Overlapping demyelinating syndromes and anti–N-methyl-D-aspartate receptor encephalitis.
OBJECTIVE
To report the clinical, radiological, and immunological association of demyelinating disorders with anti–Nmethyl- D-aspartate receptor (NMDAR) encephalitis.


METHODS
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.


RESULTS
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 (p50.011).


CONCLUSIONS
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.
Maarten J
MJ
Titulaer
Romana
R
Höftberger
Takahiro
T
Iizuka
Frank
F
Leypoldt
Lindsey
L
McCracken
Tania
T
Cellucci
Leslie A
LA
Benson
Huidy
H
Shu
Takashi
T
Irioka
Makito
M
Hirano
Gagandeep
G
Singh
Alvaro
A
Cobo Calvo
Kenichi
K
Kaida
Pamela S
PS
Morales
Paul W
PW
Wirtz
Tomotaka
T
Yamamoto
Markus
M
Reindl
Myrna R
MR
Rosenfeld
Francesc
F
Graus
Albert
A
Saiz
Josep
J
Dalmau
D000293:Adolescent; D000328:Adult; D000818:Animals; D060426:Anti-N-Methyl-D-Aspartate Receptor Encephalitis / Q000150:complications* / Q000175:diagnosis / Q000276:immunology / Q000473:pathology; D051401:Aquaporin 4 / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001921:Brain / Q000276:immunology / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003711:Demyelinating Diseases / Q000150:complications* / Q000175:diagnosis / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D059906:Neuroimaging; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology
D051401:Aquaporin 4; D001323:Autoantibodies; D063308:Myelin-Oligodendrocyte Glycoprotein; D016194:Receptors, N-Methyl-D-Aspartate