MR Mismatch and Thrombolysis
2009; Lippincott Williams & Wilkins; Volume: 40; Issue: 8 Linguagem: Inglês
10.1161/strokeaha.109.552893
ISSN1524-4628
AutoresStephen M. Davis, Geoffrey A. Donnan,
Tópico(s)Stroke Rehabilitation and Recovery
ResumoHomeStrokeVol. 40, No. 8MR Mismatch and Thrombolysis Free AccessArticle CommentaryPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessArticle CommentaryPDF/EPUBMR Mismatch and ThrombolysisAppealing but Validation Required Stephen M. Davis, MD, FRACP and Geoffrey A. Donnan, MD, FRACP Stephen M. DavisStephen M. Davis From the Department of Neurology, Royal Melbourne Hospital, Parkville Vic Australia. and Geoffrey A. DonnanGeoffrey A. Donnan From the Department of Neurology, Royal Melbourne Hospital, Parkville Vic Australia. Originally published4 Jun 2009https://doi.org/10.1161/STROKEAHA.109.552893Stroke. 2009;40:2910Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: June 4, 2009: Previous Version 1 Since the initial description of the ischemic penumbra 30 years ago, the concept of rapid restoration of blood flow to threatened brain tissue has been the "holy grail" of acute stroke therapy.1,2 Despite its drawbacks, MR imaging of perfusion diffusion mismatch remains the most widely used and practical means of in vivo assessment.There is accumulating evidence linking reperfusion with better clinical outcomes and attenuation of infarct growth in patients in patients with MR mismatch. However, validation that imaging effectively selects thrombolytic responders is still lacking. Both protagonists have highlighted areas of uncertainty in definition of MR mismatch. In our view, these include optimizing the ratio between PWI and DWI, choice of metric (we find Tmax, the time to peak of residue function, most useful), and choice of threshold to exclude benign oligemia (Tmax 4 to 6 appears to be better than Tmax 2).3,4 Another key question is the option of excluding large DWI volumes to reduce the risk of hemorrhagic transformation and poor outcome with thrombolysis. We consider that baseline core infarct volumes of >100 mL on DWI should be excluded.5,6As mentioned by both protagonists, there have been 3 key trials that have addressed the question of MR mismatch and thrombolysis, namely DEFUSE,6 EPITHET,7 and ECASS III.8 The former 2 provided biological evidence to support a strong relationship between reperfusion, attenuation of infarct growth, and improved clinical outcomes. Indeed in EPITHET, tPA significantly enhanced reperfusion in the 3- to 6-hour time window. Although neither EPITHET nor DEFUSE selected patients based on mismatch, these results do provide support for the concept of mismatch as a selection criterion in future trials. Of the 3 trials, only DIAS-2 actually used the principal of penumbral selection, with the "eyeball technique" at individual centers. How do we explain this unexpected result? As mentioned in part by our protagonists, possible explanations include the mild stroke severity in the DIAS-2 cohort, the use of CT perfusion (CTP) in about one third of cases, small sample size for a phase III trial, and the chance occurrence of late nonneurological deaths in the high-dose treatment group.A particular issue arising from DIAS-2 is the use of the "eyeball technique" in penumbral selection. Without thresholding and standardization of the perfusion metric, the probability that most of the PWI images contain benign oligemia is high. In other words, many nonpenumbral patients would have been entered into the trial. To reduce error and truly operationalize penumbral selection uniformly across centers, automated online imaging is an urgent priority. We conclude that the potential of MR mismatch remains obvious, but a number of refinements are needed. Clearly, a large Phase III trial is required for validation of the principle of MR mismatch in treatment selection. To this end, our EXTEND trial is planned to commence during 2009.DisclosuresNone.FootnotesCorrespondence to Professor Stephen Davis, Divisional Director of Neurosciences, Director of Neurology, Royal Melbourne Hospital, Parkville Vic Australia 3050. E-mail [email protected]References1 Symon L. The ischemic penumbra - the beginning. In Donnan GA, Baron JC, Davis SM, Sharp F, eds. The Ischemic Penumbra. New York: Informa Healthcare; 2007: 1–6.Google Scholar2 Donnan GA, Baron JC, Ma H, Davis SM. Penumbral selection for trials of acute stroke therapy. Lancet Neurology. In press.Google Scholar3 Christensen S, Parsons M, DeSilva D, Ebinger M, Butcher K, Fink J, Davis SM. Optimal mismatch definitions for detecting treatment response in acute stroke. Cerebrovasc Dis. 2008; 25: 1–192.MedlineGoogle Scholar4 Olivot JM, Mlynash M, Thijs VN, Kemp S, Lansberg MG, Wechsler L, Bammer R, Marks MP, Albers GW. Optimal Tmax threshold for predicting penumbral tissue in acute stroke. Stroke. 2009; 40: 469–475.LinkGoogle Scholar5 Singer OC, Humpich MC, Fiehler J, Albers GW, Lansberg MG, Kastrup A, Rovira A, Liebeskind DS, Gass A, Rosso C, Derex L, Kim JS, Neumann-Haefelin T. Risk for symptomatic intracerebral hemorrhage after thrombolysis assessed by diffusion-weighted magnetic resonance imaging. Ann Neurol. 2008; 63: 52–60.CrossrefMedlineGoogle Scholar6 Albers GW, Thijs VN, Wechsler L, Kemp S, Schlaug G, Skalabrin E, Bammer R, Kakuda W, Lansberg MG, Shuaib A, Coplin W, Hamilton S, Moseley M, Marks MP. Magnetic resonance imaging profiles predict clinical response to early reperfusion: The Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) study. Ann Neurol. 2006; 60: 508–517.CrossrefMedlineGoogle Scholar7 Davis SM, Donnan GA, Parsons MW, Levi C, Butcher KS, Peeters A, Barber PA, Bladin C, De Silva DA, Byrnes G, Chalk JB, Fink JN, Kimber TE, Schultz D, Hand PJ, Frayne J, Hankey G, Muir K, Gerraty R, Tress BM, Desmond PM. Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (Epithet): A placebo-controlled randomised trial. Lancet Neurol. 2008; 7: 299–309.CrossrefMedlineGoogle Scholar8 Hacke W, Kaste M, Bluhmki E, Brozman M, Davalos A, Guidetti D, Larrue V, Lees KR, Medeghri Z, Machnig T, Schneider D, von Kummer R, Wahlgren N, Toni D. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. 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Konstas A and Lev M (2010) CT Perfusion Imaging of Acute Stroke: The Need for Arrival Time, Delay Insensitive, and Standardized Postprocessing Algorithms?, Radiology, 10.1148/radiol.09091610, 254:1, (22-25), Online publication date: 1-Jan-2010. Lu J, Mei Q, Hou X, Manaenko A, Zhou L, Liebeskind D, Zhang J, Li Y and Hu Q (2021) Imaging Acute Stroke: From One-Size-Fit-All to Biomarkers, Frontiers in Neurology, 10.3389/fneur.2021.697779, 12 August 2009Vol 40, Issue 8 Advertisement Article InformationMetrics https://doi.org/10.1161/STROKEAHA.109.552893PMID: 19498181 Manuscript receivedMarch 17, 2009Originally publishedJune 4, 2009 KeywordsMR mismatchthrombolysisdiffusion-weighted imagingcontroversiesPDF download Advertisement SubjectsTreatment
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