Delayed increase in infarct volume after cerebral ischemia: Correlations with thrombolytic treatment and clinical outcome

BACKGROUND AND PURPOSE: Growing experimental evidence indicates that the development of cerebral ischemic damage is slower than previously believed. The aims of this work were (1) to study the evolution of CT hypoattenuation between 24 to 36 hours and 7 days in ischemic stroke patients; (2) to evaluate whether thrombolytic treatment given within 6 hours of stroke affects delayed infarction evolution; and (3) to investigate possible correlations between lesion volume changes over time and clinical outcome. METHODS: Of 620 patients included in the European Cooperative Acute Stroke Study 1 (ECASS1), we selected 450 patients whose control CT scans at day 1 (CT1) and day 7 (CT7) were available. They had been randomly divided into 2 groups: 206 patients had been treated with rtPA and 244 with placebo. CT1 and CT7 were classified according to the location of the infarct. The volume of CT hypoattenuation was measured using the formula AxBxC/2 for irregular volumes. The 95% confidence interval of inter- and intrarater variability was used to determine whether significant changes in lesion volume had occurred between CT1 and CT7. Clinical severity was evaluated by means of the Scandinavian Stroke Scale (SSS) at entry (SSS0) and at day 30 (SSS30). RESULTS: Mean lesion volumes were significantly (P<0.0001) higher at day 7 than at day 1 in all the subgroups of patients and particularly in patients with a subcortical lesion. Of the 450 patients studied, 287 (64%) did not show any significant change in lesion volume between CT1 and CT7, 143 (32%) showed a significant increase and the remaining 20 (4%) a significant decrease. No significant correlation was observed between treatment and lesion evolution between CT1 and CT7. Both clinical scores (SSS0 and SSS30) and degree of neurological recovery were significantly (P<0.05) lower in the subgroup of patients with a significant lesion volume increase than in the other 2 groups. CONCLUSIONS: In approximately two thirds of patients, infarct size is established 24 to 36 hours after stroke onset, whereas in the remaining one third, changes in lesion volume may occur later than the first 24 to 36 hours. Many factors may be responsible for delayed infarct enlargement and for a lower degree of clinical recovery, both of which may occur despite early recombinant tissue plasminogen activator treatment.