The Restless Leg Syndrome, Periodic Limb Movements in Sleep, and the Periodic Limb Movement Disorder

Chapter Points

• A diagnosis of the RLS is based on clinical history. The essential elements include URGE (Urge to move, Rest makes symptoms worse, Gets better with movement—temporary improvement in symptoms with movement, and Evening is worse [symptoms worse in the evening, at least at the onset of the syndrome]).

• Supportive clinical features for the diagnosis of RLS include a family history, improvement with dopaminergic treatment, and the presence of PLMS on PSG.

• Secondary causes of RLS included renal failure, pregnancy, iron deficiency, and medications. Medications frequently worsening RLS include first-generation antihistamines, antidepressants (except bupropion), and dopamine blockers (phenothiazines, metochlopramide).

• A diagnosis of PLMD is based on both history and PSG findings: (1) A complaint of sleep disturbance or daytime fatigue, (2) PSG findings PLMSI > 5/hr (children) and > 15/hr in adults, (3) Symptoms are not better explained by another sleep, medical, or neurologic disorder, or medication use (e.g., OSA). A diagnosis of RLS excludes a diagnosis of PLMD. A complaint of sleep disturbance must be made by the patient (in contrast to the bedmate).

• PLMS is a PSG finding. PLMS is very common in older adults and is most often asymptomatic. PLMS can be associated with OSA, narcolepsy, and RBD.

• About 80% of patients with RLS will have a PLMS index ≥ 5/hr on PSG.

• The PLMD may precede a diagnosis of RLS in children. A diagnosis of RLS is difficult in children because they may not report traditional symptoms. They may present with “growing pains.”

• Treatment options for RLS include conservative measures, dopaminergic medications (LD/CD and DAs), anticonvulsants, opiates and opioid agonists, and sedative hypnotics.

• LD/CD is a rapidly absorbed dopaminergic medication (LD is a precursor of dopamine) that is effective treatment of RLS. It is a good option for intermittent RLS. However, the medication has a short duration of action and continued use results in augmentation in up to 80% of cases (especially with doses of LD > 200 mg daily).

• The DAs ropinirole and pramipexole are FDA approved for treatment of RLS in adults and are considered the treatment of choice for daily RLS. They must be given 2 hours before symptoms to be most effective.

• Anticonvulsants are also effective for RLS/PLMD. Due to a good safety profile, gabapentin is the anticonvulsant recommended for RLS treatment. Doses of 900 to 1500 mg of gabapentin may be needed to be effective. A slow upward titration of the dose starting at 300 mg may improve tolerance to use. Gabapentin is considered a first-line medication by some clinicians if RLS is associated with pain.

• Narcotics are effective treatment for RLS. They may be especially useful in patients who develop augmentation or do not tolerate DAs. If given only at bedtime, they usually do not result in dependence. For milder cases, codeine, propoxyphene, or tramadol may be effective. For moderate RLS, hydrocodone (combined with acetaminophen in the United States) or oxycodone is often used. For severe RLS, oxycodone or methadone has been used with success.

• Sedative hypnotics may be useful in milder RLS associated with insomnia or can be combined with other classes of medications. Most of the published treatment trials used clonazepam (long half-life), but other BZRAs may also be effective.

• Augmentation describes a phenomenon that is characterized by one or more of the following: (1) earlier symptom onset, (2) greater severity of symptoms at the same dose/or escalating dose, (3) reduced latency to onset of symptoms with rest, and (4) spread of symptoms to involve new body parts (arms as well as legs).

• Low serum ferritin (<45 to 50 µg/mL) is a risk factor for development of augmentation.

• RLS patients with a ferritin less than 45 to 50 µg/mL may improve with iron supplementation. The usual dose is ferrous sulfate 325 mg tid with each dose given with 100 to 200 mg of ascorbic acid to improve absorption. Patients with augmentation may improve with iron supplementation.

The restless legs syndrome (RLS), periodic limb movements in sleep (PLMS), and the periodic limb movement disorder (PLMD) are three distinct but related entities 1–⁶ (Table 23–1). A diagnosis of RLS is based on clinical history. PLMS is a polysomnography (PSG) finding that may or may not be clinically important. The PLMD is diagnosed in patients with PLMS on PSG who have a sleep complaint (sleep-onset or maintenance insomnia or, less commonly, daytime sleepiness) not better explained by another sleep disorder.⁶ PLMS is a very common finding especially in older patients (Fig. 23–1) and is often asymptomatic.^5,7–11 Approximately 80 to 90% of patients with RLS will have findings of PLMS on PSG.¹² The percentage of patients with PLMS who have RLS has not been well-defined, but the vast majority of patients with PLMS do not have RLS. PLMS has been associated with narcolepsy, the REM sleep behavior disorder, and obstructive sleep apnea (OSA). A diagnosis of RLS excludes PLMD. PLMS is very common, RLS is common, and PLMD is thought to be rare. Chapter 12 outlines the scoring criteria for PLMS in detail with examples of illustrative tracings. This chapter emphasizes the clinical significance of PLMS.

TABLE 23–1

Different Leg Movement Conditions

	RLS	PLMS	PLMD
Diagnosis	History	PSG	PSG + History
Prevalence	Common	Very common • Asymptomatic individuals • Narcolepsy • REM sleep behavior disorder • OSA	Rare
Associated findings	• ∼80% have PLMS	• Usually asymptomatic or symptoms are not due to PLMS • A minority of patients have RLS	• Must exclude other causes of insomnia or daytime sleepiness
Relationship with other leg movement conditions	A diagnosis of RLS excludes a diagnosis of PLMD	A PSG finding not a disorder	Not diagnosed if RLS is present

OSA = obstructive sleep disorder; PLMD = periodic limb movement disorder; PLMS = periodic limb movement in sleep; PSG = polysomnography; REM = rapid eye movement; RLS = restless leg syndrome.

Restless Legs Syndrome

The RLS is a common disorder often underdiagnosed and improperly treated. In 1995, the International Restless Legs Syndrome Study Group (IRLSSG)¹¹ published a statement on the primary and associated features of the syndrome. The criteria were refined during a workshop at the National Institutes of Health (NIH).¹³ The criteria form the basis for the International Classification of Sleep Disorders, 2nd edition (ICSD-2) diagnostic criteria for RLS⁶ (Box 23–1). There are four essential diagnostic criteria for RLS (URGE = urge to move, rest induced, gets better with activity, evening and night worse).

Box 23–1

Diagnostic Criteria for Restless Legs Syndrome

A The patient reports an urge to move the legs, usually accompanied or caused by uncomfortable and unpleasant sensations in the legs.

B The urge to move or unpleasant sensations begin or worsen during periods of rest or inactivity such as lying or sitting.

C The urge to move or unpleasant sensations are partially or totally relieved by movement, such as walking or stretching, as long as the activity continues.

D The urge to move or sensations are worse, or only occur, in the evening or night.

E The condition is not better explained by another current sleep disorder, medical or neurologic disorder, medication use, or substance use disorder.

From American Academy of Sleep Medicine: ICSD-2 International Classification of Sleep Disorders, 2nd ed. Diagnostic and Coding Manual. Westchester, IL: American Academy of Sleep Medicine, 2005.

The Essential RLS Diagnostic Criteria 6,13

1. The patient reports an urge to move the legs, usually accompanied or caused by uncomfortable and unpleasant sensations in the legs. Of note, the urge to move can be present without associated symptoms. Commonly reported RLS sensations are listed in Box 23–2. Although called the “restless legs syndrome,” symptoms can occur in the arms as well as the legs in 30% to 50% of the patients.^12,13 Although RLS symptoms are usually bilateral, some patients report symptoms mainly in one extremity.¹² About 20% of RLS patients report the leg sensations to be painful. Involuntary leg movements may also be reported without an urge to move (“the legs just move on their own”). As discussed later, this is a manifestation of periodic limb movements during wake (PLMW).

Box 23–2 Abnormal Sensations in Restless Legs Syndrome

Common Patient Descriptions of Sensations

• Creepy, crawly.

• Ants crawling under the skin.

• Worms crawling in the veins.

• Pepsi-Cola in the veins.

• Nervous feet “gotta move.”

• Itching under the skin, itchy bones.

• Crazy legs/Elvis legs.

• Toothache feeling—can’t leave it alone.

• Excited nerves, electric-like shocks.

Characteristics of Sensations

• Daytime symptoms if RLS is severe.

• If RLS very severe, symptoms may not be worse at night.

• Usually bilateral but can be unilateral.

• Arms may be involved in 30–50%.

• Sensations are painful in 20%.

• May be absent—simply urge to move.

RLS = restless legs syndrome.

2. RLS symptoms begin or worsen during periods of inactivity such as lying or sitting. Being stationary and having decreased mental activity appear to both worsen symptoms.

3. The urge to move or unpleasant sensations are totally or partially relieved by movements such as walking or stretching as long as the activity continues (temporary relief). Rubbing the legs or taking hot or cold baths may improve symptoms in some patients. Of note, increased mental activity or eating can improve the symptoms (“popcorn therapy” while watching a movie).

4. The urge to move or unpleasant sensations are worse in the evening or night. If RLS has become very severe, nocturnal worsening may not be reported but should have been present earlier in the disease course. When RLS is severe, daytime symptoms can occur especially during periods of inactivity.

Supportive Clinical Features

Some patients will report atypical symptoms.¹³ The supportive clinical features of RLS (Box 23–3) may help resolve diagnostic uncertainty. They are not required for a diagnosis of RLS. In studies of groups of patients with RLS, a familial history is reported in 50% to 60% of the cases. A family history of RLS is supportive of the diagnosis. An improvement with a trial of dopaminergic treatment is also evidence that symptoms represent the RLS. However, one must be aware of the placebo effect. Placebo-controlled studies in RLS report considerable improvement in symptoms with inactive medication. The periodic limb movements in sleep index (PLMSI) is defined as the number of periodic limb movements (PLMs) per hour of sleep. The criteria for scoring a leg movement as a periodic leg movement are discussed in Chapter 12. It is difficult to define a normal PLMSI (see Fig. 23–1). In the past, some sleep centers considered a PLMSI of 5/hr or greater to be abnormal. However, many asymptomatic individuals have much higher PLMSI values,⁷–⁹ The presence of PLMS can provide supporting evidence for the presence of the RLS. One study employing a PLMSI cutoff of 5/hr reported that 80.2% of patients with RLS had PLMS (87% if 2 nights were monitored).¹² Patients with RLS often report repetitive involuntary leg movements during wakefulness when at rest especially at night. This is a manifestation of PLMW (periodic limb movements during wake).

Box 23–3

Supportive Clinical Features of Restless Legs Syndrome

Family History

• The prevalence of RLS among first-degree relatives of patients with RLS is 3 to 5 times greater than in people without RLS.

• 50–60% of patients with RLS report a family member with RLS.

Response to Dopaminergic Therapy

• Nearly all patients with RLS show at least an initial positive therapeutic response to either l-dopa or a dopamine receptor agonist at doses considered low compared with those used to treat Parkinson’s disease.

Periodic Limb Movements (During Wakefulness or Sleep)

• Involuntary movements during wake or sleep.

• PLMS occur in at least 80% of patients with RLS—however, PLMS commonly occur in other disorders and in the elderly.

• PLMW is a manifestation of RLS.

PLMS = periodic leg movements in sleep; PLMW = periodic leg movements during wake; RLS = restless legs syndrome.

Adapted from Allen RP, Picchietti D, Hening W, et al. Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the Restless Legs Syndrome Diagnosis and Epidemiology Workshop at the National Institutes of Health. Sleep Med 2003;4:101–119.

Differential Diagnosis of RLS/PLMS

The differential diagnosis of RLS/PLMS includes a number of mimics 13–¹⁶ (Table 23–2 and Box 23–4). Most of these are not associated with an urge to move. Often, the movements are not worse at night and symptoms are not temporarily improved by movement.

Box 23–4 Differential Diagnosis of Restless Legs Syndrome and Periodic Limb Movements in Sleep

Hypnic jerks—whole body jerks at sleep onset, involuntary, no urge to move.

Positional discomfort—need to move in bed to relieve pressure that compresses nerves, limits blood flow, or stretches tissue.

Neuroleptic akathisia—generalized nature of need to move the body and the occurrence in association with use of dopamine receptor antagonists (phenothiazines, metaclopramide).

Painful legs–moving toes syndrome—pain in the lower limbs with spontaneous movements of the toes or feet. The pain is most often burning and the movements consist of flexion/extension, abduction/adduction, fanning, or clawing of the toes, fingers, foot, or hand. Painless variants exist. Causes include nerve root lesions, herpes zoster, HIV, neuroleptics, chemotherapeutic agents, peripheral trauma, and polyneuropathy for alcoholism.

HIV = human immunodeficiency virus.

TABLE 23–2

Characteristics of Restless Legs Syndrome Mimics

	URGE TO MOVE	ABNORMAL SENSATIONS	WORSE IN THE EVENING/NIGHT	IMPROVED BY MOVEMENT	NEUROLOGIC STUDIES	NEUROLEPTIC USE
RLS	Yes	Usually	Always	Temporary improvement	Neurologic examination usually normal, EMG often normal	No
Hypnic jerk	No	No	Sleep onset	Single whole body jerk	Normal	No
Neuropathy	No	Yes, can be painful	Sometimes	No	Decreased sensation, abnormal EMG/nerve conduction	No
Positional discomfort	Yes	Usually	Usually	Change in position not movement	Variable	No
Neuroleptic akathisia	Inner restlessness	No	Not usually	Not usually	Variable	YES
Leg cramps	No	Pain localized to muscle	Sometimes	Stretching not movement	Normal	No
Claudication	No	Pain	Not usually	Walking may worsen	Decreased pulses	No
Painful legs, moving toes syndrome	No	Pain, burning	Not usually	No	Abnormal EMG, MRI may show lumbosacral nerve compression	No

EMG = electromyogram; MRI = magnetic resonance imaging; RLS = restless legs syndrome.

Hypnic jerks are usually single, whole body jerks that occur at sleep onset. They are not associated with abnormal sensations.

Neuropathy may present as pain and/or burning in the legs or feet but is usually associated with an abnormal neurologic examination and is not associated with an urge to move. Neuropathic pain is usually not improved with movement or rubbing. The pain may be worse at night but is usually present during the day. RLS and neuropathy can exist together.

Positional discomfort is associated with a need to move in bed to relieve pressure that compresses nerves, limits blood flow, or stretches tissue. The sensations may be painful but are improved with change in position rather than with movement.

Neuroleptic akathisia is characterized by involuntary movement of the face or extremities (such as body rocking, marching in place, or movement of the extremities) and is NOT worse during the night or at rest. There is invariably a history of use of neuroleptics (phenothiazines) and other dopamine blockers (metoclopramide). The movements are associated with inner restlessness but not abnormal sensations.

The painful legs–moving toes (PLMT) syndrome13,16 is characterized by pain in the lower limbs with spontaneous movements of the toes or feet. Variants of PLMT that are painless or involve the arms and hands also exist. The pain is most often burning in nature and commonly precedes spontaneous movements consisting of flexion/extension, abduction/adduction, fanning, or clawing of the toes, fingers, foot, or hand. Causes of PLMT include nerve root lesions, herpes zoster, human immunodeficiency virus (HIV), neuroleptics, chemotherapeutic agents, peripheral trauma, and polyneuropathy from alcoholism.

Nocturnal leg cramps are associated with localized severe pain and tightness in a muscle. These are improved with stretching but not just movement.

Claudication may be associated with pain even at rest, if severe, but is usually NOT improved with movement. Usually, claudication symptoms are worse with exertion.

Causes of RLS

Common causes of RLS are listed in Box 23–5. RLS is often divided into primary RLS (independent of other disorders) and secondary RLS (due to an identifiable cause such as a medical disorder, condition, or medication). The cause of primary RLS is not known. There may be an abnormality in iron transport into the central nervous system or utilization of iron as it relates to dopaminergic neurons. Causes of secondary RLS include renal failure, pregnancy, iron deficiency (with or without anemia), and certain medications. Medications associated with RLS include tricyclic antidepressants, serotonin reuptake inhibitors, dopamine blockers (phenothiazines, haloperidol, metoclopramide), sedating antihistamines (diphenhydramine), and antinausea medications (prochlorperazine). RLS associated with renal failure is not helped by dialysis but is cured by renal transplantation. The RLS of pregnancy commonly vanishes or improves with delivery. It is prudent to check a serum iron, total iron-binding capacity (TIBC), and ferritin in patients with RLS. It is recommended that RLS patients have a ferritin above 45 to 50 µg/mL.¹⁷ The RLS of iron deficiency may improve with iron supplementation. If the onset of RLS can be linked to the start of a given medication, a switch to an alternate medication can be tried. For example, bupropion is an antidepressant that does not worsen RLS.¹⁸ In one study, selective serotonin reuptake inhibitor (SSRI) medications and venlafaxine were more likely to be associated with PLMS than either a control group or a group taking bupropion.¹⁹ Thus, bupropion might be less likely to cause or worsen RLS.

Box 23–5 Causes of Restless Legs Syndrome

• Earlier age of onset and slower progression

• Familial occurrence more likely

Secondary RLS

• Iron deficiency

• Low normal ferritin level (<45–50 µg/L) is related to increasing severity of RLS even if hemoglobin is normal

• Pregnancy

• Neuropathy—diabetic and others

• Multiple sclerosis

• Renal failure (transplant but NOT dialysis cures RLS)

• Parkinson’s disease

• Medications

• First-generation (sedating) antihistamines (diphenhydramine)

• Antinausea medication—prochlorperazine

• Dopamine receptor blockers—metoclopramide

• Antidepressants (SSRIs, SNRIs)—exception is bupropion

RLS = restless legs syndrome; SNRIs = selective serotonin and norepinephrine reuptake inhibitors; SSRIs = selective serotonin reuptake inhibitors.

Familial Patterns and Genetics

In 50% to 60% of cases of RLS, a family history of RLS can be found.13,20 Twin studies show a high concordance rate. Most pedigrees suggest an autosomal dominant pattern; however, a recessive pattern with a carrier phenotype is also possible. Familial RLS has onset of symptoms at a younger age and is more slowly progressive. The genetics of RLS, as in many medical conditions, is complex²¹–³⁰ (Table 23–3). Linkage studies have found RLS loci but no related disease-causing sequence variants have been found. More recent genome-wide association studies have identified three genomic regions MEIS1, BTBD9, and MAP2K5/LBXCOR1. In one study, the presence of a genetic risk for the presence of PLMS was found whether or not RLS symptoms were present.²⁹

TABLE 23–3

Genetic Linkages and Associations in Restless Legs Syndrome

LINKAGES
AUTHOR	POPULATION	CHROMOSOME	MODEL
RLS-1—Desautels, 2001²²	French Canadian	12q	Recessive
RLS-2—Bonati, 2003²³	Italian	14q	Dominant
RLS-3—Chen, 2004²⁴	United States	9p	Dominant
RLS-4—Levchenko, 2006,²⁵ 2009²⁶	French Canadian	20p	Dominant
RLS-5—Pichler, 2006²⁷	Italian	2q	Dominant
ASSOCIATIONS
AUTHOR	POPULATION	CHROMOSOME	GENE
Winkelmann, 2007²⁸	French Canadian/European	2p	MEIS1, exon 9
		6p	BTBD9, intron 5
		15q	MAP2K5, LBXCOR1
Stefannson, 2007²⁹	Icelandic/US	6p	BTBD9
Winklemann, 2007³⁰	European	12q	BTBDR, intron 5

Adapted from Hening WA, Buchfuhrer MJ, Lee HB: Clinical Management of Restless Legs Syndrome. West Islip, NY: Professional Communications, 2008, pp. 56–57.

Pathophysiology of RLS

The pathophysiology of RLS is not well understood.21,31–34 Central nervous system iron homeostatic dysregulation is thought to be the basic mechanism. Cerebrospinal fluid (CSF) ferritin is lower (and transferrin is higher) in RLS patients. Magnetic resonance imaging (MRI) using special sequencing techniques can provide measures of iron concentration in specific brain regions. Using this technique, imaging showed reduced iron stores in the striatum and red nucleus.³⁴ The dopaminergic system is also believed to be involved in RLS. Iron is a cofactor for the enzyme tyrosine-hydroxylase, which is a rate-limiting step in the formation of dopamine. RLS patients show a greater circadian variation in dopamine metabolites than controls. This would be consistent with the circadian component of RLS. The current theory of the causation of RLS is sometimes called the iron-dopamine hypothesis.

Clinical Features of RLS

A number of features of RLS have clinical utility (Box 23–6). These include information about the prevalence of RLS as well as variations in the presentation of RLS and symptoms associated with RLS.

Box 23–6 Clinical Features of Restless Legs Syndrome

Prevalence of RLS

• 5–10% in general population

• Women > men

Natural Clinical Course

• Can begin at any age

• RLS can be intermittent

• Variable course

• Early onset (<50 yr)—onset is insidious

• Late onset—abrupt and more severe

Reasons RLS Patients Seek Medical Attention

• Leg discomfort

• Sleep disturbance—the primary reason most patients seek medical attention

• Sleep-onset and -maintenance insomnia

• Daytime sleepiness much less common

RLS = restless legs syndrome.

Prevalence of RLS

A number of studies have attempted to define the prevalence of RLS. The results vary considerably due to the use of different RLS diagnostic criteria and different methods (survey vs. direct patient interview).1,2,13,35,36 Approximately 5% to 10% of adults in Northern European countries report RLS symptoms. RLS is approximately 1.5 to 2 times more common in women than in men. However, much of the difference in RLS prevalence between men and women is likely due to the association of RLS with pregnancy. The Restless Legs Epidemiology, Symptoms, and Treatment Study (REST)³⁵ was a large questionnaire evaluation of 23,052 primary care patients. The study found that the overall prevalence of weekly RLS symptoms was 9.6% and that the prevalence increased with age (Fig. 23–2). A large international study of a general population (REST general population study) found that 5% of the respondents experience RLS symptoms weekly and 2.7% reported symptoms at least twice weekly and that the symptoms had a negative impact on their life.³⁶

FIGURE 23–2 Prevalence of restless legs syndrome (RLS) at different age groups for patients reporting any frequency of RLS symptoms, those reporting frequency greater than 1/wk, and sufferers (reporting RLS symptoms ≥2/wk and some impact from the symptoms when they occurred). From Hening WA, Buchfuhrer MJ, Lee HB: Clinical management of restless legs syndrome. West Islip, NY: Professional Communications, 2008; and Hening W, Walters AS, Allen RP, et al: Impact, diagnosis and management of restless legs syndrome in a primary care population: the REST (RLS Epidemiology, Symptoms, and Treatment) Primary Care Study. Sleep Med 2004;5:237–246.

Onset and Clinical Course of RLS

RLS can begin at any age and the clinical course is variable. Two patterns are commonly seen (see Box 23–6).¹³ An early onset (age < 50 yr) characterized by insidious onset, less severity, and higher familial association. A late onset RLS (age > 50 yr) is characterized by a more abrupt onset and more severe manifestations. Late-onset RLS patients also tend to have lower ferritin levels compared with early-onset RLS patients.

Sleep Disturbance Associated with RLS

The two most common complaints that cause RLS patients to seek medical attention are the uncomfortable leg sensations and the disturbance of sleep. Beyond the significant discomfort caused by RLS symptoms, the disorder can cause difficulty with sleep initiation and maintenance A recent large questionnaire study of 23,052 primary care patients identified a group of “RLS sufferers” (N = 551) with RLS symptoms twice or more weekly and a negative impact from RLS symptoms.³⁵ In this group, 43.4% complained of sleep-related symptoms but only 6% complained of daytime sleepiness. On nights that RLS symptoms were present, 69% complained of taking over 30 minutes to fall asleep and 60% complained of three or more awakenings per night (Table 23–4). Daytime sleepiness is a less common symptom than insomnia but can occur. In a general population study, the prevalence of RLS of any frequency was 7.2%, weekly RLS symptoms was 5%, and twice-weekly symptoms with distressing symptoms was 2.7%.³⁶ Of the group with RLS twice weekly or more, 81% had reported symptoms to primary physicians but only 6.2% were given a diagnosis of RLS.

TABLE 23–4

Manifestation of Restless Legs Syndrome in Restless Legs Syndrome “Sufferers” (N = 551)

At least one sleep-related symptom	43.4%
Consulted MD about symptoms	64.8%
Given RLS diagnosis	24.9%
ON NIGHTs when RLS SYMPTOMS PRESENT
>30 min to fall asleep	68.6%
≥3 awakenings	60.1%

RLS = restless legs syndrome.

Data from Hening W, Walters AS, Allen RP, et al: Impact, diagnosis and management of restless legs syndrome in a primary care population: the REST (RLS Epidemiology, Symptoms, and Treatment) Primary Care Study. Sleep Med 2004;5:237–246.

The etiology of sleep disturbance from RLS includes a delay in sleep onset due to RLS symptoms. If the patient awakens, the return to sleep may also be delayed by RLS symptoms. Because the majority of RLS patients have PLMS, it might be assumed that arousals associated with PLMS contribute to sleep disturbance. However, the PLMSI (number of PLMs/hr of sleep) is not highly correlated with any measure of sleep disturbance in most studies of RLS patients.¹² In a study of unmedicated RLS patients, Hornyak and coworkers³⁷ found that the IRLSSG rating scale (IRLS) score^38,39 (RLS symptoms severity) correlated with the PLMS arousal index but not the PLMSI. However, even the relationship between the IRLSSG rating scale (IRLS) and the PLMS arousal index was very weak (r = 0.22, P = .03).

Medical Evaluation in RLS

The diagnostic evaluation (Box 23–7) should include a history to elicit the essential and associated features of RLS. A detailed medication history including over-the-counter (OTC) medications (sedating antihistamines) is very important. The IRLSSG developed a rating scale for RLS symptoms called the IRLSSG rating scale (IRLS).^38,39 A slight revision of the validated scale³⁸ was published as an appendix to an editorial.³⁹ The IRLS is useful to quantify RLS symptom severity and the effects of treatment (Box 23–8). The scale is used in research studies but also has clinical utility in following patients on treatment.

Box 23–7 Medical Evaluation of Restless Legs Syndrome Patients

History