BACKGROUND

Early severe autonomic failure (AF) in multiple system atrophy (MSA) is a risk factor for poor survival. Postmortem studies suggested that AF is related to the degeneration of preganglionic autonomic neurons of the brainstem and spinal cord.

OBJECTIVES

Characterize cerebral alterations on brain imaging associated with cardiovascular AF.

METHODS

Cardiovascular sympathetic failure was evaluated through orthostatic hypotension (OH) based on changes in systolic and diastolic blood pressure during tilt-test (ΔSBP and ΔDBP). Reduced heart rate (HR) variability reflecting cardio-vagal impairment was assessed with a composite score formed by the root-mean square differences of successive R-R intervals (RMSSD) and HR changes during deep breathing. Voxel-based morphometry (SPM12), volumetry, and cortical thickness measurements (FreeSurfer 7.0) of T1-weighted anatomical images were used to assess gray matter (GM) atrophy in sub-tentorial structures. Multivariate analysis included age, disease severity (UMSARS), and total intracranial volume as confounding factors.

RESULTS

A total of 62 MSA patients followed at the French Reference Center were retrospectively included, aged 67.3 ± 8.6 years, 69.4% MSA-P, disease duration 4.2 ± 2.1 years. Medulla atrophy was correlated to OH (p < 0.006). Decrease in GM volume in the left anterior cerebellum (lobule V) was correlated to ΔDBP (pFWEc = 0.017). GM loss in the left interposed nucleus was correlated to ΔSBP (p < 0.003), whereas atrophy of the right dentate was associated with decreased HR variability (p < 0.003).

CONCLUSION

Medulla volume was strongly correlated with OH. Cerebellar degeneration was associated with the severity of cardiovascular AF.