Restless Legs Syndrome

Restless Legs Syndrome, or RLS for short, is a neurological disorder and is manifested by an uncontrollable urge to move the legs, usually occurring at night or in rest situations, which is often associated with pain or unpleasant sensations. Characteristic is an improvement of the symptoms by movement or physical activity. The symptoms are often the cause of sleep disturbances and reduced sleep quality.

In western industrialized countries, the age-dependent prevalence is 7-10%, making RLS one of the most common neurological disorders, along with migraine.

The exact causes of RLS have not yet been adequately elucidated. A multifactorial genesis is assumed, in which disturbances of the iron metabolism and changes of messenger systems (neurotransmitters) in the brain play a role. In addition, in many cases there is a genetic predisposition that favors the disease.

According to the guideline on restless legs syndrome published in 2022, the clinical picture arises from an interaction of genetic, socioeconomic and environmental factors as well as comorbidities (concomitant diseases).

As early as the 17th century, Thomas Willis described a form of restlessness with an urge to move. The term "restless legs syndrome" has been in use since 1945 and literally means "syndrome of restless legs".

The exact causes of the syndrome are not yet sufficiently clear and are the subject of current research. The following mechanisms are discussed as factors in the development:

• Disturbance in the iron metabolism & in the dopamine metabolism of the brain:
  Iron represents an important cofactor in the endogenous formation of dopamine. With the help of the amino acid tyrosine, the dopamine precursor L-dopa is formed. This process follows a diurnal rhythm, which could explain the worsening of symptoms at night.
  The disturbance of iron metabolism in RLS is usually limited to the brain but may also be associated with iron deficiency throughout the body. The local iron deficiency is thought to interfere with oxygen delivery to the brain. This leads to abnormalities in neurotransmitter systems such as dopamine, adenosine and glutamate and consequently to disturbances in important neural pathways in the brain (basal ganglia).
• Genetic predisposition:
  Due to an accumulation of RLS disorders within families, a genetic predisposition is assumed. A number of gene variations have already been discovered that significantly increase the risk for RLS disease.
• Other diseases:
  A number of other conditions occur clustered in combination with RLS. These include renal insufficiency, hyperuricemia, polyneuropathies, liver disease, anxiety disorders, depression, dementia, Parkinson's disease, multiple sclerosis, migraine, thyroid disease, and lung disease. Proving whether the disorders are a causal cause of RLS or whether the disorders occur coincidentally is often difficult.
• Nutrient deficiency:
  In addition to iron deficiency, deficiencies in vitamin B12, vitamin D, or folic acid can also lead to restless legs syndrome or RLS-like symptoms.
• Medications:
  Taking antidepressants, neuroleptics, antiemetics, or thyroid medications, among others, can cause RLS or RLS-like symptoms as a side effect.

The most common symptoms are:

• Urge to move and restlessness of the limbs (mainly the legs).
• Abnormal sensations such as tingling, electric, pulling, stinging, burning, formication, feeling of pressure, cramps, feeling of warmth or coldness
• Involuntary leg movements
• Pain

Symptomatology typically manifests at night or during periods of physical rest and when lying down. Usually, giving in to the urge to move leads to immediate relief of the insensations.

RLS is diagnosed primarily on the basis of typical symptoms. For the diagnosis, all five criteria must be met:

1. Urge to move the legs that is usually accompanied by pain or discomfort.
2. The urge to move the legs and the accompanying pain or discomfort worsen when the patient is resting or lying down/sitting.
3. The urge to move the legs and the accompanying pain or discomfort improve with physical activity
4. The urge to move the legs and the accompanying pain or discomfort occur exclusively in the evening or at night, or worsen in the evening or at night
5. Symptoms are not explainable by other medical diagnoses or treatments

Other tests are not necessary for diagnosis, but may be helpful. Catalogs of criteria (assessments) are usually used to describe the manifestation and severity of the disease.

Additional criteria for the diagnosis, which do not necessarily have to be fulfilled, are:

• Response (or improvement of symptoms) to dopaminergic medication (e.g. administration of L-dopa, also called L-dopa test).
• Positive family history
• Periodic leg movements during sleep in a sleep laboratory
• Sleep disturbances and resulting consequences

Treatment of restless legs syndrome is based on the patient's individual level of suffering. Therapy of concomitant diseases can alleviate or completely eliminate RLS symptoms. So far, only symptomatic treatment is possible.

Non-drug therapy approaches:

• Changes in lifestyle habits
• Good sleep hygiene
• Balanced diet and avoidance of alcohol and coffee
• Moderate physical activity

Acute relief:

• Massages
• Cooling gels
• Baths
• Mental distraction

Medication treatment:

Taking medication to relieve RLS symptoms must be discussed with a physician and should be tailored to the patient's individual symptoms. Options include:

• Treatment with dopamine-acting medications, including L-dopa and dopamine agonists (including pramipexole, ropinirole, rotigotine).
• Treatment with opioids such as oxycodone, codeine, or oxycodone in combination with naloxone
• Treatment with anticonvulsants and antiepileptic drugs such as gabapentin, pregabalin, clonazepam, carbamazepine, valproic acid, and clonidine
• Iron supplementation in combination with vitamin C for low iron blood levels

Treatment with dopaminergic medications can lead to what is called augmentation. This refers to the amplification of symptoms by the medication. In the case of augmentation by L-dopa, the therapy is switched to dopamine agonists. If augmentation is subsequently observed with this medication as well, opioids can be used.

Since the syndrome itself is not curable, only the symptoms can be treated by different therapeutic approaches. The symptoms are usually mild at first and often do not require therapy. Worsening over time is possible. Since RLS is a chronic disease, it usually requires lifelong treatment.

In the case of genetic predisposition, direct prevention of restless legs syndrome is hardly or not possible. A lifestyle consisting of sufficient sleep, a balanced diet and moderate physical activity can have a preventive effect on RLS symptoms.