Reperfusion and metabolic recovery of brain tissue and clinical outcome after ischemic stroke and thrombolytic therapy.
OBJECTIVE
It is unclear from recent clinical trials whether thrombolytic agents are capable of facilitating reperfusion and metabolic recovery over time or whether a beneficial effect is counteracted by an increase in the risk of brain hemorrhage. We studied the effect of thrombolytic treatment on metabolic recovery after reperfusion and clinical outcome.


METHODS
Patients were prospectively studied with (99m)Tc-ethyl cysteinate dimer single photon emission computed tomography ((99m)Tc-ECD-SPECT) before treatment with recombinant tissue plasminogen activator (rTPA; 0.9 mg/kg IV; n=26) or placebo (n=26) 6 to 8 hours after treatment and at 7+/-1 days. Activity deficits were graded, compared between the treatment groups, and correlated with clinical outcome and the incidence of brain hemorrhage. Metabolic recovery of ischemic brain tissue was defined as a 25% decrease on the SPECT graded scale.


RESULTS
Patients with metabolic recovery (n=28) had a better chance of being functionally unimpaired 3 months after stroke than patients without recovery (n=24) (OR 4.5, 95% CI 1.09 to 18.89) and had smaller infarcts on follow-up CT (36+/-38 versus 167+/-162 mL), regardless of whether metabolic recovery was observed within 6 to 8 hours of treatment or at 7 days. None of the 28 patients with metabolic recovery had a fatal parenchymal hemorrhage versus 5 of 24 patients without recovery (P=0.016). Treatment did not affect the incidence of brain tissue metabolic recovery.


CONCLUSIONS
Brain tissue metabolic recovery after ischemic stroke was associated with a beneficial effect on clinical outcome and was not facilitated by treatment with 0.9 mg of intravenous rTPA.
Berrouschot
J
J
Departments of Neurology, University of Leipzig, Leipzig, Germany.
Barthel
H
H
Hesse
S
S
Knapp
W H
WH
Schneider
D
D
von Kummer
R
R
D000368:Aged; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D002545:Brain Ischemia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D015427:Reperfusion Injury / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D020521:Stroke / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D010959:Tissue Plasminogen Activator; C059659:technetium Tc 99m bicisate; D003545:Cysteine