Post-acute blood biomarkers and disease progression in traumatic brain injury.
Brain
; 145(6): 2064-2076, 2022 06 30.
Article
em En
| MEDLINE
| ID: mdl-35377407
ABSTRACT
There is substantial interest in the potential for traumatic brain injury to result in progressive neurological deterioration. While blood biomarkers such as glial fibrillary acid protein (GFAP) and neurofilament light have been widely explored in characterizing acute traumatic brain injury (TBI), their use in the chronic phase is limited. Given increasing evidence that these proteins may be markers of ongoing neurodegeneration in a range of diseases, we examined their relationship to imaging changes and functional outcome in the months to years following TBI. Two-hundred and three patients were recruited in two separate cohorts; 6 months post-injury (n = 165); and >5 years post-injury (n = 38; 12 of whom also provided data â¼8 months post-TBI). Subjects underwent blood biomarker sampling (n = 199) and MRI (n = 172; including diffusion tensor imaging). Data from patient cohorts were compared to 59 healthy volunteers and 21 non-brain injury trauma controls. Mean diffusivity and fractional anisotropy were calculated in cortical grey matter, deep grey matter and whole brain white matter. Accelerated brain ageing was calculated at a whole brain level as the predicted age difference defined using T1-weighted images, and at a voxel-based level as the annualized Jacobian determinants in white matter and grey matter, referenced to a population of 652 healthy control subjects. Serum neurofilament light concentrations were elevated in the early chronic phase. While GFAP values were within the normal range at â¼8 months, many patients showed a secondary and temporally distinct elevations up to >5 years after injury. Biomarker elevation at 6 months was significantly related to metrics of microstructural injury on diffusion tensor imaging. Biomarker levels at â¼8 months predicted white matter volume loss at >5 years, and annualized brain volume loss between â¼8 months and 5 years. Patients who worsened functionally between â¼8 months and >5 years showed higher than predicted brain age and elevated neurofilament light levels. GFAP and neurofilament light levels can remain elevated months to years after TBI, and show distinct temporal profiles. These elevations correlate closely with microstructural injury in both grey and white matter on contemporaneous quantitative diffusion tensor imaging. Neurofilament light elevations at â¼8 months may predict ongoing white matter and brain volume loss over >5 years of follow-up. If confirmed, these findings suggest that blood biomarker levels at late time points could be used to identify TBI survivors who are at high risk of progressive neurological damage.
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Texto completo:
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Bases de dados:
MEDLINE
Assunto principal:
Lesões Encefálicas
/
Substância Branca
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Lesões Encefálicas Traumáticas
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Brain
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Reino Unido