Chapter 18 Sleep Laboratory Diagnosis of Restless Legs Syndrome
As stated previously in this book, the diagnosis of restless legs syndrome (RLS) relies essentially on the presence of four clinical manifestations: (1) an urge to move, usually accompanied or caused by uncomfortable and unpleasant sensations in the legs, (2) the urge to move or unpleasant sensations beginning or worsening during periods of rest or inactivity, (3) the urge to move or unpleasant sensations partially or totally relieved by movement, and (4) the urge to move or unpleasant sensations worse in the evening or night than during the day, or occur only in the evening or night.1 Other clinical features, such as a positive family history or a positive therapeutic response to dopaminergic agents, are supportive criteria that are not essential for the diagnosis of RLS but can be helpful, especially in cases of diagnostic uncertainty.
Despite the efforts of international experts of RLS to establish standard criteria,1,2 the clinical diagnosis of this condition remains, in several patients, difficult to make on the basis of the clinical evaluation solely. Thus, several attempts have been made to develop objective methods for diagnosing RLS. This includes both polysomnography (PSG) and the suggested immobilization test (SIT).
Diagnostic Polysomnography
Periodic Leg Movements in Sleep
PLMS are best described as rhythmic extensions of the big toe and dorsiflexions of the ankle with occasional flexions of the knee and hip. The movements may occur in one or, more typically, both legs simultaneously. The quantification of PLMS is routinely performed in the sleep laboratory by the recording of bilateral anterior tibialis muscle surface EMG. According to standard criteria originally developed by Coleman3 and later revised by a task force of the American Sleep Disorders Association,4 PLMS are scored only if they are part of a series of four or more consecutive movements lasting 0.5 to 5 seconds and if they are separated by intervals of 5 to 90 seconds. Different amplitude criteria were being used to score PLMS. In most laboratories, PLMS are scored only if they have an amplitude of one quarter or more of the EMG potential recorded at the time of foot or toe dorsiflexion during calibration of the PSG equipment before the nocturnal sleep recording. However, this criterion is not universally applied, and in several studies no amplitude criterion is being used. A new criterion is based on elevation above baseline.5 Traditionally, an index (number of movements per hour of sleep) of PLMS greater than 5 for the entire night has been regarded as pathological,3,4 regardless of the patient’s age or sleep complaint. The International Classification of Sleep Disorders stated that the PLMS index must be interpreted in the context of the patient’s sleep complaint, emphasizing the importance of clinical context over an absolute cutoff value.6 In addition, they suggest that a cutoff value of 15 may be more appropriate for most adult cases. However, these recommendations need to be further validated.
Sensitivity of the Periodic Leg Movements in Sleep Index in the Diagnosis of Restless Legs Syndrome
In 1965, Lugaresi and coworkers7 first reported the presence of PLMS (originally called nocturnal myoclonus) in patients with RLS. Subsequently, the study of 131 patients with RLS using Coleman’s scoring criteria showed that approximately 80% of them were found to have a PLMS index of greater than 5.8 In this study, a subgroup of 49 patients were recorded for two consecutive nights. On each night, 82% of the patients had a PLMS index greater than 5, and 76% met this criterion on both nights. However, when the highest number of PLMS for the two nights was considered for each patient, 87.8% was found to meet this criterion. When a PLMS index of greater than 10 was used as the criterion, 67.3% of patients met it on the first night, whereas 81.6% of patients met it when the worst of two nights was considered.8 A significant positive correlation (Pearson r = 0.66; p >.001) was found between PLMS indices for nights 1 and 2. More recently, Sforza and coworkers9 confirmed these results in their study of 68 patients with RLS and showed that the PLMS index of the patients (as a group) did not significantly change across two nights of PSG with a good night-to-night reproducibility. However, they found a significant intra-individual difference in the correlation coefficient for the PLMS index (r = 0.54, p =.003). The individual internight changes in PLMS index appeared independent of age, International Restless Legs Syndrome Study Group (IRLSSG) severity score, duration of the disease, and changes in sleep parameters. These results demonstrate the diagnostic interest of repeating nocturnal PSG recordings in RLS patients.
Specificity of the Periodic Leg Movements in Sleep Index: Restless Legs Syndrome Patients Versus Normal Control Subjects
The specificity of PLMS as a diagnostic tool for RLS varies considerably with age. Indeed, a high PLMS index is rather uncommon in normal children and young adults.10 The mean PLMS index increases dramatically in healthy middle-aged individuals10–16 with and without sleep complaint. For example, in a study of 70 middle-aged subjects (mean age, 40 to 60 years) without sleep complaint, the mean PLMS index was 9.6, but 27 individuals (38%) had a PLMS index greater than 5 and 22 (31%) had a PLMS index greater than 10. The mean PLMS index further increases with advancing age; the mean PLMS index was higher than 20 in healthy subjects after the age of 50.10 Age also influenced the periodicity of PLMS in healthy controls. Interval histograms of PLMS performed in different age groups showed that PLMS are not clearly periodic in healthy subjects before the age of 40 years.
One study17 assessed the sensitivity and the specificity of the PLMS index in discriminating 100 RLS patients (with a mean age of 48.8 years) from 50 gender- and age-matched healthy control subjects (with a mean age of 48.4 years). Analyses revealed that a PLMS index of 7 best discriminated between RLS patients and control subjects with a sensitivity and a specificity of 78% and 76%, respectively. The results were obtained in middle-aged individuals, but considering the marked differences in PLMS index across age groups in healthy controls, these specificity measures are expected to be much higher in children and considerably lower in the elderly.
Specificity of the Periodic Leg Movements in Sleep Index: Restless Legs Syndrome Versus Other Sleep Disorders
PLMS also occurs in a wide range of sleep disorders18,19 including narcolepsy,19–21 REM sleep behavior disorder (RBD),18,22 obstructive sleep apnea syndrome (OSAS),23–25 insomnia,18,19 and hypersomnia.18,19 Indeed, a PLMS index greater than 5 was found in 68% of 170 narcoleptic patients recorded in our laboratory.26 In a study of 40 RBD patients, 32 (80%) showed a PLMS index greater than 5 and 28 (70%) showed an index greater than 10.22 PLMS were also reported frequently in patients with OSAS. In this condition, leg movements may occur at the end of the apnea in association with an arousal response. Patients with OSAS also have PLMS independent of apnea episodes. In one study,24 leg movements with long intermovement intervals were found to be associated with respiratory events, whereas those with short intervals were identified as PLMS independent of respiration. It should be noted that, in OSAS patients, the PLMS index usually decreases with successful treatment of OSAS with nasal continuous positive airway pressure (CPAP), although in a large number of patients it remains elevated after CPAP treatment.24,25 The prevalence and characteristics of leg movements in OSAS, their relation with respiratory events, and their response to treatment remain to be elucidated.
PLMS were also reported in patients with insomnia or hypersomnia. In the absence of any other cause, insomnia or hypersomnia with PLMS is referred to as periodic leg movements disorder (PLMD). Several researchers and clinicians have questioned the status of PLMD as a specific clinical entity. Although PLMS do occur in insomnia and hypersomnia, their prevalence in people with these disorders is often the same as in groups of age-matched control subjects who report no disturbance of sleep or vigilance. Furthermore, the relationship between PLMS, sleep quality, and daytime sleepiness is still unclear in these clinical populations. Although some reports had indicated an association between the PLMS index and PSG sleep parameters27–31 or subjective sleep variables,16,32 most studies suggested that the PLMS is not related to subjective sleepiness, sleep complaints, or PSG parameters in patients with insomnia or hypersomnia.16,33–37
