Neurofilament heavy chain in secondary progressive multiple sclerosis.

IF 5 2区医学 Q1 CLINICAL NEUROLOGY

Multiple Sclerosis Journal Pub Date : 2025-03-01 Epub Date: 2025-01-22 DOI:10.1177/13524585241311212

Floriana De Angelis, Francesca Ammoscato, Richard A Parker, Domenico Plantone, Anisha Doshi, Nevin A John, Thomas Williams, Jonathan Stutters, Dave MacManus, Klaus Schmierer, Frederik Barkhof, Christopher J Weir, Gavin Giovannoni, Jeremy Chataway, Sharmilee Gnanapavan

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引用次数: 0

Abstract

Background: Biomarkers are needed to track progression in MS trials. Neurofilament heavy chain (NfH) has been underutilized due to assay limitations.

Objective: To investigate the added value of cerebrospinal fluid (CSF) NfH in secondary progressive multiple sclerosis (SPMS) using contemporary immunoassays.

Methods: This exploratory study was part of the MS-SMART trial. Clinical assessments (including expanded disability status scale, upper and lower limb function, visual acuity and symbol digit modalities test (SDMT)), CSF and serum sampling were acquired at baseline (n = 54), 48 and 96 weeks. Brain magnetic resonance imagings (MRIs) were obtained at baseline and 96 weeks. The NfL and NfH were measured using single-molecule array assay.

Results: Baseline CSF NfH and NfL correlated with information processing speed at 96 weeks, with CSF NfH showing stronger correlations (r = -0.49 for SDMT) than CSF NfL (r = -0.37 for SDMT). Baseline CSF NfL predicted poorer hand dexterity at baseline, 48 and 96 weeks. CSF NfH was the only predictor of cortical grey matter at baseline, while baseline CSF NfL was the only predictor of brain atrophy at 96 weeks. Serum neurofilaments showed limited associations.

Conclusion: CSF neurofilaments are better outcomes than serum neurofilaments in small SPMS studies. CSF NfH and NfL variably predict worsening hand function, information processing speed and brain volume loss, possibly reflecting complementary aspects of neurodegeneration.

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继发性进展性多发性硬化的神经丝重链。

背景：需要生物标志物来跟踪MS试验的进展。由于分析限制，神经丝重链（NfH）未得到充分利用。目的：探讨脑脊液（CSF） NfH在继发性进展性多发性硬化症（SPMS）中的附加价值。方法：本探索性研究是MS-SMART试验的一部分。在基线（n = 54）、48和96周时进行临床评估（包括扩展残疾状态量表、上肢和下肢功能、视力和符号手指形态测试（SDMT））、CSF和血清取样。在基线和96周时进行脑磁共振成像（mri）。采用单分子阵列法测定NfL和NfH。结果：基线CSF NfH和NfL与96周时的信息处理速度相关，其中CSF NfH的相关性（r = -0.49）强于CSF NfL （r = -0.37）。基线CSF NfL预测基线、48周和96周时较差的手灵巧性。脑脊液NfH是基线时皮质灰质的唯一预测因子，而基线脑脊液NfL是96周时脑萎缩的唯一预测因子。血清神经丝显示有限的关联。结论：在小型SPMS研究中，脑脊液神经丝优于血清神经丝。脑脊液NfH和NfL不同程度地预测了手功能恶化、信息处理速度和脑容量损失，可能反映了神经变性的互补方面。

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

Multiple Sclerosis Journal 医学-临床神经学

CiteScore

10.90

自引率

6.90%

发文量

186

审稿时长

3-8 weeks

期刊介绍： Multiple Sclerosis Journal is a peer-reviewed international journal that focuses on all aspects of multiple sclerosis, neuromyelitis optica and other related autoimmune diseases of the central nervous system. The journal for your research in the following areas: * __Biologic basis:__ pathology, myelin biology, pathophysiology of the blood/brain barrier, axo-glial pathobiology, remyelination, virology and microbiome, immunology, proteomics * __Epidemology and genetics:__ genetics epigenetics, epidemiology * __Clinical and Neuroimaging:__ clinical neurology, biomarkers, neuroimaging and clinical outcome measures * __Therapeutics and rehabilitation:__ therapeutics, rehabilitation, psychology, neuroplasticity, neuroprotection, and systematic management Print ISSN: 1352-4585