Ulm, Univ., Diss., 2008.

Restless legs syndrome (RLS) is a sensorimotor disorder that often starts at a young age and has a chronic progression throughout life. It has a very high incidence, affecting 10% of the general population. The majority of cases are familial and the genetic nature of the disorder has been demonstrated in twin studies. RLS segregates in an autosomal dominant way in the majority of families. This data has incited a search for genetic factors responsible for RLS using linkage as the approach. Dr. Rouleau's laboratory has one of the world's largest collections of RLS pedigrees. These families are mostly of French Canadian (FC) origin. / Using these families, two novel candidate loci, on chromosomes 16p and 20p, were discovered. Also, previously described candidate loci on chromosomes 9p and 14q were replicated in this cohort of families. / A duplication of a large part of a functional candidate gene in the locus on chromosome 20, Signal Regulatory Protein beta 1 (SIRPB1), was discovered in individuals affected with RLS from a FC pedigree, in which linkage to this locus was described. The duplication segregates with the disease status in the family, but its role in RLS pathogenesis has yet to be demonstrated. / No disease-causing mutations were discovered in the chromosome 16 locus. Analysis of several functional and positional candidate genes in previously described loci on chromosomes 12 and 14 did not reveal disease-causing mutations. / A follow up of these studies is necessary in order to confirm the implication of SIRPB1 in RLS pathogenesis, and to detect novel gene(s) whose deregulation leads to this disorder.

Introduction: Restless legs syndrome (RLS) is a common neurological disorder affecting 10% of the population. Most antidepressants exacerbate symptoms; however, correlational studies have noted symptom improvement with bupropion. The purpose of the current study was to examine whether, in a controlled study, bupropion would improve the symptoms of RLS, or at least not exacerbate them. Methods: This was a double-blinded, randomized controlled trial. Twenty-nine participants with moderate to severe RLS received 150 mg sustained-release bupropion once daily, and 31 control participants received a placebo. Participants were followed for 6 weeks and completed standardized tools, including the International Restless Legs Syndrome Study Group (IRLSSG) severity scale. Results: The primary outcome was change from baseline in IRLSSG severity score; lower scores were associated with improved symptoms. At 3 weeks, IRLSSG scores were 10.8 points lower in the bupropion group and 6.0 points lower in the placebo group (P = .016). At 6 weeks, IRLSSG scores were 10.4 points lower in the bupropion group and 7.6 points lower in the placebo group (P = .108). Bupropion was more effective than placebo in the treatment of RLS at 3 weeks; however, this difference was not statistically significant at 6 weeks. Conclusions: The data from our study suggest that bupropion does not exacerbate the symptoms of RLS and may be a reasonable choice if an antidepressant is needed in individuals with RLS. Larger studies that include titration of bupropion should be considered to determine if bupropion is appropriate for primary treatment of RLS, particularly considering the lower cost and favorable side effect profile compared with currently recommended first-line dopamine agonists.

No description available.

thesis submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree Doctor of Philosophy. Johannesburg, 2013 / Restless Legs Syndrome (RLS) and Periodic Limb Movements (PLM) are common neurological disorders for which the underlying aetiology is not fully understood. Currently RLS and PLM are thought to be caused by a central deficiency of dopamine or other functional abnormalities of the central nervous system. The work included in this thesis investigated different new methods of assessing the sensory and motor features of RLS and PLM, in an attempt to extend our understanding of their aetiology and improve the accuracy of diagnosis of these conditions. The first two studies in the thesis described and characterized the sensations of RLS symptoms, and whether they are influenced by the presence of pain, in an English speaking South African population. The most frequently cited descriptors were different to those used in the current RLS diagnostic criteria. Inclusion of the most commonly used RLS descriptors in the diagnostic criteria may help to improve the accuracy of RLS diagnosis. Patients who experienced painful RLS had greater McGill Pain Questionnaire scores and used different terms to describe their RLS to those that did not have painful RLS sensations. The third project quantified the responses of the Hoffman and patellar reflexes in RLS patients using electromyography and kinematics. The RLS patients exhibited hyporeflexia in the evening compared to the morning, and compared to control participants. This data suggests that RLS is not the result of a global state of hyperexcitability, as the literature suggests, but may reflect more discrete functional abnormalities of the spinal cord. A diurnal variation in the patellar reflex was found, supporting the notion of circadian variations of spinal excitability in RLS patients. The final investigation assessed the sensory qualities (discomfort and pain) of RLS in conjunction with motor activity evoked by using the Suggested Immobilization Test. Despite rating significant levels of discomfort, the majority of the RLS patients did not exhibit PLM; possibly suggesting a disconnect between the sensory and motor components of RLS. In conclusion, it is the major finding of this thesis that inclusion of new assessment techniques for the measurement of sensory and motor features of RLS and PLM provides both new insights and potential clinical tools enhancing our understanding of these disorders.

Purpose: A key objective feature in Restless Legs Syndrome (RLS) is the presence of Periodic Limb Movements (PLMs). The gold standard for documenting PLMs is through polysomnogram (PSG), an overnight sleep study in a sleep laboratory, which is expensive and often inaccessible. This work explored the ability of a portable sleep monitor (PM) to reliably record surface EMG signals, to reliably record limb movements overnight in comparison with PSG, and examined intra- and inter-rater reliability for scoring the PM recordings. Methods: The PM’s surface EMG channel was tested against a standard EMG amplifier by recording bilateral tibialis anterior muscle activity in five healthy participants. It was also tested for recording PLMs simultaneously with polysomnography at Kingston General Hospital with 40 participants referred for screening of sleep disorders. PLMs were scored using standard criteria according to the American Academy of Sleep Medicine Scoring Manual (2007) Analyses: Comparison between the two methods of surface EMG recording was through counts of muscle activity bursts. Comparison of overnight PLM counts was through t-test, Pearson’s r, Intraclass Correlation Coefficient (ICC) and Bland-Altman plots. Intra-rater reliability and inter-rater reliability between two analysts was examined by ICC. Results: Examination of the PM surface EMG recordings demonstrated an exact match of muscle activity counts between the PM and standard EMG recordings. In the PSG study, mean difference between the two PLMI values was +4.8 ± 11.1, t (34) = 2.1, p = 0.04, which was statistically significant and demonstrated systematic over-reporting by the portable monitor. The two PLMI values were strongly correlated, giving a Pearson’s r = .87, p < 0.001. ICC for absolute agreement was 0.87, (95% CI, 0.76 – 0.93), p < 0.001. Bland-Altman analysis gave 95% limits of agreement between the two PLM Indices as +27.9 (95% CI +33.0 to 20.2) to – 19.3 (95%CI -10.6 to -23.4). Conclusions: These data suggest there may be sufficient agreement between PLMI collected by PM and polysomnography to support the use of the PM for measuring PLMs. Further testing should address test retest reliability and examine the performance of the PM in a wider patient population. / Thesis (Master, Rehabilitation Science) -- Queen's University, 2012-08-24 16:40:03.381

Background: Symptoms of anxiety and depression in patients with restless legs syndrome (RLS) have been observed. However, it is unclear whether rates of threshold depression and anxiety disorders according to DSM-IV criteria in such patients are also elevated. Methods: 238 RLS patients were assessed with a standardized diagnostic interview (Munich- Composite International Diagnostic Interview for DSM-IV) validated for subjects aged 18–65 years. Rates of anxiety and depressive disorders were compared between 130 RLS patients within this age range and 2265 community respondents from a nationally representative sample with somatic morbidity of other types. Results: RLS patients revealed an increased risk of having 12-month anxiety and depressive disorders with particularly strong associations with panic disorder (OR=4.7; 95% CI=2.1–10.1), generalized anxiety disorder (OR=3.5; 95% CI= 1.7–7.1), and major depression (OR=2.6; 95% CI=1.5–4.4). In addition, lifetime rates of panic disorder and most depressive disorders as well as comorbid depression and anxiety disorders were considerably increased among RLS patients compared with controls. Conclusions: The results suggest that RLS patients are at increased risk of having specific anxiety and depressive disorders. Causal attributions of patients suggest that a considerable proportion of the excess morbidity for depression and panic disorder might be due to RLS symptomatology.

Syftet med denna systematiska litteraturstudie var att beskriva hur restless legs inverkar på individens sömn och livskvalitet. Syftet var även att granska vilka olika former av behandlingar som finns att tillgå vid restless legs. För att finna information om detta ämne har endast vetenskapliga artiklar använts. Datainsamlingen har skett via databaser, internet samt Högskolans bibliotek, och artiklar från år 1995 och framåt har valts ut. Inklusionskriterier för denna studie var att de valda artiklarna skulle vara internationella vetenskapliga artiklar i fulltext. De funna artiklarna granskades med avseende på vetenskaplig kvalitet och poängsattes utifrån för ändamålet avsedda granskningsmallar. Denna bedömning resulterade i 21 artiklar. Resultatet visade att restless legs patienter upplever sömnbristen som det största problemet. För flertalet individer som drabbas av restless legs försämrades livskvaliteten och patienterna drabbades vanligtvis av psykologiska och fysiologiska besvär. Det vanligaste sättet att behandla restless legs var att använda dopaminerga läkemedel samt bensodiazepiner, antiepileptika och opioider. Andra former av behandlingar var järn, homeopatiska läkemedel, hypnos samt fysisk aktivitet. Det förekom även att restless legs patienter på eget initiativ använde hasch eftersom det ansågs lindra symtomen.

It is known that sleep problems affect people’s wellbeing and has great consequences for public health. Restless legs syndrome (RLS) gives uncomfortable sensations in the legs at rest, leading to an irresistible need for activity. It aggravates in evening and at night. Therefore, RLS provides poorer sleep and can affect quality of life through fatigue, family life and social activities, work, and comorbidity. It is demonstrated a dysfunction of the dopaminergic system in the brain with low levels of dopamine and / or less sensitive dopamine receptors. RLS is more common in women and the prevalence increases with age and during pregnancy. Periodic limb movements are characterized by uncontrolled stretching movements of the legs, especially the toes, ankles, knees and hips during sleep. They last between 0.5 and 5 seconds, and can cause brief awakenings leading to daytime sleepiness. The clinical significance of PLM is rather controversial and PLM is sometimes seen in healthy people with no daytime symptoms. RLS is a subjective diagnosis and translated with the help of questionnaires. PLM however, can objectively be evaluated by polysomnography. Depression is common during and after pregnancy. It is not known whether women with RLS during pregnancy have a higher risk of prenatal or postpartum depression. The aims of this thesis was to  to examine the prevalence, associated symptoms and comorbidities, in particular, vasomotor symptoms, menopause, and hormone replacement therapy (HRT) use, among women who suffer from RLS and PLMs. We also evaluated the impact of RLS and PLMs on health related quality of life (HRQoL), and if RLS before and during pregnancy increases the risk of antenatal or postpartum depressive symptoms. Three different poulations were used.  Paper 1-3 were cross-sectional and included 5000 resp. 10000 randomly selected women from the general populations of Dalarna and Uppsala County. Questionnaires, polysomnographic recordings, blodtests etc. were used. Paper 4 was a longitudinal cohort study where 1428 pregnant women in Uppsala County were followed. In summary, data included in this thesis points out that RLS and PLMs are more common in women with estrogendeficiency-related symptoms of menopause. RLS-positive women had an impaired mental HRQoL compared to RLS-negative women and more often suffered from comorbidities. Data also revealed that women with RLS before and during pregnancy are at increased risk for depression during and after pregnancy.

Freiburg i. Br., Univ., Diss., 2007.