Multiphase CT angiography perfusion maps for predicting target mismatch and ischemic lesion volumes.

The complexity of CT perfusion (CTP) acquisition protocols may limit the availability of target mismatch assessment at resource-limited hospitals. We compared CTP mismatch with a mismatch surrogate generated from a simplified dynamic imaging sequence comprising widely available non-contrast CT (NCCT) and multiphase CT angiography (mCTA). Consecutive patients with anterior circulation acute ischemic stroke who received NCCT, mCTA, and CTP were retrospectively included in this study. An mCTA-perfusion (mCTA-P) dynamic series was formed by co-registering NCCT and mCTA. We simulated an ideal mCTA-P study by down-sampling CTP (dCTP) dynamic images according to mCTA timing. Ischemic core and penumbra volumes were estimated by cerebral blood flow and Tmax thresholding, respectively, on perfusion maps calculated independently for CTP, dCTP, and mCTA-P by deconvolution. Concordance in target mismatch (core < 70 ml, penumbra ≥ 15 ml, mismatch ratio ≥ 1.8) determination by dCTP and mCTA-P versus CTP was assessed. Of sixty-one included patients, forty-six had a CTP target mismatch. Concordance with CTP profiles was 90% and 82% for dCTP and mCTA-P, respectively. Lower mCTA-P concordance was likely from differences in collimation width between NCCT and mCTA, which worsened perfusion map quality due to a CT number shift at mCTA. Moderate diagnostic agreement between CTP and mCTA-P was found and may improve with optimal mCTA scan parameter selection as simulated by dCTP. mCTA-P may be a pragmatic alternative where CTP is unavailable or the risks of additional radiation dose, contrast injections, and treatment delays outweigh the potential benefit of a separate CTP scan.

Probing Evidence of Cerebral White Matter Microstructural Disruptions in Ischemic Heart Disease Before and Following Cardiac Rehabilitation: A Diffusion Tensor MR Imaging Study.

BACKGROUND: Ischemic heart disease (IHD) is linked to brain white matter (WM) breakdown but how age or disease effects WM integrity, and whether it is reversible using cardiac rehabilitation (CR), remains unclear. PURPOSE: To assess the effects of brain aging, cardiovascular disease, and CR on WM microstructure in brains of IHD patients following a cardiac event. STUDY TYPE: Retrospective. POPULATION: Thirty-five IHD patients (9 females; mean age = 59 ± 8 years), 21 age-matched healthy controls (10 females; mean age = 59 ± 8 years), and 25 younger controls (14 females; mean age = 26 ± 4 years). FIELD STRENGTH/SEQUENCE: 3 T diffusion-weighted imaging with single-shot echo planar imaging acquired at 3 months and 9 months post-cardiac event. ASSESSMENT: Tract-based spatial statistics (TBSS) and tractometry were used to compare fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in cerebral WM between: 1) older and younger controls to distinguish age-related from disease-related WM changes; 2) IHD patients at baseline (pre-CR) and age-matched controls to investigate if cardiovascular disease exacerbates age-related WM changes; and 3) IHD patients pre-CR and post-CR to investigate the neuroplastic effect of CR on WM microstructure. STATISTICAL TESTS: Two-sample unpaired t-test (age: older vs. younger controls; IHD: IHD pre-CR vs. age-matched controls). One-sample paired t-test (CR: IHD pre- vs. post-CR). Statistical threshold: P < 0.05 (FWE-corrected). RESULTS: TBSS and tractometry revealed widespread WM changes in older controls compared to younger controls while WM clusters of decreased FA in the fornix and increased MD in body of corpus callosum were observed in IHD patients pre-CR compared to age-matched controls. Robust WM improvements (increased FA, increased AD) were observed in IHD patients post-CR. DATA CONCLUSION: In IHD, both brain aging and cardiovascular disease may contribute to WM disruptions. IHD-related WM disruptions may be favorably modified by CR. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Exploring sex differences for acute ischemic stroke clinical, imaging and thrombus characteristics in the INTERRSeCT study.

Women, especially following menopause, are known to have worse outcomes following acute ischemic stroke. One primary postulated biological mechanism for worse outcomes in older women is a reduction in the vasculoprotective effects of estrogen. Using the INTERRseCT cohort, a multicentre international observational cohort studying recanalization in acute ischemic stroke, we explored the effects of sex, and modifying effects of age, on neuroradiological predictors of recanalization including robustness of leptomeningeal collaterals, thrombus burden and thrombus permeability. Ordinal regression analyses were used to examine the relationship between sex and each of the neuroradiological markers. Further, we explored both multiplicative and additive interactions between age and sex. All patients (n = 575) from INTERRseCT were included. Mean age was 70.2 years (SD: 13.1) and 48.5% were women. In the unadjusted model, female sex was associated with better collaterals (OR 1.37, 95% CIs: 1.01-1.85), however this relationship was not significant after adjusting for age and relevant comorbidities. There were no significant interactions between age and sex. In a large prospective international cohort, we found no association between sex and radiological predictors of recanalization including leptomeningeal collaterals, thrombus permeability and thrombus burden.

Differences in Stroke Recurrence Risk Between Atrial Fibrillation Detected on ECG and 14-Day Cardiac Monitoring.

BACKGROUND: Ischemic stroke and transient ischemic attack (TIA) standard-of-care etiological investigations include an ECG and prolonged cardiac monitoring (PCM). Atrial fibrillation (AF) detected after stroke has been generally considered a single entity, regardless of how it is diagnosed. We hypothesized that ECG-detected AF is associated with a higher risk of stroke recurrence than AF detected on 14-day Holter (PCM-detected AF). METHODS: We conducted a retrospective, registry-based, cohort study of consecutive patients with ischemic stroke and TIA included in the London Ontario Stroke Registry between 2018 and 2020, with ECG-detected and PCM-detected AF lasting ≥30 seconds. We quantified PCM-detected AF burden. The primary outcome was recurrent ischemic stroke, ascertained by systematically reviewing all medical records until November 2022. We applied marginal cause-specific Cox proportional hazards models adjusted for qualifying event type (ischemic stroke versus TIA), CHA2DS2-VASc score, anticoagulation, left ventricular ejection fraction, left atrial size, and high-sensitivity troponin T to estimate adjusted hazard ratios for recurrent ischemic stroke. RESULTS: We included 366 patients with ischemic stroke and TIA with AF, 218 ECG-detected, and 148 PCM-detected. Median PCM duration was 12 (interquartile range, 8.8-14.0) days. Median PCM-detected AF duration was 5.2 (interquartile range, 0.3-33.0) hours, with a burden (total AF duration/total net monitoring duration) of 2.23% (interquartile range, 0.13%-12.25%). Anticoagulation rate at the end of follow-up or at the first event was 83.1%. After a median follow-up of 17 (interquartile range, 5-34) months, recurrent ischemic strokes occurred in 16 patients with ECG-detected AF (13 on anticoagulants) and 2 with PCM-detected AF (both on anticoagulants). Recurrent ischemic stroke rates for ECG-detected and PCM-detected AF groups were 4.05 and 0.72 per 100 patient-years (adjusted hazard ratio, 5.06 [95% CI, 1.13-22.7]; P=0.034). CONCLUSIONS: ECG-detected AF was associated with 5-fold higher adjusted recurrent ischemic stroke risk than PCM-detected AF in a cohort of ischemic stroke and TIA with >80% anticoagulation rate.

Feasibility of deconvolution-based multiphase CT angiography perfusion maps in acute ischemic stroke: Simulation and concordance with CT perfusion.

OBJECTIVES: Integration of CT perfusion (CTP) with requisite non-contrast CT and CT angiography (CTA) stroke imaging may allow efficient stroke lesion volume measurement. Using surrogate images from CTP, we simulated the feasibility of using multiphase CTA (mCTA) to generate perfusion maps and assess target mismatch profiles. MATERIALS AND METHODS: Patients with acute ischemic stroke who received admission CTP were included in this study. Four CTP images (surrogate mCTA, one pre-contrast and three post-contrast, starting at the arterial peak then at 8 s intervals) were selected according to the CTP arterial time-density curve to simulate non-contrast CT and mCTA images. Cerebral blood flow (CBF) and Tmax maps were calculated using the same model-based deconvolution algorithm for the standard CTP and surrogate mCTA studies. Infarct and penumbra were delineated with CBF < 20% and Tmax > 6 s threshold, respectively. Classification accuracy of surrogate mCTA target mismatch (infarct <70 ml; penumbra ≥15 ml; mismatch ratio ≥1.8) with respect to standard CTP was assessed. Agreement between infarct and penumbra volumes from standard CTP and surrogate mCTA maps were evaluated by Bland-Altman analysis. RESULTS: Of 34 included patients, 28 had target mismatch and 6 did not by standard CTP. Accuracy of classifying target mismatch profiles with surrogate mCTA was 79% with respect to that from standard CTP. Mean  ±  standard deviation of differences (standard CTP minus surrogate mCTA) of infarct and penumbra volumes were 9.8 ± 14.8 ml and 20.1 ± 45.4 ml, respectively. CONCLUSIONS: Surrogate mCTA ischemic lesion volumes agreed with those from standard CTP and may be an efficient alternative when CTP is not practical.

Low-dose CT Perfusion with Sparse-view Filtered Back Projection in Acute Ischemic Stroke.

RATIONALE AND OBJECTIVES: Radiation dose associated with computed tomography (CT) perfusion (CTP) may discourage its use despite its added diagnostic benefit in quantifying ischemic lesion volume. Sparse-view CT reduces scan dose by acquiring fewer X-ray projections per gantry rotation but is contaminated by streaking artifacts using filtered back projection (FBP). We investigated the achievable dose reduction by sparse-view CTP with FBP without affecting CTP lesion volume estimations. MATERIALS AND METHODS: Thirty-eight consecutive patients with acute ischemic stroke and CTP were included in this simulation study. CTP projection data was simulated by forward projecting original reconstructions with 984 views and adding Gaussian noise. Full-view (984 views) and sparse-view (492, 328, 246, and 164 views) CTP studies were simulated by FBP of simulated projection data. Cerebral blood flow (CBF) and time-to-maximum of the impulse residue function (Tmax) maps were generated by deconvolution for each simulated CTP study. Ischemic volumes were measured by CBF<30% relative to the contralateral hemisphere and Tmax > 6 s. Volume accuracy was evaluated with respect to the full-view CTP study by the Friedman test with post hoc multiplicity-adjusted pairwise tests and Bland-Altman analysis. RESULTS: Friedman and multiplicity-adjusted pairwise tests indicated that 164-view CBF < 30%, 246- and 164-view Tmax > 6 s volumes were significantly different to full-view volumes (p < 0.001). Mean difference ± standard deviation (sparse minus full-view lesion volume) ranged from -1.0 ± 2.8 ml to -4.1 ± 11.7 ml for CBF < 30% and -2.9 ± 3.8 ml to -12.5 ± 19.9 ml for Tmax > 6 s from 492 to 164 views, respectively. CONCLUSION: By ischemic volume accuracy, our study indicates that sparse-view CTP may allow dose reduction by up to a factor of 3.

Time-resolved assessment of cortical venous drainage on multiphase CT angiography in patients with acute ischemic stroke.

PURPOSE: Cortical vein opacification is not routinely assessed in patients presenting with acute ischemic stroke (AIS), and the value of temporal assessment of venous outflow is not known. We evaluated the utility of assessing cortical venous drainage over time using multiphase CT angiography (mCTA). METHODS: Cortical venous drainage was assessed in patients from the Precise and Rapid Assessment of Collaterals Using Multi-Phase CTA in the Triage of Patients With Acute Ischemic Stroke for IA Therapy prospective multicenter cohort study of patients with symptoms of AIS with ICA and/or middle cerebral artery occlusion on baseline mCTA. Opacification of vein of Labbe, sphenoparietal sinus, superficial middle cerebral vein, and vein of Trolard of the affected hemisphere was graded as no (0), partial (1), or full (2) opacification in each mCTA phase. The venous opacification scores for each phase were added to generate a total venous score (TVS) (range 0-24). Primary outcome was 90-day modified Rankin score. Repeated measures analysis was used to assess the effect of phase timing on venous score on outcome. RESULTS: Of 432 patients, 284 (65.7%) had proximal arterial occlusions. Median venous opacification score per phase (range 0-8) was 3 (IQR 1-6) in the first phase and increased in the second and third phases [median (IQR): 6 (5-8) and 8 (6-8), respectively] of the mCTA. In a multivariable analysis adjusting for age, baseline National Institutes of Health Stroke Scale, and Alberta stroke program early CT score, a significant association between TVS and 90-day mRS was noted ([adjusted cOR for TVS 6-11: 0.16 (95% CI 0.05-0.51); TVS 12-17: 0.18 (95% CI 0.06-0.57); TVS 18-24: 0.20 (0.06-0.63)]. Repeated measures analysis of venous scores from all three phases showed a significant effect of time/phase on TVS (p < 0.001). CONCLUSION: This study concludes that venous opacification over time on multiphase CTA is associated with 90-day clinical outcome. There was however no added benefit of venous scoring vis-a-vis arterial collateral assessment in predicting outcome.

Determinants of Leptomeningeal Collateral Status Variability in Ischemic Stroke Patients.

BACKGROUND: Collateral status is an indicator of a favorable outcome in stroke. Leptomeningeal collaterals provide alternative routes for brain perfusion following an arterial occlusion or flow-limiting stenosis. Using a large cohort of ischemic stroke patients, we examined the relative contribution of various demographic, laboratory, and clinical variables in explaining variability in collateral status. METHODS: Patients with acute ischemic stroke in the anterior circulation were enrolled in a multi-center hospital-based observational study. Intracranial occlusions and collateral status were identified and graded using multiphase computed tomography angiography. Based on the percentage of affected territory filled by collateral supply, collaterals were graded as either poor (0-49%), good (50-99%), or optimal (100%). Between-group differences in demographic, laboratory, and clinical factors were explored using ordinal regression models. Further, we explored the contribution of measured variables in explaining variance in collateral status. RESULTS: 386 patients with collateral status classified as poor (n = 64), good (n = 125), and optimal (n = 197) were included. Median time from symptom onset to CT was 120 (IQR: 78-246) minutes. In final multivariable model, male sex (OR 1.9, 95% CIs [1.2, 2.9], p = 0.005) and leukocytosis (OR 1.1, 95% CIs [1.1, 1.2], p = 0.001) were associated with poor collaterals. Measured variables only explained 44.8-53.0% of the observed between-patient variance in collaterals. CONCLUSION: Male sex and leukocytosis are associated with poorer collaterals. Nearly half of the variance in collateral flow remains unexplained and could be in part due to genetic differences.

Impact of Multiphase Computed Tomography Angiography for Endovascular Treatment Decision-Making on Outcomes in Patients with Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Various imaging paradigms are used for endovascular treatment (EVT) decision-making and outcome estimation in acute ischemic stroke (AIS). We aim to compare how these imaging paradigms perform for EVT patient selection and outcome estimation. METHODS: Prospective multi-center cohort study of patients with AIS symptoms with multi-phase computed tomography angiography (mCTA) and computed tomography perfusion (CTP) baseline imaging. mCTA-based EVT-eligibility was defined as presence of large vessel occlusion (LVO) and moderate-to-good collaterals on mCTA. CTP-based eligibility was defined as presence of LVO, ischemic core (defined on relative cerebral blood flow, absolute cerebral blood flow, and cerebral blood volume maps) <70 mL, mismatch-ratio >1.8, absolute mismatch >15 mL. EVT-eligibility and adjusted rates of good outcome (modified Rankin Scale 0-2) based on these imaging paradigms were compared. RESULTS: Of 289/464 patients with LVO, 263 (91%) were EVT-eligible by mCTA-criteria versus 63 (22%), 19 (7%) and 103 (36%) by rCBF, aCBF, and CBV-CTP-criteria. CTP and mCTA-criteria were discordant in 40% to 53%. Estimated outcomes were best in patients who met both mCTA and CTP eligibility-criteria and were treated with EVT (62% to 87% good outcome). Patients eligible for EVT by mCTA-criteria and not by CTP-criteria receiving EVT achieved good outcome rates of 53% to 57%. Few patients met CTP-criteria and not mCTA-criteria for EVT. CONCLUSIONS: Simpler imaging selection criteria that rely on little else than detection of the occluded blood vessel may be more sensitive and less specific, thus resulting in more patients being offered EVT and arguably benefiting from it.

Computed Tomography Perfusion-Based Machine Learning Model Better Predicts Follow-Up Infarction in Patients With Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Prediction of infarct extent among patients with acute ischemic stroke using computed tomography perfusion is defined by predefined discrete computed tomography perfusion thresholds. Our objective is to develop a threshold-free computed tomography perfusion-based machine learning (ML) model to predict follow-up infarct in patients with acute ischemic stroke. METHODS: Sixty-eight patients from the PRoveIT study (Measuring Collaterals With Multi-Phase CT Angiography in Patients With Ischemic Stroke) were used to derive a ML model using random forest to predict follow-up infarction voxel by voxel, and 137 patients from the HERMES study (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) were used to test the derived ML model. Average map, Tmax, cerebral blood flow, cerebral blood volume, and time variables including stroke onset-to-imaging and imaging-to-reperfusion time, were used as features to train the ML model. Spatial and volumetric agreement between the ML model predicted follow-up infarct and actual follow-up infarct were assessed. Relative cerebral blood flow <0.3 threshold using RAPID software and time-dependent Tmax thresholds were compared with the ML model. RESULTS: In the test cohort (137 patients), median follow-up infarct volume predicted by the ML model was 30.9 mL (interquartile range, 16.4-54.3 mL), compared with a median 29.6 mL (interquartile range, 11.1-70.9 mL) of actual follow-up infarct volume. The Pearson correlation coefficient between 2 measurements was 0.80 (95% CI, 0.74-0.86, P<0.001) while the volumetric difference was -3.2 mL (interquartile range, -16.7 to 6.1 mL). Volumetric difference with the ML model was smaller versus the relative cerebral blood flow <0.3 threshold and the time-dependent Tmax threshold (P<0.001). CONCLUSIONS: A ML using computed tomography perfusion data and time estimates follow-up infarction in patients with acute ischemic stroke better than current methods.

Clinical Course of Acute Ischemic Stroke Due to Medium Vessel Occlusion With and Without Intravenous Alteplase Treatment.

BACKGROUND AND PURPOSE: Available data on the clinical course of patients with acute ischemic stroke due to medium vessel occlusion (MeVO) are mostly limited to those with M2 segment occlusions. Outcomes are generally better compared with more proximal occlusions, but many patients will still suffer from severe morbidity. We aimed to determine the clinical course of acute ischemic stroke due to MeVO with and without intravenous alteplase treatment. METHODS: Patients with MeVO (M2/M3/A2/A3/P2/P3 occlusion) from the INTERRSeCT (The Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography) and PRoveIT (Precise and Rapid Assessment of Collaterals Using Multi-Phase CTA in the Triage of Patients With Acute Ischemic Stroke for IA Therapy) studies were included. Baseline characteristics and clinical outcomes were summarized using descriptive statistics. The primary outcome was a modified Rankin Scale score of 0 to 1 at 90 days, describing excellent functional outcome. Secondary outcomes were the common odds ratio for a 1-point shift across the modified Rankin Scale and functional independence, defined as modified Rankin Scale score of 0 to 2. We compared outcomes between patients with versus without intravenous alteplase treatment and between patients who did and did not show recanalization on follow-up computed tomography angiography. Logistic regression was used to provide adjusted effect-size estimates. RESULTS: Among 258 patients with MeVO, the median baseline National Institutes of Health Stroke Scale score was 7 (interquartile range: 5-12). A total of 72.1% (186/258) patients were treated with intravenous alteplase and in 41.8% (84/201), recanalization of the occlusion (revised arterial occlusive lesion score 2b/3) was seen on follow-up computed tomography angiography. Excellent functional outcome was achieved by 50.0% (129/258), and 67.4% (174/258) patients gained functional independence, while 8.9% (23/258) patients died within 90 days. Recanalization was observed in 21.4% (9/42) patients who were not treated with alteplase and 47.2% (75/159) patients treated with alteplase (P=0.003). Early recanalization (adjusted odds ratio, 2.29 [95% CI, 1.23-4.28]) was significantly associated with excellent functional outcome, while intravenous alteplase was not (adjusted odds ratio, 1.70 [95% CI, 0.88-3.25]). CONCLUSIONS: One of every 2 patients with MeVO did not achieve excellent clinical outcome at 90 days with best medical management. Early recanalization was strongly associated with excellent outcome but occurred in <50% of patients despite intravenous alteplase treatment.

Thrombectomy vs medical management in low NIHSS acute anterior circulation stroke.

OBJECTIVE: To undertake an effectiveness and safety analysis of EVT in patients with LVO and NIH Stroke Scale (NIHSS) score ≤6 using datasets of multicenter and multinational nature. METHODS: We pooled patients with anterior circulation occlusion from 3 prospective international cohorts. Patients were eligible if presentation occurred within 12 hours from last known well and baseline NIHSS ≤6. Primary outcome was modified Rankin Scale (mRS) score 0-1 at 90 days. Secondary outcomes included neurologic deterioration at 24 hours (change in NIHSS of ≥2 points), mRS 0-2 at 90 days, and 90-day all-cause mortality. We used propensity score matching to adjust for nonrandomized treatment allocation. RESULTS: Among 236 patients who fit inclusion criteria, 139 received EVT and 97 received medical management. Compared to medical management, the EVT group was younger (65 vs 72 years; p < 0.001), had more proximal occlusions (p < 0.001), and less frequently received concurrent IV thrombolysis (57.7% vs 71.2%; p = 0.04). After propensity score matching, clinical outcomes between the 2 groups were not significantly different. EVT patients had an 8.6% (95% confidence interval [CI] -8.8% to 26.1%) higher rate of excellent 90-day outcome, despite a 22.3% (95% CI, 3.0%-41.6%) higher risk of neurologic deterioration at 24 hours. CONCLUSIONS: EVT for LVO in patients with low NIHSS score was associated with increased risk of neurologic deterioration at 24 hours. However, both EVT and medical management resulted in similar proportions of excellent clinical outcomes at 90 days. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with acute anterior circulation ischemic strokes and LVO with NIHSS < 6, EVT and medical management result in similar outcomes at 90 days.

COVID-19: Stroke Admissions, Emergency Department Visits, and Prevention Clinic Referrals.

We assessed the impact of the coronavirus disease 19 (COVID-19) pandemic on code stroke activations in the emergency department, stroke unit admissions, and referrals to the stroke prevention clinic at London's regional stroke center, serving a population of 1.8 million in Ontario, Canada. We found a 20% drop in the number of code strokes in 2020 compared to 2019, immediately after the first cases of COVID-19 were officially confirmed. There were no changes in the number of stroke admissions and there was a 22% decrease in the number of clinic referrals, only after the provincial lockdown. Our findings suggest that the decrease in code strokes was mainly driven by patient-related factors such as fear to be exposed to the SARS-CoV-2, while the reduction in clinic referrals was largely explained by hospital policies and the Government lockdown.

Vitamin B 12 deficiency and hyperhomocysteinaemia in outpatients with stroke or transient ischaemic attack: a cohort study at an academic medical centre.

OBJECTIVE: We sought to assess the current magnitude of the opportunity for secondary stroke prevention with B vitamins. DESIGN: A cohort study. SETTING: The Urgent TIA (Transient Ischaemic Attack) Clinic at an academic medical centre. MAIN OUTCOME MEASURES: We assessed the prevalence of biochemical vitamin B12 deficiency (B12Def, serum B12 <156 pmol/L), hyperhomocysteinaemia (HHcy; plasma total homocysteine [tHcy] >14 µmol/L) and metabolic B12 deficiency (MetB12Def, serum B12 <258 pmol/L and HHcy) between 2002 and 2017, by age group and by stroke subtype. RESULTS: Data were available in 4055 patients. B12Def was present in 8.2% of patients overall; it declined from 10.9% of patients referred before 2009 to 5.4% thereafter (p=0.0001). MetB12Def was present in 10.6% of patients, and HHcy was present in 19.1% of patients. Among the patients aged ≥80 years, MetB12Def was present in 18.1% and HHcy in 35%. Among the 3410 patients whose stroke subtype was determined, HHcy was present in 18.4% of patients: 23.3% of large artery atherosclerosis, 18.1% of cardioembolic, 16.3% of small vessel disease, 10.8% of other unusual aetiologies and 13.6% of undetermined subtypes (p=0.0001). CONCLUSIONS: Despite a decline in our referral area since 2009, B12Def, MetB12Def and HHcy remain common in patients with stroke/TIA. Because these conditions are easily treated and have serious consequences, all patients with stroke/TIA should have their serum B12 and tHcy measured.

Pathophysiology and Risk of Atrial Fibrillation Detected after Ischemic Stroke (PARADISE): A Translational, Integrated, and Transdisciplinary Approach.

BACKGROUND: It has been hypothesized that ischemic stroke can cause atrial fibrillation. By elucidating the mechanisms of neurogenically mediated paroxysmal atrial fibrillation, novel therapeutic strategies could be developed to prevent atrial fibrillation occurrence and perpetuation after stroke. This could result in fewer recurrent strokes and deaths, a reduction or delay in dementia onset, and in the lessening of the functional, structural, and metabolic consequences of atrial fibrillation on the heart. METHODS: The Pathophysiology and Risk of Atrial Fibrillation Detected after Ischemic Stroke (PARADISE) study is an investigator-driven, translational, integrated, and transdisciplinary initiative. It comprises 3 complementary research streams that focus on atrial fibrillation detected after stroke: experimental, clinical, and epidemiological. The experimental stream will assess pre- and poststroke electrocardiographic, autonomic, anatomic (brain and heart pathology), and inflammatory trajectories in an animal model of selective insular cortex ischemic stroke. The clinical stream will prospectively investigate autonomic, inflammatory, and neurocognitive changes among patients diagnosed with atrial fibrillation detected after stroke by employing comprehensive and validated instruments. The epidemiological stream will focus on the demographics, clinical characteristics, and outcomes of atrial fibrillation detected after stroke at the population level by means of the Ontario Stroke Registry, a prospective clinical database that comprises over 23,000 patients with ischemic stroke. CONCLUSIONS: PARADISE is a translational research initiative comprising experimental, clinical, and epidemiological research aimed at characterizing clinical features, the pathophysiology, and outcomes of neurogenic atrial fibrillation detected after stroke.

Use of Noncontrast Computed Tomography and Computed Tomographic Perfusion in Predicting Intracerebral Hemorrhage After Intravenous Alteplase Therapy.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage is a feared complication of intravenous alteplase therapy in patients with acute ischemic stroke. We explore the use of multimodal computed tomography in predicting this complication. METHODS: All patients were administered intravenous alteplase with/without intra-arterial therapy. An age- and sex-matched case-control design with classic and conditional logistic regression techniques was chosen for analyses. Outcome was parenchymal hemorrhage on 24- to 48-hour imaging. Exposure variables were imaging (noncontrast computed tomography hypoattenuation degree, relative volume of very low cerebral blood volume, relative volume of cerebral blood flow ≤7 mL/min·per 100 g, relative volume of Tmax ≥16 s with all volumes standardized to z axis coverage, mean permeability surface area product values within Tmax ≥8 s volume, and mean permeability surface area product values within ipsilesional hemisphere) and clinical variables (NIHSS [National Institutes of Health Stroke Scale], onset to imaging time, baseline systolic blood pressure, blood glucose, serum creatinine, treatment type, and reperfusion status). RESULTS: One-hundred eighteen subjects (22 patients with parenchymal hemorrhage versus 96 without, median baseline NIHSS score of 15) were included in the final analysis. In multivariable regression, noncontrast computed tomography hypoattenuation grade (P<0.006) and computerized tomography perfusion white matter relative volume of very low cerebral blood volume (P=0.04) were the only significant variables associated with parenchymal hemorrhage on follow-up imaging (area under the curve, 0.73; 95% confidence interval, 0.63-0.83). Interrater reliability for noncontrast computed tomography hypoattenuation grade was moderate (κ=0.6). CONCLUSIONS: Baseline hypoattenuation on noncontrast computed tomography and very low cerebral blood volume on computerized tomography perfusion are associated with development of parenchymal hemorrhage in patients with acute ischemic stroke receiving intravenous alteplase.

Regional Comparison of Multiphase Computed Tomographic Angiography and Computed Tomographic Perfusion for Prediction of Tissue Fate in Ischemic Stroke.

BACKGROUND AND PURPOSE: Within different brain regions, we determine the comparative value of multiphase computed tomographic angiography (mCTA) and computed tomographic perfusion (CTP) in predicting follow-up infarction. METHODS: Patients with M1-middle cerebral artery occlusions were prospectively included in this multicenter study. Regional analysis was performed for each patient within Alberta Stroke Program Early CT Score regions M2 to M6. Regional pial vessel filling was assessed on mCTA in 3 ways: (1) Washout of contrast within pial vessels; (2) Extent of maximal pial vessel enhancement compared with contralateral hemisphere; (3) Delay in maximal pial vessel enhancement compared with contralateral hemisphere. Cerebral blood flow, cerebral blood volume, and Tmax data were extracted within these Alberta Stroke Program Early CT Score regions. Twenty-four- to 36-hour magnetic resonance imaging/CT was assessed for infarct in each Alberta Stroke Program Early CT Score region (defined as >20% infarction within that region). Mixed effects logistic regression models were used to compare mCTA and CTP parameters when predicting brain infarction. Area under the receiver operating characteristics was used to assess discriminative value of statistical models. RESULTS: Seventy-seven patients were included. mCTA parameter washout and CTP parameter Tmax were significantly associated with follow-up infarction in all models (P<0.05). The area under the receiver operating characteristic for mCTA models ranged from 92% to 94% and was not different compared with all CTP models (P>0.05). Mean Tmax and cerebral blood volume values were significantly different between each washout score (P<0.01) and each delay score category (P<0.01). Mean Tmax, cerebral blood flow, and cerebral blood volume values were significantly different between each extent score category (P<0.05). CONCLUSIONS: Similar to CTP, multiphase CTA can be used to predict tissue fate regionally in acute ischemic stroke patients.