Longstanding disease-free survival in idiopathic REM sleep behavior disorder: Is neurodegeneration inevitable?

Introduction: Studies estimate that >80% of patients with idiopathic REM sleep behavior disorder (iRBD) eventually develop parkinsonism or dementia. However, a small group remains disease-free for long periods, raising the question of whether they truly have prodromal disease.
Methods: We selected subjects with iRBD who were diagnosed at least 10 years previously, and were still disease free (longstanding iRBD) (n = 11). We compared them to 'early converters' (n = 27) defined as those who phenoconverted to parkinsonism or dementia within 4 years after diagnosis, and to age- and sex-matched healthy controls (n = 68). We compared the frequency and progression of numerous markers of prodromal synucleinopathy between groups, and assessed likelihood of meeting prodromal Parkinson's disease criteria.
Results: After at least 10 years follow-up, almost all longstanding iRBD subjects showed multiple features of neurodegeneration, and 9/11 met criteria for prodromal PD. Evolution of markers was slower than early-converters, with an annual increase in prodromal PD probability of 3.9 ± 3.2% in longstanding iRBD compared to 12.4 ± 7.8% for early-convertors (p-value = 0.002). However, subjects with longstanding iRBD at their last visit had similar prodromal measures as the baseline evaluation of the early-convertors, with similarly-abnormal UPDRS scores, quantitative motor tests, cognition and autonomic symptoms and signs.
Conclusion: Although phenoconversion rates can differ dramatically between patients, almost all individuals with iRBD in our cohort appear to have underlying neurodegeneration.
(Copyright © 2018. Published by Elsevier Ltd.)