Restless legs syndrome (RLS) is a common but still poorly known sleep disorder. It was first discovered by Thomas Willis back in 1685. The syndrome was described nearly 300 years later in detail by a Swedish neurologist Karl-Axel Ekbom in his dissertation from 1945. He also introduced the term “Restless Legs Syndrome”. The disease is also known as Willis-Ekbom’s disease (WED), and the World Health Organization (WHO) has also accepted this name.
Both terms are used in scientific writing.
Due to vague and strange symptoms, the patient can suffer from this illness for years without getting the correct diagnosis. “Restless legs” may sound amusing, but sufferers feel that the symptoms are not funny at all. At worst, they make it more difficult to fall asleep and awaken the patient to walk at night. It is difficult to sit still when you have to move your feet constantly. This causes considerable social problems. One of the patients who has already died had severe coronary heart disease, heart failure and RLS. He had two extensive cardiac artery bypasses. However, in his own opinion, his most serious illness was RLS. He said: “My heart disease may cause a heart attack and kill me. But it doesn’t hurt, because the suffering from restless legs is hellish, and I would get rid of them by just dying.” This demonstrates well the effect of symptoms on the quality of life.
Prevalence of restless legs syndrome (RLS)
Approximately 5-10% of adults suffer from restless legs almost daily. The incidence of the syndrome increases with age. At a doctor’s reception at health centers 15-20% of adults suffer from RLS symptoms. RLS is clearly more common in women than in men. Low tissue iron worsen restless leg syndrome, and women lose more iron due to menstrual bleeding.
Low tissue iron is the strongest known risk factor for RLS. Serum ferritin should be at least 40 µg / l. About 33% of pregnant women suffer from restless legs, especially during the last trimester of pregnancy. Fortunately, on most of them, symptoms will alleviate or stop after pregnancy. However, there is a clear link between the number of pregnancies and RLS in German epidemiological studies. The more children a woman has given birth, the more likely it is that RLS will later appear in her life.
In children, RLS may appear as growth pain, and in school age, RLS symptoms may be confused with symptoms of attention deficit and hyperactivity, or ADHD. In fact, RLS and ADHD are related to each other. The majority of ADHD children and adolescents have RLS symptoms. In several studies, over 50% of ADHD patients had concurrent RLS. In patients with ADHD, low levels of ferritin are often observed.
In hereditary form of RLS, symptoms often begin in childhood or adolescence. If the symptoms appear only after the age of 40, this may be due to some other illness. RLS is associated with, for example, anemia, rheumatism, fibromyalgia, irritable colon and kidney disease. A large proportion of renal dialysis patients also have RLS.
Research shows that restless legs syndrome explains over 15% of older people’s insomnia. On average, about 3% of adults suffer from severe symptoms. Restless legs reduce the quality of life and, according to recent long-term follow-up studies, are also an independent risk factor for hypertension and myocardial infarction. For this reason, the doctor should always ask not only about sleep and sleep apnea, but also about possible RLS symptoms.
Previously, it was believed that RLS and Parkinson’s disease were not linked. However, recent extensive studies have suggested that RLS is more common in patients with Parkinson’s disease. Some extensive population studies have provided some indications that RLS could even anticipate Parkinson’s disease. Findings require even more detailed research and the RLS patient does not have to worry about being infected with Parkinson’s disease. If the RLS is difficult to treat, it is recommended that neurologist is also consulted. At the same time, the neurologist may exclude findings referring to Parkinson’s disease by conducting a neurological status study to the patient.
Symptoms of restless legs syndrome
Typically, the symptoms appear in the evening when going to bed and are worst between 19:00 and early morning. The most common reason for seeking a doctor is insomnia. The most important symptom is the compulsive need to move and move the legs. There are unpleasant sensations in the legs that will ease when the feet move or the patient starts walking. Patients describe the unpleasant sensation symptoms in a variety of terms: strange deep pain or creepy, bubbly, tingling, stinging, hot or burning sensations. Frequently used phrases are also: like ants crawling through my legs, like Coca-Cola bubbling through the veins. Most of the time, the feelings are reciprocal, but they may be stronger on either leg.
Typical difficult situations are sitting at meetings, dinners and traveling on an airplane. It is difficult to sit still because of the awkward symptoms. After going to bed, it is difficult for the patient to fall asleep, and night awakenings are common.
The syndrome has also been referred to as a ‘night walker’, which is because someone with severe symptoms sometimes has to walk at night for hours. In the most severe cases, limb knowledge may begin in the morning and may occur throughout the day. However, in such situations, some other cause for the patient’s symptoms should also be suspected. A disturbed night’s sleep and a lack of revitalizing sleep can lead to fatigue, anxiety and depression. As the symptoms progress, they are not always limited to the lower limbs but can also be felt in the upper limbs and elsewhere in the body.
What triggers restless legs syndrome?
Not all causes of the syndrome are known yet. Disturbances are often found in a patient’s central nervous dopamine system. Dopamine is an important neurotransmitter: In Parkinson’s disease, dopamine production has been reduced or is not working at all when dopamine-producing brain cells are destroyed, while dopamine is excreted too much in a schizophrenic patient.
Dopamine is associated with pleasure and, for example, the effect of all drugs is based on a kind of dopamine storm. However, in the case of restless legs syndrome, dopamine-producing cells work, and the syndrome has no connection to Parkinson’s disease.
In Restless Legs Syndrome, the lack of tissue iron plays an important role. Iron acts as a cofactor and allows the normal functioning of dopamine receptors. Tissue iron deficiency can be investigated by studying serum ferritin (S-ferritin). If S-ferritin is less than 40 µg / l, it can contribute to explaining Restless Legs Syndrome. Note that in the diagnosis of anemia, this value is still interpreted as normal.
Typically, the hemoglobin of an RLS patient is perfectly normal, although ferritin may be low. Patients with Parkinson’s disease often have too much iron in their brain. In RLS the situation is the opposite and there is too little iron in the brain. Dopamine and iron theory explain a significant part of restless legs, but not everything.
Particularly in a form that starts before the age of 40, it is usually a hereditary disease. In over 80% of cases, some close relative, such as a parent, sister, or grandparent, has been diagnosed with RLS. Various factors can also cause or worsen symptoms. These include, but are not limited to, the following health changes and illnesses that may include symptoms of restless legs.
Various factors that can cause or worsen symptoms of Restless Legs Syndrome:
- Bleeding and blood donation
- Iron deficiency anemia
- Kidney disease and dialysis
- Multiple sclerosis or MS disease
- Spinal cord diseases
- Inflammatory diseases
- Poor arterial circulation of the lower limbs
- Varicose veins
- Deficiency of vitamins
Medical Products that may cause RLS symtoms:
- Mirtazapine and mianserin
- Serotonin reuptake inhibitors
- Tricyclic antidepressants
- Amitriptyline, clomipramine
- Traditional neuroleptics
- Ketiapine, olanzapine and other antipsychotics
- Calcium channel blockers
- Caffeine and excessive coffee drinking
Medication for restless leg syndrome
One of the most common drugs for restless legs is mirtazapine that is also used to treat depression and insomnia. It is a modern medicine for the treatment of insomnia, which improves night sleep by slowing down the histamine-1 nervous system. However, if mirtazapine causes anxiety, malaise and forced movement, the person might suffer from restless legs syndrome.
Of the antidepressants bupropion and reboxetine, which improve norepinephrine activity are the least likely to cause RLS. Citalopram, fluoxetine and duloxetine are somewhat less well tolerated. Most symptoms are caused by mirtazapine, mianserin, paroxetine and sertraline. Patients who are clearly depressed should use appropriate medication. If he also has restless legs syndrome, it is good to start medication in restless legs along with antidepressant medication.
In hospital patients, the general problem is related to the use of metoclopramide. Metoclopramide is commonly used in emergency clinics and also in intensive care units to reduce nausea. It can be given to migraine patients to improve the absorption of analgesics. However, metoclopramide is a dopamine receptor antagonist, and it causes pain for those suffering from restless legs.
Strong morphine derivatives opioids reduce the symptoms of restless legs as they improve the functioning of the brain’s dopamine system. However, opioids used to treat pain may cause nausea, and metoclopramide is often given to prevent it. Sleep clinics have been contacted several times by hospitals, when metoclopramide is given to a patient with restless legs syndrome and it is not understood that the patient’s painful condition is due to the side effect of the drug. In these cases, the discontinuation of metoclopramide improves patient’s condition, with less need for analgesics.
Diagnosis and differential diagnostics for restless legs syndrome
Diagnosis of the restless legs syndrome requires that all of the following international symptom criteria are met.
- The compulsive urge to move one’s legs, which is usually, but not necessarily, an uncomfortable feeling of the feet.
- The compulsive need to move your legs and the potentially unpleasant feelings associated with them start or worsen when you go to rest or while sitting.
- The need for compulsive movement and possible unpleasant sensations are relieved during exercising, when walking or stretching the limbs. Other activities, such as lively conversation, may also relieve the symptoms temporary.
- Symptoms are stronger in the evening and at night than during the day. Even if the symptoms start in the afternoon with those who are troubled with restless legs, they will get worse at night.
- The patient’s symptoms are not due to any other illness, symptoms of other diseases or behaviors such as muscle pain, arthralgia or other rheumatic diseases, varicose veins, swelling of the legs or any other neurological disease.
In a typical case, a health center or occupational physician can make a diagnosis on the basis of a careful interview and clinical examination. The most important parts of the clinical trial are testing of stress reflexes and touch and vibration. In troublesome cases, it is advisable to consult a neurologist. For example, impaired tendon reflections or lack of vibration suggest potential nerve damage such as polyneuropathy. Further, the physician will determine whether the patient has diseases which are known to expose or aggravate the restless legs.
The most useful in laboratory tests is the determination of serum ferritin or tissue iron. Other laboratory tests, such as serum iron and transferrin, blood count, blood sugar, thyroid tests, vitamin B12 and folic acid, will be performed as needed. It is important to note that the lower limit of S-ferritin used in most laboratories is too low for RLS patients. The low reference limit is due to the fact that S-ferritin levels have been compared to healthy and anemia sufferers.
Hemoglobin in the RLS patient is usually normal, although serum ferritin is below 40 µg / l, which may explain some of the RLS symptoms. In men, the deficiency of ferritin is rare, and its cause needs to be investigated, among other things, to exclude bowel bleeding. Sometimes patients may have high levels of ferritin. If it is more than 300 µg / l, it should be determined whether the patient has an iron accumulation disease or iron overload. In hemochromatosis, the iron saturation of transferrin is clearly elevated. If ferritin is high and the iron saturation of transferrin is within the reference range, it may be a rare ferroportin disease. So-called DIOS (dysmetabolic iron overload syndrome) refers to iron overload associated with metabolic disorder. Such patients often have concomitant fat disease, hypertension or diabetes.
Actigraphy provides an understanding of sleep/wake cycle, which helps to determine the severity of the disease. Sleep registration is done in case of suspected sleep apnea or other sleep disorder. The sleep apnea patient may also have concurrent RLS. Thus, polysomnography, can lead to wrong tracks if the doctor has not studied the patient, bearing in mind also restless legs syndrome. Differential diagnostic studies sometimes require studies on the brain or spinal cord, as well as electronic research on the nerves and muscles (ENMG).
In practice, RLS symptoms are almost always relieved by dopaminergic drug therapy. For this reason, sometimes a treatment experiment with levodopa is performed. Levodopa, or L-dopa, is very effective, and 80% of the patients taking the medicine for the first time will relieve the symptoms by 100 milligrams of L-dopa within one hour of taking the medicine. If there is no clear help with levodopa or, for example, pramipexole, there is reason to doubt the diagnosis. As noted above, many diseases can expose to restless legs, but on the other hand, the same diseases can also cause some degree of restless leg-like symptoms.
Differential diagnosis symptoms and disorders
- Movement of feet without having restless legs syndrome
- Symptoms and diseases in the muscles
- Unintentional muscle contractions
- Fasciculation or muscle twitch, motor neuron disorders
- Myositis, inflammation or swelling of the muscles
- Anxiety disorders
- Growing pains in children
- Neuropathy, disease of the nervous system
- Nerve compression
- Sciatica symptoms
- Muscle cramps
- Painful legs and moving toes syndrome (PLMT)
- Other lower limb pain conditions
Akathisia means medication-induced pain and compulsion to move. Typical acathetic drugs are antipsychotics used by psychiatric patients. They inhibit dopamine activity. A person suffering from akathisia is unable to sit in place, but has to get up from the chair, change weight from foot to foot, or take steps involuntarily. The RLS patient, on the other hand, rises from the chair because it’s painful to sit in place due to vague sensations and the need for compulsive movement. However, leg stretching can temporarily relieve the symptoms. The akathisia patient is not able to be motionless even if he wants to.
The best drugs for treating akathisia are often dopamine antagonists that cause akathisia, such as haloperidol, peracin, and other antipsychotics. However, doses for treating akathisia are lower than doses used to treat psychosis. Again, RLS symptoms worsen with antipsychotics and are primarily treated with dopamine agonists such as pramipexole, ropinirole and rotigotine, as well as other drugs that increase the effects of central nervous system dopamine.
It is difficult for a child or young person suffering from impulse control disorders, ie ADHD, to remain stationary due to their anxiety. It can make it difficult to sit on the school bench. RLS symptoms can also be a reason that a child has difficulties to be in place. However, an accurate interview will show the worsening of symptoms in the evening. The symptoms of ADHD and restless legs may also occur concurrently, and the differential diagnosis is difficult, especially since the stimulant drugs used to treat ADHD also relieve RLS symptoms. In contrast, dopamine agonists used in the treatment of RLS generally do not improve alertness and concentration.
Anxiety disorders can also cause general anxiety, as well as various sensations and symptoms of limb tingling. Serotonin reuptake inhibitors may also be used in the treatment of anxiety, but may exacerbate RLS symptoms.
The causes of small children’s growing pains are not well known, and it is likely that RLS can often be the case. In neuropathies, symptoms also occur in the morning and in the daytime and do not usually worsen in the evening. Lower back pain and sciatic symptoms should also be identified and separated from RLS.
Muscle cramps can also be confused with restless legs. Therefore, many patients were treated with Crampiton®. Unfortunately, this medicine was usually more harmful than good and has now been withdrawn from the market. In a muscle cramp, a muscle group, such as a calf muscle, shrinks causing a painful cramp. The duration of the cramp is from a few seconds to a few minutes. Stretching, massage and drinking plenty of liquids, such as water, may be helpful in treating simple muscle cramps. An interesting point in this context is that top athletes seem to have more symptoms of restless legs than the average.
How to treat restless leg syndrome?
Many patients have found various self-care methods to bring relief to RLS.
Patient’s own proven means include putting legs up against the wall in the evening, sleeping with wool socks, cold shower, cold foot baths, ice packs, warm bath, foot massage, soothing herbal tea, massaging the Illodin® mouthwash on the leg, magnesium tablets, regular exercise, and reducing excessive coffee drinking. The benefits of the methods vary, and in mild symptoms, the aid can be sufficient. However, in the most difficult cases, more effective treatments should be considered.
Especially in women, the tissue ferrite or serum ferritin may be low. If S-ferritin is less than 40 µg / l, RLS patients should receive oral iron supplements. Iron is one of the most important trace elements, but it is also toxic, and unnecessary iron treatments should always be avoided. High iron levels have been associated with Alzheimer’s disease, Parkinson’s disease and MS. Intravenous iron may be considered if the patient has severe RLS symptoms despite appropriate medication. The current international recommendations also require that: oral iron therapy has not increased S-ferritin, S-ferritin is less than 40 µg / l, the iron saturation of transferrin is less than 25% and that hemoglobin is within the reference limits.
Generally, the patient’s treatment is started with a dopamine agonist. The dose of the dopamine agonist should be as low as possible and, for example, pramipexole should never be used in RLS more than 0.54 milligrams. Experience has shown that the majority of patients have a dose from 0.18 to 0.36 mg. For other patients, a dose of 0.09 milligrams is sufficient for years. The medicine is always taken in the evening. It is often advisable to administer the dopamine agonist in such a way that a very small dose is taken at 17-19, ie before the onset of severe symptoms in the evening and another low dose before bedtime.
The dose should never be automatically increased, but it is important to use the smallest dose with which the symptoms are tolerable and do not interfere with falling asleep or sleeping. Continuous increase in the dose of medication can lead to severe augmentation, with symptoms worse than originally, they begin earlier in the day and may occur throughout the body. In such cases, it is advisable to consult an expert who will ensure that the diagnosis is correct.
Dopamine agonists can exacerbate obsessions. They can also affect libido and potency, that is, they can affect some people’s sexual desire and ability. The use of dopamine agonists should be treated with some caution in the case of an alcoholic, a person who is susceptible to drug abuse, a gambler or a person suffering from OCD. These are known drawbacks that need to be considered before starting the medication.
In special cases, other drugs than dopamine agonists may also be used. Sometimes clonazepam is used as a treatment. However, it should be avoided due to the abundant disadvantages and the very easily occurring addiction. Anti-epileptics such as gabapentin and pregabalin also help to relieve RLS symptoms. In addition, pregabalin is used to treat anxiety and chronic pain and can help with insomnia. Occasionally, opioids are also used in severe cases and in augmentation repair. One of the uses of the combination drug oxycodone and naloxone is the secondary treatment of severe RLS when other treatments have not provided sufficient help. It is advisable to consult a neurologists experienced in the treatment of RLS when considering potent central nervous system therapies.
All drugs used in the treatment of RLS may have the disadvantage of fatigue, and the doctor should discuss the effects of the drugs on driving. Children may also have restless legs symptoms, but they should usually refrain from medication.
What is the prognosis for people with restless legs syndrome?
RLS is a lifelong condition for which there is no cure, but the severity of symptoms may vary from day to day. The symptoms of a tired person are more difficult. Approximately 80% of patients also have periodic limb movements (PLM). PLM can occur during the day but is more common during the night and can seriously disrupt sleep which causes daytime fatigue. These limb movements are associated with changes in heart rhythm and blood pressure.
Recent follow-up studies have shown that RLS and periodic limb movement disorder (PLMD) are also a risk factor for hypertension and myocardial infarction. A poorly treated or untreated illness will reduce the patient’s quality of life by the same amount or more than for example rheumatoid arthritis, heart failure, diabetes or moderate depression. Although RLS can make life almost like hell, there is something good about it: RLS may, for example, protect against Alzheimer’s disease. Good physical condition and avoidance of fast-absorbing carbohydrates seem to alleviate the symptoms of RLS.