Increased neutrophil-to-lymphocyte ratio as a possible marker to detect neuroinflammation in patients with narcolepsy type 1

Narcolepsy type 1 (NT1) is an autoimmune disease caused by the selective immune attack against orexin-producing neurons. However, the pathophysiology of narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH) remains controversial. The neutrophil-to-lymphocyte ratio (NLR) is an easily calculated parameter from the white blood cell count, which has already been extensively used as an inflammatory marker in immunological disorders. In this study, we examined the white blood cell count of patients with NT1, NT2, and IH compared to healthy controls (HC) and evaluated the NLR to test the possibility of identifying an easy biofluid marker for detecting inflammation and distinguishing patients from HC.

White blood cell count and NLR were compared between 28 patients with NT1, 17 with NT2, 11 with IH, and 21 sex/age-matched HC. These parameters were correlated with cerebrospinal fluid levels of orexin-A, the cerebrospinal fluid/serum albumin ratio (as a marker of blood-brain barrier integrity), and polysomnographic parameters.

Patients with NT1 (NLR 2.01 ± 0.44) showed significantly higher NLR than those with NT2 (NLR 1.59 ± 0.53) or IH (NLR 1.48 ± 0.37) and HC (NLR 1.48 ± 0.43). Correlation analysis did not document significant associations between NLR and the other biological markers in each group of patients. The receiver operating characteristic curve analysis detected an optimal cutoff value to discriminate patients with NT1 from those with NT2, IH, and HC for values of NLR ≥ 1.60, 1.62, and 1.59, respectively.

Patients with NT1 showed a higher NLR than those with NT2, IH, and HC, possibly reflecting lymphocyte migration within the central nervous system, supporting the hypothesis of a neuroinflammatory attack of lymphocytes against orexin-producing neurons. Considering its sensitivity, this easily obtainable biofluid marker could help to screen patients with NT1.

Conti M, Cirillo F, Maio S, et al. Increased neutrophil-to-lymphocyte ratio as a possible marker to detect neuroinflammation in patients with narcolepsy type 1. J Clin Sleep Med. 2025;21(1):101-107.