Elsevier

Sleep Medicine

Volume 10, Issue 9, October 2009, Pages 976-981
Sleep Medicine

Original Article
The four diagnostic criteria for Restless Legs Syndrome are unable to exclude confounding conditions (“mimics”)

https://doi.org/10.1016/j.sleep.2008.09.015Get rights and content

Abstract

Background

Epidemiological survey studies have suggested that a large fraction of the adult population, from five to more than 10%, have symptoms of Restless Legs Syndrome (RLS). Recently, however, it has become clear that the positive predictive value of many questionnaire screens for RLS may be fairly low and that many individuals who are identified by these screens have other conditions that can “mimic” the features of RLS by satisfying the four diagnostic criteria. We noted the presence of such confounders in a case-control family study and sought to develop methods to differentiate them from true RLS.

Methods

Family members from the case-control study were interviewed blindly by an RLS expert using the validated Hopkins telephone diagnostic interview (HTDI). Besides questions on the four key diagnostic features of RLS, the HTDI contains open-ended questions on symptom quality and relief strategies and other questions to probe the character of provocative situations and modes of relief. Based on the entire HDTI, a diagnosis of definite, probable or possible RLS or Not-RLS was made.

Results

Out of 1255 family members contacted, we diagnosed 1232: 402 (32.0%) had definite or probable RLS, 42 (3.3%) possible RLS, and 788 (62.8%) Not-RLS. Of the 788 family members who were determined not to have RLS, 126 could satisfy all four diagnostic criteria (16%). This finding indicates that the specificity of the four criteria was only 84%. Those with mimic conditions were found to have atypical presentations whose features could be used to assist in final diagnosis.

Conclusion

A variety of conditions, including cramps, positional discomfort, and local leg pathology can satisfy all four diagnostic criteria for RLS and thereby “mimic” RLS by satisfying the four diagnostic criteria. Definitive diagnosis of RLS, therefore, requires exclusion of these other conditions, which may be more common in the population than true RLS. Short of an extended clinical interview and workup, certain features of presentation help differentiate mimics from true RLS.

Introduction

In recent years, there have been several studies of the prevalence of Restless Legs Syndrome (RLS) in different populations [1], [2], [3], [4], [5] using International RLS Study Group consensus diagnostic features [6]. However, these studies have generally utilized questionnaires that were not validated on the same populations. Sensitivity (ability to detect affected individuals) and specificity (ability to exclude non-affected individuals) of diagnostic instruments have, therefore, been unknown. Only in one population study were questionnaire results confirmed by expert interview [7]. Even in that study the confirmation was not independent since the expert interviewer utilized the responses to the 3-question diagnostic questionnaire as an element of the diagnostic process. The authors reported a kappa of 0.67 for agreement between the question set and the expert diagnosis [8], better than chance but not nearly perfect.

We have been developing a systematic procedure to diagnose individuals using a validated expert telephone diagnostic interview, a preliminary version of which had a sensitivity of .97 and a specificity of .94 in a mixed sample of RLS patients and controls [9]. A more recent validation from our family case-control study shows a similar high sensitivity and specificity (⩾90%) [10] with use in a general population. We now report our experience with subjects in that case-control family study and examine in detail those who did not receive an expert diagnosis of RLS, but who endorsed one or even all four features that are the essential diagnostic features of RLS [6], [11]. Because the four diagnostic criteria are often the only criteria used in research questionnaires, it is important for us to understand the specificity, sensitivity, and positive predictive value of such limited questionnaires. Diagnostic instruments with low positive predictive values can lead to significant errors in estimating population prevalence of RLS and also determining medical and social effects of RLS. Individuals with “false RLS” may also enter into therapeutic and pathophysiologic studies of RLS and contaminate their results.

In this paper, we report our examination of the rate at which subjects without RLS can satisfy the basic diagnostic criteria for RLS. We also show how additional questions about symptoms, which are supplementary to the diagnostic criteria, can help discriminate true RLS from confounding conditions.

Section snippets

Study procedure

Only the essential details are given below. For a more in depth description of the methods, see our previous publications [10], [12]. One hundred thirty-six patient probands were recruited from the clinics of the Johns Hopkins Bayview Medical Center, while 59 control probands were recruited by patients or obtained from the local catchment area. Two RLS experts independently evaluated all the RLS and control probands in a standard clinical setting and only those with complete agreement on

Characterization of the subjects’ responses to the four basic criteria

Out of a total of 1232 family members with a diagnosis, 788 (64%) were diagnosed as not having RLS (Not-RLS group). Of these 788, 347 reported leg discomfort at rest (44%) and 336 reported an urge or need to move the legs while at rest (43%). Four hundred seventy-six reported at least one of these symptoms (64%) while 207 (26%) reported both discomfort and an urge to move. Among those with at least an urge to move at rest (N = 336), 291 (37% of the Not-RLS group) reported relief with movement and

Discussion

In this study we found that symptoms and conditions not related to RLS can frequently satisfy one or more of the features characteristic of Restless Legs Syndrome. The most common factor leading to endorsement of RLS features was the presence of leg discomfort not caused by RLS. Among the conditions frequently responsible for endorsement of RLS features are cramps, positional leg discomfort, and leg pain due to a variety of injuries or pathologic conditions; some subjects endorsed different

Acknowledgement

This study was supported by NIH grant RO1 AG 16362 which was awarded to Dr. C.J. Earley and NIH/NCRR grant M01-RR00052 received by the Johns Hopkins-Bayview GCRC.

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