Case reportDose response to melatonin treatment for disordered sleep rhythm in a blind child
Introduction
Blindness is often accompanied by disrupted circadian rhythms and sleep problems [1]. Melatonin treatment has been successful in restoring a normal sleep pattern in some blind adults and children [2], [3]. We describe results of a placebo-controlled masked study of two doses of melatonin in a blind child.
Section snippets
Case report
The patient is a 7-year-old boy with blindness, static encephalopathy and long standing sleep disorder. He suffered birth asphyxia and has septo-optic dysplasia with lack of light perception, absent pupillary light reflexes and hypopituitarism that is well controlled by growth hormone, thyroxine and cortisol. His sleep pattern is disruptive, he falls asleep between 16:00 and 18:00 h or earlier and gets up between 01:00 and 04:00 h. The family history did not disclose any sleep disorder or other
Methods
The Institutional Review Board approved the protocol and the parents gave written consent. The study consisted of three consecutive 8-week treatment phases of melatonin or placebo using a randomized double-masked design that followed an initial phase of 4 weeks of adaptation to the protocol. Placebo, low dose melatonin (7 μg/kg) and high dose melatonin (110 μg/kg) were assigned in random order by the investigational drug pharmacist. Investigators and parents remained blinded to the dose used in
Results
The order of treatment was phase 1-placebo, phase 2-low dose melatonin and phase 3-high dose melatonin. During the 4 weeks of adaptation and the 8 weeks of phase 1 the child cooperated with continuous use of the actigraph. The sleep logs and actigraphy demonstrated erratic sleep, particularly irregular sleep onset time often in the mid-afternoon – 15:30 or 16:00 h. In addition, waking times were inappropriately early, 01:00–04:00 h. The observation noted in the sleep diary that the child would
Discussion
An impact of birth asphyxia on the child's sleep problem cannot be excluded, although children with static encephalopathy without blindness typically present multiple nocturnal awakenings rather than an abnormal sleep rhythm. This child's sleep problem may be classified as advanced sleep phase syndrome, as described in some adults with blindness [9]. Alternatively, because of the anatomic abnormality of the anterior visual pathways, we surmise that this child had disrupted circadian rhythm
Acknowledgements
Supported in part by USPHS Grant RR-08084 from the National Center for Research Resources, General Clinical Research Centers Program, NIH, by the Abrahamson Pediatric Eye Institute and by grant EY00384 from the National Eye Institute (W.V.G.).
References (12)
- et al.
Circadian rhythm abnormalities in totally blind people: incidence and clinical significance
J Clin Endocrinol Metab
(1992) - et al.
Melatonin administration to blind people: phase advances and entrainment
J Biol Rhythms
(1991) - et al.
The use of melatonin to treat sleep–wake-rhythm disorders in children who are visually impaired
J Vis Impairment Blindness
(1996) - et al.
Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance
Proc Natl Acad Sci USA
(1994) - et al.
Pharmacokinetics of melatonin in human sexual maturation
J Clin Endocrinol Metab
(1996) Plasma melatonin rhythm in normal puberty: interactions of age and pubertal stages
Neuroendocrinology
(1992)
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2018, Pediatric NeurologyCitation Excerpt :This fact suggests that the biological clock rhythm in these patients is fixed at a later clock time than desired.22 A low excretion of the metabolite 6-sulfatoxymelatonin (aMT6s) in urine with an absence of circadian variation has often been reported in pediatric patients with severe psychomotor delay (frequently associated with epilepsy or blindness).23 On the other hand, in children with autism spectrum disorders and insomnia responsive to exogenous melatonin treatment, normal endogenous melatonin profiles have been demonstrated.24
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2017, Journal of Child Neurology
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Present address: The Smith-Kettlewell Eye Institute, 2318 Filmore Street, San Francisco, CA 94115-1821, USA.