Lipford, Melissa

Abstract Introduction Isolated REM sleep behavior disorder (iRBD) is characterized by loss of normal REM sleep atonia and dream enactment behavior. iRBD is strongly associated with α-synucleinopathies and risk for developing Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), yet phenoconversion risk for long-term outcomes of younger women and men remains undefined. We aimed to ascertain longitudinal outcomes and phenoconversion risk in the Mayo Clinic iRBD cohort. Methods Eighty-nine of 165 registry participants with at least one-year follow-up were included. Retrospective chart review attained baseline demographics, age at presentation, baseline Timed Up and Go (TUG) and Montreal Cognitive Assessment (MoCA) scores, and phenoconversion status (iRBD, PD, DLB, mild cognitive impairment [MCI], MSA, or other). Kaplan–Meier survival analysis and Cox proportional hazards modeling were analyzed with alpha at p < 0.05. Results 68 men and 21 women had a mean age of 63 years at polysomnographic diagnosis. At follow-up, 64 (71.9%) remained iRBD; 7 (7.9%) developed PD, 11 (12.4%) developed DLB, 3 (3.4%) developed MCI, 1 (1.1%) developed MSA, and 3 (3.4%) developed another dementia. Abnormal TUG (>12 seconds) occurred in 5.9% and abnormal MoCA (< 24) in 23.3%. Phenoconversion rates were similar in women and men (p = 0.44). Older age at PSG predicted phenoconversion, corresponding to a two-fold increase in risk with each 10-year increase (HR 2.00, 95% CI 1.15–3.52). Neither abnormal TUG nor MoCA predicted conversion. Cumulative phenoconversion was approximately 1% at 1 year, 7% at 3 years, 10% at 5 years, 30% at 10 years, 34% at 12 years, and 49% at 15 years. Mean and median time to phenoconversion was 7 years (range, 1-18 years). Conclusion We found that iRBD phenoconversion rates were lower than historically reported. Only age at presentation predicted phenoconversion, with risk doubling per decade. At 12 years, cumulative phenoconversion rate was approximately 34%. Support (if any)

Abstract Introduction Sodium oxybate is strongly recommended by the American Academy of Sleep Medicine for the treatment of narcolepsy, a chronic sleep disorder characterized by excessive daytime sleepiness (EDS). This study was conducted to characterize demographic characteristics and concomitant medication use of patients with narcolepsy treated or not treated with oxybates (OXB). Methods An electronic health record–based search identified first-time patients from Mayo Clinic and Duke Health between 2002-2024 and 2012-2024, respectively. Patients had ≥1 narcolepsy-specific ICD-9/10 code and ≥1 diagnostic mention of narcolepsy in clinical notes (via natural language processing algorithm). Patients from both Mayo Clinic and Duke Health who were or were not treated with OXB were identified. Data were analyzed descriptively. Results Of 4722 patients, 654 (Mayo Clinic, n=378; Duke Health, n=276) received OXB, and 4068 (Mayo Clinic, n=2800; Duke Health, n=1268) received non-OXB treatments. The majority of patients were white (OXB-treated: 92.1%, 73.6%; non–OXB-treated: 91.1%, 69.2%) and female (OXB-treated: 68.3%, 76.8%; non–OXB-treated: 61.7%, 68.1%). Most OXB-treated patients (65.3%; 63.4%) had narcolepsy type 1 (NT1); the majority of non–OXB-treated patients (78.1%; 64.0%) had narcolepsy type 2 (NT2). The mean (SD) age of the OXB-treated cohort was younger than the non–OXB-treated cohort at the time of diagnosis (OXB-treated: 33.9 [15.3] years, 35.7 [13.2] years; non–OXB-treated: 45.5 [19.2] years, 42.5 [17.8] years). For both cohorts, the most common concomitant medications were stimulants (OXB-treated: 50.3%, 42.8%; non–OXB-treated: 41.8%, 35.2%). Conclusion In this retrospective analysis of nearly 5000 patients from Mayo Clinic and Duke Health, approximately 1 in 8 received OXB. While sodium oxybate has been approved for >2 decades and is strongly recommended for treatment of both EDS and cataplexy in narcolepsy, substantially greater OXB utilization was observed in patients with NT1. As both patients with NT1 and NT2 can experience other narcolepsy symptoms, further OXB-related education remains critical—particularly on the efficacy of sodium oxybate in the treatment of NT2. Support (if any) Avadel Pharmaceuticals

Abstract Introduction Narcolepsy is a rare, chronic sleep disorder associated with decreased quality of life and multiple comorbid conditions, including sleep-related and psychiatric or mood disorders. This study used aggregate electronic health record (EHR) data to characterize the demographics and comorbidities of patients with narcolepsy. Methods An EHR-based search identified first-time Duke Health patients between January 1, 2012, and March 31, 2024. Included patients had ≥1 narcolepsy-specific ICD-9 (347.*) and ICD-10 (G47.4*) codes and ≥1 disease-supportive statement in clinical notes, identified using a natural language processing algorithm. A control cohort was propensity-matched for birth year, age at first institutional encounter, sex, race, number of diagnosis code instances, and mortality. Common comorbidities were compared and ranked between cohorts by odds ratio (OR). Statistical significance was determined using a chi-squared test; P values were corrected for multiple comparisons using Bonferroni correction. Results Within the EHR database of 2,617,188 patients, 1659 patients with a narcolepsy diagnosis were identified (mean age at first presentation, 32.4 years; white, 69%; female, 69%); the propensity-matched control cohort included 1659 patients (mean age at first presentation, 32.3 years; white, 69%; female, 69%). Comorbidities that occurred statistically significantly more frequently (all P< 0.0001) among the narcolepsy vs control cohort (OR [95% CI]) included sleep disorders: sleep-related movement disorders (26.26 [10.71-64.40]), hypersomnia (16.56 [12.54-21.87]), and circadian rhythm sleep disorders (15.43 [6.73-35.38]); psychiatric or mood disorders: posttraumatic stress disorder (3.08 [2.10-4.52]), attention deficit hyperactivity disorder (2.90 [2.28-3.68]), and depression (2.66 [2.27-3.11]); and pain disorders: trigeminal neuralgia (6.63 [2.80-15.70]), fibromyalgia (5.30 [3.58-7.85]), and chronic pain syndrome (3.37 [2.46-4.61]). Postural orthostatic tachycardia syndrome occurred statistically significantly more frequently (P< 0.0001) in the narcolepsy vs control cohort (7.24 [3.59-14.61]). Conclusion Consistent with prior EHR research, sleep, psychiatric, mood, and pain disorders were among the most frequently reported comorbidities of patients with narcolepsy. The results of this analysis of real-world demographic and clinical information of patients with narcolepsy may further inform clinicians of the most relevant concomitant disease states to consider when evaluating potential therapies. Support (if any) Avadel Pharmaceuticals