Objective: We report the first prospective natural history study of MSA combining progression of the disease and mortality.

Background: Multiple system atrophy (MSA) is a rare neurodegenerative disorder that is characterized by a variable combination of parkinsonism, cerebellar ataxia and autonomic failure.

Methods: 238 subjects with a diagnosis of possible or probable MSA were recruited and followed at the French Reference Center for MSA between 2007 and 2017. They were annually evaluated with the 4-dimensional UMSARS scale. Scores of Part I and part II were combined in a total UMSARS score. For part III, the blood pressure in supine position and the highest difference between the measure in supine and upright position were separately analysed. Disability in part IV was dichotomized. Due to a high probability of death, we used joint models for longitudinal data and a time-to-event to study the progression of each UMSARS-subscale over time and its determinants, and their association with survival.

Results: 157 (66%) patients had MSA-P and 75.6% had probable MSA at the first visit. The mean age at symptom onset was 60.2 years. Of the 238 patients, 98 died during follow-up with a median survival of 5.3 years since the first visit. When taking into account mortality, longer symptom duration before diagnosis, MSA-P subtype, and probable MSA diagnosis were associated with a higher total UMSARS score at baseline but no effect on progression. The progression of total UMSARS score was associated with higher risk of mortality. After adjustment for the progression of total UMSARS score, only gender remained associated (men had a higher risk of mortality). No factor was associated with the progression of supine blood pressure or orthostatic hypotension, and these subscales were not associated with mortality. The initial UMSARS IV score was higher in patients with probable MSA, more advanced age at first visit and women. After adjustment for the progression of UMSARS IV, a shorter duration between first symptoms and first visit and female gender were associated with a lower risk of mortality.

Conclusions: We confirmed the poor prognosis of the disease and found a higher level of disability for patients with MSA-P and probable MSA. The effects of these factors on mortality were mediated by the progression of UMSARS I and II. Similar to other neurodegenerative diseases, women tolerated higher levels of disability with delayed mortality. Dysautonomia had no impact on mortality, neither as initial clinical presentation nor the progression.

« Back to 2018 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/disease-progression-and-survival-of-multiple-system-atrophy-a-prospective-french-cohort-study/