Elevated serum S100B levels indicate a higher risk of hemorrhagic transformation after thrombolytic therapy in acute stroke.
OBJECTIVE
Intracerebral hemorrhage constitutes an often fatal sequela of thrombolytic therapy in patients with ischemic stroke. Early blood-brain barrier disruption may play an important role, and the astroglial protein S100B is known to indicate blood-brain barrier dysfunction. We investigated whether elevated pretreatment serum S100B levels predict hemorrhagic transformation (HT) in thrombolyzed patients with stroke.


METHODS
We retrospectively included 275 patients with ischemic stroke (mean age of 69+/-13 years; 46% female) who had received thrombolytic therapy within 6 hours of symptom onset. S100B levels were determined from pretreatment blood samples. Follow-up brain scans were obtained 24 hours after admission, and HT was classified as either hemorrhagic infarction (1, 2) or parenchymal hemorrhage (1, 2).


RESULTS
HT occurred in 80 patients (29%; 45 hemorrhagic infarction, 35 parenchymal hemorrhage). Median S100B values were significantly higher in patients with HT (0.14 versus 0.11 mug/L; P=0.017). An S100B value in the highest quintile corresponded to an OR for any HT of 2.87 (95% CI: 1.55 to 5.32; P=0.001) in univariate analysis and of 2.80 (1.40 to 5.62; P=0.004) after adjustment for age, sex, symptom severity, timespan from symptom onset to hospital admission, vascular risk factors, and storage time of serum probes. A pretreatment S100B value above 0.23 mug/L had only a moderate sensitivity (0.46) and specificity (0.82) for predicting severe parenchymal bleeding (parenchymal hemorrhage 2).


CONCLUSIONS
Elevated S100B serum levels before thrombolytic therapy constitute an independent risk factor for HT in patients with acute stroke. Unfortunately, the diagnostic accuracy of S100B is too low for it to function in this context as a reliable biomarker in clinical practice.
Department of Neurology, Johann Wolfgang Goethe University, Frankfurt am Main, Germany. foerch@em.uni-frankfurt.de
Christian
C
Foerch
Michael T
MT
Wunderlich
Florian
F
Dvorak
Marek
M
Humpich
Timo
T
Kahles
Michael
M
Goertler
Jose
J
Alvarez-Sabín
Claus W
CW
Wallesch
Carlos A
CA
Molina
Helmuth
H
Steinmetz
Matthias
M
Sitzer
Joan
J
Montaner
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001812:Blood-Brain Barrier / Q000502:physiology; D002543:Cerebral Hemorrhage / Q000097:blood* / Q000209:etiology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000097:blood*; D011237:Predictive Value of Tests; D012044:Regression Analysis; D012189:Retrospective Studies; D012307:Risk Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood*; D020521:Stroke / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000009:adverse effects*
D015415:Biomarkers; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human