The Safety and Efficacy of Pregabalin Add-on Therapy in Restless Legs Syndrome Patients

Pregabalin is increasingly being used as a first-line treatment for symptomatic control of restless legs syndrome (RLS). This study aimed to evaluate the efficacy and safety of pregabalin as add-on therapy in RLS patients already taking dopamine agonists (DA) but still in need of further management. Patients with idiopathic RLS were enrolled, and all had already been prescribed DA for at least 3 months but still had either persistent symptoms, side effects, or comorbid insomnia. An initial dose of 75 mg pregabalin was begun, adjusted as needed, and maintained at a stable dose for 4 weeks, followed by observation for a total of 8 weeks. RLS symptoms and insomnia scores were evaluated before and after add-on pregabalin treatment. Patients were monitored for side effects that could be attributed to pregabalin. A total of 32 RLS patients were enrolled, and 20 subjects remained until the endpoint. After the pregabalin add-on, the mean IRLS score showed significant improvement compared to the baseline (p < 0.001). The insomnia severity index score also improved (p = 0.036), and no serious adverse effects were observed. Our preliminary data suggests the potential for pregabalin as an add-on therapy to DA with regards to both efficacy and safety in patients who have inadequate RLS improvement.

Association Between Migraine Complicated With Restless Legs Syndrome and Vitamin D

Background: This study aimed to evaluate the prevalence of restless legs syndrome (RLS) in patients with migraine and explore its association with vitamin D deficiency, aiming to provide biological support for the comorbidity of migraine with RLS, and shed new lights into clinical diagnosis and treatment.Methods: A case-control study was performed on 175 migraine patients and 151 non-headache controls. The information of all subjects concerning headache severity [visual analog scale (VAS) score], RLS, RLS severity [International Restless Legs Scale (IRLS) score], sleep quality [Pittsburgh sleep quality index (PSQI)], anxiety and depression symptoms [hospital anxiety and depression scale (HADS)], and demographic data were collected. At the same time, serum 25-(OH) D levels were also measured (concentration <20 ng/ml was defined deficiency). Afterward, the logistic regression model was adopted to explore the risk factors for RLS in patients with migraines.Results: Compared with control group, migraine group had lower vitamin D levels [(21.10 ± 6.58) vs. (16.42 ± 5.6) ng/ml, P < 0.001], a higher rate of vitamin D deficiency (45.03 vs. 72%, P <0001), higher prevalence of RLS (6.62 vs. 22.29%, P < 0.001). Compared with the pure RLS group, RLS with the migraine group had lower vitamin D levels and higher IRLS score (P < 0.05). Compared with pure migraine group, migraine with RLS group had lower vitamin D levels [(17.36 ± 5.56) vs. (13.15 ± 4.42) ng/ml, P < 0.001], higher incidence of vitamin D deficiency (66.18 vs. 92.31%, P = 0.001), higher frequency of headache attacks (P = 0.004). Thereafter, the multivariate logistic regression model was employed to adjust confounding factors such as age, gender, season, frequency of headache attacks, PSQI score, and HADS scores. According to the results vitamin D deficiency in patients with migraines was an independent risk factor for RLS (OR = 5.03, 95%CI: 1.2–21.16, P = 0.027).Conclusions: The prevalence of RLS in migraine patients was significantly higher than that in the non-headache population. Besides, vitamin D levels decreased, while the incidence of vitamin D deficiency increased in the migraine patients complicated with RLS. Finally, the occurrence of RLS in migraine patients was significantly related to vitamin D deficiency.

A Case of a Patient with Pontine Infarction Complaining of Discomfort in Both Legs

Objective: This study examined the effectiveness of Korean medical treatment for an 81-year-old female patient with pontine infarction complaining of discomfort in both legs.Methods: The patient was hospitalized for 45 days and treated with herbal medicine (mainly Bohyulanshin-tang [補血安神湯], pharmacopuncture, acupuncture, electroacupuncture, and moxibustion). We used the International Restless Legs Scale (IRLS) and Numerical Rating Scale (NRS) and checked the duration of the symptoms to evaluate the clinical effects of the treatment.Results: After 45 days of hospitalization, the IRLS score decreased from 33 to 19, with the lowest score of 8 recorded on the twenty-seventh day after discharge. The NRS score and the duration of symptoms also improved, and the treatment effect continued following discharge.Conclusions: This study suggests that Korean medical treatment may be effective for the treatment of restless legs.

0796 Dipyridamole for the Treatment of RLS: Preliminary Results of a Cross-Over, Placebo-Controlled, Double-Blind Trial

Introduction Recent animal models of restless legs syndrome (RLS) suggest that brain iron deficiency is associated with a hypoadenosinergic state, with downregulation of adenosine A1 receptors (A1R) in the striatum. Dipyridamole is a non-selective inhibitor of ENT1/ENT2 (the main reuptake mechanism of adenosine) and increases thereby extracellular adenosine. We hypothesized that treatment with dipyridamole would improve RLS symptoms more than placebo. Methods We performed a randomized, double-blind, placebo-controlled clinical trial on 15 previously untreated idiopathic RLS patients that underwent a two week treatment with either 300 mg dipyridamol or placebo (randomized for the order of treatments), following a cross-over design. Treatment started with a dose of 100 mg/day, followed by a forced up-titration to 200 mg on day 4, and to 300 mg on day 7. Severity was assessed at baseline, day 7 and day 14 of each treatment condition by means of the IRLS and CGI scales. The primary endpoint was therapeutic response (50% improvement in IRLS total score). Results Fifteen patients (nine women), never before treated with dopaminergic agents, completed both arms of the study. Mean age was 60,2 (±7,1), and the mean duration of illness was 6,03 (±3,1) yrs. IRLS score improved during treatment with dipyridamole from a mean (±S.D.) of 24,36 (±3,3) to 9,78 (±3,4), in contrast to a change from 23,9 (±3,8) to 16,6 (±3,7) under placebo (p< 0.05). Corresponding improvements on the CGI were 61,3% and 11,8% for dipyridamole and placebo, respectively. 7/ 15 patients improved by more than 50% during treatment with dipyridamole vs. 4/15 under placebo. Main side effects were abdominal cramps, diarrhea, dizziness, and flushing. Conclusion These preliminary results suggest that dipyridamole is an effective agent on RLS symptoms. It also provides evidence of hypoadenosinergic mechanisms playing a central role in RLS. Support No funding was provided for this investigation.

Impact of Positive Airway Pressure on International Restless Legs Syndrome Score in Sleep Disordered Breathing

Study Objective: Studies have shown increased prevalence of restless legs syndrome (RLS) in sleep disordered breathing (SDB), however limited data have focused on the impact of SDB therapy on RLS. We hypothesize that positive airway pressure (PAP) will improve the International Restless Legs Syndrome (IRLS) score among SDB patients compared to patients without PAP. Methods: Patients with AHI ≥ 5 who responded positively to a RLS qualifier question from January 2010 to May 2015 were included in this retrospective study. IRLS score was used to measure RLS symptom severity. Two-sample t-tests and one-way analysis of variance were used to compare changes in IRLS score and linear regression models were created to examine IRLS change with PAP use and PAP adherence (PAP usage ≥4 h nightly for ≥70% of nights), adjusting for potential confounders. Results: In 434 patients (51.9 ± 13.4years, 50.5% female, 77.6% Caucasian; 325 PAP, 109 control), IRLS scores improved from baseline to follow-up, with the PAP group achieving significant improvement after adjustment for covariates (difference in IRLS: −1.8 (CI −3.6,0.00), p = 0.050). In self-reported PAP adherent patients, IRLS improvement was greater than controls (−5.3 ± 7.4 vs. −2.7 ± 7.6 respectively, p = 0.045), and comparable to non-adherent patients (−5.3 ± 7.4 vs. −3.0 ± 7.0, p = 0.091). Conclusions: Among SDB patients with a positive RLS qualifier, those who used PAP therapy achieved significantly greater improvement in IRLS scores than patients who did not use PAP, with more significant changes in the PAP adherent group. This is the first large clinical study to examine these relationships, providing a basis for future prospective interventional trials and informing clinicians of expected improvement in IRLS score in PAP treated SDB populations.

Prevalence of Restless Legs Syndrome in Psychiatric Population

Objective:Restless Legs Syndrome (RLS) is a common condition, with reported prevalence between 1-15% in general population. To the best of our knowledge, there is no data on the prevalence of RLS in psychiatric inpatient population.Method:With the exception of drug/alcohol dependent and gerontopsychiatric patients, patients consecutively admitted to the Centre of Mental Health at the Klinikum Ingolstadt between December 2006 and March 2007 were interviewed by an experienced clinician to assess the presence of RLS. The severity of the symptoms was assessed by the International Restless Legs Severity Scale (IRLS).Results:214 patients were interviewed (age 45.6 ±14.8, 60% females). 22 patients (10.3%) fulfilled the diagnostic criteria for RLS (age 49.2 ±15.0, 73% females, mean IRLS score 20 ± 8.9). In addition, 6.3% of RLS symptoms free patients reported to have had these symptoms in the history. There were slightly more RLS patients diagnosed with an affective disorder compared to the entire sample distribution and there were considerably less RLS patients in the group of psychotic disorders. 4.3% of the total data sample had a positive family history for RLS. As assessed by simple regression analysis there were no particular differences in medication patters between RLS patients and the entire sample.Conclusion:We report here for the first time the prevalence of RLS in psychiatric inpatients. The prevalence rate is on the upper range of that reported for the general population. In addition, 6.3% of RLS symptoms free inpatients reported to have had these symptoms in the history.

The effect of endovenous laser ablation on restless legs syndrome

Objectives Venous disease was proposed as a cause of restless legs syndrome (RLS) by Dr Karl A Ekbom in 1944, but has since remained largely unexplored. This study examines the effect of endovenous laser ablation (ELA) in patients with concurrent RLS and duplex-proven superficial venous insufficiency (SVI). Methods Thirty-five patients with moderate to very severe RLS (as defined by the 2003 National Institute of Health (NIH) RLS criteria) and duplex-proven SVI completed an international RLS rating scale questionnaire (IRLS) and underwent standard duplex examination to objectively measure the baseline severity of their conditions. They were separated into non-operative and operative cohorts. The operative cohort underwent ELA of refluxing superficial axial veins using the CoolTouch CTEV 1320 nm laser and ultrasound-guided sclerotherapy of the associated varicose veins with foamed sodium tetradecyl sulphate (STS). All patients then completed a follow-up IRLS questionnaire. Baseline and follow-up IRLS scores were compared. Results Operative correction of the SVI decreased the mean IRLS score by 21.4 points from 26.9 to 5.5, corresponding to an average of 80% improvement in symptoms. A total of 89% of patients enjoyed a decrease in their score of ≥15 points. Fifty-three percent of patients had a follow-up score of ≤5, indicating their symptoms had been largely alleviated and 31% had a follow-up score of zero, indicating a complete relief of RLS symptoms. Conclusions ELA of refluxing axial veins with the CTEV 1320 nm laser and foamed STS sclerotherapy of associated varicosities alleviates RLS symptoms in patients with SVI and moderate to very severe RLS. Recommendations SVI should be ruled-out in all patients with RLS before initiation or continuation of drug therapy.