Characteristics of hypersomnia due to inflammatory demyelinating diseases of the central nervous system

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) diagnostic criteria for inflammatory demyelinating central nervous system diseases included symptomatic narcolepsy; however, no relevant case‐control studies exist. We aimed to examine the relationship among cerebrospinal fluid orexin‐A (CSF‐OX) levels, cataplexy and diencephalic syndrome; determine risk factors for low-and-intermediate CSF‐OX levels (≤200 pg/mL) and quantify hypothalamic intensity using MRI. METHODS: This ancillary retrospective case‐control study included 50 patients with hypersomnia and 68 controls (among 3000 patients) from Akita University, the University of Tsukuba and community hospitals (200 facilities). Outcomes were CSF‐OX level and MRI hypothalamus‐to‐caudate‐nucleus‐intensity ratio. Risk factors were age, sex, hypersomnolence and MRI hypothalamus‐to‐caudate‐nucleus‐intensity ratio >130%. Logistic regression was performed for the association between the risk factors and CSF‐OX levels ≤200 pg/mL. RESULTS: The hypersomnia group (n=50) had significantly more cases of NMOSD (p<0.001), diencephalic syndrome (p=0.006), corticosteroid use (p=0.011), hypothalamic lesions (p<0.023) and early treatment (p<0.001). No cataplexy occurred. In the hypersomnia group, the median CSF-OX level was 160.5 (IQR 108.4–236.5) pg/mL and median MRI hypothalamus-to-caudate-nucleus-intensity ratio was 127.6% (IQR 115.3–149.1). Significant risk factors were hypersomnolence (adjusted OR (AOR) 6.95; 95% CI 2.64 to 18.29; p<0.001) and MRI hypothalamus‐to‐caudate‐nucleus‐intensity ratio >130% (AOR 6.33; 95% CI 1.18 to 34.09; p=0.032). The latter was less sensitive in predicting CSF-OX levels ≤200 pg/mL. Cases with MRI hypothalamus-to-caudate-nucleus-intensity ratio >130% had a higher rate of diencephalic syndrome (p<0.001, V=0.59). CONCLUSIONS: Considering orexin as reflected by CSF‐OX levels and MRI hypothalamus‐to‐caudate‐nucleus‐intensity ratio may help diagnose hypersomnia with diencephalic syndrome.