CLINICAL DETERIORATION FOLLOWING IMPROVEMENT IN THE NINDS rt-PA STROKE TRIAL
Background and Objective: Little is known about cerebral arterial reocclusion after successful thrombolysis. In the absence of arteriographic information, the NINDS rt-PA Stroke Trial investigators prospectively identified clinical deterioration following improvement (DFI) as a possible surrogate marker of cerebral arterial reocclusion following rt-PA-induced recanalization. Also, we identified any significant clinical deterioration (CD) even if not preceded by improvement. We aimed to determine the incidence of DFI and CD in each treatment group, identify baseline or post-treatment variables predictive of DFI or CD, and determine any relationship between DFI, CD and clinical outcome. Methods: DFI was defined as any 2 point deterioration on the NIHSS following an initial 2 point improvement after treatment. CD was defined as any 4 point worsening after treatment compared to baseline. All data were collected prospectively by investigators blinded to treatment allocation. A non-contrast brain CT was mandated whenever a 2 point deterioration occurred. All cases were validated by a central review committee. Results: DFI was identified in 81 of the 624 patients (13%); 44 treated with rt-PA and 37 with placebo (p=0.48). DFI occurred more often in patients with higher baseline NIHSS. CD within the first 24 hours occurred in 98 patients (16% of all patients); 43 given rt-PA and 55 placebo (p=0.19). Baseline variables associated with CD were less frequent use of pre-stroke aspirin and higher incidence of early CT changes of edema or mass effect, or dense middle cerebral artery sign. Patients with CD had higher rates of increased serum glucose and fibrin degradation products (FDP), and they also had higher rates of symptomatic intracranial hemorrhage and death. Patients who experienced either DFI or CD were less likely to have a 3 month favorable outcome. Conclusions: We found no association between DFI, CD and rt-PA treatment, and no clinical evidence to suggest reocclusion. Deterioration was strongly associated with stroke severity and poor outcome, and was less frequent in patients whose stroke occurred while they were on aspirin.