Approach

The diagnosis of RLS is primarily made clinically. Routine testing includes ferritin level measurement to exclude iron deficiency.

The diagnosis can usually be made based on history alone. The following aspects of the history support the diagnosis:

  • Symptoms are nocturnal

  • The urge to move, or dysesthesia symptoms, are worse at rest or during inactivity

  • Symptoms are relieved, if only momentarily, with movement

  • The lower extremities are more commonly affected, but in more severe cases, the torso or upper extremities can also be involved.[1][22]

The main symptom of the disorder is the urge to move the legs. Symptoms that accompany this urge are usually described as dysesthesias. They are poorly characterized but can be described as creeping, crawling, tingling, cramping, or aching of the extremities.[1][22] Due to the circadian timing of RLS symptoms, the urge to move and dysesthesias can cause insomnia, which can lead to increased sleepiness and tiredness, which in turn increases RLS symptoms.

Factors notable on patient history include pregnancy, the presence of conditions predisposing to iron deficiency, family history, and female sex.[1]​[6]​​

The patient should be asked about alcohol and caffeine intake, as minimizing such substances can improve symptoms in mild cases.[23]

Current medications should be reviewed. Drugs that can cause or worsen RLS include antidepressants (except bupropion), sedating antihistamines, neuroleptic agents, and dopamine-blocking antiemetics such as metoclopramide.[23]

Primary RLS

Primary RLS often occurs in a familial pattern with strong penetrance and is thought to follow an autosomal-dominant inheritance in many families.[4] However, linkage and genome-wide studies suggest a more complex pattern. Several different gene loci have been associated with RLS, but no specific gene mutations have been identified.[5] Patients with familial RLS show an earlier onset of the disease compared with those with sporadic RLS.[6]

Secondary RLS

Secondary RLS can occur due to iron deficiency, pregnancy, and uremia in renal insufficiency (usually in patients undergoing hemodialysis). It can remit after the resolution of these states. Certain medications have also been shown to cause or worsen RLS symptoms, including antidepressants (except bupropion), sedating antihistamines, neuroleptic agents, and dopamine-blocking antiemetics such as metoclopramide.[23]

If there is concern over iron insufficiency, whether from iron loss (e.g., due to occult bleeding) or iron dilution (such as in pregnancy), it should be screened for with appropriate laboratory tests. Many anemic patients do not develop RLS, and most patients with RLS do not have low ferritin levels.

If iron deficiency is detected, there should be further evaluation in accordance with the suspected secondary cause.

RLS has a high prevalence in patients with end-stage renal disease (ESRD) and is referred to as uremic RLS in these patients. It has been shown to affect approximately 30% of the ESRD population.[16] The precise pathogenic mechanisms are unknown, but dopamine dysfunction and reduced iron stores in the brain have been implicated, as with primary RLS. Patients requiring hemodialysis are particularly difficult to manage as prolonged rest is needed for the duration of the dialysis session; such inactivity is one of the main triggers of RLS and approximately 20% of hemodialysis patients report a premature discontinuation of their dialysis treatment due to the presence of RLS symptoms.[16]

Medications that can cause or worsen restless leg symptoms include:[23]

  • Antidepressants such as tricyclics and selective serotonin-reuptake inhibitors (bupropion is an exception and has not been shown to increase symptoms of RLS)

  • Sedating antihistamines (including those found in nonprescription medications)

  • Dopamine-blocking antiemetics such as metoclopramide

  • Neuroleptics.

Laboratory tests

RLS is a clinical diagnosis based on criteria published by the International Restless Legs Syndrome Study Group (IRLSSG).[1] Guidelines recommend that iron status should be evaluated in all patients, even in the absence of typical factors associated with iron deficiency, such as menorrhagia, gastrointestinal blood loss, or frequent blood donations.[23][26] A full iron assessment should include serum iron, ferritin, total iron-binding capacity, and percentage transferrin saturation, and should be measured in the early morning after an overnight fast.[23][27]

Further work-up for iron deficiency should follow guidelines.

Use of this content is subject to our disclaimer