Structural Alterations Associated With Cardiovascular Autonomic Failure in Multiple System Atrophy

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.