The Diagnostic and Prognostic Role of Biomarkers in Mild Traumatic Brain Injury: An Umbrella Meta-Analysis
Background: Mild traumatic brain injury (mTBI), commonly known as concussion, is a major public health issue characterized by subtle neuronal damage that traditional imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) often fail to detect. Fluid biomarkers have e...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-05-01
|
| Series: | Brain Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3425/15/6/581 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849432999235420160 |
|---|---|
| author | Ioannis Mavroudis Foivos Petridis Dimitrios Kazis Alin Ciobica Gabriel Dăscălescu Antoneta Dacia Petroaie Irina Dobrin Otilia Novac Ioana Vata Bogdan Novac |
| author_facet | Ioannis Mavroudis Foivos Petridis Dimitrios Kazis Alin Ciobica Gabriel Dăscălescu Antoneta Dacia Petroaie Irina Dobrin Otilia Novac Ioana Vata Bogdan Novac |
| author_sort | Ioannis Mavroudis |
| collection | DOAJ |
| description | Background: Mild traumatic brain injury (mTBI), commonly known as concussion, is a major public health issue characterized by subtle neuronal damage that traditional imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) often fail to detect. Fluid biomarkers have emerged as promising diagnostic and prognostic tools for mTBI. Objectives: This umbrella meta-analysis aims to evaluate the diagnostic accuracy and clinical utility of the key fluid biomarkers, S100B, glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1, neurofilament light chain (NfL)) and tau protein, in detecting mTBI and to clarify their roles as screening, confirmatory, and complementary indicators. Methods: A systematic review was performed using PubMed, Web of Science, Scopus, and Cochrane to identify the published meta-analyses that assessed the biomarkers in mTBI. Sensitivity, specificity, and diagnostic odds ratios were then calculated using random-effects models. Heterogeneity was evaluated with the I<sup>2</sup> statistic, and publication bias was assessed via funnel plots. The results of S100B demonstrated high sensitivity (91.6%) but low specificity (42.4%), making it an effective rule-out biomarker to minimize unnecessary CT scans. In contrast, GFAP exhibited moderate sensitivity (84.5%) with improved specificity (61.0%), supporting its role in confirming mTBI diagnoses. UCH-L1 revealed a sensitivity of 86.7% alongside low specificity (37.3%), indicating its potential as a complementary marker. Additionally, the NfL levels were notably elevated in sports-related concussions, while the diagnostic utility of tau protein remains inconclusive due to limited available data. Conclusions: The findings underscore the clinical promise of fluid biomarkers in the management of mTBI. S100B and GFAP are particularly valuable as screening and confirmatory markers, respectively. Nonetheless, further standardization of biomarker thresholds and additional longitudinal studies are necessary to validate the roles of UCH-L1, NfL, and Tau protein. The integration of these biomarkers into a multimodal diagnostic panel may enhance mTBI detection accuracy and facilitate improved patient stratification and management. |
| format | Article |
| id | doaj-art-323f1d2fcad14e27b618e4bf065e348f |
| institution | Kabale University |
| issn | 2076-3425 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Brain Sciences |
| spelling | doaj-art-323f1d2fcad14e27b618e4bf065e348f2025-08-20T03:27:13ZengMDPI AGBrain Sciences2076-34252025-05-0115658110.3390/brainsci15060581The Diagnostic and Prognostic Role of Biomarkers in Mild Traumatic Brain Injury: An Umbrella Meta-AnalysisIoannis Mavroudis0Foivos Petridis1Dimitrios Kazis2Alin Ciobica3Gabriel Dăscălescu4Antoneta Dacia Petroaie5Irina Dobrin6Otilia Novac7Ioana Vata8Bogdan Novac9Department of Neuroscience, Leeds Teaching Hospitals, NHS Trust, Leeds LS9 7TF, UKThird Department of Neurology, Aristotle University of Thessaloniki, 541 24 Thessaloniki, GreeceThird Department of Neurology, Aristotle University of Thessaloniki, 541 24 Thessaloniki, GreeceFaculty of Biology, “Alexandru Ioan Cuza” University of Iași, 700506 Iași, RomaniaFaculty of Biology, “Alexandru Ioan Cuza” University of Iași, 700506 Iași, RomaniaFaculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, RomaniaFaculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, RomaniaFaculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, RomaniaFaculty of Dental Medicine, Apollonia University, Pacurari Street 11, 700511 Iași, RomaniaFaculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, RomaniaBackground: Mild traumatic brain injury (mTBI), commonly known as concussion, is a major public health issue characterized by subtle neuronal damage that traditional imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) often fail to detect. Fluid biomarkers have emerged as promising diagnostic and prognostic tools for mTBI. Objectives: This umbrella meta-analysis aims to evaluate the diagnostic accuracy and clinical utility of the key fluid biomarkers, S100B, glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1, neurofilament light chain (NfL)) and tau protein, in detecting mTBI and to clarify their roles as screening, confirmatory, and complementary indicators. Methods: A systematic review was performed using PubMed, Web of Science, Scopus, and Cochrane to identify the published meta-analyses that assessed the biomarkers in mTBI. Sensitivity, specificity, and diagnostic odds ratios were then calculated using random-effects models. Heterogeneity was evaluated with the I<sup>2</sup> statistic, and publication bias was assessed via funnel plots. The results of S100B demonstrated high sensitivity (91.6%) but low specificity (42.4%), making it an effective rule-out biomarker to minimize unnecessary CT scans. In contrast, GFAP exhibited moderate sensitivity (84.5%) with improved specificity (61.0%), supporting its role in confirming mTBI diagnoses. UCH-L1 revealed a sensitivity of 86.7% alongside low specificity (37.3%), indicating its potential as a complementary marker. Additionally, the NfL levels were notably elevated in sports-related concussions, while the diagnostic utility of tau protein remains inconclusive due to limited available data. Conclusions: The findings underscore the clinical promise of fluid biomarkers in the management of mTBI. S100B and GFAP are particularly valuable as screening and confirmatory markers, respectively. Nonetheless, further standardization of biomarker thresholds and additional longitudinal studies are necessary to validate the roles of UCH-L1, NfL, and Tau protein. The integration of these biomarkers into a multimodal diagnostic panel may enhance mTBI detection accuracy and facilitate improved patient stratification and management.https://www.mdpi.com/2076-3425/15/6/581mild traumatic brain injuryconcussionbiomarkersS100BGFAPUCH-L1 |
| spellingShingle | Ioannis Mavroudis Foivos Petridis Dimitrios Kazis Alin Ciobica Gabriel Dăscălescu Antoneta Dacia Petroaie Irina Dobrin Otilia Novac Ioana Vata Bogdan Novac The Diagnostic and Prognostic Role of Biomarkers in Mild Traumatic Brain Injury: An Umbrella Meta-Analysis Brain Sciences mild traumatic brain injury concussion biomarkers S100B GFAP UCH-L1 |
| title | The Diagnostic and Prognostic Role of Biomarkers in Mild Traumatic Brain Injury: An Umbrella Meta-Analysis |
| title_full | The Diagnostic and Prognostic Role of Biomarkers in Mild Traumatic Brain Injury: An Umbrella Meta-Analysis |
| title_fullStr | The Diagnostic and Prognostic Role of Biomarkers in Mild Traumatic Brain Injury: An Umbrella Meta-Analysis |
| title_full_unstemmed | The Diagnostic and Prognostic Role of Biomarkers in Mild Traumatic Brain Injury: An Umbrella Meta-Analysis |
| title_short | The Diagnostic and Prognostic Role of Biomarkers in Mild Traumatic Brain Injury: An Umbrella Meta-Analysis |
| title_sort | diagnostic and prognostic role of biomarkers in mild traumatic brain injury an umbrella meta analysis |
| topic | mild traumatic brain injury concussion biomarkers S100B GFAP UCH-L1 |
| url | https://www.mdpi.com/2076-3425/15/6/581 |
| work_keys_str_mv | AT ioannismavroudis thediagnosticandprognosticroleofbiomarkersinmildtraumaticbraininjuryanumbrellametaanalysis AT foivospetridis thediagnosticandprognosticroleofbiomarkersinmildtraumaticbraininjuryanumbrellametaanalysis AT dimitrioskazis thediagnosticandprognosticroleofbiomarkersinmildtraumaticbraininjuryanumbrellametaanalysis AT alinciobica thediagnosticandprognosticroleofbiomarkersinmildtraumaticbraininjuryanumbrellametaanalysis AT gabrieldascalescu thediagnosticandprognosticroleofbiomarkersinmildtraumaticbraininjuryanumbrellametaanalysis AT antonetadaciapetroaie thediagnosticandprognosticroleofbiomarkersinmildtraumaticbraininjuryanumbrellametaanalysis AT irinadobrin thediagnosticandprognosticroleofbiomarkersinmildtraumaticbraininjuryanumbrellametaanalysis AT otilianovac thediagnosticandprognosticroleofbiomarkersinmildtraumaticbraininjuryanumbrellametaanalysis AT ioanavata thediagnosticandprognosticroleofbiomarkersinmildtraumaticbraininjuryanumbrellametaanalysis AT bogdannovac thediagnosticandprognosticroleofbiomarkersinmildtraumaticbraininjuryanumbrellametaanalysis AT ioannismavroudis diagnosticandprognosticroleofbiomarkersinmildtraumaticbraininjuryanumbrellametaanalysis AT foivospetridis diagnosticandprognosticroleofbiomarkersinmildtraumaticbraininjuryanumbrellametaanalysis AT dimitrioskazis diagnosticandprognosticroleofbiomarkersinmildtraumaticbraininjuryanumbrellametaanalysis AT alinciobica diagnosticandprognosticroleofbiomarkersinmildtraumaticbraininjuryanumbrellametaanalysis AT gabrieldascalescu diagnosticandprognosticroleofbiomarkersinmildtraumaticbraininjuryanumbrellametaanalysis AT antonetadaciapetroaie diagnosticandprognosticroleofbiomarkersinmildtraumaticbraininjuryanumbrellametaanalysis AT irinadobrin diagnosticandprognosticroleofbiomarkersinmildtraumaticbraininjuryanumbrellametaanalysis AT otilianovac diagnosticandprognosticroleofbiomarkersinmildtraumaticbraininjuryanumbrellametaanalysis AT ioanavata diagnosticandprognosticroleofbiomarkersinmildtraumaticbraininjuryanumbrellametaanalysis AT bogdannovac diagnosticandprognosticroleofbiomarkersinmildtraumaticbraininjuryanumbrellametaanalysis |