Kristine Votova

Background: Magnetic resonance imaging infarct topography may assist with determining stroke etiology. The influence of diffusion‐weighted imaging (DWI)‐positive lesions on etiology determination in patients with transient ischemic attack or minor stroke is not well studied. Methods and Results: We prospectively enrolled patients between 2010 and 2017 in 2 studies; participants with a final diagnosis of probable or definite transient ischemic attack or stroke were pooled for analysis. The primary outcome was the adjudicated ischemic etiology. We compared proportion of each etiology (cardioembolic, large‐vessel, small‐vessel disease, other) in patients who had DWI positivity compared with DWI negativity. We used logistic regression to determine the adjusted odds ratio (OR) for each etiology compared with undetermined by DWI positivity. The final analysis included 1498 patients: 832 (55.5%) were DWI‐positive. DWI‐positive patients were more likely to be diagnosed with small‐vessel disease (19.1% versus 5.3%) and less likely with undetermined etiology (36.9% versus 53.0%; P <0.001). After adjustment, the presence of any DWI lesion was associated with increased odds of assigning any etiology (OR, 1.8 [95% CI, 1.3–2.5]). A single DWI lesion was associated with increased odds of small‐vessel disease diagnosis (OR, 9.5 [95% CI, 6.4–14.0]), and multiple DWI lesions with reduced odds of small‐vessel disease (OR, 0.2 [95% CI, 0.1–0.4]) but increased odds of all other etiologies compared with undetermined etiology. Conclusions: Any DWI‐positive lesion after suspected transient ischemic attack or minor stroke was associated with increased odds of assigning a etiology. Presence and topography of DWI lesions on magnetic resonance imaging may assist with etiology determination and may impact stroke prevention therapies.

Background: Elevated blood pressure (BP) at emergency department (ED) presentation and advancing age have been associated with risk of ischemic stroke; however, the relationship between BP, age, and transient ischemic attack/minor stroke (TIA/MS) is not clear. Methods: A multi-site, prospective, observational study of 1084 ED patients screened for suspected TIA/MS (symptom onset < 24 h, NIHSS< 4) between December 2013 and April 2016. Systolic and diastolic BP measurements (SBP, DBP) were taken at ED presentation. Final diagnosis was consensus adjudication by stroke neurologists; patients were diagnosed as either TIA/MS or stroke-mimic (non-cerebrovascular conditions). Conditional inference trees were used to define age cut-points for predicting binary diagnosis (TIA/MS or stroke-mimic). Logistic regression models were used to estimate the effect of BP, age, sex, and the age-BP interaction on predicting TIA/MS diagnosis. Results: Over a 28-month period, 768 (71%) patients were diagnosed with TIA/MS: these patients were older (mean 71.6 years) and more likely to be male (58%) than stroke-mimics (61.4 years, 41%; each p < 0.001). TIA/MS patients had higher SBP than stroke-mimics (p < 0.001). DBP did not differ between the two groups (p = 0.191). SBP was predictive of TIA/MS diagnosis in younger patients, after accounting for age and sex; an increase of 10 mmHg systolic increased the odds of TIA/MS 18% (odds ratio [OR] 1.18, 95% CI 1.00–1.39) in patients < 60 years, and 23% (OR 1.23, 95% CI 11.12–1.35) in those 60–79 years, while not affecting the odds of TIA/MS in patients ≥80 years (OR 0.99, 95% CI 0.89–1.07). Conclusions: Raised SBP in patients younger than 80 with suspected TIA/MS may be a useful clinical indicator upon initial presentation to help increase clinicians’ suspicion of TIA/MS. Trial registration: ClinicalTrials.gov NCT03050099 (10-Feb-2017) and NCT03070067 (3-Mar-2017). Retrospectively registered.

ObjectivesThe Canadian Stroke Best Practice Recommendations suggests that patients suspected of transient ischemic attack (TIA)/minor stroke receive urgent brain imaging, preferably computed tomography angiography (CTA). Yet, high requisition rates for non-cerebrovascular patients overburden limited radiological resources, putting patients at risk. We hypothesize that our clinical decision support tool (CDST) developed for risk stratification of TIA in the emergency department (ED), and which incorporates Canadian guidelines, could improve CTA utilization.MethodsRetrospective study design with clinical information gathered from ED patient referrals to an outpatient TIA unit in Victoria, BC, from 2015-2016. Actual CTA orders by ED and TIA unit staff were compared to hypothetical CTA ordering if our CDST had been used in the ED upon patient arrival.ResultsFor 1,679 referrals, clinicians ordered 954 CTAs. Our CDST would have ordered a total of 977 CTAs for these patients. Overall, this would have increased the number of imaged-TIA patients by 89 (10.1%) while imaging 98 (16.1%) fewer non-cerebrovascular patients over the 2-year period. Our CDST would have ordered CTA for 18 (78.3%) of the recurrent stroke patients in the sample.ConclusionsOur CDST could enhance CTA utilization in the ED for suspected TIA patients, and facilitate guideline-based stroke care. Use of our CDST would increase the number of TIA patients receiving CTA before ED discharge (rather than later at TIA units) and reduce the burden of imaging stroke mimics in radiological departments. ObjectifsD’après les lignes directrices canadiennes sur les pratiques exemplaires en matière de prise en charge des accidents vasculaires cérébraux (AVC), il est recommandé de pratiquer d’urgence, dans les cas présumés d’accident ischémique transitoire (AIT) ou d’AVC léger, un examen par imagerie cérébrale, de préférence une angiographie par tomodensitométrie (TDM). Toutefois, le nombre élevé de demandes d’examen chez les patients exempts de lésions vasculaires cérébrales exerce une pression à la hausse sur les ressources disponibles en radiologie, d’où une augmentation du risque chez les patients concernés. Aussi l’étude visait-elle à vérifier si l’outil d’aide à la décision clinique (OADC) que l’équipe a élaboré pour l’évaluation du risque d’AIT au service des urgences (SU) et qui tient compte des lignes directrices en vigueur au Canada aurait permis une utilisation plus rationnelle de l’angiographie par TDM.MéthodeIl s’agit d’une étude rétrospective reposant sur la collecte de renseignements cliniques, tirés de demandes d’examens faites par des SU à un service de consultations externes spécialisé dans le traitement des AIT, à Victoria, en Colombie-Britannique, de 2015 à 2016. Ont été comparés le nombre réel de demandes d’angiographie par TDM faites par le personnel de SU et du service spécialisé dans le traitement des AIT, et le nombre hypothétique de demandes d’angiographie par TDM si l’OADC avait été utilisé au SU, à l’arrivée des patients.RésultatsSur 1679 demandes de consultation, il y a eu 954 demandes d’angiographie par TDM faites par des cliniciens. Si l’OADC avait été appliqué, le nombre total d’angiographies par TDM se serait élevé à 977 chez les patients concernés, ce qui se serait traduit, dans l’ensemble, par une augmentation de 89 (10,1 %) demandes d’examens par imagerie chez les patients ayant subi un AIT et une diminution de 98 (16,1 %) chez les patients exempts de lésions vasculaires cérébrales, sur la période de 2 ans. Ainsi, l’OADC aurait permis de faire une demande d’angiographie par TDM chez 18 (78,3 %) des patients ayant subi une récidive d’AVC, dans l’échantillon étudié.ConclusionL’application de l’OADC permettrait une utilisation plus rationnelle de l’angiographie par TDM, au SU, chez les patients atteints d’un AIT présumé, et faciliterait la prestation de soins fondés sur les lignes directrices dans les cas d’AVC. Ce faisant, il y aurait une augmentation du nombre d’angiographies par TDM pratiquées chez les patients souffrant d’un AIT avant le congé du SU (plutôt qu’après, dans les services de traitement des AIT) ainsi qu’une réduction du fardeau imposé par les affections simulant un AVC, quant au nombre d’examens par imagerie, sur les services de radiologie.

OBJECTIVE: To validate our previously developed 16 plasma-protein biomarker panel to differentiate between transient ischaemic attack (TIA) and non-cerebrovascular emergency department (ED) patients. METHOD: Two consecutive cohorts of ED patients prospectively enrolled at two urban medical centers into the second phase of SpecTRA study (training, cohort 2A, n = 575; test, cohort 2B, n = 528). Plasma samples were analyzed using liquid chromatography/multiple reaction monitoring-mass spectrometry. Logistic regression models which fit cohort 2A were validated on cohort 2B. RESULTS: Three of the panel proteins failed quality control and were removed from the panel. During validation, panel models did not outperform a simple motor/speech (M/S) deficit variable. Post-hoc analyses suggested the measured behaviour of L-selectin and coagulation factor V contributed to poor model performance. Removal of these proteins increased the external performance of a model containing the panel and the M/S variable. CONCLUSIONS: Univariate analyses suggest insulin-like growth factor-binding protein 3 and serum paraoxonase/lactonase 3 are reliable and reproducible biomarkers for TIA status. Logistic regression models indicated L-selectin, apolipoprotein B-100, coagulation factor IX, and thrombospondin-1 to be significant multivariate predictors of TIA. We discuss multivariate feature subset analyses as an exploratory technique to better understand a panel’s full predictive potential.

To evaluate the performance of a novel triage system for Transient Ischemic Attack (TIA) units built upon an existent clinical prediction rule (CPR) to reduce time to unit arrival, relative to the time of symptom onset, for true TIA and minor stroke patients. Differentiating between true and false TIA/minor stroke cases (mimics) is necessary for effective triage as medical intervention for true TIA/minor stroke is time-sensitive and TIA unit spots are a finite resource. Prospective cohort study design utilizing patient referral data and TIA unit arrival times from a regional fast-track TIA unit on Vancouver Island, Canada, accepting referrals from emergency departments (ED) and general practice (GP). Historical referral cohort (N = 2942) from May 2013–Oct 2014 was triaged using the ABCD2 score; prospective referral cohort (N = 2929) from Nov 2014–Apr 2016 was triaged using the novel system. A retrospective survival curve analysis, censored at 28 days to unit arrival, was used to compare days to unit arrival from event date between cohort patients matched by low (0–3), moderate (4–5) and high (6–7) ABCD2 scores. Survival curve analysis indicated that using the novel triage system, prospectively referred TIA/minor stroke patients with low and moderate ABCD2 scores arrived at the unit 2 and 1 day earlier than matched historical patients, respectively. The novel triage process is associated with a reduction in time to unit arrival from symptom onset for referred true TIA/minor stroke patients with low and moderate ABCD2 scores.

Objective: To derive a plasma biomarker protein panel from a list of 141 candidate proteins which can differentiate transient ischaemic attack (TIA)/minor stroke from non-cerebrovascular (mimic) conditions in emergency department (ED) settings. Design: Prospective clinical study (#NCT03050099) with up to three timed blood draws no more than 36 h following symptom onset. Plasma samples analysed by multiple reaction monitoring-mass spectrometry (MRM-MS). Participants: Totally 545 participants suspected of TIA enrolled in the EDs of two urban medical centres. Outcomes: 90-day, neurologist-adjudicated diagnosis of TIA informed by clinical and radiological investigations. Results: The final protein panel consists of 16 proteins whose patterns show differential abundance between TIA and mimic patients. Nine of the proteins were significant univariate predictors of TIA [odds ratio (95% confidence interval)]: L-selectin [0.726 (0.596–0.883)]; Insulin-like growth factor-binding protein 3 [0.727 (0.594–0.889)]; Coagulation factor X [0.740 (0.603–0.908)]; Serum paraoxonase/lactonase 3 [0.763 (0.630–0.924)]; Thrombospondin-1 [1.313 (1.081–1.595)]; Hyaluronan-binding protein 2 [0.776 (0.637–0.945)]; Heparin cofactor 2 [0.775 (0.634–0.947)]; Apolipoprotein B-100 [1.249 (1.037–1.503)]; and von Willebrand factor [1.256 (1.034–1.527)]. The scientific plausibility of the panel proteins is discussed. Conclusions: Our panel has the potential to assist ED physicians in distinguishing TIA from mimic patients.

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.

We validate our previously developed (DOI: 10.1101/089227) clinical prediction rule for diagnosing transient ischemic attack on the basis of presenting clinical symptoms and compare its performance with the ABCD2 score in first-contact patient settings. Two independent and prospectively collected patient validation cohorts were used: (a) referral cohort–prospectively referred emergency department and general practitioner patients (N = 877); and (b) SpecTRA cohort–participants recruited as part of the SpecTRA biomarker project (N = 545). Outcome measure consisted of imaging-confirmed clinical diagnosis of mild stroke/transient ischemic attack. Results showed that our clinical prediction rule demonstrated significantly higher accuracy than the ABCD2 score for both the referral cohort (70.5% vs 59.0%; p < 0.001) and SpecTRA cohort (72.8% vs 68.3%; p = 0.028). We discuss the potential of our clinical prediction rule to replace the use of the ABCD2 score in the triage of transient ischemic attack clinic referrals.

OBJECTIVE: To develop a clinical prediction model for diagnosing mild stroke/transient ischemic attack (TIA) in first-contact patient settings. DESIGN: Retrospective study design utilizing logistic regression modeling of patient clinical symptoms collected from patient chart histories and referral data. SETTING: Regional fast-track TIA clinic on Vancouver Island, Canada, accepting referrals from emergency departments (ED) and general practice (GP). PARTICIPANTS: Model development: 4187 ED and GP referred patients from 2008–2011 who were assessed at the TIA clinic. Temporal hold-out validation: 1953 ED and GP referred patients from 2012–2013 assessed at the same clinic. OUTCOMES: Diagnosis of mild stroke/TIA by clinic neurologists. RESULTS: 123 candidate predictors were assessed using univariate feature selection for inclusion in the model, and culminated in the selection of 50 clinical features. Post-hoc investigation of the selected predictors revealed 12 clinically relevant interaction terms. Model performance on the temporal hold-out validation set achieved a sensitivity/specificity of 71.8% / 72.8% using the ROC01 cutpoint (≥ 0.662), and an AUC of 79.9% (95% CI, 77.9%–81.9%). In comparison, the ABCD2 score (≥ 4) achieved a sensitivity/specificity of 70.4% / 54.5% and an AUC of 67.5% (95% CI, 65.2%–69.9%). The logistic regression model demonstrated good calibration on the hold-out set (β ₀ = −0.257); β _linear = 1.047). CONCLUSIONS: The developed diagnostic model performs better than the ABCD2 score at diagnosing mild stroke/TIA on the basis of clinical symptoms. The model has the potential to replace the use of the prognostic ABCD2 score in diagnostic medical contexts in which the ABCD2 score is currently used, such as patient triage.