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Background: In the SPOTLIGHT trial (Spot Sign Selection of Intracerebral Hemorrhage to Guide Hemostatic Therapy), patients with a computed tomography (CT) angiography spot-sign positive acute intracerebral hemorrhage were randomized to rFVIIa (recombinant activated factor VIIa; 80 μg/kg) or placebo within 6 hours of onset, aiming to limit hematoma expansion. Administration of rFVIIa did not significantly reduce hematoma expansion. In this prespecified analysis, we aimed to investigate the impact of delays from baseline imaging to study drug administration on hematoma expansion. Methods: Hematoma volumes were measured on the baseline CT, early post-dose CT, and 24 hours CT scans. Total hematoma volume (intracerebral hemorrhage+intraventricular hemorrhage) change between the 3 scans was calculated as an estimate of how much hematoma expansion occurred before and after studying drug administration. Results: Of the 50 patients included in the trial, 44 had an early post-dose CT scan. Median time (interquartile range) from onset to baseline CT was 1.4 hours (1.2–2.6). Median time from baseline CT to study drug was 62.5 (55–80) minutes, and from study drug to early post-dose CT was 19 (14.5–30) minutes. Median (interquartile range) total hematoma volume increased from baseline CT to early post-dose CT by 10.0 mL (−0.7 to 18.5) in the rFVIIa arm and 5.4 mL (1.8–8.3) in the placebo arm ( P =0.96). Median volume change between the early post-dose CT and follow-up scan was 0.6 mL (−2.6 to 8.3) in the rFVIIa arm and 0.7 mL (−1.6 to 2.1) in the placebo arm ( P =0.98). Total hematoma volume decreased between the early post-dose CT and 24-hour scan in 44.2% of cases (rFVIIa 38.9% and placebo 48%). The adjusted hematoma growth in volume immediately post dose for FVIIa was 0.998 times that of placebo ([95% CI, 0.71–1.43]; P =0.99). The hourly growth in FFVIIa was 0.998 times that for placebo ([95% CI, 0.994–1.003]; P =0.50; Table 3). Conclusions: In the SPOTLIGHT trial, the adjusted hematoma volume growth was not associated with Factor VIIa treatment. Most hematoma expansion occurred between the baseline CT and the early post-dose CT, limiting any potential treatment effect of hemostatic therapy. Future hemostatic trials must treat intracerebral hemorrhage patients earlier from onset, with minimal delay between baseline CT and drug administration. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01359202.

BackgroundThe DAWN and DEFUSE-3 trials showed the benefit of endovascular treatment (EVT) in acute ischemic stroke patients presenting beyond 6 hours from last known well (LKW) and selected by perfusion imaging criteria. The ESCAPE NA1-trial selected patients based on non-contrast CT (NCCT) Alberta Stroke Program Early CT Score (ASPECTS) and multiphase CT angiography (CTA) collateral status. This study compares baseline characteristics, workflow, and outcomes in the EVT arms of DAWN and DEFUSE-3 with late-window patients from the EVT-only arm of ESCAPE-NA1.MethodsAggregate data on baseline characteristics, workflow, reperfusion quality, final infarct volume, and clinical outcomes (modified Rankin Score [mRS] at 90 days) in subjects enrolled in the DAWN and DEFUSE-3 EVT arms were compared with similar data from the ESCAPE-NA1 control arm (EVT-only arm) presenting beyond 6 hours from LKW using descriptive statistics.ResultsBaseline characteristics among late-window patients in the ESCAPE NA1 trial were similar to those in the DAWN and DEFUSE-3 EVT arms. Median time from LKW-to-puncture in subjects enrolled in the ESCAPE NA1 trial was 9 hrs (IQR: 7.5–11 hours) when compared with DAWN (n=107; 12.8 hours, IQR: 10.6–16.7 hours) and DEFUSE-3 (n=92; 11.5 hours, IQR: 9.2–12.8 hours). Median post-treatment infarct-volume was largest in the ESCAPE NA1-patients (47 mL [IQR: 19–146] vs median 8 mL [IQR: 0–48] in the DAWN group and 35 mL [IQR: 18–82] in DEFUSE-3), while % mRS 0–2 at 90 days were similar across the three trials (ESCAPE NA1: 50/111 [45%], DAWN: 52/107 [49%], DEFUSE-3: 41/92 [45%]).ConclusionPatients enrolled beyond 6 hours from LKW in the ESCAPE-NA1 trial based on NCCT-ASPECTS and mCTA had similar clinical outcomes when compared with patients selected by perfusion imaging in the DAWN and DEFUSE-3 trials.

Background:Vascular cognitive impairment (VCI) post-stroke is frequent but may go undetected, which highlights the need to better screen cognitive functioning following a stroke.Aim:We examined the clinical utility of the Montreal Cognitive Assessment (MoCA) in detecting cognitive impairment against a gold-standard neuropsychological battery.Methods:We assessed cognitive status with a comprehensive battery of neuropsychological tests in 161 individuals who were at least 3-months post-stroke. We used receiver operating characteristic (ROC) curves to identify two cut points for the MoCA to maximize sensitivity and specificity at a minimum 90% threshold. We examined the utility of the Symbol Digit Modalities Test, a processing speed measure, to determine whether this additional metric would improve classification relative to the MoCA total score alone.Results:Using two cut points, 27% of participants scored ≤ 23 and were classified as high probability of cognitive impairment (sensitivity 92%), and 24% of participants scored ≥ 28 and were classified as low probability of cognitive impairment (specificity 91%). The remaining 48% of participants scored from 24 to 27 and were classified as indeterminate probability of cognitive impairment. The addition of a processing speed measure improved classification for the indeterminate group by correctly identifying 65% of these individuals, for an overall classification accuracy of 79%.Conclusions:The utility of the MoCA in detecting cognitive impairment post-stroke is improved when using a three-category approach. The addition of a processing speed measure provides a practical and efficient method to increase confidence in the determined outcome while minimally extending the screening routine for VCI.

ObjectiveTo assess overlap and uniqueness of established behavioral markers of speed of processing for different aspects of visual information within a cerebrovascular disease cohort, and to examine the link between these speed of processing markers and functional behavior, specifically walking.MethodsA cohort of 161 participants with cerebrovascular disease recruited to the Ontario Neurodegenerative Disease Research Initiative (ONDRI) were examined with three types of assessments: neuropsychology, saccadic eye movement and gait. Principal component analysis (PCA) and canonical correlation analysis (CCA) were performed on select variables from these assessments to reveal commonalities and discrepancies among the measures.ResultsPCA analysis revealed different variable patterns between neuropsychology and saccade assessments, with the first component characterized primarily by neuropsychology, and the second and third components more influenced by the saccade assessments. CCA analysis did not reveal association between different types of assessments with the exception of a modest, but significant, positive association between speed of processing measures from the neuropsychological assessments and gait speed.DiscussionNeuropsychological tests and the pro-saccade task can be used for assessment of speed of processing for two major features of visual information, visual perception vs. spatial location. Despite a general lack of association between different types of assessments, combining gait speed as an important contributor to the models reinforces the idea of the link between speed of processing and complex function such as walking, and provides support for the importance of attending to the potential consequences of changes in speed of processing after neurologic injury.

Objectives: In the Ontario Neurodegenerative Disease Research Initiative (ONDRI), we aimed to ask and answer: (1) How many and what types of burdens are captured by the Zarit’s Burden Interview (ZBI)? (2) Do we see categorical or spectrum-like effects for burden(s)? and (3) Which if any demographic, clinical, and cognitive measures are related to burden(s)?Methods: N = 504 participants and their study partners (e.g., family, friends) across: Alzheimer’s disease/mild cognitive impairment (AD/MCI; n = 120), Parkinson’s disease (PD; n = 136), amyotrophic lateral sclerosis (ALS; n = 38), frontotemporal dementia (FTD; n = 53), and cerebrovascular disease (CVD; n = 157). Study partners provided information about themselves, and information about the clinical participants (e.g., activities of daily living). We used Correspondence Analysis to identify types of caregiving concerns in the ZBI, then identified relationships between those concerns and demographic and clinical measures, and a cognitive battery.Results: We found three components in the ZBI. The first was “overall burden” and was (1) strongly related to increased neuropsychiatric symptoms and decreased independence in activities of daily living, (2) moderately related to cognition, and (3) showed little-to-no differences between disorders. The second and third components showed four types of caregiving concerns: current care of patient, future care of patient, personal concerns of study partner, and social concerns of study partner. Discussion: Caregiving concerns are individual experiences and emphasize the importance of support for management of activities of daily living and neuropsychiatric symptoms, and underscore individualized needs for caregiving assessment and education.

ObjectiveTo determine whether the ABC/2 method could accurately and reliably measure infarct volume and guide thrombectomy decision in acute stroke cases presenting with late or unknown onset.MethodsFour physicians who routinely use MRI for acute stroke imaging, blinded to the RAPID results, measured the diffusion-weighted imaging (DWI) infarct volume using the ABC/2 method. Measurements with ABC/2 (the index test) were compared with RAPID (the reference standard) to calculate sensitivity, specificity, and accuracy measures for various volume cutpoints. Thrombectomy decisions based on RAPID and raters' measurements using the criteria from the Diffusion-Weighted Imaging or Computerized Tomography Perfusion Assessment With Clinical Mismatch in the Triage of Wake-Up and Late-Presenting Strokes Undergoing Neurointervention With Trevo (DAWN) trial criteria were compared. Interrater and intrarater agreement was measured using kappa statistics.ResultsAccuracy with the ABC/2 method was greater than 80% for each rater and each volume cut point. Interrater and intrarater agreement was substantial to excellent for each volume cut point. Treatment decisions with ABC/2 volume estimations showed strong interrater and intrarater agreement, and led to similar thrombectomy decisions compared with RAPID in more than 85% of cases.ConclusionDWI infarct volume measurement using ABC/2 method shows strong accuracy and reliability and may be an acceptable alternative to RAPID software for the application of DAWN criteria for thrombectomy decision-making.

Background Aggressively lowering blood pressure (BP) in acute intracerebral hemorrhage (ICH) may improve outcome. Although there is no evidence that BP reduction changes cerebral blood flow, retrospective magnetic resonance imaging (MRI) studies have demonstrated sub-acute ischemic lesions in ICH patients. The primary aim of this study is to assess ischemic lesion development in patients randomized to two different BP treatment strategies. We hypothesize aggressive BP reduction is not associated with ischemic injury after ICH. Methods The Intracerebral Hemorrhage Acutely Decreasing Blood Pressure Trial II (ICH ADAPT II) is a phase II multi-centre randomized open-label, blinded-endpoint trial. Acute ICH patients (N = 270) are randomized to a systolic blood pressure (SBP) target of 2 mins apart qualify. SBP is managed with a pre-defined treatment protocol. Patients undergo MRI at 48 h, Days 7 and 30, with clinical assessment at Day 30 and 90. The primary outcome is diffusion weighted imaging (DWI) lesion frequency at 48 h. Secondary outcomes include cumulative DWI lesion rate frequency within 30 days, absolute hematoma growth, prediction of DWI lesion incidence, 30-day mortality rates, day 90 functional outcome, and cognitive status. Discussion This trial will assess the impact of hypertensive therapies on physiological markers of ischemic injury. The findings of this study will provide evidence for the link, or lack thereof, between BP reduction and ischemic injury in ICH patients. Trial registration This study is registered with clinicaltrials.gov (NCT02281838, first received October 29, 2014). Electronic supplementary material The online version of this article (doi:10.1186/s12883-017-0884-4) contains supplementary material, which is available to authorized users.

Every year, approximately 62,000 people with stroke and transient ischemic attack are treated in Canadian hospitals. The 2016 update of the Canadian Stroke Best Practice Recommendations Telestroke guideline is a comprehensive summary of current evidence-based and consensus-based recommendations appropriate for use by all healthcare providers and system planners who organize and provide care to patients following stroke across a broad range of settings. These recommendations focus on the use of telemedicine technologies to rapidly identify and treat appropriate patients with acute thrombolytic therapies in hospitals without stroke specialized expertise; select patients who require to immediate transfer to stroke centers for Endovascular Therapy; and for the patients who remain in community hospitals to facilitate their care on a stroke unit and provide remote access to stroke prevention and rehabilitation services. While these latter areas of Telestroke application are newer, they are rapidly developing, with new opportunities that are yet unrealized. Virtual rehabilitation therapies offer patients the opportunity to participate in rehabilitation therapies, supervised by physical and occupational therapists. While not without its limitations (e.g., access to telecommunications in remote areas, fragmentation of care), the evidence-to-date sets the foundation for improving access to care and management for patients during both the acute phase and now through post stroke recovery.

Background Subacute ischemic lesions in intracerebral hemorrhage ( ICH ) have been hypothesized to result from hypoperfusion. Although studies of cerebral blood flow ( CBF ) indicate modest hypoperfusion in ICH , these investigations have been limited to early time points. Arterial spin labeling ( ASL ), a magnetic resonance imaging technique, can be used to measure CBF without a contrast agent. We assessed CBF in patients with ICH using ASL and tested the hypothesis that CBF is related to systolic blood pressure ( SBP ). Methods and Results In this cross‐sectional study, patients with ICH were assessed with ASL at 48 hours, 7 days, and/or 30 days after onset. Relative CBF ( rCBF ; ratio of ipsilateral/contralateral perfusion) was measured in the perihematomal regions, hemispheres, border zones, and the perilesional area in patients with diffusion‐weighted imaging hyperintensities. Twenty‐patients (65% men; mean± SD age, 68.5±12.7 years) underwent imaging with ASL at 48 hours (N=12), day 7 (N=6), and day 30 (N=11). Median (interquartile range) hematoma volume was 13.1 (6.3–19.3) mL. Mean± SD baseline SBP was 185.4±25.5 mm Hg. Mean perihematomal rCBF was 0.9±0.2 at 48 hours at all time points. Baseline SBP and other SBP measurements were not associated with a decrease in rCBF in any of the regions of interest ( P ≥0.111). r CBF did not differ among time points in any of the regions of interest ( P ≥0.097). Mean perilesional rCBF was 1.04±0.65 and was unrelated to baseline SBP ( P =0.105). Conclusions ASL can be used to measure rCBF in patients with acute and subacute ICH . Perihematomal CBF was not associated with SBP changes at any time point. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT00963976.

Introduction: Determining stroke etiology is essential to stroke prevention. Deciding which patients require extensive cardiac investigations, and with what priority, is a topic of controversy. Hypothesis: We hypothesize that a lack of hypertension at the time of presentation with acute ischemic stroke predicts cardioembolic etiology. Methods: Patients presenting with acute (< 6 hours) ischemic stroke were consecutively enrolled from a single institution between 2015 and 2017. The primary outcome was cardioembolic etiology diagnosis at 6 months. Presenting systolic blood pressure was categorized as: hypotensive (150 mmHg). Multivariable logistic regression was used to adjust for relevant covariates, which were selected via exploratory univariate analysis (p Results: Of the 151 patients included in primary analysis, 64 (42%) were diagnosed with a cardioembolic source at 6 months. After adjusting for age, known cardiac disease (atrial fibrillation, congestive heart failure, valvular disease), and clinical severity, patients presenting with hypo or normotensive systolic pressure were significantly associated with cardioembolic diagnosis at 6 months (n= 37, aOR 3.25, 95% CI: 1.17- 9.06). The association between systolic pressure and cardioembolic diagnosis increased in a dose-like manner (hypotensive: aOR 7.66, 95% CI: 0.80-73.30, normotensive: aOR 2.99, 95% CI: 1.04-8.58). Conclusions: This study provides preliminary confirmation of our hypothesis that patients who are not hypertensive at the time of acute ischemic stroke are more likely to have suffered a stroke that is cardioembolic in origin. These patients may warrant more thorough cardiac investigations or other alterations to management.

The Canadian Stroke Best Practice Consensus Statement Acute Stroke Management during Pregnancy is the second of a two-part series devoted to stroke in pregnancy. The first part focused on the unique aspects of secondary stroke prevention in a woman with a prior history of stroke who is, or is planning to become, pregnant. This document focuses on the management of a woman who experiences an acute stroke during pregnancy. This consensus statement was developed in recognition of the need for a specifically tailored approach to the management of this group of patients in the absence of any broad-based, stroke-specific guidelines or consensus statements, which do not exist currently. The foundation for the development of this document was the concept that maternal health is vital for fetal well-being; therefore, management decisions should be based first on the confluence of two clinical considerations: (a) decisions that would be made if the patient wasn't pregnant and (b) decisions that would be made if the patient hadn't had a stroke, then nuanced as needed. While empirical research in this area is limited, this consensus document is based on the best available literature and guided by expert consensus. Issues addressed in this document include initial emergency management, diagnostic imaging, acute stroke treatment, the management of hemorrhagic stroke, anesthetic management, post stroke management for women with a stroke in pregnancy, intrapartum considerations, and postpartum management. These statements are appropriate for healthcare professionals across all disciplines and system planners to ensure pregnant women who experience a stroke have timely access to both expert neurological and obstetric care.

Introduction: Perihematomal hypoperfusion in acute intracerebral hemorrhage (ICH) has been demonstrated using CT perfusion. Although blood pressure (BP) reduction does not appear to impact perihematomal Cerebral Blood Flow (CBF), measurements using contrast are limited to a single time point. It has also been shown that up to 41% of ICH patients develop subacute diffusion-weighted imaging (DWI) lesions on MRI. Arterial Spin Labelling (ASL) is an magnetic resonance imaging (MRI) technique that allows measurement of CBF without a contrast agent, making it suitable for serial measurements. We assessed CBF in ICH patients using ASL and tested the hypothesis that perihematoma perfusion is related to BP. Methods: Patients with CT scan confirmed ICH were prospectively recruited within 6 hours of symptom onset. Acute systolic BP (SBP) targets were randomly assigned as part of an ongoing trial. The SBP target remained blinded for this analysis. Patients were assessed with ASL at 48 hours post ICH. The perihematoma region was defined using co-registered susceptibility weighted images to delineate the hematoma border. Relative CBF (rCBF) was calculated as a ratio of the ipsilateral to contralateral ASL measurements. Results: Perfusion was measured in 6 ICH patients, none of whom had DWI lesions, 55.38 (43.72, 59.75) hours after onset. Median 48 hour hematoma volume was 23.40 (18.10, 99.90) ml. Mean±SD SBP at 48 hours was 140.20 ± 10.64 mmHg. Mean perihematomal rCBF was 0.95±0.37. Mean hemispheric rCBF was 0.95 ± 0.17. Perihematomal and hemispheric CBF was not lower in the side of the hematoma ( p >0.583). Hematoma size was unrelated to rCBF (perihematomal R=0.039, 95% CI [-0.880, 0.959], p =0.682; hemispheric R=0.00, 95% CI [-0.005, 0.006], p =0.932). Systolic BP at the time of the scan, difference between baseline SBP and SBP at the time of the scan, and time spent with SBP p >0.170). Conclusion: It is feasible to measure perihematoma and hemispheric perfusion in ICH patients using ASL, which may be useful for serial CBF assessment, particularly in patients with MRI evidence of ischemia.

Introduction: Diffusion-Weighted magnetic resonance imaging (DWI) studies have demonstrated sub-acute ischemic lesions in up to 41% of patients with intracerebral hemorrhage (ICH). Retrospective studies indicated an association with acute blood pressure (BP) reduction. We conducted a prospective study of DWI lesion incidence in ICH patients. Methods: Patients with computed tomography (CT) scan confirmed ICH were prospectively recruited within 6 hours of symptom onset. Acute systolic BP (SBP) targets were randomly assigned as part of an ongoing trial. The SBP target remained blinded for this analysis. Patients were assessed with serial DWI at 48 hours. Results: Eighty-three patients (48.2% male, mean±SD age 71.9±13.4) were enrolled. MRI was obtained in 42 patients. (11 patients were medically unstable, 11 refused consent, 19 died or were treated palliatively prior to the first MRI). Median (IQR) acute hematoma volume of the patients undergoing magnetic resonance imaging was 14.11 (4.40, 38.06) ml. Median baseline NIHSS score was 12.50 (9, 20). Median (IQR) 48 hour hematoma volume was 23.30 (9.10, 65.30) ml. DWI lesions were present in 13 (31%) of patients at 48 hours (median time to scan 54.22 (39.83, 65.5) hours). Mean SBP at 48 hours in patients with lesions (154.55±27.02 mmHg) was similar to those without (149.04±27.02; p = 0.514). Systolic BP at the time of the MRI was not a predictor of ischemic lesion development at 48 hours (OR=1.015, [0.972, 1.059], p =0.507), nor was the change in BP between baseline and the scan (OR=0.994, [0.962, 1.027], p =0.716). The only predictor of 48 hour DWI incidence was hematoma volume at 48 hours (OR= 1.025, 95% CI [1.001, 1.050], p =0.044). Discussion: When enrolled prospectively within 6 hours of onset, DWI was obtained in approximately half of all ICH patients. This selection bias may be relevant to the results of both retrospective and prospective DWI studies. This study demonstrated no evidence of a relationship between actual BP achieved and DWI incidence after ICH.

Background and Purpose— The Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial (ICH ADAPT) demonstrated blood pressure (BP) reduction does not affect mean perihematoma or hemispheric cerebral blood flow. Nonetheless, portions of the perihematoma and borderzones may reach ischemic thresholds after BP reduction. We tested the hypothesis that BP reduction after intracerebral hemorrhage results in increased critically hypoperfused tissue volumes. Methods— Patients with Intracerebral hemorrhage were randomized to a target systolic BP (SBP) of Results— Seventy-five patients with intracerebral hemorrhage were randomized a median (interquartile range) of 7.8 (13.3) hours from onset. Acute hematoma volume was 17.8 (27.1) mL and mean SBP was 183±22 mm Hg. At the time of computed tomographic perfusion (2.3 [1.0] hours after randomization), SBP was lower in the P P =0.78) or P =0.62). Similar results were found in the perihematoma region. Low SBP load (fraction of time with SBP Conclusions— BP reduction does not increase the volume of critically hypoperfused borderzone or perihematoma tissue. These data support the safety of early BP reduction in intracerebral hemorrhage. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00963976.

Background: Early Neurological Worsening (ENW) is common after ICH, and predicts poor outcome. However, there is limited data as to what degree of ENW best relates to outcome. We used two ICH cohorts to refine and validate a definition of ENW that best predicted 90-day outcomes. Methods: We generated receiver operating characteristic (ROC) curves for the association between 24-hour NIHSS change and ICH outcomes using data from the VISTA collaboration. Primary outcome was poor outcome at 90 days (mRS 4-6); secondary outcomes were other mRS cutpoints (mRS 2-6, 3-6, 5-6, 6). We tested the commonly used NIHSS≥4 definition and in addition employed Youden’s J Index to select optimal cutpoints and calculated sensitivity, specificity, and predictive values. Independent predictors of poor outcome were determined via multivariable logistic regression. Definitions were validated in the prospectively collected PREDICT-ICH cohort. Results: Using 552 patients from the VISTA cohort, ROC curves of 24hr NIHSS change had an area under the curve of 0.75. NIHSS change of ≥0 at 24hrs was seen in 46.4%. Youden’s method showed an optimum cutoff at -0.5. Based on this, ENW defined as >0 (Sens 43%, Spec 91%, PPV 83%, aOR 7.13 [CI:4.05-12.55]), ≥0 (Sens 65%, Spec 73%, PPV 70%, aOR 5.05 [CI:3.25-7.85]), or ≥-1 (Sens 78%, Spec 59%, PPV 65%, aOR 6.04 [CI:3.75-9.71]) all accurately predicted poor outcome. PPV increased with higher NIHSS cutoffs, but at the cost of lower sensitivities. Regression confirmed that all definitions independently predicted outcome at all mRS cutpoints. ENW definitions reproduced well in the validation cohort of 275 patients. Conclusion: All NIHSS cut-offs for ENW predict clinical outcome, regardless of outcome definition. In particular, lack of clinical improvement at 24 hours (i.e. NIHSS is the same or higher) robustly predicted poor outcome, but may not be sufficiently reliable to determine clinical management.

Introduction: More than half of ischemic stroke patients present as minor strokes (NIHSS Hypothesis: WB-CTP can guide clinical decisions by identifying patients with ischemic episodes that would benefit from thrombolysis or early intervention. Methods: This retrospective chart review enrolled 524 consecutive patients receiving WB-CTP with a Toshiba 320 detector scanner between 08/2008 and 06/2015, for acute stroke less than 6 hours from onset and NIHSS Results: A total of 484 patients (age 17-101, 54% men, mean NIHSS 2.47) were included. Follow-up imaging was performed in 251 patients; 150 underwent MRI with diffusion-weighted imaging (DWI). A summary of diagnostic accuracy values is shown in table below. WB-CTP is highly specific with a high positive predictive value in all groups and has moderate to high negative predictive value. Positive and negative likelihood ratios were 21.24 and 0.5 in the whole group analysis. Conclusions: Positive WB-CTP findings may warrant early intervention, including thrombolysis, while negative findings alone are not a sufficient basis upon which to confidently withhold interventions.

Background and Purpose— Treatment of acute hypertension after intracerebral hemorrhage (ICH) is controversial. In the context of disrupted cerebral autoregulation, blood pressure (BP) reduction may cause decreased cerebral blood flow (CBF). We used serial computed tomography perfusion to test the hypothesis that CBF remains stable after BP reduction. Methods— Patients recruited within 72 hours of ICH were imaged with computed tomography perfusion before and after BP treatment. Change in perihematoma relative (r) CBF after BP treatment was the primary end point. Results— Twenty patients were imaged with computed tomography perfusion at a median (interquartile range) time from onset of 20.2 (25.7) hours and reimaged 2.1 (0.5) hours later, after BP reduction. Mean systolic BP in treated patients (n=16; 4 untreated as BPP P =0.37). Linear regression showed no relationship between changes in systolic BP and perihematoma rCBF (β=0.001 [−0.002 to 0.003]; P =0.63). Conclusions— CBF remained stable after acute BP reduction, suggesting some preservation of cerebral autoregulation.

Introduction CTA is used to triage acute stroke patients for potential thrombectomy. Single, multiphase 1 or dynamic 2 CTA may demonstrate areas of parenchymal hypoattenuation on source images(CTASI). These areas may represent either delayed arrival of contrast or could be ischemic/infarcted tissue. The area can be variable depending on the arrival of contrast on the time-tissue attenuation curve (TAC). Areas of hypoattenuation distal to an occlusion are perceived because of differences in contrast compared to normally-perfused areas and can be objectively measured. Patients with significant hypoattenuation may be potentially excluded from thrombectomy. We evaluated conspicuity of hypoattenuation on dynamic multiphase CTASI. Specifically, we sought to determine if there is a specific time point on the TAC curve which optimizes conspicuity. Materials and methods We retrospectively identified 45 consecutive large vessel strokes between 2012–14 who had dynamic CTA and CTP. We identified ischemic areas from areas of low CBV. An ROI was drawn on the corresponding CTASI and in normally-perfused tissue. We evaluated CTASI in 7/18 points along the TAC (Figure 1). We calculated absolute and relative change in attenuation between potentially ischemic and normally-perfused tissue. Differences in conspicuity were evaluated using a Friedman test with Bonferroni correction. Results There were 22 males/23 females, age 69, ±16, median NIHSS 10.6. All occlusions were in the anterior circulation; 64% on the left. There was a significant effect of phase on the TAC for both absolute and relative conspicuity of ischemic (Figure 2) vs normally-perfused areas (P The median absolute and relative conspicuity of ischemic:normally-perfused tissue was greatest at the peak arterial (8.6 HU, 1.15), notch (9.4 HU, 1.17) and peak venous phases (7 HU, 1.13) vs other portions of the TAC (2.5–3.3 HU, 1.04–1.09). Conclusion The conspicuity of ischemic areas distal to a large artery occlusion in acute stroke is dependent on the phase of contrast arrival on time-resolved dynamic CTASI. The greatest conspicuity of areas of hypoattenuation between ischemic and normally perfused tissue is in the middle of the TAC. References 1 Radiology 2015 May; 275 (2):510–20. 2 Stroke 2014 Sep; 45 (9):2683–28. Disclosures C. Lum: None. P. Dave: None. R. Thornhill: None. S. Chakraborty: None. D. Dowlatshahi: None.

Statin therapy has been associated with improved cerebral blood flow (CBF) and decreased perihematoma edema in animal models of intracerebral hemorrhage (ICH). We aimed to assess the relationship between statin use and cerebral hemodynamics in ICH patients. A post hoc analysis of 73 ICH patients enrolled in the Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial (ICH ADAPT). Patients presenting < 24 hours from ICH onset were randomized to a systolic blood pressure target < 150 or < 180 mm Hg with computed tomography perfusion imaging 2 hours after randomization. Cerebral blood flow maps were calculated. Hematoma and edema volumes were measured planimetrically. Regression models were used to assess the relationship between statin use, perihematoma edema and cerebral hemodynamics. Fourteen patients (19%) were taking statins at the time of ICH. Statin-treated patients had similar median (IQR Q25 to 75) hematoma volumes (21.1 (9.5 to 38.3) mL versus 14.5 (5.6 to 27.7) mL, P = 0.25), but larger median (IQR Q25 to 75) perihematoma edema volumes (2.9 (1.7 to 9.0) mL versus 2.2 (0.8 to 3.5) mL, P = 0.02) compared with nontreated patients. Perihematoma and ipsilateral hemispheric CBF were similar in both groups. A multivariate linear regression model revealed that statin use and hematoma volumes were independent predictors of acute edema volumes. Statin use does not affect CBF in ICH patients. Statin use, along with hematoma volume, are independently associated with increased perihematoma edema volume.

Background and Purpose— The pathogenesis of perihematoma edema in intracerebral hemorrhage (ICH) is unknown but has been hypothesized to be ischemic. In the ICH Acutely Decreasing Arterial Pressure Trial (ICH ADAPT), perihematoma cerebral blood flow (CBF) was reduced but was unaffected by blood pressure (BP) reduction. Using ICH ADAPT data, we tested the hypotheses that edema growth is associated with reduced CBF and lower systolic BP. Methods— Noncontrast computed tomographic scans in patients with ICH were obtained at baseline, 2 hours, and 24 hours after randomization to target systolic BPs of Results— Patients were randomized at a median (interquartile range) of 7.4 (12.8) hours after onset. Treatment groups (n=34, P =0.727). Absolute CBF was lower in the edematous region (35.67±13.1 mL/100 g per minute) when compared with that in the contralateral tissue (43.7±11.7 mL/100 g per minute; P Conclusions— Lower perihematoma CBF and BP treatment do not exacerbate edema growth. These data do not support a cytotoxic edema pathogenesis. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00963976.

Introduction: Leukoariosis(LA) is associated with poor prognosis in intracerebral hemorrhage (ICH) patients. Patients with chronic small vessel ischemic changes may be more vulnerable to decreases in cerebral perfusion, in both LA and perihematoma(PH) regions. We tested the hypotheses that acute blood pressure reduction (BP) in ICH patients is associated with decreased cerebral blood flow (CBF) in areas of LA and the PH region. Methods: In the ICH Acutely Decreasing Arterial Pressure Trial (ICH ADAPT), patients with ICH Results: Seventy-one patients were included with a mean age of 69.3±11.5 years and median (IQR) baseline NIHSS score of 10(11). LA was present in 74.6% (53/71) and the median volume was 8.5(20.6) ml. LA was associated with older age (70.9± 11.2 vs. 64.8 ±11.6, p=0.05) and larger ICH volumes (19.52(29.78) vs. 9.52(16.02) ml, p=0.007). Mean CBF in LA regions (32.5±13.5) was similar to that in normal appearing white matter (35.6±12.1, p=0.3). Despite a significant drop in SBP between aggressive (36.25(40) mmHg) and conservative (18.5(29) mmHg, p=0.01) treatment groups, relative CBF (rCBF) in LA regions was unaffected (0.88±0.1 vs. 0.89±0.09, p=0.6). Similarly, aggressive BP treatment did not affect relative CBV (0.83±0.16 vs. 0.82± 0.15, p=0.8) or Tmax (7.3±3.2 s vs. 6.5 ±2.4 s, p=0.3). The rCBF in the PH regions in patients’ with/without LA was similar (0.88±0.09 vs. 0.86±0.1, p=0.5). There was a trend to worse functional outcome at 90 days, measured with the modified Rankin Scale in patients with LA (4(4) vs. 2(1), p=0.06). Conclusion: LA is associated with larger baseline ICH volumes, but no differences in perihematoma CBF or the response to BP reduction. CBF in LA tissue is also unaffected by BP reduction. These data do not support a less aggressive approach to BP reduction in elderly patients with imaging evidence of chronic small vessel ischemia.

Blood pressure (BP) reduction after intracerebral hemorrhage (ICH) is controversial, because of concerns that this may cause critical reductions in perihematoma perfusion and thereby precipitate tissue damage. We tested the hypothesis that BP reduction reduces perihematoma tissue oxygenation. Acute ICH patients were randomized to a systolic BP target of max), and the resulting maximum cerebral metabolic rate of oxygen (CMRO2max) permitted by local hemodynamics, were calculated from raw CTP data. Sixty-five patients (median (interquartile range) age 70 (20)) were imaged at a median (interquartile range) time from onset to CTP of 9.8 (13.6) hours. Mean OEFmax was elevated in the perihematoma region (0.44±0.12) relative to contralateral tissue (0.36±0.11; P2max (3.40±1.67 mL/100 g per minute) was slightly lower relative to contralateral tissue (3.63±1.66 mL/100 g per minute; P=0.025). Despite a significant difference in systolic BP between the aggressive (140.5±18.7 mm Hg) and conservative (163.0±10.6 mm Hg; Pmax (0.43±0.12 versus 0.45±0.11; P=0.232) or CMRO2max (3.16±1.66 versus 3.68±1.85 mL/100 g per minute; P=0.857). Blood pressure reduction does not affect perihematoma oxygen delivery. These data support the safety of early aggressive BP treatment in ICH.

Background and Purpose— Acute blood pressure (BP) reduction aimed at attenuation of intracerebral hemorrhage (ICH) expansion might also compromise cerebral blood flow (CBF). We tested the hypothesis that CBF in acute ICH patients is unaffected by BP reduction. Methods— Patients with spontaneous ICH 150 mm Hg were randomly assigned to an intravenous antihypertensive treatment protocol targeting a systolic BP of Results— Treatment groups were balanced with respect to baseline systolic BP: 182±20 mm Hg (P =0.60), and for hematoma volume: 25.6±30.8 versus 26.9±25.2 mL ( P =0.66). Mean systolic BP 2 hours after randomization was significantly lower in the P P P =0.19; absolute difference, 0.03; 95% confidence interval −0.018 to 0.078). There was no relationship between the magnitude of BP change and perihematoma relative CBF in the R =0.00005; 95% confidence interval, −0.001 to 0.001) or R =0.000; 95% confidence interval, −0.001 to 0.001). Conclusions— Rapid BP lowering after a moderate volume of ICH does not reduce perihematoma CBF. These physiological data indicate that acute BP reduction does not precipitate cerebral ischemia in ICH patients. Clinical Trial Registration Information— URL: http://clinicaltrials.gov . Unique Identifier: NCT00963976.

Background: Both vasogenic and cytotoxic (ischemic) processes have been postulated to play a role in perihematoma edema formation. In the Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial (ICH ADAPT), cerebral blood flow (CBF) was measured in ICH patients assigned to systolic blood pressure (SBP) targets of Methods: Non-contrast CT scans were obtained at baseline, 2h and 24h post-randomization. Mean relative CBF (rCBF) in the perihematoma region was calculated from raw CT Perfusion data obtained at 2h. Edema volume was measured using planimetric techniques and a Hounsfield unit threshold of ≤24 at baseline and 24h. Results: ICH patients were randomized (n=33 per group) at a median (IQR) of 7.6 (12.8) h after symptom onset. Mean SBP was significantly lower in the 180 mmHg; β=0.07 [-0.13, 0.24]) predicted edema growth. Conclusion: Perihematoma edema growth is explained by ICH volume expansion. Lower perihematoma CBF and BP treatment do not exacerbate edema growth. These data are not consistent with a cytotoxic mechanism of edema formation and support the safety of early BP treatment.

Background: The Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial (ICH ADAPT) demonstrated that aggressive blood pressure (BP) reduction does not affect mean perihematoma cerebral blood flow (CBF). It remains unknown if portions of the perihematoma region or watershed vascular territories (borderzones, BZs) reach ischemic thresholds after BP reduction. We tested the hypothesis that aggressive BP reduction was associated with an increased volume of critically hypoperfused tissue in ICH ADAPT patients. Methods: ICH patients were randomized to a target systolic BP (SBP) of Results: ICH patients (n=73) were randomized a median (IQR) of 7.8 (13.3) h from onset and imaged with CTP 2.3 (1.0) h later. Acute hematoma volume was 17.8 (27.1) ml and mean SBP was 183±22 mmHg. At the time of CTP, SBP was lower in the Conclusion: BP reduction does not increase the volume of hypoperfused tissue, at any threshold examined, in the perihematoma region or any BZ. These data support the safety of early BP reduction in ICH.

Background and Purpose— Mural thickening and permeability changes in patients with amyloid angiopathy (CAA) and chronic hypertension are implicated in the pathophysiology of multiple, chronic subclinical microbleeds. The Spot sign, contrast extravasation on CT angiography, predicts hematoma expansion and is presumed to represent acute vessel damage. We hypothesize that the Spot sign is more common in patients without multiple prior chronic microbleeds. Methods— A retrospective study was conducted of 59 patients presenting within 6 hours of primary intracranial hemorrhage onset undergoing CT angiography and MRI. CT angiography spot sign presence was documented blinded to MRI. Hematoma expansion was defined as >6 mL or 30% enlargement. The Boston criteria were applied to microbleed interpretation dichotomizing subjects into probable and negative CAA. Basal ganglia, thalamic, and brain stem microbleed location were interpreted as chronic hypertensive pattern. Univariate logistic regression and ordinal logistic regression analysis identified significant predictive factors between spot-positive and -negative patients or microbleed pattern. Results— The incidence of spot positivity was 42%, 22%, and 0% for CAA-negative, chronic hypertensive, and CAA-positive patients, respectively ( P =0.01). CAA-negative patients had higher baseline National Institutes of Health Stroke Scale ( P =0.039), larger follow-up hematoma volume ( P =0.02), and poorer Rankin score ( P =0.049) than chronic hypertensive or CAA-positive patients. After age adjustment, spot-positive ( P =0.023), age-related white matter change ( P =0.041), number of microbleeds ( P P =0.027) remained significantly different between groups. Conclusion— Boston criteria-defined CAA-negative status demonstrates the highest risk of spot positivity compared with patients with probable CAA and chronic hypertension.

A 32-year-old previously healthy recreational diver presented to the Ottawa Hospital with bilateral leg weakness and paresthesias. He was an experienced recreational diver. Earlier that day he had dived to a depth of 89 feet for a 20-minute period. He climbed to 15 feet for a 3-minute safety stop.