In acute ischemic stroke, are asymptomatic intracranial hemorrhages clinically innocuous?
BACKGROUND
In patients with acute ischemic stroke, intracranial hemorrhages are categorized as symptomatic or asymptomatic based on the presence or absence of a clinically detectable neurological deterioration. Asymptomatic intracranial hemorrhages are believed by many to be clinically innocuous. We examined whether the occurrence of an asymptomatic intracranial hemorrhage affects functional outcome in patients with acute ischemic stroke (AIS) treated or not treated with recombinant tissue plasminogen activator (rt-PA).


METHODS
We combined data from the NINDS rt-PA Stroke Trial and the ATLANTIS Trials, excluding patients with symptomatic intracranial hemorrhage (n=1193). We used generalized estimating equations to test whether asymptomatic intracranial hemorrhage altered the likelihood of a normal or near-normal outcome at 90 days, as measured across 4 commonly used functional outcome scales, controlling for other variables that affect outcome. To look at additional outcomes, including the likelihood of disability and death, we used logistic regression equations. Additionally, we systematically reviewed previous studies that assessed the effect of intracranial hemorrhage in AIS.


RESULTS
In the combined database, the rate of asymptomatic intracranial hemorrhage was higher in rt-PA treated than in nontreated patients (9.9% versus 4.2%, P<0.0001). Controlling for other prognostic factors, the odds of a normal or near-normal outcome was lower when a patient had an asymptomatic intracranial hemorrhage, but this effect did not reach statistical significance (OR=0.69, 95% CI: 0.43 to 1.12, P=0.13). Similarly, the odds of not being moderately to severely disabled (modified Rankin Score < or =2) was also lower for patients with asymptomatic intracranial hemorrhage (OR=0.60, 95% CI: 0.33 to 1.08, P=0.09). Despite using a larger sample than any previously published study, the power in our study to detect a 30% decrease in the odds of a good outcome was inadequate ( approximately 32%).


CONCLUSIONS
We could not confirm or exclude a clinically significant effect for asymptomatic intracranial hemorrhages based either on our analysis or on any previously published trial. Analysis of substantially larger databases are needed to assess the import of this common clinical event.
Kent
David M
DM
Institute for Clinical Research and Health Policy Studies, Department of Medicine, Tufts-New England Medical Center, 750 Washington St, Box 63, Boston, Mass 02111, USA. dkent1@tufts-nemc.org
Hinchey
Judith
J
Price
Lori Lyn
LL
Levine
Steven R
SR
Selker
Harry P
HP
D000368:Aged; D002545:Brain Ischemia / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D020300:Intracranial Hemorrhages / Q000175:diagnosis / Q000453:epidemiology*; D008297:Male; D017063:Outcome Assessment, Health Care; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000627:therapeutic use; D020521:Stroke / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator