Restless Legs Syndrome

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Restless legs syndrome (RLS) is a dyssomnia and a neurological disorder in which the person feels a strong urge to move the lower limbs. Also called Ekbom Syndrome and Willis-Ekbom disease, RLS results in a “pins and needles” sensation that can be painful and a nuisance when trying to sleep.

The sensations have the following features:

  • Occur during periods of inactivity
  • Become more sensitive in the evening and at night
  • Are relieved by movement of the limb
  • Often cause difficulty staying or falling asleep, which leads to
    feelings of daytime tiredness or fatigue
  • May cause involuntary jerking of the limbs during sleep and
    sometimes during wakefulness

Diagnosis

RLS can be hard to diagnose because the diagnosis depends primarily on complaints by the patient and a detailed sleep and medical history. There is no blood test for it. The International Restless Legs Syndrome Study Group (IRLSSG) – a group of scientists interested in this field – lists five must-have symptoms.
(http://irlssg.org/diagnostic-criteria/)

  1. an urge to move the lower limbs
  2. the urge is accompanied with pain or unbearable sensations which gets worse when the person rests or lies down
  3. some relief from the urge results from walking or stretching
  4. the symptoms become worse at night or during rest
  5. no other obvious cause for these symptoms

How common is RLS?  If you just look people who meet the IRLSSG diagnostic criteria, estimates range from 3.9% to 14.3% of the population.  If a more strict differential diagnosis criteria is applied, the prevalence estimates range from 1.9% to 4.6%. RLS is more common in women than men and generally increases with age. The physicians’ reference site UpToDate.com states mild symptoms occur in 5 to 15% of the population and notes it is difficult to be sure because of survey methods and the subjectivity of the symptoms.

Causes of restless legs syndrome

There are two types of restless legs syndrome—primary and secondary. Primary is termed idiopathic RLS and the cause is not known definitively. It is believed to involve three overlapping factors.

The first factor involves the area of the brain’s nigrostriatal dopaminergic system. Dopamine is a neurotransmitter involved in movement and mood regulation.  Dysregulation of the dopamine system may be involved in pathogenesis of RLS as it is in Parkinson’s Disease.

The second factor involved in primary RLS is the regulation of iron. Brain imaging and autopsies have revealed low concentrations of iron in the brains of individuals afflicted with restless legs syndrome. The link between these two factors is the finding that there are fewer receptors for iron in the brain region that is responsible for making the neurotransmitter dopamine.

The third factor is genetics. This finding was based on the family history of patients suffering from primary restless legs syndrome revealing a first degree family member who also was afflicted with primary RLS. Scientists have narrowed down three or four different regions on different chromosomes as the potential sites for a genetic link to primary restless legs syndrome, but have not identified the exact gene or genes responsible. Some classify RLS in two categories: (1) the inherited type that shows up in people under age 45 (and sometimes even in children), and (2) the type that does not run in families that shows up when the patient is over 45 years old.

A genome study found several genes associated with RLS, and that “each genetic variant was associated with a more than 50% increase in risk for RLS”. Biochemically, protein tyrosine phosphatase receptor type delta is highly prevalent in people with RLS.

Peripheral neuropathy, a common nervous system disorder that is related to many medical conditions, may be related.  It is worth noting that the circulatory system does not appear to be a factor. RLS is not associated with increased risk of cardiovascular disease.

The other form of RLS called secondary RLS is usually as a result of another problem such as renal failure or normal pregnancy causing secondary restless legs syndrome.

Nobody knows for sure why RLS is more common in women, although there may be a tie-in with the endocrine system.  At older ages, the disparity between women and men declines.  It has also been found that RLS patients are much more prone to depression

Restless legs syndrome during and after pregnancy and its relation to snoring.

Rates of RLS and PLMS run higher in people with sleep-disordered breathing. Interestingly, doctors and patients have observed that CPAP treatment seems to help with RLS symptoms, although no one knows why. RLS is also thought to contribute to the persistent fatigue apnea patients sometimes have.

Treatment

RLS treatment poses an interesting cost-benefit case because the symptoms are often not debilitating for many people while the drugs used to control them are powerful neurological agents.

The American Academy of Sleep Medicine says people should be treated for RLS only if they meet specific diagnostic criteria and if they have excessive daytime sleepiness because of their RLS. Chronic RLS with two or more occurrences per week qualifies for treatment as does intermittent RLS if the outbreaks are severe enough.

Until 2005 there was no FDA-approved drug to treat RLS. In 2005 the Parkinson’s Disease drug ropinirole (Requip) which helps to increase the amount of dopamine in the brain, was approved to treat RLS. Pramipexole (Marapex) is another Parkinson’s Disease drug also used to treat RLS. The dopamine agonist pergolide is also an option as is Levodopa.  If the patient responds to the dopamine agonists, this helps clarify a solid diagnosis of RLS assuming the person does not have other symptoms related to Parkinson’s disease.

A meta-analysis published in the journal Sleep found “differences in efficacy and tolerability favouring pramipexole over ropinirole can be observed.”  These drugs are taken orally, although there has been interest in transdermal patches for controlled dosing. Binding of the legs has been attempted and works by some measures, but patients find it oppresive and it does nothing to remove the underlying problem.

Iron deficiency is a contributing factor in restless legs syndrome and if the case is mild and blood tests indicate a low iron level, iron supplementation can reverse the symptoms. The anti-seizure drug gabapentin has also been prescribed.

The benzodiazepine clonazepam is prescribed in some countries for RLS.  It is not approved by the US FDA for this condition, and US doctors do not often prescribe it. Opioids are sometimes prescribed in severe cases, but there is a dependency danger with them.

Physical restraint of the legs has been tried with the idea that this will help reduce the feeling the patient experiences. This therapy might have some efficacy, but it is not widely employed.

The federal government’s Effective Health Care Program published its Comparative Effectiveness of Treatments for Restless Legs Syndrome. The European Restless Legs Syndrome Study Group likewise published its “algorithms for the diagnosis and treatment of restless legs syndrome”.

There are speculations about a tie, or common pathogenesis, between RLS and Parkinson’s disease.  While the treatment methods have parallels, there is no firm evidence about a relationship.

Allegations of “disease mongering”

RLS first was described in scientific literature in 1672! But marketing of medications for restless legs syndrome has drawn criticism that it is a form of disease mongering – persuading healthy people that they are sick and need medicine. RLS is recognized as a real condition by the bulk of the medical community, but the fear is that these advertisements will make people think they have RLS even when they don’t. Just because your legs move in bed doesn’t mean you have this condition. Discuss you situation with your doctor in detail in order to get a better picture of whether you should be concerned about RLS.

A Misnomer

Restless Legs Syndrome is among the most mis-named of sleep disorders. The limbs aren’t technically restless, just afflicted with weird feelings.  It doesn’t just affect the legs, and it isn’t a syndrome any more.  A syndrome is what the medical world calls a cluster of symptoms with no known explanation.  At one time syndrome was the correct word for this phenomenon, but medical science has learned enough that it can no longer rightfully be classified as a syndrome. The International Restless Legs Study Group (IRLSSG) – a group of scientists interested in this field – voted in 2010 to change the condition’s name to Willis-Ekbom Disease.  Whether this new name will stick in the popular and scientific literature remains to be seen.

Additional Resources:

Essay: Giving Legs to Restless Legs: A Case Study of How the Media Helps Make People Sick

References:

  • Pichler, I., Hicks, A., Pramstaller, P., 2008, Restless Legs Syndrome: An Update on Genetics and Future Perspectives, Clinical Genetics, 73:297-305
  • Ball, E. and Caivano, C., 2008, Internal Medicine: Guidance to the Diagnosis and Management of Restless Legs Syndrome, Southern Medical Journal, 101(6):631-634
  • Baker, W., White, C., Coleman, C., 2008, Effect of Nonergot Dopamine Agonist on Symptoms of Restless Legs Syndrome, Annals of Family Medicine, 6(3):253-262
  • Saletu, B., Gruber, G., Saletu, M., Brandstatter, N., Hauer, C., Prause, W., Ritter, K., Saletu-Zyhlars, G., 2000, Sleep Laboratory Studies in Restless Legs Syndrome Patients as Compared with Normals and Acute Effects of Ropinirole, Neurophsychobiology, 41:181-189
  • Winkelman, J., Allen, R., Tenzer, P., Hening, W., 2007, Restless Legs Syndrome: Nonpharmacologic and Pharmacologic Treatments, Geriatrics, 62(10):13-17
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