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

Hideaki Ishido; Shigeru Chiba; Hana Takahashi; Megumi Isa; Yasuhiro Ogawa; Hiroki Kubota; Aya Imanishi; Yuki Omori; Taisuke Ono; Ko Tsutsui; GoEun Han; Hideaki Kondo; Hiroshi Tsuji; Kiyotaka Nakamagoe; Akiko Ishii; Keiko Tanaka; Akira Tamaoka; Tetsuo Shimizu; Seiji Nishino; Tomoyuki Miyamoto; Takashi Kanbayashi

doi:10.1136/bmjno-2023-000428

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

BMJ Neurol Open. 2023 Jun 21;5(1):e000428. doi: 10.1136/bmjno-2023-000428. eCollection 2023.

Authors

Hideaki Ishido^{1

2

3}, Shigeru Chiba^{1

4

5}, Hana Takahashi⁶, Megumi Isa⁷, Yasuhiro Ogawa⁸, Hiroki Kubota⁹, Aya Imanishi¹⁰, Yuki Omori¹¹, Taisuke Ono¹², Ko Tsutsui^{10

13}, GoEun Han¹, Hideaki Kondo^{1

14}, Hiroshi Tsuji⁶, Kiyotaka Nakamagoe⁶, Akiko Ishii⁶, Keiko Tanaka¹⁵, Akira Tamaoka^{6

16}, Tetsuo Shimizu¹⁷, Seiji Nishino¹⁸, Tomoyuki Miyamoto², Takashi Kanbayashi^{1

2

4}

Affiliations

¹ International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki, Japan.
² Neurology, Dokkyo Ika Daigaku Saitama Iryo Center, Koshigaya, Saitama, Japan.
³ Neurology, Hakusuikai Hatsuishi Hospital, Kashiwa, Chiba, Japan.
⁴ Psychiatry, Ibaraki Prefectural Medical Center of Psychiatry, Kasama, Ibaraki, Japan.
⁵ Psychiatry, Minamisaitama Hospital, Koshigaya, Saitama, Japan.
⁶ Neurology, University of Tsukuba, Tsukuba, Ibaraki, Japan.
⁷ Neurology, National Defense Medical College, Tokorozawa, Saitama, Japan.
⁸ General Medicine, Ibaraki Prefectural University of Health Sciences, Inashiki-gun, Ibaraki, Japan.
⁹ Pediatrics, Akita University, Akita, Akita, Japan.
¹⁰ Psychiatry, Akita University, Akita, Akita, Japan.
¹¹ Psychiatry, Tokyo Metropolitan Geriatric Hospital, Itabashi-ku, Tokyo, Japan.
¹² Geriatric Medicine, Kanazawa Medical University, Kahoku-gun, Ishikawa, Japan.
¹³ Psychiatry, Kato Hospital, Akita, Akita, Japan.
¹⁴ General Medicine, Institute of Biomedical Sciences, Nagasaki University, Nagasaki, Nagasaki, Japan.
¹⁵ Department of Animal Model Development, Brain Research Institute, Niigata University, Niigata, Niigata, Japan.
¹⁶ Neurology, Tsukuba Memorial Hospital, Tsukuba, Ibaraki, Japan.
¹⁷ Department of Mental Health and Welfare, Akita Mental Health and Welfare Center, Akita, Akita, Japan.
¹⁸ Psychiatry, Sleep and Circadian Neurobiology Laboratory, Stanford University, Stanford, California, USA.

Abstract

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.

Keywords: CSF; MRI; multiple sclerosis; sleep disorders.