Preliminary Evaluation of the Scandinavian Guidelines for Initial Management of Minimal, Mild, and Moderate Head Injuries with Glial Fibrillary Acidic Protein

Mira Keski-Pukkila, Justin E. Karr, Jussi P. Posti, Ksenia Berghem, Anna Kerttu Kotilainen, Kaj Blennow, Henrik Zetterberg, Grant L. Iverson, Teemu M. Luoto

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Glial fibrillary acidic protein (GFAP) has become the most promising biomarker for detecting traumatic abnormalities on head computed tomography (CT) in patients with traumatic brain injury (TBI), but most studies have not addressed the potential added value of combining the biomarker with clinical variables that confer risk for intracranial injuries. The Scandinavian Guidelines for Initial Management of Minimal, Mild, and Moderate Head Injuries in Adults were the first clinical decision rules in the field with an incorporated biomarker, the S100 astroglial calcium-binding protein B (S100B), which is used in the Mild (Low Risk) group defined by the guidelines. Our aim was to evaluate the performance of the guidelines when S100B was substituted with GFAP. The sample (N = 296) was recruited from the Tampere University Hospital’s emergency department between November 2015 and November 2016, and there were 49 patients with available GFAP results who were stratified in the Mild (Low Risk) group (thus patients undergoing biomarker triaging). A previously reported cutoff of plasma GFAP ‡140 pg/mL was used. Within the Mild (Low Risk) group (n = 49), GFAP sensitivity (with 95% confidence intervals in parentheses) for detecting traumatic CT abnormalities was 1.0 (0.40–1.00), specificity 0.34 (0.19–0.53), the negative predictive value (NPV) 1.0 (0.68–1.00), and the positive predictive value (PPV) 0.16 (0.05–0.37). The sensitivity and specificity of the modified guidelines with GFAP, when applied to all imaged patients (n = 197) in the whole sample, were 0.94 (0.77–0.99) and 0.20 (0.15–0.28), respectively. NPV was 0.94 (0.80–0.99) and PPV 0.18 (0.13–0.25). In the Mild (Low Risk) group, none of the patients with GFAP results below 140 pg/mL had traumatic abnormalities on their head CT. These findings were derived from a small patient subgroup. Future researchers should replicate these findings in larger samples and assess whether GFAP has added or comparable value to S100B in acute TBI management.

Original languageEnglish
Pages (from-to)50-60
Number of pages11
JournalNeurotrauma Reports
Volume5
Issue number1
DOIs
StatePublished - Jan 1 2024

Bibliographical note

Publisher Copyright:
© Mira Keski-Pukkila et al., 2024.

Funding

Dr. Grant Iverson serves as a scientific advisor for NanoDx™ (formerly BioDirection, Inc.), Sway Operations, LLC, and Highmark, Inc. He has a clinical and consulting practice in forensic neuropsychology, including expert testimony, involving persons who have sustained mTBIs. He acknowledges unrestricted philanthropic support from ImPACT Applications, Inc., the Mooney-Reed Charitable Foundation, the National Rugby League, and the Schoen Adams Research Institute at Spaulding Rehabilitation. The above entities were not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication. Dr. Posti has received speaker's fees from Orion corporation and the Finnish Medical Association and a travel grant from Stryker Corporation. Dr. Henrik Zetterberg has served at scientific advisory boards and/or as a consultant for AbbVie, Acumen, Alector, Alzinova, ALZPath, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave; has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, Biogen, and Roche; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). The study was financially supported by the Finnish State Research Funding and the Finnish Medical Society Duodecim. Dr. Luoto and Dr. Posti have received funding from Government’s Special Financial Transfer tied to academic research in Health Sciences (Finland). Dr. Posti and Dr. Luoto are funded by the Academy of Finland (Grant 17379 to Dr. Posti and Grant 349758 to Dr. Luoto). Dr. Posti, Dr. Luoto, and Dr. Keski-Pukkila have received grants from the Maire Taponen Foundation. Additionally, Dr. Luoto has received grants from the Finnish Brain Foundation and the Emil Aaltonen Foundation. Dr. Zetterberg is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2022-01018 and #2019-02397), the European Union’s Horizon Europe research and innovation programme under grant agreement No 101053962, Swedish State Support for Clinical Research (#ALFGBG-71320), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), the AD Strategic Fund and the Alzheimer’s Association (#ADSF-21-831376-C, #ADSF-21-831381-C, and #ADSF-21-831377-C), the Bluefield Project, the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2022-0270), the European Union’s Horizon 2020 research and innovation programme under the Marie Sk1odowska-Curie grant agreement No. 860197 (MIRIADE), the European Union Joint Programme–Neurodegenerative Disease Research (JPND2021-00694), the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, and the UK Dementia Research Institute at UCL (UKDRI-1003). The study was financially supported by the Finnish State Research Funding and the Finnish Medical Society Duodecim. Dr. Luoto and Dr. Posti have received funding from Government's Special Financial Transfer tied to academic research in Health Sciences (Finland). Dr. Posti and Dr. Luoto are funded by the Academy of Finland (Grant 17379 to Dr. Posti and Grant 349758 to Dr. Luoto). Dr. Posti, Dr. Luoto, and Dr. Keski-Pukkila have received grants from the Maire Taponen Foundation. Additionally, Dr. Luoto has received grants from the Finnish Brain Foundation and the Emil Aaltonen Foundation. Dr. Zetterberg is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2022-01018 and #2019-02397), the European Union's Horizon Europe research and innovation programme under grant agreement No 101053962, Swedish State Support for Clinical Research (#ALFGBG-71320), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), the AD Strategic Fund and the Alzheimer's Association (#ADSF-21-831376-C, #ADSF-21-831381-C, and #ADSF-21-831377-C), the Bluefield Project, the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2022-0270), the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 860197 (MIRIADE), the European Union Joint Programme–Neurodegenerative Disease Research (JPND2021-00694), the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, and the UK Dementia Research Institute at UCL (UKDRI-1003).

FundersFunder number
Stryker Corporation
European Union’s Horizon Europe research and innovation programme
Familjen Erling-Perssons Stiftelse
Suomalainen Lääkäriseura Duodecim
Schoen Adams Research Institute
Horizon 2020 Framework Programme
Emil Aaltosen Säätiö
Maire Taposen Säätiö
ImPACT Applications, Inc.
Finska Läkaresällskapet
National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre
Mooney-Reed Charitable Foundation
Finnish Brain Foundation
Olav Thon Stiftelsen
AD Strategic Fund
Horizon 2020
European Commission101053962
Vetenskapsrådet2022-01018, 2019-02397
European Union's Horizon Europe research and innovation programme-71320, 101053962
H2020 Marie Skłodowska-Curie Actions860197
UK Dementia Research InstituteUKDRI-1003
Alzheimer's Drug Discovery Foundation201809-2016862
Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden2022-0270
Academy of Finland17379, 349758
Alzheimer's Association-21-831376-C, -21-831377-C, -21-831381-C
European Union Joint Programme–Neurodegenerative Disease ResearchJPND2021-00694

    Keywords

    • computed tomography
    • emergency treatment
    • glial fibrillary acidic protein
    • guideline
    • traumatic brain injury

    ASJC Scopus subject areas

    • Developmental Neuroscience
    • Cellular and Molecular Neuroscience

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