Elsevier

Sleep Medicine

Volume 11, Issue 4, April 2010, Pages 351-355
Sleep Medicine

Original Article
Effects of melatonin and bright light administration on motor and sensory symptoms of RLS

https://doi.org/10.1016/j.sleep.2009.12.008Get rights and content

Abstract

Background

A close temporal relationship was shown between the onset of melatonin secretion at night and the worsening of restless legs syndrome (RLS) symptoms, suggesting that melatonin may play a role in the genesis of this phenomenon. To test this hypothesis we studied the effects of the administration of exogenous melatonin and, conversely, the suppression of endogenous melatonin secretion by bright light exposure on the severity of RLS symptoms.

Methods

Eight RLS subjects were studied in three conditions: at baseline, after administration of melatonin and during bright light exposure. The severity of RLS symptoms was assessed by the suggested immobilization test (SIT), which allows quantification of both sensory and motor manifestations (SIT-PLM) of RLS.

Results

Analyses showed a significant increase of SIT-PLM index when subjects received exogenous melatonin compared to both baseline and bright light conditions, but bright light exposure had no effect on leg movements compared to the baseline condition. Analyses also revealed a small but significant decrease in sensory symptoms with bright light exposure compared to baseline.

Conclusion

Exogenous melatonin may have a detrimental effect on motor symptoms, and bright light exposure produced small but significant improvement of leg discomfort. The study shows the interest of using the SIT to measure outcome of intervention in RLS. Further studies will be needed to assess the therapeutic value of bright light in RLS.

Introduction

Restless legs syndrome (RLS) is a common neurological disorder characterized by an urge to move the legs, usually accompanied or caused by unpleasant sensations which begin or worsen during periods of rest or inactivity such as lying or sitting, partially or totally relieved by movement, and worse in the evening or night than during the day [1].

A large number of these patients also have periodic leg movements during sleep (PLMS) and during wakefulness [2]. To quantify both sensory and motor manifestations of RLS during wakefulness, we developed a method called the suggested immobilization test (SIT) [3].

One of the central characteristics of RLS is the worsening of symptoms in the evening and during the night. Three studies have investigated the circadian fluctuations of RLS symptoms using the SIT [4], [5], [6] and showed that the severity of leg discomfort follows a circadian rhythm with a maximum occurring after midnight. One study [4] used a modified constant routine protocol to evaluate circadian variations of both leg discomfort and PLMW in RLS patients and controls in relation to circadian rhythms of core body temperature, melatonin secretion and subjective vigilance [7]. This study showed that the onset of melatonin secretion occurs at the same time as the worsening of symptoms at night, but salivary melatonin concentration reached its peak approximately 2 h before the acrophase of sensory or motor symptom severity. This result raised the possibility that increased melatonin secretion at night may contribute to nighttime worsening of RLS. Clinical, pharmacological, neuroimaging and neuroendocrine studies [8], [9], [10], [11], [12], [13], [14], [15], [16] suggest that decreased dopaminergic transmission may be involved in the physiopathology of RLS. Since melatonin is known to inhibit dopamine release in specific areas of the central nervous system including the striatum [17], [18], we formulated the hypothesis that the increase of melatonin at night, through its inhibition of dopamine transmission, would be responsible for the aggravation of symptoms at that time.

To test this hypothesis, we administered melatonin in the evening to see whether increased circulating levels of exogenous melatonin would increase RLS symptoms. Additionally, we exposed RLS patients to bright light in the evening, a procedure known to suppress endogenous melatonin secretion [19], [20] with the expectation that melatonin suppression would decrease the expression of RLS manifestations.

Section snippets

Subjects

Eight subjects (two men and six women; mean age ± standard deviation [SD], 53.3 ± 9.1 years; range, 38–63 years) who were drug naïve and who received a diagnosis of primary RLS participated in this study. All subjects fulfilled the four essential diagnostic criteria of RLS. They all had a severity score greater than 20 (mean of 29.1 ± 5.4, range: 20–36) on the International RLS Study Group Severity Scale [21]. They all had a habitual bedtime between 21:00 h and midnight. Exclusion criteria were the

Results

As expected, a major increase of salivary melatonin secretion was seen after oral administration of melatonin compared to baseline values (see Fig. 1). A mean melatonin concentration of 70 and 60 pg/ml was found during the first and second SIT after melatonin administration compared to 5 and 12 pg/ml in the baseline condition (p < 0.001 for both the first and the second SIT). When subjects were exposed to bright light, melatonin secretion was suppressed (mean < 5 pg/ml for both SIT 1 and 2). There

Discussion

Motor symptoms worsened during the SIT when subjects received exogenous melatonin. This result supports our hypothesis that melatonin secretion plays a role in the worsening of RLS symptoms at night. The decrease of sensory symptoms during bright light exposure is also congruent with this hypothesis, although the magnitude of this change suggests that endogenous melatonin secretion is probably not the most important contributing factor to the worsening of symptoms at night.

Why does exogenous

Limitations of the study

The results of the present study should be interpreted with caution considering the small sample size. It is also important to stress the point that subjects of the present study were severely affected with a mean RLS severity score of 29. It is possible that very severe cases are less responsive to experimental manipulation and that larger effects may be seen in subjects with milder symptoms. Severely affected patients tend to complain of sensory-motor symptoms throughout the day, suggesting a

Acknowledgment

Research supported by the Canadian Institutes of Health Research.

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