Progressive narcolepsy: how to deal with intermediate hypocretin-1 values?

According to the International Classification of Sleep Disorders, third edition guidelines, the diagnosis of narcolepsy type 1 is based on the association of excessive daytime sleepiness plus either cataplexy and electrophysiological criteria, or a cerebrospinal fluid hypocretin-1 concentration below 110 pg/mL. This threshold remains debated, and recent works have proposed alternative values in the intermediate (110 to 200 pg/mL) zone. We report the case of a patient who presented with typical clinical symptoms of narcolepsy type 1 developing over six years but in whom initial polysomnography and multiple sleep latency test were negative and cerebrospinal fluid hypocretin-1 was intermediate (132 pg/mL). Cerebrospinal fluid hypocretin-1 reassessment four years later found a dramatic decrease, < 50 pg/mL, and the multiple sleep latency test proved to be abnormal, eventually allowing to confirm the diagnosis. This case highlights the importance of reassessing patients with intermediate hypocretin-1 values and contributes to the debate on the determination of alternative cerebrospinal fluid hypocretin1 thresholds for narcolepsy type 1 diagnosis.

Ricordeau F, Bridoux A, Raverot V, Peter-Derex L. Progressive narcolepsy: how to deal with intermediate hypocretin-1 values? J Clin Sleep Med. 2023;19(7):1375-1378.