Elevated CSF neurofilament proteins predict brain atrophy: A 15-year follow-up study

Background: Body fluid and structural imaging biomarkers give information on neurodegeneration. The relationship over time is not known in multiple sclerosis. Objective: To investigate the temporal relationship of elevated cerebrospinal fluid (CSF) neurofilament (Nf) protein levels, a biomarker for axonal loss, with magnetic resonance imaging (MRI) atrophy measures. Methods: In patients with multiple sclerosis, CSF Nf heavy chain (NfH) phosphoform levels were quantified at baseline and dichotomised into normal' and high'. Atrophy was assessed by MRI at baseline and 15-year follow-up using SIENAX and FreeSurfer software. Results: High baseline CSF NfH(SMI35) levels predicted pronounced atrophy at 15-year follow-up (odds ratio (OR): 36, p<0.01), in the absence of baseline brain atrophy (OR: 28, p<0.05), for the averaged MRI normalised brain volume (1.44L vs 1.33L, p<0.05), normalised grey matter volume (0.77L vs 0.69L, p<0.01) and putamen (12.7mL vs 10.7mL, p<0.05). Region-specific calculations including the spinal cord showed that a power of >80% is reached with 14-50 patients. Conclusion: These data suggest that high CSF NfH levels are an early predictor of later brain and spinal cord atrophy using structural imaging biomarkers and can be investigated in reasonably sized patient cohorts.