Sleep Disorders in Children with Central Nervous System Tumors

Abstract

Sleep complaints are common in pediatric patients with central nervous system (CNS) tumors. These problems may result from disruption of normal homeostatic, circadian, neuroendocrine, and cardiorespiratory pathways and vary by tumor location and treatment received. Children with tumors within the hypothalamus and surrounding regions are prone to excessive daytime sleepiness. Sleep-related breathing disorders, especially those involving abnormal control of breathing, may occur in patients with tumors of the brainstem and posterior fossa. Maintaining a high index of suspicion for sleep disorders in children with CNS tumors is essential for early recognition and treatment. In this article, we will review the various sleep problems reported in pediatric brain tumor survivors, explore underlying neurobiological mechanisms, and discuss approaches to screening and diagnosis.Sleep is an essential physiologic function for growth, cognition, and physical and emotional well-being. It is particularly important in childhood, when the brain and body are undergoing rapid development. Normal sleep occurs through a complex interplay between homeostatic, circadian, neuroendocrine, and cardiorespiratory pathways. Cancer and cancer treatment may cause disruptions and imbalances in these pathways, resulting in abnormal sleep. Compared to the general population, pediatric cancer survivors are more likely to experience sleep problems. Patients with a history of brain tumors are particularly prone to sleep issues. In this article, we will review the physiology of normal sleep, describe the sleep problems and pathophysiologic mechanisms behind disrupted sleep in children with central nervous system (CNS) tumors, and discuss strategies for screening, diagnosis, and management. Sleep Mechanisms and PhysiologySleep and wakefulness. Sleep is fundamentally important in promoting growth, repair, and neurocognitive functioning. The timing, duration, and quality of sleep depend on complex, balanced interactions between sleep-promoting and wake-promoting pathways. The majority of these pathways are housed in the basal forebrain, diencephalon, and brainstem. The balance between sleep and wakefulness is governed by two distinct biologic processes: sleep-wake homeostasis (Process S) and circadian rhythm (Process C) [1]. Homeostatic drive to sleep intensifies with continued wakefulness over time and subsides as an individual sleeps. During the day, the sleep-dependent homeostatic drive is counteracted by sleep-independent circadian arousal mechanisms. Circadian rhythms are coordinated by an internal pacemaker housed in the bilateral suprachiasmatic nuclei (SCN) of the anterior hypothalamus [1]. The near-24 hour circadian rhythm is externally entrained by the light-dark cycle on Earth through direct input received by the SCN from retinal ganglion cells via the retinohypothalamic tract, which runs through the optic chiasm [2,3]. Additional input from the intergeniculate leaflet and median raphe nucleus modulate circadian phase shifts [3]. The SCN sends...

Secondary Narcolepsy as Worsening Sign in a Pediatric Case of Optic Pathway Glioma

“…Patients with tumors of the sellar/parasellar and hypothalamic region are the most vulnerable to develop these types of disorders, as orexin producing cells are located exclusively in the hypothalamus. The exact prevalence of excessive daytime sleepiness in children with cancer is difficult to assess; furthermore, sleep complaints reported by this population of children with CNS tumors additionally include fatigue (often not differentiated from sleepiness and more difficult to quantify), respiratory insufficiency (in children with tumors involving the brainstem), hypoxia, insomnia, circadian rhythm disorder, nocturnal seizures and snoring [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ].…”

“…It is a rare pediatric condition that is predominantly idiopathic, and in its secondary form can sometimes be associated with central nervous system (CNS) tumors. This occurrence is very rare, although the exact prevalence of excessive daytime sleepiness in pediatric neuro-oncology patients is difficult to assess; several case series of secondary narcolepsy have been published in adults, whereas fewer notions are available in children [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. Orexin deficiency is the major cause of this disorder and, in the case of CNS tumors, is potentially attributable to the direct damage (caused by surgery, radiation, or tumor infiltration itself) of the hypothalamic neurons that produce this excitatory neurotransmitter [ 9 ].…”

Excessive daytime sleepiness due to brain tumor

“…Patients with tumors located in the sellar and thalamic/hypothalamic regions, particularly those with craniopharyngiomas, are especially vulnerable to developing these disorders. 1,2 This is due to the close proximity of the tumor to the orexin-producing cells in the hypothalamus, which are crucial in regulating wakefulness. These cells may be damaged by the tumor itself, during surgery, and during focal or whole-brain radiation.…”