European Journal of Neurology 2001, 8: 267±268 CLINICAL CORRESPONDENCE An ischemic stroke during intravenous recombinant tissue plasminogen activator infusion for evolving myocardial infarction Gregory Youngnam Chang Department of Neurology, University of Southern California, Los Angeles, CA, USA Keywords: ischemic stroke, myocardial infarction, tissue plasminogen activator Received 31 July 2000 Accepted 6 January 2001 A 56-year-old man without a previous history of stroke received intravenous recombinant tissue plasminogen activator (tPA) for an evolving myocardial infarction. During the infusion, the patient developed aphasia and right hemiparesis. The CT and MRI con®rmed an ischemic stroke without evidence of hemorrhage. Although the cerebral hemorrhage after tPA infusion is relatively more common, in rare cases, tPA infusion may result in fragmentation of a cardiac thrombus resulting in an ischemic cerebral stroke. Introduction Intravenous recombinant tissue plasminogen activator (tPA) is being used with increasing frequency since the seminal study sponsored by the National Institute of Neurological Disorders and Stroke (National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group, 1995) demonstrated signi®cant clinical bene®t when given within ®rst 3 hours of stroke onset. Clinical worsening, when it occurs, has been due to either intracerebral hemorrhage, or presumed to be natural history of the evolving stroke. I now report a case of an ischemic stroke during intravenous tPA infusion for evolving anterior myocardial infarction (MI). Case report A 56-year-old man without a previous history of stroke came to the emergency room for crescendo angina over several days. While waiting to be admitted, he su€ered a prolonged chest pain with diaphoresis. Evolving anter1 ior wall subendocardial MI was con®rmed by the ECG changes and serum troponin measurements. Emergent coronary angioplasty was not possible as all surgical suites were occupied. A 50 mg intravenous tPA infusion was started without a bolus. Thirty minutes into the tPA infusion, the attending physician at the bedside noted sudden onset of drowsiness, aphasia and right hemiparesis. The tPA infusion was stopped. A CT scan 3 h later showed no evidence of hemorrhage, an MRI scan 2 days later con®rmed a left middle cerebral artery territory infarction (Fig. 1). The MRA showed changes consistent with di€use atherosclerosis with multivessel moderate stenosis of bilateral carotid and middle Correspondence: Gregory Y. Chang MD, Department of Neurology, Room 5641, LAC + USC Medical Center, 1200 North State Street, 90033-1084 Los Angeles, CA, USA (fax: 323-226-6367; e-mail: gychang@hsc.usc.edu). ã 2001 EFNS cerebral arteries. Trans-thoracic and trans-esophageal echocardiograms were only remarkable for left ventricular wall hypertrophy without evidence of valvular disease or intracardiac thrombus. The carotid ultrasound showed no evidence of occlusion or stenosis at the bifurcation. Discussion del Zoppo et al. (1992) reported angiographic results of 104 patients who received intravenous tPA after presenting with an acute stroke. Each patient underwent a cerebral angiogram before and after tPA infusion. Recanalization was seen in up to 38% of middle cerebral artery occlusions, demonstrating e€ectiveness of clot resolution. In a separate single case report, clot fragmentation followed by distal arterial migration was seen during an angiogram shortly after tPA infusion in a patient who had no additional neurologic deterioration (Bruckmann and Berbert, 1989). The ®rst-ever ischemic stroke occurring in 103 cases within 28 days of an acute MI has been recently published (Mooe et al., 1999). Analysis revealed that the risk of stroke onset was highest shortly after an acute MI, nearly 10 times higher than that of the control population without an MI. This risk declined rapidly to the rate of controls within several days. This high risk was attributed to intracardiac thrombus formation, artery-to-artery embolism or in situ thrombosis, in the background of a prothrombotic state secondary to MI. Although six patients were also identi®ed in whom ®rst-ever stroke occurred after receiving thrombolytic therapy, precipitation of the stroke by thrombolytic agents was unlikely, as thrombolytic agents have a half-life lasting minutes, and the earliest stroke occurred 2 days after the infusion. The present case is unique in that ®rst-time ischemic stroke occurred in the midst of tPA 267 268 G. Y. Chang by tPA use. As he also had signi®cant intracranial large vessel disease, artery-to-artery embolus from the carotid or the main trunk of the left middle cerebral artery cannot be ruled out. Although a symptomatic intracerebral hemorrhage is more common and feared side-e€ect of tPA use, in rare cases, ischemic stroke may occur during intravenous tPA infusion. References Figure 1 Left ± CT scan showing sulcal e€acement and hypodensity in the subcortical and cortical insular brain region in the left hemispheric area without evidence of hemorrhage (3 h after tPA infusion). Right ± MRI scan (FLAIR sequence) revealing left middle cerebral artery infarction 2 days after tPA infusion. infusion for an evolving MI. Most probable mechanism is fragmentation of an intracardiac thrombus Bruckmann H, Berbert A (1989). Putaminal haemorrhage after recanalization of an embolic MCA occlusion treated with tissue plasminogen activator. Neuroradiology 31:95±97. Mooe T, Olofsson BO, Stegmayr B, Eriksson P (1999). Ischemic stroke: impact of a recent myocardial infarction. Stroke 30:997±1001. National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group (1995). Tissue plasminogen activator for acute ischemic stroke. New England J Med 333:1581±1587. del Zoppo GJ, Poeck K, Pessin MS et al. (1992). Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke. Ann Neurol 32:78±86. ã 2001 EFNS European Journal of Neurology 8, 267±268