Original articleSerum melatonin kinetics and long-term melatonin treatment for sleep disorders in Rett syndrome
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
Unlinked reference
AUTHOR, PLEASE SUPPLY CITATION FOR REFERENCE [13].
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).
References (14)
- et al.
Rett syndrome – clinical studies and pathophysiological consideration
Brain Dev
(1984) - et al.
Aberrant sleep patterns in children with the Rett syndrome
Brain Dev
(1990) - et al.
Classical Rett syndrome in sisters: variability of clinical expression
Brain Dev
(1997) Pro-convulsant effects of oral melatonin in neurologically disabled children
Lancet
(1998)- et al.
Rett syndrome – natural history in 70 cases
Am J Med Genet
(1986) - et al.
Rett's syndrome: characterization of respiratory patterns and sleep
Ann Neurol
(1987) - et al.
The treatment of sleep disorders with melatonin
Dev Med Child Neurol
(1994)