American Heart Association

Monthly Archives: February 2013

Carotid Atherosclerosis and Risk of Subsequent Coronary Event

Shruti Sonni, MD

This large study by Sirimarco et al. aimed to examine the association between carotid atherosclerosis, history of atherothrombotic events (including cerebral, cardiac and peripheral vascular disease) and coronary events. 23 364 patients from the Reduction of Atherothrombosis for Continued Health (REACH) Registry with multiple cerebrovascular risk factors or established atherothrombotic events with information regarding carotid atherosclerosis were analyzed. Primary outcome was cardiovascular death, myocardial infarction (MI), or coronary hospitalization. Patients considered to have carotid atherosclerosis were those who had any evidence of carotid plaque, >70% carotid stenosis or history of carotid revascularization. The authors found that the risk of coronary events were 23.2% and 19% in subjects with and without carotid atherosclerosis respectively (an increase of 22%), and risk was increased by 52% for non-fatal MI specifically, leading to a conclusion that carotid atherosclerosis was an independent predictor of coronary events. 

The importance of this study is that, unlike prior studies, it used data from a large international registry of stable outpatients (though not community-based) to evaluate the risk of coronary events, and followed the subjects for a period of 4 years. The authors demonstrated that carotid atherosclerosis predicted risk of coronary events in patients with a history of vascular disease regardless of arterial bed affected- cerebral, cardiac or peripheral. Presence of carotid disease can improve the risk stratification for occurrence of cardiovascular disease, and is likely indicative of coronary artery disease severity. This supports the suggestion that the underlying atherogenic mechanism in carotid and coronary plaque formation are similar, maybe sharing a common inflammatory process. 

One of the limitations of this study however, as acknowledged by the authors, lies in the lack of standard evaluation of the carotid plaques. This study does not answer what the degree of stenosis or plaque amount and morphology were that predisposed to coronary events. The question arises, if carotid atherosclerosis is such a strong predictor of coronary events, can the converse also be assumed to be true? That is, is the incidence of coronary events a strong predictor of carotid atherosclerosis and a stroke risk factor that should be routinely screened for? Although the results are very insightful, the clinical application of this study is unclear. The subjects included in this analysis were those that were likely being treated with maximum medical risk therapy as a result of their prior atherothrombotic disease. Hence, it is unclear what the next diagnostic or therapeutic step in preventing future coronary events should be. 

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

Medial Premotor Cortex Shows A Reduction In Inhibitory Markers And Mediates

Nandakumar Nagaraja,  MD, MS

Premotor Cortex Shows a Reduction in Inhibitory Markers and Mediates Recovery in a Mouse Model of Focal Stroke. Stroke. 2013; 44: 483-489

Some patients with stroke regain the lost function partially or completely. Cortical reorganization adjacent to the damaged cortex is thought to be one of the mechanisms that could result in reduction in impairment. Zeiler and colleagues performed a study in a mouse model of focal motor stroke to show that reorganization in the medial premotor area (medial agranular cortex, AGm) mediates recovery of motor function and is associated with decreased inhibitory interneuron markers.

Adult male C57bl/6 mice 70-120 days old were trained to reach for the pellets placed on a sticky tape on a movable steel bar positioned 0.5cm away from the cage. They were trained until they reached 30% grasping success rate. Then the distance between the cage and the pellets was increased to 1cm to increase the difficulty of the task. 9-11days after training, focal stroke in the motor cortex for the preferred forelimb was induced by photothrombosis of cortical microvessels using a fiber optic bundle of a cold light source. This resulted in decreased skilled motor reaching accuracy that recovered after 5-6 training days.

A second stroke induced in the AGm led to decline in the skilled motor reaching accuracy that was recovered after first stroke. Stroke in AGm alone without prior infarct in motor cortex had no effect on skilled motor reaching accuracy suggesting AGm is necessary for recovery of motor function.

Animals were sacrificed 6-7 days after stroke and examined for inhibitory cortical interneuron markers parvalbumin, calretinin and calbindin. These markers were reduced only in AGm in mice that were retrained after focal motor stroke suggesting that decrease in inhibitory neurons is associated with post stroke recovery.

Understanding the mechanisms and factors associated with recovery of function could translate into implementing effective treatment strategies to minimize disability. In this study the authors have established a mouse model with double lesion approach to understand the mechanisms of post stroke recovery. Further studies at the cellular and molecular level with this mouse model may shed light on mechanism of brain plasticity in post stroke recovery.
By |February 12th, 2013|Uncategorized|0 Comments

Cerebral Microbleeds and Cognition

Jose Gutierrez, MD, MPH

Patel B, Lawrence AJ, Chung AW, Rich P, MacKinnon AD, Morris RG, et al. Cerebral Microbleeds and Cognition in Patients With Symptomatic Small Vessel Disease. Stroke. 2013; 44: 356-36. 


Leukoaraiosis, lacunar strokes, perivascular spaces, and cerebral microbleeds (CMB) are considered markers of brain small vessel disease (SVD). Although sometimes found incidentally, the significance of these MRI finding has been the focus of multiple studies. In this article, Patel et al. explored the association of CMB with cognitive function in a clinical sample of patients with lacunar stroke.
The authors collected demographic, clinical and radiographic data from 116 patients with acute stroke who were admitted to three hospitals in South London. Brain MRI images were analyzed to obtain counts of lacunar strokes and CMB as well as grey and white matter volumes, T2-lesion load, and DTI values. The first analysis included demographic and clinical predictors of the CMB count. They found that markers of other SVD manifestations were the only predictors of CMB. Interestingly, there was trend for greater prevalence of CMB in those taking statins. Using CMB as a continuous variable, the authors did not find any correlation between the cognitive indices included in this study. However, categorizing the CMH count in upper deciles vs. not, there was an association between those with the highest CMB count and impaired executive function. This association remained significant, although with reduced intensity, after controlling for covariates. Although CMB in the basal ganglia and the frontal region were correlated with worse executive function, this association became non-significant after controlling for covariates.
The authors acknowledged important limitations, which include the biased sample used for this study and the limited applicability to other groups. The lack of prospective data hinders inferences about causality. Additionally, the multivariate models did not include cardiovascular risk factors and no mention of reliability measures could be found in the manuscript.
Markers of SVD are frequently found in populations with stroke and in populations with high prevalence of cardiovascular risk factors. Some questions remain unanswered: should markers of SVD be used to improve the cardiovascular risk stratification? Are these markers revelatory of a deleterious interaction between cardiovascular risk factors and reparative mechanisms in the microvasculature? If CMB are proven independent markers of a worse cognitive function, are the mechanisms leading to CMB so unique that would warrant a different approach to the traditional, evidenced-based cardiovascular prevention? This study is an intriguing starting point to broaden the discussion about the implications of these frequent markers of SVD. 


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

Subarachnoid after ICH and Outcome

Vasileios-Arsenios Lioutas, MD

Maas MB, Nemeth AJ, Rosenberg NF, Kosteva AR, Guth JC, Liotta EM, et al. Extension of Primary Intracerebral Hemorrhage is Associated With Poor Outcomes. Stroke. 2013.

It is well known that presence of blood products in the subarachnoid space in cases of intracranial aneurysm rupture leads to activation of several pathological processes leading to brain injury. In this well performed study, Maas et al prospectively enrolled patients with ICH, seeking to test whether radiographic extension of hemorrhage into the subarachnoid space (by CT criteria) contributed to functional outcome and mortality. 14-day mortality and modified Rankin Scale at 28 and 90 days (after correction for the ICH score) were the primary outcomes.

Subarachnoid hemorrhage was convexal and ipsilateral to the intracerebral hematoma in the majority of cases, largely different from the more widely investigated aneurysmal SAH with diffuse, thick subarachnoid clot.

Univariate comparison analysis revealed that patients with subarachnoid hemorrhage extension were older, with larger intracerebral hematoma volumes, lower Glasgow Coma Scale score and more frequently associated with lobar locations. Rate of death at 14 days as well mRS score at 28 and 90 months was significantly higher in that group.

Adjusting for ICH score, (which, as a reminder includes most of the characteristics identified as more frequent in the SAH extension group), revealed a significant association between subarachnoid extension and 14-day mortality and 28-day unfavorable outcome.  A similar but weaker association with unfavourable 90-day outcome was identified.

A secondary multivariate analysis using significant variables identified in the univariate analysis showed unambiguously that SAH extension is a strong independent predictor of death by day 14 (OR 7.58, CI 1.5-36.7 p=0.012).

Why this occurs is not known with certainty, although there are a number of postulated mechanisms (mostly from the aneurysmal SAH literature) attempting to explain the harmful effect of presence of blood in the subarachnoid space.

Potential shortfalls of the study, identified by the authors as well, include the single-center character of the study, limiting the generalizability of the findings, as well as the qualitative nature of determining SAH extension and use of CT scan as detecting method. Adding quantitative measures of SAH volume and using imaging methods more sensitive than CT scan could offer additional accuracy. It would also be interesting to perform the secondary analysis using functional outcome and not only 14-day mortality as outcome measure.

Regardless, this is a well performed study that sheds light into a heretofore scarcely investigated issue, and offers objective evidence to support the intuitive suspicion that extension of hemorrhage into the subarachnoid space has a detrimental effect.

Stroke Care in the Republic of Armenia: Impressions from the Recent Stroke Treatment 2013 Conference

International Stroke Conference 2013
February 6-8, 2013

Last week I attended a stroke symposium in the Republic of Armenia entitled: Stroke Treatment 2013. This was a joint conference put on by the Yerevan State Medical University (YSMU), the Ministry of Health, the Fund for Armenian Relief (FAR) and the Armenian Medical International Committee (AMIC). It was a collaborative project headed up by Professor Viken Babikian of Boston University and the head of Neurosurgery at YSMU, Professor Rouben Fanardjian. We lectured on a host of topics related to stroke treatment and stroke prevention.

The Republic of Armenia is a developing nation that lacks the presence of a stroke system of care. This is highlighted by the fact that in its history, there has been one known case of acute stroke treatment with thrombolytic. There is one center, at the YSMU, with the capabilities to perform neuroendovascular procedures. In general neurologists are not involved with the care of acute stroke patients, which are attended to by emergency physicians and critical care anesthesiologists.

There are a lot of challenges in developing stroke care in Armenia, as in many developing nations. According to official statistics, the incidence of stroke was 176/100.000 in Armenia in 2012, with 5417 cases, and in-hospital mortality was 20.6%.

We proposed establishing a stroke center at the University Hospital of the YSMU to serve as an acute stroke center for the city of Yerevan and its region, as well as a referral center for all of Armenia. This request was made in writing to the Ministry of Health and we are awaiting their response. We put forth a plan to build the center in stages, over a period of 3 to 5 years.

Our greatest challenge may be in preparing a group of physicians and nurses specially trained in the diagnosis and treatment of stroke. Other challenges include re-organizing the Emergency Medical Services of City of Yerevan, and providing further educational programs to the EMS personnel. These efforts will not yield results without education of the general public about stroke prevention and treatment.

My experiences in Armenia have led me to have a greater appreciation for the work of the World Stroke Organization. I have also come to realize that treating and preventing stroke in the developing world is something we should all support.

– Nerses Sanossian, MD
By |February 8th, 2013|Conference|0 Comments

Peri-Procedural Arterial Spin Labeling

Claude Nguyen, MD

Nael K, Meshksar A, Liebeskind DS,  Wang DJJ, Ellingson BM, Salamon N, et al. Periprocedural Arterial Spin Labeling and Dynamic Susceptibility Contrast Perfusion in Detection of Cerebral Blood Flow in Patients With Acute Ischemic Syndrome.  Stroke. 2013.

The optimal imaging modality to identify patients with perfusion-diffusion mismatch who are suitable candidates for revascularization remains elusive. There has been a renewed interest in arterial spin-labeled (ASL) perfusion imaging for this purpose.  Compared to dynamic susceptibility contrast (DSC) perfusion, ASL does not use gadolinium, and therefore does not carry the risk of nephrogenic systemic fibrosis.  In addition, recent technical advances in its quality and acquisition speed have made ASL more appealing. 

Nael et al. sought to compare ASL and DSC perfusion in detection of cerebral blood flow (CBF) changes. They performed a retrospective analysis of patients who underwent endovascular recanalization using intra-arterial tPA (<6 hrs) or clot retrieval (<9 hrs), looking at those who had both ASL and DSC images before and after the procedure. The studies were evaluated for image quality, location, and type of perfusion abnormality. Quantitative analysis was also done by comparing ratio of relative CBF in core and hypoperfused regions with respect to the contralateral hemisphere.

In their sample size of 25 patients, Nael et al. found that the image quality of ASL was significantly lower than DSC for both pre- and post-recanalization images.  Although Nael et al. found that changes in rCBF were concordant between ASL and DSC both before and after recanalization, they showed that ASL was still limited in image quality, less sensitive in detecting rCBF changes with respect to hyperperfusion compared to DSC. 

Ultimately, the selection of patients who may benefit the most from endovascular recanalization will depend partly on advanced neuroimaging selection to detect perfusion-diffusion mismatch.  This work from Nael et al. helps clinicians understand the current limitations of ASL compared to DSC, and highlights the need for further work to optimize ASL before it can be applied to the acute clinical setting. 

Socioeconomic Status and Care After Stroke

Vasileios Lioutas, MD

Huang K, Khan N, Kwan A, Fang J, Yun L, Kapral MK. Socioeconomic Status and Care After Stroke: Results From the Registry of the Canadian Stroke Network. Stroke. 2013; 44: 477-482.

Acute stroke is a leading cause of death and disability worldwide. Access to specialized stroke centers, intravenous thrombolysis in the acute phase, post-stroke rehabilitation and secondary prevention has proven of great significance in improving outcomes. In this interesting study Huang et al are investigating the impact of socioeconomic status in stroke care looking for associations between median neighbourhood income and parameters of stroke care, focusing on post-hospitalization management. This is a retrospective analysis of 11,000 patients older than 65 years admitted to regional stroke care centers with acute stroke or TIA in Ontario, Canada.

Higher income was found to be associated with increased likelihood of admission to stroke unit, care by a neurologist during hospitalization, referral to specialized secondary stroke prevention clinic and greater number of post-discharge physician visits. Conversely, thrombolysis rates, discharge to inpatient rehabilitation facilities and access to home care nursing, physical and occupational therapy were not affected by the socioeconomic status. Medication adherence was not different among income quintiles, but universally relatively poor, especially with regards to anticoagulation (adherence rate approximately 55%).

There are some points that merit highlighting:

Though there were differences that reached statistical significance, the absolute differences were small (for instance, patients in the higher income quintile had a mean number of 4.5 physician visits versus 4.2 for the lower quintile, which nevertheless yielded a p value of <0.001).

Although the parameters investigated are known to influence stroke outcome, the ultimate question remains whether functional outcome and mortality rate are affected. Therefore, strictly speaking, only indirect extrapolations pertaining to this particular issue can be made from the current study.

Most importantly, the study was conducted with in a very specific healthcare model context with widely available access to specialized stroke services. The results are therefore applicable to settings with similarly organized stroke care, but it is questionable whether they are representative of lower income countries or even high-income societies with deeper socioeconomic disparities and fragmented healthcare systems.

Stroke’s impact on individual patients and the society as a whole is tremendous with an intricate correlation to socioeconomic status; more specifically, evidence suggests that stroke outcome is inversely related to income stratum. One interpretation of the results of this interesting study is that existence of a universal healthcare system with organized, readily and widely available stroke care resources can attenuate the effect of economic inequality on stroke care accessibility and disease outcome.


Stroke Severity as Well as Time Should Determine Stroke Patient Triage

Waimei Tai, MD

Grotta JC, Savitz SI, Persse D. Stroke Severity as Well as Time Should Determine Stroke Patient Triage. Stroke. 2013; 44: 555-557.

Recently Grotta et. al. from Baylor proposed a novel scheme of incorporating both time and severity to in the pre-hospital arena in order to more appropriately direct patients to either primary stroke centers (certified for iv thrombolytic therapy access) or to comprehensive stroke centers (certified for ability to provide both iv thrombolytic and higher level interventions).  Analogies are made to acute coronary syndrome in the cardiology arena, and differing levels of trauma centers for acute traumatic injury. Previous observational data shows that larger occlusions (internal carotid artery) are less likely to have re-canalization with iv thrombolytic alone and most need catheter based intervention to attain re-canalization. Data also suggests that higher volume stroke centers (also more likely to be comprehensive stroke centers) have better outcomes for their patients, perhaps from co-localization of multitude of experts and familiarity with stroke treatment process thereby increasing efficiency.

I think the idea of adding a fast EMS level evaluation of severity to help aid fast transport to the appropriate level of care (primary versus comprehensive stroke centers) is useful, but careful consideration of the time to primary stroke versus time to nearest comprehensive stroke center needs to weighed. We know that the earlier iv thrombolytic is used, the more likely it will benefit the patient.  As the authors suggested, evaluating the local systems of care at the county or state level is needed prior to initiating an additional level of triaging to the process.

Elevated Homocysteine and Carotid Plaque Area and Densitometry

Tareq Kasshout, MD

Alsulaimani S, Gardener H, Elkind MSV, Cheung K, Sacco RL, Rundek T. Elevated Homocysteine and Carotid Plaque Area and Densitometry in the Northern Manhattan Study. Stroke. 2013; 44: 457-461.

In a study recently published online in Stroke,Alsulaimani and colleagues are proposing an association between elevated homocysteine levels and carotid artery plaque morphology in patients who are at increased risk for stroke. Elevated homocysteine levels, in its relationship to atherosclerosis, and plaque area and morphology, which correspond to the “vulnerable” plaque histology, are subclinical markers of stroke risk.
This sub-study from the Northern Manhattan Study (NOMAS) showed that an elevated level of homocysteine is an independent risk factor for greater plaque burden. Moreover, it was associated with both echo-lucent (low-density plaques with low content of calcification) and echo-dense (high density plaques with high content of calcification). Both types of plaques, as a marker of generalized atherosclerosis, have been associated with increased risk of stroke.
The existing and consistent evidence of homocysteine as a risk factor for carotid atherosclerosis, has now been associated with two novel imaging biomarkers of atherosclerosis (carotid plaque morphology and total carotid plaque area). However, the effect of lowering homocysteine on atherosclerotic lesions in primary prevention is still unknown.

Endovascular Treatment of Intracranial Aneurysms with Flow Diverters

Aaron P. Tansy, MD

Brinjikji W, Murad MH, Lanzino G, Cloft HJ, and Kallmes DF. Endovascular Treatment of Intracranial Aneurysms With Flow Diverters: A MetaAnalysis. Stroke. 2013; 44: 442-447

Flow diversion devices are a relatively recent addition to the endovascular arsenal for the treatment of intracranial aneurysms, and have been typically employed when more common endovascular or surgical options may not be feasible such as for morphologically complex or surgically inaccessible lesions. They are a mesh structure similar to a stent passed across the aneurysm neck that functions to divert blood flow from the aneurysm, allowing it to occlude over time. 

Although small single- and multi-center studies have reported favorable results, their efficacy and safety have not been evaluated on a larger scale. Waleed Brinjikji and colleagues report in Stroke a first-of-its-kind random-effects meta-analysis of 29 studies of flow diverter treatment across varied clinical and aneurysm populations. Efficacy and safety profiles were compiled based upon rates of aneurysm occlusion, short-/long-term complications, morbidity and mortality. On average, at 6 months, flow diverters achieved a 76% occlusion rate with morbidity and mortality rates of 5 and 4% respectively. Complications over this time (SAH 4%; Ischemic stroke 6%; intraparenchymal hemorrhage 3%; perforator infarction 3%) were low, but not negligible. Further analyses evaluated effects of aneurysm size (small versus large/giant) and location (anterior versus posterior circulation) on each of these. Overall, small size and anterior location were associated with fewer complications. Importantly, for large/giant aneurysms, risk of SAH and ischemic stroke was highest; whereas, for posterior aneurysms, risk of ischemic and perforator stroke was highest.

So, should we start shelving our conventional coiling, stenting and clipping techniques for these new devices? Not so fast.  Although this analysis provides evidence that flow diverters are a feasible and effective treatment option for aneurysms, their associated rates of morbidity and mortality are not without concern. Further, this study is not without significant limitation that leaves its quality of evidence low: both as a meta-analysis and from the methodologies of the studies it includes. Therefore, its results neither can be applied to specific clinical and aneurysm populations, nor can they be used for comparison with efficacy and safety profiles of other treatments. Nevertheless, this analysis lends traction to the need for continued study of the flow diverter especially in prospective, randomized head-to-head comparison with more established endovascular and surgical methods of aneurysm treatment.