多次睡眠潜伏期试验阴性后如何诊断 1 型发作性睡病：系统检测下丘脑分泌素的价值

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 2-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 8 min or sleep onset REM periods-SOREMPs 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 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. Statement of Significance In clinical practice, cerebrospinal fluid hypocretin-1 measurement (diagnostic for narcolepsy type 1 if below 110 pg/mL) is not routinely performed in patients with suspected central disorders of hypersomnolence when the multiple sleep latency test (MSLT) is negative. Therefore, in this large consecutive cohort of adults and children with suspected hypersomnolence, we systematically performed hypocretin-1 assay after MSLT negative for narcolepsy, significantly improving the diagnostic yield by correctly identifying narcolepsy type 1 in cases unrecognized by MSLT alone. These patients have subtle phenotypical differences from those with MSLT positive for narcolepsy. We also provided some highly sensitive markers that can suggest the presence of narcolepsy type 1 despite a negative MSLT, guiding the physician to second-line assessments, to reduce misdiagnosis.