Phenotypic clusters of narcolepsy type 1: Insights from age of onset, weight gain, sleep patterns, and impulsivity

This study aimed to discern the underlying relationships between clinical manifestations and neuroimaging phenotypes among patients with narcolepsy type 1 (NT1).

Demographic characteristics, clinical manifestations, polysomnography parameters, and comorbidities were collected in 158 NT1 patients. Using R software, we applied k-medoid cluster analysis to create homogenous NT1 patient clusters. Subsequently, we identified clinical and neuroimaging features within each cluster and examined associations between neuroimaging and clinical phenotypes across different subgroups.

Four clusters were found: patients with the youngest onset-age exhibit more severe objective sleepiness. However, it is easily ignored or not reported due to mild subjective sleepiness, which may be responsible for the long delay between disease onset and diagnosis in this group of patients. Patients with teenage onset and greater weight gain showed shorter sleep latency, more obvious disturbed nocturnal sleep (DNS), the highest proportion of hallucination and sleep paralysis, as well as the highest motor impulsivity score, but minimum volumes in the left para-hippocampal gyrus (PHG) and right precuneus. Patients with teenage onset and less weight gain showed the longest sleep latency and maximum volumes in the right frontal region and left posterior cingulate cortex (PCC). Adult-onset patients reported the highest Epworth Sleepiness Scale (ESS) scores, more obvious impulsivity behavior and more sleep apnea comorbidity. Volumes in left PHG and left PCC were associated with mean sleep latency, respectively.

Narcolepsy patients with teenage onset and greater weight gain exhibit severe sleepiness, severe DNS and high motor impulsivity. Results from this research will provide a new reference for the pathogenesis, diagnosis and management of narcolepsy.