Evolution of Prodromal Multiple System Atrophy from REM Sleep Behavior Disorder: A Descriptive Study

BACKGROUND: Prodromal multiple system atrophy (MSA) has been characterized mainly by retrospective chart reviews. Direct observation and tracking of prodromal markers in MSA have been very limited OBJECTIVE: To report the baseline characteristics and evolution of prodromal markers of MSA as they were prospectively measured in patients with idiopathic/isolated REM sleep behavior disorder (iRBD) METHODS: Patients with iRBD were evaluated as part of a comprehensive protocol repeated annually. The protocol included assessment of motor, sleep, psychiatric, and autonomic symptoms supplemented by motor examination, quantitative motor testing, neuropsychological examination, orthostatic blood pressure measurement, and tests of olfaction and color vision. Patients who eventually developed MSA were described and compared with those who phenoconverted to Lewy body disease (Parkinson’s disease and dementia with Lewy bodies). RESULTS: Of 67 phenocoverters, 4 developed MSA-P and 63 developed Lewy body disease. An additional 2 MSA-C patients were seen at baseline, already with cerebellar signs. Compared to those with Lewy body disease, those with MSA-P were younger, had less severe loss of tonic REM sleep atonia, more insomnia symptoms, and better olfaction. Clinically-evident autonomic dysfunction was not invariable in prodromal stages, often developing proximate to or after motor phenoconversion. Of the autonomic symptoms, genitourinary dysfunction was the first to develop in all cases. Olfaction and cognition remained normal throughout the prodromal and clinical disease course, in clear contrast to patients with Lewy body disease. CONCLUSION: Prodromal MSA progresses rapidly, often without substantial autonomic dysfunction, and with preserved olfaction and cognition throughout its prodromal course.