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Peer review is an essential component of the scientific process. It is imperfect, to be sure, but there is widespread agreement that it is the best way to ensure that reliable scientific information is published.1–4 Being a reviewer is only 1 component of the process of publication. If you are an author or want to be an author, you have a duty to take part in reviewing your colleagues’ papers, just as your colleagues have reviewed your papers. Reviewing papers is a helpful part of learning the technical art of medical writing because you see and learn by example, both good and bad. Although it is a volunteer duty, there is a skill in providing a useful review and mentorship and experience matter in how you provide your review. Herein, I provide some steps on how to review papers for Stroke , specifically focussing on clinical papers. At many journals, including Stroke , there are a group of associate editors who handle papers through the review and publication process. These people are typically your senior peers and are also volunteers. Your job and duty as a reviewer is that you are advisory to them. The associate editors look at each paper as it comes in, and they may reject a paper outright or provide comments back to the author group for revision even before a paper is sent for peer review. In sending a paper to you as a reviewer, the associate editors seek your advice on quality, content, and context. Comments that you make to the editors directly are confidential and often helpful to them to interpret the context of a given paper. Read the title and abstract of the paper and decide whether you have the relevant expertise and interest to provide a review. If …

Introduction: No study has systematically examined stroke survivors’ challenges with fatigue. We use the Adaptive Leadership Framework for Chronic Illness (ALFCI) to synthesize what survivors’ challenges are with fatigue and how they respond or collaborate with others to achieve poststroke fatigue adaptation. Methods: We searched PubMed, CINAHL, Embase, and PsycInfo using PRISMA-ScR guidelines, gathering studies between 2012 and 2020. Qualitative studies or qualitative findings in mixed-method studies were included if they described stroke survivors’ (cerebral infarction, TIA, and brain hemorrhage) experiences with fatigue and/or care partners’ experiences to help survivors adapt to fatigue. We excluded studies which were not full-text English and did not report empirical data (e.g., literature review or editorial). We used interpretive synthesis to analyze the published qualitative data. Results: Of 714 papers identified, we retained 25 papers (22 qualitative and 3 mixed-method studies). Using ALFCI to synthesize data, we found that survivors with fatigue had many types of adaptive challenges. Fatigue made them less productive and it affected their cognitive, language, and physical functions, as well as sleeping patterns and social activities. To respond to these challenges, survivors did adaptive work such as changing mindset, using energy-conservation strategies, restructuring routines, and exercising. Care partners, health professionals, and others showed leadership by helping survivors adapt to fatigue by giving information about fatigue, assessing survivors’ fatigue levels, reducing survivors’ workload, and collaboratively negotiating for new daily routines. However, some studies indicated survivors needed fatigue education from professionals. No study interviewed care partners to examine their experiences helping survivors adapt to fatigue. Conclusions: Survivors had many types of challenges and responses towards fatigue. Care partners and others showed leadership by facilitating survivors with fatigue adaptation. Future studies can identify targets for interventions to address poor adaptation to fatigue and also explore care partners’ perspectives.

Introduction: We have recently reported the pilot use of a smartphone platform for electronic informed consenting (e-Consent) in acute stroke trials. We here report the feedback provided by legal authorized representatives (LAR) after consenting for a large vessel occlusion acute ischemic stroke (LVOS) randomized clinical trial. Methods: This is a single-center prospective study investigating the criticism of LAR after the use of e-Consent for a clinical trial of neuroprotectant in LVOS within 12 hours of last normal. REDCap (Research Electronic Data Capture) is a secure, Health Insurance Portability and Accountability Act compliant, web-based platform designed for research data capture that was used to create a survey project located on a static URL that can be remotely accessed (via smartphone browser). Regardless of the geographical position of the LAR, a standard link to the URL was sent via text message to the LAR and signed. A structured survey was applied to each LAR at least 12 hours after enrollment. Results: From February-August 2018, 33 patients were enrolled in the trial. Four LARs were unavailable, 3 expired before the questionnaire could be applied, and 1 refused to participate, leaving 25 patients for the primary analysis. Mean LAR age was 49±13 years, 68% were female, 44% black/48% white, 44% had high-school education or less. All LARs reported e-Consent to be “clear”. Eighty percent felt “ very confortable” in signing an e-Consent, 16% “somewhat” and 4% “not comfortable at all”. Four (16%) LARs would prefer paper consent. The overall experience was “excellent” in 64%, “good” in 28%, and “poor” in 8%. Seventy-two percent of surveys were done via phone and 28% in person. The patient’s median baseline and discharge NIHSS was 17[IQR 12-22] and 2[1-7], and 60% had discharge modified Rankin Scale 0-2. Male gender (75% vs 6%;p=0.04) and education level less than college (100% vs 0%);p=0.03 were associated with preference of paper over e-consent, while baseline and discharge NIHSS were not. Conclusion: e-Consent was overall very well perceived by LAR in a randomized clinical trial of LVOS. A small percentage of LAR, who were more commonly male and formally less educated, preferred paper consent.

Functional measures are recommended as primary outcome within clinical stroke trials but there is substantial heterogeneity in the assessments used. There may be a similar lack of consistency to outcome assessment in preclinical studies. Our aim was to collate studies using animal models of stroke and vascular cognitive impairment (VCI) and describe the functional assessment measures used. A focused literature search was conducted across 14 chosen journals. Inclusion was limited to original articles describing preclinical research in stroke or VCI, published between January 2005 and December 2015 inclusive. Complete articles were reviewed for functional assessments used in each trial. Primary analyses were numbers of functional tests used; frequency of use of each test and temporal trends. Of 91,956 stroke articles screened, 1,303 studies were analyzed, of these 609 did not report any functional measures and 56 had no access to full article, giving 638 articles for final analysis. For VCI, 56 papers were assessed in full, of these 16 reported no functional measures, giving 37 papers for final analysis. In stroke trials, 559 (89%) used an ischemic and 94 (14%) a hemorrhagic model. In VCI studies, 11 different models were found, with global hypoperfusion being the most common, applied in 11 (30%) articles. Of studies analyzed, the median number of tests applied per trial was 1 in both cases with only 9% of stroke trials and 16% of VCI trials reporting functional measures as primary end points. There were 74 different assessments described in stroke trials, consisting of functional tasks and neurological deficit scores (NDS). Rotarod was the most frequent assessment (15% of trials), and Bederson’s the most frequently used NDS (39% of trials). In VCI studies, there were 19 different assessments employed, with Morris Water Maze (MWM) being most popular (56% of studies). Marked inconsistencies were found in physical and functional characteristics of all assessments reported. There is heterogeneity amongst and lack of prioritizing the use of outcome measures in pre-clinical trials. These inconsistencies compromise comparison and meta-analysis. Thus, a consensus of core-set functional outcome assessments could improve consistency in animal stroke and VCI models.

Introduction: The diagnosis of vascular cognitive impairment relies on bedside tools to quantify the degree of disease burden. Given the critical importance of implementing early interventions, it is becoming increasingly important to investigate more sensitive and easily administered tools for accurately characterizing these deficits. Hypothesis: The current study aims to evaluate the effectiveness of using Miro, a tablet-based mobile application, developed by The Cognitive Healthcare Company, designed to measure the same cognitive domains as traditional pencil-and-paper tests but (1) require less administration time; (2) provide reliable scoring; (3) offer greater ease of use; and (4) capture and analyze informative data, like speech, fine motor function and eye movements, that are not typically used in clinical settings. Methods: Subjects were recruited from the Stroke and Cognitive Disorders Clinic. Subjects were randomized to undergo pencil-and-paper or iPad testing first. The battery of tests in each medium take roughly 60 minutes to complete. In this ongoing study, there will be 3 total participant visits over one year, to evaluate rate of decline or improvement in each medium. Results: 11 subjects have been enrolled in the study thus far. These subjects have a mean age of 64.6 ± 9.48 and years of education 16.3 ± 2.61.There were strong Spearman rho correlations between pencil and paper testing and iPad testing on digit span forwards (0.848, p < 0.002), digit span backwards (0.946, p < 0.001), symbol digit coding (0.936, p < 0.001), Trails A and B (0.794, p < 0.006). When asked to rate their preference on a 7-point Likert scale (1=iPad based, 4=no preference, 7=paper based), subjects reported a mean score of 3.36 (SD 1.55), demonstrating a slight but not statistically significant preference for iPad. Technicians uniformly found the iPad app easier to administer and less time-consuming for them. Conclusions: Given the growing population of individuals with vascular cognitive impairment, it is crucial to test whether this accessible, cost-effective, mobile testing modality can be effectively utilized to assess change in cognitive function after stroke. Our preliminary results indicate that iPad based interventions area promising means to meet this goal.

In the first years of your career as a stroke physician, you are concerned with the patient you thrombolyzed yesterday and worry whether there is an intracerebral hemorrhage on the follow-up scan. Besides, you stress over the statistics for the paper your professor has been telling you to write for the past 6 months. While you are doing your best to become an excellent clinical stroke physician and you are trying hard to understand the world of academics, it is difficult to find the time for organizational work. The idea that you, as a trainee, may be able to influence global clinical practice and establish an international network may seem unrealistic. However, national and international stroke organizations act as platforms for influence, collaboration, inspiration, exchange of experiences, networking, and career promotion from early on. In the following article, we summarize why it is more than worthwhile to get involved in a stroke organization and we report our own experiences as members of the European Stroke Organisation (ESO) Young Stroke Physicians Committee. Vascular neurologists at the start of their careers are at the forefront in the emergency room, working directly with all disciplines involved in stroke care. They are exposed to the daily challenges of treating patients. Whether in a tertiary stroke center or in a hospital without a stroke unit, fellows get to see strengths and weaknesses of the pathways at their institutions. Nevertheless, the ability to change basic processes in patient care and in the organization of stroke services in general is limited. Involvement in a stroke organization yields opportunities to influence the direction of stroke care and research, for example, by contributing to guidelines, reviewing grant applications, reviewing papers, and rating abstracts for conferences. Being involved in these processes will improve skills needed for writing successful grant applications. …

Our paper estimated beverage intake using data collected from a food frequency questionnaire.1 We adjusted our findings for energy intake derived from the food frequency questionnaire. Dr Archer questions the validity of this approach and quotes a group of eminent epidemiologists2 to support his stance. The paper cited by Dr Archer explains that the energy intake estimates in question should not be used as an exposure variable. However, these researchers also explicitly state that one should use self-reported energy intake for energy adjustment of other self-reported dietary constituents to improve risk estimation in studies of diet-health associations.2 The improved validity after adjusting nutrient intakes for self-reported energy intake is clearly demonstrated in the OPEN study (Observing Protein and Energy Nutrition) for food frequency questionnaire–derived protein intake.3 Because we used energy intake derived from the food frequency questionnaire as a covariate and not as an exposure, our methods are actually in line with the recommended approach cited by Dr Archer. Dr Archer also …

The recent article by Zerche et al shows that circulating N -methyl-d-aspartate-receptor subunit NR1 (NMDAR)-GluN1 autoantibodies modulate the evolution of lesion size in ischemic stroke patients.1 We think that mechanistic explanations of these exciting data could be found in previous papers published in Stroke by our group.2,3 In these papers, we showed that vaccination against the N-terminal domain of the GluN1 subunit of NMDA receptors reduces lesion size in mouse experimental stroke by preventing blood–brain barrier (BBB) breakdown. Zerche et al report that circulating NMDAR-GluN1 autoantibodies reduce stroke lesions only in patients with intact BBB before stroke (apolipoprotein E4 [APOE4] noncarriers), but not in patients with a preexisting BBB leakage (APOE4 …

Introduction: The quality of reporting of neuroimaging methods for studies of cerebral small vessel disease is unknown. We systematically reviewed studies of MRI white matter hyperintensities (WMH) of vascular origin to determine the frequency of reporting of key aspects of neuroimaging methods, and whether reporting varied by sample size, study design or journal impact factor. Methods: Three raters independently reviewed 100 consecutive papers reporting WMH severity, either as a primary outcome or covariate, to abstract 50 study characteristics based on the published STRIVE standards (Wardlaw et al Lancet Neurol 2013). Final determinations were made by consensus. An aggregate quality score (range 0-11) was created by adding one point for reporting of each of 11 key characteristics (Table). Spearman correlation or chi-square test, as appropriate, were used to test associations with quality score. Results: Papers were published between 2009 and 2013 with journal impact factors ranging from 0.56 to 15.3, with cohort (79%) and case control (21%) studies represented. Quantitative computational methods were used in 28 studies. MR field strength, MRI sequence types, type of WMH measurement method, blinding and number of raters were reported frequently, but reporting of other characteristics was inconsistent (Table). Study quality score was not correlated with journal impact factor, sample size or cohort study design. Conclusions: There is inconsistent reporting of neuroimaging methods in the small vessel disease imaging literature. Increased adherence to published reporting standards, such as the STRIVE criteria, may facilitate more objective peer review of submitted manuscripts and increase the reproducibility of published results. More work is needed to facilitate adoption of standards and checklists by authors, reviewers and editors.

Global and local (“glocal”) disparities in stroke incidence, prevalence, care, and mortality are persistent, pervasive, and progressive. In particular, the disproportionate burden of stroke in people of African ancestry compared to most other racial/ethnic groups around the world has been long standing, is expected to worsen, and so far, has defied solution, largely because conventional risk factors likely account for less than half of the Black versus White disparity in stroke outcomes. While hypotheses such as a differential impact or inadequate evaluation of traditional risk factors by race have been suggested as potentially key factors contributing to lingering racial/ethnic stroke disparities, relatively understudied novel risk factors such as psychosocial stress, environmental pollution, and inflammation; and influences of the social determinants of health are gaining the most attention (and momentum). Moreover, it is increasingly recognized that while there is a lot still to understand, there needs to be a major shift from incessantly studying the problem, to developing interventions to resolve it. Resolution will likely require targeting multilevel factors, considering contemporaneous cross-national and cross-continental data collection, creating scalable care delivery models, jointly addressing care quality and community drivers of stroke occurrence, incorporating policy makers in planning/dissemination of successful interventions, and investing in robust transdisciplinary research training programs that address the interrelated issues of health equity and workforce diversity, and regional capacity building. To this end, our international multidisciplinary team has been involved in conducting several epidemiological studies and clinical trials in the area of stroke disparities, as well as executing career enhancing research training programs in the United States and Africa. This award lecture paper shares some of the lessons we have learnt from previous studies, presents objectives/design of ongoing initiatives, and discusses plans for the future.

Introduction: Stroke secondary to intracranial atherosclerosis (ICAD) results in three distinct infarct patterns: (a) border zone infarcts (BZI) due to impaired distal perfusion (b) territorial infarcts due to distal plaque/thrombus embolization, and (c) perforator infarcts due to plaque progression. Previous studies indicate higher stroke recurrence in ICAD patients with BZI. Methods: This registered systematic review (CRD42021265230) comprised Medline and Web of Science search from inception to March 2022 for keywords (Intracranial Atherosclerosis OR Intracranial Stenosis) AND (Border zone OR Infarct Pattern) to identify papers and conference abstracts reporting initial infarct patterns and recurrence rates in patients with symptomatic ICAD. Sensitivity analyses were performed for studies including any BZI vs isolated BZI and those excluding posterior circulation strokes. The study outcome included neurological deterioration and/or stroke recurrence. For all outcome events, corresponding risk ratios (RR) and 95% confidence intervals (CI) were calculated. Risk of bias assessments will be presented. Results: Literature search yielded 4478 studies,11 met inclusion criteria (n=1315 patients, 354 with BZI, weighted proportions summarized in figure). The meta-analysis of these studies with moderate heterogeneity (I 2 =38.7%) demonstrated that RR of outcomes in BZI group compared to non-BZI group was 2.10 (95% CI 1.52-2.90). Limiting analysis to studies including any BZI, RR (and 95% CI) was 2.32 (1.58-3.40), and 3.25 (2.09-5.07) for studies only including anterior circulation strokes with low heterogeneity for both (I 2 =0%). A non-significantly high outcome rate was seen with isolated BZI (RR 2.29, 95% CI 0.94-5.62) but with moderate heterogeneity across studies (I 2 =70.25%). Conclusion: We demonstrate the presence of BZI secondary to symptomatic ICAD can be imaging biomarker to predict neurological deterioration and/or stroke recurrence.

Introduction: Despite their high risk of mortality, recurrent stroke, and dementia, stroke survivors underutilize ACP. In a non-prespecified subgroup analysis of a randomized trial to increase ACP, we compared the efficacy of the PREPARE for Your Care (PREPARE) plus an easy-to-read advance directive (AD) to an AD alone among stroke survivors. Methods: PREPARE is an interactive digital program with easy-to-read, state-specific ADs, and video stories. Stroke survivors in the PREPARE trial were identified using the International Classification of Diseases codes. The primary outcome was new ACP documentation in the electronic medical record after 12 months; secondary outcome was self-reported ACP completion of: (1) signing official papers naming a surrogate decision maker; (2) discussion of patients’ wishes with surrogates; (3) discussion of patients’ wishes with medical providers; and (4) an AD, scored 0-4. We calculated the change from baseline to 12-month follow-up. Mixed-effects regression models were used, adjusted for health literacy (adequate or limited), baseline ACP documentation, and clustering by physician. Results: Of 986 PREPARE trial participants, 91 (9.2%) were stroke survivors and 72 had complete data. The mean age was 64 years (SD, 6.8 years), 47% were women, 74% identified as a minority race/ethnicity, 40% were Spanish-speaking, 49% had limited health literacy, and 41% had ACP before enrollment. There was a trend toward greater ACP documentation in the PREPARE-arm (table). The PREPARE-arm had significantly greater increase in completed ACP elements than the AD-only arm. Discussion: The PREPARE program shows promise to engage ethnically diverse stroke survivors in ACP and should be studied further. Addition of stroke-specific content and engagement of acute stroke survivors in adaptations may increase the impact of the program.

Iwant to thank the Stroke Council, my friends, and colleagues for giving me the privilege of delivering the 2000 William Feinberg lecture. I am particularly honored to follow Lou Caplan. Lou is near the top of the list of individuals who have had the most influence on my career. The subtitle of his classic paper, “What is Wrong with Mr. Jones,”1 has become the mantra for those of us who believe it is essential to know what we are treating before we know how to treat it; otherwise we run the risk of a “confused vascular analysis.” I therefore honor Lou by declaring this the millennium of the stroke splitters; I confidently predict that the stroke lumpers will finally be vanquished sometime in the next 1000 years! The first time I specifically recall being told I was professionally confused was in 1976. I was finishing the third year of my neurology residency at the Cleveland Clinic. My chairman, Jack Conomy, called me into his office to tell me I was confused. He said I really did not want to take an EMG fellowship and that I should go into something “more challenging,” like stroke. I always took Jack’s advice, and to this day I cannot interpret an EMG. Shortly after starting my stroke fellowship at the Mayo Clinic in 1977, I noticed that many patients in Rochester, Minnesota, seemed to be on coumadin. I therefore asked Burt Sandok what the rationale was for using coumadin to prevent CVAs. Burt said, “You know, Tony, CVA stands for a ‘confused vascular analysis.’ Why don’t you review the literature and get back to me?” I didn’t realize it at the time, but this seemingly humorous anecdote would serve as the basis for my entire career. That literature review revealed many papers and …

Background: Patients with unilateral neglect after the right hemispheric lesion fail to respond normally to stimuli on the left side. Several paper-based tests for detecting neglect had been widely used. Here, we developed an application that runs on a tablet device to evaluate unilateral spatial neglect and investigated its feasibility in stroke patients. Methods: We enrolled acute ischemic stroke patients with neglect (n = 20) who had at least one of visual, auditory or tactile extinction. By comparison, stroke patients who had cortical lesions without neglect (n = 10), and healthy controls (n = 10) were recruited. The iNeglect application running on the iPad device was developed. In the table setting test of the iNeglect, the subjects were requested to drag the 12 food items on the table, and the deviation of each item from the midline was measured automatically. Line bisection tests using paper or iPad were also performed and compared. Results: Among neglect patients, mean deviation to the right side were 2.03 ± 2.11 mm of line bisection on paper, 18.47 ± 20.89 mm of line bisection on iPad, and 15.79 ± 18.17 mm of the table setting test. Patients with neglect showed larger deviation to the right side; in line bisection on paper (compared without neglect, p = 0.016 and control, p Conclusions: The iNeglect application was feasible in discriminating the patients with neglect and recognizing the right side deviation. The iNeglect application might be helpful to evaluate neglect patients and to objectify neurological deficit.

Background: Chart review demonstrated inconsistencies in the documentation of specific areas of Emergency Department Nursing stroke care indicators. These inconsistencies included the Dysphagia Screen and the documentation of time of Code Stroke called. At the time of this discovery in 2008, the patient chart was a hybrid of a paper and an electronic record. This resulted in the potential for data being captured in multiple areas of the chart, and was identified as a patient safety risk. Purpose: Increase compliance in Emergency Room nursing documentation Create clear and consistent stroke patient record via universal format Enhance the ease of use of patient record by eliminating the hybrid system in the ED Ensure reliable communication among all clinicians caring for the patient Methods: Retrospective and concurrent review of charts to determine most common opportunities for improvement Identify staff barriers to compliance, i.e. lack of standardized format to document care, and the reluctance to return to paper charting once the electronic record was efficiently utilized Create a mandatory “Time Code Stroke Called” and “Dysphagia Screen” pathway in the electronic medical for triaged patients vs. free text/paper Code Stroke log documentation Re-review charts after implementation and provide staff education of the standardized format Results: Increase in Dysphagia Screen compliance from 45.6% in 2008 , to 69.9% in 2009 , to 83% in 2010 Reliable documentation of “Code Stroke Called” is found in every record Lesson Learned: creating simple documentation for clinicians increases compliance in capturing the required elements of stroke care Conclusions: Customizing electronic medical records to eliminate hybrid charting has increased nursing documentation compliance of the Dysphagia Screen and the time of Code Stroke called in Emergency Department stroke patients at Kenmore Mercy Hospital.

Background and Purpose— Lacunar ischemic stroke accounts for 25% of all ischemic strokes, but the exact etiology is unknown. Numerous pathophysiologies have been proposed, including atheroma and endothelial dysfunction. Models of any of these pathological features would aid understanding of the etiology and help develop treatments for lacunar stroke. We therefore aimed to assess the relevance of all available potential animal models of lacunar stroke. Methods— We systematically reviewed the published literature for animal models that could represent lacunar stroke using validated search strategies. We included studies that could represent an aspect of lacunar stroke as well as those aiming to model conditions with potentially similar pathology and extracted data on species, induction method, and resulting brain and vessel lesions. Results— From 5670 papers, 41 studies (46 papers) met inclusion criteria representing over 10 different classes of stroke induction. Important data like infarct size and animal numbers were often missing. Many models’ infarcts were too large or affected the cortex. Emboli mostly caused cortical but not small subcortical lesions. Most models focused on creating ischemic lesions in brain tissue. Only one (spontaneous lesions in spontaneously hypertensive stroke-prone rats) also mimicked small vessel pathology. Here, the precursor to small vessel and brain damage was blood–brain barrier failure. Conclusion— Some animal models produce small subcortical infarcts, but few mimic the human small vessel pathology. Models of small vessel disease could help improve understanding of human lacunar disease, particularly to clarify factors associated with the small vessel morphological changes preceding brain damage. Much lacunar stroke may arise after blood–brain barrier disruption.

Response: We appreciate the opportunity to respond to Drs Nederkoorn and van der Graaf in regards to our recent paper entitled “Diagnostic Accuracy of Magnetic Resonance Angiography (MRA) for Internal Carotid Artery Disease: A Systematic Review and Meta-Analysis.”1 In agreement with their statement, we believe that a critical analysis of the existing literature and a pooled estimate of the data are a necessary and beneficial addition to this field. More than 11 000 abstracts were screened for the selection of potential articles to be included in this meta-analysis, which investigated the diagnostic accuracy of both time-of-flight (TOF) MRA and contrast-enhanced (CE) MRA. Of these abstracts, a total of 96 articles were selected for thorough examination. Of these 96, Drs Nederkoorn and van der Graaf, along with their colleagues, had published 3 articles in the period of 2002 to 2003 addressing this issue.2–4 Though it is not stated in any of the three papers that similar data involving an overlap of study …

Supplemental Digital Content is available in the text., Background and Purpose: Cilostazol, a phosphodiesterase 3’ inhibitor, is used in Asia-Pacific countries for stroke prevention, but rarely used elsewhere. In addition to weak antiplatelet effects, it stabilizes endothelium, aids myelin repair and astrocyte-neuron energy transfer in laboratory models, effects that may be beneficial in preventing small vessel disease progression. Methods: A systematic review and meta-analysis of unconfounded randomized controlled trials of cilostazol to prevent stroke, cognitive decline, or radiological small vessel disease lesion progression. Two reviewers searched for papers (January 1, 2019 to July 16, 2019) and extracted data. We calculated Peto odds ratios (ORs) and 95% CIs for recurrent ischemic, hemorrhagic stroke, death, adverse symptoms, with sensitivity analyses. The review is registered (CRD42018084742). Results: We included 20 randomized controlled trials (n=10 505), 18 in ischemic stroke (total n=10 449) and 2 in cognitive impairment (n=56); most were performed in Asia-Pacific countries. Cilostazol decreased recurrent ischemic stroke (17 trials, n=10 225, OR=0.68 [95% CI, 0.57–0.81]; P6 months) versus short term without increasing hemorrhage, and in trials with larger proportions (>40%) of lacunar stroke. Data were insufficient to assess effects on cognition, imaging, functional outcomes, or tolerance. Conclusions: Cilostazol appears effective for long-term secondary stroke prevention without increasing hemorrhage risk. However, most trials related to Asia-Pacific patients and more trials in Western countries should assess its effects on cognitive decline, functional outcome, and tolerance, particularly in lacunar stroke and other presentations of small vessel disease.

Background: Cardiac structure and function are important in determining ischemic stroke (IS) etiology, but whether there is an association with cognition post IS is unknown. Methods: IS patients admitted to Johns Hopkins Hospital (2017-2019) underwent transthoracic echocardiography. IS was classified (TOAST) by a masked reviewer. Parasternal short axis left atrial (LA) diameter was evaluated as a continuous variable with a spline at 4cm (normal ≤4cm versus enlarged >4cm); left ventricle ejection fraction (LVEF) was evaluated as a nonlinear continuous variable with two spline knots at 40% and 65%. Cognition was assessed by telephone using the Six Item Screener (SIS), which tests orientation (day, month, year) and recall (grass, paper, shoe) and was dichotomized into low (0-3, worse score) and high (4-6, better score), and conservatively imputing low category scores for non-answerers. Multivariable logistic regression determined the association of SIS category with LA or LVEF, each, adjusted for covariates. Results: Participants (N=119) were on average 60 (18-89) years, 60% male, and 59% Black. Mean LA diameter was 3.9cm ( SD =0.8) and mean LVEF 61.4% ( SD =10.5). For LA diameter ≤4cm, each 1cm increase was associated with 5.93 greater odds (95% CI=1.49-23.65) of scoring in the high SIS category, while for LA diameter >4cm each 1cm increase was associated with lower odds (OR=0.88, 95% CI=0.39-1.99) of scoring in the high SIS category (Figure 1). Decreased (OR=0.91, 95% CI=0.74-1.11), normal (OR=0.98, 95% CI=0.91-1.06) or hyperdynamic LVEF (OR=1.02, 95% CI=0.90-1.14) showed no relationship with SIS category. Conclusions: In this study, a 1cm change in LA diameter was significantly associated with a higher score on a telephone cognition screening test, if patients had a LA diameter within normal range, but without the same association with SIS if the LA diameter was >4cm. We cautiously suggest that LA function may be associated with cognition post-stroke.

Background: Patients with symptomatic intracranial stenosis (ICAS) face elevated risks of recurrent cerebrovascular events (RCE) despite optimal medical therapy. Borderzone infarcts (BZI) indirectly correlate with impaired distal perfusion, a known mechanism of recurrence. Studies assessing associations between borderzone infarcts and recurrence rates are observational and have relatively small sample size. We therefore performed a meta-analysis of published studies investigating this association. Methods: We performed a Medline and Web of Science search using the key words (Intracranial Atherosclerosis OR Intracranial Stenosis) AND (Borderzone OR Infarct Pattern) to identify studies reporting associations between index infarct pattern and RCE, defined as recurrent ischemic stroke or neurological deterioration, or new infarct on follow up neuroimaging in patients with symptomatic ICAS. We included relevant papers and scientific abstracts with more than 20 patients included. For all outcome events we calculated the corresponding risk ratios (RRs) and 95% confidence intervals (95% CI). Results: We identified 178 studies using Web of Science and 384 studies using Medline with only 6 studies (591 patients) meeting our inclusion criteria (2 prospective and 4 retrospective). The weighted proportion of patients with BZI was 32.5% (28.7%-36.4%). During a follow-up period of 7-950 days, 33.1% (26.3%-40.5%) of patients with BZI had RCE and 63.6% (30.8%-89.1%) had new infarction on a 6-8 week follow up brain MRI. In meta-analysis, BZI was associated with increased rates of RCE (RR 2.40 95% CI 1.71-3.37) and new infarct(s) on follow up brain MRI (RR 2.55 95% CI 1.31-4.94). The findings were unchanged when the analysis was limited to 90-day RCE risks only (RR 2.22 95% 1.49-3.29). Conclusions: BZI are associated with over 2-fold increased risk of RCE and recurrent infarct in patients with symptomatic ICAS. Prospective studies are needed to validate these findings.

Background: Dual antiplatelet therapy with clopidogrel and aspirin prescription is standard for various clinical settings such as Acute Coronary Syndrome. However, the therapy is less effective on a large portion of the Asian population due to clopidogrel resistance. Oenanthe javanica (O. J.) has been used in traditional Chinese medicine for a range of ailments. In this study, we aimed to evaluate Oenanthe javanica extract’s antithrombotic effects and its potential to be used in Dual Antiplatelet Therapy (DAPT) to overcome clopidogrel resistance. Method: Prothrombin time (PT), activated partial thromboplastin time (aPTT), ADP and ASPI were measured using blood samples collected from 2 healthy volunteers. One volunteer took 2 75mg clopidogrel (CPG) tablets 2 hours before the experiment. The blood samples were incubated with O. J. extract for 30min before the measurement. For in vivo experiments, FeCl 3 thrombosis were induced to right common carotid arteries of Sprague Dawley rats (270-300g). The rats were divided into 5 groups (N=5-6): Control group, O. J. group, CPG group, CPG+O. J. group, and CPG+ASA group. O. J. extract was orally administered 200mg/kg per day for 3 days. CPG and ASA were orally administered 10mg/kg 2 hours before the experiment. Thrombosis was induced using filter paper doused with 10μL of 20% FeCl 3 solution. After the induction, blood flow was measured for 55min and thrombus weight was measured. Results: O. J. extract did not have any effect on PT, aPTT, and ASPI. However, O. J. extract did have an effect on ADP value, even though the volunteer had clopidogrel resistance. In FeCl 3 thrombosis model, O. J., CPG, CPG+ASA, and CPG+O. J. group all significantly increased the time-to-occlusion (TTO) compared to the Control group. This was true for thrombus weight as well. Conclusion: Our results indicate that O. J. extracts is a potential antiplatelet agent for dual antiplatelet therapy for patients with clopidogrel resistance.

To the Editor: Kimura and colleagues,1 in presenting their study on the impact of nortriptyline on cognitive impairment after stroke, do not describe clearly the research design they have used. In the paper’s title and in the text, they report the study as a randomized placebo-controlled trial, but they also describe it as a secondary analysis of data pooled from 2 previous trials—in other words, a meta-analysis. Although the paper does not directly reference the trials that were included, the details of research grants which supported the present work match those for 2 previously published trials,2 3 as do many of the methodological details. There are discrepancies, for example, in descriptions of the trials’ entry criteria and in the numbers of subjects included, but overall the evidence suggests that the present paper reports a meta-analysis of these 2 trials. We need to be clear which sort of study this is for 2 reasons. First, if it is a meta-analysis, then it …

Introduction: Stroke is a leading cause of mortality globally, with 85% of stroke death occurring in low- and middle-income countries (LMICs). Translation of evidence-based stroke prevention interventions from their original setting to the novel context in which they will be implemented is often unreported; especially in LMICs where it has been severely understudied. Thus, our objective was to investigate how adaptation has been examined within research on stroke prevention interventions in LMICs through a scoping review of the available literature in order to highlight benefits and best-practices, identify gaps, and develop a greater understanding of these efforts that will ultimately support attempts to address the global burden of stroke. Methods: This review was conducted in accordance with PRISMA-ScR guidelines. Five databases were searched (PubMed, PsycINFO, CINAHL, EMBASE, and Web of Science), for eligible studies using a search strategy developed in consultation with a research librarian. Two reviewers independently assessed the retrieved articles for selection based on the inclusion criteria (peer-reviewed empirical papers or protocols, reported on adaptation of stroke prevention interventions, and occurred in at least one LMIC) through a two phase process consisting of (1) title and abstract screening and (2) full-text screening. Discrepancies were resolved through discussion until consensus was reached. Data were charted and a narrative synthesis, guided by the FRAME framework, was used to analyze and interpret the findings. Results: Of 380 articles retrieved, a total of six articles reporting adaptation of primary (n=4) or secondary (n=2) stroke prevention interventions in LMICs were identified. Types of interventions included use of community health workers (n = 2), use of mHealth tools (n=2), and interventions aimed at risk factor modification (n = 2). Adaptations were proactively planned, with multiple adaptation goals reported. Conclusions: This is the first review of its kind to focus on adaptation of evidence-based stroke prevention interventions in LMICs. Through our systematic investigation, we highlight the need for additional research to assess the processes and outcomes of stroke prevention interventions.

Introduction: Limited data exist about the safety and efficacy of repeat mechanical thrombectomy (MT) in patients with recurrent large vessel occlusion (rLVO). Here, we present a case series examining the outcome of early and delayed rLVO and the safety of repeat MT. Methods: We reviewed our prospectively-collected endovascular database for acute ischemic stroke (AIS) patients with LVO who underwent MT between July 2012 and February 2020. We included patients with recurrent stroke requiring repeat MT after successful first MT, either in the same vessel or in a different vascular territory, within 24 hours up to 924 days and compared it with patients who underwent single MT. Baseline demographics, angiographic, procedural, and outcomes data were compared in AIS patients who underwent recurrent MT (RT) versus single MT (ST). We completed a meta-analysis that evaluated papers from 2015 to 2020 which examined reocclusion after MT. Result: A total of 738 MT patients were included, of which 726 (98.4%) were in the ST group and 12 (1.6%) in the RT group (Table 1). Baseline characteristics were well balanced between the cohorts. The most common site of occlusion was in the MCA territory. Last known well (559 ± 982 vs. 267 ± 301 minutes, p = 0.358) was similar between the groups. There was no difference in the median number of passes (2 IQR 1-3, p=0.61) in the ST and RT groups, respectively. In the RT group, the mean time between repeat occlusion was 132.5 ± 275 days. Revascularization success, sICH rates (25% vs. 7.1%, p= 0.306), and mean 90-day mRS (1.3 ± 2.3 vs. 1.8 ± 2.7, p = 0.63) did not differ between the first MT (FT) and RT cohorts. No association between reocclusion and MT device (aspiration or stent-retriever), tPA given, statin, antiplatelet or anticoagulation therapy was found in the meta-analysis. Conclusion: Repeat MT in patients with early or delayed reocclusion appears to be safe. Larger, prospective studies are needed to evaluate these findings.

Objective: To describe the clinical features of stroke patients from rural and urban areas and to identify possible associations with clinical outcomes. Introduction: There is little information in Latin America about risk factors, treatments, and outcomes in stroke patients from rural areas and urban people. The rural population faces multiple healthcare access barriers that might influence stroke outcomes. This paper describes and analyzes clinical features in stroke patients according to their location. Methods: Prospective cohort study of Colombian stroke patients using demographic and clinical data collected between 2018 and 2020 in a high complexity hospital from southwestern Colombia, as part of a pilot stroke network consisting of rural primary centers and a mothership center. Mode of transport to the stroke center, timing, clinical characteristics, interventions, and modified Rankin scale (mRS) at discharge and 3 months were assessed. Results: We included 579 stroke patients (66.14% ischemic), with a median age of 70 years (60-81). Urban subjects showed higher prevalence of dyslipidemia (p=0.009), previous hemorrhagic stroke (p=0.036), and TIA (p=0.002). Approximately 35% of cases were initially evaluated at a rural primary care center. These subjects exhibited a higher NIHSS scores (10 IQR 5-19 vs. 5 IQR 2-13; p=0.000) with a longer window (p Conclusions: Rural patients from southwestern Colombia were more likely to present with severe strokes even though they had lower rates of cardiovascular risk factors. They arrived later to the stroke center, but the final diagnosis was reached faster. Nonetheless, disability was higher at discharge and 3-months follow-up.

To the Editor: Zeng and colleagues1 recently published a potentially important study on the spontaneous stroke in 2-kidney, 2-clip renovascular hypertensive rats. Blood pressure rose to an average of 225 mm Hg 6 weeks postoperatively. Animals displaying neurological symptoms were killed on the third day, and those surviving without neurological symptoms were killed at postoperative week 40. Stroke occurred in 34, including 7 hematomas in 55 animals (61.8%). Microscopic examination revealed fibrinoid necrosis, hyaline degeneration, and hyperplasia of the walls of arterioles and small arteries with or without cell proliferation in the brain. These vascular lesions were not observed in the hypertensive animals without gross brain lesions. I read this paper with great interest, because we published a paper on the cerebral hemorrhage in renovascular hypertensive rabbits over 30 years ago.2 Despite the species difference, there are many similarities between the 2 studies. I would like to compare the recent study by Zeng and colleagues with our old one and offer some comments. In our old study,2 we made rabbits hypertensive by the 2-kidney, 2-clip or 1-kidney, 1-clip procedure. The 2-kidney, 2-clip group was divided into one with moderate …

Abstract: The coronavirus disease 2019 (COVID-19) pandemic has broad implications on stroke patient triage. Emergency medical services providers have to ensure timely transfer of patients while minimizing the risk of infectious exposure for themselves, their co-workers, and other patients. This statement paper provides a conceptual framework for acute stroke patient triage and transfer during the COVID-19 pandemic and similar healthcare emergencies in the future.

Background and purpose: Spatial neglect (SN) occurs frequently in patients with stroke, resulting in worse recovery. Without screening, the presence of SN may remain undetected and prevent initiation of alleviating strategies. There is limited evidence available to suggest bedside identification of SN in the subacute phase following stroke. Thus we set out to identify effective screening tests for SN. Method: The following index tests were used; (a) six conventional subtests of The Behavioural Inattention test (BIT), (b) an additional figure copying test, (c) a newly developed neglect experience questionnaire, and (d) an additional component added to the National Institute of Health Stroke Scale (NIHSS). The Catherine Bergego Scale (CBS) functioned as a reference frame to ascertain the presence of SN. Results: Consecutive stroke patients (N=125) were included from the Neurological Department of Landspitali University Hospital in Iceland, within two weeks following stroke. Of those 30 patients had SN. If all subtests of the BIT were administered, approximately 35% of stroke patients without SN would be incorrectly identified with the disorder. Statistically more patients without SN were identified as having SN if ≥ three tests of the BIT was administered (p=0.002). If patients did not, at stroke onset, comprehend why they had to go to the hospital, this was correlated to the presence of SN. The star cancellation and figure copying were the most sensitive paper-and pen tests to identify SN. Inclusion of an additional item to NIHSS correctly identified SN in 86% instances. Conclusion: Results contests the common belief that use of more tests increase identification of SN. Rather we found that the use a large test battery decreases sensitivity in the subacute phase following stroke. A short question about patients’ experiences of stroke onset and adding a novel item to the NIHSS provided new pragmatic ways of identifying SN. Results have been used to inform a larger cross-country study between Iceland and Lithuania, where psychometric properties of screening strategies are being further validated.

Background and Purpose: In September 2017, a new Hyperacute Stroke Unit (HASU) was opened in a metropolitan hospital with over 400 acute stroke admissions per year, offering endovascular clot retrieval (ECR) and IV thrombolysis; 185 ECR procedures completed in 2018. The HASU opening coincided with publication of the 2017 Australian Clinical Guidelines for Stroke Management. The Guidelines state stroke severity be assessed using a validated tool, such as the National Institute of Health Stroke Scale (NIHSS). A Quality Improvement workshop, March 2018, identified attendance of correct and reliable assessment for stroke severity as a service gap. Goal = Improve NIHSS completion on all stroke patients on presentation to hospital and 24hours post endovascular clot retrieval. This was to be achieved within 90 days of project implementation with the focus on nursing education; a new skill addition to the ward environment. Methods: Education workshops (August-September 18) were implemented with the goal of building knowledge, skills and confidence along with gaining NIHSS certification. All clinical and registered nurses were provided designated time to attend workshops. Workshops were also provided to Medical officers (January 2019) allocated to the Stroke team. Cognitive aids to assist with reducing variability in application of the NIHSS were created. These included NIHSS navigation aids to the electronic medical record, NIHSS app upload to mobile phones, paper based NIHSS assessment to assist the bedside nurses and ward round note templates with auto text for NIHSS completion. Data from three months pre and post implementation was collected and compared using the Australian Stroke Clinical Registry (AuSCR). All patients admitted with stroke were included in this analysis (Jan 18-April 19). Results: NIHSS completion on patient presentation increased by 12% (n=325). NIHSS completion at 24hrs for patients post ECR increased by 22% (n=163). 31 registered nurses trained; 8 medical officers trained. Conclusions: Targeted, multimodal strategies improved completion of NIHSS on presentation and particularly, 24hrs post ECR. Further implementation in the emergency department is required to gain improvements in NIHSS completion on presentation.

Objective: To analyze and characterize industry payment to vascular neurologists from 2013 to 2018 using open Payments Database. Methods: This is a retrospective analysis of open payments database, which is available publicly. We calculated the percentage of vascular neurologists in the United States receiving payments and payment characteristics. We have analyzed the top 1% payment to vascular neurologist with detailed payment category analysis, payment regional trends, and sponsors each year. The number of board-certified vascular neurologists is available from the database of the American Board of Psychiatry and Neurology. Results: From Jan 2013 to Dec 2018, industry payments to vascular neurologists have increased significantly each year, while a relatively stable fraction (17%) of US vascular neurologists received industry payments totaling $ 3,782,222 (6 years combined). The median payment per physician ranges from $ 115 to $ 241, while 90th percentile payments vary from $1,766 to $ 4,988 with a maximum payment up to $190,551. Nine payment categories are available and the highest amounts were paid for "Consulting Fee". The payment proportion from top 10 sponsors consists of 75% of the total amount since 2013. The payment to the south region has a steady growth rate among the other regions and has the highest payment amount of $ 470,551 in 2018. Top 1% vascular neurologists received more than 60% of the total payment. Among the top 1% vascular neurologists, 73% are likely to be key leaders in the field. Among the top 1%, 42% are specialized in neuro-intervention and less than 15% have Authored AHA/ASA guideline papers. Conclusion: Payments to vascular neurologists is highly skewed with the top 1% receiving around one-third of all payments, less than 15% of these vascular neurologists have authored AHA/ASA guidelines. The industry is known to target key leaders in the field whether this is translating to changes in clinical practice should be looked into more thoroughly.

Background and Purpose: With increased volume of both young adult stroke patients and mechanical thrombectomy for reversal of LVO, young adult stroke survivors (YASS) are increasingly discharged directly home with minimal neurological deficits. No studies have examined the psychosocial experiences of these YASS and whether these experiences are associated with stroke-specific quality of life (SSQOL). The purpose of this study was to describe YASS post-stroke symptoms, their understanding and perception of those symptoms, and to examine relationships among psychosocial variables: anxiety, depression, fatigue, illness threat perceptions and SSQOL. Methods: A cross-sectional, exploratory design was used. YASS 18-55 years of age and 1-18 months post-stroke who received a thrombectomy at a metropolitan CSC and discharged directly home were recruited. Demographic and clinical data (e.g. NIHSS, mRS, TICI scores) were collected from the hospital’s EMR. Participants completed questionnaires to assess psychosocial variables using an online or paper survey. Descriptive statistics and Spearman rho correlations were performed. Results: Participants ( N = 14) had a mean age 45 years (SD = 6.2), were 4-18 months post-stroke, 71% female, 57% Black, and had low discharge NIHSS scores ( M = 2, SD = 2.6). Five participants had clinically severe fatigue with three borderline cases. There was one case of clinically significant anxiety with one borderline case, and one case of clinically significant depression with three borderline cases. All participants perceived some level of threat of their symptoms, and overall SSQOL was decreased. Higher levels of fatigue, anxiety, depression and illness perception threat were significantly related to lower SSQOL. Conclusions: In spite of having minimal to no physical deficits, these YASS described psychosocial symptoms, notably fatigue, that may impact recovery and transition back to the community. Symptom assessments, provision of education, resources and ongoing support before and after discharge home may be beneficial. Standard practice is a 90-day post-procedure patient assessment, however earlier post-procedure follow-up may help providers identify and address these symptoms.

Introduction: Recurrent ischemic stroke is more likely to have a worse prognosis. However, it is little known whether recurrent stroke is an independent risk factor for poor prognosis. We aim to investigate the difference of mortality and recurrent rate of first ever and recurrent ischemic strokes, as well as to explore the potential reasons. Method: We analyzed patients with ischemic stroke enrolled in the China National Stroke Registry which was a nationwide, multicenter, and prospective registry of consecutive patients with acute cerebrovascular events from 2007 to 2008. Date including hypertension, diabetes mellitus, hyperlipidemia, heart disease, etc. were obtained from paper-based registry forms. Multivariable analysis using logistic regression was performed to assess the risk of worse prognosis of recurrent ischemic stroke compared to first-ever stroke. Result: A total of 8 181 patients with first-ever stroke and 4 234 patients with recurrent stroke were enrolled in the study. For patients with first-ever stroke, the mortality, recurrence, composite Events(modified Rankin Scale=3-6, which means death or disability) rate is 7.2%, 10.3%, 22.6%, respectively at 3-month; and 9.0%, 13.0%, 29.0% at 6-month; as well as 11.4%, 14.7%, 28.5% at 1 year, respectively. For patients with recurrent stroke, the mortality, recurrence, composite events rate is 10.5%, 16.1%, 30.8% respectively at 3-month, and 13.9%, 20.3%, 41.7% at 6-month, as well as 17.3%, 23.6%, 42.1% at 1 year, respectively. Multivariable analysis showed that patients with recurrent stroke had a higher risk of death, recurrence and disability at 3-month, 6 month and 1 year (table 1). Conclusion: After adjusting for multiple risk factors, recurrent stroke is still an independent risk factor for poor prognosis of ischemic stroke, which further emphasizes the importance of secondary prevention of ischemic stroke, and the specific causes need to be furtherly investigated.