James E. Jan

Use of melatonin in the treatment of paediatric sleep disorders

Abstract: A group of Vancouver health professionals, including the authors, have studied the use of oral melatonin in the treatment of chronic sleep disorders in children with disabilities since the Fall of 1991. This review article is based on the first 100 patients, half of whom were visually impaired or blind. Children with neurological, neuropsychiatric, and developmental disabilities are predisposed to chronic sleep‐wake cycle disturbances. Disorders such as blindness, deafblindness, mental retardation, autism, and central nervous system diseases, among others, diminish the ability of these individuals to perceive and interpret the multitude of cues for synchronizing their sleep with the environment. Melatonin, which benefitted slightly over 80% of our patients, appears to be a safe, inexpensive, and a very effective treatment of sleep‐wake cycle disorders. The oral dose of fast release melatonin taken at bed‐time ranged from 2.5 mg to 10 mg. Side effects or the development of tolerance have not been observed. Since the causes of sleep difficulties are extremely variable, not all children are candidates for treatment. For successful melatonin treatment, clinical experience is required, and the influences of other health problems and medications need to be considered. Further clinical and laboratory research in this field is imperative because melatonin treatment offers enormous health, emotional, social, and economic benefits to society, especially since multidisabled children with chronic sleep difficulties do not respond well to current therapeutic regimes.

Cortical visual impairment in children

Cortical visual impairment (CVI) in children is most commonly caused by peri- or post-natal hypoxia-ischemia, but may also occur following other insults, e.g., trauma, epilepsy, infections, drugs or poisons, and certain neurologic diseases. The disorder differs considerably in etiology, physical findings, and, perhaps, prognosis, from the cortical blindness seen in adults. The same event that causes CVI by damaging the geniculate and/or extrageniculate visual pathways may also damage other areas of the brain, or the retina, optic nerves, or chiasm. Thus, children with CVI often have other neurological problems. Diagnosis may require the participation of a multidisciplinary team and the use of special visual testing techniques. Due to the uncertainty concerning the prognosis in CVI, clinicians should remain optimistic about the childs potential for some vision recovery.

A randomized, placebo-controlled trial of controlled release melatonin treatment of delayed sleep phase syndrome and impaired sleep maintenance in children with neurodevelopmental disabilities

Abstract:  The purpose of this study was to determine the efficacy of controlled‐release (CR) melatonin in the treatment of delayed sleep phase syndrome and impaired sleep maintenance of children with neurodevelopmental disabilities including autistic spectrum disorders. A randomized double‐blind, placebo‐controlled crossover trial of CR melatonin (5 mg) followed by a 3‐month open‐label study was conducted during which the dose was gradually increased until the therapy showed optimal beneficial effects. Sleep characteristics were measured by caregiver who completed somnologs and wrist actigraphs. Clinician rating of severity of the sleep disorder and improvement from baseline, along with caregiver ratings of global functioning and family stress were also obtained. Fifty‐one children (age range 2–18 years) who did not respond to sleep hygiene intervention were enrolled. Fifty patients completed the crossover trial and 47 completed the open‐label phase. Recordings of total night‐time sleep and sleep latency showed significant improvement of approximately 30 min. Similarly, significant improvement was observed in clinician and parent ratings. There was additional improvement in the open‐label somnolog measures of sleep efficiency and the longest sleep episode in the open‐label phase. Overall, the therapy improved the sleep of 47 children and was effective in reducing family stress. Children with neurodevelopmental disabilities, who had treatment resistant chronic delayed sleep phase syndrome and impaired sleep maintenance, showed improvement in melatonin therapy.

PERMANENT CORTICAL VISUAL IMPAIRMENT IN CHILDREN

Fifty patients with permanent cortical visual impairment were evaluated. They had a characteristic behaviour profile, usually with residual sight but poor visual attention. 30 of the 50 also had damage to the anterior visual pathway. Visual evoked potential mapping was shown to have a clear advantage over visual evoked responses, and using that in conjunction with CT and clinical data enabled several subgroups of cortical visual impairment to be identified. The diagnosis probably is more common than previously recognised, and should be suspected when there is greater delay in visual development in other areas and the degree of visual loss is unexplained by ocular findings. Using traditional criteria for cortical blindness may mean that many children are not diagnosed, which has serious implications for their rehabilitation.

Melatonin treatment of sleep–wake cycle disorders in children and adolescents

Lerner, a dermatologist who isolated melatonin (MLT) in 1959, was the first to report on its hypnotic properties, and was also the first to self-administer this hormone. Later, in 1971, Anton-Tay and coworkers injected MLT into volunteers who quickly fell asleep. In adults, MLT treatment appears to have beneficial effects in those who have sleep disorders due to delayed sleep onset, shift work, and jet lag. MLT can enhance adaptation to forced phase shift in simulated shift-work and jet-lag conditions. However, better controlled, long-term studies are still required. MLT may also benefit certain types of adult insomnia.

Sleep Hygiene for Children With Neurodevelopmental Disabilities

Sleep disturbances in children with neurodevelopmental disabilities are common and have a profound effect on the quality of life of the child, as well as the entire family. Although interventions for sleep problems in these children often involve a combination of behavioral and pharmacologic strategies, the first line of treatment is the promotion of improved sleep habits or “hygiene.” Despite the importance of sleep-hygiene principles, defined as basic optimal environmental, scheduling, sleep-practice, and physiologic sleep-promoting factors, clinicians often lack appropriate knowledge and skills to implement them. In addition, sleep-hygiene practices may need to be modified and adapted for this population of children and are often more challenging to implement compared with their healthy counterparts. This first comprehensive, multidisciplinary review of sleep hygiene for children with disabilities presents the rationale for incorporating these measures in their treatment, outlines both general and specific sleep-promotion practices, and discusses problem-solving strategies for implementing them in a variety of clinical practice settings.

Long-term sleep disturbances in children: A cause of neuronal loss

Short-term sleep loss is known to cause temporary difficulties in cognition, behaviour and health but the effects of persistent sleep deprivation on brain development have received little or no attention. Yet, severe sleep disorders that last for years are common in children especially when they have neurodevelopmental disabilities. There is increasing evidence that chronic sleep loss can lead to neuronal and cognitive loss in children although this is generally unrecognized by the medical profession and the public. Without the restorative functions of sleep due to total sleep deprivation, death is inevitable within a few weeks. Chronic sleep disturbances at any age deprive children of healthy environmental exposure which is a prerequisite for cognitive growth more so during critical developmental periods. Sleep loss adversely effects pineal melatonin production which causes disturbance of circadian physiology of cells, organs, neurochemicals, neuroprotective and other metabolic functions. Through various mechanisms sleep loss causes widespread deterioration of neuronal functions, memory and learning, gene expression, neurogenesis and numerous other changes which cause decline in cognition, behaviour and health. When these changes are long-standing, excessive cellular stress develops which may result in widespread neuronal loss. In this review, for the first time, recent research advances obtained from various fields of sleep medicine are integrated in order to show that untreated chronic sleep disorders may lead to impaired brain development, neuronal damage and permanent loss of developmental potentials. Further research is urgently needed because these findings have major implications for the treatment of sleep disorders.

The role of the thalamus in sleep, pineal melatonin production, and circadian rhythm sleep disorders

Abstract:  The thalamus has a strong nonphotic influence on sleep, circadian rhythmicity, pineal melatonin production, and secretion. The opening of the sleep gate for nonrapid eye movement sleep is a thalamic function but it is assisted by melatonin which acts by promoting spindle formation. Thus, melatonin has a modulatory influence on sleep onset and maintenance. A remarkable similarity exists between spindle behavior, circadian rhythmicity, and pineal melatonin production throughout life. Together, the thalamic and chronobiological control of sleep leads to a new and improved understanding of the pathophysiology of circadian rhythm sleep disorders and also of the principles of sleep hygiene interventions.

Behavioural characteristics of children with permanent cortical visual impairment.

The common behavioral features of 50 children with permanent cortical visual impairment (CVI) are described. CVI is frequently associated with specific behavioural characteristics. The majority of these children have residual vision, but they all have variable and inconsistent visual performance, including visual acuity. They see better in familiar environments and when they understand what to look for and where to look for it. They often use touch to identify objects. Their ability to identify colours is much stronger than their perception of form. Many turn their heads to the side when they are reaching. Nystagmus and visual self‐stimulation are exceptionally rare. They appear to have great difficulty with the cognitive evaluation of visual perception in spatial terms. Head elevation is worst in those with least vision, and without head elevation the possibility of visual stimulation is further restricted.

Melatonin therapy for circadian rhythm sleep disorders in children with multiple disabilities: what have we learned in the last decade?

In this discussion, children are considered to have multiple disabilities and low functioning when they have a combination of severe neurodevelopmental disabilities, such as visual impairment, epilepsy, intellectual deficits, cerebral palsy, attention-deficit–hyperactivity disorder (ADHD), autism, eating difficulties, and other neuropsychiatric problems.