Elsevier

Brain and Development

Volume 21, Issue 1, January 1999, Pages 59-62
Brain and Development

Original article
Serum melatonin kinetics and long-term melatonin treatment for sleep disorders in Rett syndrome

https://doi.org/10.1016/S0387-7604(98)00072-2Get rights and content

Abstract

We studied the circadian rhythm of serum melatonin levels in two patients with classical Rett syndrome having severe sleep disorders; serum melatonin levels were measured before and during melatonin treatment using radioimmnoassay. Patient 1 had a free-running rhythm of sleep-wake cycle from 3 years of age. At the age of 4 years, the peak time of melatonin was delayed 6 h compared to normal control and the peak value was at the lower limit. Patient 2 had a fragmented sleep pattern accompanied by night screaming from 1 year and 6 months of age. At the age of 10 years, the peak time of melatonin secretion was normal but the peak value was at the lower limit. These patients were given 5 mg melatonin orally prior to bedtime. Exogenous melatonin dramatically improved the sleep-wake cycle in patient 1. In patient 2, exogenous melatonin showed a hypnotic effect but early morning awakenings occurred occasionally. When melatonin treatment was stopped, the sleep disorders recurred and re-administration of 3 mg melatonin was effective in both patients. The effect was maintained over 2 years without any adverse effects. These findings suggests that sleep disorders in patients with Rett syndrome may relate with an impaired secretion of melatonin.

Introduction

Rett syndrome is a neurodevelopmental disorder characterized by autistic behavior, dementia, truncal ataxia, and stereotyped movement of hands. Sleep disorders are commonly observed in patients with Rett syndrome 1, 2, 3, 4, and are serious problems for not only the patients but also their caregivers. Melatonin plays a role in regulation of the sleep-wake cycle. Oral administration of melatonin has been shown to be effective for treating sleep disorders in neurologically disabled children 5, 6, 7. Recently, it was reported that 4-week melatonin treatment was effective for sleep disorders in Rett syndrome [8]. However, the circadian rhythm of melatonin in Rett syndrome has never been studied. We studied the circadian rhythm of serum melatonin levels in two patients with Rett syndrome and sleep disorders. After that we tested the efficacy and the safety of long-term melatonin treatment for sleep disorders.

Section snippets

Materials and methods

Two girls with Rett syndrome having sleep disorders failed to respond to conventional treatments, and their family became exhausted. Their symptoms were compatible with the criteria for classical Rett syndrome [9]. The patients have strabismus but sight. Their mothers recorded the patients' 24-h sleep pattern. Serum melatonin levels of the patients were examined before and during melatonin treatment. The patients were kept under room light illumination from 06:00 to 20:00 h. Using a heparinized

Results

The patients showed different types of sleep disorders; patient 1 had a free-running sleep-wake cycle, and patient 2 had a fragmented sleep pattern accompanied by screaming during the night. Both patients got to sleep within 30 min of oral administration of 5 mg melatonin. Patient 1 dramatically returned to a normal sleep-wake cycle, and patient 2 sometimes had early morning awakenings. Repeated hematological tests urinalysis, and endocrinological tests during the treatment were normal.

Discussion

Recently, McArthur and Budden [8]reported that nine girls with Rett syndrome underwent a 4-week melatonin treatment in a double-blind placebo-controlled, crossover protocol; exogenous melatonin decreased the mean sleep-onset latency, and improved total sleep time and sleep efficiency, in three patients with the worse sleep quality. This study was the first full paper reporting on melatonin treatment in Rett syndrome, however, it was a short time trial and did not examine the melatonin secretion

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Acknowledgements

We thank Dr. Yoshio Makita for his helpful comments on this manuscript. This study was supported by a grant-in-aid for Scientific Research from the Ministry of Education, Science, and Culture, Japan (No. 10250557).

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