The Association Between The Serum Level Of Neurofilament Light Chain And White Matter Fiber Tract Injury In Patients With Amyotrophic Lateral Sclerosis

Background and aims:Neurofilament light chain(NFL)is a neuron-specific cytoskeletal protein,the serum level of which rises upon axonal damage in the central nervous system.Studies have confirmed that the serum NFL level was significantly increased in patients with amyotrophic lateral sclerosis(ALS).The serum NFL has emerged as a biomarker of ALS.Diffusion tensor imaging(DTI)provides a validated way of assessing white matter fiber tract microstructural alterations.Up to now,the studies abroad relating the serum NFL level to white matter fiber tract degeneration in patients with ALS were few and with inconsistent conclusions,and no research on it has been seen in China.This study aimed to explore the correlation between the serum NFL level and DTI measures in damaged white matter fiber tract in Chinese ALS patients for the first time.Methods:A total of 15 ALS patients and 15 healthy controls(HC)were included in the department of Neurology at Nanjing First Hospital from September 2018 to December,2020.The serum NFL levels were measured by Single-molecule Array.All participants underwent DTI scans on a 3.0T Magnetic Resonance Imaging system.All subjects’ DTI data was processed on the Pipeline for Analyzing brai N Diffusion im Age software,and the fractional anisotropy(FA)values were analyzed using the tract based spatial statistics.In abnormal white matter fiber tract with significant FA differences between the two groups,the correlation between the serum NFL level of ALS patients and the FA values was investigated by Spearman’s correlation analysis.P < 0.05 was considered statistically significant.Results:The median level of serum NFL was 75.04 pg/ml in ALS group,significantly higher than the level of 9.78 pg/ml in the HC group(P < 0.001).The serum NFL level in ALS patients was positively correlated with the number of upper motor neuron(UMN)involved segments in medulla,cervical,thoracic and lumbosacral regions(P =0.033).There was no significant correlation between the serum NFL level and sex,age,disease duration,the site of symptom onset,Revised ALS Functional Rating Scale scores or treatment of Riluzole in the ALS group.Compared with the HC group,FA values of the bilateral corticospinal tract,the bilateral superior longitudinal fasciculus,the left inferior longitudinal fasciculus,the bilateral Inferior fronto-occipital fasciculus and the left anterior thalamic radiation were lower in ALS patients with statistically significant differences(P < 0.05).Spearman’s correlation analysis showed that there was no significant correlation between the serum NFL level and FA values in the abnormal white matter fiber tract(P > 0.05).Conclusions:The serum NFL level was significantly increased in ALS patients and was positively correlated with the number of UMN involved segments.The patients with ALS had significant differences in DTI scalars in white matter fiber tract on the level of posterior limb of internal capsule and the cerebral peduncle,which was a symbol to distinguish ALS from other neurodegeneration diseases.Although we didn’t find the relationship between the serum NFL level and white matter fiber tract alterations revealed by DTI parameters in ALS patients,it should be further investigated in a larger Chinese ALS population.