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Retrospective Pediatric Cohort Study Validates NEOS Score and Demonstrates Applicability in Children With Anti-NMDAR
Marc Nikolaus1, Philipp Rausch1, Kevin Rostásy1
1From the Department of Pediatric Neurology (M.N., A.M.K., M.S., E.K.) and Center for Chronically Sick Children, Charité-Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health (BIH); Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, University Hospital Schleswig Holstein, Campus Kiel; Department of Genetics and Bioinformatics (P.R.), Kiel; Department of Pediatric Neurology (K.R., A.B.), Children's Hospital Datteln, University Witten/Herdecke, Datteln, Germany; Neuropediatric Unit (R.W.), Karolinska University Hospital, Astrid Lindgren Children's Hospital, Stockholm, Sweden; Department of Pediatrics (J.J., J.D.), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Division of Pediatric Pulmonology, Allergology and Endocrinology, Department of Pediatrics and Adolescent Medicine (M.B.), Medical University of Vienna, Austria; Department of Pediatric Neurology (M.S.), University Children's Hospital Augsburg; Division of Pediatric Neurology, Department of Pediatrics (K.D.), Hospital Kassel; Department of Pediatrics (M.H., A.Q.), Division of Neuropediatrics and Social Pediatrics, Medical University Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen; Division of Pediatric Neurology, Department of Pediatrics (A.B.), München Klinik Harlaching, Munich; Department of Pediatrics and Pediatric Neurology (H.R.), Georg August University, Göttingen; Department of Paediatric and Adolescent Medicine (C.S.), St Joseph Hospital, Berlin; Department of Pediatrics (K.v.), Vivantes Hospital Friedrichshain, Berlin; Department of Pediatrics (M.D.), Ernst von Bergmann Hospital, Potsdam; Department of Neurology (C.F., F.B.), Charité-Universitätsmedizin Berlin and Berlin School of Mind and Brain, Humboldt-Universität zu Berlin; Charité-Universitätsmedizin Berlin (A.M.K.), Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Institute of Cell Biology and Neurobiology; Charité-Universitätsmedizin Berlin (M.S., E.K.), Corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health (BIH), NeuroCure Clinical Research Center Berlin, Germany.
Background And Objectives:
Anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) is the most common form of autoimmune encephalitis in children and adults. Although our understanding of the disease mechanisms has progressed, little is known about estimating patient outcomes. Therefore, the NEOS (anti-NMDAR Encephalitis One-Year Functional Status) score was introduced as a tool to predict disease progression in NMDARE. Developed in a mixed-age cohort, it currently remains unclear whether NEOS can be optimized for pediatric NMDARE.
Methods:
This retrospective observational study aimed to validate NEOS in a large pediatric-only cohort of 59 patients (median age of 8 years). We reconstructed the original score, adapted it, evaluated additional variables, and assessed its predictive power (median follow-up of 20 months). Generalized linear regression models were used to examine predictability of binary outcomes based on the modified Rankin Scale (mRS). In addition, neuropsychological test results were investigated as alternative cognitive outcome.
Results:
The NEOS score reliably predicted poor clinical outcome (mRS ≥3) in children in the first year after diagnosis (p = 0.0014) and beyond (p = 0.036, 16 months after diagnosis). A score adapted to the pediatric cohort by adjusting the cutoffs of the 5 NEOS components did not improve predictive power. In addition to these 5 variables, further patient characteristics such as the "Herpes simplex virus encephalitis (HSE) status" and "age at disease onset" influenced predictability and could potentially be useful to define risk groups. NEOS also predicted cognitive outcome with higher scores associated with deficits of executive function (p = 0.048) and memory (p = 0.043).
Discussion:
Our data support the applicability of the NEOS score in children with NMDARE. Although not yet validated in prospective studies, NEOS also predicted cognitive impairment in our cohort. Consequently, the score could help identify patients at risk of poor overall clinical outcome and poor cognitive outcome and thus aid in selecting not only optimized initial therapies for these patients but also cognitive rehabilitation to improve long-term outcomes.
