Neurofilament heavy chain in secondary progressive multiple sclerosis

BACKGROUND: Biomarkers are needed to track progression in MS trials. Neurofilament heavy chain (NfH) has been underutilized due to assay limitations. OBJECTIVE: To investigate the added value of cerebrospinal fluid (CSF) NfH in secondary progressive multiple sclerosis (SPMS) using contemporary immunoassays. METHODS: This exploratory study was part of the MS-SMART trial. Clinical assessments (including expanded disability status scale, upper and lower limb function, visual acuity and symbol digit modalities test (SDMT)), CSF and serum sampling were acquired at baseline (n = 54), 48 and 96 weeks. Brain magnetic resonance imagings (MRIs) were obtained at baseline and 96 weeks. The NfL and NfH were measured using single-molecule array assay. RESULTS: Baseline CSF NfH and NfL correlated with information processing speed at 96 weeks, with CSF NfH showing stronger correlations (r = -0.49 for SDMT) than CSF NfL (r = -0.37 for SDMT). Baseline CSF NfL predicted poorer hand dexterity at baseline, 48 and 96 weeks. CSF NfH was the only predictor of cortical grey matter at baseline, while baseline CSF NfL was the only predictor of brain atrophy at 96 weeks. Serum neurofilaments showed limited associations. CONCLUSION: CSF neurofilaments are better outcomes than serum neurofilaments in small SPMS studies. CSF NfH and NfL variably predict worsening hand function, information processing speed and brain volume loss, possibly reflecting complementary aspects of neurodegeneration.