Absence of Markers of Inflammation in Blood and Cerebrospinal Fluid in Routine Analysis of Adult and Paediatric Narcolepsy Type 1

Narcolepsy Type 1 (NT1) is caused by selective loss of hypocretin-producing hypothalamic neurons, likely mediated by immune mechanisms in genetically predisposed individuals. Evidence of inflammation in routine blood and cerebrospinal fluid (CSF) analyses remains inconsistent. We investigated whether standard plasma and CSF inflammatory markers differ between NT1 at variable latency from disease onset and other central disorders of hypersomnolence (CDH, non-NT1). Consecutive untreated patients evaluated for suspected CDH at a tertiary sleep centre between January 2022 and December 2024 underwent standardized diagnostic assessment including lumbar puncture. Routine blood markers (white blood cell count, neutrophil-to-lymphocyte ratio [NLR], C-reactive protein, erythrocyte sedimentation rate) and CSF parameters (cell count, protein, glucose, CSF/serum albumin quotient, IgG index, oligoclonal bands) were compared between NT1 and non-NT1 patients. Sensitivity analyses stratified patients by age group, disease duration and HLA-DQB1*06:02 status. We recruited 166 patients with NT1 and 136 with non-NT1 CDH. NT1 patients were younger and had higher body mass index. No significant differences in blood or CSF assay (including NLR, oligoclonal bands, blood-brain barrier permeability, or intrathecal IgG synthesis) were detected after adjustment for age and body mass index. Findings were consistent in paediatric and adult subgroups and in HLA-DQB1*06:02-positive patients. No differences in blood or CSF assays were associated with disease duration (< 1 year vs. 1-3 years vs. > 3 years) in NT1. In conclusion, routine plasma and CSF inflammatory markers do not distinguish NT1 from other CDH, even close to disease onset, supporting the need for more sensitive biomarkers to assess inflammation in NT1.