Serum NfL and GFAP as biomarkers of progressive neurodegeneration in TBI

Author:

Shahim Pashtun12345ORCID,Pham Dzung L.46,van der Merwe Andre J.145,Moore Brian145,Chou Yi‐Yu45,Lippa Sara M.67,Kenney Kimbra67,Diaz‐Arrastia Ramon8,Chan Leighton1

Affiliation:

1. Rehabilitation Medicine Department National Institutes of Health (NIH) Clinical Center Bethesda Maryland USA

2. National Institutes of Neurological Disorders and Stroke, NIH Bethesda Maryland USA

3. Department of Neurology MedStar Georgetown University Hospital, Pasquerilla Healthcare Center Washington District of Columbia USA

4. The Military Traumatic Brain Injury Initiative (MTBI2) Bethesda Maryland USA

5. The Henry M. Jackson Foundation for the Advancement of Military Medicine Bethesda Maryland USA

6. Uniformed Services University of the Health Sciences Bethesda Maryland USA

7. National Intrepid Center of Excellence, Walter Reed National Military Medical Center Bethesda Maryland USA

8. Department of Neurology University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA

Abstract

AbstractBACKGROUNDWe examined spatial patterns of brain atrophy after mild, moderate, and severe traumatic brain injury (TBI), the relationship between progression of brain atrophy with initial traumatic axonal injury (TAI), cognitive outcome, and with serum biomarkers of brain injury.METHODSA total of 143 patients with TBI and 43 controls were studied cross‐sectionally and longitudinally up to 5 years with multiple assessments, which included brain magnetic resonance imaging, cognitive testing, and serum biomarkers.RESULTSTBI patients showed progressive volume loss regardless of injury severity over several years, and TAI was independently associated with accelerated brain atrophy. Cognitive performance improved over time. Higher baseline serum neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) were associated with greater rate of brain atrophy over 5 years.DISCUSSSIONSpatial patterns of atrophy differ by injury severity and TAI is associated with the progression of brain atrophy. Serum NfL and GFAP show promise as non‐invasive prognostic biomarkers of progressive neurodegeneration in TBI.Highlights In this longitudinal study of patient with mild, moderate, and severe traumatic brain injury (TBI) who were assessed with paired magnetic resonance imaging (MRI), blood biomarkers, and cognitive assessments, we found that brain atrophy after TBI is progressive and continues for many years even after a mild head trauma without signs of brain injury on conventional MRI. We found that spatial pattern of brain atrophy differs between mild, moderate, and severe TBI, where in patients with mild TBI , atrophy is mainly seen in the gray matter, while in those with moderate to severe brain injury atrophy is predominantly seen in the subcortical gray matter and whiter matter. Cognitive performance improves over time after a TBI. Serum measures of neurofilament light or glial fibrillary acidic protein are associated with progression of brain atrophy after TBI.

Publisher

Wiley

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