Published Online
on November 20, 2003

A more recent version of this article appeared on December 1, 2003

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Submitted on July 28, 2003
Accepted on July 31, 2003

Extracellular Concentrations of Non-Transmitter Amino Acids in Peri-Infarct Tissue of Patients Predict Malignant Middle Cerebral Artery Infarction

Bert Bosche MD^*; Christian Dohmen MD; Rudolf Graf PhD; Michael Neveling MD; Frank Staub MD; Lutz Kracht MD; Jan Sobesky MD; Fritz-Georg Lehnhardt MD; and Wolf-Dieter Heiss MD

From the Max Planck Institute for Neurological Research (B.B., C.D., R.G., L.K., J.S., W-D.H.), Cologne, Germany; and Departments of Neurology (B.B., C.D., M.N., J.S., F-G.L., W-D.H.) and Neurosurgery (F.S.), University of Cologne, Cologne, Germany.

^* To whom correspondence should be addressed. E-mail: bbosche{at}pet.mpin-koeln.mpg.de.

Background and Purpose--Space-occupying brain edema is a life-threatening complication in patients with large middle cerebral artery (MCA) infarction. To determine predictors of this detrimental process, we investigated alterations of extracellular non-transmitter amino acid concentrations in peri-infarct tissue.

Methods--Thirty-one patients with infarctions covering >50% of the MCA territory in early cranial CT scans were included in the study. Probes for microdialysis, intracranial pressure, and tissue oxygen pressure were placed into the noninfarcted ipsilateral frontal lobe. Positron emission tomography imaging was performed in 16 of these patients to measure cerebral blood flow in the tissue around the neuromonitoring probes.

Results--Fourteen of the 31 patients developed a malignant MCA infarction, and 17 did not. The patients in the malignant group had significantly lower extracellular concentrations of non-transmitter amino acids than those in the benign group in the first 12 hours of neuromonitoring. At this time, CBF values determined in regions of interest around the probes by positron emission tomography and tissue oxygen pressure showed that the monitored tissues were not yet infarcted, and no differences in transmitter amino acids concentrations were found between the 2 groups. Furthermore, extracellular concentrations of non-transmitter amino acids were negatively correlated with size of infarction.

Conclusions--We assume that reduction of non-transmitter amino acid concentrations reflects an expansion of the extracellular space by vasogenic edema formation in peri-infarct tissue of patients with malignant MCA infarction. Our findings facilitate early prediction of malignant edema formation and may help to increase knowledge of the pathophysiology of the peri-infarct zone of large MCA infarction.

Key words: amino acids • brain edema • cerebral infarction • middle cerebral artery

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