The Epidemiology of Restless Legs Syndrome

Published on 12/04/2015 by admin

Last modified 12/04/2015

Print this page

This article have been viewed 1748 times

Chapter 7 The Epidemiology of Restless Legs Syndrome

Although a description of symptoms of restless legs syndrome (RLS) first appeared in the clinical literature more than three centuries ago,¹ little is known about the disease on a population level. The publication of the so-called minimal criteria of RLS in 1995² and their revision in 2003³ have fostered research on the population level, and the number of conducted epidemiological studies or those in defined special populations is increasing considerably. However, there are still no published studies on the incidence of the syndrome. In contrast to the limited epidemiological data, many neurophysiological, pharmacological, and brain-imaging studies have been performed over the past two decades. Even though this research has shed some light on the pathophysiology of the disease and has led to effective treatment, the etiology of RLS remains unclear. Population-based epidemiological research can complement knowledge gained in laboratory settings by providing precise estimates of disease prevalence and incidence, generating and testing etiological hypotheses through the analysis of risk factors, clarifying the roles of genetic markers in association studies of cases and controls sampled from the same source population, and evaluating disease outcomes from a population perspective. As with many other examples, in particular from cardiovascular disease, epidemiological research will help to better understand the etiology of RLS and thus eventually lead to improved treatment options and, equally important, permit the development of preventive strategies.

Assessment of Restless Legs Syndrome in Population Studies

RLS is generally diagnosed from a patient’s report of specific symptoms. The medical history or a diagnostic work-up can help in excluding other conditions or in classifying the syndrome as idiopathic or secondary, but no single diagnostic test can as yet detect the presence or absence of the disease. Thus, RLS is one of the few disorders that can be assessed through specific questions of participants in community-based studies. In 1995, the International Restless Legs Syndrome Study Group (IRLSSG) agreed on four “minimal diagnostic criteria,”² paving the way for the development of a standardized questionnaire that can be implemented in epidemiological studies. These 1995 “minimal diagnostic criteria” included the following:

• The desire, usually associated with paresthesias/dysesthesias, to move the limbs

• Motor restlessness

• Symptoms that are worse or exclusively present at rest (lying or sitting), with at least partial and temporary relief with activity

• Symptoms that are worse in the evening or at night

Prior to the publication of the standard diagnostic criteria for RLS in 1995, three studies ⁴^–⁶ were either conducted or initiated using nonstandard definitions of RLS. The question sets used in these studies were not validated. Following the introduction of the standard criteria, several additional population-based studies⁷^–¹⁴ were carried out. Two of these studies were conducted in Germany and used a newly developed standardized brief questionnaire with the following questions that were based on the minimal diagnostic criteria just listed:

• Do you have unpleasant leg sensations (like crawling, paraesthesias, or pain) combined with a motor restlessness and an urge to move?

• Do these symptoms occur only at rest, and does moving improve them?

• Are these symptoms worse in the evening or at night compared with the morning?

Only respondents who were answering affirmatively to all three questions were classified as cases. In the first study,¹⁵ this questionnaire was validated against a case classification done by study physicians who conducted standardized neurological examinations on all participants. A comparison of the RLS classification based on the three questions with the classification by the examining neurologist yielded a high degree of concordance (κ statistic = 0.67).¹⁶ The statistical properties of this short questionnaire were also good, with a sensitivity of 87.5%, a specificity of 95.6%, and a likelihood ratio of 18.9. This set of three questions is the only instrument to date that has been validated against a physician diagnosis in studies of the general population.

The 1995 published criteria were slightly revised during a National Institutes of Health (NIH)-sponsored workshop in May 2002. Based on the validated questionnaire used in the German studies, this workshop also gave recommendations ³ for the assessment of RLS in population studies, or more generally in epidemiological research. The workshop participants recommended the following criteria:

• An urge to move the legs, usually accompanied or caused by uncomfortable and unpleasant sensations in the legs. (Sometimes the urge to move is present without the uncomfortable sensations and sometimes the arms or other body parts are involved in addition to the legs.)

• The urge to move or unpleasant sensations that begin or worsen during periods of rest or inactivity, such as lying or sitting.

• The urge to move or unpleasant sensations are partially or totally relieved by movement, such as walking or stretching, at least as long as the activity continues.

• The urge to move or unpleasant sensations are worse in the evening or night than during the day or only occur in the evening or night. (When symptoms are very severe, the worsening at night may not be noticeable but must have been previously present.)

The workshop did not address the problem of how to operationalize these criteria; i.e., how to exactly phrase questions that address these criteria. But the latter is important for the comparison of RLS case frequencies assessed with instruments in different languages or among participants with different cultural backgrounds. Thus, the question arises as to whether an RLS case classified by the use of a short questionnaire in English is comparable in its clinical characteristics with a case assessed through, for example, an Italian questionnaire despite a claim that both questionnaires address the minimal diagnostic criteria. The answer to this question is even more problematic if the comparison is done across more diverse languages or cultural backgrounds, such as in Asian populations.

Prevalence and Incidence of Restless Legs Syndrome

Although much clinical data on the pathophysiology of RLS exist, for a long time little was known about the epidemiology of this syndrome. To date the number of published epidemiological studies that give prevalence estimates on a population level has sharply increased. However, the number of those studies that used the minimal criteria developed by the International Restless Legs Syndrome Study Group is still limited.

Figure 7-1 shows prevalences in studies⁴^–⁶ ^,11 ^,17 ^,18 that did not apply the minimal diagnostic criteria but used their own questions or questionnaires, mostly because they were conducted before the minimal criteria were defined and published. As one might expect, there is considerable variation in the reported prevalences. The first two studies, conducted in Canada and Japan, each used two questions to assess RLS, whereas the others only applied a single question. The percentage of positive answers to each used question in the studies is listed in Figure 7-1. These percentages are shown for men and women separately if gender-specific answers were reported in the respective publication. The footnote under each bar clarifies the country in which the study was conducted, giving an acronym of the study (if listed in the publication), reports the number of study participants and their age range, and shows the response rate among those invited to participate if provided in the respective publication; otherwise, a question mark is shown.