Redefining the Cerebral Ischemic Core-Penumbra-Oligemia Continuum

During acute ischemic stroke, cerebral tissue undergoes different stages of ischemic damage and evolves towards irreversible injury at a varying pace depending on local perfusion and metabolic factors. This complex ischemic pathological process represents a dynamic continuum that has been historically conceptualized as a binary ischemic core-penumbra model. Although this simplification has proven useful for explaining the evolution of tissue damage in acute stroke, important nuances with clinical implications might be underappreciated. In this review, we critically appraise the pathophysiology and conventional clinical concepts adopted to explain infarct evolution in the early phases of ischemic stroke. We discuss recent mounting evidence that challenges the traditional compartmentalization of the ischemic core, penumbra, and oligemia, calling for more nuanced pathophysiological tissue concepts. For example, clinical benefits and the harmful hemorrhagic transformation associated with reperfusion therapies are observed across a spectrum of core volumes, challenging the deterministic assumptions of the core-penumbra hypothesis. Automated image processing systems reinforce this simplification of stroke pathophysiology, leading to misinterpretation of the range of truth in human imaging. We propose a modified definition of the core-penumbra-oligemia continuum that includes 6 levels of ischemic progression and their corresponding clinical implications: (1) benign oligemia, (2) vulnerable oligemia, (3) durable penumbra, (4) critical penumbra, (5) nonleaky core, and (6) leaky core. This more granular classification could better reflect the continuum of pathological ischemic changes and vulnerability. The proposed 6 levels can provide a framework for future neuroimaging efforts to better understand tissue fate and infarct evolution in ischemic stroke, ultimately informing treatment decision-making and refining targeting for new therapeutic approaches.

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Publication Details

Journal
Stroke
Published
2026-05-08
DOI
https://doi.org/10.1161/strokeaha.126.055331
Primary Topic
Acute Ischemic Stroke Management
Type
article
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article

Redefining the Cerebral Ischemic Core-Penumbra-Oligemia Continuum

Umberto Pensato, B Kim, M Almekhlafi, Diego Gutiérrez Vásquez et al.
Stroke
Acute Ischemic Stroke Management
article

Redefining the Cerebral Ischemic Core-Penumbra-Oligemia Continuum

Umberto Pensato, B Kim, M Almekhlafi, Diego Gutiérrez Vásquez, Giorgio Busto, Jean‐Marc Olivot, Johanna M. Ospel, Tyler Henry, Felix Ng, Mark W. Parsons, Aravind Ganesh, Bijoy K. Menon, Bruce C.V. Campbell, Gabriel Broocks, Andrew M. Demchuk, Maarten G. Lansberg, Andrea Zini, Gregory W. Albers, Vignan Yogendrakumar, Vivek Yedavalli, Enrico Fainardi, Nishita Singh, Thanh N. Nguyen, Michael D. Hill
article en

Abstract

During acute ischemic stroke, cerebral tissue undergoes different stages of ischemic damage and evolves towards irreversible injury at a varying pace depending on local perfusion and metabolic factors. This complex ischemic pathological process represents a dynamic continuum that has been historically conceptualized as a binary ischemic core-penumbra model. Although this simplification has proven useful for explaining the evolution of tissue damage in acute stroke, important nuances with clinical implications might be underappreciated. In this review, we critically appraise the pathophysiology and conventional clinical concepts adopted to explain infarct evolution in the early phases of ischemic stroke. We discuss recent mounting evidence that challenges the traditional compartmentalization of the ischemic core, penumbra, and oligemia, calling for more nuanced pathophysiological tissue concepts. For example, clinical benefits and the harmful hemorrhagic transformation associated with reperfusion therapies are observed across a spectrum of core volumes, challenging the deterministic assumptions of the core-penumbra hypothesis. Automated image processing systems reinforce this simplification of stroke pathophysiology, leading to misinterpretation of the range of truth in human imaging. We propose a modified definition of the core-penumbra-oligemia continuum that includes 6 levels of ischemic progression and their corresponding clinical implications: (1) benign oligemia, (2) vulnerable oligemia, (3) durable penumbra, (4) critical penumbra, (5) nonleaky core, and (6) leaky core. This more granular classification could better reflect the continuum of pathological ischemic changes and vulnerability. The proposed 6 levels can provide a framework for future neuroimaging efforts to better understand tissue fate and infarct evolution in ischemic stroke, ultimately informing treatment decision-making and refining targeting for new therapeutic approaches.

Stroke
Boston Medical Center (US), Dalhousie University (CA), The Royal Melbourne Hospital (AU), Humanitas University (IT), Johns Hopkins University (US), Universität Hamburg (DE), Pontificia Universidad Católica de Chile (CL), University of Calgary (CA), Ottawa Hospital (CA), Seoul National University Bundang Hospital (KR), MSH Medical School Hamburg – University of Applied Sciences and Medical University (DE), Helios Hospital Schwerin (DE), University Medical Center Hamburg-Eppendorf (DE), Azienda Ospedaliero-Universitaria Careggi (IT), Istituto delle Scienze Neurologiche di Bologna (IT), Ingham Institute (AU), Hôpital Paule de Viguier (FR), IRCCS Humanitas Research Hospital (IT), University of Florence (IT), University of Manitoba (CA), Stanford University (US)
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Acute Ischemic Stroke Management
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