Natural history study of MSA in North America: A prospective cohort study

Abstract

Background: Multiple system atrophy (MSA) is a fatal and poorly understood rare neurodegenerative disorder. Here we describe the baseline characteristics of patients with MSA enrolled in a prospective multicenter natural history study of the NIH-sponsored U.S. Autonomic Disorders Consortium. Methods: Patients with a clinical diagnosis of MSA were prospectively enrolled at 5 participating centers. Demographic data, clinical variables, and autonomic testing results were included. Results: One hundred and nine patients with MSA (45 women) have been enrolled. MSA-C was predominant (60 patients, 55%). Mean age at symptom onset was 56.5 ± 8.8 and at enrollment was 61.2 ± 8.04 years old. MiniMental score was 28.9 ± 1.4 indicating normal cognition. Both the E:I ratio (1.09 ± 0.08) and the Valsalva ratio (1.24 ± 0.28) were low, indicating cardiovagal impairment. In the supine position, blood pressure (SBP/DBP)was 146 ± 24/82 ± 15mmHg, and heart rate (HR) was 74 ± 11 bpm (mean± SD). After 3-min head-up tilt, BP fell to 111 ± 23/67 ± 16mmHg andHR increased to 82 ± 11 bpm. Plasma norepinephrine level while supine was 278 ± 163 pg/ml and increased only to 409 ± 229 pg/ml upon head-up tilt indicating impaired baroreflex-mediated sympathetic activation. UPSIT score was 32.3 ± 4.1 indicating preserved olfaction. Symptoms suggesting REM behavior disorder were reported by 67%. Conclusions: Our results confirm that: i) symptom onset in MSA is remarkable consistent at 56 years; ii) overt cognitive impairment is not a typical feature; iii) sympathetic and cardiovagal deficits are present; iv) olfaction is preserved, and; v) sleep behavioral problems are frequent. Longitudinal evaluation of these patients will provide additional information on the natural history of the disease.