Long-term effects of adjunctive eslicarbazepine acetate in adult Asian patients with refractory focal seizures: Post hoc analysis of a phase III trial.

A post hoc analysis of data from Asian patients included in the study BIA-2093-304 was conducted to evaluate the long-term safety/tolerability and efficacy of adjunctive eslicarbazepine acetate (ESL) in adult Asian patients with refractory focal seizures. Part I was a randomized controlled trial, in which patients received ESL (800 or 1200 mg once daily [QD]) or placebo, assessed over a 12-week maintenance period. Patients completing Part I could enter two open-label extension periods (Part II, 1 year; Part III, ≥2 years), during which all received ESL (400-1600 mg QD). Safety/tolerability was assessed by evaluating treatment-emergent adverse events (TEAEs). Efficacy assessments included responder and seizure freedom rates. The safety population included 125, 92, and 23 Asian patients in Parts I, II, and III, respectively. Incidence of ESL-related TEAEs was 61.3%, 45.7%, and 17.4% during Parts I, II, and III, respectively. ESL-related TEAEs (most commonly, dizziness, somnolence, and headache) were consistent with ESL's known safety profile. During Part I, responder rates were higher with ESL 800 (41.7%) and 1200 mg QD (44.4%) versus placebo (32.6%), although not statistically significant. Seizure freedom rates with ESL 800 (5.5%) and 1200 mg QD (11.1%) were also higher versus placebo (0%) (p < 0.05 for ESL 1200 mg QD versus placebo). At the end of Part II, responder and seizure freedom rates were 60.3% and 14.7%, respectively. In summary, adult Asian patients with refractory focal seizures were responsive to treatment with ESL as adjunctive therapy and generally showed treatment tolerance well for up to 3 years. No new/unexpected safety findings were observed.

Erectile dysfunction in patient with obstructive sleep apnea: effects of continuous positive airway pressure.

BACKGROUND: Obstructive sleep apnea (OSA) is linked to various health complications, including erectile dysfunction (ED), which is more prevalent in individuals with OSA. This study explored ED in Korean OSA patients and assessed the impact of continuous positive airway pressure (CPAP) therapy on ED. METHODS: A total of 87 male patients with OSA from four different sleep centers underwent physical measurements and completed sleep and mental health (MH) questionnaires, including the Korean version of the International index of erectile function (IIEF), before and three months after initiating CPAP therapy. RESULTS: After three months of CPAP therapy, the patients demonstrated a significant improvement in ED as measured on the IIEF. However, the study found no significant correlation between the duration of CPAP use and the improvement in IIEF score. It did identify the SF36 quality of life assessment as a significant factor influencing ED improvement after CPAP. CONCLUSIONS: ED is a prevalent issue that escalates with age and is associated with OSA. CPAP therapy has shown potential in alleviating ED symptoms, particularly in those with underlying psychological conditions, although further research is required to confirm these findings and understand the underlying mechanisms.

Long-term dopamine agonist treatment fails to restore altered central sensory processing in restless legs syndrome: Evidence from current perception threshold measurements.

OBJECTIVES: Although some studies have examined the impact of short-term dopamine agonist treatment on altered central sensory processing in patients with restless legs syndrome (RLS), there is a scarcity of research investigating the effect of long-term treatment with these drugs. The aim of this study is to investigate the long-term impact of dopamine agonist treatment on altered central sensory processing in RLS patients using current perception threshold (CPT) testing. METHODS: We conducted a study of 24 RLS patients, measuring their CPT values before and after dopamine agonist treatment for at least 2 months. Patients were classified as responders or non-responders based on their decrease in International Restless Legs Syndrome (IRLS) score. Clinical parameters were collected and compared pre- and post-treatment. RESULTS: The mean duration of treatment with dopamine agonist was 13.6 ± 11.0 months. Our results showed that dopamine agonist treatment significantly improved clinical parameters, including the IRLS score, Visual Analogue Scale, and RLS Quality of Life questionnaire. However, CPT values did not show significant changes for all stimulus frequencies after treatment. Furthermore, we did not find any difference in CPT values before and after treatment in both responders and non-responders. CONCLUSIONS: Our study demonstrated that long-term treatment with dopamine agonists effectively reduces RLS symptoms, but does not reverse the altered central sensory processing observed on CPT testing in RLS patients. These results support the notion that the pathophysiology of RLS is multifactorial and not solely driven by dopaminergic dysfunction.

Association Between Electronic Device Use at Bedtime and COVID-19 Vaccine-Related Adverse Events During the COVID-19 Pandemic in Korean Adults: A Nationwide Cross-Sectional Population-Based Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to heightened mood disturbances linked to increased electronic device use at bedtime (EUB). General anxiety may contribute to an increased likelihood of experiencing nocebo responses, which have been reported to be associated with COVID-19 vaccine-related adverse events (CAEs). However, no related studies have been conducted to examine this association to date. METHODS: We executed a nationwide cross-sectional study to explore these correlations during the pandemic. Using data from the 2022 National Sleep Survey of South Korea, we analyzed the sleep health of 4,000 adults aged 20-69 years between January and February 2022. Shift workers and those with severe sleep disorders were excluded. Participants with EUB more than four days a week were labeled as high frequency EUB, and those reporting CAEs after both vaccine doses were marked as having a presence of CAEs. The survey also included details about anthropometric data, socioeconomic status, and sleep status. RESULTS: Of the 3,702 participants, 92.6% had received two or more vaccine doses, with 41.2% experiencing CAEs. Furthermore, 73.7% had a high EUB frequency. Factors associated with CAE reporting included younger age, female sex, and high EUB frequency, while heavy alcohol use was found to be less likely to be associated with CAE reporting. Notably, a high EUB frequency was significantly associated with reported CAEs (odds ratio, 1.223; 95% confidence interval, 1.028-1.455; P = 0.023). CONCLUSION: A nationwide online survey conducted in South Korea during the pandemic found that individuals who engaged in the relatively frequent use of electronic devices during bedtime had worse sleep quality and increased COVID-19-related adverse events compared with those using these devices less frequently. These findings have the potential to enhance our understanding of the impact of the use of electronic devices at bedtime on health.

An FP's guide to caring for patients with seizure and epilepsy.

Optimizing your care requires that you distinguish between provoked and unprovoked seizures and focus on key elements of the patient's history.

Redefining the role of the cerebellum in restless legs syndrome.

OBJECTIVES: We aimed to investigate alterations in cerebellar volume and the intrinsic cerebellar network in patients with restless legs syndrome (RLS). METHODS: We recruited 69 patients with RLS and 50 healthy controls who underwent brain magnetic resonance imaging (MRI), including three-dimensional T1-weighted imaging. The total cerebellar volume and cerebellar volume subdivisions were analyzed through automatic cerebellum anatomical parcellation using U-Net with locally constrained optimization program. The intrinsic cerebellar network was calculated through brain analysis using a graph theory program based on the cerebellar volume subdivisions. The cerebellar volumes and intrinsic cerebellar networks were compared between patients with RLS and healthy controls. RESULTS: The cerebellar volume and subdivisions in patients with RLS did not show significant differences compared to those in healthy controls. However, significant alterations were observed in the intrinsic cerebellar network of patients with RLS. Increased mean clustering coefficient (0.185 vs. 0.114; p = 0.047) and small-worldness index (0.927 vs. 0.800; p = 0.047) were observed in patients with RLS. Additionally, total cerebellar volume was negatively correlated with the Pittsburgh Sleep Quality Index (r = -0.398; p = 0.020) and Insomnia Severity Index (ISI; r = -0.396; p = 0.011). Negative correlations were additionally observed between the right X lobule volume and the International Restless Legs Syndrome Severity Scale (r = -0.425; p = 0.008) and between the vermis VIII volume and ISI score (r = -0.399; p = 0.011). CONCLUSION: We demonstrated alterations in the intrinsic cerebellar network in patients with RLS compared with healthy controls, showing increased connectivity with increased segregation in patients with RLS. This suggests a potential role of the cerebellum in RLS pathophysiology.

Correlation of Diffusion Tensor Tractography with Restless Legs Syndrome Severity.

This prospective study investigated white matter tracts associated with restless legs syndrome (RLS) severity in 69 patients with primary RLS using correlational tractography based on diffusion tensor imaging. Fractional anisotropy (FA) and quantitative anisotropy (QA) were analyzed separately to understand white matter abnormalities in RLS patients. Connectometry analysis revealed positive correlations between RLS severity and FA values in various white matter tracts, including the left and right cerebellum, corpus callosum forceps minor and major, corpus callosum body, right cingulum, and frontoparietal tract. In addition, connectometry analysis revealed that the FA of the middle cerebellar peduncle, left inferior longitudinal fasciculus, left corticospinal tract, corpus callosum forceps minor, right cerebellum, left frontal aslant tract, left dentatorubrothalamic tract, right inferior longitudinal fasciculus, left corticostriatal tract superior, and left cingulum parahippocampoparietal tract was negatively correlated with RLS severity in patients with RLS. However, there were no significant correlations between QA values and RLS severity. It is implied that RLS symptoms may be potentially reversible with appropriate treatment. This study highlights the importance of considering white matter alterations in understanding the pathophysiology of RLS and in developing effective treatment strategies.

Structural and functional multilayer network analysis in restless legs syndrome patients.

The combination of brain structural and functional connectivity offers complementary insights into its organisation. Multilayer network analysis explores various relationships across different layers within a single system. We aimed to investigate changes in the structural and functional multilayer network in 69 patients with primary restless legs syndrome (RLS) compared with 50 healthy controls. Participants underwent diffusion tensor imaging (DTI) and resting state-functional magnetic resonance imaging (rs-fMRI) using a three-tesla MRI scanner. We constructed a structural connectivity matrix derived from DTI using a DSI program and made a functional connectivity matrix based on rs-fMRI using an SPM program and CONN toolbox. A multilayer network analysis, using BRAPH program, was then conducted to assess the connectivity patterns in both groups. At the global level, significant differences there were between the patients with RLS and healthy controls. The average multiplex participation was lower in patients with RLS than in healthy controls (0.804 vs. 0.821, p = 0.042). Additionally, several regions showed significant differences in the nodal level in multiplex participation between patients with RLS and healthy controls, particularly the frontal and temporal lobes. The regions affected included the inferior frontal gyrus, medial orbital gyrus, precentral gyrus, rectus gyrus, insula, superior and inferior temporal gyrus, medial and lateral occipitotemporal gyrus, and temporal pole. These results represent evidence of diversity in interactions between structural and functional connectivity in patients with RLS, providing a more comprehensive understanding of the brain network in RLS. This may contribute to a precise diagnosis of RLS, and aid the development of a biomarker to track treatment effectiveness.

Glymphatic system dysfunction in restless legs syndrome: evidenced by diffusion tensor imaging along the perivascular space.

STUDY OBJECTIVES: There is growing evidence pointing at glymphatic system dysfunction in diseases with circadian disruption, such as sleep disorders. Lower diffusivity in the direction of perivascular space has been shown in several neurological and sleep-related disorders; however, its role in restless legs syndrome (RLS) is unclear. We hypothesized that similarly, in RLS the diffusivity in glymphatic system is decreased. Here, we aimed to evaluate glymphatic system functionality in patients with RLS, compare it to healthy controls, and analyze the correlation between its function and clinical characteristics. METHODS: Sixty-nine patients with primary RLS and 51 healthy controls were recruited at a tertiary hospital. All participants underwent diffusion tensor imaging (DTI) and magnetic resonance imaging (MRI) using a 3T MRI scanner, and the DTI along the perivascular space (DTI-ALPS) index was calculated using DTI data. We compared the DTI-ALPS index between the patients with RLS and healthy controls. We also conducted the correlation analysis between the DTI-ALPS index and clinical characteristics, including age, age of onset, symptom duration, and RLS severity. RESULTS: DTI-ALPS index differed significantly between the patients with RLS and healthy controls; the DTI-ALPS index in the patients with RLS was lower than that in the healthy controls (1.48 vs. 0.60, p = 0.008). There was no significant correlation between the DTI-ALPS index and clinical characteristics. CONCLUSION: A significantly lower DTI-ALPS index in patients with RLS suggests that the glymphatic system function is impaired in patients with RLS.

Ferric carboxymaltose effects on restless legs syndrome and on brain iron in patients with iron deficiency anemia.

OBJECTIVE: Brain iron status is fundamental in RLS pathogenesis. The aim of this study was to determine the clinical efficacy and brain iron concentration improvement in RLS patients with IDA, using 1500 mg FCM. METHODS: This is a randomized, double-blinded, placebo-controlled study. RLS patients with IDA were grouped into either 1500 mg FCM or placebo. The primary outcomes were the change from baseline on the International Restless Legs Syndrome Study Group scale (IRLS) and brain iron measured by QSM and R2∗. RESULTS: A total of 18 RLS patients with IDA were enrolled, 10 in the FCM group and 8 in the placebo. At the week 6 endpoint, the FCM group showed significant improvement in both IRLS (-13.60 ± 9.47 vs. -3.63 ± 5.40, p = 0.011) and VAS (-40.50 ± 28.81 vs. -0.63 ± 28.28, p = 0.004) from baseline. Change from baseline with R2∗ techniques showed a treatment effect for the thalamus and QSM technique for both the substantia nigra and pulvinar. A correlation was proved between the IRLS difference and the difference of QSM in thalamus (p = 0.028). CONCLUSION: This study demonstrates that 1500 mg FCM effectively treats RLS symptoms in IDA patients over six weeks, with MRI measurements of improved brain iron content serving as a potential biomarker for RLS patients.

Insomnia during coronavirus disease 2019 pandemic in Korea: a National sleep survey.

Coronavirus disease 2019 (COVID-19) pandemic has caused widespread increase in stress and affected sleep quality and quantity, with up to 30% prevalence of sleep disorders being reported after the declaration of the pandemic. This study aimed to assess perceived changes due to the pandemic in the prevalence of insomnia and excessive daytime sleepiness (EDS) in Korea, and identify the associated factors. An online survey was conducted among 4000 participants (2035 men and 1965 women) aged 20-69 years enrolled using stratified multistage random sampling according to age, sex, and residential area, between January, 2021 and February, 2022. The questionnaire included various items, such as socio-demographics, Insomnia Severity Index, and Epworth Sleepiness Scale (ESS). Insomnia was defined as difficulty falling asleep and difficulty maintaining sleep more than twice a week. EDS was classified as an ESS score ≥ 11. Insomnia was reported by 32.9% (n = 1316) of the participants (37.3% among women and 28.6% among men). Multivariate logistic regression revealed that insomnia was associated with female sex [odds ratio (OR) = 1.526, 95% confidence interval (CI) = 1.297-1.796], night workers (OR 1.561, 95% CI 1.160-2.101), and being unmarried (OR 1.256, 95% CI 1.007-1.566). EDS was reported by 12.8% (n = 510) of the participants (14.7% among men and 10.7% among women). EDS was associated with male sex (OR 1.333, 95% CI 1.062-1.674), and being employed (OR 1.292, 95% CI 1.017-1.641). During the COVID-19 pandemic, the prevalence of insomnia increased in Korea, while there was no significant change in EDS compared with pre-pandemic evidence.

Alterations of the thalamic nuclei volumes and intrinsic thalamic network in patients with restless legs syndrome.

We aimed to investigate the alterations of thalamic nuclei volumes and intrinsic thalamic network in patients with primary restless legs syndrome (RLS) compared to healthy controls. Seventy-one patients with primary RLS and 55 healthy controls were recruited. They underwent brain MRI using a three-tesla MRI scanner, including three-dimensional T1-weighted images. The intrinsic thalamic network was determined using graph theoretical analysis. The right and left whole thalamic volumes, and the right pulvinar inferior, left ventral posterolateral, left medial ventral, and left pulvinar inferior nuclei volumes in the patients with RLS were lower than those in healthy controls (0.433 vs. 0.447%, p = 0.034; 0.482 vs. 0.502%, p = 0.016; 0.013 vs. 0.015%, p = 0.031; 0.062 vs. 0.065%, p = 0.035; 0.001 vs. 0.001%, p = 0.034; 0.018 vs. 0.020%, p = 0.043; respectively). There was also a difference in the intrinsic thalamic network between the groups. The assortative coefficient in patients with RLS was higher than that in healthy controls (0.0318 vs. - 0.0358, p = 0.048). We demonstrated the alterations of thalamic nuclei volumes and intrinsic thalamic network in patients with RLS compared to healthy controls. These changes might be related to RLS pathophysiology and suggest the pivotal role of the thalamus in RLS symptoms.

Sleep and Circadian Rhythm in Relation to COVID-19 and COVID-19 Vaccination-National Sleep Survey of South Korea 2022.

BACKGROUND: Currently, information on sleep and circadian patterns in relation to COVID-19 or vaccination remains limited. We aimed to investigate sleep and circadian patterns according to history of COVID-19 and COVID-19 vaccination side effects. METHODS: We used data from the National Sleep Survey of South Korea 2022, a nationwide cross-sectional population-based survey regarding sleep-wake behaviors and sleep problems among Korean adults. Analysis of covariance (ANCOVA) and logistic regression analyses were performed to explore the different sleep and circadian patterns according to the history of COVID-19 or self-reported side effects of the COVID-19 vaccination. RESULTS: The ANCOVA showed that individuals with a history of COVID-19 presented a later chronotype than individuals without a history of COVID-19. Individuals who had experienced vaccine-related side effects had a shorter sleep duration, poorer sleep efficiency, and worse insomnia severity. Multivariable logistic regression analysis showed a later chronotype related to COVID-19. A short sleep duration, poorer sleep efficiency, and worse insomnia severity were associated with self-reported side effects of the COVID-19 vaccination. CONCLUSIONS: Individuals who recovered from COVID-19 had a later chronotype than those without a history of COVID-19. Individuals who had experienced vaccine-related side effects presented with poorer sleep than those without side effects.

Does REM Sleep-Dependent Obstructive Sleep Apnea Have Clinical Significance?

(1) Background: The clinical significance of rapid eye movement (REM) sleep-dependent obstructive sleep apnea (OSA) remains controversial because various criteria have been used to describe it. This study determined the clinical significance of REM-OSA in Koreans using data from patients with sufficient total sleep time (TST) and REM sleep duration. (2) Methods: We investigated 1824 patients with OSA who were diagnosed by polysomnography (PSG). REM-OSA was defined as an overall apnea-hypopnea index (AHI) ≥ 5, NREM-AHI < 15, and REM-AHI/NREM-AHI ≥ 2. Demographic and medical data were collected from digital medical records and sleep questionnaires. We compared clinical and PSG data between REM-OSA and REM sleep-nondependent OSA (nREM-OSA). (3) Results: In total, 140 patients (20.2%) were categorized as REM-OSA. Those patients were predominantly female (53.6% vs. 21.7% of the overall cohort, p < 0.001). REM-OSA is frequent in the mild (69.3% vs. 18.8%) to moderate (30% vs. 27.9%) range of OSA (p < 0.001). (4) Conclusions: The prevalence of REM-OSA was similar to that in previous study findings: frequent in mild to moderate OSA and females, which is consistent with results in Western populations. Our findings suggest that REM-OSA does not have clinical significance as a subtype of OSA.

Multidimensional Early Prediction Score for Drug-Resistant Epilepsy.

BACKGROUND AND PURPOSE: Achieving favorable postoperative outcomes in patients with drug-resistant epilepsy (DRE) requires early referrals for preoperative examinations. The purpose of this study was to investigate the possibility of a user-friendly early DRE prediction model that is easy for nonexperts to utilize. METHODS: A two-step genotype analysis was performed, by applying 1) whole-exome sequencing (WES) to the initial test set (n=243) and 2) target sequencing to the validation set (n=311). Based on a multicenter case-control study design using the WES data set, 11 genetic and 2 clinical predictors were selected to develop the DRE risk prediction model. The early prediction scores for DRE (EPS-DRE) was calculated for each group of the selected genetic predictors (EPS-DREgen), clinical predictors (EPS-DREcln), and two types of predictor mix (EPS-DREmix) in both the initial test set and the validation set. RESULTS: The multidimensional EPS-DREmix of the predictor mix group provided a better match to the outcome data than did the unidimensional EPS-DREgen or EPS-DREcln. Unlike previous studies, the EPS-DREmix model was developed using only 11 genetic and 2 clinical predictors, but it exhibited good discrimination ability in distinguishing DRE from drug-responsive epilepsy. These results were verified using an unrelated validation set. CONCLUSIONS: Our results suggest that EPS-DREmix has good performance in early DRE prediction and is a user-friendly tool that is easy to apply in real clinical trials, especially by nonexperts who do not have detailed knowledge or equipment for assessing DRE. Further studies are needed to improve the performance of the EPS-DREmix model.

Alterations of Functional Connectivity in Patients With Restless Legs Syndrome.

Restless legs syndrome (RLS) is a common neurological illness marked by a strong desire to move one's legs, usually in association with uncomfortable sensations. Recent studies have investigated brain networks and connectivity in RLS. The advent of network analysis has greatly improved our understanding of the brain and various neurological disorders. A few studies have investigated alterations in functional connectivity in patients with RLS. This article reviews functional connectivity studies of patients with RLS, which have identified significant alterations relative to healthy controls in several brain networks including thalamic, salience, default-mode, and small-world networks. In addition, network changes related to RLS treatment have been found, including to repetitive transcranial magnetic stimulation, transcutaneous spinal cord direct-current stimulation, and dopaminergic drugs. These findings suggest that the underlying pathogenesis of RLS includes alterations in the functional connectivity in the brain and that RLS is a network disorder.

Structural brain connectivity in patients with restless legs syndrome: a diffusion tensor imaging study.

STUDY OBJECTIVES: To evaluate alterations of global and local structural brain connectivity in patients with restless legs syndrome (RLS). METHODS: Patients with primary RLS and healthy controls were recruited at a sleep center where they underwent diffusion tensor imaging (DTI) of the brain. We calculated the network measures of global and local structural brain connectivity based on the DTI in both groups using DSI studio program and a graph theory. RESULTS: A total of 69 patients with primary RLS and 51 healthy controls were included in the study. We found a significant difference in the global structural connectivity between the groups. The transitivity in the patients with RLS was lower than that in healthy controls (0.031 vs. 0.033, p = 0.035). Additionally, there were significant differences in the local structural connectivity between the groups. The characteristic path length (r = 0.283, p = 0.018), radius of graph (r = 0.260, p = 0.030), and diameter of graph (r = 0.280, p = 0.019) were all positively correlated with RLS severity, whereas the mean clustering coefficient (r = -0.327, p = 0.006), global efficiency (r = -0.272, p = 0.023), small-worldness index (r = -0.325, p = 0.006), and transitivity (r = -0.351, p = 0.003) were negatively correlated with RLS severity. CONCLUSION: We identified changes in the global structural connectivity of patients with RLS using graph theory based on DTI, which showed decreased segregation in the brain network compared to healthy controls. These changes are well correlated with RLS severity. We also found changes in local structural connectivity, especially in regions involved in sensorimotor function, which suggests that these areas play a pivotal role in RLS. These findings contribute to a better understanding of the pathophysiology of RLS symptoms.

Prevalence of restless legs syndrome during the 2019 coronavirus disease pandemic in South Korea: A nationwide cross-sectional population-based study.

Background: The 2019 coronavirus disease (COVID-19) pandemic has been associated with a significant increase in sleep disorders. This study aimed to determine the prevalence of restless leg syndrome (RLS) and the effect of COVID-19 on RLS during the pandemic in Korea. Methods: The National Sleep Survey of South Korea 2022 was employed in this study. This study was a large population-based web survey using a structural questionnaire of a four thousand representative sample of individuals aged 20-69 years in Korea. The survey was conducted between January 2022 and February 2022 during the COVID-19 pandemic. RLS was diagnosed using the Korean version of the paradigm of questions for epidemiological studies of RLS. Chronic persistent RLS was defined for individuals with RLS symptoms at least twice a week. Results: Six hundred forty-nine (16.2%) and 172 (4.3%) patients were classified as having RLS and chronic persistent RLS, respectively. Female sex, being employed, the presence of COVID-19 vaccine-related adverse events, decreased sleep duration, the presence of EDS, and current treatment for insomnia were significantly associated with chronic persistent RLS. Conclusion: During the COVID-19 pandemic, the prevalence of RLS and chronic persistent RLS in the adult Korean population was higher than that reported in previous studies.

Usefulness of electronic stimulation in restless legs syndrome: a pilot study.

PURPOSE: This study aims to investigate the effect of electronic stimulation (ES) as a non-pharmacological treatment in restless legs syndrome (RLS). METHODS: This is a randomized, single-blind study. A total of 46 patients were included, consisting of an active group and a sham group with 22 and 24 members, respectively. The stimulation was administered to bilateral lower legs using the tapping mode (3 Hz) on a handheld ES device, and symptom changes were measured in both groups. The effects of the stimuli were analyzed with repeated measures ANOVA. RESULTS: The symptom severity was significantly reduced in the active group, and showed significant interaction effects in the time * group (F = 4.441, p = 0.031). Although both the active and sham groups reported improved symptoms upon receiving longer periods of treatment, the effect of the ES was greater in the active group. CONCLUSIONS: ES treatment resulted in symptom improvement when using ideal levels of stimulation intensity. ES can be considered as a non-pharmacological treatment option for RLS.

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.