Table of Contents

Restless Legs Syndrome (RLS)

Primer

Restless Legs Syndrome (RLS), also known as Willis-Ekbom Disorder (WED) is a motor-sensory neurological sleep disorder characterized by uncomfortable sensations in the lower extremities that are accompanied by an almost irresistible urge to move the legs or arms. These uncomfortable experiences are typically described as creeping, crawling, tingling, burning, or itching sensations. Symptoms typically occur at night and are relieved by movement.

Prevalence
Prognosis

Comorbidity

Risk Factors

Symptoms

DSM-5 Diagnostic Criteria

The diagnosis of RLS is a clinical diagnosis, and primarily on patient self-report and history. The symptoms of RLS can delay sleep onset and awaken the individual from sleep and are associated with significant sleep fragmentation. The relief obtained from moving the legs may no longer be apparent in severe cases. RLS is associated with daytime sleepiness and is frequently accompanied by significant clinical distress or functional impairment.

Criterion A

An urge to move the legs, usually accompanied by or in response to uncomfortable and unpleasant sensations in the legs, characterized by all of the following:

  1. The urge to move the legs begins or worsens during periods of rest or inactivity
  2. The urge to move the legs is partially or totally relieved by movement.
  3. The urge to move the legs is worse in the evening or at night than during the day, or occurs only in the evening or at night.
Criterion B

The symptoms in Criterion A occur at least 3 times per week and have persisted for at least 3 months.

Criterion C

The symptoms in Criterion A are accompanied by significant distress or impairment in social, occupational, educational, academic, behavioral, or other important areas of functioning.

Criterion D

The symptoms in Criterion A are not attributable to another mental disorder or medical condition (e.g., arthritis, leg edema, peripheral ischemia, leg cramps) and are not better explained by a behavioural condition (e.g., positional discomfort, habitual foot tapping).

Criterion E

The symptoms are not attributable to the physiological effects of a drug of abuse or medication (e.g., akathisia).

Paediatric Diagnosis

Paediatric Diagnosis

Diagnosis of RLS in children can be difficult because of the self-report component. While Criterion A for adults assumes that the description of "urge to move" is by the patient, a paediatric diagnosis requires a description in the child's own words rather than by a parent or caretaker. Typically children age 6 years or older are able to provide detailed, adequate descriptors of RLS.

However, children rarely use or understand the word "urge," reporting instead that their legs "have to" or "got to" move. Also, potentially related to prolonged periods of sitting during class, two-thirds of children and adolescents report daytime leg sensations. Thus, for diagnostic Criterion A3, it is important to compare equal duration of sitting or lying down in the day to sitting or lying down in the evening or night. Nocturnal worsening tends to persist even in the context of paediatric RLS. As with RLS in adults, there is a significant negative impact on sleep, mood, cognition, and function. Impairment in children and adolescents is manifested more often in behavioural and educational domains.

Mnemonic

The mnemonic URGE can be used to remember the core features of RLS:
  • U - Urge to move limbs
  • R - Rest worsens the sensation
  • G - Getting up to move offers temporary relief
  • E - Evening is worse for symptoms

Periodic Limb Movement Disorder (PLMD)

Periodic Limb Movements (PLMs) vs. Periodic Limb Movements Disorder (PLMD) vs. Restless Legs Syndrome (RLS)

  • Restless Legs Syndrome (RLS) refers to the symptom, while Periodic Limb Movements (PLMs) refers to the sign.
  • Periodic Limb Movements Disorder (PLMD) is a diagnosis is based on polysomnography findings (i.e. - can only be diagnosed with a sleep study).
  • Restless Leg Syndrome (RLS) is a clinical diagnosis and does not require a sleep study.
    • Up to 90% of individuals diagnosed with RLS have Periodic Limb Movements (PLMs) when sleep recordings are taken over multiple nights. Asymptomatic PLMs does not require treatment.
  • The difference between PLMD and RLS is that PLMD involves an involuntary action. The patient often sleeps through an episode of leg movements in PLMD. In RLS, however, patients are awake the whole time and are jerking or kicking their legs in an effort to overcome the discomfort their brains are perceiving. In summary, RLS keeps the patient awake, but PLMD occurs when the patient is already asleep.

Periodic Limb Movements (PLMs)

PLMD = PLMs plus sleep dysfunction.

Screening Questions

Differential Diagnosis

Important differential diagnoses to consider include:

  • Leg cramps, muscle cramps - nocturnal leg cramps do not typically present with the desire to move the limbs, and there are rarely frequent limb movements.
  • Positional discomfort
  • Anxiety-induced restlessness
  • Arthralgias/arthritis
  • Myalgias
  • Positional ischemia (numbness)
  • Leg edema
  • Peripheral neuropathy - symptoms will be present throughout the day, and there is no night time worsening
  • Peripheral artery disease
  • Radiculopathy
  • Habitual foot tapping
  • Neuroleptic-induced or other medication-induced akathisia - symptoms will be present throughout the day, and there is no night time worsening
  • Myelopathy
  • Symptomatic venous insufficiency
  • Eczema
  • Orthopaedic problems

Multiple Diagnoses Can Occur!

Although it is important to rule out other conditions that could mimic RLS, any of these similar conditions can also co-occur in an individual with RLS.

Physical Exam Tips

Knotting of the muscle (i.e. - muscle cramps) on examination, relief with a single postural shift, limitation to joints, soreness on palpation (myalgia), and other abnormalities on physical examination are not characteristic of RLS.

Use the Your Clinical Judgment to Help You

In cases where the diagnosis is unclear, asking around PLMs or a family history of RLS can be helpful. Other clinical features, such as response to a dopaminergic agent can also help with the differential diagnosis.
Restless Leg vs. Akathisia
Secondary Causes

Pathophysiology

Investigations

Ferritin

Polysomnography

Polysomnography demonstrates significant abnormalities in RLS, commonly increased latency to sleep, and higher arousal index. Polysomnography with a preceding immobilization test may provide an indicator of the motor sign of RLS, periodic limb movements, under standard conditions of sleep and during quiet resting, both of which can provoke RLS symptoms.

Treatment

Iron Supplementation

If there is iron deficiency, it is reasonable to start with iron supplementation as a first-choice and might be an easy “fix” if the serum ferritin level is <75.

Medications

First-line treatment for RLS is with dopamine agonists.[5]

Treatment for RLS

1st line (α2δ Subunit Gaba-ergic Agonists) • Gabapentin (300 to 2000 mg PO q evenings
)
• pregabalin (50 to 450 mg PO daily)
2nd line (Dopamine agonists) • Rotigotine (Neupro) patch (1 mg to 4 mg patch/24 hours)
• Pramipexole (0.125 to 0.5 mg PO qHS
)
L-dopa should no longer be used due to the high risk for augmentation!
3rd line Opioids:
Codeine (15 to 120 mg PO daily), Tramadol (50 mg to 100 mg PO prn), methadone (5 to 30 mg PO daily)
Benzodiazepines:
Clonazepam (0.5 to 3 mg PO daily), temazepam (15 to 30mg PO daily)
Other treatments:
Clonidine, baclofen, carbamazapine, B12, folate

Treating two conditions with one medication

  • If your patient has chronic pain, then you should treat with GABA-ergic agonists, like pregabalin
  • If your patient has ADHD, then you should treat with clonidine

Avoid Using Serotonergic Antidepressants

Although treatment of RLS will can reduce depressive symptoms, using serotonergic antidepressants (i.e. - SRRIs, SNRIs) can actually induce or aggravate RLS in some individuals.

Resources

For Patients
For Providers
Articles
Research

References

1) Miyamoto, M., Miyamoto, T., Iwanami, M., Suzuki, K., & Hirata, K. (2009). Pathophysiology of restless legs syndrome. Brain and nerve= Shinkei kenkyu no shinpo, 61(5), 523-532.
2) Mizuno, S., Mihara, T., Miyaoka, T., Inagaki, T., & Horiguchi, J. U. N. (2005). CSF iron, ferritin and transferrin levels in restless legs syndrome. Journal of sleep research, 14(1), 43-47.
3) Walters, A. S., Ondo, W. G., Zhu, W., & Le, W. (2009). Does the endogenous opiate system play a role in the Restless Legs Syndrome?: A pilot post-mortem study. Journal of the neurological sciences, 279(1-2), 62-65.
4) Aul EA, Davis BJ, Rodnitzky RL. The importance of formal serum iron studies in the assessment of restless legs syndrome. Neurology. 1998;51(3):912.
5) Trenkwalder, C., Stiasny, K., Pollmächer, T., Wetter, T., Schwarz, J., Kohnen, R., ... & Oertel, W. H. (1995). L-dopa therapy of uremic and idiopathic restless legs syndrome: a double-blind, crossover trial. Sleep, 18(8), 681-688.