Volume 22, Number 2
June 2015
Neurologic and Psychiatric Disorders and Sleep: Bi-directional Relationship on the Complex Interplay and Potential Interventions The main facts in human life are five: birth, food, sleep, love and death.” —E.M. Forster
S
leep is a quintessential component of life that is guaranteed to manifest on a nightly to near-nightly basis, even if attempts are made to avoid it. Albeit, there is not a definitive or well-elucidated concept for its occurrence; there is, however, significant evidence that either its deprivation or excess is detrimental to the maintenance of health and increases contribution to diseases. For example, Banks and Dinges1 documented behavioral and physiological effects of voluntary sleep deprivation in humans, revealing such deleterious consequences as impaired cognition and labile mood with micro–sleep intrusions into wakefulness, thereby, suggesting these to be consequences of disordered sleep. Sleep disorders are present in approximately 25%-40% of typically developing children2,3 and even more concerning in 50%-80% of children with comorbid neurologic or psychiatric disease.4-7 Mahatma Gandhi had stated “Each night, when I go to sleep, I die. And the next morning, when I wake up, I am reborn,” a prophetic metaphor emphasizing the critical importance of sleep and its homeostatic role in health maintenance. Sleep-dependent changes have been identified in membrane synthesis, oligodendrocyte proliferation, and myelin growth,8-10 indicating that neuronal activity during sleep could induce myelin growth and enhance functional connectivity in the developing brain.7 In fact, evidence from animal studies show that sleep is required for neurodevelopmental processes in specific brain circuits during critical periods of life.11-13 This special issue presents the current state of knowledge of pediatric sleep disorders in relation to psychiatric and neurologic disease. A total of 9 articles written by authors with a wealth of clinical experience and expertise have Disclosure: None of the authors have any financial support or conflicts of interest to disclose. No off-label use of drugs or products have been discussed in the article.
1071-9091/15/$ - see front matter & 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.spen.2015.04.003
addressed many of these key areas in child neurology and psychiatry as it relates to sleep disorders in children. The series begins with Fahed Hakim, Leila kheirandishGozal, and David Gozal providing an in-depth evaluation of the relationship between pediatric obstructive sleep apnea (OSA), pediatric obesity, and the disruption of metabolic homeostasis in these patients. The authors highlight the alarming epidemic of “globesity,” which is the worldwide trend toward obesity in children. They highlight the shift OSA in children being a result of adenotonsillar hypertrophy, to an increasingly common consequence of obesity, emphasizing the significant interplay of excessive weight in children as a cause of OSA, and also as a resulting consequence of metabolic disruption seen in patients with OSA. The alarmingly similar trend to the adult pathology also confers the secondary consequences of development of comorbid cardiovascular, endocrinologic, and neurologic diseases. However, the pediatric population experiences unique consequence, such as attention-deficit hyperactivity disorder like behavior, impaired academic performance, as well as long-lasting neurocognitive deficit. In the second article, Sejal V. Jain and Sanjeev V. Kothare discuss the intimately intertwined relationship between epilepsy and sleep. The article highlights the reciprocal effects of both sleep and sleep disorders on the electroencephalogram and on seizures, paying special attention to a specific subset of sleep-specific epilepsy syndromes, as well as the effect of antiepileptic drug treatment on sleep architecture. In the next article, Thomas J. Dye, Sejal V. Jain and Sanjeev V. Kothare also tackle the difficult task of discussing the evaluation of excessive daytime somnolence in a separate article on central hypersomnias. They provide an outline of the approach to the clinical evaluation and assessment to distinguish between primary and secondary hypersomnias, with reference to the recently published diagnostic criteria of the International Classification of Sleep Disorders, third edition. Claudia Dosi, Mariagrazia Figura, Raffaele Ferri, and Oliviero Bruni focus on the frequently encountered comorbid presentation of disordered sleep with cephalgias, 75
A.M. Morse and S.V. Kothare
76 emphasizing the genetically based neurophysiological and neuroanatomical substrates that predispose these patients to both pathologies. They highlight the most commonly encountered sleep disorders and provide a better understanding of the specific relationship to development of headache. They conclude with the bidirectional relationship and resultant importance of assessment and treatment of sleep disorders, as a part of headache management. Next, Kanwaljit Singh and Andrew W. Zimmerman address the frequently encountered issue of disordered sleep in autism and attention-deficit hyperactivity disorder. The authors discuss the burden and prevalence of different types of sleep disorders represented in the literature in these patients, as well as the proposed pathophysiology and etiology of the sleep problems. They acknowledge the significant heterogeneity of both the patient population and types of sleep disorders in these patients. This concept, thereby lays the foundation for their discussion about the difficulty in identifying a uniform method of evaluation and effective management of sleep disorders in these patients owing to the significant variability found. Suresh Kotagal next provides some insight to the relationship between sleep with static and progressive neurodegenerative disorders, such as Down syndrome, neuronal ceroid lipofuscinosis, Prader-Willi syndrome, and cerebral palsy. He focuses on the critical importance of the recognition and corrective management of sleep disorders and the resultant improvement in quality of life, in a concise disease-specific format. Sleep and its role in learning and memory have for many years interested scientists and researchers. The following paper by Kiran P. Maski provides a primer on sleep-dependent memory consolidation in children and adolescents, highlighting the link between sleep and neuronal plasticity. She then goes on to review the literature suggesting that there is a relationship between disordered sleep and neurodevelopmental disorders, thereby reinforcing the positive relationship between homeostatic sleep with learning and memory. Interventions available for disorders of sleep are numerous and can be quite difficult to navigate, especially when treating pediatric patients. Identification of appropriate pharmacologic treatment is more difficult in children and adolescents owing to minimal education received on these medications and limited data available in children in the literature, along with lack of Food and Drug Administration approval for their use. To overcome this obstacle, Mathew M. Troester and Rafael Pelayo present a very informative article discussing the indications, dosing, and suggested mechanisms of action for therapy, highlighting an approach to decipher which sleep disorder is present and its corresponding treatment. Finally, Anna Ivanenko and Ujjwal Ramtekkar conclude the series with an article focusing on the relationship between the development, severity, and prognosis of psychiatric disorders with comorbid sleep disturbance by providing a comprehensive review of literature and an
outline of treatment approaches for sleep interventions in this patient population. The authors provide a psychiatric illness–specific review, highlighting the increased frequency and specific subsets of sleep disorder associated with each psychiatric disorder and conclude with a review of sleep interventions with evidence of improvement in psychiatric outcome. However, the most striking statement may be regarding the relationship of disordered sleep to the elevated risk for suicidality and high-risk behavior, potentially suggesting that sleep assessment and treatment can be a potentially lifesaving or changing component in psychiatric care. We hope that this series provides a strong foundation on the implications of disordered sleep on neurologic and psychiatric disease, as well as contribute to a better understanding of possible treatment options. More so, we hope this series encourages interest and further investigation into the complex relationship between both homeostatic sleep and disordered sleep in relation to disease, maintenance of health, and neurodevelopmental outcomes. Anne Marie Morse, DO Sanjeev V. Kothare, MD
References 1. Banks S, Dinges D: Behavioral and physiological consequences of sleep restriction. J Clin Sleep Med 3:519-528, 2007 2. Ivanenko A, Gururaj BR: Classification and epidemiology of sleep disorders. Child Adolesc Psychiatr Clin N Am 18:839-848, 2009 3. Hodge D, Carollo TM, Lewin M, et al: Sleep patterns in children with and without autism spectrum disorders: developmental comparisons. Res Dev Disabil 35:1631-1638, 2014 4. Richdale AL, Schreck KA: Sleep problems in autism spectrum disorders: prevalence, nature, & possible biopsychosocial aetiologies. Sleep Med Rev 13:403-411, 2009 5. Stores G, Wiggs L, Campling G: Sleep disorders and their relationship to psychological disturbance in children with epilepsy. Child Care Health Dev 24:5-19, 1998 6. Richdale A: Sleep disorders in autism and Asperger's syndrome In: Stores G, Wiggs L, eds., Sleep disturbances in disorders of development: its significance and management. London; MacKeith Press, 2001, pp 181-191, 2001 7. Johnson CR: Sleep problems in children with mental retardation and autism. Child Adolesc Psychiatr Clin N Am 5:673-683, 1996 8. Bellesi M, Pfister-Genskow M, Maret S, et al: Effects of sleep and wake on oligodendrocytes and their precursors. J Neurosci 33:14288-14300, 2013 9. Cirelli C: A molecular window on sleep: changes in gene expression between sleep and wakefulness. Neuroscientist 11:63-74, 2005. [Eng] 10. Kurth S, Olini N, Huber R, et al: Sleep and early cortical development. Curriculum Sleep Med Rep 1:64-73, 2015 11. Jha SK, Jones BE, Coleman T, et al: Sleep-dependent plasticity requires cortical activity. J Neurosci 25:9266-9274, 2005 12. Kayser MS, Yue Z, Sehgal A: A critical period of sleep for development of courtship circuitry and behavior in Drosophila. Science 344: 269-274, 2014 13. Shaffery JP, Lopez J, Roffwarg HP: Brain-derived neurotrophic factor (BDNF) reverses the effects of rapid eye movement sleep deprivation (REMSD) on developmentally regulated, long-term potentiation (LTP) in visual cortex slices. Neurosci Lett 513:84-88, 2012
June 2015
Neurologic and Psychiatric Disorders and Sleep: Bi-directional Relationship on the Complex Interplay and Potential Interventions The main facts in human life are five: birth, food, sleep, love and death.” —E.M. Forster
S
leep is a quintessential component of life that is guaranteed to manifest on a nightly to near-nightly basis, even if attempts are made to avoid it. Albeit, there is not a definitive or well-elucidated concept for its occurrence; there is, however, significant evidence that either its deprivation or excess is detrimental to the maintenance of health and increases contribution to diseases. For example, Banks and Dinges1 documented behavioral and physiological effects of voluntary sleep deprivation in humans, revealing such deleterious consequences as impaired cognition and labile mood with micro–sleep intrusions into wakefulness, thereby, suggesting these to be consequences of disordered sleep. Sleep disorders are present in approximately 25%-40% of typically developing children2,3 and even more concerning in 50%-80% of children with comorbid neurologic or psychiatric disease.4-7 Mahatma Gandhi had stated “Each night, when I go to sleep, I die. And the next morning, when I wake up, I am reborn,” a prophetic metaphor emphasizing the critical importance of sleep and its homeostatic role in health maintenance. Sleep-dependent changes have been identified in membrane synthesis, oligodendrocyte proliferation, and myelin growth,8-10 indicating that neuronal activity during sleep could induce myelin growth and enhance functional connectivity in the developing brain.7 In fact, evidence from animal studies show that sleep is required for neurodevelopmental processes in specific brain circuits during critical periods of life.11-13 This special issue presents the current state of knowledge of pediatric sleep disorders in relation to psychiatric and neurologic disease. A total of 9 articles written by authors with a wealth of clinical experience and expertise have Disclosure: None of the authors have any financial support or conflicts of interest to disclose. No off-label use of drugs or products have been discussed in the article.
1071-9091/15/$ - see front matter & 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.spen.2015.04.003
addressed many of these key areas in child neurology and psychiatry as it relates to sleep disorders in children. The series begins with Fahed Hakim, Leila kheirandishGozal, and David Gozal providing an in-depth evaluation of the relationship between pediatric obstructive sleep apnea (OSA), pediatric obesity, and the disruption of metabolic homeostasis in these patients. The authors highlight the alarming epidemic of “globesity,” which is the worldwide trend toward obesity in children. They highlight the shift OSA in children being a result of adenotonsillar hypertrophy, to an increasingly common consequence of obesity, emphasizing the significant interplay of excessive weight in children as a cause of OSA, and also as a resulting consequence of metabolic disruption seen in patients with OSA. The alarmingly similar trend to the adult pathology also confers the secondary consequences of development of comorbid cardiovascular, endocrinologic, and neurologic diseases. However, the pediatric population experiences unique consequence, such as attention-deficit hyperactivity disorder like behavior, impaired academic performance, as well as long-lasting neurocognitive deficit. In the second article, Sejal V. Jain and Sanjeev V. Kothare discuss the intimately intertwined relationship between epilepsy and sleep. The article highlights the reciprocal effects of both sleep and sleep disorders on the electroencephalogram and on seizures, paying special attention to a specific subset of sleep-specific epilepsy syndromes, as well as the effect of antiepileptic drug treatment on sleep architecture. In the next article, Thomas J. Dye, Sejal V. Jain and Sanjeev V. Kothare also tackle the difficult task of discussing the evaluation of excessive daytime somnolence in a separate article on central hypersomnias. They provide an outline of the approach to the clinical evaluation and assessment to distinguish between primary and secondary hypersomnias, with reference to the recently published diagnostic criteria of the International Classification of Sleep Disorders, third edition. Claudia Dosi, Mariagrazia Figura, Raffaele Ferri, and Oliviero Bruni focus on the frequently encountered comorbid presentation of disordered sleep with cephalgias, 75
A.M. Morse and S.V. Kothare
76 emphasizing the genetically based neurophysiological and neuroanatomical substrates that predispose these patients to both pathologies. They highlight the most commonly encountered sleep disorders and provide a better understanding of the specific relationship to development of headache. They conclude with the bidirectional relationship and resultant importance of assessment and treatment of sleep disorders, as a part of headache management. Next, Kanwaljit Singh and Andrew W. Zimmerman address the frequently encountered issue of disordered sleep in autism and attention-deficit hyperactivity disorder. The authors discuss the burden and prevalence of different types of sleep disorders represented in the literature in these patients, as well as the proposed pathophysiology and etiology of the sleep problems. They acknowledge the significant heterogeneity of both the patient population and types of sleep disorders in these patients. This concept, thereby lays the foundation for their discussion about the difficulty in identifying a uniform method of evaluation and effective management of sleep disorders in these patients owing to the significant variability found. Suresh Kotagal next provides some insight to the relationship between sleep with static and progressive neurodegenerative disorders, such as Down syndrome, neuronal ceroid lipofuscinosis, Prader-Willi syndrome, and cerebral palsy. He focuses on the critical importance of the recognition and corrective management of sleep disorders and the resultant improvement in quality of life, in a concise disease-specific format. Sleep and its role in learning and memory have for many years interested scientists and researchers. The following paper by Kiran P. Maski provides a primer on sleep-dependent memory consolidation in children and adolescents, highlighting the link between sleep and neuronal plasticity. She then goes on to review the literature suggesting that there is a relationship between disordered sleep and neurodevelopmental disorders, thereby reinforcing the positive relationship between homeostatic sleep with learning and memory. Interventions available for disorders of sleep are numerous and can be quite difficult to navigate, especially when treating pediatric patients. Identification of appropriate pharmacologic treatment is more difficult in children and adolescents owing to minimal education received on these medications and limited data available in children in the literature, along with lack of Food and Drug Administration approval for their use. To overcome this obstacle, Mathew M. Troester and Rafael Pelayo present a very informative article discussing the indications, dosing, and suggested mechanisms of action for therapy, highlighting an approach to decipher which sleep disorder is present and its corresponding treatment. Finally, Anna Ivanenko and Ujjwal Ramtekkar conclude the series with an article focusing on the relationship between the development, severity, and prognosis of psychiatric disorders with comorbid sleep disturbance by providing a comprehensive review of literature and an
outline of treatment approaches for sleep interventions in this patient population. The authors provide a psychiatric illness–specific review, highlighting the increased frequency and specific subsets of sleep disorder associated with each psychiatric disorder and conclude with a review of sleep interventions with evidence of improvement in psychiatric outcome. However, the most striking statement may be regarding the relationship of disordered sleep to the elevated risk for suicidality and high-risk behavior, potentially suggesting that sleep assessment and treatment can be a potentially lifesaving or changing component in psychiatric care. We hope that this series provides a strong foundation on the implications of disordered sleep on neurologic and psychiatric disease, as well as contribute to a better understanding of possible treatment options. More so, we hope this series encourages interest and further investigation into the complex relationship between both homeostatic sleep and disordered sleep in relation to disease, maintenance of health, and neurodevelopmental outcomes. Anne Marie Morse, DO Sanjeev V. Kothare, MD
References 1. Banks S, Dinges D: Behavioral and physiological consequences of sleep restriction. J Clin Sleep Med 3:519-528, 2007 2. Ivanenko A, Gururaj BR: Classification and epidemiology of sleep disorders. Child Adolesc Psychiatr Clin N Am 18:839-848, 2009 3. Hodge D, Carollo TM, Lewin M, et al: Sleep patterns in children with and without autism spectrum disorders: developmental comparisons. Res Dev Disabil 35:1631-1638, 2014 4. Richdale AL, Schreck KA: Sleep problems in autism spectrum disorders: prevalence, nature, & possible biopsychosocial aetiologies. Sleep Med Rev 13:403-411, 2009 5. Stores G, Wiggs L, Campling G: Sleep disorders and their relationship to psychological disturbance in children with epilepsy. Child Care Health Dev 24:5-19, 1998 6. Richdale A: Sleep disorders in autism and Asperger's syndrome In: Stores G, Wiggs L, eds., Sleep disturbances in disorders of development: its significance and management. London; MacKeith Press, 2001, pp 181-191, 2001 7. Johnson CR: Sleep problems in children with mental retardation and autism. Child Adolesc Psychiatr Clin N Am 5:673-683, 1996 8. Bellesi M, Pfister-Genskow M, Maret S, et al: Effects of sleep and wake on oligodendrocytes and their precursors. J Neurosci 33:14288-14300, 2013 9. Cirelli C: A molecular window on sleep: changes in gene expression between sleep and wakefulness. Neuroscientist 11:63-74, 2005. [Eng] 10. Kurth S, Olini N, Huber R, et al: Sleep and early cortical development. Curriculum Sleep Med Rep 1:64-73, 2015 11. Jha SK, Jones BE, Coleman T, et al: Sleep-dependent plasticity requires cortical activity. J Neurosci 25:9266-9274, 2005 12. Kayser MS, Yue Z, Sehgal A: A critical period of sleep for development of courtship circuitry and behavior in Drosophila. Science 344: 269-274, 2014 13. Shaffery JP, Lopez J, Roffwarg HP: Brain-derived neurotrophic factor (BDNF) reverses the effects of rapid eye movement sleep deprivation (REMSD) on developmentally regulated, long-term potentiation (LTP) in visual cortex slices. Neurosci Lett 513:84-88, 2012
