title: Bortezomib for treatment of therapy-refractory anti-NMDA receptor encephalitis.
abstract: We assessed the therapeutic potential of the plasma-cell-depleting proteasome inhibitor bortezomib in severe and therapy-refractory cases of anti-NMDA receptor (anti-NMDAR) encephalitis.
  
  
  
  Five severely affected patients with anti-NMDAR encephalitis with delayed treatment response or resistance to standard immunosuppressive and B-cell-depleting drugs (corticosteroids, IV immunoglobulins, plasma exchange, immunoadsorption, rituximab, cyclophosphamide) who required medical treatment and artificial ventilation on intensive care units were treated with 1-6 cycles of 1.3 mg/m2bortezomib. Occurrence of adverse events was closely monitored.
  
  
  
  Bortezomib treatment showed clinical improvement or disease remission, which was accompanied by a partial NMDAR antibody titer decline in 4 of 5 patients. With respect to disease severity, addition of bortezomib to the multimodal immunosuppressive treatment regimen was associated with an acceptable safety profile.
  
  
  
  Our study identifies bortezomib as a promising escalation therapy for severe and therapy-refractory anti-NMDAR encephalitis.
  
  
  
  This retrospective case series provides Class IV evidence that bortezomib reduces antibody titers and improves the clinical course of patients with severe anti-NMDAR encephalitis.
authors.affiliation: From the Department of Neurology (F.S., H.P., A.M.M., S.K., A.N., M.K., K.R., A.M.), German Center for Neurodegenerative Diseases (H.P.), NeuroCure Clinical Research Center (S.K., A.M.), Department of Rheumatology and Clinical Immunology (T.A., F.H.), and Center for Stroke Research Berlin (A.M.), Charité-Universitätsmedizin Berlin, Germany. franziska.scheibe@charite.de.
authors.forename: Franziska
authors.initials: F
authors.lastname: Scheibe
authors.affiliation: From the Department of Neurology (F.S., H.P., A.M.M., S.K., A.N., M.K., K.R., A.M.), German Center for Neurodegenerative Diseases (H.P.), NeuroCure Clinical Research Center (S.K., A.M.), Department of Rheumatology and Clinical Immunology (T.A., F.H.), and Center for Stroke Research Berlin (A.M.), Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Prüss
authors.affiliation: From the Department of Neurology (F.S., H.P., A.M.M., S.K., A.N., M.K., K.R., A.M.), German Center for Neurodegenerative Diseases (H.P.), NeuroCure Clinical Research Center (S.K., A.M.), Department of Rheumatology and Clinical Immunology (T.A., F.H.), and Center for Stroke Research Berlin (A.M.), Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Annerose M
authors.initials: AM
authors.lastname: Mengel
authors.affiliation: From the Department of Neurology (F.S., H.P., A.M.M., S.K., A.N., M.K., K.R., A.M.), German Center for Neurodegenerative Diseases (H.P.), NeuroCure Clinical Research Center (S.K., A.M.), Department of Rheumatology and Clinical Immunology (T.A., F.H.), and Center for Stroke Research Berlin (A.M.), Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kohler
authors.affiliation: From the Department of Neurology (F.S., H.P., A.M.M., S.K., A.N., M.K., K.R., A.M.), German Center for Neurodegenerative Diseases (H.P.), NeuroCure Clinical Research Center (S.K., A.M.), Department of Rheumatology and Clinical Immunology (T.A., F.H.), and Center for Stroke Research Berlin (A.M.), Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Nümann
authors.affiliation: From the Department of Neurology (F.S., H.P., A.M.M., S.K., A.N., M.K., K.R., A.M.), German Center for Neurodegenerative Diseases (H.P.), NeuroCure Clinical Research Center (S.K., A.M.), Department of Rheumatology and Clinical Immunology (T.A., F.H.), and Center for Stroke Research Berlin (A.M.), Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Köhnlein
authors.affiliation: From the Department of Neurology (F.S., H.P., A.M.M., S.K., A.N., M.K., K.R., A.M.), German Center for Neurodegenerative Diseases (H.P.), NeuroCure Clinical Research Center (S.K., A.M.), Department of Rheumatology and Clinical Immunology (T.A., F.H.), and Center for Stroke Research Berlin (A.M.), Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Klemens
authors.initials: K
authors.lastname: Ruprecht
authors.affiliation: From the Department of Neurology (F.S., H.P., A.M.M., S.K., A.N., M.K., K.R., A.M.), German Center for Neurodegenerative Diseases (H.P.), NeuroCure Clinical Research Center (S.K., A.M.), Department of Rheumatology and Clinical Immunology (T.A., F.H.), and Center for Stroke Research Berlin (A.M.), Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Alexander
authors.affiliation: From the Department of Neurology (F.S., H.P., A.M.M., S.K., A.N., M.K., K.R., A.M.), German Center for Neurodegenerative Diseases (H.P.), NeuroCure Clinical Research Center (S.K., A.M.), Department of Rheumatology and Clinical Immunology (T.A., F.H.), and Center for Stroke Research Berlin (A.M.), Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Falk
authors.initials: F
authors.lastname: Hiepe
authors.affiliation: From the Department of Neurology (F.S., H.P., A.M.M., S.K., A.N., M.K., K.R., A.M.), German Center for Neurodegenerative Diseases (H.P.), NeuroCure Clinical Research Center (S.K., A.M.), Department of Rheumatology and Clinical Immunology (T.A., F.H.), and Center for Stroke Research Berlin (A.M.), Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meisel
mesh_terms: D000328:Adult; D060426:Anti-N-Methyl-D-Aspartate Receptor Encephalitis / Q000276:immunology / Q000628:therapy*; D001323:Autoantibodies / Q000097:blood / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D000069286:Bortezomib / Q000009:adverse effects / Q000627:therapeutic use*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D011480:Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology; D012121:Respiration, Artificial; D019233:Retreatment; D012189:Retrospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D011480:Protease Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; D000069286:Bortezomib