Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA.
IRCCS, Fondazione Don Carlo Gnocchi, Milan, Italy.
Eur J Neurol. 2022 Aug;29(8):2299-2308. doi: 10.1111/ene.15374. Epub 2022 May 6.
Hypoperfusion, vascular pathology, and cardiovascular risk factors are associated with disease severity in multiple sclerosis (MS). We aimed to assess relationships between cerebral arterial blood flow (CABF) and serum neurofilament light chain (sNfL) as neuronal damage biomarkers.
Total CABF was measured in 137 patients (86 with clinically isolated syndrome/relapsing-remitting (RR) MS and 51 with progressive MS [PMS]) and 48 healthy controls using Doppler ultrasonography. sNfL was quantitated using a single-molecule assay (Simoa). Examination using 3.0-T magnetic resonance imaging (MRI) allowed quantification of T2 lesions and whole-brain volume (WBV). Multiple linear regression models determined the sNfL association with CABF after correction for demographic and MRI-derived variables.
After adjustment for age, sex and body mass index (BMI), total CABF remained statistically significant and model comparisons showed that CABF explained an additional 2.6% of the sNfL variance (β = -0.167, p = 0.044). CABF also remained significant in a stepwise regression model (β = 0.18, p = 0.034) upon the inclusion of T2 lesion burden and WBV effects. Patients in the lowest CABF quartile (CABF ≤ 761 ml/min) had significantly higher sNfL levels (34.6 vs. 23.9 pg/ml, age and BMI-adjusted-p = 0.042) when compared to the highest quartile (CABF ≥ 1130 ml/min).
Lower CABF is associated with increased sNfL in MS patients, highlighting the relationship between cerebral hypoperfusion and axonal pathology.
低灌注、血管病变和心血管危险因素与多发性硬化症（MS）的疾病严重程度相关。我们旨在评估脑动脉血流（CABF）和血清神经丝轻链（sNfL）之间的关系，作为神经元损伤的生物标志物。
使用多普勒超声测量了 137 名患者（86 名患有临床孤立综合征/复发缓解型 MS 和 51 名患有进展型 MS）和 48 名健康对照者的总 CABF。使用单分子分析法（Simoa）定量 sNfL。使用 3.0-T 磁共振成像（MRI）进行检查，可量化 T2 病变和全脑容积（WBV）。多元线性回归模型确定了 sNfL 与 CABF 之间的关联，校正了人口统计学和 MRI 衍生变量。
在调整年龄、性别和体重指数（BMI）后，总 CABF 仍具有统计学意义，模型比较表明 CABF 解释了 sNfL 方差的额外 2.6%（β=-0.167，p=0.044）。在逐步回归模型中，当纳入 T2 病变负荷和 WBV 效应时，CABF 仍然具有统计学意义（β=0.18，p=0.034）。在最低 CABF 四分位数（CABF≤761ml/min）的患者中，sNfL 水平明显更高（34.6 vs. 23.9pg/ml，年龄和 BMI 校正后 p=0.042），与最高四分位数（CABF≥1130ml/min）相比。
MS 患者 CABF 降低与 sNfL 升高相关，突出了脑低灌注与轴突病理之间的关系。
