Glymphatic dysfunction and its association with clinical symptom severity in narcolepsy type 1: a case-control DTI-ALPS study.

BACKGROUND

Narcolepsy type 1 (NT1) is characterized by excessive daytime sleepiness and cataplexy, primarily caused by hypothalamic orexin deficiency. Beyond neurotransmitter dysregulation, recent evidence suggests that impaired metabolic waste clearance may contribute to its pathophysiology. This study aimed to assess glymphatic function in NT1 using diffusion tensor image analysis along the perivascular space (DTI-ALPS) and to explore its relationship with clinical and polysomnographic features.

METHODS

A total of 92 NT1 patients and 45 age- and sex-matched healthy controls underwent 3.0 T DTI and overnight polysomnography. The ALPS index was calculated to quantify glymphatic efficiency. Correlation and regression analyses examined associations between ALPS values and Epworth Sleepiness Scale (ESS), Multiple Sleep Latency Test (MSLT), and other clinical parameters. Receiver operating characteristic (ROC) analysis evaluated the predictive performance of ALPS for NT1 diagnosis.

RESULTS

The ALPS index was significantly lower in NT1 patients than in controls (1.24 ± 0.07 vs. 1.33 ± 0.06, P < 0.001), indicating impaired glymphatic function. Reduced ALPS values correlated with higher ESS scores (r = − 0.39, P < 0.001), shorter MSLT latency (r = 0.36, P = 0.002), and greater cataplexy severity. Each 0.1-unit decrease in ALPS increased the odds of NT1 by 2.8-fold (adjusted OR = 2.78, 95% CI 1.43–5.41, P = 0.003). The ALPS index showed good diagnostic accuracy (AUC = 0.81), which improved when combined with MSLT (AUC = 0.87, P = 0.018).

CONCLUSIONS

NT1 is associated with significant glymphatic dysfunction, and the degree of impairment correlates with symptom severity. The DTI-ALPS index provides a quantitative and noninvasive biomarker that may aid in disease evaluation and individualized management of narcolepsy.