Published Research - General Sleep and RLS (WED)

[cornelia]

From Medscape Medical News
SLEEP 2009: Intravenous Iron is Effective in Restless-Legs Syndrome
Jim Kling

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Optional Message: Ha Joke, positief nieuws m.b.t. iron infusions Corrie

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Dr. Daniel Mikol discusses the findings from the multicenter REGARD study.Click here. June 16, 2009 (Seattle, Washington) — A double-blind, placebo-controlled study shows that intravenous (IV) iron, specifically ferric carboxymaltose (FCM), is a safe and effective treatment for moderate to severe restless-legs syndrome (RLS).

Previous open-label trials of IV treatment with iron dextran have demonstrated greatly reduced RLS symptoms, but a controlled trial of IV iron sucrose showed little improvement. One reason for these differences may be that different iron formulations can have dramatic differences in uptake and half-life in tissues.

FCM is a formulation that can be given in a single dose by IV infusion. It has little risk of anaphylaxis, which can be a problem with other iron formulations, and its half-life is 16 hours, with tissue availability up to 4 weeks following treatment. The researchers performed a controlled study to evaluate the efficacy of IV FCM in RLS patients.

"We got dramatic responses," Richard Allen, PhD, a research associate in neurology at Johns Hopkins Medicine, in Baltimore, Maryland, said during his presentation here at SLEEP 2009: 23rd Annual Meeting of the Associated Professional Sleep Societies.

Positive Results

The team recruited only patients with primary moderate to severe RLS who were free of RLS medications and randomly assigned them to IV FCM treatment (24 patients), with an initial 500-mg dose followed by 1000 mg on day 5, or a placebo group (21 patients).

They evaluated patients at baseline using the International Restless Legs Syndrome Study Group Scale (IRLS), Medical Outcomes Study Sleep Scale (MOS sleep), and RLS Quality of Life (RLS-QoL) measurements and then carried out repeated IRLS and MOS sleep assessments on days 14 and 28 and RLS-QoL on day 28. They also obtained the clinician's global impression of improvement (CGI-I) at days 14 and 28.

The day-28 evaluation revealed several positive results. Treated patients had a significant decrease in the IRLS scale vs controls. The number of remitters, defined as an IRLS ≤10, was higher among treated patients than those on placebo, and 4 of these achieved scores less than 5, vs none among the placebo patients.

Improvements in MOS sleep scores and the RLS-QoL scale were also seen. Significantly more treated patients had an improved or very much improved CGI-I vs those on placebo.

Change in Study End Points with IV FCM Treatment vs Placebo in RLS Patients from Baseline to Day 28 End Point IV FCM Treatment Placebo P
IRLS score -8.9 -4.0 .04
Remitters (IRLS < 10), n (%) 7 (29) 1 (4. .051
IRLS scores < 5, n (%) 4 (17) 0 (0) .11
Improvement on MOS Sleep Score (points) 24 19 .09
Improvement on RLS-QoL (points) 23 18 .024
Improvement in CGI-I (% of patients) 58 14 .005


The results were also lasting. After 1 month, 75% of treated patients did not require additional medication. This number dropped to 38% at 3 months and 25% at 5.5 months.

In earlier studies, Dr. Allen's team used magnetic resonance imaging to demonstrate a deficit in iron concentration in the brains of RLS patients. "It suggests that we might need to start working on how we can (best) deliver iron to the brain," he told Medscape Neurology.

Reorienting RLS Research?

Michael Silber, MBchB, professor of neurology at the Mayo Clinic College of Medicine, in Rochester, Minnesota, who attended the conference, agreed that the study should reorient research.

"It suggests we're looking at the wrong thing — that we need to be looking at iron in the brain [in RLS]," he told Medscape Neurology. Clinically, Dr. Silber said that IV FCM is a useful option for patients who are iron-deficient and cannot absorb iron supplements orally. "It's an encouraging report," he said.

The study received support from Luitpold Pharmaceuticals. Dr. Silber disclosed no relevant financial relationships.

SLEEP 2009: 23rd Annual Meeting of the Associated Professional Sleep Societies: Abstract 0902. Presented June 10, 2009.


Corrie

[ViewsAskew]

Thank you, Corrie! I am thrilled to see that published. It's something we can take to our doctors and say, "HEY! You shouldn't withhold this."

Dale - this might help you. I hope you read this section.

[SquirmingSusan]

Thanks Corrie. Great information in there. I didn't know that iron glucose didn't produce good results in studies. I had that for one set of iron infusions. I'm so glad they're figuring this out.

[ViewsAskew]

Studyfinds genes for ADHD....and one of them is connected to RLS.

[ViewsAskew]

Happy, happy, happy dance!!!!

Gotta love our researchers. GOOOOOOOOOOOOOOOOOO Mayo.

Now, will this change our lives overnight? Nope. But, it adds validity and leads to more knowledge. Eventually, they WILL put it all together.


(same text copied below in case the link breaks at some point)

Public release date: 21-Jul-2009
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Contact: Kevin Punsky
punsky.kevin@mayo.edu
904-953-2299
Mayo Clinic
Mayo Clinic researchers find first potential pathogenic mutation for restless legs syndrome

JACKSONVILLE, Fla. — An international team of researchers led by scientists at the Mayo Clinic campus in Florida have found what they believe is the first mutated gene linked to restless legs syndrome, a common neurologic disorder.

The researchers, who reported the findings in the July 21 issue of Neurology, doubt that a large proportion of the millions of people who suffer from the syndrome have this mutated MEIS1 gene. They point out, however, that understanding the function of both the normal and abnormal genes will shed some insights into this mysterious disorder.

Restless legs syndrome affects between 5 and 11 percent of the population in Europe and in North America. The condition is characterized by unpleasant sensations in the legs at rest, especially in the evening, that are temporarily relieved by movement. Because restless legs syndrome often interrupts sleep, people commonly are diagnosed after they consult a sleep specialist for assistance.

"We think restless legs syndrome may be due to a number of clinical factors, but we also believe that there is a strong genetic component to the disorder," says the study's lead investigator, Carles Vilariño-Güell, Ph.D., a neuroscientist at Mayo Clinic, Jacksonville.

"The mutation we found is in a portion of the protein that is identical in species as distinct to human as frogs and fish, which tells us that this portion is very important for the proper function of the protein and that the mutation has a very high chance of causing disease," he says.

While common variants (different versions) of MEIS1 and BTBD9, another associated gene, have been found in families with a high incidence of restless legs syndrome, it is not clear that those variants are capable of causing disease, Dr. Vilariño-Güell says.

"This mutation, on the other hand, is the first that we think can be a real candidate for causing or promoting restless legs syndrome," he says.

Researchers did not find mutations in the BTBD9 gene in study participants, but they found one in the MEIS1 gene that resulted in the production of an aberrant protein. The family that has the MEIS1 mutation consists of six members. Three who had restless legs syndrome had the mutation and the other three without the disease did not. "The presence of the mutation in all affected individuals supports a pathogenic role for the MEIS1 gene, and we now need to confirm this finding with other international research groups who study restless legs syndrome," Dr. Vilariño-Güell says.

Researchers from Canada, Ireland, and Norway also participated in the study. In total 378 restless legs syndrome patients and 853 healthy participants were evaluated for the presence of this newly discovered mutation in their DNA. This analysis only identified one additional individual from Ireland who did not present any symptoms of restless legs syndrome. This suggests that the gene defect may need additional triggers to develop the syndrome, Dr. Vilariño-Güell says. "This gene is probably not the most common cause of restless legs syndrome in the population we studied, but it may be more prevalent in other regions of the world," he says.

###

The study was funded by the National Institutes of Health, and a research grant from Mayo Clinic.

About Mayo Clinic

Mayo Clinic is the first and largest integrated, not-for-profit group practice in the world. Doctors from every medical specialty work together to care for patients, joined by common systems and a philosophy of "the needs of the patient come first." More than 3,300 physicians, scientists and researchers and 46,000 allied health staff work at Mayo Clinic, which has sites in Rochester, Minn., Jacksonville, Fla., and Scottsdale/Phoenix, Ariz. Collectively, the three locations treat more than half a million people each year. Mayo Clinic Health Manager is operated by Mayo Foundation for Medical Education and Research. To obtain the latest news releases from Mayo Clinic, go to www.mayoclinic.org/news. For more on Mayo Clinic research, go to www.mayo.edu. MayoClinic.com (www.mayoclinic.com) is available as a resource for your health stories.

[cornelia]

Got this article this morning:

Sending Restless Legs Syndrome (RLS) Into Remission

Dr. Leonard Weinstock finds link between gastrointestinal problems and RLS

08.10.2009 – St. Louis, MO - Every night Molly Roberts would go to bed hoping for a good night’s sleep, and every morning she would wake up unrested with aching muscles. Her symptoms baffled her primary care doctor, and Roberts thought she might never wake up well-rested. Little did she know that the pain and restlessness from her Restless Legs Syndrome (RLS) was likely caused by a problem with her digestive tract.

Following a visit to St. Louis-based Gastroenterologist Dr. Leonard Weinstock, she discovered she also had an overgrowth of bacteria in her small intestine, a condition known as SIBO. Weinstock’s groundbreaking research recently discovered a link between RLS and SIBO.

His research trials have found that if one treats the SIBO, the RLS is often goes into remission as well. “While many new drugs help treat the symptoms of RLS. This research shows us the cause of the disease and in turn allows us to treat the RLS rather than just helping the symptoms,” explains Weinstock.

This discovery has given his patients a new outlook on life and freedom from RLS. Weinstock found the link after treating a patient for Irritable Bowel Syndrome (IBS) who was also suffering from RLS. Following the treatment for IBS, the patient’s RLS also appeared to be in remission. This discovery led to a number of trials, all of which had the same overall result.

“When a patient was diagnosed with SIBO, given a course of treatment that included rifaximin, an antibiotic that is not absorbed by the bloodstream, we found that the patient showed quick, dramatic and continuing relief of RLS symptoms,” explains Weinstock.

Based on a standard RLS severity scale, Weinstock’s patients have shown significant improvement. In the most recent study, which included 14 patients, nine patient’s scores dropped an average of 65 percent after one course of antibiotics. Two patients who received a second round of antibiotics after an initial lack of response no longer had any symptoms. An additional patient was cured after discovering that she had celiac disease and started on a gluten-free diet.

Molly Roberts is one of the many success stories. Following two courses of treatment under Weinstock’s care, she is finally sleeping well and appears to be cured of her RLS.

Weinstock continues to study the link between SIBO and RLS and other conditions such as celiac disease, IBS and Crohn’s disease. “Gastroenterology is full of detective work, and we will continue to study to find the links between the GI tract and conditions throughout the body,” he says.

What is RLS?
Every night thousands of people lose sleep because of a gnawing, tingling urge to move their legs. They have extreme difficulty getting a good night of sleep and are often in constant pain. RLS occurs in seven to 15 percent of the population, particularly older adults and pregnant women. The symptoms of RLS can be life altering, and the syndrome often baffles the medical community. In recent years a number of drugs have been introduced to help the symptoms of RLS, but until now the cause has yet to be determined.

What is SIBO?
Small intestinal bacterial overgrowth (SIBO) is a condition where abnormally large numbers of bacteria are present in the small intestine. Symptoms often include diarrhea, bloating, excess gas and abdominal pain. SIBO is often associated with IBS, diabetes, celiac disease and Crohn’s disease.

Corrie

[ViewsAskew]

That's the second link regarding gut and RLS. Very interesting.

[Neco]

Interesting.. But my IBS hit me after the RLS came on, and I think is a little irresponsible for him to call this "the cure" for RLS instead of "A cure for one potential form of RLS".

[Wayne]

That is interesting. I don't have irritable bowels or any other gastro problem that I know of.

However, I can remember my 10 day Cipro antibiotic treatment in which for 2 days I didn't take any med to fall asleep.

[ViewsAskew]

Absolutely, Zach. I think I'm getting immune to even noticing those statements....everyone thinks THEIR treatment is the ONLY treatment. Since multiple genes exist, it's likely RLS has multiple causes...one thing will NOT cure all most likely.

[cornelia]

This abstract I just read: nothing new for us, but I thought I'd post it, because it explains augmentation and what to do about it in a vey comprehensive and clear way:

Management of restless legs syndrome augmentation.Williams AM, Garcia-Borreguero D.
Diego Garcia-Borreguero, MD, PhD, Sleep Research Institute, 19 Alberto Alcocer, 28036 Madrid, Spain. dgb@iis.es.

Augmentation is the main complication of long-term dopaminergic treatment of restless legs syndrome (RLS). Although augmentation was first described in 1996 and is characterized by an overall increase in severity of RLS symptoms (earlier onset of symptoms during the day, faster onset of symptoms when at rest, spreading of symptoms to the upper limbs and trunk, and shorter duration of the treatment effect), precise diagnostic criteria were not established until 2003. These criteria were updated in 2007 to form a new definition of augmentation based on multicenter studies. Augmentation should be differentiated from early morning rebound, natural progression of the disease, tolerance, and neuroleptic-induced akathisia. Treatment strategies will depend on the degree of clinical significance but will be based on the use of longer-acting drugs and a reduction or substitution of the dopaminergic agents. The most effective preventive measure is to keep the dose of the dopaminergic medication as low as possible, ensuring that it does not exceed the dose recommended by regulatory authorities. RLS augmentation needs to be treated only if it is clinically relevant-that is, if it has a significant impact on the patient's daily activities. Mild cases should be followed closely, however. In severe cases, a change of treatment (sometimes even within the same class of drugs) can be effective, although before taking this step, it should be verified that all factors that may affect augmentation (changes in lifestyle, iron deficiency, serotonin reuptake inhibitors) have been excluded

Corrie

[ViewsAskew]

This study used MRI to measure iron concentrations on the brain of RLS patients. No anomalies where found. This study was unable to replicate earlier studies showing a difference.

[ViewsAskew]

Holy cow - a new study links erectile dysfunction with RLS. Apparently, older men had more likelihood of erectile dysfunction if they had RLS. The more frequently the RLS, the greater the percentage with ED.

I wonder how that applies to women...

[cornelia]

I wish these studies showed an overall consistency; it makes me feel confused. As in this iron study and the erectile dysfunction one, in which it says that anti-depressants didn't make much difference at all. I hate this.

Corrie

[Neco]

It's like they're shooting in the dark.. Which I suppose isn't far from the truth, but that doesn't help us form a cohesive message, or help decide where further research needs to be focused.