Time course of serum neuron-specific enolase. A predictor of neurological outcome in patients resuscitated from cardiac arrest.

BACKGROUND AND PURPOSE The prediction of neurological outcome in comatose cardiac arrest survivors has enormous ethical and socioeconomic implications. The purpose of the present study was to investigate the prognostic relevance of the time course of serum neuron-specific enolase (NSE) as a biochemical marker of hypoxic brain damage. METHODS Serial analysis of serum NSE levels was performed in 56 patients resuscitated from witnessed, nontraumatic, normothermic, in- or out-of-hospital cardiac arrest. The neurological outcome was evaluated with the use of the cerebral performance category (CPC) within 6 months after restoration of spontaneous circulation (ROSC). The Mann-Whitney U test was used to compare patients with good (CPC 1 to 2) and bad (CPC 3 to 4) neurological outcome. The diagnostic performance at different time points after ROSC was described in terms of areas under receiver operating characteristic curves according to standard methods. RESULTS Patients with a bad neurological outcome (CPC 3 to 4) had significantly higher NSE levels than those with a good neurological outcome at 12 (P=0.004), 24 (P=0.04), 48 (P<0.001), and 72 hours (P<0.001) after ROSC. The maximum NSE level measured within 72 hours after ROSC was also significantly higher in patients with a bad neurological outcome (P<0.001). The NSE value at 72 hours after ROSC was the best predictor of neurological outcome (area under the curve=0.92+/-0.04). In addition, we also found a significant difference in the time course of NSE concentrations during the first 3 days after ROSC. CONCLUSIONS Serum NSE levels are valuable adjunctive parameters for assessing neurological outcome after cardiac arrest.

[1]  D. Schmechel,et al.  Neurone-specific enolase is a molecular marker for peripheral and central neuroendocrine cells , 1978, Nature.

[2]  S. Mckinstry,et al.  Serum neurone‐specific enolase as an indicator of stroke volume , 1996, European journal of clinical investigation.

[3]  F. Goodwin,et al.  MEASUREMENT OF NEURON‐SPECIFIC (NSE) AND NON‐NEURONAL (NNE) ISOENZYMES OF ENOLASE IN RAT, MONKEY AND HUMAN NERVOUS TISSUE , 1979, Journal of neurochemistry.

[4]  F. Plum,et al.  Prognosis in nontraumatic coma. , 1981, Annals of internal medicine.

[5]  F. Goodwin,et al.  Brain endolases as specific markers of neuronal and glial cells. , 1978, Science.

[6]  F. Sterz,et al.  Early prediction of individual outcome after cardiopulmonary resuscitation , 1993, The Lancet.

[7]  M. Pasanen,et al.  Evaluation of hypoxic brain injury with spinal fluid enzymes, lactate, and pyruvate , 1992, Critical care medicine.

[8]  S. Felber,et al.  Early determination of neurological outcome after prehospital cardiopulmonary resuscitation. , 1995, Stroke.

[9]  D. Schmechel,et al.  Neuron specific enolase, a clinically useful marker for neurons and neuroendocrine cells. , 1987, Annual review of neuroscience.

[10]  S. Mckinstry,et al.  Serum neurone specific enolase (NSE) levels as an indicator of neuronal damage in patients with cerebral infarction , 1991, European journal of clinical investigation.

[11]  K. Buchanan,et al.  Serum neurone-specific enolase concentrations in patients with neurological disorders. , 1994, Clinica chimica acta; international journal of clinical chemistry.

[12]  P. Ambros,et al.  First experience with prognostic factors in unselected neuroblastoma patients. The Austrian Neuroblastoma 87 Study. , 1995, European journal of cancer.

[13]  S. Iwasaki,et al.  Specific Changes in Human Brain Following Reperfusion After Cardiac Arrest , 1994, Stroke.

[14]  V. Rohde,et al.  The prognostic value of somatosensory and motor evoked potentials in comatose patients. , 1992, Neurosurgery.

[15]  D. Lomanto,et al.  Serum neuron-specific enolase in diagnosis and follow-up of gastrointestinal neuroendocrine tumors. , 1992, Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine.

[16]  Predicting outcome from hypoxic-ischemic coma. , 1985, JAMA.

[17]  H. Reiber,et al.  Neuron‐Specific Enolase Concentrations in Blood as a Prognostic Parameter in Cerebrovascular Diseases , 1994, Stroke.

[18]  R. Thompson,et al.  Immunoreactive nervous system of specific enolase (14-3-2 protein) in human serum and cerebrospinal fluid. , 1980, Clinica chimica acta; international journal of clinical chemistry.

[19]  A. Rivett,et al.  Activity of neuron-specific enolase in normal and lesioned rat brain , 1983, Brain Research.

[20]  F. Goodwin,et al.  Blood Platelets Contain a Neuron‐Specific Enolase Subunit , 1980, Journal of neurochemistry.

[21]  Recommended guidelines for uniform reporting of data from out-of-hospital cardiac arrest: the Utstein Style. Task Force of the American Heart Association, the European Resuscitation Council, the Heart and Stroke Foundation of Canada, and the Australian Resuscitation Council. , 1991 .

[22]  G. Davies-Jones,et al.  Enolase isoenzymes in the cerebrospinal fluid of patients with diseases of the nervous system. , 1983, Journal of neurology, neurosurgery, and psychiatry.

[23]  I. Chalmers.  Better perinatal health. Shanghai. , 1980, Lancet.

[24]  C. Schmidt,et al.  A predictive parameter in patients with brain related complications after cardiac surgery? , 1997, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[25]  H. Mrochen,et al.  Changes of neuron-specific enolase concentration in plasma after cardiac arrest and resuscitation. , 1991, Molecular and chemical neuropathology.

[26]  S. M. Sumi,et al.  Predicting outcome in hypoxic-ischemic coma. A prospective clinical and electrophysiologic study. , 1991, Electroencephalography and clinical neurophysiology.

[27]  E. Brunko,et al.  Prognostic value of early cortical somatosensory evoked potentials after resuscitation from cardiac arrest. , 1987, Electroencephalography and clinical neurophysiology.

[28]  O. Kemmotsu,et al.  Acute brain swelling after out‐of‐hospital cardiac arrest: Pathogenesis and outcome , 1993, Critical care medicine.

[29]  W. Montgomery,et al.  Standards and guidelines for cardiopulmonary resuscitation and emergency cardiac care. , 1986, Circulation.

[30]  A. Raabe,et al.  Serum S-100 and neuron-specific enolase for prediction of regaining consciousness after global cerebral ischemia. , 1998, Stroke.

[31]  D. Krieger,et al.  Serum neuron-specific enolase as early predictor of outcome after cardiac arrest. , 1997, Critical care medicine.

[32]  P. Diehr,et al.  Prediction of awakening after out-of-hospital cardiac arrest. , 1983, The New England journal of medicine.

[33]  B. Hogl,et al.  A comparison of the prognostic value of neuron-specific enolase serum levels and somatosensory evoked potentials in 13 reanimated patients. , 1995, European journal of emergency medicine : official journal of the European Society for Emergency Medicine.

[34]  M. Kaste,et al.  Neurological outcome after out-of-hospital cardiac arrest. Prediction by cerebrospinal fluid enzyme analysis. , 1989, Archives of neurology.

[35]  M. Kaste,et al.  Magnetic Resonance Imaging Findings Associated With Cardiac Arrest , 1993, Stroke.

[36]  J. Pujol,et al.  Experimental Brain Ischemia: Neuron‐Specific Enolase Level in Cerebrospinal Fluid as an Index of Neuronal Damage , 1984, Journal of neurochemistry.

[37]  R. Arriagada,et al.  Normal serum neuron specific enolase (NSE) value after the first cycle of chemotherapy , 1998, Cancer.

[38]  G. Moonen,et al.  Neuron‐Specific Enolase as a Marker of in Vitro Neuronal Damage. Part I: Assessment of Neuron‐Specific Enolase as a Quantitative and Specific Marker of Neuronal Damage , 1993, Journal of neurosurgical anesthesiology.

[39]  P. Safar,et al.  The use of cytosolic enzyme increase in cerebrospinal fluid of patients resuscitated after cardiac arrest , 1994 .

[40]  H. Hårdemark,et al.  S-100 protein and neuron-specific enolase in cerebrospinal fluid and serum: markers of cell damage in human central nervous system. , 1987, Stroke.

[41]  F. Barone,et al.  Neuron-specific enolase increases in cerebral and systemic circulation following focal ischemia , 1993, Brain Research.

[42]  C. Bassetti,et al.  Prognostic value of EEG in post-anoxic coma after cardiac arrest. , 1987, European neurology.

[43]  F. Sterz,et al.  Limitation of life support after resuscitation from cardiac arrest: practice in Belgium and Austria. , 1997, Resuscitation.

[44]  B. Fauvage,et al.  Isoelectric electroencephalogram and loss of evoked potentials in a patient who survived cardiac arrest. , 1993, Critical care medicine.

[45]  T. Noseworthy,et al.  National estimates of intensive care utilization and costs: Canada and the United States. , 1990, Critical care medicine.

[46]  B. Kjos,et al.  Early CT findings of global central nervous system hypoperfusion. , 1983, AJR. American journal of roentgenology.

[47]  P. Lewi,et al.  PREDICTIVE VALUE OF GLASGOW COMA SCORE FOR AWAKENING AFTER OUT-OF-HOSPITAL CARDIAC ARREST , 1988, The Lancet.

[48]  MarkusHorn,et al.  Neuron-Specific Enolase in Gerbil Brain and Serum After Transient Cerebral Ischemia , 1995 .

[49]  O. Burghuber,et al.  Serum neuron‐specific enolase is a useful tumor marker for small cell lung cancer , 1990, Cancer.

[50]  A. Umemura,et al.  Serum neuron-specific enolase levels after subarachnoid hemorrhage. , 1991, Surgical neurology.

[51]  A. Evans,et al.  Serum neuron‐specific enolase in children with neuroblastoma. Crelationship to stage and disease course , 1986 .

[52]  J. Rupright,et al.  Hypoxic brain injury: evaluation by single photon emission computed tomography. , 1996, Archives of physical medicine and rehabilitation.