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Table of Contents    
ORIGINAL ARTICLE
Year : 2018  |  Volume : 66  |  Issue : 4  |  Page : 1020-1027

Evaluation of the diagnostic yield of ARQIP: A new restless legs syndrome diagnostic questionnaire and validation of its Hindi translation


1 Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
2 Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India

Date of Web Publication18-Jul-2018

Correspondence Address:
Dr. Garima Shukla
Department of Neurology, All India Institute of Medical Sciences, New Delhi - 110 029
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.236962

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 » Abstract 


Background: Restless legs syndrome (RLS) is misdiagnosed due to a variety of clinical presentations and lack of a diagnostic biomarker. Sociocultural differences in patients' reporting of symptoms further contribute to this under diagnosis. We developed an expanded diagnostic tool for RLS, incorporating all International RLS Study Group (IRLSSG) diagnostic criteria with a number of additional questions mainly focusing on specific sociocultural influences in RLS symptom reporting among Indians. The purpose of this study was to examine the change in the diagnostic yield of RLS, if any, through administration of this expanded questionnaire.
Materials and Methods: The AIIMS RLS questionnaire for Indian patients (ARQIP) was developed in English language, and then translated into Hindi. All consecutive patients attending Neurology and sleep disorders clinic with complaints of leg discomfort were recruited in the study. Two examiners evaluated all patients with complaints of leg discomfort seen by a senior Sleep Medicine expert, one using only IRLSSG diagnostic criteria and the other using the ARQIP. Patients were categorized as RLS or “no-RLS” by the expert, and this was considered as the “standard” for analysis.
Results: A total of 155 participants (78 males, 50.3%) with a mean age of 44.1 ± 14.5 years were enrolled. A total of 105 patients were diagnosed as having RLS (group 1) and the rest as having “non-RLS” (group 2). The ARQIP was found to have a much higher sensitivity (100% vs 73%), specificity (44% vs 32.7%), negative predictive value (100% vs 36.4%), and positive predictive value (79% vs 70%) compared to the standard questionnaire. The diagnostic yield of this tool was 26.7% (Confidence interval = 100–73.3).
Conclusions: The ARQIP for RLS diagnosis, validated in this study, has been observed to have a high sensitivity and a negative predictive value with a high diagnostic accuracy.


Keywords: AIIMS Restless legs Syndrome Questionnaire, Hindi version, validation
Key Message: An expanded diagnostic tool for restless leg syndrome (RLS), incorporating all International RLS Study Group (IRLSSG) diagnostic criteria, along with a number of additional questions, related to the description as well as the relieving factors for the discomfort, has been described. On examination of the change in diagnostic yield through administration of this expanded questionnaire, as compared to a simple questionnaire based solely on the IRLSSG diagnostic criteria, revealed that the expanded questionnaire was observed to have a high sensitivity and a negative predictive value with a high diagnostic accuracy.


How to cite this article:
Shukla G, Bajpai G, Gupta A, Katoch J, Mohammed A, Pandey R M, Goyal V, Srivastava A, Behari M. Evaluation of the diagnostic yield of ARQIP: A new restless legs syndrome diagnostic questionnaire and validation of its Hindi translation. Neurol India 2018;66:1020-7

How to cite this URL:
Shukla G, Bajpai G, Gupta A, Katoch J, Mohammed A, Pandey R M, Goyal V, Srivastava A, Behari M. Evaluation of the diagnostic yield of ARQIP: A new restless legs syndrome diagnostic questionnaire and validation of its Hindi translation. Neurol India [serial online] 2018 [cited 2018 Nov 18];66:1020-7. Available from: http://www.neurologyindia.com/text.asp?2018/66/4/1020/236962




Restless legs syndrome (RLS), also known as Willis–Ekbom disease (WED), is a sensorimotor disorder, which was initially described in literature in 1685 by Sir Thomas;[1] half a century later, the newly formed International RLS Study Group (IRLSSG) proposed and published a set of criteria to allow for a more uniform diagnosis.[2] The growth in the field of RLS has been voluminous and is still continuing, and hence the need for reappraisal of the original criteria arose. Additional scientific scrutiny and clinical experience led to the first revision of the criteria in 2003, which mainly substituted the third essential criterion “motor restlessness” with “relief with movement” and the phrase 'urge to move legs' was emphasized and used in each criterion.[3]

The salient features of the second revision of RLS criteria in the year 2012 were:[4]

  1. Addition of a fifth essential criterion, differential diagnosis, to improve specificity by requiring that RLS/WED symptoms not be confused with similar symptoms from other conditions
  2. Addition of a specifier to delineate clinically significant RLS/WED
  3. Addition of course specifiers to classify RLS/WED as chronic persistent or intermittent
  4. Merging of the pediatric with the adult diagnostic criteria.


RLS is a common, yet one of the most under-diagnosed and easily treatable neurological entities.[5],[6],[7] Prevalence estimates for RLS/WED are between 2.4% and 10.8% in Europe and the USA.[5],[8] Large epidemiological studies in Western populations have reported a high prevalence; 11.1% prevalence was found in the REST study (n = 23052) and 8.8% prevalence was found in the INSTANT study (n = 10263).[9] The lowest prevalence rates have been reported from East Asia and South America; 1.8% in Japan,[10] 1.6% in Taiwan,[11] 1.1% in Korea,[12] and 2% in native South American populations.[13] In fact, the prevalence rate of RLS among chronic kidney disease (CKD) patients in Japan was found to be 3.5%, which is less than Western data in the healthy population.[14] These rates vary between countries even when uniform inclusion criteria are used; this is thought to be due to different assessment procedures (mail, face-to-face interviews, etc.), different genetic data of study populations, as well as age and sex composition and different languages spoken by the study population.

In India, as yet, there are no large-scale epidemiological studies. Most of the Indian publications quote western data. A few studies from our country have shown varying controls studied in comparison with special populations such as Parkinson's disease. The two epidemiological studies from South India found prevalence rates of RLS to be approximately 2%,[15],[16] whereas the prevalence of RLS among patients with iron deficiency,[17] Parkinson's disease,[18],[19] CKD,[20] and depression [21] is much higher.

The lack of diagnosis is because of paucity of clinical suspicion, which is now improving with expanding knowledge and sensitization of primary care physicians, neurologists, and other medical personnel regarding this condition. Another major factor in under-recognition of this common condition, among our population, is the wide variation in the clinical presentation of patients suffering from RLS. This, as has been previously reported by us, is mainly due to sociocultural differences in perception and the choice of language used or the practices and beliefs about the relieving maneuvers.[22] The clinical presentation may not meet all the standard IRLSSG criteria, and hence, results in a missed diagnosis. Based on the experience with the large numbers of patients diagnosed in specialty sleep disorders clinics, we developed an expanded diagnostic tool for RLS, incorporating all IRLSSG diagnostic criteria, along with a number of additional questions, mainly related to the relieving factors as well as the description of the discomfort.

The purpose of this study was to examine the change in diagnostic yield, if any, through administration of this expanded questionnaire as compared to a simple questionnaire based solely on the IRLSSG diagnostic criteria.


 » Materials and Methods Top


This study was conducted prospectively to test the diagnostic utility (sensitivity, specificity, positive and negative predictive values, and likelihood ratio) for a new RLS questionnaire, especially constructed with incorporation of unique sociocultural characteristics of clinical presentation of the syndrome among the Indian population.

Development of the instrument

The AIIMS RLS questionnaire for Indian patients (ARQIP) was developed using specific questions that allowed determination of the four key IRLSSG diagnostic criteria, along with several other features which are characteristic to our population.

Part one of this expanded questionnaire registered the demographic details of the patient including name, age, sex, residential address, contact number, email, marital status, occupational status, and handedness.

Part two included the description of the presenting complaints expressed as either (a) sensory phenomena of pain, twisting, burning, pricking, or tingling sensation, or just discomfort, or (b) motor phenomena of repetitive limb movements at rest or in sleep or the need for night-time massage or jerking legs or pressing against bed, to initiate sleep, or (c) insomnia, with complaints of delayed sleep initiation or repeated night-time awakenings or non-refreshing sleep.

This part also registered the duration of symptoms, the body part affected, and whether symptoms were unilateral or bilateral, and symmetrical or asymmetrical.

The third part of the instrument covered the four diagnostic criteria of RLS.

The fourth part of the questionnaire included supportive symptoms of RLS, as follows:

  1. Symptoms worse on awakening
  2. Repetitive limb movements in the awake stage
  3. Repetitive limb movements during sleep
  4. Delayed sleep initiation
  5. Frequent awakenings due to limb discomfort
  6. Greater than 50% benefit of dopaminergic therapy, if given
  7. Excessive daytime fatigue
  8. Symptoms much worse at night when the patients have had excessive physical activity during the daytime
  9. Family history of fulfillment of all the four diagnostic criteria
  10. Family history of nightly need for leg massaging for sleep.


The fifth part of our questionnaire incorporated relieving factors other than walking. This part was specifically constructed to include socio-culturally characteristic features commonly reported by patients with RLS among our population; leg massaging and/or the need for leg massage before falling asleep. These included:

  1. Moving or voluntary jerking limbs in bed
  2. Pressing limbs against a hard surface such as the foot-board of the bed
  3. Tying a cloth tightly around the calves
  4. Immersing legs and feet in hot or cold water
  5. Other relieving maneuvers.


Part six included any coexisting behavioral or psychiatric manifestations.

Parts seven and eight included details of prior diagnosis of any other neurological or primary sleep disorder, and the eighth part recorded any significant past history.

Part nine recorded the pedigree chart for RLS, and the last part ten recorded relevant investigations, mainly the hemogram, hepatic and renal function tests, and serum ferritin.

On the basis of the new questionnaire, patients were diagnosed to have RLS when they gave positive responses to at least 2 essential diagnostic criteria (part 3 of the questionnaire) along with at least 3 supportive features (part 4) and at least 2 relieving maneuvers (part 5).

The other parts of the questionnaire mainly included other important details pertinent to the investigation of patients with RLS; these were mainly demographic information and questions pertaining to associated conditions, which were relevant to the management of patients.

Translation

The expanded questionnaire was written in English language as most of the official work is conducted in this language [Appendix A-1]. Two bilingual experts (JK and AM) translated it into Hindi (versions 1 and 2). The two versions were discussed in detail to keep the language closest to the original version. This version 3 was discussed with the clinical sleep expert (GS) for appropriate changes and was translated by GB back to English [version 4] to check the consistency with the original performa. It was then translated again to Hindi by AG to produce the final version 5. Both Hindi and English versions were administered, each 1 month apart, to 30 educated individuals who were well-versed with both languages to check for the consistency of the results.

The expanded questionnaire also contained the four diagnostic criteria; this part was translated and applied separately as a part of this study.

The translation and its validation were performed for this physician-administered questionnaire so as to ensure uniformity in the use of specific words for specific questions by anyone who is administering the questionnaire.

Participants

After approval of the protocol from the Institute Ethics committee, consecutive patients attending Neurology clinic and Sleep disorders clinic with complains of leg discomfort, seen by a senior sleep disorders expert (GS), were recruited.

Inclusion criteria

All patients presenting with discomfort in the lower limbs, suspected to be suffering from RLS, were included in the study. The patients diagnosed as confirmed cases of RLS by GS, served as cases, and those not confirmed served as non-cases.

Exclusion criteria

  • Patients not giving consent.
  • Patients with an established diagnosis of RLS, with greater than 1 year complete relief from symptoms (with or without therapy) [to avoid the recall bias].


Testing protocol

Two examiners at different stations evaluated the patient presenting to the clinic. Examiner 1 (GB) applied the IRLSSG diagnostic criteria expressed as questions. The four questions were asked in person, or via a telephonic interview if the patient was absent or only a family member had reported.

Examiner 2 (AG) administered the ARQIP. The patient was then finally evaluated by the senior sleep disorders expert (GS) and all patients were given the diagnosis of RLS or “no-RLS” during the same visit or the next visit by the expert. This diagnosis was considered as a “standard” for analysis purposes.

Statistical analysis

Statistical analysis was carried out by Open epicalculator and the STATA 11.0 statistical software, StataCorpLP, Texas, USA, to determine the sensitivity, specificity, positive and negative predictive values, likelihood ratio for positive and negative test results, and diagnostic yield of the new instrument. Descriptive statistics were used for categorical variables, and independent t-test for comparison of age in the two groups.


 » Results Top


Study population

A total of 155 participants (50.3% males, 49.6% females) with an average age of 44.1 ± 14.5 years (range: 6–74 years) were enrolled during the study period. With comprehensive expert clinical interview, 105 of these patients were diagnosed to have RLS (group 1) and the rest were categorized as the “non-RLS” (group 2). There was no difference in the mean age between groups 1 and 2 (42.8 ± 15.1 years versus 46.7 ± 13.1, years, respectively) [P = 0.13].

Sensitivity and specificity of the diagnostic criteria

The standard questionnaire based only on the four-point IRLSSG diagnostic criteria and the ARQIP were both compared with the standard, i.e., the expert's diagnosis. The standard questionnaire was found to have a sensitivity (proportion of truly diseased persons in the screened population who were identified as diseased by the screening test) of 73.3%, specificity (proportion of persons without the disease who had low scores on the screening test, i.e., the probability that the test will correctly identify a non-diseased person) of 32.7%, positive and negative predictive values of 70% and 36.4%, respectively, and a diagnostic accuracy of 60.4% [Table 1]. The ARQIP had a sensitivity and specificity of 100% and 44%, respectively, and positive and negative predictive values of 79% and 100%, respectively, with a diagnostic accuracy of 81.9%. The diagnostic yield of this tool was then found to be 26.7% (confidence interval [CI] = 100–73.3).
Table 1: Diagnostic value of the standard criteria (IRLSSG) versus that of the ARQIP for RLS diagnosis

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The likelihood ratio for the standard questionnaire (IRRLSG criteria alone) was found to be 1.1 and for the ARQIP, it was 1.8.


 » Response Rates to Components of the Standard Irlssg Criteria-Based Questionnaire and the ARQIP Top


In both the groups diagnosed by the expert interview, the standard questionnaire had a high positivity on question 1 (90% and 96%) and the lowest positivity on question 3 (63% and 76%).

Out of the four standard questions in the standard IRLSSG criteria based questionnaire, the number of patients with negative responses in the RLS group, were:

Q1: (Discomfort in leg or urge to move leg) = 0

Q2: (Discomfort more at rest) = 3

Q3: (Discomfort relieved by movement or walking) = 29

Q4: (Discomfort more in the evening) = 7.

The third question in the IRLSSG criteria was answered in the negative most frequently, and in contrast, all these patients answered positively for other relieving maneuvers, especially massaging of limbs.

In contrast, a number of components of the ARQIP had high positive response rates, as detailed in [Table 2]. While relief with massaging of limbs was reported in the positive by nearly 80% of the patients, several other components also showed high positive response rates; however, none of these positive response rates was in the range of >90%, implying that while most of the additional components in the ARQIP were extremely useful for RLS diagnosis, none had an exclusively high diagnostic value (positive response rate).
Table 2: Positive response rates for Parts 2, 4, 5, 6, and 9 of the ARQIP

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 » Discussion Top


This study was designed with the aim of examining an increase in the diagnostic yield, if any, of a new expanded RLS questionnaire, primarily based on unique sociocultural characteristics of the syndrome in Indian population. The main findings were of increase in sensitivity to 100% from nearly 73%, for a standard questionnaire based on the four main diagnostic criteria, with a modest increase in specificity as well. Diagnostic accuracy of the extended criteria was 82% as compared to 60% for the standard criteria. These parameters assessing the diagnostic criteria were calculated considering the clinical diagnosis by a sleep expert (GS) as the gold standard.

Hening and Allen evaluated the IRLSSG criteria for their specificity, mainly testing them for one important supplemental point, i.e., RLS mimics. They evaluated 1255 family members and diagnosed 1232 cases among them; 402 (32.0%) had definite or probable RLS, 42 (3.3%) possible RLS, and 788 (62.8%) did not have 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%. This was for the first time that specificity, sensitivity, and positive predictive value of the RLS criteria were evaluated.[23]

Questionnaire studies with just the four IRLSSG diagnostic criteria in the Western populations have been found to show a high sensitivity (86%) but low specificity (45%).[24] When used in general population studies, this yields positive predictive values of, at best, approximately 50–55% for identification of RLS/WED.[8] This is quite similar to our results in the Indian population. Yet, a possible explanation for the low specificity is that ours is a quaternary care apex center and patients are a highly-selected group referred for difficult to diagnose and treat neurological conditions. This may account for a higher prevalence than is seen in the general population of conditions mimicking RLS, such as radiculopathy and neuropathy. It has been shown that adding questions to exclude common mimics can improve the specificity with only a small loss of sensitivity, e.g., the Cambridge–Hopkins diagnostic questionnaire with questions specific to common mimics has a high specificity of 94.4% and a sensitivity of 87.2%.[25]

However, the purpose of our study was to improve the sensitivity and diagnostic yield so that true cases are not missed out. Our contention was that the prevalence of RLS in our country is not less, as shown in the few population based studies (approximately 2.1%), compared to the Western populations (5–11%) but instead it was just expressed differently by patients. As these features are not detailed in any questionnaire simply based on the limited IRLSSG criteria, treating physicians possibly miss out detecting several true cases, accounting for the low prevalence.[7]

The low specificity of both the questionnaires in the population attending our clinics cautions against over-diagnosis of RLS. However, at the inception, this was pre-empted and we believe that over-diagnosing RLS may not be a disadvantage. A large Swedish study on 5000 women showed impaired well-being among women with RLS.[26],[27] A recent study demonstrated poor health-related quality of life among adolescents and young adults suffering from RLS. RLS associated sleep deprivation may have many adverse health effects.[22] There are recent studies showing that RLS is related to nocturnal/supine hypertension and blood pressure fluctuations, suggesting a neuropathological association between the autonomic and sleep dysfunctions in patients with Parkinson's disease.[28] It has also been shown that end-stage renal disease (ESRD) patients with RLS demonstrated an increased likelihood of cardiovascular or cerebrovascular events and mortality.[29] The number of conditions in which RLS is found with much higher prevalence than the general population is large, and many patients presenting with RLS may for the first time be detected to have conditions, such as iron deficiency,[30] diabetes,[31] or neuropathy,[32] on investigation. Apart from these obvious advantages of early diagnosis of RLS and of keeping a low threshold for suspecting it, timely symptomatic treatment as well as treatment of the associated conditions, such as iron deficiency and diabetes, can lead to huge gains as far as overall health and well-being of patients is concerned. At the same time, these treatments are neither invasive, nor known to cause any major adverse effects, if they are tried to bring about relief to patients with chronic leg discomfort, in whom the diagnosis of RLS is made.

Apart from this, the economic burden of the disease is mainly due to productivity losses, which are as high as 20% in RLS/WED patients.[27] On the contrary, the actual treatment cost for RLS is low. Annualized direct expenditures based on these 3-month data for RLS-specific healthcare resources only were estimated to be $350 for participants who received treatment for the primary RLS ($187 for the medical visits, $129 for the medications) that they had; these figures were $490 for RLS sufferers ($274 for the medical visits, $171 for the medications).[27] The economic burden of RLS has not been studied in India; however, it is estimated to be far less by Salas and Kwan, than is seen in this study, with the free availability of generic drugs and the gain in man-hours, thus improving productivity of the suffering individuals. A cross-sectional health survey with face-to-face interviews with 1312 participants in the Dortmund Health Study showed that about every fourth RLS case knows about the diagnosis and overall every fifth RLS case wishes to be administered medication to effectively reduce symptoms. The figure is corresponding to 1.6% of the whole study population.[33]

With treatment of RLS ranging from being as simple as supplementation of an iron tablet to a single night dose of a dopamine agonist, to which most of our patients responded, and a few of them being symptom-free and treatment-free after a few months of treatment, we propose that it is better to over-diagnose and treat, underlining the importance and the utility of the expanded questionnaire, namely the ARQIP.

Another point highlighted by the present study is the high response rate to the questions based on “relieving maneuvers” in Part 5 of the ARQIP. While the most common relieving maneuver reported was “massage of limbs,” most patients also reported an “urge to massage limbs” instead of “urge to move,” in part 3 of the ARQIP. While this is a culturally characteristic feature of RLS in India, the relieving effects of massage are widely recognized and are also studied as part of a nonpharmacological treatment for the RLS.[34]

Limitations

The main limitation of the study was that the questionnaire developed and validated was lengthier than the existing set of questions based on the diagnostic criteria alone. However, with adequate practice, (because it does not take more than 10 minutes for completion), this lengthier questionnaire will probably not limit the widespread utilization of this tool across India and the Indian subcontinent.


 » Conclusion Top


This study validates a new expanded diagnostic questionnaire for recognizing RLS, especially among the Indian population, and highlights the high sensitivity and positive predictive value of the same. It is expected that the use of this expanded questionnaire would aid in timely recognition and treatment of this common, often disabling disorder, with simple treatment strategies.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

  [Table 1], [Table 2]



 

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