Ischemic stunning of the brain: early recanalization without immediate clinical improvement in acute ischemic stroke.
OBJECTIVE
Early arterial recanalization (ER) with intravenous tissue plasminogen activator (tPA) can lead to dramatic clinical recovery, whereas some patients do not experience immediate clinical improvement.


METHODS
Consecutive patients received tPA 0.9 mg/kg IV within 3 hours after symptom onset. All had M1 or M2 middle cerebral artery occlusions on pretreatment transcranial Doppler. Patients were continuously monitored for 2 hours after bolus. ER was defined as the Thrombolysis in Brain Ischemia intracranial flow increase by >or=1 grade. Stroke severity (National Institutes of Health Stroke Scale [NIHSS]) and recovery (modified Rankin Scale) were assessed independently of transcranial Doppler.


RESULTS
One hundred twenty patients (mean age, 68+/-15 years; 63 women; median NIHSS, 17; range, 5 to 29; 90% with >or=10 points) received tPA at a median of 120 minutes, 50% within the first 2 hours. ER was observed in 73 patients (32 complete, 41 partial). No immediate clinical changes (n=23) or worsening (by 1 to 6 points on NIHSS, n=4) was observed in 37% of ERs (nonresponders). Complete ER was found in 8 of these 27 patients. At 24 hours, 22 of 27 patients (82%) had persisting deficits of NIHSS >or=10 points, yet 37% of these nonresponders (10 of 27) still achieved good outcome (modified Rankin score, 0 to 2) at 3 months. Among nonresponders with good outcome, 100% had detectable residual flow signals, and 70% had compensatory flow diversion on prebolus transcranial Doppler compared with 65% and 29% of nonresponders with poor outcome (P<0.05). Compared with responders (n=46), nonresponders had similar prebolus median NIHSS of 16 to 17 points, bolus times of 120 to 132 minutes, median speed of thrombolysis (30 minutes), and ER times of 190 to 193 minutes after onset. Reocclusion occurred in 3 of 4 patients with clinical worsening, 30% of other nonresponders, and 22% of responders. Symptomatic hemorrhage rate was 4% in both groups. At 3 months, mortality was 33% in nonresponders compared with 9% in responders (P=0.001).


CONCLUSIONS
After successful arterial ER with tPA therapy, lack of early clinical changes or worsening is relatively common (37%) and appears to be independent of time to tPA bolus or reperfusion. However, with tPA alone, at least one third of these nonresponders still achieved good outcomes at 3 months, suggesting the possibility of a "stunned brain" syndrome with delayed recovery. Several different mechanisms may potentially account for this phenomenon.
Alexandrov
Andrei V
AV
Center for Noninvasive Brain Perfusion Studies, Stroke Treatment Team, University of Texas-Houston Medical School, 77030, USA. avalexandrov@att.net
Hall
Christiana E
CE
Labiche
Lise A
LA
Wojner
Anne W
AW
Grotta
James C
JC
D000208:Acute Disease; D000368:Aged; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology*; D002545:Brain Ischemia / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D018450:Disease Progression; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D007275:Injections, Intravenous; D008297:Male; D012720:Severity of Illness Index; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use; D017211:Treatment Failure
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator