Which of the following is the predominant symptom of primary hypersomnolence disorder?

Introduction

Excessive daytime sleepiness (EDS) is a highly prevalent complaint associated with significant negative effects on health, workplace and academic performance, absenteeism, and overall health and safety, such as motor vehicle collisions (Blachier et al., 2012; Jaussent et al., 2012; Jaussent et al., 2013; Ohayon, 2008; Ohayon, 2012; Strohl et al., 2013). Furthermore, EDS represents a substantial cost burden to the health care system (Jennum & Kjellberg, 2010; Kapur et al., 2002). In clinical practice, EDS is not only the cardinal symptom for the diagnosis of disorders of central nervous system origin such as narcolepsy or idiopathic hypersomnia (American Academy of Sleep Medicine, 2005), but it is the most frequent complaint reported in sleep disorders centers (Roehrs, Carskadon, Dement, & Roth, 2011; Vgontzas & Kales, 1999). Epidemiological studies have shown that the prevalence of EDS ranges between 4 and 20%, depending on the methods and definitions used (Ohayon, 2008). These studies have also shown that the prevalence of EDS is strongly modulated by age, being highest in children, adolescents, and young adults (10–15%), decreasing during middle age (about 6%), and peaking again in the elderly (Bixler et al., 2005; Calhoun et al., 2011; Millman, 2005; Vela-Bueno, Fernandez-Mendoza, & Olavarrieta-Bernardino, 2009). Figure 1 shows this age modulation of the prevalence of EDS in the general population from young age to older adulthood (Bixler et al., 2005).

In this chapter, we will review the multifactorial modulation of EDS. First, we will clarify the definitions used. Second, we will explore each of the most researched factors etiologically linked to EDS. Third, we will explore how each potential factor associated with EDS may be modulated by age within each section. Although narcolepsy and idiopathic hypersomnia are important disorders that should not be neglected (Dauvilliers, Lopez, Ohayon, & Bayard, 2013), this chapter focuses on the modulation of EDS by highly common sleep, mood, and metabolic factors.

Publisher Summary

This chapter deals with excessive daytime sleepiness (EDS), which is mild drowsiness to falling asleep continually throughout the day. Many people confuse fatigue or tiredness with EDS, but EDS is characterized by the inability to stay awake, alert, and optimally functional throughout the day. EDS is a prevalent problem in modern society and is reflected in its growing predominance in patients seen in clinical practice. The costs to society and individual can be great, and reflected in lost productivity, memory and concentration, and growing evidence of health effects, both accidents related as well as an increased risk for chronic, life-threatening illnesses. Several syndromes of EDS have been identified, and the diagnosis of these syndromes may sometimes be difficult without evaluation by a sleep specialist. Treatment options are available for the majority of patients. The causes of EDS are numerous and a thorough evaluation is necessary to determine the etiology in an individual case. The recent phenomenal progress in the pathophysiology of narcolepsy is promising, but provides just a glimpse into the work that needs to be done to understand the other primary causes of EDS.

Excessive Daytime Sleepines

EDS is defined as the inability to stay awake and alert during the major waking episodes of the day, resulting in undesirable lapses into drowsiness or sleep. One epidemiological study showed a relationship between EDS and subsequent development of PD. All were free of prevalent PD and dementia. Having a complaint of ‘being sleepy most of the day’ was defined as having EDS. EDS was assessed in 3078 men aged 71–93 years from 1991 to 1993. Follow-up for incident PD was based on three repeat neurological assessments from 1994 to 2001. During the course of follow-up, 43 men developed PD (19.9/10 000 person-years). After age adjustment, there was more than a threefold excess in the risk of PD in men with EDS versus men without EDS (p = 0.004). Additional adjustment for insomnia, cognitive function, depressed mood, midlife cigarette smoking and coffee drinking, and other factors failed to alter the association between EDS and PD. Other sleep-related features such as insomnia, daytime napping, early morning grogginess, and frequent nocturnal awakening showed little relation with the risk of PD. The authors of this study concluded that EDS may be associated with an increased risk of developing PD.

There are no other studies that have evaluated the presence of PD as a predictor for neurodegenerative diseases linked to EDS such as DLB and AD.

Overview

EDS is a common complaint in modern society. A 2008 Sleep in America poll noted 18% of Americans are excessively sleepy. Prevalence of EDS worldwide ranges between 9% and 26% (Ebben, 2020). The three main causes of EDS not attributable to medical or psychiatric conditions are insufficient sleep, poor sleep hygiene, and demanding work schedules. Effective treatment of EDS is an important public health issue given significant direct and indirect costs at the individual level, but also in society. Though medications remain the predominant treatment for symptom of EDS, this chapter focuses on the alternative, nonpharmacological treatments available to address EDS related to the hypersomnias of central origin. It is increasingly evident that to obtain the best possible outcomes, a comprehensive approach to the treatment of EDS is warranted (Conroy et al., 2012).

EDS is the primary symptom of hypersomnolence, yet other associated symptoms varying within and across individuals due to age, lifestyle, and underlying cause can include trouble awakening (i.e., sleep drunkenness or inertial sleepiness), deficient energy levels, slowed thinking and response time, nervousness, irritation, agitation, slowed speech, hallucinations (hypnopompic or hypnogogic), disorientation, memory difficulties, restlessness, headaches, gastrointestinal symptoms, and appetite changes (decreased or excessive).

Chronic hypersomnolence is characterized by the presence of EDS sufficient to cause distress or disruptions in functioning for at least 3 months. Prevalence rates of hypersomnolence vary based on the population studied, but range between 10% and 25% (Adenuga and Attarian, 2014). When considering those with mood disorders, 10%–40% also have comorbid chronic hypersomnolence.

Sleep propensity during wakefulness

EDS has been investigated more from the perspective of frequency or severity rather than the duration of the symptom. EDS occurring at least 3 days per week has been reported in 4–20.6% of the general population, while severe EDS was reported at 5%. In most studies, men and women are affected equally.

A uniform operational definition of EDS is still lacking. Consequently, there is great variance in the results of studies trying to estimate prevalence. This does not help in reaching any definite conclusion. Most of the studies limited the assessment of EDS to a single question answered by either ‘yes’ or ‘no’. In some studies, there was no further attempt to validate the responses using instruments. Along with single questions to assess EDS, validated questionnaires such as the Epworth Sleepiness Scale (ESS) and the Stanford Sleepiness Scale (SSS) are often used. Laboratory evaluation of sleep by objective methods such as all-night polysomnography (PSG), the multiple sleep latency test (MSLT) or the maintenance of wakefulness test (MWT) are used to evaluate excessive sleepiness and reduced alertness. Since prolonged nocturnal PSG is typically not performed in clinical practice, epidemiological studies conducted in the general population have mostly focused on EDS and rarely assess nocturnal and diurnal sleep quantity using objective measures.

Introduction

EDS is an inability to stay awake and alert during the day with periods of irrepressible need for sleep (American Academy of Sleep Medicine, 2014) It is associated with a higher risk of automobile accidents and reduced quality of life (Slater and Steier, 2012).

The International Classification of Sleep Disorders, Third Edition (ICSD-3), uses the term hypersomnolence to describe the symptom of EDS and hypersomnia for disorders characterized by this symptom (American Academy of Sleep Medicine, 2014). In this way, EDS is not a disorder but a symptom with diverse potential causes (Ohayon, 2008). EDS can result from sleep deprivation, which affects around one-third of Americans (Centers for Disease Control and Prevention, 2011), sleep disorders, medical and psychiatric conditions, and medications and other substances.

Chronic or recurrent EDS not caused by other sleep disorders is the primary symptom in CDH. While CDH are rare, they lead to significant impairment and present both diagnostic and therapeutic challenges.

Sleep propensity during wakefulness

EDS has generally been investigated from the perspective of frequency or severity. The duration of the symptom has rarely been investigated. EDS occurring at least three days per week has been reported in between 4% and 21% of the general population, while severe EDS was reported in about 5–7% (Jaussent et al., 2017). In most studies, men and women are equally affected. Inconsistencies in EDS prevalence can be explained by differences in demographics (age, specifically), cultural and geographical factors, EDS assessment and definition, and study design.

A uniform operational definition of EDS is still lacking. Consequently, there is a great variance in results, which does not make any definite conclusions possible. Most of the studies limited the assessment of EDS to a single question answered by either “yes or no,” in some cases even not validated. Along with single question to assess EDS, validated questionnaires as the Epworth Sleepiness Scale (ESS) (Johns, 1991), the Stanford Sleepiness Scale (MacLean et al., 1992), and Karolinska Sleepiness Scale (Kaida et al., 2006) are often used. Other subjective measures to consider: Nonrestorative Sleep Scale (Wilkinson and Shapiro, 2013), Toronto Hospital Alertness Test (Shahid et al., 2016) and ZOGIM Alertness scales (Shapiro et al., 2006). Laboratory evaluation of sleep by objective methods such as all-night PSG (Boulos et al., 2019), MSLT (Arand and Bonnet, 2019) or MWT (Sangal et al., 1992), Oxford Sleep Resistance Test and Psychomotor Vigilance Task (Bennett et al., 1997) are used to evaluate reduced alertness and excessive sleepiness. Since prolonged nocturnal PSG is typically not performed in clinical practice, epidemiological studies conducted in the general population have mostly focused on EDS, rarely assessing nocturnal and diurnal sleep quantity.

Association

EDS has a negative impact on attention and activity levels. Often, in younger individuals and children, EDS may have a paradoxical effect of increasing irritability and restlessness or hyperactivity. Its impact on behavior in children was surveyed using the Strengths and Difficulties Questionnaire, which reported a negative effect on behavior in children with narcolepsy and EDS as compared to controls. This suggests that EDS as a symptom was contributing to peer difficulties, emotional disturbance, and conduct problems in this group of children.

The association of EDS with mood and behavioral changes is considered to be causal to some extent. Kaplan and Harvey have postulated hypersomnia as a triggering or maintaining factor for depression taking into consideration its positive predictive value for depression and other mood disorders, contribution to treatment resistance of depression, and the finding that isolated episodes of excessive sleepiness trigger short-lived dysphoric phases. The French harmony study hypothesizes that the biological defect found in narcolepsy with cataplexy may be linked to the higher prevalence of depression in this group as compared to other EDS groups and this suggests that in narcolepsy patients, the mechanism of depression is not entirely related to EDS itself.

Automatic behavior may occur in individuals who are excessively sleepy. These behaviors, though not purposeless, are often not appropriate for the situation the individual is in. They are often seen when the individual is partly asleep or in a state of sleep drunkenness. The person may describe not being aware or having partial awareness of a route they have taken while driving or a house chore that they have done. The recollection of the event may be incomplete or totally absent. It is important to differentiate these from other parasomnias and ictal automatisms.