Cytotoxic Edema and Intra-parenchymal Hemorrhage: A Mediated Pathway to Mortality and Functional Outcome in Cerebral Venous Sinus Thrombosis- A sub-analysis of the CLOT-VENUS Registry

Nashwa Abdelhakim; Milagros Galecio-Castillo; Piyush Kalakoti; Leonardo Cruz-Criollo; Aaron Rodriguez-Calienes; Anderson Brito; Jorge Cespedes; Amir Shaban; Anish Venkatesan; Vanessa Cano Nigenda; Andres Alberto Mercado Pompa; Nicholas M. Mohr; Adrian Pereda-Castillo; Kevin Enríquez Peregrino; Hector Valdez Ruvalcaba; Brian J. Smith; James C. Torner; Miguel A. Barboza; Antonio Arauz; Santiago Ortega-Gutierrez

doi:10.1007/s12975-026-01426-9

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Cytotoxic Edema and Intra-parenchymal Hemorrhage: A Mediated Pathway to Mortality and Functional Outcome in Cerebral Venous Sinus Thrombosis- A sub-analysis of the CLOT-VENUS Registry

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Cytotoxic Edema and Intra-parenchymal Hemorrhage: A Mediated Pathway to Mortality and Functional Outcome in Cerebral Venous Sinus Thrombosis- A sub-analysis of the CLOT-VENUS Registry

Nashwa Abdelhakim, Milagros Galecio-Castillo, Piyush Kalakoti, Leonardo Cruz-Criollo, Aaron Rodriguez-Calienes, Anderson Brito, Jorge Cespedes, Amir Shaban, Anish Venkatesan, Vanessa Cano Nigenda, …

Translational stroke research, Vol.17(2), 41

04/14/2026

DOI: 10.1007/s12975-026-01426-9

PMID: 41975110

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Abstract

Cytotoxic edema (CE) is a radiographic marker of early tissue injury in cerebral venous thrombosis (CVT) associated with poor outcomes, yet its mechanistic pathway remains unclear. We investigated whether intraparenchymal hemorrhage (IPH) mediates the association between CE and outcomes. We conducted a retrospective cohort study using the multicenter CLOT-VENUS registry, including acute CVT patients treated at two Comprehensive Stroke Centers in the USA and Mexico (2004–2024). CE was defined as hyperintensities around IPH or venous infarct with DWI restricted diffusion and corresponding low ADC, confirming true restricted diffusion. IPH was defined as hemorrhagic transformation of venous infarction or intracerebral hemorrhage on GRE MRI and/or NCCT. Mediation analyses assessed whether IPH mediated CE associations with in-hospital mortality and functional outcomes. Among 394 patients (mean age 42.7 years; 65.5% female), 128 (32.5%) demonstrated CE and 111(30.2%) IPH. CE was associated with in-hospital mortality (aOR 2.63, 95% CI 1.01–7.12) and poor 6-month mRS (aOR 1.71, 95% CI 1.06–2.74). CE was associated with IPH, which in turn was associated with mortality (aOR 8.73, 95% CI 2.93–30.45) and poor mRS (aOR 1.96, 95% CI 1.18–3.25). Adjustment for IPH rendered the CE-outcome associations non-significant. IPH accounted for 76.8% of CE’s effect on mortality and 83.8% on 6-month mRS. Our findings suggest that IPH likely mediates the effect of CE on outcomes in CVT. Although the temporal sequence could not be confirmed, the results underscore the value of early CE detection for timely intervention.

Cerebral venous thrombosis

Cytotoxic edema

CVT

Intraparenchymal Hemorrhage

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Title: Subtitle: Cytotoxic Edema and Intra-parenchymal Hemorrhage: A Mediated Pathway to Mortality and Functional Outcome in Cerebral Venous Sinus Thrombosis- A sub-analysis of the CLOT-VENUS Registry
Creators: Nashwa Abdelhakim - University of Iowa
Milagros Galecio-Castillo - University of Iowa Health Care
Piyush Kalakoti - University of Iowa
Leonardo Cruz-Criollo - University of Iowa
Aaron Rodriguez-Calienes - University of Iowa
Anderson Brito - University of Iowa
Jorge Cespedes - University of Iowa, Neurology
Amir Shaban - University of Iowa
Anish Venkatesan - University of Iowa
Vanessa Cano Nigenda - Instituto Nacional de Neurología y Neurocirugía
Andres Alberto Mercado Pompa - México City, México
Nicholas M. Mohr - University of Iowa
Adrian Pereda-Castillo - Instituto Nacional de Neurología y Neurocirugía
Kevin Enríquez Peregrino - Instituto Nacional de Neurología y Neurocirugía
Hector Valdez Ruvalcaba - Instituto Nacional de Neurología y Neurocirugía
Brian J. Smith - University of Iowa
James C. Torner - University of Iowa
Miguel A. Barboza - Rafael Advanced Defense Systems (Israel)
Antonio Arauz - Instituto Nacional de Neurología y Neurocirugía
Santiago Ortega-Gutierrez - University of Iowa Health Care
Resource Type: Journal article
Publication Details: Translational stroke research, Vol.17(2), 41
DOI: 10.1007/s12975-026-01426-9
PMID: 41975110
NLM abbreviation: Transl Stroke Res
ISSN: 1868-4483
eISSN: 1868-601X
Publisher: Springer Nature
Grant note: the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH): R03NS126804-01A1
This research was supported by the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH) under award number R03NS126804-01A1.
Language: English
Date published: 04/14/2026
Academic Unit: Neurology; Radiology; Epidemiology; Emergency Medicine; Iowa Neuroscience Institute; Biostatistics; Surgery; Anesthesia; Injury Prevention Research Center; Neurosurgery; Holden Comprehensive Cancer Center
Record Identifier: 9985153400002771

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