Italian ReN&IS Registry Reveals Narcolepsy Type 1 Dominance, Highlights Diagnostic Gaps in Hypersomnolence
Background
Central disorders of hypersomnolence, including narcolepsy type 1 (NT1), narcolepsy type 2 (NT2), and idiopathic hypersomnia (IH), are rare, chronic neurological conditions marked by severe excessive daytime sleepiness (EDS). These conditions are often under-recognized and significantly impair quality of life. Current diagnostic and treatment approaches face challenges due to the heterogeneity of symptoms and lack of comprehensive real-world data. Large, harmonized datasets are crucial for improving phenotypic characterization, enhancing diagnostic accuracy, and advancing translational research in this complex field.
Study Design
The Italian Registry for Narcolepsy and Central Disorders of Hypersomnolence (ReN&IS) is a national, multicenter, observational registry established in 2022. This preliminary analysis presents baseline findings from 480 cases enrolled across 20 Italian referral centers between March 2022 and September 2025. Researchers collected and compared demographic features, disease presentation, diagnostic assessment, medical comorbidities, current treatment patterns, and symptoms' evolution across the diagnostic groups of NT1, NT2, and IH patients.
Results
From the 480 cases entered into the ReN&IS, NT1 accounted for the vast majority at 80.0%, followed by NT2 at 14.6%, and IH at 5.4%. NT1 patients exhibited a younger age at onset and enrollment compared to both NT2 and IH groups. They also demonstrated the highest burden of REM-sleep-related symptoms and distinct biomarker profiles, including HLA DQB1*06:02 positivity and low cerebrospinal fluid orexin-A levels.
Despite most patients receiving interventions (non-pharmacological in 58-77% and pharmacological in 88-94%), residual EDS remained a significant issue, affecting 65-85% of patients across the different groups. No significant differences were observed across the groups regarding the prevalence of obesity and other medical comorbidities, such as cardiovascular, pulmonary, and connective tissue diseases.
Key Findings
- Narcolepsy Type 1 (NT1) comprised 80.0% of central hypersomnolence cases in the Italian registry.
- Narcolepsy Type 2 (NT2) accounted for 14.6% and Idiopathic Hypersomnia (IH) for 5.4% of cases.
- NT1 patients showed younger age at onset and enrollment, with clear
HLA DQB1*06:02positivity and loworexin-Alevels. - Residual excessive daytime sleepiness (EDS) was common, affecting 65-85% of patients despite interventions.
- Medical comorbidities like obesity, cardiovascular, and pulmonary diseases did not significantly differ across groups.
Why It Matters
This first nationwide, real-world characterization of central disorders of hypersomnolence in Italy provides critical insights into the prevalence and clinical presentation of these conditions. The registry highlights persistent diagnostic and therapeutic gaps, particularly the high rates of residual excessive daytime sleepiness despite current treatments. For clinicians, this data underscores the need for more effective interventions and improved diagnostic pathways. For researchers, the ReN&IS offers a robust platform for future longitudinal and translational studies, potentially informing the development of novel therapies or optimized treatment protocols for these debilitating sleep disorders. This foundational data is essential for advancing the understanding and management of these rare conditions.
narcolepsy
idiopathic-hypersomnia
hypersomnolence
registry
observational-study
italy