California Center for Sleep Disorders

Background and purposeMost patients with isolated rapid eye movement sleep behaviour disorder (iRBD) progress to a parkinsonian alpha‐synucleinopathy. However, time to phenoconversion shows great variation. The aim of this study was to investigate whether cholinergic and dopaminergic dysfunction in iRBD patients was associated with impending phenoconversion.MethodsTwenty‐one polysomnography‐confirmed iRBD patients underwent baseline 11C‐donepezil and 6‐Fluoro‐(18F)‐l‐3,4‐dihydroxyphenylalanine (18F‐DOPA) positron emission tomography (PET). Potential phenoconversion was monitored for up to 8 years. PET images were analysed according to patients' diagnoses after 3 and 8 years using linear regression. Time‐to‐event analysis was made with Cox regression, dividing patients into low and high tracer uptake groups.ResultsFollow‐up was accomplished in 17 patients. Eight patients progressed to either Parkinson's disease (n = 4) or dementia with Lewy bodies (n = 4), while nine remained non‐phenoconverters. Compared with non‐phenoconverters, 8‐year phenoconverters had lower mean 11C‐donepezil uptake in the parietal (p = 0.032) and frontal cortex (p = 0.042), whereas mean 11C‐donepezil uptake in 3‐year phenoconverters was lower in the parietal cortex (p = 0.005), frontal cortex (p = 0.025), thalamus (p = 0.043) and putamen (p = 0.049). Phenoconverters within 3 years and 8 years had lower 18F‐DOPA uptake in the putamen (p < 0.001). iRBD patients with low parietal 11C‐donepezil uptake had a 13.46 (95% confidence interval 1.42;127.21) times higher rate of phenoconversion compared with those with higher uptake (p = 0.023). iRBD patients with low 18F‐DOPA uptake in the most affected putamen were all phenoconverters with higher rate of phenoconversion (p = 0.0002).ConclusionsThese findings suggest that cortical cholinergic dysfunction, particularly within the parietal cortex, could be a biomarker candidate for predicting short‐term phenoconversion in iRBD patients. This study aligns with previous reports suggesting dopaminergic dysfunction is associated with forthcoming phenoconversion.

Abstract Introduction White-Sutton syndrome is a rare autosomal dominant genetic disorder associated with POGZ de novo genetic variants. Patients with White-Sutton syndrome experience a wide spectrum of disease most common being neurocognitive delays, however various sleep disturbances have also been reported. The incidence of obstructive sleep apnea in patients with White-Sutton syndrome has been previously only defined in cohort studies utilizing subjective screening questionnaires. Report of case(s) We present a case of a 14-year-old male with past medical history of White-Sutton Syndrome who was referred to the sleep clinic by Pediatric Hematology-Oncology for an evaluation of sleep disordered breathing as part of a secondary polycythemia work-up. Patient’s height was 173.6 cm, weight was 111.8 kg, and BMI was 37.1. Patient’s prior laboratory work-up was remarkable for polycythemia with hematocrit of 50.5% and hemoglobin of 16.8 g/dL. He also had a reassuring bicarbonate level of 22 and no documented daytime oxygen desaturations. The PSG was scored using adult criteria due to the patient’s height and weight. He was diagnosed with moderate obstructive sleep apnea with an apnea-hypopnea index (AHI) of 15.5 per hour and a nadir oxygenation saturation of 89%. Conclusion To the author’s knowledge, this is the first case report of a pediatric patient with White-Sutton syndrome with diagnosed obstructive sleep apnea via polysomnography. This is also the first case report of a pediatric patient undergoing polycythemia work-up who was subsequently diagnosed with obstructive sleep apnea. Support (if any)

Abstract 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&amp;lt; 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&amp;lt; 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&amp;lt; 0.01) and trouble staying awake during the day (item #9; -33.6% for TOMAC vs. -2.1% for sham; p&amp;lt; 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.