International Validation of the Erasmus Guillain-Barré Syndrome Respiratory Insufficiency Score.

OBJECTIVE: This study aimed to validate the Erasmus Guillain-Barré Syndrome Respiratory Insufficiency Score in the International Guillain-Barré Syndrome Outcome Study cohort, and to improve its performance and region-specificity. METHODS: We examined data from the first 1,500 included patients, aged ≥6 years and not ventilated prior to study entry. Patients with a clinical variant or mild symptoms were also included. Outcome was mechanical ventilation within the first week from study entry. Model performance was assessed regarding the discriminative ability (area under the receiver operating characteristic curve) and the calibration (observed vs predicted probability of mechanical ventilation), in the full cohort and in Europe/North America and Asia separately. We recalibrated the model to improve its performance and region-specificity. RESULTS: In the group of 1,023 eligible patients (Europe/North America n = 842, Asia n = 104, other n = 77), 104 (10%) required mechanical ventilation within the first week from study entry. Area under the curve values were ≥0.80 for all validation subgroups. Mean observed proportions of mechanical ventilation were lower than predicted risks: full cohort 10% versus 21%, Europe/North America 9% versus 21%, and Asia 17% versus 23%. After recalibration, predicted risks for the full cohort and Europe/North America corresponded to observed proportions. INTERPRETATION: This prospective, international cohort study validated the Erasmus Guillain-Barré Syndrome Respiratory Insufficiency Score, and showed that the model can be used in the full spectrum of Guillain-Barré syndrome patients. In addition, a more accurate, region-specific version of the model was developed for patients from Europe/North America. ANN NEUROL 2022;91:521-531.

Consensus disease definitions for neurologic immune-related adverse events of immune checkpoint inhibitors.

Expanding the US Food and Drug Administration-approved indications for immune checkpoint inhibitors in patients with cancer has resulted in therapeutic success and immune-related adverse events (irAEs). Neurologic irAEs (irAE-Ns) have an incidence of 1%-12% and a high fatality rate relative to other irAEs. Lack of standardized disease definitions and accurate phenotyping leads to syndrome misclassification and impedes development of evidence-based treatments and translational research. The objective of this study was to develop consensus guidance for an approach to irAE-Ns including disease definitions and severity grading. A working group of four neurologists drafted irAE-N consensus guidance and definitions, which were reviewed by the multidisciplinary Neuro irAE Disease Definition Panel including oncologists and irAE experts. A modified Delphi consensus process was used, with two rounds of anonymous ratings by panelists and two meetings to discuss areas of controversy. Panelists rated content for usability, appropriateness and accuracy on 9-point scales in electronic surveys and provided free text comments. Aggregated survey responses were incorporated into revised definitions. Consensus was based on numeric ratings using the RAND/University of California Los Angeles (UCLA) Appropriateness Method with prespecified definitions. 27 panelists from 15 academic medical centers voted on a total of 53 rating scales (6 general guidance, 24 central and 18 peripheral nervous system disease definition components, 3 severity criteria and 2 clinical trial adjudication statements); of these, 77% (41/53) received first round consensus. After revisions, all items received second round consensus. Consensus definitions were achieved for seven core disorders: irMeningitis, irEncephalitis, irDemyelinating disease, irVasculitis, irNeuropathy, irNeuromuscular junction disorders and irMyopathy. For each disorder, six descriptors of diagnostic components are used: disease subtype, diagnostic certainty, severity, autoantibody association, exacerbation of pre-existing disease or de novo presentation, and presence or absence of concurrent irAE(s). These disease definitions standardize irAE-N classification. Diagnostic certainty is not always directly linked to certainty to treat as an irAE-N (ie, one might treat events in the probable or possible category). Given consensus on accuracy and usability from a representative panel group, we anticipate that the definitions will be used broadly across clinical and research settings.