Exogenous Melatonin in Periodic Limb Movement Disorder: An Open Clinical Trial and a Hypothesis EXOGENOUS MELATONIN IN PLMD Study Objectives: The etiology of Periodic Limb Movement Disorder (PLMD) as well as the precise role of melatonin in human physiology

SOME 35 YEARS AFTER THE FIRST COMPLETE DESCRIPTION OF PERIODIC LIMB MOVEMENT DISORDER (PLMD) BY LUGARESI,1 many drugs proved to be effective in improving symptoms,2,3,4 but the etiology of the disorder is still virtually unknown. PLMD may occur as a distinct disorder, in association with various drug treatments or other sleep disorders such as apnea5 or narcolepsy,6 and, very frequently, with restless legs syndrome (RLS).7 Together, PLMD and RLS represent the fourth most common cause of insomnia with frequent complaints of daytime disturbances.7 We previously reported a patient suffering from the symptoms of REM sleep behavior disorder (RBD), who responded to melatonin treatment with a clinical improvement, a reduction of motor activity during sleep, an increase of the percentage of REM sleep and a better preservation of REM sleep associated muscle atonia.8 As to the mode of action of melatonin in this patient we considered a specific effect on RBD, an effect on REM sleep regulation or the direct reduction of sleep motor activity. Thus, in order to create hypotheses, we treated in open-labeled trials: 1) patients with RBD;9 2) patients with a quantitative REM sleep deficit (yet unreported); and 3) patients suffering from symptoms of PLMD about whom we report here. We chose PLMD, because it represents a well-operationalized motor disorder of sleep. PLMD is characterized by periodic episodes of repetitive and highly stereotyped limb movements which occur during sleep. The frequency of PLMs differs between individuals, but is intraindividually remarkably stable.10,11 The purpose of the presented pilot study was to obtain first evidence for the hypothesis that exogenous melatonin can reduce the number of PLM`s and thereby improves clinical symptoms of PLMD.