Cerebral edema in intracerebral hemorrhage: pathogenesis, natural history and potential treatments from translation to clinical trials

Kailash Krishnan; Paula B.  Campos; Thanh N. Nguyen; Wei Tan; Siang L.  Chan; Jason P.  Appleton; Zhe Kang  Law; Milo  Hollingworth; Matthew  Kirkman; Timothy J.   England; Christine Roffe; Mary Macleod; Jesse Dawson; Ulvi  Bayraktutan; David J. Werring; Nikola Sprigg; Philip M  Bath

doi:10.3389/fstro.2023.1256664

Cerebral edema in intracerebral hemorrhage: pathogenesis, natural history and potential treatments from translation to clinical trials

Kailash Krishnan^* (Corresponding Author), Paula B. Campos, Thanh N. Nguyen, Wei Tan, Siang L. Chan, Jason P. Appleton, Zhe Kang Law, Milo Hollingworth, Matthew Kirkman, Timothy J. England, Christine Roffe, Mary Macleod, Jesse Dawson, Ulvi Bayraktutan, David J. Werring, Nikola Sprigg, Philip M Bath

^*Corresponding author for this work

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Abstract

Acute Intracerebral Hemorrhage (ICH) is the most devastating stroke-subtype and is associated with significant morbidity and mortality. Poor prognosis is associated with primary brain injury from the presenting hematoma and despite advances in clinical trials of evacuation or reducing expansion, management is largely limited to supportive care and secondary prevention. Recent research has led to better understanding of the pathophysiology of cerebral edema surrounding the hematoma (perihematomal edema), identification of treatment targets and potential interventions. Some therapies have progressed to testing in phase 2 and 3 clinical trials while novel agents are in development. This review focuses on the pathogenesis of perihematomal edema, natural history, and summarizes the results of potential interventions including preclinical and clinical studies. This review also lists the gaps in current evidence and suggests directions for future trials of perihematomal edema which could potentially change clinical practice.

Original language	English
Article number	125666
Number of pages	20
Journal	Frontiers in Stroke
Volume	2
DOIs	https://doi.org/10.3389/fstro.2023.1256664
Publication status	Published - 29 Sept 2023

Bibliographical note

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.

Keywords

intracerebral hemorrhag
cerebral edem
translation
Clinical trial
Treatment
pathophysiology

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© 2023 Krishnan, Campos, Nguyen, Tan, Chan, Appleton, Law, Hollingworth, Kirkman, England, Roffe, Macleod, Dawson, Bayraktutan, Werring, Sprigg and Bath. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Final published version, 517 KBLicence: CC BY

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Krishnan, K., Campos, P. B., Nguyen, T. N., Tan, W., Chan, S. L., Appleton, J. P., Law, Z. K., Hollingworth, M., Kirkman, M., England, T. J., Roffe, C., Macleod, M., Dawson, J., Bayraktutan, U., Werring, D. J., Sprigg, N., & Bath, P. M. (2023). Cerebral edema in intracerebral hemorrhage: pathogenesis, natural history and potential treatments from translation to clinical trials. Frontiers in Stroke, 2, Article 125666. https://doi.org/10.3389/fstro.2023.1256664

Krishnan, K, Campos, PB, Nguyen, TN, Tan, W, Chan, SL, Appleton, JP, Law, ZK, Hollingworth, M, Kirkman, M, England, TJ, Roffe, C, Macleod, M, Dawson, J, Bayraktutan, U, Werring, DJ, Sprigg, N & Bath, PM 2023, 'Cerebral edema in intracerebral hemorrhage: pathogenesis, natural history and potential treatments from translation to clinical trials', Frontiers in Stroke, vol. 2, 125666. https://doi.org/10.3389/fstro.2023.1256664

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abstract = "Acute Intracerebral Hemorrhage (ICH) is the most devastating stroke-subtype and is associated with significant morbidity and mortality. Poor prognosis is associated with primary brain injury from the presenting hematoma and despite advances in clinical trials of evacuation or reducing expansion, management is largely limited to supportive care and secondary prevention. Recent research has led to better understanding of the pathophysiology of cerebral edema surrounding the hematoma (perihematomal edema), identification of treatment targets and potential interventions. Some therapies have progressed to testing in phase 2 and 3 clinical trials while novel agents are in development. This review focuses on the pathogenesis of perihematomal edema, natural history, and summarizes the results of potential interventions including preclinical and clinical studies. This review also lists the gaps in current evidence and suggests directions for future trials of perihematomal edema which could potentially change clinical practice.",

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AU - Dawson, Jesse

AU - Bayraktutan, Ulvi

AU - Werring, David J.

AU - Sprigg, Nikola

AU - Bath, Philip M

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AB - Acute Intracerebral Hemorrhage (ICH) is the most devastating stroke-subtype and is associated with significant morbidity and mortality. Poor prognosis is associated with primary brain injury from the presenting hematoma and despite advances in clinical trials of evacuation or reducing expansion, management is largely limited to supportive care and secondary prevention. Recent research has led to better understanding of the pathophysiology of cerebral edema surrounding the hematoma (perihematomal edema), identification of treatment targets and potential interventions. Some therapies have progressed to testing in phase 2 and 3 clinical trials while novel agents are in development. This review focuses on the pathogenesis of perihematomal edema, natural history, and summarizes the results of potential interventions including preclinical and clinical studies. This review also lists the gaps in current evidence and suggests directions for future trials of perihematomal edema which could potentially change clinical practice.

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JF - Frontiers in Stroke

M1 - 125666

ER -

Cerebral edema in intracerebral hemorrhage: pathogenesis, natural history and potential treatments from translation to clinical trials

Abstract

Bibliographical note

Keywords

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