Pediatric anti-NMDAR encephalitis with demyelination on brain MRI: A single center study.

OBJECTIVE: To explore the clinical characteristics, immunotherapy response, and prognosis of pediatric anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis associated with demyelination on brain magnetic resonance (MRI). METHODS: We retrospectively reviewed the medical records of children diagnosed with anti-NMDAR encephalitis in our hospital between January 2016 and December 2021. All children with evidence of demyelination on brain MRI were included. RESULTS: A total of 183 anti-NMDAR encephalitis children were included; 8.7 % (16/183) of them had demyelination on brain MRI. Nine were positive for myelin oligodendrocyte glycoprotein (MOG)-IgG, while two were positive for both MOG-IgG and glial fibrillary acidic protein (GFAP)-IgG. Four patients had a history of acquired demyelinating syndromes and encephalitis, respectively, while nine (56.3 %) had atypical symptoms of anti-NMDAR encephalitis. All children had supratentorial demyelination on brain MRI; four of them had additional infratentorial lesions. All children received first-line immunotherapy; four were administered repeated first-line immunotherapy and/or rituximab because of poor initial response. During the follow-up, 37.5 % (6/16) of the children relapsed, but all responded well to immunotherapy. There were no significant differences in mRS score before immunotherapy, response to first-line immunotherapy, and long-term prognosis between anti-NMDAR encephalitis children with and without demyelination. However, patients with demyelination were more likely to have a history of acquired demyelinating syndromes or unexplained cortical encephalitis and to relapse. CONCLUSION: Pediatric anti-NMDAR encephalitis can co-occur with demyelination and has a high rate of MOG-IgG positivity. A history of acquired demyelinating syndromes or unexplained cortical encephalitis and atypical symptoms may indicate demyelination in children with anti-NMDAR encephalitis. Pediatric anti-NMDAR encephalitis with demyelination is more likely to relapse and needs a closer follow-up. However, it remains unknown whether more intensive immunotherapy is required in these patients.

Elevated serum levels of the NLRP3 inflammasome are associated with the severity of anti-NMDAR encephalitis in children.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common autoimmune encephalitis, mainly impacting young females and children. The involvement of the Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and related cytokines in pediatric individuals with this condition remains unclear. METHODS: We collected information from 27 children who had anti-NMDAR encephalitis and 12 individuals with non-inflammatory neurological disorders as controls. We used an enzyme-linked immunosorbent assay (ELISA) to identify NLRP3 inflammasome, interleukin (IL)-1ß, and IL-18 expression in cerebrospinal fluid (CSF) and matching serum samples. The modified Rankin Scale (mRS) score was performed throughout the acute phase and at the 6-month follow-up to determine the severity of the disease. The area under the curve (AUC) of the receiver operating characteristic curve was utilized to calculate the prediction efficacy. RESULTS: When compared to controls, individuals with anti-NMDAR encephalitis had significantly increased serum expression of the NLRP3 inflammasome (p < 0.001), IL-1ß (p < 0.05), and IL-18 (p < 0.01). In the acute phase, mRS scores were correlated positively with serum levels of NLRP3 inflammasome (p = 0.008), IL-1ß (p = 0.023), and IL-18 (p < 0.001). A positive connection was also found between serum levels of NLRP3 inflammasome and IL-1ß (p = 0.005). Furthermore, the expression of IL-1ß and IL-18 in serum correlated with the 6-month follow-up outcome. The AUC for NLRP3 inflammasome in distinguishing patients with severe neurologic impairments from those with moderate impairments was 0.808 (95 % CI: 0.645-0.972). CONCLUSION: In our investigation, children with anti-NMDAR encephalitis have more severe first clinical presentations when their serum concentrations of the NLRP3 inflammasome and related cytokines were higher. These findings provide a potential role for the NLRP3 inflammasome pathway in the pathogenesis of NMDAR encephalitis and provide a basis for targeted therapeutic interventions.

External Assessment of the Anti-N-Methyl-D-Aspartate Receptor Encephalitis One-Year Functional Status Score in Chinese Pediatric Patients.

Objective: to assess the performance of the Anti-N-Methyl-D-Aspartate Receptor encephalitis (NMDAR) One-Year Functional Status (NEOS) score in predicting one-year functional outcome in Chinese children with anti-NMDAR encephalitis. Methods: children with anti-NMDAR encephalitis at the Children's Hospital of Chongqing Medical University were retrospectively enrolled from January 2014 to December 2020. Patients were categorized into two groups based on the modified Rankin Scale (mRS) at one-year follow-up. Discrimination of the NEOS score was assessed by the area under curve (AUC) of the receiver operating characteristic curve. Calibration of the NEOS score was assessed by comparing predicted probabilities with observed probabilities using a calibration curve and the Hosmer-Lemeshow test. The clinical practicability of the NEOS score was evaluated by performing a decision curve analysis. Results: one hundred seventy-five children (101 females and 74 males) with anti-NMDAR encephalitis and a median age of 7.7 years were enrolled. Of those, 149 (85.1%) had a good outcome at 1 year (mRS ≤ 2), and the remaining 26 (14.9%) had a poor outcome (mRS > 2). Patients with a higher NEOS score had a significantly higher mRS at one-year follow-up [Spearman r = 0.3878, 95% confidence interval (CI): 0.2500-0.5103, P < 0.001]. The AUC of the NEOS score was 0.870 (95% CI: 0.801-0.938, P < 0.001). The observed probability and predicted probability showed moderate consistency in the calibration curve and the Hosmer-Lemeshow test (P = 0.912). The decision curve analysis showed that using the NEOS score to predict one-year outcomes could provide additional net benefit during clinical practice. Conclusions: the NEOS score is a potentially reliable model to predict the one-year functional outcome in Chinese children with anti-NMDAR encephalitis.

Clinical Characteristics of Children With Anti-N-Methyl-d-Aspartate Receptor Encephalitis After Japanese Encephalitis.

BACKGROUND: Viral encephalitis is an important trigger for anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. We analyzed the clinical characteristics of anti-NMDAR encephalitis after Japanese encephalitis (JE) in children. METHODS: Clinical data of 185 children with anti-NMDAR encephalitis were retrospectively reviewed. Patients with a history of viral encephalitis other than JE or who were identified with other autoantibodies were excluded. RESULTS: Twenty children with anti-NMDAR encephalitis after JE were enrolled with a median age of 6 years and 10 months (interquartile range [IQR]: 3 years to 11 years and 5 months). The median time from JE to anti-NMDAR encephalitis was 29 (IQR: 25 to 32) days. At 12 months, most patients (17 of 18) recovered to at least their baseline modified Rankin scale (mRS) scores caused by JE. One hundred forty two children with classical anti-NMDAR encephalitis were enrolled. Compared with classical anti-NMDAR encephalitis, patients after JE had significantly more decreased level of consciousness (50% vs 18.3%, P = 0.003), more autonomic dysfunction (30.0% vs 9.9%, P = 0.021), fewer psychiatric or behavioral symptoms (70.0% vs 90.8%, P = 0.016), fewer seizures (25.0% vs 68.3%, P < 0.001), lesser improvement 4 weeks after immunotherapy (35.0% vs 73.2%, P = 0.001), and worse outcomes at 12 months (median mRS: 1 vs 0, P < 0.001). CONCLUSIONS: Anti-NMDAR encephalitis after JE in children mainly occurred within two months. Their clinical manifestation may differ from classical anti-NMDAR encephalitis. The prognosis of children with anti-NMDAR encephalitis after JE probably depends on the neurological sequelae after JE.