Our goal was to examine i) associations between MRI features and indices of disease burden and ii) utility of these features for longitudinal tracking of disease progression.

We prospectively enrolled possible or probable MSA patients whose disease was still relatively early (unified multiple system atrophy rating scale [UMSARS] I: 5-16 and able to walk unaided) to undergo standardized T1 MPRAGE images on 3 T MRI scanners for morphometric MRI analysis. There were 17 early MSA (9 MSA-C and 8 MSA-P) and 15 normal subjects with MRI scans at baseline and a subset with follow-up scans at 12-months.  MRI volumes were computed using Freesurfer v5.3 and scaled to head size. Indices of disease burden included symptom and functional deficit scale (UMSARS I), motor deficit scale (UMSARS II), autonomic deficit scale (CASS+TST), and autonomic symptom score (COMPASS).

All MSA specific regions strongly correlated with both UMSARS I and UMSARS II (r=-0.63 to -0.65, p<0.001) with these regions explaining over 50% of the variability.  CASS+TST had stronger correlation with striatum (r=-0.58, p<0.001) compared to correlations with brainstem (r=-0.43, p=0.015) and cerebellar WM (r=-0.47, p=0.006). COMPASS was only associated with striatum volume (r=-0.58, p<0.001). There was a marked decrease in MSA specific regional volumes over one-year period for both brainstem and cerebellar WM in MSA, which was not seen in controls. There was also significant decrease in MSA-P observed in the striatum volume.