The disorder known as the restless legs syndrome may regularly delay the onset of sleep and usually occurs in its early stages. Ekbom called it asthenia crurum paresthetica and also, anxietas tibiarum. This disorder is surprisingly prevalent, affecting more than 2 percent of the population. The patient may complain of unpleasant aching and drawing sensations in the calves and thighs, often associated with creeping or crawling feelings; other descriptions have included “worms,” “internal itch,” and “coldness,” and the legs may feel tired, heavy, and weak. The location in the legs distinguishes the problem from the separate condition of acral paresthesias. The symptoms are provoked by rest, and rapidly, but temporarily, relieved by moving the legs. An urge to move the legs can be suppressed voluntarily for a brief period but is ultimately irresistible. Moving the limbs alleviates the sensation briefly. It is interesting that a small proportion of patients have similar symptoms in the arms after many years of symptoms. There may be variants of nocturnal restlessness in other parts of the body such as the abdomen, as suggested by Pérez-Díaz and colleagues. Their patients described an unpleasant abdominal musculature restlessness that required movement for relief and was eliminated with dopamine agonists.
Fatigue worsens restless legs syndrome, and there is a tendency for it to be worse in warm weather. In a few patients, mainly older ones with a severe form of the nighttime disorder, these movements and an associated myoclonus spill over into wakefulness and are accompanied by restlessness, foot spasms, foot stamping, body rocking, and marching that are only partly under voluntary control. The daytime phenomena may require several medications used simultaneously for control.
The syndrome is usually idiopathic and persists for years. However, iron-deficiency anemia and low ferritin levels are associated with the syndrome in many instances, as is renal failure, particularly with dialysis, alcohol before sleep, thyroid disease, pregnancy, and certain drugs, such as antidepressants and antihistamines. Occasionally, it is a prelude to a peripheral neuropathy, particularly in relation to uremia. Also, reduced levels of iron in the cerebrospinal fluid (CSF) have been found with restless legs syndrome and with periodic limb movements of sleep (see below). The basis for this relationship to iron is not well defined and the proportion of cases explained by this varies among studies, but it makes it advisable to check for reduced iron stores and anemia in most patients with restless leg syndrome. One hypothesis is that a disturbance of iron storage in the basal ganglia causes a decrement in dopamine binding by dopamine receptors and transporters, as has been described in studies using PET and single-photon emission tomography (SPECT) scans. Another potential relationship, unproved, is that iron is a cofactor for the enzyme, tyrosine hydroxylase, which is required to produce dopamine.