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Overlapping demyelinating syndromes and anti–N‐methyl‐D‐aspartate receptor encephalitis
Author(s) -
Titulaer Maarten J.,
Höftberger Romana,
Iizuka Takahiro,
Leypoldt Frank,
McCracken Lindsey,
Cellucci Tania,
Benson Leslie A.,
Shu Huidy,
Irioka Takashi,
Hirano Makito,
Singh Gagandeep,
Cobo Calvo Alvaro,
Kaida Kenichi,
Morales Pamela S.,
Wirtz Paul W.,
Yamamoto Tomotaka,
Reindl Markus,
Rosenfeld Myrna R.,
Graus Francesc,
Saiz Albert,
Dalmau Josep
Publication year - 2014
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.24117
Subject(s) - encephalitis , neuromyelitis optica , medicine , myelin oligodendrocyte glycoprotein , pathology , multiple sclerosis , immunology , experimental autoimmune encephalomyelitis , virus
Objective To report the clinical, radiological, and immunological association of demyelinating disorders with anti–N‐methyl‐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 (p = 0.011). Interpretation 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