Determinants of disease severity and 12-month functional outcome in pediatric ovarian Teratoma-Associated Anti-NMDA...

Pediatric ovarian teratoma-associated anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) represents a clinically important but relatively uncommon subgroup, and evidence regarding factors associated with acute severity and long-term functional outcome in this population remains limited.

We conducted a single-center retrospective cohort study of pediatric patients with surgically resected, histopathologically confirmed ovarian teratoma-associated NMDARE. Baseline and acute-phase characteristics were summarized in the full cohort (N = 97). Acute severity was defined by ICU admission with organ support and/or mechanical ventilation. Twelve-month functional outcome was assessed using the modified Rankin Scale (mRS) and dichotomized as good (mRS≤2) versus poor (mRS>2); outcome analyses were performed in the complete-case cohort (N = 71). Univariable and multivariable logistic regression identified factors independently associated with poor outcome. Discriminative performance was evaluated using ROC curve analysis.

Among 97 patients, median age at onset was 14.2 years (IQR 12.3-16.5) and 95.9% were female. Mature teratoma accounted for 80.4%. The median onset-to-resection interval was 18 days (IQR 11-29), and 34.0% underwent resection >21 days after onset. Severe disease occurred in 29 patients (29.9%) and was associated with higher symptom burden (median symptom categories 5.0 vs 3.0, P < 0.001), more frequent MRI abnormalities (62.1% vs 33.8%, P = 0.009) and multifocal MRI lesions (27.6% vs 7.4%, P = 0.013), and higher rates of EEG background slowing (89.7% vs 61.8%, P = 0.014) and extreme delta-brush (44.8% vs 13.2%, P = 0.001). In the 12-month outcome cohort (N = 71), 76.1% achieved mRS≤2 and 23.9% had mRS>2; relapse occurred in 8.5% and death in 2.8%. Multivariable analysis identified central hypoventilation (aOR 4.18, 95%CI 1.62-10.78), symptom categories ≥4 (aOR 2.94, 1.14-7.61), multifocal MRI lesions (aOR 3.12, 1.01-9.65), extreme delta-brush (aOR 3.37, 1.18-9.63), and onset-to-resection >21 days (aOR 2.81, 1.05-7.49) as independent correlates of poor functional outcome. The combined clinical plus imaging-EEG model showed the highest discrimination (AUC 0.86, 95%CI 0.76-0.95), with sensitivity 88.2% and specificity 74.1% at the optimal cutoff.

In pediatric ovarian teratoma-associated NMDARE, higher acute-phase clinical burden, multifocal MRI abnormalities, extreme delta-brush, central hypoventilation, and delayed tumor resection were independently associated with poor 12-month functional outcome.