Faculty Bibliography

Background and Purpose/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED:= .06). Conclusion/UNASSIGNED: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.

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.

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.

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.

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.

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".

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.

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.

BACKGROUND AND PURPOSE/OBJECTIVE: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<pO<0.56). CONCLUSIONS:This pilot survey provides the first quantitative evidence that National Institutes of Health Stroke Scale score is not the only determinant of treatment decision. A National Institutes of Health Stroke Scale score of 2 is the potential equipoise point, with the least consensus on treatment decision. These preliminary findings require validation in larger population surveys.