Many studies demonstrate increased sleep latency, increased number of awakenings, insufficient hours of sleep, and a lower sleep efficiency in RLS patients [5, 6, 13–15] (Fig. 3.1). High percentages of patients with moderate or severe RLS reported taking 30 min or more to fall asleep and waking three or more times per night because of RLS symptoms [5]. Patients with moderate to severe RLS may sleep an average of 3–5 h per night and may chronically have less sleep time than patients with almost any other persistent sleep disorder [16], including insomnia [3]. Budhiraja and colleagues conducted an overnight polysomnographic study demonstrating that participants with RLS symptoms had higher prevalence of insomnia with daytime consequences [15]. Another polysomnographic study documented that the mean sleep efficiency was reduced in RLS patients, approximately at 50%, and was below 35% (<3 h sleep per night) in one-fifth of RLS patients [17]. The authors suggested that the reduced sleep efficiency correlates with the reported clinical severity of RLS [16]; for patients with mild RLS, sleep disturbances may be less of a problem [4].

Hornyak et al. comparing a group of 45 patients with RLS to a group of age- and sex-matched healthy controls reported shorter total sleep times and lower sleep efficiencies in the RLS group [13]. Interestingly, according to the one-epoch criterion, sleep onset latency was comparable in RLS patients and in controls as documented also by Saletu et al. [18]. This finding is surprising, as most patients complain about difficulties in initiating sleep, but the discrepancy might be explained by the clinical observation that some RLS patients fall asleep rapidly but cannot maintain sleep (Fig. 3.2).

Furthermore, RLS patients showed a markedly fragmented sleep with numerous periods of waking with increased arousals represented by an augmented arousal index and a sleep fragmentation index significantly higher in the RLS group compared to controls [13, 19, 20].

Moreover, RLS patients presented an increased number of periodic limb movements per hour of sleep (PLMS index) associated with or shortly followed by arousal (PLMS-arousal index), compared to healthy controls [3, 8, 13]. These either could cause the patient to wake up or prevent he/she from reaching deeper stages of sleep. PLM may also occur during relaxed wakefulness (PLMW), delaying the onset of sleep [21].

More recently, Hornyak and colleagues reported evidence of REM sleep disturbance, with longer REM sleep latency and decreased percentage of REM sleep in the RLS group. It might have occurred as a consequence of sleep interruptions which were in turn due to the nocturnal occurrence of RLS symptoms, or as a consequence of the earlier bedtimes in the sleep laboratory or it could be related to the pathology of RLS itself [13].

Interestingly, modest reductions of sleep time and specific loss of REM sleep, even in healthy normal-sleep subjects, appear to be related to hyperalgesia the following morning [22], an observation which may be especially relevant in RLS patients in light of the mechanical hyperalgesia described in this disorder [23].

As would be expected, chronic sleep loss observed in RLS patients leads inevitably to significant consequences on the daytime function. The consequences of chronic sleep deprivation have been investigated intensively in recent years.

Across studies, there was converging evidence that around 20–25% of subjects with untreated idiopathic RLS are likely to experience increased daytime sleepiness [24].

In the REST general population study, more than half of the RLS cohort reported disturbances in daytime functioning such as exhaustion or fatigue, daytime sleepiness, difficulty in concentrating during the next afternoon and during the next evening [6]. One large epidemiological study found significantly higher complaints of decreased vigor in a population judged to have clinically significant RLS symptoms compared to normal controls [6, 25]. Bassetti et al. reported a significantly high degree of daytime fatigue among their 55 RLS patients [26], a finding consistent with the report that RLS sufferers, due to their daytime fatigue, have more work difficulties and driving impairment [27].

Budhiraja and colleagues, obtaining data from the Tucson Cohort of the Sleep Heart Health Study, including 535 participants who answered questions regarding RLS symptoms, documented that participants with RLS had a higher prevalence of daytime sleepiness (38.2%) [15]. Fulda and Wetter, considering 26 studies reporting ESS scores in untreated idiopathic RLS patients, estimated that 29.6% of RLS subjects had an ESS score >10 and 22.8% had an ESS score >11 [24]. EDS in RLS has been noted in two population-based studies [28, 29] suggesting that patients with more frequent RLS symptoms had more elevated ESS scores [29].

Nevertheless, daytime sleepiness, unlike insomnia, does not occur for most RLS patients, and moreover, when sleepiness occurs, it appears to be less severe than expected for the degree of sleep disruption reported by RLS patients [10, 24]: intriguingly, the relatively modest degree of sleepiness is not concordant with the profound sleep debt and insomnia reported by these patients [24] (Fig. 3.3).

The assessment of daytime sleepiness in RLS patients is complicated by the fact that daytime napping is often impossible especially for those with more severe symptoms, impeding to perform Multiple Sleep Latency Test (MSLT) and Maintenance Wakefulness Test (MWT). Nevertheless, Kallweit et al. examined 27 RLS patients finding that 10 out of 27 patients reported EDS (ESS > 10). The 10 sleepy patients underwent video polysomnography (PSG) and MSLT demonstrating that RLS patients with sleepiness had a higher amount of total sleep time (p = 0.029) and a mean pathological sleep latency on MSLT (6.4 min). Under dopaminergic treatment, both RLS severity and ESS improved [30].

Gamaldo and colleagues studied 20 RLS subjects and 13 sleep-restricted controls using morning and evening Suggested Immobilization Test (SIT) which served as a modified MWT. The authors showed that the RLS subjects had a longer sleep latency on the morning and evening SIT than controls [31].

Other studies found no significant differences in the degree of sleepiness reported by patients, nor in the ESS scores, between the RLS and controls [18, 26]. Kushida and colleagues reported that RLS patients may present no significant daytime sleepiness, but rather a subtle breakthrough of decreased daytime alertness. It appears that diminished alertness is likely to result from an indirect effect of sleep disruption during the previous nights and it is proportional to the degree of sleep debt [10]. However, failure to observe the profound sleepiness expected from sleep disruption could suggest some mechanism among RLS individuals that compensates for daytime sleepiness. Such a compensatory mechanism might be more effective against some of the morbidities associated with sleep loss, such as sleepiness, and less effective in reducing other ones, such as irritability, mood liability, or problems with alertness [10]. An alternative hypothesis is that the RLS-associated discomfort experienced by these patients results in a dissociation between their desire to fall asleep during the day and their reported or objective ability to fall asleep [10].

The study by Gamaldo et al. supports the data that RLS subjects often do not report significant daytime sleepiness, despite chronic sleep loss, but a greater sustained alertness than sleep-restricted controls [31]. Thus, RLS disease state itself appears to enhance alertness in the face of sleep loss, a finding in contrast to that reported in Parkinson’s disease, strongly associated with increased daytime sleepiness independent of drug treatments [32, 33]. So, despite the common beneficial response to dopaminergic treatments seen in the two conditions, PD and RLS appear to demonstrate markedly different effects on sleep–wake mechanisms, indicating differences in status of the dopaminergic arousal system in the two disorders [31].

In this point of view, the heightened degree of alertness demonstrated by RLS patients may be in contrast with the perceived impairment in mood, vigor, and vigilance commonly reported in literature [31]. Perhaps the mixed results seen in the studies may be caused by semantic errors, leading subjects to describe the same condition in heterogeneous ways [18, 26]. Drowsiness, vigilance, vigor, and daytime fatigue may all be influenced by the chronic sleep disruption observed in RLS patients; nevertheless they are separated aspects which could be differently affected by sleep deprivation.

Excessive daytime sleepiness and poor sleep quality were reported also in secondary RLS forms, associated with end-stage renal disease (ESRD), diabetes, and pregnancy.

Gigli and colleagues evaluated the prevalence of RLS in a large multicentric series of 601 ESRD patients undergoing dialytic treatment, administering a questionnaire [34]. The percentage of RLS patients was 21.5%. The group of patients suffering from RLS, in comparison with the control group, was significantly more affected by symptoms of insomnia, and had more fragmented and less restful nightly sleep associated with a significant daytime somnolence [34].

In the same way, examining 400 patients on hemodialysis, Araujo and colleagues, found that 21.5% of them presented RLS. Of these RLS patients, 69.8% presented a poorer quality of sleep (PSQI > 5), compared to negative RLS patients, and 38.4% showed excessive daytime sleepiness (ESS > 10) [35].

Sabbatini and colleagues showed that morning patients (patients who underwent dialyses in the morning) were more subjected to insomnia [36], whereas a questionnaire-based study showed that patients on evening hemodialysis had better sleep quality and less daytime symptoms [37]. Even though it is unclear which factors of dialysis are implicated in the development of RLS in uremic patients, considering that sleep-deprived patients are at risk of cardiovascular disease [38], disordered sleep can be an important factor in reducing the life expectancy of patients with ESRD [39].

Skomro and colleagues examined the prevalence and characteristics of sleep disturbances in a population of 58 adult type 2 diabetic outpatients attending endocrinology clinics [40]. Sleep complaints were common among these patients: over 55% of diabetics complained of daytime sleepiness (ESS > 10), and frequent daytime naps were reported by 25.9% of diabetics and 16.7% of controls. RLS was common in both groups, affecting over 24% of diabetics patients and 12.5% of the nondiabetic controls and even though the differences were not statistically significant, ESS scores were higher in the diabetics with RLS than in non-RLS diabetics.