To assess one-year progression of biomarkers and clinical symptoms in Multiple System Atrophy (MSA)

Fluid biomarkers potentially quantify disease severity, monitor disease progression, and predict clinical symptoms in MSA. We assessed changes in clinical severity and neurofilament light chain (NfL) over a 12-month period.

We enrolled 15 participants who met criteria for clinically possible or probable MSA. Neurologic examination and clinical assessments included the Unified Multiple System Atrophy Rating Scale (UMSARS part 1 and 2) and the Natural History and Neuroprotection in Parkinson Plus Syndromes (PPS) rating scale (assessing motor severity). Plasma neurofilament light chain (NfL) was obtained every 3 months, and cerebral spinal fluid (CSF) every 6 months. Longitudinal changes were assessed using a random effects model with random intercept. Clinical associations were assessed using a linear regression model.

Across all participants, plasma NfL increased at an average rate of 0.56 pg/mL/month (p<0.001). The rate of CSF NfL increase over time was not statistically significant. There was a significant correlation between plasma and CSF NfL levels (r= 0.63, p=0.04), and over time one standard deviation increase in CSF NfL correlated with a 0.7304 standard deviation increase in plasma NfL (r= 0.7304 p<0.001). To evaluate the associations between baseline NfL and clinical symptoms over time, we applied a simple linear regression, using baseline plasma or CSF NfL as a predictor of clinical change at 6 and 12 months. Baseline plasma and CSF NfL were independently associated with 6 and 12-month change in total PPS and UMSARS part 2 (p<0.05). Plasma NfL was additionally associated with 6 and 12-month progression of UMSARS part 1 (p<0.05). 

Plasma and CSF NfL are associated with clinical worsening in MSA. Plasma NfL significantly increased over 12 months. These data suggest that NfL may be a marker of disease modification in studies of MSA.