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Sleep disorders in anti-NMDAR encephalitis
Helena Ariño1, Amaia Muñoz-Lopetegi1, Eugenia Martinez-Hernandez1
1From Clinical and Experimental Neuroimmunology (H.A., A.M.-L., E.M.-H., T.A., M.R.-J., D.E., F.G., G.S., J.C.-F., A.C., J.D., J.S.), Institut d'Investigació Biomèdica August Pi i Sunyer; Departments of Neurology (A.M.-L., E.M.-H., D.E., N.M., J.D., J.S.) and Child and Adolescent Psychiatry and Psychology (T.A., G.S., J.C.-F.), Hospital Clinic, and Pediatric Neuroimmunology Unit (T.A.), Sant Joan de Déu Children's Hospital, University of Barcelona, Spain; Department of Neurology (J.D.), University of Pennsylvania, Philadelphia; and Institució Catalana de Recerca i Estudis Avançats (J.D.), Barcelona, Spain.
Objective:
To describe the sleep disorders in anti-NMDA receptor encephalitis (anti-NMDARe).
Methods:
Patients recovering from anti-NMDARe were invited to participate in a prospective observational single-center study including comprehensive clinical, video-polysomnography (V-PSG) sleep assessment, and neuropsychological evaluation. Age- and sex-matched healthy participants served as controls.
Results:
Eighteen patients (89% female, median age 26 years, interquartile range [IQR] 21-29 years) and 21 controls (81% female, median age 23 years, IQR 18-26 years) were included. In the acute stage, 16 (89%) patients reported insomnia and 2 hypersomnia; nightmares occurred in 7. After the acute stage, 14 (78%) had hypersomnia. At study admission (median 183 days after disease onset, IQR 110-242 days), 8 patients still had hypersomnia, 1 had insomnia, and 9 had normal sleep duration. Patients had more daytime sleepiness than controls (higher Barcelona Sleepiness Index, p = 0.02, and Epworth Sleepiness Score, p = 0.04). On V-PSG, sleep efficiency was similar in both groups, but patients more frequently had multiple and longer confusional arousals in non-REM (NREM) sleep (videos provided). In addition, 13 (72%) patients had cognitive deficits; 12 (67%) had psychological, social, or occupational disability; and 33% had depression or mania. Compared with controls, patients had a higher body mass index (median 23.5 [IQR 22.3-30.2] vs 20.5 [19.1-21.1] kg/m2; p = 0.007). Between disease onset and last follow-up, 14 (78%) patients developed hyperphagia, and 6 (33%) developed hypersexuality (2 requiring hospitalization), all associated with sleep dysfunction.
Conclusions:
Sleep disturbances are frequent in anti-NMDARe. They show a temporal pattern (predominantly insomnia at onset; hypersomnia during recovery), are associated with behavioral and cognitive changes, and can occur with confusional arousals during NREM sleep.
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