Acute Management of Head Injuries: A Clinical Study Focused on Blood-Based Biomarkers

Mira Minkkinen

Research output: Book/ReportDoctoral thesisCollection of Articles

Abstract

Traumatic brain injury (TBI) is a leading cause of emergency department (ED) admissions as well as a global health burden. The vast majority of patients have mild TBI (MTBI) with minor or negligible clinical manifestations of the injury. Patient management is largely dictated by the use of computed tomography (CT), although up to 80% of the imaged patients have no trauma lesions on their CTs. In an effort to reduce unnecessary CT imaging, considerable research has been devoted to developing clinical decision rules and blood biomarkers capable of guiding the clinical management of patients with MTBI.

In 2013, a significant milestone was achieved when the Scandinavian Guidelines for Initial Management of Minimal, Mild, and Moderate Head Injuries in Adults incorporated the blood-based biomarker S100 astroglial calcium-binding protein B (S100B) into a clinical decision rule. Nevertheless, recent years have witnessed the emergence of a new promising biomarker, glial fibrillary acidic protein (GFAP), which has exhibited superior performance across various study cohorts and settings. Still, despite older adults being overrepresented in the TBI patient age distribution, biomarker studies that address them remain lacking.

Within this project, three individual studies were conducted based on a prospective cohort of adult patients with head injury who presented to the ED of Tampere University Hospital between November 2015 and November 2016. The first study included analyses of the potential of blood levels of GFAP, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), neurofilament light (NF-L), and tau for detecting acute traumatic CT abnormalities among older adults. The second study was a prospective validation study of the Scandinavian guidelines. Lastly, the third study examined the performance of the Scandinavian guidelines when the original biomarker S100B was replaced with GFAP. The median age in the study sample was high, providing special insights into the effects of age in all three studies.

The results of the first study indicated that blood levels of GFAP were the only to significantly discriminate between patients with and without traumatic CT abnormalities among older adults (U(83) = 280, p < .001, r = 0.44; area under the curve = 0.79, 95% confidence interval [CI] = 0.67–0.91]. In the second study, the Scandinavian guidelines were found to have a sensitivity of 0.94 (95% CI 0.77–0.99) and a specificity of 0.19 (95% CI 0.13–0.26) for predicting traumatic intracranial CT abnormalities. The positive and negative predictive values (PPV and NPV, respectively) for intracranial CT abnormalities were 0.18 (95% CI 0.12–0.25) and 0.94 (95% CI 0.78–0.99), respectively. Noteworthily, the guidelines would have failed to identify two patients with intracranial CT abnormalities who did not have a guideline-based indication for a head CT. Finally, in the third study, the modified Scandinavian guidelines with GFAP demonstrated a sensitivity and specificity of 0.94 (95% CI 0.77–0.99) and 0.20 (95% CI 0.15–0.28), respectively. The NPV was 0.94 (95% CI 0.80–0.99) and the PPV was 0.18 (95% CI 0.13–0.25). Importantly, the modified guidelines incorporating GFAP did not miss any additional patients with traumatic CT abnormalities.

Collectively, the results underscore the potential of GFAP as a reliable biomarker for detecting CT abnormalities in a specific subset of older adults with head injuries. Moreover, the Scandinavian guidelines demonstrated validity as a tool for determining the necessity of head CT scans in patients with head injury. The guidelines performed with high sensitivity and acceptable specificity when a biomarker with perhaps more promise was used (i.e., GFAP). To further solidify the applicability of these findings in clinical practice, studies on larger study samples and detailed analyses examining the confounding factors that impact biomarker levels are warranted.
Original languageEnglish
Place of PublicationTampere
ISBN (Electronic)978-952-03-3162-7
Publication statusPublished - 2023
Publication typeG5 Doctoral dissertation (articles)

Publication series

NameTampere University Dissertations - Tampereen yliopiston väitöskirjat
Volume906
ISSN (Print)2489-9860
ISSN (Electronic)2490-0028

Fingerprint

Dive into the research topics of 'Acute Management of Head Injuries: A Clinical Study Focused on Blood-Based Biomarkers'. Together they form a unique fingerprint.

Cite this