Thrombolysis for Cerebral Ischemia

The care for patients with acute ischemic stroke has been revolutionized by the clinical application of fibrinolysis. Intravenous recombinant tissue plasminogen activator (rt-PA) has been proven to improve functional outcomes following acute ischemic stroke and can be administered to a select group of patients up to 4.5 h after symptom onset. Time from symptom onset to thrombolysis is the most important determinant of the success of treatment, with greatest efficacy if given within 90 min. Hospitals should implement standardized processes and protocols for acute stroke to guide immediate patient assessment, brain imaging, drug administration, and post-thrombolysis care. In this article we review the clinical application of thrombolysis, care of acute stroke patients, current evidence regarding fibrinolysis, and future direction of penumbral imaging to select candidates for reperfusion therapies

Clinical monitoring scales in acute brain injury: assessment of coma, pain, agitation, and delirium.

Serial clinical examination represents the most fundamental and basic form of neurological monitoring, and is often the first and only form of such monitoring in patients. Even in patients subjected to physiological monitoring using a range of technologies, the clinical examination remains an essential tool to follow neurological progress. Key aspects of the clinical examination have now been systematized into scoring schemes, and address consciousness, pain, agitation, and delirium (PAD). The Glasgow Coma Scale has been the traditional tool to measure consciousness, but the full outline of unresponsiveness (FOUR) score has recently been validated in a variety of settings, and at present, both represent clinically useful tools. Assessment of PAD in neurologically compromised patients present special challenges. For pain, the Numeric Rating Scale is the preferred initial approach, with either the Behavioral Pain Scale or the Critical Care Pain Observation Tool in subjects who are not able to respond. The Nociception Coma Scale-Revised may be useful in patients with severe disorders of consciousness. Conventional sedation scoring tools for critical care, such as the Richmond Area Sedation Scale (RASS) and Sedation-Agitation Scale (SAS) may provide reasonable tools in some neurocritical care patients. The use of sedative drugs and neuromuscular blockers may invalidate the use of some clinical examination tools in others. The use of sedation interruption to assess neurological status can result in physiological derangement in unstable patients (such as those with uncontrolled intracranial hypertension), and is not recommended

How often is occult atrial fibrillation in cryptogenic stroke causal vs. incidental? A meta-analysis

IntroductionLong-term cardiac monitoring studies have unveiled low-burden, occult atrial fibrillation (AF) in some patients with otherwise cryptogenic stroke (CS), but occult AF is also found in some individuals without a stroke history and in patients with stroke of a known cause (KS). Clinical management would be aided by estimates of how often occult AF in a patient with CS is causal vs. incidental.MethodsThrough a systematic search, we identified all case–control and cohort studies applying identical long-term monitoring techniques to both patients with CS and KS. We performed a random-effects meta-analysis across these studies to determine the best estimate of the differential frequency of occult AF in CS and KS among all patients and across age subgroups. We then applied Bayes' theorem to determine the probability that occult AF is causal or incidental.ResultsThe systematic search identified three case–control and cohort studies enrolling 560 patients (315 CS, 245 KS). Methods of long-term monitoring were implantable loop recorder in 31.0%, extended external monitoring in 67.9%, and both in 1.2%. Crude cumulative rates of AF detection were CS 47/315 (14.9%) vs. KS 23/246 (9.3%). In the formal meta-analysis, the summary odds ratio for occult AF in CS vs. KS in all patients was 1.80 (95% CI, 1.05–3.07), p = 0.03. With the application of Bayes' theorem, the corresponding probabilities indicated that, when present, occult AF in patients with CS is causal in 38.2% (95% CI, 0–63.6%) of patients. Analyses stratified by age suggested that detected occult AF in patients with CS was causal in 62.3% (95 CI, 0–87.1%) of patients under the age of 65 years and 28.5% (95 CI, 0–63.7%) of patients aged 65 years and older but estimates had limited precision.ConclusionCurrent evidence is preliminary, but it indicates that in cryptogenic stroke when occult AF is found, it is causal in about 38.2% of patients. These findings suggest that anticoagulation therapy may be beneficial to prevent recurrent stroke in a substantial proportion of patients with CS found to have occult AF

Clinical and Radiologic Correlations of Central Pontine Myelinolysis Syndrome

OBJECTIVE: To characterize clinical and radiologic features of patients with central pontine myelinolysis (CPM) and identify variables that predict outcome

Prediction of potential for organ donation after cardiac death in patients in neurocritical state: a prospective observational study

Background Successful donation of organs after cardiac death (DCD) requires identification of patients who will die within 60 mm of withdrawal of life-sustaining treatment (WLST). We aimed to validate a straightforward model to predict the likelihood of death within 60 min of WLST in patients with irreversible brain injury. Methods In this multicentre, observational study, we prospectively enrolled consecutive comatose patients with irreversible brain injury undergoing WLST at six medical centres in the USA and the Netherlands. We assessed four clinical characteristics (corneal reflex, cough reflex, best motor response, and oxygenation index) as predictor variables, which were selected on the basis of previous findings. We excluded patients who had brain death or were not intubated. The primary endpoint was death w Findings We included 178 patients, 82 (46%) of whom died within 60 mm of WLST. Absent corneal reflexes (odds ratio [OR] 2.67, 95% CI 1.19-6.01; p=0.0173; 1 point), absent cough reflex (4.16, 1.79-9.70; p=0.0009; 2 points), extensor or absent motor responses (2.99, 1.22-7.34; p=0.0168; 1 point), and an oxygenation index score of more than 3.0 (2.31, 1.10-4.88; p=0.0276; 1 point) were predictive of death within 60 mm of WLST. 59 of 82 patients who died within 60 min of WLST had DCD-N scores of 3 o Interpretation The DCD-N score can be used to predict potential candidates for DCD in patients with non-survivable brain injury. However, this score needs to be tested specifically in a cohort of potential donors participating in DCD protocols

Refining Angiographic Biomarkers of Revascularization

Background and purposeAngiographic revascularization grading after intra-arterial stroke therapy is limited by poor standardization, making it unclear which scale is optimal for predicting outcome. Using recently standardized criteria, we sought to compare the prognostic performance of 2 commonly used reperfusion scales.MethodsInclusion criteria for this multicenter retrospective study were acute ischemic stroke attributable to middle cerebral artery M1 occlusion, intra-arterial therapy, and 90-day modified Rankin scale score. Post-intra-arterial therapy reperfusion was graded using the Thrombolysis in Myocardial Infarction (TIMI) and Modified Thrombolysis in Cerebral Infarction (mTICI) scales. The scales were compared for prediction of clinical outcome using receiver-operating characteristic analysis.ResultsOf 308 patients, mean age was 65 years, and median National Institutes of Health Stroke Scale score was 17. The mean time from stroke onset to groin puncture was 305 minutes. There was no difference in the time to treatment between patients grouped by final TIMI (ie, 0 versus 1 versus 2 versus 3) or mTICI grades (ie, 0 versus 1 versus 2a versus 2b versus 3). Good outcome (modified Rankin scale, 0-2) was achieved in 32.5% of patients, and mortality rate was 25.3% at 90 days. There was a 6.3% rate of parenchymal hematoma type 2. In receiver-operating characteristic analysis, mTICI was superior to TIMI for predicting 90-day modified Rankin scale 0 to 2 (c-statistic: 0.74 versus 0.68; P<0.0001). The optimal threshold for identifying a good outcome was mTICI 2b to 3 (sensitivity 78.0%; specificity 66.1%).ConclusionsmTICI is superior to TIMI for predicting clinical outcome after intra-arterial therapy. mTICI 2b to 3 is the optimal biomarker for procedural success

Refining Angiographic Biomarkers of Revascularization

Background and purposeAngiographic revascularization grading after intra-arterial stroke therapy is limited by poor standardization, making it unclear which scale is optimal for predicting outcome. Using recently standardized criteria, we sought to compare the prognostic performance of 2 commonly used reperfusion scales.MethodsInclusion criteria for this multicenter retrospective study were acute ischemic stroke attributable to middle cerebral artery M1 occlusion, intra-arterial therapy, and 90-day modified Rankin scale score. Post-intra-arterial therapy reperfusion was graded using the Thrombolysis in Myocardial Infarction (TIMI) and Modified Thrombolysis in Cerebral Infarction (mTICI) scales. The scales were compared for prediction of clinical outcome using receiver-operating characteristic analysis.ResultsOf 308 patients, mean age was 65 years, and median National Institutes of Health Stroke Scale score was 17. The mean time from stroke onset to groin puncture was 305 minutes. There was no difference in the time to treatment between patients grouped by final TIMI (ie, 0 versus 1 versus 2 versus 3) or mTICI grades (ie, 0 versus 1 versus 2a versus 2b versus 3). Good outcome (modified Rankin scale, 0-2) was achieved in 32.5% of patients, and mortality rate was 25.3% at 90 days. There was a 6.3% rate of parenchymal hematoma type 2. In receiver-operating characteristic analysis, mTICI was superior to TIMI for predicting 90-day modified Rankin scale 0 to 2 (c-statistic: 0.74 versus 0.68; P<0.0001). The optimal threshold for identifying a good outcome was mTICI 2b to 3 (sensitivity 78.0%; specificity 66.1%).ConclusionsmTICI is superior to TIMI for predicting clinical outcome after intra-arterial therapy. mTICI 2b to 3 is the optimal biomarker for procedural success

Toward a positive aging phenotype for older women: observations from the women's health initiative.

BackgroundTo develop a positive aging phenotype, we undertook analyses to describe multiple dimensions of positive aging and their relationships to one another in women 65 years of age and older and evaluate the performance of individual indicators and composite factors of this phenotype as predictors of time to death, years of healthy living, and years of independent living.MethodsData from Women's Health Initiative clinical trial and observational study participants ages 65 years and older at baseline, including follow-up observations up to 8 years later, were analyzed using descriptive statistics and principal components analysis to identify the factor structure of a positive aging phenotype. The factors were used to predict time to death, years of healthy living (without hospitalization or diagnosis of a serious health condition), and years of independent living (without nursing home admission or use of special services).ResultsWe identified a multidimensional phenotype of positive aging that included two factors: Physical-Social Functioning and Emotional Functioning. Both factors were predictive of each of the outcomes, but Physical-Social Functioning was the strongest predictor. Each standard deviation of increase in Physical-Social Functioning was accompanied by a 23.7% reduction in mortality risk, a 19.4% reduction in risk of major health conditions or hospitalizations, and a 26.3% reduction in risk of dependent living.ConclusionsPhysical-Social Functioning and Emotional Functioning constitute important components of a positive aging phenotype. Physical-Social Functioning was the strongest predictor of outcomes related to positive aging, including years of healthy living, years of independent living, and time to mortality