Long-term Functional Outcomes and Relapse of Anti-NMDA Receptor Encephalitis: A Cohort Study in Western China

Abstract

Objective: To study the factors associated with relapse and functional outcomes in patients with anti-NMDA receptor encephalitis in Western China.

Methods: The Outcome of the anti-NMDA receptor Encephalitis Study in Western China was initiated in October 2011 to collect prospective observational data from consecutively enrolled patients with anti-NMDA receptor encephalitis.

Results: We consecutively enrolled 244 patients (median age: 26 years, range: 9-78 years; females: 128 [52.45%]) between October 2011 and September 2019. Fatality occurred in 17 (6.96%) patients, and tumors were found in 38 (15.57%) patients. The median follow-up duration was 40 (6-96) months. Of these patients, 84.8% showed clinical improvements within 4 weeks after immunotherapy, with a median modified Rankin Scale of 2 (interquartile range [IQR]: 2-3), and 80.7% (median: 1, IQR: 0-2) and 85.7% (median: 0, IQR: 0-1) had substantial recovery (i.e., mild or no residual symptoms) at 12 and 24 months, respectively. The overall prognosis was still improving at 42 months after onset. Disturbance of consciousness during the first month was the only independent predictor (OR: 2.91, 95% CI: 1.27-6.65; p = 0.01) of a poor functional neurologic outcome. Overall, 15.9% of the patients had one or multiple relapses, with 82.0% experiencing the first relapse within 24 months and 76.9% experiencing relapses that were less severe than the initial episodes. Relapse-related risk factors included the female sex and delayed treatment (p < 0.05).

Conclusions: Most patients achieved favorable long-term functional outcomes. Some patients experienced one or multiple relapses, especially female patients. Timely immunotherapy at onset may reduce the risk of relapse.

Figure 1. Demographic and Clinical Outcomes Evaluated at Different Follow-up Points (3, 6, 12, 18, 24, and 48 Months After Disease Onset) of 244 Patients With Anti-NMDA Receptor Encephalitis

(A) The proportions of patients with cumulative clinical symptoms stratified by different ages at onset. (B) The distributions of patients by age, sex, and the presence or absence of tumors. The modified Rankin Scale scores of the patients with anti-NMDA receptor encephalitis at different follow-up points are shown in (C) for all patients and stratified by patients with (D) a monophasic course and (E) a relapsing course.

Figure 2. Disease and Treatment Courses in 39 Patients With Relapsing Disease

Each line shows 1 disease and the treatment course of the patient with relapse. The black triangles represent a disease event, which included the disease initial onset and relapse episode. The numbers in the triangles and squares represent the modified Rankin Scale scores during the event and at last follow-up, respectively. CYC = cyclophosphamide; IVIG = IV immunoglobulin; IVMP = IV methylprednisolone; MMF = mycophenolate mofetil; NMDAR = NMDA receptor; OP = oral prednisone; PE = plasma exchange; RTX = rituximab.

Figure 3. Kaplan-Meier Curves Showing the Frequency of Relapse-free Disease in 244 Patients With Anti-NMDA Receptor Encephalitis

The plots show that patients who (A) were female and (B) had delayed immunotherapy were associated with an increased risk of relapse.