Excitotoxicity and metabolic changes in association with infarct progression.

Abstract

We investigated to what extent excitotoxicity and metabolic changes in the peri-infarct region of patients with malignant hemispheric stroke are associated with delayed infarct progression. In 18 patients with malignant hemispheric stroke, 2 microdialysis probes were implanted within the peri-infarct tissue at a distance of 5 and 15 mm to the infarct. Precise probe placement was achieved by intraoperative laser speckle imaging. Glutamate, glucose, pyruvate, and lactate levels were monitored for 5 days after surgery. Delayed infarct progression was determined from serial MRI on the day after surgery and after the monitoring period. Initial stroke volume ranged from 122 to 479 cm3 with a median of 295 cm3. Nine of 18 patients (50%) had delayed infarct progression (median, 44 cm3; range, 19-93 cm3). In these patients, glucose and individual pyruvate levels were significantly lower when compared with patients without infarct progression, whereas glutamate and the lactate-pyruvate ratio were significantly elevated in patients with infarct progression early after surgery (12-36 hours) at the 15-mm microdialysis probe location. Lactate was elevated but without difference between groups. Excitotoxic or metabolic impairment was associated with delayed infarct progression and could serve as a treatment target.