Optimal Definition of Early Neurological Deterioration in Thrombolysis-Treated Acute Ischemic Stroke: ENCHANTED Study

The aim of the study was to examine early neurological deterioration (END) using different definitions according to the National Institutes of Health Stroke Scale (NIHSS) and Glasgow Coma Scale (GCS) scores for their ability to predict 90-day unfavorable functional outcomes in acute ischemic stroke (AIS) patients from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED).

ENCHANTED was an international, multicenter, 2 × 2 quasi-factorial, prospective, randomized open-trial of low-dose versus standard-dose intravenous alteplase, and intensive versus guideline-recommended blood pressure lowering in thrombolysis-eligible patients with AIS. Mild, moderate, and significant END_NIHSS were defined as an increase in the NIHSS score of ≥1, ≥2, and ≥4 points, respectively. Mild and moderate-significant END_GCS were defined as a decrease in the GCS score of ≥1 and ≥2 points, respectively. In all cases, END also included death within 24 h. Any END was defined as an increase of ≥1 point in the NIHSS score, a decrease of ≥1 point in the GCS score, or death within 24 h. Receiver operating characteristic curve analyses were used to assess the predictive performance of different definitions of END for death or major disability (modified Rankin scale scores: 3-6) and all-cause mortality.

Among the 4,434 AIS patients, END ranged from 7.9% to 23.0% depending on definition, with the highest frequency for "any END." The discriminative ability of any END was superior to mild END_NIHSS and mild END_GCS for predicting 90-day death or major disability (area under the curve [AUC] 0.666 vs. 0.638 and 0.616; p < 0.001) and all-cause mortality (AUC 0.722 vs. 0.692 and 0.720; p = 0.001). Compared to patients without any END, those with any END had higher odds of 90-day death or major disability (odds ratio [OR]: 7.04, 95% confidence interval [CI]: 5.87-8.44) and all-cause mortality (OR: 6.27, 95% CI: 4.87-8.07).

In thrombolysis-eligible AIS patients, a broad definition of END identifies more patients with underlying acute neurological deterioration and demonstrated the strongest discriminative ability for 90-day outcomes.