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

Background and Purpose-Growing experimental evidence indicates that the dev elopment of cerebral ischemic damage is slower than previously believed. Th e aims of this work were (1) to study the evolution of CT hypoattenuation b etween 24 to 36 hours and 7 days in ischemic stroke patients; (2) to evalua te whether thrombolytic treatment given within 6 hours of stroke affects de layed infarction evolution; and (3) to investigate possible correlations be tween lesion volume changes over time and clinical outcome, Methods-Of 620 patients included in the European Cooperative Acute Stroke S tudy 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 a nd CT7 were classified according to the location of the infarct, The volume of CT hypoattenuation was measured using the formula A X B X C/2 for irreg ular volumes. The 95% confidence interval of inter- and intrarater variabil ity was used to determine whether significant changes in lesion volume had occurred between CT1 and CT7. Clinical severity was evaluated by means of t he 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 t han 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 s how any significant change in lesion volume between CT1 and CT7, 143 (32%) showed a significant increase and the remaining 20 (4%) a significant decre ase. No significant correlation was observed between treatment and lesion e volution between CT1 and CT7, Both clinical scores (SSS0 and SSS30) and deg ree of neurological recovery were significantly (P<0.05) lower in the subgr oup of patients with a significant lesion volume increase than in the other 2 groups. Conclusions-In approximately two thirds of patients, infarct size is establ ished 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. M any factors may be responsible for delayed infarct enlargement and for a lo wer degree of clinical recovery, both of which may occur despite early reco mbinant tissue plasminogen activator treatment.