Restless legs syndrome, which causes an irresistible desire to move legs, appears to be a hereditary condition that’s more prominent among French Canadian women and may be caused by a combination of genetic influences and environmental effects. According to a large-scale study published in the Archives of Neurology, siblings of people affected by restless legs syndrome are three and a half times more likely to develop the disease.

The investigation, which builds on previous research that suggested the ailment is clustered in families, is the work of scientists from the University of Montreal, Sainte-Justine University Hospital Research Center, University of Montreal Hospital Research Center, Hôpital du Sacré-Cœur de Montréal, Montreal Heart Institute, Douglas Mental Health University Institute and McGill University.

“Until now, there has been a lack of large-scale, systematic and clinical studies precisely measuring the degree of heritability of restless legs syndrome in families – information that is critical if we are to advance genetic studies and discover the cause of this condition,” says senior author Guy Rouleau, a professor at the University of Montreal Faculty of Medicine, director of the Sainte-Justine University Hospital Research Center and a scientist at the University of Montreal Hospital Research Center.

The research team studied 671 individuals diagnosed with restless legs syndrome in Quebec, Canada: 192 who were assessed at the Hôpital du Sacré-Cœur de Montréal sleep center and 479 affected family members who responded to diagnostic interviews. In cases where one family member was diagnosed with restless legs syndrome, the condition appeared in 77 percent in other family members who participated in the study. By age 60, siblings of an individual with the condition were about 3.6 times more likely to have restless legs syndrome compared to people without an affected sibling. Offspring of parents with the condition had 1.8 times the risk of developing restless legs syndrome by the age of 40.

“Restless legs syndrome is prevalent in 10 to 15 percent of French-Canadians, yet the neurological disorder is often misdiagnosed. Restless legs syndrome is a chronic disorder with an average of 24 years of suffering, affects people of all ages and usually begins before the age of 30. Most family members who are diagnosed with the disease experience moderate symptoms of restless legs syndrome,” says first author says Lan Xiong, a Université de Montréal researcher. “Our findings indicate that familial restless legs syndrome is more prominent among female relatives, particularly those who also have anemia or iron deficiency conditions, and who have multiple pregnancies.”

The research team suggested that restless legs syndrome clusters in families due to genetic influences, environmental effects or the combination of both. “The cumulative total of family members affected by restless legs syndrome should be of interest to all concerned physicians, geneticists and epidemiologists,” says Dr. Rouleau. “We also recommend that scientists and clinicians further examine how environmental risk factors, combined with genetic predisposition, may contribute to the occurrence of restless legs syndrome in families.”

Source: Sylvain-Jacques Desjardins, University of Montreal via EurekAlert

New data presented at the 62nd American Academy of Neurology annual meeting in Toronto, Canada, showed that patients with moderate to severe Restless Legs Syndrome (RLS) using rotigotine achieved sustained improvements in symptoms over 5 years of treatment[1].

“Many people with RLS will have spent months or years trying to get a diagnosis and find a treatment that can help them. So these 5-year results provide additional evidence that once they start using rotigotine people with RLS may experience long term relief from their symptoms, and a significant proportion may become symptom free,” said Diego Garcia-Borreguero, MD, Director Sleep Research Institute, Madrid, Spain.

This study of rotigotine in patients with moderate to severe RLS was the longest ever open label prospective follow-up of a placebo-controlled phase II trial in RLS. The final 5-year results confirm the safety and efficacy of rotigotine seen at previous interim analyses[2,3], with over a third of patients followed up remaining symptom free after five years of treatment.

Of the 295 patients with moderate to severe RLS who entered the study, 126 (43%) completed the 5-year follow up. The mean dose of rotigotine was 2.43mg/24 hours after initial titration and 3.09mg/24 hours at the end of the study. Fifty nine per cent of patients were classified as remitters (IRLS< 10), and 39% as symptom-free (IRLS=0).

The study looked at improvement in symptoms based on the International Restless Legs Syndrome Study Group Rating Scale (IRLS)[4]*. The total IRLS score ranges from 0 (no symptoms) to 40 (very severe symptoms). A score of >20 indicates severe RLS. The mean IRLS* score was 27.8 at baseline, improving by 18.7 points to 9.0 at the end of the study. Sustained improvements were also seen in quality of life and other RLS rating scales.

Most adverse events (AEs) were mild to moderate in intensity, the most common AEs being application site reactions (58%), nasopharyngitis (19%), back pain (14%), nausea (12%) and fatigue (11%). Thirty per cent of patients discontinued the study due to an AE.

A comparison of 1, 2 and 5-year efficacy data (with 220, 191 and 126 patients respectively) showed that improvements in RLS symptoms remained stable throughout the follow-up period. Improvements in IRLS scores were 17.4 points at 1 year[2], 17.2 points at 2 years[3], and 18.7 points at 5 years[1].

* The International Restless Legs Syndrome Study Group Rating Scale (IRLS)[4] is a ten-item scale developed and validated by The International Restless Legs Syndrome Study Group and considered to be the best scale for evaluating the severity and frequency of RLS symptoms and the degree to which they affect sleep and daily life. It is administered by clinicians and includes questions related to the severity of sensory and motor symptoms, sleep disturbance, daytime somnolence and impact of RLS on activities of daily living and mood.

Source: UCB

These interim results from the FREEDOM study compared patients’ responses to the Medical Outcomes Study (MOS) Sleep Survey and the International RLS Study Group Rating Scale (IRLS) at baseline and four months. Specifically, significant improvements identified in this planned interim analysis included:

• Overall sleep quality (as measure by the MOS Sleep Problems Indices I and II) significantly improved from baseline to month four. (Index I: P=<0.001; Index II: P<0.0001)
• Four of the 5 individual sleep scale s- sleep adequacy, daytime somnolence (or “drowsiness”), sleep initiation and maintenance, and respiratory disturbances displayed significant improvement.
• There was a significant reduction in the number of patients reporting RLS at 4 months compared to baseline. (P=0.02)
• Of those patients who experienced RLS at baseline (n=58), 36% no longer experienced RLS at month four.

Dr. Brigitte Schiller, MD, Acting Chief Medical Officer and Vice President of Scientific Affairs for Satellite Healthcare headquartered in Mountain View, CA, is one of the presenters of FREEDOM study data during the 30th Annual Dialysis Conference in Seattle.

“Various studies suggest a high prevalence of sleep-related disorders and RLS, among End-stage Renal Disease (ESRD) patients. These interim results from the ongoing FREEDOM study demonstrate the positive impact of daily home hemodialysis on these disorders, which can have a significant impact on patients’ quality of life,” says Dr. Schiller. “Quality sleep is essential, and to ESRD patients in particular, as it has been proven to affect other areas of patients’ overall health. Although these findings are only at four months, longer-term follow up is underway to determine whether the positive impact of daily home dialysis on sleep patterns and RLS persists at one year.”

“NxStage continues to invest in proving the wide range of clinical and quality of life benefits possible with more frequent hemodialysis,” says Jeff Burbank, CEO of NxStage Medical, Inc. “These results add to the growing evidence supporting daily home hemodialysis with our System One versus conventional, thrice-weekly in-center therapy.”

The ongoing FREEDOM study is the largest study of its kind to measure the clinical and economic benefits of daily home hemodialysis treatment, as compared to conventional, thrice-weekly in-center hemodialysis treatment for patients requiring dialysis therapy. All daily home hemodialysis patients in the FREEDOM study use the NxStage System One as their treatment delivery system, and all have Medicare as their primary insurance payer.

About NxStage Medical

NxStage Medical, Inc. (Nasdaq: NXTM) is a medical device company, headquartered in Lawrence, Massachusetts, USA, that develops, manufactures and markets innovative products for the treatment of End Stage Renal Disease (ESRD) and acute kidney failure.

Forward-Looking Statements

This release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this release that are not clearly historical in nature are forward-looking, and the words “anticipate,” “believe,” “expect,” “estimate,” “plan,” and similar expressions are generally intended to identify forward-looking statements. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors including those that are discussed in NxStage’s filings with the Securities and Exchange Commission, including the Quarterly Report on Form 10-Q for the quarter ended September 30, 2009. NxStage is under no obligation to (and expressly disclaims any such obligation to) update or alter its forward-looking statements, whether as a result of new information, future events or otherwise.

Source: NxStage Medical, Inc

Results show that erectile dysfunction was 16 percent more likely in men with RLS symptoms that occur five to 14 times per month (odds ratio of 1.16) and 78 percent more likely in men whose RLS symptoms occur 15 or more times a month (OR=1.78). The associations were independent of age, body mass index, use of antidepressants, anxiety and other possible risk factors for RLS. Fifty-three percent of RLS patients and 40 percent of participants without RLS reported having erectile dysfunction, which was defined as a poor or very poor ability to have and maintain an erection sufficient for intercourse.

The results suggest it is likely that the two disorders share common mechanisms, said lead author Xiang Gao, MD, PhD, instructor at Harvard Medical School, associate epidemiologist at Brigham and Women’s Hospital and research scientist at the Harvard School of public health in Boston, Mass.

“The mechanisms underlying the association between RLS and erectile dysfunction could be caused by hypofunctioning of dopamine in the central nervous system, which is associated with both conditions,” said Gao.

Data were collected from 23,119 men who participated in the Health Professionals Follow-up study, a large ongoing U.S. cohort of male dentists, optometrists, osteopaths, podiatrists, pharmacists and veterinarians. Participants were between the ages of 56 and 91 years, with a mean age of 69 years. To reduce possible misclassification of RLS, participants with diabetes and arthritis were excluded.

Participants were questioned in 2002 about RLS diagnosis and severity based on the International RLS study group criteria. RLS was defined as having unpleasant leg sensations combined with restlessness and an urge to move; with symptoms appearing only at rest, improving with movement, worsening in the evening or at night compared with the morning, and occurring five or more times per month.

About four percent of participants had RLS (944 of 23,119 men), and about 41 percent (9,433 men) had erectile dysfunction. Men with RLS were older and were more likely to be Caucasian. The prevalence of erectile dysfunction also increased with age.

The authors noted that the association between RLS and erectile dysfunction also could be related in part to other sleep disorders that co-occur with RLS. For example, obstructive sleep apnea and sleep deprivation may decrease circulating testosterone levels.

They also pointed out that the cross-sectional design of the study did not allow for a determination of causality. Further epidemiological studies are needed to clarify the relationship between the RLS and erectile dysfunction and to explore the biological mechanisms underlying the association.

Sleep is the official journal of the Associated Professional Sleep Societies, LLC (APSS), a joint venture of the American Academy of Sleep Medicine and the Sleep Research Society. The APSS publishes original findings in areas pertaining to sleep and circadian rhythms. Sleep, a peer-reviewed scientific and medical journal, publishes 12 regular issues and 1 issue comprised of the abstracts presented at the SLEEP Meeting of the APSS.

For a copy of the study, “Restless Legs Syndrome and Erectile Dysfunction,” or to arrange an interview with an AASM spokesperson, please contact Kelly Wagner, AASM public relations coordinator, at (708) 492-0930, ext. 9331, or kwagner@aasmnet.org.

AASM is a professional membership organization dedicated to the advancement of sleep medicine and sleep-related research. As the national accrediting body for sleep disorders centers and laboratories for sleep related breathing disorders, the AASM promotes the highest standards of patient care. The organization serves its members and advances the field of sleep health care by setting the clinical standards for the field of sleep medicine, advocating for recognition, diagnosis and treatment of sleep disorders, educating professionals dedicated to providing optimal sleep health care and fostering the development and application of scientific knowledge.

Source: Kelly Wagner, American Academy of Sleep Medicine

“There are significant ethnic differences in the prevalence of restless legs syndrome, but the exact causes of higher prevalence among Caucasians are unknown,” said Ammar Alkhazna, MD, University of Missouri, Kansas City, MO. “This likely reflects a combination of factors, including a genetic predisposition to RLS, diet — including iron intake — medications, and possibly culture.”

To determine the incidence of RLS among AA and NAA patients, Dr. Alkhazna and his colleagues analyzed standardized interview responses from 190 patients seen at a primary clinic. Of the patients, 103 were AA (42 percent were men) and 87 were NAA, of which 40 percent were men and the majority were Caucasians. Among AA, the diagnosis of RLS was definite in 12 percent of patients, while among NAA, the diagnosis of RLS was definite in 36 percent. In the AA group, the prevalence of RLS was 12 percent for both genders. In the NAA group, the prevalence of RLS among men was 29 percent and 40 percent among women.

“Some risk factors for restless legs syndrome appear to be more common among women,” said Dr. Alkhazna. “Women are more likely to be iron deficient than men and have rheumatoid arthritis, which are known risk factors for RLS.”

Researchers also found that the overall prevalence of definite RLS was 23 percent, which is significantly more than many previous studies have reported at 3 to 10 percent. Dr. Alkhazna explains that this increased prevalence of RLS could be attributed to the specific study population.

“We believe our study results reflect at least our clinic’s patient population. Because our patient population is multiracial and quite diverse, we expect our results would be similar in other large, urban centers with similar pools of patients,” said Dr. Alkhazna. “However, as many diseases and medications can lead to the development of restless legs syndrome, there will likely be a difference between populations attending medical clinics as opposed to those who are well and healthy.”

“Restless legs syndrome is a common sleep disorder that may not be easily recognized by patients and clinicians,” said Kalpalatha Guntupalli, MD, FCCP, President of the American College of Chest Physicians. “Educating clinicians and patients about the signs and symptoms of RLS may raise awareness about this overlooked condition and lead to earlier diagnosis and treatment.”

CHEST 2009 is the 75th annual international scientific assembly of the American College of Chest Physicians, held October 31-November 5 in San Diego, CA. The ACCP represents 17,400 members who provide patient care in the areas of pulmonary, critical care, and sleep medicine in the United States and throughout the world. The ACCP’s mission is to promote the prevention and treatment of diseases of the chest through leadership, education, research, and communication.

Source: American College of Chest Physicians

The 12 week study involved 58 people with RLS. Of the group, 30 people received the drug pregabalin and the rest received placebo. Sleep studies were performed at the beginning and end of the research.

Researchers found nearly two-thirds of the people who took pregabalin had no RLS symptoms while taking the drug. For people who still had symptoms, those symptoms had improved by 66 percent while taking the drug, compared to the placebo group where symptoms worsened by 29 percent.

Sleep also improved for those taking pregabalin. The study showed the group spent more time in slow wave sleep, otherwise known as Stage 3 or deep sleep, and they spent less time in the lighter sleep stages known as Stage 1 or Stage 2 sleep compared to those taking placebo.

“Since RLS symptoms get worse at night, it’s difficult for people with RLS to get adequate sleep,” said study author Diego Garcia-Borreguero, MD, Director of the Sleep Research Institute in Madrid, Spain. “However, our findings show pregabalin helped people get more deep sleep. The drug was well tolerated and is a promising alternative to current treatments because of its superior effects on quality of sleep.”

Pregabalin has been approved for epilepsy, nerve pain, generalized anxiety and fibromyalgia.

RLS is characterized by an urge to move the legs, generally accompanied by unpleasant numbness, tingling, or burning sensations; an increase in symptoms during rest and a partial, temporary relief from symptoms through activity; and a worsening of symptoms in the evening or at night. Symptoms tend to progress with age.

Source: American Academy of Neurology

If you have RLS (restless legs syndrome) you have a disorder which causes a strong urge to move your legs. This urge is frequently accompanied with strange and unpleasant sensations in your legs. Patients say the only way to relieve those unpleasant feelings is to move their legs.

The following words are from patients as they describe the unpleasant feelings in their legs which trigger their urge to move them:

• Aching
• Burning
• Crawling
• Creeping
• Electric shocks
• Itching
• Tugging
• Tingling

Some patients experience those sensations in their arms as well.

A significant number of patients say the sensations occur when they are resting or inactive, and not exclusively after they go to bed. Symptoms tend to worsen in the evening and at night, and are often relieved for a short while in the morning.

Periodic Limb Movement Disorder (PLMD)

The patient’s leg twitches or jerks uncontrollably about every 10 to 60 seconds. It usually occurs during sleep and is considered to be a type of sleeping disorder. PLMD makes the sufferer wake up frequently during the night, this undermines the quality and length of sleep. Most people with RLS have PLMD.

Restless legs syndrome can affect sleep

The majority of patients with RLS find it hard to fall asleep, and when they do, they find it difficult to stay asleep throughout the night. Consequently, many RLS sufferers find they are tired and sleepy during the day. Irregular and insufficient sleep can affect the patient’s ability to learn, work, concentrate, and carry out normal routine tasks and activities. Lack of sleep can eventually lead to mood swings, irritability, depression, an undermined immune system, and other physical and health problems.

RLS is classed from mild to severe.

This depends on:

• How often the symptoms occur
• How severe the symptoms are
• How effective moving around is in relieving the symptoms
• The degree of sleep disturbance suffered

There are two main types of Restless Legs Syndrome

RLS may be triggered by other conditions and diseases

The following diseases and symptoms have been known to trigger RLS:

• Diabetes
• Iron deficiency
• Kidney failure
• Parkinson disease
• Peripheral neuropathy
• Pregnancy
• Rheumatoid arthritis

When the RLS is triggered by a disease or condition the symptoms will start abruptly – there is not a gradual onset. Patients with the type of RLS that usually starts later in life will experience worse symptoms if the RLS is triggered by a medical condition or because they are taking certain medications.

What is the outlook for a Restless Leg Patient? What is the prognosis?

Symptoms of RLS generally worsen over time. Some people, however, may experience weeks or months without any symptoms at all.

If the RLS has been triggered by a condition, illness or medication, it may go away as soon as the trigger has gone, or has been relieved. Women who get RLS during their pregnancy tend to get better as soon as their baby is born. RLS patients who had kidney failure and then a kidney transplant will generally get better after the transplant (just dialysis will not usually relieve RLS).

What is the treatment for Restless Legs Syndrome?

Treating an underlying condition

If the underlying condition/illness that triggers the RLS is treated, the RLS might either go away or improve – this is especially the case with iron deficiency and peripheral neuropathy.

Lifestyle changes and OTC medications

Some simple lifestyle changes and OTC (over-the-counter) medications may help alleviate RLS symptoms, such as:

• Painkillers – if symptoms are very mild, ibuprofen has been found to relieve patients’ symptoms.
• Warm baths – relaxing in a warm bath and massaging your legs may help relax your muscles and reduce the intensity of symptoms
• Warm or cool packs – some patients prefer warm packs, other find cool packs work better, while some say that alternating from hot-cold-hot works best.
• Relaxation techniques – experts say that stress can make RLS worse. Relaxation techniques, such as Yoga and Tai Chi are known to help RLS patients enormously.
• Sleep routine and environment – RLS patients who are tired tend to experience worsened symptoms. A cool and quiet bedroom helps people sleep better. Go to bed at the same time every night, and get up at the same time every morning. Many patients say they have managed to get a better night’s sleep by going to bed a bit later.
• Exercise and physical activity – exercise can help RLS, but can also make it worse. The majority of patients comment that moderate exercise helps symptoms a lot, while too much exercise sometimes makes them worse. Many also say that working out late in the evening does not help them.
• Caffeine – some patients have found that their symptoms improve if they either cut back on caffeine or stop consuming it altogether. Drinks containing coffee, tea, chocolate and many sodas have caffeine in them. If abstaining from caffeine helps relieve symptoms, it will do so usually after a few weeks – so, it is important to persevere.
• Alcohol – some patients have found that either cutting down on alcohol or abstaining completely helps.
• Tobacco – this can be an RLS trigger for some people. So, either cutting down or giving up smoking altogether may help.

Medication

When other therapies have not worked, the doctor may prescribe medication for RLS. A doctor may prescribe one of the medicines below, or a combination – this depends on the individual patient.

• Alpha 2 agonists – these may help in cases of primary RLS, but will have no effect on periodic limb movement during sleep. They are used to stimulate the alpha 2 receptors in the brain stem. Alpha 2 agonists activate neurons that make the part of the nervous system that controls muscle movement and sensations less active. Catapres (clonidine hydrochloride) is an Alpha 2 agonist.
• Anticonvulsants – these are for patients who experience pain, neuropathy, or have symptoms during the daytime. Anticonvulsants are used for treating muscle spasms. Neurontin (gabapentin) is a popular anticonvulsant.
• Benzodiazepines – these (sedative) medications help the patient sleep through the symptoms of RLS. If a patient with RLS has persistent sleeping problems the doctor may prescribe a benzodiazepine. Restoril (temazepam), Xanax (alprazolam), and Konopin (clonazepam) are common benzodiazepines.
• Dopaminergic agents – these raise the levels of dopamine – a neurotransmitter – in the brain. They are used for treating the unpleasant leg sensations experienced by RLS patients. Levodopa and carbidopa are common dopaminergic agents.
• Dopamine agonists – these also raise brain dopamine levels. Some elderly patients may find the side-effects are not worth the benefits. However, dopamine agonists are said to have a smaller probability of side-effects compared to levodopa. Dopamine agonists are used for the treatment of unpleasant leg sensations. Permax (pergolide mesylate), (Parlodel) bromocriptine mesylate, Mirapex (pramipexole), and Requip (ropinirole hydrochloride) are common dopamine agonists.
• Opiates – these are used for treating pain, but they can also relieve RLS symptoms. Doctors may prescribe these when other medications have failed. Codeine and propoxyphene are examples of low dose opiates, while are oxycodone hydrochloride, methadone hydrochloride, and levorphanol tartrate are examples of common high dose opiates. For further information about opioids please visit All About Opioids and Opioid-Induced Constipation (OIC).

Parkinson’s disease and Epilepsy drugs are sometimes used for RLS patients as they can reduce involuntary movements.

Diagnosis of Restless Legs Syndrome

The doctor relies on a good medical history and a physical examination when making a diagnosis. According to Wikipedia, sleep registration in a laboratory (polysomnography) is not necessary for the diagnosis.

When considering the differential diagnosis the doctor should look out for peripheral neuropathy, radiculopathy (conditions which have caused damage to the nerve roots which connect the spine to the rest of the nervous system) and leg cramps – in these conditions the urge to move is less pronounced than the level of pain.

The doctor must also consider akathisia, a side effect of some antidepressants and antipsychotic medications – there is a more constant form of leg restlessness without discomfort or unpleasant sensations.

A Doppler ultrasound evaluation of the vascular system will eliminate any venous disorders, which commonly trigger RLS.

Written by – Christian Nordqvist

It is estimated that 5-10 percent of adults in the United States have RLS and the disorder often has a substantial impact on sleep, daily activities and quality of life.

For the study, researchers questioned 65,554 women and 23,119 men, all of whom were health professionals who took part in the Health Professionals Follow-Up Study or the Nurses’ Health Study II. None of the participants had diabetes, arthritis or were pregnant. Of the groups, 6.4 percent of the women and 4.1 percent of the men were identified as having RLS.

The research found men and women with a body mass index (BMI) score over 30 were nearly one-and-a-half times more likely to have RLS than people who were not obese.

In addition, people who were in the top 20 percent of the group for highest waist circumference were more than one-and-a-half times more likely to have RLS than the bottom 20 percent of the group with the lowest belly size. The results were the same regardless of age, smoking, use of antidepressants or anxiety.

“These results may be important since obesity is a modifiable risk factor that is becoming increasingly common in the U.S.,” said study author Xiang Gao, MD, PhD, with the Harvard School of Public Health in Boston. “More research is needed to confirm whether obesity causes RLS and whether keeping a low BMI score and small waist size could help prevent RLS.”

Gao says some studies suggest that obese people have lower dopamine receptor levels in the brain. “Since decreased dopamine function is believed to play a critical role in RLS as well, this could be the link between the two.” Dopamine is a chemical naturally produced by the body that transmits signals between nerve cells.

The study was supported by a grant from the National Institutes of Health and the National Institute of Neurological Disorders and Stroke.

The American Academy of Neurology, an association of more than 21,000 neurologists and neuroscience professionals, is dedicated to improving patient care through education and research. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as multiple sclerosis, restless legs syndrome, Alzheimer’s disease, narcolepsy, and stroke.

Source: American Academy of Neurology (AAN)

During the last trimester of pregnancy, levels of the estrogenic steroid hormone estradiol were 34,211 pg/mL in women with RLS and 25,475 pg/mL in healthy controls. At three months postpartum, estradiol levels had dropped to 30.73 pg/mL in the RLS group and 94.92 pg/mL in controls. Other hormone levels did not differ significantly between the study groups.

According to the authors the data strongly suggest that estrogens play an important role in RLS during pregnancy. The study also supports previous reports of high RLS incidence in the last trimester of pregnancy when estradiol is maximally elevated.

“Our findings strongly support the concept that neuroactive hormones play a relevant pathophysiological role in RLS,” said principal investigator Thomas Pollmacher, MD, director of the Center for Medical Health at Klinikum Ingolstadt and professor of psychiatry at Ludwig Maximilians University in Munich, Germany. “This information will increase the understanding of RLS in pregnancy and will assist in the development of specific therapeutic approaches.”

The American Academy of Sleep Medicine describes RLS as a sleep-related movement disorder that involves an almost irresistible urge to move the legs at night. This urge tends to be accompanied by unusual feelings or sensations, called “paresthesias,” that occur deep in the legs. These uncomfortable sensations often are described as a burning, tingling, prickling or jittery feeling. RLS can profoundly disturb a person’s ability to go to sleep or return to sleep after an awakening.

The AASM reports that RLS occurs 1.5 to two times more often in women than in men. Eighty percent to 90 percent of people with RLS also experience periodic limb movements (PLMs) during sleep, which are involuntary jerking or twitching movements of the feet or legs.

According to the authors RLS symptoms often occur for the first time during pregnancy. Symptoms typically worsen during pregnancy and improve or even disappear after delivery. The risk of developing RLS increases gradually with the number of pregnancies.

The study also found that women with RLS had more PLMs than controls before and after delivery. PLMs decreased significantly after delivery in women with RLS and stayed low in women without RLS.

Only minor differences appeared between the two study groups in subjective sleep quality and objective sleep measures. One explanation suggested by the authors is that only RLS patients who did not need pharmacological treatment were selected for the study; RLS symptoms of participants were in the mild to moderate range.

The study involved nine healthy pregnant women (mean age 32.9 years) who were placed in a control group and 10 pregnant women (mean age 31.6 years) who fulfilled diagnostic criteria for RLS. Eight women from the RLS group reported symptoms previous to the present pregnancy, and all members of the RLS group described worsening of symptoms during pregnancy. The mean age of onset for RLS symptoms was 22.6 years.

Sleep data and leg movements were recorded during overnight polysomnography around the 36th week of gestation and again at 12 weeks postpartum. Blood samples were taken each morning after the polysomnography and before breakfast. Accompanying questionnaires on sleep and RLS symptoms also were collected.

Journal reference:

Elevated Estradoil Plasma Levels in Women with Restless Legs during Pregnancy. Sleep, Feb 2009

Restless legs syndrome affects between 5 and 11 percent of the population in North America and Europe, says Dr. Lin. The cause may be a number of clinical factors, such as iron deficiency, but it has a strong genetic component as well. “In most people, it is likely due to a number of different causes, but genes are very likely the most important factor in affected families,” he says.

Medications, especially agents that increase transmission of dopamine in brain neurons, are effective in many people and worked for his new patient, says Dr. Lin. “The syndrome may appear as a nuisance for most people, however it can also seriously affect some people’s quality of life,” he says.

Dr. Lin’s patient told him that many of her relatives also have the same trouble sleeping — difficulties she could trace back through her ancestry.

With the patient’s approval, that information was relayed to “gene hunters” in Mayo Clinic’s neurosciences department. These investigators have established an international reputation for their ability to find the genetic roots of rare, as well as common, neurological disorders. Dr. Lin accompanied investigators to Indiana, the hub of the extended family, which is believed to be of English descent, to interview dozens of individuals spanning multiple generations. They found that 30 relatives were affected by restless legs syndrome, and discovered that almost three times as many females had the condition compared to males.

Now, the researchers are reporting in the February issue of Mayo Clinic Proceedings that the restless legs syndrome found in this family is likely due to a gene mutation that has never been linked to the disorder.
To date, five loci, or areas on the genome, have been linked to restless legs syndrome in other families around the world, but this family does not have any of those mutations.

“That means this family likely has a novel gene that is causing the disease,” says the study’s lead investigator, Carles Vilariño-Güell, Ph.D., a neuroscientist at Mayo Clinic’s campus in Jacksonville. The researchers have not yet pinpointed the culprit gene, but say they are getting close.

This study is important, Dr. Vilariño-Güell says, because this family is one of the largest with restless legs syndrome ever studied, and the disorder spans multiple generations. Therefore, the gene linked to the syndrome is widespread among the affected relatives, increasing the chances that the researchers will soon zero in on the gene responsible.

“With so many people in this family affected by the syndrome, we have a lot of power to find the gene mutation causing disease,” he says.

Once a gene is discovered, researchers can investigate its normal function and the mutation’s effect, and then can “try to overcome that problem with drug therapy,” he says. They can also trace the molecular route from the gene mutation to the disorder, and see if the other loci linked to the syndrome lie along this pathway. So far, no one has found a definitive link between restless legs syndrome and a specific gene mutation, but large families hold the clues for these discoveries, says Dr. Vilariño-Güell.

Co-authors of the study include Matthew Farrer, Ph.D., and Zbigniew Wszolek, M.D.

The study was funded by The Mayo Foundation Research Committee, the National Institutes of Health, and the Pacific Alzheimer Research Foundation.

Adapted from materials provided by Mayo Clinic.