Cases Of RLS Research Articles

Sleep disorders in patients with chronic tinnitus

Tinnitus has a lifetime prevalence of 25% in Germany. A common comorbidity in chronic cases are sleep disorders. The aims of this study were to detect sleep disorders and to identify possible associations with tinnitus parameters.Fifty patients with chronic tinnitus were recruited. The patients underwent audiometry, polysomnography, and completed standardised questionnaires on tinnitus and sleep behaviour.Data were available in 30 men and 9 women (age 50.2 ± 11 y, BMI 28.8 ± 4.4 kg/m²). The median duration of tinnitus was 36 (9; 120) months with a severity score of 2.00 (1.00; 3.00). The mean Tinnitus Questionnaire (TF) score was 43.6 ± 17.1, the Epworth Sleepiness Scale (ESS) score was 8.41 ± 4.27, the Pittsburgh Sleep Quality Index (PSQI) score was 9.21 ± 4.32, and the Screening Scale for Chronic Stress (SSCS) score was 58.13 ± 9.58.Sleep diagnoses included 18 cases of insomnia, 4 cases of RLS, and 11 cases of OSA. Patients with sleep comorbidities showed higher tinnitus severity, PSQI scores, and body weight compared to those without sleep disorders.Worse sleep quality was associated with higher tinnitus severity (p=0.038) and more disruptive tinnitus (p=0.03). Patients with subjectively highly disruptive tinnitus reported higher chronic stress scores. Tinnitus duration was correlated with OSA-severity (p=0.026).More than two-thirds of tinnitus patients showed sleep disorders as comorbidity. A sleep screening appears useful in cases of increased tinnitus severity. Whether CPAP therapy is helpful in reducing tinnitus symptoms could not be conclusively determined but deserves further attention.

Two cases of pediatric RLS and elevated CK – an association or a coincidence?

Two cases of pediatric RLS and elevated CK – an association or a coincidence?

No association between plasma hepcidin levels and restless legs syndrome - results from the Danish Blood Donor Study

BackgroundRestless Legs Syndrome (RLS) is a neurological sensorimotor disorder that occurs in the evening and night, thereby often impacting quality of sleep in sufferers. The aetiology of RLS is not completely understood although iron dysregulation has been suggested as a likely pathway. The relationship between RLS and the iron regulatory protein hepcidin has not been studied in large cohorts. We aimed to assess whether an association between plasma hepcidin variation and RLS exists in a large cohort of healthy individuals. MethodsPlasma hepcidin levels were measured in 9708 Danish blood donors from the Danish Blood Donor Study all of whom correctly completed the validated Cambridge–Hopkins RLS-questionnaire for RLS assessment. ResultsA total of 466 blood donors were determined as current RLS cases in the sample (4.8%). RLS cases had a significantly higher proportion of females (56.7% vs 46.7%; P < 0.001) and were older (median age [IQR] 40.6 years vs 38.0 years; P = 0.010) than controls. RLS cases were also more frequent smokers (P = 0.004). No significant differences were found in body mass index (BMI), alcohol consumption, time of donation and donation history between cases and controls. No difference in plasma hepcidin levels was observed between RLS cases and controls (median concentration [IQR]: 10.5 ng/ml [6.3–16.4] in RLS cases vs 10.5 ng/ml [6.0–16.5] in controls). Using a logistic regression model, we found that hepcidin levels were not associated with RLS after adjusting for age, sex, alcohol consumption, smoking status, donation time and donation history (OR = 1.00 [0.99–1.02] per 1 ng/ml increase of hepcidin; P = 0.429). ConclusionOur study in Danish blood donors did not find an association between RLS and plasma hepcidin levels. Our findings suggest that plasma hepcidin's role as a potential diagnostic biomarker of RLS is inadequate.

THE POSSIBLE LINK BETWEEN VITAMIN D LEVELS AND RESTLESS LEG SYNDROME: A HOSPITAL-BASED CASE-CONTROL STUDY FROM KASHMIR, INDIA

Background &amp; Objectives: Various pathophysiological mechanisms and risk factors have been identified in patients with restless leg syndrome and there exist other factors also that are yet to be identified and are under-researched. Evidence suggests a possible link between Vitamin D deficiency and Restless leg syndrome.The aim was to study the Vitamin D levels in patients diagnosed with RLS and to find a correlation between Vitamin D and RLS. Methods: This was a case-control study carried out in the outpatient department of the Institute of Mental Health and Neurosciences Kashmir.A total of 144 subjects were enrolled in the study. Fifty-one were diagnosed cases of RLS and 93 were healthy controls.The Vitamin D levels were analysed by the chemiluminescent immunoassay method in both cases as well as controls.The descriptive statistics were used for various socio-demographic and clinical variables.The data were analysed by chi-square test, t-test and multivariate logistic regression analysis. Results: The vitamin D levels were significantly low in the RLS group in comparison to the control group. There was a significant correlation between vitamin D levels, vitamin D deficiency and restless leg syndrome (OR= 1.01, p-value 0.005 and OR= 5.40, p-value &lt;0.0001 respectively). Interpretation &amp;conclusions: Vitamin D levels were low in patients with RLS. This signifies vitamin D may have some role in the pathophysiology of RLS.Vitamin D regulates the nervous system development and function therefore, its use can be considered in the management of RLS when other modalities cannot prove as a promising agent.

Genetic and epidemiological characterization of restless legs syndrome in Québec.

Currently, a total of 19 genetic loci are associated with the risk for developing RLS. This study aimed to assess these RLS predisposing genetic variants, as well as investigate the epidemiological profile and diagnostic features of individuals with RLS in the Québec population, using an interviewer-administered questionnaire. A total of 18 RLS-associated variants were genotyped in the Québec population-based CARTaGENE cohort. A case-control series consisting of 1,362 RLS cases and 1,379 age-matched unaffected controls was used to conduct a genetic and epidemiological association study that integrated the first four RLS diagnostic features of affected individuals, as well as additional RLS-related questions (e.g. frequency of the symptoms and number of total pregnancies in female). Five RLS-predisposing variants were significantly associated after Bonferroni correction and an additional five variants were nominally associated with RLS (p < 0.05). BTBD9 was the strongest genetic risk factor in our cohort (rs9296249, OR = 1.71, p = 9.57 × 10-10). The patient group that met all four essential diagnostic criteria of RLS provided the most significant genetic findings. These results suggest that employing the questionnaire which included standard diagnostic criteria of RLS could improve the accuracy of the survey-based studies.

Development and Validation of RLS Diagnostic Questionnaire for Indian Population

Restless legs syndrome is a common condition affecting nearly 2% Indian population. Certain questionnaires for screening or diagnostic purpose have been developed in the West, and they were translated to Hindi. However, those questionnaires have been found to have limitations in Indian context considering the cultural effect on vocabulary for the description of symptoms. Based on the IRLSSG criteria, a 12-item questionnaire was developed. Most of the items had dichotomous responses. This questionnaire was tested in subjects having RLS. Control group consisted of subjects suffering from clinically significant anxiety, myalgia of legs, arthralgia in legs, burning feet syndrome, nocturnal leg cramps and somatic symptoms disorder persistent pain type; conditions that could mimic RLS. Face validity and content validity were examined. Internal consistency of the questionnaire was assessed. Diagnostic outcome from the new questionnaire was assessed against clinical diagnosis, which is considered as gold standard at present. This study included 49 cases of RLS and 44 subjects in control group. Female preponderance was noted in both groups (69.4% in RLS group and 63.6% in control group; P = 0.55). Mean age of subjects in both groups was comparable (38.1 ± 2.3 years in RLS and 40.1 ± 2.5 years in control group; P = 0.10). New diagnostic questionnaire had sensitivity of 73.4% (95% CI = 58.9–85.0) and specificity of 88.6% (95% CI = 75.4–96.2). Positive predictive value was 87.8% (95% CI = 75.6–94.3%) and negative predictive value was 75% (95% CI = 65–82.8) with the diagnostic accuracy of 80.6% (95% CI = 71.1–88.1). New questionnaire correlated well with clinical diagnosis (r = 0.62; P < 0.001). This questionnaire is a short and reliable method for diagnosis of RLS in Indian population.

Role of MEIS1 in restless legs syndrome: From GWAS to functional studies in mice.

MEIS1 is a transcription factor playing an important role in the development of several organs, including central and peripheral nervous systems. A genetic locus spanning the MEIS1 coding region has been associated with the risk of RLS in genome-wide association studies, with increasing evidence that MEIS1 is the causal RLS gene. The RLS-linked genetic signal has been mapped to an intronic regulatory element within MEIS1. This element plays a role in the ganglionic eminences of the developing forebrain, with the RLS risk allele related to a reduced activation of the enhancer. This suggests that the ganglionic eminences play an important role in the development of genetic susceptibility to RLS. In addition, rare variants within MEIS1 have been shown to contribute to the disease risk. These variants were identified first in RLS families and later found in further RLS cases by targeted sequencing. Some of these variants alone are sufficient to suppress MEIS1 function in neural development, providing further evidence of the importance of neurodevelopmental processes in the pathological mechanism of MEIS1 in RLS. Heterozygous Meis1 inactivation in mice causes hyperactivity at the onset of the inactive period, consistent with human RLS. In addition, these mice revealed an effect of MEIS1 on the dopaminergic system at both the spinal and supraspinal level. More studies are needed in human genetics to determine the exact role of MEIS1 variants in the risk of RLS, as well as in functional genetics and animal studies to further elucidate the pathological mechanism of MEIS1 in RLS.

Restless legs syndrome is associated with major comorbidities in a population of Danish blood donors

BackgroundRestless Legs Syndrome (RLS) is characterized by uncomfortable nocturnal sensations in the legs making sedentary activities and sleep difficult, and is thus linked with psychosocial distress. Due to the symptomatology and neurobiology of RLS (disrupting brain iron and dopamine) it is likely that RLS associates with poorer health-related quality of life (HRQL) and depressive disorder. The objective of this study was to investigate the RLS-HRQL and the RLS-depressive disorder links in a generally healthy population that is not biased by medications. MethodsComplete data, including the Cambridge–Hopkins RLS questionnaire, the 12-item short-form standardized health survey (SF-12), the Major Depression Inventory (MDI), body mass index, smoking status, alcohol consumption, and education were available for 24,707 participants enrolled in the Danish Blood Donor Study from May 1, 2015 to February 1, 2017. Information on quality of sleep was available for all RLS cases. T-tests and multivariable logistic regression models were applied to examine the associations of RLS and MDI scores, and the physical and mental component scores (PCS and MCS) of SF-12, respectively. Analyses were conducted separately for men and women. ResultsRLS associated with poorer MCS and poorer PCS. Moreover, Participants with RLS were more likely to classify with depressive disorder. Poor quality of sleep was associated with depressive disorder and poorer MCS among RLS cases, and with poorer PCS in female RLS cases. ConclusionThus, we demonstrated that RLS is associated with a significantly lower HRQL and a higher prevalence of depressive disorder among otherwise healthy individuals.

Prevalence of restless legs syndrome and associated factors in an otherwise healthy population: results from the Danish Blood Donor Study

ObjectiveRestless legs syndrome (RLS) is a neurological sensorimotor disorder characterized by uncomfortable sensations in the legs. RLS often occurs as a comorbid condition. Besides an increased risk of iron deficiency, blood donors are considered to be generally healthy. Blood donors are therefore an ideal population for studying factors associated with RLS occurrence, herein the role of iron. It is suggested that RLS is linked to sex, age, low socioeconomic status, unhealthy lifestyle, and iron deficiency. The objective of this study is therefore to estimate the RLS prevalence and identify associated biological, sociodemographic, economic, and lifestyle factors in a population of blood donors. MethodsA total of 13,448 blood donors enrolled in the Danish Blood Donor Study from May 2015 to May 2016. RLS cases were identified using the validated Cambridge–Hopkins RLS-questionnaire. Logistic regression models were applied to assess the relationship between RLS and data on socially related factors collected using questionnaires and population registers. ResultsIn this study, 7.2% women and 4.5% men were classified with RLS. RLS was associated with: female sex, high age, smoking, frequent alcohol consumption, and low education. RLS-related symptoms were associated with obesity, parity and donation intensity three years prior to inclusion among women. RLS was not related to: reduced plasma ferritin, employment status, and income. ConclusionsRLS is a frequent disorder in otherwise healthy individuals. The associations discovered in this study can be utilized in preventing or reducing RLS symptoms.

Restless Legs Syndrome and Hypertension in Mexican Women.

RLS is a common chronic disorder characterized by an irresistible need to move the lower limbs that affects sleep. Poor sleep has been associated with increased blood pressure (BP). Thus, we evaluated the cross-sectional relationship between RLS and hypertension (HTN) in a large cohort study in Mexico. In 2011, 54,925 female participants from the Mexican Teachers' Cohort responded to a four-item questionnaire based on the International Restless Legs Syndrome Study Group's minimal diagnostic criteria. Women also reported diagnosis and treatment of HTN. We used multivariable logistic regression models to estimate prevalence odds ratios (ORs) for HTN, adjusting for lifestyle and dietary factors. We also estimated adjusted prevalence ORs for HTN by frequency of RLS symptoms. We identified 9,230 cases (17%) of RLS, and the prevalence of HTN was 13.1% among women with RLS and 9.4% among those without RLS. The multivariable-adjusted prevalence OR for HTN comparing women with to those without RLS was 1.18 (95% confidence interval [CI]: 1.10-1.26). Compared to those without RLS, the prevalence OR of HTN in women reporting a symptom frequency of once a month or less was 1.14 (95% CI: 1.00-1.30); among those with symptoms two to four times a month, the OR was 1.17 (95% CI: 1.05-1.30); and for those with symptoms at least two times a week, the OR was 1.22 (95% CI: 1.10-1.35). We observed an association between RLS and HTN. Future studies should evaluate the impact of treating RLS on BP.

Brainstem Stroke-Related Restless Legs Syndrome: Frequency and Anatomical Considerations

Background: Given the discordant results of studies that have reported cases of RLS associated with brainstem stroke and the absence of RLS in large series describing the clinical spectrum of brainstem infarctions, we decided to assess RLS in all patients admitted for brainstem stroke. Methods: All patients who were consecutively referred to the Strasbourg stroke unit for brainstem infarction were prospectively evaluated for RLS. The different parameters analyzed were the topography of the ischemic lesions (magnetic resonance imaging), the different symptoms (sensory, motor, cerebellar, cranial nerves and dysarthria) and the NIH stroke scale. Statistical analyses used the Bayesian paradigm. Results: Thirty patients have been included, and RLS was observed in three patients (10%). Two patients suffered from an exacerbation of symptoms anterior to the stroke, and the other patient a de novo, but transient, RLS. Patients with stroke-induced sensory symptoms have a higher risk to develop brainstem stroke-related RLS as compared to patients without sensory symptoms. Conclusion: The results suggest that RLS should be systematically screened in patients affected with brainstem stroke, especially in the case of stroke-induced sensory symptoms. Clinicians should be aware of this association, especially as efficient treatments are available and allow improving the management of patients affected with stroke. i 2014 S. Karger AG, Basel

Restless legs syndrome

SummaryRestless legs syndrome (RLS) is characterised by an uncontrollable urge to move, in particular the lower limbs, often accompanied by discomfort or a painful sensation that occurs typically at night. It is categorized under the ICD-Classification of extrapyramidal and movement disorders. As patients often suffer from insomnia due to the involuntary nocturnal leg movements and irritable sensations in the legs, RLS is also classified as a sleep-related movement disorder. The incidence of a mild form of RLS is frequent, although it often remains undiagnosed.After the exclusion of other diseases by differential diagnosis, RLS is diagnosed on the basis of a clinical test administering a single dose of levodopa. There are two forms of RLS: idiopathic and secondary. The secondary form is encountered in an astonishing number of diseases, including renal insufficiency, diabetes, chronic obstructive pulmonary disease (COPD) and iron deficiency. The treatment of RLS is complex and the benefits and risks of pharmacotherapy should be considered carefully. Non-ergoline dopamine agonists (e.g. ropinirole, pramipexole) are the first-line treatment in severe cases of RLS. Transdermal rotigotine is also a promising treatment option. Opioids in combination with naloxone are recommended for patients suffering from severe pain. In mild cases of RLS, patients benefit from a balanced lifestyle with gentle physical activity and avoiding the excessive consumption of caffeine or alcohol.

In restless legs syndrome, during changes in vigilance, the forced EEG shifts from alpha activity to delta or high alpha may lead to the altered states of dopamine receptor function and the symptoms

RLS cases may carry a genetic vulnerability called EEG alpha activity gate dyscontrols which appear during changes in vigilance and generally during sleep. It is triggered by forced EEG shifts either from alpha activity to delta or high alpha. Expressions of alpha activity gate dyscontrols may have a gate effect that trigger a second vulnerability-dopamine receptor specific individual sensitivity (DRSIS) and this leads to a deficiency in dopamine transmissions at diencephalospinal dopamine system (DSDS). Due to altered gene expressions in states of dopamine receptor function, DRSIS EEGs and RLS symptoms may be interpreted as follows: A. Disinhibition state is alpha activity gate dyscontrols induced inhibition of DSDS inhibitory dopamine modulations. Dopaminergic disinhibitions inhibit inhibitory interneurons of sensory and motor nuclei neurons that are involved in RLS. These sleep sensitive inhibitory interneurons possibly have GABA-ergic functions in sleep. (I) DSDS thalamic neurons' disinhibitory effects in thalamus on GABA-ergic interneurons of: (a) Intralaminar nuclei non-discriminative sensation neurons at thalamocortical premotor network leading to symptom of "a sense of urgency to move" generally referenced to legs.(b) Reticular thalamic nucleus (RTN) neurons. At polysomnography,during NREM sleep, disinhibited RTN neurons show alpha activity gate dyscontrol 1. These are recurrent subtypes of CAP in alpha band (7-12 Hz) pointing a difficulty in shifting to subtypes of CAP in low delta bands (0.25-2.5 Hz) and sleep fragmentations.(II) Supraspinal disinhibitory projections from DSDS thalamic neurons on GABA-ergic interneurons of: (a) Sensory neurons at posterior horns of spinal cord leading to dysesthesias, generally referenced to legs.(b) Medullary-reticulospinal neurons and by way of independent spinal rhythm generators on motoneurons leading to periodic limb movements in sleep.B. Activation state is an increase in symptoms. Sensory intralaminar and motor pontin nuclei neurons are in fact excitatory but are disinhibited in RLS. Due to altered gene expression, these neurons begin to perceive 'disinhibition' as reduced inhibition. Their glutamate receptors may activate deficient dopamine transmissions on RTN leading to alpha activity gate dyscontrol 2. This implies a failure in preventing shifts to frequent subtypes of CAP in high alpha and low beta bands (12-13 Hz) resulting in an increase of sensorimotor symptoms and appearance of motor restlessness, behavioral arousals and insomnia. C. Inhibition state is spontaneous relief from sensorimotor symptoms. Short or long-term synaptic plasticities of dopamine receptors towards activations initiate negative feedbacks from inhibitory interneurons. They are supported by inhibitory dopamine modulations- alertness and some awareness generally with regular high alpha EEGs, supraspinal inhibitions and a reverse movement pattern of PLMS during standing up and continuing to walk.

Non-opioid analgesics and the risk of restless leg syndrome—a spurious association?

Objectives: The aim of this study was to evaluate the prevalence and risk factors of restless leg syndrome in a secondary care patient population maintained on tricyclic and serotonin re-uptake inhibiting antidepressants. Study design: Prospective observational study. Study population: Two hundred and forty-three patients of a single practice specializing in the treatment of affective and anxiety disorders. Patients younger than 30 years and those with neurologic diseases such as Parkinson's disease, multiples sclerosis and dementia were excluded, as well as those with schizophrenia or other illusional disturbances, eating disorders, histories of opioid or codeine-containing analgesic abuse or of alcohol or illicit drug abuse. Patients remained in the study population only if they had gained complete or partial recovery of their anxiety and/or depressive symptoms and been treated for at least 6 months in the practice's ambulatory care (85.0% of the patients were finally included). Methods: Histories of leg discomfort, akathisia, medication use and socio-demographic factors were assessed at the time of enrolment. RLS was assumed if all minimal criteria of the international RLS study group were fulfilled. RLS patients also had a neurologic examination focusing on signs and symptoms of neuropathy. It is unclear whether those without RLS were also examined neurologically. RLS case status was assessed at 6-month intervals for patients in the study. It is unclear if the reported RLS prevalence reflects case status at enrolment and/or during the treatment course. The prevalence of various pain syndromes, as well as the intake of analgesics and average coffee intake per day was compared between those with and without RLS. Lifetime and current treatment exposure to antidepressants and dopamine antagonists was evaluated according to RLS status. It is unclear what the mean treatment time was. Various univariant, descriptive statistics were used. The statistical analysis and logistic regression was applied using RLS case status as the dependent and co-morbidities, and medications/treatments as independent variables. Results: The prevalence of RLS among the patients included in the analysis was 27.0%, with female patients more often affected than men (31.0% vs. 19.0%). RLS symptom severity during the course of treatment was low for 43 of 65 cases. Somatic co-morbidities were more prevalent in RLS affected women and less prevalent in RLS affected men than in gender specific non-RLS patients. No significant differences were observed for lifetime exposure to dopamine antagonist between those with and without RLS (38.0% vs. 35.0%). Chronic pain syndromes were observed more often in RLS cases (women: 86.0% vs. 32.0%, men: 62.5% vs. 29.0%). Twelve percent of those without RLS and 75.0% of RLS cases had a history of regular intake of analgesics prior to study enrolment. In a multivariate logistic regression model the authors found RLS case status to be associated with the intake of analgesics (OR: 25.5, P<0.001), psychiatric co-morbidity (OR: 2.97, P=0.01) and an interaction between age and the intake of analgesics (OR: 2.6, P=0.03). Conclusions: A 27.0% prevalence of RLS was found in this highly selected population treated with tricyclic and serotonin re-uptake inhibiting antidepressants. The authors infer from their results that regular intake of analgesics is a risk factor for RLS and that the observed association of gender with RLS might be explained by a higher intake of analgesics in women compared to men. They further conclude that the intake of analgesics, rather than the pain co-morbidity itself, enhances the risk of RLS.

Mirtazapine-induced restless legs

Two cases of restless legs syndrome in association with mirtazapine treatment of 5–6 weeks are presented. Rather than akathisia related to serotonine reuptake inhibitors, which usually emerges during the first weeks of treatment, our cases resemble previously described mianserin-induced RLS cases. This suggests that although blockade of 5-HT2 receptors by mirtazapine may be protective against acute akathisia, it does not protect against slowly developing restless legs syndrome similar to that induced by mianserin. © 1997 John Wiley & Sons, Ltd.

The phenylpropionic acid load test: experience with 72 children at-risk for beta-oxidation disorders.

The urinary excretion of metabolites of orally administered phenylpropionic acid (PPA) in 72 children, aged 2 days to 16 years, thought to be at-risk of medium acyl CoA dehydrogenase deficiency has been studied. Forty had presented as Reye Syndrome, 9 as a Reye-like syndrome and 24 were sibs of decreased RS, sibs of RLS cases or sibs of infants who had died suddenly and without explanation where an autopsy revealed the presence of very heavy fatty infiltration of the liver. These studies demonstrated that PPA metabolites are maximally excreted during the 3 hours following the oral load and that this urine collection should be diagnostic. PPA loading is a relatively simple, safe test which is part of the investigation of a patient suspected of having an inborn error of metabolism.