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

IF 6.6 1区医学 Q1 CLINICAL NEUROLOGY Epilepsia Pub Date : 2024-10-14 DOI:10.1111/epi.18149

Mette Heiskanen, Ivette Banuelos, Eppu Manninen, Pedro Andrade, Elina Hämäläinen, Noora Puhakka, Asla Pitkänen

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Abstract

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 T₂ 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 T₂ 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.

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血浆神经丝重链是实验性脑外伤后发生严重癫痫的预后生物标志物。

研究目的本研究旨在检测损伤后血浆中磷酸化神经丝重链（pNF-H）的浓度（pNF-H是轴突损伤的标志物）是否是创伤后癫痫发生的预后生物标志物：方法：在创伤性脑损伤（TBI）48小时后，对143只大鼠（10只天真大鼠、21只对照组大鼠、112只侧液叩击伤大鼠）的尾静脉血浆进行采样，通过酶联免疫吸附试验对pNF-H进行定量。在受伤后第 6 个月，对大鼠进行为期 30 天的连续视频脑电图监测，以检测无诱因癫痫发作并评估癫痫严重程度。此外，还进行了躯体运动（综合神经评分）和空间记忆（莫里斯水迷宫）测试以及定量 T2 磁共振成像，以评估合并症和病变严重程度：112只创伤性脑损伤大鼠中，25%（28/112）出现癫痫（创伤性脑损伤+），75%（84/112）未出现癫痫（创伤性脑损伤-）。TBI+ 大鼠的血浆 pNF-H 浓度高于 TBI- 大鼠（p 2 D2 信号异常体积（p 意义：血浆 pNF-H 是一种有希望转化为临床预后的生物标志物，可用于诊断频繁发作或发作集群的创伤后癫痫。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Epilepsia 医学-临床神经学

CiteScore

10.90

自引率

10.70%

发文量

319

审稿时长

2-4 weeks

期刊介绍： Epilepsia is the leading, authoritative source for innovative clinical and basic science research for all aspects of epilepsy and seizures. In addition, Epilepsia publishes critical reviews, opinion pieces, and guidelines that foster understanding and aim to improve the diagnosis and treatment of people with seizures and epilepsy.