Suresh Kotagal

Suresh Kotagal; Peering beyond hypersomnia and cataplexy of childhood narcolepsy: the role of sleep-dependent memory consolidation, Sleep, , zsae261, https

Obstructive sleep apnea (OSA), a disease associated with excessive sleepiness and increased cardiovascular risk, affects an estimated 1 billion people worldwide. The present study examined proteomic biomarkers indicative of presence, severity, and treatment response in OSA. Participants (n = 1391) of the Stanford Technology Analytics and Genomics in Sleep study had blood collected and completed an overnight polysomnography for scoring the apnea–hypopnea index (AHI). A highly multiplexed aptamer-based array (SomaScan) was used to quantify 5000 proteins in all plasma samples. Two separate intervention-based cohorts with sleep apnea (n = 41) provided samples pre- and post-continuous/positive airway pressure (CPAP/PAP). Multivariate analyses identified 84 proteins (47 positively, 37 negatively) associated with AHI after correction for multiple testing. Of the top 15 features from a machine learning classifier for AHI ≥ 15 vs. AHI < 15 (Area Under the Curve (AUC) = 0.74), 8 were significant markers of both AHI and OSA from multivariate analyses. Exploration of pre- and post-intervention analysis identified 5 of the 84 proteins to be significantly decreased following CPAP/PAP treatment, with pathways involving endothelial function, blood coagulation, and inflammatory response. The present study identified PAI-1, tPA, and sE-Selectin as key biomarkers and suggests that endothelial dysfunction and increased coagulopathy are important consequences of OSA, which may explain the association with cardiovascular disease and stroke.

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. We retrospectively reviewed CSF orexin samples and clinical records from patients evaluated at Mayo Clinic from 2019 to 2021. 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. 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. none