Immunotherapies for Anti-N-M-methyl-D-aspartate Receptor Encephalitis: Multicenter Retrospective Pediatric Cohort Study in China

Abstract

Background: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis has been discovered for more than a decade, but the establishment of standardized immunotherapy protocol for pediatric patients still needs more clinical evidence.Methods: A multicenter, retrospective study was conducted on pediatric patients diagnosed with anti-NMDAR encephalitis between November 2011 and December 2018. The clinical records including clinical manifestations, immunotherapy strategies, and outcomes were collected and analyzed.Results: A total of 386 patients were included in our study and the median onset age was 8.00 (IQR 4.83–10.90) years. All patients received first-line immunotherapy and the majority (341, 88.3%) used the standard combination of methylprednisolone pulses (MEP) and intravenous immunoglobulins (IVIG), but 211 patients did not show satisfactory improvement (mRS ≥ 3). Mainly three treatment strategies were applied after first-line immunotherapy: second-line immunotherapy, repetitive first-line immunotherapy, and maintaining oral prednisolone. For patients with mRS ≥ 4 after first-line immunotherapy, the incidence of poor outcome (mRS ≥ 3) in oral prednisolone group was higher than that in other treatment groups (p = 0.039). No difference in complete recovery rate (mRS = 0) was found between patients receiving second-line and repetitive first-line immunotherapy, or patients using long-term and short-term prednisolone. Out of 149 patients who received anti-myelin oligodendrocyte glycoprotein antibody (MOG-Ab) test, 27 (18.12%) were positive. Patients with concomitantly positive MOG-Ab showed milder conditions compared to patients with typical anti-NMDAR encephalitis and were more inclined to relapses. We also identified female, MOG-Ab positive, and not receiving second-line and/or repetitive first-line immunotherapy were risk factors for relapses.Conclusions: For patients with mRS ≥ 4 after first-line immunotherapy and patients with concomitantly positive MOG-Ab, second-line immunotherapy is recommended. When second-line immunotherapy is not applicable, repetitive first-line immunotherapy can be considered as an option. Both second-line and repetitive first-line immunotherapy are beneficial to reduce relapse rate. The duration of sequential oral prednisolone can be shortened after fully evaluating patients' conditions.

Evaluating the incidence and predictors of anti-NMDAR encephalitis in a contemporary cohort of patients diagnosed with dermoid tumors: A national inpatient sample analysis

“…Lastly, once anti-NMDAR encephalitis is diagnosed, several medical and surgical interventions have been shown to augment patient recovery. Immunotherapy is the treatment of choice for anti-NMDAR encephalitis, and medications such as steroids, intravenous immunoglobulin, and plasma exchange have been shown to demonstrate the greatest improvement in patient neurologic status [28,29]. Second-line immunotherapies include cyclophosphamide and rituximab [28,29].…”

“…Immunotherapy is the treatment of choice for anti-NMDAR encephalitis, and medications such as steroids, intravenous immunoglobulin, and plasma exchange have been shown to demonstrate the greatest improvement in patient neurologic status [28,29]. Second-line immunotherapies include cyclophosphamide and rituximab [28,29]. At the same time, surgical resection of the dermoid tumor has been shown to improve patient neurologic status to the point of complete recovery [30].…”

Anti-NMDA Receptor Autoimmune Encephalitis: Diagnosis and Management Strategies

“…Guang et al also reported only 47.4% (183/386) children had abnormal CSF studies. 19 Increased intracranial pressure can be seen in 26.2%–39.5% patients. 11 , 17 …”

“… 11 Guang et al showed tumors in only 4 (1.0%) pediatric patients (2 teratoma, 1 optic glioma, 1 Ewing’s sarcoma). 19 …”

Autoimmune diseases and cancers overlapping with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD): A systematic review

“… 3 This finding implies a difference in the immunopathogenic mechanisms involved in the development of each entity, such that AQP4-IgG + NMOSD is more attributable to a defect in immune tolerance, while MOGAD is more likely to be an aberrant autoimmune response to certain triggers, such as infection, vaccination, or malignancy. 3 …”