Background: Recent evidence from animal models has demonstrated that tPA can be neurotoxic to the hippocampus and cerebellum. Since tPA is used in patients with myocardial infarction and has been approved for the treatment of acute ischemic stroke, we carried out a pilot study to investigate whether its administration could result in any clinically relevant neuropsychological dysfunction, with particular attention to those structures most involved in the animal model. Patient and Methods: Patients with acute myocardial infarction (AMI) who were subjected to thrombolysis with r-tPA and without evidence of prior or concomitant neurological-neuropsychological damage, were eligible. Controls consisted of patients with AMI not candidate for thrombolysis or patients with severe angina admitted to the intensive care unit. A detailed neurological and neuropsychological evaluation was performed, which included mood, visual and verbal memory, psychomotor speed processing and motor dexterity and visuomotor sequence learning. Results: Ten patients and 13 controls were included. No significant differences between both groups were found, although all the subjects performed in the lower limits of the normal range on the Purdue pegboard test (motor dexterity) and digit-symbol test (psychomotor speed). There was no evidence of depression, as assessed by the Hamilton scale, that could have interfered with performance. Declarative memory (Rey auditory-verbal learning test) as well as visual memory (Rey-Osterrieth figure copy) and visuomotor sequence learning (serial reaction time task) were normal, without between-group differences. Conclusions: tPA administration at the usual doses did not result in detectable neuropsychological abnormalities in patients with myocardial ischemia.

Keywords:
Plasminogen activator, Neuropsychology, Myocardial ischemia, Thrombolysis
1.
The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group: Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581–1587.
2.
Tsirka SE, Rogove AD, Strickland S: Neuronal cell death and tPA. Nature 1996;384:123–124.
3.
Tsirka SE: Clinical implications of the involvement of tPA in neuronal cell death. J Mol Med 1997;75:341–347.
4.
Tsirka SE, Rogove AD, Bugge TH, Degen JL, Strickland S: An extracellular proteolytic cascade promotes neuronal degeneration in the mouse hippocampus. J Neurosci 1997;17:543–552.
5.
Wang YF, Tsirka SE, Strickland S, Stieg PE, Soriano SG, Lipton SA: Tissue plasminogen activator (tPA) increases neuronal damage after focal cerebral ischemia in wild-type and tPA-deficient mice. Nat Med 1998;4:228–231.
6.
Murtomaki S, Trenkner E, Wright JM, Saksela O, Liesi P: Increased proteolytic activity of the granule neurons may contribute to neuronal death in the weaver mouse cerebellum. Dev Biol 1995;168:635–648.
7.
Tsirka SE, Bugge TH, Degen JL, Strickland S: Neuronal death in the central nervous system demonstrates a non-fibrin substrate for plasmin. Proc Natl Acad Sci USA 1997;94:9779–9781.
8.
Seeds NW, Williams BL, Bickford PC: Tissue plasminogen activator induction in Purkinje neurons after cerebellar motor learning. Science 1995;270:1992–1994.
9.
Klein GM, Li H, Sun P, Buchan AM: Tissue plasminogen activator does not increase neuronal damage in rat models of global and focal ischemia. Neurology 1999;52:1381–1384.
10.
Mecenas PE, Tsirka SE, Salles F, Strickland S: Removal of tissue plasminogen activator does not protect against neuronal degeneration in the cerebellum of the weaver mouse. Brain Res 1997;772:233–238.
11.
Spreen O, Strauss E: A Compendium of Neuropsychological Tests. New York, Oxford University Press, 1991.
12.
Lezak M: Neuropsychological Assessment, ed 3. New York, Oxford University Press, 1995.
13.
Mitrushina MN, Boone KB, D’Elia LF: Handbook of Normative Data for Neuropsychological Assessment. New York, Oxford University Press, 1999.
14.
Nissen MJ, Bullemer P: Attentional requirements of learning: Evidence from performance measures. Cogn Psychol 1987;19:1–32.
15.
Gomez-Beldarrain M, Garcia-Monco JC, Rubio B, Pascual-Leone A: Effect of focal cerebellar lesions on procedural learning in the serial reaction time task. Exp Brain Res 1998;120:25–30.
16.
Gomez Beldarrain M, Grafman J, Pascual-Leone A, Garcia-Monco JC: Procedural learning is impaired in patients with prefrontal lesions. Neurology 1999;52:1853–1860.
17.
Hamilton M: A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56–62.
18.
Smithline HA, Mader TJ, Crenshaw BJ: Do patients with acute medical conditions have the capacity to give informed consent for emergency medicine research? Acad Emerg Med 1999;6:776–780.
© 2002 S. Karger AG, Basel
2002
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.