sign of Reversible Ischemia. Stroke. 2015

Much emphasis is being placed on early stroke diagnosis in the acute care setting, especially being able to pick up signs of early ischemic changes on CT scan. These can include loss of demarcation of subcortical structures, sulcal effacement and loss of gray-white matter junction differentiation. Using these early ischemic signs to detect viable tissue during acute ischemic stroke is becoming more popular as these assessments are rapidly done, rather than pursuing lengthier perfusion imaging procedures. There is no consensus on the exact interpretation and meaning of early ischemic findings and the significance of these findings as they are related to long-term outcome and thus the group out of Emory University decided to further pursue whether there are beneficial or detrimental signs on non-contrast CT that can indicate future outcome. 

The group selected 108 patients that underwent intra-arterial therapy during a three year period at their institution and found that signs of isolated sulcal effacement (ISE- defined as the presence of sulcal effacement with an intact gray-white matter junction) was present in eight patients (7.4%) with an average age of 55 years and average NIHSS of 16. 5 of these patients had a MCA-M1 occlusions and 3 had an ICA-T occlusion. The areas of ISE were correlated with CTA scans showing dilated leptomeningeal vessels within the areas of effacement and perfusion scans showing that there was a normal to increased CBV and prolonged Tmax in these areas signifying areas of collateral flow that may be at risk. The group was able to achieve TICI 2b-3 reperfusion in all patients and follow up imaging later confirmed that in all cases, there was no infarct in the ISE area on the patients’ initial imaging and long term outcome showed that five of the patients had an mRS of 0-2 at 3 months.

The group’s data points toward not only good outcome for early recanalization in patients with ISE but also provides some support for the idea that perfusion imaging may not even be required in such cases as a clinical presentation of large vessel occlusion in conjunction with a scan of ISE (with good ASPECTS score) may be enough to show that there is tissue at risk. Rapid recanalization would support the often quoted mantra that “time is brain” and further lead to improved outcome in these patients. The work is also supporting the idea that isolated sulcal effacement is actually a sign of robust collateral flow and not a sign of parenchymal injury as was once thought. Of course, all collaterals are not created equal and this may explain why 3 of the 8 patients still did not have a good outcome (mRS >2) but perhaps larger observational studies are in order to provide better correlation.


VASOGRADE in DCI- Does it Scale?

Abdel Kaleel, MD, MSc

de Oliveira Manoel AL, Jaja BN, Germans MR, Yan H, Qian W, Kouzmina E, et al.The VASOGRADE: A Simple Grading Scale for Prediction of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage. Stroke. 2015

VASOGRADE, a grading scale mostly derived from the WFNS grade and modified Fisher scale, has been proposed for risk stratification after aneurysmal subarachnoid hemorrhage. The purpose of this study was to validate this scale, particularly its relationship with the development of Delayed Cerebral Ischemia (DCI). Consecutive patients between January 2012 and June 2013 at the St. Michael’s Hospital in Toronto, Canada were assessed, having been divided into three VASOGRADE categories: VASOGRADE-Green (modified Fisher scale 1 or 2 and World Federation of Neurosurgical Societies scale (WFNS) 1 or 2); VASOGRADE-Yellow (modified Fisher 3 or 4 and WFNS 1-3); and VASOGRADE-Red (WFNS 4 or 5, irrespective of modified Fisher grade. A total of 746 patients were included in the final analysis. The primary outcome was delayed cerebral ischemia (DCI). DCI was present in 151 patients with 15%, 9%, and 37% of VASOGRADES Green, Yellow, and Red groups having developed DCI, respectively. Patients who were identified as VASOGRADE Red had a significantly higher risk of development of DCI and patients who were classified as VASOGRADE Yellow had a tendency for a higher risk for DCI. Overall, DCI status was appropriately identified in almost 70% of patients. Multiple clinical applications of VASOGRADE’s use in DCI were proposed, including decision on disposition/length of stay and treatment aggressiveness, in addition to its ability to predict DCI risk.

The contribution of convexal subarachnoid hemorrhage to disease progression in cerebral amyloid angiopathy

Rajbeer Singh Sangha, MD

Beitzke M, Enzinger C, Wünsch G, Asslaber M, Gattringer T, and Fazekas F, et al. Contribution of Convexal Subarachnoid Hemorrhage to Disease Progression in Cerebral Amyloid Angiopathy. Stroke. 2015 

Cerebral amyloid angiopathy (CAA) is emerging as a rather common cerebral small vessel disease and a major cause of spontaneous ICH. Diverse etiologies have been suggested for the occurrence of convexal subarachnoid hemorrhage, including cerebral amyloid angiopathy (CAA).1 The authors of this study looked at a 9-year-period of patients with spontaneous convexal subarachnoid hemorrhage (cSAH) and performed longitudinal analysis of clinical and neuroimaging data with the assumption that CAA is associated with cortical subarachnoid hemorrhage, cortical superficial siderosis and lobar ICH.

The authors identified 1178 patients diagnosed with SAH. Two-hundred-forty-nine (21%) had nontraumatic, non-aneurysmal SAH and 45 (3.8%) fulfilled the criteria of cSAH. Out of the 45 patients, seven had to be excluded due to lack of imaging and they found that 76% of the remaining (38 patients) had imaging features consistent with CAA at baseline. Post-contrast MRI was performed on 16 patients and extravasation of gadolinium at the site of the acute cSAH was seen on all post-contrast scans. During follow up for a period of 24±22 (range 1-78) months, 15 (39%) had experienced recurrent cSAHs and 14 (37%) had suffered lobar ICHs. Interestingly, of the 22 new ICHs, 17 occurred at sites of previous cSAHs or cSS. Another interesting finding was that follow-up imaging revealed that there was cortical SAH expansion into the nearby brain parenchyma and evolution of a lobar ICH in 4 patients.

The authors postulate through observational data that frequent recurrence of CAA-related cortical SAH was associated with substantial risk for future symptomatic ICH; while they believe intracerebral bleeding can occur from extension of cortical SAH and leakage of meningeal vessels the exact pathophysiological mechanism still eludes us. In order to confirm the observations from this study a much larger set of patients would have to be analyzed to make any definitive conclusions. Perhaps with better imaging techniques and more sensitive sequencing in MRI, we will be able to pick up asymptomatic cSAH in patients more often which may help in predicting future risk of a lobar ICH.

1. Katoh M, Yoshino M, Asaoka K, et al. A restricted subarachnoid hemorrhage in the cortical sulcus in cerebral amyloid angiopathy: could it be a warning sign? Surg Neurol 2007;68:457– 460.

Author Interview: Valery L. Feigin, MD, PhD

New Strategy to Reduce the Global Burden of Stroke
Interview conducted by Deepa P. Bhupali, MD

Dr. Bhupali: Can you give a brief overview on the tool you developed and address in your article? 
Dr. Feigin:
The Stroke Riskometer was developed with the main purpose of improving primary prevention of stroke on a global level.
The application provides users with their absolute and relative risks of stroke, along with how that risk is modified as their health care profiles change. Users can monitor their results, chart progress, receive education regarding stroke symptoms, and if they choose to, share their information via email with a person of their choice. The application is available on iOS and Android platforms, and there are two versions: the Lite version which is free and the Pro version which can be purchased. The Pro version provides additional information on how to reduce stroke risk, based on one’s individual risk profile, but both versions calculate and identify risk factors, provide stroke education and offer the ability to collect data for research. This research will provide significant epidemiological insights, which are vital to improved prevention and treatment of stroke 

Dr. Bhupali: What prompted you and your co-authors to create this tool?
Dr. Feigin:
Our work grew out of two major observations. First, stroke is a major non-communicable disorder (NCD). Despite decrease in incidence and mortality, the overall number of people affected by NCDs – stroke, MI, diabetes, dementia – is growing. This suggests that primary prevention is not sufficiently effective. If this is not addressed and we carry on with business as usual, the burden will continue to grow.
Secondly, there is a research problem. Despite pushes for epidemiological research for NCDs, the majority of countries don’t have reliable data on frequency, determinants and distribution of stroke and other NCDs. This is not because of a lack of understanding regarding research methodology. The void in data is largely related to the expense of conducting the research. Consequently, without accurate data, we cannot develop evidence based health care, planning and prevention strategies. We hope to address these two major problems — the growing burden and lack of data — with this app. This is what excites us.  

Dr. Bhupali: What is innovative about this work?
Dr. Feigin:
There is currently nothing else comparable to the app’s ability to capture accurate data from around the world. As an example of that, the application will be available in world’s most common languages, giving it the ability to reach the global population. Additionally, we worked very hard on the privacy aspects of this application and have implemented unique strategies to guarantee the security of users’ data and their anonymity, if they consent to participate in data collection.

Dr. Bhupali: What is one of the challenges you anticipate in introducing this tool?
Dr. Feigin:
At this time, our main challenge is to let people know that the app is available. We want people to know that there is a tool that will inform them about their absolute and relative stroke risk, provide education regarding stroke symptoms and will monitor their progress and recalculate their stroke risk based on the improvements they seek to make to their health. 

Dr. Bhupali: What is the key take-away message from your article?
Dr. Feigin:
Stroke is highly preventable. It does not happen at random, rather it affects people who are at risk of having a stroke – and these people can reduce their risk.
We implore people to use the app now – learn about your risk factors and how to manage them. Stroke is much easier to prevent than to treat, we want to let people know that they can help prevent stroke and safeguard their health and well-being. 

For more information on Dr. Feigin and the Stroke Riskometer click here.
To read the article in Stroke click here.