Narcolepsy with cataplexy is characterized by excessive daytime sleepiness, cataplexy, and other REM sleep phenomena. Previous MRI studies were cross-sectional in design and could not adequately address if disease progression leads the brain structural abnormalities in narcolepsy. Our analysis in patients using longitudinally collected brain MRIs (n = 17; 2 scans per patient; scan interval: 4.7 ± 1.9 years) revealed widespread progressive cortical thinning in bilateral dorsolateral frontal and fusiform cortices, right anterior cingulate (corrected p < 0.05). Cross-sectional analyses showed faster progressive cortical thinning in patients than controls (n = 83, one scan per subject available), which we confirmed significant in the analysis of a small-set of longitudinal control data (n = 10). The pattern of progressive thinning in patients was overlapped well with those found in structural and functional studies of narcolepsy. We also found a faster progression of cortical thinning and worse disease severity (decreased sleep efficiency, increased sleep latency and arousal index) over time in a subgroup of patients with earlier disease onset (n = 9, onset age: 15.9 ± 2.5 years old) compared to later disease onset (n = 8, 25.3 ± 4.9). The faster progressive cortical thinning and worse disease severity over time in the patients with early-onset suggest compelling evidence of disease progression existing in this phenotype of narcolepsy syndrome. Our result based on a small dataset, however, demands a more careful investigation of the underlying mechanism.
Keywords: Cortical thinning; Early-onset; Longitudinal study; Narcolepsy.