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CSF-Based Volumetric Imaging Biomarkers Highlight Incidence and Risk Factors for Cerebral Edema After Ischemic Stroke

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Abstract

Background

Cerebral edema has primarily been studied using midline shift or clinical deterioration as end points, which only captures the severe and delayed manifestations of a process affecting many patients with stroke. Quantitative imaging biomarkers that measure edema severity across the entire spectrum could improve its early detection, as well as identify relevant mediators of this important stroke complication.

Methods

We applied an automated image analysis pipeline to measure the displacement of cerebrospinal fluid (ΔCSF) and the ratio of lesional versus contralateral hemispheric cerebrospinal fluid (CSF) volume (CSF ratio) in a cohort of 935 patients with hemispheric stroke with follow-up computed tomography scans taken a median of 26 h (interquartile range 24–31) after stroke onset. We determined diagnostic thresholds based on comparison to those without any visible edema. We modeled baseline clinical and radiographic variables against each edema biomarker and assessed how each biomarker was associated with stroke outcome (modified Rankin Scale at 90 days).

Results

The displacement of CSF and CSF ratio were correlated with midline shift (r = 0.52 and − 0.74, p < 0.0001) but exhibited broader ranges. A ΔCSF of greater than 14% or a CSF ratio below 0.90 identified those with visible edema: more than half of the patients with stroke met these criteria, compared with only 14% who had midline shift at 24 h. Predictors of edema across all biomarkers included a higher National Institutes of Health Stroke Scale score, a lower Alberta Stroke Program Early CT score, and lower baseline CSF volume. A history of hypertension and diabetes (but not acute hyperglycemia) predicted greater ΔCSF but not midline shift. Both ΔCSF and a lower CSF ratio were associated with worse outcome, adjusting for age, National Institutes of Health Stroke Scale score, and Alberta Stroke Program Early CT score (odds ratio 1.7, 95% confidence interval 1.3–2.2 per 21% ΔCSF).

Conclusions

Cerebral edema can be measured in a majority of patients with stroke on follow-up computed tomography using volumetric biomarkers evaluating CSF shifts, including in many without visible midline shift. Edema formation is influenced by clinical and radiographic stroke severity but also by chronic vascular risk factors and contributes to worse stroke outcomes.

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Author information

Authors and Affiliations

  1. Department of Neurology, Washington University School of Medicine, 660 S Euclid Avenue, Campus Box 8111, St. Louis, MO, USA

    Quoc Bui, Atul Kumar, Yasheng Chen, Ali Hamzehloo, Jin-Moo Lee & Rajat Dhar

  2. Department of Emergency Medicine, Washington University School of Medicine, St. Louis, MO, USA

    Laura Heitsch

  3. Department of Neurology, Jagiellonian University Medical College, Krakow, Poland

    Agnieszka Slowik

  4. Department of Neurology, Helsinki University Hospital, Helsinki, Finland

    Daniel Strbian

Authors
  1. Quoc Bui
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  2. Atul Kumar
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  3. Yasheng Chen
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  4. Ali Hamzehloo
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Contributions

RD and JML conceived of the study. QB carried out the primary analyses. Data were collected by AH, AK, YC, and LH. Additional data were provided and reviewed by AS and DS. RD and QB drafted the manuscript, tables, and figures. All authors reviewed and edited the manuscript and approved the final version.

Corresponding author

Correspondence to Rajat Dhar.

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Conflicts of interest

JML reports grants from Biogen and personal fees from Regenera outside the submitted work. RD reports consulting fees from Marinus Pharma.

Ethical Approval/Informed Consent

All research was conducted under approval of the institutional ethics review board, and all study participants provided informed consent for data collection.

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Bui, Q., Kumar, A., Chen, Y. et al. CSF-Based Volumetric Imaging Biomarkers Highlight Incidence and Risk Factors for Cerebral Edema After Ischemic Stroke. Neurocrit Care 40, 303–313 (2024). https://doi.org/10.1007/s12028-023-01742-0

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