- Email: [email protected]
S28.1 Symposium summary
S32
2nd WASM World Congress, Bangkok, 4–8 February 2007 / Sleep Medicine 8 Suppl. 1 (2007) S11–S47
S26D RBD as the initial manifestation of a neurodegenerative disorder A. Iranzo. Neurology Service, Hospital Clinic of Barcelona, Barcelona, Spain RBD as an early marker for a parkinsonian neurodegenerative disorder was reported in 1996 (Schenck et al., Neurology), in which 38% of men >50 years of age diagnosed with idiopathic RBD eventually developed parkinsonism (usually PD) at a mean interval of 12.7 years after the onset of RBD. After an additional 7 years of follow-up, the conversion rate from idiopathic RBD to parkinsonian RBD had risen to 65% of these patients. No other neurologic disorder had emerged during this time period, with one exception. Clonazepam therapy at bedtime was highly effective in controlling RBD in most patients irrespective of whether patients had idiopathic or symptomatic RBD. Similar findings were recently reported from our center (Iranzo et al. 2006, Lancet Neurology) in which 45% of 44 patients (mean age, 74.1 years; 39 males) developed a neurologic disorder after a mean interval of 11.5 years from the onset of RBD. Emerging disorders were PD (n = 9), dementia with Lewy bodies (n = 6), multiple system atrophy with predominant cerebellar syndrome (n = 1), and mild cognitive impairment with prominent visuospatial dysfunction (n = 4). The longer the follow-up interval, the greater the probability of finding a neurologic disorder. Clonazepam therapy controlled RBD in 35 of 36 treated patients. Therefore, in patients presenting to a sleep disorders center, RBD often antedates the development of a neurodegenerative disorder. Consequently, close follow-up of patients diagnosed with idiopathic RBD could enable early detection of neurodegenerative disease. This finding may be of great interest when early effective treatment strategies and neuroprotective drugs become available.
1. Identify the cultural differences in acceptance of therapy for Obstructive sleep Apnea. 2. present practices of the PAP delivery in South East Asia, North America and Europe. 3. Identify the various types of positive airway pressure (PAP) devices for the treatment of sleep disordered breathing. 4. Identify the various methods used in the application PAP devices in titration and follow-up. 5. Identify various hurdles in achieving long term compliance. 6. Identify current techniques to improve long term compliance with PAP therapy. The presentations are followed by a Panel Discussion with Sunil Sharma, J.C. Suri, Thom R. Feroah, Vincentia Castronovo, and a representative from Respironics Inc. S27.2 North American model of delivering and improving PAP therapeutic adherence S. Sharma. University of South Carolina, Columbia, SC, USA Abstract not available at time of printing. Declaration of conflict of interest: Speaker for Takeda pharmaceuticals. S27.A Indian model of delivering and improving PAP therapeutic adherence J.C. Suri. Vardhaman Mahavir Medical College and Safdarjung Hospital, New Delhi, India Abstract not available at time of printing.
S26.E RBD and co-morbid sleep disorders: mechanisms and therapeutic strategies
S27.B European method of delivering and improving PAP therapeutic adherence
R. Silvestri. Clinica Neurologica I, Policlinico G. Martino, Via Consolare Valeria, Messina, Italy
V. Castronovo. Milan, Italy Abstract not available at time of printing.
Abstract not available at time of printing.
S27. Compliance: From sleep lab to successful long-term treatment
S27.C Treatment options for SDB with a focus on positive airway (PAP) devices T.R. Feroah. Medical College of Wisconsin, Milwaukee, WI, USA Abstract not available at time of printing. Declaration of conflict of interest: Respironics speaker
S27.1 Symposium summary S. Sharma. Division of Pulmonary/Critical Care/Sleep Medicine, University of South Carolina, Columbia, SC, USA One of the biggest hurdles in treatment of Obstructive sleep Apnea is acceptance and compliance. Several studies have determined the compliance to be 50−55% at best. Various mechanisms have been proposed to improve compliance from education to trouble shooting of side-effects. New interfaces are continually being invented to reduce patient discomfort. Yet a lot has to be done. Improvement in compliance can significantly improve patient care and outcome specially cardiovascular sequelae. Different parts of the world have different issues regarding acceptance and compliance and different ways to resolve them. Yet there is little interaction between health care providers to understand geographical and local issues of each region and learn from them. A free exchange of ideas will improve understanding and provide a platform to form novel methods to improve long term compliance. • Chair: Sunil Sharma, MD, University of South Carolina, Columbia, SC, USA. [email protected] • 1st speaker: Dr. J.C. Suri, Vardhaman Mahavir Medical College and Safdarjung Hospital, New Delhi, India • 2nd speaker: Vincentia Castronovo, PhD, Milan, Italy • 3rd speaker: Thom R. Feroah, PhD, Medical College of Wisconsin. Milwaukee, Wisconsin, USA • 4th speaker/discussant: Peter White, Respironics Symposium objectives: At the completion of this symposium the attendees should be able to
S27.D From liability to an asset P. White. Respironics Inc., USA Advances in design and concept of PAP devices and interface for improving comfort, long term adherence and portability.
S28. Sleep disordered breathing in children and adolescents
S28.1 Symposium summary M. Kalra. Cincinnati Children’s Hospital, Cincinnati, OH, USA The symposium will address the current key issues in childhood sleep disordered breathing: high risk group of obesity, inflammation and OSA, and outcomes of surgical treatment. The epidemiology and pathogenesis of obstructive sleep apnea in the obese child and adolescent will be reviewed. The role of inflammation in the development of childhood sleep disordered breathing as well as the potential for novel therapies will then be discussed. Finally, the outcomes of adenotonsillectomy for childhood obstructive sleep apnea syndrome will be presented. • Chair: Maninder Kalra, MD, MS, Assistant Professor of Pediatrics, Pulmonary Medicine, Cincinnati Children’s Hospital, Cincinnati, OH, USA
Parallel Symposia / Sleep Medicine 8 Suppl. 1 (2007) S11–S47 • Co-chair: Asher Tal, MD, Professor of Pediatrics, Head, Department of Pediatrics B, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, PO Box 151, Beer-Sheva, Israel • 1st speaker: Maninder Kalra, MD, MS • 2nd speaker: Asher Tal, MD • 3rd speaker: Aviv D. Goldbart, Department of Pediatrics B, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, PO Box 151, Beer-Sheva, Israel Childhood obstructive sleep apnea (OSA) is associated with metabolic, cardiovascular and neuron-cognitive sequelae. Inflammation is now believed to play an important role in the pathogenesis of OSA and has been proposed as a key pathway linking OSA to associated morbidity. With the epidemic increase in childhood obesity, a high risk group for OSA, the morbidity due to untreated OSA is becoming a major public health concern. Adenotonsillectomy is the first-line of treatment for childhood OSA. However, efficacy of this treatment may vary across groups. Knowledge about outcomes of surgical and non-surgical treatment options is thus essential for the management of the child with OSA. Symposium Objectives: 1. To discuss the epidemiology and pathogenesis of obstructive sleep apnea (OSA) in the obese child and adolescent. 2. To develop an understanding of the role of inflammation in the development of childhood sleep disordered breathing and mediation of associated morbidity. 3. Review the outcomes of adenotonsillectomy for childhood OSA and discuss the role of adenotonsillectomy in the management of childhood OSA. S28.A Obesity and obstructive sleep apnea in children and adolescents M. Kalra. Cincinnati Children’s Hospital, Cincinnati, OH, USA Obstructive sleep apnea (OSA) is a disorder characterized by partial or complete narrowing of the pharyngeal airway during sleep, resulting in repeated episodes of airflow cessation, oxygen desaturation, and sleep disruption. The etiology of OSA is multifactorial, consisting of a complex interplay between factors related to upper airway anatomy and neuromuscular control of upper airway. As in adults, a high prevalence of OSA has been reported in obese children; the prevalence increasing with increment in the degree of obesity. Obesity can contribute to the pathogenesis of OSA through decrease in the size of the upper airway due to deposits of adipose tissue in the soft tissues surrounding the airway and through increased upper airway collapsibility. The increased airway collapsibility resulting from the effect of either local or visceral adipose tissue deposits on airway lumen, airway length, and contractile strength of the pharyngeal dilators. When untreated, OSA in children is associated with neurocognitive deficits and cardiovascular and metabolic sequelae. With increase in prevalence of childhood overweight and obesity, a high risk group for OSA, morbidity due to delay in diagnosis and therefore treatment of OSA has major public health implications. Although overnight polysomnography is the “gold standard” for evaluating this condition, it is expensive and as of yet available in only a limited number of facilities. Until diagnostic testing for OSA in children is readily available and less costly, there is a need to prioritize patients for polysomnography. Among obese children, measures of general adiposity and local adipose tissue deposits can be one approach to prioritize patients. We believe that this would ultimately lead to reduced morbidity by facilitating early diagnosis and treatment. Additionally, knowledge of risk factors associated with OSA in obese children may increase our understanding of the pathogenesis of this disorder.
S33
pediatric OSAS, and therefore, adenotonsillectomy (T&A) is the treatment of choice in most cases. However, there is lack of prospective randomized controlled trials to prove the beneficial effect of T&A in children with OSAS. T&A results in a significant improvement of the respiratory abnormalities as measured by over-night polysomnography in children with OSAS before and after T&A. In addition, an improvement in sleep fragmentation (number of arousals per hour) was documented. A review of the available reports on the effects of T&A in children indicates an improvement in right ventricular function and reduction of pulmonary hypertension, improved growth as a result of an increase in growth hormone secretion, reduction in nocturnal enuresis, and most important, a significant improvement of neurocognitive function to the normal range, in children 5 to 9 years of age. The general morbidity, as reflected by the health care utilization cost, decreased significantly one year following T&A in children with OSAS as compared with children who did not undergo T&A, as well as normal controls. Surgical intervention seems to be the treatment of choice in otherwise normal children with OSAS who present an apnea–hypopnea index of >5 events per hour. Prospective controlled trials are needed to refine the polysomnographic parameters that indicate the need for surgery, the optimal age for intervention, and the long-term results of the intervention. S28.C Inflammation and childhood sleep disordered breathing A. Goldbart. Department of Pediatrics B, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel Several pathogenetic mechanisms leading to Sleep Disordered Breathing (SDB) and its consequences are known. Although there is a clear role for intermittent hypoxia and sleep fragmentation, they cannot always be correlated to the severity of the disease or its consequences in children with SDB. Adults with SDB present inflammatory changes in their upper airway mucosal surfaces and muscular apparatus as well as systemic inflammation represented by increased levels of CRP, a marker of cardiovascular risk that decreases following conventional therapy (such as CPAP). CRP is also reported to be increased in children with moderate to severe SDB. There is now accumulating evidence on the role several inflammatory pathways are playing in children with SDB. Induced sputum and exhaled condensates representing the airway biologic properties demonstrate increased percentage of neutrophils and particulate eicosanoids like cysteynil leukotrienes that can be correlated to the degree of SDB severity. Adenotonsillar tissue of children with SDB present overexpression of inflammatory associated receptors at the gene and protein level, and neutrophilic inflammation in the upper airway was reported by several investigators. Recently anti inflammatory therapy was able to improve polysomnographic respiratory parameters and reduce adenoid tissue size in children. The role played by inflammation in the collapsibility of the upper airway may involve the dysfunction of upper airway musculature adenotonsillar hypertrophy and perhaps changes in local airway innervations. Based on the current understanding of the morbidity affecting children with SDB, inflammation emerges as a major player of these consequences that may be modulated by genetic susceptibility and environmental causes (diet, physical activity). The hypothesis suggesting inflammation to be involved in the pathogenesis of SDB will be carefully reviewed and new unpublished data will be presented.
S29. Cyclic alternating pattern as a window to sleep physiology and pathology
S29.1 Symposium summary S28.B Outcomes of adenotonsillectomy for childhood OSA A. Tal. Department of Pediatrics, Soroka University Medical Center, Ben-Gurion University, Beer-Sheva, Israel Obstructive Sleep Apnea Syndrome (OSAS) is common in children (2−3%). Hypertrophied adenoids and tonsils is the most common etiology in
R.J. Thomas. Pulmonary Office, Beth Israel Deaconess Medical Center, Boston. MA, USA Sleep-related oscillations entrain, and are entrained by, physiological and pathological influences. Continuous improvement in our understanding of one of the oscillatory phenomena of sleep, the cyclic alternating pattern,
2nd WASM World Congress, Bangkok, 4–8 February 2007 / Sleep Medicine 8 Suppl. 1 (2007) S11–S47
S26D RBD as the initial manifestation of a neurodegenerative disorder A. Iranzo. Neurology Service, Hospital Clinic of Barcelona, Barcelona, Spain RBD as an early marker for a parkinsonian neurodegenerative disorder was reported in 1996 (Schenck et al., Neurology), in which 38% of men >50 years of age diagnosed with idiopathic RBD eventually developed parkinsonism (usually PD) at a mean interval of 12.7 years after the onset of RBD. After an additional 7 years of follow-up, the conversion rate from idiopathic RBD to parkinsonian RBD had risen to 65% of these patients. No other neurologic disorder had emerged during this time period, with one exception. Clonazepam therapy at bedtime was highly effective in controlling RBD in most patients irrespective of whether patients had idiopathic or symptomatic RBD. Similar findings were recently reported from our center (Iranzo et al. 2006, Lancet Neurology) in which 45% of 44 patients (mean age, 74.1 years; 39 males) developed a neurologic disorder after a mean interval of 11.5 years from the onset of RBD. Emerging disorders were PD (n = 9), dementia with Lewy bodies (n = 6), multiple system atrophy with predominant cerebellar syndrome (n = 1), and mild cognitive impairment with prominent visuospatial dysfunction (n = 4). The longer the follow-up interval, the greater the probability of finding a neurologic disorder. Clonazepam therapy controlled RBD in 35 of 36 treated patients. Therefore, in patients presenting to a sleep disorders center, RBD often antedates the development of a neurodegenerative disorder. Consequently, close follow-up of patients diagnosed with idiopathic RBD could enable early detection of neurodegenerative disease. This finding may be of great interest when early effective treatment strategies and neuroprotective drugs become available.
1. Identify the cultural differences in acceptance of therapy for Obstructive sleep Apnea. 2. present practices of the PAP delivery in South East Asia, North America and Europe. 3. Identify the various types of positive airway pressure (PAP) devices for the treatment of sleep disordered breathing. 4. Identify the various methods used in the application PAP devices in titration and follow-up. 5. Identify various hurdles in achieving long term compliance. 6. Identify current techniques to improve long term compliance with PAP therapy. The presentations are followed by a Panel Discussion with Sunil Sharma, J.C. Suri, Thom R. Feroah, Vincentia Castronovo, and a representative from Respironics Inc. S27.2 North American model of delivering and improving PAP therapeutic adherence S. Sharma. University of South Carolina, Columbia, SC, USA Abstract not available at time of printing. Declaration of conflict of interest: Speaker for Takeda pharmaceuticals. S27.A Indian model of delivering and improving PAP therapeutic adherence J.C. Suri. Vardhaman Mahavir Medical College and Safdarjung Hospital, New Delhi, India Abstract not available at time of printing.
S26.E RBD and co-morbid sleep disorders: mechanisms and therapeutic strategies
S27.B European method of delivering and improving PAP therapeutic adherence
R. Silvestri. Clinica Neurologica I, Policlinico G. Martino, Via Consolare Valeria, Messina, Italy
V. Castronovo. Milan, Italy Abstract not available at time of printing.
Abstract not available at time of printing.
S27. Compliance: From sleep lab to successful long-term treatment
S27.C Treatment options for SDB with a focus on positive airway (PAP) devices T.R. Feroah. Medical College of Wisconsin, Milwaukee, WI, USA Abstract not available at time of printing. Declaration of conflict of interest: Respironics speaker
S27.1 Symposium summary S. Sharma. Division of Pulmonary/Critical Care/Sleep Medicine, University of South Carolina, Columbia, SC, USA One of the biggest hurdles in treatment of Obstructive sleep Apnea is acceptance and compliance. Several studies have determined the compliance to be 50−55% at best. Various mechanisms have been proposed to improve compliance from education to trouble shooting of side-effects. New interfaces are continually being invented to reduce patient discomfort. Yet a lot has to be done. Improvement in compliance can significantly improve patient care and outcome specially cardiovascular sequelae. Different parts of the world have different issues regarding acceptance and compliance and different ways to resolve them. Yet there is little interaction between health care providers to understand geographical and local issues of each region and learn from them. A free exchange of ideas will improve understanding and provide a platform to form novel methods to improve long term compliance. • Chair: Sunil Sharma, MD, University of South Carolina, Columbia, SC, USA. [email protected] • 1st speaker: Dr. J.C. Suri, Vardhaman Mahavir Medical College and Safdarjung Hospital, New Delhi, India • 2nd speaker: Vincentia Castronovo, PhD, Milan, Italy • 3rd speaker: Thom R. Feroah, PhD, Medical College of Wisconsin. Milwaukee, Wisconsin, USA • 4th speaker/discussant: Peter White, Respironics Symposium objectives: At the completion of this symposium the attendees should be able to
S27.D From liability to an asset P. White. Respironics Inc., USA Advances in design and concept of PAP devices and interface for improving comfort, long term adherence and portability.
S28. Sleep disordered breathing in children and adolescents
S28.1 Symposium summary M. Kalra. Cincinnati Children’s Hospital, Cincinnati, OH, USA The symposium will address the current key issues in childhood sleep disordered breathing: high risk group of obesity, inflammation and OSA, and outcomes of surgical treatment. The epidemiology and pathogenesis of obstructive sleep apnea in the obese child and adolescent will be reviewed. The role of inflammation in the development of childhood sleep disordered breathing as well as the potential for novel therapies will then be discussed. Finally, the outcomes of adenotonsillectomy for childhood obstructive sleep apnea syndrome will be presented. • Chair: Maninder Kalra, MD, MS, Assistant Professor of Pediatrics, Pulmonary Medicine, Cincinnati Children’s Hospital, Cincinnati, OH, USA
Parallel Symposia / Sleep Medicine 8 Suppl. 1 (2007) S11–S47 • Co-chair: Asher Tal, MD, Professor of Pediatrics, Head, Department of Pediatrics B, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, PO Box 151, Beer-Sheva, Israel • 1st speaker: Maninder Kalra, MD, MS • 2nd speaker: Asher Tal, MD • 3rd speaker: Aviv D. Goldbart, Department of Pediatrics B, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, PO Box 151, Beer-Sheva, Israel Childhood obstructive sleep apnea (OSA) is associated with metabolic, cardiovascular and neuron-cognitive sequelae. Inflammation is now believed to play an important role in the pathogenesis of OSA and has been proposed as a key pathway linking OSA to associated morbidity. With the epidemic increase in childhood obesity, a high risk group for OSA, the morbidity due to untreated OSA is becoming a major public health concern. Adenotonsillectomy is the first-line of treatment for childhood OSA. However, efficacy of this treatment may vary across groups. Knowledge about outcomes of surgical and non-surgical treatment options is thus essential for the management of the child with OSA. Symposium Objectives: 1. To discuss the epidemiology and pathogenesis of obstructive sleep apnea (OSA) in the obese child and adolescent. 2. To develop an understanding of the role of inflammation in the development of childhood sleep disordered breathing and mediation of associated morbidity. 3. Review the outcomes of adenotonsillectomy for childhood OSA and discuss the role of adenotonsillectomy in the management of childhood OSA. S28.A Obesity and obstructive sleep apnea in children and adolescents M. Kalra. Cincinnati Children’s Hospital, Cincinnati, OH, USA Obstructive sleep apnea (OSA) is a disorder characterized by partial or complete narrowing of the pharyngeal airway during sleep, resulting in repeated episodes of airflow cessation, oxygen desaturation, and sleep disruption. The etiology of OSA is multifactorial, consisting of a complex interplay between factors related to upper airway anatomy and neuromuscular control of upper airway. As in adults, a high prevalence of OSA has been reported in obese children; the prevalence increasing with increment in the degree of obesity. Obesity can contribute to the pathogenesis of OSA through decrease in the size of the upper airway due to deposits of adipose tissue in the soft tissues surrounding the airway and through increased upper airway collapsibility. The increased airway collapsibility resulting from the effect of either local or visceral adipose tissue deposits on airway lumen, airway length, and contractile strength of the pharyngeal dilators. When untreated, OSA in children is associated with neurocognitive deficits and cardiovascular and metabolic sequelae. With increase in prevalence of childhood overweight and obesity, a high risk group for OSA, morbidity due to delay in diagnosis and therefore treatment of OSA has major public health implications. Although overnight polysomnography is the “gold standard” for evaluating this condition, it is expensive and as of yet available in only a limited number of facilities. Until diagnostic testing for OSA in children is readily available and less costly, there is a need to prioritize patients for polysomnography. Among obese children, measures of general adiposity and local adipose tissue deposits can be one approach to prioritize patients. We believe that this would ultimately lead to reduced morbidity by facilitating early diagnosis and treatment. Additionally, knowledge of risk factors associated with OSA in obese children may increase our understanding of the pathogenesis of this disorder.
S33
pediatric OSAS, and therefore, adenotonsillectomy (T&A) is the treatment of choice in most cases. However, there is lack of prospective randomized controlled trials to prove the beneficial effect of T&A in children with OSAS. T&A results in a significant improvement of the respiratory abnormalities as measured by over-night polysomnography in children with OSAS before and after T&A. In addition, an improvement in sleep fragmentation (number of arousals per hour) was documented. A review of the available reports on the effects of T&A in children indicates an improvement in right ventricular function and reduction of pulmonary hypertension, improved growth as a result of an increase in growth hormone secretion, reduction in nocturnal enuresis, and most important, a significant improvement of neurocognitive function to the normal range, in children 5 to 9 years of age. The general morbidity, as reflected by the health care utilization cost, decreased significantly one year following T&A in children with OSAS as compared with children who did not undergo T&A, as well as normal controls. Surgical intervention seems to be the treatment of choice in otherwise normal children with OSAS who present an apnea–hypopnea index of >5 events per hour. Prospective controlled trials are needed to refine the polysomnographic parameters that indicate the need for surgery, the optimal age for intervention, and the long-term results of the intervention. S28.C Inflammation and childhood sleep disordered breathing A. Goldbart. Department of Pediatrics B, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel Several pathogenetic mechanisms leading to Sleep Disordered Breathing (SDB) and its consequences are known. Although there is a clear role for intermittent hypoxia and sleep fragmentation, they cannot always be correlated to the severity of the disease or its consequences in children with SDB. Adults with SDB present inflammatory changes in their upper airway mucosal surfaces and muscular apparatus as well as systemic inflammation represented by increased levels of CRP, a marker of cardiovascular risk that decreases following conventional therapy (such as CPAP). CRP is also reported to be increased in children with moderate to severe SDB. There is now accumulating evidence on the role several inflammatory pathways are playing in children with SDB. Induced sputum and exhaled condensates representing the airway biologic properties demonstrate increased percentage of neutrophils and particulate eicosanoids like cysteynil leukotrienes that can be correlated to the degree of SDB severity. Adenotonsillar tissue of children with SDB present overexpression of inflammatory associated receptors at the gene and protein level, and neutrophilic inflammation in the upper airway was reported by several investigators. Recently anti inflammatory therapy was able to improve polysomnographic respiratory parameters and reduce adenoid tissue size in children. The role played by inflammation in the collapsibility of the upper airway may involve the dysfunction of upper airway musculature adenotonsillar hypertrophy and perhaps changes in local airway innervations. Based on the current understanding of the morbidity affecting children with SDB, inflammation emerges as a major player of these consequences that may be modulated by genetic susceptibility and environmental causes (diet, physical activity). The hypothesis suggesting inflammation to be involved in the pathogenesis of SDB will be carefully reviewed and new unpublished data will be presented.
S29. Cyclic alternating pattern as a window to sleep physiology and pathology
S29.1 Symposium summary S28.B Outcomes of adenotonsillectomy for childhood OSA A. Tal. Department of Pediatrics, Soroka University Medical Center, Ben-Gurion University, Beer-Sheva, Israel Obstructive Sleep Apnea Syndrome (OSAS) is common in children (2−3%). Hypertrophied adenoids and tonsils is the most common etiology in
R.J. Thomas. Pulmonary Office, Beth Israel Deaconess Medical Center, Boston. MA, USA Sleep-related oscillations entrain, and are entrained by, physiological and pathological influences. Continuous improvement in our understanding of one of the oscillatory phenomena of sleep, the cyclic alternating pattern,