Twenty Years After: Another Case Report of Melatonin Effects on REM Sleep Behavior Disorder, Using Serial Dopamine Transporter Imaging

Abstract

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.

Melatonin for Rapid Eye Movement Sleep Behavior Disorder in Parkinson's disease: A Randomised Controlled Trial

“…These results challenge the current clinical assumptions on the efficacy of melatonin for RBD, 8,9 although previous studies included small samples with a variety of disorders, questioning their generalizability to PD. [6][7][8][9][11][12][13][14][23][24][25] The effects of prior trials were often mixed, with several participants not responding to FIG. 2.…”

“…The post-observation period assessed whether the effects would persist. 8,11 Ethical approval was obtained from the Human Research Ethics Committees of the University of Sydney and Royal Prince Alfred Hospital, Australia. The trial was prospectively registered (ACTRN12613000648729) with its protocol published online: anzctr.org.au/ACTRN12613000648729.aspx.…”

“…11 However, current guidelines are based on mainly case series and small open-label studies. 6,7,9,[11][12][13][14][15][16] Only one previous randomized controlled trial (RCT) assessed the efficacy of 3 mg of melatonin in just 8 subjects with mixed neurological disorders, showing a modest improvement on the clinical global impression (CGI) and REM epochs without atonia. 8 However, another small RCT recently showed that 2 (n = 7) or 6 mg (n = 9) of PR melatonin did not improve CGI versus placebo (n = 9) in subjects with clinically isolated RBD.…”

Melatonin: Clinical Perspectives in Neurodegeneration

“…Whereas, the scan prior to melatonin treatment had clear signs of PD, the scan recorded 2 years later was considered borderline, with absence of any sign of PD 4 years after the first scan. The results were interpreted as a possible neuroprotective role for melatonin in synucleinopathy (205).…”

“…Indeed, the conversion rate to synucleinopathy in clonazepam-treated RBD patients is high (208, 209). Although no comparable data are available yet for melatonin-treated RBD patients, a recent observation by Kunz and Bes deserves to be considered (205). The investigators reported the increase in DA transporter density (as assessed by DA transporter scintigraphy) over successive years in a 72-year-old RBD male patient treated with 2 mg of slow release melatonin daily.…”