American Heart Association

Monthly Archives: February 2016

The MRI Spot Sign: A Marker of Clinical outcomes in Patients with Primary ICH

Peggy Nguyen, MD
 

Schindlbeck KA, Santaella A, Galinovic I, Krause T, Rocco A, Nolte CH, et al. Spot Sign in Acute Intracerebral Hemorrhage in Dynamic T1-Weighted Magnetic Resonance Imaging. Stroke. 2016

The spot sign on CTA has been previously correlated with hematoma expansion, mortality, and poor clinical outcomes in patients with primary ICH. In practice, the CTA spot sign is likely to be of greatest relevance, given hyperacute stroke imaging is still largely predicated on CT imaging. However, MR imaging has increasingly been used early in the course of acute stroke imaging, but there is no equivalent sign that has been validated. Here, the authors report on an equivalent MR spot sign on contrast enhance T1 weighted imaging in 50 consecutive primary ICH patients presenting within 24 hours of an acute stroke syndrome. 


Contrast enhancement within the hematoma on MR (spot sign) was demonstrated in 23 of 50 patients (46%) with primary ICH. Larger spot signs were seen with larger hematomas and correlated with the outcome based on mRS; specifically when spot signs were dichotomized as large (> 1 mL) vs small (< 1mL), large spot signs were characterized by larger hematoma volumes (36 mL vs 5 mL) and worse outcomes (median mRS 5). When patients were dichotomized according to presence or absence of a spot sign, patients with the spot sign had worse outcomes (median mRS 4) despite similar NIHSS on admission. On follow up imaging, however, no significant difference was seen in regards to hematoma expansion between those who had a spot sign and those who did not.

Although the MR spot sign was not demonstrated to be predictive of hematoma expansion, it was predictive of clinical outcome. Given that MR allows evaluation of hematoma age and often provides additional information on possible etiology of hemorrhage, the validation of an equivalent spot sign on MR adds another tool to the arsenal of MR interpretation for ICH.

Beyond Atrial Fibrillation: Atrial Cardiopathies as a Cause of Unexplained Stroke (Diagnosis of Stroke Etiology)

International Stroke Conference (ISC)
February 17-19, 2016

February 17, 2016
At an invited symposium at the ISC, attendees were treated to a thorough discussion regarding extended monitoring for AF, biomarkers for AF, and atrial cardiopathy.

First, Dr. Bernstein reviewed recent trials demonstrating the importance and yield of prolonged cardiac monitoring to detect AF in patients with cryptogenic stroke. As we know, approximately 30% of stroke remains cryptogenic after a standard stroke work-up. In EMBRACE, patients with cryptogenic stroke or TIA were randomized to standard of care of 30 days of monitoring. Prolonged monitoring doubled the rate of AF diagnosis (14.8% at 4 weeks as compared to 2.2% after 24 hours and 7.4% after 1 week) and led to an increase in appropriate therapy. In CRYSTAL AF, a similar population was randomized to standard of care and an insertable cardiac monitor. AF diagnosis increased in a time-dependent manner. At ISC 2016, FIND-AF was presented, which randomized all-comer stroke patients to standard of care or 3 10-day monitoring episodes. 4.5% of patients in the control were found to have AF, versus 13.5% at 6 months with up to 3 10-day sessions.

These trials all suggest the importance of prolonged cardiac monitoring. Dr. Bernstein astutely conveyed the opportunities inherent to this data: we may be able to determine the dose-dependence and thresholds of toxicity with regards to AF and stroke.

Second, we were treated to a discussion of structural and serum biomarkers of AF. The goal of biomarker development is to guide early detection of AF in order to initiate early therapy to prevent early recurrent cerebrovascular events. Noteworthy potential biomarkers include cardiac MRI (delayed enhancement reveals atrial fibrosis), atrial blood flow dynamics, and BNP and ANP, for which there are a range of potential cut-offs.

Third, Hooman Kamel provided an overview of electrocardiographic markers of atrial dysfunction that may be independent of AF. He argues that it is important to search for occult AF because 70% of patients with cryptogenic stroke (e.g. in EMBRACE) do not have AF even after prolonged study, suggesting that other mechanisms of disease may have a role. He notes that endothelial dysfunction, fibrosis, impaired myocyte function, and chamber dilation are noted in patients with AF. He conducted multiple studies in various, large cohorts (MESA, Cardiovascular Health Study, ARIC, NOMAS) to demonstrate that the P-wave terminal force on EKG (lead V1) is associated with ischemic stroke and, more specifically, cryptogenic and non-lacunar stroke. This association suggests that atrial cardiopathy may independently be a risk for cardioembolic stroke, with AF perhaps indicating more severe atrial cardiopathy.

Last, Shadhi Yaghi reviewed the therapeutic implications of the atrial cardiopathy model. He has also discussed some of these views in an article in Neurology (2015). A major advantage of the atrial cardiopathy model is that it shrinks the cryptogenic stroke population, which allows more targeted, individualized therapy for secondary stroke prevention. Studies to evaluate the effectiveness of anti-coagulation for secondary prevention in patients with stroke or TIA and markers of atrial dysfunction should be considered. Additionally, this model may allow for prediction of AF, which could, prompt a search for therapies to halt or reverse atrial cardiopathy and also prompt trials for primary prevention of stroke.

In summary, patients with cryptogenic stroke and TIA should undergo prolonged cardiac monitoring to prompt appropriate secondary prevention (anti-coagulation). Structural and serum biomarkers of AF may help us identify patients who can be initiated on anti-coagulation earlier after a stroke, before AF is conclusively diagnosed. AF may be a marker of severe atrial cardiopathy, which may be independently associated with ischemic stroke; emerging data will inform approaches to primary and secondary stroke prevention in patients with risk for cardioembolic stroke in the absence of documented AF.

– Neal S. Parikh, MD

By |February 24th, 2016|Conference|0 Comments

Taiwanese observational cohort suggests better safety and efficacy profile for dabigatran in Asian patients with non-valvular atrial fibrillation

Danny R. Rose, Jr., MD

Chan YH, Yen KC, See LC, Chang SH, Wu LS, Lee HF, et al. Cardiovascular, Bleeding, and Mortality Risks of Dabigatran in Asians With Nonvalvular Atrial Fibrillation. Stroke. 2016

Dabigatran, a competitive direct thrombin inhibitor used for prevention of stroke and systemic embolism in non-valvular atrial fibrillation (AF) patients, was approved by the FDA in 2010 based on the results of the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial. Post-marketing studies have raised concerns regarding risk of severe bleeding, particularly in the elderly population and in those with renal impairment. Additionally, as the majority of published studies regarding dabigatran use enrolled patients from the USA and Europe, limited data exists regarding the thromboembolic and bleeding risks in patients of Asian ethnicity. Chan et al. utilized the Taiwan National Health Insurance Research Database (NHIRD) to investigate the efficacy and safety of dabigatran compared to warfarin in AF patients through an observational cohort study.


The authors selected 9,940 dabigatran users and 9,913 warfarin users who were prescribed their respective treatments after June 1, 2012. Propensity score weighting was used to balance covariates across the two study groups, as the dabigatran group was older, had a higher proportion of hypertension, diabetes mellitus, stroke or TIA history, a lower proportion of prescribing anti-platelet agents, and higher CHA2DS2-VASC and HAS-BLED scores compared with the warfarin group. The median follow-up period was 0.67 years for dabigatran users and 0.73 years for warfarin users and was defined as the time from the index date until the first occurrence of any of the six study outcomes or the end of the study period (December 31, 2013).

The six outcomes studied were ischemic stroke, acute myocardial infarction, intracranial hemorrhage (identified using atraumatic hemorrhage discharge diagnosis codes), major gastrointestinal bleeding (requiring transfusion), all major bleeding events, and all-cause mortality. Although some patients accumulated multiple outcomes during the duration of the study, only the initial outcome was counted as patient management was changed due to the outcome in question.

Compared with the warfarin group, the dabigatran group was associated with a significantly reduced risk of ischemic stroke, intracranial hemorrhage, all hospitalized major bleeding events, and all-cause mortality (all p<0.0001) and a marginal decreased risk of acute myocardial infarction (HR 0.67, p=0.0803). There was no difference in major gastrointestinal bleeding between the two study groups (HR 0.99, p=0.9658).

This study highlights potential differences in the risk profile of patients of Asian ethnicity with respect to ischemic and hemorrhagic events while therapeutically anticoagulated. The results stand in contrast to the results of the RE-LY trial, which showed a significant reduction in the risk of both ischemic and hemorrhagic stroke and increased gastrointestinal bleeding risk at the 150 mg dose, which was the dose that was approved by the FDA for use in the USA. Interestingly, a majority (88%) of the patients in this cohort were prescribed the 110 mg dose, which showed comparable stroke and gastrointestinal bleeding risk to warfarin with a significant reduction in the risk of intracranial hemorrhage. The authors speculated this prescribing discrepancy may be due to a combination of a lower average BMI in Asian patients, higher risk of warfarin-related intracranial hemorrhage in Asian patients leading to physician discretion with dosing, and increased proportion of patients that are elderly with chronic kidney or liver disease due to restrictions on dabigatran prescribing under the Taiwanese national health system.

The study’s findings were compatible with subgroup analysis from RE-LY looking at the Asian participants that comprised 15.3% of that study’s population. Given that Asian patients tended to have more complications with warfarin and better efficacy and fewer complications with dabigatran, it may be reasonable to reconsider using dabigatran as a first-line therapy in this specific population. This decision making should also be made with the understanding of the limitations of observational cohort data as compared to prospective randomized data. Whether these findings would extend to a larger prospective randomized trial or with other novel oral anticoagulants with different mechanisms of action in the Asian population remains to be seen and represents an interesting potential avenue for future study.

By |February 22nd, 2016|prevention|0 Comments

Stroke Controversies: Debate

International Stroke Conference (ISC)
February 17-19, 2016

February 19, 2016
Another standing room only session at the ISC 2016, the Stroke Controversies: Debate was a spirited back and forth session exploring three topics of clinical equipoise between thought leaders in their respective fields, of which there are no easy answers.
 
Debate #1: Should we bypass primary stroke centers (PSC)? Arguing in favor, Dr. Goyal points out that tPA does not work very well for proximal large vessel occlusions, the NNT is as low as 2.6 for endovascular therapy, time is brain and we lose time (and therefore brain) transferring from a PSC to a comprehensive stroke center (CSC). Dr. Johnston agreed that in some cases, i.e. if the patient does not qualify for tPA, it may be reasonable, but endovascular treatment is only proven safe and efficacious for a minority of patients. As of now, there is no way to effectively screen patients in the field, and bypassing a PSC may in these situations delay treatment with tPA.

I interpreted this as a debate between pragmatism and idealism. The ideal might be bypassing a PSC, but pragmatically, within our current system of stroke care, this may lead to saving time for a subset of patients with large vessel occlusion at the expense of delaying tPA for the majority of patients, especially within the context of the resources that we have. We need a better work flow to minimize delays in transfers if we continue to rely on PSCs, or alternatively, better screening measures in the field if we want to bypass them.

Debate #2: Embolic stroke, atrial fibrillation, and cerebral microbleeds: Is there a role for anticoagulation? Dr. Diener presented the pro side, arguing that afib increases the risk of stroke and while some microbleeds, such as with amyloid angiopathy, may be a contraindication, others are markers of small vessel disease. NOACs have a more favorable profile for ICH than warfarin and has been demonstrated to not increase microbleeds. Dr. Greenberg, however, iterated the dismal outcome of anticoagulation related ICH (up to 50%), and pointed out that microbleeds lead to 5 ICH events/100 person years. A decision analysis modeling the risk/benefit ratio of anticoagulation has previously identified an ICH risk of 1.4% as the tipping point where risk of anticoagulation outweighed benefits.

There is no easy resolution to this debate. With safer NOACs being introduced, it would seem reasonable to anticoagulate, even in the presence of microbleeds. In parallel, as treatments of ICH continue to advance, the mortality of anticoagulation related ICH will hopefully decline to the point where we will no longer fear it.

Debate #3: Should we assess the outcome of severe strokes early (3 months) or late in clinical trial? Both Dr. Dawson, who argued in favor of an early assessment, as well as Dr. Broderick, who argued in favor or a late assessment, used data from the MISTIE II and IMS III to support their points, which perhaps points to the true equipoise in this question. Dr. Dawson’s point was that in general, the longer a trial is conducted, the more confounders are introduced and often, additional time does not add information that significantly changes the interpretation of the results. Given the resources available, a better approach may be to recruit more patients within a shorter trial rather than follow less patients for a longer time frame. Dr. Broderick argued that especially with severe strokes, there are patients who recover later, and delayed follow up allows for better cost effect analysis.

Much like the first debate, some of this is a question of what is practical vs what is ideal. Delayed recovery is still important for the patient and the physician, and a later assessment allows us to fully capture all of these patients; it will allow us to answer the question of the sustainability of recovery. However, with limited funds for trials, it may be difficult to implement this. 

– Peggy Nguyen, MD

Anticoagulation in stroke patients with atrial fibrillation and multiple cerebral microbleeds: A controversial topic


Embolic Stroke, Atrial Fibrillation, and Microbleeds: Is there a role for anticoagulation?
 

José G. Merino, MD

Anticoagulation with vitamin K antagonists or one of the new oral anticoagulants (NOACs) is indicated to prevent recurrent stroke for most stroke patients with atrial fibrillation (AF). In these patients the risk of stroke is very high, around 7% to 10% per year, but Coumadin and other anticoagulants can decrease the risk substantially. The most feared risk of anticoagulation -intracerebral hemorrhage (ICH)- is relatively low and the benefits of treatment outweigh the risks.
But does the presence of certain comorbidities change the risk-benefit equation and make anticoagulation too risky for some patients? Patients who have had a lobar ICH, for example, may have an increased risk for recurrent ICH and thus may not be candidates for anticoagulation. Are patients with cerebral microbleeds (CMBs) also ineligible for anticoagulation?

In Stroke, a Controversies article addresses the hypothetical case of a 73-year old man with stroke, AF and 8 cortical CMBs. Hans-Cristoph Diener argues that anticoagulation, perhaps with a NOAC, is indicated because of the very high risk of recurrent stroke in patients with AF and the uncertainty about the risk of ICH in patients with CMBs. Steven Greenberg disagrees and argues that the risk of anticoagulation may be greater than the potential benefit because patients with cortical CMBs may have cerebral amyloid angiopathy (CAA), a condition that leads to ICH, and the fatality rate for anticoagulated patients with ICH is very high. Until there is a better understanding on the relationship between CMBs, anticoagulation, ICH, recurrent stroke and clinical outcome, clinicians must be mindful that anticoagulation may harm their patients with multiple cortical CMBs, particularly when CAA is suspected.

Both authors, along with Magdy Selim and Carlos Molina, editors of the Controversy Section, agree that the decision about anticoagulation in patients with multiple cortical CBMs is challenging and urge clinicians to engage patients in the decision about anticoagulation in this setting by acknowledging the gaps in our understanding of the relationship of AF, CAA, recurrent stroke, ICH and the use of anticoagulants; informing patients (and their families) about alternative strategies and possible outcomes; and eliciting their preferences (how do they weigh the reduced risk of recurrent stroke with increased risk of ICH, for example.) This controversy highlights the value of shared decision making in the face of clinical uncertainty.

By |February 19th, 2016|controversy|0 Comments

Selecting Ischemic Stroke Patients for Acute Endovascular Therapy: The State of the Evidence

International Stroke Conference (ISC)
February 17-19, 2016

February 17, 2016
Since endovascular treatment has become standard of care, we are still grappling with the question of which patients have the most benefit, and really, are there patients that would not benefit. This was a standing room only session at ISC 2016 reviewing how much we know (and don’t know) about selecting patients for endovascular treatment, broken down into five major topics.


·    Topic 1: Stroke severity – There is a paucity of data for outcomes in low severity strokes after both endovascular treatment and IV tPA. Many of these patients were excluded from the major IV tPA clinical trials. In terms of endovascular treatment, of 1200+ patients in the 5 endovascular trials, only 14 patients had low NIHSS of 0-5. Subgroup analyses of patients grouped by NIHSS as well as a meta-analysis of the 5 endovascular trials did not show a treatment effect of NIHSS on outcome. Ongoing trials to address this knowledge gap are forthcoming, including PRISMS, TEMPO2, and VISTA.

·     Topic 2: Age – Similar to topic 1, evidence is limited. The endovascular trials did provide some subgroup analyses on dichotomized age groups, but most of the breakpoints were at ages significantly younger than 80. For example, for SYNTHESIS, analysis was dichotomized at the age group of 67. For IMS 3, it was dichotomized at 65 years. In neither trial did age have a treatment effect on outcome. MR CLEAN did have patients over age 80 and showed a benefit but with a wide confidence interval due to small numbers. Bottom line, age alone is not a sufficient reason to withhold treatment.

·     Topic 3: Imaging – Are there specific imaging markers that should dictate moving forward with endovascular treatment? Pre-specified analysis of data from MR CLEAN for patients with ASPECTS 0-4, 5-7, and 8-10 showed no safety concerns but suggested benefit was likely greatest in the middle group, although the group in the lowest ASPECTS score was underpowered. Presence of mismatch on perfusion in MR CLEAN did not have a significant interaction on benefit; however, collateral imaging, based on a collateral grade on CTA did. The guideline for treatment is currently non-contrast CTH and CTA, to identify intracranial ICA or M1 occlusion and an ASPECTS of 6 or above, but forthcoming studies including DEFUSE 3 will help to refine this paradigm.

·    Topic 4: Time – When is it too late?  The reality is that although time is brain, treatment is focused on penumbra salvage, and penumbra growth is time dependent and individualized. Growth rate is likely determined by presence or absence of collaterals. Results of DEFUSE 2 suggests that if you have good collaterals, what matters is that you re-perfuse, not the time from ictus. DAWN and DEFUSE3 will look at imaging selection and thresholds for endovascular treatment in stroke patients in the extended window after 6 hours and wake-up strokes.


·    Topic 5: Occlusion site – The mantra seems to be, just because we can reach the occlusion, doesn’t mean we should. Among things to consider are: (1) the pattern of occlusion – i.e. is there a tandem occlusion, is it an iatrogenic occlusion, (2) tissue viability – if the area is infarcted, there may not be a benefit, and in fact, may be harmful, to re-perfuse, (3) the eloquence of the area affected, and (4) individualized disability. Occlusion of the distal sites, especially M2, tend to be clinically heterogeneous, and an approach that takes into account all the aforementioned is recommended.

– Peggy Nguyen, MD
By |February 18th, 2016|Conference|1 Comment

Endovascular therapy for posterior circulation strokes: the time has come

The role of modern endovascular treatment has been extensively studied for anterior circulation strokes, leading to clear guidelines outlining the management in this patient group. This is not the case for posterior circulation strokes, which have been excluded from the pivotal endovascular stroke trials. Therefore, the authors aimed to characterize the predictors of successful recanalization and outcomes of endovascular therapy for posterior circulation stroke patients.

Consecutive large vessel posterior circulation stroke patients who underwent endovascular treatment (thrombectomy, aspiration or both) within 24 hours at 8 centers within the USA between March 2012 and July 2015 were included. Patients with large brainstem strokes were excluded although no parameters to estimate the extent of infarct were provided. Imaging modality choice depended on each center’s acute stroke imaging protocol and local investigators were in charge of its analysis. Successful recanalization and functional outcomes were defined as a Thrombolysis in Cerebral Infarction (TICI) score of 2b-3 and a Modified Rankin Score (mRS) of 0-2, respectively.

A total of 100 patients were included in the analysis after 2 individuals who achieved successful recanalization with local intra-arterial thrombolysis alone, were excluded. The population baseline characteristics were similar to those seen in anterior circulation stroke trials, except for a male predominance (67%), higher mean admission NIHSS score (19.2), higher rate of general anesthesia (60%), and low rate of t-PA administration (32%). The occlusion sites in order of frequency were the Basilar artery (including top of the Basilar), Posterior Cerebral artery and Vertebral artery. Interestingly, the symptom onset to groin puncture time was 562 +/- 466 minutes but successful recanalization was still achieved in 80% of cases (58% with stent retrievers and 42% with aspiration devices). Adverse events including symptomatic ICH and mortality were seen in 5% and 30% of cases, respectively. Indeed, only 35% of patients had a favorable outcome at 3 months, a number that is similar to that achieved in the control group of some of the landmark endovascular trials (E.g. SWIFT PRIME). When looking into the univariate analysis of predictors of favorable versus poor clinical outcomes, the authors found that lower baseline NIHSS scores, shorter symptom-onset-to-groin-puncture, higher percentage of t-PA administration and successful recanalization rate, were overrepresented in those with favorable outcomes at 3 months. Lesser general anesthesia administration showed a trend towards better outcomes. However, the multivariate analysis revealed that only successful recanalization and shorter treatment times (symptom-onset-to-groin-puncture and symptom-onset-to-recanalization) were the only independent predictors of good functional outcomes at 3 months. The rate of favorable clinical outcomes was inversely correlated to the symptom-onset-to-groin-puncture time in a multivariate analysis that included only patients who achieved successful recanalization alone (not significant when looking at the entire population). Additionally, the initiation of endovascular therapy within 6 hours from symptom onset increased the likelihood of favorable clinical outcomes by two-fold in this population. The type of recanalization strategy (stent retriever versus aspiration) did not impact the clinical outcomes or the recanalization rates.

Overall, this paper illustrates the early stages of endovascular acute stroke therapy for posterior circulation stroke patients. Time to treatment, particularly within the first 6 hours, appears to be a strong predictor of favorable clinical outcomes, a concept that has been well described in anterior circulation strokes. In addition to this, both endovascular techniques (stent retrievers or aspiration devices) appear to be effective in achieving successful recanalization in this population. However, readers should be cautions when interpreting the results derived from this paper considering its retrospective design, the non-randomized nature of patient selection, the heterogeneity of acute stroke care protocols and imaging interpretation and modalities in different centers, the small sample size and the lack of Bonferroni correction for the subgroup analyses. The time for prospective randomized trials investigating endovascular therapy for posterior circulation stroke patients has come!

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

Hemorrhagic stroke risk increased with certain NSAIDs: A meta-analysis of the data

Peggy Nguyen, MD

Ungprasert P, Matteson EL, and Thongprayoon C. Nonaspirin Nonsteroidal Anti-Inflammatory Drugs and Risk of Hemorrhagic Stroke: A Systematic Review and Meta-Analysis of Observational Studies. Stroke. 2016

The risk of cardiovascular events with NSAIDs has recently been publicized in the general media, with the FDA strengthening its warning on the association of NSAIDs with myocardial infarction and strokes in the past year. The relationship between NSAIDs and stroke risk, however, particularly hemorrhagic stroke, is ill-defined. The authors here performed a comprehensive meta-analysis reviewing the risk of hemorrhagic stroke in patients taking NSAIDs.

This meta-analysis identified 10 studies (7 case-control, 3 cohort studies) encompassing 1,489,120 patients. There was some heterogeneity across the studies, but most studies identified NSAID exposure as use of any NSAIDs until the index date or within 30 days prior to index date. Pertinently, there was a small, but not statistically significant, increased risk of hemorrhagic stroke (RR 1.09, 95% CI 0.98 – 1.22). Statistical analysis was also done for individual NSAIDs when data was available from a minimum of 3 studies, with a statistically significant increase for hemorrhagic stroke with diclofenac (RR 1.27, 95% CI 1.02 – 1.59) and meloxicam (RR 1.27, 95% CI 1.08 – 1.50). The highest risk estimate was seen in rofecoxib users, although it was not statistically significant (RR 1.35, 95% CI 0.88 – 2.06). The statistical significance was not significantly changed with sensitivity analyses, although the relative risk was increased for diclofenac and meloxicam in one analysis to 1.46 and 1.48, respectively.


As the authors point out, the results of the meta-analysis should be interpreted with caution. The lack of a significant association with NSAIDs as a whole may be a function of the reversibility of NSAID inhibition on COX-1. Selection bias may exist; due to the cardiovascular warning associated with NSAIDs, the exposed group may in fact be healthier than the non-exposed group, in which case, the risk of hemorrhagic stroke may actually be underestimated. Nevertheless, the results are at least suggestive that in patients who are at increased risk for hemorrhagic stroke, for example, a patient with amyloid angiopathy, it is not unreasonable that these medications be avoided.

Hypothermia for large hemispheric infarction?

Alexander E. Merkler, MD 

Su Y, Fan L, Zhang Y, Zhang Y, Ye H, Gao D, et al. Improved Neurological Outcome With Mild Hypothermia in Surviving Patients With Massive Cerebral Hemispheric Infarction. Stroke. 2016 

Mild hypothermia is an established neuroprotectant and has shown to improve neurological outcomes in both cardiac arrest and neonatal hypoxic-ischemic injury. Its role in stroke has yet to be established, and ongoing multicenter trials are underway.

Massive cerebral hemispheric infarction (MCHI) occurs in a subset of patients with stroke and confers a very high degree of mortality and morbidity. Without decompressive hemicraniectomy, mortality is over 70%, and in patients who receive a decompressive hemicraniectomy, approximately 40% of survivors are left disabled with a modified Rankin scale (mRS) of 4 (unable to walk without assistance and unable to attend to own bodily needs without assistance). Further strategies are therefore necessary to reduce morbidity and neurological impairment in patients with MCHI. 

In the current manuscript, Dr. Su et al assess the role of mild hypothermia on neurologic outcomes in patients with MCHI. Patients were eligible if they were 18-80 years of age, had a unilateral MCHI (based on the same definition used in previous large trials investigating decompressive hemicraniectomy) within 48 hours, and were deemed ineligible to receive decompressive hemicraniectomy due to use of antithrombotic medications or refusal to undergo surgical treatment. Patients were randomized to receive mild hypothermia versus normothermia. Hypothermia was initiated as soon as possible after admission and continued for at least 24 hours. The temperature of patients in the control group was sustained between 36.5˚C – 37.5˚C to maintain normothermia. The primary outcomes were mortality and mRS at 6 months. An mRS of 0 to 3 was considered a good neurological outcome.

Overall, 33 patients were enrolled. There was no difference in mortality; however, although non-significant, there was a trend towards improved neurological outcomes in the patients who received therapeutic hypothermia. Seven of every eight surviving patients who received hypothermia versus four out of ten surviving patients who did not undergo hypothermia achieved a good neurological outcome. In fact, 3 patients in the hypothermia group and 0 patients in the control group achieved an mRS of 1 or 2. Complications were significantly more common in the hypothermia group and included arrhythmia, electrolyte disturbance, gastrointestinal bleeding, and hyperglycemia.

Limitations are 1) only patients who did not undergo decompressive hemicraniectomy were included, and 2) patients who received hypothermia were on average 10 years younger than the control group.

Hypothermia may prove to be a useful tool to improve functional outcome in patients who suffer from MCHI, especially in those in whom decompressive hemicraniectomy is not performed. Future studies are necessary to confirm these results.

By |February 11th, 2016|treatment|0 Comments

Prediction models for functional outcome in acute ischemic stroke patients. Closer to the truth?

Luciana Catanese, MD

Leiva-Salinas C, Patrie JT, Xin W, Michel P, Jovin T, and Wintermark M. Prediction of Early Arterial Recanalization and Tissue Fate in the Selection of Patients With the Greatest Potential to Benefit From Intravenous Tissue-Type Plasminogen Activator. Stroke. 2016

To date, there are no available prediction models to guide physicians in the accurate selection of ischemic stroke patients that will benefit from acute recanalization therapies. CT perfusion (CTP) parameters such as ischemic core volume, penumbra and mismatch profile have shown promising results but not independent from recanalization rates. Therefore, the authors aimed to determine whether the prediction of functional outcomes in acute ischemic stroke (AIS) patients was more accurate when using prediction models including CTP and recanalization parameters versus those without.

Five different hypothetical prognosis algorithms were designed for this purpose, one based on whether or not patients received tPA, a second one based on ASPECTS score of >=7 versus <7, a third one based on the site of occlusion, a fourth one based on volume of ischemic core and penumbra and a fifth one based on a matrix of predicted recanalization (using the ‘iSTROKEMD’ application) and volume of ischemic core and penumbra at baseline. Comparison of sensitivity, specificity, positive and negative predictive value as well as accuracy was made between such algorithms to predict good clinical outcomes, defined as mRS of 0-2 at 90 days.

Retrospective data from 173 patients taken from a repository published previously who were >=18 years, presented within 4.5 hours from symptom onset, had available CT, CTA and CTP on admission as well as CTA or MRA between 1 and 48 hours and who were considered for tPA but did not undergo endovascular therapy were analyzed. Overall, about half of patients were male (median age ~70), had a median ASPECT score of 7, ~50% M1 occlusions and 71.6 % received tPA (54% recanalization versus 34.6% without). Good outcome inversely correlated with admission NIHSS and was overrepresented in those treated with tPA when adjusting for age and baseline NIHSS, as seen in prior studies. Overall, the algorithm that combined the a-priori calculation of the prediction of recanalization with the volume of baseline PCT ischemic core and penumbra was the most accurate in predicting good outcomes with an accuracy of 77.7%. The following table displays the statistical measures of the performance of the different approaches in predicting functional outcomes.


The combination of predicted recanalization and perfusion parameters may be superior in prognosticating good clinical outcomes when compared to other predictors in isolation. However, considering the evolving nature of both CTP thresholds and softwares in accurately and universally measuring ischemic core and penumbra volumes, the small and non-randomized sample, restrospective analysis and lack of inclusion of patients with and without endovascular recanalization, among others, the interpretation of these results is limited. Successful recanalization and baseline tissue fate seem to influence outcomes in AIS patients that undergo recanalization. Closer to the truth but not quite there yet.