Predicting Functional Outcome and Response to Therapy of Anti-NMDAR Encephalitis at Diagnosis (NEOSII)

Predicting Functional Outcome and Response to Therapy of Anti-NMDAR Encephalitis at Diagnosis: The NEOSII Score

The goal of this international cohort study is to develop a prediction model for long-term outcome and response to first-line immunotherapy of anti-NMDAR Encephalitis, already at the moment of diagnosis.

Study Overview

• Status: Completed
• Conditions: Anti-NMDA (N-Methyl D-Aspartate) Receptor Encephalitis

Detailed Description

Anti-NMDARE is a severe, but treatable neurological condition, with considerable and variable long-term disability. The previously developed anti-NMDAR Encephalitis One-Year Functional Status (NEOS) score predicts outcome a month into treatment. To predict outcome and response to immunotherapy at the time of diagnosis would be a serious improvement. This would timely identify patients in need for aggressive treatment and avoid harmful side-effects in those with good outcome. International data from five anti-NMDAR encephalitis cohorts will be combined to attain these goals.

The investigators strive to have less than 10% missing data on all variables and will impute data were needed. The datasets will then be split - with equal distributions of cohorts and good/poor outcome - to develop (70%) and validate (30%) the NEOS2 model. The primary outcome is functioning one year after diagnosis. A secondary analysis is targeted to predict the effect of first-line therapy. Potentially relevant predictive variables are identified with a univariable analysis on the original data, confirmed with backwards selection on the imputed datasets. After checking for multicollinearity and linearity of the variables, identified variables are added to a mixed effects logistic regression model on the original and imputed datasets, to identify the final set of predictive variables. To make the models opportune for daily medical practice, the investigators will assign points to (categories of) the included variables, based on the coefficients.

• Study Type: Observational
• Enrollment (Actual): 714

Contacts and Locations

Study Locations

• Netherlands
  • Rotterdam, Netherlands
    • Erasmus Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Retrospective data of five (inter)national anti-NMDAR encephalitis cohorts.

Description

Inclusion Criteria:

• Diagnosed with anti-NMDAR encephalitis (according to the Graus criteria)

Exclusion Criteria:

• Preceding Herpes Simplex encephalitis
• Premorbid dependency (modified Rankin Scale > 2)

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort
Dutch National anti-NMDAR Encephalitis Cohort
German anti-NMDAR Encephalitis Cohort (GENERATE)
Spanish anti-NMDAR Encephalitis Cohort
French anti-NMDAR Encephalitis Cohort
Japanese anti-NMDAR Encephalitis Cohort

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional status one year after diagnosis, on the modified Rankin Scale.	The score on the modified Rankin Scale will be applied as the original ordinal scale as well as dichotomized, where scores 0-2 represent "independent functioning" (without or with symptoms) and scores 3-6 increasing levels of depencency	One year after diagnosis

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Return to school or work	Time-to-event analysis on the ability to return to school or work during follow-up, including timing of resumption of work after diagnosis.	Throughout follow-up time after diagnosis (different per patient, depending on date of diagnosis). Average 3 years (min 0 - max 22 years)
Relapse rate	Time-to-event analysis on relapses during total available follow-up time, including time of relapse after diagnosis.	Throughout follow-up time after diagnosis (different per patient, depending on date of diagnosis). Average 3 years (min 0 - max 22 years)
Response to first-line immunotherapy	One point improvement (one point lower than at diagnosis) on the modified Rankin Scale (ranging from 0 - no symptoms - to 6 - deceased - as the most severe category) within two weeks from therapy commencement.	Two weeks after administration of first-line immunotherapy

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Investigators: Principal Investigator: Maarten J. Titulaer, Assoc. Porf., Erasmus Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Actual): July 1, 2023
• Study Completion (Actual): July 1, 2024

Study Registration Dates

• First Submitted: August 19, 2023
• First Submitted That Met QC Criteria: August 28, 2023
• First Posted (Actual): September 5, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 3, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Prognosis; Immunotherapy
• Additional Relevant MeSH Terms: Neuroinflammatory Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Autoimmune Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Neurodegenerative Diseases; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Paraneoplastic Syndromes; Encephalitis; Anti-N-Methyl-D-Aspartate Receptor Encephalitis
• Other Study ID Numbers: NEOSII

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No