American Heart Association

Yearly Archives: 2013

Robots to serve as stroke outcome surrogate?

In this paper, the authors describe how robotic measurements may be used a surrogate marker of motor function—a “biomarker” of stroke recovery in those with hemiparesis after stroke. The concept is that a robotic measurement may have more precision in measurement, such that early differences in functional recovery can be detected. This may decrease the enrollment numbers needed to demonstrate effectiveness in clinical trials of motor recovery and neuroprotection.  The authors compared robot assisted measurements in kinematics and kinetics (RMK2) to standard clinical rating scales such as the NIHSS, mRS, Fugel-Meyer and Motor Power.

RMK2 measurements are actually a composite of 35 measurements of arm average speed, peak speed, ability to move against resistance, among others. A complicated technique using neural networks to build non-linear models of the clinical scalses was used for comparison. The study found that in stroke patients (evaluated at multiple time points up to 90 days), robotic measurements correlated with standard rating scales with high correlation coefficients (r2 of approximately 0.6). The authors predicted that the standardized effect size would be increased by 1.47, allowing for greater sensitivity in measuring recovery. 

The authors point out that the population used in this study was highly selected, and utility in hemiplegic patients is unknown. The handedness of subjects in the paper was also not clear. A majority of the subjects did not complete all visits. Taking these limitations into account, there is potential for robotic measurements to become a standard of motor outcome in clinical trials. The promise of saving money and completing trials sooner, fuels the progress of robotic technology. We look forward to the future of robots as biomarkers and neuroprotection in stroke!
By |December 12th, 2013|Uncategorized|0 Comments

A systemic review and meta-analysis of the utility of MRA for the detection of intracranial aneurysms

Adam de Havenon, MD

Sailer AMH, Wagemans BAJM, Nelemans PJ, de Graaf R, and van Zwam WH. Diagnosing Intracranial Aneurysms With MR Angiography:Systematic Review and Meta-Analysis. Stroke. 2013

The gold standard for diagnosing and characterizing intracranial aneurysms is digital subtraction angiography (DSA), but it’s an expensive and potentially dangerous procedure that isn’t available at many smaller medical centers. In its stead, computed tomography angiography (CTA) is the test of choice, particularly in the acute setting. However, it is widely accepted that any ionizing radiation is harmful regardless of dose and some patients will not tolerate iodinated contrast. Magnetic resonance angiography (MRA) helps fill this void, but historically has been considered significantly less sensitive and specific than either DSA or CTA.

This review and meta-analysis by Anna Sailer and colleagues is the first to revisit the topic in a systematic way since 2000 and includes data from 12 studies comparing MRA to DSA for the detection of ruptured and unruptured intracranial aneurysms dating from 1999 to 2012 with 960 patients and 772 aneurysms. During that time period, MRA technique has changed considerably, from contrast-enhanced MRA to time-of-flight (TOF), 1.5T field strength to 3T, and hardcopy films to digital images with 3D multiplanar reconstructions.

The pooled sensitivity and specificity of MRA in these studies was 95% and 89% with false negative and false positive aneurysms located primarily at the skull base and middle cerebral artery. The use of digital images, in particular freehand 3D reconstruction performed by the radiologist, improved detection, while the increase in field strength from 1.5 to 3T showed a trend towards higher performance, but did not reach statistical significance, and MRA TOF was not superior to contrast-enhanced MRA. The prior meta-analysis on MRA from 2000 reported a pooled sensitivity and specificity of 95% and 89%. It’s not exactly a compelling evolution, and given that a recent meta-analysis of CTA suggests sensitivity and specificity of 95% and 96%, it will remain the non-invasive diagnostic test of choice when reliable and rapid result are needed. This study reinforces the utility of MRA for sub-acute and serial evaluation, and of the newer techniques such as 3D reconstruction and TOF.
By |December 10th, 2013|Uncategorized|0 Comments

Early speech therapy hastens shift in cortical activation, improves outcomes post-stroke

Matthew Edwardson, MD

Mattioli F, Ambrosi C, Mascaro L, Scarpazza C, Pasquali P, Frugoni M, et al. Early Aphasia Rehabilitation Is Associated With Functional Reactivation of the Left Inferior Frontal Gyrus: A Pilot Study. Stroke. 2013

Functional MRI (fMRI) studies reveal a typical pattern of cortical activation during spontaneous recovery of language following stroke. The acute phase is characterized by reduced activation in the left hemisphere, the subacute phase by activation of bilateral speech areas, and the chronic phase by a shift back to the left hemisphere. These changes correlate with improvement in various aspects of speech production. However, the effects of speech therapy on these activation patterns, particularly in the acute phase, remain unknown.

To address this question, Mattioli and colleagues randomized 12 patients with mild-moderate aphasia to 1 hr per day of speech therapy for 2 wks versus no speech therapy. Therapy was started very early (mean 2.2 days post-stroke). Investigators performed the Aachen aphasia test and fMRI with a language comprehension task at baseline, 2 wks, and 6 months post-stroke. At the 2 wk time point, subjects in the speech therapy group demonstrated improved naming and written language abilities compared to control subjects; this effect persisted at 6 months. In regard to cortical activation, at 2 wks post-stroke only subjects in the speech therapy group showed increased cortical activation in the left inferior frontal gyrus (Broca’s area); the control group subjects had increased activation primarily in the right inferior frontal gyrus (Broca homologue). By 6 month follow-up, both groups demonstrated activation of language areas primarily in the left hemisphere.

This is the first study to explore the effects of aggressive speech therapy in the acute phase post-stroke on cortical activation patterns. The authors nicely demonstrate both the long-term benefit of early speech therapy and a shift in cortical activation toward the left hemisphere as a result of speech therapy. It remains uncertain whether the shift in activation patterns to the right hemisphere in the subacute phase during spontaneous language recovery (seen in this study in control subjects 2 wks post-stroke) is adaptive or maladaptive. Considering that speech therapy group subjects quickly shifted activation back to the left hemisphere and achieved better long-term outcomes, this study may support a maladaptive role for right cortical activation patterns. Perhaps the faster we can promote this left-shift, the better the long-term language function will be. It follows that we may need to get more aggressive with early language therapy for stroke patients. To justify such a change, larger trials are needed comparing different doses and timing of language therapy post-stroke.
By |December 6th, 2013|Uncategorized|0 Comments

Predicting Outcome in Pediatric ICH

Beslow et al. recently published a prospective study of 79 children (full term infants to age 18) with ICH which examined the reliability of the author’s pediatric hemorrhage score to predict outcome at 3 months. Outcomes were measured by functional recovery 3 months after presentation with ICH, using the King’s Outcome Scale for Childhood Head Injury, or KOSCHI). The study rationale was that although such scores exist for adults, children with ICH have lower mortality than adult and thus unique prediction tools are required for the pediatric population. The elements included in the pediatric ICH score include: ICH size (adjusted for total brain volume), presence of hydrocephalus, infratentorial location, and herniation. A score greater than or equal to 2 predicted poor outcomes of death or severe disability, and a score greater than or equal to 1 predicted moderate disability or worse, both with high sensitivity and specificity.

The benefits of this score are that it is easy to use and implement. The simple scoring system, from 0 to 5, would be simple to implement in clinical practice. Although those with a higher score are more likely to have severe disability or death, the prospective validation in one population may need to be repeated in another patient group, before it can be used to counsel family members considering whether to withdraw care. As the authors point out, this may unfairly bias the poor outcomes observed in higher scores. Another question that came to mind, is would outcomes be different if we looked at children between birth and one year, and greater than one year separately? This score provides further attention to the much understudied problem of pediatric stroke, of which a large percentage is hemorrhagic. Moving forward, pediatric neurologists and intensivists have a new tool to integrate into clinical practice.
By |December 5th, 2013|Uncategorized|0 Comments

Post-Stroke participation restriction: A new measure of disability to broaden our understanding of stroke survivorship

Tareq Kass-Hout, MD

Skolarus LE, Burke JF, Brown DL, and Freedman VA. Understanding Stroke Survivorship: Expanding the Concept of Poststroke Disability. Stroke. 2013

Skolarus et al. conducted a data analysis recently published online in stroke and identify a different aspect of disability post stroke that we often ignore: post-stroke participation restriction. The authors also investigate the extent to which post-stroke participation restriction is accounted for by cognitive impairment, language disorders, and/or psychiatric symptoms.

Patients, a total of 892, were from the National Health and Aging Trends Study (NHATS) database and matched with a control group based on demographics and co-morbidities. The authors defined post-stroke participation restriction as reductions/absence in social activities valued by respondents because of their health or functioning. The analysis showed that stroke survivors are two times more likely to have participation restriction (attending religious service, clubs/classes and going out for enjoyment) than the control group, this was true after adjusting for physical capacity. Also, psychiatric symptoms such as depression and anxiety, and aphasia/dysarthria were independent predictors of participation restrictions.

In short, this study is proposing a new, yet very important, post-stroke disability measure, which is participation restriction. I consider this analysis an eye opener for stroke specialist to pay extra attention aiming to minimize post-stroke disability by improving physical capacity, reducing depressive and anxiety symptoms, and improving aphasia/dysarthria.

Novel imaging techniques to characterize cerebral cavernous malformations (CCM)

Known by many neurologists by the board-ready “popcorn” appearance on MRI, cerebral cavernous malformations (CCMs) are characterized by low-pressure capillary dillitations with a propensity to seep or leak blood due to vascular permeability, and thus accumulate iron depositions over time. Sequelae include epilepsy, focal deficits and stroke, and depending of size and symptoms, CCMs may require surgical intervention. In their current article, authors Mikati et al describe novel MRI imaging techniques to help characterize and follow CCMs over time, specifically Dynamic Contrast Enhanced Quantitative Perfusion (DCEQP) to measure vascular permeability, and Quantitative Susceptibility Mapping (QMI) to assess iron deposition.

In a previous article, the authors described the decrease of iron deposition and lesion burden in murine CCM models by Rho Kinase (ROCK) inhibition by Fasudil, and were looking for a method to monitor this potential therapy in a clinical setting. Twenty-one patients with CCM were imaged, all but 5 with a familial form of CCMs. A positive correlation was found between the mean QSM susceptibility and mean permeability of the lesions via DCEQP, which would make sense, as leaky lesions would seem more likely to accumulate iron deposition. The authors note that these findings were independent of lesion volume, differing contrast agents used or whether patients were on a statin. 

The study is somewhat limited by small sample size and a disproportionate number of familial vs. sporadic cases of CCM, but illustrates novel MRI imaging techniques that could help monitor potential treatments over time. If these results continue to hold out over larger and more diverse sample sizes, then DCEQP could be a measure of “active” or ongoing permeability, and QMI could help measure the overall burden of this activity. In a non-invasive manner, both could not only help monitor a response to new treatments for CCMs, but also help determine whether treatment is even indicated.

By |December 3rd, 2013|Uncategorized|0 Comments

Stroke…Where Would You Want to Be?

Hassanain Toma, MD

Cumbler E, Wald H, Bhatt DL, Cox M, Xian Y, Reeves M, et al. Quality of Care and Outcomes for In-Hospital Ischemic Stroke: FindingsFrom the National Get With The Guidelines-Stroke. Stroke. 2013

A significant number of ischemic strokes occur in patients hospitalized for various medical conditions. Cumbler et al. sought to analyze the quality of care and clinical outcomes for such patients. They used the national Get With The Guidelines-Stroke (GWTG-Stroke) of the American Heart Association to retrospectively compare the care of in-hospital patients to stroke patients that present from the community. Their data suggest that in-hospital stroke patients experienced more severe strokes (NIHSS 9 vs 4), received lower adherence to process-based quality measures (60.8% vs 82.0%), are less likely to ambulate independently (odds ratio 0.42), and have a higher mortality (odds ratio 2.72).

Their finding is shocking to me because I often tell my patients “there is no where better to have a stroke than while hospitalized”.  According to this study, this is clearly not the case! Although, this study showed that in-hospital stroke patients tend to be sicker, the outcomes are the same even after adjusting for multiple variables.  The authors provide a good discussion for the disparity, without clear answers. 

Fewer strokes after PCI vs. CABG, even long-term

Nirali Vora, MD

Athappan G, Chacko P, Patvardhan E, Gajulapalli RD, Tuzcu EM, and Kapadia SR. Late Stroke: Comparison of Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Patients With Multivessel Disease and Unprotected Left Main Disease: A Meta-Analysis and Review of Literature. Stroke. 2013

Quiz: A patient has left main CAD and can be treated with percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). Don’t worry, I’m not asking you to choose a procedure since our cardiology colleagues will take care of that. But, you should know the stroke risk with each procedure.

  1. Which procedure carries a higher risk of stroke? CABG per SYNTAX trial 2.2% vs. 0.6%, p=0.03, at 1 year. 
  2. Does the lower stroke rate in PCI catch up to CABG in the long-term?Maybe. SYNTAX 5 year follow up 3.7% vs. 2.4%, p=0.09 at 5 years.

Notice how the PCI rate of stroke went up (0.6 -> 2.4)? The focus of this newly published meta-analysis was to look at a larger sample size and determine if the stroke rates really do equalize between the two interventions after ≥1 year follow up. The authors identified 80,000 patients with more than half of the patients were followed 2+ years out.

The PCI group persistently had a significantly lower cumulative stroke rate than the CABG group, even when looking at 1 vs. 2 vs. 3 vs. 4 vs. 5 years out. In the 5+ years group, there was no significant difference but there were only ~1600 patients. There was no significant difference among diabetics, but there was a trend favoring PCI. In looking at RCTs only, PCI did better in the 30 day perioperative period, but then had no difference with CABG in terms of stroke at 1 year. The authors suggest that the increased rates of stroke in PCI in the later period may be do to post-revascularization atrial fibrillation; or in my opinion, the ongoing vascular risks factors for the patient population overall.

Bottom line for me: there are more strokes after CABG than PCI, even >1 year post-op. However, determining the optimal coronary intervention will be patient dependent and incorporate all-cause mortality, recurrent MI, target revascularization, and cost effectiveness in addition to stroke.

By |November 29th, 2013|Uncategorized|0 Comments

Developing stroke systems of care in Mexico: Many challenges but more opportunities

Mexican Academy of Neurology (AMN)
November 2-9, 2013

Two weeks ago the Mexican Academy of Neurology (AMN) held its 37th Annual Meeting in the beautiful city of Merida, Yucatan, a culinary, musical and archaeological paradise. I was honoured to participate, along with Drs. Antonio  Arauz, José Luis Ruiz-Sandoval  and Marco Antonio Alegría, in a symposium on developing stroke systems of care organized by Dr. Fernando Barinagarrementería.

Mexico is an upper middle-income country (GDP $1.178 trillion) with 121 million inhabitants. It has a long tradition of implementing public health initiatives and now has universal health care coverage. The life expectancy at birth is 77 years. But almost 20 years after the publication of the NINDS tPA study, <3% of patients with a stroke are treated with lytics or other acute interventions, despite the fact that 24% of patients arrive to the hospital within 3 hours of onset (almost half get to the hospital within 6 hours.) As in many other countries, including the US, many factors contribute to this low treatment rate, including a fragmented health care system, the lack of a coordinated EMS and in-hospital response, unavailability of lytics in some hospitals, limited access to imaging, poor knowledge of stroke signs and symptoms among the general population, and physicians’ fear about the risks of acute stroke treatments.

But these challenges highlight several opportunities for intervention. The symposium participants and the audience agreed on the need to implement a coordinated system of stroke care in Mexico that involves the public, civil society, physician groups, first responders, hospitals, public health organizations and the government. I was encouraged to see that representatives from the Ministry of Health and the Seguro Popular were in the audience, and my hope is that they left the meeting with a greater awareness of the burden of stroke and the human, social and economic benefits of rapid diagnosis, transportation and treatment of stroke patients.

The Mexican Stroke Association (AMEVASC) is the largest organization of stroke physicians in the country. It is a small but very active group whose members work together to increase public awareness of stroke and its warning signs, promote high quality stroke care in hospitals, and engage in stroke research. They have established national ischemic stroke and ICH registries and participate in investigator-led and multicentre international stroke studies such as IST-3 and SPS3. They have also developed practice guidelines for stroke treatment and prevention. All the speakers at the symposium (myself included) are members of AMEVASC, the organization that is leading the effort to improve care at the state and national level.

At the end of the symposium participants endorsed the Merida Declaration, a call to action to physicians, hospitals, EMS providers, the public, NGOs and state and national governments to work together to develop stroke systems of care throughout the country. This is the first step in the development of a system of care that will identify stroke centres and promote the rapid and accurate identification of stroke patients, swift transport to hospitals, prompt attention in the emergency room, and access to effective treatments for patients with stroke in Mexico.

– Jose Merino, MD
By |November 29th, 2013|Conference|0 Comments

Collateral flow: utilizing CTP for rapid assessment of viable collaterals in acute stroke

It has long been apparent that the outcomes of all ischemic stroke patients are not alike, even those with remarkably similar occlusions found on vessel imaging who arrive in a similar time frame and receive similar care. “Good collaterals” are often pinpointed as a major factor that could cause these differences, however methods of effectively gauging collaterals have historically been time consuming or not available or possible in the acute setting. In their current article, authors Cortijo et al find that CT perfusion studies, specifically a calculated relative CBV (rCBV) may be an effective indicator of collateral flow, and thus may be useful in directing therapy in the acute setting.

From 2009 to 2012, 68 patients were enrolled. All participants had to have an MCA–territory stoke, vessel imaging, a CT perfusion (CTP), and IV tPA therapy. TCDs were used to measure recanalization of occluded vessels after treatment. CT perfusion source imaging (CTP-SI) was used to score collateral flow, with values of 0-1 graded “poor” (<50% filling) and 2-3 graded “good” (>50%). rCBV was calculated by comparing the CBV of the affected hemisphere to the unaffected side. Collateral score was significantly associated with mean rCBV (p<0.001), with ROC curve-derived best cutoff values between good and poor collaterals found to be 0.93 (sens 70%, spec 87%). While none of the patients with a low rCBV (<0.93) had a good 90 day outcome in the absence of early MCA recanalization, 52.9% of the patients with high rCBV (>0.93, thus indication of “good” collaterals) became functionally independent despite having a persistent MCA occlusion 2 hours after tPA-bolus.

Studies such as IMS-3 and MR-RESCUE have made a strong case that further delineation of ideal patient populations may be necessary to optimize outcomes post-stroke with intervention beyond IV-tPA. While this study has it’s limitations, such as a small sample size, it is promising that imaging modalities that are relatively fast and accessible like CTP may give us quick insight into the potential “durability” of a stroke bed, and thus give us some guidance as to whether intervention beyond IV tPA may be indicted.

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