Publications by authors named "Steven Warach"

137 Publications

Patient Characteristics and Outcomes Associated with Decline in Stroke Volumes During the Early COVID-19 Pandemic.

J Stroke Cerebrovasc Dis 2020 Dec 26;30(6):105569. Epub 2020 Dec 26.

Department of Neurointerventional Surgery, Ascension Columbia St. Mary's Hospital, Milwaukee, WI. Electronic address:

Background And Purpose: Delayed evaluation of stroke may contribute to COVID-19 pandemic-related morbidity and mortality. This study evaluated patient characteristics, process measures and outcomes associated with the decline in stroke presentation during the early pandemic.

Methods: Volumes of stroke presentations, intravenous thrombolytic administrations, and mechanical thrombectomies from 52 hospitals from January 1-June 30, 2020 were analyzed with piecewise linear regression and linear spline models. Univariate analysis compared pandemic (case) and pre-pandemic (control) groups defined in relation to the nadir of daily strokes during the study period. Significantly different patient characteristics were further evaluated with logistic regression, and significantly different process measures and outcomes were re-analyzed after propensity score matching.

Results: Analysis of 7,389 patients found daily stroke volumes decreased 0.91/day from March 12-26 (p < 0.0001), reaching a nadir 35.0% less than expected, and increased 0.15 strokes/day from March 27-June 23, 2020 (p < 0.0001). Intravenous thrombolytic administrations decreased 3.3/week from February 19-March 31 (p = 0.0023), reaching a nadir 33.4% less than expected, and increased 1.4 administrations/week from April 1-June 23 (p < 0.0001). Mechanical thrombectomy volumes decreased by 1.5/week from February 19-March 31, 2020 (p = 0.0039), reaching a nadir 11.3% less than expected. The pandemic group was more likely to ambulate independently at baseline (p = 0.02, OR = 1.60, 95% CI = 1.08-2.42), and less likely to present with mild stroke symptoms (NIH Stroke Scale ≤ 5; p = 0.04, OR = 1.01, 95% CI = 1.00-1.02). Process measures and outcomes of each group did not differ, including door-to-needle time, door-to-puncture time, and successful mechanical thrombectomy rate.

Conclusion: Stroke presentations and acute interventions decreased during the early COVID-19 pandemic, at least in part due to patients with lower baseline functional status and milder symptoms not seeking medical care. Public health messaging and initiatives should target these populations.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762709PMC
December 2020

Restart TICrH: An Adaptive Randomized Trial of Time Intervals to Restart Direct Oral Anticoagulants after Traumatic Intracranial Hemorrhage.

J Neurotrauma 2021 Apr 6. Epub 2021 Apr 6.

Liverpool Centre for Cardiovascular Science, Institute of Life Course & Medical Sciences, University of Liverpool, Liverpool, United Kingdom.

Anticoagulants prevent thrombosis and death in patients with atrial fibrillation and venous thromboembolism (VTE) but also increase bleeding risk. The benefit/risk ratio favors anticoagulation in most of these patients. However, some will have a bleeding complication, such as the common trip-and-fall brain injury in elderly patients that results in traumatic intracranial hemorrhage. Clinicians must then make the difficult decision about when to restart the anticoagulant. Restarting too early risks making the bleeding worse. Restarting too late risks thrombotic events such as ischemic stroke and VTE, the indications for anticoagulation in the first place. There are more data on restarting patients with spontaneous intracranial hemorrhage, which is very different than traumatic intracranial hemorrhage. Spontaneous intracranial hemorrhage increases the risk of rebleeding because intrinsic vascular changes are widespread and irreversible. In contrast, traumatic cases are caused by a blow to the head, usually an isolated event portending less future risk. Clinicians generally agree that anticoagulation should be restarted but disagree about when. This uncertainty leads to long restart delays causing a large, potentially preventable burden of strokes and VTE, which has been unaddressed because of the absence of high quality evidence. Restart Traumatic Intracranial Hemorrhage (the "r" distinguished intracranial from intracerebral) (TICrH) is a prospective randomized open label blinded end-point response-adaptive clinical trial that will evaluate the impact of delays to restarting direct oral anticoagulation (1, 2, or 4 weeks) on the composite of thrombotic events and bleeding in patients presenting after traumatic intracranial hemorrhage.
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http://dx.doi.org/10.1089/neu.2020.7535DOI Listing
April 2021

IAT-TiMeS: Intra-Arterial Thrombectomy Transfer Metric Study in Texas.

J Stroke Cerebrovasc Dis 2021 Mar 15;30(3):105602. Epub 2021 Jan 15.

Institute for Stroke and Cerebrovascular Disease and Department of Neurology, The University of Texas Health Science Center at Houston, Houston, Texas, USA. Electronic address:

Objective: We aim to report intra-arterial thrombectomy transfer metrics for ischemic stroke patients that were transferred to hub hospitals for possible intra-arterial thrombectomy in multiple geographic regions throughout the state of Texas and to identify potential barriers and delays in the intra-arterial thrombectomy transfer process.

Method: We prospectively collected data from 8 participating Texas comprehensive stroke/thrombectomy capable centers from 7 major regions in the State of Texas. We collected baseline clinical and imaging data related to the pre-transfer evaluation, transfer metrics, and post-transfer clinical and imaging data.

Results: A total of 103 acute ischemic stroke patients suspected/confirmed to have large vessel occlusions between December 2016 to May 2019 that were transferred to hubs as possible intra-arterial thrombectomy candidates were enrolled. A total of 56 (54%) patients were sent from the spoke to the hub via ground ambulance with 47 (46%) patients traveling via air ambulance. The median spoke arrival to hub arrival time was 174 min, median spoke arrival to departure from spoke was 131 min, and median travel time was 39 min. The spoke arrival time to transfer initiation was 68 min. CT-perfusion obtained at the spoke and earlier initiation of transfer were statistically associated with shorter transfer times.

Conclusion: Transfer of intra-arterial thrombectomy patients in Texas may take over 4 h from spoke arrival to hub arrival. This time may be shortened by earlier transfer initiation and acceptance.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105602DOI Listing
March 2021

Restarting and timing of oral anticoagulation after traumatic intracranial hemorrhage: a review and summary of ongoing and planned prospective randomized clinical trials.

Trauma Surg Acute Care Open 2020 3;5(1):e000605. Epub 2020 Dec 3.

Department of Neurology, The University of Texas at Austin Dell Medical School, Austin, Texas, USA.

Anticoagulant-associated traumatic intracranial hemorrhage (tICrH) is a devastating injury with high morbidity and mortality. For survivors, treating clinicians face the dilemma of restarting oral anticoagulation with scarce evidence to guide them. Thromboembolic risk is high from the bleeding event, patients' high baseline risks, that is, the pre-existing indication for anticoagulation, and the risk of immobility after the bleeding episode. This must be balanced with potentially devastating hematoma expansion or new hemorrhagic lesions. Retrospective evidence and expert opinion support restarting oral anticoagulants in most patients with tICrH, but timing is uncertain. Researchers have failed to make clear distinctions between tICrH and spontaneous intracranial hemorrhage (sICrH), which have differing natural histories. While both appear to benefit from restarting, sICrH has a higher rebleeding risk and similar or lower thrombotic risk. Clinical equipoise on restarting is also divergent. In sICrH, equipoise is centered on whether to restart. In tICrH, it is centered on when. Several prospective randomized clinical trials are ongoing or about to start to examine the risk-benefit of restarting. Most of them are restricted to patients with sICrH, with antiplatelet control groups. Most are also restricted to direct oral anticoagulants (DOACs), as they are associated with a lower overall risk of ICrH. There is some overlap with tICrH via subdural hematoma, and one trial is specific to restart timing with DOACs in only traumatic cases. This is a narrative review of the current evidence for restarting anticoagulation and restart timing after tICrH along with a summary of the ongoing and planned clinical trials.
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http://dx.doi.org/10.1136/tsaco-2020-000605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716676PMC
December 2020

Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data.

Lancet 2020 11 8;396(10262):1574-1584. Epub 2020 Nov 8.

Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.

Background: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers.

Methods: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903.

Findings: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22-25·50]; p=0·024).

Interpretation: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death.

Funding: None.
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http://dx.doi.org/10.1016/S0140-6736(20)32163-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734592PMC
November 2020

Lone Star Stroke Consortium: A Collaborative State-Funded Model for Research.

Stroke 2020 12 29;51(12):3778-3786. Epub 2020 Oct 29.

Department of Neurology, Dell Medical School, The University of Texas at Austin (S.J.W.).

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http://dx.doi.org/10.1161/STROKEAHA.120.031547DOI Listing
December 2020

Tenecteplase Thrombolysis for Acute Ischemic Stroke.

Stroke 2020 11 13;51(11):3440-3451. Epub 2020 Oct 13.

Department of Neurology, Dell Medical School, University of Texas at Austin.

Tenecteplase is a fibrinolytic drug with higher fibrin specificity and longer half-life than the standard stroke thrombolytic, alteplase, permitting the convenience of single bolus administration. Tenecteplase, at 0.5 mg/kg, has regulatory approval to treat ST-segment-elevation myocardial infarction, for which it has equivalent 30-day mortality and fewer systemic hemorrhages. Investigated as a thrombolytic for ischemic stroke over the past 15 years, tenecteplase is currently being studied in several phase 3 trials. Based on a systematic literature search, we provide a qualitative synthesis of published stroke clinical trials of tenecteplase that (1) performed randomized comparisons with alteplase, (2) compared different doses of tenecteplase, or (3) provided unique quantitative meta-analyses. Four phase 2 and one phase 3 study performed randomized comparisons with alteplase. These and other phase 2 studies compared different tenecteplase doses and effects on early outcomes of recanalization, reperfusion, and substantial neurological improvement, as well as symptomatic intracranial hemorrhage and 3-month disability on the modified Rankin Scale. Although no single trial prospectively demonstrated superiority or noninferiority of tenecteplase on clinical outcome, meta-analyses of these trials (1585 patients randomized) point to tenecteplase superiority in recanalization of large vessel occlusions and noninferiority in disability-free 3-month outcome, without increases in symptomatic intracranial hemorrhage or mortality. Doses of 0.25 and 0.4 mg/kg have been tested, but no advantage of the higher dose has been suggested by the results. Current clinical practice guidelines for stroke include intravenous tenecteplase at either dose as a second-tier option, with the 0.25 mg/kg dose recommended for large vessel occlusions, based on a phase 2 trial that demonstrated superior recanalization and improved 3-month outcome relative to alteplase. Ongoing randomized phase 3 trials may better define the comparative risks and benefits of tenecteplase and alteplase for stroke thrombolysis and answer questions of tenecteplase efficacy in the >4.5-hour time window, in wake-up stroke, and in combination with endovascular thrombectomy.
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http://dx.doi.org/10.1161/STROKEAHA.120.029749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606819PMC
November 2020

Stroke Thrombolysis With Tenecteplase to Reduce Emergency Department Spread of Coronavirus Disease 2019 and Shortages of Alteplase.

JAMA Neurol 2020 Oct;77(10):1203-1204

Department of Neurology, Geffen School of Medicine at UCLA, Los Angeles, California.

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http://dx.doi.org/10.1001/jamaneurol.2020.2396DOI Listing
October 2020

Quantitative Analysis of the Cerebral Vasculature on Magnetic Resonance Angiography.

Sci Rep 2020 06 23;10(1):10227. Epub 2020 Jun 23.

Department of Neurology, Dell Medical School at The University of Texas, Austin, Texas, USA.

The arterial connections in the Circle of Willis are a central source of collateral blood flow and play an important role in pathologies such as stroke and mental illness. Analysis of the Circle of Willis and its variants can shed light on optimal methods of diagnosis, treatment planning, surgery, and quantification of outcomes. We developed an automated, standardized, objective, and high-throughput approach for categorizing and quantifying the Circle of Willis vascular anatomy using magnetic resonance angiography images. This automated algorithm for processing of MRA images isolates and automatically identifies key features of the cerebral vasculature such as branching of the internal intracranial internal carotid artery and the basilar artery. Subsequently, physical features of the segments of the anterior cerebral artery were acquired on a sample and intra-patient comparisons were made. We demonstrate the feasibility of using our approach to automatically classify important structures of the Circle of Willis and extract biomarkers from cerebrovasculature. Automated image analysis can provide clinically-relevant vascular features such as aplastic arteries, stenosis, aneurysms, and vessel caliper for endovascular procedures. The developed algorithm could facilitate clinical studies by supporting high-throughput automated analysis of the cerebral vasculature.
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http://dx.doi.org/10.1038/s41598-020-67225-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311427PMC
June 2020

Reversible diffusion-weighted imaging lesions in acute ischemic stroke: A systematic review.

Neurology 2020 03 4;94(13):571-587. Epub 2020 Mar 4.

From the Department of Neurology (N.N.), University of Florida College of Medicine, Gainesville; Department of Radiology and Biomedical Engineering (J.R.F.), University of Florida, Gainesville; Dell Medical School (S.W.), University of Texas at Austin; and Department of Neurology (J.G.M.), Georgetown University School of Medicine, Washington, DC.

Objectives: To systematically review the literature for reversible diffusion-weighted imaging (DWIR) lesions and to describe its prevalence, predictors, and clinical significance.

Methods: Studies were included if the first DWI MRI was performed within 24 hours of stroke onset and follow-up DWI or fluid-attenuated inversion recovery (FLAIR)/T2 was performed within 7 or 90 days, respectively, to measure DWIR. We abstracted clinical, imaging, and outcomes data.

Results: Twenty-three studies met the study criteria. The prevalence of DWIR was 26.5% in DWI-based studies and 6% in FLAIR/T2-based studies. DWIR was associated with recanalization or reperfusion of the ischemic tissue with or without the use of tissue plasminogen activator (t-PA) or endovascular therapy, earlier treatment with t-PA, shorter time to endovascular therapy after MRI, and absent or less severe perfusion deficit within the DWI lesion. DWIR was associated with early neurologic improvement in 5 of 6 studies (defined as improvement in the NIH Stroke Scale (NIHSS) score by 4 or 8 points from baseline or NIHSS score 0 to 2 at 24 hours after treatment or at discharge or median NIHSS score at 7 days) and long-term outcome in 6 of 7 studies (defined as NIHSS score ≤1, improvement in the NIHSS score ≥8 points, or modified Rankin Scale score up to ≤2 at 30 or 90 days) likely due to reperfusion.

Conclusions: DWIR is seen in up to a quarter of patients with acute ischemic stroke, and it is associated with good clinical outcome following reperfusion. Our findings highlight the pitfalls of DWI to define ischemic core in the early hours of stroke.
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http://dx.doi.org/10.1212/WNL.0000000000009173DOI Listing
March 2020

Neuroimaging in Ischemic Stroke Is Different Between Men and Women in the DEFUSE 3 Cohort.

Stroke 2020 02 12;51(2):481-488. Epub 2019 Dec 12.

From the Department of Neurology (A.N.D., N.D.Z., S.J.W.), Dell Medical School at The University of Texas, Austin.

Background and Purpose- Clinical deficits from ischemic stroke are more severe in women, but the pathophysiological basis of this sex difference is unknown. Sex differences in core and penumbral volumes and their relation to outcome were assessed in this substudy of the DEFUSE 3 clinical trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke). Methods- DEFUSE 3 randomized patients to thrombectomy or medical management who presented 6 to 16 hours from last known well with proximal middle cerebral artery or internal carotid artery occlusion and had target core and perfusion mismatch volumes on computed tomography or magnetic resonance imaging. Using univariate and adjusted regression models, the effect of sex was assessed on prerandomization measures of core, perfusion, and mismatch volumes and hypoperfusion intensity ratio, and on core volume growth using 24-hour scans. Results- All patients were included in the analysis (n=182) with 90 men and 92 women. There was no sex difference in the site of baseline arterial occlusion. Adjusted by age, baseline National Institutes of Health Stroke Scale, baseline modified Rankin Scale score, time to randomization, and imaging modality, women had smaller core, hypoperfusion, and penumbral volumes than men. Median (interquartile range) volumes for core were 8.0 mL (1.9-18.4) in women versus 12.6 mL (2.7-29.6) in men, for T>6 seconds 89.0 mL (63.8-131.7) versus 133.9 mL (87.0-175.4), and for mismatch 82.1mL (53.8-112.8) versus 108.2 (64.1-149.2). The hypoperfusion intensity ratio was lower in women, 0.31 (0.15-0.46) versus 0.39 (0.26-0.57), =0.006, indicating better collateral circulation, which was consistent with the observed slower ischemic core growth than men within the medical group (=0.003). Conclusions- In the large vessel ischemic stroke cohort selected for DEFUSE 3, women had imaging evidence of better collateral circulation, smaller baseline core volumes, and slower ischemic core growth. These observations suggest sex differences in hemodynamic and temporal features of anterior circulation large artery occlusions. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT02586415.
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http://dx.doi.org/10.1161/STROKEAHA.119.028205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121881PMC
February 2020

End of life: Expert care and support, not physician-hastened death.

Neurology 2019 10 17;93(17):729-734. Epub 2019 Sep 17.

From the Houston Methodist Neurological Institute (J.C.M), TX; Weill Cornell Medicine (J.C.M, A.C.C., K.M.F), New York, NY; Mayo Clinic (A.J.A.), Rochester, MN; Memorial Sloan Kettering Cancer Center (A.C.C., K.M.F), New York, NY; Baylor College of Medicine (J.S.K); McGovern Medical School (R.A.M., R.M.), University of Texas Health Science Center at Houston; Sydney University Medical School (E.A.M.), Australia; Stanford Health Care (M.P.M), Palo Alto, CA; private practice (S.J.V.), Erwinna, PA; and Dell Medical School (S.W.), University of Texas at Austin.

In legal physician-hastened death, a physician prescribes medication with the primary intent of causing the death of a willing terminally ill patient. This practice differs radically from palliative sedation, intended to relieve a patient's suffering rather than cause a patient's death. In this position paper, we argue that the practice of physician-hastened death is contrary to the interests of patients, their families, and the sound ethical practice of medicine. Therefore, the American Academy of Neurology should advise its members against this practice, as it had done until 2018.
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http://dx.doi.org/10.1212/WNL.0000000000008356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946468PMC
October 2019

Direct Assessment of Health Utilities Using the Standard Gamble Among Patients With Primary Intracerebral Hemorrhage.

Circ Cardiovasc Qual Outcomes 2019 09 13;12(9):e005606. Epub 2019 Sep 13.

Department of Neurology and Institute for Stroke and Cerebrovascular Diseases, McGovern Medical School (K.B.S., E.G.M., A.B.B., J.R.M., L.D.M., S.I.S., F.S.V.), UTHealth, Houston, TX.

Background: Standard gamble (SG) directly measures patients' valuation of their health state. We compare in-hospital and day-90 SG utilities (SGU) among intracerebral hemorrhage patients and report a 3-way association between SGU, EuroQoL-5 dimension, and modified Rankin Scale at day 90.

Methods And Results: Patients with intracerebral hemorrhage underwent in-hospital and day-90 assessments for the modified Rankin Scale, EuroQoL-5 dimension, and SG. SG provides patients a choice between their current health state and a hypothetical treatment with varying chances of either perfect health or a painless death. Higher SGU (scale, 0-1) indicates lower risk tolerance and thus higher valuation of the current health state. Logistic regression was used to estimate the likelihood of low SGU (≤0.6), and Wilcoxon paired signed-rank test compared in-hospital and day-90 SGU. In-hospital and day-90 SG was obtained from 381 and 280 patients, respectively, including 236 paired observations. Median (interquartile range) in-hospital and day-90 SGUs were 0.85 (0.40-0.98) and 0.98 (0.75-1.00; <0.001). In-hospital SGUs were lower with advancing age (=0.007), higher National Institutes of Health Stroke Scale, and intracerebral hemorrhage scores (<0.001). Proxy-based assessments resulted in lower SGUs; median difference (95% CI), -0.2 (-0.33 to -0.07). After adjustment, higher National Institutes of Health Stroke Scale and proxy assessments were independently associated with lower SGU, along with an effect modification of age by race. Day-90 SGU and modified Rankin Scale were significantly correlated; however, SGUs were higher than the EuroQoL-5 dimension utilities at higher modified Rankin Scale levels.

Conclusions: Divergence between directly (SGU) and indirectly (EuroQoL-5 dimension) assessed utilities at high levels of functional disability warrant careful prognostication of intracerebral hemorrhage outcomes and should be considered in designing early end-of-life care discussions with families and patients.
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http://dx.doi.org/10.1161/CIRCOUTCOMES.119.005606DOI Listing
September 2019

Optimal delay time to initiate anticoagulation after ischemic stroke in atrial fibrillation (START): Methodology of a pragmatic, response-adaptive, prospective randomized clinical trial.

Int J Stroke 2019 12 18;14(9):977-982. Epub 2019 Aug 18.

Department of Neurology, University of Texas Dell Medical School, Austin, TX, USA.

Rationale: An estimated 15% of all strokes are associated with untreated atrial fibrillation. Long-term secondary stroke prevention in atrial fibrillation is anticoagulation, increasingly with non-vitamin K oral anticoagulants. The optimal time to initiate anticoagulation following an atrial fibrillation-related stroke that balances hemorrhagic conversion with recurrent stroke is not yet known.

Aims: To determine if there is an optimal delay time to initiate anticoagulation after atrial fibrillation-related stroke that optimizes the composite outcome of hemorrhagic conversion and recurrent ischemic stroke.

Sample Size Estimates: The study will enroll 1500 total subjects split between a mild to moderate stroke cohort (1000) and a severe stroke cohort (500).

Methods And Design: This study is a multi-center, prospective, randomized, pragmatic, adaptive trial that randomizes subjects to four arms of time to start of anticoagulation. The four arms for mild to moderate stroke are: Day 3, Day 6, Day 10, and Day 14. The time intervals for severe stroke are: Day 6, Day 10, Day 14, and Day 21. Allocation involves a response adaptive randomization via interim analyses to favor the arms that have a better risk-benefit profile.

Study Outcomes: The primary outcome event is the composite occurrence of an ischemic or hemorrhagic event within 30 days of the index stroke. Secondary outcomes are also collected at 30 and 90 days.

Discussion: The optimal timing of direct oral anticoagulants post-ischemic stroke requires prospective randomized testing. A pragmatically designed trial with adaptive allocation and randomization to multiple time intervals such as the START trial is best suited to answer this question in order to directly inform current practice on this question.
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http://dx.doi.org/10.1177/1747493019870651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401695PMC
December 2019

Sex Differences in Outcome After Endovascular Stroke Therapy for Acute Ischemic Stroke.

Stroke 2019 09 15;50(9):2420-2427. Epub 2019 Aug 15.

Department of Neurology, Ronald Reagan UCLA Medical Center, Santa Monica (D.S.L., J.L.S.).

Background and Purpose- We determined the effect of sex on outcome after endovascular stroke thrombectomy in acute ischemic stroke, including lifelong disability outcomes. Methods- We analyzed patients treated with the Solitaire stent retriever in the combined SWIFT (Solitaire FR With the Intention for Thrombectomy), STAR (Solitaire FR Thrombectomy for Acute Revascularization), and SWIFT PRIME (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment) cohorts. Ordinal and logistic regression were used to examine known factors influencing outcome after endovascular stroke thrombectomy and study the effect of sex on the association between these factors and outcomes, including age and time to reperfusion. Years of optimal life after thrombectomy were defined as disability-adjusted life years and calculated by projecting disability through adjusted poststroke life expectancy by sex. Results- Among 389 patients treated with endovascular stroke thrombectomy, 55% were females, and median National Institutes of Health Stroke Scale was 17 (interquartile range, 8-28). There were no differences between females versus males in presenting deficit severity (National Institutes of Health Stroke Scale score, 17 versus 17, P=0.21), occlusion location (69% versus 64% M1, P=0.62), presenting infarct extent (Alberta Stroke Program Early CT Score 8 versus 8, P=0.24), rate of substantial reperfusion (Thrombolysis in Cerebral Infarction 2b/3, 87% versus 83%, P=0.37), onset to reperfusion time (294 versus 302 minutes, P=0.46). Despite older ages (69 versus 64, P<0.001) and higher rate of atrial fibrillation (45% versus 30%, P=0.002) for females compared with males, adjusted rates of functional independence at 90 days were similar (odds ratio, 1.0; 95% CI, 0.6-1.6). After adjusting for age at presentation and stroke severity, females had more years of optimal life (disability-adjusted life year) after endovascular stroke thrombectomy, 10.6 versus 8.5 years (P<0.001). Conclusions- Despite greater age and higher rate of atrial fibrillation, females experienced comparable functional outcomes and greater years of optimal life after intervention compared with males.
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http://dx.doi.org/10.1161/STROKEAHA.118.023867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710145PMC
September 2019

Neuroimaging evolution of ischemia in men and women: an observational study.

Ann Clin Transl Neurol 2019 03 21;6(3):575-585. Epub 2019 Feb 21.

Department of Neurology Dell Medical School at The University of Texas Austin Texas.

Objective: We present an exploratory study for identification of sex differences in imaging biomarkers that could further refine selection of patients for acute reperfusion therapy and trials based on sex and imaging targets.

Methods: The Lesion Evolution in Stroke and Ischemia On Neuroimaging (LESION) study included consecutive acute stroke patients who underwent MRI within 24 h of time from last known well and prior to therapy. Those demonstrating a potential therapeutic target on imaging were identified by presence of: (1) arterial occlusion on angiography, (2) focal ischemic region on perfusion maps, or (3) a mismatch of perfusion versus diffusion imaging lesion size. The prevalence of imaging targets within clinically relevant time intervals was calculated for each patient and examined. The relationship of time from stroke onset to probability of detection of imaging targets was evaluated.

Results: Of 7007 patients screened, of which 86.7% were scanned with MRI, 1092 patients (477/615 men/women) were included in LESION. The probability of imaging target detection was significantly different between men and women, with women more likely to present with all assessed imaging targets, odds ratios between 1.36 and 1.59,  < 0.02, adjusted for NIHSS, age, and time from last known well to MRI scan. This trend held for the entire 24-h studied.

Interpretation: Women present more often with treatable ischemic stroke than men. The greater probability of potentially viable and/or treatable imaging targets in women at all time points suggests that tissue injury is slower to evolve in women.
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http://dx.doi.org/10.1002/acn3.733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6414486PMC
March 2019

Timing of anticoagulation after recent ischaemic stroke in patients with atrial fibrillation.

Lancet Neurol 2019 01 8;18(1):117-126. Epub 2018 Nov 8.

Department of Neurology, Lund University, Skane University Hospital, Lund, Sweden.

Background: About 13-26% of all acute ischaemic strokes are related to non-valvular atrial fibrillation, the most common cardiac arrhythmia globally. Deciding when to initiate oral anticoagulation in patients with non-valvular atrial fibrillation is a longstanding, common, and unresolved clinical challenge. Although the risk of early recurrent ischaemic stroke is high in this population, early oral anticoagulation is suspected to increase the risk of potentially harmful intracranial haemorrhage, including haemorrhagic transformation of the infarct. This assumption, and current treatment guidelines, are based on historical, mostly observational data from patients with ischaemic stroke and atrial fibrillation treated with heparins, heparinoids, or vitamin K antagonists (VKAs) to prevent recurrent ischaemic stroke. Randomised controlled trials have subsequently shown that direct oral anticoagulants (DOACs; ie, apixaban, dabigatran, edoxaban, and rivaroxaban) are at least as effective as VKAs in primary and secondary prevention of atrial fibrillation-related ischaemic stroke, with around half the risk of intracranial haemorrhage. However, none of these DOAC trials included patients who had experienced ischaemic stroke recently (within the first few weeks). Clinicians therefore remain uncertain regarding when to commence DOAC administration after acute ischaemic stroke in patients with atrial fibrillation.

Recent Developments: Prospective observational studies and two small randomised trials have investigated the risks and benefits of early DOAC-administration initiation (most with a median delay of 3-5 days) in mild-to-moderate atrial fibrillation-associated ischaemic stroke. These studies reported that early DOAC treatment was associated with a low frequency of clinically symptomatic intracranial haemorrhage or surrogate haemorrhagic lesions on MRI scans, whereas later DOAC-administration initiation (ie, >7 days or >14 days after index stroke) was associated with an increased frequency of recurrent ischaemic stroke. WHERE NEXT?: Adequately powered randomised controlled trials comparing early to later oral anticoagulation with DOACs in ischaemic stroke associated with atrial fibrillation are justified to confirm the acceptable safety and efficacy of this strategy. Four such randomised controlled trials (collectively planned to include around 9000 participants) are underway, either using single cutoff timepoints for early versus late DOAC-administration initiation, or selecting DOAC-administration timing according to the severity and imaging features of the ischaemic stroke. The results of these trials should help to establish the optimal timing to initiate DOAC administration after recent ischaemic stroke and whether the timing should differ according to stroke severity. Results of these trials are expected from 2021.
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http://dx.doi.org/10.1016/S1474-4422(18)30356-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524642PMC
January 2019

Patients with large brain infarcts might also benefit from thrombectomy.

Authors:
Steven Warach

Lancet Neurol 2019 01 6;18(1):22-23. Epub 2018 Nov 6.

Dell Medical School, University of Texas at Austin, Austin, TX 78746, USA. Electronic address:

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http://dx.doi.org/10.1016/S1474-4422(18)30357-0DOI Listing
January 2019

Impact of Lesion Load Thresholds on Alberta Stroke Program Early Computed Tomographic Score in Diffusion-Weighted Imaging.

Front Neurol 2018 23;9:273. Epub 2018 Apr 23.

Klinik und Poliklinik für Neurologie, Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.

Background And Aims: Assessment of ischemic lesions on computed tomography or MRI diffusion-weighted imaging (DWI) using the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is widely used to guide acute stroke treatment. However, it has never been defined how many voxels need to be affected to label a DWI-ASPECTS region ischemic. We aimed to assess the effect of various lesion load thresholds on DWI-ASPECTS and compare this automated analysis with visual rating.

Materials And Methods: We analyzed overlap of individual DWI lesions of 315 patients from the previously published predictive value of fluid-attenuated inversion recovery study with a probabilistic ASPECTS template derived from 221 CT images. We applied multiple lesion load thresholds per DWI-ASPECTS region (>0, >1, >10, and >20% in each DWI-ASPECTS region) to compute DWI-ASPECTS for each patient and compared the results to visual reading by an experienced stroke neurologist.

Results: By visual rating, median ASPECTS was 9, 84 patients had a DWI-ASPECTS score ≤7. Mean DWI lesion volume was 22.1 (±35) ml. In contrast, by use of >0, >1-, >10-, and >20%-thresholds, median DWI-ASPECTS was 1, 5, 8, and 10; 97.1% (306), 72.7% (229), 41% (129), and 25.7% (81) had DWI-ASPECTS ≤7, respectively. Overall agreement between automated assessment and visual rating was low for every threshold used (>0%: κ = 0.020 1%: κ = 0.151; 10%: κ = 0.386; 20% κ = 0.381). Agreement for dichotomized DWI-ASPECTS ranged from fair to substantial (≤7: >10% κ = 0.48; >20% κ = 0.45; ≤5: >10% κ = 0.528; and >20% κ = 0.695).

Conclusion: Overall agreement between automated and the standard used visual scoring is low regardless of the lesion load threshold used. However, dichotomized scoring achieved more comparable results. Varying lesion load thresholds had a critical impact on patient selection by ASPECTS. Of note, the relatively low lesion volume and lack of patients with large artery occlusion in our cohort may limit generalizability of these findings.
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http://dx.doi.org/10.3389/fneur.2018.00273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926541PMC
April 2018

Intravenous thrombolysis in unwitnessed stroke onset: MR WITNESS trial results.

Ann Neurol 2018 05 27;83(5):980-993. Epub 2018 Apr 27.

Dell Medical School, University of Texas at Austin, Austin, TX.

Objective: Most acute ischemic stroke (AIS) patients with unwitnessed symptom onset are ineligible for intravenous thrombolysis due to timing alone. Lesion evolution on fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) correlates with stroke duration, and quantitative mismatch of diffusion-weighted MRI with FLAIR (qDFM) might indicate stroke duration within guideline-recommended thrombolysis. We tested whether intravenous thrombolysis ≤4.5 hours from the time of symptom discovery is safe in patients with qDFM in an open-label, phase 2a, prospective study (NCT01282242).

Methods: Patients aged 18 to 85 years with AIS of unwitnessed onset at 4.5 to 24 hours since they were last known to be well, treatable within 4.5 hours of symptom discovery with intravenous alteplase (0.9mg/kg), and presenting with qDFM were screened across 14 hospitals. The primary outcome was the risk of symptomatic intracranial hemorrhage (sICH) with preplanned stopping rules. Secondary outcomes included symptomatic brain edema risk, and functional outcomes of 90-day modified Rankin Scale (mRS).

Results: Eighty subjects were enrolled between January 31, 2011 and October 4, 2015 and treated with alteplase at median 11.2 hours (IQR = 9.5-13.3) from when they were last known to be well. There was 1 sICH (1.3%) and 3 cases of symptomatic edema (3.8%). At 90 days, 39% of subjects achieved mRS = 0-1, as did 48% of subjects who had vessel imaging and were without large vessel occlusions.

Interpretation: Intravenous thrombolysis within 4.5 hours of symptom discovery in patients with unwitnessed stroke selected by qDFM, who are beyond the recommended time windows, is safe. A randomized trial testing efficacy using qDFM appears feasible and is warranted in patients without large vessel occlusions. Ann Neurol 2018;83:980-993.
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http://dx.doi.org/10.1002/ana.25235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6095471PMC
May 2018

Rationale and Design of a Statewide Cohort to examine efficient resource utilization for patients with Intracerebral hemorrhage (EnRICH).

BMC Neurol 2018 Mar 21;18(1):31. Epub 2018 Mar 21.

Department of Neurology and the Institute for Stroke and Cerebrovascular Disease, McGovern Medical School, University of Texas - Health, Houston, TX, USA.

Background: Intracerebral hemorrhage is a devastating disease with no specific treatment modalities. A significant proportion of patients with intracerebral hemorrhage are transferred to large stroke treatment centers, such as Comprehensive Stroke Centers, because of perceived need for higher level of care. However, evidence of improvement in patient-centered outcomes for these patients treated at larger stroke treatment centers as compared to community hospitals is lacking. METHODS / DESIGN: "Efficient Resource Utilization for Patients with Intracerebral Hemorrhage (EnRICH)" is a prospective, multisite, state-wide, cohort study designed to assess the impact of level of care on long-term patient-centered outcomes for patients with primary / non-traumatic intracerebral hemorrhage. The study is funded by the Texas state legislature via the Lone Star Stroke Research Consortium. It is being implemented via major hub hospitals in large metropolitan cities across the state of Texas. Each hub has an extensive network of "spoke" hospitals, which are connected to the hub via traditional clinical and administrative arrangements, or by telemedicine technologies. This infrastructure provides a unique opportunity to track outcomes for intracerebral hemorrhage patients managed across a health system at various levels of care. Eligible patients are enrolled during hospitalization and are followed for functional, quality of life, cognitive, resource utilization, and dependency outcomes at 30 and 90 days post discharge. As a secondary aim, an economic analysis of the incremental cost-effectiveness of treating intracerebral hemorrhage patients at higher levels of care will be conducted.

Discussion: Findings from EnRICH will provide much needed evidence of the effectiveness and efficiency of regionalized care for intracerebral hemorrhage patients. Such evidence is required to inform policy and streamline clinical decision-making.
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http://dx.doi.org/10.1186/s12883-018-1036-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863437PMC
March 2018

Intravenous Thrombolysis at 3.5 Hours From Onset of Pediatric Acute Ischemic Stroke.

Pediatr Emerg Care 2020 Jan;36(1):e4-e7

From the Seton Dell Medical School Stroke Institute, Austin, TX.

Acute thrombolysis has a proven benefit for adults presenting with acute ischemic stroke, but data within the pediatric population are extremely limited. We report the case of a 14-year-old girl who presented with right-sided weakness and ataxia, loss of sensation, and altered mental status. Magnetic resonance imaging with diffusion-weighted imaging showed an acute lesion in the distribution of the left posterior cerebral artery, and magnetic resonance angiogram demonstrated occlusion of the third branch of the left posterior cerebral artery. With parental consent, clinicians decided to infuse an adult dose of weight-adjusted intravenous alteplase at 3.5 hours from onset of symptoms, with subsequent improvement in National Institutes of Health Stroke Scale score from 11 to 3. Computed tomography angiogram at 24 hours showed recanalization of the occluded vessel with no evidence of intracranial hemorrhage. Stroke Scale score at discharge was 3, with modified Rankin Scale scores at discharge of 1 and at 90 days of 0. This case highlights the importance of magnetic resonance imaging in diagnosing pediatric acute ischemic stroke and suggests consideration of thrombolysis in select confirmed pediatric stroke cases. However, a rigorous evidence base is lacking, and clinical trials have not been successful in recruiting patients.
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http://dx.doi.org/10.1097/PEC.0000000000001419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6077109PMC
January 2020

Blood-brain barrier leakage increases with small vessel disease in acute ischemic stroke.

Neurology 2017 Nov 25;89(21):2143-2150. Epub 2017 Oct 25.

From the NEUROFARBA Department (F.A., D.I.), University of Florence, Italy; National Institute of Neurological Disorders and Stroke (R.L., M.L.), NIH, Bethesda, MD; Institute of Cardiovascular and Medical Sciences (F.A.), Queen Elizabeth University Hospital, Glasgow, UK; Department of Neurology (S.J.W.), Dell Medical School, University of Texas at Austin; and Institute of Cardiovascular & Medical Sciences (K.R.L.), University of Glasgow, UK.

Objective: In patients with acute ischemic stroke, we aimed to investigate the relation between preexisting small vessel disease (SVD) and the amount of blood-brain barrier (BBB) leakage in ischemic and nonischemic area before IV thrombolysis.

Methods: We retrospectively accessed anonymous patient-level data from the Stroke Imaging Repository and the Virtual International Stroke Trials Archive resources and included patients treated with IV thrombolysis with pretreatment MRI. We rated SVD features using validated qualitative magnetic resonance (MR) scales. Leakage of BBB was assessed with postprocessing of perfusion-weighted images. We evaluated associations between SVD features (individually and summed in a global SVD score) and BBB leakage using linear regression analysis, adjusting for major clinical confounders.

Results: A total of 212 patients, mean age (±SD) 69.5 years (±16.1), 102 (48%) male, had available MR before IV thrombolysis. Evidence of BBB leakage was present in 175 (80%) and 205 (94%) patients in the ischemic and nonischemic area, respectively. Lacunar infarcts (β = 0.17, = 0.042) were associated with BBB leakage in the ischemic area, and brain atrophy was associated with BBB leakage in both ischemic (β = 0.20, = 0.026) and nonischemic (β = 0.27, = 0.001) areas. Increasing SVD grade was independently associated with BBB leakage in both ischemic (β = 0.26, = 0.007) and nonischemic (β = 0.27, = 0.003) area.

Conclusions: Global SVD burden is associated with increased BBB leakage in both acutely ischemic and nonischemic area. Our results support that SVD score has construct validity, and confirm a relation between SVD and BBB disruption also in patients with acute stroke.
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http://dx.doi.org/10.1212/WNL.0000000000004677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696647PMC
November 2017

Translational Stroke Research: Vision and Opportunities.

Stroke 2017 09 27;48(9):2632-2637. Epub 2017 Jul 27.

From the National Institute of Neurological Disorders and Stroke, National Institutes of Health (F.B., J.I.K., R.A.C., L.B.J., S.J., L.M.M., C.S.M., I.R., W.K.); Department of Neurology, Massachusetts General Hospital, Boston (C.A., E.H.L., L.H.S.); Oregon Health & Science University, Portland (S.A.B., M.P.S.-P.); Department of Neurology and Neurological Surgery, University of Washington, Seattle (K.B.); Department of Neurology and Rehabilitation Medicine, University of Cincinnati, OH (J.P.B.); Department of Neurology, University of California, Los Angeles (S.T.C.); Brain Mind Research Institute, Weill Cornell Medicine, New York, NY (S.C., C.I.); Department of Neurological Sciences, University of Vermont, Burlington (M.J. C.); Brain and Mind Research Institute, University of Ottawa, Ontario (D.C.); Department of Neurology, University of California, Irvine, Orange (S.C.C.); Department of Neurological Surgery, University of California, San Francisco (A.R.F.); Stemetix, Inc, Needham, MA (S.F.); Division of Biomedical Sciences, University of California, Riverside (B.D.F.); Department of Neurology, Brown University, Providence, RI (K.L.F.); Department of Neurology, University of California, San Diego (T.M.H.); Department of Emergency Medicine, Medical University of South Carolina, Charleston (E.C.J.); Department of Neurology, University of Virginia, Charlottesville (K.C.J.); Department of Critical Care Medicine (P.M.K.) and Department of Neurology (L.R.W.), University of Pittsburgh, PA; School of Pharmacy, University of North Carolina, Chapel Hill (H.K.); Cedars-Sinai Medical Center, Los Angeles, CA (P.D.L.); University of Gothenburg, Sweden (C.M.); Department of Neurology, University of Texas Health Science Center, Houston (L.D.M., S.I.S.); Mayo Clinic, Jacksonville, FL (J.F.M.); Department of Neurology, University of Miami Miller School, FL (M.A.P.-P.); Department of Neurosurgery, Stanford University, CA (G.K.S.); Division of Fundamental Neurobiology, Krembil Research Institute, Toronto, ON (M.T.); Department of Neurology, University of Texas, Austin (S.W.); and Department of Neurosurgery and Anesthesiology, Loma Linda University, CA (J.H.Z.).

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http://dx.doi.org/10.1161/STROKEAHA.117.017112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5599159PMC
September 2017

Endovascular Thrombectomy for Ischemic Stroke: The Second Quantum Leap in Stroke Systems of Care?

JAMA 2016 Sep;316(12):1265-6

Dell Medical School, University of Texas at Austin, Austin.

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http://dx.doi.org/10.1001/jama.2016.12266DOI Listing
September 2016

Trauma-Specific Brain Abnormalities in Suspected Mild Traumatic Brain Injury Patients Identified in the First 48 Hours after Injury: A Blinded Magnetic Resonance Imaging Comparative Study Including Suspected Acute Minor Stroke Patients.

J Neurotrauma 2017 01 10;34(1):23-30. Epub 2016 Jun 10.

1 Stroke Diagnostics and Therapeutics Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health , Bethesda, Maryland.

We assessed the utility of a brief MRI protocol, appropriate for the acute setting, to detect acute traumatic brain injury (TBI) in patients with suspected mild TBI (mTBI) and distinguish traumatic from nontraumatic brain injury by comparing trauma with nontrauma patients. Twenty-two patients with suspected mTBI were included in this exploratory study over a period of 9 months. Median time from injury to MR scanning was 5.4 h (interquartile range 3.6-15.3). To determine the specificity of certain findings for TBI, 61 patients presenting with suspected minor acute stroke were included as a comparative group using the same MRI methods. A selected series of MRI sequences (diffusion-weighted imaging, fluid attenuated inversion recovery [FLAIR], and T2* weighted) were independently evaluated by two neuroradiologists blinded to clinical diagnosis, for presence of specific findings. In a separate session, all cases in which at least one MRI sequence above was positive were classified as TBI, stroke, or indeterminate. Intracranial MRI abnormalities were observed in 47 (57%) of the 83 studied patients. Based on findings on MRI, 12 (55%) of 22 suspected mTBI patients were classified as having traumatic injury. Nine (47%) of the 19 suspected mTBI patients with a negative CT had findings on MRI. Abnormalities on MRI consistent with trauma were observed most frequently on postcontrast FLAIR (83%) and T2*-weighted (58%) sequences. We demonstrated the ability of a fast MRI protocol to identify trauma-related abnormalities not seen on CT, and differentiate acute trauma from nonspecific chronic disease in a blinded cohort of mTBI patients.
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http://dx.doi.org/10.1089/neu.2015.4338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5198056PMC
January 2017

Acute Stroke Imaging Research Roadmap III Imaging Selection and Outcomes in Acute Stroke Reperfusion Clinical Trials: Consensus Recommendations and Further Research Priorities.

Stroke 2016 05 12;47(5):1389-98. Epub 2016 Apr 12.

From the Department of Neurology, Dell Medical School, University of Texas at Austin (S.J.W.); Stroke Branch, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, MD (M.L.); Department of Neurology (G.W.A., M.G.L.), Department of Radiology (R.B.), Neuroradiology Section, Department of Radiology (J.J.H., M.P.M., M.W.), Stanford University School of Medicine, CA; Department of Neurology, John Hunter Hospital, Hunter Medical Research Institute, University of Newcastle, Callaghan, New South Wales, Australia (A.B., M.W.P.); Departments of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia (B.C.V.C.); Department of Radiology, University of Iowa Hospitals and Clinics Iowa City (C.D.); Departments of Neurology (P.K.) and Neuroadiology (A.V.), University of Cincinnati, OH; Neurovascular Imaging Research Core and UCLA Stroke Center, Department of Neurology, University of California, Los Angeles (D.S.L.); Department of Radiology, AMC, Amsterdam, The Netherlands (C.B.L.M.M.); Calgary Stroke Program, Departments of Clinical Neurosciences and Radiology, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada (B.K.M.); Institute of Neurosciences and Psychology, University of Glasgow, Southern General Hospital, Glasgow, Scotland, United Kingdom (K.W.M.); Texas Stroke Institute, Plano (A.J.Y.); Department of Neurology, The University of Tennessee Health Science Center, Memphis (A.V.A.); INSERM U894, Centre Hospitalier Sainte-Anne, Sorbonne Paris Cité, Paris, France (J.-C.B.); Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom (J.-C.B.); Department of Neurosurgery, State University of New York at Stony Brook (D.J.F.); Department of Neurology, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH (A.J.F.); Department of Radiology, Hospital Josep Tru

Background And Purpose: The Stroke Imaging Research (STIR) group, the Imaging Working Group of StrokeNet, the American Society of Neuroradiology, and the Foundation of the American Society of Neuroradiology sponsored an imaging session and workshop during the Stroke Treatment Academy Industry Roundtable (STAIR) IX on October 5 to 6, 2015 in Washington, DC. The purpose of this roadmap was to focus on the role of imaging in future research and clinical trials.

Methods: This forum brought together stroke neurologists, neuroradiologists, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke (NINDS), industry representatives, and members of the US Food and Drug Administration to discuss STIR priorities in the light of an unprecedented series of positive acute stroke endovascular therapy clinical trials.

Results: The imaging session summarized and compared the imaging components of the recent positive endovascular trials and proposed opportunities for pooled analyses. The imaging workshop developed consensus recommendations for optimal imaging methods for the acquisition and analysis of core, mismatch, and collaterals across multiple modalities, and also a standardized approach for measuring the final infarct volume in prospective clinical trials.

Conclusions: Recent positive acute stroke endovascular clinical trials have demonstrated the added value of neurovascular imaging. The optimal imaging profile for endovascular treatment includes large vessel occlusion, smaller core, good collaterals, and large penumbra. However, equivalent definitions for the imaging profile parameters across modalities are needed, and a standardization effort is warranted, potentially leveraging the pooled data resulting from the recent positive endovascular trials.
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http://dx.doi.org/10.1161/STROKEAHA.115.012364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6058693PMC
May 2016

Identification of imaging selection patterns in acute ischemic stroke patients and the influence on treatment and clinical trial enrollment decision making.

Int J Stroke 2016 Feb;11(2):180-90

Stanford University School of Medicine, Stanford, CA, USA Department of Radiology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.

Background And Purpose: For the STroke Imaging Research (STIR) and VISTA-Imaging Investigators The purpose of this study was to collect precise information on the typical imaging decisions given specific clinical acute stroke scenarios. Stroke centers worldwide were surveyed regarding typical imaging used to work up representative acute stroke patients, make treatment decisions, and willingness to enroll in clinical trials.

Methods: STroke Imaging Research and Virtual International Stroke Trials Archive-Imaging circulated an online survey of clinical case vignettes through its website, the websites of national professional societies from multiple countries as well as through email distribution lists from STroke Imaging Research and participating societies. Survey responders were asked to select the typical imaging work-up for each clinical vignette presented. Actual images were not presented to the survey responders. Instead, the survey then displayed several types of imaging findings offered by the imaging strategy, and the responders selected the appropriate therapy and whether to enroll into a clinical trial considering time from onset, clinical presentation, and imaging findings. A follow-up survey focusing on 6 h from onset was conducted after the release of the positive endovascular trials.

Results: We received 548 responses from 35 countries including 282 individual centers; 78% of the centers originating from Australia, Brazil, France, Germany, Spain, United Kingdom, and United States. The specific onset windows presented influenced the type of imaging work-up selected more than the clinical scenario. Magnetic Resonance Imaging usage (27-28%) was substantial, in particular for wake-up stroke. Following the release of the positive trials, selection of perfusion imaging significantly increased for imaging strategy.

Conclusions: Usage of vascular or perfusion imaging by Computed Tomography or Magnetic Resonance Imaging beyond just parenchymal imaging was the primary work-up (62-87%) across all clinical vignettes and time windows. Perfusion imaging with Computed Tomography or Magnetic Resonance Imaging was associated with increased probability of enrollment into clinical trials for 0-3 h. Following the release of the positive endovascular trials, selection of endovascular only treatment for 6 h increased across all clinical vignettes.
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http://dx.doi.org/10.1177/1747493015616634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762013PMC
February 2016