Overview.
Difficulty in placing the legs comfortably at rest and resisting the urge to move them
May be related to genetics and a variety of diseases
Cannot be cured completely, but a healthy lifestyle can help alleviate symptoms
Generally does not affect life expectancy, but can have a serious impact on quality of life.
What is Restless Legs Syndrome?
Definition
Restless legs syndrome is a common neurologic sensorimotor disorder that primarily involves the legs.
It is characterized by extreme discomfort in the legs at rest, which is alleviated by constant movement of the legs.
It is not life-threatening, but seriously affects the quality of life.
Types
According to the age of onset
Early-onset Restless Legs Syndrome: the age of onset is ≤45 years old, most of them have a family history, and most of them have a slow progression of the disease.
Late-onset restless legs syndrome: age of onset is higher than 45 years old, most of them have no family history, and the disease progresses relatively rapidly.
Classification according to etiology
Primary Restless Legs Syndrome: the cause is unknown and may be related to genetics or abnormal dopamine function in the brain.
Secondary Restless Legs Syndrome: secondary to some kind of disease, such as polyneuritis, chronic renal failure.
Types according to severity
Mild: occasional periodic episodes, mildly interfering with sleep, not causing obvious sleep disorders.
Moderate: ≤ 2 episodes per week, delayed sleep onset, moderate interference with sleep, normal daytime functioning is slightly affected.
Severe: >3 episodes per week, severe interference with nighttime sleep, daytime functioning significantly affected.
Prevalence
The prevalence of the disease in the general population ranges from 5% to 15%.
In Europe and the United States, the prevalence is about 9.6%. It is rare in East Asian countries.
The disease can occur at any age and is most common in middle-aged and elderly people.
It is more common in women, with a male-to-female ratio of 1:2-3.
Questions you may be concerned about
Does restless legs syndrome develop only in the legs?
Restless legs syndrome is mainly characterized by an indescribable discomfort in the lower limbs, but it may also affect other parts of the body.
The pathogenesis of the disease is unclear and may be related to damage to the central nervous system and peripheral nervous system.
In the early stages of the disease, the symptoms mainly appear in the lower limbs, but some people also have discomfort in the upper limbs, mostly symmetrical attacks.
As the disease progresses, the discomfort may spread to the trunk, face, and hips.
Does restless legs syndrome only occur at night?
Restless legs syndrome does not only occur at night, but symptoms can be more pronounced at night.
The onset of the disease may be related to a dopamine system disorder. Some studies have shown that dopamine levels are lowest at night, when the attacks are at their peak.
In terms of symptomatology, the disease is less severe in the early morning and in the morning, and is most severe in the evening and at night, and is more pronounced in the resting state than during activity. Typically, when lying in bed at night, the discomfort is so intense that it is often necessary to kick, pound or massage the legs to alleviate the discomfort.
Can Restless Legs Syndrome be cured?
Primary Restless Legs Syndrome is usually difficult to cure, while secondary Restless Legs Syndrome may be cured.
The pathogenesis of primary Restless Legs Syndrome is not clear. Treatment is mainly symptomatic, and in a few cases, symptoms may disappear on their own for several years.
Secondary Restless Legs Syndrome can be treated for the cause of the disease, and with the elimination of the cause of the disease, the symptoms of the disease will also disappear. For example, symptoms may resolve after kidney transplantation in patients with uremia, iron treatment in patients with iron deficiency anemia, and folic acid supplementation in patients with folic acid deficiency.
Etiology
The cause of the disease has not been fully clarified, and it is suspected that it may be genetically related, especially for those who develop the disease before the age of 40. The onset of the disease in patients older than 45 years of age is strongly associated with iron deficiency. It can also be caused by pregnancy, kidney failure, and spinal cord injury.
Causes
It is not completely clear and may be related to the following factors.
Heredity
More than 50% of patients with primary disease have a family history of autosomal dominant inheritance, especially in patients younger than 40 years of age.
Recent genome-wide correlation studies have shown that the disease is associated with MEIS1, BTBD9 and MAP2K5/SKOR1 gene variants.
Iron deficiency
It has been suggested that impaired serum iron transport in functional brain regions is the main etiology of the disease.
Epidemiologic studies suggest that patients with onset greater than 45 years of age are strongly associated with low serum ferritin and that iron supplementation is effective in treating the disease.
Dopaminergic neuron damage
This refers to damage to dopamine neurons in the central nervous system and is one of the more recognized causes of the disease.
Supplementation with medications that act accordingly may provide significant symptomatic relief.
Blood circulation disorder
One of the suspected etiologic factors. Treatment to improve circulation in the lower extremities has resulted in significant symptomatic relief.
Endogenous opioid peptide release
It has been found that the more severe the disease, the more endogenous opioid peptides are released in the brain.
The use of exogenous opioids has been shown to be effective in the treatment of this disease.
Other conditions
Secondary restless legs syndrome is most often secondary to a condition such as polyneuritis, spinal cord injury, chronic renal failure, Parkinson’s disease, rheumatoid arthritis, dry syndrome, hypothyroidism, peripheral neuropathy, folic acid and vitamin B12 deficiency.
Pregnancy or hormonal changes may temporarily exacerbate the signs and symptoms of the disease. Some women will develop the disease for the first time during pregnancy, especially in late pregnancy. However, symptoms usually disappear after delivery.
Pathogenesis
The pathogenesis of the disease is unknown. It is currently believed that brain iron deficiency, dopaminergic abnormalities in the central nervous system, and genetic factors are the main pathogenic mechanisms of restless legs syndrome.
Iron plays an important role in myelin synthesis, energy supply, dopamine synthesis and synaptic dopamine receptor D2 expression. Iron deficiency can cause dysfunction of the dopaminergic system, which leads to the disease.
Dopaminergic neuronal damage refers mainly to dopamine neuronal damage in the non-nigrostriatal system of the central nervous system.
Symptoms.
Typical symptoms are that the legs feel nowhere and anyhow uncomfortable at rest, which can be temporarily relieved by activity and may reappear after cessation of activity. As the symptoms tend to come on at night, they can easily lead to poor sleep. It can occur at any age and is more pronounced in the elderly.
Main Symptoms
Site of onset
Mainly involves both lower limbs, mostly symmetrical attacks.
Some people may experience discomfort in the upper limbs.
Later, as the disease progresses, symptoms may also appear on the trunk, face and hips.
Onset pattern
Symptoms are mild in the early morning and in the morning.
Symptoms are most severe in the evening and at night.
Symptoms are obvious at rest (prolonged sitting, lying down, sleeping), and may be relieved by movement or pounding of the legs.
It can occur at any age, but the older the patient, the more pronounced the symptoms.
Typical symptoms
Lower limb discomfort
Symptoms may involve the ankles, knees, or directly involve the whole lower limbs, nearly half of the people may involve the upper limbs.
In quiet state or at night when sleeping, both lower limbs have extreme discomfort that is hard to name.
There is numbness, tearing, ants, creeping, burning, tingling and swelling in the deep part of the lower limbs. Unbearable or impossible to describe in words. A few people have significant pain.
Symptoms occur at rest and can be partially or completely relieved by moving the legs.
Symptoms are strong at night when lying in bed, and reach a peak after midnight, often requiring forced kicking, joint mobilization, or massaging of the legs at night to alleviate the discomfort.
Forced to keep moving the lower limbs
A strong desire to move the legs is triggered by extreme discomfort in the lower limbs.
There may be movements such as walking back and forth, constantly shaking or flexing and stretching the lower limbs, and tossing and turning in bed.
This often leads to hyperactivity, and in severe cases, the patient is forced to get up at night and keep walking.
Complications
Periodic limb movement disorder
80% of patients have periodic limb movement disorder, which is characterized by repetitive stereotyped triple flexion of the hip, knee, and ankle joints (thigh, calf, and dorsiflexion of the foot) during sleep, resulting in dorsiflexion of the toes.
Stereotyped, repetitive flexion movements of the legs can lead to nocturnal awakenings.
Sleep disorders
Due to the worsening of symptoms at night and forced movement of the limbs, the vast majority of patients suffer from concomitant sleep disorders, resulting in difficulty falling asleep and increased awakenings during sleep.
Prolonged insomnia will result in daytime sleepiness, decreased work ability, slow reaction time, weight loss, and decreased appetite.
Psychosomatic disorders
Restless Legs Syndrome causes patients to have strong discomfort symptoms, forced movement of the limbs at night that prevents them from falling asleep, and prolonged and repeated occurrences, which can easily lead to depression and other psychosomatic disorders.
Medical treatment
Neurology is usually consulted.
Department of Neurology
Department of Neurology
If you experience significant discomfort in your lower limbs during quiet or sleep, or if you frequently move your lower limbs during sleep, which interferes with your normal life or sleep, you should consult a doctor promptly.
Preparation for medical treatment
Consultation: Registration, Preparation of documents, Frequently Asked Questions
Tips for medical treatment
Try to record the symptoms, onset pattern and triggers, etc., so as to give the doctor more references.
Preparation Checklist
症状清单
What are the main symptoms?
When do they worsen? When do they decrease?
How long have the symptoms been present? How long did they last?
Is sleep affected? Do you need to get up and walk around at night?
Is there any discomfort in the lower extremities that is difficult to describe?
病史清单
Is there a family history of restless leg syndrome?
Is there a history of iron deficiency anemia?
Are there any diseases such as chronic renal failure, rheumatoid arthritis, or folic acid deficiency?
检查清单
Laboratory tests: routine blood tests, folic acid and vitamin B12 tests, blood biochemistry tests.
Other tests: polysomnography, electromyography, magnetic resonance imaging of the head
用药清单
Dobasic Hydrazide, Carzobidopa Controlled Release Tablets, Ropinirole, Pregabalin, Pramipexole, Ferrous Sulfate, Clonazepam, Codeine, Hydrocodone, Methadone
Diagnosis
The diagnosis is usually made on the basis of symptoms, but some other tests are usually needed to rule out other conditions, such as neurological examination, polysomnography, and blood tests.
Diagnosis is based on
Medical History
The patient may have a history of the following conditions.
A family history of restless legs syndrome.
Have a history of iron deficiency anemia.
History of polyneuritis, chronic renal failure, Parkinson’s disease, rheumatoid arthritis, dry syndrome, hypothyroidism, peripheral neuropathy, folic acid and vitamin B12 deficiency.
Clinical manifestations
Symptoms
Indescribable discomfort in both legs, leading to a strong desire to move the limbs, mainly the lower limbs.
Inability to sleep and constant movement of the limbs to relieve the abnormal sensations.
Symptoms worsen at rest and at night.
Often accompanied by transient pain and itching in the legs.
Physical signs
Physical examination of the affected limbs has no obvious abnormality, usually only the corresponding manifestations of the primary disease.
In iron deficiency, there are brittle and thin nails, easy to break, sunken or spoon-shaped, pale skin, etc.; in end-stage renal disease, there is ammonia odor and edema in the oral cavity.
Laboratory tests
Laboratory tests may indicate anemia, abnormal renal function, high blood sugar and other abnormalities.
Routine blood test: It is mainly used for the preliminary judgment of whether there is anemia or infection. If anemia exists, serum iron and ferritin tests are also needed to determine whether iron deficiency exists.
Folic acid and vitamin B12 examination: used for preliminary judgment of whether there is folic acid and vitamin B12 deficiency.
Blood biochemistry test: mainly used to determine whether the liver and kidney functions are abnormal and whether the blood sugar is elevated.
Polysomnography
Polysomnography shows that 70%～80% of adults with restless legs syndrome are accompanied by periodic leg movements, while most of the patients are accompanied by prolonged latency to fall asleep, reduced sleep efficiency and increased number of awakenings, suggesting sleep disorders such as difficulty in falling asleep, poor quality of sleep, and easy awakening.
Electromyography
It is mainly used to check whether there is neuromuscular injury in the lower limbs.
Cranial Magnetic Resonance Imaging (MRI)
An imaging test that can be used to rule out brain disorders.
Genetic examination
For those with a family history of the disease, tests for relevant genes may be performed to determine the type of gene responsible for the development of the disease.
Diagnostic Criteria
Basic diagnostic criteria
Strong desire to move the legs, often accompanied by a variety of uncomfortable sensory symptoms.
Appears or worsens at rest.
Partial or complete relief after activity.
Aggravated in the evening and at night.
Evidence supporting the diagnosis
Positive family history.
Presence of periodic limb movements.
Dopaminergic medication is effective.
Relevant clinical features
Varied clinical course: fluctuating in mild cases, chronic progressive in moderate to severe cases.
Sleep disturbances: daytime fatigue and malaise.
Physical examination and ancillary tests are usually unremarkable, except for primary pathologies such as iron deficiency, pregnancy, and end-stage renal disease.
Differential diagnosis
Peripheral neuropathy
Similarity: abnormal sensory and motor symptoms in the limbs, aggravated at night.
Differences: symptoms occur symmetrically in the distal extremities (hands and feet), slowly involving the proximal extremities, and symptoms cannot be relieved by moving the limbs.
Sitting still is not possible
Similarity: forced limb movement.
Differences: caused by taking dopamine receptor blockers (including antipsychotics, antiemetics), there is a subjective uneasiness of thought, no family history, most do not affect sleep. There are often mild extrapyramidal symptoms (stony face, muscle tremors, slow movements, drooling, etc.).
Nocturnal leg muscle spasms
Similarities: nocturnal leg muscle spasms, pain, relieved by activity.
Differences: pain is more severe, mostly occurs unilaterally, flexion and extension of the leg, standing, walking can reduce the symptoms, there is no obvious ants, burning sensation and other forms of discomfort, may be able to touch the contracture of the muscle.
Arteriosclerosis of the lower extremities
Similarity: Discomfort in the legs.
Difference: Atherosclerosis of the lower extremities is a clinical symptom that occurs when the arterial walls of the limbs become diseased, affecting the supply of blood flow. It is characterized by aggravation after exercise and alleviation after rest, and ultrasound and CT can help to differentiate it from other forms of atherosclerosis.
Elderly pruritus
Similarity: itching and discomfort of the lower limbs.
Differences: Pruritus in old age is mostly induced by sebaceous gland hypoplasia, decreased sebum secretion, dry skin and degenerative atrophy, or excessive washing and ironing, and can occur in the limbs and trunk.
Treatment
This disease can not be completely cured, to relieve symptoms and improve sleep, you can first improve the lifestyle, such as smoking cessation, moderate exercise, etc., and at the same time, treat the disease factors that cause this disease, such as iron deficiency patients for iron supplementation, etc..
If relief is not obvious, then follow the doctor’s instructions for drug treatment, such as pramipexole.
Treatment of the cause of the disease
Removing the cause of the disease
The cause of the disease is identified through various tests and treated accordingly.
If you have uremia, dialysis or kidney transplantation will be performed.
For those with iron deficiency anemia, iron supplementation through medication (ferrous succinate, etc.) and diet (animal blood, chicken heart, etc.) is recommended.
Those with folic acid deficiency can take folic acid supplements under the guidance of a doctor.
Removal of triggers
Factors that can trigger the disease should also be avoided, such as caffeine-containing drugs, foods, and beverages.
Certain medications may trigger the disease and should be avoided or replaced with other alternatives as prescribed by your doctor.
Avoid smoking and alcoholism.
Avoid spicy, irritating foods such as chili peppers, raw garlic, and mustard.
Medication
In mild cases, medication is generally not needed, but may be used temporarily to reduce symptoms in special cases where long distance travel or prolonged sedentary periods are required. Moderate or severe cases often require regular medication to relieve symptoms.
Dopaminergic drugs
Dopaminergic medications are preferred for the treatment of restless legs syndrome and are administered in smaller doses without morning rebound (sudden worsening of symptoms in the morning).
Compounded dopa preparations
Individuals with mild symptoms who need to travel for long periods of time on transportation (e.g., airplane, car, train, etc.).
Commonly used drugs: Dobazepine, Cazodopa controlled release tablets, etc.
Adverse effects: nausea, vomiting, palpitations, hypotension, etc.
Dopa agonists
70% to 90% of patients have good results with these drugs.
Applicable groups: moderate to severe patients, those with frequent attacks, those who need short-term treatment.
Commonly used drugs: pramipexole, ropinirole, rotigotine patch.
Adverse effects: headache, constipation, peripheral edema, hallucinations, hyperphagia, etc. Some people may have symptoms of impulse control disorders such as pathological gambling, excessive shopping, and hypersexuality.
Antiepileptic drugs
Applicable people: those who have poor efficacy, ineffectiveness or intolerance of adverse effects when using dopaminergic drugs may choose or combine with antiepileptic drugs.
Commonly used drugs: gabapentin, pregabalin, etc.
Adverse effects: sedation, ataxia, etc.
Iron
Applicable people: people with iron deficiency.
Commonly used drugs: ferrous sulfate plus vitamin C.
Adverse reactions: nausea, vomiting, epigastric pain, constipation, etc.
Benzodiazepine drugs
Commonly used drugs: clonazepam.
Adverse reactions: common abnormal excitement, nervousness and irritability, muscle weakness, less frequent behavioral disorders, inability to concentrate, irritability (children are more common).
Opioids
Individuals with refractory restless legs syndrome who have failed to respond to dopa agonists and other treatments.
Commonly used drugs: codeine, hydrocodone, methadone, oxycodone, tramadol.
Adverse effects: constipation, urinary retention, drowsiness, cognitive changes, respiratory depression, drug dependence.
Prognosis.
Generally does not affect life expectancy, but severely affects quality of life. Symptoms persist for life in most patients, some subside spontaneously, usually within 4 weeks of delivery if associated with pregnancy.
Cure
The disease does not heal on its own and has a chronic course.
Aggressive treatment may relieve symptoms, and in a few cases, symptoms may be reduced or disappear for several years. If related to pregnancy, it usually disappears within 4 weeks after delivery.
Symptoms persist for life in most patients.
Problems such as deterioration and drug tolerance may occur.
The disease does not shorten life expectancy, and the disease itself has no significant effect on life expectancy, but it may cause problems in various body systems and affect health due to complications such as long-term sleep disorders and depression.
Harmfulness
The disease is accompanied by sleep disorders in the vast majority of cases due to worsening of symptoms at night, forced movement of limbs, and periodic limb movement disorders.
Discomfort caused by the condition, as well as persistent sleep disorders, may lead to psychological problems such as depression and anxiety.
Prolonged sleep disorders can affect daytime functioning and increase the risk when performing some hazardous activities or working at heights.
Daily
Good sleep habits, regular exercise, quitting smoking, and avoiding coffee and alcohol intake in the evening provide better relief.
Massage, hot packs, hot baths, and yoga may also help. Consult your doctor for professional help when you are not sleeping well.
Daily Management
Life Management
Take regular baths and massage your leg muscles by soaking your legs in a bathtub or soaking tub and carefully massaging your leg muscles.
Moderate physical exercise, especially before bedtime, focusing on both lower limbs.
Ensure adequate sleep time, try to avoid staying up late and create a good sleep environment.
Enhance immunity through regular work and rest, avoiding late nights, and moderate exercise.
Quit smoking.
Dietary management
Eat a light diet (low salt, low sugar, less oil), more high-protein foods, fresh fruits and vegetables, avoid spicy and irritating foods such as chili peppers, and avoid alcohol.
Avoid intake of coffee, strong tea, etc. before bedtime.
Psychological support
Maintain a good state of mind, correctly understand the disease, build up confidence, positively resolve negative emotions, avoid anxiety and depression, and communicate more with family and friends.
Prevention
The cause of this disease is unknown, there is no effective preventive measures, to actively treat the primary disease and avoid suspected triggering factors.
Actively treat the primary disease, such as chronic renal failure, Parkinson’s disease, rheumatoid arthritis and so on.
Avoid smoking, alcoholism and drinking large amounts of coffee for a long time.
Maintain a balanced nutritional intake of high protein foods such as eggs, milk and soy products, and high vitamin foods such as fresh fruits and vegetables.
Avoid late nights and excessive stress.
Do moderate physical exercise.