Plasma Glial Fibrillary Acidic Protein (GFAP) as a Biomarker of Acute Focal Brain Injury
Nil Saez Calveras1, Alexander Asturias2, James Yu2, Barbara Stopschinski1, Jaime Vaquer-Alicea3, Padraig O'Suilleabhain1, Marc Diamond1, Bhavya Shah2
1Neurology, 2Radiology, 3Biochemistry, University of Texas Southwestern Medical Center
Objective:
This study aimed to assess plasma biomarker changes following an acute focal brain injury using Magnetic Resonance-guided High-Intensity Focused Ultrasound (MRgHIFU) thalamotomy.
Background:
Biomarkers such as glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), amyloid-beta (Aβ40 and Aβ42), and phosphorylated tau 181 (pTau-181) have been proposed as indicators of acute brain injury. However, the validation of acute brain injury biomarkers has faced challenges, including the absence of pre-insult measurements, variability in injury timing and location, and interindividual differences. MRgHIFU thalamotomy, a precise technique used in patients with essential tremor (ET) and tremor-dominant Parkinson’s disease (TDPD), offers a controlled setting to study the relationship between focal brain injury and plasma biomarker changes.
Design/Methods:
This prospective study included 30 ET and TDPD patients undergoing MRgHIFU thalamotomy at a single academic institution. Blood samples were collected at three time points: preprocedure, 1 hour post-procedure, and 48 hours post-procedure. Plasma levels of GFAP, NfL, Aβ40 and Aβ42, and pTau-181 were measured using the Quanterix Single Molecule Arrays (SiMoA) assay.
Results:
GFAP levels significantly increased 48 hours post-MRgHIFU in all patients with a thalamotomy lesion. GFAP levels were highly sensitive (89.7%) and specific (96.6%) in detecting the presence of a HIFU lesion with a cutoff value of 216.2 pg/ml. NfL, Aβ40, and Aβ42, also showed statistically significant increases post-procedure but were less robust than GFAP. No changes were observed in pTau-181 levels post-MRgHIFU.
Conclusions:
Plasma GFAP emerged as a highly sensitive and reliable biomarker for detecting acute brain injury following MRgHIFU thalamotomy. The significant post-procedure GFAP increase suggests its potential as an early diagnostic tool for focal brain injuries, particularly in acute stroke. Further research is needed to validate the GFAP injury cutoff identified in this study and to explore its broader clinical utility in the early detection of focal brain lesions.
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