Restless Legs Syndrome

What Is Restless Legs Syndrome (RLS)?

Restless legs syndrome (RLS) and periodic limb movements during sleep (PLMS) should not be confused with each other. Indeed, restless legs syndrome is a neurological disorder with established effects on the quality of life and health. In contrast, periodic leg movements during sleep is a polysomnographic finding of unknown clinical significance. While the majority of RLS patients also have PLMS witnessed during nocturnal polysomnography, many patients with PLMS do not have restless legs syndrome.

RLS is increasingly recognized as an important neurological disorder. It is about twice more common in women versus men and increases with aging. Awareness has come from public education efforts by the RLS Foundation and the realization by the pharmaceutical industry that a significant part of the population is affected by restless legs syndrome (3% severely affected). In spite of these efforts, however, the disorder is often not considered by neurologists, academia and funding agencies as an important condition.

What causes restless legs syndrome (RLS)?

Research in the area of RLS has advanced over the last few years. First, there has been a growing realization that low brain iron metabolism may be a critical pathway in the pathophysiology of RLS. Blood ferritin levels are often lower in RLS patients (typically below 50 µg/L), and iron deficiency seems to be most pronounced when measured in the brain or CSF. Iron deficiency can also produce anemia (low hemoglobin and red blood cell count) and fatigue. If iron deficiency is discovered, it is important to establish its cause.

The cause of RLS also likely involved abnormal Dopamine. Dopamine is an important neurochemical in the brain that is involved in sleep, movements (for example low dopamine is partially responsible for Parkinson's disease), and the control of pleasurable emotions. For this reason some of the treatment used for Parkinson's diseases called Dopaminergic agonist can be effective in the treatment of RLS, although they shoud be used with caution.

Genetic factors are strong predictors of RLS. First, RLS commonly runs in family, especially when it is severe and start early in life. DNA changes in five genes have been associated with RLS. These genes are MEIS1, BTBD9, MAP2K5/LBXCOR1, and PTPRD. Interestingly, these genes are mostly DNA binding factors and some are highly expressed in the spinal cord. Although unproven, it is likely that polymorphisms at the level of these genes modulate how the spinal cord process sensory inputs and/or regulate spinal cord motor reflexes. This disturbance would also explain the association of RLS with Periodic Leg Movements during sleep (PLMS).

Environmental factors and other medical problems are also associated with RLS. Most notably, RLS is frequently exacerbated or may start during pregnancy. Second, in addition to iron deficiency, RLS can be caused or exacerbated by renal/kidney failure, spinal cord/back pain issue, and is likely more frequent in people who have damaged peripheral nerves ending, such as in those with peripheral neuropathy (for example in patients with long term diabetes).

RLS may be associated with other conditions, and has been suggested to predispose to depression and heart disease.