Neurofilament light chain serum levels correlate with 10‐year MRI outcomes in multiple sclerosis

Abstract

ObjectiveTo assess the value of annual serum neurofilament light (NfL) measures in predicting 10‐year clinical and MRI outcomes in multiple sclerosis (MS).MethodsWe identified patients in our center's Comprehensive Longitudinal Investigations in MS at Brigham and Women's Hospital (CLIMB) study enrolled within 5 years of disease onset, and with annual blood samples up to 10 years (n = 122). Serum NfL was measured using a single molecule array (SIMOA) assay. An automated pipeline quantified brain T2 hyperintense lesion volume (T2LV) and brain parenchymal fraction (BPF) from year 10 high‐resolution 3T MRI scans. Correlations between averaged annual NfL and 10‐year clinical/MRI outcomes were assessed using Spearman's correlation, univariate, and multivariate linear regression models.ResultsAveraged annual NfL values were negatively associated with year 10 BPF, which included averaged year 1–5 NfL values (unadjusted P < 0.01; adjusted analysis P < 0.01), and averaged values through year 10. Linear regression analyses of averaged annual NfL values showed multiple associations with T2LV, specifically averaged year 1–5 NfL (unadjusted P < 0.01; adjusted analysis P < 0.01). Approximately 15–20% of the BPF variance and T2LV could be predicted from early averaged annual NfL levels. Also, averaged annual NfL levels with fatigue score worsening between years 1 and 10 showed statistically significant associations. However, averaged NfL measurements were not associated with year 10 EDSS, SDMT or T25FW in this cohort.InterpretationSerum NfL measured during the first few years after the clinical onset of MS contributed to the prediction of 10‐year MRI brain lesion load and atrophy.

Serum neurofilament light chain levels associations with gray matter pathology: a 5‐year longitudinal study

“…Our findings of higher baseline sNfL levels, higher concurrent inflammatory activity, and future WBV atrophy are in line with several previous reports . Associations between baseline sNfL levels, T 2 ‐LV, and Gd–enhancing lesions have been demonstrated as early as at the first demyelinating event, and are able to significantly predict conversion to clinically definite MS .…”

“…Moreover, studies report up to 17.8% and 4.9% increase in sNfL levels for every Gd–enhancing lesion and new/enlarging T 2 lesion, respectively . In a 10‐year follow‐up study, sNfL levels measured at the 5‐year time point were associated with greater WBV loss till year 10 . Correspondingly, a 5‐year longitudinal study showed similar sNfL effect size and associations with greater WBV atrophy measured both at 2 and 5‐year follow‐up .…”

Blood neurofilament light as a potential endpoint in Phase 2 studies in MS

“…High NfL levels in blood were also associated with higher risk of future relapses and EDSS worsening . Blood NfL levels predicted disability worsening after up to 8 years and lesion load and atrophy after 10 years in patients with MS . Notably, NfL predicted future brain and spinal cord atrophy .…”

“…However, a number of studies have shown that blood NfL levels are significantly higher in patients with MS and were reduced after treatment with fingolimod, natalizumab, and rituximab in CSF but also in several observational studies in the blood . NfL levels at baseline correlate with clinical (such as a recent relapse and an EDSS score) as well as MRI‐related measures (such as T2 lesion volume and number of gadolinium‐enhancing lesions and brain volume loss) . High NfL levels in blood were also associated with higher risk of future relapses and EDSS worsening .…”

Neurofilaments: The C-Reactive Protein of Neurology

“…It is therefore interesting that even early measures of blood NF-L in newly diagnosed MS patients can predict brain atrophy [22] and lesion load on MRI [23], probably reflecting high disease activity since this can be modified by initiation of effective treatment [108]. However, NF-L levels have shown poor correlation to disability scores such as the Extended Disability Status Scale (EDSS) [22][23][24]93,109,110]. This is most likely due to the emphasis on gait performance in the EDSS that may overestimate the influence of spinal cord lesions over cerebral lesions, which can be extensive even at low EDSS scores.…”