The case vignette above provides a very common example of how the leg activity, known today as PLMS, is often observed and reported on a sleep study. These movements, however, were not formally described until the 1950s, when Dr. Charles Symonds documented five patients who were relaxed when awake but had fits of jerking extremities while asleep. Initially thinking that these repetitive, jerking movements were in some way related to epileptic activity, Symonds devised the term “nocturnal myoclonus” to describe them [6]. This relationship to seizures was disproven, however, in the 1960s and 1970s with polysomnography (PSG) and EEG [7]. Later, in 2000, these movements were observed to occur in the upper extremities as well [8].

PLMS are benign, intermittent episodes of repetitive, stereotyped limb movements. These movements predominate in the legs and commonly consist of extension of the great toe accompanied by partial flexion of the ankle, knee, and hip [2]. These movements are referred to as PLMS when they occur during sleep; they are called PLMW when they occur during wakefulness. Like other sleep movements, PLMS are usually first noticed by bed partners. Although PLMS can cause partial awakening from sleep, patients, like Lucy, are typically unaware of the associated sleep disruption and therefore have limited QoL impact.

Only when the features consistent with PLMS are reported in conjunction with a decline in functional sleep quality or daytime complaints is an all-night polysomnogram required. EEG is necessary to differentiate between PLMS and PLMW. At-home activity monitors are also available and should be considered for PLM measurement and recording.

Although PLMS are becoming better characterized, the exact etiologic mechanisms involved in these phenomena remain unclear. While there is currently no known anatomic localization of a primary defect, it is thought that a loss of the normal sleep-related inhibition of the spinal leg flexor reflexes may be involved. Ordinarily, sleep inhibits spinal flexor reflexes in the limbs. However, in recent studies measuring the Hoffman’s reflex in sleeping patients, it has been documented that patients with PLMS exhibit decreased spinal inhibition (i.e., increased spinal excitability) [9]. PLMS have also been shown to reliably coincide with the cyclical changes in blood pressure, respiratory rate, and autonomic arousal that occur during the transition from the deeper to more arousable states of sleep. It has therefore been hypothesized that these leg movements are being triggered by central signals, which are suppressed during sleep, that fire down the spinal cord in tandem with those responsible for the cyclic alternating patterns (CAP) of the various stages of sleep (including the above autonomic changes) [10].

PLMS become more common with age. In a recent pediatric sleep study, greater than 5 % of cases referred to a sleep specialist exhibited a PLMS index >5 per hour, with approximately 1 % of cases having PLMS without a sleep condition or comorbid disorder [11]. For patients older than the age of 65, 45 % exhibited a PLMS index of >5 per hour [12].

These data indicate that PLMS are relatively commonplace in the general population and occur frequently in healthy individuals. They are very nonspecific disease markers that may represent an abnormal motor manifestation associated with a number of disease states (Table 12.1). For example, PLMS occur in greater than 80 % of patients with RLS [11]. Additionally, in a study investigating a REM sleep behavior disorder cohort, 70 % exhibited a PLMS index >10 per hour. Further evidence suggests that PLMS may also be associated with a number of medications, including selective serotonin reuptake inhibitors (SSRIs), tricyclics, and neuroleptics [10].

Together, these data suggest that PLMS should be viewed primarily as markers; epiphenomenon of possible disease risk (e.g., RLS) and not movements constituting a true disorder in and of themselves.

Twenty years after her sleep study, Lucy (now age 42) presents again to sleep clinic complaining of insomnia and “creepy crawly things in her legs” that compel her to continuously move her legs around. These sensations regularly begin between 8 and 9 P.M. every evening. Lucy wakes up feeling unrestored and feels like her mind is “fuzzy” throughout the day. Based upon these symptoms, additional historical features were solicited. They include a prior history of alcohol abuse (although she has been sober for the last 5 years) and a family history of similar symptoms in her mother. In the clinic, Lucy looks exhausted. The rest of her physical exam, however, is unremarkable.

Although the field of sleep medicine was not established until the twentieth century, the phenomenon of RLS was described as early as 1672, when Dr. Sir Thomas Willis wrote of a disorder involving “leaping and contractions of the tendons” so profound that patients were “no more able to sleep than if they were in the place of the greatest torture [13].” Despite Willis’ observations, this syndrome was largely ignored until 1945, when Dr. Karl-Axel Ekbom presented eight similar cases and further characterized the disease, coining the term “restless legs” in his doctoral thesis [14]. In recent years, however, this syndrome has adopted a new name, Willis-Ekbom disease (WED), in honor of these two pioneers and in recognition that the adjective “restless” does not truly characterize all of the symptoms patients describe with this disorder (see below).

RLS is considered a sensorimotor disorder because the syndrome encompasses a sensory disturbance that can lead to a voluntary or involuntary movement response. The currently accepted clinical diagnostic criteria for RLS as defined by the International Restless Legs Syndrome Study Group (IRLSSG) are listed in Table 12.2 [5]. The principal symptom of RLS is the feeling of a demanding urge to move the legs that occurs while resting, often in the evening or night. The diagnosis requires all four of the basic essential criteria plus the exclusion of common RLS “mimics” (Table 12.2). These mimics and the patients expression of significant impairment as a result of these symptoms close to those of RLS and can often be differentiated only by careful history-taking [5]. In one study, these physician-diagnosed mimics accounted for 16 % of all patients satisfying these four criteria for RLS [15]. A broad differential is thus required before a diagnosis of RLS can be determined. There are separate pediatric criteria for diagnosis of restless legs syndrome. These are discussed in a separate chapter.

Factors not required but considered supportive of a diagnosis of RLS include a sleep disturbance leading to reduced sleep quality or quantity, PLMS that occur with a frequency greater than expected for age, a first-degree relative with RLS, and a significant reduction in symptoms shortly after starting dopaminergic therapy [16].

Variants of RLS have also been characterized, and it is important to consider these as well in the differential. For example, patients experiencing involuntary movements during sleep that manifest in a circadian pattern, occur during periods of relaxed wakefulness in the evening/night, and cause significant sleep disturbance are considered to have a separate diagnosis known as quiescegenic nocturnal dyskinesia (QND). A distinguishing feature of patients with QND is that they do not report the uncomfortable sensations experienced by those with RLS [17].

RLS can be classified as either primary or secondary. Primary RLS is generally considered to be idiopathic, but has been linked to several biological mechanisms (see below).