American Heart Association

Monthly Archives: October 2013

Cognitive screening acutely requires more study

Nirali Vora, MD

Lees R, Corbet S, Johnston C, Moffitt E, Shaw G, Quinn T. Test Accuracy of Short Screening Tests for Diagnosis of Delirium or Cognitive Impairment in an Acute Stroke Unit Setting. Stroke. 2013

Stroke survivors with cognitive dysfunction have higher mortality and delayed recovery. In the acute setting, it can be very hard to diagnose, often complicated by delirium or aphasia.

What screening tool do you use to identify cognitive deficits in your stroke patients?

source: 4-A test

There is no right answer. Quinn’s group performed brief cognitive screening tests in 111 consecutive ischemic and hemorrhagic stroke patients with median NIHSS 3 admitted to a single UK stroke unit. They used the MoCA as a reference standard, but were unsure where to draw the threshold for deficits (traditionally ≤26 which would mean 89% of this cohort is affected, but prior stroke publications have used ≤24 or ≤20). Using the 26 point cutoff, they found the 4 A-test had favorable sensitivity (0.86) and specificity (0.78) for cognition and actually was sensitive (1.00) and somewhat specific (0.82) for delirium when using the CAM tool as a reference standard.  The other tests (clock drawing, 4-AMT, Cog-4, GCS, SQ) did not do as well at the traditional MoCA threshold. The authors’ conclusion, rightly so, was that there is no validated screening device for cognition in acute stroke and more studies are needed to find a sensitive one.  Even the gold standard is unknown at this point.  

Do you change your treatment plan if you discover the patient has cognitive deficits?  I don’t believe there is a different set of rehab or medication to use at this point. We do get more cautious about what environment to discharge the patient to – aftercare vs. home with significant supervision. I don’t start an cholinesterase inhibitor though; definitely not in the acute setting. Which begs the question – should cognitive screening take place acutely? If it’s just being done to “screen” high risk patients for later, why not just use more traditional methods (e.g. MoCA) in the office at the first or second follow up? This article simultaneously discusses delirium, and we certainly would get aggressive about treating and even preventing delirium with non-pharmacologic measures and antipsychotics to maintain sleep-wake cycle, for example. In what other situations is acute cognitive screening post-stroke useful? 

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

White matter changes on brain imaging in stroke subtypes

Seby John, MD

Li L, Simoni M, Küker W, Schulz UG, Christie S, Wilcock GK, et al. Population-Based Case–Control Study of White Matter Changes on BrainImaging in Transient Ischemic Attack and Ischemic Stroke. Stroke. 2013

Scrolling through MRIs, we often notice white matter changes (WMC), and radiology reports such as “nonspecific T2/FLAIR hyperintensities in the periventricular white matter, most likely secondary to chronic microvascular ischemic change” are all too familiar.  Previous studies have reported an association between WMC and incident/recurrent ischemic stroke. However, most studies found this association only with small vessel stroke (SVS).

Peter Rothwell’s group sought to investigate presence of WMC per stroke subtype. WMC in patients with first-ever TIA or ischemic stroke (n=1601) were compared to controls without history of ischemic events (n=313). Presence and severity of WMC on CT and/or MRI were graded using the modified Blennow/Fazekas and ARWMC scales respectively. After adjusting for age, sex, diabetes and hypertension, the authors found that moderate-to-severe WMC were more frequent in SVS, as compared to strokes from large vessel, cardioembolic or indeterminate etiology. This association was strongest in younger patients, and was lost at older ages.

Apart from research implications regarding the mechanisms explaining WMC and SVS, this study gives us useful information for clinical practice. Consider a non-stroke neurologist who sees WMC on brain imaging done for non-vascular complaints. In the correct clinical context, they can be reassured that it is likely from small vessel disease and studying the carotids or the heart may not be indicated. Rather, emphasis on optimal risk factor management would be more important. If seen on CT, perhaps this may suffice since CT and MRI-based comparisons were consistent in this study. I think this applies less in stroke clinics, since patients will more than likely need a thorough etiological evaluation. With sweeping reimbursement changes expected from the Affordable Care Act, this may provide some help with stratification of test ordering. 

Is the Group Judgment Better than an Individuals Assessment of Stroke Functional Outcome?

Waimei Tai, MD

McArthur KS, Johnson PCD, Quinn TJ, Higgins P, Langhorne P, Walters MR. Improving the Efficiency of Stroke Trials: Feasibility and Efficacy ofGroup Adjudication of Functional End Points. Stroke. 2013

MacArthur et. al performed an interesting study to demonstrate that group adjudication of stroke functional outcome using the modified Rankin Score (mRS) had better kappa (interobserver agreement score) than individually scored mRS. Local site investigators performed mRS interviews and submitted their scores to the registry. Blinded coordinating center adjudicators then reviewed recorded video interviews and individually adjudicated. Where there was disagreement, they conferred and then submitted a group score.

Using sample size calculations, they demonstrated this can potentially reducing the trial sample size and increasing trial power by improving the reliability of the of the mRS assessments.

An interesting sub-study they performed was to use translator services for group adjudication of mRS for primary interviews performed in Chinese. The interobserver agreement continued to remain high (kappa=0.9)

This suggests that group adjudication can potentially improve the reliability of mRS functional outcomes and thus, potentially reduce the onerous burden of large sample size in intervention studies that may have modest measurable benefit in functional outcomes.

While I like the idea of have individual and subsequent group adjudications, this does add additional costs in other ways to the clinical trial process with recording video and subsequent transfer to coordinating centers as well as additional adjudication work by the coordinating center. Due to advances in technology, it’s possible that these recordings of subject interviews can be feasible and replicated. In addition, it’s possible that having the mRS interviews be recorded may improve the quality of the mRS interviews being conducted.

Anything that can improve the power of studies and reduce sample size and thus, reduce the cost and duration of clinical studies should be looked upon favorably as barriers to bringing good interventions to market and community use is still high and ever growing.

Suprascapular Nerve Block For Hemiplegic Shoulder Pain

Vivek Rai, MD

Adey-Wakeling Z, Crotty M, Shanahan E. Suprascapular Nerve Block for Shoulder Pain in the First Year After Stroke: A Randomized Controlled Trial. Stroke. 2013

Shoulder pain is a frequent complication in hemiplegic arm after stroke often attributed to multiple etiologic factors including biomechanical changes, spasticity and centrally mediated pain mechanisms. Suprascapular nerve block (SSNB) has been shown to be an effective treatment in arthritic conditions but its efficacy is hemiplegic shoulder pain (HSP) is largely speculative.

Adey-Wakeling et al undertook this rather small, randomized control trial (total patients randomized = 64) to study the efficacy of SSNB with methylprednisolone and bupivacaine in treatment of HSP. Visual analog scale was used for measurement of pain. Although there was marked placebo response (which is common in subjective outcome trials), pain reduction was superior and statistically significant with SSNB in comparison to sham injections during the 12-week study period.

SSNB is an emerging intervention for treatment of HSP and this is the largest randomized controlled trial in this field so far. The trial shows promising results. I will consider SSNB for pain control, like any other invasive procedure, only if other conservative treatments have failed. Also, this was a small trial with a short duration of follow up. A longer period of follow-up and, I suppose, repeat injections will be necessary in patients who find this intervention useful. It will be interesting to see this long-term data, which is also necessary to show this procedure as a practical and efficacious treatment for HSP over extended period of time.

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

THRIVEing for simplicity: Predicting outcomes after ischemic stroke

Peter Hannon, MD

Flint AC, Faigeles BS, Cullen SP, Kamel H, Rao VA, Gupta R, et al. THRIVE Score Predicts Ischemic Stroke Outcomes and Thrombolytic Hemorrhage Risk in VISTA. Stroke. 2013

Prediction of outcomes after stroke is tricky business, and a lot of time and energy has gone into finding effective tools to help with this. Validated clinical predictors such as ASPECTS, DRAGON, HIAT-2 and iScore, to name a few, vary in complexity and what kind of imaging, if any, is needed to help predict outcome. Utilizing the Virtual International Stroke Trials Archive (VISTA), authors Flint et al. describe using the Totaled Health Risks in Vascular Events (THRIVE) score to predict outcomes after ischemic stroke and risk after IV tPA administration.

Originally described in 2010 as a tool to predict outcomes after endovascular intervention, the THRIVE score is based on age, NIHSS, and whether or not a patient has HTN, DM and/or Afib. In this study, a THRIVE score was evaluated for 5724 stoke patients reviewed in the VISTA database, then rated against outcomes at 3 months and whether there was hemorrhage after tPA intervention. Additionally, the THRIVE score was compared head-to-head to HIAT, HIAT-2 and SPAN-100 for outcomes prediction. Per authors, the THRIVE score strongly predicts clinical outcome, mortality, and the risk of hemorrhage after IV tPA, and was found to be superior to HIAT, HIAT2, HAT and SPAN-100 in several direct comparisons using ROC curve analysis. 

The THRIVE score is advantageous in its simplicity, specifically that imaging is not required, and can be quickly and easily performed at the bedside. While there is no foolproof method to predict outcomes after stroke, it is becoming increasingly evident that there are a number of ‘sweet spots’ of combinations of CVA risk factors and imaging modalities that can be rapidly utilized to give us guidance. This study highlights the usefulness of simple and efficient clinical outcomes prediction scores, as well as the invaluable role that large scale stroke trials databases play in validating them. 

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

Higher volume stroke centers administer tPA more and they do it faster.

Alireza Noorian, MD

Bray BD, Campbell J, Geoffrey CC, Hoffman A, Tyrrell PJ, Wolfe CDA, et al. Bigger, Faster?: Associations Between Hospital Thrombolysis Volume and Speed of Thrombolysis Administration in Acute Ischemic Stroke. Stroke. 2013

Thrombolysis with tissue plasminogen activator (tPA) has been shown to improve the outcome when given within 4.5 hours following the symptom onset in acute ischemic stroke, the faster  given to the patient, the higher the chance of reaching better outcomes. In addition to pre-hospital delays, the time period from patient arrival to the hospital to the time tPA administration is started (arrival-tPA time), is affected by the hospital pathways in identification of stroke, investigation and initiation of treatment. There have been very few studies on the hospital characteristics and their rapidity and efficiency in shortening arrival-tPA times.

Bray et al, studied the association between hospital thrombolysis volume and arrival-tPA time. The study was performed through reviewing data from consecutive acute stroke patients in the Stroke Improvement National Audit Programme (SINAP), a prospective database from 106 UK hospitals. The hospital thrombolysis volume per year was categorized into three groups of low (0-24), medium(25-49) and high (≥50).

The study has demonstrated that the thrombolysis rate was higher in higher volume hospitals and the high volume centers achieved the quickest arrival to scanner and arrival-tPA times, while there was no difference between low and medium volume hospitals, suggestive of a potential threshold effect. There was no difference in complication rates suggesting that faster times were not at the expense of patient safety.   

In conclusion, they suggest that concentrating stroke thrombolytic services into a smaller number of higher volume centers, can potentially improve treatment times. This is an important implication for configuration of stroke care networks in the community and certification processes. 

The Hub Has Spoken.Tertiary Care Center Transfers and Patient Outcomes

Jennifer Dearborn, MD

Ali, SF, Singhal, AB, Viswanathan, A,  Rost, NS, and Schwamm LH. Characteristics and Outcomes Among Patients Transferred to a Regional Comprehensive Stroke Center for Tertiary Care. Stroke. 2013

Ali et. al. use the GWTG database to describe acute ischemic stroke (AIS) patients admitted to a tertiary care center (almost 50% of patients were transfers). The rationale implied by this study is that with public reporting of healthcare quality data and third party payers, there is concern that tertiary care centers will be reprimanded for higher mortality rates, explained by care of the “sicker” patients referred in. 

In this single center study, patients transferred from community facilities had more severe strokes, as measured by the NIH stroke scale, and were younger on average than patients presenting through the emergency department. Many received t-PA through the “drip and ship” model. Importantly, transfer status was not independently associated with in-hospital mortality. This being said, without adjustment for medical co morbidities or stroke severity, transfer patients came in sicker, with overall increased in-patient mortality. 

This study is important evidence that community hospitals are frequently giving t-PA, and utilizing the hub-and-spoke model to benefit acute treatment of stroke patients. Tertiary care centers receiving these patients are well equipped to deal with the medical complications and provide excellent specialized care. However, payers and other rating agencies must take into account metrics of stroke severity and co morbidities of patients when grading hospitals on outcomes such as in-hospital mortality. 

This study is examines outcomes measures such as in-hospital mortality in a tertiary care center between transfers and non-transfers, within the environment of pay-for-performance standards. Future directions should focus on recording better metrics of patient outcomes in the GWTG database, such as modified Rankin Scale or 90-day mortality, so that we can better understand the hub-and-spoke’s impact on the community.

Prediction of post stroke hemorrhagic transformation using CT perfusion

Vivek Rai, MD

Yassi N, Parsons MW, Christensen S, Sharma G, Bivard A, Donnan GA, et al. Prediction of Poststroke Hemorrhagic Transformation Using Computed Tomography Perfusion. Stroke 2013.

Intracerebral hemorrhage is a feared complication of thrombolysis that has been shown to be associated with increased mortality. In addition to several clinical risk factors, several MRI based studies have identified predictive parameters for hemorrhagic transformation after thrombolysis such as DWI lesion volume, severe hypoperfusion (High TMax), low CBV and late phase T2* signal loss in perfusion sequences. While MRI parameters seem to be informative, MRI remains a difficult study to obtain during acute phase of stroke. 

Yassi and colleagues sought to identify optimal CT Perfusion parameters for prediction of parenchymal hemorrhage (PH) after stroke in this study on 132 patients of which about half underwent thrombolysis. They report that TMax >14 sec volumes of >5 ml allowed prediction of PH with sensitivity 79% and specificity 68%. The results are in line with similar work with MRI. The study shows that assessment of severely ischemic tissue, which in turn predicts hemorrhagic transformation, is possible with CTP and that TMax may be an optimal parameter for this. 

While this is an important finding that advances our understanding of perfusion studies; the application of the study in clinical setting remains unclear. At present, I will continue to rely on clinical criteria for prediction of hemorrhagic transformation in patients treated with IV thrombolysis. On the other hand, this might be an important parameter to consider in patients undergoing endovascular treatment especially in extended time window.

Paramedics in an ambulance-based trial for acute stroke. The RIGHT trial (Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial)

Seby John, MD

Ankolekar S, Fuller M, Cross I, Renton C, Cox P, Sprigg N, et al. Feasibility of an Ambulance-Based Stroke Trial, and Safety of Glyceryl Trinitrate in Ultra-Acute Stroke: The Rapid Intervention With Glyceryl Trinitrate in Hypertensive Stroke Trial (RIGHT, ISRCTN66434824). Stroke. 2013

Time is brain. This is the sobering reality that every vascular neurologist grapples with when managing acute ischemic stroke (AIS). With the knowledge that millions of neurons are dying each passing minute, it is imperative to deliver treatment quickly. However, delays in diagnosis and treatment initiation are commonplace, with only an estimated 1-3% of AIS patients in the US receiving tPA. There is a desperate need to improve treatment strategies, and this requires a concerted effort among all providers caring for stroke patients.

Paramedics are often the first responders and form a crucial link in the treatment chain. In this study from Nottingham, UK; Ankolekar et al assessed the feasibility of performing a paramedic-delivered ambulance-based prospective randomized controlled trial. Patients with probable AIS (<4 hours) and systolic blood pressure (SBP) >140 mm Hg were randomized to transdermal glyceryl trinitrate (GTN) or no treatment. The GTN treated group had significantly lower SBP at 2 hours and improved functional outcome (shift in mRS by 1). There were no differences in mortality or serious adverse events. 

With only 41 patients recruited, this study was not powered to assess the effect of GTN on functional outcomes and the results likely represent a chance finding. Authors plan to conduct the RIGHT-2 trial to further analyze this. However, the success of the study was the demonstration that paramedics were able to independently screen, consent, randomize, treat and measure outcomes. The median time to randomization from stroke onset was an impressive 55 minutes, and the diagnosis of stroke or TIA was confirmed in 88% of patients. 

With newer paradigms of pre-hospital stroke treatment on the horizon like the mobile stroke unit (ambulance housing CT scanner and utilizing telemedicine); paramedic treatment of AIS in the hyperacute period with thrombolysis and neuroprotectants will soon become a reality. This will be a future game-changer for our patients.

IV-TPA in the extended time window appears safe in U.S. population

Matthew Edwardson, MD

Cronin CA, Langenberg P, Dutta TM, and Kittner SJ. Transition of European Cooperative Acute Stroke Study III Results to Clinical Practice: Ninety-Day Outcomes in a US Cohort. Stroke. 2013

The ECASS III trial provided strong evidence for the safety and efficacy of IV-TPA in the 3-4.5 hr time window post-stroke. After publication of ECASS III, the American Stroke Association endorsed the use of IV-TPA in the extended time window, but the U.S. FDA did not due to prior conflicting results from the ATLANTIS trial conducted in North America (ATLANTIS tested IV-TPA in the 3-5 hr window). What emerged is widespread off-label use of IV-TPA in the 3-4.5 hr window by U.S. physicians. Cronin and colleagues studied this practice by comparing outcomes in patients treated from 0-3 hrs and 3-4.5 hrs post-stroke.

The authors conducted a prospective cohort study enrolling 296 patients treated with IV-TPA at 18 primary stroke centers in Maryland. The authors found no difference between those treated from 0-3 and 3-4.5 hrs with regard to favorable outcome (mRS 0-1 or 0-2), mortality, or symptomatic ICH. Community hospitals were much less likely to treat patients in the extended time window (15.8%) than academic medical centers (38.3%). Regarding the additional ECASS III exclusion criteria for the extended time window, only age > 80 and combined history of prior stroke and diabetes influenced the number of patients treated.

It is difficult to draw hard conclusions from this study about the safety and efficacy of IV-TPA in the extended time window, but it does inform regarding the adoption of this practice in the U.S. The efficacy of IV-TPA decreases exponentially with time post-stroke, therefore one would expect worse outcomes in patients treated in the extended time window compared to the 0-3 hr time window. The fact that the authors did not see any difference in morbidity or mortality between groups is encouraging, however, those treated in the extended time window also had less severe strokes. What’s most interesting about this study is the reduced rate of IV-TPA treatment in community hospitals. This is not surprising considering the lack of FDA approval and that community hospitals often treat relative contraindications as absolute contraindications out of fear of litigation. This study corroborates the favorable results found in ECASS III and highlights reduced treatment rates in the extended time window in the U.S. Perhaps the time has come to resurrect a new version of the ATLANTIS trial testing the 3-4.5 hr time window so we can finally get our stroke patients the treatment they deserve.