Clinical and Autonomic Features Suggest Phenoconversion from Sporadic Adult-onset Ataxia to Clinically Probable Multiple System Atrophy
Tina Liu1, Monica Krause1, Negin Badihian1, William Harmsen2, Lauren Jackson1, Marianna Suarez1, Eduardo Benarroch1, Paola Sandroni1, Phillip Low1, Wolfgang Singer1, Elizabeth Coon1
1Neurology, 2Biostatistics, Mayo Clinic
Objective:
To determine factors that predict phenoconversion from sporadic adult-onset ataxia (SAOA) to multiple system atrophy (MSA).
Background:
Sporadic adult-onset ataxia (SAOA) is a neurodegenerative cerebellar disease that causes progressive ataxia excluding other causes, including neurodegenerative ataxia such as multiple system atrophy (MSA). Some SAOA patients later develop autonomic failure to meet diagnostic criteria for MSA. Identifying risk factors in SAOA patients for developing MSA poses benefits for early diagnosis and future early intervention.
Design/Methods:
We performed a retrospective review of all patients referred for ataxia of unknown etiology initially diagnosed with SAOA from 1999 to 2018 at Mayo Clinic, Minnesota. Patients later diagnosed with MSA were classified as phenoconverters. Clinical variables, demographic information, and autonomic function studies were analyzed to assess factors that predicted later diagnosis of MSA.
Results:
Among 169 patients with SAOA at presentation, 60 (35.5%) phenoconverted to MSA. Clinical features influencing phenoconversion to MSA included: early autonomic symptoms, stridor, bladder symptoms, REM sleep disorder, and orthostatic intolerance. MSA phenoconverters more likely endorsed REM sleep disorder (38.3%) compared to nonconverters (11.9%). Age of onset, parkinsonism, and falls remained similar between the two groups. More patients with MSA underwent autonomic function tests (70% vs 41.3%) and thermoregulatory sweat tests (58.3% vs 33%) compared to the SAOA group.
On autonomic testing, phenoconverters had higher supine systolic blood pressures with greater orthostatic drop and higher median composite autonomic severity scores. There was a similar rate of abnormal thermoregulatory sweat tests between MSA (75%) and SAOA (68.8%) groups while MSA phenoconverters had higher mean percentages of anhidrosis (31.2%) than the SAOA group (13.9%).
Conclusions:
Our findings suggest that at least a third of SAOA patients phenoconvert to MSA. While these results are limited due to the retrospective nature, presenting clinical features and autonomic function tests may be helpful to identify SAOA patients likely to develop MSA.