What Is Restless Leg Syndrome (Willis-Ekbom Disease)?

Restless leg syndrome (RLS) or Willis-Ekbom disease is a neurological disorder characterized by an irresistible urge to move the legs due to itching, throbbing, and uncomfortable sensations.

RLS is a common disease that affects about 10% of the general population [1].

1. What Is the Main Cause of Restless Leg Syndrome?

Although the cause is unknown, it is thought that the main cause of restless leg syndrome (RLS) is associated with an imbalance in the function of the neurotransmitter dopamine due to low levels of iron in the brain and body [1].

Dopamine is an organic chemical involved in the transmission of instructions between neurons to control muscle movements and reward-motivated behavior [2].

Other potential causes involve heredity, pregnancy, attention deficit hyperactivity disorder (ADHD), and medications.

1.1. What Is the Relation Between Restless Leg Syndrome and Heredity?

A role of heredity in RLS is associated with the high frequency of family history of RLS in patients diagnosed with this disease [3].

Monozygotic and dizygotic twin studies confirmed heredity involvement in RLS by showing the existence of a high concordance of RLS in monozygotic twins compared with that in dizygotic twins.

1.2. What Is the Relation Between Restless Leg Syndrome and Pregnancy?

Due to hormonal changes during the third semester of pregnancy, some women may experience RLS which disappears after delivery [4].

These changes involve an increase in the production of hormones, including estrogens, prolactin, progesterone, and thyroid hormone.

A reduction of iron and folate levels during pregnancy also appears to contribute to RLS due to their involvement in the synthesis of dopamine which further highlights the role of dopamine as the main cause of restless leg syndrome.

The prevalence of RLS during pregnancy was estimated to be in the range of 2.9-32% which is about 2-3 times higher than that in non-pregnant women.

1.3. What Is the Relation Between Restless Leg Syndrome and ADHD?

A relation Between Restless Leg Syndrome and ADHD was proposed by a study that showed that 44% of individuals with ADHD also had RLS.

Another important piece of information to add is that both ADHD and RLS have alterations related to dopamine levels in the brain [5].

1.4. What Is the Relation Between Restless Leg Syndrome and Medications?

Certain medications have been associated with restless leg syndrome, such as antidepressants (e.g., SSRIs, Tricyclics), withdrawal from sedative-hypnotic drugs (e.g., benzodiazepines), antiemetics (e.g., anticholinergics), antipsychotics, anticonvulsants, and antihistamines (e.g., diphenhydramine) [6].

Furthermore, alcohol and opioid withdrawal have also been associated with RLS.

2. Who Is Prone to Restless Leg Syndrome?

Restless leg syndrome (RLS) can develop at any age but is more common in women than men. There are also some factors that can increase the risk of RLS:

• Low Iron Levels
• Kidney Failure
• Neuropathy
• Rheumatoid Arthritis
• Diabetes Mellitus
• Celiac Disease
• Alcohol
• Iron Deficiency Anemia
• Parkinson’s Disease

2.1. Low Iron Levels

Iron is an essential cofactor in the production of dopamine and its deficiency can trigger RLS. Low iron levels can be due to blood loss through internal hemorrhage (e.g., gastrointestinal bleeding), excessive menstrual bleeding, frequent blood donations, or malabsorption.

2.2. Kidney Failure

Patients with chronic kidney disease on dialysis have decreased levels of iron due to the depletion of its storage in the blood.

2.3. Neuropathy

Increased levels of glucose in the blood such as during diabetes can lead to damage of nerves resulting in RLS.

2.4. Rheumatoid Arthritis

There is an elevated prevalence of RLS in patients with rheumatoid arthritis reaching between 27.7-31% [7].

2.5. Alcohol

Excessive consumption of alcohol (alcoholism) can lead to damage of nerves leading to RLS.

2.6. Celiac Disease

Celiac disease is an intestinal chronic disease characterized by a loss of appetite, malabsorption, and diarrhea due to gluten intolerance.

Celiac disease can also lead to iron deficiency which may lead to RLS. In fact, a study showed that 40% of studied patients with celiac disease had an iron deficiency [8].

2.7. Parkinson’s Disease

The characteristic dysfunction of dopamine in Parkinson’s Disease may explain why RLS is observed in some PD patients [9].

2.8. Iron Deficiency Anemia

Iron deficiency anemia is caused by a lack of iron in the body resulting in a reduction of the number of red blood cells leading to anemia. This lack of iron can also affect dopamine production.

3. What Symptoms Come with Restless Leg Syndrome?

Restless leg syndrome manifests with the following symptoms:

• An urge to move the legs due unpleasant sensations in the legs.
• An urge to move the legs during periods of rest or inactivity.
• The urge to move the legs may partially or totally be relieved by movement, such as walking or stretching.
• The urge to move the legs is increased in the evening or night than during the day.

4. Is Restless Leg Syndrome Psychological?

Although restless leg syndrome (RLS) is considered a neurological disease, a study that included 38 patients with RLS and 42 non-RLS controls, showed that patients with RLS have a lower internal locus of control (ability to impact its own health) and negative sleep-related personality traits compared to the non-RLS controls [10].

A negative sleep-related personality trait is associated with lower self-confidence, depression, higher mental arousal, and poorer quality of life.

5. How do you get rid of restless legs syndrome?

The treatment of RLS is aimed at relieving the associated symptoms that are caused by underlying physical conditions such as diabetes, celiac disease, or iron deficiency.

Medications to relieve the symptoms of RLS involve the use of dopaminergic drugs to improve dopamine effects, opioids to relieve the symptoms of severe RLS, and benzodiazepines for restful sleep.

Changes in lifestyle such as stopping alcohol, exercising (e.g., aerobics, stretching), taking iron supplements, respecting a regular sleep pattern, can help relieve some of the moderate symptoms.

Conclusion

Restless leg syndrome (RLS) can cause uncomfortable sensations that can affect sleep and the quality of life of the affected individual. The cause is unknown, but many studies highlighted the potential involvement of dopamine as the main cause.

RLS is also associated with several diseases which share with RLS the deficiency in iron which is an essential cofactor in the production of dopamine. However, other diseases and conditions such as diabetes or alcoholism can lead to nerve damage due to high blood levels of glucose or alcohol, respectively.

Although there is no specific treatment for RLS, dealing with this disease involves symptomatic treatments that aim at alleviating or reducing the undesirable and overwhelming manifestations of RLS.