Plasma neurofilament heavy chain is a prognostic biomarker for the development of severe epilepsy after experimental traumatic brain injury.

Autor: Heiskanen M; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland., Banuelos I; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland., Manninen E; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland., Andrade P; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland., Hämäläinen E; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland., Puhakka N; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland., Pitkänen A; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Jazyk: angličtina
Zdroj: Epilepsia [Epilepsia] 2024 Dec; Vol. 65 (12), pp. 3703-3716. Date of Electronic Publication: 2024 Oct 14.
DOI: 10.1111/epi.18149
Abstrakt: Objective: This study was undertaken to test whether the postinjury plasma concentration of phosphorylated neurofilament heavy chain (pNF-H), a marker of axonal injury, is a prognostic biomarker for the development of posttraumatic epilepsy.
Methods: Tail vein plasma was sampled 48 h after traumatic brain injury (TBI) from 143 rats (10 naïve, 21 controls, 112 with lateral fluid percussion injury) to quantify pNF-H by enzyme-linked immunosorbent assay. During the 6th postinjury month, rats underwent 30 days of continuous video-electroencephalographic monitoring to detect unprovoked seizures and evaluate epilepsy severity. Somatomotor (composite neuroscore) and spatial memory (Morris water maze) testing and quantitative T 2 magnetic resonance imaging were performed to assess comorbidities and lesion severity.
Results: Of the 112 TBI rats, 25% (28/112) developed epilepsy (TBI+) and 75% (84/112) did not (TBI-). Plasma pNF-H concentrations were higher in TBI+ rats than in TBI- rats (p < .05). Receiver operating characteristic curve analysis indicated that plasma pNF-H concentration distinguished TBI+ rats from TBI- rats (area under the curve [AUC] = .647, p < .05). Differentiation was stronger when comparing TBI+ rats exhibiting severe epilepsy (≥3 seizures/month) with all other TBI rats (AUC = .732, p < .01). Plasma pNF-H concentration on day 2 (D2) distinguished TBI+ rats with seizure clusters from other TBI rats (AUC = .732, p < .05). Higher plasma pNF-H concentration on D2 after TBI correlated with lower neuroscores on D2 (p < .001), D6 (p < .001), and D14 (p < .01). Higher pNF-H concentration on D2 correlated with greater T 2 signal abnormality volume on D2 (p < .001) and D7 (p < .01) and larger cortical lesion area on D182 (p < .01). Plasma pNF-H concentration on D2 did not correlate with Morris water maze performance on D37-D39.
Significance: Plasma pNF-H is a promising clinically translatable prognostic biomarker for the development of posttraumatic epilepsy with frequent seizures or seizure clusters.
(© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)
Databáze: MEDLINE
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