title: Extra-central nervous system target for assessment and treatment in refractory anti-N-methyl-d-aspartate receptor encephalitis.
abstract: Anti-N-methyl-d-aspartate-type glutamate receptor autoimmune encephalitis can arise in the setting of ovarian teratoma and often responds to resection. When it occurs in the absence of tumor, failure to respond to treatment may be more likely, and affected patients often require intensive care. To further understand the mechanisms and potential management, we present findings from an autopsy conducted on a young woman who died of refractory autoimmune encephalitis of this type. Rituximab was administered 70 days before death, and both 37 and 14 days before death, CD19+lymphocytes were only 0.1% of blood cells. Ten sessions of plasmapheresis were performed after rituximab treatment. Nonetheless, the autoantibodies were present in serum 4 days before death, demonstrating ongoing antibody production. The hippocampus and medial temporal lobe demonstrated inflammation with T cell and prominent microglial involvement, but no plasma cells or plasmablasts were found there, or anywhere in the brain, despite an extensive search. Examination of lymph node tissue identified many plasma cells along sinusoids. These findings demonstrate that the antibody-producing cells are long-lived and can reside in lymphoid tissue. Awareness of continuing antibody production, the extra-central nervous system site, the indication for cytotoxic therapy, and the potential for biopsy assessment may lead to more effective treatment.
authors.affiliation: Department of Pathology, Johns Hopkins Hospital, Ross 512, 720 Rutland Ave, Baltimore, MD 21205. Electronic address: dwnauen@jhmi.edu.
authors.forename: David W
authors.initials: DW
authors.lastname: Nauen
mesh_terms: D060426:Anti-N-Methyl-D-Aspartate Receptor Encephalitis / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D001323:Autoantibodies / Q000276:immunology; D001344:Autopsy; D001921:Brain / Q000473:pathology*; D005260:Female; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D017628:Microglia / Q000276:immunology / Q000473:pathology; D010956:Plasmapheresis; D000069283:Rituximab / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D013702:Temporal Lobe / Q000473:pathology; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D007155:Immunologic Factors; D000069283:Rituximab
keywords: Anti-NMDAR encephalitis; Autopsy; Biopsy; Neurointensive care; Refractory encephalitis