Fatal ischaemic brain oedema after early thrombolysis with tissue plasminogen activator in acute stroke

Two patients with acute major, disabling cerebral infarction with presumed middle cerebral artery occlusion were treated with the clot specific thrombolytic agent tissue plasminogen activator roughly three and a half hours after the onset of symptoms. Both patients had a normal computed tomography (CT) scan before treatment. No appreciable systemic bleeding complications occurred, apart from bruising. One patient had bleeding into the subarachnoid space from a microscopic angioma, which was found at necropsy. Haematological monitoring of the two patients showed pronounced fibrinogenolysis and alpha 2 antiplasmin consumption in one. One patient showed transient improvement during the infusion. In both cases extensive infarction, partly haemorrhagic in one, with massive concomitant oedema was found on repeated CT. Both patients deteriorated and eventually died as a consequence of transtentorial herniation. In the one patient who came to necropsy a moderate, probably pre-existing smooth stenosis of the ipsilateral carotid artery was found, all cerebral vessels being patent. It is concluded that thrombolytic treatment with a clot specific agent such as tissue plasminogen activator started three to four hours after a major ischaemic stroke may be hazardous, not because of haemorrhagic transformation of the original ischaemia but because early reperfusion may promote massive, potentially fatal cerebral oedema.