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Age-at-onset in restless legs syndrome: A clinical and polysomnographic study.

Whittom S, Dauvilliers Y, Pennestri MH, Vercauteren F, Molinari N, Petit D, Montplaisir J.

Sleep Disorders Center, Centre d’étude du sommeil et des rythmes biologiques, Hôpital du Sacré-Coeur de Montréal, 5400 boul. Gouin Ouest, Montréal, Que., Canada H4J 1C5; Department of Psychology, Université de Montréal, Canada.

OBJECTIVE: To determine the distribution of age-at-onset in a large cohort of patients with restless legs syndrome (RLS) and to compare clinical and polysomnographic characteristics of patients with early and late age-at-onset of RLS. METHODS: Two hundred and fifty patients with RLS were studied. Information on age-at-onset, etiology, familial history and symptoms severity of RLS was obtained. Age-at-onset density functions were determined from bootstrap methods and kernel density estimators. RESULTS: Age-at-onset showed a significant bimodal distribution with a large peak occurring at 20years of age and a smaller peak in the mid-40s. Early- and late-onset RLS could be separated with a cut-off at 36years of age. Distributions of age-at-onset differed as a function of presence/absence of a familial history and etiology of RLS. Age-at-onset clearly differentiated patients with a primary RLS (early onset) from those with secondary RLS. Finally, early-onset RLS was associated with increased RLS severity with higher indices of periodic leg movements in sleep (PLMS) associated with microarousals and periodic leg movements during wakefulness (PLMW). CONCLUSIONS: Early- and late-onset RLS could be distinguished depending on familial history and etiology of RLS. Our data suggest that different pathological processes are involved in these two groups, the early-onset group being highly genetically determined.

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Restless Leg Syndrome affects an estimated 2.7% of the general population in the U.S.A..

Often sufferers think they are the only ones to be afflicted by this peculiar condition and are relieved when they find out that many others also suffer from it. The severity and frequency of the disorder vary tremendously. Many people only experience symptoms when they try to sleep, while others experience symptoms during the day. It is common to have symptoms on long car rides or during any long period of inactivity (like watching television or a movie, attending a musical or theatrical performance, etc.) Approximately 80-90% of people with RLS also have PLMD, Periodic Limb Movement Disorder, which causes slow “jerks” or flexions of the affected body part. These occur during sleep (PLMS = Periodic Limb Movement while Sleeping) or while awake (PLMW - Periodic Limb Movement while Waking).

About 10 percent of adults in North America and Europe may experience RLS symptoms, according to the National Sleep Foundation, which reports that “lower prevalence has been found in India, Japan and Singapore,” indicating that ethnic factors, including diet, may play a role in the prevalence of this syndrome

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RLS can result in:

• Restlessness – An inability to sit still because the leg sensations are too annoying or painful
• Insomnia – Difficulty falling asleep or staying asleep
• Daytime sleepiness

Restless Legs Syndrome is most common in:

• Middle-aged or older people
• Women, slightly more than men
• Pregnant women during last months of pregnancy
• Relatives of people who have RLS

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Study suggests cause for restless legs syndrome Chicago, Ill. — Restless legs syndrome (RLS) may sound like something right out of a 1950s horror flick. And for some sufferers, it is. This affliction causes an irresistible urge to move the legs often accompanied by creepy-crawly sensations in the legs. The sensations are only relieved by movement, and become worse as the sun goes down. Night after night this sleeplessness occurs for the millions who suffer with RLS and their partners. Because little is known about what causes RLS, researchers at Penn State College of Medicine and Johns Hopkins University went looking for answers. The team, led by James Connor, Ph.D., professor and interim chair, Department of Neuroscience and Anatomy, Penn State College of Medicine, performed the first-ever autopsy analysis of the brains of people with RLS. This research, presented June 5 at the Association of Professional Sleep Societies meeting in Chicago, uncovered a possible explanation for this syndrome. “We found that, although there are no unique pathological changes in the brains of patients with RLS, it appears that cells in a portion of the mid-brain aren’t getting enough iron,” Connor said. “It was a relief to many that there was no neurodegeneration, or loss or damage of brain cells, like we see in Parkinson’s and Alzheimer’s disease.” The discovery of a physical cause for this disorder establishes it as a sensory motor rather than a psychological disorder. Because cells aren’t lost or damaged but rather iron-deficient, there is more hope that treatments can be developed. For the study, Connor examined brain tissue acquired through the Restless Legs Syndrome Foundation’s brain collection at the Harvard Brain Bank. Tissue from seven people with RLS was examined and five samples from people with no neurological conditions served as controls. Cross-sectional slides of the substantia nigra, the portion of the middle brain thought to play a role in RLS, allowed the research team to thoroughly examine the cells’ structures and functions. To avoid bias, during examination, the investigator did not know whether the sample was that of a patient with or without RLS. Although it’s been long-suspected that iron deficiency had something to do with RLS, Connor’s study found that a specific receptor for iron transport is lacking in patients with RLS. When that mechanism malfunctions, enough iron gets into the brain cells to keep them alive, but not enough so that they function optimally. That missing iron may cause a misfiring of neural signals to the legs creating the creepy-crawly feelings. “This doesn’t necessarily mean that a person has dietary iron-deficiency and needs supplements,” Connor said. “It means only that these receptors aren’t packaging and delivering an adequate amount of iron to the specific cells in this portion of the brain.” This explains why some patients find temporary relief from iron supplements, but it is important that any supplementation therapy be managed by a physician. Although not FDA-approved for the treatment of RLS, a few prescription drugs, which have been approved for other conditions, have temporarily relieved symptoms in some patients. One such drug is that used in Parkinson’s disease to calm tremors. The cells in the brain in RLS that are iron deficient are the cells that make the neurotransmitter dopamine. Dopamine synthesis requires iron and this is the likely reason that small amounts of the drugs that are used to treat Parkinson’s patients can be effective in RLS. Connor’s next step is to continue to pinpoint other potential breakdowns in the iron packaging and transport system to this part of the brain, including the genes that regulate the iron transport proteins. “We hope these discoveries lead to a test that could diagnose this syndrome, and a potential target for a therapy to bring long-term relief to those suffering with restless legs syndrome,” Connor said. This study was funded in part by grants from the National Institutes of Health and the Restless Legs Syndrome Foundation. Other members of the research team were: P.J. Boyer, M.D., Ph.D., Departments of Neuroscience and Anatomy, and Pathology, S. L. Menzies, Department of Neuroscience and Anatomy, and B. Dellinger, Department of Pathology, Penn State College of Medicine, Penn State Milton S. Hershey Medical Center; R.P. Allen, Ph.D., Department of Neurology, Johns Hopkins Bayview Medical Center; W.G. Ondo, M.D., Department of Neurology, Baylor College of Medicine, Houston; C.J. Earley, M.D., Ph.D., Department of Neurology, Johns Hopkins Bayview Medical Center.

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Restless Leg Syndrome affects an estimated 2.7% of the general population in the U.S.A..

Often sufferers think they are the only ones to be afflicted by this peculiar condition and are relieved when they find out that many others also suffer from it. The severity and frequency of the disorder vary tremendously. Many people only experience symptoms when they try to sleep, while others experience symptoms during the day. It is common to have symptoms on long car rides or during any long period of inactivity (like watching television or a movie, attending a musical or theatrical performance, etc.) Approximately 80-90% of people with RLS also have PLMD, Periodic Limb Movement Disorder, which causes slow “jerks” or flexions of the affected body part. These occur during sleep (PLMS = Periodic Limb Movement while Sleeping) or while awake (PLMW - Periodic Limb Movement while Waking).

About 10 percent of adults in North America and Europe may experience RLS symptoms, according to the National Sleep Foundation, which reports that “lower prevalence has been found in India, Japan and Singapore,” indicating that ethnic factors, including diet, may play a role in the prevalence of this syndrome

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 About 47 million Americans are sleep deprived while doctors report the average adult should snooze for about six hours a night.

However, catching some “Z’s” might be hard if you have a medical condition like restless leg syndrome (RLS).

Experts on sleep disorders are meeting this week at the Minneapolis Convention Center to talk about the latest technology.

One new invention is helping people understand what it’s like for patients with RLS. The invention is called a restless leg syndrome simulator and it’s a big boot that mimics the horrible symptoms that RLS patients feel.

“It’s described as a burning, itching, pulling, drawing sensation, and it’s better when they get up and walk and it’s worse when they’re resting,” said Dr. Patrick Wright with the Minnesota Sleep Institute in Minneapolis.

Up to 10 percent of the U.S. population may have this neurological condition. It makes it hard for patients to fall asleep and get an entire nights sleep.

“Often we find that people with RLS because of their symptoms are unable to sleep, and the symptoms sometimes don’t become alleviated until late very into the night, sometimes, the early morning,” said Katherine O’Connor with Boehringer Ingelheim, the maker of the simulator.

“Restless legs during the day, may equal periodic limb movements or leg kicking at night and that disturbs their sleep and then they’re tired the next day,” said Wright.

The simulator also visually shows the drowsy effects of a sleep deprived person. However, it’s hard to really to imagine what the condition is like unless you step into the shoes of a RLS suffer.

“It does give a sensation of buzzing or tingling in your legs, which is what many patients describe,” said Wright.

There is no known cause for RLS, but there are some things you can do to help with the sometimes painful symptoms.

“Trying to avoid caffeine helps, exercise is helpful, hot baths are helpful, but when we gets beyond the point of that, then we need to use some medication,” said Wright.

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What treatments are available for Restless Legs Syndrome?

Although no cure exists for Restless Legs Syndrome, different types of treatment can be used to manage the condition and relieve discomfort.

There are three treatment approaches for RLS:

• Self-help (see below) - If your symptoms are mild, self-help may be sufficient treatment.
• Medications (see below) - For those with severe RLS, where the disorder disrupts sleep or daily activities, medications may be the proper treatment approach.
• Treatment of the underlying condition – If your Restless Legs Syndrome is caused by an underlying condition, your doctor will treat that condition. Treatment of the underlying condition often cures the RLS.

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