Restless legs syndrome: Cause, Symptoms, Diagnosis, Treatment

Restless legs syndrome (RLS), also known as Willis-Ekbom disease, is a common neurological sensory motor disease that significantly affects sleep and quality of life, with an incidence of up to 5% ~ 14% in the United States. Restless leg syndrome can occur at any age. The prevalence rate increases year by year with the increase of age, and the prevalence rate is higher in women than in men. RLS is divided into primary RLS and secondary RLS. The etiology of primary RLS is unknown, and some patients have familial heritability. Secondary RLS is commonly seen in uremia, iron deficiency anemia, Parkinson’s disease, metabolic disease, multifocal neuropathy, etc.


  1. Restless leg syndrome is mainly manifested as extreme discomfort (such as tearing, peristalsis, burning, itching and even pain) in both lower extremities during sleep or in a quiet state at night. The most common discomfort area is the lower legs, occasionally involving the thighs and upper limbs. Discomfort in the legs causes the patient to constantly move their lower limbs or walk out of bed. After the movement of limbs, the discomfort can be relieved, but once sitting down or lying down, the above discomfort symptoms appear again.
  2. Leg discomfort often occurs in the evening, with the peak from midnight to early morning. Symptoms are relatively mild during the day.
  3. During sleep or wakefulness, 80% of patients will also have recurrent periodic rigid involuntary movements of one or both lower limbs, such as rhythmic toe dorsiflexion and ankle dorsiflexion, occasionally hip and knee flexion.
  4. Restless legs syndrome seriously interferes with sleep, causes difficulty in falling asleep, increases the number of awakenings at night, leads to fatigue, memory loss, depression, blood pressure fluctuations, and affects the quality of life.


Restless leg syndrome can be divided into primary RLS and secondary RLS according to the etiology.

Primary RLS usually has a family history, and existing studies support the autosomal dominant inheritance of the disease, with the major suspected pathogenic genes located on chromosomes 12q, 14q, and 9q.

The secondary RLS is related to some physiological or pathological states, and various risk factors may increase the risk of restless leg syndrome. Among them, the change of hormone expression during pregnancy is the main cause of restless leg syndrome in pregnant women. Iron deficiency was significantly related to the prevalence of restless legs syndrome. The prevalence of restless legs syndrome increased significantly when the serum ferritin level was lower than 45-50g / L. Secondary restless legs syndrome is also common in patients with renal insufficiency.


Due to the lack of specific laboratory indicators, the current diagnosis of restless leg syndrome mainly relies on a detailed clinical history. And the diagnostic criteria are as follows,

  1.  There is a strong and often irresistible urge to move your legs, usually accompanied by uncomfortable sensations. Symptoms often appear or worsen at rest or quiet, such as sitting or lying down. After the movement of the lower limbs, such as walking or stretching, the symptoms partially or completely relieve. There are significant diurnal differences in symptoms. The leg discomfort are worse during the night and subside or disappear during the day.
  2. It should be excluded by other medical or behavioral condition, such as leg spasm, improper posture, muscle pain, varicose veins, leg edema, arthritis or habitual leg shaking.
  3. Patients often suffer from anxiety, depression, and sleep disorders that affect their physical, psychological, social, and daily lives.


Restless leg syndrome is generally considered to be a chronic disease requiring long-term treatment, including both non-drug and drug therapy.

Non-drug treatments include leg massages, hot baths, good sleep habits and usage of heating pads or ice packs for the legs. Also, patients should avoid factors that aggravate symptoms of restless legs syndrome, including sleep deprivation (SD), bad sleep habits, usage of certain drugs, like antidepressants, nerve blockers, and dopaminergic receptor blockers anti-nausea drugs (such as metoclopramide). Moreover, caffeine, nicotine and alcohol can also aggravate restless leg syndrome.

Currently, the first-line drugs for RLS are calcium channel agonists (such as gabapentin, and lyrica) and the dopamine agonist, like pramipexole. But it is important to note that the long-term use of dopamine agonists may lead to sudden exacerbation of symptoms. For young patients, benzodiazepines such as clonazepam can reduce the number of nighttime awakenings and improve sleep. If the patient’s serum ferritin is insufficient, iron supplementation is recommended, which may help relieve symptoms. In summary, drug and non-drug therapy can provide temporary relief and control of symptoms, however there is a possibility of recurrence for this disease.

* The Content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition.