To diagnose Narcolepsy type 1 after a negative Multiple Sleep Latency Test: the contribution of systematic hypocretin measurement

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ID: 314949
2026
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Abstract
Abstract Study Objectives We evaluated the diagnostic potential of detecting narcolepsy type 1 (NT1) by systematically measuring cerebrospinal fluid hypocretin-1 (CSF-HCRT1) in patients with suspected central disorder of hypersomnolence (CDH), after the multiple sleep latency test (MSLT) was negative for narcolepsy criteria. Materials and Methods Consecutive untreated patients with suspected CDH were hospitalized at the Bologna Narcolepsy Center (Italy) from 2013 to 2024. They underwent a standardized protocol of two-day continuous polysomnography (PSG), MSLT, and systematic CSF-HCRT1 measurement. Our focus was the identification of additional NT1 cases through the detection of low CSF-HCRT1 < 110 pg/mL among those with negative PSG-MSLT for narcolepsy (i.e., mean sleep latency>8 min or sleep onset REM periods-SOREMPs<2). Features of patients with CSF-HCRT1 < 110 pg/mL and negative PSG-MSLT were explored. Results Out of 870 patients with suspected CDH (all with CSF-HCRT1 assay, 52% males, 30.1% pediatric), 342 had PSG-MSLT criteria consistent with narcolepsy with cataplexy (NT1). Sixty-four had PSG-MSLT criteria consistent with narcolepsy but did not have cataplexy (31.3% with CSF-HCRT1 deficiency). In the remaining 464 cases with a PSG-MSLT negative for narcolepsy, CSF-HCRT1 < 110 was detected in 34 (five without cataplexy), increasing NT1 diagnoses by 9.9% and re-classifying 7.3% of MSLT negative cases (p < 0.001 vs. PSG-MSLT+cataplexy). Among the 378 cases with CSF-HCRT1 < 110, the 34 patients with negative PSG-MSLT carried HLA-DQB1*0602 less often (88.2% vs. 96.5%, p = 0.046), had fewer SOREMPs, and higher CSF-HCRT1 values in comparison to the 344 positive at the first PSG-MSLT. Conclusions In suspected CDH, systematically measuring CSF-HCRT1 in the presence of a negative PSG-MSLT identifies about 10% additional NT1 cases (of which 15% without cataplexy), otherwise possibly misdiagnosed.
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Authors Francesco Biscarini, Stefano Vandi, Giulia Neccia, Martina Gnazzo, F. Ingravallo, Emmanuel Mignot, G Plazzi, Fabio Pizza
Journal Sleep & breathing = Schlaf & Atmung
Year 2026
DOI
10.1093/sleep/zsag142
URL
https://doi.org/10.1093/sleep/zsag142
Keywords Keywords not found

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