A five-year longitudinal study reveals progressive cortical thinning in narcolepsy and faster cortical thinning in...

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.