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. Setting: Japanese university hospitals. Design: Case study. Patients: Seven Japanese patients whose initial diagnoses were multiple sclerosis and who were exhibiting excessive daytime sleepiness. Main Outcome Measures: 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. Conclusion: 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.