Ruoff, Chad M

Abstract Introduction Central sleep apnea (CSA) is associated with several medical conditions (e.g., heart failure, atrial fibrillation) and medications (e.g., opioids, ticagrelor, sodium oxybate and valproic acid). We report a case of a 31-year-old female with bipolar disorder treated with valproic acid diagnosed with central sleep apnea on polysomnography, which revealed an apnea-hypopnea index of 150/hour, central apnea index of 112/hour, nadir oxygen saturation of 78%, and 38.6 minutes with oxygen saturation ≤ 88%. Echocardiogram, electrocardiogram, brain magnetic resonance imaging, serum acylcarnitine and serum ammonia levels were unremarkable. Total and free serum valproic acid level was 33 and < 3 mcg/mL, respectively. Two cases of central sleep apnea associated with valproic acid use, both of which improved upon discontinuation of valproic acid, have been reported in the literature. We started the patient on positive airway pressure and suggested she taper off valproic acid and then repeat polysomnography. Given the possible association between central sleep apnea and valproic acid use, we retrospectively analyzed patients receiving valproic acid at time of polysomnography. Methods We retrospectively identified patients between 2005-2017 who were prescribed valproic acid (n=6,169), and of these 72 received valproic acid within 90 days of polysomnography. After chart review, we were able to confirm that 29 received valproic acid at time of polysomnography via blood levels or clear chart documentation. Results Four patients (13.8 %) demonstrated a central apnea index ≥ 5 per hour (mean apnea-hypopnea index 39.2/hour +/- 32.2/ hour including a central apnea index 11.7 +/- 6.6/hour) during polysomnography. Although one patient (3.4 %), a 2-year-old child with Dravet syndrome and refractory/drug resistant generalized epilepsy, was diagnosed clinically with central sleep apnea, the other three patients were diagnosed with obstructive sleep apnea and had other potential reason(s) for the elevated central apnea index (e.g., opioid use as needed for migraines). Conclusion Our case describes a third report of central sleep apnea possibly associated with valproic acid, and our retrospective study indicates that this association is rare. Prospective sleep studies on patients before and after receiving valproic acid are warranted to determine if valproic acid causes central sleep apnea. Support (if any)

Abstract Introduction The ICSD-3-TR defines idiopathic hypersomnia in terms of objective sleep times as sleeping at least 11 hours using 24-hour polysomnography or wrist actigraphy averaged over at least 7 days. Published studies on sleep duration are generally limited by lower sleep duration cut-offs (e.g., ≥ 9 hours), so prevalence data on longer sleep durations are missing. This study used clinical questionnaire data from Mayo Clinic patients to characterize longer sleep times and excessive daytime sleepiness in this population. Methods We retrospectively identified patients who answered questions about subjective sleep times and excessive daytime sleepiness, using the Epworth Sleepiness Scale (ESS), as part of their evaluation in a sleep clinic across the Mayo Clinic Enterprise from 2017 to 2023. Demographic data and sleep disorder diagnoses were then analyzed. Results Patients (N=25,480) with subjective nocturnal sleep times of ≥ 9 (n=2721, 10.7%), ≥ 10 (n=1059, 4.2%), and ≥ 11 hours (n=349, 1.4%) had an ESS ≥ 10 in 33.5%, 41.0%, and 51.3% of the time, respectively. 3.6% (age 53.2±19.7; 58.9% female), 1.7% (age 53.1±20.4; 58.1% female), and 0.7% (age 49.8±19.9; 58.1% female) of the patients reported an ESS ≥ 10 and subjective nocturnal sleep times of ≥ 9, ≥ 10, and ≥ 11 hours per night, respectively. After adjusting for age and sex, patients with more than one diagnostic entry compared to those with one or fewer diagnostic entries for idiopathic hypersomnia with long sleep time (OR=12.75, 95% CI [6.09, 24.52], p< 0.001) and narcolepsy with cataplexy (OR=5.53, 95% CI [1.31, 15.84], p=0.005) were significantly more likely to report ESS ≥ 10 and subjective nocturnal sleep times ≥ 11 hours per night. Conclusion Less than 1% of patients presenting to a Mayo Clinic sleep specialist have self-reported metrics (i.e., ESS ≥ 10 and subjective nocturnal sleep times ≥ 11 per night) consistent with basic clinical features of idiopathic hypersomnia with long sleep time. Additional data analyses (e.g., comorbid conditions, social history, and laboratory results) are underway. 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 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