The main purpose of this research study is to help prove in an objective way that restless legs syndrome (RLS) is caused by pinched and damaged foot nerves called neuromas. RLS is a medical condition in which there is an almost irresistible urge to move the legs in response to uncomfortable, difficult-to-describe leg sensations that are usually worse in the evening and especially noticeable when inactive such as sitting in a chair watching TV or when resting in bed trying to go to sleep or back to sleep after awakening.

Since there are no objective lab tests for RLS, the diagnosis is based on fulfillment of 4 essential criteria:

a.	an urge to move the legs is present that is usually associated with uncomfortable or unpleasant sensations in the legs
b.	the urge to move or the unpleasant sensations begin or worsen during periods of rest or inactivity such as lying or sitting
c.	the urge to move or unpleasant sensations are partially or totally relieved by movement of the legs, such as by walking or stretching, at least as long as the activity continues
d.	the urge to move or unpleasant sensations are worse in the evening or night than during the day or only occur in the evening or night.

Most patients with RLS, while asleep, also have involuntary leg movements called periodic limb movements of sleep (PLMS). Sometimes the RLS patient's spouse is quite aware of the leg movements having been kicked in the night, although usually the leg movements are less obvious and only noticeable with prolonged observation or only detectable during an overnight sleep study. During such a sleep study, brain wave monitoring of patients with RLS/PLMS often shows that the nighttime leg movements are associated with brain stimulation and arousal to a lighter stage of sleep. When many such brain arousals happen through the night, the natural pattern of deep sleep may be severely disrupted. Such disturbed sleep is of poorer quality and is less refreshing which results in morning sluggishness and increased daytime fatigue.

The cause(s) of RLS and PLMS have not been determined. Neurologists believe that they originate in the brain in areas that control movement and may be related to localized low levels of dopamine (a chemical messenger between nerve cells) or related to disordered brain iron metabolism, but these theories have never been proven.

RLS and PLMS generally are lifelong conditions for which there is no cure. RLS is treated with medications targeting the brain and categories of drugs that have been used to treat symptoms (with varying success) include mainly dopaminergic drugs but also sedatives, anti-seizure drugs, and pain medications such as narcotics. Two dopaminergic drugs have been approved by the FDA for the treatment of RLS: ropinirole ("Requip") in 2005 and pramipexole ("Mirapex") in 2006. However such drugs are far from ideal because, in addition to the problem of side effects, some patients may not respond to these drugs or symptoms may only partially improve. Also, any improvement only occurs while continuing to take the drug, and finally, symptoms may sometimes become much worse after an initial period of improvement, a phenomenon called augmentation.

For the last 5 years, Drs. Lettau and Gudas have been studying foot nerve entrapments ("pinched nerves") called neuromas which form at points where nerves must stretch under ligaments in the ball of each foot. Repeated irritation and damage to the nerves at those stretch points eventually results in fibrous thickening and enlargement of the nerve tissue into a lump called a neuroma. This most commonly involves a nerve in the ball of the foot between the third and fourth toes ("Morton's Neuroma"), but neuromas also often form at the entrapment/stretch point of the nerves between the second/third and fourth/fifth toes. Neuromas may cause varying degrees of unilateral or bilateral foot pain and numbness brought on or made worse by tight shoes, high heels, or prolonged walking or standing. When neuromas become more severely symptomatic, they may cause neuropathic symptoms such as burning, tingling, numbness, electric shock shooting pains, and hypersensitivity. Neuromas are treated with a series of injections (local anesthetic combined with either steroids and/or alcohol solution) given into the neuroma-containing space in the ball of the foot. It is believed that these injections serve to calm the nerve irritability which usually results in improvement or sometimes even complete resolution of the neuropathic symptoms (burning pain, etc.).

During the year 2002, Drs. Lettau and Gudas discovered that many patients with such neuropathic foot symptoms (burning, tingling, electric shocks, numbness, etc.) who had been previously diagnosed with "peripheral neuropathy," actually had neuromas in both feet as the cause of their symptoms. The causative role of neuromas in these patients was demonstrated by the fact that their chronic pain symptoms improved (in some cases markedly so) with standard neuroma injection treatment. In addition to improvement in their neuropathic foot pains, many patients also reported that they were sleeping much better. Such patients reported not only a decrease in their RLS-type leg restlessness but also that their spouse had noted a decrease in their PLMS-type nighttime leg movements, all as a direct result of their bilateral neuroma injections. These reports prompted further study of patients who had RLS/PLMS both with and without neuropathic foot pains.

Over the last 4 years, Drs. Lettau and Gudas have evaluated over 100 adult patients who had RLS/PLMS and such patients were consistently found to have physical evidence of neuromas on examination of their feet and standard treatment of their bilateral neuromas usually resulted in prompt improvement of the symptoms of RLS/PLMS, which in turn improved the quality of their sleep. 15 such patients were studied intensively before and after neuroma treatment and 9 of these patients had complete relief of RLS symptoms for an average of over 2 months after a series of neuroma injections. These results were the subject of a published medical report on bilateral neuromas as a cause of RLS (full text freely available online at www.scmanet.org/Downloads/e-Journal/2005/November.pdf ). However, despite this report, the prevailing theory remains that RLS comes from the brain, so it is necessary to do a larger, more scientifically objective second study to further support the foot neuroma origin of RLS by comparing the responses of two groups of adults with RLS - one group to receive a series of 3 bilateral neuroma treatment injections over 3 weeks and a second "control" group to receive only placebo (balanced salt-water) injections over a similar time period. Neither group will be told whether they are getting the actual treatment solution or placebo over the 3 weeks. After the 3 weeks are up, the patients who had received the placebo, will be told of their status and will be given the real injection treatments over the next 3 weeks. A total of up to 60 adults (30 in each study group) will be enrolled, all from the Charleston area.