Lower cerebral arterial blood flow is associated with greater serum neurofilament light chain levels in multiple sclerosis patients

Background and purpose 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. Methods and Materials 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. Results 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). Conclusion Lower CABF is associated with increased sNfL in MS patients, highlighting the relationship between cerebral hypoperfusion and axonal pathology. The relapsing‐remitting multiple sclerosis (RRMS) patients in the lowest cerebral arterial blood flow (CABF) quartile (total CABF ≤ 789 ml/min) had significantly higher serum neurofilament light chain (sNfL) levels (estimated marginal means of 28.4 vs. 16.6 pg/ml; age‐ and body mass index‐adjusted p = 0.01) when compared to RRMS patients within the highest CABF quartile (total CABF ≥ 1115.5 ml/min). No significant findings in the progressive multiple sclerosis quartile analysis were observed.