Correspondence

Clinical Recovery from Acute Ischemic Stroke after Early Reperfusion of the Brain with Intravenous Thrombolysis

N Engl J Med 1999; 340:894-895March 18, 1999

Article

To the Editor:

A 1995 study found that treatment with tissue plasminogen activator (t-PA) was efficacious for intravenous thrombolysis if given within three hours after the onset of ischemic stroke.1 The drug most likely improves the outcome by inducing early reperfusion of ischemic but not infarcted brain tissue.2,3 The earlier t-PA is given, the better the chance of clinical improvement and a good outcome.4 We describe a case in which early intravenous treatment with t-PA, monitored noninvasively by transcranial Doppler ultrasonography, produced dramatic clinical improvement.

While at work, an 85-year-old right-handed woman suddenly became mute and weak on her right side at 2:50 p.m. She arrived at the hospital at 3:32 p.m., and computed tomography of the brain at 3:50 p.m. revealed no early ischemic changes or hemorrhage. At 4:05 p.m., transcranial Doppler ultrasonography showed minimal flow in the distal segment of the left middle cerebral artery (Figure 1Figure 1Transcranial Doppler Ultrasonogram of the Middle Cerebral Artery in a Woman with Acute Ischemic Stroke.), indicating near-occlusion. The distal portion of the middle cerebral artery was monitored at a constant angle with use of a 2-MHz transducer mounted on a head frame.

Treatment with t-PA (0.9 mg per kilogram of body weight intravenously)1 was initiated at 4:12 p.m. At 4:46 p.m., there was a sudden microembolic signal on the ultrasonogram (arrow in Figure 1), followed by the restoration of a normal wave form, suggesting complete reperfusion of the middle cerebral artery. Five minutes later, the patient began to regain strength in her right arm. At 5 p.m. she began smiling, laughing, and using single words to speak with family members. By 5:10 p.m. she could speak in full sentences and had no residual motor weakness. She had only mild difficulties with comprehension and repetition when she was assessed at 5:26 p.m. She was admitted to the stroke unit and monitored according to post-thrombolytic guidelines.5 By the next morning she had no residual deficit. Treatment with 325 mg of aspirin daily and 5000 U of subcutaneous heparin twice daily was initiated 24 hours after the infusion of t-PA. The patient was sent home with advice to continue taking aspirin, and she returned to work full time six days after the event. She remained free of neurologic symptoms four months later.

Other than age, the patient had no risk factors for stroke. Magnetic resonance imaging 12 hours after the onset of symptoms revealed normal intracranial vessels and no infarction. Neither transthoracic nor transesophageal echocardiography revealed any cardiac or aortic sources of embolism. Carotid duplex ultrasonography showed plaques without clinically significant stenosis.

Noninvasive monitoring with transcranial Doppler ultrasonography provided a unique opportunity to document the speed of neurologic recovery after reperfusion. Successful early recanalization of an occlusion of the middle cerebral artery led to rapid clinical improvement in our patient. Noninvasive monitoring of thrombolytic therapy may provide important insights into the recovery of the brain from ischemia.

Andrew M. Demchuk, M.D.
Robert A. Felburg, M.D.
Andrei V. Alexandrov, M.D., R.V.T.
University of Texas–Houston, Houston, TX 77030

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Citing Articles (16)

Citing Articles

1. 1

   Kazumi Kimura, Juya Aoki, Yuki Sakamoto, Kazuto Kobayashi, Kenichi Sakai, Takeshi Inoue, Yasuyuki Iguchi, Kensaku Shibazaki. (2011) Administration of edaravone, a free radical scavenger, during t-PA infusion can enhance early recanalization in acute stroke patients — A preliminary study. Journal of the Neurological Sciences
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2. 2

   Kazumi Kimura, Yuki Sakamoto, Yasuyuki Iguchi, Kensaku Shibazaki, Junya Aoki, Kenichiro Sakai, Junichi Uemura. (2011) Admission hyperglycemia and serial infarct volume after t-PA therapy in patients with and without early recanalization. Journal of the Neurological Sciences 307:1-2, 55-59
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3. 3

   Kazumi Kimura, Yuki Sakamoto, Yasuyuki Iguchi, Kensaku Shibazaki. (2011) Serial changes in ischemic lesion volume and neurological recovery after t-PA therapy. Journal of the Neurological Sciences 304:1-2, 35-39
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4. 4

   Joan Montaner, David Salat, Teresa García-Berrocoso, Carlos A. Molina, Pilar Chacón, Marc Ribó, José Alvarez-Sabín, Anna Rosell. (2010) Reperfusion Therapy for Acute Stroke Improves Outcome by Decreasing Neuroinflammation. Translational Stroke Research 1:4, 261-267
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5. 5

   Kazumi Kimura, Yasuyuki Iguchi, Kensaku Shibazaki, Junya Aoki, Masao Watanabe, Noriko Matsumoto, Shinji Yamashita. (2010) Early stroke treatment with IV t-PA associated with early recanalization. Journal of the Neurological Sciences 295:1-2, 53-57
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   Kazumi Kimura, Yasuyuki Iguchi, Shinji Yamashita, Kensaku Shibazaki, Kazuto Kobayashi, Takeshi Inoue. (2008) Atrial fibrillation as an independent predictor for no early recanalization after IV-t-PA in acute ischemic stroke. Journal of the Neurological Sciences 267:1-2, 57-61
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   I. FERNANDEZ-CADENAS, J. ALVAREZ-SABIN, M. RIBO, M. RUBIERA, M. MENDIOROZ, C. A. MOLINA, A. ROSELL, J. MONTANER. (2007) Influence of thrombin-activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 gene polymorphisms on tissue-type plasminogen activator-induced recanalization in ischemic stroke patients. Journal of Thrombosis and Haemostasis 5:9, 1862-1868
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   Georgios Tsivgoulis, Andrei V. Alexandrov. (2007) Ultrasound-enhanced thrombolysis in acute ischemic stroke: Potential, failures, and safety. Neurotherapeutics 4:3, 420-427
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   Georgios Tsivgoulis, Andrei V. Alexandrov. (2007) Ultrasound Enhanced Thrombolysis: Applications in Acute Cerebral Ischemia. Journal of Clinical Neurology 3:1, 1
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    Andrei V. Alexandrov. (2006) Ultrasound enhanced thrombolysis for stroke. International Journal of Stroke 1:1, 26-29
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    Andrei V. Alexandrov, Andrew M. Demchuk, W. Scott Burgin, David J. Robinson, James C. Grotta. (2004) Ultrasound-Enhanced Thrombolysis for Acute Ischemic Stroke: Phase I. Findings of the CLOTBUST Trial. Journal of Neuroimaging 14:2, 113-117
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    Andrew R. Xavier, Adnan I. Qureshi, Jawad F. Kirmani, Abutaher M. Yahia, Rohit Bakshi. (2003) Neuroimaging of Stroke: A Review. Southern Medical Journal 96:4, 367-379
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    Ken UCHINO, Mark A. MOEHRING, Andrei V. ALEXANDROV. (2003) Ultrasound Enhanced Thrombolysis for Ischemic Stroke. Neurosonology 16:3, 139-145
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    Matthew E Norman, Donavon Albertson, Brian R Younge. (2001) Ophthalmic Manifestations of Lightning Strike. Survey of Ophthalmology 46:1, 19-24
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    K Rajamani, M Gorman. (2001) Trancranial Doppler in stroke. Biomedicine & Pharmacotherapy 55:5, 247-257
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    Sophia Sundararajan, Lewis B. Morgenstern. (2000) Thrombolysis for acute stroke: Is it for everyone?. Current Atherosclerosis Reports 2:2, 97-103
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