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Sleep-wake disturbances are defined as perceived or actual alterations in sleep that result in impaired daytime function. Patients with sleep-wake disturbances may complain of difficulty initiating or maintaining sleep, waking too early, waking up feeling unrefreshed as well as reporting fatigue, hypersomnia, somnolence, or excessive daytime sleepiness during the wake period.
In the literature, these terms defining daytime sleepiness are often used interchangeably, leading to a lack of clarity. Unlike other cancers, there is limited information concerning sleep-wake disturbances in adults with primary brain tumors throughout the illness trajectory. A review article focused on management of both fatigue and sleep describes the omission of patient with primary brain tumors in intervention studies designed to reduce sleep-wake disturbance in other solid tumor patients.
The purpose of this paper is to synthesize the knowledge of sleep-wake disturbances, with a focus on the prevalence and mechanisms of insomnia and hypersomnia in adult patients with primary intracranial tumors and to apply what is known from other solid tumors about screening, assessment, interventions, and implications to advance both research and practice.
Authors AB and MS explored articles for sleep assessment and interventions in cancer.
The key words searched were brain tumor, glioma, lesion, sleep disturbance, sleep-wake disturbance, intervention, adult, adult patients, and survivors. Insomnia has often been reported to be the most common sleep disturbance in cancer patients; however, a recent review determined that the prevalence of specific sleep-wake disturbances in cancer cannot be established from published literature. The majority of evidence on the occurrence and risk of sleep-wake disturbances has been published in patients with other solid tumor malignancies. Studies exploring sleep-wake disturbance in the primary brain tumor patient population.
Insomnia is the most common sleep-wake disorder in patients with primary brain tumors, but additional sleep-wake disorders, including sleep-related breathing eg, obstructive sleep apnea and movement disorders eg, restless legs syndrome , also may occur. Other clinical and environmental factors may contribute to sleep-wake disturbances in the brain-tumor population.
Clinicians frequently interrupt hospitalized patients who are sleeping and may alter their sleep-wake and activity-rest cycle.
In summary, sleep-wake disturbance has been commonly reported in other solid-tumor malignancies and neurologic illnesses, but there is a paucity of studies in adult brain-tumor patients. These data would provide insights into the frequency and severity of these symptoms and their impact on patient outcomes as well as provide the foundation for future investigations of pathogenesis and treatment interventions.
Specific mutations and single nucleotide variants have been reported to be associated with both fatigue and sleep-wake disorders. Polymorphisms in genes associated with regulation of the circadian system and those associated with inflammation have been proposed.
However, sleep-wake is a complex process and involves the interaction of products of many genes as well as the influence of zeitgerber and other environmental influences. The influence of gene-environment interactions on sleep outcomes has not been extensively investigated.
In breast cancer patients, variations in 3 cytokine genes interleukin 1 receptor 2 [ IL1R2] , IL13 , and NFKB2 predicted the development of more severe sleep-wake disturbances. Assessment and management of sleep-wake disturbance in the primary brain tumor patient population. Cranial radiation remains the most common and significant factor reported to be associated with hypersomnia and sleep disturbances in primary brain-tumor patients.
Faithfull and Brandas 56 , 57 described a somnolence syndrome in malignant glioma patients that occurred during and immediately following cranial radiation therapy. Symptoms included fatigue, excessive drowsiness, incoordination, and inability to concentrate that occurred in a cyclical pattern. Gapstur et al. Sickness models propose that increased secretion of IL-1 and IL-6 may lead to stimulation of the HPA, causing symptoms including sleep-wake disturbance, fatigue, and depression.
In the case of brain radiation, inflammation may be the underlying mechanism leading to fatigue and the cascade of additional symptoms either directly or based on its disruption of underlying circadian rhythms.
Those who receive cranial radiation may demonstrate longer sleep duration, circadian rhythms with greater amplitude, less fragmentation, and poorer tolerance for alterations in the timing of sleep. No tool with established reliability and validity in adults with cancer is used routinely to screen for sleep-wake disturbances comorbid with cancer in primary care, oncology, or neuro-oncology clinics.
The Pan-Canadian practice guideline suggests asking patients with cancer about the presence of sleep problems and then asking about the relationship between the problem and daily functioning. In summary, screening and assessment for sleep-wake disturbances in brain-tumor patients is not conducted routinely and, when performed, a variety of measurements are available for use. In the clinical setting, Fig. For patients with sleep-wake disturbance that is not responsive to intervention or if sleep disturbances other than insomnia or hypersomnia do not resolve, referral for further evaluation by a sleep specialist should be considered.
Polysomnography, which is the gold standard for assessing and diagnosing sleep disorders such as sleep apnea and restless legs syndrome, may be performed. More detailed assessment may be needed in the research setting, and the choice of instrument is dependent on the type of sleep-wake disturbance of interest. An advantage of the PSQI is that it screens for sleep apnea, restless legs syndrome, and other sleep-wake disorders in addition to insomnia. Management of altered sleep-wake is complex and includes assessment and interventions geared to promoting improvement in the fundamental causes of the sleep-wake disturbance.
Interventions to improve sleep-wake disturbances in cancer patients have been primarily implemented in women with breast cancer and have not been tested in patients with brain tumors. Assessment for and modification of contributing factors and reinforcing sleep hygiene and sleep promotion activities see Fig. These preventative and educational strategies can be used in conjunction with nonpharmacological or pharmacological interventions, depending on the suspected underlying etiology and considering individual patient needs and deficits.
In general, pharmacological interventions should be initiated for a short duration and monitored due to unwanted adverse drug events. All interventions need follow-up and ongoing re-evaluation. The initial step in treatment is based on assessment and diagnosis of the sleep disorder, as described above. Other sleep-wake disorders, such as central or obstructive sleep apnea and restless legs syndrome, need to be ruled out. Insomnia is thought to be a disorder of hyperarousal; other factors such as neurophysiological and neuroendocrine dysregulation, anxiety, cancer treatments, or altered circadian rhythmicity have also been reported as etiologic factors of insomnia in patients with cancer.
Specific interventions have been found to be helpful in patients with other solid tumor malignancies and are described in detail below.
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Cognitive Behavioral Therapy Insomnia CBT-I , mindfulness-based stress reduction MBSR , and exercise are the interventions with the most evidence for improving sleep and reducing other associated symptoms in patients with other solid tumors. CBT-I is a type of psychotherapy that has been used to help with a variety of behavioral changes.
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The main aim of CBT-I is to explore and gain understanding about how a person thinks and feels and the relationship with the resulting behavior, so that new strategies for healthy thinking, coping, and behaviors can be explored. For sleep disturbance, CBT-I strategies include sleep restriction, stimulus control, and sleep hygiene modification.
CBT-I has been shown to improve sleep-wake disturbances in patients with cancer most extensively in women with breast cancer with meta-analysis reporting significant improvements in sleep for patients with cancer who participate in CBT-I. Sleep restriction during the day may be a component of CBT-I and are especially helpful in brain-tumor patients inclined to nap. In these patients who have cognitive deficits, involvement of a caregiver to utilize and inforce these strategies may be necessary.
It is hypothesized that after CBT-I, patients may experience a change in neural network dysregulation and other biological mechanisms that could lead to a change in sleep behavior. It aims to teach people to deal more effectively with an experience through awareness of feelings, thoughts, and bodily sensations, using practices such as body scan and exercises for yoga and meditation. Meta-analyses have shown that MBSR interventions may be a novel approach for managing sleep-wake disturbances in patients with cancer.
Evaluation of physical and cognitive deficits that would either preclude participation eg, receptive aphasia or require modifications eg, hemiparesis should be considered and communicated to the parties involved including patient, caregiver, and provider. Exercise is defined as physical exertion imposed on the body with the aim of improving or maintaining physical and mental fitness level or health.
A variety of activities can be performed as exercise, but the most important elements are frequency, intensity, time, and type. Aerobic exercise has been reported to improve mental health and promote structural changes in the brain. Exercise may help regulate disruption in the circadian rhythm in addition to building vasculature and promoting neurogenesis in patients with primary brain tumors who have suffered damage to these functions. The interventions noted above have not been fully evaluated in the brain-tumor patient population, but evidence supporting their utility for other solid tumor patients warrants consideration for their use in the clinical setting and further studies evaluating their utility for brain-tumor patients.
Other nonpharmacological interventions eg, light-therapy need further study in order to determine their effectiveness on sleep-wake disturbances in patients with cancer. Pharmacological approaches may be important short-term adjuncts for the brain-tumor patient with sleep-wake disturbance because nonpharmacological interventions may take time and effort to implement or not be feasible in selected patients. CBT-I may also be used alone or in combination with low-risk pharmacological agents. The decision to use pharmacological agents must be made carefully based on patient assessment including history of sleep-wake disturbance, concomitant medications, and comorbid conditions.
For instance, if insomnia is medication-induced eg, corticosteroids , lowering the dose or altering the time taken during the day may improve sleep. If there are existing comorbid conditions or symptom clusters such as depression, anxiety, or seizures, one medication may be given to improve insomnia along with the other factors. In this situation, there are antidepressant, anxiolytic, or barbiturate medications that can be prescribed to be taken at bedtime for their sedative effects.