American Heart Association

Monthly Archives: March 2016

Hyperglycemia is Associated With Worse Clinical Outcomes in Intracerebral Hemorrhage (ICH)

Jay Shah, MD

Saxena A, Anderson CS, Wang X, Sato S, Arima H, Chan E, et al. Prognostic Significance of Hyperglycemia in Acute Intracerebral Hemorrhage: The INTERACT2 Study. Stroke. 2016

Known prognostic factors of intracerebral hemorrhage (ICH) are hematoma volume and clinical severity. Hyperglycemia is associated with adverse outcomes in various medical conditions but its impact on ICH is relatively unknown. In this study, the authors seek to quantify risk associations of hyperglycemia and diabetes in patients that participated in the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). This study evaluated intense versus standard blood pressure control in ICH patients. Blood glucose level and history of diabetes was recorded at enrollment. Primary outcome was death or major disability. Secondary outcomes included serious adverse events such as neurological deterioration. 

1348 (51%) patients had hyperglycemia and 292 (11%) had diabetes. After adjusting for confounding factors, hyperglycemic patients were significantly more often female, had greater cortical hematomas, higher systolic blood pressure and larger hematomas with intraventricular extension. There was a continuous relationship between baseline glucose level and death or disability (OR 1.29). Hyperglycemic patients had significantly greater frequency of early neurologic deterioration but there was no difference in hematoma expansion. 

This study shows that elevated glucose levels and diabetes are associated with worse outcomes. An interesting element to these results indicate that the adverse outcomes are specific to the effects of hyperglycemia rather than simply a history of diabetes which impacted outcomes by increased cardiovascular event risk. While hyperglycemia and diabetes are certainly related, this suggests that adequate control of diabetes, and this lower blood glucose levels, may negate the potential risk of adverse outcomes following ICH. However, it is important to realize that INTERACT2 was not powered to evaluate hyperglycemia and therefore a causal relationship between hyperglycemia and outcomes cannot necessarily be established. Nonetheless, the study does elucidate a potential relationship and determining the pathophysiological mechanism remains an important biological query. Animal studies suggest that hyperglycemia plays a role in free radical generation which in turn disrupts blood-brain barrier and enhances edema. A possible limitation of this study is that hyperglycemia is based on a single time point and future studies should address effect of persistent hyperglycemia on outcomes. Ultimately, a trial designed to specifically control hyperglycemia should elucidate further this relationship and whether intervention improves outcomes. 

By |March 18th, 2016|treatment|0 Comments

IV t-PA in Previously Dependent Patients: To Do or Not to Do

Luciana Catanese, MD

Gensicke H, Strbian D, Zinkstok SM, Scheitz JF, Bill O, Hametner C, et al. Intravenous Thrombolysis in Patients Dependent on the Daily Help of Others Before Stroke. Stroke. 2016

IV t-PA treatment (IVT) trials have mainly focused on outcomes of acute ischemic stroke (AIS) patients who have the highest potential for recovery (baseline mRS 0-2), leaving several questions unanswered for those who were previously dependent (mRS 3-5).  
In this edition of Stroke, Dr. Gensicke, et al. designed a prospective and explorative multicenter study to address the impact of preexisting dependency on outcomes and complications in a large population of IVT-treated stroke patients. The 3-month mRS score defined outcomes. Data of 7430 patients was prospectively collected from 12 European Centers including 6941 and 486 patients with a baseline mRS 0-2 (independent) and 3-5 (dependent), respectively. The most common causes of pre-existing dependency in order of frequency were dementia (45.6%), degenerative or traumatic bone disease (19.7%), prior strokes (16.6%) and heart diseases (16.6%). Interestingly, previously dependent patients were more often female, had more severe strokes, more vascular risk factors and were more often on antithrombotic medications than the independent ones. Although dependent patients were more likely to die (adjustedOR 2.19) at 3 months, there was no difference in the likelihood of poor outcomes at 3 months or the rate of symptomatic ICH between groups. Unexpectedly, the odds of poor outcome were indeed lower in pre-stroke dependent patients if age and stroke severity were taken into account. Such a finding is likely to be related to the greater capacity of previously independent patients to have poor outcomes (mRS 0-2➞6) compared to previously dependent ones (mRS 3-5➞6) and the lower potential for functional worsening in those already dependent at baseline, rather than a true physiologic effect.

Overall, results of this trial are consistent with prior data that shows that previously dependent patients are sicker at baseline with more comorbidities and prescribed medications, tend to score higher on the NIHSS due to the accumulation of deficits and have a higher overall mortality. However, whether or not dependent patients still benefit from IVT remains unanswered and more research looking into this topic is warranted. In the meantime, IVT should continue to be offered to previously dependent AIS patients.

By |March 17th, 2016|treatment|0 Comments

Thrombus Length Estimation on Delayed Gadolinium-Enhanced T1

Russell Mitesh Cerejo, MD

Yan S, Chen Q, Xu M, Sun J, Liebeskind DS, Lou M. Thrombus Length Estimation on Delayed Gadolinium–Enhanced T1. Stroke. 2016

The authors, in keeping with their previous studies on thrombus morphology on MRI, have found a new method to assess for thrombus length. They further correlated this thrombus length with recanalization and outcomes with IV thrombolysis. They evaluated patients over ~5 years with acute stroke due to M1 occlusion, received IV thrombolysis and had MRI pre and post thrombolysis. 

They obtained delayed gadolinium-enhanced T1 (dGE-T1) after perfusion imaging and co-registered the imaging with the time of flight MRA. Thrombus length on dGE-T1 was 8.18 ± 4.56 mm (range 1.63-30.26 mm). Recanalization occurred in 38 (51.4%) patients and no recanalization in 36 (48.6%). Thrombus length on dGE-T1 was significantly longer in patients without recanalization in univariate analysis. Thrombus length and M1 occlusion were independent predictors for no recanalization of MCA. Thrombus length of 6.77 mm, yielded a sensitivity of 77.8% and a specificity of 57.9%, and odds ratio 4.81 (95% CI: 1.742 to 13.292; p=0.002). No one achieved recanalization after IVT when length of thrombus exceeded 14 mm on dGE-T1 (see figure).

This study highlights the utility of MRI in assessing thrombus length without increasing the scan time or the contrast load. This may also be useful in acute stroke therapy to determine thrombus length and success of mechanical thrombectomy. 

Discovering the Role of Ipsilesional Parietofrontal Motor Circuits in Stroke and Motor Recovery Through Functional Brain Imaging

Danny R. Rose, Jr., MD

The advent of functional brain imaging has greatly advanced the understanding of how interregional interactions and connectivity in the brain are disrupted by ischemic stroke and are modified in patients as they recover motor function after stroke. Most studies have focused on frontal motor circuits, including the primary motor cortices (M1), dorsal (PMd) and ventral premotor cortices (PMv), and the supplementary motor area (SMA). Studies in healthy subjects suggest that the posterior parietal cortices also play an important role in motor tasks, particularly dexterous hand function which is crucial for functional activities. Data from both resting-state connectivity studies and longitudinal whole-brain analyses suggest a reduced information flow from the ipsilesional parietal brain regions to ipsilesional M1 and secondary motor areas after stroke that are followed by time-dependent changes in neuronal connectivity during recovery. By using functional magnetic resonance imaging (fMRI) and dynamic causal modeling (DCM), Schulz et al. investigated interactions between parietal cortices and frontal motor areas of the ipsilesional hemisphere in stroke patients as compared to healthy controls, as well as whether the degree of neuronal coupling correlates with residual functional deficit.

Fifteen patients (7 male, one left-handed, aged 68±8.5 years) were included roughly three months after first-ever ischemic stroke. Residual motor function was determined by a combination of grip force, the Nine-hole-peg test (NHP), and the Fugl-Meyer score for the upper extremity (UEFM). These assessments were compared to those of seventeen healthy controls of comparable age and sex (10 male, one left-handed, aged aged 64±9.9 years). Participants underwent event-related functional brain imaging while performing 30 isometric visually-guided whole hand grips with the paretic hand using a grip force response device. Controls were pseudo-randomly assigned to move either their right or left hand. All participants underwent functional imaging using a gradient echo-planar imaging sequence with a 3T MRI scanner. Image analysis was performed to identify areas of task-related brain activation for each patient, and these areas were quantified using blood oxygenation level dependent (BOLD) parameter estimates for five ipsilesional areas (M1, PMv, SMA, anterior (aIPS) and caudal part of the intraparietal sulcus (cIPS).

Dynamic causal modeling was utilized to analyze interregional connectivity using a priori assumptions. The coupling parameters were divided into three matrices. The A matrix represented the “resting state” of task-independent interregional coupling. The B matrix represented the changes in coupling parameters elicited by the task input, and the C matrix specified regions receiving exogenous inputs. Group-wise Bayesian model averaging was applied to derive mean coupling estimates for each connection weighted by the model probabilities. Two-tailed Wilcoxon rank sum exact tests were used to determine the significance of differences between stroke patients and controls. Spearman’s correlation coefficient was used to evaluate the relationship between coupling estimates and clinical scores.

In stroke patients, the task studied induced a significant increase in BOLD signal in the ipsilesional M1, PMv, SMA, aIPS, and cIPS both in the ipsilesional and contralesional hemispheres. Accounting for spatial variability in focal brain activation, it was found that both cases and controls had similar subject-specific peak coordinates and Euclidean distances between individual and group-level coordinates. The stroke patients and controls showed comparable grip-related effective connectivity values, with the most prominent increase in information flow being found from SMA to M1 and PMv to M1. Stroke patients also exhibited enhanced facilitatory connectivity from aIPS or M1 and M1 to aIPS (p<0.05). Interestingly, there were no significant correlations between clinical performance and coupling estimates.

This study extends previous findings suggesting that parietal brain region interactions with frontal motor areas may facilitate plastic changes after stroke. It is likely that posterior parietal brain regions act as important nodes for sensorimotor integration, particularly when visual rather proprioceptive feedback was given, as was the case in this study. The lack of association between coupling and residual motor function was unexpected. The authors posit that this may suggest that direct activity of the posterior parietal cortex may be more integrative, relying more on other parameters and less directly reflective of functional motor activity. The issue was also raised that current measures of dexterous hand function may not be adequate to assess minute, nuanced improvements, which has been an issue when relating clinical scoring to functional imaging in multiple areas of research. This study also has many of the other limitations when clinically correlating functional brain imaging data (i.e.. motor tasks not specifically designed to activate the area in question, possibility of “hidden” accessory pathways that were not directly studied, inability to control for differences in cognitive processing when performing task). Regardless, the study provides a valuable insight into the role of the ipsilesional parietofrontal motor network and its importance with respect to motor functioning and recovery after stroke.

Risk Analysis of Unruptured Intracranial Aneurysms: Prospective 10-Year Cohort Study

Peggy Nguyen, MD

Murayama Y, Takao H, Ishibashi T, Saguchi T, Ebara M, Yuki I, et al. Risk Analysis of Unruptured Intracranial Aneurysms: Prospective 10-Year Cohort Study. Stroke. 2016

The optimal management of unruptured aneurysms, whether by clipping or coiling, has never been defined in a randomized study.  Inferences can be made from what we know about the natural course of unruptured aneurysms, which have been previously studied in the ISUIA and UCAS. In this study, the authors add to the literature with a 10-year follow up of unruptured aneurysms to define the risk factors of rupture and looked at outcomes of rupture.

A total of 2665 patients with 3434 unruptured intracranial aneurysms (UIAs) were referred to

the institution, of which 1556 patients with 1960 aneurysms were conservatively observed and 937 aneurysms were repaired (793 by coiling, 144 by surgical clipping). In the

conservatively managed group:

  • The mean follow up duration was 7388 aneurysm-years.
  • 56 aneurysms ruptured with an overall annual incidence of subarachnoid hemorrhage of 0.76% with mean duration to rupture from initial consultation being 547 days.
  • Independent risk factors for aneurysm rupture were: (1) aneurysm size, (2) specific location, (3) presence of a daughter sac, and (4) history of SAH.
  • The annual rupture rate of aneurysms < 5 mm was 0.33%, > 5 mm was 3.1%, 7-9 mm was 2.9%, 10-24 mm was 10.2%, and 25+ mm was 33.1%; a cut-off point of 5 mm was associated with a higher risk of rupture, smaller than the 7 mm size which was previously demonstrated.
  • Vertebro-basilar aneurysms demonstrated a significantly higher risk of rupture compared to other locations.
  • Of ruptured aneurysms, only 46.4% patients returned to normal life; 28.6% resulted in an mRS of 3-5, 26.8% resulted in death. 

Given the devastating effects of aneurysm rupture, as confirmed in this study, would it be prudent to coil/clip these aneurysms, even when incidental and unruptured? Unfortunately, this study does not necessarily answer the question of what the best management would be for unruptured aneurysms; it does, however, confirm the size relationship of aneurysm and rupture, at a smaller size than previously reported, which prompts additional questions on what, exactly, is the size of aneurysm which we should be concerned about.

By |March 14th, 2016|prevention|0 Comments

Arterial Spin Labeling MRI Estimation of Antegrade and Collateral Flow in Unilateral Middle Cerebral Artery Stenosis

Russell Mitesh Cerejo, MD

Lyu J, Ma N, Liebeskind DS, Wang DJJ, Ma L, Xu Y, et al. Arterial Spin Labeling Magnetic Resonance Imaging Estimation of Antegrade and Collateral Flow in Unilateral Middle Cerebral Artery Stenosis. Stroke. 2016

The authors in their above titled paper describe a novel way to non-invasively assess for

antegrade and collateral blood flow in intracranial stenosis patients. They evaluated 41 consecutive patients with symptomatic intracranial stenosis of the M1 segment of the middle cerebral artery due to atherosclerosis. These patients underwent three-dimensional pseudo-continuous arterial spin labeling (3D pCASL) with 3.0T MRI. The calculated perfusion on the CBF map of post labeling delay (PLD) 1.5s as early-arriving flow, and perfusion on the CBF map of PLD 2.5s as combination of early-arriving flow, late-arriving antegrade flow and late-arriving retrograde flow. The mean early arriving flow proportion was 78.3%±14.9%. The mean late-arriving retrograde flow proportion was 16.1%±10.2%. Half patients underwent cerebral angiography with calculation of Modified TICI scale and ASITN/SIR collateral grade.

The authors found significant correlations between early-arriving flow and late-arriving flow on two-PLD pCASL with conventional angiographic antegrade and collateral scales, suggesting that the early-arriving flow and late-arriving retrograde flow to the territory supplied by the stenotic MCA may primarily represent antegrade and collateral flow, respectively.

This is an interesting study, which has tried to use a novel non-invasive technique to assess for collaterals that are important not only in chronic stenoses but also acute occlusions.

Preexisting Heart Disease Underlies Newly Diagnosed Atrial Fibrillation After Acute Ischemic Stroke

Allison E. Arch, MD

Rizos T, Horstmann S, Dittgen F, Täger T, Jenetzky E, Heuschmann P, et al. Preexisting Heart Disease Underlies Newly Diagnosed Atrial Fibrillation After Acute Ischemic Stroke. Stroke. 2016

Atrial fibrillation (afib) is a risk factor for ischemic stroke. In patients who just had a stroke, a proportion of them will be diagnosed with afib in the post-stroke period. Does afib diagnosed immediately after a stroke carry the same risk for future stroke as afib that was already a known diagnosis? Is it associated with cardiovascular disease, or does the stroke itself cause a neurogenic arrhythmia that may not portend the same future stroke risk? These are the questions that Rizos and colleagues addressed in their single center observational study.

The authors included 1,397 stroke patients who were entered into a prospective database. In the 320 patients who had afib recorded in the hospital, 64% had a known diagnosis of afib. The remaining 36% had a new diagnosis of afib. Comparing those with known afib to those newly diagnosed, both groups had the same amounts of coronary artery disease, left atrial dilation, and low ejection fractions on echocardiogram. In other words, the newly diagnosed afib group had the same cardiovascular profile as the known afib group. Therefore, patients with new afib and stroke may just have afib due to underlying cardiovascular disease, and not from neurogenic strain on the heart.

This has implications for secondary stroke prevention. Whether or not atrial fibrillation was a known or a new diagnosis at the time of ischemic stroke, Rizos and colleagues show that both groups have the same underlying cardiovascular risk profile. Therefore, one may conclude that both groups should undergo the same stroke secondary prevention strategies.  

Author Interview: Braxton D. Mitchell, PhD

Genome-Wide Association Analysis of Young-Onset Stroke Identifies a Locus on Chromosome 10q25 Near HABP2
Interview conducted by Michelle Christina Johansen, MD

Dr. Johansen: Dr. Mitchell, could you summarize for us the major findings of your recent article in Stroke?
Dr. Mitchell: Our study focused on young onset stroke since stroke occurring at younger ages may have a stronger genetic component. We performed a large genome-wide association study, or GWAS, that included 5,500 ischemic stroke cases and over 30,000 controls amassed from 8 different studies. We identified a DNA variant that was significantly associated with stroke, with the risk allele increasing stroke risk in young people by about 40%. This variant is near a gene called HABP2, which encodes an enzyme involved in the regulation of the clotting cascade. In an independent population from Sweden, we then found this variant also to be associated with enzyme levels.

Our study also suggests that the effects at the HABP2 locus may be specific to (or at least more pronounced in) early onset stroke because the association was largely absent in METASTROKE studies, a very large consortium that includes predominantly older stroke cases.

Dr. Johansen: Why do you feel that there is a stronger genetic component for stroke in the young?
Dr. Mitchell: It is clear from family and twin studies that stroke aggregates in families. The best available evidence suggests that stroke at younger ages has an even stronger genetic basis than stroke occurring at older ages. For example, younger stroke cases more often report a parental history of stroke than older stroke cases.

One unanswered question is whether the stronger familial aggregation observed in early- compared to later-onset stroke is due to differences in the in the distribution of stroke subtypes at different ages. For example, large artery and small vessel stroke are more prominent at older compared to younger ages, while stroke due to other determined etiologies are more common at younger ages. It is thus possible that the enrichment of stroke with some of these other causes accounts for the stronger genetic component for stroke in the young.

Dr. Johansen: How did you reach 60 years old as the parameter for stroke in the young?
Dr. Mitchell: We wanted to differentiate stroke occurring in young and middle age vs that occurring in older ages. Our decision to use a threshold of 60 years for early onset stroke, instead of say 50 or 55 years, was in part a practical one so that we would have a large enough sample for our study.

Dr. Johansen: Why do you feel that you were unable to find any subtype specific stroke susceptibility loci in your cohort?
Dr. Mitchell: We did perform additional analyses to determine if the stroke-associated variant we detected in HABP2 was associated with particular subtypes. In this analysis, we found the variant to be associated with each of the three major stroke subtypes, cardioembolic stroke, large artery atherosclerotic stroke, and small vessel occlusion. However, one major caveat is that the sample sizes were much smaller in these subtype-specific analyses, so we cannot be fully confident in these results. We are aware that the 7 or so variants robustly associated with ischemic stroke in very large GWAS studies all seem to be subtype-specific. Whether this is also true for the variant in HABP2 is premature to say.

Dr. Johansen: What do you feel is the biggest strength of your study?
Dr. Mitchell: I think our study has three major strengths. First, our study included a very large number of early onset cases. Second, not only did we detect a statistically significant association of this variant with stroke, but in an independent population of non-stroke cases, we also found this variant to be associated with circulating plasma levels of factor VII-activating protease levels, the product of this gene. Third, because the association was largely absent in the METASTROKE Consortium, we are able to conclude that the locus is probably specific to younger onset cases.

Dr. Johansen: How do you foresee the findings of this study influencing further research?
Dr. Mitchell: First, these results reinforce the heterogeneous nature of stroke as HABP2 does not appear to be associated with common forms of late onset stroke. Second, these results suggest the need to look comprehensively at genetic determinants of thrombosis and coagulation in early onset ischemic stroke. A better understanding the pathogenesis of early onset stroke may improve strategies to prevent recurrences. In addition, the pathways involved may have relevance also to some forms of older onset stroke.

Dr. Johansen: There are some naysayers who challenge the clinical value of GWAS stroke studies. Would you like to respond to this criticism?
Dr. Mitchell: I don’t believe that GWAs studies were ever intended to provide clinical or predictive value for most complex diseases. Most loci identified through GWAs have relatively small effect sizes and they do not do a very good job, even in aggregate, of predicting disease, although there are a few exceptions, such as for age-related macular degeneration. But GWAS have been enormously important in identifying variants and genes associated with a large number of diseases. This understanding is essential for development of new drugs targeting novel mechanisms.

Impaired Higher-Level Functional Capacity Predicts Stroke Occurrence

Ilana Spokoyny, MD

Murakami K, Tsubota-Utsugi M, Satoh M, Asayama K, Inoue R, Ishiguro A, et al. Impaired Higher-Level Functional Capacity as a Predictor of Stroke in Community-Dwelling Older Adults: The Ohasama Study. Stroke. 2016

Does impairment of higher level functional capacity (intellectual, social, and instrumental activities of daily living such as cooking, cleaning, shopping) predict stroke in patients who are independent in basic ADLs? Should we probe as deeply into our patients’ higher level functional capacity as we do into their past medical history? The authors of this study address these important questions in a study of 1500 Japanese patients over age 60. These patients were independent for basic ADLs, and had not had a prior stroke.

After following the patients for about 10 years, the authors found that 191 of 1493 developed a first-time stroke. As expected, age played a role: those with impaired higher level functional capacity were older than those with normal capacity, and those who had strokes were older than those who did not. Overall TMIG-IC score (measurement of higher level functional capacity) was associated with significantly higher probability of developing stroke overall in multivariate analysis. The intellectual activity subscore was the only subscore which remained significant for the overall group. When the group was stratified by age, sex, and hypertension, the intellectual activity subscore was significantly associated with stroke in women only. Social role was significantly associated with stroke in those patients 75 years or older.

It is important to ask if the association is causative – or whether there are common risk factors for stroke as well as impairment in higher level functional capacity. In this study, the association persisted after adjusting for age and risk factors. The authors suggest that higher level functional impairment may represent early cerebrovascular disease, such as silent strokes. Determining the degree of white matter disease and correlating with higher level functional status would be the logical next step to follow this study. Determining baseline function, including higher level functional capacity, is useful and may help predict stroke. It would be interesting to compare the post-stroke level of independence of stroke patients with and without baseline higher level functional impairment. I suspect that those with higher level functional impairment, even if they were independent for basic ADLs, would have more significant post-stroke disability after adjusting for location and size of stroke. Lower cognitive reserve may portend a more protracted course and more difficulty rehabilitating from a stroke. Having data on a patient’s baseline status would be helpful in predicting stroke occurrence (shown in this study) and possibly predicting outcomes post-stroke.

Intracranial Arterial Remodeling and the Risk of Stroke

Alexander E. Merkler, MD

Qiao Y, Anwar Z, Intrapiromkul J, Liu L, Zeiler SR, Leigh R, et al. Patterns and Implications of Intracranial Arterial Remodeling in Stroke Patients. Stroke. 2016

Intracranial atherosclerotic disease (ICAD) is a common cause of stroke; patients with ICAD face high rates of recurrent stroke despite aggressive medical and lifestyle modification. Currently, the diagnosis of ICAD is based on the degree of vessel stenosis, but perhaps, as Drs. Qiao et al discuss, this is not the best measure of either plaque burden, or more importantly, stroke risk.

Based on coronary plaque research, Drs. Qiao et al studied the impact of vessel remodeling in ICAD. Although plaque may lead to hemodynamic stenosis, remodeling of the vessel may either preserve (positive remodeling) or further impair (negative remodeling) the degree of stenosis. In addition, although positive remodeling may preserve the vessel lumen, it may make plaque more vulnerable to rupture or lead to clinical symptoms.

In this study, the authors used High-resolution black blood MRI (BBMRI) to assess vessel remodeling in ICAD and its association with ischemic events. Forty-five patients with ICAD with >50% stenosis in a large intracranial artery who also had a stroke or TIA in the distribution referable to that stenosis were included. The authors identified 137 plaques, of which 56 exhibited positive remodeling, 53 negative remodeling, and 28 intermediate remodeling. There was higher burden of plaque within the posterior circulation as compared to the anterior circulation and positive remodeling was more frequent in the posterior circulation (58% vs 31%). Furthermore, positive remodeling was associated with a trend towards culprit plaque classification. Finally, the authors found that the lumen begins to narrow (ie when remodeling fails to preserve the lumen) when plaque burden reached 55.3%.

This study challenges the current theory that ICAD is purely based on degree of vessel stenosis. As in the coronary vessels, remodeling occurs when plaque is present and may either augment or decrease the vessel lumen size. Furthermore, intracranial remodeling may lead to an underestimation of plaque burden (based on the current definition of vessel stenosis >50%), and therefore an underdiagnosis of ICAD, particularly in the posterior circulation. Further research to assess remodeling and its impact on stroke risk is warranted.