A longitudinal case report illustrating diagnostic complexity among overlapping sleep-wake phenotypes

The coexistence of multiple primary sleep disorders in a single patient is uncommon and poses significant diagnostic and therapeutic challenges. We report a 45-year-old woman with severe mixed sleep apnea (OSA/CSA), NREM parasomnia (night terrors), sleep-related eating disorder (SRED), nightmare disorder (with RBD like behavior but no REM atonia on PSG), and central hypersomnolence phenotype minimally affected with PAP optimization and delayed sleep-wake phase disorder. Symptoms began more than two decades earlier and included violent dream-enactment behaviors, hypnopompic hallucinations, sleep inertia, and chronic excessive daytime sleepiness (EDS). Treatment required multi-modal therapy. Positive airway pressure therapy successfully treated sleep disordered breathing while pitolisant and solriamfetol produced the most durable improvement in daytime sleepiness. Together melatonin plus clonazepam reduced parasomnia frequency and severity. Several other agents (including prazosin, sodium oxybate, paroxetine, and modafinil) were tried and discontinued for limited benefit or adverse effects. Notably, GLP-1 receptor agonist (GLP-1 RA) therapy for obesity was followed by a substantial weight loss and coincided with resolution of SRED. Because this occurred alongside improved sleep stability, PAP adherence, behavioral adaptation, and medication changes, causality cannot be inferred. The observation may justify further study of metabolic and incretin-related pathways in sleep-related eating behaviors. Overall, this case highlights the complexity of overlapping sleep-wake disorders, the need for individualized pharmacologic sequencing, and a potential emerging role for GLP-1 agonists in SRED.