Original ArticleThe four diagnostic criteria for Restless Legs Syndrome are unable to exclude confounding conditions (“mimics”)
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.
References (23)
- et al.
Prevalence, severity and risk factors of restless legs syndrome in the general adult population in two Scandinavian countries
Sleep Med
(2005) - et al.
Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health
Sleep Med
(2003) - et al.
The Johns Hopkins telephone diagnostic interview for the restless legs syndrome: preliminary investigation for validation in a multi-center patient and control population
Sleep Med
(2003) - et al.
Validation of the Hopkins telephone diagnostic interview for restless legs syndrome
Sleep Med
(2008) - et al.
Impact, diagnosis and treatment of restless legs syndrome (RLS) in a primary care population: the REST (RLS epidemiology, symptoms, and treatment) primary care study
Sleep Med
(2004) - et al.
Sex and the risk of restless legs syndrome in the general population
Arch Intern Med
(2004) - et al.
Restless Legs Syndrome Prevalence and impact: REST general population study
Arch Intern Med
(2005) - et al.
Restless legs syndrome: epidemiological and clinicogenetic study in a South Tyrolean population isolate
Mov Disord
(2006) - et al.
Eidemiology of restless legs syndrome in Korean adults
Sleep
(2008) - et al.
Prevalence and risk factors of RLS in an elderly population: the MEMO study. Memory and morbidity in Augsburg elderly
Neurology
(2000)
Iron metabolism and the risk of Restless Legs Syndrome in an elderly general population – The MEMO-Study. Memory and morbidity
J Neurol
Cited by (225)
The evolution of diagnostic rules and Standards for Sleep-Related Movement Disorders (SRMD)
2023, Encyclopedia of Sleep and Circadian Rhythms: Volume 1-6, Second EditionDescription of sleep-related movement disorders
2023, Encyclopedia of Sleep and Circadian Rhythms: Volume 1-6, Second EditionThe Management of Restless Legs Syndrome: An Updated Algorithm
2021, Mayo Clinic ProceedingsMaternal and neonatal outcomes associated with restless legs syndrome in pregnancy: A systematic review
2020, Sleep Medicine ReviewsCitation Excerpt :A majority of studies used a questionnaire that assessed for four key diagnostic criteria defined by the IRLSSG in 2003 [62]. These criteria have since been shown to have a false-positive rate of up to 16% if there are no additional efforts taken to exclude mimics [63]. In 2014, a revised version of the IRLSSG consensus diagnostic criteria added a fifth essential characteristic, specifying that symptoms described by the first four criteria could not be attributed to another ‘medical or behavioural’ condition [1].