Acute Cerebrovascular Syndrome Research Articles

Time to Retire the Concept of Transient Ischemic Attack

This Viewpoint argues that evidence shows that transient ischemic attacks are neither benign nor transient and should be retired as a neurological diagnostic term in favor of acute ischemic cerebrovascular syndrome.

Neurologic manifestations associated with COVID-19: a multicentre registry

ObjectivesTo provide an overview of the spectrum, characteristics and outcomes of neurologic manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. MethodsWe conducted a single-centre retrospective study during the French coronavirus disease 2019 (COVID-19) epidemic in March–April 2020. All COVID-19 patients with de novo neurologic manifestations were eligible. ResultsWe included 222 COVID-19 patients with neurologic manifestations from 46 centres in France. Median (interquartile range, IQR) age was 65 (53–72) years and 136 patients (61.3%) were male. COVID-19 was severe or critical in 102 patients (45.2%). The most common neurologic diseases were COVID-19–associated encephalopathy (67/222, 30.2%), acute ischaemic cerebrovascular syndrome (57/222, 25.7%), encephalitis (21/222, 9.5%) and Guillain-Barré syndrome (15/222, 6.8%). Neurologic manifestations appeared after the first COVID-19 symptoms with a median (IQR) delay of 6 (3–8) days in COVID-19–associated encephalopathy, 7 (5–10) days in encephalitis, 12 (7–18) days in acute ischaemic cerebrovascular syndrome and 18 (15–28) days in Guillain-Barré syndrome. Brain imaging was performed in 192 patients (86.5%), including 157 magnetic resonance imaging (70.7%). Among patients with acute ischaemic cerebrovascular syndrome, 13 (22.8%) of 57 had multiterritory ischaemic strokes, with large vessel thrombosis in 16 (28.1%) of 57. Brain magnetic resonance imaging of encephalitis patients showed heterogeneous acute nonvascular lesions in 14 (66.7%) of 21. Cerebrospinal fluid of 97 patients (43.7%) was analysed, with pleocytosis found in 18 patients (18.6%) and a positive SARS-CoV-2 PCR result in two patients with encephalitis. The median (IQR) follow-up was 24 (17–34) days with a high short-term mortality rate (28/222, 12.6%). ConclusionsClinical spectrum and outcomes of neurologic manifestations associated with SARS-CoV-2 infection were broad and heterogeneous, suggesting different underlying pathogenic processes.

Abstract TP390: Clinical Characteristics and Outcomes in Nonagenarian and Centenarian Patients With Acute Cerebrovascular Syndrome

Background and Purpose: The number of elderly patients with acute cerebrovascular syndrome (ACVS) is increasing. The management of ACVS is difficult especially in very elderly patients such as nonagenarians and centenarians. Therefore, we aimed to clarify the clinical characteristics, treatments, and complications of these patients. Methods: We enrolled 80 patients aged over 90 in a group of 1,420 patients with ACVS who were admitted to our hospital between July 2013 and June 2018. We assessed clinical data and conducted brain MRI/MRA scans, carotid ultrasonograms, echocardiograms, 24hr Holter electrocardiograms and chest-abdominal CT scans to evaluate the severity of atherosclerotic change, stroke subtype, and cardiovascular status in these patients. We categorized them as follows: atherothrombotic brain embolism (ATBE: n=11, 14%), atherothrombotic brain infarction (ATBI: n=9, 11%), cardioembolic infarction (CEI: n=25, n=31%), lacunar infarction (LI: n=15, 19%), transient ischemic attack (TIA: n=6, 8%), and embolic stroke of undetermined source (ESUS: n=14, 18%). Results: Patient age was 92±3 years and 19% were male. Median baseline NIHSS was 9 and median baseline modify Rankin Scale (mRS) was 3. The brain natriuretic peptide (BNP) level was significantly higher in the CEI group (358±206pg/ml) compared to the ATBI group (104±48pg/ml, p<0.001), the ESUS group (130±82pg/ml, p<0.001), the LI group (85±42pg/ml, p<0.001), and the ATBE group (62±49pg/ml, p<0.001). The D-dimer level was correlated to the baseline NIHSS (r=0.44, p<0.01). There were no significant differences of D-dimer level among the stroke subgroups. Anticoagulation for the initial therapy was done in 62 patients (77%) including 2 patients who received thrombolysis. Major complications were aspiration pneumonia (11%), urinary tract infection (10%), bleeding in other organs (6%), and congestive heart failure (5%). The median mRS at discharge was 4 and in-hospital mortality rate was 3.8%. Conclusion: The BNP level was useful to identify the CEI group. Although the ACVS treatment of nonagenarians and centenarians are thought to be high risk for bleeding, the clinical and neurological outcomes were acceptable despite many complications.

Identification of dizzy patients who will develop an acute cerebrovascular syndrome: a descriptive study among emergency department patients.

To calculate the incidence of subsequent acute cerebrovascular syndrome in emergency department patients with vertigo or dizziness symptoms and to determine predictors of subsequent acute cerebrovascular syndrome in these patients. Descriptive and retrospective hospital based-population study among emergency department patients with vertigo or dizziness symptoms in 1year. One year follow-up since the medical visit was performed. Chi-square and Fisher tests were used for qualitative variables; Mann-Whitney U test for quantitative variables. A multivariate model was created. 1243 dizzy patients who visited emergency department during 2015 were identified, finally 928 were included. 12 acute cerebrovascular syndromes were identified; 8 strokes and 4 transient ischemic attacks. Percentages over the sample size: 1.29% for acute cerebrovascular syndromes, 0.43% for transient ischemic attack and 0.86% for stroke. Odds ratio values to develop an event over the general population were 7.24 for acute cerebrovascular syndrome, 95% CI (3.98-13.12); 14.9 for transient ischemic attack, 95% CI (4.8-40.9) and 5.86 for stroke, 95% CI (2.72-12.0). Atrial fibrillation and diabetes mellitus were identified as significant risk factors to develop an acute cerebrovascular syndrome. Emergency department patients with symptoms of vertigo or dizziness had sevenfold higher risk of acute cerebrovascular syndromes than the general population. Atrial fibrillation and diabetes mellitus are risk factors associated with high risk of acute cerebrovascular syndromes in these patients.

Partial loss of function of colony-stimulating factor 1 receptor in a patient with white matter abnormalities.

Mutations in colony-stimulating factor 1 receptor (CSF1R) cause adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). Patients with ALSP can be misdiagnosed as having acute ischemic stroke due to hyperintensity lesions on diffusion-weighted magnetic resonance imaging. Mutant CSF1R proteins identified in ALSP show a complete loss of autophosphorylation of CSF1R. We conducted mutation screening of CSF1R in 123 patients with definite acute ischemic cerebrovascular syndrome and positive family history of stroke. The pathogenicity of identified variants was evaluated using functional analyses. The levels of autophosphorylation of CSF1R in response to treatment with ligands of CSF1R were examined in cells transfected with wild-type and mutant CSF1R. We identified eight CSF1R variants, six were known non-pathogenic polymorphisms, whereas the other two were missense variants inducing substitution of amino acid residues (p.Glu573Lys and p.Gly747Arg). Functional assay showed that the levels of autophosphorylation of p.Gly747Arg were similar to those of wild-type when treated with ligands. The autophosphorylation of p.Glu573Lys was detectable, but significantly decreased compared with those of wild-type CSF1R (P < 0.001, two-way anova with Bonferroni). The clinical presentation of the patient with p.Glu573Lys was consistent with cerebral embolism. The patient did not have typical clinical findings of ALSP. However, periventricular white matter abnormalities, unrelated to the recent infarct, were evident on brain magnetic resonance imaging. In contrast to ALSP-associated missense mutations, CSF1R p.Glu573Lys variant in a patient with acute ischemic cerebrovascular syndrome showed a partial loss of autophosphorylation of CSF1R; its clinical significance warrants further investigation.

Differential Proteomics for Distinguishing Ischemic Stroke from Controls: a Pilot Study of the SpecTRA Project

A diagnostic blood test for stroke is desirable but will likely require multiple proteins rather than a single “troponin.” Validating large protein panels requires large patient numbers. Mass spectrometry (MS) is a cost-effective tool for this task. We compared differences in the abundance of 147 protein markers to distinguish 20 acute cerebrovascular syndrome (ACVS) patients who presented to the Emergency Department of one urban hospital within < 24 h from onset) and from 20 control patients who were enrolled via an outpatient neurology clinic. We targeted proteins from the stroke literature plus cardiovascular markers previously studied in our lab. One hundred forty-one proteins were quantified using MS, 8 were quantified using antibody protein enrichment with MS, and 32 were measured using ELISA, with some proteins measured by multiple techniques. Thirty proteins (4 by ELISA and 26 by the MS techniques) were differentially abundant between mimic and stroke after adjusting for age in robust regression analyses (FDR < 0.20). A logistic regression model using the first two principal components of the proteins significantly improved discrimination between strokes and controls compared to a model based on age alone (p < 0.001, cross-validated AUC 0.93 vs. 0.78). Significant proteins included markers of inflammation (47%), coagulation (40%), atrial fibrillation (7%), neurovascular unit injury (3%), and other (3%). These results suggest the potential value of plasma proteins as biomarkers for ACVS diagnosis and the role of plasma-based MS in this area.

Abstract TMP119: The Second Report of Japanese Sub-Analysis of TIAregistry.org

Background: TIAregistry.org is an international, multicenter-cooperative, prospective registry in patients with TIA or minor stroke within 7 days after the onset. Main analyses of one-year follow-up data have been reported (N Engl J Med 2016;374:1533-42). This was the second report on Japanese sub-analysis of TIAregistry.org. Methods: The patients recruited in TIAregistry.org were classified into two groups (345 Japanese and 3,238 non-Japanese). We compared subtype of acute cerebrovascular syndrome (ACVS) at baseline and recurrent ischemic stroke subtype according to the TOAST classification during one-year follow-up period as well as short- to long- term risk of stroke between Japanese and non-Japanese patients. We also determined predictors of one-year stroke in Japanese patients. Results: There was significant difference between Japanese and non-Japanese in the baseline ACVS subtype (38.3% vs 22.9% in small vessel occlusion, and 13% vs 33.9% in undetermined cause, p &lt;0.001) and recurrent stroke subtype (8.0% vs 17.4% in cardio-embolism, 24.0% vs 3.7% in other determined cause, and 4.0% vs 24.2% in undetermined cause, p&lt; 0.001). The risk of stroke at 2-day was similar between Japanese and non-Japanese, while the risk at 7-, 30- and 90-day, and 12-month were higher in Japanese than in non-Japanese. The risks of recurrent stroke in Japanese were diabetes mellitus (HR 2.88, 95% CI 1.06-4.90, p = 0.03), regular alcohol consumption (HR 2.56, 95% CI 1.15-5.78, p = 0.02), and large artery atherosclerosis in TOAST classification (HR 8.35, 95% CI 1.16-63.43, p = 0.02). In multi-variate analysis, the significant predictors of one-year stroke risk were prior coronary artery disease (HR 6.08, 95% CI 1.28-28.81, p = 0.02) and regular alcohol consumption (HR 2.28, 95% CI 1.02-5.17, p = 0.04). Conclusions: There were differences in baseline TOAST classification and recurrent TOAST stroke subtype between Japanese and non-Japanese. The very short-term risk of stroke was similar between Japanese and non-Japanese, while the later-term risk was higher in Japanese than in non-Japanese. The independent predictors of one-year stroke were history of coronary artery disease and regular alcohol drinking in Japanese patients.

Acute cerebrovascular syndrome

Acute cerebrovascular syndrome

Association between carotid plaque characteristics and acute cerebral infarction determined by MRI in patients with type 2 diabetes mellitus

BackgroundType 2 diabetes mellitus (T2DM) might aggravate the carotid plaque vulnerability, and increase the risk for ischemic stroke. Few studies reported the acute stroke subtype with carotid plaque characteristics in T2DM patients. This study aimed to investigate the association between carotid plaque characteristics and acute cerebral infarct (ACI) lesion features determined by MRI in T2DM patients.MethodsPatients with acute cerebrovascular syndrome in internal carotid artery territory were recruited. All patients were stratified into T2DM and non-T2DM groups and underwent both carotid and brain MRI scans. Ipsilateral carotid plaque morphological and compositional characteristics, intracranial and extracranial carotid artery stenosis were also determined. Stroke subtype based on the Trial of ORG 10172 in Acute Stroke Treatment classification and ACI lesion patterns were evaluated.ResultsOf the recruited 140 patients, 68 (48.6%) patients had T2DM (mean age 64.16 ± 11.38 years, 40 males). T2DM patients exhibited higher prevalence of carotid type IV–VI lesions, larger plaque burden as well as larger lipid-rich necrotic core (LRNC) compared with non-T2DM patients. Among the patients with carotid LRNC on symptomatic side, more concomitant large perforating artery infarct patterns and larger ACI size in the internal carotid artery territory were found in T2DM group than those in non-T2DM group. Carotid plaque with LRNC% > 22.0% was identified as an independent risk factor for the presence of ACI lesions confined to the carotid territory in T2DM patients, regardless of other risk factors.ConclusionsThis study shows that more concomitant large perforating artery infarct patterns and larger ACI size in the internal carotid artery territory were found in the T2DM patients with ipsilateral carotid LRNC plaque than those in non-T2DM patients. Quantification of the carotid plaque characteristics, particularly the LRNC% by MRI has the potential usefulness for stroke risk stratification.

Dabigatran following acute transient ischemic attack and minor stroke II (DATAS II).

Rationale Patients with transient ischemic attack or minor stroke are at high risk of early recurrent cerebrovascular events. Anticoagulation with heparin or warfarin acutely after ischemic stroke is at least as efficacious as aspirin for preventing recurrent events but is associated with an increased risk of clinical worsening due to hemorrhagic transformation. Aim and hypothesis We aim to demonstrate the safety of early anticoagulation with dabigatran, an oral direct thrombin inhibitor, in acute cerebrovascular syndrome patients. The primary hypothesis is that symptomatic hemorrhagic transformation rates in dabigatran and aspirin-treated patients will be similar. Sample size estimates At least 136 participants in two groups required to demonstrate an absolute between-group difference in the rate of hemorrhagic transformation of 5.6% with 80% power, assuming alpha = 5%. Methods and design A randomized, multicenter open-label clinical trial (NCT02295826). Three-hundred participants with a transient ischemic attack/ischemic stroke (National Institutes of Health Stroke Scale ≤ 9) will undergo magnetic resonance imaging within 72 h of symptom onset and will be randomized to aspirin 81 mg daily or dabigatran 150 mg twice daily for 30 days. Participants undergo repeat magnetic resonance imaging at 30 days and clinical assessment to 90 days. Study outcomes The primary outcome is the symptomatic hemorrhagic transformation rate. Secondary outcomes include recurrent stroke and new ischemic lesions on repeat magnetic resonance imaging. Discussion This study will determine the safety of early anticoagulation with dabigatran in patients with acute transient ischemic attack/ischemic stroke and will inform the design of a phase III randomized trial aimed at demonstrating reduced recurrent early ischemic events after acute transient ischemic attack/stroke.

LO62: Systolic blood pressure is a strong predictive marker for TIA and mild stroke in younger patients

Introduction: Age and systolic blood pressure (SBP) are important predictors of Acute Cerebrovascular Syndrome (ACVS). Yet, the effect of SBP is confounded by age, making its independent contribution to ACVS risk difficult to quantify. Here we use logistic regression to explore the role of SBP in younger and older ED patients. Methods: Data comprised 1019 ED patients (ACVS 70%, 30% non-ACVS) enrolled during a 28-month period of an ongoing prospective, observational, multi-site stroke biomarker study (SpecTRA). We used logistic regression to examine the effects of age, sex, and the age:SBP interaction as predictive markers of the diagnosis of ACVS. Results: Participants (53% male) ranged in age from 18 to 97 years (Q1=58, median=70, Q3=80). SBP ranged from 84 to 248 mmHg (Q1=137, median=154, Q3=174). In our initial regression model, age, sex, SBP and the age:SBP interaction were all significant (p&amp;lt;0.01). Using cubic regression splines for age, sbp and their interaction yields the same conclusion (p&amp;lt;0.01). To better understand the role of SBP in younger vs. older patients, we stratified the sample at the median age (70 years of age). In the younger group (n=510), participants were 55% male, 60% ACVS, and had SBP ranging from 91 to 236 mmHg (Q1=133, median=148, Q3=165). In the older group (n=509), participants were 51% male, 82% ACVS and had SBP ranging from 84 to 248 mmHg (Q1=143, median=159, Q3=179), a shift of approximately 10 mmHg between the groups. The logistic regression model was then fit separately to each group without the age:SBP interaction term. In the younger group, we found SBP to be highly significant (p&amp;lt;0.001), with an odds-ratio (OR) of 1.18 per 10 mmHg (95% CI: 1.10-1.29). In the older group, we found that SBP was not significant (p=0.91), with an OR of 1.00 per 10 mmHg (95% CI: 0.91-1.08). Age and sex were also significant risk factors in the younger group (each p&amp;lt;0.01), though not in the older group (both p&amp;gt;0.07). Conclusion: Our findings suggest that for ED patients suspected of ACVS, SBP is a clinically relevant predictor for younger patients, with higher SBP associated with an increased risk of ACVS, regardless of patient age and sex. SBP does not appear to be a strong predictor for patients over 70. ED physicians can leverage this finding by attributing greater importance to elevated SBP in younger patients than older patients when working toward a clinical suspicion of ACVS.

LO87: Use of a clinical prediction rule would lead to more effective CTA utilization for urgent brain imaging of suspected TIA/mild stroke in the emergency department

Introduction: Canadian stroke best practice guidelines recommend patients suspected of Acute Cerebrovascular Syndrome (ACVS) receive urgent brain imaging, preferably CTA. Yet, high requisition rates for non-ACVS patients overburdens limited radiological resources. We hypothesize that our clinical prediction rule (CPR) previously developed for diagnosis of ACVS in the emergency department (ED), and which incorporates Canadian guidelines, could improve CTA utilization. Methods: Our data consists of records for 1978 ED-referred patients to our TIA clinic in Victoria, BC from 2015-2016. Clinic referral forms captured all data needed for the CPR. For patients who received CTA, orders were placed in the ED or at the TIA clinic upon arrival. We use McNemar’s test to compare the sensitivity (sens) and specificity (spec) of our CPR vs. the baseline CTA orders for identifying ACVS. Results: Our sample (49.5% male, 60.6% ACVS) has a mean age of 70.9±13.6 yrs. Clinicians ordered 1190 CTAs (baseline) for these patients (60%). Where CTA was ordered, 65% of patients (n=768) were diagnosed as ACVS. To evaluate our CPR, predicted probabilities of ACVS were computed using the ED referral data. Those patients with probabilities greater than the decision threshold and presenting with at least one focal neurological deficit clinically symptomatic of ACVS were flagged as would have received a CTA. Our CPR would have ordered 1208 CTAs (vs. 1190 baseline). Where CTA would have been ordered, 74% of patients (n=893) had an ACVS diagnosis. This is a significantly improved performance over baseline (sens 74.5% vs. 64.1%, p&amp;lt;0.001; spec 59.6% vs. 45.9%, p&amp;lt;0.001). Specifically, the CPR would have ordered an additional 18 CTAs over the 2-yr period, while simultaneously increasing the number of imaged-ACVS patients by 125 with imaging 107 fewer non-ACVS patients. Conclusion: Using ED physician referral data, our CPR demonstrates significantly higher sensitivity and specificity for CTA imaging of ACVS patients than baseline CTA utilization. Moreover, our CPR would assist ED physicians to apply and practice the Canadian stroke best practice guidelines. ED physician use of our CPR would increase the number of ACVS patients receiving CTA imaging before ED discharge (rather than later at TIA clinics), and ultimately reduce the burden of false-positives on radiological departments.

Abstract WP46: Sex Differences in Therapeutic Targets in Ischemic Stroke

Sex differences exist in stroke epidemiology, acute presentation, treatment, and post-stroke clinical outcome. Neuroimaging can objectively identify potential pathological therapeutic targets and is reflective clinical observations. MCA occlusion (MCAO) is measurable by angiography and the presence of penumbra by diffusion-perfusion mismatch. We present evaluation of sex differences in the Lesion Evolution in Stroke and Ischemia On Neuroimaging (LESION) Project to determine if the probability of MCAO and penumbra depend on sex. We hypothesize imaging-based evidence is consistent with clinical observations of sex differences in severity and interactions with age and race. Methods: Patients included in the LESION study were diagnosed with acute ischemic cerebrovascular syndrome, had a brain MRI obtained within 24 hours from last known well and NIHSS&gt;3 or were treated with acute intervention with a pre-treatment MRI. MR imaging included DWI, FLAIR, MRA and PWI, which were co-localized over the entire brain. Patients with M1 or M2 abnormalities were graded as MCAO. The probability of having an MCAO or measurable pathological target was qualitatively evaluated as a function of sex with adjustment for age and race. Results: Women were more likely than men (all p&lt;0.05) to have a measurable of MCAO (OR [CI’s]) = (1.43 [1.08-1.89]), perfusion defect (1.42 [1.02-2.0]), or a diffusion-perfusion mismatch (1.35 [1.02-1.80]) (Table). This sex difference remained after adjusting for time from onset, NIHSS and age. Women over 70 years are most likely to have a measurable therapeutic target and white women are more likely to have a penumbral pattern than men or non-white women (p&lt;0.05). Conclusion: This preliminary imaging-based evidence is encouraging that sex differences in imaging biomarkers exist in a representative sample of acute stroke patients. This study shows that sex differences exist not only in the clinical phenotype, but in presence of a biological target.

Internal Carotid Artery Stenosis Associated with Hyoid Bone:Can Hyoid Bone be a Risk Factor for Acute Cerebrovascular Syndrome?

Eagle syndrome is a well-known disease caused by elongation of the styloid process and/or calcification of the stylohyoid ligament, which interferes with adjacent anatomical structures, giving rise to acute cerebrovascular syndrome(ACVS)and/or pain. Although hyoid bone is also a stylohyoid complex, its association with ACVS is not well known. Thus, we investigated the anatomical relationship between the internal carotid artery(ICA)and the hyoid bone. Between January 2014 and December 2015, three-dimensional computed tomographic angiography(3D-CTA)of the neck was performed for 218 patients. Of the patients, an abnormal anatomical relationship was noted in 10(4.6%)cases. In 5 cases, the ICA was entrapped by the hyoid bone. In 3 cases, the ICA was in contact with or adjusted to the hyoid bone. In 2 cases, the ICA was compressed by the hyoid bone, causing ACVS. In 7 cases, the position and course of the ICA were inward. In 4 of these cases, the hyoid bone was repositioned back to its normal location. Moreover, in 1 case, the course of the ICA was repositioned back to its normal location beside the hyoid bone. The anatomical position of the hyoid bone may vary more than expected and can be a risk factor for ACVS. In particular, in cases of ACVS where the ICA has an inward course, the relationship between the ICA and the hyoid bone should be proactively examined.

P.065 The impact of a risk algorithm on time-to-care: targeting triage for acute cerebrovascular syndrome (ACVS) patients in a rapid TIA clinic

Background: Approximately, one-third of TIA clinics use the ABCD2 score to triage referrals. However, the usefulness of the score is limited because of its low specificity for non-cerebrovascular/mimic conditions. Timely access of referred patients to specialized TIA clinics may reduce recurrent stroke. Methods: The SpecTRA project implemented a novel electronic triage system in the TIA clinic that services Vancouver Island (BC), which replaced the existing ABCD2 triage model. A clinical classifier generating an ACVS probability score was calculated on the basis of the clinic referral form information. Next, a time-varying ABCD2-based risk score derived from Johnston et al. (2007) was calculated, which is then weighted by the ACVS probability score to produce a finalized triage score. Time-to-care was compared pre- (2013/14) and post- (2014/15) implementation. Results: One year results show a statistically significant improvement in that time-to-care for ACVS patients (ABCD2 4/5) was one day earlier with the new triage system (median= 4days since symptom onset; N=250) compared to the previous year (median=5days; N=255) (Mann-Whitney U=38130, p&lt; 0.001). No difference in unit arrival times (median= 5days) for non-cerebrovascular patients was observed (Mann-Whitney U=5563, p= 0.15). Conclusions: The performance of our ACVS triage system highlights quality improvement potential in time-to-care for outpatient TIA clinics.

LO011: Identification of mild acute cerebrovascular syndrome (ACVS) in the emergency department: validation of an ACVS clinical classifier to help distinguish mimics

Introduction: National guidelines (NICE, AHA) for management of Acute Cerebrovascular Syndrome (ACVS) in the Emergency Department (ED) recommend the use of ABCD2 score to risk stratify patients despite its poor specificity and low diagnostic accuracy. The SpecTRA project previously developed a clinical classifier for ACVS vs. Mimic derived from historical clinical data collected during a 5-year period at an outpatient stroke clinic (Victoria, BC). Here we present a prospective evaluation of the performance of our clinical classifier on prospectively collected ED patient data compared to the industry-standard ABCD2. Methods: The prospective cohort consisted of ED patients (N=555, Male=54%, Mean (SD) Age=68.7(15.5), ACVS=70%) enrolled between Jan 2014 and May 2015 at Victoria General Hospital (BC) and Foothills Medical Centre (Calgary, AB). ABCD2 and clinical classifier scores were calculated from clinical data from the ED. We compared the performance of the two classifiers using DeLong’s test of Dependent Receiver Operating Curves (ROC). In keeping with national guidelines, we used a score of 4 or more to assess sensitivity, specificity and accuracy (sens/spec and acc) of the ABCD2; for our clinical classifier, we used the cut point previously determined to maximize agreement between predictions and true class labels in the historical data. Results: Our new clinical classifier significantly outperformed the ABCD2 (z=2.44, p=0.015) with an AUC of 0.72, (95% CI: 0.68, 0.77) vs. 0.66 (0.61, 0.71). In terms of sens/spec and acc, our classifier achieved 0.78/0.55 with acc 71% compared to 0.75/0.46 with acc 66% for the ABCD2 (using the previously specified cut points). Conclusion: Our ACVS clinical classifier showed better performance than the ABCD2 score on a prospective sample of ED patients. The improved specificity of the clinical classifier relative to existing prognostic tools would reduce the number of non-ACVS patients referred for early treatment as well as conserve medical resources. Our ongoing multi-site study will evaluate the utility of the ACVS classifier embedded in a logic-enabled e-fillable form. This form will also provide risk-based thresholds guiding timely ordering of CTA as well as links to clinical treatment guidelines. Longer-term, the e-form and classifiers will be further enhanced to include plasma-based protein biomarker data.

Abstract TMP95: Large Centralized TIA Assessment Unit Associated With Reduction of Recurrent Stroke by up to 70%

Introduction: Transient neurological symptoms are a common presentation in emergency departments (ED). Access to stroke specialists and advanced imaging to identify acute cerebrovascular syndrome is resource intensive. Diversion to specialized TIA units improves logistics but incurs delay. Observational studies suggest efficacy of TIA units but are limited by sample size. We hypothesized that management through a centralized TIA service reduces risk of recurrent stroke. Methods: Vancouver Island (VI) introduced a centralized TIA unit in 2004 to which over 15,000 referrals (ED &amp; GP) have been made. Long-term follow-up is possible as all VI residents (∼750,000) have one electronic health record for ED visits and hospital admissions. Large referral volumes and variable unit capacity have subjected patients to a wide range of delays-to-treatment. We used variation in secondary prevention delays to examine unit efficacy. We assessed hospitalized stroke and stroke death in all ED-referred patients comparing those seen in the unit within 90 days of symptom onset with those not seen within that time. Results: Between 2005 and 2013 there were 11,330 referrals, of which 4,017 were from the ED and referred within 2 weeks of symptom onset. The transition times between symptom onset, referral, arrival at the unit and stroke (or censoring time) were modeled using a multi-state model (Putter et al. 2007). Age, ABCDD, gender and the unit intervention were found to be associated with transition times. The hazard of stroke for patients who attended the unit was estimated as 30% that of those who did not attend (p=0.098). Predicted stroke-free survival curves are shown for a 70 year old woman. ARR at 90-days ranged from 4.2% downto 1.4% for High to Low ABCDD respectively. Conclusion: This large observational study reinforces published studies suggesting TIA units reduce risk of recurrent stroke within 90 days.

Implementation of a Community-Based Triage for Patients with Suspected Transient Ischemic Attack or Minor Stroke Study: A Prospective Multicenter Observational Study

Japan has the highest number of magnetic resonance imaging units in the world, and citizens can freely choose medical care at any hospital or clinic. We aimed to investigate the triage of patients with suspected transient ischemic attack (TIA) or minor stroke in this unique Japanese healthcare system. In this cohort study, patients with suspected TIA or minor stroke (National Institutes of Health Stroke Scale score <4) within 7 days after onset were prospectively enrolled and followed for 1 year. The high-risk group was defined as having at least one of the following 5 items at the initial visit: (1) atrial fibrillation, (2) carotid stenosis, (3) crescendo TIA, (4) definite focal brain symptoms, or (5) ABCD2 score of 4 or higher. After the initial assessment, the patients were diagnosed as having acute ischemic cerebrovascular syndrome (AICS) or stroke mimic. AICS was classified into 3 categories including definite, probable, and possible AICS, based on evidence of neurological deficits and brain infarction on the imaging study. A total of 353 patients were enrolled and 89.8% of the patients were examined by diffusion-weighted imaging at the initial visit. Kaplan-Meier analyses demonstrated a statistically significant difference in subsequent stroke risk when the patients were triaged by the ABCD2 score (P = .031), 5-item high-risk categorization (P = .032), or AICS classification (P = .001). This study demonstrates that hospitals and clinics with imaging facilities play a major role in triage and that the ABCD2 score, 5-item high-risk categorization, and AICS classification are useful as triage tools for patients with suspected TIA or minor stroke.

Pathophysiology of acute cerebrovascular syndrome in patients with carotid artery stenosis: a magnetic resonance imaging/single-photon emission computed tomography study.

The mechanisms underlying acute cerebrovascular syndrome in patients with carotid artery stenosis remain unclear. To assess the relationships among infarct localization, hemodynamics, and plaque components. This prospective study included 38 patients with acute cerebrovascular syndrome resulting from ipsilateral carotid artery stenosis. Cerebral infarct localization was categorized into 3 patterns (cortical, border zone, and mixed pattern). Carotid plaque components were evaluated with T1-weighted magnetic resonance imaging and time-of-flight imaging. Cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) were also quantified. Infarcts were identified in 38 patients with the use of diffusion-weighted magnetic resonance imaging. On the basis of the assessment of hemodynamics, the cortical pattern was seen in 18 of 21 patients with type 1 ischemia (normal CBF, normal CVR), whereas the mixed pattern was seen in 2 patients with type 2 ischemia (normal CBF, impaired CVR) and 12 of 15 patients with type 3 ischemia (impaired CBF, impaired CVR). The plaque components were categorized into fibrous (4 patients), lipid-rich (14 patients), and intraplaque hemorrhage (IPH; 20 patients). Of the patients with fibrous plaque, 2 had border-zone and 2 had mixed-pattern infarcts. Of the patients with lipid-rich plaque, 7 had cortical and 6 had mixed-pattern infarcts. Of patients with intraplaque hemorrhage, 11 had cortical and 9 had mixed-pattern infarcts. Cortical infarction occurs as a result of vulnerable plaque. Reduced cerebral perfusion induces border-zone infarction. Both factors are implicated in mixed-pattern infarction. Developments in noninvasive diagnostic modalities allow us to explore the mechanisms behind acute cerebrovascular syndrome in carotid artery stenosis and to determine the ideal therapies.

急性脳血管症候群としての一過性脳虚血発作

要旨：発症後早期の一過性脳虚血発作（TIA）は急性虚血性脳卒中（AIS）を続発する危険性が高い．TIA とAIS は同一スペクトラム上にある急性脳虚血病態であり，発症後早期のTIA はAIS とともに急性脳血管症候群（ACVS）の概念に包括し，救急疾患として対処すべきである．ACVS の概念は急性冠症候群（ACS）の概念に相当するが，ACVS はACS と病態を共有するアテローム血栓症のみならず，心原性塞栓症や小血管病もあり，その病態はより複雑である．また，ACVS にはACS のような実用的バイオマーカーがまだ存在しない．循環器の分野ではACS のハートアタックキャンペーンにより死亡率が大幅に減少したという成功例があり，脳神経の分野でもACVS の概念によるTIA の啓発は死亡または身体障害の最大の原因である脳卒中を予防する水際作戦として大きな効果が期待される．