Maarten G. Lansberg, MD, PhD

All Publications

• Power of an Adaptive Trial Design for Endovascular Stroke Studies Simulations Using IMS (Interventional Management of Stroke) III Data STROKE Lansberg, M. G., Bhat, N. S., Yeatts, S. D., Palesch, Y. Y., Broderick, J. P., Albers, G. W., Lai, T. L., Lavori, P. W. 2016; 47 (12): 2931-2937

  Abstract

  Adaptive trial designs that allow enrichment of the study population through subgroup selection can increase the chance of a positive trial when there is a differential treatment effect among patient subgroups. The goal of this study is to illustrate the potential benefit of adaptive subgroup selection in endovascular stroke studies.We simulated the performance of a trial design with adaptive subgroup selection and compared it with that of a traditional design. Outcome data were based on 90-day modified Rankin Scale scores, observed in IMS III (Interventional Management of Stroke III), among patients with a vessel occlusion on baseline computed tomographic angiography (n=382). Patients were categorized based on 2 methods: (1) according to location of the arterial occlusive lesion and onset-to-randomization time and (2) according to onset-to-randomization time alone. The power to demonstrate a treatment benefit was based on 10 000 trial simulations for each design.The treatment effect was relatively homogeneous across categories when patients were categorized based on arterial occlusive lesion and time. Consequently, the adaptive design had similar power (47%) compared with the fixed trial design (45%). There was a differential treatment effect when patients were categorized based on time alone, resulting in greater power with the adaptive design (82%) than with the fixed design (57%).These simulations, based on real-world patient data, indicate that adaptive subgroup selection has merit in endovascular stroke trials as it substantially increases power when the treatment effect differs among subgroups in a predicted pattern.

  View details for DOI 10.1161/STROKEAHA.116.015436

  View details for Web of Science ID 000389424200022

  View details for PubMedID 27895297

• Comparison of stroke volume evolution on diffusion-weighted imaging and fluid-attenuated inversion recovery following endovascular thrombectomy. International journal of stroke Federau, C., Christensen, S., Mlynash, M., Tsai, J., Kim, S., Zaharchuk, G., Inoue, M., Straka, M., Mishra, N. K., Kemp, S., Lansberg, M. G., Albers, G. W. 2016

  Abstract

  To compare the evolution of the infarct lesion volume on both diffusion-weighted imaging and fluid-attenuated inversion recovery in the first five days after endovascular thrombectomy.We included 109 patients from the CRISP and DEFUSE 2 studies. Stroke lesion volumes obtained on diffusion-weighted imaging and fluid-attenuated inversion recovery images both early post-procedure (median 18 h after symptom onset) and day 5, were compared using median, interquartile range, and correlation plots. Patients were dichotomized based on the time after symptom onset of their post procedure images (≥18 h vs. <18 h), and the degree of reperfusion (on Tmax>6 s; ≥ 90% vs. < 90%).Early post-procedure, median infarct lesion volume was 19 ml [(IQR) 7-43] on fluid-attenuated inversion recovery, and 23 ml [11-64] on diffusion-weighted imaging. On day 5, median infarct lesion volume was 52 ml [20-118] on fluid-attenuated inversion recovery, and 37 ml [16-91] on diffusion-weighted imaging. Infarct lesion volume on early post-procedure diffusion-weighted imaging, compared to fluid-attenuated inversion recovery, correlated better with day 5 diffusion-weighted imaging and fluid-attenuated inversion recovery lesions (r = 0.88 and 0.88 vs. 0.78 and 0.77; p < 0.0001). Median lesion growth was significantly smaller on diffusion-weighted imaging when the early post-procedure scan was obtained ≥18 h post stroke onset (5 ml [-1-13]), compared to <18 h (13 ml [2-47]; p = 0.03), but was not significantly different on fluid-attenuated inversion recovery (≥18 h: 26 ml [12-57]; <18 h: 21 ml [5-57]; p = 0.65). In the <90% reperfused group, the median infarct growth was significantly larger for diffusion-weighted imaging and fluid-attenuated inversion recovery (diffusion-weighted imaging: 23 ml [8-57], fluid-attenuated inversion recovery: 41 ml [13-104]) compared to ≥90% (diffusion-weighted imaging: 6 ml [2-24]; p = 0.003, fluid-attenuated inversion recovery: 19 ml [8-46]; p = 0.001).Early post-procedure lesion volume on diffusion-weighted imaging is a better estimate of day 5 infarct volume than fluid-attenuated inversion recovery. However, both early post-procedure diffusion-weighted imaging and fluid-attenuated inversion recovery underestimate day 5 diffusion-weighted imaging and fluid-attenuated inversion recovery lesion volumes, especially in patients who do not reperfuse.

  View details for PubMedID 27811306

• A benchmarking tool to evaluate computer tomography perfusion infarct core predictions against a DWI standard JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Cereda, C. W., Christensen, S., Campbell, B. C., Mishra, N. K., Mlynash, M., Levi, C., Straka, M., Wintermark, M., Bammer, R., Albers, G. W., Parsons, M. W., Lansberg, M. G. 2016; 36 (10): 1780-1789

  Abstract

  Differences in research methodology have hampered the optimization of Computer Tomography Perfusion (CTP) for identification of the ischemic core. We aim to optimize CTP core identification using a novel benchmarking tool. The benchmarking tool consists of an imaging library and a statistical analysis algorithm to evaluate the performance of CTP. The tool was used to optimize and evaluate an in-house developed CTP-software algorithm. Imaging data of 103 acute stroke patients were included in the benchmarking tool. Median time from stroke onset to CT was 185 min (IQR 180-238), and the median time between completion of CT and start of MRI was 36 min (IQR 25-79). Volumetric accuracy of the CTP-ROIs was optimal at an rCBF threshold of <38%; at this threshold, the mean difference was 0.3 ml (SD 19.8 ml), the mean absolute difference was 14.3 (SD 13.7) ml, and CTP was 67% sensitive and 87% specific for identification of DWI positive tissue voxels. The benchmarking tool can play an important role in optimizing CTP software as it provides investigators with a novel method to directly compare the performance of alternative CTP software packages.

  View details for DOI 10.1177/0271678X15610586

  View details for Web of Science ID 000385349400011

  View details for PubMedID 26661203

  View details for PubMedCentralID PMC5076783

• Development of a Mobile Tool That Semiautomatically Screens Patients for Stroke Clinical Trials. Stroke; a journal of cerebral circulation Spokoyny, I., Lansberg, M., Thiessen, R., Kemp, S. M., Aksoy, D., Lee, Y., Mlynash, M., Hirsch, K. G. 2016; 47 (10): 2652-2655

  Abstract

  Despite several national coordinated research networks, enrollment in many cerebrovascular trials remains challenging. An electronic tool was needed that would improve the efficiency and efficacy of screening for multiple simultaneous acute clinical stroke trials by automating the evaluation of inclusion and exclusion criteria, improving screening procedures and streamlining the communication process between the stroke research coordinators and the stroke clinicians.A multidisciplinary group consisting of physicians, study coordinators, and biostatisticians designed and developed an electronic clinical trial screening tool on a HIPAA (Health Insurance Portability and Accountability Act)-compliant platform.A web-based tool was developed that uses branch logic to determine eligibility for simultaneously enrolling clinical trials and automatically notifies the study coordinator teams about eligible patients. After 12 weeks of use, 225 surveys were completed, and 51 patients were enrolled in acute stroke clinical trials. Compared with the 12 weeks before implementation of the tool, there was an increase in enrollment from 16.5% of patients screened to 23.4% of patients screened (P<0.05). Clinicians and coordinators reported increased satisfaction with the process and improved ease of screening.We created a semiautomated electronic screening tool that uses branch logic to screen patients for stroke clinical trials. The tool has improved efficiency and efficacy of screening, and it could be adapted for use at other sites and in other medical fields.

  View details for DOI 10.1161/STROKEAHA.116.013456

  View details for PubMedID 27608822

  View details for PubMedCentralID PMC5039105

• Analysis of perfusion MRI in stroke: To deconvolve, or not to deconvolve. Magnetic resonance in medicine Meijs, M., Christensen, S., Lansberg, M. G., Albers, G. W., Calamante, F. 2016; 76 (4): 1282-1290

  Abstract

  There is currently controversy regarding the benefits of deconvolution-based parameters in stroke imaging, with studies suggesting a similar infarct prediction using summary parameters. We investigate here the performance of deconvolution-based parameters and summary parameters for dynamic-susceptibility contrast (DSC) MRI analysis, with particular emphasis on precision.Numerical simulations were used to assess the contribution of noise and arterial input function (AIF) variability to measurement precision. A realistic AIF range was defined based on in vivo data from an acute stroke clinical study. The simulated tissue curves were analyzed using two popular singular value decomposition (SVD) based algorithms, as well as using summary parameters.SVD-based deconvolution methods were found to considerably reduce the AIF-dependency, but a residual AIF bias remained on the calculated parameters. Summary parameters, in turn, show a lower sensitivity to noise. The residual AIF-dependency for deconvolution methods and the large AIF-sensitivity of summary parameters was greatly reduced when normalizing them relative to normal tissue.Consistent with recent studies suggesting high performance of summary parameters in infarct prediction, our results suggest that DSC-MRI analysis using properly normalized summary parameters may have advantages in terms of lower noise and AIF-sensitivity as compared to commonly used deconvolution methods. Magn Reson Med 76:1282-1290, 2016. © 2015 Wiley Periodicals, Inc.

  View details for DOI 10.1002/mrm.26024

  View details for PubMedID 26519871

• Detection of Atrial Fibrillation Among Patients With Stroke Due to Large or Small Vessel Disease: A Meta-Analysis. Journal of the American Heart Association Demeestere, J., Fieuws, S., Lansberg, M. G., Lemmens, R. 2016; 5 (9)

  Abstract

  Recent trials have demonstrated that extended cardiac monitoring increases the yield of paroxysmal atrial fibrillation (AF) detection in patients with cryptogenic stroke. The utility of extended cardiac monitoring is uncertain among patients with stroke caused by small and large vessel disease. We conducted a meta-analysis to estimate the yield of AF detection in this population.We searched PubMed, Cochrane, and SCOPUS databases for studies on AF detection in stroke patients and excluded studies restricted to patients with cryptogenic stroke or transient ischemic attack. We abstracted AF detection rates for 3 populations grouped by stroke etiology: large vessel stroke, small vessel stroke, and stroke of undefined etiology (a mixture of cryptogenic, small vessel, large vessel, and other stroke etiologies). Our search yielded 30 studies (n=5687). AF detection rates were similar in patients with large vessel (2.2%, 95% CI 0.3-5.5; n=830) and small vessel stroke (2.4%, 95% CI 0.4-6.1; n=520). No studies had a monitoring duration longer than 7 days. The yield of AF detection in the undefined stroke population was higher (9.2%; 95% CI 7.1-11.5) compared to small vessel stroke (P=0.02) and large vessel stroke (P=0.02) populations.AF detection rate is similar in patients with small and large vessel strokes (2.2-2.4%). Because no studies reported on extended monitoring (>7 days) in these stroke populations, we could not estimate the yield of AF detection with long-term cardiac monitoring. Randomized controlled trials are needed to examine the utility of AF detection with long-term cardiac monitoring (>7 days) in this patient population.

  View details for PubMedID 27671319

• Effects of Alteplase for Acute Stroke on the Distribution of Functional Outcomes: A Pooled Analysis of 9 Trials. Stroke; a journal of cerebral circulation Lees, K. R., Emberson, J., Blackwell, L., Bluhmki, E., Davis, S. M., Donnan, G. A., Grotta, J. C., Kaste, M., von Kummer, R., Lansberg, M. G., Lindley, R. I., Lyden, P., Murray, G. D., Sandercock, P. A., Toni, D., Toyoda, K., Wardlaw, J. M., Whiteley, W. N., Baigent, C., Hacke, W., Howard, G. 2016; 47 (9): 2373-2379

  Abstract

  Thrombolytic therapy with intravenous alteplase within 4.5 hours of ischemic stroke onset increases the overall likelihood of an excellent outcome (no, or nondisabling, symptoms). Any improvement in functional outcome distribution has value, and herein we provide an assessment of the effect of alteplase on the distribution of the functional level by treatment delay, age, and stroke severity.Prespecified pooled analysis of 6756 patients from 9 randomized trials comparing alteplase versus placebo/open control. Ordinal logistic regression models assessed treatment differences after adjustment for treatment delay, age, stroke severity, and relevant interaction term(s).Treatment with alteplase was beneficial for a delay in treatment extending to 4.5 hours after stroke onset, with a greater benefit with earlier treatment. Neither age nor stroke severity significantly influenced the slope of the relationship between benefit and time to treatment initiation. For the observed case mix of patients treated within 4.5 hours of stroke onset (mean 3 hours and 20 minutes), the net absolute benefit from alteplase (ie, the difference between those who would do better if given alteplase and those who would do worse) was 55 patients per 1000 treated (95% confidence interval, 13-91; P=0.004).Treatment with intravenous alteplase initiated within 4.5 hours of stroke onset increases the chance of achieving an improved level of function for all patients across the age spectrum, including the over 80s and across all severities of stroke studied (top versus bottom fifth means: 22 versus 4); the earlier that treatment is initiated, the greater the benefit.

  View details for DOI 10.1161/STROKEAHA.116.013644

  View details for PubMedID 27507856

• Risk of intracerebral haemorrhage with alteplase after acute ischaemic stroke: a secondary analysis of an individual patient data meta-analysis. The Lancet. Neurology Whiteley, W. N., Emberson, J., Lees, K. R., Blackwell, L., Albers, G., Bluhmki, E., Brott, T., Cohen, G., Davis, S., Donnan, G., Grotta, J., Howard, G., Kaste, M., Koga, M., von Kummer, R., Lansberg, M. G., Lindley, R. I., Lyden, P., Olivot, J. M., Parsons, M., Toni, D., Toyoda, K., Wahlgren, N., Wardlaw, J., del Zoppo, G. J., Sandercock, P., Hacke, W., Baigent, C. 2016; 15 (9): 925-933

  Abstract

  Randomised trials have shown that alteplase improves the odds of a good outcome when delivered within 4·5 h of acute ischaemic stroke. However, alteplase also increases the risk of intracerebral haemorrhage; we aimed to determine the proportional and absolute effects of alteplase on the risks of intracerebral haemorrhage, mortality, and functional impairment in different types of patients.We used individual patient data from the Stroke Thrombolysis Trialists' (STT) meta-analysis of randomised trials of alteplase versus placebo (or untreated control) in patients with acute ischaemic stroke. We prespecified assessment of three classifications of intracerebral haemorrhage: type 2 parenchymal haemorrhage within 7 days; Safe Implementation of Thrombolysis in Stroke Monitoring Study's (SITS-MOST) haemorrhage within 24-36 h (type 2 parenchymal haemorrhage with a deterioration of at least 4 points on National Institutes of Health Stroke Scale [NIHSS]); and fatal intracerebral haemorrhage within 7 days. We used logistic regression, stratified by trial, to model the log odds of intracerebral haemorrhage on allocation to alteplase, treatment delay, age, and stroke severity. We did exploratory analyses to assess mortality after intracerebral haemorrhage and examine the absolute risks of intracerebral haemorrhage in the context of functional outcome at 90-180 days.Data were available from 6756 participants in the nine trials of intravenous alteplase versus control. Alteplase increased the odds of type 2 parenchymal haemorrhage (occurring in 231 [6·8%] of 3391 patients allocated alteplase vs 44 [1·3%] of 3365 patients allocated control; odds ratio [OR] 5·55 [95% CI 4·01-7·70]; absolute excess 5·5% [4·6-6·4]); of SITS-MOST haemorrhage (124 [3·7%] of 3391 vs 19 [0·6%] of 3365; OR 6·67 [4·11-10·84]; absolute excess 3·1% [2·4-3·8]); and of fatal intracerebral haemorrhage (91 [2·7%] of 3391 vs 13 [0·4%] of 3365; OR 7·14 [3·98-12·79]; absolute excess 2·3% [1·7-2·9]). However defined, the proportional increase in intracerebral haemorrhage was similar irrespective of treatment delay, age, or baseline stroke severity, but the absolute excess risk of intracerebral haemorrhage increased with increasing stroke severity: for SITS-MOST intracerebral haemorrhage the absolute excess risk ranged from 1·5% (0·8-2·6%) for strokes with NIHSS 0-4 to 3·7% (2·1-6·3%) for NIHSS 22 or more (p=0·0101). For patients treated within 4·5 h, the absolute increase in the proportion (6·8% [4·0% to 9·5%]) achieving a modified Rankin Scale of 0 or 1 (excellent outcome) exceeded the absolute increase in risk of fatal intracerebral haemorrhage (2·2% [1·5% to 3·0%]) and the increased risk of any death within 90 days (0·9% [-1·4% to 3·2%]).Among patients given alteplase, the net outcome is predicted both by time to treatment (with faster time increasing the proportion achieving an excellent outcome) and stroke severity (with a more severe stroke increasing the absolute risk of intracerebral haemorrhage). Although, within 4·5 h of stroke, the probability of achieving an excellent outcome with alteplase treatment exceeds the risk of death, early treatment is especially important for patients with severe stroke.UK Medical Research Council, British Heart Foundation, University of Glasgow, University of Edinburgh.

  View details for DOI 10.1016/S1474-4422(16)30076-X

  View details for PubMedID 27289487

• Pretreatment blood-brain barrier disruption and post-endovascular intracranial hemorrhage. Neurology Leigh, R., Christensen, S., Campbell, B. C., Marks, M. P., Albers, G. W., Lansberg, M. G. 2016; 87 (3): 263-269

  Abstract

  This study sought to confirm the relationship between the degree of blood-brain barrier (BBB) damage and the severity of intracranial hemorrhage (ICH) in a population of patients who received endovascular therapy.The degree of BBB disruption on pretreatment MRI scans was analyzed, blinded to follow-up data, in the DEFUSE 2 cohort in which patients had endovascular therapy within 12 hours of stroke onset. BBB disruption was compared with ICH grade previously established by the DEFUSE 2 core lab. A prespecified threshold for predicting parenchymal hematoma (PH) was tested.Of the 108 patients in the DEFUSE 2 trial, 100 had adequate imaging and outcome data and were included in this study; 24 developed PH. Increasing amounts of BBB disruption on pretreatment MRIs was associated with increasing severity of ICH grade (p = 0.004). BBB disruption on the pretreatment scan was associated with PH (p = 0.020) with an odds ratio for developing PH of 1.69 for each 10% increase in BBB disruption (95% confidence interval 1.09-2.64), although a reliably predictive threshold was not identified.The amount of BBB disruption on pretreatment MRI is associated with the severity of ICH after acute intervention. This relationship has now been identified in patients receiving IV, endovascular, and combined therapies. Further study is needed to determine its role in guiding treatment.

  View details for DOI 10.1212/WNL.0000000000002862

  View details for PubMedID 27316247

• Evolution of Volume and Signal Intensity on Fluid-attenuated Inversion Recovery MR Images after Endovascular Stroke Therapy RADIOLOGY Federau, C., Mlynash, M., Christensen, S., Zaharchuk, G., Cha, B., Lansberg, M. G., Wintermark, M., Albers, G. W. 2016; 280 (1): 184-192

  Abstract

  Purpose To analyze both volume and signal evolution on magnetic resonance (MR) fluid-attenuated inversion recovery (FLAIR) images between the images after endovascular therapy and day 5 (which was the prespecified end point for infarct volume in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution [DEFUSE 2] trial) in a subset of patients enrolled in the DEFUSE 2 study. Materials and Methods This study was approved by the local ethics committee at all participating sites. Informed written consent was obtained from all patients. In this post hoc analysis of the DEFUSE 2 study, 35 patients with FLAIR images acquired both after endovascular therapy (median time after symptom onset, 12 hours) and at day 5 were identified. Patients were separated into two groups based on the degree of reperfusion achieved on time to maximum greater than 6-second perfusion imaging (≥90% vs <90%). After coregistration and signal normalization, lesion volumes and signal intensity were assessed by using FLAIR imaging for the initial lesion (ie, visible after endovascular therapy) and the recruited lesion (the additional lesion visible on day 5, but not visible after endovascular therapy). Statistical significance was assessed by using Wilcoxon signed-rank, Mann-Whitney U, and Fisher exact tests. Results All 35 patients had FLAIR lesion growth between the after-revascularization examination and day 5. Median lesion growth was significantly larger in patients with <90% reperfusion (27.85 mL) compared with ≥90% (8.12 mL; P = .003). In the initial lesion, normalized signal did not change between after endovascular therapy (median, 1.60) and day 5 (median, 1.58) in the ≥90% reperfusion group (P = .97), but increased in the <90% reperfusion group (from 1.60 to 1.73; P = .01). In the recruited lesion, median normalized signal increased significantly in both groups between after endovascular therapy and day 5 (after endovascular therapy, from 1.19 to 1.56, P < .001; and day 5, from 1.18 to 1.63, P < .001). Conclusion Patients with ≥90% reperfusion after endovascular therapy have significantly less lesion growth on FLAIR images between after therapy and day 5 compared with patients who have <90% reperfusion. Therefore, the effect of reperfusion therapies on lesion volumes are likely more apparent at day 5 than after therapy. (©) RSNA, 2016.

  View details for DOI 10.1148/radiol.2015151586

  View details for Web of Science ID 000378721900020

  View details for PubMedID 26761721

• Acute Stroke Imaging Research Roadmap III Imaging Selection and Outcomes in Acute Stroke Reperfusion Clinical Trials Consensus Recommendations and Further Research Priorities STROKE Warach, S. J., Luby, M., Albers, G. W., Bammer, R., Bivard, A., Campbell, B. C., Derdeyn, C., Heit, J. J., Khatri, P., Lansberg, M. G., Liebeskind, D. S., Majoie, C. B., Marks, M. P., Menon, B. K., Muir, K. W., Parsons, M. W., Vagal, A., Yoo, A. J., Alexandrov, A. V., Baron, J., Fiorella, D. J., Furlan, A. J., Puig, J., Schellinger, P. D., Wintermark, M. 2016; 47 (5): 1389-1398

  Abstract

  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.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.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.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.

  View details for DOI 10.1161/STROKEAHA.115.012364

  View details for Web of Science ID 000375049700044

  View details for PubMedID 27073243

• Effect of endovascular reperfusion in relation to site of arterial occlusion. Neurology Lemmens, R., Hamilton, S. A., Liebeskind, D. S., Tomsick, T. A., Demchuk, A. M., Nogueira, R. G., Marks, M. P., Jahan, R., Gralla, J., Yoo, A. J., Yeatts, S. D., Palesch, Y. Y., Saver, J. L., Pereira, V. M., Broderick, J. P., Albers, G. W., Lansberg, M. G. 2016; 86 (8): 762-770

  Abstract

  To assess whether the association between reperfusion and improved clinical outcomes after stroke differs depending on the site of the arterial occlusive lesion (AOL).We pooled data from Solitaire With the Intention for Thrombectomy (SWIFT), Solitaire FR Thrombectomy for Acute Revascularisation (STAR), Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2), and Interventional Management of Stroke Trial (IMS III) to compare the strength of the associations between reperfusion and clinical outcomes in patients with internal carotid artery (ICA), proximal middle cerebral artery (MCA) (M1), and distal MCA (M2/3/4) occlusions.Among 710 included patients, the site of the AOL was the ICA in 161, the proximal MCA in 389, and the distal MCA in 160 patients (M2 = 131, M3 = 23, and M4 = 6). Reperfusion was associated with an increase in the rate of good functional outcome (modified Rankin Scale [mRS] score 0-2) in patients with ICA (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.7-7.2) and proximal MCA occlusions (OR 6.2, 95% CI 3.8-10.2), but not in patients with distal MCA occlusions (OR 1.4, 95% CI 0.8-2.6). Among patients with M2 occlusions, a subset of the distal MCA cohort, reperfusion was associated with excellent functional outcome (mRS 0-1; OR 2.2, 95% CI 1.0-4.7).The association between endovascular reperfusion and better clinical outcomes is more profound in patients with ICA and proximal MCA occlusions compared to patients with distal MCA occlusions. Because there are limited data from randomized controlled trials on the effect of endovascular therapy in patients with distal MCA occlusions, these results underscore the need for inclusion of this subgroup in future endovascular therapy trials.

  View details for DOI 10.1212/WNL.0000000000002399

  View details for PubMedID 26802090

• Identification of imaging selection patterns in acute ischemic stroke patients and the influence on treatment and clinical trial enrollment decision making. International journal of stroke Luby, M., Warach, S. J., Albers, G. W., Baron, J., Cognard, C., Dávalos, A., Donnan, G. A., Fiebach, J. B., Fiehler, J., Hacke, W., Lansberg, M. G., Liebeskind, D. S., Mattle, H. P., Oppenheim, C., Schellinger, P. D., Wardlaw, J. M., Wintermark, M. 2016; 11 (2): 180-190

  Abstract

  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.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.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.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.

  View details for DOI 10.1177/1747493015616634

  View details for PubMedID 26783309

• Inter-rater agreement analysis of the Precise Diagnostic Score for suspected transient ischemic attack. International journal of stroke Cereda, C. W., George, P. M., Inoue, M., Vora, N., Olivot, J., Schwartz, N., Lansberg, M. G., Kemp, S., Mlynash, M., Albers, G. W. 2016; 11 (1): 85-92

  Abstract

  No definitive criteria are available to confirm the diagnosis of transient ischemic attack. Inter-rater agreement between physicians regarding the diagnosis of transient ischemic attack is low, even among vascular neurologists. We developed the Precise Diagnostic Score, a diagnostic score that consists of discrete and well-defined clinical and imaging parameters, and investigated inter-rater agreement in patients with suspected transient ischemic attack.Fellowship-trained vascular neurologists, blinded to final diagnosis, independently reviewed retrospectively identical history, physical examination, routine diagnostic studies, and brain magnetic resonance imaging (diffusion and perfusion images) from consecutive patients with suspected transient ischemic attack. Each patient was rated using the 8-point Precise Diagnostic Score score, composed of a clinical score (0-4 points) and an imaging score (0-4 points). The composite Precise Diagnostic Score determines a Precise Diagnostic Score Likelihood of Brain Ischemia Scale: 0-1 = unlikely, 2 = possible, 3 = probable, 4-8 = very likely.Three raters reviewed data from 114 patients. Using Precise Diagnostic Score, all three raters scored a similar percentage of the clinical events as being "probable" or "very likely" caused by brain ischemia: 57, 55, and 58%. Agreement was high for both total Precise Diagnostic Score (intraclass correlation coefficient of 0.94) and for the Likelihood of Brain Ischemia Scale (agreement coefficient of 0.84).Compared with prior studies, inter-rater agreement for the diagnosis of transient brain ischemia appears substantially improved with the Precise Diagnostic Score scoring system. This score is the first to include specific criteria to assess the clinical relevance of diffusion-weighted imaging and perfusion lesions and supports the added value of magnetic resonance imaging for assessing patients with suspected transient ischemic attack.

  View details for DOI 10.1177/1747493015607507

  View details for PubMedID 26763024

• Magnetic resonance imaging-based endovascular versus medical stroke treatment for symptom onset up to 12?h. International journal of stroke Wouters, A., Lemmens, R., Christensen, S., Wilms, G., Dupont, P., Mlynash, M., Schneider, A., Laage, R., Cereda, C. W., Lansberg, M. G., Albers, G. W., Thijs, V. 2016; 11 (1): 127-133

  Abstract

  Recent trials have shown a clear benefit of endovascular therapy for stroke patients presenting within 6 h after stroke onset. Imaging-based selection may identify a cohort with a favorable response to endovascular therapy, in an even later time window.We performed an indirect comparison between outcomes seen in DEFUSE 2, a prospective cohort study of patients who received a baseline MRI before endovascular therapy, and a control group from AXIS 2 receiving standard medical care up to 12 h after symptom onset.Patients from AXIS 2 with a confirmed large vessel occlusion were selected as a control group for DEFUSE 2-patients. The primary endpoint was good functional outcome at day 90 (Modified Rankin Score 0-2). We performed a stratified analysis based on the presence of the target mismatch for both studies and reperfusion status in DEFUSE 2.We compared good functional outcome in 108 patients from AXIS 2 and 99 patients from DEFUSE 2. In DEFUSE 2-patients with the target mismatch profile in whom reperfusion was achieved, the rate of good functional outcome was increased compared to target mismatch patients in AXIS 2, 54% versus 29% (OR 3.2, 95% CI 1.1-9.4). In target mismatch patients treated between 6 and 12 h after stroke onset, this association between study and good functional outcome remained present (OR 9.0, 95% CI 1.1-75.8).This indirect comparison suggests that endovascular treatment resulting in substantial reperfusion is associated with improved outcome in target mismatch patients even beyond 6 h after stroke onset. Confirmation is needed from future clinical trials that randomize patients beyond the 6 h time window.

  View details for DOI 10.1177/1747493015607503

  View details for PubMedID 26763028

• Yield of CT perfusion for the evaluation of transient ischaemic attack. International journal of stroke Kleinman, J. T., Mlynash, M., Zaharchuk, G., Ogdie, A. A., Straka, M., Lansberg, M. G., Schwartz, N. E., Singh, P., Kemp, S., Bammer, R., Albers, G. W., Olivot, J. 2015; 10: 25-29

  Abstract

  BACKGROUND: Magnetic resonance diffusion-weighted imaging and perfusion-weighted imaging are able to identify ischaemic 'footprints' in transient ischaemic attack. Computed tomography perfusion (CTP) may be useful for patient triage and subsequent management. To date, less than 100 cases have been reported, and none have compared computed tomography perfusion to perfusion-weighted imaging (PWI). We sought to define the yield of computed tomography perfusion for the evaluation of transient ischaemic attack. METHODS: Consecutive patients with a discharge diagnosis of possible or definite transient ischaemic event who underwent computed tomography perfusion were included in this study. The presence of an ischaemic lesion was assessed on noncontrast computed tomography, automatically deconvolved CTP(TMax) (Time till the residue function reaches its maximum), and when available on diffusion-weighted imaging and PWI(TMax) maps. RESULTS: Thirty-four patients were included and 17 underwent magnetic resonance imaging. Median delay between onset and computed tomography perfusion was 4·4 h (Interquartile range [IQR]: 1·9-9·6), and between computed tomography perfusion and magnetic resonance imaging was 11 h (Interquartile range: 3·8-22). Noncontrast computed tomography was negative in all cases, while CTP(TMax) identified an ischaemic lesion in 12/34 patients (35%). In the subgroup of patients with multimodal magnetic resonance imaging, an ischaemic lesion was found in six (35%) patients using CTP(TMax) versus nine (53%) on magnetic resonance imaging (five diffusion-weighted imaging, nine perfusion-weighted imaging). The additional yield of CTP(TMax) over computed tomography angiography was significant in the evaluation of transient ischaemic attack (12 vs. 3, McNemar, P = 0·004). CONCLUSIONS: CTP(TMax) found an ischaemic lesion in one-third of acute transient ischaemic attack patients. Computed tomography perfusion may be an acceptable substitute when magnetic resonance imaging is unavailable or contraindicated, and has additional yield over computed tomography angiography. Further studies evaluating the outcome of patients with computed tomography perfusion lesions in transient ischaemic attack are justified at this time.

  View details for DOI 10.1111/j.1747-4949.2012.00941.x

  View details for PubMedID 23228203

• Response to endovascular reperfusion is not time-dependent in patients with salvageable tissue. Neurology Lansberg, M. G., Cereda, C. W., Mlynash, M., Mishra, N. K., Inoue, M., Kemp, S., Christensen, S., Straka, M., Zaharchuk, G., Marks, M. P., Bammer, R., Albers, G. W. 2015; 85 (8): 708-714

  Abstract

  To evaluate whether time to treatment modifies the effect of endovascular reperfusion in stroke patients with evidence of salvageable tissue on MRI.Patients from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2 (DEFUSE 2) cohort study with a perfusion-diffusion target mismatch were included. Reperfusion was defined as a decrease in the perfusion lesion volume of at least 50% between baseline and early follow-up. Good functional outcome was defined as a modified Rankin Scale score ≤2 at day 90. Lesion growth was defined as the difference between the baseline and the early follow-up diffusion-weighted imaging lesion volumes.Among 78 patients with the target mismatch profile (mean age 66 ± 16 years, 54% women), reperfusion was associated with increased odds of good functional outcome (adjusted odds ratio 3.7, 95% confidence interval 1.2-12, p = 0.03) and attenuation of lesion growth (p = 0.02). Time to treatment did not modify these effects (p value for the time × reperfusion interaction is 0.6 for good functional outcome and 0.3 for lesion growth). Similarly, in the subgroup of patients with reperfusion (n = 46), time to treatment was not associated with good functional outcome (p = 0.2).The association between endovascular reperfusion and improved functional and radiologic outcomes is not time-dependent in patients with a perfusion-diffusion mismatch. Proof that patients with mismatch benefit from endovascular therapy in the late time window should come from a randomized placebo-controlled trial.

  View details for DOI 10.1212/WNL.0000000000001853

  View details for PubMedID 26224727

• The growth rate of early DWI lesions is highly variable and associated with penumbral salvage and clinical outcomes following endovascular reperfusion INTERNATIONAL JOURNAL OF STROKE Wheeler, H. M., Mlynash, M., Inoue, M., Tipirnini, A., Liggins, J., Bammer, R., Lansberg, M. G., Kemp, S., Zaharchuk, G., Straka, M., Albers, G. W. 2015; 10 (5): 723-729

  Abstract

  The degree of variability in the rate of early diffusion-weighted imaging expansion in acute stroke has not been well characterized.We hypothesized that patients with slowly expanding diffusion-weighted imaging lesions would have more penumbral salvage and better clinical outcomes following endovascular reperfusion than patients with rapidly expanding diffusion-weighted imaging lesions.In the first part of this substudy of DEFUSE 2, growth curves were constructed for patients with >90% reperfusion and <10% reperfusion. Next, the initial growth rate was determined in all patients with a clearly established time of symptom onset, assuming a lesion volume of 0 ml just prior to symptom onset. Patients who achieved reperfusion (>50% reduction in perfusion-weighted imaging after endovascular therapy) were categorized into tertiles according to their initial diffusion-weighted imaging growth rates. For each tertile, penumbral salvage [comparison of final volume to the volume of perfusion-weighted imaging (Tmax > 6 s)/diffusion-weighted imaging mismatch prior to endovascular therapy], favorable clinical response (National Institutes of Health Stroke Scale improvement of ≥8 points or 0-1 at 30 days), and good functional outcome (90-day modified Rankin score of ≤2) were calculated. A multivariate model assessed whether infarct growth rates were an independent predictor of clinical outcomes.Sixty-five patients were eligible for this study; the median initial growth rate was 3·1 ml/h (interquartile range 0·7-10·7). Target mismatch patients (n = 42) had initial growth rates that were significantly slower than the growth rates in malignant profile (n = 9 patients, P < 0·001). In patients who achieved reperfusion (n = 38), slower early diffusion-weighted imaging growth rates were associated with better clinical outcomes (P < 0·05) and a trend toward more penumbral salvage (n = 31, P = 0·103). A multivariate model demonstrated that initial diffusion-weighted imaging growth rate was an independent predictor of achieving a 90-day modified Rankin score of ≤2.The growth rate of early diffusion-weighted imaging lesions in acute stroke patients is highly variable; malignant profile patients have higher growth rates than patients with target mismatch. A slower rate of early diffusion-weighted imaging growth is associated with a greater degree of penumbral salvage and improved clinical outcomes following endovascular reperfusion.

  View details for DOI 10.1111/ijs.12436

  View details for Web of Science ID 000356718000025

  View details for PubMedID 25580662

  View details for PubMedCentralID PMC4478123

• A score based on age and DWI volume predicts poor outcome following endovascular treatment for acute ischemic stroke INTERNATIONAL JOURNAL OF STROKE Liggins, J. T., Yoo, A. J., Mishra, N. K., Wheeler, H. M., Straka, M., Leslie-Mazwi, T. M., Chaudhry, Z. A., Kemp, S., Mlynash, M., Bammer, R., Albers, G. W., Lansberg, M. G. 2015; 10 (5): 705-709

  Abstract

  The Houston Intra-Arterial Therapy score predicts poor functional outcome following endovascular treatment for acute ischemic stroke based on clinical variables. The present study sought to (a) create a predictive scoring system that included a neuroimaging variable and (b) determine if the scoring systems predict the clinical response to reperfusion.Separate datasets were used to derive (n = 110 from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2 study) and validate (n = 125 from Massachusetts General Hospital) scoring systems that predict poor functional outcome, defined as a modified Rankin Scale score of 4-6 at 90 days.Age (P < 0·001; β = 0·087) and diffusion-weighted imaging volume (P = 0·023; β = 0·025) were the independent predictors of poor functional outcome. The Stanford Age and Diffusion-Weighted Imaging score was created based on the patient's age (0-3 points) and diffusion-weighted imaging lesion volume (0-1 points). The percentage of patients with a poor functional outcome increased significantly with the number of points on the Stanford Age and Diffusion-Weighted Imaging score (P < 0·01 for trend). The area under the receiver operating characteristic curve for the Stanford Age and Diffusion-Weighted Imaging score was 0·82 in the derivation dataset. In the validation cohort, the area under the receiver operating characteristic curve was 0·69 for the Stanford Age and Diffusion-Weighted Imaging score and 0·66 for the Houston Intra-Arterial Therapy score (P = 0·45 for the difference). Reperfusion, but not the interactions between the prediction scores and reperfusion, were predictors of outcome (P > 0·5).The Stanford Age and Diffusion-Weighted Imaging and Houston Intra-Arterial Therapy scores can be used to predict poor functional outcome following endovascular therapy with good accuracy. However, these scores do not predict the clinical response to reperfusion. This limits their utility as tools to select patients for acute stroke interventions.

  View details for DOI 10.1111/ijs.12207

  View details for Web of Science ID 000356718000022

  View details for PubMedID 24207136

• Worse stroke outcome in atrial fibrillation is explained by more severe hypoperfusion, infarct growth, and hemorrhagic transformation INTERNATIONAL JOURNAL OF STROKE Tu, H. T., Campbell, B. C., Christensen, S., Desmond, P. M., De Silva, D. A., Parsons, M. W., Churilov, L., Lansberg, M. G., Mlynash, M., Olivot, J., Straka, M., Bammer, R., Albers, G. W., Donnan, G. A., Davis, S. M. 2015; 10 (4): 534-540

  Abstract

  BACKGROUND: Atrial fibrillation is associated with greater baseline neurological impairment and worse outcomes following ischemic stroke. Previous studies suggest that greater volumes of more severe baseline hypoperfusion in patients with history of atrial fibrillation may explain this association. We further investigated this association by comparing patients with and without atrial fibrillation on initial examination following stroke using pooled multimodal magnetic resonance imaging and clinical data from the Echoplanar Imaging Thrombolytic Evaluation Trial and the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution studies. METHODS: Echoplanar Imaging Thrombolytic Evaluation Trial was a trial of 101 ischemic stroke patients randomized to intravenous tissue plasminogen activator or placebo, and Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution was a prospective cohort of 74 ischemic stroke patients treated with intravenous tissue plasminogen activator at three to six hours following symptom onset. Patients underwent multimodal magnetic resonance imaging before treatment, at three to five days and three-months after stroke in Echoplanar Imaging Thrombolytic Evaluation Trial; before treatment, three to six hours after treatment and one-month after stroke in Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution. Patients were assessed with the National Institutes of Health Stroke Scale and the modified Rankin scale before treatment and at three-months after stroke. Patients were categorized into definite atrial fibrillation (present on initial examination), probable atrial fibrillation (history but no atrial fibrillation on initial examination), and no atrial fibrillation. Perfusion data were reprocessed with automated magnetic resonance imaging analysis software (RAPID, Stanford University, Stanford, CA, USA). Hypoperfusion volumes were defined using time to maximum delays in two-second increments from >4 to >8 s. Hemorrhagic transformation was classified according to the European Cooperative Acute Stroke Studies criteria. RESULTS: Of the 175 patients, 28 had definite atrial fibrillation, 30 probable atrial fibrillation, 111 no atrial fibrillation, and six were excluded due to insufficient imaging data. At baseline, patients with definite atrial fibrillation had more severe hypoperfusion (median time to maximum >8 s, volume 48 vs. 29 ml, P = 0·02) compared with patients with no atrial fibrillation. At outcome, patients with definite atrial fibrillation had greater infarct growth (median volume 47 vs. 8 ml, P = 0·001), larger infarcts (median volume 75 vs. 23 ml, P = 0·001), more frequent parenchymal hematoma grade hemorrhagic transformation (30% vs. 10%, P = 0·03), worse functional outcomes (median modified Rankin scale score 4 vs. 3, P = 0·03), and higher mortality (36% vs. 16%, P = 0·03) compared with patients with no atrial fibrillation. Definite atrial fibrillation was independently associated with increased parenchymal hematoma (odds ratio = 6·05, 95% confidence interval 1·60-22·83) but not poor functional outcome (modified Rankin scale 3-6, odds ratio = 0·99, 95% confidence interval 0·35-2·80) or mortality (odds ratio = 2·54, 95% confidence interval 0·86-7·49) three-months following stroke, after adjusting for other baseline imbalances. CONCLUSION: Atrial fibrillation is associated with greater volumes of more severe baseline hypoperfusion, leading to higher infarct growth, more frequent severe hemorrhagic transformation and worse stroke outcomes.

  View details for DOI 10.1111/ijs.12007

  View details for Web of Science ID 000354494000023

  View details for PubMedID 23489996

• Reperfusion of Very Low Cerebral Blood Volume Lesion Predicts Parenchymal Hematoma After Endovascular Therapy STROKE Mishra, N. K., Christensen, S., Wouters, A., Campbell, B. C., Straka, M., Mlynash, M., Kemp, S., Cereda, C. W., Bammer, R., Marks, M. P., Albers, G. W., Lansberg, M. G. 2015; 46 (5): 1245-1249

  Abstract

  Ischemic stroke patients with regional very low cerebral blood volume (VLCBV) on baseline imaging have increased risk of parenchymal hemorrhage (PH) after intravenous alteplase-induced reperfusion. We developed a method for automated detection of VLCBV and examined whether patients with reperfused-VLCBV are at increased risk of PH after endovascular reperfusion therapy.Receiver operating characteristic analysis was performed to optimize a relative CBV threshold associated with PH in patients from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2 (DEFUSE 2) study. Regional reperfused-VLCBV was defined as regions with low relative CBV on baseline imaging that demonstrated normal perfusion (Tmax <6 s) on coregistered early follow-up magnetic resonance imaging. The association between VLCBV, regional reperfused-VLCBV and PH was assessed in univariate and multivariate analyses.In 91 patients, the greatest area under the curve for predicting PH occurred at an relative CBV threshold of <0.42 (area under the curve, 0.77). At this threshold, VLCBV lesion volume ≥3.55 mL optimally predicted PH with 94% sensitivity and 63% specificity. Reperfused-VLCBV lesion volume was more specific (0.74) and equally sensitive (0.94). In total, 18 patients developed PH, of whom 17 presented with VLCBV (39% versus 2%; P=0.001), all of them had regional reperfusion (47% versus 0%; P=0.01), and 71% received intravenous alteplase. VLCBV lesion (odds ratio, 33) and bridging with intravenous alteplase (odds ratio, 3.8) were independently associated with PH. In a separate model, reperfused-VLCBV remained the single independent predictor of PH (odds ratio, 53).These results suggest that VLCBV can be used for risk stratification of patients scheduled to undergo endovascular therapy in trials and routine clinical practice.

  View details for DOI 10.1161/STROKEAHA.114.008171

  View details for Web of Science ID 000353559800032

  View details for PubMedID 25828235

  View details for PubMedCentralID PMC4414872

• Apparent diffusion coefficient threshold for delineation of ischemic core. International journal of stroke Purushotham, A., Campbell, B. C., Straka, M., Mlynash, M., Olivot, J., Bammer, R., Kemp, S. M., Albers, G. W., Lansberg, M. G. 2015; 10 (3): 348-353

  Abstract

  MRI-based selection of patients for acute stroke interventions requires rapid accurate estimation of the infarct core on diffusion-weighted MRI. Typically used manual methods to delineate restricted diffusion lesions are subjective and time consuming. These limitations would be overcome by a fully automated method that can rapidly and objectively delineate the ischemic core. An automated method would require predefined criteria to identify the ischemic core.The aim of this study is to determine apparent diffusion coefficient-based criteria that can be implemented in a fully automated software solution for identification of the ischemic core.Imaging data from patients enrolled in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) study who had early revascularization following intravenous thrombolysis were included. The patients' baseline restricted diffusion and 30-day T2 -weighted fluid-attenuated inversion recovery lesions were manually delineated after coregistration. Parts of the restricted diffusion lesion that corresponded with 30-day infarct were considered ischemic core, whereas parts that corresponded with normal brain parenchyma at 30 days were considered noncore. The optimal apparent diffusion coefficient threshold to discriminate core from noncore voxels was determined by voxel-based receiver operating characteristics analysis using the Youden index.51 045 diffusion positive voxels from 14 patients who met eligibility criteria were analyzed. The mean DWI lesion volume was 24 (± 23) ml. Of this, 18 (± 22) ml was ischemic core and 3 (± 5) ml was noncore. The remainder corresponded to preexisting gliosis, cerebrospinal fluid, or was lost to postinfarct atrophy. The apparent diffusion coefficient of core was lower than that of noncore voxels (P < 0·0001). The optimal threshold for identification of ischemic core was an apparent diffusion coefficient ≤620 × 10(-6 ) mm(2) /s (sensitivity 69% and specificity 78%).Our data suggest that the ischemic core can be identified with an absolute apparent diffusion coefficient threshold. This threshold can be implemented in image analysis software for fully automated segmentation of the ischemic core.

  View details for DOI 10.1111/ijs.12068

  View details for PubMedID 23802548

• Interhospital variation in reperfusion rates following endovascular treatment for acute ischemic stroke. Journal of neurointerventional surgery Liggins, J. T., Mlynash, M., Jovin, T. G., Straka, M., Kemp, S., Bammer, R., Marks, M. P., Albers, G. W., Lansberg, M. G. 2015; 7 (4): 231-233

  Abstract

  Patients who have successful reperfusion following endovascular therapy for acute ischemic stroke have improved clinical outcomes. We sought to determine if the chance of successful reperfusion differs among hospitals, and if hospital site is an independent predictor of reperfusion.Nine hospitals recruited patients in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2), a prospective cohort study of endovascular stroke treatment conducted between 2008 and 2011. Patients were included for analysis if they had a baseline Thrombolysis in Cerebral Infarction (TICI) score of 0 or 1. Successful reperfusion was defined as a TICI reperfusion score of 2b or 3 at completion of the procedure. Collaterals were assessed using the Collateral Flow Grading System and were dichotomized as poor (0-2) or good (3-4). The association between hospital site and successful reperfusion was first assessed in an unadjusted analysis and subsequently in a multivariate analysis that adjusted for predictors of successful reperfusion.36 of 89 patients (40%) achieved successful reperfusion. The rate of reperfusion varied from 0% to 77% among hospitals in the univariate analysis (χ(2) p<0.001) but hospital site did not remain as an independent predictor of reperfusion in multivariate analysis (p=0.81) after adjustment for the presence of good collaterals (p<0.01) and use of the Merci retriever (p<0.05).Reperfusion rates vary among hospitals, which may be related to differences in treatment protocols and patient characteristics. Additional studies are needed to identify all of the factors that underlie this variability as this could lead to strategies that reduce interhospital variability in reperfusion rates and improve clinical outcomes.

  View details for DOI 10.1136/neurintsurg-2014-011115

  View details for PubMedID 24662608

• Alberta Stroke Program Early Computed Tomographic Scoring Performance in a Series of Patients Undergoing Computed Tomography and MRI: Reader Agreement, Modality Agreement, and Outcome Prediction. Stroke; a journal of cerebral circulation McTaggart, R. A., Jovin, T. G., Lansberg, M. G., Mlynash, M., Jayaraman, M. V., Choudhri, O. A., Inoue, M., Marks, M. P., Albers, G. W. 2015; 46 (2): 407-412

  Abstract

  In this study, we compare the performance of pretreatment Alberta Stroke Program Early Computed Tomographic scoring (ASPECTS) using noncontrast CT (NCCT) and MRI in a large endovascular therapy cohort.Prospectively enrolled patients underwent baseline NCCT and MRI and started endovascular therapy within 12 hours of stroke onset. Inclusion criteria for this analysis were evaluable pretreatment NCCT, diffusion-weighted MRI (DWI), and 90-day modified Rankin Scale scores. Two expert readers graded ischemic change on NCCT and DWI using the ASPECTS. ASPECTS scores were analyzed with the full scale or were trichotomized (0-4 versus 5-7 versus 8-10) or dichotomized (0-7 versus 8-10). Good functional outcome was defined as a 90-day modified Rankin Scale score of 0 to 2.Seventy-four patients fulfilled our study criteria. The full-scale inter-rater agreement for CT-ASPECTS and DWI-ASPECTS was 0.579 and 0.867, respectively. DWI-ASPECTS correlated with functional outcome (P=0.004), whereas CT-ASPECTS did not (P=0.534). Both DWI-ASPECTS and CT-ASPECTS correlated with DWI volume. The receiver operating characteristic analysis revealed that DWI-ASPECTS outperformed both CT-ASPECTS and the time interval between symptom onset and start of the procedure for predicting good functional outcome (modified Rankin Scale score, ≤2) and DWI volume ≥70 mL.Inter-rater agreement for DWI-ASPECTS was superior to that for CT-ASPECTS. DWI-ASPECTS outperformed NCCT ASPECTS for predicting functional outcome at 90 days.

  View details for DOI 10.1161/STROKEAHA.114.006564

  View details for PubMedID 25538199

• Diagnostic yield of extenced cardiac patch monitoring in patients with stroke or TIA FRONTIERS IN NEUROLOGY Tung, C. E., Su, D., Turakhia, M. P., Lansberg, M. G. 2015; 5

  View details for DOI 10.3389/fneur.2014.00266

  View details for Web of Science ID 000363750000001

• Imaging selection in ischemic stroke: feasibility of automated CT-perfusion analysis INTERNATIONAL JOURNAL OF STROKE Campbell, B. C., Yassi, N., Ma, H., Sharma, G., Salinas, S., Churilov, L., Meretoja, A., Parsons, M. W., Desmond, P. M., Lansberg, M. G., Donnan, G. A., Davis, S. M. 2015; 10 (1): 51-54

  Abstract

  Advanced imaging may refine patient selection for ischemic stroke treatment but delays to acquire and process the imaging have limited implementation.We examined the feasibility of imaging selection in clinical practice using fully automated software in the EXTEND trial program.CTP and perfusion-diffusion MRI data were processed using fully-automated software to generate a yes/no 'mismatch' classification that determined eligibility for trial therapies. The technical failure/mismatch classification error rate and time to image and treat with CT vs. MR-based selection were examined.In a consecutive series of 776 patients from five sites over six-months the technical failure rate of CTP acquisition/processing (uninterpretable maps) was 3·4% (26/776, 95%CI 2·2-4·9%). Mismatch classification was overruled by expert review in an additional 9·0% (70/776, 95%CI 7·1-11·3%) due to artifactual 'perfusion lesion'. In 154 consecutive patients at one site, median additional time to acquire CTP after non-contrast CT was 6·5 min. Subsequent RAPID processing time varied from 3-10 min across 20 trial centers (median 5 min 20 s). In the EXTEND trial, door-to-needle times in patients randomized on the basis of CTP (n = 47) were median 78 min shorter than MRI-selected (n = 16) patients (P < 0·001).Automated CTP-based mismatch selection is rapid, robust in clinical practice, and associated with faster treatment decisions than MRI. This technological advance has the potential to improve the standardization and reproducibility of interpretation of advanced imaging and extend use to practice settings beyond highly specialized academic centers.

  View details for DOI 10.1111/ijs.12381

  View details for Web of Science ID 000346156500017

  View details for PubMedID 25319251

• Correlation of AOL recanalization, TIMI reperfusion and TICI reperfusion with infarct growth and clinical outcome JOURNAL OF NEUROINTERVENTIONAL SURGERY Marks, M. P., Lansberg, M. G., Mlynash, M., Kemp, S., McTaggart, R., Zaharchuk, G., Bammer, R., Albers, G. W. 2014; 6 (10): 724-728

  View details for DOI 10.1136/neurintsurg-2013-010973

  View details for Web of Science ID 000344939800007

• Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet Emberson, J., Lees, K. R., Lyden, P., Blackwell, L., Albers, G., Bluhmki, E., Brott, T., Cohen, G., Davis, S., Donnan, G., Grotta, J., Howard, G., Kaste, M., Koga, M., von Kummer, R., Lansberg, M., Lindley, R. I., Murray, G., Olivot, J. M., Parsons, M., Tilley, B., Toni, D., Toyoda, K., Wahlgren, N., Wardlaw, J., Whiteley, W., del Zoppo, G. J., Baigent, C., Sandercock, P., Hacke, W. 2014; 384 (9958): 1929-1935

  Abstract

  Alteplase is effective for treatment of acute ischaemic stroke but debate continues about its use after longer times since stroke onset, in older patients, and among patients who have had the least or most severe strokes. We assessed the role of these factors in affecting good stroke outcome in patients given alteplase.We did a pre-specified meta-analysis of individual patient data from 6756 patients in nine randomised trials comparing alteplase with placebo or open control. We included all completed randomised phase 3 trials of intravenous alteplase for treatment of acute ischaemic stroke for which data were available. Retrospective checks confirmed that no eligible trials had been omitted. We defined a good stroke outcome as no significant disability at 3-6 months, defined by a modified Rankin Score of 0 or 1. Additional outcomes included symptomatic intracranial haemorrhage (defined by type 2 parenchymal haemorrhage within 7 days and, separately, by the SITS-MOST definition of parenchymal type 2 haemorrhage within 36 h), fatal intracranial haemorrhage within 7 days, and 90-day mortality.Alteplase increased the odds of a good stroke outcome, with earlier treatment associated with bigger proportional benefit. Treatment within 3·0 h resulted in a good outcome for 259 (32·9%) of 787 patients who received alteplase versus 176 (23·1%) of 762 who received control (OR 1·75, 95% CI 1·35-2·27); delay of greater than 3·0 h, up to 4·5 h, resulted in good outcome for 485 (35·3%) of 1375 versus 432 (30·1%) of 1437 (OR 1·26, 95% CI 1·05-1·51); and delay of more than 4·5 h resulted in good outcome for 401 (32·6%) of 1229 versus 357 (30·6%) of 1166 (OR 1·15, 95% CI 0·95-1·40). Proportional treatment benefits were similar irrespective of age or stroke severity. Alteplase significantly increased the odds of symptomatic intracranial haemorrhage (type 2 parenchymal haemorrhage definition 231 [6·8%] of 3391 vs 44 [1·3%] of 3365, OR 5·55, 95% CI 4·01-7·70, p<0·0001; SITS-MOST definition 124 [3·7%] vs 19 [0·6%], OR 6·67, 95% CI 4·11-10·84, p<0·0001) and of fatal intracranial haemorrhage within 7 days (91 [2·7%] vs 13 [0·4%]; OR 7·14, 95% CI 3·98-12·79, p<0·0001). The relative increase in fatal intracranial haemorrhage from alteplase was similar irrespective of treatment delay, age, or stroke severity, but the absolute excess risk attributable to alteplase was bigger among patients who had more severe strokes. There was no excess in other early causes of death and no significant effect on later causes of death. Consequently, mortality at 90 days was 608 (17·9%) in the alteplase group versus 556 (16·5%) in the control group (hazard ratio 1·11, 95% CI 0·99-1·25, p=0·07). Taken together, therefore, despite an average absolute increased risk of early death from intracranial haemorrhage of about 2%, by 3-6 months this risk was offset by an average absolute increase in disability-free survival of about 10% for patients treated within 3·0 h and about 5% for patients treated after 3·0 h, up to 4·5 h.Irrespective of age or stroke severity, and despite an increased risk of fatal intracranial haemorrhage during the first few days after treatment, alteplase significantly improves the overall odds of a good stroke outcome when delivered within 4·5 h of stroke onset, with earlier treatment associated with bigger proportional benefits.UK Medical Research Council, British Heart Foundation, University of Glasgow, University of Edinburgh.

  View details for DOI 10.1016/S0140-6736(14)60584-5

  View details for PubMedID 25106063

• Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials LANCET Emberson, J., Lees, K. R., Lyden, P., Blackwell, L., Albers, G., Bluhmki, E., Brott, T., Cohen, G., Davis, S., Donnan, G., Grotta, J., Howard, G., Kaste, M., Koga, M., von Kummer, R., Lansberg, M., Lindley, R. I., Murray, G., Olivot, J. M., Parsons, M., Tilley, B., Toni, D., Toyoda, K., Wahlgren, N., Wardlaw, J., Whiteley, W., del Zoppo, G. J., Baigent, C., Sandercock, P., Hacke, W. 2014; 384 (9958): 1929-1935

  View details for DOI 10.1016/S0140-6736(14)60584-5

  View details for Web of Science ID 000345450100028

• Angiographic outcome of endovascular stroke therapy correlated with MR findings, infarct growth, and clinical outcome in the DEFUSE 2 trial INTERNATIONAL JOURNAL OF STROKE Marks, M. P., Lansberg, M. G., Mlynash, M., Kemp, S., McTaggart, R. A., Zaharchuk, G., Bammer, R., Albers, G. W. 2014; 9 (7): 860-865

  View details for DOI 10.1111/ijs.12271

  View details for Web of Science ID 000342581900013

• Pittsburgh outcomes after stroke thrombectomy score predicts outcomes after endovascular therapy for anterior circulation large vessel occlusions. Stroke; a journal of cerebral circulation Rangaraju, S., Liggins, J. T., Aghaebrahim, A., Streib, C., Sun, C., Gupta, R., Nogueira, R., Frankel, M., Mlynash, M., Lansberg, M., Albers, G., Jadhav, A., Jovin, T. G. 2014; 45 (8): 2298-2304

  Abstract

  Prognostication tools that predict good outcome in patients with anterior circulation large vessel occlusions after endovascular therapy are lacking. We aim to develop a tool that incorporates clinical and imaging data to predict outcomes after endovascular therapy.In a derivation cohort of anterior circulation large vessel occlusion stroke patients treated with endovascular therapy within 8 hours from time last seen well (n=247), we performed logistic regression to identify independent predictors of good outcome (90-day modified Rankin Scale, 0-2). Factors were weighted based on β-coefficients to derive the Pittsburgh Outcomes After Stroke Thrombectomy (POST) score. POST was validated in an institutional endovascular database (University of Pittsburgh Medical Center, n=393) and the Diffusion-Weighted Imaging Evaluation for Understanding Stroke Evolution Study-2 (DEFUSE-2) data set (n=105), as well as in patients treated beyond 8 hours (n=194) and in octogenarians (n=111).In the derivation cohort, independent predictors (P<0.1) of good outcome included 24- to 72-hour final infarct volume (in cm(3), P<0.001), age (years, P<0.001), and parenchymal hematoma types 1 and 2 (H, P=0.01). POST was calculated as age+0.5×final infarct volume+15×H. Patients with POST score <60 had a 91% chance of good outcome compared with 4% with POST score ≥120. POST accurately predicted good outcomes in the derivation (area under the curve [AUC]=0.85) and validation cohorts (University of Pittsburgh Medical Center, AUC=0.81; DEFUSE-2, AUC=0.86), as well as in patients treated beyond 8 hours (AUC, 0.85) and octogenarians (AUC=0.76). POST had better predictive accuracy for good and poor outcome than the ischemic stroke predictive risk score (iSCORE).POST score is a validated predictor of outcome in patients with anterior circulation large vessel occlusions after endovascular therapy.

  View details for DOI 10.1161/STROKEAHA.114.005595

  View details for PubMedID 25005445

• Comparison of magnetic resonance imaging mismatch criteria to select patients for endovascular stroke therapy. Stroke; a journal of cerebral circulation Mishra, N. K., Albers, G. W., Christensen, S., Marks, M., Hamilton, S., Straka, M., Liggins, J. T., Kemp, S., Mlynash, M., Bammer, R., Lansberg, M. G. 2014; 45 (5): 1369-1374

  Abstract

  The Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 2 (DEFUSE 2) study has shown that clinical response to endovascular reperfusion differs between patients with and without perfusion-diffusion (perfusion-weighted imaging-diffusion-weighted imaging, PWI-DWI) mismatch: patients with mismatch have a favorable clinical response to reperfusion, whereas patients without mismatch do not. This study examined whether alternative mismatch criteria can also differentiate patients according to their response to reperfusion.Patients from the DEFUSE 2 study were categorized according to vessel occlusion on magnetic resonance angiography (MRA) and DWI lesion volume criteria (MRA-DWI mismatch) and symptom severity and DWI criteria (clinical-DWI mismatch). Favorable clinical response was defined as an improvement of ≥8 points on the National Institutes of Health Stroke Scale (NIHSS) by day 30 or an NIHSS score of ≤1 at day 30. We assessed, for each set of criteria, whether the association between reperfusion and favorable clinical response differed according to mismatch status.A differential response to reperfusion was observed between patients with and without MRA-DWI mismatch defined as an internal carotid artery or M1 occlusion and a DWI lesion <50 mL. Reperfusion was associated with good functional outcome in patients who met these MRA-DWI mismatch criteria (odds ratio [OR], 8.5; 95% confidence interval [CI], 2.3-31.3), whereas no association was observed in patients who did not meet these criteria (OR, 0.5; 95% CI, 0.08-3.1; P for difference between the odds, 0.01). No differential response to reperfusion was observed with other variations of the MRA-DWI or clinical-DWI mismatch criteria.The MRA-DWI mismatch is a promising alternative to DEFUSE 2's PWI-DWI mismatch for patient selection in endovascular stroke trials.

  View details for DOI 10.1161/STROKEAHA.114.004772

  View details for PubMedID 24699054

• Effect of collateral blood flow on patients undergoing endovascular therapy for acute ischemic stroke. Stroke; a journal of cerebral circulation Marks, M. P., Lansberg, M. G., Mlynash, M., Olivot, J., Straka, M., Kemp, S., McTaggart, R., Inoue, M., Zaharchuk, G., Bammer, R., Albers, G. W. 2014; 45 (4): 1035-1039

  Abstract

  Our aim was to determine the relationships between angiographic collaterals and diffusion/perfusion findings, subsequent infarct growth, and clinical outcome in patients undergoing endovascular therapy for ischemic stroke.Sixty patients with a thrombolysis in cerebral infarction (TICI) score of 0 or 1 and internal carotid artery/M1 occlusion at baseline were evaluated. A blinded reader assigned a collateral score using a previous 5-point scale, from 0 (no collateral flow) to 4 (complete/rapid collaterals to the entire ischemic territory). The analysis was dichotomized to poor flow (0-2) versus good flow (3-4). Collateral score was correlated with baseline National Institutes of Health Stroke Scale, diffusion-weighted imaging volume, perfusion-weighted imaging volume (Tmax ≥6 seconds), TICI reperfusion, infarct growth, and modified Rankin Scale score at day 90.Collateral score correlated with baseline National Institutes of Health Stroke Scale (P=0.002) and median volume of tissue at Tmax ≥6 seconds (P=0.009). Twenty-nine percent of patients with poor collateral flow had TICI 2B-3 reperfusion versus 65.5% with good flow (P=0.009). Patients with poor collaterals who reperfused (TICI 2B-3) were more likely to have a good functional outcome (modified Rankin Scale score 0-2 at 90 days) compared with patients who did not reperfuse (odds ratio, 12; 95% confidence interval, 1.6-98). There was no difference in the rate of good functional outcome after reperfusion in patients with poor collaterals versus good collaterals (P=1.0). Patients with poor reperfusion (TICI 0-2a) showed a trend toward greater infarct growth if they had poor collaterals versus good collaterals (P=0.06).Collaterals correlate with baseline National Institutes of Health Stroke Scale, perfusion-weighted imaging volume, and good reperfusion. However, target mismatch patients who reperfuse seem to have favorable outcomes at a similar rate, irrespective of the collateral score.http://www.clinicaltrials.gov. Unique identifier: NCT01349946.

  View details for DOI 10.1161/STROKEAHA.113.004085

  View details for PubMedID 24569816

• Early diffusion-weighted imaging reversal after endovascular reperfusion is typically transient in patients imaged 3 to 6 hours after onset. Stroke; a journal of cerebral circulation Inoue, M., Mlynash, M., Christensen, S., Wheeler, H. M., Straka, M., Tipirneni, A., Kemp, S. M., Zaharchuk, G., Olivot, J., Bammer, R., Lansberg, M. G., Albers, G. W. 2014; 45 (4): 1024-1028

  Abstract

  The aim of this study was to assess the frequency and extent of early diffusion-weighted imaging (DWI) lesion reversal after endovascular therapy and to determine whether early reversal is sustained or transient.MRI with DWI perfusion imaging was performed before (DWI 1) and within 12 hours after (DWI 2) endovascular treatment; follow-up MRI was obtained on day 5. Both DWIs were coregistered to follow-up MRI. Early DWI reversal was defined as the volume of the DWI 1 lesion that was not superimposed on the DWI 2 lesion. Permanent reversal was the volume of the DWI 1 lesion not superimposed on the day 5 infarct volume. Associations between early DWI reversal and clinical outcomes in patients with and without reperfusion were assessed.A total of 110 patients had technically adequate DWI before endovascular therapy (performed median [interquartile range], 4.5 [2.8-6.2] hours after onset); 60 were eligible for this study. Thirty-two percent had early DWI reversal >10 mL; 17% had sustained reversal. The median volume of permanent reversal at 5 days was 3 mL (interquartile range, 1.7-7.0). Only 2 patients (3%) had a final infarct volume that was smaller than their baseline DWI lesion. Early DWI reversal was not an independent predictor of clinical outcome and was not associated with early reperfusion.Early DWI reversal occurred in about one third of patients after endovascular therapy; however, reversal was often transient and was not associated with a significant volume of tissue salvage or favorable clinical outcome.

  View details for DOI 10.1161/STROKEAHA.113.002135

  View details for PubMedID 24558095

• Hypoperfusion Intensity Ratio Predicts Infarct Progression and Functional Outcome in the DEFUSE 2 Cohort. Stroke; a journal of cerebral circulation Olivot, J. M., Mlynash, M., Inoue, M., Marks, M. P., Wheeler, H. M., Kemp, S., Straka, M., Zaharchuk, G., Bammer, R., Lansberg, M. G., Albers, G. W. 2014; 45 (4): 1018-1023

  Abstract

  We evaluate associations between the severity of magnetic resonance perfusion-weighted imaging abnormalities, as assessed by the hypoperfusion intensity ratio (HIR), on infarct progression and functional outcome in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2).Diffusion-weighted magnetic resonance imaging and perfusion-weighted imaging lesion volumes were determined with the RAPID software program. HIR was defined as the proportion of TMax >6 s lesion volume with a Tmax >10 s delay and was dichotomized based on its median value (0.4) into low versus high subgroups as well as quartiles. Final infarct volumes were assessed at day 5. Initial infarct growth velocity was calculated as the baseline diffusion-weighted imaging (DWI) lesion volume divided by the delay from symptom onset to baseline magnetic resonance imaging. Total Infarct growth was determined by the difference between final infarct and baseline DWI volumes. Collateral flow was assessed on conventional angiography and dichotomized into good and poor flow. Good functional outcome was defined as modified Rankin Scale ≤2 at 90 days.Ninety-nine patients were included; baseline DWI, perfusion-weighted imaging, and final infarct volumes increased with HIR quartiles (P<0.01). A high HIR predicted poor collaterals with an area under the curve of 0.73. Initial infarct growth velocity and total infarct growth were greater among patients with a high HIR (P<0.001). After adjustment for age, DWI volume, and reperfusion, a low HIR was associated with good functional outcome: odds ratio=4.4 (95% CI, 1.3-14.3); P=0.014.HIR can be easily assessed on automatically processed perfusion maps and predicts the rate of collateral flow, infarct growth, and clinical outcome.

  View details for DOI 10.1161/STROKEAHA.113.003857

  View details for PubMedID 24595591

• Patients with single distal MCA perfusion lesions have a high rate of good outcome with or without reperfusion INTERNATIONAL JOURNAL OF STROKE Lemmens, R., Christensen, S., Straka, M., De Silva, D. A., Mlynash, M., Campbell, B. C., Bammer, R., Olivot, J., Desmond, P., Marks, M. P., Davis, S. M., Donnan, G. A., Albers, G. W., Lansberg, M. G. 2014; 9 (2): 156-159

  Abstract

  Reperfusion is associated with good functional outcome after stroke. However, minimal data are available regarding the effect of reperfusion on clinical outcome and infarct growth in patients with distal MCA branch occlusions.The aim of this study was to evaluate this association and to determine the impact of the perfusion-diffusion mismatch.Individual patient data from three stroke studies (EPITHET, DEFUSE and DEFUSE 2) with baseline MRI profiles and reperfusion status were pooled. Patients were included if they had a single cortical perfusion lesion on their baseline MRI that was consistent with a distal MCA branch occlusion. Good functional outcome was defined as a score of 0-2 on the modified Rankin Scale at day 90 and infarct growth was defined as change in lesion volume between the baseline DWI and the final T2/FLAIR.Thirty patients met inclusion criteria. Eighteen (60%) had a good functional outcome and twenty (67%) had reperfusion. Reperfusion was not associated with good functional outcome in the overall cohort (OR: 1·0, 95% CI 0·2-4·7) and also not in the subset of patients with a PWI-DWI mismatch (n = 17; OR: 0·7, 95% CI 0·1-5·5). Median infarct growth was modest and not significantly different between patients with (0 ml) and without reperfusion (6 ml); P = 0·2.The overall high rate of good outcomes in patients with distal MCA perfusion lesions might obscure a potential benefit from reperfusion in this population. A larger pooled analysis evaluating the effect of reperfusion in patients with distal MCA branch occlusions is warranted as confirmation of our results could have implications for the design of future stroke trials.

  View details for DOI 10.1111/ijs.12230

  View details for Web of Science ID 000329829700005

  View details for PubMedID 24373557

  View details for PubMedCentralID PMC3907940

• Diagnostic Yield of Extended Cardiac Patch Monitoring in Patients with Stroke or TIA. Frontiers in neurology Tung, C. E., Su, D., Turakhia, M. P., Lansberg, M. G. 2014; 5: 266-?

  Abstract

  It is important to evaluate patients with transient ischemic attack (TIA) or stroke for atrial fibrillation (AF) because the detection of AF changes the recommended anti-thrombotic regimen from treatment with an antiplatelet agent to oral anticoagulation. This study describes the diagnostic yield of a patch-based, single-use, and water-resistant 14-day continuous cardiac rhythm monitor (ZIO Patch) in patients with stroke or TIA.We obtained data from the manufacturer and servicer of the ZIO Patch (iRhythm Technologies). Patients who were monitored between January 2012 and June 2013 and whose indication for monitoring was TIA or stroke were included. The duration of monitoring, the number and type of arrhythmias, and the time to first arrhythmia were documented.One thousand one hundred seventy-one monitoring reports were analyzed. The mean monitor wear time was 10.9 days and the median wear time was 13.0 days (interquartile range 7.2-14.0). The median analyzable time relative to the total wear time was 98.7% (IQR 96.0-99.5%). AF was present in 5.0% of all reports. The mean duration before the first episode of paroxysmal AF (PAF) was 1.5 days and the median duration was 0.4 days. 14.3% of first PAF episodes occurred after 48 h. The mean PAF burden was 12.7% of the total monitoring duration.Excellent quality of the recordings and very good patient compliance coupled with a substantial proportion of AF detection beyond the first 48 h of monitoring suggest that the cardiac patch is superior to conventional 48-h Holter monitors for AF detection in patients with stroke or TIA.

  View details for DOI 10.3389/fneur.2014.00266

  View details for PubMedID 25628595

• Bilateral internal carotid artery occlusion associated with the antiphospholipid antibody syndrome. Case reports in neurology Anand, P., Mann, S. K., Fischbein, N. J., Lansberg, M. G. 2014; 6 (1): 50-54

  Abstract

  A 39-year-old woman presented with a right-hemispheric stroke 1 year after she had suffered a left-hemispheric stroke. Her diagnostic workup was notable for bilateral occlusions of the internal carotid arteries at their origins and a positive lupus anticoagulant antibody test. There was no evidence of carotid dissection or another identifiable cause for her carotid occlusions. These findings suggest that the antiphospholipid antibody syndrome may be implicated in the pathological changes that resulted in occlusions of the extracranial internal carotid arteries. Young stroke patients who present with unexplained internal carotid artery occlusions may benefit from testing for the presence of antiphospholipid antibodies.

  View details for DOI 10.1159/000360473

  View details for PubMedID 24707268

• Ferumoxytol enhanced resting state fMRI and relative cerebral blood volume mapping in normal human brain. NeuroImage D'Arceuil, H., Coimbra, A., Triano, P., Dougherty, M., Mello, J., Moseley, M., Glover, G., Lansberg, M., Blankenberg, F. 2013; 83: 200-209

  Abstract

  The brain demonstrates spontaneous low-frequency (<0.1Hz) cerebral blood flow (CBF) fluctuations, measurable by resting state functional MRI (rs-fMRI). Ultra small superparamagnetic iron oxide particles have been shown to enhance task-based fMRI signals (cerebral blood volume fMRI or CBV-fMRI), compared to the BOLD effect, by a factor of ≈2.5 at 3T in primates and humans. We evaluated the use of ferumoxytol for steady state, resting state FMRI (CBV-rs-fMRI) and relative cerebral blood volume (rCBV) mapping, at 3T, in healthy volunteers. All standard resting state networks (RSNs) were identified in all subjects. On average the RSN Z statistics (MELODIC independent components) and volumes of the visual and default mode (DMN) networks were comparable. rCBV values were averaged for the visual (Vis) and DMN networks and correlated with the corresponding DMN and visual network Z statistics. There was a negative correlation between the rCBV and the Z statistics for the DMN, for both BOLD and CBV-rs-fMRI contrast (R(2)=0.63, 0.76). A similar correlation was not found for the visual network. Short repetition time rs-fMRI data were Fourier transformed to evaluate the effect of ferumoxytol on cardiac and respiratory fluctuations in the brain rs-BOLD, CBV signals. Cardiac and respiratory fluctuations decreased to baseline within large vessels post ferumoxytol. Robust rs-fMRI and CBV mapping is possible in normal human brain.

  View details for DOI 10.1016/j.neuroimage.2013.06.066

  View details for PubMedID 23831413

• Acute Stroke Imaging Research Roadmap II STROKE Wintermark, M., Albers, G. W., Broderick, J. P., Demchuk, A. M., Fiebach, J. B., Fiehler, J., Grotta, J. C., Houser, G., Jovin, T. G., Lees, K. R., Lev, M. H., Liebeskind, D. S., Luby, M., Muir, K. W., Parsons, M. W., von Kummer, R., Wardlaw, J. M., Wu, O., Yoo, A. J., Alexandrov, A. V., Alger, J. R., Aviv, R. I., Bammer, R., Baron, J., Calamante, F., Campbell, B. C., Carpenter, T. C., Christensen, S., Copen, W. A., Derdeyn, C. P., Haley, C., Khatri, P., Kudo, K., Lansberg, M. G., Latour, L. L., Lee, T., Leigh, R., Lin, W., Lyden, P., Mair, G., Menon, B. K., Michel, P., Mikulik, R., Nogueira, R. G., Ostergaard, L., Pedraza, S., Riedel, C. H., Rowley, H. A., Sanelli, P. C., Sasaki, M., Saver, J. L., Schaefer, P. W., Schellinger, P. D., Tsivgoulis, G., Wechsler, L. R., White, P. M., Zaharchuk, G., Zaidat, O. O., Davis, S. M., Donnan, G. A., Furlan, A. J., Hacke, W., Kang, D., Kidwell, C., Thijs, V. N., Thomalla, G., Warach, S. J. 2013; 44 (9): 2628-2639

  View details for DOI 10.1161/STROKEAHA.113.002015

  View details for Web of Science ID 000329982500063

  View details for PubMedID 23860298

• Comparison of the response to endovascular reperfusion in relation to site of arterial occlusion. Neurology Lemmens, R., Mlynash, M., Straka, M., Kemp, S., Bammer, R., Marks, M. P., Albers, G. W., Lansberg, M. G. 2013; 81 (7): 614-618

  Abstract

  We explored the relationship between the site of vascular occlusion and the response to endovascular treatment in patients with acute ischemic stroke and also considered the impact of mismatch profile.DEFUSE-2 was a prospective cohort study of patients treated with endovascular therapy. Patients with internal carotid artery (ICA) and middle cerebral artery (MCA) involvement were included in this substudy. Mismatch and reperfusion status was assessed on MRI. Favorable clinical response was defined as an improvement of at least 8 points on the NIH Stroke Scale.Reperfusion rates were comparable in both groups (61% for ICA and 59% for MCA). In the setting of reperfusion, percentages of favorable clinical response were similar between patients with stroke due to ICA (65%) and MCA (63%) occlusions. When reperfusion was not achieved, favorable outcomes were less frequent with obstructions of the ICA (9%) than the MCA (52%). Among target mismatch patients, the adjusted odds ratio for favorable clinical response associated with reperfusion was 39.7 (95% confidence interval 1.4-1,132.8) for ICA occlusions vs 5.1 (95% confidence interval 1.4-19.3) for MCA occlusions.Endovascular reperfusion is associated with favorable clinical response regardless of the location of the arterial occlusion. This association is strongest for target mismatch patients with ICA occlusions. Target mismatch patients with either ICA or MCA occlusions appear to be good candidates for endovascular reperfusion therapy.

  View details for DOI 10.1212/WNL.0b013e3182a08f07

  View details for PubMedID 23851962

• Clinical outcomes strongly associated with the degree of reperfusion achieved in target mismatch patients: pooled data from the diffusion and perfusion imaging evaluation for understanding stroke evolution studies. Stroke; a journal of cerebral circulation Inoue, M., Mlynash, M., Straka, M., Kemp, S., Jovin, T. G., Tipirneni, A., Hamilton, S. A., Marks, M. P., Bammer, R., Lansberg, M. G., Albers, G. W. 2013; 44 (7): 1885-1890

  Abstract

  BACKGROUND AND PURPOSE: To investigate relationships between the degree of early reperfusion achieved on perfusion-weighted imaging and clinical outcomes in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution studies. We hypothesized that there would be a strong correlation between the degree of reperfusion achieved and clinical outcomes in target mismatch (TMM) patients. METHODS: The degree of reperfusion was calculated on the basis of the difference in perfusion-weighted imaging volumes (time to maximum of tissue residue function [Tmax]>6 s) between the baseline MRI and the early post-treatment follow-up scan. Patients were grouped into quartiles, on the basis of degree of reperfusion achieved, and the association between the degree of reperfusion and clinical outcomes in TMM and no TMM patients was assessed. Favorable clinical response was determined at day 30 on the basis of the National Institutes of Health Stroke Scale and good functional outcome was defined as a modified Rankin Scale score ≤2 at day 90. RESULTS: This study included 121 patients; 98 of these had TMM. The median degree of reperfusion achieved was not different in TMM patients (60%) versus No TMM patients (64%; P=0.604). The degree of reperfusion was strongly correlated with both favorable clinical response (P<0.001) and good functional outcome (P=0.001) in TMM patients; no correlation was present in no TMM. The frequency of achieving favorable clinical response or good functional outcome was significantly higher in TMM patients in the highest reperfusion quartile versus the lower 3 quartiles (88% versus 41% as odds ratio, 10.3; 95% confidence interval, 2.8-37.5; and 75% versus 34% as odds ratio, 5.9; 95% confidence interval, 2.1-16.7, respectively). A receiver operating characteristic curve analysis identified 90% as the optimal reperfusion threshold for predicting good functional outcomes. CONCLUSIONS: The degree of reperfusion documented on perfusion-weighted imaging after reperfusion therapies corresponds closely with clinical outcomes in TMM patients. Reperfusion of ≥90% of the perfusion lesion is an appropriate goal for reperfusion therapies to aspire to.

  View details for DOI 10.1161/STROKEAHA.111.000371

  View details for PubMedID 23704106

• Details of a prospective protocol for a collaborative meta-analysis of individual participant data from all randomized trials of intravenous rt-PA vs. control: statistical analysis plan for the Stroke Thrombolysis Trialists' Collaborative meta-analysis INTERNATIONAL JOURNAL OF STROKE Emberson, J., Lees, K. R., Howard, G., Bluhmki, E., Tilley, B., Albers, G., Baigent, C., Blackwell, L., Davis, S., Donnan, G., Grotta, J., Hacke, W., Kaste, M., von Kummer, R., Lansberg, M., Lindley, R., Lyden, P., Sandercock, P., Toni, D., Wahlgren, N., Wardlaw, J., Whiteley, W., del Zoppo, G. J. 2013; 8 (4): 278-283

  View details for DOI 10.1111/ijs.12040

  View details for Web of Science ID 000319398900023

• Interaction between time to treatment and reperfusion therapy in patients with acute ischemic stroke. Journal of neurointerventional surgery Lansberg, M. G., Dabus, G. 2013; 5: i48-51

  View details for DOI 10.1136/neurintsurg-2013-010728

  View details for PubMedID 23572462

• Advanced imaging improves prediction of hemorrhage after stroke thrombolysis ANNALS OF NEUROLOGY Campbell, B. C., Christensen, S., Parsons, M. W., Churilov, L., Desmond, P. M., Barber, P. A., Butcher, K. S., Levi, C. R., De Silva, D. A., Lansberg, M. G., Mlynash, M., Olivot, J., Straka, M., Bammer, R., Albers, G. W., Donnan, G. A., Davis, S. M. 2013; 73 (4): 510-519

  View details for DOI 10.1002/ana.23837

  View details for Web of Science ID 000319523800012

• Advanced imaging improves prediction of hemorrhage after stroke thrombolysis. Annals of neurology Campbell, B. C., Christensen, S., Parsons, M. W., Churilov, L., Desmond, P. M., Barber, P. A., Butcher, K. S., Levi, C. R., De Silva, D. A., Lansberg, M. G., Mlynash, M., Olivot, J., Straka, M., Bammer, R., Albers, G. W., Donnan, G. A., Davis, S. M. 2013; 73 (4): 510-519

  Abstract

  OBJECTIVE: Very low cerebral blood volume (VLCBV), diffusion, and hypoperfusion lesion volumes have been proposed as predictors of hemorrhagic transformation following stroke thrombolysis. We aimed to compare these parameters, validate VLCBV in an independent cohort using DEFUSE study data, and investigate the interaction of VLCBV with regional reperfusion. METHODS: The EPITHET and DEFUSE studies obtained diffusion and perfusion magnetic resonance imaging (MRI) in patients 3 to 6 hours from onset of ischemic stroke. EPITHET randomized patients to tissue plasminogen activator (tPA) or placebo, and all DEFUSE patients received tPA. VLCBV was defined as cerebral blood volume<2.5th percentile of brain contralateral to the infarct. Parenchymal hematoma (PH) was defined using European Cooperative Acute Stroke Study criteria. Reperfusion was assessed using subacute perfusion MRI coregistered to baseline imaging. RESULTS: In DEFUSE, 69 patients were analyzed, including 9 who developed PH. The >2 ml VLCBV threshold defined in EPITHET predicted PH with 100% sensitivity, 72% specificity, 35% positive predictive value, and 100% negative predictive value. Pooling EPITHET and DEFUSE (163 patients, including 23 with PH), regression models using VLCBV (p<0.001) and tPA (p=0.02) predicted PH independent of clinical factors better than models using diffusion or time to maximum>8 seconds lesion volumes. Excluding VLCBV in regions without reperfusion improved specificity from 61 to 78% in the pooled analysis. INTERPRETATION: VLCBV predicts PH after stroke thrombolysis and appears to be a more powerful predictor than baseline diffusion or hypoperfusion lesion volumes. Reperfusion of regions of VLCBV is strongly associated with post-thrombolysis PH. VLCBV may be clinically useful to identify patients at significant risk of hemorrhage following reperfusion. ANN NEUROL 2013;

  View details for DOI 10.1002/ana.23837

  View details for PubMedID 23444008

• Early Diffusion-Weighted Imaging and Perfusion-Weighted Imaging Lesion Volumes Forecast Final Infarct Size in DEFUSE 2 STROKE Wheeler, H. M., Mlynash, M., Inoue, M., Tipirneni, A., Liggins, J., Zaharchuk, G., Straka, M., Kemp, S., Bammer, R., Lansberg, M. G., Albers, G. W. 2013; 44 (3): 681-685

  Abstract

  It is hypothesized that early diffusion-weighted imaging (DWI) lesions accurately estimate the size of the irreversibly injured core and thresholded perfusion-weighted imaging (PWI) lesions (time to maximum of tissue residue function [Tmax] >6 seconds) approximate the volume of critically hypoperfused tissue. With incomplete reperfusion, the union of baseline DWI and posttreatment PWI is hypothesized to predict infarct volume.This is a substudy of Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study 2 (DEFUSE 2); all patients with technically adequate MRI scans at 3 time points were included. Baseline DWI and early follow-up PWI lesion volumes were determined by the RAPID software program. Final infarct volumes were assessed with 5-day fluid-attenuated inversion recovery and were corrected for edema. Reperfusion was defined on the basis of the reduction in PWI lesion volume between baseline and early follow-up MRI. DWI and PWI volumes were correlated with final infarct volumes.Seventy-three patients were eligible. Twenty-six patients with >90% reperfusion show a high correlation between early DWI volume and final infarct volume (r=0.95; P<0.001). Nine patients with <10% reperfusion have a high correlation between baseline PWI (Tmax >6 seconds) volume and final infarct volume (r=0.86; P=0.002). Using all 73 patients, the union of baseline DWI and early follow-up PWI is highly correlated with final infarct volume (r=0.94; P<0.001). The median absolute difference between observed and predicted final volumes is 15 mL (interquartile range, 5.5-30.2).Baseline DWI and early follow-up PWI (Tmax >6 seconds) volumes provide a reasonable approximation of final infarct volume after endovascular therapy.

  View details for DOI 10.1161/STROKEAHA.111.000135

  View details for Web of Science ID 000315447400024

  View details for PubMedID 23390119

  View details for PubMedCentralID PMC3625664

• Selection of patients for intra-arterial therapy--authors' reply. Lancet neurology Lansberg, M. G., Albers, G. W. 2013; 12 (3): 225-226

  View details for DOI 10.1016/S1474-4422(13)70019-X

  View details for PubMedID 23415563

• The Effects of Alteplase 3 to 6 Hours After Stroke in the EPITHET-DEFUSE Combined Dataset Post Hoc Case-Control Study STROKE Ogata, T., Christensen, S., Nagakane, Y., Ma, H., Campbell, B. C., Churilov, L., Lansberg, M. G., Straka, M., De Silva, D. A., Mlynash, M., Bammer, R., Olivot, J., Desmond, P. M., Albers, G. W., Davis, S. M., Donnan, G. A. 2013; 44 (1): 87-93

  Abstract

  Two phase 2 studies of alteplase in acute ischemic stroke 3 to 6 hours after onset, Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET; a randomized, controlled, double-blinded trial), and Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution Study (DEFUSE; open-label, treatment only) using MR imaging-based outcomes have been conducted. We have pooled individual patient data from these to assess the response to alteplase. The primary hypothesis was that alteplase would significantly attenuate infarct growth compared with placebo in mismatch-selected patients using coregistration techniques.The EPITHET-DEFUSE study datasets were pooled while retaining the original inclusion and exclusion criteria. Significant hypoperfusion was defined as a Tmax delay >6 seconds), and coregistration techniques were used to define MR diffusion-weighted imaging/perfusion-weighted imaging mismatch. Neuroimaging, parameters including reperfusion, recanalization, symptomatic intracerebral hemorrhage, and clinical outcomes were assessed. Alteplase and placebo groups were compared for the primary outcome of infarct growth as well for secondary outcome measures.From 165 patients with adequate MR scans in the EPITHET-DEFUSE pooled data, 121 patients (73.3%) were found to have mismatch. For the primary outcome analysis, 60 patients received alteplase and 41 placebo. Mismatch patients receiving alteplase had significantly attenuated infarct growth compared with placebo (P=0.025). The reperfusion rate was also increased (62.7% vs 31.7%; P=0.003). Mortality and clinical outcomes were not different between groups.The data provide further evidence that alteplase significantly attenuates infarct growth and increases reperfusion compared with placebo in the 3- to 6- hour time window in patients selected based on MR penumbral imaging.

  View details for DOI 10.1161/STROKEAHA.112.668301

  View details for Web of Science ID 000312883800016

  View details for PubMedID 23250996

• MRI profile and response to endovascular reperfusion after stroke (DEFUSE 2): a prospective cohort study LANCET NEUROLOGY Lansberg, M. G., Straka, M., Kemp, S., Mlynash, M., Wechsler, L. R., Jovin, T. G., Wilder, M. J., Lutsep, H. L., Czartoski, T. J., Bernstein, R. A., Chang, C. W., Warach, S., Fazekas, F., Inoue, M., Tipirneni, A., Hamilton, S. A., Zaharchuk, G., Marks, M. P., Bammer, R., Albers, G. W. 2012; 11 (10): 860-867

  Abstract

  Whether endovascular stroke treatment improves clinical outcomes is unclear because of the paucity of data from randomised placebo-controlled trials. We aimed to establish whether MRI can be used to identify patients who are most likely to benefit from endovascular reperfusion.In this prospective cohort study we consecutively enrolled patients scheduled to have endovascular treatment within 12 h of onset of stroke at eight centres in the USA and one in Austria. Aided by an automated image analysis computer program, investigators interpreted a baseline MRI scan taken before treatment to establish whether the patient had an MRI profile (target mismatch) that suggested salvageable tissue was present. Reperfusion was assessed on an early follow-up MRI scan (within 12 h of the revascularisation procedure) and defined as a more than 50% reduction in the volume of the lesion from baseline on perfusion-weighted MRI. The primary outcome was favourable clinical response, defined as an improvement of 8 or more on the National Institutes of Health Stroke Scale between baseline and day 30 or a score of 0-1 at day 30. The secondary clinical endpoint was good functional outcome, defined as a modified Rankin scale score of 2 or less at day 90. Analyses were adjusted for imbalances in baseline predictors of outcome. Investigators assessing outcomes were masked to baseline data.138 patients were enrolled. 110 patients had catheter angiography and of these 104 had an MRI profile and 99 could be assessed for reperfusion. 46 of 78 (59%) patients with target mismatch and 12 of 21 (57%) patients without target mismatch had reperfusion after endovascular treatment. The adjusted odds ratio (OR) for favourable clinical response associated with reperfusion was 8·8 (95% CI 2·7-29·0) in the target mismatch group and 0·2 (0·0-1·6) in the no target mismatch group (p=0·003 for difference between ORs). Reperfusion was associated with increased good functional outcome at 90 days (OR 4·0, 95% CI 1·3-12·2) in the target mismatch group, but not in the no target mismatch group (1·9, 0·2-18·7).Target mismatch patients who had early reperfusion after endovascular stroke treatment had more favourable clinical outcomes. No association between reperfusion and favourable outcomes was present in patients without target mismatch. Our data suggest that a randomised controlled trial of endovascular treatment for patients with the target mismatch profile is warranted.National Institute for Neurological Disorders and Stroke.

  View details for DOI 10.1016/S1474-4422(12)70203-X

  View details for Web of Science ID 000309634300011

  View details for PubMedID 22954705

• Patients With the Malignant Profile Within 3 Hours of Symptom Onset Have Very Poor Outcomes After Intravenous Tissue-Type Plasminogen Activator Therapy STROKE Inoue, M., Mlynash, M., Straka, M., Lansberg, M. G., Zaharchuk, G., Bammer, R., Albers, G. W. 2012; 43 (9): 2494-2496

  Abstract

  The malignant profile has been associated with poor outcomes after reperfusion in the 3- to 6-hour time window. The aim of this study was to estimate the incidence and prognostic implications of the malignant profile, as identified by CT perfusion, in intravenous tissue-type plasminogen activator-treated patients who were imaged <3 hours from stroke onset.The incidence of the malignant profile, based on the previously published optimal perfusion-weighted imaging definition, was assessed in consecutive patients using a fully automated software program (RApid processing of Perfusion and Diffusion [RAPID]). A receiver operating characteristic curve analysis was done to identify time to maximum and core volume thresholds that optimally identify patients with poor outcome (modified Rankin Scale 5-6).Forty-two patients had an interpretable CT perfusion performed within 3 hours of symptom onset. Mean age was 74±14 years and median (interquartile range) National Institutes of Stroke Scale score was 13 (6-19). Four patients (9.5%) met the prespecified criteria for the malignant profile and all 4 had poor outcome. Receiver operating characteristic analysis determined that the best CT perfusion measure to identify patients with poor outcome was a cerebral blood flow based infarct core >53 mL (100% specificity and 67% sensitivity). This criterion identified 5 patients as malignant (12%). The poor outcome rate in these patients was 100% versus 7.1% in the 37 nonmalignant patients (P<0.001).The incidence of the malignant profile on CT perfusion is approximately 10% in tissue-type plasminogen activator-eligible patients imaged within 3 hours of symptom onset. The clinical outcome of these patients is very poor despite intravenous tissue-type plasminogen activator therapy.

  View details for DOI 10.1161/STROKEAHA.112.653329

  View details for Web of Science ID 000308416300050

  View details for PubMedID 22811464

• Clinical Assessment of Standard and Generalized Autocalibrating Partially Parallel Acquisition Diffusion Imaging: Effects of Reduction Factor and Spatial Resolution AMERICAN JOURNAL OF NEURORADIOLOGY Andre, J. B., Zaharchuk, G., Fischbein, N. J., Augustin, M., Skare, S., Straka, M., Rosenberg, J., Lansberg, M. G., Kemp, S., Wijman, C. A., Albers, G. W., Schwartz, N. E., Bammer, R. 2012; 33 (7): 1337-1342

  Abstract

  PI improves routine EPI-based DWI by enabling higher spatial resolution and reducing geometric distortion, though it remains unclear which of these is most important. We evaluated the relative contribution of these factors and assessed their ability to increase lesion conspicuity and diagnostic confidence by using a GRAPPA technique.Four separate DWI scans were obtained at 1.5T in 48 patients with independent variation of in-plane spatial resolution (1.88 mm(2) versus 1.25 mm(2)) and/or reduction factor (R = 1 versus R = 3). A neuroradiologist with access to clinical history and additional imaging sequences provided a reference standard diagnosis for each case. Three blinded neuroradiologists assessed scans for abnormalities and also evaluated multiple imaging-quality metrics by using a 5-point ordinal scale. Logistic regression was used to determine the impact of each factor on subjective image quality and confidence.Reference standard diagnoses in the patient cohort were acute ischemic stroke (n = 30), ischemic stroke with hemorrhagic conversion (n = 4), intraparenchymal hemorrhage (n = 9), or no acute lesion (n = 5). While readers preferred both a higher reduction factor and a higher spatial resolution, the largest effect was due to an increased reduction factor (odds ratio, 47 ± 16). Small lesions were more confidently discriminated from artifacts on R = 3 images. The diagnosis changed in 5 of 48 scans, always toward the reference standard reading and exclusively for posterior fossa lesions.PI improves DWI primarily by reducing geometric distortion rather than by increasing spatial resolution. This outcome leads to a more accurate and confident diagnosis of small lesions.

  View details for DOI 10.3174/ajnr.A2980

  View details for Web of Science ID 000307628200025

  View details for PubMedID 22403781

• Automated Perfusion Imaging for the Evaluation of Transient Ischemic Attack STROKE Kleinman, J. T., Zaharchuk, G., Mlynash, M., Ogdie, A. A., Straka, M., Lansberg, M. G., Schwartz, N. E., Kemp, S., Bammer, R., Albers, G. W., Olivot, J. 2012; 43 (6): 1556-1560

  Abstract

  Diffusion-weighted imaging (DWI) is recommended for the evaluation of transient ischemic attack. Perfusion imaging can increase the yield of MRI in transient ischemic attack. We evaluated automated bolus perfusion (the time when the residue function reaches its maximum [TMax] and mean transit time [MTT]) and arterial spin labeling (ASL) sequences for the detection of ischemic lesions in patients with transient ischemic attack.We enrolled consecutive patients evaluated for suspicion of acute transient ischemic attack by multimodal MRI within 36 hours of symptom onset. Two independent raters assessed the presence and location of ischemic lesions blinded to the clinical presentation. The prevalence of ischemic lesions and the interrater agreement were 1,410 assessed.From January 2010 to 2011, 93 patients were enrolled and 90 underwent perfusion imaging (69 bolus perfusion and 76 ASL). Overall, 25 of 93 patients (27%) were DWI-positive and 14 (15%) were perfusion-positive but DWI-negative (ASL n=9; TMax n=9; MTT n=2). MTT revealed an ischemic lesion in fewer patients than TMax (7 versus 20, P=0.004). Raters agreed on 89% of diffusion-weighted imaging cases, 89% of TMax, 87% o10f010 MTT, and 90% of ASL cases. The interrater agreement was good for DWI, TMax, and ASL (κ=0.73, 0.72, and 0.74, respectively) and fair for MTT (κ=0.43). Diffusion and/or perfusion were positive in 39 of 69 (57%) patients with a discharge diagnosis of possible ischemic event.Our results suggest that in patients referred for suspicion of transient ischemic attack, automated TMax is more sensitive than MTT, and both ASL and TMax increase the yield of MRI for the detection of ischemic lesions.

  View details for DOI 10.1161/STROKEAHA.111.644971

  View details for Web of Science ID 000304523800025

  View details for PubMedID 22474058

• Antithrombotic therapy in peripheral artery disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest Alonso-Coello, P., Bellmunt, S., McGorrian, C., Anand, S. S., Guzman, R., Criqui, M. H., Akl, E. A., Olav Vandvik, P., Lansberg, M. G., Guyatt, G. H., Spencer, F. A. 2012; 141 (2): e669S-90S

  Abstract

  This guideline focuses on antithrombotic drug therapies for primary and secondary prevention of cardiovascular disease as well as for the relief of lower-extremity symptoms and critical ischemia in persons with peripheral arterial disease (PAD).The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement.The most important of our 20 recommendations are as follows. In patients aged ≥ 50 years with asymptomatic PAD or asymptomatic carotid stenosis, we suggest aspirin (75-100 mg/d) over no therapy (Grade 2B) for the primary prevention of cardiovascular events. For secondary prevention of cardiovascular disease in patients with symptomatic PAD (including patients before and after peripheral arterial bypass surgery or percutaneous transluminal angioplasty), we recommend long-term aspirin (75-100 mg/d) or clopidogrel (75 mg/d) (Grade 1A). We recommend against the use of warfarin plus aspirin in patients with symptomatic PAD (Grade 1B). For patients undergoing peripheral artery percutaneous transluminal angioplasty with stenting, we suggest single rather than dual antiplatelet therapy (Grade 2C). For patients with refractory claudication despite exercise therapy and smoking cessation, we suggest addition of cilostazol (100 mg bid) to aspirin (75-100 mg/d) or clopidogrel (75 mg/d) (Grade 2C). In patients with critical limb ischemia and rest pain unable to undergo revascularization, we suggest the use of prostanoids (Grade 2C). In patients with acute limb ischemia due to acute thrombosis or embolism, we recommend surgery over peripheral arterial thrombolysis (Grade 1B).Recommendations continue to favor single antiplatelet therapy for primary and secondary prevention of cardiovascular events in most patients with asymptomatic PAD, symptomatic PAD, and asymptomatic carotid stenosis. Additional therapies for relief of limb symptoms should be considered only after exercise therapy, smoking cessation, and evaluation for peripheral artery revascularization.

  View details for DOI 10.1378/chest.11-2307

  View details for PubMedID 22315275

  View details for PubMedCentralID PMC3278062

• Approach to outcome measurement in the prevention of thrombosis in surgical and medical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest Guyatt, G. H., Eikelboom, J. W., Gould, M. K., Garcia, D. A., Crowther, M., Murad, M. H., Kahn, S. R., Falck-Ytter, Y., Francis, C. W., Lansberg, M. G., Akl, E. A., Hirsh, J. 2012; 141 (2): e185S-94S

  Abstract

  This article provides the rationale for the approach to making recommendations primarily used in four articles of the Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines: orthopedic surgery, nonorthopedic surgery, nonsurgical patients, and stroke. Some of the early clinical trials of antithrombotic prophylaxis with a placebo or no treatment group used symptomatic VTE and fatal PE to measure efficacy of the treatment. These trials suggest a benefit of thromboprophylaxis in reducing fatal PE. In contrast, most of the recent clinical trials comparing the efficacy of alternative anticoagulants used a surrogate outcome, asymptomatic DVT detected at mandatory venography. This outcome is fundamentally unsatisfactory because it does not allow a trade-off with serious bleeding; that trade-off requires knowledge of the number of symptomatic events that thromboprophylaxis prevents. In this article, we review the merits and limitations of four approaches to estimating reduction in symptomatic thrombosis: (1) direct measurement of symptomatic thrombosis, (2) use of asymptomatic events for relative risks and symptomatic events from randomized controlled trials for baseline risk, (3) use of baseline risk estimates from studies that did not perform surveillance and relative effect from asymptomatic events in randomized controlled trials, and (4) use of available data to estimate the proportion of asymptomatic events that will become symptomatic. All approaches have their limitations. The optimal choice of approach depends on the nature of the evidence available.

  View details for DOI 10.1378/chest.11-2289

  View details for PubMedID 22315260

• Primary and secondary prevention of cardiovascular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest Vandvik, P. O., Lincoff, A. M., Gore, J. M., Gutterman, D. D., Sonnenberg, F. A., Alonso-Coello, P., Akl, E. A., Lansberg, M. G., Guyatt, G. H., Spencer, F. A. 2012; 141 (2): e637S-68S

  Abstract

  This guideline focuses on long-term administration of antithrombotic drugs designed for primary and secondary prevention of cardiovascular disease, including two new antiplatelet therapies.The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement.We present 23 recommendations for pertinent clinical questions. For primary prevention of cardiovascular disease, we suggest low-dose aspirin (75-100 mg/d) in patients aged > 50 years over no aspirin therapy (Grade 2B). For patients with established coronary artery disease, defined as patients 1-year post-acute coronary syndrome, with prior revascularization, coronary stenoses > 50% by coronary angiogram, and/or evidence for cardiac ischemia on diagnostic testing, we recommend long-term low-dose aspirin or clopidogrel (75 mg/d) (Grade 1A). For patients with acute coronary syndromes who undergo percutaneous coronary intervention (PCI) with stent placement, we recommend for the first year dual antiplatelet therapy with low-dose aspirin in combination with ticagrelor 90 mg bid, clopidogrel 75 mg/d, or prasugrel 10 mg/d over single antiplatelet therapy (Grade 1B). For patients undergoing elective PCI with stent placement, we recommend aspirin (75-325 mg/d) and clopidogrel for a minimum duration of 1 month (bare-metal stents) or 3 to 6 months (drug-eluting stents) (Grade 1A). We suggest continuing low-dose aspirin plus clopidogrel for 12 months for all stents (Grade 2C). Thereafter, we recommend single antiplatelet therapy over continuation of dual antiplatelet therapy (Grade 1B).Recommendations continue to favor single antiplatelet therapy for patients with established coronary artery disease. For patients with acute coronary syndromes or undergoing elective PCI with stent placement, dual antiplatelet therapy for up to 1 year is warranted.

  View details for DOI 10.1378/chest.11-2306

  View details for PubMedID 22315274

• Antithrombotic Therapy in Peripheral Artery Disease Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines CHEST Alonso-Coello, P., Bellmunt, S., McGorrian, C., Anand, S. S., Guzman, R., Criqui, M. H., Akl, E. A., Vandvik, P. O., Lansberg, M. G., Guyatt, G. H., Spencer, F. A. 2012; 141 (2): E669S-E690S

  View details for DOI 10.1378/chest.11-2307

  View details for Web of Science ID 000208839900019

• Approach to Outcome Measurement in the Prevention of Thrombosis in Surgical and Medical Patients Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines CHEST Guyatt, G. H., Eikelboom, J. W., Gould, M. K., Garcia, D. A., Crowther, M., Murad, M. H., Kahn, S. R., Falck-Ytter, Y., Francis, C. W., Lansberg, M. G., Akl, E. A., Hirsh, J. 2012; 141 (2): E185S-E194S

  View details for DOI 10.1378/chest.11-2289

  View details for Web of Science ID 000208839900007

• Primary and Secondary Prevention of Cardiovascular Disease Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines CHEST Vandvik, O., Lincoff, A. M., Gore, J. M., Gutterman, D. D., Sonnenberg, F. A., Alonso-Coello, P., Akl, E. A., Lansberg, M. G., Guyatt, G. H., Spencer, F. A. 2012; 141 (2): E637S-E668S

  View details for DOI 10.1378/chest.11-2306

  View details for Web of Science ID 000208839900018

• Antithrombotic and thrombolytic therapy for ischemic stroke: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest Lansberg, M. G., O'Donnell, M. J., Khatri, P., Lang, E. S., Nguyen-Huynh, M. N., Schwartz, N. E., Sonnenberg, F. A., Schulman, S., Vandvik, P. O., Spencer, F. A., Alonso-Coello, P., Guyatt, G. H., Akl, E. A. 2012; 141 (2): e601S-36S

  Abstract

  This article provides recommendations on the use of antithrombotic therapy in patients with stroke or transient ischemic attack (TIA).We generated treatment recommendations (Grade 1) and suggestions (Grade 2) based on high (A), moderate (B), and low (C) quality evidence.In patients with acute ischemic stroke, we recommend IV recombinant tissue plasminogen activator (r-tPA) if treatment can be initiated within 3 h (Grade 1A) or 4.5 h (Grade 2C) of symptom onset; we suggest intraarterial r-tPA in patients ineligible for IV tPA if treatment can be initiated within 6 h (Grade 2C); we suggest against the use of mechanical thrombectomy (Grade 2C) although carefully selected patients may choose this intervention; and we recommend early aspirin therapy at a dose of 160 to 325 mg (Grade 1A). In patients with acute stroke and restricted mobility, we suggest the use of prophylactic-dose heparin or intermittent pneumatic compression devices (Grade 2B) and suggest against the use of elastic compression stockings (Grade 2B). In patients with a history of noncardioembolic ischemic stroke or TIA, we recommend long-term treatment with aspirin (75-100 mg once daily), clopidogrel (75 mg once daily), aspirin/extended release dipyridamole (25 mg/200 mg bid), or cilostazol (100 mg bid) over no antiplatelet therapy (Grade 1A), oral anticoagulants (Grade 1B), the combination of clopidogrel plus aspirin (Grade 1B), or triflusal (Grade 2B). Of the recommended antiplatelet regimens, we suggest clopidogrel or aspirin/extended-release dipyridamole over aspirin (Grade 2B) or cilostazol (Grade 2C). In patients with a history of stroke or TIA and atrial fibrillation we recommend oral anticoagulation over no antithrombotic therapy, aspirin, and combination therapy with aspirin and clopidogrel (Grade 1B).These recommendations can help clinicians make evidence-based treatment decisions with their patients who have had strokes.

  View details for DOI 10.1378/chest.11-2302

  View details for PubMedID 22315273

• Antithrombotic and Thrombolytic Therapy for Ischemic Stroke Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines CHEST Lansberg, M. G., O'Donnell, M. J., Khatri, P., Lang, E. S., Nguyen-Huynh, M. N., Schwartz, N. E., Sonnenberg, F. A., Schulman, S., Vandvik, P. O., Spencer, F. A., Alonso-Coello, P., Guyatt, G. H., Akl, E. A. 2012; 141 (2): E601S-E636S

  View details for DOI 10.1378/chest.11-2302

  View details for Web of Science ID 000208839900017

• Cost comparison between the atraumatic and cutting lumbar puncture needles NEUROLOGY Tung, C. E., So, Y. T., Lansberg, M. G. 2012; 78 (2): 109-113

  Abstract

  The aim of this study was to determine which type of spinal needle is preferred from a cost perspective, taking into account costs of the spinal needle and treatment of postlumbar puncture headache.A decision-analytic model was created to determine the cost of diagnostic lumbar punctures using atraumatic and cutting needles. We assumed a health care system perspective and based the analysis on the treatment of a patient facing event probabilities derived from prior studies. The economic outcome measure was the difference in estimated costs between the 2 needles. One-way and probabilistic sensitivity analyses tested the robustness of the model.Lumbar puncture performed with the atraumatic needle is associated with an average cost savings of $26.07 per patient. Average total health care costs are $166.08 with the atraumatic needle, compared to $192.15 with the cutting needle. There is 94% certainty that the atraumatic needle is cost-saving compared to the cutting needle based on probabilistic sensitivity analysis. Use of the atraumatic needle over the cutting needle by neurologists alone may result in $10.4 million in cost savings to the US health care system per year.The atraumatic spinal needle is associated with an overall cost savings to the US health care system. The balance of costs and benefits favors the use of the atraumatic needle over the cutting needle for diagnostic lumbar puncture.

  View details for Web of Science ID 000299159700010

  View details for PubMedID 22205758

• The infarct core is well represented by the acute diffusion lesion: sustained reversal is infrequent JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Campbell, B. C., Purushotham, A., Christensen, S., Desmond, P. M., Nagakane, Y., Parsons, M. W., Lansberg, M. G., Mlynash, M., Straka, M., De Silva, D. A., Olivot, J., Bammer, R., Albers, G. W., Donnan, G. A., Davis, S. M. 2012; 32 (1): 50-56

  Abstract

  Diffusion-weighted imaging (DWI) is commonly used to assess irreversibly infarcted tissue but its accuracy is challenged by reports of diffusion lesion reversal (DLR). We investigated the frequency and implications for mismatch classification of DLR using imaging from the EPITHET (Echoplanar Imaging Thrombolytic Evaluation Trial) and DEFUSE (Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution) studies. In 119 patients (83 treated with IV tissue plasminogen activator), follow-up images were coregistered to acute diffusion images and the lesions manually outlined to their maximal visual extent in diffusion space. Diffusion lesion reversal was defined as voxels of acute diffusion lesion that corresponded to normal brain at follow-up (i.e., final infarct, leukoaraiosis, and cerebrospinal fluid (CSF) voxels were excluded from consideration). The appearance of DLR was visually checked for artifacts, the volume calculated, and the impact of adjusting baseline diffusion lesion volume for DLR volume on perfusion-diffusion mismatch analyzed. Median DLR volume reduced from 4.4 to 1.5 mL after excluding CSF/leukoaraiosis. Visual inspection verified 8/119 (6.7%) with true DLR, median volume 2.33 mL. Subtracting DLR from acute diffusion volume altered perfusion-diffusion mismatch (T(max)>6 seconds, ratio>1.2) in 3/119 (2.5%) patients. Diffusion lesion reversal between baseline and 3 to 6 hours DWI was also uncommon (7/65, 11%) and often transient. Clinically relevant DLR is uncommon and rarely alters perfusion-diffusion mismatch. The acute diffusion lesion is generally a reliable signature of the infarct core.

  View details for DOI 10.1038/jcbfm.2011.102

  View details for Web of Science ID 000299010000008

  View details for PubMedID 21772309

  View details for PubMedCentralID PMC3323290

• MRI guides diagnostic approach for ischaemic stroke JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY Kumar, M. A., Vangala, H., Tong, D. C., Campbell, D. M., Balgude, A., Eyngorn, I., Beraud, A. S., Olivot, J. M., Hsia, A. W., Bernstein, R. A., Wijman, C. A., Lansberg, M. G., Mlynash, M., Hamilton, S., Moseley, M. E., Albers, G. W. 2011; 82 (11): 1201-1205

  Abstract

  Identification of ischaemic stroke subtype currently relies on clinical evaluation supported by various diagnostic studies. The authors sought to determine whether specific diffusion-weighted MRI (DWI) patterns could reliably guide the subsequent work-up for patients presenting with acute ischaemic stroke symptoms.273 consecutive patients with acute ischaemic stroke symptoms were enrolled in this prospective, observational, single-centre NIH-sponsored study. Electrocardiogram, non-contrast head CT, brain MRI, head and neck magnetic resonance angiography (MRA) and transoesophageal echocardiography were performed in this prespecified order. Stroke neurologists determined TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification on admission and on discharge. Initial TOAST stroke subtypes were compared with the final TOAST subtype. If the final subtype differed from the initial assessment, the diagnostic test deemed the principal determinant of change was recorded. These principal determinants of change were compared between a CT-based and an MRI-based classification schema.Among patients with a thromboembolic DWI pattern, transoesophageal echocardiography was the principal determinant of diagnostic change in 8.8% versus 0% for the small vessel group and 1.7% for the other group (p<0.01). Among patients with the combination of a thromboembolic pattern on MRI and a negative cervical MRA, transoesophageal echocardiography led to a change in diagnosis in 12.1%. There was no significant difference between groups using a CT-based scheme.DWI patterns appear to predict stroke aetiologies better than conventional methods. The study data suggest an MRI-based diagnostic algorithm that can potentially obviate the need for echocardiography in one-third of stroke patients and may limit the number of secondary extracranial vascular imaging studies to approximately 10%.

  View details for DOI 10.1136/jnnp.2010.237941

  View details for Web of Science ID 000295920000006

  View details for PubMedID 21551473

• Greater Effect of Stroke Thrombolysis in the Presence of Arterial Obstruction ANNALS OF NEUROLOGY De Silva, D. A., Churilov, L., Olivot, J., Christensen, S., Lansberg, M. G., Mlynash, M., Campbell, B. C., Desmond, P., Straka, M., Bammer, R., Albers, G. W., Davis, S. M., Donnan, G. A. 2011; 70 (4): 601-605

  Abstract

  Recanalization of arterial obstruction is associated with improved clinical outcomes. There are no controlled data demonstrating whether arterial obstruction status predicts the treatment effect of intravenous (IV) tissue plasminogen activator (tPA). We aimed to determine if the presence of arterial obstruction improves the treatment effect of IV tPA over placebo in attenuating infarct growth.We analyzed 175 ischemic stroke patients treated in the 3-6 hour time window from the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) trial (randomized to IV tPA or placebo) and Diffusion and perfusion imaging Evaluation For Understanding Stroke Evolution (DEFUSE) study (all treated with IV tPA). Infarct growth was calculated as the difference between baseline diffusion-weighted imaging (DWI) and final T2 lesion volumes. Baseline arterial obstruction of large intracranial arteries was graded on magnetic resonance angiography (MRA).Among the 116 patients with adequate baseline MRA and final lesion assessment, 72 had arterial obstruction (48 tPA, 24 placebo) and 44 no arterial obstruction (33 tPA, 11 placebo). Infarct growth was lower in the tPA than placebo group (median difference 26ml, 95% confidence interval [CI], 1-50) in patients with arterial obstruction, but was similar in patients with no arterial obstruction (median difference 5ml, 95%CI, -3 to 9). Infarct growth attenuation with tPA over placebo treatment was greater among patients with arterial obstruction than those without arterial obstruction by a median of 32ml (95%CI, 21-43, p < 0.001).The treatment effect of IV tPA over placebo was greater with baseline arterial obstruction, supporting arterial obstruction status as a consideration in selecting patients more likely to benefit from IV thrombolysis.

  View details for DOI 10.1002/ana.22444

  View details for Web of Science ID 000296396700013

  View details for PubMedID 22028220

  View details for PubMedCentralID PMC3205432

• Cost-Effectiveness of Tissue-Type Plasminogen Activator in the 3-to 4.5-Hour Time Window for Acute Ischemic Stroke STROKE Tung, C. E., Win, S. S., Lansberg, M. G. 2011; 42 (8): 2257-2262

  Abstract

  The aim of this study was to determine the cost-effectiveness of tissue-type plasminogen activator (tPA) treatment in the 3- to 4.5-hour time window after ischemic stroke.Decision-analytic and Markov state-transition models were created to determine the cost-effectiveness of treatment of ischemic stroke patients with intravenous tPA administered in the 3- to 4.5-hour time window compared with medical therapy without tPA. Health benefits were measured in quality-adjusted life-years (QALYs). The economic outcome measure of the model was the difference in estimated healthcare costs between the 2 treatment alternatives. The incremental cost-effectiveness ratio was calculated by dividing the cost difference by the difference in QALYs. One-way sensitivity and probabilistic analyses were performed to test the robustness of the model.The administration of tPA compared with standard medical therapy resulted in a lifetime gain of 0.28 QALYs for an additional cost of $6050, yielding an incremental cost-effectiveness ratio of $21 978 per QALY. One-way sensitivity analyses demonstrated that the incremental cost-effectiveness ratio was most sensitive to the cost of hospitalization for patients who received tPA. Based on probabilistic analysis, there is an 88% probability that tPA is the preferred treatment at a willingness-to-pay threshold of $50 000 per QALY.The balance of costs and benefits favors treatment with intravenous tPA in the 3- to 4.5-hour time window. This supports, from a societal perspective, the use of tPA therapy in this treatment time window for acute ischemic stroke.

  View details for DOI 10.1161/STROKEAHA.111.615682

  View details for Web of Science ID 000293077400034

  View details for PubMedID 21719767

• TWO ACES Transient Ischemic Attack Work-Up as Outpatient Assessment of Clinical Evaluation and Safety STROKE Olivot, J., Wolford, C., Castle, J., Mlynash, M., Schwartz, N. E., Lansberg, M. G., Kemp, S., Albers, G. W. 2011; 42 (7): 1839-1843

  Abstract

  To evaluate a novel emergency department-based TIA triage system.We developed an approach to TIA triage and management based on risk assessment using the ABCD(2) score in combination with early cervical and intracranial vessel imaging. It was anticipated that this triage system would avoid hospitalization for the majority of TIA patients and result in a low rate of recurrent stroke. We hypothesized that the subsequent stroke rate among consecutively encountered patients managed with this approach would be lower than predicted based on their ABCD2 scores.From June 2007 to December 2009, 224 consecutive patients evaluated in the Stanford emergency department for a possible TIA were enrolled in the study. One hundred fifty-seven were discharged to complete their evaluation at the outpatient TIA clinic; 67 patients were hospitalized. One hundred sixteen patients had a final diagnosis of TIA/minor stroke or possible TIA. The stroke rates at 7, 30, and 90 days were 0.6% (0.1%-3.5%) for patients referred to the TIA clinic and 1.5% (0.3%-8.0%) for the hospitalized patients. Combining both groups, the overall stroke rate was 0.9% (0.3%-3.2%), which is significantly less than expected based on ABCD2 scores (P=0.034 at 7 days and P=0.001 at 90 days).This emergency department-based inpatient versus outpatient TIA triage system led to a low rate of hospitalization (30%). Recurrent stroke rates were low for both the hospitalized and outpatient subgroups.

  View details for DOI 10.1161/STROKEAHA.110.608380

  View details for Web of Science ID 000292090900019

  View details for PubMedID 21617143

• RAPID Automated Patient Selection for Reperfusion Therapy A Pooled Analysis of the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) and the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) Study STROKE Lansberg, M. G., Lee, J., Christensen, S., Straka, M., De Silva, D. A., Mlynash, M., Campbell, B. C., Bammer, R., Olivot, J., Desmond, P., Davis, S. M., Donnan, G. A., Albers, G. W. 2011; 42 (6): 1608-1614

  Abstract

  The aim of this study was to determine if automated MRI analysis software (RAPID) can be used to identify patients with stroke in whom reperfusion is associated with an increased chance of good outcome.Baseline diffusion- and perfusion-weighted MRI scans from the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution study (DEFUSE; n=74) and the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET; n=100) were reprocessed with RAPID. Based on RAPID-generated diffusion-weighted imaging and perfusion-weighted imaging lesion volumes, patients were categorized according to 3 prespecified MRI profiles that were hypothesized to predict benefit (Target Mismatch), harm (Malignant), and no effect (No Mismatch) from reperfusion. Favorable clinical response was defined as a National Institutes of Health Stroke Scale score of 0 to 1 or a ≥ 8-point improvement on the National Institutes of Health Stroke Scale score at Day 90.In Target Mismatch patients, reperfusion was strongly associated with a favorable clinical response (OR, 5.6; 95% CI, 2.1 to 15.3) and attenuation of infarct growth (10 ± 23 mL with reperfusion versus 40 ± 44 mL without reperfusion; P<0.001). In Malignant profile patients, reperfusion was not associated with a favorable clinical response (OR, 0.74; 95% CI, 0.1 to 5.8) or attenuation of infarct growth (85 ± 74 mL with reperfusion versus 95 ± 79 mL without reperfusion; P=0.7). Reperfusion was also not associated with a favorable clinical response (OR, 1.05; 95% CI, 0.1 to 9.4) or attenuation of lesion growth (10 ± 15 mL with reperfusion versus 17 ± 30 mL without reperfusion; P=0.9) in No Mismatch patients.MRI profiles that are associated with a differential response to reperfusion can be identified with RAPID. This supports the use of automated image analysis software such as RAPID for patient selection in acute stroke trials.

  View details for DOI 10.1161/STROKEAHA.110.609008

  View details for Web of Science ID 000291032700038

  View details for PubMedID 21493916

  View details for PubMedCentralID PMC3104106

• Meta-analysis of randomized intra-arterial thrombolytic trials for the treatment of acute stroke due to middle cerebral artery occlusion JOURNAL OF NEUROINTERVENTIONAL SURGERY Fields, J. D., Khatri, P., Nesbit, G. M., Liu, K. C., Barnwell, S. L., Lutsep, H. L., Clark, W. M., Lansberg, M. G. 2011; 3 (2): 151-155

  Abstract

  Randomized clinical trials supporting the use of intra-arterial administration of thrombolytics (IAT) for the treatment of stroke due to middle cerebral artery (MCA) occlusion have been positive on some, but not all, endpoints. A meta-analysis was performed to estimate with more precision the effect of IAT on several key clinical endpoints.All randomized trials of IAT in the treatment of MCA stroke were identified by PUBMED search and by hand search of potentially relevant references. Trial methodologies were assessed for compatibility in study protocols and statistical analysis. A meta-analysis was performed evaluating the effect of IAT on functional outcome at 90 days and symptomatic intracranial hemorrhage (SICH) within 24 h.Three trials met the criteria for the meta-analysis. IAT treated patients were significantly more likely to have a modified Rankin scale (mRS) ≤ 1 (31% vs 20%, OR 2.0, 95% CI 1.2 to 3.4, p=0.01); mRS ≤ 2 (43% vs 31%, OR 1.9, 95% CI 1.2 to 3.0, p=0.01); and NIH Stroke Scale score 0 or 1 (23% vs 12%, OR 2.4, 95% CI 1.3 to 4.4, p=0.007) at the 90 day follow-up. There was no effect on mortality at 90 days (20% vs 19%, OR 0.84, 95% CI 0.5 to 1.5). The risk of SICH was significantly increased in the active treatment arms (11% vs 2%, OR 4.6, 95% CI 1.3 to 16, p=0.02).Our meta-analysis demonstrates that all standard functional endpoints for stroke trials were substantially improved in the active treatment arms. Despite an increased risk of SICH, there was no effect on mortality. These results support endovascular treatment of acute ischemic stroke due to MCA occlusion with intra-arterial thrombolytics.

  View details for DOI 10.1136/jnis.2010.002766

  View details for Web of Science ID 000290303800007

  View details for PubMedID 21990808

• Refining the Definition of the Malignant Profile Insights From the DEFUSE-EPITHET Pooled Data Set STROKE Mlynash, M., Lansberg, M. G., De Silva, D. A., Lee, J., Christensen, S., Straka, M., Campbell, B. C., Bammer, R., Olivot, J., Desmond, P., Donnan, G. A., Davis, S. M., Albers, G. W. 2011; 42 (5): 1270-1275

  Abstract

  To refine the definition of the malignant magnetic resonance imaging profile in acute stroke patients using baseline diffusion-weighted magnetic resonance imaging (DWI) and perfusion-weighted magnetic resonance imaging (PWI) findings from the pooled DEFUSE/EPITHET database.Patients presenting with acute stroke within 3 to 6 hours from symptom onset were treated with tissue plasminogen activator or placebo. Baseline and follow-up DWI and PWI images from both studies were reprocessed using the same software program. A receiver operating characteristic curve analysis was used to identify Tmax and DWI volumes that optimally predicted poor outcomes (modified Rankin Scale 5-6) at 90 days in patients who achieved reperfusion.Sixty-five patients achieved reperfusion and 46 did not reperfuse. Receiver operating characteristic analysis identified a PWI (Tmax>8 s) volume of >85 mL as the optimal definition of the malignant profile. Eighty-nine percent of malignant profile patients had poor outcome with reperfusion versus 39% of patients without reperfusion (P=0.02). Parenchymal hematomas occurred more frequently in malignant profile patients who experienced reperfusion versus no reperfusion (67% versus 11%, P<0.01). DWI analysis identified a volume of 80 mL as the best DWI threshold, but this definition was less sensitive than were PWI-based definitions.Stroke patients likely to suffer parenchymal hemorrhages and poor outcomes following reperfusion can be identified from baseline magnetic resonance imaging findings. The current analysis demonstrates that a PWI threshold (Tmax>8 s) of approximately 100 mL is appropriate for identifying these patients. Exclusion of malignant profile patients from reperfusion therapies may substantially improve the efficacy and safety of reperfusion therapies. Clinical Trial Registration Information- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00238537.

  View details for DOI 10.1161/STROKEAHA.110.601609

  View details for Web of Science ID 000289835900023

  View details for PubMedID 21474799

  View details for PubMedCentralID PMC3248048

• The Acute Diffusion Lesion Reliably Represents Infarct Core: Clinically Relevant Reversibility Is Rare International Stroke Conference Campbell, B. C., Purushotham, A., Christensen, S., Desmond, P. M., Nagakane, Y., Parsons, M. W., Lansberg, M. G., Mlynash, M., Straka, M., De Silva, D. A., Olivot, J., Bammer, R., Albers, G. W., Donnan, G. A., Davis, S. M. LIPPINCOTT WILLIAMS & WILKINS. 2011: E71–E71

  View details for Web of Science ID 000287479400102

• TIA Clinic Triage Strategy Reduces the Cost of TIA Evaluation International Stroke Conference Mlynash, M., Castle, J., Olivot, J., Wolford, C., Schwartz, N. E., Lansberg, M. G., Edwards, G., Kemp, S., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2011: E250–E250

  View details for Web of Science ID 000287479401072

• Worse Stroke Outcome In Atrial Fibrillation Links To More Severe Hypoperfusion International Stroke Conference Tu, H. T., Campbell, B. C., Christensen, S., De Silva, D. A., Parsons, M. W., Churilov, L., Olivot, J., Lansberg, M. G., Mlynash, M., Straka, M., Bammer, R., Albers, G. W., Desmond, P. M., Donnan, G. A., Davis, S. M. LIPPINCOTT WILLIAMS & WILKINS. 2011: E119–E119

  View details for Web of Science ID 000287479400248

• Higher rCBV Values In The PWI/DWI Mismatch Area Predict Favorable Clinical Outcome In Acute Ischemic Stroke International Stroke Conference Lee, J., Lansberg, M. G., Mlynash, M., Straka, M., Bammer, R., Olivot, J., Kemp, S., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2011: E112–E112

  View details for Web of Science ID 000287479400228

• Mri Based Tia Triage Study International Stroke Conference Wolford, C., Mlynash, M., Schwartz, N. E., Purushotham, A., Lansberg, M., Kemp, S., Albers, G. W., Olivot, J. LIPPINCOTT WILLIAMS & WILKINS. 2011: E210–E210

  View details for Web of Science ID 000287479400572

• The Combination Of Reperfusion And Recanalization Predicts Favorable Outcome Better Than Reperfusion Or Recanalization Alone In Target Mismatch Patients International Stroke Conference Lee, J., Lansberg, M. G., Mlynash, M., De Silva, D. A., Christensen, S., Straka, M., Campbell, B. C., Bammer, R., Olivot, J., Desmond, P., Donnan, G. A., Davis, S. M., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2011: E66–E67

  View details for Web of Science ID 000287479400088

• Postthrombolysis hemorrhage risk is affected by stroke assessment bias between hemispheres NEUROLOGY Audebert, H. J., Singer, O. C., Gotzler, B., Vatankhah, B., Boy, S., Fiehler, J., Lansberg, M. G., Albers, G. W., Kastrup, A., Rovira, A., Gass, A., Rosso, C., Derex, L., Kim, J. S., Heuschmann, P. 2011; 76 (7): 629-636

  Abstract

  Stroke symptoms in right hemispheric stroke tend to be underestimated in clinical assessment scales, resulting in greater infarct volumes in right as compared to left hemispheric strokes despite similar clinical stroke severity. We hypothesized that patients with right hemispheric nonlacunar stroke are at higher risk for secondary intracerebral hemorrhage after thrombolysis despite similar stroke severity.We analyzed data of 2 stroke cohorts with CT-based and MRI-based imaging before thrombolysis. Initial stroke severity was measured with the NIH Stroke Scale (NIHSS). Lacunar strokes were excluded through either the presence of cortical symptoms (CT cohort) or restriction to patients with prestroke diffusion-weighted imaging (DWI) lesion size >3.75 mL (MRI cohort). Probabilities of having a parenchymal hematoma were determined using multivariate logistic regression.A total of 392 patients in the CT cohort and 400 patients in the MRI cohort were evaluated. Although NIHSS scores were similar in strokes of both hemispheres (median NIHSS: CT: 15 vs 13, MRI: 14 vs 16), the frequencies of parenchymal hematoma were higher in right hemispheric compared to left hemispheric strokes (CT: 12.4% vs 5.7%, MRI: 10.4% vs 6.8%). After adjustment for potential confounders (but not pretreatment lesion volume), the probability of parenchymal hematoma was higher in right hemispheric nonlacunar strokes (CT: odds ratio [OR] 2.3; 95% confidence interval [CI] 1.08-4.89; p = 0.032) and showed a borderline significant effect in the MRI cohort (OR 2.1; 95% CI 0.98-4.49; p = 0.057). Adjustment for pretreatment DWI lesion size eliminated hemispheric differences in hemorrhage risk.Higher hemorrhage rates in right hemispheric nonlacunar strokes despite similar stroke severity may be caused by clinical underestimation of the proportion of tissue at bleeding risk.

  View details for DOI 10.1212/WNL.0b013e31820ce505

  View details for Web of Science ID 000287363800010

  View details for PubMedID 21248275

• Fluid-Attenuated Inversion Recovery Hyperintensity in Acute Ischemic Stroke May Not Predict Hemorrhagic Transformation CEREBROVASCULAR DISEASES Campbell, B. C., Costello, C., Christensen, S., Ebinger, M., Parsons, M. W., Desmond, P. M., Barber, P. A., Butcher, K. S., Levi, C. R., De Silva, D. A., Lansberg, M. G., Mlynash, M., Olivot, J., Straka, M., Bammer, R., Albers, G. W., Donnan, G. A., Davis, S. M. 2011; 32 (4): 401-405

  Abstract

  Fluid-attenuated inversion recovery (FLAIR) hyperintensity within an acute cerebral infarct may reflect delayed onset time and increased risk of hemorrhage after thrombolysis. Given the important implications for clinical practice, we examined the prevalence of FLAIR hyperintensity in patients 3-6 h from stroke onset and its relationship to parenchymal hematoma (PH).Baseline DWI and FLAIR imaging with subsequent hemorrhage detection (ECASS criteria) were prospectively obtained in patients 3-6 h after stroke onset from the pooled EPITHET and DEFUSE trials. FLAIR hyperintensity within the region of the acute DWI lesion was rated qualitatively (dichotomized as visually obvious or subtle (i.e. only visible after careful windowing)) and quantitatively (using relative signal intensity (RSI)). The association of FLAIR hyperintensity with hemorrhage was then tested alongside established predictors (very low cerebral blood volume (VLCBV) and diffusion (DWI) lesion volume) in logistic regression analysis.There were 49 patients with pre-treatment FLAIR imaging (38 received tissue plasminogen activator (tPA), 5 developed PH). FLAIR hyperintensity within the region of acute DWI lesion occurred in 48/49 (98%) patients, was obvious in 18/49 (37%) and subtle in 30/49 (61%). Inter-rater agreement was 92% (κ = 0.82). The prevalence of obvious FLAIR hyperintensity did not differ between studies obtained in the 3-4.5 h and 4.5-6 h time periods (40% vs. 33%, p = 0.77). PH was poorly predicted by obvious FLAIR hyperintensity (sensitivity 40%, specificity 64%, positive predictive value 11%). In univariate logistic regression, VLCBV (p = 0.02) and DWI lesion volume (p = 0.03) predicted PH but FLAIR lesion volume (p = 0.87) and RSI (p = 0.11) did not. In ordinal logistic regression for hemorrhage grade adjusted for age and baseline stroke severity (NIHSS), increased VLCBV (p = 0.002) and DWI lesion volume (p = 0.003) were associated with hemorrhage but FLAIR lesion volume (p = 0.66) and RSI (p = 0.35) were not.Visible FLAIR hyperintensity is almost universal 3-6 h after stroke onset and did not predict subsequent hemorrhage in this dataset. Our findings question the value of excluding patients with FLAIR hyperintensity from reperfusion therapies. Larger studies are required to clarify what implications FLAIR-positive lesions have for patient selection.

  View details for DOI 10.1159/000331467

  View details for Web of Science ID 000299642300014

  View details for PubMedID 21986096

  View details for PubMedCentralID PMC3214893

• A comparison of cooling techniques to treat cardiac arrest patients with hypothermia. Stroke research and treatment Finley Caulfield, A., Rachabattula, S., Eyngorn, I., Hamilton, S. A., Kalimuthu, R., Hsia, A. W., Lansberg, M. G., Venkatasubramanian, C., BAUMANN, J. J., Buckwalter, M. S., Kumar, M. A., Castle, J. S., Wijman, C. A. 2011; 2011: 690506-?

  Abstract

  Introduction. We sought to compare the performance of endovascular cooling to conventional surface cooling after cardiac arrest. Methods. Patients in coma following cardiopulmonary resuscitation were cooled with an endovascular cooling catheter or with ice bags and cold-water-circulating cooling blankets to a target temperature of 32.0-34.0°C for 24 hours. Performance of cooling techniques was compared by (1) number of hourly recordings in target temperature range, (2) time elapsed from the written order to initiate cooling and target temperature, and (3) adverse events during the first week. Results. Median time in target temperature range was 19 hours (interquartile range (IQR), 16-20) in the endovascular group versus. 10 hours (IQR, 7-15) in the surface group (P = .001). Median time to target temperature was 4 (IQR, 2.8-6.2) and 4.5 (IQR, 3-6.5) hours, respectively (P = .67). Adverse events were similar. Conclusion. Endovascular cooling maintains target temperatures better than conventional surface cooling.

  View details for DOI 10.4061/2011/690506

  View details for PubMedID 21822470

• Utility of the anesthetic test dose to avoid catastrophic injury during cervical transforaminal epidural injections SPINE JOURNAL Smuck, M., Maxwell, M. D., Kennedy, D., Rittenberg, J. D., Lansberg, M. G., Plastaras, C. T. 2010; 10 (10): 857-864

  Abstract

  Reports of serious complications from cervical transforaminal epidural corticosteroid injections often consider accidental intra-arterial injection the most likely mechanism of injury. As a result, many physicians have instituted methods to prevent intravascular injections. Routine use of the anesthetic test dose is one such method. The utility of the anesthetic test dose in this function has not been characterized in the current literature.The aim of this study was to determine the utility of injecting an anesthetic test dose before cervical transforaminal epidural corticosteroid injection and estimate the rate of false-negative intravascular contrast injection using live fluoroscopy and digital subtraction angiography (DSA).Two-center retrospective study.A consecutive cohort of men and women, ages of 23 to 83, who underwent cervical transforaminal epidural injection and received the anesthetic test dose after contrast injection was negative for vascular uptake, observed using live fluoroscopy or DSA.Response to the anesthetic test dose was documented in each procedure note and recorded as either positive or negative.Records of three physiatrists at two academic spine centers (Center A and Center B) were reviewed to identify all patients who received a cervical transforaminal epidural injection during the preceding 5 years, resulting in a cohort of consecutively treated patients at each center. Each patient record was reviewed for demographics, indication for injection, procedure level and side, needle gauge, use of DSA, volume and type of anesthetic test dose used, and result of test dose injection. The test dose was considered positive if the following occurred: agitation or other sudden central nervous system change; gross motor deficits and/or paresthesias in the trunk, legs, or contralateral arm; systemic symptoms of anesthetic toxicity including cardiac arrhythmia, perioral numbness, metallic taste, dizziness, and/or ringing in the ear. For analysis, injections were separated into groups to compare results at Center A to Center B and to compare injections that used DSA to those that did not. The incidence of a positive response was calculated as a percentage from the total number of injections in the group. Differences between groups were analyzed for statistical significance using the Fisher exact test.Six hundred seventy-eight injections were included. Of these, 349 were performed at Center A with test doses given after contrast injection under live fluoroscopy. The remaining 329 were performed at Center B, 183 also using live fluoroscopy, and 146 using DSA. The overall incidence of a positive anesthetic test dose was 0.59% (4/678). There was no significant difference between the incidence at each of the two centers (0.86% [3/349] vs. 0.30% [1/329]; p=.63). The overall incidence after live fluoroscopy was 0.75% (4/532) and after DSA was 0% (0/146), but this difference was not statistically significant (p=.58). Positive symptoms elicited by test dose administration included midneck and contralateral arm pain, metallic taste, dizziness, tachycardia, full body paresthesias, auditory changes, slurred speech, and motor ataxia. In all four cases with a positive response, the procedure was immediately terminated, symptoms resolved, and no lasting complications were observed.The routine use of an anesthetic test dose appears to be safe and capable of detecting potentially dangerous intravascular injections undetected by conventional techniques. Positive responses occur in a small portion of those who receive the test dose injection. Further studies are required to determine the optimal dose and concentration of anesthetic to be used and the time required for observation after test dose administration.

  View details for DOI 10.1016/j.spinee.2010.07.003

  View details for Web of Science ID 000283190400002

  View details for PubMedID 20692210

• Capsular warning syndrome caused by middle cerebral artery stenosis JOURNAL OF THE NEUROLOGICAL SCIENCES Lee, J., Albers, G. W., Marks, M. P., Lansberg, M. G. 2010; 296 (1-2): 115-120

  Abstract

  The capsular warning syndrome is a term used to describe recurrent stereotyped lacunar transient ischemic attacks (TIAs). This syndrome is associated with a high risk of developing a completed stroke. The presumed mechanism for this syndrome is angiopathy of a lenticulostriate artery. We describe the case of a 33-year-old man who presented with the capsular warning syndrome who was successfully treated with angioplasty. The patient's capsular warning syndrome manifested as recurrent episodes of transient left hemiparesis. Symptoms recurred one to three times daily despite treatment with antithrombotics. Cerebral angiography demonstrated stenosis of the right middle cerebral artery (MCA) with decreased flow to a dominant lenticulostriate artery. Angioplasty of the right middle cerebral artery increased flow to the lenticulostriate artery and the TIAs resolved following the procedure. In select cases intracranial angioplasty, may be an effective treatment for patients with capsular warning syndrome.

  View details for DOI 10.1016/j.jns.2010.06.003

  View details for Web of Science ID 000281272300022

  View details for PubMedID 20619422

  View details for PubMedCentralID PMC2932463

• STROKE Taking stock-patient selection for acute stroke therapy NATURE REVIEWS NEUROLOGY Lansberg, M. 2010; 6 (7): 358-359

  View details for DOI 10.1038/nrneurol.2010.75

  View details for Web of Science ID 000279624100002

  View details for PubMedID 20639911

• Outcome prediction in mechanically ventilated neurologic patients by junior neurointensivists NEUROLOGY Caulfield, A. F., GABLER, L., Lansberg, M. G., Eyngorn, I., Mlynash, M., Buckwalter, M. S., Venkatasubramanian, C., Wijman, C. A. 2010; 74 (14): 1096-1101

  Abstract

  Physician prediction of outcome in critically ill neurologic patients impacts treatment decisions and goals of care. In this observational study, we prospectively compared predictions by neurointensivists to patient outcomes at 6 months.Consecutive neurologic patients requiring mechanical ventilation for 72 hours or more were enrolled. The attending neurointensivist was asked to predict 6-month 1) functional outcome (modified Rankin scale [mRS]), 2) quality of life (QOL), and 3) whether supportive care should be withdrawn. Six-month functional outcome was determined by telephone interviews and dichotomized to good (mRS 0-3) and poor outcome (mRS 4-6).Of 187 eligible patients, 144 were enrolled. Neurointensivists correctly predicted 6-month functional outcome in 80% (95% confidence interval [CI], 72%-86%) of patients. Accuracy for a predicted good outcome was 63% (95% CI, 50%-74%) and for poor outcome 94% (95% CI, 85%-98%). Excluding patients who had life support withdrawn, accuracy for good outcome was 73% (95% CI, 60%-84%) and for poor outcome 87% (95% CI, 74%-94%). Accuracy for exact agreement between neurointensivists' mRS predictions and actual 6-month mRS was only 43% (95% CI, 35%-52%). Predicted accuracy for QOL was 58% (95% CI, 39%-74%) for good/excellent and 67% (95% CI, 46%-83%) for poor/fair. Of 27 patients for whom withdrawal of care was recommended, 1 patient survived in a vegetative state.Prediction of long-term functional outcomes in critically ill neurologic patients is challenging. Our neurointensivists were more accurate in predicting poor outcome than good outcome in patients requiring mechanical ventilation >or=72 hours.

  View details for Web of Science ID 000276354400005

  View details for PubMedID 20368630

• Validation of the Malignant Profile in the DEFUSE-EPITHET Pooled Database International Stroke Conference Lee, J., Lansberg, M. G., Mlynash, M., De Silva, D. A., Christensen, S., Straka, M., Campbell, B. C., Bammer, R., Olivot, J., Donnan, G. A., Davis, S. M., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2010: E258–E258

  View details for Web of Science ID 000276106100270

• Large and Severe Baseline PWI Volumes Predict Poor Response to Intravenous tPA vs. Placebo in the Pooled DEFUSE-EPITHET Database International Stroke Conference De Silva, D. A., Mlynash, M., Lansberg, M. G., Lee, J., Christensen, S., Straka, M., Campbell, B. C., Bammer, R., Olivot, J. M., Donnan, G. A., Davis, S. M., Albers, G. A. LIPPINCOTT WILLIAMS & WILKINS. 2010: E208–E208

  View details for Web of Science ID 000276106100092

• DEFUSE and EPITHET: Two Different Studies With One Consistent Message International Stroke Conference Lansberg, M. G., Lee, J., Christensen, S., Straka, M., De Silva, D. A., Mlynash, M., Campbell, B. C., Bammer, R., Olivot, J., Davis, S. M., Donnan, G. A., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2010: E295–E295

  View details for Web of Science ID 000276106100410

• Optimal Definition of the Malignant Profile in the DEFUSE-EPITHET Pooled Database International Stroke Conference Mlynash, M., De Silva, D. A., Lansberg, M. G., Lee, J., Christensen, S., Straka, M., Campbell, B. C., Bammer, R., Olivot, J., Donnan, G. A., Davis, S. M., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2010: E207–E207

  View details for Web of Science ID 000276106100088

• Optimal Perfusion Thresholds for Prediction of Tissue Destined for Infarction in the Combined EPITHET and DEFUSE Dataset International Stroke Conference Christensen, S., Campbell, B. C., de la Ossa, N. P., Lansberg, M., Straka, M., De Silva, D. A., Nagakane, Y., Ogata, T., Mlynash, M., Bammer, R., Olivot, J., Desmond, P., Albers, G. W., Donnan, G. A., Davis, S. M. LIPPINCOTT WILLIAMS & WILKINS. 2010: E297–E297

  View details for Web of Science ID 000276106100416

• Does Presence of Arterial Obstruction Influence the Treatment Effect of Intravenous tPA Over Placebo in the 3-6 Hour Time Window? International Stroke Conference De Silva, D. A., Churilov, L., Olivot, J. M., Christensen, S., Lansberg, M. G., Mlynash, M., Straka, M., Campbell, B. C., Bammer, R., Albers, G. W., Davis, S. M., Donnan, G. A. LIPPINCOTT WILLIAMS & WILKINS. 2010: E207–E208

  View details for Web of Science ID 000276106100091

• Symptomatic Intracranial Hemorrhage Rates With IV tPA Treatment by Stroke Subtype International Stroke Conference De Silva, D. A., Thomalla, G., Oppenheim, C., Albers, G. W., Lansberg, M. G., Kang, D., Hjort, N., Liebeskind, D. S., Hao, Q., Neumann-Haefelin, T., Singer, O. C., Nighoghossian, N., Derex, L., Shara, N., Donnan, G. A., Davis, S. M., Kidwell, C. S. LIPPINCOTT WILLIAMS & WILKINS. 2010: E363–E363

  View details for Web of Science ID 000276106100673

• Factors Predicting the Presence of Acute Ischemic Lesions on Diffusion Weighted in the Stanford TIA Study (Two Aces) International Stroke Conference Olivot, J. M., Wolford, C., Mlynash, M., Castle, J., Lansberg, M., Schwartz, N., Kemp, S., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2010: E273–E273

  View details for Web of Science ID 000276106100329

• Diagnostic Accuracy of MRI in Spontaneous Intra-cerebral Hemorrhage (DASH): Initial Results International Stroke Conference Wijman, C. A., Snider, R. W., Venkatasubramanian, C., Caulfield, A. F., Buckwalter, M., Eyngorn, I., Fischbein, N., Gean, A., Schwartz, N., Lansberg, M., Mlynash, M., Kemp, S., Thai, D., Narayana, R. K., Marks, M., Bammer, R., Moseley, M., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2010: E210–E211

  View details for Web of Science ID 000276106100102

• Favorable Outcome From A Locked-In State Despite Extensive Pontine Infarction By MRI NEUROCRITICAL CARE Samaniego, E. A., Lansberg, M. G., DeGeorgia, M., Venkatasubramanian, C., Wijman, C. A. 2009; 11 (3): 369-371

  Abstract

  Outcome prediction of patients who are in a locked-in state is challenging. Extensive pontine infarction on diffusion weighted imaging MRI (DWI) has been proposed as a poor prognosticator. We report on three patients with a locked-in state with unexpected favorable recoveries despite DWI evidence of widespread pontine ischemia.Report of three cases.Three young patients (32-, 30-, and 16-years-old) presented with a locked-in state caused by pontine infarction. The first patient did not receive any acute stroke therapies, the second patient underwent endovascular therapy 20 h after symptom onset resulting in partial recanalization of the basilar artery, and the third patient progressed to a locked-in state despite having received intravenous tissue plasminogen activator. The DWI of all three patients demonstrated acute and widespread pontine infarction involving more than two-thirds of the pons. Two patients regained full independence in their activities of daily living. The third patient remained wheelchair bound, but lives with her family, eats independently, uses a typewriter and wrote a book.Patients who are in a locked-in state may have substantial functional recovery despite DWI evidence of extensive pontine infarction.

  View details for DOI 10.1007/s12028-009-9268-y

  View details for Web of Science ID 000271943800011

  View details for PubMedID 19707888

• Profiles of Neurological Outcome Prediction Among Intensivists NEUROCRITICAL CARE Racine, E., Dion, M., Wijman, C. A., Illes, J., Lansberg, M. G. 2009; 11 (3): 345-352

  Abstract

  Advances in intensive care medicine have increased survival rates of patients with critical neurological conditions. The focus of prognostication for such patients is therefore shifting from predicting chances of survival to meaningful neurological recovery. This study assessed the variability in long-term outcome predictions among physicians and aimed to identify factors that may account for this variability.Based on a clinical vignette describing a comatose patient suffering from post-anoxic brain injury intensivists were asked in a semi-structured interview about the patient's specific neurological prognosis and about prognostication in general. Qualitative research methods were used to identify areas of variability in prognostication and to classify physicians according to specific prognostication profiles. Quantitative statistics were used to assess for associations between prognostication profiles and physicians' demographic and practice characteristics.Eighteen intensivists participated. Functional outcome predictions varied along an evaluative dimension (fair/good-poor) and a confidence dimension (certain-uncertain). More experienced physicians tended to be more pessimistic about the patient's functional outcome and more certain of their prognosis. Attitudes toward quality of life varied along an evaluative dimension (good-poor) and a "style" dimension (objective-subjective). Older and more experienced physicians were more likely to express objective judgments of quality of life and to predict a worse quality of life for the patient than their younger and less experienced counterparts.Various prognostication profiles exist among intensivists. These may be dictated by factors such as physicians' age and clinical experience. Awareness of these associations may be a first step to more uniform prognostication.

  View details for DOI 10.1007/s12028-009-9225-9

  View details for Web of Science ID 000271943800008

  View details for PubMedID 19430929

• Improving Dynamic Susceptibility Contrast MRI Measurement of Quantitative Cerebral Blood Flow using Corrections for Partial Volume and Nonlinear Contrast Relaxivity: A Xenon Computed Tomographic Comparative Study JOURNAL OF MAGNETIC RESONANCE IMAGING Zaharchuk, G., Bammer, R., Straka, M., Newbould, R. D., Rosenberg, J., Olivot, J., Mlynash, M., Lansberg, M. G., Schwartz, N. E., Marks, M. M., Albers, G. W., Moseley, M. E. 2009; 30 (4): 743-752

  Abstract

  To test whether dynamic susceptibility contrast MRI-based CBF measurements are improved with arterial input function (AIF) partial volume (PV) and nonlinear contrast relaxivity correction, using a gold-standard CBF method, xenon computed tomography (xeCT).Eighteen patients with cerebrovascular disease underwent xeCT and MRI within 36 h. PV was measured as the ratio of the area under the AIF and the venous output function (VOF) concentration curves. A correction was applied to account for the nonlinear relaxivity of bulk blood (BB). Mean CBF was measured with both techniques and regression analyses both within and between patients were performed.Mean xeCT CBF was 43.3 +/- 13.7 mL/100g/min (mean +/- SD). BB correction decreased CBF by a factor of 4.7 +/- 0.4, but did not affect precision. The least-biased CBF measurement was with BB but without PV correction (45.8 +/- 17.2 mL/100 g/min, coefficient of variation [COV] = 32%). Precision improved with PV correction, although absolute CBF was mildly underestimated (34.3 +/- 10.8 mL/100 g/min, COV = 27%). Between patients correlation was moderate even with both corrections (R = 0.53).Corrections for AIF PV and nonlinear BB relaxivity improve bolus MRI-based CBF maps. However, there remain challenges given the moderate between-patient correlation, which limit diagnostic confidence of such measurements in individual patients.

  View details for DOI 10.1002/jmri.21908

  View details for Web of Science ID 000270522900007

  View details for PubMedID 19787719

  View details for PubMedCentralID PMC2851938

• Geography, Structure, and Evolution of Diffusion and Perfusion Lesions in Diffusion and Perfusion Imaging Evaluation For Understanding Stroke Evolution (DEFUSE) STROKE Olivot, J., Mlynash, M., Thijs, V. N., Purushotham, A., Kemp, S., Lansberg, M. G., Wechsler, L., Gold, G. E., Bammer, R., Marks, M. P., Albers, G. W. 2009; 40 (10): 3245-3251

  Abstract

  The classical representation of acute ischemic lesions on MRI is a central diffusion-weighted imaging (DWI) lesion embedded in a perfusion-weighted imaging (PWI) lesion. We investigated spatial relationships between final infarcts and early DWI/PWI lesions before and after intravenous thrombolysis in the Diffusion and perfusion imaging Evaluation For Understanding Stroke Evolution (DEFUSE) study.Baseline and follow-up DWI and PWI lesions and 30-day fluid-attenuated inversion recovery scans of 32 patients were coregistered. Lesion geography was defined by the proportion of the DWI lesion superimposed by a Tmax (time when the residue function reaches its maximum) >4 seconds PWI lesion; Type 1: >50% overlap and Type 2: < or = 50% overlap. Three-dimensional structure was dichotomized into a single lesion (one DWI and one PWI lesion) versus multiple lesions. Lesion reversal was defined by the percentage of the baseline DWI or PWI lesion not superimposed by the early follow-up DWI or PWI lesion. Final infarct prediction was estimated by the proportion of the final infarct superimposed on the union of the DWI and PWI lesions.Single lesion structure with Type 1 geography was present in only 9 patients (28%) at baseline and 4 (12%) on early follow-up. In these patients, PWI and DWI lesions were more likely to correspond with the final infarcts. DWI reversal was greater among patients with Type 2 geography at baseline. Patients with multiple lesions and Type 2 geography at early follow-up were more likely to have early reperfusion.Before thrombolytic therapy in the 3- to 6-hour time window, Type 2 geography is predominant and is associated with DWI reversal. After thrombolysis, both Type 2 geography and multiple lesion structure are associated with reperfusion.

  View details for DOI 10.1161/STROKEAHA.109.558635

  View details for Web of Science ID 000270229800016

  View details for PubMedID 19679845

• Efficacy and Safety of Tissue Plasminogen Activator 3 to 4.5 Hours After Acute Ischemic Stroke A Metaanalysis STROKE Lansberg, M. G., Bluhmki, E., Thijs, V. N. 2009; 40 (7): 2438-2441

  Abstract

  The Third European Cooperative Acute Stroke Study (ECASS-3) demonstrated a benefit of treatment with intravenous tissue plasminogen activator (tPA) for acute stroke in the 3- to 4.5-hour time-window. Prior studies, however, have failed to demonstrate a significant benefit of tPA for patients treated beyond 3 hours. The purpose of this study was to produce reliable and precise estimates of the treatment effect of tPA by pooling data from all relevant studies.A metaanalysis was undertaken to determine the efficacy of tPA in the 3- to 4.5-hour time-window. The effect of tPA on favorable outcome and mortality was assessed.The metaanalysis included data from patients treated in the 3- to 4.5-hour time-window in ECASS-1 (n=234), ECASS-2 (n=265), ECASS-3 (n=821) and The Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) (n=302). tPA treatment was associated with an increased chance of favorable outcome (odds ratio 1.31; 95% CI: 1.10 to 1.56; P=0.002) and no significant difference in mortality (odds ratio 1.04; 95% CI: 0.75 to 1.43; P=0.83) compared to placebo treated patients.Treatment with tPA in the 3- to 4.5-hour time-window is beneficial. It results in an increased rate of favorable outcome without adversely affecting mortality.

  View details for DOI 10.1161/STROKEAHA.109.552547

  View details for Web of Science ID 000267467900026

  View details for PubMedID 19478213

• Treatment Time-Specific Number Needed to Treat Estimates for Tissue Plasminogen Activator Therapy in Acute Stroke Based on Shifts Over the Entire Range of the Modified Rankin Scale STROKE Lansberg, M. G., Schrooten, M., Bluhmki, E., Thijs, V. N., Saver, J. L. 2009; 40 (6): 2079-2084

  Abstract

  To make informed treatment decisions, patients and physicians need to be aware of the benefits and risks of a proposed treatment. The number needed to treat (NNT) for benefit and harm are intuitive and statistically valid measures to describe a treatment effect. The aim of this study is to calculate treatment time-specific NNT estimates based on shifts over the entire spectrum of clinically relevant functional outcomes.The pooled data set of the first 6 major randomized acute stroke trials of intravenous tissue plasminogen activator was used for this study. The data were stratified by 90-minute treatment time windows. NNT for benefit and NNT for harm estimates were determined based on expert generation of joint outcome distribution tables. NNT for benefit estimates were also calculated based on joint outcome distribution tables generated by a computer model.NNT for benefit estimates based on the expert panel were 3.6 for patients treated between 0 and 90 minutes, 4.3 with treatment between 91 and 180 minutes, 5.9 with treatment between 181 and 270 minutes, and 19.3 with treatment between 271 and 360 minutes. The computer simulation yielded very similar results. The NNT for harm estimates for the corresponding time intervals are 65, 38, 30, and 14.Up to 4(1/2) hours after symptom onset, tissue plasminogen activator therapy is associated with more benefit than harm, whereas there is no evidence of a net benefit in the 4(1/2)- to 6-hour time window. The NNT estimates for each 90-minute epoch provide useful and intuitive information based on which patients may be able to make better informed treatment decisions.

  View details for DOI 10.1161/STROKEAHA.108.540708

  View details for Web of Science ID 000266302200025

  View details for PubMedID 19372447

• Relationships Between Cerebral Perfusion and Reversibility of Acute Diffusion Lesions in DEFUSE Insights from RADAR STROKE Olivot, J., Mlynash, M., Thijs, V. N., Purushotham, A., Kemp, S., Lansberg, M. G., Wechsler, L., Bammer, R., Marks, M. P., Albers, G. W. 2009; 40 (5): 1692-1697

  Abstract

  Acute ischemic lesions with restricted diffusion can resolve after early recanalization. The impact of superimposed perfusion abnormalities on the fate of acute diffusion lesions is unclear.Data were obtained from DEFUSE, a prospective multicenter study of patients treated with IV tPA 3 to 6 hours after stroke onset. Thirty-two patients with baseline diffusion and perfusion lesions and 30 day FLAIR scans were coregistered. The acute diffusion lesion was divided into 3 regions according to the Tmax delay of the superimposed perfusion lesion: normal baseline perfusion; mild-moderately hypoperfused (2 s8 s). The reversal rate was calculated as the percentage of the acute diffusion lesion that did not overlap with the final infarct on 30-day FLAIR. Diffusion reversal rates were compared based on whether a favorable clinical response occurred and whether early recanalization was achieved.On average, 54% of the acute diffusion lesion volume had normal perfusion. Diffusion reversal rates were significantly increased among cases with favorable clinical response and in patients with early recanalization, especially in regions with normal baseline perfusion. The portion of the diffusion lesion with normal perfusion had significantly higher mean apparent diffusion coefficient values and reversal rates.Acute ischemic lesions with restricted diffusion are most likely to recover if reperfusion occurs within 6 hours of symptom onset, and reversibility is associated with early recanalization and favorable clinical outcome. We propose the term RADAR (Reversible Acute Diffusion lesion Already Reperfused) to describe regions of acute restricted diffusion with normal perfusion.

  View details for DOI 10.1161/STROKEAHA.108.538082

  View details for Web of Science ID 000265579800027

  View details for PubMedID 19299632

• SENSE Diffusion-weighted Imaging Improves Diagnostic Sensitivity in Acute Ischemic Stroke American-Association-International-Stroke Conference 2009 Schwartz, N. E., Newbould, R. D., Skare, S., Zaharchuk, G., Mlynash, M., Olivot, J., Lansberg, M. G., Eyngorn, I., Thai, D., Albers, G. W., Bammer, R. LIPPINCOTT WILLIAMS & WILKINS. 2009: E115–E115

  View details for Web of Science ID 000264709500133

• Tissue Plasminogen Activator Does Not Benefit Most Eligible Patients With Stroke ARCHIVES OF NEUROLOGY Lansberg, M. G., Schwartz, N. E. 2009; 66 (4): 540-541

  View details for Web of Science ID 000265104400025

  View details for PubMedID 19364946

• Perfusion MRI (Tmax and MTT) correlation with xenon CT cerebral blood flow in stroke patients NEUROLOGY Olivot, J., Mlynash, M., Zaharchuk, G., Straka, M., Bammer, R., Schwartz, N., Lansberg, M. G., Moseley, M. E., Albers, G. W. 2009; 72 (13): 1140-1145

  Abstract

  While stable xenon CT (Xe-CT) cerebral blood flow (CBF) is an accepted standard for quantitative assessment of cerebral hemodynamics, the accuracy of magnetic resonance perfusion-weighted imaging (PWI-MRI) is unclear. The Improved PWI Methodology in Acute Clinical Stroke Study compares PWI findings with Xe-CT CBF values in patients experiencing symptomatic severe cerebral hypoperfusion.We compared mean transit time (MTT) and Tmax PWI-MRI with the corresponding Xe-CT CBF values in 25 coregistered regions of interest (ROIs) of multiple sizes and locations in nine subacute stroke patients. Comparisons were performed with Pearson correlation coefficients (R). We performed receiver operating characteristic (ROC) curve analyses to define the threshold of Tmax and absolute MTT that could best predict a Xe-CT CBF <20 mL/100 g/minute.The subjects' mean (SD) age was 50 (15) years, the median (interquartile range [IQR]) NIH Stroke Scale score was 2 (2-6), and the median (IQR) time between MRI and Xe-CT was 12 (-7-19) hours. The total number of ROIs was 225, and the median (IQR) ROI size was 550 (360-960) pixels. Tmax correlation with Xe-CT CBF (R = 0.63, p < 0.001) was stronger than absolute MTT (R = 0.55, p < 0.001), p = 0.049. ROC curve analysis found that Tmax >4 seconds had 68% sensitivity, 80% specificity, and 77% accuracy and MTT >10 seconds had 68% sensitivity, 77% specificity, and 75% accuracy for predicting ROIs with Xe-CT CBF <20 mL/100 g/minute.Our results suggest that in subacute ischemic stroke patients, Tmax correlates better than absolute mean transit time (MTT) with xenon CT cerebral blood flow (Xe-CT CBF) and that both Tmax >4 seconds and MTT >10 seconds are strongly associated with Xe-CT CBF <20 mL/100 g/minute. CBF = cerebral blood flow; DBP = diastolic blood pressure; DEFUSE = Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution; DWI = diffusion-weighted imaging; EPITHET = Echoplanar Imaging Thrombolytic Evaluation Trial; FOV = field of view; ICA = internal carotid artery; IQR = interquartile range; MCA = middle cerebral artery; MTT = mean transit time; NIHSS = NIH Stroke Scale; PWI = perfusion-weighted imaging; PWI-MRI = magnetic resonance perfusion-weighted imaging; ROC = receiver operating characteristic; ROI = region of interest; SBP = systolic blood pressure; SVD = singular value decomposition; Xe-CT = xenon CT.

  View details for DOI 10.1212/01.wnl.0000345372.49233.e3

  View details for Web of Science ID 000264709000007

  View details for PubMedID 19332690

  View details for PubMedCentralID PMC2680065

• Yield of combined perfusion and diffusion MR imaging in hemispheric TIA NEUROLOGY Mlynash, M., Olivot, J., Tong, D. C., Lansberg, M. G., Eyngorn, I., Kemp, S., Moseley, M. E., Albers, G. W. 2009; 72 (13): 1127-1133

  Abstract

  Transient ischemic attacks (TIA) predict future stroke. However, there are no sensitive and specific diagnostic criteria for TIA and interobserver agreement regarding the diagnosis is poor. Diffusion-weighted MRI (DWI) demonstrates acute ischemic lesions in approximately 30% of TIA patients; the yield of perfusion-weighted MRI (PWI) is unclear.We prospectively performed both DWI and PWI within 48 hours of symptom onset in consecutive patients admitted with suspected hemispheric TIAs of <24 hours symptom duration. Two independent raters, blinded to clinical features, assessed the presence and location of acute DWI and PWI lesions. Lesions were correlated with suspected clinical localization and baseline characteristics. Clinical features predictive of a PWI lesion were assessed.Forty-three patients met the inclusion criteria. Thirty-three percent had a PWI lesion and 35% had a DWI lesion. Seven patients (16%) had both PWI and DWI lesions and 7 (16%) had only PWI lesions. The combined yield for identification of either a PWI or a DWI was 51%. DWI lesions occurred in the clinically suspected hemisphere in 93% of patients; PWI lesions in 86%. PWI lesions occurred more frequently when the MRI was performed within 12 hours of symptom resolution, in patients with symptoms of speech impairment, and among individuals younger than 60 years.The combination of early diffusion-weighted MRI and perfusion-weighted MRI can document the presence of a cerebral ischemic lesion in approximately half of all patients who present with a suspected hemispheric transient ischemic attack (TIA). MRI has the potential to improve the accuracy of TIA diagnosis. ACA = anterior cerebral artery; CI = confidence interval; DWI = diffusion-weighted MRI; ICA = internal carotid artery; MCA = middle cerebral artery; MRA = magnetic resonance angiography; MTT = mean transit time; OR = odds ratios; PCA = posterior cerebral artery; PWI = perfusion-weighted MRI; RR = risk ratios; TIA = transient ischemic attacks; TOAST = Trial of Org 10172 in Acute Stroke Treatment.

  View details for DOI 10.1212/01.wnl.0000340983.00152.69

  View details for Web of Science ID 000264709000005

  View details for PubMedID 19092109

• Cost-effectiveness analysis of mechanical thrombectomy in acute ischemic stroke Clinical article JOURNAL OF NEUROSURGERY Patil, C. G., Long, E. F., Lansberg, M. G. 2009; 110 (3): 508-513

  Abstract

  Mechanical thrombectomy is increasingly being used for the treatment of large-vessel ischemic stroke in patients who arrive outside of the 3-hour tissue plasminogen activator time window. In this study, the authors evaluated the cost and effectiveness of mechanical thrombectomy compared with standard medical therapy in patients who are ineligible to receive tissue plasminogen activator.Clinical outcomes of an open-label study of mechanical thrombectomy were compared with a hypothetical control group with a lower recanalization rate (18 vs 60%) and a lower rate of symptomatic intracranial hemorrhage (0.6 vs 7.8%) than the active treatment group. A Markov cost-effectiveness model was built to compare the health benefits and costs associated with mechanical thrombectomy compared with standard medical therapy. All probabilities, quality-of-life factors, and costs were estimated from the published literature. Univariate sensitivity analyses were performed to assess how variations in model parameters affect health and economic outcomes.Treatment of acute ischemic stroke with mechanical thrombectomy increased survival time by 0.54 quality-adjusted life years (QALYs), compared with standard medical therapy (2.37 vs 1.83 QALYs), at an increased cost of $6600. This yielded an incremental cost-effectiveness ratio (ICER) of $12,120 per QALY gained, a value generally considered cost-effective. Sensitivity analysis showed that mechanical thrombectomy remained cost-effective (ICER < $50,000 per QALY gained) for all model inputs varied over a reasonable range, except for age at stroke treatment. For patients older than 82 years of age, the treatment was only borderline cost-effective (ICER of $50,000-100,000 per QALY gained).The treatment of large-vessel ischemic stroke with mechanical thrombectomy appears to be costeffective. These results require validation when data from a randomized, controlled trial of mechanical thrombectomy become available.

  View details for DOI 10.3171/2008.8.JNS08133

  View details for Web of Science ID 000263868000017

  View details for PubMedID 19025358

• Optimal Tmax Threshold for Predicting Penumbral Tissue in Acute Stroke STROKE Olivot, J., Mlynash, M., Thijs, V. N., Kemp, S., Lansberg, M. G., Wechsler, L., Bammer, R., Marks, M. P., Albers, G. W. 2009; 40 (2): 469-475

  Abstract

  We sought to assess whether the volume of the ischemic penumbra can be estimated more accurately by altering the threshold selected for defining perfusion-weighting imaging (PWI) lesions.DEFUSE is a multicenter study in which consecutive acute stroke patients were treated with intravenous tissue-type plasminogen activator 3 to 6 hours after stroke onset. Magnetic resonance imaging scans were obtained before, 3 to 6 hours after, and 30 days after treatment. Baseline and posttreatment PWI volumes were defined according to increasing Tmax delay thresholds (>2, >4, >6, and >8 seconds). Penumbra salvage was defined as the difference between the baseline PWI lesion and the final infarct volume (30-day fluid-attenuated inversion recovery sequence). We hypothesized that the optimal PWI threshold would provide the strongest correlations between penumbra salvage volumes and various clinical and imaging-based outcomes.Thirty-three patients met the inclusion criteria. The correlation between infarct growth and penumbra salvage volume was significantly better for PWI lesions defined by Tmax >6 seconds versus Tmax >2 seconds, as was the difference in median penumbra salvage volume in patients with a favorable versus an unfavorable clinical response. Among patients who did not experience early reperfusion, the Tmax >4 seconds threshold provided a more accurate prediction of final infarct volume than the >2 seconds threshold.Defining PWI lesions based on a stricter Tmax threshold than the standard >2 seconds delay appears to provide more a reliable estimate of the volume of the ischemic penumbra in stroke patients imaged between 3 and 6 hours after symptom onset. A threshold between 4 and 6 seconds appears optimal for early identification of critically hypoperfused tissue.

  View details for DOI 10.1161/STROKEAHA.108.526954

  View details for Web of Science ID 000262784900021

  View details for PubMedID 19109547

• Risk of Symptomatic Intracerebral Hemorrhage in Patients Treated with Intra-Arterial Thrombolysis CEREBROVASCULAR DISEASES Singer, O. C., Berkefeld, J., Lorenz, M. W., Fiehler, J., Albers, G. W., Lansberg, M. G., Kastrup, A., Rovira, A., Liebeskind, D. S., Gass, A., Rosso, C., Derex, L., Kim, J. S., Neumann-Haefelin, T. 2009; 27 (4): 368-374

  Abstract

  In intra-arterial (IA) thrombolysis trials, higher rates of symptomatic intracerebral haemorrhage (sICH) were found than in trials with intravenous (IV) recombinant tissue plasminogen activator (tPA); this observation could have been due to the inclusion of more severely affected patients in IA thrombolysis trials. In the present study, we investigated the rate of sICH in IA and combined IV + IA thrombolysis versus IV thrombolysis after adjusting for differences in clinical and MRI parameters.In this multicenter study, we systematically analyzed data from 645 patients with anterior-circulation strokes treated with either IV or IA thrombolysis within 6 h following symptom onset. Thrombolytic regimens included (1) IV tPA treatment (n = 536) and (2) IA treatment with either tPA or urokinase (n = 74) or (3) combined IV + IA treatment with either tPA or urokinase (n = 35).44 (6.8%) patients developed sICH. sICH patients had significantly higher scores on the National Institutes of Health Stroke Scale (NIHSS) at admission and pretreatment DWI lesions. The sICH risk was 5.2% (n = 28) in IV thrombolysis, which is significantly lower than in IA (12.5%, n = 9) or IV + IA thrombolysis (20%, n = 7). In a binary logistic regression analysis including age, NIHSS score, time to thrombolysis, initial diffusion weighted imaging lesion size, mode of thrombolytic treatment and thrombolytic agent, the mode of thrombolytic treatment remained an independent predictor for sICH. The odds ratio for IA or IV + IA versus IV treatment was 3.466 (1.19-10.01, 95% CI, p < 0.05).In this series, IA and IV + IA thrombolysis is associated with an increased sICH risk as compared to IV thrombolysis, and this risk is independent of differences in baseline parameters such as age, initial NIHSS score or pretreatment lesion size.

  View details for DOI 10.1159/000202427

  View details for Web of Science ID 000264862500010

  View details for PubMedID 19218803

• Patients with Acute Stroke Treated with Intravenous tPA 3-6 Hours after Stroke Onset: Correlations between MR Angiography Findings and Perfusion- and Diffusion-weighted Imaging in the DEFUSE Study RADIOLOGY Marks, M. P., Olivot, J., Kemp, S., Lansberg, M. G., Bammer, R., Wechsler, L. R., Albers, G. W., Thijs, V. 2008; 249 (2): 614-623

  Abstract

  To study magnetic resonance (MR) angiography findings in patients with acute stroke treated with intravenous tissue plasminogen activator (tPA) in relationship to perfusion- and diffusion-weighted imaging changes and clinical outcome.Patients treated with intravenous tPA 3-6 hours after stroke onset (with informed consent) were evaluated in a HIPAA-compliant multicenter prospective study approved by all institutional review boards. MR imaging and MR angiography studies were performed before and 3-6 hours after treatment. MR angiography studies that were technically adequate at both time points were evaluated for occlusion, decreased flow, any early recanalization, and degree of recanalization. These results were compared with favorable clinical response (an improvement in National Institutes of Health Stroke Scale score of >or=8 points at 30 days or a modified Rankin scale score of 0 or 1 at 30 days) in patients with and those without mismatch between perfusion- and diffusion-weighted imaging at baseline.Seventy-four patients were enrolled in the initial investigation; pre- and posttreatment MR angiography studies were both technically adequate in 62 patients. MR angiography demonstrated occlusion or decreased flow in 46 patients. Patients with isolated middle cerebral artery (MCA) occlusion and early recanalization at MR angiography had higher rates of favorable clinical response than those with tandem internal carotid artery-MCA occlusion and early recanalization (P = .05). Any early recanalization was not associated with favorable clinical response, but degree of recanalization did correlate with favorable clinical response (P = .048). Favorable clinical response was more frequently seen in patients with mismatch between perfusion- and diffusion-weighted imaging findings at baseline who experienced early recanalization than in those who did not have early recanalization (odds ratio = 6.2; 95% confidence interval: 1.3, 30.2; P = .021). No relationship between early recanalization and favorable clinical response was seen in patients without mismatch.Early recanalization seen at MR angiography before and after treatment coupled with diffusion- and perfusion-weighted imaging data may predict clinical outcome in patients with stroke treated with tPA 3-6 hours after symptom onset.

  View details for DOI 10.1148/radiol.2492071751

  View details for Web of Science ID 000260215400027

  View details for PubMedID 18936316

• The MRA-DWI mismatch identifies patients with stroke who are likely to benefit from reperfusion STROKE Lansberg, M. G., Thijs, V. N., Bammer, R., Olivot, J., Marks, M. P., Wechsler, L. R., Kemp, S., Albers, G. W. 2008; 39 (9): 2491-2496

  Abstract

  The aim of this exploratory analysis was to evaluate if a combination of MR angiography (MRA) and diffusion-weighted imaging (DWI) selection criteria can be used to identify patients with acute stroke who are likely to benefit from early reperfusion.Data from DEFUSE, a study of 74 patients with stroke who received intravenous tissue plasminogen activator in the 3- to 6-hour time window and underwent MRIs before and approximately 4 hours after treatment were analyzed. The MRA-DWI mismatch model was defined as (1) a DWI lesion volume less than 25 mL in patients with a proximal vessel occlusion; or (2) a DWI lesion volume less than 15 mL in patients with proximal vessel stenosis or an abnormal finding of a distal vessel. Favorable clinical response was defined as an improvement on the National Institutes of Health Stroke Scale score of at least 8 points between baseline and 30 days or a National Institutes of Health Stroke Scale score

  View details for DOI 10.1161/STROKEAHA.107.508572

  View details for Web of Science ID 000258727000015

  View details for PubMedID 18635861

• Relationships between infarct growth, clinical outcome, and early recanalization in Diffusion and perfusion imaging For Understanding Stroke Evolution (DEFUSE) STROKE Olivot, J., Mlynash, M., Thijs, V. N., Kemp, S., Lansberg, M. G., Wechsler, L., Schlaug, G., Bammer, R., Marks, M. P., Albers, G. W. 2008; 39 (8): 2257-2263

  Abstract

  The purpose of this study was to determine the relationships between ischemic lesion growth, recanalization, and clinical response in stroke patients with and without a perfusion/diffusion mismatch.DEFUSE is an open label multicenter study in which 74 consecutive acute stroke patients were treated with intravenous tPA 3 to 6 hours after stroke onset. Magnetic resonance imaging (MRI) scans were obtained before, 3 to 6 hours after, and 30 days after treatment. Lesion growth was defined as the difference between the final infarct volume (30 day FLAIR) and the baseline diffusion lesion. Baseline MRI profiles were used to categorize 44 patients into Mismatch versus Absence of Mismatch subgroups. Early recanalization was assessed in 28 patients with an initial vessel lesion on magnetic resonance angiography. Infarct growth was compared based on whether a favorable clinical response (FCR) occurred and whether early recanalization was achieved.In the Mismatch subgroup, FCR was associated with less infarct growth P=0.03 and early recanalization was predictive of both FCR (odds ratio: 22, P=0.047) and reduced infarct growth P=0.024. There was no significant relationship between recanalization, infarct growth, and clinical outcome in the Absence of Mismatch subgroup. A threshold of <7 cc of growth had the highest sensitivity and specificity for predicting a FCR in Mismatch patients (odds ratio: 65, P=0.015, sensitivity 82%, specificity 75%).In contrast to Absence of Mismatch patients, significant associations between recanalization, reduced infarct growth, and favorable clinical response were documented in patients with a perfusion/diffusion mismatch who were treated with tPA within 3 to 6 hours after stroke onset. These findings support the Mismatch hypothesis but require validation in a larger study.

  View details for DOI 10.1161/STROKEAHA.107.511535

  View details for Web of Science ID 000257993400011

  View details for PubMedID 18566302

• Concurrent presentation of perimesencephalic subarachnoid hemorrhage and ischemic stroke. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Lansberg, M. G. 2008; 17 (4): 248-250

  Abstract

  Perimesencephalic subarachnoid hemorrhage (SAH) is a relatively benign form of SAH. The etiology of this condition is unknown but venous leakage has been believed to be the most likely cause. This report describes a patient with perimesencephalic SAH who presented with a concurrent acute pontine infarct demonstrated on diffusion-weighted magnetic resonance imaging. These findings suggest that in some instances perimesencephalic SAH is caused by rupture of a perforating artery.

  View details for DOI 10.1016/j.jstrokecerebrovasdis.2008.03.005

  View details for PubMedID 18589349

• Optimal outcome measures for detecting clinical benefits of early reperfusion: insights from the DEFUSE Study. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Kakuda, W., Hamilton, S., Thijs, V. N., Lansberg, M. G., Kemp, S., Skalabrin, E., Albers, G. W. 2008; 17 (4): 235-240

  Abstract

  There is no consensus regarding which clinical outcome scales are the most sensitive indicators of early reperfusion in patients with acute stroke.Patients with acute stroke enrolled in the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) study with a perfusion-/diffusion-weighted imaging mismatch at baseline magnetic resonance imaging were studied. Prespecified secondary outcome measures were evaluated at both 30 and 90 days after treatment with intravenous tissue plasminogen activator. A nonparametric recursive partitioning algorithm was also used to identify the optimal dichotomous splits for differentiating patients who experienced early reperfusion from those who did not.In all, 34 of the 74 patients enrolled in DEFUSE met the inclusion criteria for this study. Statistically significant benefits of reperfusion were documented on multiple outcome measures. The most powerful predefined outcome measure was improvement in the National Institutes of Health Stroke Scale (NIHSS) score of greater than or equal to 11 points between baseline and day 90 and/or a day-90 NIHSS score of 0 to 1 (odds ratio 22.5, P = .0021). The recursive partitioning algorithm analysis identified an improvement of greater than or equal to 10 on the NIHSS score between baseline and 30 days and an NIHSS score of less than or equal to 2 at 30 days as optimal end points.For patients with stroke and a perfusion-/diffusion-weighted imaging mismatch treated with intravenous tissue plasminogen activator at 3 to 6 hours, a substantial change in the baseline NIHSS score (> or =10 points) is a potent discriminator of patients who experience early reperfusion from those who do not. In addition, an NIHSS score of less than or equal to 2 appears to be an excellent end point for phase II studies of reperfusion therapies.

  View details for DOI 10.1016/j.jstrokecerebrovasdis.2008.03.001

  View details for PubMedID 18589345

• Optimal definition for PWI/DWI mismatch in acute ischemic stroke patients JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Kakuda, W., Lansberg, M. G., Thijs, V. N., Kemp, S. M., Bammer, R., Wechsler, L. R., Moseley, M. E., Parks, M. P., Albers, G. W. 2008; 28 (5): 887-891

  Abstract

  Although the perfusion-weighted imaging/diffusion-weighted imaging (PWI/DWI) mismatch model has been proposed to identify acute stroke patients who benefit from reperfusion therapy, the optimal definition of a mismatch is uncertain. We evaluated the odds ratio for a favorable clinical response in mismatch patients with reperfusion compared with no reperfusion for various mismatch ratio thresholds in patients enrolled in the diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study. A mismatch ratio of 2.6 provided the highest sensitivity (90%) and specificity (83%) for identifying patients in whom reperfusion was associated with a favorable response. Defining mismatch with a larger PWI/DWI ratio may provide greater power for detecting beneficial effects of reperfusion.

  View details for DOI 10.1038/sj.jcbfm.9600604

  View details for Web of Science ID 000255261300003

  View details for PubMedID 18183031

• MRI-based diagnostic evaluation has substantial impact on final stroke diagnosis 33rd International Stroke Conference Kumar, M. A., Campbell, D. M., Vangala, H. L., Eyngorn, I., Olivot, J. M., Beraud, A. S., Belgude, A., Lansberg, M. G., Schnittger, I., Wijman, C. A., Tong, D. C., Mlynash, M., Albers, G. W., Moseley, M. LIPPINCOTT WILLIAMS & WILKINS. 2008: 569–69

  View details for Web of Science ID 000252726100222

• Delirium following abrupt discontinuation of fluoxetine CLINICAL NEUROLOGY AND NEUROSURGERY Blum, D., Maldonado, J., Meyer, E., Lansberg, M. 2008; 110 (1): 69-70

  Abstract

  Sudden discontinuation of serotonin reuptake inhibitors (SRI) can lead to a number of psychological (e.g., nervousness, anxiety, crying spells, psychomotor agitation, irritability, depersonalization, decreased mood, memory disturbances, confusion, decreased concentration, and/or slowed thinking) and somatic (e.g., nausea, dizziness, headache) symptoms. Recent studies have shown that withdrawal symptoms are common with paroxetine, venlafaxine and fluvoxamine, but relatively rare and mild with fluoxetine cessation, likely as a result of its longer half-life. We report an unusual case of a patient who developed delirium after abrupt discontinuation of fluoxetine.

  View details for DOI 10.1016/j.clineuro.2007.08.016

  View details for Web of Science ID 000252799500013

  View details for PubMedID 17913343

• Risk for symptomatic intracerebral hemorrhage after thrombolysis assessed by diffusion-weighted magnetic resonance imaging ANNALS OF NEUROLOGY Singer, O. C., Humpich, M. C., Fiehler, J., Albers, G. W., Lansberg, M. G., Kastrup, A., Rovira, A., Liebeskind, D. S., Gass, A., Rosso, C., Derex, L., Kim, J. S., Neumann-Haefelin, T. 2008; 63 (1): 52-60

  Abstract

  The risk for symptomatic intracerebral hemorrhage (sICH) associated with thrombolytic treatment has not been evaluated in large studies using diffusion-weighted imaging (DWI). Here, we investigated the relation between pretreatment DWI lesion size and the risk for sICH after thrombolysis.In this retrospective multicenter study, prospectively collected data from 645 patients with anterior circulation stroke treated with intravenous or intraarterial thrombolysis within 6 hours (<3 hours: n = 320) after symptom onset were pooled. Patients were categorized according to the pretreatment DWI lesion size into three prespecified groups: small (< or =10 ml; n = 218), moderate (10-100 ml; n = 371), and large (>100 ml; n = 56) DWI lesions.In total, 44 (6.8%) patients experienced development of sICH. The sICH rate was significantly different between subgroups: 2.8, 7.8, and 16.1% in patients with small, moderate, and large DWI lesions, respectively (p < 0.05). This translates to a 5.8 (2.8)-fold greater sICH risk for patients with large DWI lesions as compared with patients with small (or moderate) DWI lesions. The results were similar in the large subgroup (n = 536) of patients treated with intravenous tissue plasminogen activator. DWI lesion size remained an independent risk factor when including National Institutes of Health Stroke Scale, age, time to thrombolysis, and leukoariosis in a logistic regression analysis.This multicenter study provides estimates of sICH risk in potential candidates for thrombolysis. The sICH risk increases gradually with increasing DWI lesion size, indicating that the potential benefit of therapy needs to be balanced carefully against the risk for sICH, especially in patients with large DWI lesions.

  View details for DOI 10.1002/ana.21222

  View details for Web of Science ID 000253008700008

  View details for PubMedID 17880020

• Risk factors of symptomatic intracerebral hemorrhage after tPA therapy for acute stroke STROKE Lansberg, M. G., Thijs, V. N., Bammer, R., Kemp, S., Wijman, C. A., Marks, M. P., Albers, G. W. 2007; 38 (8): 2275-2278

  Abstract

  Studies evaluating predictors of tPA-associated symptomatic intracerebral hemorrhage (SICH) have typically focused on clinical and CT-based variables. MRI-based variables have generally not been included in predictive models, and little is known about the influence of reperfusion on SICH risk.Seventy-four patients were prospectively enrolled in an open-label study of intravenous tPA administered between 3 and 6 hours after symptom onset. An MRI was obtained before and 3 to 6 hours after tPA administration. The association between several clinical and MRI-based variables and tPA-associated SICH was determined using multivariate logistic regression analysis. SICH was defined as a > or = 2 point change in National Institutes of Health Stroke Scale Score (NIHSSS) associated with any degree of hemorrhage on CT or MRI. Reperfusion was defined as a decrease in PWI lesion volume of at least 30% between baseline and the early follow-up MRI.SICH occurred in 7 of 74 (9.5%) patients. In univariate analysis, NIHSSS, DWI lesion volume, PWI lesion volume, and reperfusion status were associated with an increased risk of SICH (P<0.05). In multivariate analysis, DWI lesion volume was the single independent baseline predictor of SICH (odds ratio 1.42; 95% CI 1.13 to 1.78 per 10 mL increase in DWI lesion volume). When early reperfusion status was included in the predictive model, the interaction between DWI lesion volume and reperfusion status was the only independent predictor of SICH (odds ratio 1.77; 95% CI 1.25 to 2.50 per 10 mL increase in DWI lesion volume).Patients with large baseline DWI lesion volumes who achieve early reperfusion appear to be at greatest risk of SICH after tPA therapy.

  View details for DOI 10.1161/STROKEAHA.106.480475

  View details for Web of Science ID 000248455100016

  View details for PubMedID 17569874

• Evaluation of the clinical-diffusion and perfusion-diffusion mismatch models in DEFUSE STROKE Lansberg, M. G., Thijs, V. N., Hamilton, S., Schlaug, G., Bammer, R., Kemp, S., Albers, G. W. 2007; 38 (6): 1826-1830

  Abstract

  The perfusion-diffusion mismatch (PDM) model has been proposed as a tool to select acute stroke patients who are most likely to benefit from reperfusion therapy. The clinical-diffusion mismatch (CDM) model is an alternative method that is technically less challenging because it does not require perfusion-weighted imaging. This study is an evaluation of these 2 models in the DEFUSE dataset.DEFUSE is an open-label multicenter study in which acute stroke patients were treated with intravenous tPA between 3 and 6 hours after symptoms onset and an MRI was obtained before and 3 to 6 hours after treatment. Presence of PDM and CDM was determined for each patient.Based on conventional predefined mismatch criteria, PDM was present in 54% of the DEFUSE population and CDM in 62%. There was no agreement beyond chance between the 2 mismatch models (kappa 0.07). The presence of PDM was associated with an increased chance of favorable clinical response after reperfusion (OR, 5.4; P=0.039). Reperfusion was not associated with a significant increase in the rate of favorable clinical response in patients with CDM (OR, 2.2; P=0.34). Using optimized mismatch criteria, determined retrospectively based on DEFUSE data, the OR for favorable clinical response was 70 (P=0.001) for PDM and 5.1 (P=0.066) for CDM.The PDM model appears to be more accurate than the CDM model for selecting patients who are likely to benefit from reperfusion therapy in the 3- to 6-hour time window.

  View details for DOI 10.1161/STROKEA.HA.106.480145

  View details for Web of Science ID 000246827100026

  View details for PubMedID 17495217

• Symptomatic intracerebral hemorrhage following thrombolytic therapy for acute ischemic stroke: A review of the risk factors CEREBROVASCULAR DISEASES Lansberg, M. G., Albers, G. W., Wijman, C. A. 2007; 24 (1): 1-10

  Abstract

  Symptomatic intracerebral hemorrhage (SICH) following thrombolytic therapy for acute ischemic stroke is associated with a high rate of morbidity and mortality. Knowledge of the risk factors associated with SICH following thrombolyitc therapy may provide insight into the pathophysiological mechanisms underlying the development of SICH, lead to the development of treatments that reduce the risk of SICH and have implications for the design of future stroke trials.Relevant studies were identified through a search in Pubmed. Included studies used multivariate analyses to identify independent risk factors for SICH following thrombolytic therapy. For each variable that was found to have a significant association with SICH, a secondary literature search was conducted to identify additional reports on the specific relationship between that variable and SICH.Twelve studies met inclusion criteria for the systematic review. Extent of hypoattenuated brain parenchyma on pretreatment CT and elevated serum glucose or history of diabetes were independent risk factors for thrombolysis-associated SICH in six of the twelve studies. Symptom severity was an independent risk factor in three of the studies and advanced age, increased time to treatment, high systolic blood pressure, low platelets, history of congestive heart failure and low plasminogen activator inhibitor levels were found to be independent risk factors for SICH in a single study. Although these data should not alter the current guidelines for the use of rt-PA in acute stroke, they may help develop future strategies aimed at reducing the rate of thrombolysis-associated SICH.

  View details for DOI 10.1159/000103110

  View details for Web of Science ID 000247435300001

  View details for PubMedID 17519538

• Magnetic resonance imaging profiles predict clinical response to early reperfusion: The diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study ANNALS OF NEUROLOGY Albers, G. W., Thijs, V. N., Wechsle, L., Kemp, S., Schlaug, G., Skalabrin, E., Bammer, R., Kakuda, W., Lansberg, M. G., Shuaib, A., Coplin, W., Hamilton, S., Moseley, M., Marks, M. P. 2006; 60 (5): 508-517

  Abstract

  To determine whether prespecified baseline magnetic resonance imaging (MRI) profiles can identify stroke patients who have a robust clinical response after early reperfusion when treated 3 to 6 hours after symptom onset.We conducted a prospective, multicenter study of 74 consecutive stroke patients admitted to academic stroke centers in North America and Europe. An MRI scan was obtained immediately before and 3 to 6 hours after treatment with intravenous tissue plasminogen activator 3 to 6 hours after symptom onset. Baseline MRI profiles were used to categorize patients into subgroups, and clinical responses were compared based on whether early reperfusion was achieved.Early reperfusion was associated with significantly increased odds of achieving a favorable clinical response in patients with a perfusion/diffusion mismatch (odds ratio, 5.4; p = 0.039) and an even more favorable response in patients with the Target Mismatch profile (odds ratio, 8.7; p = 0.011). Patients with the No Mismatch profile did not appear to benefit from early reperfusion. Early reperfusion was associated with fatal intracranial hemorrhage in patients with the Malignant profile.For stroke patients treated 3 to 6 hours after onset, baseline MRI findings can identify subgroups that are likely to benefit from reperfusion therapies and can potentially identify subgroups that are unlikely to benefit or may be harmed.

  View details for DOI 10.1002/ana.20976

  View details for Web of Science ID 000242545100006

  View details for PubMedID 17066483

• "Paradoxical" transtentorial herniation due to CSF drainage in the presence of a hemicraniectomy NEUROLOGY Fields, J. D., Lansberg, M. G., Skirboll, S. L., Kurien, P. A., Wijman, C. A. 2006; 67 (8): 1513-1514

  View details for Web of Science ID 000241494800046

  View details for PubMedID 17060591

• Proof-of-principle phase II MRI studies in stroke - Sample size estimates from dichotomous and continuous data STROKE Donnan, G. A., Davis, S. M., Phan, T. G., Ludbrook, J., Byrnes, G., Parsons, M., Barber, A. P., Reutens, D. C., Rose, S. E., Chalk, J., Demchuk, A. M., Coutts, S. B., Simon, J. E., Tomanek, A., Roether, J., Weiller, C., Fiehler, J., Thomalla, G., Kucinski, T., Schellinger, P. D., Hacke, W., Gass, A., Szabo, K., Hennerici, M., Siebler, M., Villringer, A., Junge-Huelsing, G. J., Pedraza, S., Davalos, A., Castillo, J., Albers, G. W., Lansberg, M. G., Thijs, V. N., Bammer, R., Moseley, M. E., Marks, M., Warach, S., Baird, A., Kidwell, C., Saver, J., Sorensen, G., Fisher, M., Nighoghossian, N., Muir, K. 2006; 37 (10): 2521-2525

  Abstract

  Since the failure of a number of phase III trials of neuroprotection in ischemic stroke, the need for smaller phase II studies with MRI surrogates has emerged. There is, however, little information available about sample size requirements for such phase II trials and rarely enough patients in single studies to make robust estimates. We have formed an international collaborative group to assemble larger datasets and from these have generated sample size tables for MRI-based infarct expansion as the outcome measure.Twelve centers from Australia, Europe, and North America contributed data from patients with hemispheric ischemic stroke. Infarct expansion was defined from initial diffusion-weighted images and later fluid-attenuated inversion recover or T2 images. Sample size estimates were calculated from data on infarct expansion ratios treated as dichotomous or continuous variables. A nonparametric approach was used because the distribution of infarct expansion was resistant to all forms of transformation.As an example, a 20% absolute reduction in infarct expansion ratio (< or = 1), 80% power, and alpha = 0.05 requires 99 patients in each arm. To achieve an equivalent effect size with a continuous approach requires 61 patients.These tables will be useful in planning phase II trials of therapy with the use of MRI outcome measures. For positive studies, biologically plausible surrogates such as these may provide a rationale for proceeding to phase III trials.

  View details for DOI 10.1161/01.STR.0000239696.61545.4b

  View details for Web of Science ID 000240938700021

  View details for PubMedID 16931782

• MRI characteristics of cerebral air embolism from a venous source NEUROLOGY Caulfield, A. F., Lansberg, M. G., Marks, M. P., Albers, G. W., Wijman, C. A. 2006; 66 (6): 945-946

  View details for Web of Science ID 000236292300037

  View details for PubMedID 16567722

• Mechanical thrombectomy following intravenous thrombolysis in the treatment of acute stroke ARCHIVES OF NEUROLOGY Lansberg, M. G., Fields, J. D., Albers, G. W., Jayaraman, M. V., Do, H. M., Marks, M. P. 2005; 62 (11): 1763-1765

  Abstract

  The efficacy of intravenous thrombolytics in acute stroke is limited by low rates of recanalization of occluded arteries. Treatment with intravenous thrombolytics followed by mechanical thrombectomy is a novel approach that may increase recanalization rates without compromising time to initiation of treatment.To report our experience with 2 patients who received this combination therapy and outline plans for a prospective pilot study.Case studies at a university hospital.Patients treated with intravenous thrombolytics within 3 hours of symptom onset subsequently underwent computed tomographic angiography. If an occlusion of a proximal cerebral vessel was shown by a computed tomographic angiogram, mechanical thrombectomy was performed. Patients were observed for 1 month after treatment.National Institutes of Health Stroke Scale (NIHSS) score.The computed tomographic angiography of 2 patients showed complete occlusion of the M1 branch of the middle cerebral artery following administration of intravenous thrombolytics. The NIHSS scores were 21 and 13. In both cases, blood flow through the occluded artery was restored with mechanical thrombectomy and dramatic neurologic improvement occurred. There were no complications. The NIHSS scores were 0 and 2 at 1-month follow-up.Treatment with intravenous thrombolytics followed by mechanical thrombectomy may improve outcomes in acute stroke patients and a pilot safety trial is warranted.

  View details for Web of Science ID 000233250900017

  View details for PubMedID 16286552

• Clinical importance of microbleeds in patients receiving IV thrombolysis NEUROLOGY Kakuda, W., Thijs, V. N., Lansberg, M. G., Bammer, R., Wechsler, L., Kemp, S., Moseley, M. E., Marks, M. P., Albers, G. W. 2005; 65 (8): 1175-1178

  Abstract

  Cerebral microbleeds (MBs) detected on gradient echo (GRE) imaging may be a risk factor for hemorrhagic complications in patients with stroke treated with IV tissue plasminogen activator (tPA).The authors prospectively evaluated patients with acute ischemic stroke treated with IV tPA between 3 and 6 hours of symptom onset. MRI scans, including GRE imaging, were performed prior to tPA treatment, 3 to 6 hours after treatment and at day 30. The authors compared the frequency of hemorrhagic complications after thrombolysis in patients with and without MBs on their baseline GRE imaging.Seventy consecutive patients (mean age, 71 +/- 29 years; 31 men, 39 women) were included. MBs were identified in 11 patients (15.7%) on baseline GRE imaging. There was no significant difference in the frequency of either symptomatic or asymptomatic hemorrhagic complications after thrombolysis between patients with and without MBs at baseline. None of the 11 patients with MBs (0%) at baseline had a symptomatic intracerebral hemorrhage compared with 7 of 59 patients who did not have baseline MBs (11.9%). In addition, no patients with baseline MBs had asymptomatic hemorrhagic transformation observed at the site of any pre-treatment MB.The presence of cerebral microbleeds on gradient echo imaging does not appear to substantially increase the risk of either symptomatic or asymptomatic brain hemorrhage following IV tissue plasminogen activator administered between 3 and 6 hours after stroke onset.

  View details for Web of Science ID 000232813600008

  View details for PubMedID 16247042

• Who is most likely to benefit from tPA? The perfusion-diffusion and clinical-diffusion mismatch models disagree 30th International Stroke Conference Lansberg, M. G., Thijs, V. N., Bammer, R., Wechsler, L. R., O'Donnell, M. J., Olshen, R. A., Wijman, C. A., Kemp, S. M., Albers, G. W. LIPPINCOTT WILLIAMS & WILKINS. 2005: 437–37

  View details for Web of Science ID 000227523800098

• Evolution of apparent diffusion coefficient, diffusion-weighted, and T2-weighted signal intensity of acute stroke AMERICAN JOURNAL OF NEURORADIOLOGY Lansberg, M. G., Thijs, V. N., O'Brien, M. W., Ali, J. O., de Crespigny, A. J., Tong, D. C., Moseley, M. E., Albers, G. W. 2001; 22 (4): 637-644

  Abstract

  Serial study of such MR parameters as diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC), ADC with fluid-attenuated inversion recovery (ADC(FLAIR)), and T2-weighted imaging may provide information on the pathophysiological mechanisms of acute ischemic stroke. Our goals were to establish the natural evolution of MR signal intensity characteristics of acute ischemic lesions and to assess the potential of using specific MR parameters to estimate lesion age.Five serial echo-planar DWI studies with and without an inversion recovery pulse were performed in 27 patients with acute stroke. The following lesion characteristics were studied: 1) conventional ADC (ADC(CONV)); 2) ADC(FLAIR); 3) DWI signal intensity (SI(DWI)); 4) T2-weighted signal intensity (SI(T2)), and 5) FLAIR signal intensity (SI(FLAIR)).The lesion ADC(CONV) gradually increased from low values during the first week to pseudonormal during the second week to supranormal thereafter. The lesion ADC(FLAIR) showed the same pattern of evolution but with lower absolute values. A low ADC value indicated, with good sensitivity (88%) and specificity (90%), that a lesion was less than 10 days old. All signal intensities remained high throughout follow-up. SI(DWI) showed no significant change during the first week but decreased thereafter. SI(T2) initially increased, decreased slightly during week 2, and again increased after 14 days. SI(FLAIR) showed the same initial increase as the SI(T2) but remained relatively stable thereafter.Our findings further clarify the time course of stroke evolution on MR parameters and indicate that the ADC map may be useful for estimating lesion age. Application of an inversion recovery pulse results in lower, potentially more accurate, absolute ADC values.

  View details for Web of Science ID 000168156800009

  View details for PubMedID 11290470

• Evolution of cerebral infarct volume assessed by diffusion-weighted magnetic resonance imaging ARCHIVES OF NEUROLOGY Lansberg, M. G., O'Brien, M. W., Tong, D. C., Moseley, M. E., Albers, G. W. 2001; 58 (4): 613-617

  Abstract

  Knowledge of the natural evolution of ischemic brain lesions may be a crucial aspect in the assessment of future stroke therapies.To establish daily changes of ischemic cerebral lesion volume using diffusion-weighted magnetic resonance imaging.Prospective cohort study.Referral center.Serial magnetic resonance imaging scans were performed in consecutive untreated stroke patients. The baseline scan was obtained within 48 hours after symptom onset; subsequent scans, 12 to 48 hours, 3 to 4 days, 5 to 7 days, and 30 days after baseline. Lesion volumes were measured on each scan by 2 independent observers.Daily change in lesion volume.A total of 112 magnetic resonance imaging scans were obtained in 24 patients. An early increase in lesion volume was seen in all patients. Maximum lesion volume was reached at a mean of 74 hours. Lesion volumes increased by a mean (+/- SEM) of 21% +/- 12% during day 2 and 10% +/- 12% during day 3. No significant change occurred during day 4. During days 5, 6, and 7, statistically significant mean (+/- SEM) decreases of 6% +/- 8%, 3% +/- 4%, and 4% +/- 5%, respectively, were observed.Ischemic lesions follow a relatively consistent pattern of growth during the first 3 days and subsequent decrease in size. These data in conjunction with data regarding the evolution of lesion volume during the first 24 hours after symptom onset may be useful in the design of pilot studies of therapies for acute stroke.

  View details for Web of Science ID 000167935900011

  View details for PubMedID 11295992

• Comparison of diffusion-weighted MRI and CT in acute stroke - Reply NEUROLOGY Marks, M. P., Albers, G., Lansberg, M. 2000; 55 (11): 1760-1760

  View details for Web of Science ID 000165770600041

• Is early ischemic lesion volume on diffusion-weighted imaging an independent predictor of stroke outcome? A multivariable analysis STROKE Thijs, V. N., Lansberg, M. G., Beaulieu, C., Marks, M. P., Moseley, M. E., Albers, G. W. 2000; 31 (11): 2597-2602

  Abstract

  The heterogeneity of stroke makes outcome prediction difficult. Neuroimaging parameters may improve the predictive value of clinical measures such as the National Institutes of Health Stroke Scale (NIHSS). We investigated whether the volume of early ischemic brain lesions assessed with diffusion-weighted imaging (DWI) was an independent predictor of functional outcome.We retrospectively selected patients with nonlacunar ischemic stroke in the anterior circulation from 4 prospective Stanford Stroke Center studies evaluating early MRI. The baseline NIHSS score and ischemic stroke risk factors were assessed. A DWI MRI was performed within 48 hours of symptom onset. Clinical characteristics and early lesion volume on DWI were compared between patients with an independent outcome (Barthel Index score >/=85) and a dependent outcome (Barthel Index score <85) at 1 month. A logistic regression model was performed with factors that were significantly different between the 2 groups in univariate analysis.Sixty-three patients fulfilled the entry criteria. One month after symptom onset, 24 patients had a Barthel Index score <85 and 39 had a Barthel Index score >/=85. In univariate analysis, patients with independent outcome were younger, had lower baseline NIHSS scores, and had smaller lesion volumes on DWI. In a logistic regression model, DWI volume was an independent predictor of outcome, together with age and NIHSS score, after correction for imbalances in the delay between symptom onset and MRI.DWI lesion volume measured within 48 hours of symptom onset is an independent risk factor for functional independence. This finding could have implications for the design of acute stroke trials.

  View details for Web of Science ID 000165107100009

  View details for PubMedID 11062281

• Advantages of adding diffusion-weighted magnetic resonance imaging to conventional magnetic resonance imaging for evaluating acute stroke ARCHIVES OF NEUROLOGY Lansberg, M. G., Norbash, A. M., Marks, M. P., Tong, D. C., Moseley, M. E., Albers, G. W. 2000; 57 (9): 1311-1316

  Abstract

  Accurate localization of acute ischemic lesions in patients with an acute stroke may aid in understanding the etiology of their stroke and may improve the management of these patients.To determine the yield of adding diffusion-weighted magnetic resonance imaging (DWI) to a conventional magnetic resonance imaging (MRI) protocol for acute stroke.A prospective cohort study.A referral center.Fifty-two patients with a clinical diagnosis of acute stroke who presented within 48 hours after symptom onset were included. An MRI scan was obtained within 48 hours after symptom onset. A neuroradiologist (A.M.N.) and a stroke neurologist (G.W.A.) independently identified suspected acute ischemic lesions on MRI sequences in the following order: (1) T2-weighted and proton density-weighted images, (2) fluid-attenuated inversion recovery images, and (3) diffusion-weighted images and apparent diffusion coefficient maps.Diagnostic yield and interrater reliability for the identification of acute lesions, and confidence and conspicuity ratings of acute lesions for different MRI sequences.Conventional MRI correctly identified at least one acute lesion in 71% (34/48) to 80% (39/49) of patients who had an acute stroke; with the addition of DWI, this percentage increased to 94% (46/49) (P<.001). Conventional MRI showed only moderate sensitivity (50%-60%) and specificity (49%-69%) compared with a "criterion standard." Based on the diffusion-weighted sequence, interrater reliability for identifying acute lesions was moderate for conventional MRI (kappa = 0.5-0.6) and good for DWI (kappa = 0.8). The observers' confidence with which lesions were rated as acute and the lesion conspicuity was significantly (P<.01) higher for DWI than for conventional MRI.During the first 48 hours after symptom onset, the addition of DWI to conventional MRI improves the accuracy of identifying acute ischemic brain lesions in patients who experienced a stroke.

  View details for Web of Science ID 000089283000010

  View details for PubMedID 10987898

• Yield of diffusion-weighted MRI for detection of potentially relevant findings in stroke patients NEUROLOGY Albers, G. W., Lansberg, M. G., Norbash, A. M., Tong, D. C., O'Brien, M. W., Woolfenden, A. R., Marks, M. P., Moseley, M. E. 2000; 54 (8): 1562-1567

  Abstract

  To determine whether diffusion-weighted imaging (DWI) could identify potentially clinically relevant findings in patients presenting more than 6 hours after stroke onset when compared with conventional MRI.MRI with both conventional (T2 and proton density images) and echoplanar imaging (DWI and apparent diffusion coefficient maps) was performed 6 to 48 hours after symptom onset (mean, 27 hours) in 40 consecutive patients with acute stroke. All acute lesions were identified first on conventional images, then on DWI, by a neuroradiologist who was provided with the suspected lesion location, based on a neurologist's examination before imaging. Abnormalities were rated as potentially clinically relevant if they were detected only on DWI and 1) confirmed the acute symptomatic lesion to be in a different vascular territory than suspected clinically, 2) revealed multiple lesions in different vascular territories suggestive of a proximal source of embolism, or 3) clarified that a lesion, thought to be acute on conventional imaging, was not acute.The initial clinical impression of lesion localization was incorrect in 12 patients (30%). Clinically significant findings were detected by DWI alone in 19 patients (48%). DWI demonstrated the symptomatic lesion in a different vascular territory than suspected clinically or by conventional MRI in 7 patients (18%) and showed acute lesions in multiple vascular distributions in 5 patients (13%). In 8 patients (20%), DWI clarified that lesions thought to be acute on conventional MRI were actually old.In patients imaged 6 to 48 hours after stroke onset, DWI frequently provided potentially clinically relevant findings that were not apparent on conventional MRI.

  View details for Web of Science ID 000086642000007

  View details for PubMedID 10762494

• Comparison of diffusion-weighted MRI and CT in acute stroke NEUROLOGY Lansberg, M. G., Albers, G. W., Beaulieu, C., Marks, M. P. 2000; 54 (8): 1557-1561

  Abstract

  To compare diffusion-weighted MRI (DWI) and CT with respect to accuracy of localizing acute cerebral infarction; sensitivity, specificity, and interrater reliability for identifying more than one-third middle cerebral artery (MCA) territory involvement; and correlation of acute lesion volume with final infarct volume.Nineteen consecutive stroke patients underwent CT and DWI within 7 hours of stroke onset and a follow-up DWI examination 36 hours after symptom onset, which served as the "gold standard" for lesion location and extent of MCA involvement. Each scan was evaluated for acute ischemic lesions by two experienced observers. After 30 days, T2-weighted MRI was obtained for assessment of the final infarct volume.The acute CT and DWI scans were obtained on average 2.6 and 5.1 hours after symptom onset. On DWI the acute lesion was identified correctly in all instances and on CT it was identified correctly in 42 to 63% of patients. Sensitivity for detection of more than 33% MCA involvement was better for DWI (57 to 86%) than for CT (14 to 43%), whereas specificity was excellent for both. Interrater reliability was moderately good for both (kappa, 0.6 for DWI; 0.5 for CT). A positive correlation (r = 0.79; p = 0.001) existed between lesion volume on acute DWI and final infarct volume, whereas no correlation was found between CT volume and final infarct volume.When compared with CT, DWI was more accurate for identifying acute infarction and more sensitive for detection of more than 33% MCA involvement. In addition, lesion volume on acute DWI, but not on acute CT, correlated strongly with final infarct volume. Additional studies are required to demonstrate whether these advantages of DWI are clinically relevant in the management of patients with acute stroke.

  View details for Web of Science ID 000086642000006

  View details for PubMedID 10762493

• MRI abnormalities associated with partial status epilepticus NEUROLOGY Lansberg, M. G., O'Brien, M. W., Norbash, A. M., Moseley, M. E., Morrell, M., Albers, G. W. 1999; 52 (5): 1021-1027

  Abstract

  To report neuroimaging findings in patients with complex partial status epilepticus.During status epilepticus, neuroimaging may be used to exclude other neurologic conditions. Therefore, it is important to identify the neuroimaging features that are associated with status epilepticus. In addition, MRI characteristics may provide insight into the pathophysiologic changes during status epilepticus.The history and neuroimaging examination results of three patients with complex partial status epilepticus were reviewed. Studies obtained during status epilepticus included diffusion-weighted MRI (DWI), MR angiography (MRA), postcontrast T1-weighted MRI, T2-weighted MRI, and CT. Follow-up MRI was obtained in two patients, and autopsy results were available for the third.Some of the MRI and CT findings during partial status epilepticus mimicked those of acute ischemic stroke: DWI and T2-weighted MRI showed cortical hyperintensity with a corresponding low apparent diffusion coefficient, and CT showed an area of decreased attenuation with effacement of sulci and loss of gray-white differentiation. However, the lesions did not respect vascular territories, there was increased signal of the ipsilateral middle cerebral artery on MRA, and leptomeningeal enhancement appeared on postcontrast MRI. On follow-up imaging, the abnormalities had resolved, but some cerebral atrophy was present.The radiologic characteristics of status epilepticus resemble those of ischemic stroke but can be differentiated based on lesion location and findings on MRA and postcontrast MRI. The MRI abnormalities indicated the presence of cytotoxic and vasogenic edema, hyperperfusion of the epileptic region, and alteration of the leptomeningeal blood-brain barrier. These changes reversed, but they resulted in some regional brain atrophy.

  View details for Web of Science ID 000079516900022

  View details for PubMedID 10102423

• Intra-arterial rtPA treatment of stroke assessed by diffusion- and perfusion-weighted MRI STROKE Lansberg, M. G., Tong, D. C., Norbash, A. M., Yenari, M. A., Moseley, M. E. 1999; 30 (3): 678-680

  Abstract

  Diffusion-weighted MRI (DWI) and perfusion-weighted MRI (PWI) are new techniques that can be used for the evaluation of acute ischemic stroke. However, their potential role in the management of patients treated with recombinant tissue plasminogen activator (rtPA) has yet to be determined.The authors present the case of a 73-year-old man who was treated with intra-arterial rtPA, and they compare findings on DWI and PWI scans with angiography. PWI revealed decreased cerebral perfusion corresponding to an area that was not successfully recanalized, but revealed no abnormality in regions in which blood flow was restored. DWI was unremarkable in the region that was reperfused early (3 hours) but revealed hyperintensity in an area that was reperfused 3. 5 hours after symptom onset and in the area that was not reperfused.Findings on PWI correlated well with angiography, and DWI detected injured tissue in the hyperacute stage, whereas conventional MRI findings were negative. This suggests that these techniques may be useful to noninvasively evaluate the success of thrombolytic therapy.

  View details for Web of Science ID 000078913700040

  View details for PubMedID 10066870

• Headache with neurological deficits and CSF lymphocytosis: A transient ischemic attack mimic. Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association Lansberg, M. G., Woolfenden, A. R., Norbash, A. M., Smith, D. B., Albers, G. W. 1999; 8 (1): 42-44

  Abstract

  Headache with neurological deficits and cerebrospinal fluid (CSF) lymphocytosis (HaNDL) is a benign condition with a transient ischemic attack (TIA)-like presentation. It is a disease of young adults that is characterized by headache, transient focal neurological symptoms, and lymphocytic pleocytosis. The onset of neurological symptoms after cerebral angiography in patients with this disease has occasionally been reported. The authors present the case of a 28-year-old man with episodes of left-sided numbness and weakness associated with headache. He underwent cerebral angiography as part of his evaluation, after which he experienced an episode of right hemiplegia and aphasia. A subsequent magnetic resonance image (MRI) revealed two small new infarcts in the left parietal cortex. A diagnosis of HaNDL was made based mainly on clinical symptoms and CSF analysis. The symptoms resolved with conservative therapy. HaNDL is a benign condition that can present with symptoms similar to a TIA. Although HaNDL remains a diagnosis of exclusion, caution is required when considering cerebral angiography in the evaluation of patients with a HaNDL-like syndrome, because these patients seem prone to developing neurological symptoms after angiography.

  View details for PubMedID 17895137