May 2019 By PsychDB.com

Restless Legs Syndrome (RLS)

Restless Legs Syndrome (RLS), also known as Willis-Ekbom Disorder (WED) is a 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 sensations typically described as creeping, crawling, tingling, burning, or itching.

Prevalence

Prevalence rates of RLS but can be between 5-10% in the general population. Females are up to 2 times more likely than males to have RLS. RLS also increases with age. The prevalence of RLS may be lower in Asian populations. The onset of RLS typically occurs in the second or third decade. The prevalence of RLS during pregnancy is 2 to 3 times greater than in the general population.

Comorbidity

Depressive disorders, anxiety disorders, and attentional disorders are commonly comorbid with RLS and are discussed in the section “Functional Consequences of Restless Legs Syndrome.” The main medical disorder comorbid with RLS is cardiovascular disease. There may be an association with numerous other medical disorders, including hypertension, narcolepsy, migraine, Parkinson's disease, multiple sclerosis, peripheral neuropathy, obstructive sleep apnea, diabetes mellitus, fibromyalgia, osteoporosis, obesity, thyroid disease, and cancer. Iron deficiency, pregnancy, and chronic renal failure are also comorbid with RLS.

The symptoms of motor restlessness are:

  • Worse at rest, and frequent movements of the legs occur in an effort to relieve the uncomfortable sensations
  • Worse in the evening or night, and in some individuals they occur only in the evening or night. This is a unique feature of RLS; in the timing of the symptoms, it appears to have a circadian component, often peaking in the evening.

The most common consequences of RLS are sleep disturbance, including reduced sleep time, sleep fragmentation, and overall disturbance. RLS can result in daytime sleepiness or fatigue and is frequently accompanied by significant distress or impairment in social or cognitive functioning.

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.

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

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. 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. The difference between Periodic Limb Movements Disorder (PLMD) and Restless Leg Syndrome (RLS) is that PLM is an involuntary action. The patient often sleeps through an episode of leg movements. 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 PLM occurs when the patient is already asleep.

PLMD (Periodic Limb Movement Disorder)

PLMS plus sleep dysfunction.

  • Do you kick your legs at night?
  • Does your partner report you kick your legs at night?

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
  • In RLS, you always have an urge to move
  • Pain occurs in 25% of RLS cases
  • RLS cause initial insomnia, not middle insomnia
  • Hypersomnia can result in RLS
  • Always time of onset
Secondary Causes
  • Iron deficiency, uremia, RA, peripheral neuropathy, diabetes, pregnancy, spinal cord lesion, medications (e.g. - antipsychotics)
  • SSRIs can also exacerbate RLS

Pathophysiological mechanisms are still being investigated. RLS is thought to be due to disturbances in the central dopaminergic system as a reduction of D2 receptor binding is seen in the caudate and putamen (on SPECT/PET).[1] The positive treatment effects of dopamine agonists (D2 and D3 non-ergot) also further suggest that RLS is due to dysfunctional central dopaminergic pathways. Low brain iron concentrations, disturbances in iron metabolism, and disturbances in brain iron transport are also thought to be involved. In CSF samples, iron and ferritin values are lower and transferrin levels are higher in individuals with RLS.[2] The endogenous opiate system may also be involved.[3]

Genome-wide association studies (GWAS) have found that RLS is significantly associated with common genetic variants in intronic or intergenic regions in MEISl, BTBD9, and MAP2K5 on chromosomes 2p, 6p, and 15q, respectively. The BTBD9 variant confers a very large risk when even a single allele is present.

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.

Medications

First-line treatment for RLS is with dopamine agonists.[4]

Treatment for RLS

1st line Dopamine Ergot Agonists: Ropinirole (0.25 to 3 mg
 PO daily), pramipexole (0.125 to 1.5 mg PO daily
), L-Dopa (100 to 200mg PO daily)
2nd line α2δ Subunit Gaba-ergic Agonists: Gabapentin (300-2000 mg PO daily
), pregabalin (50-200 mg PO daily)
3rd line Opioids: Codeine (15-120 mg PO daily), methadone (5-30 mg PO daily)

Benzodiazepines: Clonazepam (0.5-3 mg PO daily), temazepam (15-30mg 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.

Iron Supplementation

In some cases, iron supplementation is a reasonable first-choice and might be an easy “fix” if the ferritin level is <50.

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