Restless Legs Syndrome Is Due To Decreased Brain Iron Acquisition - New Study

A new study suggests that the cause of restless legs syndrome may be due to the difference in brain iron acquisition in these individuals. In many individuals with restless legs syndrome, the amount of iron in the brain is low.

The research report by scientists from Penn State College of Medicine and Johns Hopkins University was published in the March 11 2011 issue of the scholarly journal, Brain.

In this study, they observed differences in the profile of iron management proteins between restless legs syndrome and control individuals at the level of the blood-brain barrier indicating that the low brain iron concentration in the former group may be due to misregulation of iron transport across this interface. Based upon their data they further conclude that the iron reservoir for the brain is endothelial cells (cells lining the inner side of the blood vessel) at this interface. If this reservoir is not sufficiently filled, the iron level in the brain can decrease. The authors further add that the blood-brain barrier is not merely a transport system, but the microvessels in this barrier can regulate iron storage as well as uptake into the brain.

The study was performed using choroid plexus from 14 individuals with primary restless legs syndrome and 18 normal controls. These tissues were obtained at autopsy. Choroid plexus are found in the ventricles of the brain and produce cerebrospinal fluid. They also tested microvessels from the motor cortex of 11 restless legs syndrome and 14 control brains obtained at autopsy.

They found that iron and heavy chain ferritin staining was reduced in the epithelial cells of choroid plexus in restless legs syndrome. Expression of heavy chain ferritin, transferrin and its receptor in the microvessels from restless legs syndrome was also significantly decreased compared with the controls.

The authors of this study were James Connor, Padmavathi Ponnuru, Xin-Shen Wang and Stephanie Paton from the Penn State College of Medicine at Hershey, PA and Richard Allen and Christopher Earley from Johns Hopkins University Baltimore, Baltimore, MD.

Restless legs syndrome is a neurological disorder characterized by unpleasant sensations such as throbbing, pulling or creeping in the legs and an urgency to move the legs. Symptoms occur primarily at night when a person is relaxing or at rest and can increase in severity during the night. The discomfort is usually relieved by moving the legs.

Sleep deprivation may affect job, personal relations, and activities of daily living. According to the National Institute of Neurological Disorders and Stroke "as many as 10 percent of the U.S. population may have restless legs syndrome."

Though the cause of restless legs syndrome is not known, genetic factors and decreased iron levels in the brain are implicated in this disorder. The specific genetic element, or the mechanism underlying the decreased iron concentrations in restless legs syndrome brains remain a mystery. The study by James Connor and colleagues was conducted based upon their hypothesis that the source of brain iron deficit is at the blood-brain interface.

In an earlier study, the first-ever autopsy study of brains from people with restless legs syndrome, the same authors had found that receptors which help cells absorb iron are abnormally regulated in cells that produce the nerve-signaling chemical dopamine. That study was published in the August 12, 2003, issue of Neurology. The current research report extend this study by identifying potential mechanisms underlying low iron levels in the brain of individuals with restless legs syndrome.

A number of studies have linked restless legs syndrome to deficiencies of dopamine and iron. Medications that affect dopamine levels, such as the drug levodopa, relieve symptoms of the disease in some people. Injections of large doses of iron also relieve symptoms in some cases. However, it has never been clear exactly what causes the symptoms of this disease.

Restless legs syndrome is generally a lifelong condition for which there is no cure.

Source: James R. Connor, Padmavathi Ponnuru, Xin-Sheng Wang, Stephanie M. Patton, Richard P. Allen and Christopher J. Earley. Profile of altered brain iron acquisition in restless legs syndrome. Brain (2011) March 11 (online advance publication) doi: 10.1093/brain/awr012.