Restless Legs Syndrome

Key points

Restless Legs Syndrome (RLS) is a typical neurological sleep disorder: the affected patient perceives the irrepressible desire to move the lower limbs, the only apparent remedy to find relief and comfort for pain, discomfort and aching in the legs.

Causes

The primary form of restless legs syndrome is likely hereditary, transmitted by an autosomal dominant mechanism. The secondary variant of RLS can be caused by: amyloidosis, rheumatoid arthritis, celiac disease, diabetes, folate and iron deficiency, Lyme disease, kidney disease, Parkinson's, uremia.

Symptoms
Patients with restless legs syndrome struggle to define symptoms precisely: nocturnal leg twitches, motor restlessness, uncontrolled leg movements, need to move the lower limbs, itching / tickling, tingling in the legs.

Diagnosis
There is no fully reliable diagnostic test to ascertain restless legs syndrome. In general, the doctor limits himself to analyzing the symptoms according to some standard criteria, drawn up by the National Institutes of Health.

Medicines and treatments

RLS dependent on iron deficiency / Vit. B9-B12 → martial therapy / folate and / or vitamin B12 supplementation
Drug-dependent RLS → modulation of the dosage of the responsible drugs / substitution with other drugs with similar activity
If restless legs syndrome seriously affects sleep quality → anxiolytic, antiepileptic, antiparkinsonian, opioid drugs

What is restless legs syndrome?

Restless legs syndrome (or Ekbom syndrome) is a "neurological disease characterized by sensory symptoms and motor disturbances in the lower limbs, which occur mainly during rest. For this reason, restless legs syndrome is included on the list of sleep disorders.
Restless Legs Syndrome is abbreviated as RLS, which stands for Restless LegsSyndrome: the term was coined around 1940 by a Swedish neurologist, who first accurately described the clinical evidence of the disease.
Restless Legs Syndrome is a disease with a sneaky onset, which is however responsible for suffering and discomfort that dramatically affect the quality of life of those affected.
The characteristic symptoms associated with restless legs syndrome are rather difficult to define: most of the patients affected, in fact, struggle in the precise description of the disorder.
In any case, it is possible to report three general characteristics that are constantly encountered in the disease:

Unpleasant sensitivity disorders in the lower limbs
Involuntary movements of the legs, sometimes also of the arms
Urgent need to move legs: movement (e.g. walking, shaking limbs) provides temporary, but immediate relief

As for the treatments, at the moment no drug is able to completely cancel the disorder; however, there are therapies available to relieve and control symptoms.

Incidence

Restless legs syndrome affects 3-9% of the global population: it is not possible to report precise statistics, since the disorder often remains undiagnosed.
In most cases, the prevalence of the disease increases with age: in fact, the characteristic symptoms of restless legs begin after the age of 40, and gradually become more pronounced with the inexorable passage of time. Despite what has been said, about one third of affected patients complain of the first symptoms already around the age of 20.
Restless Legs Syndrome is an almost female-only discomfort that affects many women during pregnancy.

Classification

There are two variants of restless legs syndrome:

Primary (idiopathic) form: Generally slow onset, the primary variant of restless legs syndrome is generally not related to any specific and identifiable cause. Characteristic symptoms may be hidden for months or years, and tend to worsen with aging. The primary form of RLS is thought to be genetically transmitted by an autosomal dominant mechanism.
Secondary form: typical of patients over the age of 40, the secondary form of restless legs syndrome is an expression of particular clinical conditions *, or is the consequence of a particular drug therapy. The onset is not as slow as the primitive variant: normally, secondary RLS occurs suddenly, and the affected subject often complains of characteristic symptoms even during the day.

Causes *

Before listing the possible triggering causes and risk factors associated with restless legs syndrome, let us remember that over 60% of patients are genetically predisposed to the syndrome.
As analyzed, it is not possible to trace the triggering cause of the primitive form of RLS: it is in fact the subtle variant of the disease, with a slow course, which tends to worsen with age.
Different speech for the secondary form: in this case, the restless legs syndrome seems to be related to some pathologies. In particular, it seems that iron deficiency (ferritin in the blood peripheral neuropathy plays a leading role in the triggering of restless legs syndrome.

PeWhy does iron deficiency predispose someone to restless legs syndrome?

Iron is the essential cofactor for the formation of L-dopa, a precursor of dopamine. Dopamine is a substance responsible for transmitting messages contained in the brain districts, which in turn control movement and coordination. Iron deficiency prevents the correct synthesis of L-DOPA: this explains the reason why iron deficiency predisposes a patient to restless legs syndrome.

However, additional diseases involved in the manifestation of RLS have also been identified:

Amyloidosis
Rheumatoid arthritis
Celiac disease
Diabetes mellitus
Deficiency of folate, magnesium and vitamin B 12
Autoimmune disorders (e.g. Sjögren's syndrome)
Venous insufficiency
Frequent blood donations
Diseases of the thyroid gland
Lyme disease
End-stage renal disease (Renal failure): it is observed that 25-50% of patients with end-stage renal disease, especially on hemodialysis, are also affected by restless legs syndrome. In such situations, kidney transplantation can relieve symptoms, significantly improving the patient's clinical picture.
Parkinson's disease
Spinal disorders (e.g. lumbosacral radiculopathy)
Uremia

Risk factors

Some predisposing factors for restless legs syndrome have been identified:

Pregnancy: Restless Legs Syndrome affects 25-40% of pregnant women. It is a temporary disorder, which tends to regress after a few weeks after birth. However, scientific evidence shows that pregnant women affected by RLS are 4 times more at risk of developing the disorder again during senescence than mothers not affected by the syndrome during gestation.
Long-term therapy with specific drugs: even the administration of some medicines can predispose the patient to restless legs syndrome. If the patient is already affected by the disease, the administration of the following active ingredients can exacerbate the symptoms.
- Anticonvulsants
- Tricyclic antidepressants
- Antidopaminergics (e.g. neuroleptics, antiemetics)
- Anti-histamines
- Beta blockers (drugs to treat hypertension)
- Lithium derivatives (used, for example, for the treatment of Graves-Basedow's disease)
- Diphenhydramine (hypnotic / sedative)
- Serotonin reuptake inhibitors (second generation antidepressants)

Opioid withdrawal may also be a trigger for RLS.
Furthermore, it seems that an abuse of foods containing caffeine and alcohol can predispose a person to restless legs syndrome.