American Heart Association

Monthly Archives: September 2013

Patient and carer satisfaction in centralised hyperacute stroke units in London

Nandakumar Nagaraja, MD

Moynihan B, Paul S, Markus HS. User Experience of a Centralized Hyperacute Stroke Service: A Prospective Evaluation. Stroke. 2013

To improve access to thrombolysis, 8 Hyperacute Stroke Units (HASU) were implemented in London in 2010. All suspected acute stroke patients were diverted by ambulance to the HASU. After the hyperacute phase, patients were discharged home or transferred back to the local stroke recovery unit on day 3. Because of the potential for worse patient experience with the discontinuity of care from early repatriation to local stroke unit, the authors prospectively evaluated the patient and carer experiences using a modified Picker Questionnaire.
The study found higher satisfaction rates among both patients and carers. Patients discharged home from HASU had higher satisfaction rates compared to those transferred back to the local stroke unit. Thrombolysis rates increased from 6 to 9.4%. The onset to treatment time was unchanged but there was significant decrease in the door to needle time from 65 to 49 minutes. 
The study highlights that patient and caregiver satisfaction is not significantly compromised while achieving higher thrombolysis rates in HASU setting. It also highlights the fact that patients and carers are looking for highest level of care and they do not seem to mind travelling longer distances if better and higher level of stroke care is provided. Increased volume of activity was thought to be one of the factors related to shorter door to needle time. This is probably comparable to the Primary and Comprehensive stroke centers in US with higher volumes of strokes having better door to needle times compared to other centers. 

By |September 17th, 2013|Uncategorized|0 Comments

Intravenous tPA hemorrhage risk in the renally impaired

Claude Nguyen, MD

Tütüncü S, Ziegler AM, Scheitz JF, Slowinski T, Rocco A, Endres M, et al. Severe Renal Impairment Is Associated With Symptomatic Intracerebral Hemorrhage After Thrombolysis for Ischemic Stroke. Stroke. 2013

Intravenous tPA affords varying degrees of risk based on the patient’s medical history. One of the areas thought to put patients at higher risk is renal impairment. Tutuncu et al. looked at this by retrospectively reviewing 740 patients who received IV tPA. Excluding those on dialysis, a large proportion of them (83%) had renal impairment, with 5% being severe impairment (GFR <30ml/min). In the group with severe impairment, there was a higher proportion of patients with symptomatic ICH and parenchymal hemorrhage, even after adjusting for variables such as age, hypertension history, and peripheral arterial disease.  
The authors go on to hypothesize that the reason for increased bleeding risk could be related to endothelial platelet dysfunction, as well as worsening white matter disease in those patients. The group points out that they were unable to account for the severity of preexisting white matter disease in their model, and that their findings were based on one creatinine reading upon admission. Despite these limitations and its retrospective nature, these results are slowly helping to better define individual risk in thrombolytic therapy, and a reminder that IV tPA is not a “one-size-fits-all” medication. 
By |September 16th, 2013|Uncategorized|0 Comments

Gene links moya-moya and intracranial athero in Japan

Nirali Vora, MD

Miyawaki S, Imai H, Shimizu M, Yagi S, Ono H, Mukasa H, et al. Genetic Variant RNF213 c.14576G>A in Various Phenotypes ofIntracranial Major Artery Stenosis/Occlusion. Stroke. 2013

I always thought bad intracranial artery stenosis/occlusion (ICASO) in East Asian folks was from modifiable atherosclerosis and felt any label of a genetic “moya-moya” was incorrect. Was I wrong? 

This Japanese group looked at a previously identified ring finger protein gene variant, “RNF213c.14576G>A,” which has been associated with moya-moya in East Asians. In this case control study, they confirm the strong genetic association to definite, bilateral moya-moya (OR 144) > unilateral moya-moya (OR 54) > ICASO (OR 16.8) and no association in the control group or patients with extracranial athero, aneurysms, or ICH.

Makes you wonder if ICASO is on a spectrum with moya moya disease. The variant’s biochemical function is presently unknown, but could provide a clue regarding pathogenesis of vessel disease common in this population. 

While I won’t be rushing to an EC-IC bypass if the variant shows up on my 23andme report, I would be very aggressive with vascular risk reduction and have a higher threshold for vessel imaging in East Asians.

By |September 13th, 2013|Uncategorized|1 Comment

Age correlates with critical pressure for arterial wall rupture

Peter Hannon, MD

Ciszek B, Cieslicki K, Krajewski P, Piechnik SK. Critical Pressure for Arterial Wall Rupture in Major Human CerebralArteries. Stroke. 2013

Hypertension has long been known to be a causative factor in intracranial hemorrhage, but how much of that is from direct effect? Piechnik and colleagues have investigated this concept via observation of the pressure required for rupture of cadaveric cerebral arteries. 31 vessel segments of the main cerebral arteries at the level of the circle of Willis were collected. Donor age ranged from 24-80 years, and vessel segments averaged 1-2cm in length and 2.6mm in diameter. Segments were mounted on a flared needle, and the open end and perforators were clipped/ligated.  Saline was used to pressurize the vessels until rupture, and vessels were then inspected microscopically.

The average rupture pressure was 2.35 +/- 0.55atm, which authors note exceeds the highest observed systolic blood pressure seen in en-vivo by several times. Pressure and vessel dilation at rupture correlated inversely to age, with vessels from older donors breaking at lower pressures and % dilatation. Compensating for age trends, ANOVA did not reveal significant differences between rupture pressures and vessel location, presence of bifurcation and type of rupture. Similarly, the presence of plaque (n=3) or aneurism (n=2) did not result in any statistically significant effect on rupture pressure or maximum vessel distensibility.

Observed rupture pressures were well above physiologic stress, thus making the case that additional pathology is required for vessels to be prone to bleeding, and that the known correlation of HTN and ICH is likely secondary (at least to some degree) to chronic changes. It would be interesting to see similar experiments directed at perforators, as these vessels are often implicated in IPH. Age does appear to play a significant role in vessel compliance, which reinforces the need for aggressive stroke prevention in the elderly, and may additionally play a role in the setting of angioplasty or intervention in this population. 

By |September 12th, 2013|Uncategorized|0 Comments

Is There an Association between INR Levels, NIH Stroke Scale at Stroke Onset, And Functional Outcome at Discharge?

Hassanain Toma, MD

Nakamura A, Ago T, Kamouchi M, Hata J, Matsuo R, Kuroda J, et al. Intensity of anticoagulation and clinical outcomes in acute cardioembolic stroke: the Fukuoka Stroke Registry. Stroke. 2013

Nakamura et al. sought to clarify whether INR levels in patients with cardioemoblic strokes are associated with the severity of neurological deficits (NIHSS) on admission, and functional outcomes (modified Rankin Scale) at discharge.  They performed a retrospective cohort study of 602 cardioembolic-stroke patient from their multicenter hospital based stroke registry in Japan. They stratified their cohort according to admission INR levels: <1.50, >1.50-1.99, and ≥2.00.

Their analysis revealed that the odds ratio of developing severe neurological deficits (NIHSS>10) when comparing the reference group (INR <1.5) with the INR of 1.50-1.99, and ≥2.00 groups, were 0.43 (95% CI, 0.43–1.00;), and 0.41 (95% CI, 0.20–0.83), respectively.  Furthermore, the odds ratio of developing poor functional outcome (mRS ≥4) was 0.2 (95% CI, 0.06–0.55) in patients with INR ≥2.00 compared to the INR <1.5 group.  They concluded that the severity of neurological deficits were inversely associated with INR on admission.

This is certainly good news, in terms of prognosis, for acute stroke patients that present to the hospital with an INR of ≥2.00, especially since tPA is contraindicated in this group. But how about the unfortunate patients that present with an INR of 1.50-1.99? According to this study, although their NIHSS at admission is expected to be relatively low, their functional outcome will not differ from those who present with an INR of <1.50.  This begs the question of whether one should treat this population with tPa, which highlights a significant shortcoming in this study; the authors should have compared a cutoff INR of 1.7. The 2013 guidelines for use of tPA precludes patients with an INR ≥ 1.7.  Assuming the authors administered tPA based on these guidelines, this may explain why functional outcome was not significant in patients that presented with INR of 1.50-1.99.  It would be interesting to compare functional outcome in patients that presented with an INR of ≥1.7, as this may lead to a change in future tPA-administration guidelines.

Furthermore, the data suggests a possible oversight of the authors in making additional valuable conclusions.  Their data revealed that a significant number of patients were bridged with heparin. They also revealed that gastrointestinal bleeding occurred in 11 patients with PT-INR <2.0, whereas no patient with PT-INR ≥2.0 developed it. Furthermore symptomatic hemorrhagic infarction occurred in 27 patients with PT-INR <2.0 and one patient with PT-INR ≥2.0. Assuming they applied the standard North American practice of bridging patients who’s INR <2.0, they could have provided an odds ratio of bleeding complication when patients are bridged with heparin. I guess for this we will have to defer to the results of the BRIDGE Study.

By |September 11th, 2013|Uncategorized|0 Comments

New Ordinal scale to quantify total MRI burden of cerebral small vessel disease

Gillian Gordon Perue MBBS; DM

Klarenbeek P, VanOostenbrugge RJ, Rouhl RP, Knottnerus IL, Staals J, Ambulatory Blood Pressure in Patients With Lacunar Stroke: AssociationWith Total MRI Burden of Cerebral Small Vessel Disease. Stroke. 2013

Studies that evaluate the association between cerebral small vessel disease (cSVD) and preclinical MRI biomarkers such as asymptomatic lacunar stroke, white matter disease, enlarged perivascular spaces, and cerebral microbleeds  often examine each biomarker in isolation. However, I am sure we have all seen several of these biomarkers occuring in one patient.  

In a recent article in Stroke Klarenbeek etal introduce a new pragmatic ordinal scale that quantifies the total burden of cSVD on MRI.  In this scale, one point is assigned to the presence of each of the preclinical biomarkers. The scale ranged from  zero to four (0-4)points. Then in a cross sectional study of first ever lacunar strokes, 24 hour ambulatory blood pressures were recorded and follow up MRI scan ( 1.5 or 3T) done to assess total burden of cSVD. In an ordinal regression analysis, the association between daytime and nighttime mean blood pressures and the total burden of cSVD were explored.

Among 122 patients, eighteen (15%) had no biomarkers of cSVD, twenty-four (20%) had one, the majority (n= 45;  37%) had two biomarkers and only six patients (5%) had all four biomarkers. Consistent with the known literature, higher mean ambulatory blood pressure levels were associated with increasing total burden of cSVD after adjusting for age and sex. However there was no clear trend in the appearance of each biomarker in relation to levels of hypertension and any combination of one or more biomarkers was seen to occur.
This article is important as it begins to unify in one scale all known preclinical markers of cSVD and suggests a research standard for validation and use in future research trials. It would be quite interesting  to follow these patients longitudinally and determine whether patients with night time dips in blood pressure (so called dippers vs. non dippers) had a difference in total MRI burden of cSVD. What effect, if any, does antihypetensive treatment have on the burden of cSVD? While the results of this article is not likely to change my current clinical practice, this cohort is definitely one to watch.

By |September 10th, 2013|Uncategorized|0 Comments

PEG Score to Predict Surgical Feeding Tube Placement

Matthew Edwardson, MD

Dubin P, Boehme A, Siegler J, Shaban A, Sudkamp J, Albright K, et al. New Model for Predicting Surgical Feeding Tube Placement in Patients With an Acute Stroke Event. Stroke. 2013

Prediction of which stroke patients will eventually require surgical feeding tube placement is challenging, and having this knowledge early in the hospital course would facilitate reduced length of stay. Dubin and colleagues addressed this problem by developing the PEG score.

The authors retrospectively analyzed data from 407 patients with ischemic or hemorrhagic stroke admitted to Tulane University Hospital. Using logistical regression analysis they came up with separate “PEG” scores for ischemic and hemorrhagic stroke (ischemic stroke PEG score: age >80 years=1, 24-hour NIHSS score 8-14=1, NIHSS >14=2, black race=1, cortical location=1; hemorrhagic stroke PEG score: 24-hour NIHSS score 8-14=1, NIHSS>14=2, black race=1, midline shift >3mm=1, edema on follow up head CT=1). A PEG score ≥ 3 was highly predictive of surgical feeding tube placement in both groups (OR 15.68 and 12.49 for ischemic and hemorrhagic stroke respectively). 

Before you rush to send all of your patients with high PEG scores for surgical feeding tube placement on hospital day 2, some peculiarities of this study suggest further validation is warranted. Baseline dysarthria and level of consciousness were important variables in prior prediction algorithms, but were not significant in the PEG score analysis. Possibly more concerning, black race was predictive in the PEG score analysis. To my knowledge, there is no physiologic reason why those of black race should have more difficulty recovering swallowing ability after stroke. This might suggest that the small subset of patients with black race had worse strokes than the rest of the cohort. Other possibilities include a cultural reason for poor participation in swallowing trials or bias on the part of the speech pathologist and/or physician that those of black race were less likely to recover swallowing ability. The authors should be commended for trying to advance our knowledge of a poorly studied aspect of post-stroke management. However, the questions raised here suggest further work is required to validate the PEG score using data from other stroke registries or in prospective fashion.

By |September 9th, 2013|Uncategorized|0 Comments

To Give or Not to Give: Intravenous Thrombolysis in Patients with Acute Ischemic Stroke and Infective Endocarditis

Deepa P. Bhupali, MD

Asaithambi G, Adil MM, and Qureshi AI. Thrombolysis for Ischemic Stroke Associated With Infective Endocarditis:Results From the Nationwide Inpatient Sample. Stroke. 2013

Intravenous thrombolysis is one of the most effective treatments we have for acute ischemic stroke. The established guidelines for administering tPA do not and cannot address every single clinical situation in which tPA should be considered. Given its integral role in treatment of stroke, it is valuable to continue to evaluate different clinical situations in which IV tPA may be effective.

Qureshi and his team looked at the use of IV tPA in patients with acute ischemic stroke with infective endocarditis (IE). They examined data from the Nationwide Inpatient Sample (NIS) from 2002-2010 to determine the rates and outcomes of ischemic stroke patients with IE treated with IV tPA. Outcomes were defined as rates of post-thrombolytic ICH and favorable outcome (discharge disposition of home/self-care). They found that the rate of post-thrombolytic ICH was significantly higher and the rate of favorable outcome was significantly lower in patients with IE as compared to patients without IE.

The study highlights the fact that caution and careful decision making should be used when considering intravenous thrombolysis in patients with acute ischemic stroke and with IE, but beyond that, it is difficult to apply their data and findings to specific clinical situations. As Qureshi’s team acknowledges, because their data is extracted from the NIS, we don’t have access to certain information that would have been helpful in this study. When was the diagnosis of IE made in relationship to diagnosis of stroke and administration of tPA? What was the patient’s level of functioning prior to hospitalization? What was the degree of neurological deficit at time of treatment? What was the door to needle time? What was the severity of the ICH after tPA? These questions are relevant when considering the utility of administering tPA in situations that do not yet have clearly defined guidelines.

This paper directs our attention to the potential risks of tPA in patients with acute stroke and IE and emphasizes the need for careful clinical decision making. It also leaves us hungry for more research in this area.

By |September 6th, 2013|Uncategorized|0 Comments

Admission Insular Infarction >25% is the Strongest Predictor of Large Mismatch Loss in Proximal MCA Stroke

Sebina Bulic, MD

Kamalian S, Kemmling A, Borgie RC, Morais LT, Payabvash S, Franceschi AM, et al. Admission Insular Infarction >25% Is the Strongest Predictor of Large Mismatch Loss in Proximal Middle Cerebral Artery Stroke. Stroke. 2013

Time is a brain. We have heard it so many times that we are conditioned to think and act in such manner, mainly, because it is true. That is why we keep searching for the simple and reliable tools to guide us in rapid assessment and selection of the patients with penumbral “tissue-at-risk” which would benefit from timely reperfusion. Current widely used clinical and imaging scores are (this is not all inclusive list): CT and MRI ASPECTS, THRIVE, NIHSS, recently published HIAT2. MRI and CT perfusion are commonly mentioned, but not readily used methods in a clinical practice. 

In a period of 5 years, Kamalian and collegues, from Mass. General retrospectively analyzed prospectively acquired data for the 45 patients with M1 occlusion. All of patients had NCCT followed by CTA. Mean time to DWI and MR perfusion was about 5 hours as per institution protocol. Two non radiologist blinded to all correlative clinical and other imaging data, evaluated scans for percentage of insular infarction with substantial interobserver agreement for the percent insula ribbon infarction (PIRI) ratings which represented combined effect of infarction and pial collateral flow. PIRI score was stratified “0”=normal, “1”<25%, “2”=25-49%, “3”=50- 74%, and “4”≥75% insula involvement. Percent-mismatch-loss was calculated as an outcome measure. They also compared this score with NIHSS score, DWI ASPECT score, DWI infarct volume, or CTA-collateral score. 

Optimal operating PIRI score was found to be 1 with PIRI score >1 and patient’s age were the best independent predictor of large mismatch loss. Also each additional step increase in PIRI score had strong correlation with the further mismatch loss. 

Field of endovascular neurointervention is at flux; several recent studies were discouraging (execution, patent selection and devices used can be questioned). New, better and safer devices were recently introduced, Therefore, the insula score may help to further stratify patients with small infarcts who are likely to undergo significant infarct extension and in whom rapid treatment would be expected to yield the greatest benefit. 

By |September 5th, 2013|Uncategorized|0 Comments

Genome wide analysis of blood pressure variability and ischemic stroke

Seby John, MD

Yadav S, Cotlarciuc I, Munroe PB, Khan MS, Nalls MA, Bevan S, et al. Genome wide analysis of blood pressure variability and ischemic stroke. Stroke. 2013

Ischemic stroke is a heterogenous disease with multiple etiologies contributing to overall risk. Modifiable risk factors account for only about 60% of the population-attributable risk. Genetics and genomic factors appear to influence the development of vascular disease at all stages, and there is compelling data that genetics plays a major role in the risk of ischemic stroke.

In 2010, Peter Rothwell published a series of papers regarding visit-to-visit variability of systolic blood pressure (BP) being a strong predictor of ischemic stroke. In this article, Yadav et al tudied genetic loci that could influence BP variability by conducting genomewide association studies (GWAS). 3802 subjects were recruited from the UK-Ireland subset of the Anglo-Scandinavian Cardiac Outcome Trial (ASCOT). The GWAS identified a cluster of 17 correlated SNPs within the NLGN1 gene (3q26.31) that were associated with BP variability, with rs976683 having the strongest association. The NLGN1 gene encodes a neuronal cell surface protein implicated in the growth and remodeling of the vascular system. However, analysis of rs976683 in an independent ischemic stroke population from 7 international cohorts (8,624 cases and 12,722 controls) found no association for overall stroke or its subtypes.

Human genome sequencing has allowed for GWAS that may permit the discovery of variant alleles associated with common conditions like stroke. Such studies have identified gene loci associated with stroke risk that also overlap with heart and vascular disease (eg. 4q25 locus near the PITX2 gene is associated with atrial fibrillation and cardioembolic stroke). A limitation of GWAS studies, however, is that the small effect-size of genes may prevent the detection of association with a disease. This limitation may have been a factor in this study as well. 

At this time, the role of genetic factors in stroke is small. Apart from obtaining a family history and in monogenic disorders like CADASIL, the clinical utility of the genetic role remains low. However, such studies are important since they may provide novel clinical applications for stroke in the future, including biomarker development and improvements in risk profiling and classification.

By |September 4th, 2013|Uncategorized|0 Comments