Published online before print November 20, 2003, doi: 10.1161/01.STR.0000103835.62512.2B
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(Stroke. 2003;34:2914.)
© 2003 American Heart Association, Inc.
Original Contributions |
Editorial Comment—"Malignant" or Not: Is There a Role for In Vivo Neurochemistry?
Department of Neurology, University of Heidelberg, Heidelberg, Germany
Large infarctions of the middle cerebral artery (MCA) territory still represent a challenge for neurointensive care. Some patients may develop a space-occupying brain edema leading to raised intracranial pressure, midline shift, and, in the worst case, herniation with subsequent death. Clinical deterioration with decreasing levels of consciousness and evolvement of brain stem signs usually occurs within 2 to 5 days following symptom onset.1 Prognosis of these so-called malignant MCA infarctions (MMI) is poor: In prospective case series, 80% died from herniation despite maximum conservative therapy.2
In order to prevent or reverse edema formation, to lower increased intracranial pressure, to improve cerebral perfusion, and to attenuate deleterious ischemic processes, more drastic rescue therapies such as craniectomy or therapeutic hypothermia have been applied. Moderate hypothermia initiated within 14 hours after stroke onset resulted in a mortality rate of 44% in an open case series.3 Decompressive surgery at a mean time of 39 hours after stroke onset reduced mortality to <35% in another case series,4 while earlier craniectomy at a mean time of 21 hours between stroke onset and surgery was associated with a further reduced mortality rate of 16% and improved clinical outcome.5 Early enough commencement of these strategies seems crucial for the prevention of a malignant stroke course. However, these therapeutic strategies are invasive, they may involve long-term sedation and ventilation on intensive care units, and they are associated with various serious side-effects.
Therefore, reliable data predicting MMI are required as early as possible in the course of stroke to make a decision on which patients may develop malignant brain edema and, thus, may benefit from more aggressive therapeutic measures. One diagnostic tool predicting MMI beside stroke syndrome severity is brain imaging. A prospective study of 99m-technetium-ethyl-cysteinate-dimer single-photon emission CT within 6 hours of symptom onset predicted mortality with 82% sensitivity and 98% specificity.6 Conventional CCT scan showing hypodensity covering >50% of the MCA territory within the first 6 hours predicted fatal outcome in another prospective study.7 In a recent study on 37 patients with acute MCA infarction and proximal vessel occlusion,8 quantitative analysis of early (within 6 hours) perfusion- and diffusion-weighted MRI predicted MMI with high sensitivity and specificity.
Neurochemical monitoring with cerebral microdialysis may be another tool potentially predicting the future course of severe stroke. So far, cerebral microdialysis in stroke patients has been used to monitor ongoing neurochemical changes in infarcted or noninfarcted brain tissue: Increasing extracellular glutamate concentrations measured in brain areas adjacent to infarcted tissue reflect pending or developing brain edema with subsequent secondary neuronal ischemia.9,10 Decreasing concentrations of glutamate and glycerol are observed in peri-infarct tissue under hypothermic conditions.11 However, standard microdialysate analyses for glutamate, glycerol, lactate, and pyruvate are not sensitive to predict MMI early enough for successful implementation of invasive therapies.12
Bosche et al included 31 patients with infarctions covering >50% of the MCA territory on initial CCT scans in their currently published study.13 Fourteen of them developed MMI. Concentrations of non-transmitter amino acids as measured by microdialysis in the non-infarcted ipsilateral frontal lobe within the first 12 hours after stroke onset were significantly lower in MMI patients. Additionally, they correlated negatively with final infarct size. The authors assumed that the expansion of the extracellular space by vasogenic edema reduced the concentrations of these structural non-transmitter amino acids. The predictive value of their determination had a sensitivity and specificity of about 80%.
These data are unique in that they provide evidence that early neurochemical monitoring of non-transmitter amino acids within 12 hours of stroke onset may help to predict MMI. However, the method is currently limited by the use of a non-routine HPLC analysis system, which is not widely commercially available as an easily implemented bed-side test. Therefore, before these parameters can be used in clinical practice, they will need to show robust validity in multiple stroke centers as well as in larger prospective studies.
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- Schwab S, Schwarz S, Spranger M, Keller E, Bertram M, Hacke W. Moderate hypothermia in the treatment of patients with severe middle cerebral artery infarction. Stroke. 1998; 29: 2461–2466.
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[Abstract/Free Full Text] - Bosche B, Dohmen C, Graf R, Neveling M, Staub F, Kracht L, et al. Extracellular concentrations of non–transmitter amino acids in peri-infarct tissue of patients predict malignant middle cerebral artery infarction. Stroke. 2003; 34: 2908–2915.
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