Ventilatory control in young patients with narcolepsy type 1: A case-control study

Narcolepsy type 1 (NT1), characterized by orexin deficiency, may impair ventilatory control due to orexin neurons' role in CO₂/pH chemosensitivity. Animal studies suggest attenuated hypercapnic-hyperoxic responses in orexin-deficient models, but human data are limited.

In this cross-sectional case-control study, we compared ventilatory control in children and adolescents with NT1 to that of controls matched for sex, age, body mass index, and apnea-hypopnea index (AHI). Ventilatory control was assessed using the hypercapnic, hyperoxic ventilatory response (HCVR) rebreathing test and by measuring controller gain during tidal breathing in wakefulness. HCVR was used to assess central CO₂ chemosensitivity, whereas controller gain was interpreted as an indirect marker of peripheral CO₂ chemosensitivity.

Twenty-one patients with NT1 were included and matched to twenty-one controls. The median age of NT1 was 16.9 years, with an interquartile range of [14.8; 19.8]. NT1 patients exhibited significantly reduced controller gain (0.68 [0.42; 1.32] vs. 1.87 [1.05; 3.12] L/(min.mmHg), p = 0.007) but preserved HCVR slope (1.19 [0.98; 1.91] vs. 1.80 [1.55; 2.50] L/(min.mmHg), p = 0.191). In exploratory analyses, the AHI, central apnea index, and hypopnea index were higher in patients with markedly reduced cerebrospinal fluid orexin levels than in other patients with NT1.

These findings are in favor of decreased peripheral chemosensitivity in children and adolescents with NT1. This alteration does not appear to be strongly related to the degree of CSF orexin deficiency and may reflect factors other than disease severity, as previously suggested for DQB1*06:02 status.