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Predicting Clinical Outcomes 7–10 Years after Severe Traumatic Brain Injury: Exploring the Prognostic Utility of the IMPACT Lab Model and Cerebrospinal Fluid UCH-L1 and MAP-2

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Abstract

Background

Severe traumatic brain injury (TBI) is a major contributor to disability and mortality in the industrialized world. Outcomes of severe TBI are profoundly heterogeneous, complicating outcome prognostication. Several prognostic models have been validated for acute prediction of 6-month global outcomes following TBI (e.g., morbidity/mortality). In this preliminary observational prognostic study, we assess the utility of the International Mission on Prognosis and Analysis of Clinical Trials in TBI (IMPACT) Lab model in predicting longer term global and cognitive outcomes (7–10 years post injury) and the extent to which cerebrospinal fluid (CSF) biomarkers enhance outcome prediction.

Methods

Very long-term global outcome was assessed in a total of 59 participants (41 of whom did not survive their injuries) using the Glasgow Outcome Scale-Extended and Disability Rating Scale. More detailed outcome information regarding cognitive functioning in daily life was collected from 18 participants surviving to 7–10 years post injury using the Cognitive Subscale of the Functional Independence Measure. A subset (n = 10) of these participants also completed performance-based cognitive testing (Digit Span Test) by telephone. The IMPACT lab model was applied to determine its prognostic value in relation to very long-term outcomes as well as the additive effects of acute CSF ubiquitin C-terminal hydrolase-L1 (UCH-L1) and microtubule associated protein 2 (MAP-2) concentrations.

Results

The IMPACT lab model discriminated favorable versus unfavorable 7- to 10-year outcome with an area under the receiver operating characteristic curve of 0.80. Higher IMPACT lab model risk scores predicted greater extent of very long-term morbidity (β = 0.488 p = 0.000) as well as reduced cognitive independence (β =  − 0.515, p = 0.034). Acute elevations in UCH-L1 levels were also predictive of lesser independence in cognitive activities in daily life at very long-term follow-up (β = 0.286, p = 0.048). Addition of two CSF biomarkers significantly improved prediction of very long-term neuropsychological performance among survivors, with the overall model (including IMPACT lab score, UCH-L1, and MAP-2) explaining 89.6% of variance in cognitive performance 7–10 years post injury (p = 0.008). Higher acute UCH-L1 concentrations were predictive of poorer cognitive performance (β =  − 0.496, p = 0.029), whereas higher acute MAP-2 concentrations demonstrated a strong cognitive protective effect (β = 0.679, p = 0.010).

Conclusions

Although preliminary, results suggest that existing prognostic models, including models with incorporation of CSF markers, may be applied to predict outcome of severe TBI years after injury. Continued research is needed examining early predictors of longer-term outcomes following TBI to identify potential targets for clinical trials that could impact long-ranging functional and cognitive outcomes.

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Funding

This study was partially funded by the National Institutes of Health (Grant R01NS052831-05; Grant 5T32HD007414-27).

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Authors and Affiliations

  1. Brain Injury Clinical Research Center, Kennedy Krieger Institute, Baltimore, MD, USA

    Adrian M. Svingos

  2. Department of Physical Medicine and Rehabilitation, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Adrian M. Svingos

  3. Departments of Anesthesiology, Neurosurgery, and Neuroscience, University of Florida, Gainesville, FL, USA

    Steven A. Robicsek

  4. Banyan Biomarkers Inc, Gainesville, FL, USA

    Ronald L. Hayes

  5. Department of Emergency Medicine, University of Florida, Gainesville, FL, USA

    Kevin K. Wang

  6. Brain Rehabilitation Research Center, Malcom Randall Department of Veterans Affairs Medical Center, Gainesville, FL, USA

    Kevin K. Wang & Russell M. Bauer

  7. Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA

    Claudia S. Robertson

  8. Pharmacotherapy and Outcomes Science and Neurosurgery, Virginia Commonwealth University Medical College of Virginia Campus, Richmond, VA, USA

    Gretchen M. Brophy

  9. Department of Emergency Medicine, Orlando Health Orlando Regional Medical Center, Orlando, FL, USA

    Linda Papa

  10. Department of Anesthesiology, Perioperative Medicine and Pain Management, University of Miami Miller School of Medicine, Miami, FL, USA

    Andrea Gabrielli

  11. Department of Psychology, University of Houston, Houston, TX, USA

    H. Julia Hannay

  12. Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, USA

    Russell M. Bauer & Shelley C. Heaton

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  1. Adrian M. Svingos
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Contributions

A.M.S. contributed substantially to the conception, design, data acquisition, analyses, interpretation of data, and drafting/revising of the work. S.C.H. and R.M.B. substantially contributed to the conception, design, analyses, and drafting/revising of the work. S.A.R. contributed substantially to the conception, data acquisition, and drafting/revising of the work. R.L.H., K.K.W., C.S.R., L.P., and H.J.H. contributed significantly to the conception, design, and drafting/revision of the work. G.M.B. and A.G. contributed substantially to data acquisition and drafting/revising of the work. The final manuscript was approved by all authors.

Corresponding author

Correspondence to Shelley C. Heaton.

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RLH and KKW have equity in and receive compensation from Banyan Biomarkers, Inc. The other authors do not have any conflicts of interest to disclose.

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All study procedures were approved by the institutional review board.

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Svingos, A.M., Robicsek, S.A., Hayes, R.L. et al. Predicting Clinical Outcomes 7–10 Years after Severe Traumatic Brain Injury: Exploring the Prognostic Utility of the IMPACT Lab Model and Cerebrospinal Fluid UCH-L1 and MAP-2. Neurocrit Care 37, 172–183 (2022). https://doi.org/10.1007/s12028-022-01461-y

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