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Association of Dynamic Trajectories of Time-Series Data and Life-Threatening Mass Effect in Large Middle Cerebral Artery Stroke

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Abstract

Background

Life-threatening, space-occupying mass effect due to cerebral edema and/or hemorrhagic transformation is an early complication of patients with middle cerebral artery stroke. Little is known about longitudinal trajectories of laboratory and vital signs leading up to radiographic and clinical deterioration related to this mass effect.

Methods

We curated a retrospective data set of 635 patients with large middle cerebral artery stroke totaling 95,463 data points for 10 longitudinal covariates and 40 time-independent covariates. We assessed trajectories of the 10 longitudinal variables during the 72 h preceding three outcomes representative of life-threatening mass effect: midline shift ≥ 5 mm, pineal gland shift (PGS) > 4 mm, and decompressive hemicraniectomy (DHC). We used a “backward-looking” trajectory approach. Patients were aligned based on outcome occurrence time and the trajectory of each variable was assessed before that outcome by accounting for cases and noncases, adjusting for confounders. We evaluated longitudinal trajectories with Cox proportional time-dependent regression.

Results

Of 635 patients, 49.0% were female, and the mean age was 69 years. Thirty five percent of patients had midline shift ≥ 5 mm, 24.3% of patients had PGS > 4 mm, and 10.7% of patients underwent DHC. Backward-looking trajectories showed mild increases in white blood cell count (10–11 K/UL within 72 h), temperature (up to half a degree within 24 h), and sodium levels (1–3 mEq/L within 24 h) before the three outcomes of interest. We also observed a decrease in heart rate (75–65 beats per minute) 24 h before DHC. We found a significant association between increased white blood cell count with PGS > 4 mm (hazard ratio 1.05, p value 0.007).

Conclusions

Longitudinal profiling adjusted for confounders demonstrated that white blood cell count, temperature, and sodium levels appear to increase before radiographic and clinical indicators of space-occupying mass effect. These findings will inform the development of multivariable dynamic risk models to aid prediction of life-threatening, space-occupying mass effect.

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Funding

CJO receives support from NIH/NINDS K23NS116033; American Heart Association 23CDA1041762. EJB receives support from R01HL092577; American Heart Association AF AHA 18SFRN34110082. LT receives support from AHA 18SFRN34150007. DMG receives support from R01 NS102574. SMS receives support from RO1 EY024019.

Author information

Authors and Affiliations

  1. Department of Neurology, Boston Medical Center, 1 Boston Medical Center PI, Boston, MA, 02118, USA

    Charlene J. Ong, Ivy So Yeon Kim, Jack Pohlmann, Yihan Zhang & David M. Greer

  2. Chobanian and Avedisian School of Medicine, Boston University School of Medicine, 85 E Concord St, Boston, MA, 02118, USA

    Charlene J. Ong, Yili Du, Leigh Ann Malinger & David M. Greer

  3. Department of Neurology, Brigham & Women’s Hospital, Harvard Medical School, 75 Francis St, Boston, MA, 02115, USA

    Charlene J. Ong, Stefanos Chatzidakis & Stelios M. Smirnakis

  4. Department of Epidemiology, Boston University School of Public Health, 715 Albany St, Boston, MA, 02118, USA

    Qiuxi Huang, Emelia J. Benjamin & Josée Dupuis

  5. Department of Cardiology, Boston Medical Center and Boston University Chobanian and Avedisian School of Medicine, 85 E Concord St, Boston, MA, 02118, USA

    Emelia J. Benjamin

  6. Department of Epidemiology, Biostatistics and Occupational Health, McGill University, 2001 McGill College, Montreal, QC, Canada

    Josée Dupuis

  7. Department of Neurology, Jamaica Plain Veterans Administration Medical Center, 150 S Huntington Ave, Boston, MA, 02130, USA

    Stelios M. Smirnakis

  8. Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, 800 Washington St, Boston, MA, 02111, USA

    Ludovic Trinquart

  9. Tufts Clinical and Translational Science Institute, Tufts University, 419 Boston Ave, Medford, MA, 02155, USA

    Ludovic Trinquart

  10. New York University Langone Hospital and NYU Grossman School of Medicine, 550 1St Ave, New York, NY, 10016, USA

    Benjamin Brush

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  1. Charlene J. Ong
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Contributions

CJO, QH, DMG, and SMS conceived the idea of the presented analyses and designed the overall study. JP, IK, and YZ organized and collected the patient data for analysis. IK, BB, CJO, SC, and LAM performed manual reviews of patient notes to extract various features such as stroke onset times, medications, procedures, and outcomes. BB developed algorithms for automated feature extraction from radiology reports. SC, BB, and CJO manually reviewed and radiographic images to measure swelling and determine radiographic outcomes. QH and JP performed statistical analysis, visualization, and interpretation. LT, EJB, and JD provided oversight and review of the statistical analysis. CJO and QH drafted the manuscript. QH, IK, YD, and LAM designed figures. SC, BB, LT, SMS, EJB, JD, and DMG helped with reviews and revisions. CJO provided overall study direction and critical review. All authors contributed to the article and approved the submitted version.

Corresponding author

Correspondence to Charlene J. Ong.

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Conflicts of interest

The authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or nonfinancial interest in the subject matter or materials discussed in this article.

Ethical Approval/Informed Consent

The study was approved to be conducted by the Mass General Brigham Institutional Review Board (2017P002564). All methods were performed in accordance with the relevant guidelines and regulations set forth by the institutional review board. Because of the retrospective nature of the study, the Mass General Brigham Institutional Review Board waived the need of obtaining informed consent.

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Ong, C.J., Huang, Q., Kim, I.S.Y. et al. Association of Dynamic Trajectories of Time-Series Data and Life-Threatening Mass Effect in Large Middle Cerebral Artery Stroke. Neurocrit Care (2024). https://doi.org/10.1007/s12028-024-02036-9

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