Restless legs syndrome

RLS is a neurologic disorder that is characterized by a strong urge to move the legs, usually occurring in the evening or at night and worsening during rest or inactivity.

The exact causes of RLS are unknown, but certain nucleotide polymorphisms (BTBD9, Meis1, MAP2K5/LBXCOR1, and PTPRD) have been associated with an increased risk, and a positive family history is frequently observed. Iron deficiency, alterations in dopaminergic systems, dysruptions in circadian physiology, and altered thalamic function have been implicated in the pathophysiology of RLS.

The prevalence of RLS in the US is estimated at 10%.

Risk factors for restless leg syndrome include female gender, pregnancy, iron deficiency, advanced age, a positive family history, CKD, peripheral neuropathy, multiple sclerosis, Parkinson's disease, and other neuropathies. Conditions such as ADHD, migraine, Guillain-Barré syndrome, thyroid disease, chronic venous disorder, Sjögren's syndrome, rheumatoid arthritis, ankylosing spondylitis, IBD, and post-stroke status are also associated with an increased risk. Certain medications, including antidepressants, neuroleptics, and dopaminergic antagonists, may contribute to the development of the syndrome.

Restless leg syndrome is associated with poor sleep quality, insomnia and daytime sleepiness, reduced productivity and QoL, and the severity of symptoms can fluctuate and tends to worsen with age. Loss of efficacy and augmentation are two main types of treatment failures occurring in patients receiving long-term treatment for RLS. Augmentation refers to a medication-induced worsening of the symptoms. The augmentation rate for pramipexole, ropinirole, and rotigotine is 65% at 10 years, 24% at 5 years, and 13% at 5 years, respectively.