Members of the Clinical Investigators Group are listed in the Appendix on page 17.
Overlapping demyelinating syndromes and anti–N-methyl-D-aspartate receptor encephalitis
Article first published online: 13 MAR 2014
© 2014 American Neurological Association
Annals of Neurology
Volume 75, Issue 3, pages 411–428, March 2014
How to Cite
Titulaer, M. J., Höftberger, R., Iizuka, T., Leypoldt, F., McCracken, L., Cellucci, T., Benson, L. A., Shu, H., Irioka, T., Hirano, M., Singh, G., Cobo Calvo, A., Kaida, K., Morales, P. S., Wirtz, P. W., Yamamoto, T., Reindl, M., Rosenfeld, M. R., Graus, F., Saiz, A. and Dalmau, J. (2014), Overlapping demyelinating syndromes and anti–N-methyl-D-aspartate receptor encephalitis. Ann Neurol., 75: 411–428. doi: 10.1002/ana.24117
- Issue published online: 1 APR 2014
- Article first published online: 13 MAR 2014
- Accepted manuscript online: 11 FEB 2014 06:50AM EST
- Manuscript Revised: 3 FEB 2014
- Manuscript Accepted: 3 FEB 2014
- Manuscript Received: 27 AUG 2013
To report the clinical, radiological, and immunological association of demyelinating disorders with anti–N-methyl-D-aspartate receptor (NMDAR) encephalitis.
Clinical and radiological analysis was done of a cohort of 691 patients with anti-NMDAR encephalitis. Determination of antibodies to NMDAR, aquaporin-4 (AQP4), and myelin oligodendrocyte glycoprotein (MOG) was performed using brain immunohistochemistry and cell-based assays.
Twenty-three of 691 patients with anti-NMDAR encephalitis had prominent magnetic resonance imaging (MRI) and/or clinical features of demyelination. Group 1 included 12 patients in whom anti-NMDAR encephalitis was preceded or followed by independent episodes of neuromyelitis optica (NMO) spectrum disorder (5 cases, 4 anti-AQP4 positive) or brainstem or multifocal demyelinating syndromes (7 cases, all anti-MOG positive). Group 2 included 11 patients in whom anti-NMDAR encephalitis occurred simultaneously with MRI and symptoms compatible with demyelination (5 AQ4 positive, 2 MOG positive). Group 3 (136 controls) included 50 randomly selected patients with typical anti-NMDAR encephalitis, 56 with NMO, and 30 with multiple sclerosis; NMDAR antibodies were detected only in the 50 anti-NMDAR patients, MOG antibodies in 3 of 50 anti-NMDAR and 1 of 56 NMO patients, and AQP4 antibodies in 48 of 56 NMO and 1 of 50 anti-NMDAR patients (p < 0.0001 for all comparisons with Groups 1 and 2). Most patients improved with immunotherapy, but compared with anti-NMDAR encephalitis the demyelinating episodes required more intensive therapy and resulted in more residual deficits. Only 1 of 23 NMDAR patients with signs of demyelination had ovarian teratoma compared with 18 of 50 anti-NMDAR controls (p = 0.011).
Patients with anti-NMDAR encephalitis may develop concurrent or separate episodes of demyelinating disorders, and conversely patients with NMO or demyelinating disorders with atypical symptoms (eg, dyskinesias, psychosis) may have anti-NMDAR encephalitis. Ann Neurol 2014;75:411–428