Backes D, Vergouwen MDI, Velthuis BK, van der Schaaf IC, Bor ASE, Ale Algra A, and Rinkel GJE. Difference in Aneurysm Characteristics Between Ruptured and Unruptured Aneurysms in Patients With Multiple Intracranial Aneurysms. Stroke. 2014
Jennifer Dearborn, MD
Jia Q, Liu G, Zheng H, Zhao X, Wang C, Wang Y, et al. Impaired Glucose Regulation Predicted 1-Year Mortality of Chinese Patients With Ischemic Stroke: Data From Abnormal Glucose Regulationin Patients With Acute Stroke Across China. Stroke. 2014
Impaired glucose tolerance is a spectrum, and often clinical outcomes in stroke are addressed with consideration only to diabetic patients. This study sought to characterize impaired glucose tolerance and prediabetes in outcomes after stroke in a Chinese population. The ACROSS-China study enrolled 2,639 patients with ischemic stroke and measured glucose tolerance using the WHO criteria of impaired fasting glucose and/or impaired 2-hour glucose tolerance test. The outcome of the study was stroke mortality. The HR of death at one year was 3.2 (95% CI 1.6, 6.6) after adjustments. The majority of the stroke deaths at one year were categorized as secondary to the stroke itself. 12% of participants died at one year, and the median NIHSS on admission was 4 in both groups, so severity of presenting stroke seemed not to account for the difference in mortality. There was no difference on dependency or stroke recurrence between groups at one year.
This large, well-orchestrated prospective study shows convincing evidence that stroke mortality is increased by glucose intolerance. Several questions, however, remain after consideration of these results. The first is, what were some details about the deaths in study, and how could these characteristics account for the comorbidity of glucose intolerance? For example, were the majority of deaths within the first 30-days, because thereafter, the death was likely not secondary to the stroke itself, but more likely complications of infection, VTE, MI, or other post-stroke complications. Lastly, is it important to consider the difference between diabetics and pre-diabetics in terms of mortality, as this was not delineated. This is important evidence that measuring the impact of glucose intolerance after stroke is critical to improve post-stroke care.
Golledge J, Clancy P, Maguire J, Lincz L, Koblar S, McEvoy M, Attia J, et al. Plasma Angiopoietin-1 Is Lower After Ischemic Stroke and Associated With Major Disability But Not Stroke Incidence. Stroke. 2014
Whiteley WN, Thompson D, Murray G, Cohen G, Lindley RI, Wardlaw J, and Sandercock P. Targeting Recombinant Tissue-Type Plasminogen Activator in Acute Ischemic Stroke Based on Risk of Intracranial Hemorrhage or Poor Functional Outcome: An Analysis of the Third International Stroke Trial. Stroke. 2014
Given the extensive data now available from multiple clinical trials of IV-TPA, one might expect to find clinical factors predisposing patients to harm versus benefit that could help guide treatment decisions. Whiteley and colleagues explored this question by analyzing data from the IST-3 trial. They were able to predict which subjects were most likely to experience symptomatic ICH (sICH) or poor functional outcome. Surprisingly, the patients at highest risk for sICH or poor functional outcome also received the most benefit from IV-TPA.
The authors used logistic regression to develop a new model to predict sICH and poor functional outcome in subjects from the IST-3 trial and compared this new model to several other prediction models validated on prior datasets. Nearly all of the models showed at least moderate ability to predict sICH and poor functional outcome. A very simplified model that included only age and NIHSS was equally effective at prediction. The models were stratified into mild, moderate, and severe risk of sICH or poor functional outcome. Paradoxically, the authors found that IV-TPA was most beneficial for those subjects who fell into the severe categories.
This study reinforces lessons learned from IST-3 and provides insights into our lack of a precise predictor for those who will develop sICH. IST-3 made the case for eliminating advanced age and high NIHSS as contraindications to IV-TPA. The current study puts these findings into perspective. The very factors that predict a higher rate of sICH and poor functional outcome also predict less long term disability in response to treatment with IV-TPA. Of course those with large vessel occlusion are more likely to benefit from IV-TPA and more likely to have sICH, which may explain these counterintuitive results. The current study also highlights the need to identify a much more specific prediction marker for sICH. Using current sICH markers to decide when to withhold TPA does more harm than good. While awaiting a better biomarker for sICH, we should forge ahead and not exclude patients from IV-TPA simply because of advanced age or high NIHSS.
Inoue M, Mlynash M, Christensen S, Wheeler HM, Straka M, Tipirneni A, et al. Early Diffusion-Weighted Imaging Reversal After EndovascularReperfusion Is Typically Transient in Patients Imaged 3 to 6 Hours AfterOnset. Stroke. 2014
Research and data have tempered the stroke world’s excitement for endovascular therapy. Selecting the patients that would benefit from this procedure has been difficult. This article speaks to the importance of timing. Let’s start interventional reperfusion in less than 6 hours and in these cases, whether or not the DWI is reversible won’t be as important.
Wake-Up is a multicenter trial using imaging based criteria for entry, funded by the European Union, to determine if emergency stroke care (and r-tPa) can be extended to those who wake up with a stroke. Galinovic et al. seek to demonstrate in this paper how interrater agreement in FLAIR signal can be improved by using quantitative techniques. The ratio of DWI signal to FLAIR signal (or DWI-FLAIR mismatch) may provide important information about the timing of a stroke to less than 4.5 hours of onset, which is the cutoff for approved r-tpa use. The trial uses for inclusion in addition to the mismatch, the exclusion of hemorrhage, and a DWI lesion <1/3 the MCA territory.
As FLAIR positivity is subjective, the opinions of 2 senior neuroradiologist were taken as the “gold standard” and 6 individuals rated 143 cases. Additional raters processed a subset to compare relative signal intensity (rSI) in the contralateral tissue. An ROC-analysis was used to find the threshold, which corresponded with the “gold standard of FLAIR positivity. Raters on an additional subset of cases prospectively tested this threshold.
The raters had a low rate of agreement between each other (kappa <0.5). The signal threshold (called rSI) did not improve the interrater agreement. The importance of this study is that it demonstrates that aspects of FLAIR positivity cannot be quantified, and are indeed subjective (and dependent on the rater experience). Automated methods such as rSI can be used as a “back up” to the human eye, as the authors suggest, but did not add additional information when used with the subjective analysis. The efforts to standardize imaging biomarkers used in treatment decisions is important, especially to compare results across trials and look forward to extended trial results to a clinical population.
Mochari-Greenberger et al. reviewed data from a 2012 American Heart Association commissioned telephone study to evaluate knowledge of stroke warning symptoms in women > 25 years of age. A survey of 1,205 English speaking women revealed that their knowledge about stroke symptoms were low. 51% knew that sudden weakness or numbness on one side of the body or face was a stroke warning sign. But, less than 20% knew that loss of vision or unexplained dizziness may be a stroke symptom. Fortunately, 84% of them knew to call 911 if they thought they were having a stroke.
There were no significant differences by racial/ethnic group (black, White, Hispanic, or other), but this was likely limited to a survey of English speaking participants only. The survey was also conducted via open ended questions (similar to previously performed surveys sponsored by the AHA) which may require a higher level of knowledge awareness than passive recognition.
What is more heartening is that 4 out of 5 women knew to call the ambulance when they thought they were having a stroke. Of course, if they happen to have unilateral numbness or weakness, of which 50% of them would recognize it being a stroke, it means that only 4 out of 10 women would be able to connect the dots to that “I’m having one sided weakness, I must be having a stroke and therefore, call 911” moment.
This recent survey suggests some modest advancement in stroke symptom knowledge and activation to call for help, but a lot of education still needs to take place.
2. Educate not only patients but also their family members and caregivers because frequently the patients may not be aware they are experiencing symptoms of stroke (anytime you interface with the patient or their loved one is an opportunity for stroke education!)
3. Reach out to influential members of the community, educate them about stroke symptoms and have them spread the word (I had one stroke survivor who was actively involved in church, so, volunteer to take brochures and preach gospel and stroke symptoms to their congregation!)
Mechanical Discordance of the Left Atrium and Appendage: A Novel Mechanism of Stroke in Atrial Fibrillation
Warraich HJ, Gandhavadi M, and Manning WJ. Mechanical Discordance of the Left Atrium and Appendage: A NovelMechanism of Stroke in Paroxysmal Atrial Fibrillation. Stroke. 2014
The majority of left atrial thrombi involve the left atrial appendage. The surface ECG may not always reflect underlying left atrial appendage mechanical function, rather surface ECG p-wave reflects atrial body activation. Transesophageal echocardiography has the ability to record left atrial appendage pulse wave Doppler and determine weather flow pattern corresponds to the mechanical function of the sinus rhythm of atrial fibrillation.
In this retrospective trial, a total of 208 consecutive patients with available TEE were screened, for which TEE LAA data were available on 201 (96%) patients. Discordance between the ECG/mitral valve motion rhythm and the LAA PWD phenotype was noted in 15 (7.5%) patient with 7 (3.5%) demonstrating AF discordance (SR on ECG/MVM and AF phenotype on LAA PWD) and 8 (4.0%) demonstrated SR discordance (AF ECG/MVM and SR LAA PWD).
The AF discordance group had significantly higher prevalence of LAA SEC, larger LAA area, longer length, lower LAA ejection velocity, and higher CHADS2-VASc. LAA thrombus was noted in 6 patients, all of whom had AF concordance.
Prothrombotic AF phenotype persists in the majority of the paroxysmal AF patients despite SR on the surface ECG recording. The authors are advocating use of anticoagulation in AF phenotype patients independent of the surface ECG. I agree that assessment of LAA phenotype in all patients undergoing TEE is warranted, but I would take a step back and rethink their suggestion for use of anticoagulation. In the post CRYSTAL-AF era, left atrial appendage pulse wave Doppler phenotyping could help in better selection of the patients that would benefit from the anticoagulation, but this would need to be answered in the prospective randomized trial.
Little is known about what happen to Mexican Americans (MA’s) -the largest Hispanic population in the United States, after they suffer from stroke. Lisabeth et al. looked at a large database of patients specifically in one geographic region, that has a substantial population of Mexican Americans (South Texas).
Out of over 1,000 patients in the cohort, 720 had full interview and clinical data during post stroke recovery. The researchers learned that MAs had on average slightly higher NIHSS at 90 days (3, compared with non-Hispanic whites (NHW) with NIHSS of 2), more likely to have disability requiring assistance with activities of daily living, and worse cognitive outcomes. In general MA’s tended to be younger and lived longer than the NHW cohort.
This suggests that more work should be done to study these discrepancies and learn what types of interventions maybe most effective in prevention of strokes in a younger population, as well as better care in the post-stroke recovery phase to prevent long term morbidity.
Because the MAs tend to be younger, the impact on better stroke care could have a great social and economic impact, as these patients tend to live longer.
Unfortunately, likely for a multitude of reasons (not fully delineated in this study) but what I suspect to be a combination of lower social economic status, low health literacy, lower general literacy, MA’s maybe less likely to receive the full multi-disciplinary care needed for stroke patients, and even after receiving care, may have less long term impact on their disease condition.
Fortunately as the NINDS has made it a goal to focus on stroke disparities and more attention and further research efforts will expand to learn about the ethnic-social differences in stroke epidemiology.