Journal Article

DZNE-2025-01431

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Development and validation of the NEOS2 score for prediction of long-term outcomes and improvement after first-line immunotherapy in patients with anti-NMDAR encephalitis: an international cohort study

Brenner, J. ; Bastiaansen, A. E. M. ; Guasp, M. ; Muñiz-Castrillo, S. ; Iizuka, T. ; de Bruijn, M. A. A. M. ; Muñoz-Lopetegi, A. ; Martínez-Hernández, E. ; Picard, G. ; Vogrig, A. ; Millot, M. ; Finke, C. ; Geis, C. ; Lewerenz, J. ; Melzer, N. ; Prüss, H.DZNE* ; Räuber, S. ; Ringelstein, M. ; Rostàsy, K. ; Sühs, K.-W. ; Thaler, F. S. ; Wandinger, K.-P. ; Wurdack, K. ; Crijnen, Y. S. ; Kerstens, J. ; van Steenhoven, R. W. ; Veenbergen, S. ; Schreurs, M. W. J. ; van den Berg, R. ; Volovici, V. ; Neuteboom, R. F. ; de Vries, J. M. ; Sillevis Smitt, P. A. E. ; Nagtzaam, M. M. P. ; Franken, S. C. ; Ratuszny, D. ; Menge, T. ; Bertolini, A. ; Bien, C. ; Berger, R. ; Tauber, S. ; Angstwurm, K. ; Seifert-Held, T. ; Kraft, A. ; Klausewitz, J. ; Ayzenberg, I. ; Eisenhut, K. ; Roessling, R.Extern* ; Heiden, M. ; Kümpfel, T. ; Dalmau, J. ; Leypoldt, F. ; Honnorat, J. ; Titulaer, M. J.

2026
Elsevier [Amsterdam]

This record in other databases:  

Please use a persistent id in citations: doi:10.1016/j.lanepe.2025.101562

Abstract: Background: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a severe disease that primarily affects young people and can improve with adequate treatment. We aimed to refine the anti-NMDAR Encephalitis One-year functional Status (NEOS) score by developing NEOS2, an updated model using readily available data at the time of diagnosis. We assessed the predictive value of the NEOS2-score for (1) improvement following first-line treatment, (2) functional outcome at one-year follow-up, and (3) resumption of school or work within three years. Methods: In this international (France, Germany, Japan, the Netherlands and Spain) cohort study in patients with a definite anti-NMDAR encephalitis diagnosis (according to the clinical criteria plus antibody testing in CSF), we performed logistic regression analyses to develop and validate multivariable models to predict -based upon variables available at diagnosis- short (ΔmRS two weeks after first-line treatment), middle (modified Rankin Scale [mRS] at one year), and long-term (return to school or work within three years) outcomes. We included clinical variables and biomarkers available at diagnosis. Findings: We included 702 patients (mean age 23 years, 95%-CI 2–69; 79% female, 21% male) diagnosed between the discovery of the disease in 2007 and 2022. Most patients (96%; 672/702) had received first-line immunotherapy, and 38% (233/615) showed improvement within two weeks. One year after diagnosis, 80% (517/644) had a favourable functional outcome (mRS≤2). At three years, 73% (203/278) had resumed work/school. In multivariable analysis, higher age (odds ratio [OR] 0·35, 95%-CI 0·29–0·43, p < 0·0001), treatment delay (OR 0·49, 95%-CI 0·41–0·58, p < 0·0001), movement disorders (OR 0·32, 95%-CI 0·24–0·41, p < 0·0001), ICU-requirement (OR 0·34, 95%-CI 0·26–0·44, p < 0·0001) and increased CSF leucocyte count (OR 0·65, 95%-CI 0·60–0·71, p < 0·0001) independently predicted poorer outcomes (NEOS2, accuracy AUC 80%, 95%-CI 75–86%). The same variables, excluding age, were relevant in predicting improvement following first-line immunotherapy (NEOS2-T AUC 81–84%, 95%-CI 77–86%). Return-to-work or -school served as a useful measure of longer-term outcomes, predicted with equal accuracy as one-year functional outcome (NEOS2-W AUC 80%, 95%-CI 75–85%). The NEOS2-score, applied as an ordinal measure, enabled nuanced predictions of outcome probabilities across the score spectrum, ranging from a high (80%; n = 20/25) likelihood of improving after first-line immunotherapy and achieving a good outcome (100%; n = 32/32) to a high risk of first-line treatment failure (97%; n = 77/79) and no return to school/work (94%; n = 15/16). Interpretation: The NEOS2-score, readily available at diagnosis and easy to apply, can identify patients with either a favourable or poor prognosis, and those who may benefit from early intensified treatment. The value of the NEOS2-score for guiding treatment decisions and as a stratification tool in studies on optimal treatment regimens, should be confirmed in further prospective studies.

Note: Funding: This study was funded by Dioraphte (charity; project 2001 0403).

---

Contributing Institute(s):

1. Autoimmune Encephalopathies (AG Prüß)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

---

Database coverage:
; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Social and Behavioral Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 20 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Social Sciences Citation Index ; Web of Science Core Collection

---