The estimated prevalence of EDS in PD is 29–49 % [1, 2]. In one study investigating the prevalence of EDS and risk factors in a newly diagnosed PD cohort (n = 126), it was found at 3-year follow-up that 49 % experienced EDS. Dopamine agonist treatment and non-tremor dominant motor PD phenotype were most strongly associated with EDS [2]. Other studies have shown that male sex, reduced daily activities of living, and a high daily levodopa equivalent dopaminergic dosage are associated with EDS [1, 3]. In addition, the presence of anxiety and baseline postural instability causing gait difficulty are other factors correlated with EDS in PD [3]. Longitudinal studies have shown an increasing trend between the prevalence of EDS in PD and cognitive decline and disease progression [4].

The estimated prevalence of sleep attacks in PD is 1–4 %, and episodes of sudden sleep onset in PD are 7–42 % [5]. Sleep attacks are defined as abrupt episodes of unexpected sleep that occur during normal activities. Patients may or may not be aware of sleepiness prior to the onset of sleep attacks. Older age, male sex, longer disease duration, disturbed nighttime sleep, and dopaminergic medications have been associated with sleep attacks [6]. In those treated with dopamine agonists, there is a two- to threefold increase in sleep attacks when compared to those who are on levodopa [5]. Genetic polymorphisms in the dopamine D2 receptor gene Taq1A and preprohypocretin have also been significantly associated with sleep attacks in PD [7].

Due to the impairment of daytime sleepiness, an important issue for PD patients is whether they should drive a motor vehicle. A study of 6,620 patients with PD found that 15 % had been involved in and 11 % had caused at least one motor vehicle accident in the past 5 years [8]. PD patients who felt moderately impaired by PD, had an increased Epworth Sleepiness Scale (ESS) score or experienced sudden onset sleeping while driving, had an increased risk of causing accidents. Accidents tended to occur in easy driving situations [8]. Another study compared patients with PD to controls on the ability to perform on a simulated driving test [9]. Subjects with PD committed more errors during both baseline and distractions, driving slower with higher speed variability during distraction. Declining driving performance was associated with multiple symptoms including increased daytime sleepiness [9].

Subjective questionnaires and objective tests have been designed to evaluate EDS. The Epworth Sleepiness Scale (ESS) is a questionnaire that assesses how likely patients are to doze off in eight everyday situations that vary in the levels of stimulation, immobility, and relaxation. A score of 10 or above out of 24 is considered pathologic sleepiness.

Additional questionnaires that can be used to assess sleepiness in PD are the UPDRS Part II, the Pittsburg Sleep Quality Index (PSQI), the Scales for Outcomes in PD-Sleep Scale (SCOPA), the Parkinson’s Disease Sleep Scale (PDSS) and its second edition (PDSS-2). Questions address subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction. Sleep disturbances are addressed as part of the overall picture of disease impact.

The first version of PDSS is a visual analogue scale that addresses 15 commonly reported symptoms associated with sleep disturbances such as nighttime sleep awakenings, movements in sleep, and daytime sleepiness. This has been further extended in the PDSS-2, which has five categories and addresses other sleep disturbances such as restless legs syndrome, akinesia, pain, and sleep apnea.

The overnight polysomnogram (PSG) is useful to diagnose, or rule out, underlying sleep disorders including sleep apnea, periodic limb movement disorder (PLMD), REM sleep behavior disorder (RBD), and parasomnias. These sleep disorders, often found in PD patients [10–12], can cause a fragmented nighttime sleep resulting in daytime sleepiness. Studies have found deficiencies in total sleep time, sleep latency, slow-wave sleep, REM sleep, and sleep efficiency in patients with PD [13, 14].

The multiple sleep latency test (MSLT), which typically follows overnight polsomnography, assesses the ability or tendency to fall asleep. The MSLT measures the speed at which a subject falls asleep when given the opportunity to sleep, and whether a patient goes into REM sleep. It consists of five 20-min nap opportunities 2 h apart. Studies have shown pathologic sleepiness, defined as a mean sleep latency <5 min, is prevalent in PD. A study of 27 PD patients found a mean sleep latency of <5 min in 40 of the 134 nap opportunities during MSLTs [15].

Actigraphy is a noninvasive method of monitoring human rest/activity cycles. One study of actigraphy demonstrated that PD patients had a 1.5-fold to twofold lower daytime motor activity level than controls, which suggests daytime sleepiness or limited physical activity [16]. Additionally, the study showed a 1.5-fold to twofold higher nighttime motor activity which represents the fragmented sleep often reported in patients with PD.

The cause of EDS in PD is often multifactorial with the most relevant effects coming from dopaminergic medications and the disease process itself. The progressive cell loss in the dopaminergic and non-dopaminergic neurons and networks that modulate sleep–wake mechanisms in PD is a major contributing factor to the etiology of sleep disturbances in PD. In addition to the nigrostriatal pathway, PD affects areas of the brainstem, such as the pedunculopontine nucleus, the ventrolateral tegmental area, the locus coeruleus, the dorsal raphe nucleus, and thalamic nuclei, which are involved in maintaining alertness [17]. Circadian sleep–wake dysrhythmia in PD may reflect the central nervous system pathophysiology affecting the retinohypothalamic tract and suprachiasmatic nucleus.

Hypocretin (orexin), which is known to be decreased in narcolepsy, is also thought to be related to the EDS seen in PD; however, the data to support this has varied. One study measuring ventricular cerebrospinal fluid levels found an almost 25 % reduction in PD patients [18]. Another study of 16 PD patients with symptoms of narcolepsy found a correlation with increased objective sleepiness and decreased cerebrospinal fluid (CSF) hypocretin. In addition, in two patients with severe disease serial CSF hypocretin levels decreased over time. Overall, the study concluded that dopamine deficiency correlated with poorer sleep quality and hypocretin signaling related to EDS in PD patients [19]. However, not all studies have shown loss of hypocretin in PD. A study measuring hypocretin levels in cerebrospinal fluid collected by lumbar puncture in 62 patients with PD did not find a decreased level [20].

Medications used to treat PD often lead to EDS both through direct pharmacologic effects and/or by disturbing nighttime sleep. Dopaminergic agents, antidepressants, and amantadine can all cause EDS by disturbing nighttime sleep. Withdrawal from benzodiazepines and other sedatives can cause rebound insomnia resulting in EDS. Anticholinergic agents, through M1 muscarinic receptors, increase REM latency and suppress REM sleep and can cause sedating effects during the day. Trihexyphenidyl increases nighttime wakefulness that can result in daytime sleepiness [21].

Levodopa and dopamine agonists can adversely affect nighttime sleep resulting in EDS. A study of PD patients taking levodopa found that 74 % had a disruption of nighttime sleep [22].

Studies have shown that dopamine agonists increase daytime sleepiness [23–26]. Studies comparing dopamine agonists found that both ergot and nonergot dopamine agonists caused EDS [24–26]. Total dopamine dose, rather than the choice of dopamine agonist, was the best predictor of EDS [26]. In one study of 15 patients evaluated before and 8 months after starting dopaminergic medications, the ESS was significantly increased and the mean sleep latency on MSLT was significantly decreased after treatment [25].

Rotigotine resulted in a higher percentage of patients with improvement in all items of the PDSS-2 except distressing dreams and distressing hallucinations at night [27]. There were significant improvements compared with placebo in the categories of wake with painful limb posturing (increase of 25 % vs decrease by 95 %), limb pain causing waking (decrease in 31 % vs decrease by 83 %), and cramps in limbs causes waking (decrease by 47 % vs 78 %) [27]. Another study looking at nocturnal sleep disturbances using the UPDRS Part III and PDSS-2 with an optimized titration of rotigotine found significant improvement in scores on both scales versus placebo [28].

Catechol O-methyltransferase inhibitors enhance dopaminergic activity, which can lead to worsening of levodopa-induced adverse effects, including sleep disorders and hallucinations [29]. Selegiline, which is metabolized to amphetamine, is one of the most likely to cause sleep-onset insomnia that can lead to EDS [30]. Rasagiline is not metabolized to amphetamine metabolites; it may not have the same degree of insomnia as selegiline [31].

Deep brain stimulation (DBS), used for treatment of Parkinson’s disease refractory to medications, has also been shown to help improve sleep. DBS of the subthalamic nucleus (STN) has been shown to improve nighttime sleep. In a study of five patients 3 months after surgery, there was an increase in total sleep time and slow-wave sleep as well as a reduction of wakefulness after sleep onset and at 1-year follow-up [17].

A similar improvement in sleep quality was found with DBS of the globus pallidus internal (GPi) segment and the pedunculopontine tegmental nucleus (PPTg). However, unlike STN-DBS, stimulation of the PPTg improved not only nighttime sleep but also ameliorated excessive daytime sleepiness [32]. The ESS was reduced by more than 50 % with PPTg-DBS at 1-year follow up. This improvement was seen both with PPTg stimulation only at night or on for 24 h/day. It is hypothesized that stimulation of the PPTg, which is part of the reticular activating pathway, induces a recovery of the activity of this pathway and therefore improves sleep quality and daytime alertness [32].

In PD different types of insomnia, sleep related breathing disorders, circadian rhythms disorders, parasomnias, RLS, and other sleep related movement disorders have been reported. The associations and impact of each of these sleep disorders on EDS have not been systematically studied and remain controversial. Clinical studies have found controversial results as to whether sleep apnea is increased in PD. Research studies in PD have shown an increased rate of snoring (71.8 %) [33] and sleep apnea (20 %) [34]. Notably, no correlation was found between apnea/hypopnea index (AHI) and the MSLT, and the authors concluded that sleep apnea may not be a major factor contributing to the severity of sleepiness in most patients with PD [34]. Two case reports of patients with PD and OSA found that CPAP clearly restored more daytime activity [35].

Insomnia is found in 54–60 % of PD patients [36]. Sleep fragmentation and early awakenings are the most common types of insomnia symptoms reported with minimal differences in sleep initiation. While insomnia may contribute to tiredness, fatigue, and EDS in PD, several studies found inverse relationship between daytime sleepiness and overnight sleep quality.

The prevalence of RLS has been shown to be significantly higher in the PD population compared to sex-matched controls [37]. Daytime fatigue is commonly reported in patients with RLS. There have been controversial results regarding the incidence of periodic limb movement disorder (PLMD) in PD [38].

RBD is characterized by acting out of vivid dreams in vigorous and often violent ways during REM sleep. RBD appeared to predict subsequent development of dementia, as well as cognitive fluctuations and hallucinations [39].

Circadian rhythm sleep disorders result from the misalignment sleep patterns and normal daytime activities. Excessive daytime sleepiness and nighttime sleep disturbance often lead to irregular sleep–wake patterns in PD.

In PD motor symptoms, depression and pain can affect sleep. Disruptive nighttime motor symptoms include tremor, nocturnal dystonia, and nocturnal akinesia. Depression often adversely affects sleep in PD causing difficulty falling asleep, staying asleep, and early morning awakenings. Pain is noted in about 50 % of patients with PD [40], which may cause difficulty falling asleep and staying asleep. Disruptive nighttime motor symptoms, depression, and pain all fragment nighttime sleep leading to daytime fatigue and EDS.

Hallucinations can disrupt sleep and affect almost 33 % of patients with PD. PD patients with hallucinations have increased awakenings, decreased sleep efficiency, and more daytime sleepiness [41].

EDS in PD can be related to sleep disruption, sleep deprivation, medication side effects, underlying sleep disorders, or from the primary disease. The clinician must first determine which factors are involved in producing the EDS. Promoting good sleep hygiene and emphasizing the importance of daytime light exposure and daytime activity are crucial. Good sleep hygiene includes maintaining a regular sleep–wake schedule, spending an appropriate amount of time in bed (~8 h), and avoiding caffeine and frequent naps during the day (Table 8.2). Adjusting doses of dopaminergic medication can help promote daytime alertness and increase quality of sleep at night. The physician must determine if the patient has an underlying sleep disorder and treat as appropriate.