Background and Purpose-Matrix metalloproteinase-9 (MMP-9) activity has been associated with hemorrhagic transformation (HT) in experimental models of cerebral ischemia. Our aim was to investigate the relationship between MMP-9 concentrations in blood within 24 hours of stroke onset and subsequent HT of cerebral infarction. Methods-We studied 250 patients with a hemispheric ischemic stroke of 7.8Ϯ4.5 hours' duration. Early CT signs of cerebral infarction were evaluated on admission. The HT and infarct volume were analyzed from the CT performed on days 4 through 7. MMP-9 levels were determined by enzyme-linked immunosorbent assay in blood samples obtained on admission. Results-HT was observed in 38 patients (15.2%): 24 (63.2%) had a hemorrhagic infarction, and 14 (36.8%) had a parenchymal hematoma. A total of 108 patients (43%) received anticoagulants before the second CT scan. Systolic and diastolic blood pressures, body temperature, frequency of early CT signs of ischemia (92% versus 22%), and treatment with anticoagulants (79% versus 37%) were significantly higher in the group with HT (PϽ0.001). Mean infarct volume was 126Ϯ60 cm 3 in the HT group and 90Ϯ68 cm 3 in the group without HT (Pϭ0.003). Median (quartiles) plasma MMP-9 concentrations were higher in the HT group (193 [163, 213] versus 62 [40, 93] ng/mL, PϽ0.001), even in the 24 patients seen within 3 hours of symptom onset (Pϭ0.014). MMP-9 levels Ն140 ng/mL had a positive and negative predictive value of HT of 61% and 97%, respectively. MMP-9 Ն140 ng/mL was associated with HT (odds ratio, 12; 95% confidence interval, 3 to 51; PϽ0.001) after adjustment for potential confounders and final infarct volume. Conclusions-High

High plasma levels of proinflammatory molecules within 24 hours of intracerebral hemorrhage onset are correlated with the magnitude of the subsequent perihematoma brain edema, whereas poor neurologic outcome and the volume of the residual cavity are related to increased plasma glutamate concentrations.

Acute stroke patients with an NIHSS score of > or =8 and DWI volume of < or =25 mL have a higher probability of infarct growth and early neurologic deterioration. The new concept of CDM may identify patients with tissue at risk of infarction for thrombolytic or neuroprotective drugs.

Background and Purpose-The mechanisms involved in the neurological deterioration of acute lacunar strokes are unknown. Although accumulating evidence suggests that glutamate release plays a role in the progression of territorial infarctions, it remains to be established whether excitotoxicity also participates in lacunar stroke progression. We investigated whether excitatory and inhibitory amino acid concentrations in blood predict subsequent progressive motor deficits in lacunar infarctions. Methods-We studied 113 consecutive patients with lacunar infarct, defined by clinical and computed tomography/ magnetic resonance imaging criteria, within the first 24 hours after stroke onset. Neurological deterioration was defined as a decrease of Ն1 points in the motor items of the Canadian Stroke Scale in the first 48 hours after admission. Glutamate, glycine, and GABA were determined by high-performance liquid chromatography in plasma samples obtained on admission. Predictive values, sensitivity, specificity, and accuracy of specific glutamate and GABA concentrations and glutamateϫglycine/GABA index for progression of lacunar stroke were calculated. Results-Twenty-seven patients (23.9%) had neurological worsening. Plasma concentrations of glutamate (253Ϯ70 versus 123Ϯ73 mol/L, meanϮSD) were higher and those of GABA (140Ϯ63 versus 411Ϯ97 nmol/L) were lower in the progressing group than in the nonprogressing group (both PϽ0.001). Glutamate concentrations Ͼ200 mol/L and GABA levels Ͻ240 nmol/L had a positive predictive value for neurological deterioration of 67% and 84%, respectively. A excitotoxic index Ͼ106 had a positive predictive value of 85%. Conclusions-These findings suggest that an imbalance between the glutamate and GABA concentrations may play a role in the pathophysiology of progressing lacunar infarctions.

Molecular markers of early neurologic deterioration may play a role as mediators of lesion growth in cerebral ischemia. Plasma glutamate concentration is the most powerful and independent predictor biomarker of lesion enlargement in the acute phase of ischemic stroke, and so may well be useful as a signature of tissue at risk of infarction.