Elsevier

Sleep Medicine

Volume 12, Issue 6, June 2011, Pages 610-613
Sleep Medicine

Original Article
Restless legs syndrome is associated with irritable bowel syndrome and small intestinal bacterial overgrowth

https://doi.org/10.1016/j.sleep.2011.03.007Get rights and content

Abstract

Background

Restless legs syndrome (RLS) is linked to gastrointestinal disorders. The prevalence of irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth (SIBO) in RLS patients was determined.

Methods

RLS subjects were recruited from unbiased ads that did not mention gastrointestinal symptoms. RLS diagnosis was confirmed by a neurologist and utilized the International RLS Study Group criteria. General population controls (GPC) were spouses of gastrointestinal clinic patients and were excluded for RLS. Completely healthy controls (CHC) were excluded for RLS and gastrointestinal symptoms. IBS was diagnosed by Rome II criteria. SIBO was diagnosed by the lactulose breath test (LBT).

Results

There were 32 RLS subjects (23F/9M; 57 yo), 25 GPC (13F/12M; 58 yo) and 30 CHC (19F/11M; 44 yo). Twenty-nine had RLS unassociated with other GI diseases, one had celiac disease, and two had gastric resections. IBS was diagnosed in 28% of RLS subjects compared to 4% GPC (p = 0.0317). SIBO was diagnosed in 69% of RLS subjects compared to 28% of GPC (p = 0.0033) and 10% of CHC. Using a false positive rate of 10%, 59% of positive LBT results are associated with RLS.

Conclusions

IBS and SIBO are common in RLS. Three hypotheses developed are (a) RLS patients are selectively immunocompromised or genetically predisposed and thus more subject to SIBO; (b) SIBO leads to autoimmune changes, and subsequent auto-antibodies attack brain and/or peripheral nerves and (c) SIBO inflammation leads to increased hepcidin and CNS iron deficiency which, in turn, leads to RLS. These hypotheses bear further investigation.

Introduction

Restless legs syndrome (RLS) is defined as a compelling urge to move the legs that is often associated with discomfort, worse during rest or inactivity, relieved by movement, and worse in the evening or night [1]. The symptoms of RLS often disrupt sleep, resulting in a lack of energy, negative mood and disturbance of daily living [2]. In addition, RLS may be comorbid with gastrointestinal (GI) disorders that also reduce health-related quality of life [3], [4].

Several pathophysiological processes have been implicated in RLS. Evidence suggests that dopaminergic dysfunction [5], [6], [7] and altered control of iron homeostasis are key players [8], [9], [10]. Other proposed pathophysiological mechanisms for RLS include peripheral neuropathy [11], [12], [13] and alterations in spinal sensorimotor circuits [14].

In our previous studies, the prevalence of RLS in patients with celiac disease or Crohn’s disease was 25% and 30%, respectively, compared with a prevalence of 9–10% of their spouses [3], [4]. These data suggest that there may be an underlying pathophysiological process predisposing patients with GI disorders to RLS and that identification of such a mechanism could lead to additional therapeutic options for patients suffering from RLS; however, such a common mechanism has yet to be identified.

Given that several disorders associated with RLS, including celiac disease and Crohn’s disease, have also been linked with immune and inflammatory processes [15], [16], it is possible these may also be pathophysiological mechanisms, thus uniting GI disorders and RLS. In addition, several GI disorders (e.g., celiac disease, Crohn’s disease, functional bowel syndrome, irritable bowel syndrome [IBS]) and several disorders highly-associated with RLS (e.g., rheumatoid arthritis, diabetes and end stage renal disease) have been associated with small intestinal bacterial overgrowth (SIBO) [17], [18], [19], [20], [21], [22], [23]. There are several studies that have shown IBS to have demonstrated an inflammatory component in the pathophysiology [24], [25], [26].

The present study determined the prevalence of IBS in patients with RLS. Owing to the association of SIBO with IBS (recent meta-analysis indicated that 54% of patients with IBS also have SIBO), [17] the presence of SIBO in RLS patients was examined by indirect testing using the noninvasive lactulose breath test (LBT).

Section snippets

Methods

This investigation was approved by a human studies committee (Sterling Institutional Review Board; Atlanta, GA) and informed consent was given by all RLS patients. This was a prospective study of the prevalence of IBS and SIBO in RLS patients versus controls. Thirty-three patients with RLS were recruited from newspaper and radio ads in which the presence or absence of GI symptoms was neither encouraged nor discouraged. In addition, these exclusion criteria also eliminated common conditions

Results

Thirty-two patients with RLS (23 female, 9 male; mean age, 57 ± 10 years) were studied. These were compared to 25 general population controls (GPC: 13 female, 12 male; mean age, 58 ± 8 years) and 30 completely healthy controls (CHC: 19 female, 11 male, 44 ± 14 years).

All RLS patients fulfilled the International RLS criteria and 27 were previously diagnosed and treated for RLS by a neurologist. The remaining five had confirmation of the diagnosis of RLS as determined by the interview by the RLS

Discussion

The major finding of this study was the high prevalence of IBS and SIBO in patients with RLS in a general population recruited using unbiased methods. In the current study, 9/32 (28%) of RLS patients had IBS compared to 1/25 (4%) general population controls (p = 0.0317). As a point of comparison, our control population compares favorably to the literature where 6.7% of 5009 individuals in the general population were found to have IBS also using the Rome II criteria [22]. Small intestinal

Conflict of interest

The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest associated with this article can be viewed by clicking on the following link: doi:10.1016/j.sleep.2011.03.007.

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Acknowledgements

This was an investigator initiated study. Dr. Walters has received research funding from the National Institutes of Health. Dr. Walters has served as a consultant to UCB Pharma and was a speaker at a CME symposium sponsored by UCB Pharma. Dr. Weinstock has received research funding from Salix Pharmaceuticals, Inc.

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