Treatment of NMDA Receptor Encephalitis
First-Line Immunotherapy
Immediate Treatment Initiation
Immunotherapy should be initiated as soon as infection is excluded based on basic CSF results (cell count, protein, glucose), without waiting for antibody confirmation 1, 2
For severe presentations (decreased consciousness, dyskinetic movements, autonomic instability, seizures), combination therapy should be used from the outset rather than sequential monotherapy 1, 2
Standard severe presentation warrants pulse-dose methylprednisolone (1g IV daily for 3-5 days) plus either IVIG or plasma exchange 1, 2
Choosing Between IVIG and Plasma Exchange
IVIG is preferred for agitated patients (easier to administer), those with bleeding disorders, or when central line placement poses risks 1, 2
Plasma exchange (5-10 sessions every other day) is preferred for patients with severe hyponatremia, high thromboembolic risk, associated demyelination, or when corticosteroids are contraindicated 1, 2
Plasma exchange combined with corticosteroids shows superior modified Rankin score improvement compared to corticosteroids alone in NMDAR encephalitis 1, 2
Second-Line Therapy
Timing and Selection
If no meaningful clinical, radiological, or electrophysiological improvement occurs within 2-4 weeks after completing combined first-line therapy, second-line agents should be initiated 1, 2
Rituximab is preferred for NMDAR encephalitis and other antibody-mediated autoimmunity (targets B-cells and indirectly suppresses T-cell activity) 1, 2
Cyclophosphamide is reserved for suspected cell-mediated autoimmunity, such as classical paraneoplastic syndromes with intracellular antibodies 1, 2
Rituximab has a more favorable toxicity profile than cyclophosphamide, making it the first choice for most newly diagnosed cases 1
Tumor Screening and Removal
Cancer screening with CT chest/abdomen/pelvis with contrast should be performed in all patients, as up to 50% of women over age 18 with NMDAR encephalitis have ovarian teratomas 4, 5, 2
If initial CT is negative, mammogram/breast MRI, pelvic ultrasound, and/or whole body FDG-PET should be considered guided by individual cancer risk factors 2
Tumor removal (particularly ovarian teratoma) is a critical component of treatment, as the tumor often triggers the autoimmune response 4, 5
Refractory Cases
For patients showing no objective or subjective improvement with conventional second-line therapies, novel approaches including tocilizumab (IL-6 inhibitor) or bortezomib should be considered 1, 2
Evidence for third-line agents is minimal but they represent options when standard therapies fail 1, 2
Bridging and Maintenance Therapy
- After acute treatment, bridging therapy with gradual oral prednisone taper, monthly IVIG, or monthly IV methylprednisolone should be initiated to prevent relapse 1, 2