Unexplained Early Neurological Deterioration After Intravenous Thrombolysis: Incidence, Predictors, and Associated Factors

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Background and Purpose—

Early neurological deterioration (END) after anterior circulation stroke is a serious clinical event strongly associated with poor outcome. Regarding specifically END occurring within 24 hours of intravenous recombinant tissue-type plasminogen activator, apart from definite causes such as symptomatic intracranial hemorrhage and malignant edema whose incidence, predictors, and clinical management are well established, little is known about END without clear mechanism (ENDunexplained).


We analyzed 309 consecutive patients thrombolysed intravenously ≤4.5 hours from onset of anterior circulation stroke. ENDunexplained was defined as a ≥4-point deterioration on 24-hour National Institutes of Health Stroke Scale, without definite mechanism on concomitant imaging. ENDunexplained and no-END patients were compared for pretreatment clinical and imaging (including magnetic resonance diffusion and diffusion/perfusion mismatch volumes) data and 24-hour post-treatment clinical (including blood pressure and glycemic changes) and imaging (24-hour recanalization) data, using univariate logistic regression. Exploratory multivariate analysis was also performed after variable reduction, with bootstrap analysis for internal validation.


Among 33 END patients, 23 (7% of whole sample) had ENDunexplained. ENDunexplained was associated with poor 3-month outcome (P<0.01). In univariate analysis, admission predictors of ENDunexplained included no prior use of antiplatelets (P=0.02), lower National Institutes of Health Stroke Scale score (P<0.01), higher glycemia (P=0.03), larger mismatch volume (P=0.03), and proximal occlusion (P=0.01), with consistent results from the multivariate analysis. Among factors recorded during the first 24 hours, only no recanalization was associated with ENDunexplained in multivariate analysis (P=0.02).


ENDunexplained affected 7% of patients and accounted for most cases of END. Several predictors and associated factors were identified, with important implications regarding underlying mechanisms and potential prevention of this ominous event.

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