Localizing deficits in white matter tracts of patients with narcolepsy with cataplexy: tract-specific statistical analysis

White matter alterations related to hypocretin pathway have been less evaluated in patients who have narcolepsy with cataplexy (NC), as compared to the identified exploration of gray matter and have varied among structural brain magnetic resonance imaging studies. The aim of this study was to investigate the disruption of specific white matter tracts in drug-naïve patients with NC, by using a tract-specific statistical analysis (TSSA). Forty drug-naïve NC patients with cataplexy and 42 heathy controls were enrolled in the study. All participants completed diffusion weighted imaging, polysomnography, and neuropsychological testing. At that time, we automatically identified fourteen major fiber tracts using diffusion tensor imaging techniques and analyzed the group comparison of fractional anisotropy (FA) values for each tract between the NC and controls, controlling for the participant’s age and gender. The mean age of the NC patients was 26.9 years and the onset age of daytime sleepiness and cataplexy was 16.7 years and 19.9 years, respectively. Relative to the controls, the NC patients showed that there were identified decreased FA values in the bilateral inferior fronto-occipital fasciculus (IFO). The Epworth sleepiness scale was positively correlated with FA values for the left IFO and right cingulate. The REM sleep latency was positively correlated with FA values for the left IFO, cingulate, and uncinate fasciculus in patients. This TSSA study revealed disintegration of the IFO in the NC patients and suggested that disintegration of WM tracts connected to the frontal cortex contributes to clinical manifestations of narcolepsy.