Overlapping demyelinating syndromes and anti–N-methyl-D-aspartate receptor encephalitis.

Abstract

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).

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.

• Authors: Maarten J Titulaer, Romana Höftberger, Takahiro Iizuka, Frank Leypoldt, Lindsey McCracken, Tania Cellucci, Leslie A Benson, Huidy Shu, Takashi Irioka, Makito Hirano, Gagandeep Singh, Alvaro Cobo Calvo, Kenichi Kaida, Pamela S Morales, Paul W Wirtz, Tomotaka Yamamoto, Markus Reindl, Myrna R Rosenfeld, Francesc Graus, Albert Saiz, Josep Dalmau
• Journal: Annals of neurology (Ann Neurol) Vol. 75 Issue 3 Pg. 411-28 (Mar 2014) ISSN: 1531-8249 [Electronic] United States
• PMID: 24700511 (Publication Type: Journal Article)

Chemical References

• Aquaporin 4
• Autoantibodies
• Myelin-Oligodendrocyte Glycoprotein
• Receptors, N-Methyl-D-Aspartate

Topics

• Adolescent
• Adult
• Animals
• Anti-N-Methyl-D-Aspartate Receptor Encephalitis (complications, diagnosis, immunology, pathology)
• Aquaporin 4 (immunology)
• Autoantibodies (immunology)
• Brain (immunology, pathology)
• Child
• Child, Preschool
• Demyelinating Diseases (complications, diagnosis, immunology, pathology)
• Female
• Humans
• Infant
• Male
• Middle Aged
• Myelin-Oligodendrocyte Glycoprotein (immunology)
• Neuroimaging
• Rats
• Receptors, N-Methyl-D-Aspartate (immunology)