The spectrum of overlapping anti-NMDAR encephalitis and demyelinating syndromes: a systematic review of presentation, diagnosis, management, and outcomes

Ann Med. 2025 Dec;57(1):2517813. doi: 10.1080/07853890.2025.2517813. Epub 2025 Jul 3.

Abstract

Background: Anti-NMDAR encephalitis frequently overlaps with demyelinating diseases (MOGAD, NMOSD, MS), creating complex syndromes with diverse presentations and challenging management.

Methods: Systematic search of databases including MEDLINE, Google Scholar, Embase, Scopus, Cochrane Library, and Web of Science up to March 2024 for studies on co-existing anti-NMDAR encephalitis and demyelinating syndromes. Data extracted on clinical characteristics, diagnostics, treatments, and outcomes.

Results: Twenty-five studies identified 256 patients (16.2%) with co-existing Anti-NMDAR encephalitis and demyelinating syndromes, primarily MOGAD (94.5%), with fewer cases involving NMOSD or MS. The Anti-NMDAR + MOGAD subgroup exhibited seizures (51-72.7%), psychiatric symptoms (45.5-71.4%), cognitive dysfunction (30.6%), and movement disorders (30.6%). All patients had CSF anti-NMDAR antibodies, with MOG (60%) or AQP4 (25%) antibodies. Use of standardized, cell-based assays and adherence to established criteria are essential to avoid false positives, particularly for MOG. MRI abnormalities were seen in 75% of patients. First-line immunotherapies were effective in 70% of cases; 80% of refractory cases responded to second-line therapies.

Conclusions: Anti-NMDAR encephalitis overlapping with demyelinating diseases is challenging. Tailored treatments based on detailed immune profiles are key to better outcomes.

Keywords: Anti-NMDAR encephalitis; multiple sclerosis; myelin oligodendrocyte glycoprotein antibody-associated disease; neuromyelitis optica spectrum disorder; overlapping syndrome.

Publication types

  • Systematic Review

MeSH terms

  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis* / complications
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis* / diagnosis
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis* / immunology
  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis* / therapy
  • Autoantibodies
  • Demyelinating Diseases* / complications
  • Demyelinating Diseases* / diagnosis
  • Demyelinating Diseases* / immunology
  • Demyelinating Diseases* / therapy
  • Humans
  • Treatment Outcome

Substances

  • Autoantibodies