Intrathecal Inflammatory Profile and Gray Matter Damage Predict Progression Independent of Relapse Activity in Early Multiple Sclerosis.

IF 7.8 1区医学 Q1 CLINICAL NEUROLOGY

Neurology® Neuroimmunology & Neuroinflammation Pub Date : 2025-07-01 Epub Date: 2025-05-01 DOI:10.1212/NXI.0000000000200399

Damiano Marastoni, Elisa Colato, Matteo Foschi, Agnese Tamanti, Stefano Ziccardi, Chiara Eccher, Francesco Crescenzo, Albulena Bajrami, Gian Marco Schiavi, Valentina Camera, Daniela Anni, Federica Virla, Maddalena Guandalini, Ermanna Turano, Francesca Benedetta Pizzini, Stefania Montemezzi, Bruno Bonetti, Owain Howell, Roberta Magliozzi, Richard S Nicholas, Antonio Scalfari, Cristina Granziera, Ludwig Kappos, Massimiliano Calabrese

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引用次数: 0

Abstract

Background and objectives: The objective of this study was to determine, at the time of diagnosis, a CSF and MRI profile of intrathecal compartmentalized inflammation predictive of progression independent of relapse activity (PIRA) in early relapsing-remitting multiple sclerosis (RRMS).

Methods: This five-year prospective study included 80 treatment-naïve patients with RRMS enrolled at time of diagnosis. All patients underwent a lumbar puncture, regular neurologic evaluations including an Expanded Disability Status Scale (EDSS) assessment every 6 months, and an annual 3T brain MRI. PIRA was defined as having a confirmed disability progression independent of relapse activity. CSF levels of 68 inflammatory molecules were evaluated in combination with white matter and cortical lesion number (CLn) and volume, and regional gray matter thickness and volume.

Results: During the follow-up, 23 patients with RRMS (28.8%) experienced PIRA. At diagnosis, participants with PIRA were older (44.0 ± 10.7 vs 37.4 ± 12.4, p = 0.017) and with more disability (median EDSS score [interquartile range] of 3 [range 2-4] for PIRA vs 1.5 [range 1-2] for no PIRA group, p < 0.001). Random forest selected LIGHT, CXCL13, sTNFR1, sTNFR2, CCL7, MIF, sIL6Rbeta, IL35, CCL2, and IFNβ as the CSF markers best associated with PIRA. sTNFR1 (hazard ratio [HR] 10.11 [2.61-39.10], p = 0.001), sTNFR2 (HR 5.05 [1.63-15.64], p = 0.005), and LIGHT (HR 1.79 [1.11-2.88], p = 0.018) were predictors of PIRA at regression analysis. Baseline thalamus volume (HR 0.98 [0.97-0.99], p = 0.005), middle frontal gyrus thickness (HR 0.05 [0.01-0.72], p = 0.028), and CLn (HR 1.15 [1.05-1.25], p = 0.003) were MRI predictors of PIRA.

Discussion: A specific intrathecal inflammatory profile associated with TNF superfamily markers, CLn, and atrophy of several cortical and deep gray matter regions, assessed at time of diagnosis, is predictive of PIRA in early MS.

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鞘内炎症特征和灰质损伤预测早期多发性硬化症的进展与复发活动无关。

背景和目的：本研究的目的是确定，在诊断时，脑脊液和MRI的鞘内区隔性炎症预测进展独立于复发活动（PIRA）在早期复发-缓解型多发性硬化症（RRMS）。方法：这项为期五年的前瞻性研究包括80例treatment-naïve RRMS患者在诊断时入组。所有患者都进行了腰椎穿刺，定期进行神经系统评估，包括每6个月进行一次扩展残疾状态量表（EDSS）评估，以及每年进行一次3T脑MRI。PIRA被定义为具有独立于复发活动的确定的残疾进展。结合白质和皮质病变数（CLn）和体积，以及区域灰质厚度和体积，评估68种炎症分子的CSF水平。结果：随访期间，23例RRMS患者（28.8%）出现PIRA。在诊断时，患有PIRA的参与者年龄更大（44.0±10.7 vs 37.4±12.4,p = 0.017），残疾程度更高（PIRA组的EDSS中位评分[四分位数范围]为3[范围2-4]，而无PIRA组的EDSS中位评分[四分位数范围]为1.5[范围1-2]，p < 0.001）。随机森林选择LIGHT、CXCL13、sTNFR1、sTNFR2、CCL7、MIF、sIL6Rbeta、IL35、CCL2和IFNβ作为与PIRA最相关的CSF标志物。回归分析显示，sTNFR1（风险比[HR] 10.11 [2.61 ~ 39.10], p = 0.001）、sTNFR2（风险比[HR] 5.05 [1.63 ~ 15.64], p = 0.005）和LIGHT（风险比[HR] 1.79 [1.11 ~ 2.88], p = 0.018）是PIRA的预测因子。基线丘脑体积（HR 0.98 [0.97-0.99], p = 0.005）、额中回厚度（HR 0.05 [0.01-0.72], p = 0.028）和CLn （HR 1.15 [1.05-1.25], p = 0.003）是PIRA的MRI预测指标。讨论：在诊断时评估与TNF超家族标志物、CLn和几个皮质和深部灰质区域萎缩相关的特定鞘内炎症谱，可预测早期MS的PIRA。

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

Neurology® Neuroimmunology & Neuroinflammation Neuroscience-Neurology

CiteScore

15.60

自引率

2.30%

发文量

219

审稿时长

8 weeks

期刊介绍： Neurology Neuroimmunology & Neuroinflammation is an official journal of the American Academy of Neurology. Neurology: Neuroimmunology & Neuroinflammation will be the premier peer-reviewed journal in neuroimmunology and neuroinflammation. This journal publishes rigorously peer-reviewed open-access reports of original research and in-depth reviews of topics in neuroimmunology & neuroinflammation, affecting the full range of neurologic diseases including (but not limited to) Alzheimer's disease, Parkinson's disease, ALS, tauopathy, and stroke; multiple sclerosis and NMO; inflammatory peripheral nerve and muscle disease, Guillain-Barré and myasthenia gravis; nervous system infection; paraneoplastic syndromes, noninfectious encephalitides and other antibody-mediated disorders; and psychiatric and neurodevelopmental disorders. Clinical trials, instructive case reports, and small case series will also be featured.