Validation of the self-completed Cambridge-Hopkins questionnaire (CH-RLSq) for ascertainment of restless legs syndrome (RLS) in a population survey.

BACKGROUND AND PURPOSE: Epidemiological studies of restless legs syndrome (RLS) have been limited by lack of a well validated patient-completed diagnostic questionnaire that has a high enough specificity to provide a reasonable positive predictive value. Most of the currently used patient completed diagnostic questionnaires have neither been validated nor included items facilitating the differential diagnosis of RLS from conditions producing similar symptoms. The Cambridge-Hopkins diagnostic questionnaire for RLS (CH-RLSq) was developed with several iterations to include items covering the basic diagnostic features of RLS and to provide some basic differential diagnosis. This validation study sought to determine the sensitivity and specificity of the RLS diagnosis based on this questionnaire. PATIENTS AND METHODS: The CH-RLSq was completed by 2005 blood donors who were asked to consent to being contacted for a telephone diagnostic interview. A scoring criterion was established for ascertainment of RLS based on the clinical definition of the disorder and the exclusion of "mimic" conditions. A weighted sample (N=185) of all completed questionnaires was selected for expert clinical diagnosis of RLS using the validated Hopkins Telephone Diagnostic Interview (HDTI). The telephone interviewers were blinded to all questionnaire responses. RESULTS: A telephone diagnosis was obtained on 183 of the sample's 185 questionnaires. The questionnaire's normalized sensitivity and specificity were 87.2% and 94.4%, respectively, for RLS compared to not RLS. The positive predictive values in this sample were 85.5%. CONCLUSIONS: The Cambridge-Hopkins RLS questionnaire provides a reasonable level of sensitivity and specificity for ascertainment of RLS in population-based studies

RLS and blood donation.

BACKGROUND AND PURPOSE: The link between brain iron deficiency and RLS is now well established. In a related observation, several conditions that can deplete iron stores have been linked to increased probability of RLS. Blood donation has been linked to iron deficiency. It has thus been hypothesized that donating blood may be a risk factor for developing RLS. PATIENTS AND METHODS: Two thousand and five UK blood donors, ranging from first-time donors to some who had donated more than 70 times, completed the validated Cambridge-Hopkins RLS questionnaire (CH-RLSq) following their donation session. The questionnaire included a set of questions designed to diagnose RLS. The donors' histories of blood donations were determined both from self-report and from the National Blood Service database. RESULTS: A number of statistical models were constructed to determine whether the probability of RLS diagnosis was related to the history of blood donations. Controlling for age and sex, no evidence was found to suggest that a greater number or frequency of blood donations increased the risk of RLS. Even amongst sub-groups especially vulnerable to iron depletion through blood donation, such as vegetarians or low weight individuals, no evidence for an increased risk of RLS could be found. CONCLUSIONS: We found no evidence that the frequency or number of blood donations up to the UK maximum of three times a year would increase the risk of RLS

Investigation of altering single-nucleotide polymorphism density on the power to detect trait loci and frequency of false positive in nonparametric linkage analyses of qualitative traits

Genome-wide linkage analysis using microsatellite markers has been successful in the identification of numerous Mendelian and complex disease loci. The recent availability of high-density single-nucleotide polymorphism (SNP) maps provides a potentially more powerful option. Using the simulated and Collaborative Study on the Genetics of Alcoholism (COGA) datasets from the Genetics Analysis Workshop 14 (GAW14), we examined how altering the density of SNP marker sets impacted the overall information content, the power to detect trait loci, and the number of false positive results. For the simulated data we used SNP maps with density of 0.3 cM, 1 cM, 2 cM, and 3 cM. For the COGA data we combined the marker sets from Illumina and Affymetrix to create a map with average density of 0.25 cM and then, using a sub-sample of these markers, created maps with density of 0.3 cM, 0.6 cM, 1 cM, 2 cM, and 3 cM. For each marker set, multipoint linkage analysis using MERLIN was performed for both dominant and recessive traits derived from marker loci. Our results showed that information content increased with increased map density. For the homogeneous, completely penetrant traits we created, there was only a modest difference in ability to detect trait loci. Additionally, as map density increased there was only a slight increase in the number of false positive results when there was linkage disequilibrium (LD) between markers. The presence of LD between markers may have led to an increased number of false positive regions but no clear relationship between regions of high LD and locations of false positive linkage signals was observed

Progressive development of augmentation during long-term treatment with levodopa in restless legs syndrome: results of a prospective multi-center study

The European Restless Legs Syndrome (RLS) Study Group performed the first multi-center, long-term study systematically evaluating RLS augmentation under levodopa treatment. This prospective, open-label 6-month study was conducted in six European countries and included 65 patients (85% treatment naive) with idiopathic RLS. Levodopa was flexibly up-titrated to a maximum dose of 600 mg/day. Presence of augmentation was diagnosed independently by two international experts using established criteria. In addition to the augmentation severity rating scale (ASRS), changes in RLS severity (International RLS severity rating scale (IRLS), clinical global impression (CGI)) were analyzed. Sixty patients provided evaluable data, 35 completed the trial and 25 dropped out. Augmentation occurred in 60% (36/60) of patients, causing 11.7% (7/60) to drop out. Median time to occurrence of augmentation was 71 days. The mean maximum dose of levodopa was 311 mg/day (SD: 105). Patients with augmentation compared to those without were significantly more likely to be on higher doses of levodopa (≥300 mg, 83 vs. 54%, P = 0.03) and to show less improvement of symptom severity (IRLS, P = 0.039). Augmentation was common with levodopa, but could be tolerated by most patients during this 6-month trial. Patients should be followed over longer periods to determine if dropout rates increase with time