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• W2034688033 abstract "HomeStrokeVol. 42, No. 9Letter by Gaberel et al Regarding Article, “Dose Effect of Intraventricular Fibrinolysis in Ventricular Hemorrhage” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Gaberel et al Regarding Article, “Dose Effect of Intraventricular Fibrinolysis in Ventricular Hemorrhage” Thomas Gaberel, MD, Evelyne Emery, MD, PhD and Denis Vivien, PhD Thomas GaberelThomas Gaberel Search for more papers by this author , Evelyne EmeryEvelyne Emery Search for more papers by this author and Denis VivienDenis Vivien Search for more papers by this author Originally published4 Aug 2011https://doi.org/10.1161/STROKEAHA.111.627091Stroke. 2011;42:e548–e549Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2011: Previous Version 1 To the Editor:We read with great interest the article recently published in Stroke by Staykov et al entitled “Dose Effect of Intraventricular Fibrinolysis in Ventricular Hemorrhage.”1 This well-shaped observational study compared the use of a low dose (1 mg 3 times a day) and a high dose (4 mg twice daily) of tissue plasminogen activator (tPA) for intraventricular fibrinolysis (IVF) in intraventricular hemorrhage secondary to spontaneous supratentorial intracranial hemorrhage. The authors showed that there was no difference between the 2 doses of tPA used in term of intraventricular hemorrhage resolution in the third and fourth ventricles, a similar safety profile, and finally no difference in functional outcome.We recently performed a meta-analysis dealing with IVF in intraventricular hemorrhage secondary to spontaneous supratentorial intracranial hemorrhage.2 One of the sensitivity analyses we have performed compared the impact on mortality of the 2 main fibrinolytics agents used, tPA and urokinase. Surprisingly, there was no benefit of IVF on mortality for tPA when compared with urokinase for which the benefit was clear. For review purposes, we performed a post hoc analysis that was not included in our under press article comparing the impact of IVF on functional outcome for the 2 fibrinolytic agents.As reported on the Figure, considering long-term functional outcome (good functional outcome, modified Rankin Scale score of 0, 1, 2, or 3), IVF appears beneficial for urokinase and not for recombinant tPA.Download figureDownload PowerPointFigure. Pooled OR of good functional outcome at ≥3 months. Sensitivity analysis comparing urokinase and rtPA. EVD indicates extraventricular drainage; IVF, intraventricular fibrinolysis; rtPA, recombinant tissue plasminogen activator.To explain such difference, we evoked the potential neurotoxicity of tPA, well established in in vitro and in preclinical studies, especially when used in acute ischemic stroke.3 Accordingly, when used for IVF, it has been shown that tPA could increase perihematomal edema.4 So the neurotoxicity of tPA might mask the beneficial effect of the clot lysis.Before we read the article by Staykov et al, we considered that a lower dose of tPA, as used in the Clot Lysis Evaluation Accelerated Resolution of Intraventricular Hemorrhage Trial (CLEAR-IVH) 3 trial (1 mg 3 times a day) could achieve clot lysing without a toxic effect. Interestingly, Staykov's study reveals that tPA provided the same results in terms of functional outcome whatever the dose used (1 mg 3 times a day and 4 mg twice daily).So this article raises 3 hypotheses: (1) tPA-mediated neurotoxicity can occur until low doses of tPA; (2) there is no impact of the neurotoxicity of tPA on functional outcome in IVF; and (3) tPA is not neurotoxic when used for IVF.We think that IVF is a hopeful treatment in intraventricular hemorrhage. However, the potential neurotoxicity of tPA must be considered. Basic research and clinical trial will have to compare tPA with fibrinolytic agents that are supposed to be not neurotoxic such as Desmoteplase.Thomas Gaberel, MD Department of Neurosurgery Caen University Hospital Caen, France INSERM, U919 Sérine Protease and Pathophysiology of the Neurovascular Unit SP2U GIP Cyceron University Caen Lower Normandy Caen, FranceEvelyne Emery, MD, PhD Department of Neurosurgery Caen University Hospital Caen, France INSERM, U919 Sérine Protease and Pathophysiology of the Neurovascular Unit SP2U GIP Cyceron University Caen Lower Normandy Caen, FranceDenis Vivien, PhD INSERM, U919 Sérine Protease and Pathophysiology of the Neurovascular Unit SP2U GIP Cyceron University Caen Lower Normandy Caen, FranceDisclosuresNone.FootnotesStroke welcomes Letters to the Editor and will publish them, if suitable, as space permits. Letters must reference a Stroke published-ahead-of-print article or an article printed within the past 3 weeks. The maximum length is 750 words including no more than 5 references and 3 authors. Please submit letters typed double-spaced. Letters may be shortened or edited. Include a completed copyright transfer agreement form (available online at http://stroke.ahajournals.org and http://submit-stroke.ahajournals.org). References 1. Staykov D, Wagner I, Volbers B, Huttner HB, Doerfler A, Schwab S , et al.. Dose effect of intraventricular fibrinolysis in ventricular hemorrhage. Stroke. 2011; 42:2061–2064.LinkGoogle Scholar2. Gaberel T, Magheru C, Parienti JJ, Huttner HB, Vivien D, Emery E. Intraventricular fibrinolysis versus external ventricular drainage alone in intraventricular hemorrhage: a meta-analysis. Stroke. 2011; in press. LinkGoogle Scholar3. Yepes M, Roussel BD, Ali C, Vivien D. Tissue-type plasminogen activator in the ischemic brain: more than a thrombolytic (review). Trends Neurosci. 2008; 32:48–55.CrossrefMedlineGoogle Scholar4. Ducruet AF, Hickman ZL, Zacharia BE, Grobelny BT, Narula R, Guo KH , et al.. Exacerbation of perihematomal edema and sterile meningitis with intraventricular administration of tissue plasminogen activator in patients with intracerebral hemorrhage. Neurosurgery. 2010; 66:648–655.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Gaberel T, Magheru C and Emery E (2012) Management of non-traumatic intraventricular hemorrhage, Neurosurgical Review, 10.1007/s10143-012-0399-9, 35:4, (485-495), Online publication date: 1-Oct-2012. September 2011Vol 42, Issue 9 Advertisement Article InformationMetrics © 2011 American Heart Association, Inc.https://doi.org/10.1161/STROKEAHA.111.627091PMID: 21817144 Originally publishedAugust 4, 2011 PDF download Advertisement SubjectsIntracranial HemorrhageTreatment" @default.
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