Molecular markers of brain damage – clinical and ethical implications with particular focus on cardiac arrest

Issue title: Molecular Markers of Brain Damage – Current State and Future Perspectives

Article type: Research Article

Authors: Snyder-Ramos, Stephanie A. | Böttiger, Bernd W.

Affiliations: Department of Anaesthesiology, University of Heidelberg, Im Neuenheimer Feld 110, D-69120 Heidelberg, Germany

Note: [] Corresponding author: Stephanie Alexandra Snyder-Ramos, MD, Department of Anaesthesiology, University Hospital Heidelberg, Im Neuenheimer Feld 110, D-69120 Heidelberg, Germany. Tel.: +49 6221 56 6351; Fax: +49 6221 56 5345; E-mail: stephanie_snyder-ramos@med.uni-heidelberg.de

Abstract: Although 25–50% of patients suffering from cardiac arrest can be stabilised haemodynamically, the hospital discharge rate is only 2–14%. One of the major causes of this discrepancy is persistent brain damage. Studies to assess the prognostic value of early prediction of neurologic and overall outcome in patients with cardiac arrest have not yet produced precise and generally accepted diagnostic rules. As apparative diagnostic methods often fail to predict neurologic outcome, the role of molecular markers has come a focus of common interest for early outcome prediction. This systematic review article aims to give an overview on the most important molecular markers for neurologic and overall outcome prediction and outline the advantages, clinical implications and ethical issues in patients undergoing cardiopulmonary resuscitation after cardiac arrest. For this purpose, the traditional marker for brain damage, the neuron-specific enolase, a gamma gamma isomer of enolase and cytoplasmatic enzyme of glycolysis, and the astroglial protein S100, a calcium-binding protein regulating neuronal differentiation, outgrowth, and apoptosis, are analysed and their role discussed as a marker for brain damage in general and recovery after cardiopulmonary resuscitation following cardiac arrest. Neuron-specific enolase has been investigated as a neuro-marker after brain damage and for outcome prediction in unconscious patients. Whereas the protein S100 has proven to be a good marker for neuronal damage after isolated brain injury, its role in cardiac surgery is not as clear: at least, in the early postoperative phase S100 is not a sole marker for neurologic damage, as release of S100 from cardiac tissue and other sources has also been demonstrated. However, the persistent elevation of S100 after cardiac surgery is specific for neurologic impairment. Most interestingly, after cardiac arrest the protein S100 has shown to be a good survival marker for overall outcome prediction. Although it cannot be absolutely determined whether cerebral or cardiac release of S100 is predominant in this clinical setting, recent studies have revealed that S100 serum levels are a useful diagnostic tool for outcome prediction. In contrast, after cardiac arrest serum levels of protein S100 did not reach a 100% specificity and sensitivity in clinical studies, and, therefore, elevated S100 in these patients has to be interpreted with caution. Nonetheless, low S100 serum levels have been correlated with good outcome and, therefore, even if all other diagnostic tests indicate poor outcome, all therapeutic efforts must be undertaken, as no single study has shown that normal S100 serum levels were associated with poor prognosis.

Keywords: molecular neuro-marker of brain damage (S100, NSE), cardiac arrest, cardiopulmonary resuscitation, neurologic and overall outcome, prognosis

Journal: Restorative Neurology and Neuroscience, vol. 21, no. 3-4, pp. 123-139, 2003