The Latest Trends in Sleep Medicine

The field of sleep medicine has gone through tremendous evolution since the discovery of REM sleep in 1953 and remarkable research in recent years has led to multiple advances in sleep medicine. Among the most important improvements are the approval of the new medication for treating excessive daytime sleepiness in patients with obstructive sleep apnea and narcolepsy, treatment of central sleep apnea with phrenic nerve stimulation, treatment of obstructive sleep apnea with hypoglossal nerve stimulation, and emerging evidence on possible medication treatment of obstructive sleep apnea. These are exciting times in the field of sleep medicine, which is now a specialty in its own right. Technological advances are helping us break down diagnoses (e.g., further differentiating Narcolepsy into Type 1 and Type) and lead to novel ways of home sleep apnea testing (like peripheral arterial tonometry) and computerized interpretation of home sleep studies. We have potential tools in some areas of sleep medicine, such as obstructive sleep apnea, that can be used as part of a strategy for deep phenotyping of patients in precision medicine. Not only that, areas such as chronic insomnia and restless legs syndrome show promise for precision medicine application, especially after the identification of genetic markers and application of our understanding of the pharmacogenetics of commonly used medications in sleep medicine. Undoubtedly, much greater progress will be made in the coming years. We believe that the contributions of this book authored by international and respected experts will be useful to the respiratory and sleep medicine clinicians, whose efforts are still needed in treating and improving the quality and length of life in patients with complex sleep disorders.

I am delighted to present a state-of-the-art, up-to-date, comprehensive sleep medicine textbook. You will recognize many world-renowned scholars and scientists in the list of authors in this book. The credit goes to Dr. Imran Iftikhar's vision and tireless work in compiling this well-rounded book covering all essential topics of sleep physiology, pathology, latest research, and interventions. Content experts have written each chapter in this book with extensive subject experience. I thank and congratulate all authors and Dr. Iftikhar for putting together an enormous resource for new and seasoned sleep doctors alike. This book's format also lends itself nicely to non sleep health care workers. Ultimately, this textbook will improve the standard of sleep medicine and benefit patients suffering from sleep disorders.

The International Classification for Sleep Disorders- third edition (ICSD-3) has classified central disorders of hypersomnolence as, Narcolepsy type 1 and type 2, idiopathic hypersomnia (IH), Kleine–Levin syndrome (KLS), hypersomnia due to a medical or neurologic disorder, hypersomnia due to medication or substance, hypersomnia associated with psychiatric disorders, and insufficient sleep syndrome. A number of pharmacological treatment options are now available for Narcolepsy type 1 and type 2. However, for conditions like IH and KLS, much work is still being done to understand the underlying pathophysiologic mechanisms and consequently, these conditions have the least amount of high-grade evidence on pharmacologic options, and most medicines are used ‘off-label’. This chapter focuses on treating non narcoleptic hypersomnia syndromes- those commonly encountered in Sleep disorders clinics such as residual hypersomnia despite having a patient adherent to therapeutic positive airway pressure settings, to some uncommon conditions like IH and an exceedingly rare condition like KLS. New medications like solriamfetol and pitolisant and their possible use in some of these conditions is also discussed in this chapter

Circadian rhythm disorders are a group of sleep disorders where one’s endogenous circadian clock for sleep does not align with one’s environmental sleep wake schedule. The misalignment leads to complaints of poor sleep and wake time consequences such as excessive sleepiness, poor concentration, and even mood symptoms. Treatments vary depending on the disorder, but consist of re-entraining the circadian sleep clock using bright light and melatonin as well as developing sleep promoting behaviors.

Restless legs syndrome (RLS) is a common disorder of unknown cause. The management of RLS is directed at relieving its symptoms. Secondary causes and factors associated with increased symptoms should be recognized and treated whenever possible. Iron stores should be assessed in everyone with RLS, and iron replacement is recommended for iron deficiency patients. Patients with mild intermittent symptoms may be treated with non-pharmacological therapy, but when this is not effective, pharmacological treatment should be selected based on the timing of the symptoms and patients’ needs. Patients with moderate to severe RLS usually need medications on a daily basis to control their symptoms. A range of medications is now available for the management of RLS. Dopaminergic agonists are currently the first-line drugs for patients with moderate to severe RLS; however, drug-related problems like augmentation could restrict their use for long-term therapy. Alpha-2-delta calcium channel ligands are also considered first-line drugs for moderate to severe RLS patients. Opioids can be considered as a treatment option for RLS patients who have failed other therapies. When monitored properly, they can be safe and suitable for long-term therapy. In conclusion, the therapeutic strategy should be tailored to accommodate each patient's presentation and needs.

Drowsy driving is a widespread problem that results in accidents and injuries, costing lives and money. Drowsy driving can occur due to inadequate sleep, circadian rhythm influences and sleep disorders. It is agnostic to the driver affecting any age, sex, amount of prior driving experience and can include those who drive cars, trucks, buses and motorcycles. Laws and regulations are spotty on drowsy driving in part due to the challenges in defining it and confirming it.

 Converging evidence indicates a link between sleep disordered breathing and arrhythmias. Several OSA-related immediate, intermediate and chronic pathways lead to augmented arrhythmic propensity. The more immediate and intermediate pathways include intermittent hypoxia, autonomic nervous system fluctuations during respiratory events and intrathoracic pressure swings leading to atrial stretch and hypercapnia. Chronic pathways include increased systemic inflammation, oxidative stress, enhanced prothrombotic state and vascular dysfunction. While the more immediate and intermediate pathways are linked to a reduction in the atrial effective refractory period, triggered and abnormal automaticity, the persistence of reentrant arrhythmias and the potential to prolong the QT interval, the more chronic pathways are ultimately linked to cardiac structural and electrical remodeling This paper provides an overview of the main pathophysiologic mechanisms underlying the association between sleep apnea and arrhythmias and discusses the impact of sleep apnea on arrhythmia management. 

Central sleep apnea (CSA) occurs when there is a recurrent temporary failure of the pontomedullary breathing pacemaker and subsequent cessation of breathing during sleep. The pathophysiological changes of low cardiac output states are the most common causes of CSA. Thus, CSA occurs most frequently in patients with underlying cardiovascular disease and specifically heart failure (HF). However, cessation of inspiratory effort is also observed in other physiologic and pathophysiologic states such as high-altitude induced periodic breathing, narcotic induced CSA, and idiopathic CSA, along with any processes that may compress the brainstem. CSA is associated with immediate negative consequences, including intermittent hypoxia and sympathetic activation. Several studies have reported an association between CSA and worsened mortality in HF patients. Therefore, the treatment of CSA has been considered part of standard care, especially in patients with HF. In these patients, treatment of CSA can improve sympathetic activation, quality of life and decrease arrhythmias. Previously, the mainstay of treatment for CSA was continuous positive airway pressure (CPAP) therapy and then, as technology evolved, Adaptive Servo Ventilation (ASV). Recent data have suggested increased mortality in patients with HF with reduced ejection fraction (HFrEF) treated with ASV for CSA with EF <45, excluding this otherwise efficacious modality from usage in the majority of patients with CSA. Upon this background, the recent introduction of a novel therapeutic modality, transvenous phrenic nerve stimulation (TPNS), provides a valid treatment option that should be considered in all patients with CSA. In this chapter, we will introduce this treatment modality to the reader and attempt to provide a comprehensive overview of its operation, efficacy data, and application to the treatment of patients with CSA.

REM Sleep Behavior Disorder (RBD), often known as injurious dream enacting behaviors secondary to loss of atonia in REM sleep, was first described in 1986. While in the younger population, RBD can be associated with narcolepsy, posttraumatic stress disorder (PTSD) and antidepressant use, in middle-aged and older adults, RBD is almost always associated with a neurodegenerative disorder of synuclein––primarily Parkinson’s disease and dementia with Lewy bodies. For this reason, so-called isolated, or idiopathic RBD (iRBD), is in the great majority of cases a prodromal manifestation of neurodegeneration. Diagnosis of RBD requires video polysomnography to rule out common mimics. Specific diagnostic procedures and thresholds of electromyography (EMG) activity for the diagnosis of RBD have been developed and show high accuracy. Epidemiological studies have placed the overall prevalence of RBD around 2% across all age groups. Sleep-related injurious behaviors are common in RBD, especially in men, explaining the higher proportion of males diagnosed with RBD. In the management of RBD, safety is therefore paramount. Prognostic counselling is often warranted in iRBD, given the high rate of conversion to overt synucleinopathy. Offending agents, such as serotonergic medications, should be reduced or discontinued as possible as they exacerbate RBD behaviors. Pharmacological management involves primarily melatonin and/or clonazepam, while transdermal rivastigmine and, in select cases, sodium oxybate may be considered in treatment-resistant cases. 

Advances in upper airway evaluation, along with the improved understanding of OSA phenotypes and evolving approaches to surgical techniques, have enabled targeted multi-level interventions for obstructive sleep apnea (OSA). A variety of surgical techniques to address the nasal cavity, palate, oropharynx, hypopharynx, tongue, epiglottis and facial skeleton exist. Surgery has proven to be an effective treatment modality that reduces objective and subjective OSA measures as well as associated neurocognitive and cardiovascular morbidities.

 Cognitive behavioral therapy for insomnia (CBT-I) is a multi-component treatment that typically combines sleep education, sleep hygiene instructions, stimulus control therapy, sleep restriction therapy, cognitive therapy, and relaxation training. CBT-I is considered the first line treatment for chronic insomnia due to evidence of its efficacy, including sustained improvement in insomnia over the long term. Compared to pharmacological treatment, CBT-I has similar short-term efficacy but better longterm durability. CBT-I improves subjective measures of time spent awake at night, resulting in improved sleep continuity. CBT-I is typically delivered in 4-8 face to face individual sessions, though the efficacy of different formats has also been demonstrated, including group therapy, telehealth, and digital therapeutics. Individuals with chronic insomnia frequently have medical and psychiatric comorbidities, and the efficacy of CBT-I has been demonstrated in numerous comorbid populations.

 Sleep difficulties and disorders are among the most prevalent problems of ageing. In addition to changes in sleep duration and quality, sleep architecture also changes as age progresses. Age by itself does not result in sleep disorders; rather, these changes are associated with psychosocial and health factors in the elderly such as the existence of multiple comorbidities, polypharmacy, and age-related changes in circadian rhythm. Older adults have increased prevalence of various primary sleep disorders, including restless leg syndrome, insomnia, sleep-disordered breathing, circadian rhythm disturbances and periodic limb syndrome. Challenges in identifying, diagnosing, and treating sleep disorders in older adults with dementia also exist, which further complicates the management of sleep disorders in these patients. Poor sleep not only impacts the quality of life and cognitive functioning but is also associated with increased morbidity and mortality and thus requires careful screening and assessment in the elderly population.