American Heart Association

Monthly Archives: December 2013

Carotid Bifurcation Geometry is an Independent Predictor of Early Wall Thickening at the Carotid Bulb

Sebina Bulic, MD

Bijari PB, Wasserman BA, Steinman DA. Carotid Bifurcation Geometry Is an Independent Predictor of Early Wall Thickening at the Carotid Bulb. Stroke. 2013

Flow dynamics with disruption of the laminar flow, vessel geometry and their relationship to the ICA atherosclerosis have always been interesting subject of research and discussion. Furthermore, the association of the vessel geometry and ICA atherosclerosis has been well established, but those studies did not take into consideration atherosclerotic risk factors, which independently can change vessel geometry. Interestingly, traditional risk factors influenced more CCA IMT than ICA IMT as one would expect. This gave more weight to the bifurcation geometry and change in hemodynamics as risk factor for ICA IMT.

Bijari et al. investigated prospectively obtained imaging and risk factor data. Selected patients were divided into 3 groups: The first group included 467 patients with no arterial stenosis. The second group consisted of 346 patients from the first group who were selected based on ICA and CCA wall thickness, previously established thresholds for inward remodeling, and from this group, 294 patients were identified with no lumen irregularities, thus third group was the least likely to have luminal geometry changed due to wall thickening.

In this study, vessels were evaluated using 3D MRI. Mean and maximal wall thickness was reported for CCA and ICA. Flare (maximum bifurcation cross section divided by CCA3 cross section) and curvature (term in description similar to length CCA3-distal ICA divided by straight line between these two points) were adopted for this study.

Result of this study demonstrated that geometric factors such as flare and curvature represent independent factors ICA wall thickness as previously suspected, in addition to previously identified effect on flow dynamics.

Despite some flaws in the design of this study as identified by the authors, it is wonderful to see confirmation of previously suspected relationships in the “segment specific” influence of hemodynamics on carotid wall thickness. 
By |December 30th, 2013|Uncategorized|0 Comments

Does statin use increase the risk of cerebral hemorrhage after thrombolysis?

Vivek Rai, MD

Scheitz JF, Seiffge DJ, Tütüncü S, Gensicke H, Audebert HJ, Bonati LH, et al. Dose-Related Effects of Statins on Symptomatic Intracerebral Hemorrhage and Outcome After Thrombolysis for Ischemic Stroke. Stroke. 2013.

Statins have been shown to have beneficial effect on outcomes after stroke. However, there is conflicting data suggesting increased risk of symptomatic intra-cerebral hemorrhage (sICH) after intravenous thrombolysis (IVT) with prior use of statins. Also, there is no data about whether this effect is dose-dependent. Scheitz et al conducted this retrospective data analysis from two large prospective thrombolysis registries from University Hospital Charité Berlin, Germany (2005-2012) and University Hospital Basel, Switzerland (1998-2012) to study whether statins have dose-dependent effects on risk of sICH and outcome after IVT for ischemic stroke.

Authors stratified satin doses in three groups, low-dose – simvastatin 20 mg or equivalent, medium-dose – simvastatin 40 mg or equivalent and high-dose – simvastatin 80 mg or equivalent or higher. They report that among 1446 patients analyzed, sICH occurred in 4% (n=53) and frequency of sICH was 2%, 6% and 13% in patients with low-, medium- and high-dose statin treatment, respectively (p<0.01) suggesting increased dose-dependent risk of sICH with prior statin use. On the other hand, Statin users more often achieved favorable outcome (mRS 0-2) compared to non- statin users (58% versus 51%, p=0.03).
In my view, this study adds to the current body of evidence suggesting that statin use is associated with improved outcomes after stroke, although it may increase the risk of sICH after thrombolysis. In addition, the increased risk of sICH could be dependent on multiple factors, such as extent of LDL lowering with statins, imaging parameters like lesion volume and pre-existing leukoaraiosis to name a few, but this information is not available in this study. Although, the study will not change my clinical practice but I will be using this information in discussions about benefits and risks of statin use.

By |December 27th, 2013|Uncategorized|0 Comments

Who’s at risk for stroke after TIA? The new Canadian TIA score

Seby John, MD

Perry JJ, Sharma M, Sivilotti MLA, Sutherland J, Worster A, Émond M, et al. A Prospective Cohort Study of Patients With Transient Ischemic Attack to Identify High-Risk Clinical Characteristics. Stroke. 2013

In this article, Perry and colleagues identify clinical factors associated with the occurrence of stroke after a TIA, and propose a new stratification score. So after the California score, ABCD and ABCD2, we now have the Canadian TIA score. An ounce of prevention is worth a pound of cure certainly holds true for TIA management. Patients after TIA are at high short-term risk of stroke, and immediate medical/surgical interventions reduce this risk. Hence, the continuing efforts to refine TIA triage.

This was a prospective study done in 8 Canadian ERs where patients with TIA were enrolled. The WHO definition of TIA was used which did not require imaging to exclude infarction. Clinical features that strongly correlated with developing a stroke included: first ever TIA, language disturbance, duration > 10 minutes, unilateral weakness, gait disturbance, elevated BP, atrial fibrillation, infarction on CT, and elevated blood glucose. Vertigo, lightheadedness and visual loss were less associated with an impending stroke. Based on this, a 13 variable score was developed with score ranging from -3 to 23 to predict the probability of stroke within 7 days (range 0.01% to greater than 27.6%)
This study gives clinicians valuable information about which clinical features are worrisome and may be a harbinger of stroke. However, much like the previous TIA scores, I don’t feel the Canadian TIA score by itself should be used to make decisions. My bottom line is that all patients presenting with a TIA should be emergently evaluated at minimum with basic labs, neurovascular imaging and electrocardiogram +/- echocardiography, and institutions should devise mechanisms to best accomplish this. Subsequently, this score can be used to decide whether the patient should be admitted or observed. However, if resources are limited and screening is impossible, this score may help choose patients for selective specialist assessment and investigations. Validation studies are needed. 

By |December 26th, 2013|Uncategorized|0 Comments

Stent vs CEA: predictors of ischemic lesions after intervention

Peter M. Hannon, MD

What factors might make an individual more likely to have a stroke after CEA or stenting for symptomatic stenosis? As part of the MRI substudy of the Internal Carotid Stenting Study (ICSS), authors looked to answer just this question. The original ICSS trial results in 2010 showed increased risk of stroke and all cause death in the stenting group, and increased risk of MI in the CEA group.  In this substudy, authors investigated 231 patients that had MRIs before and after intervention. Of those patients that had a 1 month follow-up MRI, they found that 28/44 (64%) in the stenting group and 6/10 (60%) in the CEA group had early DWI lesions with at least one persistent flair change at 1 month. Factors that predicted acute DWI lesions in the stenting group were age (>71yo), male gender and patients with stroke as the qualifying event. SBP > 158.5 was found to predict more acute lesions in the CEA group. More severe white matter disease was found to predict more acute lesions in both groups. Authors specifically note that while more acute and persist MRI lesions were found in the stenting group, that the probability of conversion from acute lesions to persistent lesions was less in the stenting group, which they feel was most likely explained by smaller acute lesions.

While the study sample size was small, these findings seem to mirror other studies such as CREST in which older patients did worse with stenting and more patients had peri-procedural strokes with stenting. Clearly, patient selection is critical in deciding the optimal treatment choice for symptomatic carotid disease, especially in our older patient. While stenting is certainly indicated in specific patient populations, the results of this study seem to reinforce the interim safety results of ICSS–that CEA “should remain the treatment of choice for patients suitable for surgery.”
By |December 24th, 2013|Uncategorized|0 Comments

How old is it? Time from symptom discovery estimates age of wake-up stroke.

Matthew Edwardson, MD

Kim BJ, Kim H, Lee DH, KwonSU, Kim SJ, Kim JS, et al. Diffusion-Weighted Image and Fluid-Attenuated Inversion Recovery Image Mismatch: Unclear-Onset Versus Clear-Onset Stroke. Stroke. 2013

Around 1/4th of stroke patients first notice symptoms upon awakening and are therefore ineligible for thrombolytic therapy. However, many of these patients probably had their strokes close to the time of awakening and would be good candidates for thrombolytics. FLAIR positivity on MRI may provide this “tissue clock”, as FLAIR changes appear gradually over the first several hours after stroke as a result of ischemia related neuronal edema. Indeed, two ongoing trials – MR-WITNESS in the U.S. and WAKE-UP in Europe – hope to address the safety and efficacy of thrombolysis in patients with wake-up stroke using FLAIR as a surrogate for symptom onset time. One aspect of wake-up stroke that has never been addressed is how the time from symptom discovery correlates with the progression of these FLAIR changes.

Kim and colleagues retrospectively compared DWI-FLAIR mismatch in 114 patients with wake-up stroke and 145 patients with stroke of known symptom onset time, all presenting within 6 hrs of symptom discovery. The authors found that when MRI was performed within 2 hrs of symptom discovery the two groups had the same proportion of patients with DWI-FLAIR mismatch (50% vs. 51.5%, p = 0.92), but this proportion plummeted in the wake-up stroke group at 2-3 hrs (16.1% vs. 44%, p = 0.02), 3-4 hrs (13.8% vs. 36.4%, p = 0.04), and 4–5 h (5.6% vs. 29.6%, p = 0.05) (wake-up vs. non-wake-up respectively).

The results of this study imply that a large percentage of patients with wake-up stroke presenting rapidly after symptom discovery have infarcts that are still early in their time course – early enough to benefit from thrombolytic therapy. The authors suggest using 2 hrs from symptom discovery time as a potential selection criterion for multimodal MRI-based thrombolysis in wake-up stroke. However, if FLAIR positivity is truly an accurate gauge of infarct age this time cutoff seems unnecessary and would cause you to withhold treatment from the small percentage of patients with stroke onset just prior to awakening. I find the implications of this study much more interesting for CT-based thrombolysis in wake-up stroke. A minority of stroke neurologists currently treat wake-up strokes with off-label TPA in the setting of a pristine head CT. In settings where MRI is not readily available, using this 2 hr cutoff from symptom discovery time may dramatically increase the proportion of patients truly in the time window for thrombolytics. Perhaps 2 hrs from symptom discovery will become an important inclusion criterion for a future trial of CT-based thrombolysis for wake-up stroke.

By |December 23rd, 2013|Uncategorized|0 Comments

Socioeconomic deprivation linked to reduced survival after stroke in England

Vivek Rai, MD

Chen R, McKevitt C, Rudd AG, and Wolfe CDA. Socioeconomic Deprivation and Survival After Stroke: Findings From the Prospective South London Stroke Register of 1995 to 2011. Stroke. 2013.

Socioeconomic deprivation (SED) has been implicated in increased risk of stroke and increased mortality afterwards. The data about SED affecting long term outcomes after stroke is rather inconsistent. In the West the number of Black and Minority Ethnic (BME) populations has been increasing over the last 2 decades, and patients of BME groups are more likely to experience socioeconomic disadvantage and health care inequality. In this retrospective analysis, Chen et al investigated the association of SED and short and long term survival after stroke in multi-ethnic study population in stroke register in England. 

The authors used Carstairs Index (A validated index of SED based on four census indicators: low social class, lack of car ownership, overcrowding and male unemployment) to define the severity of SED. Data from 4398 patients of stroke, collected between 1995 to 2011 using a prospective stroke registry, was analyzed. Patients with severe SED had significantly high mortality (Hazard Ratio = 1.23 for 3-month-mortality and 1.13 for 17-year-mortality). Black patients with 4th quartile SED had increased 3-month mortality but this was not significant when adjusted for acute stroke care provisions.

This is yet another study that demonstrates disparity in health care and health outcomes based on socioeconomic factors. Similar results have been shown in US, Canada, Austria and China. The study highlights the need to identify these patients and involve them and their families in health care. How do we achieve that? Can these studies help in formulating healthcare policies that result in more equitable outcomes? How can physicians contribute? So far, these are some of the questions that remain unanswered. 
By |December 20th, 2013|Uncategorized|0 Comments

Factors associated with onset-to-door time in TIA patients admitted to stroke centers

Sebina Bulic, MD

TIA is the golden opportunity for the aggressive work up and stroke risk reduction in symptomatic patients and should represent neurologic urgency.

In this study from Japan, data was collected from 13 stroke centers and retrospectively analyzed.  Four hundred and twenty one patients with TIA within 7 days were dichotomized in the following 5 categories: <3 hours, 3-6 hours, 7-12 hours, 13-24 hours and >24 hours. Factors associated with the time from symptom onset to arrival at a stroke center were assessed.

Motor weakness, speech disturbance, and duration of symptoms > 10 minutes were
independently associated with a shorter onset to door time. Interestingly a history of TIA and hypertension, and a referral from another medical facility were  independently associated with a longer onset to door time. Onset to door time and stroke during the acute admission, which was the primary outcome did not have relationship.

Patient population and healthcare delivery system in Japan is very different from the United States, thus I don’t know if results of this study would be applicable here. What I found interesting was that a history of TIA and hypertension were  independently associated with a longer onset to door time. I would have never assumed that, and this is worrisome for me. Do we really provide such poor education to our at risk population?
By |December 19th, 2013|Uncategorized|0 Comments

The inflammation theories in intracerebral hemorrhage

Seby John, MD

Di Napoli M, Parry-Jones AR, Smith CJ, Hopkins SJ, Slevin M, Masotti L, et al. C-Reactive Protein Predicts Hematoma Growth in Intracerebral Hemorrhage. Stroke. 2013

Intracerebral hemorrhage remains the most deadly form of stroke with high morbidity and mortality. Approximately 40% of ICHs will expand and this is an independent predictor of poor clinical outcomes. How this expansion occurs is unknown and several studies have attempted to predict which hemorrhages will expand. 

Di Napoli et al. studied the link between plasma C-reactive protein (CRP) and early hematoma growth (EHG) after spontaneous ICH (sICH). CRP was measured within 6 hours in patients with primary or vitamin-K antagonist associated sICH, without infection. ICH volume was measured at baseline and within 24 hour using CT brain imaging. They found that median CRP levels were significantly higher in patients who developed EHG compared to those who didn’t. A CRP level >10 mg/l was independently predictive of EHG and early neurological worsening, both of which were associated with increased 30-day mortality. High CRP was also more frequently associated with larger hematomas, severe clinical presentation, IVH, and death at follow-up. The authors conclude that CRP maybe able to identify patients at risk for EHG, thus helping with patient care and prognostication.
This study offers support for the inflammation hypothesis causing primary and secondary injury in ICH. 

Much has been learnt in recent years regarding the pathophysiology of injury, and seems to be mediated by a complex intertwined progression of inflammatory cascades, red cell lysis and thrombin production. Although complicated, interruption of any players in these cascades can be feasible therapeutic targets to prevent injury. The trials of steroid use for ICH in the 1970s and ‘80s showed no benefit, but may have been off set by adverse effects. 

With a better understanding of inflammatory signaling molecules, the dawn of targeted treatment for ICH may be in sight.

By |December 18th, 2013|Uncategorized|0 Comments

Multi-vessel cervical artery dissection: The CADISP group results

Seby John, MD

Béjot Y, Aboa-Eboulé C, Debette S, Pezzini A, Tatlisumak T, Engelter S, et al. Characteristics and Outcomes of Patients With Multiple Cervical Artery Dissection. Stroke. 2013

Cervical artery dissection (CeAD) although rare in the general population is an important cause of stroke. This is especially the case in younger patients where CeAD is the leading cause of stroke in patients < 45 years. This paper comes from the CADISP (Cervical Artery Dissections and Ischemic Stroke Patients) multicenter international consortium that has the largest series of patients with CeAD. Béjot and colleagues compare the characteristics and short-term outcomes of patients with single versus multiple artery CeAD.

Out of 983 patients with CeAD, 15.2% had multi-vessel dissection. Multiple CeAD was more often associated with cervical pain at admission, a remote history of head or neck surgery, recent infection and cervical manipulation. Adjusted analysis showed that hypertension was significant associated with multiple CeAD. Interestingly, imaging evidence of cervical fibromuscular dysplasia (FMD) and presence of pseudoaneurysms were more common in patients with multiple CeAD. We do not have details on treatment, but 3-month modified Rankin score was similar between the two groups, and there were no deaths. Rate of CeAD recurrence was low in both groups. 

Although these results are unlikely to change management, I think it provides useful information. The finding of multiple CeAD being associated with an underlying vasculopathy should prompt us to search carefully for systemic vasculopathies such as FMD. There is little we can do about environmental triggers, but perhaps it sheds light on the pathophysiology. A previous paper from the CADISP group reported that hypertension could be a risk factor for CeAD.  Hypertension was more common in patients with multi-vessel CeAD.  Could this be contributing to the mechanism? Fortunately, the outcomes in multi-artery CeAD also appear favorable although severe cases of stroke or death may have been missed.

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

How to Optimize Secondary Prevention Medication Use in Stroke Survivors

Waimei Tai, MD

Thrift AG, Kim J, Douzmanian V, Gall SL, Arabshahi S, Loh M, et al. Discharge Is a Critical Time to Influence 10-Year Use of Secondary Prevention Therapies for Stroke. Stroke. 2013

Thrift et. al did an interesting analysis of discharge prescription of appropriate secondary intervention drugs (statin, blood pressure reduction agents, and antithrombotics) to persistent use at annual intervals up to 10 years out post-stroke. They used a large registry of stroke survivors from the North East Melbourne Stroke Incidence Study and followed the patients out for up to 10 years.  The odds ratio of medication persistence was 32 at two years (meaning that if patients were prescribed the medications at discharge- they were 32 times more likely to still be taking them at 2 years post stroke). The strength of the association from discharge medication prescription to subsequent medication use declined as the years progressed.

One of the strengths of the study is also its weakness. It has long term follow up with stroke survivors- and certainly in the last 10+ years, evidence for stroke prevention has changed, and thus, increases in blood pressure and statin prescribing maybe reflective more of changing practice patterns due to the evidence base for these medications increasing, rather than the acute discharge prescription patterns as being studied. The authors acknowledge this, and nonetheless, even for patients who

Providers currently working at primary or comprehensive stroke centers know that it’s a regulatory requirement to optimize discharge medication prescriptions. I think there’s a good evidence base to suggest this and this study bolsters the evidence base to do appropriate medication prescribing at time of discharge to improve not only short term, but long term medication persistence as well.

We know these simple generic medications work. Now we just have to get our patients to take them. What else can we do to improve medication persistence and adherence in the long run?
By |December 13th, 2013|Uncategorized|0 Comments