Sex-Related Differences in Utilization and Outcomes of Extracorporeal Cardio-Pulmonary Resuscitation for Refractory Cardiac Arrest.

Sparse data exist on sex-related differences in extracorporeal cardiopulmonary resuscitation (ECPR) for refractory cardiac arrest (rCA). We explored the role of sex on the utilization and outcomes of ECPR for rCA by retrospective analysis of the Extracorporeal Life Support Organization (ELSO) International Registry. The primary outcome was in-hospital mortality. Exploratory outcomes were discharge disposition and occurrence of any specific extracorporeal membrane oxygenation (ECMO) complications. From 1992 to 2020, a total of 7,460 adults with ECPR were identified: 30.5% women; 69.5% men; 55.9% Whites, 23.7% Asians, 8.9% Blacks, and 3.8% Hispanics. Women's age was 50.4 ± 16.9 years (mean ± standard deviation) and men's 54.7 ± 14.1 (p < 0.001). Ischemic heart disease occurred in 14.6% women vs. 18.5% men (p < 0.001). Overall, 28.5% survived at discharge, 30% women vs. 27.8% men (p = 0.138). In the adjusted analysis, sex was not associated with in-hospital mortality (odds ratio [OR] = 0.93 [confidence interval {CI} = 0.80-1.08]; p = 0.374). Female sex was associated with decreased odds of neurologic, cardiovascular, and renal complications. Despite being younger and having fewer complications during ECMO, women had in-hospital mortality similar to men. Whether these findings are driven by biologic factors or disparities in health care warrants further investigation.

User-Centered Mobile Applications for Stroke Survivors (MAPPS): A Mixed-Methods Study of Patient Preferences.

OBJECTIVE: Investigate stroke survivors' (SS) preferences for a hypothetical mHealth app for post-stroke care and to study the influence of demographic variables on these preferences. DESIGN: Mixed-methods, sequential, observational study. SETTING: Focus groups (phase 1) were conducted to identify SS perceptions and knowledge of mHealth applications (apps). Using grounded theory approach, recurring themes were identified. A multiple-choice questionnaire of 5 desired app features was generated using these themes and mailed to SS (national survey, phase 2). SS' demographics and perceived usefulness (yes/no) for each feature were recorded. In-person usability testing (phase 3) was conducted to identify areas of improvement in user interfaces of existing apps. Summative telephone interviews (phase 4) were conducted for final impressions supplementary to national survey. PARTICIPANTS: SS aged >18 years recruited from study hospital, national stroke association database, stroke support and advocacy groups. Non-English speakers and those unable to communicate were excluded. INTERVENTIONS: None. MAIN OUTCOME MEASURES: (1) Percentage of SS (phase 2) identifying proposed app features to be useful. (2) Influence of age, sex, race, education, and time since stroke on perceived usefulness. RESULTS: Ninety-six SS participated in focus groups. High cost, complexity, and lack of technical support were identified as barriers to adoption of mHealth apps. In the national survey (n=1194), ability to track fitness and diet (84%) and communication (70%) were the most and least useful features, respectively. Perceived usefulness was higher among younger SS (P<.001 to .006) and SS of color (African American and Hispanic) (ORs 1.73-4.41). Simple design and accommodation for neurologic deficits were main recommendations from usability testing. CONCLUSIONS: SS are willing to adopt mHealth apps that are free of cost and provide technical support. Apps for SS should perform multiple tasks and be of simple design. Greater interest for the app's features among SS of color may provide opportunities to address health inequities.

Neurologic Improvement in Acute Cerebral Ischemia: Frequency, Magnitude, Predictors, and Clinical Outcomes.

BACKGROUND AND OBJECTIVES: Investigations of rapid neurologic improvement (RNI) in patients with acute cerebral ischemia (ACI) have focused on RNI occurring after hospital arrival. However, with stroke routing decisions and interventions increasingly migrating to the prehospital setting, there is a need to delineate the frequency, magnitude, predictors, and clinical outcomes of patients with ACI with ultra-early RNI (U-RNI) in the prehospital and early postarrival period. METHODS: We analyzed prospectively collected data of the prehospital Field Administration of Stroke Therapy-Magnesium (FAST-MAG) randomized clinical trial. Any U-RNI was defined as improvement by 2 or more points on the Los Angeles Motor Scale (LAMS) score between the prehospital and early post-emergency department (ED) arrival examinations and classified as moderate (2-3 point) or dramatic (4-5 point) improvement. Outcome measures included excellent recovery (modified Rankin Scale [mRS] score 0-1) and death by 90 days. RESULTS: Among the 1,245 patients with ACI, the mean age was 70.9 years (SD 13.2); 45% were women; the median prehospital LAMS was 4 (interquartile range [IQR] 3-5); the median last known well to ED-LAMS time was 59 minutes (IQR 46-80 minutes), and the median prehospital LAMS to ED-LAMS time was 33 minutes (IQR 28-39 minutes). Overall, any U-RNI occurred in 31%, moderate U-RNI in 23%, and dramatic U-RNI in 8%. Any U-RNI was associated with improved outcomes, including excellent recovery (mRS score 0-1) at 90 days 65.1% (246/378) vs 35.4% (302/852), p < 0.0001; decreased mortality by 90 days 3.7% (14/378) vs 16.4% (140/852), p < 0.0001; decreased symptomatic intracranial hemorrhage 1.6% (6/384) vs 4.6% (40/861), p = 0.0112; and increased likelihood of being discharged home 56.8% (218/384) vs 30.2% (260/861), p < 0.0001. DISCUSSION: U-RNI occurs in nearly 1 in 3 ambulance-transported patients with ACI and is associated with excellent recovery and decreased mortality at 90 days. Accounting for U-RNI may be useful for routing decisions and future prehospital interventions. TRIAL REGISTRATION INFORMATION: clinicaltrials.gov. Unique identifier: NCT00059332.

Duration of Hyperoxia and Neurologic Outcomes in Patients Undergoing Extracorporeal Membrane Oxygenation.

OBJECTIVES: To evaluate the impact of duration of hyperoxia on neurologic outcome and mortality in patients undergoing venoarterial extracorporeal membrane oxygenation. DESIGN: A retrospective analysis of venoarterial extracorporeal membrane oxygenation patients admitted to the Johns Hopkins Hospital. The primary outcome was neurologic function at discharge defined by modified Rankin Scale, with a score of 0-3 defined as a good neurologic outcome, and a score of 4-6 defined as a poor neurologic outcome. Multivariable logistic regression analysis was performed to evaluate the association between hyperoxia and neurologic outcomes. SETTING: The Johns Hopkins Hospital Cardiovascular ICU and Cardiac Critical Care Unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured first and maximum Pao2 values, area under the curve per minute over the first 24 hours, and duration of mild, moderate, and severe hyperoxia. Of 132 patients on venoarterial extracorporeal membrane oxygenation, 127 (96.5%) were exposed to mild hyperoxia in the first 24 hours. Poor neurologic outcomes were observed in 105 patients (79.6%) (102 with vs 3 without hyperoxia; p = 0.14). Patients with poor neurologic outcomes had longer exposure to mild (19.1 vs 15.2 hr; p = 0.01), moderate (14.6 vs 9.2 hr; p = 0.003), and severe hyperoxia (9.1 vs 4.0 hr; p = 0.003). In a multivariable analysis, patients with worse neurologic outcome experienced longer durations of mild (adjusted odds ratio, 1.10; 95% CI, 1.01-1.19; p = 0.02), moderate (adjusted odds ratio, 1.12; 95% CI, 1.04-1.22; p = 0.002), and severe (adjusted odds ratio, 1.19; 95% CI, 1.06-1.35; p = 0.003) hyperoxia. Additionally, duration of severe hyperoxia was independently associated with inhospital mortality (adjusted odds ratio, 1.18; 95% CI, 1.08-1.29; p < 0.001). CONCLUSIONS: In patients undergoing venoarterial extracorporeal membrane oxygenation, duration and severity of early hyperoxia were independently associated with poor neurologic outcomes at discharge and mortality.

Exploring the Collateral Damage of the COVID-19 Pandemic on Stroke Care: A Statewide Analysis.

[Figure: see text].

A New Transcranial Doppler Scoring System for Evaluating Middle Cerebral Artery Stenosis.

BACKGROUND AND PURPOSE: Transcranial Doppler (TCD) criteria for cerebrovascular stenosis are only based on velocity with unsatisfactory positive predictive value (PPV) in previous studies. We refined a published scoring system that integrates several characteristics of TCD data in diagnosing middle cerebral artery (MCA) stenosis. METHODS: Using the TCD-digital subtraction angiography (DSA) database from Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) trial, velocity, spectrum pattern, diffuse ratio, and asymmetry ratio were assessed. The cutpoints were defined for each parameter and a point value was assigned to each category within that parameter. A summed score was calculated for each MCA. The accuracy was assessed for different cutpoints in predicting ≥50% MCA stenosis measured by DSA. Logistic regression and C-statistics were used for analysis. RESULTS: A total of 114 MCAs were included in vessel-based and 87 patients were included in patient-based analysis. Compared to the velocity-only cutpoints in SONIA, the score results in much improved PPV while negative predictive value (NPV) remains unchanged. The score based on mean velocity (score 0: <140 cm/s, score 3: ≥140 cm/s), spectrum pattern (score 0: no turbulence; score 1: mild turbulence; 2: significant turbulence), and asymmetry ratio (score 0: ratio <1.5, score 1: ratio 1.5-2; score 2: ratio ≥2.1) has the highest NPV while PPV remains favorable (PPV: 72% [95% CI 54-90%]; NPV: 84% [95% CI: 75-93%], area under curve [AUC]: .76 [95% CI: .66-.86]). CONCLUSIONS: The multiparameter scoring system incorporating several characteristics of TCD measures yielded higher PPV while maintaining high NPV compared with the single-parameter velocity criteria in diagnosing MCA ≥50% stenosis.

Medical Mobile Applications for Stroke Survivors and Caregivers.

BACKGROUND: Recent studies estimate nearly half of the US population can access mobile medical applications (apps) on their smartphones. The are no systematic data available on apps focused on stroke survivors/caregivers. OBJECTIVE: To identify apps (a) designed for stroke survivors/caregivers, (b) dealing with a modifiable stroke risk factor (SRF), or (c) were developed for other purposes but could potentially be used by stroke survivors/caregivers. METHODS: A systematic review of the medical apps in the US Apple iTunes store was conducted between August 2013 and January 2016 using 18 predefined inclusion/exclusion criteria. SRFs considered were: diabetes, hypertension, smoking, obesity, atrial fibrillation, and dyslipidemia. RESULTS: Out of 30,132 medical apps available, 843 (2.7%) eligible apps were identified. Of these apps, (n = 74, 8.7%) apps were specifically designed for stroke survivors/caregivers use and provided the following services: language/speech therapy (n = 28, 37%), communication with aphasic patients (n = 19, 25%), stroke risk calculation (n = 11, 14%), assistance in spotting an acute stroke (n = 8, 10%), detection of atrial fibrillation (n = 3, 4%), direction to nearby emergency room (n = 3, 4%), physical rehabilitation (n = 3, 4%), direction to the nearest certified stroke center (n = 1, < 2%), and visual attention therapy (n = 1, <2%). 769 apps identified that were developed for purposes other than stroke. Of these, the majority (n = 526, 68%) addressed SRFs. CONCLUSIONS: Over 70 medical apps exist to specifically support stroke survivors/caregivers and primarily targeted language and communication difficulties. Apps encompassing most stroke survivor/caregiver needs could be developed and tested to ensure the issues faced by these populations are being adequately addressed.

Does the Magnitude of the Electrocardiogram QT Interval Dispersion Predict Stroke Outcome?

BACKGROUND: QT dispersion, maximal interlead difference in QT interval on 12-lead electrocardiogram (ECG), measures cardiac repolarization abnormalities. Data are conflicting whether QT dispersion predicts adverse outcome in acute ischemic stroke (AIS) patients. Our objective is to determine if QT dispersion predicts: (1) short-term clinical outcome in AIS, and (2) stroke location (insular versus noninsular cortex). METHODS: Admission ECGs from 412 consecutive patients with acute stroke symptoms from 2 university-based stroke centers were reviewed. QT dispersion was measured. A neuroradiologist reviewed brain imaging for insular cortex involvement. Favorable clinical outcomes at discharge were modified Rankin Scale (mRS) score of 0-1, discharge National Institutes of Health Stroke Scale (NIHSS) score less than 2, and discharge to home. Multiple logistic regressions were performed for each outcome measure and to determine the association between insular infarct and QT dispersion. RESULTS: Of 145 subjects in the final analysis, median age was 65 years (interquartile range [IQR] 56-75), male patients were 38%, black patients were 68%, median QT dispersion was 78 milliseconds (IQR 59-98), and median admission NIHSS score was 4 (IQR 2-6). QT dispersion did not predict short-term clinical outcome for mRS score (odds ratio [OR] = 1.001, 95% confidence interval [CI] .99-1.01, P = .85), NIHSS at discharge (OR = .994, 95% CI .98-1.01, P = .30), or discharge disposition (OR = 1.001, 95% CI .99-1.01, P = .81). Insular cortex involvement did not correlate with QT dispersion magnitude (OR = 1.009, 95% CI .99-1.02, P = .45). CONCLUSIONS: We could not demonstrate that QT dispersion is useful in predicting short-term clinical outcome at discharge in AIS. Further, the magnitude of QT dispersion did not predict insular cortical stroke location.

Ischemic Stroke Predictors in Patients Presenting with Dizziness, Imbalance, and Vertigo.

OBJECTS: To identify predictors of acute ischemic stroke (AIS) among patients presenting to the Emergency Department (ED) with dizziness, imbalance, or vertigo (DIV) based on demographic and clinical characteristics. METHODS: We identified patients admitted to the hospital after presenting to the ED with DIV from the Statewide Planning and Research Cooperative System database of New York from 2010 to 2014. Demographic and clinical characteristics were systematically collected. Multivariable logistic regression was used to determine predictors of a discharge diagnosis of AIS. RESULTS: Among 77,993 patients with DIV, 3857 (4.9%) had a discharge diagnosis of AIS. Admission presentation of imbalance, African-American race, history of hypertension, diabetes mellitus, hypercholesterolemia, tobacco use, atrial fibrillation, and prior AIS due to extracranial artery atherosclerosis were each positively associated with an AIS diagnosis independently. Factors negatively associated with an AIS discharge diagnosis included: admission presentation of vertigo, female sex, age > 81, history of anemia, coronary artery disease, asthma, depressive disorders, and anxiety disorders. CONCLUSIONS: Multiple potential positive and negative predictive AIS risk factors were identified. Combining with currently available centrally-caused dizziness prediction tools, these newly identified factors could provide more accurate AIS risk stratifying method for DIV patients.

To Treat or Not to Treat?

Background and Purpose- The 2015 updated US Food and Drug Administration alteplase package insert altered several contraindications. We thus explored clinical factors influencing alteplase treatment decisions for patients with minor stroke. Methods- An expert panel selected 7 factors to build a series of survey vignettes: National Institutes of Health Stroke Scale (NIHSS), NIHSS area of primary deficit, baseline functional status, previous ischemic stroke, previous intracerebral hemorrhage, recent anticoagulation, and temporal pattern of symptoms in first hour of care. We used a fractional factorial design (150 vignettes) to provide unconfounded estimates of the effect of all 7 main factors, plus first-order interactions for NIHSS. Surveys were emailed to national organizations of neurologists, emergency physicians, and colleagues. Physicians were randomized to 1 of 10 sets of 15 vignettes, presented randomly. Physicians reported the subjective likelihood of giving alteplase on a 0 to 5 scale; scale categories were anchored to 6 probabilities from 0% to 100%. A conjoint statistical analysis was applied. Results- Responses from 194 US physicians yielded 156 with complete vignette data: 74% male, mean age 46, 80% neurologists. Treatment mean probabilities for individual vignettes ranged from 6% to 95%. Treatment probability increased from 24% for NIHSS score =1 to 41% for NIHSS score =5. The conjoint model accounted for 25% of total observed response variance. In contrast, a model accounting for all possible interactions accounted for 30% variance. Four of the 7 factors accounted jointly for 58% of total relative importance within the conjoint model: previous intracerebral hemorrhage (18%), recent anticoagulation (17%), NIHSS (13%), and previous ischemic stroke (10%). Conclusions- Four main variables jointly account for only a small fraction (<15%) of the total variance related to deciding to treat with intravenous alteplase, reflecting high variability and complexity. Future studies should consider other variables, including physician characteristics.

Transatlantic Differences in Management of Carotid Stenosis: BRIDGing the Gap in StrokE Management (BRIDGE) Project.

BACKGROUND AND PURPOSE: Management of carotid stenosis remains controversial despite several trials evaluating carotid endarterectomy (CEA) and carotid angioplasty/stenting (CAS). We compared attitudes in the management of carotid stenosis between selected experts within Europe and North America. METHODS: A 3-phase Delphi survey was e-mailed to select stroke experts from Europe (n = 390) and North America (n = 289). Those completing the initial survey were shown all responses after each survey round. Consensus was defined as ≥80% agreement. RESULTS: For phases 1, 2, and 3, response rates were 32%, 62%, and 73%, respectively. Overall, 100 (15%) of 679 participated in all 3 phases, 19% Europeans versus 9% North Americans (P = .0007). The European group reached consensus in 6 of 15 statements; The North American group reached consensus in 4 of 15. Ninety percentage of Europeans versus 70% of North Americans (P = .017) stated CEA is superior to CAS for symptomatic carotid stenosis. This difference was not significant in the final model (adjusted odds ratio: 3.72 [95% confidence interval: 0.95-14.5]). Sixty-nine percentage of North Americans agreed there is a stronger indication for CAS over CEA in patients younger than 65 years for symptomatic carotid stenosis, whereas 55% of Europeans (P = .023) disagreed. For asymptomatic carotid stenosis, when asked how likely they would recommend CAS, 62% North Americans said "sometimes" versus 60% of Europeans said "never" (P = .06). CONCLUSION: The majority of North American and European respondents did not consider the 2 procedures equivalent and seemed to indicate that CEA was preferred for the management of carotid stenosis. These findings need to be further explored to help establish evidence-based guidelines.

From head to toe: Sex and gender differences in the treatment of ischemic cerebral disease.

Stroke is a major cause of mortality and morbidity, particularly in the older ages. Women have a longer life expectancy and are more likely to experience stroke than men. Interestingly, the increased risk of ischemic stroke in women seems to be independent from age or classical cardiovascular risk factors. Notwithstanding the fact that stroke outcomes and survival are usually poorer in women, current evidence suggests that thrombolysis, antiplatelet and anticoagulant therapies are more beneficial in women than in men. A possible explanation of this paradox might be that females are often undertreated and they have fewer chances to be submitted to an effective and timely treatment for stroke than the male counterpart. The first step in the attempt to solve this obvious discrimination is surely to emphasize any reasons for differences in the therapeutic approach in relation to gender and then to denounce the lack of a sustainable motivation for them. In this article, we aimed to review the existing literature about gender-related differences on efficacy, administration and side effects of the most common drugs used for the treatment of ischemic stroke. The most striking result was the evidence that the therapeutic approach for stroke is often different according to patients' gender with a clear detrimental prognostic effect for women. A major effort is necessary to overcome this problem in order to ensure equal right to treatment without any sexual discrimination.

Stroke and Etonogestrel/Ethinyl Estradiol Ring (NuvaRing): Clinical, Radiological, and Prognostic Features.

BACKGROUND: A recent study found that NuvaRing (a vaginal contraceptive ring containing 15 µg ethinyl estradiol and 120 µg etonogestrel) has 2.5 times increased relative risk of thrombotic stroke compared to nonuse. OBJECTIVE: We studied a case series of 19 such patients as well as prior published case reports to clarify clinical, radiological, and prognostic features. METHODS: Medical records and imaging for 18 cases were initially systematically reviewed for consultation in a class action lawsuit. One case was seen personally outside of litigation. All 19 cases were entered into a database detailing clinical, radiological, and prognostic features as well as other potential risk factors. A literature search identified 8 additional cases. RESULTS: Average age at stroke was 31.7 ± 9.8 years; average duration of NuvaRing use prior to stroke was 11.2 months. Arterial stroke occurred in 10 of 19 (52%); 1 of 10 (10%) was hemorrhagic. Venous sinus thrombosis was present in 11 of 19 (58%) on initial imaging; 6 of 11 (54%) were hemorrhagic. The most common presenting symptom was headache (7 of 19 [37%]) and motor weakness (7 of 19 [37%]). A hypercoagulable condition was present in 3 of 19 (16%); 3 of 19 (16%) had history of hypercoagulable disease in a first-degree relative. Mortality was .5%; 8 of 19 (42%) fully recovered and 3 of 19 (15%) were discharged to rehabilitation. CONCLUSIONS: In this largest case series of NuvaRing-associated stroke to date, approximately half of the strokes are venous and half are arterial. Stroke typically occurred within the first year of use, and as soon as 2 weeks after NuvaRing initiation.

First translational 'Think Tank' on cerebrovascular disease, cognitive impairment and dementia.

As the human population continues to age, an increasing number of people will exhibit significant deficits in cognitive function and dementia. It is now recognized that cerebrovascular, metabolic and neurodegenerative diseases all play major roles in the evolution of cognitive impairment and dementia. Thus with our more recent recognition of these relationships and our need to understand and more positively impact on this world health problem, "The Leo and Anne Albert Charitable Trust" (Gene Pranzo, Trustee with significant support from Susan Brogan, Meeting Planner) provided generous support for this inaugural international workshop that was held from April 13-16, 2015 at the beautiful Ritz Carlton Golf Resort in North Naples, Florida. Researchers from SUNY Downstate Medical Center, Brooklyn, NY organized the event by selecting the present group of translationally inclined preclinical, clinical and population scientists focused on cerebrovascular disease (CVD) risk and its progression to vascular cognitive impairment (VCI) and dementia. Participants at the workshop addressed important issues related to aging, cognition and dementia by: (1) sharing new data, information and perspectives that intersect vascular, metabolic and neurodegenerative diseases, (2) discussing gaps in translating population risk, clinical and preclinical information to the progression of cognitive loss, and (3) debating new approaches and methods to fill these gaps that can translate into future therapeutic interventions. Participants agreed on topics for group discussion prior to the meeting and focused on specific translational goals that included promoting better understanding of dementia mechanisms, the identification of potential therapeutic targets for intervention, and discussed/debated the potential utility of diagnostic/prognostic markers. Below summarizes the new data-presentations, concepts, novel directions and specific discussion topics addressed by this international translational team at our "First Leo and Anne Albert Charitable Trust 'Think Tank' VCI workshop".

Acute Ischemic Stroke with Very Early Clinical Improvement: A National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Trials Exploratory Analysis.

BACKGROUND: A high proportion of patients excluded from recombinant tissue plasminogen activator (rt-PA) treatment because of rapid improvement occurring before treatment decision had incomplete recovery. The National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Trials dataset allows for systematic analyses of very early postrandomization improvement (VEPRIM) in stroke severity as a National Institutes of Health Stroke Scale (NIHSS) score was available for all subjects enrolled in the study at baseline (NIHSSB) and at 2 hours after randomization (NIHSS2H). We explored various definitions of VEPRIM to characterize predictive values for clinical outcomes. METHODS: Post hoc analyses of the NINDS rt-PA Stroke Trials were conducted. VEPRIM was defined as the difference between the NIHSSB and the NIHSS2H scores using 3 approaches: raw, percent, and normalized change. We assessed the association between VEPRIM and 3-month favorable outcome (mRS score of 0-1), symptomatic intracerebral hemorrhage (sICH), and death. RESULTS: In the 624 subjects, every VEPRIM definition was independently associated with an increased probability of favorable outcome: for each unit of change within the VEPRIM definitions, there were 2%-24% (all P < .05) relative increased probability of favorable outcome, 2%-15% (all P < .05) decreased likelihood of death, and 2%-13% (all P < .05) decreased likelihood of sICH. Adjusting for NIHSSB and prestroke mRS scores, there was a significant rt-PA treatment effect for improvement seen for all 3 VEPRIM definitions. CONCLUSIONS: VEPRIM predicted favorable outcomes independent of definition and treatment arm. Patients with VEPRIM by any definition, while doing better than patients without VEPRIM, also derived increased clinical benefit when treated with rt-PA compared to placebo. Even with VEPRIM, a substantial percentage of patients had unfavorable outcomes.

Thresholds of impaired cerebral hemodynamics that predict short-term cognitive decline in asymptomatic carotid stenosis.

Subjects with asymptomatic carotid stenosis (ACS) may be at risk of cognitive impairment due to cerebral hypoperfusion. In this study, we aimed to detect a threshold of cerebral hemodynamics which is able to identify subjects at risk of cognitive deterioration. In subjects with ACS, cerebral vasomotor reactivity (CVR) was assessed with the breath-holding index (BHI) transcranial Doppler-based method. Cognitive deterioration was defined as a decrease in the MMSE score by ≥2 points after one year. In order to define the threshold of impaired BHI, a ROC curve analysis was performed adopting the binary difference of MMSE score as the outcome and continuous BHI as the testing variable. A total of 548 subjects completed the follow-up. Cognitive deterioration was observed in 119 patients (21.7%). The BHI value ipsilateral to the stenosis was the strongest predictor of cognitive deterioration among the variables tested. The best cut-point to discriminate between normal and abnormal BHI resulted ≤0.89. The post-test probability of cognitive deterioration for an abnormal BHI was 44%, while a normal BHI showed a post-test probability of 9% for the same outcome. The present investigation provides a threshold of reduced CVR that can be useful to identify subjects with ACS at risk of cognitive deterioration.

Expansion of Intravenous Tissue Plasminogen Activator Eligibility Beyond National Institute of Neurological Disorders and Stroke and European Cooperative Acute Stroke Study III Criteria.

Intravenous tPA is the standard treatment for acute ischemic stroke. Multiple contraindications for thrombolysis developed during the design of the clinical trials may be overly cautious and limit the number of patients who may be eligible and potentially benefit from treatment. As clinicians have become more comfortable with off-label use of tPA, new data on the safety of thrombolysis have become available and shaped the current guidelines. This article updates our knowledge on the evidence available for these contraindications to help guide the clinician in choosing the optimal approach to some of the most commonly encountered clinical scenarios.

Rapidly improving stroke symptoms: a pilot, prospective study.

BACKGROUND: Rapidly improving stroke symptoms (RISSs) are a controversial exclusion for intravenous recombinant tissue plasminogen activator (rt-PA) for acute ischemic stroke (AIS). We estimated the frequency of 4 prespecified RISS definitions and explored their relationship to clinical outcome. METHODS: Pilot, prospective study of AIS patients admitted within 4.5 hours of symptom onset. Serial assessments using National Institute of Health Stroke Scale (NIHSS) were performed every 20 ± 5 minutes until a rt-PA treatment decision was made, independent of the study. Improvement was calculated as the difference between baseline NIHSS and treatment decision NIHSS. RISS was defined as a 4-point or greater improvement, 25% or greater, 50% or greater, and according to the previously reported TREAT (The Re-examining Acute Eligibility for Thrombolysis) criteria. Unfavorable outcome was defined as modified Rankin Scale score more than 1 at 90 days after stroke. Logistic regression determined if RISS definition(s) related to the outcome. RESULTS: Fifty patients with AIS were enrolled: mean age 65 years; median baseline NIHSS score 5 (interquartile range, 2-11). RISS frequencies were 10%-22% based on definition. Median treatment decision NIHSS score is 5 (interquartile range, 2-9). Twenty-three (46%) patients received rt-PA. None of the 3 non-TREAT RISS definitions was independently associated with the outcome. Five of fifty (10%) were RISS according to the TREAT criteria, all 5 had good outcome without rt-PA. CONCLUSIONS: A Serial NIHSS assessment before treatment decision is feasible and may help determine the frequency and magnitude of RISS. This is the first prospective estimate of RISS frequency and outcome according to various prespecified definitions. The TREAT RISS frequency as a more restrictive definition may better predict good outcome of RISS in future, larger studies.

To treat or not to treat? Pilot survey for minor and rapidly improving stroke.

BACKGROUND AND PURPOSE: Minor strokes and rapidly improving stroke symptoms are frequent exclusions for intravenous tissue-type plasminogen activator. We explored factors influencing tissue-type plasminogen activator treatment decision for minor strokes/rapidly improving stroke symptoms. METHODS: A pilot survey, including 110 case scenarios, was completed by 17 clinicians from 2 academic medical centers. Respondents were asked whether they would treat each case with tissue-type plasminogen activator at 60 minutes after emergency department admission. Cases varied by (1) National Institutes of Health Stroke Scale score at treatment decision time, (2) symptom pattern over time (improvement or worsening and then improving), (3) type of neurological deficit (3 main domains: motor, visual/sensory/ataxia, and language/neglect), and (4) age/occupation (4 profiles). Logistic regression was used to predict probability of omission (pO). A binomial regression model was used to predict probability of treatment decision. RESULTS: Predicted probability of treatment decision was affected by National Institutes of Health Stroke Scale score (P<0.001) and age/occupation profiles (P<0.001) but not by symptom patterns (P=0.334). There were significant, albeit modest, main effects on probability of treatment decision for neurological domains. Responses were most likely omitted (P=0.027) for cases improvement pattern and language/neglect domain (pO=0.74; 95% confidence interval, 0.52-0.89) and with visual/sensory/ataxia domain (pO=0.74; confidence interval, 0.37-0.93) when compared with improvement pattern and motor domain (pO=0.17; confidence interval, 0.06-0.42) and to any worsening and then improving patterns (0.37