Predicting major neurological improvement with intravenous recombinant tissue plasminogen activator treatment of stroke.
OBJECTIVE
In the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study, major neurological improvement within 24 hours (MNI) occurred significantly more frequently with recombinant tissue plasminogen activator (rtPA) treatment than with placebo. We explored the relationship between MNI and 3-month favorable outcome and sought clinical predictors of MNI.


METHODS
Data from 312 rtPA-treated patients from the NINDS trial were used to assess the ability of MNI to predict favorable outcome at 3 months as defined by a modified Rankin Scale score of 0 to 1. Next, a multivariable predictive model was developed for MNI within the same data set. Clinical variables examined included age, time to treatment (TTT), diabetes, pretreatment glucose, baseline National Institutes of Health Stroke Scale score, pretreatment blood pressure, history of atrial fibrillation, weight >100 kg, and a dense artery sign. Finally, this model was used to forecast into the placebo group of the NINDS trial to assess the uniqueness of the predictors in the rtPA-treated group.


RESULTS
MNI had a positive predictive value and negative predictive value of 0.70 for predicting favorable 3-month outcome. Only age [odds ratio (OR), 0.68; 95% confidence interval (CI), 0.47 to 0.99] and TTT (OR, 0.56; 95% CI, 0.34 to 0.91) appear to be independently associated with MNI. The model performed only moderately well (area under the receiver-operating characteristic curve, 0.66). Age (OR, 0.67; 95% CI, 0.45 to 0.99) but not TTT was associated with MNI in the placebo group.


CONCLUSIONS
MNI may be a useful surrogate for thrombolytic activity and is predictive of favorable 3-month outcome. When rates of MNI in different populations of stroke patients treated with thrombolysis are compared, adjustments for age and TTT may be necessary.
Brown
Devin L
DL
Department of Neurology, University of Virginia Health System, Charlottesville, USA. devinb@umich.edu
Johnston
Karen C
KC
Wagner
Douglas P
DP
Haley
E Clarke
EC
D000367:Age Factors; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D016208:Databases, Factual / Q000706:statistics & numerical data; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007275:Injections, Intravenous; D015233:Models, Statistical; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D012372:ROC Curve; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D020127:Recovery of Function / Q000187:drug effects*; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D020521:Stroke / Q000175:diagnosis* / Q000188:drug therapy*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator