Mechanisms of Unexplained Neurological Deterioration After Intravenous Thrombolysis

Abstract

Background and Purpose— Unstable clinical course characterizes the first 24 hours after thrombolysis for anterior circulation stroke, including early neurological deterioration (END), a secondary complication consistently predictive of poor outcome. Apart from straightforward causes, such as intracerebral hemorrhage and malignant edema, the mechanism of END remains unclear in the majority of cases (END unexplained ). Based on the core/penumbra model, we tested the hypothesis that END unexplained is caused by infarct growth beyond the initial penumbra and assessed the associated vascular patterns. Methods— From our database of consecutive thrombolyzed patients (n=309), we identified 10 END unexplained cases who had undergone both admission and 24-hour MRI. Diffusion-weighted imaging lesion growth both within and beyond the acute penumbra (T max >6 seconds) was mapped voxelwise. These 10 cases were compared with 30 no-END controls extracted from the database blinded to 24-hour diffusion-weighted imaging to individually match cases (3/case) according to 4 previously identified clinical and imaging variables. Results— As predicted, lesion growth beyond initial penumbra was present in 9 of 10 END unexplained patients (substantial in 8) and its volume was significantly larger in cases than controls (2 P =0.047). All END unexplained cases had proximal arterial occlusion initially, of which only 2 had recanalized at 24 hours. Conclusions— In this exploratory study, most instances of END unexplained were related to diffusion-weighted imaging growth beyond acute penumbra. Consistent presence of proximal occlusion at admission and lack of recanalization at 24 hours in most cases suggest that hemodynamic factors played a key role, via for instance systemic instability/collateral failure or secondary thromboembolic processes. Preventing END after tissue-type plasminogen activator using, eg, early antithrombotics may therefore be feasible.