To highlight a case of treatment-refractory anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis with favorable response to rapid initiation of bortezomib.

Anti-NMDAR encephalitis is a rare autoimmune disorder that presents with neuropsychiatric symptoms. Bortezomib is a proteasome inhibitor that depletes plasma cells responsible for producing autoantibodies. Bortezomib has shown mixed results in treatment of anti-NMDAR encephalitis, and the optimal timing of initiation is unknown.

A 23-year-old woman presented to the emergency department with one day of disorganized speech, hallucinations, and thought blocking. On hospital day (HD) 2, she developed seizures and was presumptively diagnosed with anti-NMDAR encephalitis, later confirmed by antibody titers in serum and cerebrospinal fluid. Despite first-line treatments of high-dose corticosteroids, plasmapheresis, and ovarian teratoma resection—she developed mutism, dyskinesias, and severe autonomic dysfunction. Patient required ventilation via tracheostomy and intensive medical management of paroxysmal sympathetic hyperactivity.

The patient received rituximab on HD 15, intravenous immunoglobulin on HD 17, and a second trial of corticosteroids on HD 41-45 without improvement. By HD 56, the patient remained severely impaired with seizures, mutism, and autonomic dysfunction. At this point, three cycles of bortezomib were initiated, with 2.15 mg administered subcutaneously for four doses per cycle. Each dose was administered with 20 mg dexamethasone. Between the first and second cycle, there was resolution of autonomic dysfunction, dyskinesias, seizures, and mutism. Patient no longer requires ventilation and a Passy Muir valve was placed to facilitate speech.  The patient’s modified Rankin Scale (mRS) score improved from +5 to +4. Her Clinical Assessment Scale in Encephalitis (CASE) score improved from 26 to 13. However, the patient does not demonstrate speech, consistent signs of attention, or ability to follow commands.

This case highlights the potential benefit of rapid initiation of bortezomib after second-line treatment failure. More extensive studies are needed to determine optimal timing and efficacy of bortezomib.