Kallmünzer, Bernd

Seiffge, David J.

Volbers, Bastian

Frontiers in Neurology

OPEN FAU Online-Publikationssystem der Friedrich-Alexander-Universität Erlangen-Nürnberg

TYPE EditorialPUBLISHED 14 August 2023DOI 10.3389/fneur.2023.1245890OPEN ACCESSEDITED AND REVIEWED BYThanh N. Nguyen,Boston University, United States*CORRESPONDENCEBastian Volbersbastian.volbers@gmx.netRECEIVED 23 June 2023ACCEPTED 03 August 2023PUBLISHED 14 August 2023CITATIONVolbers B, Kallmünzer B and Sei ge DJ (2023)Editorial: Pushing the boundaries in acuteischemic stroke treatment.Front. Neurol. 14:1245890.doi: 10.3389/fneur.2023.1245890COPYRIGHT© 2023 Volbers, Kallmünzer and Sei ge. This isan open-access article distributed under theterms of the Creative Commons AttributionLicense (CC BY). The use, distribution orreproduction in other forums is permitted,provided the original author(s) and thecopyright owner(s) are credited and that theoriginal publication in this journal is cited, inaccordance with accepted academic practice.No use, distribution or reproduction ispermitted which does not comply with theseterms.Editorial: Pushing the boundariesin acute ischemic stroketreatmentBastian Volbers1,2*, Bernd Kallmünzer2 and David J. Sei ge11Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland,2Department of Neurology, University of Erlangen-Nürnberg, Erlangen, GermanyKEYWORDSacute ischemic stroke, thrombolysis (for acute ischemic stroke), mechanicalthrombectomy, extended time window, telestroke network, non-contrast computertomography (NCCT), cardiac myxoma, intracerebral hemorrhage (ICH)Editorial on the Research TopicPushing the boundaries in acute ischemic stroke treatmentOver the past few decades, there have been significant advancements in the treatmentof acute ischemic stroke. Intravenous thrombolysis and mechanical thrombectomy havebecome established procedures, and the time window for treatment has been extended.However, it is important to note that still only a small percentage, ∼10–20%, of all ischemicstroke patients are eligible for acute reperfusion treatment. This situation gives rise to variouschallenges. Patient selection and treatment selection remain complex tasks, as many patientsarrive at the hospital too late for intervention, the availability of multimodal neuroimagingmay be limited, and adverse events can hinder the effectiveness of treatment.Concerning the limited availability of multimodal imaging to select ischemic strokepatients for intravenous thrombolysis (IVT) in the extended time window, Emde et al.performed a review about existing data to support IVT treatment based on non-contrastCT (NCCT). This is of interest, as multimodal imaging may not be widely available in ruralareas as well as in low- or middle-income countries and primary stroke centers (1). Mainlybased on the TRUST-CT registry (2) and the TWIST trial (using tenecteplase) (3) currentdata suggests that, particularly for patients with wake-up strokes and those presenting within6 h of symptom onset, IVT is safe and could lead to favorable functional outcomes (2).However, favorable outcomes could not be shown if tenecteplase is used (3). In cases wherethere is a high Alberta Stroke Program Early CT Score (ASPECTS) and a clinical mismatchbetween symptom severity and radiological findings, treatment may be considered, evenin the absence of advanced imaging. However, since randomized controlled data is scarce,thrombolysis should be evaluated with care especially if tenecteplase is used, ASPECTS islow and time since onset comes close to or exceeds 6 h. Regardingmechanical thrombectomyin the late time window, treatment decisions based on NCCT imaging (ASPECTS>5) alsoappear to be safe and effective (4), and this is more commonly used in clinical practice whenadvanced imaging is not available (1).However, if there is an indication to perform mechanical thrombectomy, a highlyspecialized infrastructure is needed to get the patient to the treatment (-site) in time. Here,Riegler et al. examined the time-to-care metrics in an established tele-stroke-network innorthern Germany. Their study presents the findings from an analysis of 92 stroke patientseligible for mechanical thrombectomy (MT) who initially received treatment at a hospitalFrontiers inNeurology 01 frontiersin.orgVolbers et al. 10.3389/fneur.2023.1245890without MT capabilities and were subsequently transferred toa comprehensive stroke center (CSC). The authors comparedpatients initially admitted to rural hospitals within a telestrokenetwork with those presenting at metropolitan primary strokecenters. They found that the administration of intravenousthrombolysis (IVT) was significantly faster in metropolitanhospitals (37 vs. 65min, p < 0.01). This is not surprising,since metropolitan hospitals do not require additional tele-videoconsultation before thrombolysis. However, the delay from arrivalat the CSC to groin puncture was shorter for patients transferredfrom rural telestroke centers (42 vs. 60min, p < 0.01), while theoverall treatment time from arrival at the primary hospital togroin puncture did not significantly differ between the two groups(210 vs. 208min, p = 0.96). These results again demonstrate theimportance and effectiveness of telestroke networks in treatingstroke patients in rural areas, especially if a transfer to a strokecenter is needed. However, it requires optimal organization, clearand rigorous standard operating procedures (SOPs), strict qualitymonitoring, and regular, high quality training to ensure highprocess quality.Further publications of our Research Topic dealt with areasthat have been less well elucidated so far including safetyand efficacy of mechanical thrombectomy (MT) in large vesselocclusions (LVO) associated with cardiac myxoma and the naturalhistory of carotid-artery free-floating thrombus. In their caseseries including eleven patients with left-atrium cardiac myxomaassociated LVO treated with MT, Rao et al. found a favorableoutcome rate of 60% at 3 months. Interestingly, they performed ahistopathological examination of the retrieved thrombus materialof five patients and found myxoma components within thethrombus. In this context, it is reassuring and encouragingthat, even if thrombus formation may differ from “classical”embolic thrombi, mechanical thrombectomy is an effective andsafe treatment option in those patients. Müller et al. found ahigh recurrence rate of ischemic stroke (20%) in patients withcarotid-artery free-floating thrombus within the first week afterthe index event. While those results confirm the general clinicalexperience, the optimal management of those patients urgentlyneeds to be elucidated.Altenbernd et al. assessed the sensitivity and specificity of CT-angiography (CTA) compared to digital subtraction angiography(DSA) to further push the diagnostic boundaries in patientswith intracerebral hemorrhage (ICH). Although DSA remains thepreferred diagnostic modality for detecting macrovascular causesof ICH, CTA can effectively investigate most cases of lobar ICHand identify the underlying cause of bleeding. The authors observedfalse-negative findings in CTA only in 3/125 patients (2%; twoarteriovenous malformations (AVMs) measuring <2 cm and onesmall dural fistula). Thus, further research may focus on theselection of those patients with negative CTA results who maybenefit from an additional DSA.Finally, we included a study protocol by Staszewski et al. fora prospective, open label, single-center study assessing the efficacyof Cerebrolysin treatment as an add-on therapy to mechanicalthrombectomy. Cerebrolysin is associated with cytoprotectiveeffects by promoting cellular survival while inhibiting glutamateexcitotoxicity, free radical formation, and pro-inflammatorymediators such as TNF-α, IL-1β and IL-6. The authors representthe hypothesis that the addition of Cerebrolysin within 8 h ofstroke onset, in carefully selected patients based on clinicaland radiological criteria (moderate to severe stroke, smallischemic core and good collateral status), can enhance theeffectiveness of thrombectomy. Suggested mechanisms include theinitiation of cytoprotective mechanisms and the prevention ofreperfusion injury.We congratulate all contributors for their outstanding andforward-looking work and hope that our Research Topic willcontribute to improving the treatment and care of patients withischemic stroke or intracerebral hemorrhage.Author contributionsBV, BK, and DS made substantial contributions to theconception or design of the work, provide approval for publicationof the content, and agreed to be accountable for all aspects of thework in ensuring that questions related to the accuracy or integrityof any part of the work are appropriately investigated and resolved.BV drafted the manuscript. BK and DS revised it critically forimportant intellectual content. All authors contributed to the articleand approved the submitted version.Conflict of interestThe authors declare that the research was conducted in theabsence of any commercial or financial relationships that could beconstrued as a potential conflict of interest.Publisher’s noteAll claims expressed in this article are solely those of theauthors and do not necessarily represent those of their affiliatedorganizations, or those of the publisher, the editors and thereviewers. Any product that may be evaluated in this article, orclaim that may be made by its manufacturer, is not guaranteed orendorsed by the publisher.References1. Nguyen TN, Klein P, Berberich A, Nagel S, Abdalkader M, Herning A, et al. Latewindow imaging selection for endovascular therapy of large vessel occlusion stroke: aninternational survey. Stroke: Vascular and Interventional Neurology. (2023) 3:e000595.doi: 10.1161/SVIN.122.0005952. Sykora M, Kellert L, Michel P, Eskandari A, Feil K, Rémi J, et al. Thrombolysisin stroke with unknown onset based on non-contrast computerized tomography(TRUST CT). J Am Heart Associat. (2020) 9:e014265. doi: 10.1161/JAHA.119.014265Frontiers inNeurology 02 frontiersin.orgVolbers et al. 10.3389/fneur.2023.12458903. Roaldsen MB, Eltoft A, Wilsgaard T, Christensen H, Engelter ST, IndredavikB, et al. Safety and efficacy of tenecteplase in patients with wake-up strokeassessed by non-contrast CT (TWIST): a multicentre, open-label, randomisedcontrolled trial. Lancet Neurol. (2023) 22:117–26. doi: 10.1016/S1474-4422(22)00484-74. Dhillon PS, Butt W, Jovin TG, Podlasek A, McConachie N, Lenthall R,et al. Endovascular thrombectomy versus best medical therapy for late presentationacute ischemic stroke with proximal large-vessel occlusion selected on the basis ofnoncontrast computed tomography: a retrospective analysis of 2 prospectively definedcohorts. Stroke. (2023) 3:e000686. doi: 10.1161/SVIN.122.000686Frontiers inNeurology 03 frontiersin.org

Editorial: Pushing the boundaries in acute ischemic stroke treatment

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Editorial: Pushing the boundaries in acute ischemic stroke treatment

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