American Heart Association

Monthly Archives: October 2015

Functional gain in stroke rehabilitation a predictor of long-term mortality

Peggy Nguyen, MD

Scrutinio D, Monitillo V, Guida P, Nardulli R, Multari V, Monitillo F, et al. Functional Gain After Inpatient Stroke Rehabilitation: Correlates and Impact on Long-Term Survival. Stroke. 2015

A common scenario vascular neurologists encounter are patients who ask us questions that run the gamut of: What’s going to happen after I leave the hospital or after I leave rehabilitation? The world of stroke has recently been focused on acute interventions at presentation and predictors of outcome acutely, but long-term, what are some of the things we can advise our patients? Here, the authors performed a cross-section study evaluating the association of stroke rehabilitation, as measured by improvement in functional independence motor (FIM) score on admission and discharge, with long-term mortality, as well as predictors of successful stroke rehabilitation.

1010 consecutive patients admitted for stroke rehabilitation with an FIM score < 80 and a recent (< 90 day from onset) ischemic or hemorrhagic stroke were enrolled in the study. Variables identified as independent positive correlates of FIM gain were younger age, being married, lower NIHSS score at time of rehabilitation admission, decreased time from stroke onset to rehabilitation admission, and presence of aphasia. Over a median follow up of 6.17 years, 36.9% of the subjects died. Age, coronary heart disease, atrial fibrillation, total cholesterol, and FIM gain were found to be independently associated with mortality. After adjusting for mortality risk markers, FIM gain remained a predictor of long-term mortality risk.  

These study yielded some interesting results. The finding that FIM gain is a predictor of long-term mortality suggests that better functional improvement with rehabilitation decreases long-term mortality risk in stroke survivors. Of course, as the authors also point out, this association may also be confounded by the finding that younger age and lower NIHSS were associated with higher FIM gain; therefore, mortality may be a reflection of severity of stroke in an older population rather than rehabilitation, but this may still be helpful in how we counsel our patients as we transition them to rehabilitation. In addition, the finding that a higher FIM gain is associated with less time between stroke onset to rehabilitation is highly relevant and, again, not only helps us when counseling patients and their families, but may also aid in decision making at discharge.

By |October 16th, 2015|rehabilitation|1 Comment

Ultrasound and clinical predictors of recurrent ischemia in symptomatic internal carotid artery occlusion

Sebina Bulic, MD 

Schneider J, Sick B, Luft AR, and Wegener S. Ultrasound and Clinical Predictors of Recurrent Ischemia in Symptomatic Internal Carotid Artery Occlusion. Stroke. 2015

Development of cerebral collaterals is a dynamic process and cannot be described with a snapshot imaging. Furthermore in hyperacute stroke presence of collaterals harbors potential for the penumbral preservation until chemical or mechanical revascularization and the absence of collateral pathways can increase risk of hemodynamic compromise in patients with stroke. 

This interesting retrospective analysis evaluated 68 patients with symptomatic ICA occlusion. Risk factors for recurrent ipsiateral ischemic event and TCD flow patterns were evaluated. 14 (20.6 %) patients at a median time of 29.5 days (IQR 8 – 89) during the median follow up of 6 months (IQR 4 – 24) had ipsilateral ischemic event.

TIA and DM were as expected predictive of recurrent event, as described in ABCD2 score. Interestingly, Stroke was not. Also usual suspects such as smoking, A-Fib, HTN etc. were not associated with ischemic event. Shockingly, use of statin and antiplatelets was associated with ischemic events.

Presence all four collateral pathways (ACoA, PCoA, LM, OA) was associated with ischemia. What does this mean? Maybe population with ischemic events has baseline more atherosclerosis and previously established collaterals. It is hard to find explanation. Increase in P2 velocities may be predictive of presence of secondary collateral pathways, but wouldn’t we expect increase in velocities of contralateral MCA and contralateral or both A2 segments as well?

It is hard to make conclusions from this retrospective study with small number of patients, but I command investigators for raising awareness of potential use of neurosonology in the management of patients with stroke. Application of neurosonology (Carotid duplex, TCD, TCI) can be challenging in the community because this methodology is operator dependent, however it can be invaluable in established and accredited laboratories.

In my opinion this article highlights one thing, TIA is a neurologic emergency and our opportunity to change long-term outcomes.

Faith-based behavioral intervention in a Hispanic community shows modest benefit in promoting healthy lifestyle choices – Results of the SHARE trial

Danny R. Rose, Jr., MD

Brown DL, Conley KM, Sánchez BN, Resnicow K, Cowdery JE, Sais E, et al. A Multicomponent Behavioral Intervention to Reduce Stroke Risk Factor Behaviors: The Stroke Health and Risk Education Cluster-Randomized Controlled Trial. Stroke. 2015
Despite ample evidence regarding the importance modifiable risk factors for stroke prevention, optimal implementation of appropriate community interventions to promote positive lifestyle modifications remains uncertain. This is a particular concern for ethnic minority populations such as African Americans and Hispanic-Latinos, which have a higher prevalence of poorly controlled blood pressure and a greater burden of stroke. Given that these groups tend to have less favorable diet and exercise profiles and poorer access to preventative services, the need for developing culturally sensitive community preventative programs has been stressed. As a faith-based community intervention was feasible in studies centering on Protestant churches in the African-American community, Brown et al. used a similar approach, targeting 10 Catholic parishes within the Diocese of Corpus Christi, Texas.

The study randomized 10 Catholic churches and included 760 subjects, divided into control group and intervention groups. The intervention group received a one-year individual level program with culturally sensitive self-help materials focused on healthy eating, physical activity and blood pressure control, as well as newsletters, motivational interviewing calls and a 2 hour workshop on supportive peer counseling. Interventions were also done on the cluster level, promoting availability of lower sodium foods and fruits and vegetables at parish functions and programs to encourage healthy eating and physical activity. The control subjects received skin cancer awareness materials or sunblock at 3 and 9 months to maintain contact every three months, including assessments. Subjects were assessed during home visits for baseline and 12-month follow-up data, and with an interim 6-month telephone assessment. All three evaluations included validated questionnaires addressing dietary intake and physical activity. At baseline and 12 months, assessments included an average of recent blood pressure measurements, a fasting lipid panel, glucose and glycosolated hemoglobin, height and weight, waist circumference, a BP medication adherence question, and Self-Determination Theory measures. There were no significant baseline differences between the intervention and control groups. Over half of the subjects (56.3%) completed the baseline, 6 month and 12 month assessments, with about a quarter of subjects (25.8%) completing only the baseline and 12 month assessments; 28 subjects (3.7%) completed only the baseline and 6 month assessments.

There were significant improvements with the intervention for 2 of the 3 co-primary outcomes (decreased dietary sodium intake, p=0.04, and increased dietary fruit and vegetable intake, p=0.04). There was no impact on moderate or greater intensity physical activity. Similarly, there was no effect on systolic BP, a secondary outcome. Total dietary and saturated fat intake decreased in the intervention group, which was statistically significant after adjusting for age, sex, education and social desirability. There was no intervention effect for the remaining biological exploratory outcomes. Assessment of the Self-Determination Theory related outcomes, designed to measure perceived competence and motivation to adopt lifestyle modifications, showed a significant increase in perceived competence to eat more fruits and vegetables (p=0.01) and decrease in subjects reporting lack of motivation for dietary change (p=0.05). Self-reported adherence to the interventions was also assessed, with 74 percent of subjects completing at least one motivational call, 63 percent reporting having read at least one newsletter, 80 percent using the healthy eating guide and 55 percent using the exercise guide.

The outcomes of this study mirror similar community interventions finding a relatively modest effect of the intervention on risk factor modification. This and similar studies are subject to the inherent limitations of self-report and and the authors’ discussed their disappointment at the relatively low adherence rate in their study with respect to the interventions. Similar community and population-based risk factor intervention studies that utilize resource intensive, multi-faceted approaches to promote lifestyle modification tend to have only modest results, highlighting the complexity of the problem and what is likely a considerable amount of social and cultural underpinnings of poor diet and lack of physical activity. Additional studies are needed to identify and implement resource efficient programs for promoting healthier lifestyle choices. These programs should ideally involve a collaborative effort between healthcare providers, community leaders and government officials.

By |October 14th, 2015|prevention|0 Comments

Aggressive vascular risk factor modification did not reduce cognitive decline following ischemic stroke

Jay Shah, MD

Matz K, Teuschl Y, Firlinger B, Dachenhausen A, Keindl M, Seyfang L, et al. Multidomain Lifestyle Interventions for the Prevention of Cognitive Decline After Ischemic Stroke: Randomized Trial. Stroke. 2015

There is a strong relationship between stroke and dementia. In addition to motor impairments, stroke also leads to cognitive impairment in majority of stroke patients. 30% of such patients deteriorate in a delayed fashion 3-15 months following infarct. Therefore, intervening prior to this deterioration is extremely important in order to decrease risk and progression to dementia. Modifiable vascular risk factors are also linked with an increased risk for cognitive impairment. Therefore, risk factor modification can potentially decrease risk of cognitive decline.

In this study, the authors evaluate whether a 24-month intensive multi-domain intervention can prevent post-stroke cognitive decline compared to standard care. Patients with an ischemic stroke within 3 months were randomly assigned to either group. The intervention consisted of intensive management and motivation for compliance with clinical therapy, blood pressure, lipid and glycemic control, healthy diet, regular physical activity and cognitive training. Cognition was assessed at baseline and 1 and 2 years within the following domains: executive function, working memory, general memory, processing speed and visual spatial ability.

Ultimately, data from 159 patients were obtained (76 intervention and 83 control). At 24 months, 8 patients in the intervention group had cognitive decline compared to 10 in the control group. During the 24 months, participants in the intervention and control group showed no improvement on the Alzheimer’s Disease Assessment Scale-cognitive subscale.

This study did not show a benefit for intensive intervention. This could be due to the relatively low number of patients and thus, the study could have been underpowered to detect an effect. Since dementia is a slowly developing disease, a follow-up period of 24 months may have been too short to capture a difference. Although common for all clinical trials, drop-outs were more frequent in the intervention group in the first year. This, perhaps, suggests the impracticality of intensive intervention due to declining compliance. Furthermore, this type of intervention requires a well-organized medical community with numerous resources. This can be economically unfeasible for many communities.

By |October 13th, 2015|prevention|0 Comments

NIHSS Item Profiles as Predictor of Patient Outcome

Russell Mitesh Cerejo, MD

Abdul-Rahim AH, Fulton RL, Sucharew H, Kleindorfer D, Khatri P, Broderick JP, et al. National Institutes of Health Stroke Scale Item Profiles as Predictor of Patient Outcome: External Validation on Safe Implementation of Thrombolysis in Stroke–Monitoring Study Data. Stroke. 2015

Dr. Abdul-Rahim and colleagues set out to validate the NIHSS Item profiles (see table) as predictors of outcomes in patients receiving thrombolysis therapy for ischemic stroke in a prospectively collected database.

They applied the NIHSS item profiles to 6843 patients from the SITS-MOST cohort with A being the most severe profile to F being the mildest. There was no notable difference in the onset to treatment delay nor in the dosage of tPA across the profiles. Ordinal analysis of mRS at day 90, adjusted for age, sex and pre-stroke mRS, confirmed greater odds of better outcome across all profiles, B-F, when compared against Profile A. The dichotomized outcomes and the overall survival analysis at 90 days, mirrored the findings from the ordinal analysis. There were statistically significant differences for good outcome, mortality and survival rates when comparing Profile C with Profile D, with Profile D consistently associated with worse outcomes than Profile C. Profiles C and E, which shared a common median baseline NIHSS, did not differ in terms of mortality and survival rates, when compared to each other after adjustment.

To compare the performance of symptoms profiles generated from baseline NIHSS with the 24-hour NIHSS, they applied the probabilities of profile membership onto 24-hour NIHSS data, to generate six distinct 24hour-NIHSS item profiles (Profiles a to f). There were clear distinctions in the survival curves between Profiles a and b versus the remaining profiles. There were significant differences in discrimination ability for the dichotomized outcomes between the baseline- and 24hour-NIHSS items profiles.

Identifying NIHSS for their individual components may be crucially important rather than just an overall score as shown by the authors in this paper. This classification may also be helpful in triaging patients given its prognostic value. 

Interleukin 16 may lead to carotid plaque stabilization and reduce risk of stroke

Alexander E. Merkler, MD

Grönberg C, Bengtsson E, Fredrikson GN, Nitulescu M, Asciutto G, Persson A, et al. Human Carotid Plaques With High Levels of Interleukin-16 Are Associated With Reduced Risk for Cardiovascular Events. Stroke. 2015

Over the years, we have learned that carotid artery disease is more complex than degree of stenosis. Two patients with identical severities of carotid artery stenosis may have entirely different phenotypes: one patient may develop recurrent strokes or TIAs and the other may remain asymptomatic. Ongoing research evaluating “vulnerable plaque” characteristics such as intraplaque hemorrhage, necrosis, or lipid core volume will hopefully guide physicians to better predict which patients are at risk for stroke and may benefit from a carotid artery intervention.

Interleukin 16 (IL-16) is a cytokine with both pro and anti-inflammatory properties. In the current study, Grönberg et al evaluate whether high levels of IL-16 found in human carotid artery plaques may confer protection against stroke. The authors evaluated 206 asymptomatic and symptomatic carotid artery plaques from human subjects who received carotid endarterectomies. Symptomatic patients had >70% stenosis and asymptomatic patients had >80% stenosis. 

The authors found that IL-16 mRNA expression was significantly higher in plaques from patients with asymptomatic carotid disease as compared to plaques from symptomatic carotid artery disease. In addition, high levels of IL-16 protein in carotid plaques were associated with a decreased incidence of future cerebrovascular events. Furthermore, high levels of IL-16 were associated with markers of plaque stability including elastin and collagen.

Some limitations to consider include 1) the lack of MRI data on radiographical plaque morphology –ie: amount of hemorrhage or calcification and 2) lack of causality – instead of high levels of IL-16 being protective against stroke, perhaps, in patients with symptomatic carotid disease, stroke may lead to decreased levels of IL-16 through post-stroke immunodepression and subsequent plaque destabilization.

Overall, IL-16 seems to be associated with carotid plaque stabilization and a reduced risk of stroke. If these findings are proven true, IL-16 could be a useful target to help reduce complications from large artery atherosclerosis.

Stroke and uncontrolled risk factors in Sri Lanka, a sample of the urban developing world

Neal S. Parikh, MD

Chang T, Gajasinghe S, and Arambepola C. Prevalence of Stroke and Its Risk Factors in Urban Sri Lanka: Population-Based Study. Stroke. 2015

In this issue of Stroke, researchers seek to establish the prevalence of stroke in Colombo, Sri Lanka. Though the aim may appear narrow at first glance, the results are striking and deserve the attention of those interested in global health and health disparities.

The researchers conducted a cross-sectional, survey-based study of the adult inhabitants of densely-populated Colombo, Sri Lanka. The survey they used is a validated tool and depends on patient report of clinical symptoms consistent with stroke. Their methodology was designed to comprehensively sample the diversity of Colombo. A remarkable 96.9% response rate yielded 2,313 people in 782 households. 

The prevalence was 10.4 strokes per 1000 adults. Stroke occurred in a 2:1 ratio favoring men and at a young mean age of 58.2 years. Two-thirds of stroke survivors experienced changes or cessation of employment. It is noteworthy that 62.5% of these patients had hypertension, 33.3% had diabetes and 45.8% were smokers.

If we are to extrapolate from this data and other data from India and China cited by the authors, young men and women in the urbanizing developing world are subject to high rates of stroke at young age and often face unemployment subsequently. In parts of the world with limited acute stroke treatment due to resource and infrastructure limitations, the importance of addressing readily modifiable risk factors such as hypertension and smoking cannot be overstated.

Predictors of outcome after endovascular therapy in basilar occlusion strokes

Peggy Nguyen, MD

Yoon W, Kim SK, Heo TW, Baek BH, Lee YY, and Kang HK. Predictors of Good Outcome After Stent-Retriever Thrombectomy in Acute Basilar Artery Occlusion. Stroke. 2015

Within the past year, the landscape of ischemic stroke treatment has rapidly changed with the publications of multiple positive trials of endovascular treatment. Thrombectomy has quickly been incorporated into the comprehensive care of the ischemic stroke patient; however, data regarding thrombectomy in patients with posterior circulation strokes, specifically basilar artery occlusions, remains uncertain. The major endovascular trials largely included those with anterior circulation strokes, namely ICA and MCA occlusions, with evidence being the strongest for causative occlusions of the ICA or M1. To address this deficit in our clinical knowledge, the authors here performed a retrospective analysis of patients with basilar occlusion strokes with the goal of identifying predictors of good outcome following endovascular therapy.

Of 50 consecutively enrolled patients in their comprehensive stroke center with basilar occlusion strokes who underwent mechanical thrombectomy, 54% (27/50) achieved a good outcome, considered as a modified Rankin scale of ≤ 2 at 3 month follow up, with mortality being 12% (6/50) at 3 months. There were no instances of symptomatic hemorrhage during the hospitalization. Authors identified two variables which independently predicted good outcomes: (1) a low initial stroke severity, defined by baseline NIHSS and (2) a high posterior circulation-ASPECTS (the pc-ASPECTS scoring system has previously been published elsewhere, see Puetz, et al. Stroke 2008) on pretreatment MRI-DWI sequence. Notably, no patients with a pc-ASPECTS of 3-5 (n=7) had a good outcome at 3 months while all patients with a pc-ASPECTS of 9 (n=6) had a good outcome. When dichotomized into groups with pc-ASPECTS ≥ 7 versus those < 7, patients with pc-ASPECTS ≥ 7 had a significantly higher rate of good outcome (66.7% vs 29.4%). Other variables which were associated with good outcome in univariate analysis were young age, absence of hypertension, and absence of bilateral thalamic infarction.

The most updated AHA/ASA guidelines only state that although the benefits are uncertain, use of endovascular therapy with stent retrievers may be reasonable for certain patients with a causative basilar occlusion, but criteria for selection are still unclear. Although it may vary from institution to institution, in our large urban academic center, the ASPECTS score is calculated on all ischemic stroke patients presenting for possible thrombectomy, but the pc-ASPECTS score has not been largely utilized. Although there are some limitations to this study, including the retrospective, non-controlled design, and the small number of patients, this along with other studies may prompt me to start thinking about a pc-ASPECTS score on my patients when they pass through the door to intervention.

By |October 6th, 2015|treatment|0 Comments

Some Painful News about Central Post-Stroke Pain

Ilana Spokoyny, MD 

Mulla SM, Wang L, Khokhar R, Izhar Z, Agarwal A, Couban R. Management of Central Poststroke Pain: Systematic Review of Randomized Controlled Trials. Stroke. 2015 

Post-stroke pain may present immediately after a stroke, or develop years later. The prevalence is unclear, but estimated to be anywhere from 2 to 25 percent in the first year after stroke. The underlying mechanisms are not well understood, which in turn limits effective treatment strategies. The results of this systematic review of randomized controlled trials evaluating therapies for central post-stroke pain (CPSP) are inconsistent with the clinical practice guidelines of three major Pain professional groups. While the three groups recommend tricyclic antidepressants and anticonvulsants as first-line therapy, this review found (very low certainty evidence) that anticonvulsants, tricyclic antidepressants, opioid antagonists, and electroacupuncture have no effect on reducing CPSP.

The authors found low certainty evidence that apipuncture (acupuncture using bee venom) may reduce pain, anticonvulsants may improve sleep, repetitive transcranial magnetic stimulation has no effect on depressive symptoms or patient-reported global improvement, and TCAs do not improve depressive symptoms but do produce significantly more side effects. The results for anticonvulsants were based on 4 trials, with a total of 307 patients. The results for TCAs were based on one trial with 15 participants, which is the basis for the recommendation by the three pain professional groups. This trial reported that there was a significant decrease in pain intensity with amitriptyline during the fourth and final week of treatment, but the authors of this systematic review analyzed the data and did not find a significant effect. The results for opioid antagonists, TMS, apipuncture, and electroacupuncture were all based on single trials.

The review was done in a very comprehensive manner, including the breadth of sources evaluated, inclusion of pharmacologic and non-pharmacologic therapies, and the systematic approach for assessing eligibility of studies. They also evaluated many patient-important outcomes (not just improvement of pain), and graded the level of certainty in the evidence using the GRADE approach in which randomized controlled trials begin as “high certainty” and drop down due to risk of bias, inconsistency, indirectness, imprecision, and publication bias.

Eight English-language studies were ultimately included, after an initial review of 5,015 initial entries including 324 full text articles. Studies were eligible if they enrolled at least 10 patients with CPSP, randomly assigned them to a treatment or control arm, and collected outcome data at least 14 days post treatment. If a study enrolled a mixed clinical population, they were included if the results of the CPSP patients were reported separately or at least 80% of the sample were CPSP patients. Risk of bias was assessed for each study based on presence of random sequence generation, allocation concealment, blinding of participants and study personnel, and incomplete outcome data.

To me, the take-home message is really the (poor) level of evidence, rather than the negative results. If very low level evidence suggests a treatment is ineffective, it may just need to be studied in a more thorough and bias-free manner. The authors recommend large, multi-center, randomized trials using standard instruments with established outcome measures, longer observation periods, and reduction of bias. Ideally, these types of studies would be carried out on existing therapies to assess their true utility in the treatment of CPSP while we continue to develop new treatment strategies.

By |October 5th, 2015|treatment|0 Comments

PD-L1 monoclonal antibody for prevention of inflammation after acute ischemic stroke

Alexander E. Merkler, MD

Bodhankar S, Chen Y, Lapato A, Dotson AL, Wang J, Vandenbark AA, et al. PD-L1 Monoclonal Antibody Treats Ischemic Stroke by Controlling Central Nervous System Inflammation. Stroke. 2015
Treatment options for acute ischemic stroke are limited. Although tPA and endovascular clot retrieval are beneficial, they are time-limited treatments which are not available to the majority of patients with stroke. Although targeting post-stroke inflammation is not a new concept, new advances in immunotherapy may lead to huge advances in post-stroke therapy.

Post-stroke inflammation begins with release of reactive oxygen species, which may trigger a cascade of activating complement, platelets, and endothelial cells leading to further neurological injury. Reperfusion, one of the goals of early acute ischemic stroke treatment, may also enhance the inflammatory process and lead to additional injury to brain tissue.

Dr. Bodhankar et al assess a new immunotherapy aimed at reducing the inflammation related to post-stroke reperfusion injury. The current study builds on their prior research, which showed that Programmed Death 1 (PD-1) receptor and its two ligands (PD-L1 and PD-L2) regulate the function of inflammatory immune cells and that mice deficient in the PD-L1 ligand had smaller infarct volumes when exposed to middle cerebral artery occlusion (MCAO). Based on the potentially pathogenic role of PD-L1 ligand, in the current study, the authors assess the effectiveness of blocking PD-L1 using a monoclonal antibody and assess outcomes via measuring stroke infarct volume and neurologic function.

Mice were exposed to transient focal ischemia via 1 hour of MCAO in the right brain hemisphere followed by 96h of reperfusion. Mice were given either monoclonal anti-PD-L1 antibody or an isotype matched control 4 hours following MCAO. First, the results support the theory that stroke and/or reperfusion leads to inflammation as both groups of mice had elevated leukocyte counts in the affected hemisphere, but not in the unaffected hemisphere. Second, as compared to mice treated with the control drug, mice treated with the monoclonal anti-PD-L1 antibody had a reduced number of pro-inflammatory cells in the ischemic hemisphere, supporting the anti-inflammatory effect of the antibody. Third, and most importantly, at 96 hours, infarct volume and neurological deficit were significantly reduced in mice that received the monocloncal antibody as compared to the matched controls. Noteworthy, however, is that 5 of the 73 monocloncal antibody treated mice developed severe hemorrhage and were excluded from the analysis while not of the control mice developed this complication.

Overall, the study provides exciting new vigor to post-stroke immunotherapy treatment. Blocking PD-L1 may be a viable treatment strategy in reducing post-stroke inflammation and thereby stroke infarct volume and neurological injury.