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October 2016

Bortezomib Treatment for Patients With Anti-N-Methyl-d-Aspartate Receptor Encephalitis

Author Affiliations
  • 1Department of Neurology, St Josef Hospital, Ruhr University of Bochum, Bochum, Germany
  • 2Section of Hematology and Oncology, Medical Department, St Josef Hospital, Ruhr University of Bochum, Bochum, Germany
JAMA Neurol. 2016;73(10):1251-1253. doi:10.1001/jamaneurol.2016.2588

Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis, an autoimmune disease associated with ovarian teratoma, predominantly affects young females.1 Because antibodies against subunits of the NMDAR contribute to the pathogenesis, methods targeting humoral immunity are therapeutically efficacious.2 However, some patients have an unsatisfactory outcome after high-dose corticosteroids, apheresis therapies, or CD20-targeted B-cell depletion with rituximab.2 We describe 2 patients with severe anti-NMDAR encephalitis who received the proteasome inhibitor bortezomib (Velcade), which was well tolerated and followed by marked remission.

A black woman in her early 30s was admitted with acute agitation, hallucinations, and catatonia. She developed autonomic instability and central hypoventilation. Anti-NMDAR encephalitis was diagnosed, and paraneoplastic staging revealed an ovarian teratoma that was surgically removed. Although the patient received plasma exchange, rituximab, cyclophosphamide, and high-dose corticosteroids, no clinical improvement occurred (Figure, A). She was mechanically ventilated for 7 months and transferred to our clinic. She was nonresponsive and had orofacial dyskinetic movements and tetraparesis. Her CD19-positive B cells were completely depleted. She only slightly improved after receiving plasma exchange, corticosteroids, and intravenous immunoglobulins. Because of severe residual deficits, she was subsequently treated with bortezomib (4 subcutaneous injections of 1.3 mg/m2 on days 1, 4, 8, and 11; comedication with 400 mg of acyclovir sodium twice a day and 960 mg of cotrimoxazole twice a day, 3 times a week for 2 months) after obtaining informed consent for off-label use from her legal guardian. Her therapy was well tolerated with no adverse effects. In the following months, clinical deficits and serum anti-NMDAR antibody titers markedly improved. Until her last follow-up, she remained stable and had only minor cognitive impairment of alertness and nonverbal short-term memory (Table).