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How Would Studying Populations Other Than Those Of European Ancestry Used In This Study Add To What Is Known About Genetic Causes Of Rls

GAR: Considering differential prevalence of RLS across different populations, such as very low prevalence in Asian countries compared to Europe or North America,1 studies in non-European populations would help identify new genetic factors, not only the ones associated with an increased risk of RLS, but also the ones that may decrease the risk or protect from the disease. Therefore, it would expand our knowledge on the genetic and epidemiological background of RLS. 

Guy A. Rouleau, MD, PhD

Btbd9 Map2k5 And Skor1 Expression In Lcl Thalamus And Pons Samples Of Rls Patients With The Corresponding Risk Variants

Given our previous report highlighting the decreased levels of MEIS1 mRNA and protein in LCL and thalamus in RLS cases who carry a MEIS1-risk haplotype, we examined if other RLS GWAS-risk variants,, might also affect the expression of the genes harboring them. For this purpose we used quantitative RT-PCR Taqman assays and biological material to test for variations in the expression levels of these genes in RLS patients with these risk variants, similar to our previous report.

First, we tested the rs3923809 SNP that is located in intron 5 of BTBD9 . When mRNA expression was measured in LCL no significant variations were seen between individuals with G/G, A/G and A/A alleles, though we had access to only four LCL of individuals homozygous for the non-risk allele . Next we measured mRNA levels of two brain regions to further explore the effects of this SNP. On average in the pons and thalamus of RLS patients who were heterozygous carriers of the risk allele there appeared to be an increased level of BTBD9 mRNA, though the distribution of individual samples was too broad to conclude if there was a significant difference between individuals carrying either the A/A or A/G alleles. Moreover, the lack of access to brains from cases homozygous for the G/G allele prevented us from arriving at a conclusion.

Figure 1

Restless Legs Syndrome Brain Stimulation Study Supports Motor Cortex Excitability As A Cause

Press release:

Johns Hopkins Medicine researchers say new experiments using magnetic pulse brain stimulation on people with moderate to severe restless legs syndrome have added to evidence that the condition is due to excitability and hyperarousal in the part of the brain’s motor cortex responsible for leg movement.

The researchers say their findings, published online in Sleep Medicine on May 31, may help devise safer, more effective ways to treat RLS and the chronic sleep deprivation it causes, using electrical or magnetic pulses to calm or interrupt the hyperarousal. Some 10 percent of adults in the U.S. experience RLS at one time or another, and about 1 in 500 report that the condition is severe and chronic enough to interfere with their quality of life, work productivity or mental health, according to the National Sleep Foundation.

People with severe RLS describe symptoms of the condition as an overwhelming urge to move their legs when they are at rest. They may feel pain, or the sensation of soda bubbles in their veins or worms crawling in their legs, with relief coming only when standing or deliberately moving their legs. Long-term effects include fatigue, anxiety and depression, much of it linked to repeated interruption of sound sleep. Standard treatments, which may carry significant side effects, include medications that behave like the neurotransmitter dopamine, opioids and anti-seizure drugs.

Case Control Association Study Of An Additional Snp Near The ~87kb Meis1 Binding Site

An association study including unrelated and consecutively recruited RLS patients in Montreal, Canada and controls of European ancestry, recruited as previously described. The average age at enrollment of RLS patients was 52.5?±?14.9 years, with 38.5% men. Patients were diagnosed based on the international RLS study group criteria. The average age at enrollment of the control population was 53.0?±?16.1 years, with 38.2% men. There is no significant difference in sex and age between the cases and controls. The frequency of the risk allele of rs4776976 is 0.848 in RLS cases and 0.776 in controls, respectively; and the genotype distribution fits with the Hardy-Weinberg equilibrium. The p value for the association test of the C risk allele is 0.0001267. The RLS risk allele of rs4776976 is the most common allele in the European population while the non-risk T allele of rs4776976 is the less frequent ; as observed on gnom Aggregation Database.

We first tested if the rs4776976 SNP might influence SKOR1 expression and so our mRNA expression data was revisited using the two possible genotypes . No significant effect of the risk allele was observed on SKOR1 expression in the LCL, pons or thalamus patient samples.

What Is Restless Legs Syndrome Symptoms Causes Diagnosis Treatment And Prevention

Do you have Restless leg at night? Know what causes it ...

Barbara KeanSanjai Sinha, MD

Restless legs syndrome is a disorder that causes an overwhelming urge to move the legs, usually to alleviate unpleasant sensations.

Also known as Willis-Ekbom disease, RLS occurs when the legs are at rest and is typically most severe in the evening and night, potentially disrupting a person’s sleep and affecting daily activities.

Restless Legs Syndrome: From Pathophysiology To Clinical Diagnosis And Management

  • 1Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • 2Department of Psychiatry, Harvard Medical School, Belmont, MA, United States
  • 3Division of Alcohol and Drug Abuse, Mailman Neuroscience Research Center, McLean Hospital, Belmont, MA, United States

Early Multiple Sclerosis Symptoms: Restless Leg Syndrome Numbness And Weakness

Sensory problems, including restless leg syndrome , numbness and weakness, are the first sign of multiple sclerosis . Sensory problems can occur in 20 to 50 percent of individuals with multiple sclerosis with a condition known as paresthesia. The condition can be caused by prolonged sitting or standing or remaining in a certain position for a long period of time.

Restless leg syndrome is a condition that makes the legs feel tingling when they are at rest and creates an overwhelming sensation to move them. Studies have shown that individuals with MS are three times more likely to experience restless leg syndrome compared to the general population. Cervical cord damage plays a large role in the development of RLS and can occur more in those with multiple sclerosis.

Feelings and sensations of restless leg syndrome include crawling underneath the skin, tingling, burning or creeping. Symptoms may be relieved with movement of the legs, but this relief is temporary. Furthermore, it’s impossible to keep your legs moving constantly, which makes the hours during sleep the most difficult. Many individuals suffer from sleep deprivation when they have RLS.

Weakness in multiple sclerosis can be caused two different ways: It can result from spasms or fatigue or it can result from damaged nerves. The first cause of weakness can result in loss of strength or loss of control of extremities. Due to the second cause of weakness signals may become disrupted and not reach the extremities.

Identification Of Restless Legs Syndrome Genes By Mutational Load Analysis

Clinic for Neurosurgery, University Medical Center, Georg August University Göttingen, Göttingen, Germany

Center of Parkinsonism and Movement Disorders, Paracelsus-Elena Hospital, Kassel, Germany

Munich Cluster for Systems Neurology, Munich, Germany

Max Planck Institute of Psychiatry, Munich, Germany

Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom

Helmholtz Zentrum München GmbH, German Research Center for Environmental Health, Institute of Neurogenomics, Neuherberg, Germany

Munich Cluster for Systems Neurology, Munich, Germany

Department of Neurogenetics and Institute of Human Genetics, Technical University of Munich, Munich, Germany

Address correspondence to

Dr Winkelmann, Department of Neurogenetics, Technical University of Munich, Trogerstrasse 32, D-81675, Munich, Germany; E-mail: and Dr Oexle, Institute of Neurogenomics, Helmholtz Zentrum München GmbH, German Research Center for Environmental Health, Ingolstaedter Landstrasse 1, D-85764, Neuherberg, Germany;

Helmholtz Zentrum München GmbH, German Research Center for Environmental Health, Institute of Neurogenomics, Neuherberg, Germany

Address correspondence to

Clinic for Neurosurgery, University Medical Center, Georg August University Göttingen, Göttingen, Germany

Center of Parkinsonism and Movement Disorders, Paracelsus-Elena Hospital, Kassel, Germany

Munich Cluster for Systems Neurology, Munich, Germany

Address correspondence to

Genetic Association Study Of Restless Legs Syndrome In Chinese Population

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High Levels Of Rare Gut Bacteria May Be Linked To Restless Legs Syndrome

Press release:

SAN ANTONIO – Small intestine bacterial overgrowth may be more prevalent among patients with restless legs syndrome , according to preliminary findings from a small, new study.

Results show that SIBO was found in all seven participants who have RLS. In contrast, the prevalence of SIBO in the general population is estimated to be no more than 15%.

“We’ve observed extremely high rates of small intestinal bacterial overgrowth in the RLS group,” said lead author Daniel Jin Blum, Ph.D., D.B.S.M., an adjunct clinical instructor at Stanford Center for Sleep Sciences and Medicine in Redwood City, California. “Exploring the relationship between RLS and gut microbial health has the potential to open novel avenues for possible detection, prevention and treatment for RLS and other sleep disorders.”

SIBO is a condition in which rare gut-residing bacteria are over-represented in the gut. RLS is a sensorimotor disorder characterized by a complaint of a strong, nearly irresistible urge to move the limbs that is often accompanied by other uncomfortable sensations. These symptoms begin or worsen during periods of rest or inactivity such as lying down or sitting, are partially or totally relieved by movement such as walking or stretching, and occur exclusively or predominantly in the evening or at night.

###

This study was funded by a Pau Innovation Gift Fund Seed Grant.

Treatment For Restless Legs Syndrome Focuses On Relieving The Symptoms

March 1, 2013

Dear Mayo Clinic:

Is restless legs syndrome hereditary? Is there an effective treatment, or does a diagnosis of RLS mean I will have it for life?

Answer:

Restless legs syndrome, or RLS, is not always hereditary. But it does run in some families, and several genetic links have been found for RLS. While restless legs syndrome is most often a chronic condition, treatment is available that often can effectively control its symptoms.

Restless legs syndrome is a condition characterized by an unpleasant or uncomfortable urge to move your legs. Some people describe it as a crawling, pulling or burning sensation in their thighs, calves or feet. The sensation is temporarily relieved when you get up and move around, especially by walking, or when you shift or stretch your legs. RLS symptoms typically begin after you have been sitting or lying down for some time. Symptoms also tend to get worse in the evenings and at night, and are less bothersome during the day.

In many cases of RLS, the cause is unknown. But RLS appears to be hereditary in about half the people who have it. Several specific gene variations have been associated with this disorder. Familial RLS symptoms often begin earlier in life — usually before age 40 — than they do in forms of the disease that are not hereditary.

— Erik St Louis, M.D., Neurology, Mayo Clinic, Rochester, Minn.

Reduced Level Of Meis1 Is Directly Associated With Reduced Skor1 Level

We previously reported the MEIS1 risk haplotype to be associated with decreased levels of both its mRNA and protein. Hence, we decided to test if silencing MEIS1 would result in a reduction of SKOR1 mRNA. Using an siRNA specifically targeting MEIS1 we reduced the expression of the gene in HeLa cells and found a coincident 64% decrease of SKOR1 mRNA level . This observation further supports the existence of a link between MEIS1 and SKOR1 and suggests that MEIS1 is an upstream activator of SKOR1.

Latest Perspectives In Genetic Risk Factors For Restless Legs Syndrome

How to Deal with Restless Leg Syndrome?

European Neurological Review, http://doi.org/10.17925/ENR.2013.08.02.90

Abstract:
Overview

The high frequency of positive family history of restless legs syndrome in patients with this disease and the observed high concordance rates in monozygotic compared with dizygotic twins support a major role of genetic factors in the development of RLS. Although a number of variants for several genes may increase the risk of RLS, no definitive causative genes have been identified to date. In this review, we summarise the studies performed on families with RLS, twin studies, linkage studies, genome-wide association studies, case-control association studies and exome sequencing in RLS. The strongest candidate genes are of PTPRD, BTBD9 and MEIS.

Keywords

Restless legs syndrome, genetics, family history, linkage studies, genetic polymorphisms, risk factors

Article:

In this review, we summarise the main findings related with genetic risk of RLS. The potential causes of secondary RLS are beyond the scope of this review.

Search Strategy References for this review were identified by searching in PubMed from 1966 until 31 July 2013. The term ‘restless legs syndrome’ was crossed with ‘genetics’, ‘genes’ and ‘risk factors’, and the related references were selected.

Levchenko and colleagues48 described an autosomal-dominant locus for RLS in a French-Canadian pedigree on chromosome 16p12.1 that spanned 1.18 Mb with a maximum multipoint LOD scores of 3.5 over the total of 10 markers.

What Does Your Study Add To Existing Research On Genetic Causes Of Rls

GAR: Unlike previous methods that are focused on the effect of each genetic variant on gene expression individually, this study examined the association between overall expression of genes in different tissues and RLS. This approach led to the identification of candidate genes and pathways for RLS that were not detected by previous genome-wide association studies . 

Large Study Gives Hints About Genetic Causes Of Restless Legs Syndrome

An international team led by the Technical University of Munich and the Helmholtz Center has carried out a large genome-wide association study on the genetic causes of restless legs syndrome . They discovered 13 new genetic risk variants and identified underlying candidate biological processes.

Patients with RLS experience a strong urge to move at night and suffer from unpleasant sensations such as pain or tingling in the legs. Up to 10% of the European population is affected. Many of those affected have to contend not only with the actual symptoms but also with consequences such as sleep deficiency, depression, or anxiety. In severe cases, patients have to take medication throughout life.

Little is known about the molecular causes and the precise mechanisms of the condition. Juliane Winkelmann, MD, professor of neurogenetics at the TUM and head of the Institute of Neurogenomics at the Helmholtz Center Munich, and her team have been researching this neurological disorder for over a decade. She and her team have already found that genetic factors play a role. With the help of international partners from Cambridge University in the UK and the US company 23andMe, they have now carried out study of 45,000 patients. The findings are published in Lancet Neurology.

Restless Legs Syndrome: An Update On Genetics And Future Perspectives

Institute of Genetic Medicine, European Academy, Bolzano, Italy

Department of Neurology, University of Lübeck, Lübeck, Germany

Department of Neurology, General Regional Hospital, Bolzano, Italy

Institute of Genetic Medicine, European Academy, Bolzano, Italy

Department of Neurology, University of Lübeck, Lübeck, Germany

Department of Neurology, General Regional Hospital, Bolzano, Italy

Restless Legs Syndrome Study Identifies 13 New Genetic Risk Variants

Date:
University of Cambridge
Summary:
A new study into the genetics underlying restless legs syndrome has identified 13 previously-unknown genetic risk variants, while helping inform potential new treatment options for the condition.

A new study into the genetics underlying restless legs syndrome has identified 13 previously-unknown genetic risk variants, while helping inform potential new treatment options for the condition.

As many as one in ten people of European ancestry is affected by restless legs syndrome, in which sufferers feel an overwhelming urge to move, often in conjunction with unpleasant sensations, usually in the legs. Rest and inactivity provoke the symptoms, whereas movement can lead to temporary relief. The condition is chronic and can get progressively worse, with long-lasting effects on patients’ mental and physical health. People with restless legs syndrome have substantially impaired sleep, reduced overall quality of life, and increased risk of depression, anxiety disorders, hypertension, and, possibly, cardiovascular disease.

For around one in 50 people, the condition can be severe enough to require chronic medication, which may in turn have potentially serious side effects.

Studies of families and twins have shown that there is a strong genetic component to the disorder and led to the discovery of six genetic variants that increased the risk of developing the condition.

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Top 15 Natural Home Remedies For Restless Leg Syndrome Treatment

Have you ever experienced persistent sensations in your legs which keep you awake while the rest of your body is ready to sleep? Or have some people told you that it is inside your head? And sometimes you have some symptoms such as pulling, creeping, throbbing and an uncontrollable urge to move your legs. In addition, they become more prominent at night when you are at rest or you are relaxing. If you have these symptoms, you may have restless leg syndrome. But don’t worry. Even though it is associated with obesity, nerve disease, heart disease, kidney failed, pregnancy, high blood pressure, smoking, diabetes, iron deficiency, and anemia, there are some ways you can treat it. You can have prescription according to the doctor. Or you can apply some natural home remedies to treat it at home. Do you want to know what they are? If your answer is “yes”, please continue reading this article on our page AllRemedies.comwhich will present to you the best natural home remedies for restless leg syndrome treatment that you can follow to get rid of it at home.

Can Restless Legs Syndrome Develop Into Something More Serious

Most people with restless legs syndrome have the “idiopathic” form, meaning there’s no known cause. For them, there is no risk of RLS developing into something more serious, like Parkinson’s disease.

Restless legs syndrome can get worse in people with other medical conditions if they don’t get those conditions treated.

What Is The Prognosis For People With Restless Legs Syndrome

RLS is generally a lifelong condition for which there is no cure.  However, current therapies can control the disorder, minimize symptoms, and increase periods of restful sleep.  Symptoms may gradually worsen with age, although the decline may be somewhat faster for individuals who also suffer from an associated medical condition.  A diagnosis of RLS does not indicate the onset of another neurological disease, such as Parkinson’s disease.  In addition, some individuals have remissions—periods in which symptoms decrease or disappear for days, weeks, months, or years—although symptoms often eventually reappear.  If RLS symptoms are mild, do not produce significant daytime discomfort, or do not affect an individual’s ability to fall asleep, the condition does not have to be treated.  

Brain Structure Linked To Symptoms Of Restless Legs Syndrome

Restless Leg Syndrome » Fort Myers Vein Specialists

Press release:

MINNEAPOLIS – People with restless legs syndrome may have changes in a portion of the brain that processes sensory information, according to a study published in the April 25, 2018, online issue of Neurology®, the medical journal of the American Academy of Neurology.

Restless legs syndrome is a disorder that causes uncomfortable sensations in the legs, accompanied by an irresistible urge to move them. It often occurs in the evening and at night, sometimes affecting a person’s ability to sleep. In some cases, exercise may reduce symptoms. Iron supplements may also be prescribed if there is an iron deficiency. For more serious cases, there are also medications, but many have serious side effects if taken too long.

“Our study, which we believe is the first to show changes in the sensory system with restless legs syndrome, found evidence of structural changes in the brain’s somatosensory cortex, the area where sensations are processed,” said study author Byeong-Yeul Lee, PhD, of the University of Minnesota in Minneapolis. “It is likely that symptoms may be related to the pathological changes in this area of the brain.”

The brain’s somatosensory cortex is part of the body’s somatosensory system, which is made up of nerves and pathways that react to changes either inside or outside the body. This system helps a person perceive touch, temperature, pain, movement and position.

Treatment And Medication Options For Restless Legs Syndrome

  • Iron A trial of iron supplements is often recommended as a first treatment if your blood test indicates low or low-normal ferritin, a protein in the body that binds to iron.
  • Anti-seizure drugs These can be effective in decreasing sensory disturbances such as creeping and crawling as well as nerve pain. The U.S. Food and Drug Administration has approved gabapentin enacarbil for the treatment of moderate to severe RLS.
  • Dopaminergic agents These have been shown to reduce symptoms of RLS when taken at nighttime. The FDA has approved , pramipexole, and rotigotine to treat moderate to severe RLS.
  • Opioid drugs Methadone, codeine, hydrocodone, or oxycodone are sometimes prescribed to treat individuals with more severe symptoms of RLS who do not respond well to other medications.
  • Benzodiazepines Medications such as clonazepam and lorazepam are sometimes prescribed to treat anxiety, muscle spasms, and insomnia.
  • Hot baths
  • Massages
  • Lifestyle changes, including implementing a regular exercise program, maintaining regular sleep patterns, and limiting use of tobacco, alcohol, and caffeine

Being active throughout the day helps alleviate symptoms for some. This gives your muscles the chance to exert the energy that they would otherwise exert at night.

Some people find that good sleep habits can also help with symptoms of RLS.

These habits can include:

Diet Recommendations For People With Restless Leg Syndrome

There aren’t any specific dietary guidelines for people with RLS. But it’s a good idea to review your diet to make sure you’re getting enough essential vitamins and nutrients. Try to cut high-calorie processed foods with little or no nutritional value.

Some people with symptoms of RLS are deficient in particular vitamins and minerals. If that’s the case, you can make some changes to your diet or take dietary supplements. It all depends on what your test results show.

If you’re deficient in iron, try adding more of these iron-rich foods to your diet:

  • dark green leafy vegetables

Those strange sensations in your legs can be uncomfortable or painful. And those symptoms can make it almost impossible to fall asleep and stay asleep.

Sleep deprivation and fatigue are dangerous to your health and well-being.

In addition to working with your doctor to find relief, there are a few things you can do to improve your chances of restful sleep:

Restless Legs Syndrome And Periodic Limb Movement Disorder

Most people who have RLS also have a condition called periodic limb movement disorder . PLMD involves repetitive flexing or twitching of the limbs while asleep at night. It is different from RLS in that these movements are not accompanied by uncomfortable sensations and because they occur during sleep, patients are often not aware of them. However, PLMD-associated movements can cause a person to wake up and therefore can compound sleep issues in patients who also have RLS.

Although most people with RLS have PLMD, many with PLMD do not have RLS.

Weighted Blankets Can Reduce Prickly Feeling And Anxiety

A weighted blanket can offer a constant but gentle counterstimulation to override the feeling of restless legs.

There’s one more reason to suspect weighted blankets might help, Dr. Vensel-Rundo says.

Some research suggests restless legs may be connected with anxiety. So, if it helps you relieve anxiety, a weighted blanket may also help with your restless legs.

Restless Sleep May Be An Early Sign Of Parkinsons Disease

Press release:

Researchers from Aarhus University have discovered that patients with the RBD sleep behaviour disorder lack dopamine and have a form of inflammation of the brain. This means that they are at risk of developing Parkinson’s disease or dementia when they grow older.

Do you sleep restlessly and hit out and kick in your sleep? This could be a sign of a disorder associated with diseases of the brain. Researchers from Aarhus University have studied the condition of the dopamine producing nerve cells in the brain and cells that participate in the brain’s immune system in people suffering from the sleep disorder Rapid eye movement sleep behaviour disorder, RBD.

The study shows that patients suffering from RBD have a risk of developing Parkinson’s disease or dementia in the future, because they already suffer from a lack of dopamine in the brain. Parkinson’s disease occurs precisely because the group of nerve cells in the brain that produce dopamine stop working.

The RBD sleep disorder is characterised by disturbances in the part of sleep where dreams take place. Healthy people are relaxed and lie still during dream sleep, while people suffering from RBD live out their dreams so that while sleeping they can hit out, kick and shout.

The findings have just been published in the neurological journal The Lancet Neurology.

Parkinson’s disease

The study is a case-control study.


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