Early Dramatic Recovery During Intravenous Tissue Plasminogen Activator Infusion

Abstract

Acute-stroke patients receiving standard intravenous tissue plasminogen activator (tPA) have been noted to experience early dramatic recoveries. The prevalence, clinical characteristics, and outcome of patients experiencing dramatic recovery is not well described. We prospectively studied all patients presenting with acute middle cerebral artery (MCA) stroke syndromes and transcranial Doppler (TCD) evidence of an MCA obstruction. All patients received intravenous tPA per the National Institute of Neurological and Communicative Disorders and Stroke protocol, with serial National Institutes of Health Stroke Scale (NIHSS) scores and continuous TCD monitoring. Dramatic recovery was defined as an improvement of > or =10 NIHSS points or a decrease to an NIHSS score of < or =3 by the end of infusion. Outcome at the end of infusion, at 24 hours, and at long-term follow-up were obtained. The timing and pattern of deficit recovery during dramatic recovery was also studied. Dramatic recovery occurred in 22% of all patients. Compared with patients who did not experience dramatic recovery, those patients who did had significantly lower end-infusion NIHSS (median 2 and range 0 to 16 for dramatic-recovery patients versus median 17 and range 6 to 35 for non-dramatic-recovery patients, P<0.01) and 24-hour NIHSS (median 2 and range 0 to 16 for dramatic-recovery patients versus median 13 and range 2 to 35 for non-dramatic-recovery patients, P<0.01). A long-term modified Rankin Score benefit was noted (median 1 and range 0 to 6 for dramatic-recovery patients versus median 4 and range 0 to 6 for non-dramatic-recovery patients, P<0.01). Baseline clinical characteristics were similar. The only difference was improved TCD-determined flow values at the end of infusion (normal restoration of flow was 58% in dramatic-recovery patients versus 14% in non-dramatic-recovery patients, P<0.01). A characteristic pattern of recovery of deficit was noted. Early dramatic recovery in acute MCA stroke patients treated with intravenous tPA is relatively frequent. The benefit of dramatic recovery is maintained at 24 hours and over the long term. TCD monitoring suggests that dramatic recovery is a result of early restoration of MCA flow during the tPA infusion. The consistent pattern of early clinical recovery may help explain the mechanisms by which thrombolysis improves outcome and could suggest targets for enhancing the therapeutic effect of intravenous tPA.