LAUSR

Background: Early Neurological Worsening (ENW) is common after ICH, and predicts poor outcome. However, there is limited data as to what degree of ENW best relates to outcome. We used two ICH cohorts to refine and validate a definition of ENW that best predicted 90-day outcomes. Methods: We generated receiver operating characteristic (ROC) curves for the association between 24-hour NIHSS change and ICH outcomes using data from the VISTA collaboration. Primary outcome was poor outcome at 90 days (mRS 4-6); secondary outcomes were other mRS cutpoints (mRS 2-6, 3-6, 5-6, 6). We tested the commonly used NIHSS≥4 definition and in addition employed Youden’s J Index to select optimal cutpoints and calculated sensitivity, specificity, and predictive values. Independent predictors of poor outcome were determined via multivariable logistic regression. Definitions were validated in the prospectively collected PREDICT-ICH cohort. Results: Using 552 patients from the VISTA cohort, ROC curves of 24hr NIHSS change had an area under the curve of 0.75. NIHSS change of ≥0 at 24hrs was seen in 46.4%. Youden’s method showed an optimum cutoff at -0.5. Based on this, ENW defined as >0 (Sens 43%, Spec 91%, PPV 83%, aOR 7.13 [CI:4.05-12.55]), ≥0 (Sens 65%, Spec 73%, PPV 70%, aOR 5.05 [CI:3.25-7.85]), or ≥-1 (Sens 78%, Spec 59%, PPV 65%, aOR 6.04 [CI:3.75-9.71]) all accurately predicted poor outcome. PPV increased with higher NIHSS cutoffs, but at the cost of lower sensitivities. Regression confirmed that all definitions independently predicted outcome at all mRS cutpoints. ENW definitions reproduced well in the validation cohort of 275 patients. Conclusion: All NIHSS cut-offs for ENW predict clinical outcome, regardless of outcome definition. In particular, lack of clinical improvement at 24 hours (i.e. NIHSS is the same or higher) robustly predicted poor outcome, but may not be sufficiently reliable to determine clinical management.