Introduction: REM sleep behavior disorder (RBD) is considered a prodromal phase of α-synucleinopathy like Parkinson disease (PD). PD is characterized by a progressive decline of dopamine (DA) in the striatum. Here we report the surprising increase in DA transporter density over successive years in an RBD patient treated with melatonin. Case Presentation: A then 72-year-old man was clinically suspected to suffer from PD in 2011. DA transporter scintigraphy (DaTSCAN) revealed reduced DA transporter density, and the patient was diagnosed with developing PD. Because of outacting dreams every night (speaking, yelling, kicking, pushing) he was referred to our clinic. Video-assisted polysomnography (PSG) confirmed the diagnosis of RBD in 2012. Management and Outcome: Melatonin treatment (2 mg slow release/day; 30 min prior to habitual bedtime; always at the same clock time) was initiated after PSG and continued. After 6 months of gradual improvement, clinical signs of RBD were absent. Control PSG in 2014 confirmed normalized REM sleep with atonia. Furthermore, no clinical sign of neurodegeneration occurred ever since. Additional DaTSCANs were performed in 2013 and 2015. Whereas the 2011 scan prior to melatonin treatment bore clear signs of PD, the 2013 scan was considered borderline and the 2015 scan without any sign of PD. Discussion: To the best of our knowledge, DA transporter density increase over time has never been reported in a single subject, neither healthy aged individuals nor patients suffering from RBD or PD. We interpret these results as a possible neuroprotective role for melatonin in synucleinopathy.

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