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Introduction Tonic motor activation (TOMAC) is a noninvasive medical device therapy that has been shown to reduce symptoms of refractory restless legs syndrome (RLS). Here, we evaluated the effects of TOMAC on subjective sleep quality. Methods One hundred and thirty-three adults with primary moderate-severe refractory RLS were 1:1 randomized to TOMAC or sham control for 4 weeks. Participants were instructed to self-administer a 30-minute TOMAC session bilaterally over the head of the fibula to electrically stimulate the peroneal nerve whenever RLS symptoms presented. Sleep quality was assessed through prespecified analysis of changes to Medical Outcomes Study Sleep Scale (MOS-Sleep) Sleep Problems Index I (MOS-I) and II (MOS-II) scores from baseline to Week 4. Post hoc t-tests were conducted on each MOS-Sleep item included in the MOS-I or MOS-II. Results MOS-I score changed by -11.8 points (48.5 to 36.7) for TOMAC and -2.8 points for sham (44.5 to 41.7), a difference of -9.0 points (p< 0.001). MOS-II score changed by -13.7 points (52.5 to 38.9) for TOMAC and -4.0 points for sham (48.3 to 44.3), a difference of -9.7 points (p< 0.001), which exceeds the proposed minimal clinically important difference (MCID) of 6 points. Post hoc analysis demonstrated statistically significant reductions in trouble falling asleep (item #7; -34.0% for TOMAC vs. -5.8% for sham; p< 0.01) and trouble staying awake during the day (item #9; -33.6% for TOMAC vs. -2.1% for sham; p< 0.05), which exceeded the standard MCID threshold of 30% relative to baseline. Conclusion For adults with refractory RLS, TOMAC improved subjective sleep quality, sleep latency, and daytime somnolence relative to sham control. Each of these improvements represented clinically important improvements. These data demonstrate that TOMAC can provide meaningful improvements to sleep quality and daytime functioning for patients with refractory RLS. Support (if any) Funding was provided by Noctrix Health, Inc.

Introduction There is a large population of patients who have become refractory to first-line treatments for Restless Legs Syndrome, partially due to augmentation to dopamine agonist medications. For patients with refractory RLS, tonic motor activation (TOMAC) is a noninvasive medical device therapy with promising short-term safety and efficacy. Here, we evaluated the response to TOMAC over a longer duration of >24 weeks. Methods In the RESTFUL study, 133 patients with primary moderate-severe refractory RLS were 1:1 randomized to TOMAC or sham control for weeks 1 to 4 followed by open-label TOMAC for weeks 5 to 8. The final 50 participants to complete the RESTFUL study were invited to continue TOMAC treatment for an additional 24 weeks (weeks 9 to 32) in an extension study. Participants were instructed to self-administer one 30-minute TOMAC session bilaterally over the peroneal nerve whenever RLS symptoms presented. Efficacy was assessed by comparing responses from baseline (RESTFUL study entry, week 0) to week 32 on Clinician Global Impressions-Improvement (CGI-I) responder rate, Patient Global Impressions-Improvement (PGI-I) responder rate, and International RLS Study Group Rating Scale (IRLS) total score. Additional analyses compared responses from week 8 (RESTFUL study completion) to week 32. Results Of the 50 eligible participants, 44 consented to the extension study and 42 completed. CGI-I responder rate relative to baseline increased from 64% at week 8 to 76% at week 32. PGI-I responder rate relative to baseline increased from 68% at week 8 to 77% at week 32. IRLS total score reduced from 24.5 at baseline to 17.1 at week 8 to 12.9 at week 32, a reduction of 11.6 points from baseline to week 32. There were no moderate or severe device-related AEs. Conclusion TOMAC resulted in substantial and clinically significant reduction in RLS symptom severity that was maintained through >24 weeks of treatment. Furthermore, there was a trend towards increased efficacy with continued use of TOMAC. These data suggest that TOMAC could represent a potential long-term treatment for the chronic condition of refractory RLS. Support (if any) Funding was provided by Noctrix Health, Inc.

It is well known that after stress of various types, there may be a diminished output of urine which, in most instances, has no deleterious effect. Pringle et al 1 first noted this in 1905 on patients after surgical procedures. It has also been observed following trauma and general anesthesia. 2,3 This response has been extensively investigated and various hypotheses have been offered, such as depression of renal blood flow or conservation of sodium secondary to hormonal influences. Objections to these hypotheses were that the change in renal blood flow is usually transient, and the decrease in urinary output occurs prior to sodium conservation. 4 The absence of this response in patients with diabetes insipidus, the characteristics of the urine (low volume and high specific gravity), and the similarity in blood and urine values to those of patients given vasopressin injection (Pitressin) and a water load suggested that there

Purpose Seizures and antiepileptic drugs (AED) may disrupt sleep patterns in patients with epilepsy, thus evaluation of lacosamide effects on objective and subjective sleep measures is warranted. Methods A multicenter, interventional, open-label study (NCT01530386) was conducted in healthy subjects without confounding effects of concomitant AED use, co-morbidities, or disease state to determine whether lacosamide impacts sleep parameters after 22 days of lacosamide exposure. After overnight polysomnography (PSG) to assess baseline parameters, lacosamide was initiated at 100mg/day (50mg twice daily) and increased by 100mg/day weekly to 300mg/day (the mid-range maintenance dose for adjunctive therapy). The primary variable was change from baseline to post-treatment in wake after sleep onset (WASO). Secondary variables included additional objective sleep measures, subject-reported measures of sleep quality, daytime sleepiness, and tolerability. Change from baseline in WASO was analyzed using the Wilcoxon rank-sum test. Results A total of 27 subjects received ≥1 dose of lacosamide and 25 subjects completed the study. For WASO, median change from baseline was a 6-min reduction (95% confidence interval: −38, 77.5; p =0.1074) after lacosamide treatment; this was considered not clinically relevant. No clinically relevant changes were observed in any secondary variables. Thirteen subjects (48%) reported a treatment-emergent adverse event, none of which was severe or led to study discontinuation. Conclusion Lacosamide 300mg/day had no effect on objective or subjective sleep parameters in healthy subjects and was generally well tolerated.