Longitudinal Plasma Biomarker Profiles Predict Neurological Outcome in Traumatic Spinal Cord Injury

IF 7.7 1区医学 Q1 CLINICAL NEUROLOGY Annals of Neurology Pub Date : 2025-02-05 DOI:10.1002/ana.27198

Judith Fraussen PhD, Sjors G. J. G. In't Veld PhD, Charlotte C. M. van Laake-Geelen MD, PhD, Bart Depreitere MD, PhD, Jens Deckers MD, Dieter Peuskens MD, Erwin M. J. Cornips MD, PhD, Sven Bamps MD, Charlotte E. Teunissen PhD, Veerle Somers PhD

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Abstract

Objective

Traumatic spinal cord injury (SCI) is diagnosed by imaging and clinical scoring using the American Spinal Injury Association Impairment Scale (AIS). These methods have limited value for prognosis. Here, the prognostic value of plasma neurofilament-light (NfL), glial fibrillary acidic protein (GFAP), and contactin-1 (CNTN-1) was analyzed.

Methods

Biomarker levels were determined in the plasma of traumatic SCI patients (n = 37) and healthy controls (n = 22). SCI samples (n = 112) were collected at different time points from 0 to 4 days to 18 weeks post-injury. NfL and GFAP were measured by single molecule array (Simoa) technology, CNTN-1 by Luminex. Baseline and outcome AIS and motor scores were collected as a measure of injury severity.

Results

NfL, GFAP, and CNTN-1 showed different kinetics in SCI patients over time. Baseline biomarker levels could identify AIS-A SCI patients (NfL + GFAP) and discriminate between patients with a motor score change <5 and those with a change ≥5 (NfL + GFAP+CNTN-1). Longitudinally, NfL could identify AIS-A patients up to 12 weeks post-SCI and discriminate between patients with a motor score change <5 and those with a change ≥5 up to 18 weeks post-SCI. Further, baseline biomarker levels positively (NfL + GFAP) or negatively (CNTN-1) correlated with outcome injury severity and together could accurately predict AIS conversion (AUC 0.863) and motor score change (AUC 0.857). This predictive ability was maintained in subacute/chronic SCI stages.

Interpretation

In conclusion, plasma NfL, GFAP, and CNTN-1 are potential prognostic biomarkers in SCI. This is important for patient stratification in clinical trials, prediction of neurological outcome and informed decision-making in SCI treatment and rehabilitation. ANN NEUROL 2025;97:1180–1189

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纵向血浆生物标志物谱预测创伤性脊髓损伤的神经预后。

目的：应用美国脊髓损伤协会损伤量表（AIS）对外伤性脊髓损伤（SCI）进行影像学诊断和临床评分。这些方法对预后的价值有限。本文分析了血浆神经丝光（NfL）、胶质纤维酸性蛋白（GFAP）和接触蛋白-1 （CNTN-1）的预后价值。方法：对创伤性脊髓损伤患者（n = 37）和健康对照（n = 22）的血浆中生物标志物水平进行测定。在损伤后0 ~ 4天至18周的不同时间点采集SCI样本112例。采用单分子阵列（Simoa）技术检测NfL和GFAP，采用Luminex检测CNTN-1。收集基线和结局AIS和运动评分作为损伤严重程度的衡量标准。结果：随着时间的推移，脊髓损伤患者的NfL、GFAP和CNTN-1表现出不同的动力学。基线生物标志物水平可以识别AIS-A型SCI患者（NfL + GFAP），并区分运动评分改变的患者。解释：总之，血浆NfL、GFAP和CNTN-1是潜在的SCI预后生物标志物。这对于临床试验中的患者分层、神经预后预测以及脊髓损伤治疗和康复的知情决策都很重要。Ann neurol 2025。

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来源期刊

Annals of Neurology 医学-临床神经学

CiteScore

18.00

自引率

1.80%

发文量

270

审稿时长

3-8 weeks

期刊介绍： Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.