Pathology of Restless Legs Syndrome


Restless Legs Syndrome is primarily a sensory disorder. According to the RLS Foundation, approximately 12 million people in the U.S. are affected, women more than men. In approximately 80 percent of patients, RLS is associated with recurrent leg jerks during sleep at intervals of 20 to 30 seconds, which makes sleeping difficult. RLS is divided into three types: intermittent, daily and refractory. According to American Family Physician, genetics contributes to the pathology of primary RLS. Abnormalities in dopamine, or iron function, pregnancy and uremia contribute to the pathology of secondary RLS.


Diagnosis is based on four symptoms: a strong urge to move legs accompanied by creepy sensations or itching in the legs; worsening RLS symptoms while resting; relieved RLS symptoms when walking; and worsening RLS symptoms in the evening and when lying down, or while reading.


Although the underlying cause of RLS hasn’t been positively identified, progress has been made in understanding this common disorder. According to Movement Disorder Virtual University, research has shown approximately 50 percent of patients with RLS have a family history of the disorder. So, primary RLS has a genetic origin. According to, sites on the chromosomes have been identified where genes for RLS may be present. However, no gene has been identified as having a causal relationship to RLS, and the exact mode of inheritance is unknown.


Most RLS symptoms respond to treatment with dopaminergic agents. Conversely, the use of dopamine receptor antagonists worsen symptoms. However, finding a metabolic defect or signaling in the dopamine system has been elusive. Dopaminergic receptor agonists (pergolide, pramipexole and ropinirole) are first-line agents of moderate to severe RLS. According to Earley, gabapentin may also be effective.


Iron deficiency is a rare cause. However, serum iron stores (as measured by serum ferritin) should be checked. Not all patients with RLS are iron deficient and not all patients who are iron deficient exhibit symptoms of RLS.


RLS symptoms often occur for the first time during pregnancy. Symptoms typically worsen during pregnancy and improve or disappear after delivery. The risk of developing RLS increases gradually with the number of pregnancies. Elevation in estradiol levels during pregnancy is more marked in pregnant women with RLS than in controls. In addition, there is a high RLS incidence in the last trimester of pregnancy when estradiol is maximally elevated.

About this Author

Based in New Jersey, John Riefler III has been writing since 1987. His articles have appeared in “MD Magazine,” “Emergency Medicine” and “Hospital Practice.” Riefler holds a Bachelor of Science in biology from Bucknell University, a Master of Science in microbiology from M.U.S.C. and an M.D. from St. George’s U. School of Medicine.