Restless Legs Syndrome: Causes, Treatments

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What is Restless Legs Syndrome?

Many conditions can cause legs to move uncontrollably, including leg tremors (due to certain health conditions) and leg cramps (post exercise or due to vitamin/mineral deficiency). There is even a condition that causes the legs to move uncontrollably during sleep, referred to as Periodic Leg Movements (If it results in excessive awakenings it’s called Periodic Leg Movement Disorder.) However, all these are separate from the condition we identify as Restless Legs Syndrome (RLS).

The nature of the syndrome is simply the urge to move the legs, usually accompanied by or caused by uncomfortable and/or unpleasant sensations in the legs, often during sleepUnlike people with the conditions mentioned above, people with Restless Legs Syndrome feel better once they get up, move and walk.

How is the diagnosis of Restless Legs Syndrome made?There is no specific test or x-ray screening to confirm the diagnosis. Instead, it’s usually identified by** clinical findings**.  The International RLS Study Group created the acronym URGE to describe the group of symptoms that make the diagnosis:

U rge to move one’s legs, sometimes accompanied by uncomfortable sensations deep in the legs.

R est induced, meaning that the urge to move is precipitated by inactivity, frequently during sleep.

G ets better with activity, such as walking.

E vening and nighttime are the most common times for the symptoms to appear.

A sleep study is not necessary for the diagnosis of RLS, but it may be necessary to identify comorbid conditions.

What is the actual mechanism behind this condition?The best way to understand Restless Legs Syndrome is to realize that, unlike tremors or cramps, it’s not a problem that originates with the muscles or peripheral nerves.  Instead the origin of the problem lies deep in the brain.  Specifically, the neurotransmitter dopamine is largely responsbile for the condition.  The fact that the symptoms appear in the evening or during the night suggest that there is a circadian pattern to the secretion of dopamine.

Is Restless Legs Syndrome linked to Parkinson’s disease, another condition with a dopamine component?Both diseases have a dopamine “issue,” and that’s why the treatment for both diseases is similar.  When levodopa (the precursor of the neurotransmitter dopamine) levels are low, that translates to low levels of dopamine in the brain.  That in turn means that adequate dopamine does not get to striatal nerve terminals.  So levodopa is a treatment for both Parkinson’s disease and for Restless Legs Syndrome.  It’s also important to note that in many cases, having Restless Legs Syndrome is a prognostic sign that Parkinson’s disease will likely develop at a later age.

What can cause Restless Legs Syndrome?In Primary RLS, there is a deficiency of iron at the brain level, which is necessary for the synthesis of dopamine.   Unlike with an anemia, replacement with oral iron will not solve the problem.

There are also strong familial associations in RLS.  The association with family history often means developing the condition before the age of 40, and it then carries a worse prognosis.

There is also Secondary RLS,in which the condition is precipitated by other health issues. Most commonly, renal failure is associated with a risk of developing RLS.   It can also be precipitated by pregnancy and by some medications, including certain antidepressants. This last issue can be a problem, since depression is commonly found in people with RLS

Is it true that recently RLS has been given a new name?

Yes, the Restless Legs Foundation has renamed RLS with the new name, Willis-Ekbom disease. It is named after Sir Thomas Willis who first described the condition in the early 17th century.  His findings were largely ignored until the 20th century, when the neurologist Karl Ekbom coined the term Restless Legs Syndrome. _His_findings were also largely ignored until he died in 1970.  Only after his death was the condition re-visited and classified.

How serious is Willis-Ekbom disease?

As the condition progresses in severity, it affects the ability to rest, relax, and experience sustained deep sleep. The effects of sleep deprivation become cumulative and have all the associated consequences, inckluding increased sensitivity to pain and earlier cognitive deficits that typically come with age.  Dementia is also more pronounced, and when Parkinson’s disease develops it is more advanced in nature.

Current treatmentTreatment is available in the form of “dopaminergic” drugs that increase the production of dopamine in the brain. The list of drugs include: Levo Dopa (carbidopa), Mirapex, Requip and possibly some opioids. When the drug therapy (Carbidopa) ceases to be effective (a process called augmentation), then the other similar medications, Pramipexole (Mirapex) and Ropinorole (Requip), are used. ** Carbidopa does have significant side effects, as do the other drugs, which makes treating the condition quite challenging.Curiously, one of the side effects of these therapies is compulsive behavior**. That means that these drugs should not be used in individuals who have a gambling problem or other impulsive behavior.

Very frequently, the treatment requires changing the medications and trying to find the optimal doses that are well tolerated by the patient.

This is a condition that should be managed by a skillful and educated health care provider with a lot of experience in treating the condition.

A hopeful outcome

With proper management, the symptoms of Willis-Ekbom disease (RLS) can be controlled and therefore quality of life improvement is certainly possible.

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Eli Hendel, M.D. is a board-certified Internist and pulmonary specialist with board certification in Sleep Medicine. He is an Assistant Clinical Professor of Medicine at Keck-University of Southern California School of Medicine, Qualified Medical Examiner for the State of California Department of Industrial Relations, and Director of Intensive Care Services at Glendale Memorial Hospital.His areas of expertise in private practice include asthma, COPD, sleep disorders, obstructive sleep apnea, and occupational lung diseases.