Chronic White Matter Inflammation and Serum Neurofilament Levels in Multiple Sclerosis.
Chronic White Matter Inflammation and Serum Neurofilament Levels in Multiple Sclerosis.
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DOI：
10.1212/wnl.0000000000012326
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发表时间：
2021-08-10
期刊：
影响因子：
9.9
通讯作者：
Granziera C
中科院分区：
文献类型：
--
作者：
Maggi P;Kuhle J;Schädelin S;van der Meer F;Weigel M;Galbusera R;Mathias A;Lu PJ;Rahmanzadeh R;Benkert P;La Rosa F;Bach Cuadra M;Sati P;Théaudin M;Pot C;van Pesch V;Leppert D;Stadelmann C;Kappos L;Du Pasquier R;Reich DS;Absinta M;Granziera C
为了评估多发性硬化症（MS）患者体内通过顺磁边缘MRI病变（PRLs）检测到的慢性白质炎症是否与血清神经丝轻链（sNfL）水平升高有关，sNfL是神经轴突损伤的标志。在118例没有钆增强病变或近期复发的MS患者中，我们分析了3d -亚毫米期MRI和sNfL水平。对另外20例尸检MS病例的25个MS病变进行了组织病理学评估。在单变量分析中，与PRL≤1的参与者（n = 75）相比，PRL≥2的参与者（n = 43）具有更高的年龄调整sNfL百分位数（中位数，91和68；p < 0.001）和更高的多发性硬化症严重程度量表评分（MSSS中位数，4.3和2.4;p = 0.003）。在多变量分析中，PRLs≥2的患者sNfL百分位数水平较高（β值，16.3；95%可信区间[CI]， 4.6-28.0; p < 0.01），而疾病改善治疗（DMT）、扩展残疾状态量表（EDSS）评分和T2病变负荷对sNfL没有影响。在类似的模型中，在prl≥4的病例中sNfL百分位数水平最高（n = 30; βadd, 30.4; 95% CI, 15.6-45.2; p < 0.01）。随后的多变量分析显示，PRLs≥2的患者也有较高的mss (βadd, 1.1; 95% CI, 0.3-1.9; p < 0.01)，而mss不受DMT或T2病变负荷的影响。在组织病理学上，慢性活动性病变和阴燃性病变均表现出病灶边缘比病灶中心更严重的急性轴突损伤（边缘vs中心：p = 0.004和p = 0.0002）。慢性白质炎症与非急性MS中sNfL水平升高和疾病严重程度相关，表明PRL有助于临床相关的炎症驱动的神经退行性变。
To assess whether chronic white matter inflammation in patients with multiple sclerosis (MS) as detected in vivo by paramagnetic rim MRI lesions (PRLs) is associated with higher serum neurofilament light chain (sNfL) levels, a marker of neuroaxonal damage. In 118 patients with MS with no gadolinium-enhancing lesions or recent relapses, we analyzed 3D-submillimeter phase MRI and sNfL levels. Histopathologic evaluation was performed in 25 MS lesions from 20 additional autopsy MS cases. In univariable analyses, participants with ≥2 PRLs (n = 43) compared to those with ≤1 PRL (n = 75) had higher age-adjusted sNfL percentiles (median, 91 and 68; p < 0.001) and higher Multiple Sclerosis Severity Scale scores (MSSS median, 4.3 and 2.4; p = 0.003). In multivariable analyses, sNfL percentile levels were higher in PRLs ≥2 cases (βadd, 16.3; 95% confidence interval [CI], 4.6–28.0; p < 0.01), whereas disease-modifying treatment (DMT), Expanded Disability Status Scale (EDSS) score, and T2 lesion load did not affect sNfL. In a similar model, sNfL percentile levels were highest in cases with ≥4 PRLs (n = 30; βadd, 30.4; 95% CI, 15.6–45.2; p < 0.01). Subsequent multivariable analysis revealed that PRLs ≥2 cases also had higher MSSS (βadd, 1.1; 95% CI, 0.3–1.9; p < 0.01), whereas MSSS was not affected by DMT or T2 lesion load. On histopathology, both chronic active and smoldering lesions exhibited more severe acute axonal damage at the lesion edge than in the lesion center (edge vs center: p = 0.004 and p = 0.0002, respectively). Chronic white matter inflammation was associated with increased levels of sNfL and disease severity in nonacute MS, suggesting that PRL contribute to clinically relevant, inflammation-driven neurodegeneration.