1. Increased serum neurofilament light chain levels, a biomarker for neuroaxonal damage, may be associated with a prodromal or subclinical phase in the setting of multiple sclerosis (MS).
Evidence Rating Level: 3 (Average)
While most patients affected by multiple sclerosis (MS) experience initial symptoms in early adulthood, there is increasing evidence that the pathophysiologic processes contributing to the disease occur long before diagnosis. Serum neurofilament light chain (sNfL) is a sensitive biomarker for ongoing neuroaxonal degeneration. In this nested case-control study among 120 US military personnel with serum samples stores in the US Department of Defense Serum Repository, researchers compared sNfL levels in 60 cases to matched controls to assess whether sNfL levels are elevated before clinical MS onset. Researchers found that serum NfL levels were higher in case patients with MS compared with matched control samples drawn a median of 6 years (range 4 to 10 years) prior to MS clinical onset (p=0.04). Interestingly, the difference in serum sNFL levels increased as the time to case clinical onset decreased (p=0.008). Researchers also found that in comparing samples from the same case, an increase in presymptomatic sNfL levels was associated with a higher MS risk (RR for 5 pg/mL increase: 7.50, 95% CI 1.72 to 32.80, p=0.007). This study therefore shows that sNfL levels were increased for years prior to the onset of clinical MS, and therefore, MS may have a prodromal phase, characterized by subclinical neuroaxonal damage.
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