Abstract
OBJECTIVE: To evaluate the therapeutic potential of bortezomib, a proteasome inhibitor that target plasma cells, in order to revive stalled recovery in patients with anti-N-methyl-d-aspartate (NMDA) receptor encephalitis who remain bedridden even after aggressive immunotherapy. METHODS: We consecutively enrolled patients with anti-NMDA receptor encephalitis who remained bedridden after first-line immunotherapy (steroids and intravenous immunoglobulin), second-line immunotherapy (rituximab), and tocilizumab treatment, and treated them with subcutaneous bortezomib. Clinical response, functional recovery, and changes in antibody titer in the serum and cerebrospinal fluid were measured. RESULTS: Before the bortezomib treatment, the five patients with severe refractory anti-NMDA receptor encephalitis were in a vegetative state. During the 8 months of follow-up period, three patients improved to minimally conscious states within 2 months of bortezomib treatment, one failed to improve from a vegetative state. However, no patient achieved functional recovery as measured by the modified Rankin Scale score (mRS). Three patients advanced to a cyclophosphamide with bortezomib and dexamethasone regimen, which only resulted in additional adverse events, without mRS improvement. Among the four patients whose antibody titer was followed, two demonstrated a twofold decrease in the antibody titer in serum and/or cerebrospinal fluid after 2 cycles of bortezomib. INTERPRETATION: Although there were some improvements in severe refractory patients, clinical response to bortezomib was limited and not clearly distinguishable from the natural course of the disease. The clinical benefit of bortezomib in recent studies requires further validation in different clinical settings.