Citations

Abstract Introduction Regular exercise improves sleep quality by reducing sleep onset latency, extending total sleep duration, and enhancing sleep efficiency, which may alleviate daytime sleepiness. However, the specific impact of exercise on daytime sleepiness remains unclear, with conflicting findings in the literature. We analyzed existing interventional studies which used Epworth Sleepiness Scale (ESS) to measure changes in degree of daytime sleepiness before and after an exercise regimen, allowing us to explore the relationship between exercise and daytime sleepiness. Methods Following PRISMA guidelines, a systematic search was conducted in electronic database of PubMed and Google Scholar from 1991 to the present. Thorough screening and inclusion criteria were applied to identify relevant studies which included ESS assessment before and after an exercise intervention. Also assessed sleep quality by Pittsburgh Sleep Quality Index (PSQI). Results Seven studies met all the inclusion criteria and were included in this study. Exercise exhibited a significantly beneficial impact on sleepiness measured by ESS in four out of seven studies we included in review while two studies showed a marginal reduction in ESS without statistical significance, and one study indicated no change. Additionally, exercise showed an improvement in sleep quality in four out of five studies that included PSQI. Variability in results was noted, influenced by factors such as exercise type, intensity, duration, and timing, as well as individual adherence. Additionally, exercise interventions improved sleep quality, as suggested by reduced scores in PSQI which may indirectly improve daytime sleepiness. Conclusion This analysis of existing interventional studies on exercise and daytime sleepiness suggests exercise can be beneficial for reducing daytime sleepiness and improving sleep quality. While the exact mechanism remains elusive, several factors contribute to the impact of both acute and chronic exercise on daytime sleepiness such as improved sleep quality, regulation of circadian rhythm, neurotransmitters release, stress reduction, increased energy levels, and weight reduction ultimately alleviating daytime sleepiness. Future research will be essential for addressing gaps on how exercise regimen and the underlying mechanisms may prove efficacious on improving daytime sleepiness. Support (if any) Mayo Clinic Florica Research Accelerator for Clinicians Engaged in Research Program

Abstract Introduction Restless legs syndrome (RLS) is a common disorder of unpleasant sensations during inactivity, an urge to move the legs, and hyperarousal. The pathophysiology is incompletely understood. Treatments are not always successful or carry side effects. Methods (Case Report) Results A 45-year-old woman presented with over a decade of RLS and sleep-onset insomnia. The diagnosis was based on the International RLS Study Group criteria. The severity was assessed by the nightly occurrence and Insomnia Severity Index (ISI) of 25. Interfering neurologic or sleep disorders, medications, and abnormal blood work were ruled out. Different dopamine agonists resulted in augmentation. Caffeine was stopped. Polysomnography revealed periodic limb movement with sleep fragmentation. Gabapentin was partially effective and poorly tolerated at high doses, but continued at 600 mg. While using Dextromethorphan (DXM) for an upper respiratory infection, the patient found dramatic improvement of her RLS symptoms. Independently, she discontinued Gabapentin, and continued DXM 30 mg for 6 months, with consistent improvement. ISI decreased to 10. Ultimately, considering its expense, DXM was tapered, and Tramadol initiated. The pathophysiology of RLS is partially understood. Studies showed abnormalities in iron regulation, low adenosine tone, enhanced glutamatergic activity, inflammation, and a genetic predisposition, as contributing factors. Alpha-2-delta calcium channel ligands inhibit the presynaptic glutamate release. Central nervous system iron deficiency may increase glutamatergic tone. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, inhibits the activation of NMDA receptor by glutamate and decreases glutamate presynaptic release. Ketamine was reported to effectively treat RLS. DXM, another NMDA receptor antagonist, has not been reported to treat RLS in the literature. Additionally, an association between inflammation and RLS was described, and limited data showed anti-inflammatory effect of DXM. Conclusion Patients with RLS suffer from their symptoms’ burden. Approved medications could carry side effects, or augmentation. We report a case of severe RLS with dramatic and sustained improvement with DXM. Support (if any)

Objectives: To assess the prevalence of sleep disturbance among patients evaluated at a clinic for patients afflicted with Post-acute sequelae of COVID-19 (PASC). Methods: Sleep disturbance was assessed with the Patient-Reported Outcomes Measurement Information System-Sleep Disturbance (PROMIS-SD) framework among adult patients of the PASC clinic. Results: Among 312 patients, the mean age was 46.2 years, and 70.2% were women. About 41.0% of patients had no sleep disturbance; sleep disturbance was mild to moderate in 51.3% and severe in 7.7%. PROMIS-SD score was negatively correlated with the time from the initial positive COVID-19 test to the initial consultation in the PASC clinic (Pearson r = −.094; r 2 = .0088). Conclusions: The PROMIS-Sleep Disturbance framework can serve as a tool to assess the burden of sleep disturbances in PASC patients.

Abstract Introduction Consumption of diet rich in high saturated fats has been associated with a higher degree of daytime sleepiness. A whole-food, plant-based (WFPB) dietary pattern, which is low in saturated fat, has been shown to be beneficial in weight loss and other health conditions. Patients with obstructive sleep apnea (OSA) frequently experience excessive daytime sleepiness despite treatment. This study aims to assess the effect of a short term (21 days) WFPB diet on daytime sleepiness in patients with obstructive sleep apnea. Methods Patients were recruited from the Mayo Clinic Jacksonville sleep clinic who have a diagnosis of OSA who are on PAP therapy but have daytime sleepiness with Epworth Sleepiness Scale (ESS) score of 5 or above. Participants were asked to follow a strict WFPB diet for 21 days using the Fork Over Knives handbook as a guide. They were also asked to complete ESS before switching to and after completing a WFPB diet for 21 days. Results A total of 10 participants completed the 21-day WFPB diet. Eight out of ten participants had reported a reduction in daytime sleepiness. Overall, we found a mean decrease in ESS score of 3.8 in all participants, with 3 patients had a significant decrease in ESS score of ≥ 7. All participants completed the study with ≥ 90% adherence to a WFPB diet. In addition, participants also reported a mean weight loss of 4.2 kg. Two participants noted headaches during this 21-day period. Conclusion Significant improvement with daytime sleepiness was found in patients who switched to a WFPB diet for 21 days. No significant correlation between improvement in ESS and weight loss was found. Support (if any)

Abstract Introduction COVID-19 primarily affects the respiratory system, however, a number of clinical sequela have emerged in patients recovered from COVID-19. Besides the most commonly reported symptoms of fatigue and dyspnea, early studies have found that sleep disturbance is also a common complaint. The aim of this study is to survey for sleep disturbance, degree of fatigue and daytime sleepiness in a group of post-hospitalized COVID-19 patients. Methods Patients who were discharged from Mayo Clinic hospitals after COVID-19 hospitalization were recruited in this study. Patients who have an existing diagnosis of sleep apnea or other sleep disorders were excluded from this study. Mayo Clinic patients who never had COVID-19 infection, nor a history of sleep disorders or other sleep disorders were also recruited as controls. Patients completed Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and Fatigue Severity Scale (FSS) questionnaires via REDCap. Wilcoxon rank sum test was used to evaluate the difference between cases and controls in continuous variables and Fisher’s exact test was used to compare categorical variables. Multivariable linear regression model was used to evaluate the difference in sleep and fatigue scores between cases and controls with baseline characters adjusted. All tests were two-sided with p value <0.05 considered statistically significant. Results A total of 62 patients who completed the questionnaires were included in the analysis. Among them, 33 had COVID-19. Cases were significantly older with higher BMI compared to controls. Global PSQI score (median=10 vs 6, p=0.015), ESS total score (median=8 vs 5, p=0.018) and FSS total score (median=30 vs 22, p=0.009) were all significantly higher for cases compared to control patients. After adjusting for age and BMI, the difference stayed statistically significant. The mean difference between cases vs controls was found to be 2.7 (95%CI:0.2-5.2, p=0.038), 2.93 (95% CI: 0.66-5.2, p=0.014), and 12.62 (95% CI:5.22-20.03, p=0.001) for PSQI, ESS, and FSS scores, respectively. Conclusion Preliminary results showed that sleep disturbance (PSQI) and daytime symptoms (measured by ESS and FSS) are found to be significantly higher among post COVID-19 hospitalized patients compared to controls. Support (If Any) This work is supported by the Mayo Clinic in Florida Department of Medicine Catalyst for Advancing in Academics award and the Mayo Clinic in Florida Research Accelerator for Clinicians Engaged in Research Program.

Abstract Introduction Orexin deficiency in cerebrospinal fluid (CSF) was first reported in human narcolepsy in 2001, included in diagnostic criteria for narcolepsy in 2014, and made clinically available at the Mayo Clinic in 2019. The purpose of this publication is to report orexin test utilization and results, and other clinically relevant findings from patients evaluated at Mayo Clinic. Methods We retrospectively reviewed CSF orexin samples and clinical records from patients evaluated at Mayo Clinic from 2019 to 2021. Results A total of 98 internal samples (Rochester, n=56; Arizona, n=25, and Florida, n=17) from 95 patients (mean age 32.4 +/- 16.6 years with 20 %, 52 %, and 28 % of patients < 18, 18 – 40, and > 40 years, respectively, at time of CSF collection; 62 % female) have been submitted for CSF orexin measurement (mean CSF orexin 335.17 +/- 158.3 pg/ml; deficient < 110 pg/ml, n=11, 64 % <=40 years with mean age 32.9 +/- 17.0 years; intermediate 110 – 200 pg/ml, n=8, 100 % <= 40 years with mean age 21.1 +/- 12.8 years; normal > 200 pg/ml, n=79, 57 % <=40 years with mean age 33.5 +/- 16.7). No significant correlation was found between orexin levels, and time of collection (i.e., diurnal variation), gender, or age. Repeat testing was performed on three individuals (ages 10, 14, and 19 years) with a change in category of orexin level found in one patient from an intermediate to a normal level. Conclusion Orexin deficiency was found in 12 % of the patients (64 % of the deficient samples were found at ages <= 40 years). This result may reflect the fact that this test is frequently pursued in clinical patients presenting with inconclusive findings and/or comorbidities. Intermediate orexin levels found in 8 % of the samples (100 % <= 40 years). Although most of the patients tested were female (62.2%) and most were 40 years or younger (72%), no significant correlation was found between orexin levels, and time of collection (i.e., diurnal variation), gender, or age. Support (If Any) none