Overlapping demyelinating syndromes and anti-N-methyl-D-aspartate receptor encephalitis Academic Article uri icon

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  • 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.


  • 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 date

  • March 2014

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