Tashman, Yasemin

Abstract Introduction Hypoglossal nerve stimulators (HGNS) are used in patients with moderate-to-severe obstructive sleep apnea (OSA) who are unable to tolerate or do not respond to continuous positive airway pressure (CPAP) therapy. However, a subgroup of patients fail to achieve resolution of OSA with HGNS alone. Previous studies have shown that lower BMI, lower nadir oxygenation, decreased sleep latency, and higher VOTE score on drug-induced sleep endoscopy (DISE) predict better treatment outcome. We hypothesize that baseline diagnostic polysomnography (PSG) may further predict which patients will achieve successful therapeutic outcome with HGNS therapy. Methods We conducted a retrospective analysis of all adult patients who underwent HGNS implantation at Mayo Clinic Arizona between 2019-2025 and had a pre-implantation diagnostic PSG available for review. Treatment success was defined by Sher Criteria: >50% reduction in post-treatment apnea hypopnea index (AHI) to a final AHI of < 20/hr. Responders met Sher criteria and non-responders did not meet Sher criteria. Demographics, sleep questionnaire results, PSG variables, and VOTE score on DISE were collected and analyzed using Spearman’s rank correlation of reduction in AHI. Results Twenty-three patients (11M/12F, median age: 69[IQR:64,75] years) met inclusion criteria. Median baseline AHI was 24[IQR:19,37]/hr. Median post-implant AHI was 8 [IQR:3, 14]/hr. Responders (n=15, 65%) and non-responders (n=8, 35%) demonstrated median post-implant AHI of 4.5[IQR:2.3,7.3]/hr and 15.7[IQR:12.3,28.5]/hr, respectively. Treatment response was associated with less time with SpO2 < 88% (T88%) (21min [IQR:3,64] vs. 73[IQR:36,105mins]; p=0.023) and higher central apnea index (CAI) (1[IQR:0.1,3] vs. 0[IQR:0,1], p=0.03) on pre-implantation PSG. Conclusion In this small cohort of OSA patients, less nocturnal hypoxemia as defined by T88% and higher baseline central apnea index were predictors of better treatment response to HGNS therapy as measured by Sher criteria. We hypothesize that greater nocturnal hypoxemia likely reflects more severe airway obstruction during sleep. Our analysis also showed that responders had higher baseline CAI than non-responders, however we believe this association is not clinically significant and likely driven by one outlier (CAI 13/hr). Further analysis in a larger HGNS cohort is needed to confirm these findings. Data enrichment efforts and more sophisticated analyses are underway. Support (if any)

Abstract Introduction Restless Legs Syndrome (RLS) affects up to 3% of the adult population in the United States, with approximately one-third of these individuals experiencing medically refractory disease. Historically, treatments for RLS have included iron replacement, dopamine agonists, and alpha-2-delta ligands. However, dopamine agonists are often associated with augmentation, a phenomenon in which RLS symptoms worsen. This includes increased severity, earlier onset, spread of symptoms to other parts of the body, and the need for higher doses of medications. Over the past decade, the use of opioid therapy for refractory RLS has become more widely accepted. Buprenorphine-naloxone, a combination medication, includes buprenorphine, a partial agonist at the mu-opioid receptor, which is less likely to cause respiratory depression, overdose, or euphoria compared to full agonists. Naloxone, an opioid antagonist, is included to deter misuse. Here, we share the treatment responses of three patients with refractory RLS who were treated with buprenorphine-naloxone. Report of case Pre- and post-treatment IRLS were compared in three Sleep Medicine patients (two females, aged 70, and one male, aged 72) on therapeutic doses of buprenorphine-naloxone. Patient charts were reviewed for medication side effects. Previous treatments included dopamine agonists, alpha-2-delta ligands, iron supplementation, benzodiazepines, methadone, and melatonin. Pre-treatment IRLS scores were 13, 13, and 24, classified as moderate to severe. The formulations used included buprenorphine-naloxone 2-0.5 mg sublingual tablets and buprenorphine-naloxone 2-0.5 mg 1/8 films. Therapeutic daily doses of buprenorphine-naloxone ranged from 7.5 to 60 morphine milligram equivalents (MME) per day. Post-treatment IRLS scores were 0, 2, and 3, representing an average reduction of over 15 points on the IRLS. Average time between pre- and post-treatment IRLS was 29 months. Side effects were reported by one patient, including fatigue, depressive symptoms, and reflux, but none of the patients experienced side effects that limited the use of the medication. Conclusion In this case series, we demonstrate the positive impact of buprenorphine-naloxone in managing refractory RLS, as evidenced by substantial reductions in IRLS scores from moderate to severe levels. We hope to encourage clinicians to consider buprenorphine-naloxone as an effective and well-tolerated treatment option for patients with refractory RLS. Support (if any)

Abstract Introduction A previously published case report suggested that alcohol might cause false-negative results in home sleep apnea testing (HSAT) utilizing Peripheral Arterial Tonometry (PAT). Alcohol is consumed by nearly a third of people globally. Based on this, along with rapid growth in PAT HSAT utilization, we aimed to prospectively study the interaction between alcohol consumption and PAT HSAT technology. We hypothesized that alcohol use would significantly attenuate sleep disordered breathing metrics in contrast to existing literature suggesting alcohol may exacerbate sleep apnea. Methods We planned to recruit subjects (N=100) from Mayo Clinic Arizona sleep clinic who were being evaluated for sleep-disordered breathing and elected to undergo home sleep apnea testing (WatchPAT ONE). Participants were required to report social alcohol use (no more than 1-3 drinks per day). The first and second home sleep apnea test were conducted on separate nights (night 1: without alcohol; night 2: with alcohol). Patients also completed a questionnaire, detailing their normal alcohol intake as well as intake during the respective sleep tests. Statistical analysis included paired sample t-test as well as a descriptive analysis. Results A total of 75 subjects were recruited (mean age [± SD] 56.8 ± 11.9; 90.7% male; mean BMI 29.8 ± 5.8) and 56 patients completed both sleep tests. The mean apnea hypopnea index (AHI) was not statistically different (p=0.784) between night 1 and night 2 (without alcohol: 19.6/hour ± 21.0; with alcohol: 19.3 ± 21.5, respectively). Similarly, no statistically significant difference was found in the AHI during REM and NREM sleep. Conclusion Preliminary data does not suggest a statistically significant difference in AHI without or with alcohol. While no significant change in AHI was observed, this study highlights the need for further investigation into the impact alcohol may have on PAT technology. Further analyses and data enrichment are underway. Support (if any) Mayo Foundation

Abstract Introduction Obstructive sleep apnea (OSA) is characterized by repetitive airway narrowing or collapse during sleep. Hypoglossal nerve stimulation (HNS) is one alternative therapy. After device implantation and activation, it is patient-titrated based on symptoms. A sleep study then confirms effective settings based on an apnea-hypopnea index (AHI) below 5. Symptomatic control alone may not entail low AHI. Objective data with overnight oximetry during titration may help bridge this. We describe a patient in whom Wellue pulse oximeter was used during self-titration of the Inspire HNS. Report of case(s) A 63 year-old male presented in June 2022 for HNS evaluation due to gasping and witnessed apneas. AutoPAP trial had failed. In November 2022 diagnostic polysomnography revealed an AHI of 18 and lowest oxygen saturation (OS) of 80%. Sleep endoscopy in February 2023 confirmed no concentric collapse at the level of the velum. He underwent HNS implantation in May 2023 and activation in June. Initial sensation and functional thresholds were 0.6 volts. Amplitude range was 0.6 to 1.6 volts, pulse width 90 microseconds, rate 33 hertz, pause time 15 minutes, electrode configuration [+,-,+], and duration 8 hours. In July, he felt 0.7 volts controlled symptoms. A Watchpat home sleep study revealed an AHI of 46.2 and lowest OS of 82%. He purchased a pulse oximeter and was shown the oxygen desaturation index (ODI) at >3%. On increasing to 1.0 volts, oximetry revealed ODI 8.65 averaged over 4 nights. At 1.1 volts, ODI improved to 0.9-4.14. Since ODI was below 5, he had subsequent in-laboratory titration, revealing at 1.1 volts the residual AHI was 2.5. The lowest OS was 89% with a mean of 95%. Conclusion The post-activation procedure for HNS utilizes symptom-based self-titration. Sleep studies may reveal continued apnea despite self-reported symptom control. We suspect overnight oximetry during self-titration may improve efficacy. In this case, after self-titration with oximetry to decide an amplitude setting, home and in-laboratory sleep studies confirmed effective control. This preliminarily suggests that overnight oximetry used with HNS during the self-titration phase may improve titration outcomes as confirmed by formal polysomnography. Support (if any)

Abstract Introduction Sleep-related painful erection (SRPE) is a rare parasomnia characterized by painful penile erections during rapid eye movement sleep. Normal, painless erections continue to occur while awake. Approximately thirty cases have been reported in the literature. Multiple theories about potential pathophysiology have been proposed including neurologic dysfunction of the ischiocavernosus and bulbocavernosus, correlation with obstructive sleep apnea, and/or autonomic dysfunction. There is no known single effective treatment to date resulting in durable response despite multiple attempts at therapy. Report of case(s) A 39-year-old male presented with SRPE. This started in 2018 and occurred in the second half of the night every twenty minutes, contributing to discomfort and poor sleep quality. While awake, his erections were painless. He was prescribed baclofen at doses up to 30mg daily decreasing episode frequency to 1-6 times per night, but disabling somnolence precluded continuation. Pelvic physiotherapy was unhelpful while imipramine and clonazepam provided partial relief. Tadalafil was ineffective and cinitapride was not available in the United States. Oxycodone used for pain after a motor vehicle accident did effectively treat him for five hours per night, so morphine was trialed. This was effective for two weeks, but symptoms returned. In April 2022, he was begun on sodium oxybate. With an initial dose of 2.25 g twice nightly, symptoms were treated for four hours a night. After increasing to 2.75 g twice nightly, the SRPE was effectively treated. As of September 2022, he is taking sodium oxybate 3 g at bedtime, 3 g 3.5 hours later and the final 3 g at the 7th hour, promoting 9.5 hours of sleep without SRPE. Conclusion This 39-year-old male who presented with SRPE was trialed on multiple therapies without success, and ultimately successfully treated with an appropriate and titrated dose of sodium oxybate. This may represent a new treatment option, which we hypothesize may act by modulating GABA to result in relaxation of the bulbospongiosus and ischiocavernosus muscles. Further studies should include the study of both the efficacy of this drug for SRPE as well as potential mechanisms of action. Support (if any)

Abstract Introduction Placing a magnet over a Permanent Pacemaker (PPM) or Implanted Cardioverter-Defibrillator (ICD) may cause the device to pace asynchronously or inhibit tachyarrhythmia detection, respectively, potentially preventing delivery of electrical shocks. Manufacturers for masks used with positive airway pressure devices have started using magnets in place of more traditional headgear clips to connect the headgear to mask. Mask manufactures do not list presence of a PPM/ICD as a contraindication to use of a mask with magnet but do recommend keeping the mask some distance away from PPM/ICD. A published case series describes two patients with magnet response events captured during PPM/ICD interrogation that correlated with nightly use of CPAP. The authors were able to replicate the response by placing the mask with magnet directly over the patient’s pulse generate site. Although we advise all patients with implanted device to avoid use of masks with magnets, select patients refuse to stop using mask with magnets regardless of our policy. We, therefore, started offering these patients referral for PPM/ICD interrogation to evaluate for an interaction between mask with magnet and PPM/ICD as next best alternative. Methods We retrospectively reviewed all patients (n=10) referred for routine PPM/ICD interrogation to test whether the mask with magnet interacted with PPM/ICD when mask on face as during normal use (i.e., simulated normal use) or magnetic area of mask placed directly over the PPM/ICD (i.e., direct contact). Results Although no interaction was detected in any patient (n=10) with simulated normal use (0 %), one interaction was documented with direct contact (10 %). Conclusion Although simulated normal use of masks with magnets did not demonstrate any interactions, it is concerning that one patient (10 % of patients) demonstrated an interaction with direct contact of magnetic area of mask over the PPM/ICD. It is not uncommon for patients to remove a mask during the night while sleeping. This preliminary data along with the published case series calls for further research and increased awareness of this potential interaction for both sleep and cardiac health care providers. Support (If Any) None

Abstract Introduction The ICSD-3 describes NREM-related parasomnias as abnormal sleep related complex movements where motor behavior occurs in the setting of absent or very minimal higher cognitive function. A population-based twin study reported that 3.9% of men and 3.1 % of women sleepwalk (SW) with 30% reported experiencing injury (Hublin 1997). Sleep related eating disorder (SRED) may be a variant of SW with a reported prevalence of 0.5-5 % (Michalska 2016). This study examined SW and SRED in a population-based sample permitting review of associated features, risk factors and outcomes. Methods The records-linkage system of the Rochester Epidemiology Project that includes all adults residing in Olmsted County MN was searched for documentation of patients seeking care for at least two episodes of sleepwalking and/or sleep eating. Records from 2007-2016 were included. Results 56 cases were identified with 50 (89 %) having SW and 16 (29%) SRED. The gender breakdown was 50% male and 50% female with the mean age at diagnosis of 40 (SD 13). Childhood parasomnia events were reported by 23/36 (62%) and a family history in 21/35 (64%). Data were unavailable for the others. The number of parasomnia incidents was ≥ 10 for 21 (37%). A variety of experiences were documented, including leaving the bedroom (39%), injury (25%), and exiting through a window/balcony (5%). Associated factors were sleep deprivation (52%), untreated obstructive sleep apnea (34%), antidepressant use (41%), zolpidem use (18%), circadian disruption (14%) and alcohol use (9%). Polysomnography was conducted for 41 (74%). Documented interventions were medication discontinuation (18%) and starting a benzodiazepine (16%). In 21%, no treatment was given. Conclusion This population-based study of adults with clinician diagnosed recurrent SW and SRED revealed equal rates in men and women. The majority of patients with SRED also had SW. 25% of cases were associated with injuries. Support Rochester Epidemiology Project supported by NIH R01 AG034676 and AG052425 and the Mayo Foundation.