Identifying and treating the cause — not just the symptoms — of Restless Legs Syndrome (RLS)
"Gastroenterology is full of detective work, and that is one of the reasons I was drawn to it."
Night after night, Molly Roberts climbed into bed knowing she wouldn't get any rest. Once asleep, she would begin "river dancing," as she calls it, with flailing legs and restless kicking that resembled the high-stepping Irish style of dance. Every morning, she would get up tired, muscles aching, wondering what was wrong. Her own physician decided she was suffering from too much stress.
"I thought I might have to live with this," says Roberts, 27, an office manager for a St. Louis real estate development firm. "I believed I just wasn't a good sleeper. And I didn't see any end to it in sight."
Then one evening, she saw a television commercial that gave a name to her problem: Restless Legs Syndrome (RLS). With that, Roberts began an online search that led her to Leonard B. Weinstock, MD, clinical associate professor in the Departments of Internal Medicine and Surgery, who was engaged in some intriguing research on RLS, irritable bowel syndrome (IBS) and the link between them and small intestinal bacterial overgrowth (SIBO).
For several years, Weinstock had been interested in RLS, which occurs in 7 percent to 15 percent of the population, particularly older adults and pregnant women. It comes in two forms: primary RLS, with an unknown cause; and a secondary type, connected to some 20 neurologic, metabolic, rheumatologic or gastrointestinal conditions. Altogether, it may account for up to 25 percent of insomnia in the United States.
"RLS is a major problem, but it is still under-recognized and even trivialized," says Weinstock. "It was first described in 1685 as 'The Watching Evil,' then given its current name in 1945. Now it's a household term because of advertising, but those drugs treat the effect of the disease rather than the cause — and that is what I am looking for."
Weinstock also was looking at the role of SIBO in a range of gastrointestinal problems, including IBS, which causes abdominal pain, bloating and gas. Following the lead of studies by earlier researchers, he began treating IBS patients with antibiotics, combining them with motility drugs to combat slow intestinal muscle activity. In 2005, the introduction of the antibiotic rifaximin, which targets the small intestine, proved a major step forward.
But identifying patients with SIBO was a problem, so in 2005 Weinstock acquired a gas chromatography machine, which tests for bacterial content using a breath test. It measures gases produced by small bowel bacteria which consume intestinal nutrients, ferment them and alter the digestive process. Bacteria also attach to the intestinal lining, causing inflammation.
Why do people develop SIBO and then IBS? The pieces of that puzzle were coming together for Weinstock, who heard colleagues at a California conference say that 20 percent of IBS patients remember exactly when it started: a case of food poisoning, often acquired during travel. Just then he had a patient with IBS and Restless Legs Syndrome, which had begun on a trip 14 years earlier.
"This was the exciting link: Something had happened during that exposure to food poisoning that caused IBS, and the researchers in California showed that these patients had SIBO," Weinstock says. "So I began thinking about my patient who had a clear-cut case of post-infectious IBS, as well as a case of post-infectious RLS. Could that patient have post-infectious SIBO, too?"
In that case, treatment with rifaximin showed quick, dramatic and continuing relief of symptoms. Immediately, Weinstock did breath tests on 254 other patients and discovered 13 with SIBO and RLS. With Stephen P. Duntley, MD, associate professor of neurology and an RLS expert, he published a study in the May 2008 issue of the journal Digestive Diseases and Sciences showing that 10 patients had up to 80 percent improvement. Among eight followed long-term, five had a complete end to their symptoms.
"RLS can have severe negative effects on a patient's quality of life, with new evidence pointing to cardiovascular health consequences," says Duntley, who also is director of the Sleep Medicine Center. "Since we do not know its cause in most patients, cure is not possible, and we treat RLS symptomatically. But, if further research confirms the link between chronic intestinal infection and RLS, a cure may be possible for some patients."
Body iron stores are often low in patients with RLS and this exacerbates their symptoms, says Duntley. While the deficiency's cause remains unknown, he believes that the inflammation of the small intestine, caused by bacterial overgrowth, affects the iron regulatory hormone hepcidin and leads to this iron deficiency.
Meanwhile, Weinstock has since treated 14 other RLS patients, recording their data. He has a chart showing the effect of antibiotic therapy on them, using the standard RLS severity scale. Overall, the impact has been significant: The score dropped an average of 65 percent in nine patients with one course of antibiotics and completely in two patients who received a second round of antibiotics after initial lack of response. An additional patient was cured after discovering that she had celiac disease and started on a gluten-free diet.
"Gastroenterology is full of detective work, and that is one of the reasons I was drawn to it," says Weinstock. "To be able to say that I now understand why a patient can have a syndrome for 14 years and then, with a short course of therapy, reverse all the symptoms, is exciting."
Weinstock and Duntley are undertaking a new double-blind study, intended to recruit 30 patients with RLS: Twenty will receive antibiotic treatment and 10 will get a placebo. They hope to conclude the study by this fall and, if results are positive, seek major funding for a national project.
Weinstock also is branching out into studies of SIBO and Crohn's Disease, SIBO and chronic prostatitis, as well as an increased risk of RLS in patients with celiac disease. He says he would like to foster a new appreciation for the role of SIBO in many unexplained conditions. "SIBO is a common phenomenon and can present in subtle ways, yet affect the body significantly," he says.
As for Molly Roberts, she found that she did indeed fit the RLS profile, since her 10-year history of the disease had begun with a case of food poisoning when she was a teenager. In Weinstock's office, she underwent one course of antibiotics, then a second — and now believes she is cured. "I have so much more energy than I have had in years," she says. "I am amazed at what I have been able to accomplish."