Symptomatic narcolepsy in patients with neuromyelitis optica and multiple sclerosis: new neurochemical and immunological implications.
OBJECTIVE
To characterize factors that contribute to symptomatic narcolepsy and excessive daytime sleepiness in neuromyelitis optica and multiple sclerosis.


METHODS
Japanese university hospitals.


METHODS
Case study.


METHODS
Seven Japanese patients whose initial diagnoses were multiple sclerosis and who were exhibiting excessive daytime sleepiness.


METHODS
Lesions on magnetic resonance imaging, cerebrospinal fluid hypocretin-1 levels, and serum anti-aquaporin 4 (AQP4) antibody titer.


RESULTS
Bilateral and symmetrical hypothalamic lesions associated with marked or moderate hypocretin deficiency were found in all 7 cases. Four of these patients met the International Classification of Sleep Disorders 2 narcolepsy criteria. Three patients, including 2 patients with narcolepsy, were seropositive for anti-AQP4 antibody and diagnosed as having neuromyelitis optica-related disorder.


CONCLUSIONS
Since AQP4 is highly expressed in the hypothalamic periventricular regions, an immune attack on AQP4 may be partially responsible for the bilateral and hypothalamic lesions and hypocretin deficiency in narcolepsy/excessive daytime sleepiness associated with autoimmune demyelinating diseases.
Kanbayashi
Takashi
T
Department of Neuropsychiatry, Akita University School of Medicine, Akita City, Japan.
Shimohata
Takayoshi
T
Nakashima
Ichiro
I
Yaguchi
Hiroaki
H
Yabe
Ichiro
I
Nishizawa
Masatoyo
M
Shimizu
Tetsuo
T
Nishino
Seiji
S
D000328:Adult; D051401:Aquaporin 4 / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000134:cerebrospinal fluid; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000276:immunology* / Q000378:metabolism*; D009290:Narcolepsy / Q000150:complications / Q000276:immunology* / Q000378:metabolism*; D009471:Neuromyelitis Optica / Q000150:complications / Q000276:immunology* / Q000378:metabolism*; D009479:Neuropeptides / Q000134:cerebrospinal fluid; D000068797:Orexins; D055815:Young Adult
C496030:AQP4 protein, human; D051401:Aquaporin 4; C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins