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Aktuelle Neurologie 2002; 29(9): 431-446
DOI: 10.1055/s-2002-35270
Übersicht
© Georg Thieme Verlag Stuttgart · New York

Hypoxisch-ischämische Enzephalopathie

Hypoxic-Ischemic Brain InjuryW.  Müllges1 , G.  Stoll1
  • 1Neurologische Klinik der Julius-Maximilians-Universität Würzburg
Wir danken Herrn Dr. G. Burrows, Medizinische Universitätsklinik Würzburg, und Prof. Dr. K. V. Toyka für die kritische Durchsicht des Manuskripts
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Publication History

Publication Date:
05 November 2002 (online)

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Zusammenfassung

Diese Übersicht beschreibt die Pathophysiologie und Nosologie der hypoxisch-ischämischen Hirnschädigung. Nach einer kurzen Einführung in die Mechanismen des hypoxischen neuronalen Zelltods werden die verschiedenen Möglichkeiten zur Einschätzung der Prognose insbesondere nach Reanimationen unter klinischen und zusatzdiagnostischen Gesichtspunkten für die Perakutphase und an den folgenden Tagen erörtert. Am sichersten ist eine Prognose zu stellen anhand serieller klinischer-neurologischer Untersuchung und somatosensibel evozierten Potenzialen. Zwei unabhängige Studien zeigten aktuell den therapeutischen Nutzen einer Behandlung mit moderater Hypothermie nach Reanimation.

Abstract

This article reviews the pathophysiology and clinical course of anoxic brain damage. A short introduction into the mechanisms of hypoxic neuronal death is given. Clinical, brain imaging, biochemical, and electrophysiological parameters of the hyperacute period as well as during the following days are discussed especially with respect to outcome prediction after cardiopulmonary resuscitation. Most useful parameters are derived from serial clinical neurologic examination and from somatosensory evoked potentials. Recently, two clinical studies showed benefit from treatment with moderate hypothermia after cardiopulmonary resuscitation.

Literatur

  • 1 Ginsberg M D. Models of cerebral ischemia in the rodent. In: Schurr A (ed) Cerebral ischemia and resuscitation. Boca Baton; CRC Press 1990: 2-25
    Google Scholar
  • 2 Stoll G, Jander S, Schroeter M. Inflammation and glial responses in ischemic brain lesions.  Prog Neurobiol. 1998;  56 149-171
    CrossrefPubMedGoogle Scholar
  • 3 Pulsinelli W A, Brierley J B, Plum F. Temporal profile of neuronal damage in a model of transient forebrain ischemia.  Ann Neurol. 1982;  11 491-498
    CrossrefPubMedGoogle Scholar
  • 4 Böttiger B W, Schmitz B, Wiessner C. et al . Neuronal stress response and neuronal cell damage after cardiocirculatory arrest in rats.  J Cereb Blood Flow Metab. 1998;  18 1077-1087
    CrossrefPubMedGoogle Scholar
  • 5 Hossmann K A, Oschlies U, Schwindt W, Krep H. Electron microscopic investigation of rat brain after brief cardiac arest.  Acta Neuropath (Berl). 2001;  101 101-113
    PubMedGoogle Scholar
  • 6 Block F. Global ischemia and behavioural deficits.  Prog Neurobiol. 1999;  58 279-295
    CrossrefPubMedGoogle Scholar
  • 7 Petito C K, Feldman E, Pulsinelli W A, Plum F. Delayed hippocampal damage in humans following cardiorespiratory arrest.  Neurology. 1987;  37 1281-1286
    PubMedGoogle Scholar
  • 8 Haupt W F, Firsching R, Hansen H C. et al . Das akute postanoxische Koma: klinische, elektrophysiologische, biochemische und bildgebende Befunde.  Intensivmed. 2000;  37 597-607
    CrossrefPubMedGoogle Scholar
  • 9 Dirnagl U, Iadecola C, Moskowitz M A. Pathobiology of ischemic stroke: an integrated view.  Trends Neurosci. 1999;  22 391-397
    CrossrefPubMedGoogle Scholar
  • 10 Linnik M D, Zobrist R H, Hatfield M D. Evidence supporting a role for programmed cell death in focal cerebral ischemia in rats.  Stroke. 1993;  24 2002-2009
    PubMedGoogle Scholar
  • 11 O'Donnell B R, Bickler P E. Influence of pH on calcium influx during hypoxia in rat cortical brain slices.  Stroke. 1994;  25 171-177
    PubMedGoogle Scholar
  • 12 Love S. Oxidative stress in brain ischemia.  Brain Pathol. 1999;  9 119-131
    PubMedGoogle Scholar
  • 13 Allen S M, Rothwell N J. Cytokines and acute neurodegeneration.  Nature Rev Neurosci. 2001;  2 734-744
    PubMedGoogle Scholar
  • 14 Hossmann K A. The hypoxic brain.  Adv Exp Med Biol. 1999;  474 155-169
    PubMedGoogle Scholar
  • 15 Hossmann K A. Glutamate-mediated injury in focal cerebral ischemia: the excitotoxin hypothesis revised.  Brain Pathol. 1994;  4 23-36
    PubMedGoogle Scholar
  • 16 Bagenholm R, Nilsson U A, Kjellmer I. Formation of free radicals in hypoxic ischemic brain damage in the neonatal rat.  Brain Res. 1997;  773 132-138
    CrossrefPubMedGoogle Scholar
  • 17 Böttiger B W, Krumnikl J J, Gass P. et al . The cerebral „no-reflow” phenomenon after cardiac arrest in rats - influence of low-flow reperfusion.  Resuscitation. 1997;  34 79-87
    CrossrefPubMedGoogle Scholar
  • 18 Shaffner D H, Eleff S M, Koehler R C, Traystman R J. Effect of no-flow interval and hypothermia on cerebral blood flow and metabolism during cardiopulmonary resuscitation in dogs.  Stroke. 1998;  29 2607-2615
    PubMedGoogle Scholar
  • 19 Palmer C. Hypoxic-ischemic encephalopathy, therapeutic approaches against microvascular injury, and role of neurophils, PAF, and free radicals.  Clinics Perinatol. 1995;  22 481-517
    PubMedGoogle Scholar
  • 20 Vanucci R C, Towfighi J, Brucklacher R M, Vannuci S J. Effect of extreme hypercapnia on hypoxic-ischemic brain damage in the immature rat.  Pediatr Res. 2001;  49 799-803
    PubMedGoogle Scholar
  • 21 Oku K, Kuboyama K, Safar P. et al . Cerebral and systemic arteriovenous oxygen monitoring after cardiac arrest. Inadequate cerebral oxygen delivery.  Resuscitation. 1987;  27 141-152
    PubMedGoogle Scholar
  • 22 Vannucci R C, Christensen M A, Yagen J Y. Nature, time course, and extent of cerebral edema in perinatal hypoxic-ischemic brain damage.  Paed Neurol. 1993;  9 29-34
    PubMedGoogle Scholar
  • 23 Cohan S L, Mun S K, Petite S J. et al . Cerebral blood flow in humans following resuscitation from cardiac arrest.  Stroke. 1989;  20 761-765
    PubMedGoogle Scholar
  • 24 Nedelcu J, Klein M A, Aguzzi A. et al . Biphasic edema after hypoxic-ischemic brain injury in neonatal rats reflects early neuronal and late glial damage.  Pediatr Res. 1999;  46 297-304
    PubMedGoogle Scholar
  • 25 Gueugniaud P Y, Garcia-Darennes F, Gaussorgues P. et al . Prognostic significance of early intracranial and cerebral perfusion pressures in post-cardiac arrest anoxic coma.  Intensive Care Med. 1991;  17 392-398
    CrossrefPubMedGoogle Scholar
  • 26 Mishra O P, Delivoria-Papadopoulos M. Cellular mechanisms of hypoxic injury in the developing brain.  Brain Res Bull. 1999;  48 233-238
    CrossrefPubMedGoogle Scholar
  • 27 Adams N, Strauss M, Schluchter M, Redline S. Relation of measures of sleep-disordered breathing to neuropsychological functioning.  Am J Respir Crit Care Med. 2001;  163 1626-1631
    PubMedGoogle Scholar
  • 28 Wijdicks E FM, Parisi J E, Sharbrough F W. Prognostic value of myoclonus status in comatose survivors of cardiac arrest.  Ann Neurol. 1994;  35 239-243
    CrossrefPubMedGoogle Scholar
  • 29 Hallett M, Chadwick D, Adam J, Marsden C D. Reticular reflex myoclonus: a physiological type of human post-hypoxic myoclonus.  J Neurol Neurosurg Psychiatr. 1977;  40 253-264
    CrossrefPubMedGoogle Scholar
  • 30 Lance J W, Adams R D. Negative myoclonus in posthypoxic patients.  Mov Disord. 2001;  16 162-163
    CrossrefPubMedGoogle Scholar
  • 31 Wehrhahn K J, Brown P, Thompson P D, Marsden C D. The clinical features and prognosis of chronic posthypoxic myoclonus.  Mov Disord. 1997;  12 216-220
    CrossrefPubMedGoogle Scholar
  • 32 Kassell N F, Torner J C, Haley E C. et al . The international cooperative study on the timing of aneurysm surgery.  J Neurosurg. 1990;  73 18-36
    CrossrefPubMedGoogle Scholar
  • 33 Fujioka M, Okuchi K, Sakaki T. et al . Specific changes in human brain following reperfusion after cardiac arrest.  Stroke. 1994;  25 2091-2095
    PubMedGoogle Scholar
  • 34 Wijdicks E FM, Campeau N G, Miller G M. MR imaging in comatose survivors of cardiac resuscitation.  AJNR. 2001;  22 1561-1565
    PubMedGoogle Scholar
  • 35 Arbelaez A, Castillo M, Muktierij S K. Diffusion-weighted MR imaging of global ischemic cerebral anoxia.  AJNR. 1999;  20 999-1007
    PubMedGoogle Scholar
  • 36 Behar K L, Rothman D L, Hossmann K A. NMR spectroscopic investigation of the recovery of energy and acid-base homeostasis in the cat brain after prolonged ischemia.  J Cereb Blood Flow Metabol. 1989;  9 655-665
    PubMedGoogle Scholar
  • 37 Lechleitner P, Felber G, Birbamer S. et al . Proton magnetic resonance spectroscopy of brain after cardiac resuscitation.  Lancet. 1992;  340 913
    PubMedGoogle Scholar
  • 38 Falini A, Barkovich A J, Calabrese G. et al . Progressive brain failure after diffuse hypoxic ischemic brain injury: a serial MR and proton MR spectroscopic study.  AJNR. 1998;  19 648-652
    PubMedGoogle Scholar
  • 39 Rupright J, Woods E A, Singh A. Hypoxic brain injury: evaluation by single photon emission computed tomography.  Arch Phys Med Rehabil. 1996;  77 1205-1208
    CrossrefPubMedGoogle Scholar
  • 40 Zijlstra J G, Schaafsma A, deJong B M. et al . Early positron emission tomography in posthypoxic encephalopathy.  Int Care Med. 1997;  23 S186
    PubMedGoogle Scholar
  • 41 Niedermeyer E, Sherman D L, Geocadin R J. et al . The burst-suppression electroencephalogram.  Clin EEG. 1999;  30 99-105
    PubMedGoogle Scholar
  • 42 Rothstein T L. The role of evoked potentials in anoxic-ischemic coma and severe brain trauma.  J Clin Neurophysiol. 2000;  17 486-497
    PubMedGoogle Scholar
  • 43 Hume A L, Cant B R, Shaw N A. Central somatosensory conduction time in comatose patients.  Ann Neurol. 1979;  5 379-384
    CrossrefPubMedGoogle Scholar
  • 44 Madl C, Kramer L, Domanovits H. et al . Improved outcome prediction in unconscious cardiac arrest survivors with sensory evoked potentials compared with clinical assessment.  Crit Care Med. 2000;  28 721-726
    CrossrefPubMedGoogle Scholar
  • 45 Lesnick J E, Michelle J J, Simeone F A. et al . Alteration of somatosensory evoked potentials in response to global ischemia.  J Neurosurg. 1984;  60 490-494
    PubMedGoogle Scholar
  • 46 Gendo A, Kramer L, Häfner M. et al . Time-dependency of sensory evoked potentials in comatose cardiac arrest survivors.  Intensive Care Med. 2001;  27 1305-1311
    CrossrefPubMedGoogle Scholar
  • 47 Guerit J M, de Tourtchaninoff M, Soveges L, Mahieu P. The prognostic value of three-modality evoked potentials in anoxic and traumatic comas.  Neurophysiol Clin. 1993;  23 209-226
    PubMedGoogle Scholar
  • 48 Guerit J M. The interest of multimodality evoked potentials in the evaluation of chronic coma.  Acta Neurol Belg. 1994;  94 174-182
    PubMedGoogle Scholar
  • 49 Ganes T, Lundar T. EEG and evoked potentials in comatose patients with severe brain damage.  Electroencephalogr and Clin Neurophysiol. 1988;  69 6-13
    PubMedGoogle Scholar
  • 50 Sohmer H, Freeman S, Gafni M, Goiten K. The depression of the auditory nerve brain stem evoked response.  Electroencephalogr Clin Neurophysiol. 1986;  64 334-338
    PubMedGoogle Scholar
  • 51 Roine R O, Somer H, Kaste M. et al . Neurological outcome after out-of-hospital cardiac arrest.  Arch Neurol. 1989;  46 753-756
    CrossrefPubMedGoogle Scholar
  • 52 Schaarschmidt H, Prange H W. Neuron specific enolase - a marker of cerebral damage in blood.  J Clin Chem Clin Biochem. 1989;  27 835-836
    PubMedGoogle Scholar
  • 53 Rosén H, Sunnerhagen S, Herlitz J. et al . Serum levels of the brain-derived proteins S100 and NSE predict long-term outcome after cardiac arrest.  Resuscitation. 2001;  49 183-191
    CrossrefPubMedGoogle Scholar
  • 54 Dauberschmidt R, Zinsmeyer J, Mochen H, Meyer M. Changes of neuron-specific enolase concentration in plasma after cardiac arrest and resuscitation.  Molecul Chem Neuropathol. 1991;  14 237-245
    PubMedGoogle Scholar
  • 55 Rosén H, Rosengren L, Herlitz J, Blomstrand C. Increased serum levels of the S-100 protein are associated with hypoxic brain damage after cardiac arrest.  Stroke. 1998;  29 473-477
    PubMedGoogle Scholar
  • 56 DiBari M, Chiarlone M, Fumagalli S. et al . Cardiopulmonary resuscitation of older, in hospital patients: immediate efficiacy and long-term outcome.  Crit Care Med. 2000;  28 2320-2325
    PubMedGoogle Scholar
  • 57 Engdahl J, Bang A, Lindquist J, Herlitz J. Can we define patients with no and those with some chance of survival when found in asystole out of hospital?.  Am J Cardiol. 2000;  86 610-614
    CrossrefPubMedGoogle Scholar
  • 58 Hamel M B, Goldman L, Teno J. et al . Identification of comatose patients at high risk for death or severe disability.  JAMA. 1995;  273 1842-1848
    CrossrefPubMedGoogle Scholar
  • 59 Rogove H J, Safar P, Sutton-Tyrrell K, Abramson N S. Old age does not negate good cerebral outcome after cardiopulmonary resuscitation: analyses from the brain resuscitation trials.  Crit Care Med. 1995;  23 18-25
    PubMedGoogle Scholar
  • 60 Young G B, Kreeft J H, McLachlan R S, Demelo J. EEG and clinical associations with mortality in comatose patients in a general intensive care unit.  J Clin Neurophysiol. 1999;  16 354-360
    CrossrefPubMedGoogle Scholar
  • 61 Zoch T W, Desbiens N A, DeStefano F. et al . Short- and long-term survival after cardiopulmonary resuscitation.  Arch Intern Med. 2000;  160 1969-1973
    CrossrefPubMedGoogle Scholar
  • 62 Mullie A, Verstringe P, Buylaert W. et al . Predictive value of Glasgow Coma Score for awakening after out-of-hospital cardiac arrest.  Lancet. 1988;  ii 137-140
    PubMedGoogle Scholar
  • 63 Zandbergen E GJ, de Haan R J, Koelman J HTM, Hijdra A. Prediction of poor outcome in anoxic-ischemic coma.  J Clin Neurophysiol. 2000;  17 498-510
    PubMedGoogle Scholar
  • 64 Rewers M, Tilgreen R E, Crawford M E, Hjortso N C. One-year survival after out-of-hospital cardiac arrest in Copenhagen according to the Utstein style.  Resuscitation. 2000;  47 137-146
    CrossrefPubMedGoogle Scholar
  • 65 Timerman A, Sauaia N, Piegas L S. et al . Prognostic factors of the results of cardiopulmonary resuscitation in a cardiology hospital.  Arq Bras Cardiol. 2001;  77 142-160
    PubMedGoogle Scholar
  • 66 Bulut S, Aengevaeren W R, Luijten H J, Verheugt F W. Successful out-of-hospital cardiopulmonary resuscitation: what is the optimal in-hospital treatment strategy?.  Resuscitation. 2000;  47 155-161
    CrossrefPubMedGoogle Scholar
  • 67 Bates D, Caronna J J, Cartlidge E F. et al . A prospective study of nontraumatic coma: methods and results in 310 patients.  Ann Neurol. 1977;  2 211-220
    CrossrefPubMedGoogle Scholar
  • 68 Chen R, Bolton C F, Young G B. Prediction of outcome in patients with anoxic coma: a clinical and electrophysiologic study.  Crit Care Med. 1996;  24 672-678
    CrossrefPubMedGoogle Scholar
  • 69 Levy D E, Caronna J J, Singer B H. et al . Predicting outcome from hypoxic-ischemic coma.  JAMA. 1985;  253 1420-1426
    CrossrefPubMedGoogle Scholar
  • 70 Snyder B D, Loewenson R B, Gumnit R J. et al . Neurologic prognosis after cardiopulmonary arrest. II. Level of consciousness.  Neurology. 1980;  30 52-58
    PubMedGoogle Scholar
  • 71 Grubb N R, O'Carroll R, Cobbe S M. et al . Chronic memory impairment after cardiac arrest outside hospital.  BMJ. 1996;  313 143-146
    PubMedGoogle Scholar
  • 72 Wilson B A. Cognitive functioning of adult survivors of cerebral hypoxia.  Brain Inj. 1996;  10 863-874
    CrossrefPubMedGoogle Scholar
  • 73 Ahmed I. Use of somatosensory evoked responses in the prediction of outcome from coma.  Clin Electroencephalogr. 1988;  19 78-86
    PubMedGoogle Scholar
  • 74 Bassetti C, Bomio F, Mathis J, Hess C W. Early prognosis of coma after cardiac arrest. A prospective clinical, electrophysiological, and biochemical study of 60 patients.  J Neurol Neurosurg Psychiatr. 1996;  61 610-615
    PubMedGoogle Scholar
  • 75 Multi-Society Task Force on PVS . Medical aspects of the persistent vegetative states (I und II).  N Engl Med. 1994;  330 1499-1508, 1572 - 1579
    CrossrefPubMedGoogle Scholar
  • 76 Fertl E, Vass K, Sterz F. et al . Neurological rehabilitation of severely disabled cardiac arrest survivors.  Resuscitation. 2000;  47 231-239
    CrossrefPubMedGoogle Scholar
  • 77 Hagel K, Rietz S. Die Prognose des apallischen Syndroms.  Anästhesist. 1998;  47 677-682
    PubMedGoogle Scholar
  • 78 Rosenberg G A, Johnson S F, Brenner R P. Recovery of cognition after prolonged vegetative state.  Ann Neurol. 1977;  2 167-168
    CrossrefPubMedGoogle Scholar
  • 79 Sazbon L, Zagreba F, Ronen J. et al . Course and outcome of patients in vegetative state of nontraumatic aetiology.  J Neurol Neurosurg Psychiatr. 1993;  56 407-409
    PubMedGoogle Scholar
  • 80 Puchalski C M, Zhong Z, Jacobs M M. et al . Patients who want their family and physician to make resuscitation decisions for them: observations from SUPPORT and HELP.  J Am Geriatr Soc. 2000;  48 (S5) 84-90
    PubMedGoogle Scholar
  • 81 Shewmon D A, DeGiorgio C M. Early prognosis in anoxic coma. Reliability and rationale.  Neurol Clin. 1989;  7 823-843
    PubMedGoogle Scholar
  • 82 Saltuari L, Marosi M. Coma after cardiac arrest: will he recover all right?.  Lancet. 1994;  343 1052
    CrossrefPubMedGoogle Scholar
  • 83 Herlitz J, Andreasson A C, Bang A. et al . Long-term prognosis among survivors after in-hospital arrest.  Resuscitation. 2000;  45 167-171
    CrossrefPubMedGoogle Scholar
  • 84 Edgren E, Hedstrand U, Kelsey S. et al . Assessment of neurological prognosis in comatose survivors of cardiac arrest.  Lancet. 1994;  343 1055-1059
    CrossrefPubMedGoogle Scholar
  • 85 Berek K, Schinnerl A, Traweger C. et al . The prognostic significance of coma-rating, duration of anoxia, and cardiopulmonary resuscitation in out-of-hospital cardiac arrest.  J Neurol. 1997;  244 556-561
    PubMedGoogle Scholar
  • 86 Gallagher E J, Lombardi G, Gennis P. Effectiveness of bystander cardiopulmonary resuscitation and survival following out-of-hospital cardiac arrest.  JAMA. 1995;  274 1922-1925
    CrossrefPubMedGoogle Scholar
  • 87 Longstreth W T, Diehr P, Inui T S. Prediction of awakening after out-of-hospital cardiac arrest.  N Engl J Med. 1983;  308 1378-1382
    CrossrefPubMedGoogle Scholar
  • 88 McCullough P A, Thompson R J, Tobin K J. et al . Validation of a decision support tool for the evaluation of cardiac arrest victims.  Clin Cardiol. 1998;  21 195-200
    PubMedGoogle Scholar
  • 89 McCullough P A, Sandberg K R, Thompson R J. Predicting outcomes after cardiopulmonary resuscitation.  Arch Intern Med. 2001;  161 615-616
    CrossrefPubMedGoogle Scholar
  • 90 Snyder B D, Gumnit R J, Leppik I E. et al . Neurologic prognosis after cardiopulmonary arrest. IV. Brainstem reflexes.  Neurology. 1981;  31 1092-1097
    PubMedGoogle Scholar
  • 91 Zandbergen E GJ, de Haan R J, Stoutenbeck C P. et al . Systematic review of early prediction of poor outcome in anoxic-ischaemic coma.  Lancet. 1998;  352 1808-1812
    CrossrefPubMedGoogle Scholar
  • 92 Earnest M P, Breckinridge J C, Yarnell P R, Oliva P B. Quality of survival after out-of-hospital cardiac arrest: predictive value of early neurologic evaluation.  Neurology. 1979;  29 56-60
    PubMedGoogle Scholar
  • 93 Pifferi S, Codazzi D, Savioli M, Langer M. Early prediction of neurologic prognosis after post-anoxic coma.  Intensive Care Med. 1998;  24 535-536
    CrossrefPubMedGoogle Scholar
  • 94 Wolf R L, Zimmerman R A, Clancy R, Haselgrove J H. Quantitative apparent diffusion coefficient measurements in term neonates for early detection of hypoxic-ischemic brain injury.  Radiology. 2001;  218 825-833
    CrossrefPubMedGoogle Scholar
  • 95 Synek V M. Prognostically important EEG coma patterns in diffuse anoxic and traumatic encephalopathies in adults.  J Clin Neurophysiol. 1988;  5 161-174
    PubMedGoogle Scholar
  • 96 Synek V M. EEG abnormality grades and subdivisions of prognostic importance in traumatic and anoxic coma in adults.  Clin Electroencephalogr. 1988;  19 160-166
    CrossrefPubMedGoogle Scholar
  • 97 Young G B, McLachlan R S, Kreeft J H, Demelo J D. An electroencephalographic classification for coma.  Can J Neurol Sci. 1997;  24 320-325
    CrossrefPubMedGoogle Scholar
  • 98 Rothstein T L, Thomas E M, Sumi S M. Predicting outcome in hypoxic ischemic coma. A prospective clinical and electrophysiologic study.  Electroencephalogr Clin Neurophysiol. 1991;  79 101-107
    CrossrefPubMedGoogle Scholar
  • 99 Synek V M. Value of a revised EEG coma scale for prognosis after cerebral anoxia and diffuse head injury.  Clin Electroencephalogr. 1990;  21 25-30
    PubMedGoogle Scholar
  • 100 Berkhoff M, Donati F, Bassetti C. Postanoxic alpha (theta) coma: a reappraisal of its prognostic significance.  Clin Neurophysiol. 2000;  111 297-304
    CrossrefPubMedGoogle Scholar
  • 101 Kaplan P W, Genoud D, Ho T W, Jallon P. Etiology, neurologic correlations, and prognosis in alpha coma.  Clin Neurophysiol. 1999;  110 205-213
    CrossrefPubMedGoogle Scholar
  • 102 Fauvage B, Combes P. Isoelectric electroencephalogram and loss of evoked potentials in a patient who survived cardiac arrest.  Crit Care Med. 1993;  21 472-475
    PubMedGoogle Scholar
  • 103 Madl C, Grimm G, Kramer L. et al . Early prediction of individual outcome after cardiopulmonary resuscitation.  Lancet. 1993;  341 855-858
    CrossrefPubMedGoogle Scholar
  • 104 Sherman A L, Tirshwell D L, Micklesen P J. et al . Somatosensory potentials, CSF creatine kinase BB activity, and awakening after cardiac arrest.  Neurology. 2000;  54 889-894
    PubMedGoogle Scholar
  • 105 Longstreth W T, Clayson K J, Sumi S M. Cerebrospinal fluid and serum creatine kinase BB activity after out-of-hospital cardiac arrest.  Neurology. 1981;  31 455-458
    PubMedGoogle Scholar
  • 106 Martens P. Serum neuron-specific enolase as a prognostic marker for irreversible brain damage in comatose cardiac arrest survivors.  Acad Emerg Med. 1996;  3 126-131
    PubMedGoogle Scholar
  • 107 Martens P, Raabe A, Johnsson P. Serum S-100 and Neuron-specific enolase for prediction of regaining consciousness after global cerebral ischemia.  Stroke. 1998;  29 2363-2366
    CrossrefPubMedGoogle Scholar
  • 108 Roine R O, Somer H, Kaste M. et al . Neurological outcome after out-of-hospital cardiac arrest.  Arch Neurol. 1989;  46 753-756
    CrossrefPubMedGoogle Scholar
  • 109 Tirshwell D L, Longstreth W T, Rauch-Matthews M E. et al . Cererbrospinal fluid creatine kinase BB isoencyme activity and neurologic prognosis after cardiac arrest.  Neurology. 1997;  48 352-357
    PubMedGoogle Scholar
  • 110 Kärkelä J, Bock E, Kaukinen S. CSF and serum brain-specific creatine kinase isoenzyme (CK-BB), neuron-specific enolase (NSE) and neural cell adhesion molecule (NCAM) as prognostic markers for hypoxic brain injury after cardiac arrest in man.  J Neurol Sci. 1993;  116 100-109
    CrossrefPubMedGoogle Scholar
  • 111 Zandbergen E GJ, de Haan R J, Hijdra A. Systematic review of prediction of poor outcome in anoxic-ischaemic coma with biochemical markers of brain damage.  Intensive Care Med. 2001;  27 1661-1667
    CrossrefPubMedGoogle Scholar
  • 112 Prange H W, Aue G, Frauendorf H, Reiber H. Die neuronenspezifische Enolase als Prognosemarker bei zerebraler Hypoxie.  Intensivmed. 1995;  32 17-22
    PubMedGoogle Scholar
  • 113 Schörkhuber W, Kittler H, Sterz F. et al . Time course of serum neuron-specific enolase. A predictor of neurological outcome in patients resuscitated from cardiac arrest.  Stroke. 1999;  30 1598-1603
    PubMedGoogle Scholar
  • 114 Fogel W, Krieger D, Veith M. et al . Serum neuron-specific enolase as early predictor of outcome after cardiac arrest.  Crit Care Med. 1997;  25 1133-1138
    CrossrefPubMedGoogle Scholar
  • 115 Torossian A, Zielmann S, Schaarschmidt H. et al . Erste Ergebnisse der Wertigkeit der Neuronen-spezifischen Enolase als prognostische Variable nach Reanimation.  Anästhesist. 1992;  41 720-721
    PubMedGoogle Scholar
  • 116 Mussack T, Biberthaler P, Kanz K G. et al . S-100b, sE-selectin, and sP-selectin for evaluation of hypoxic brain damage in patients after cardiopulmonary resuscitation: a pilot study.  World J Surg. 2001;  25 539-543
    CrossrefPubMedGoogle Scholar
  • 117 Gluckman P D, Pinal C S, Gunn A J. Hypoxic-ischemic brain injury in the newborn: pathophysiology and potential strategies for interventions.  Semin Neonatol. 2001;  6 109-120
    PubMedGoogle Scholar
  • 118 Gire C, Nicaise C, Roussel M. et al . Encephalopathie hypoxo-ischemique du nouveau-ne a terme.  Neurophysiol Clin. 2000;  30 97-107
    PubMedGoogle Scholar
  • 119 Goodwin S R, Friedman W A, Bellefleur M. Is it time to use evoked potentials to predict outcome in comatose children and adults?.  Crit Care Med. 1991;  19 518-524
    PubMedGoogle Scholar
  • 120 Heindl U T, Laub M C. Outcome of persistent vegetative state following hypoxic or traumatic brain injury in children and adolescents.  Neuropediatrics. 1996;  27 94-100
    PubMedGoogle Scholar
  • 121 Gray P H, Tudehope D I, Masel J P. et al . Perinatal hypoxic ischemic brain injury: prediction of outcome.  Dev Med Child Neurol. 1993;  35 965-973
    PubMedGoogle Scholar
  • 122 Amess P N, Penrice J, Wylezinska M. et al . Early brain proton magnetic resonance spectroscopy and neonatal neurology related to neurodevelopmental outcome at 1 year in term infants after presumed hypoxic-ischemic brain injury.  Dev Med Child Neurol. 1999;  41 436-465
    CrossrefPubMedGoogle Scholar
  • 123 Sie L T, van der Knapp M S, van Wezel-Meijler G. et al . Early MR features of hypoxic-ischemic brain injury in neonates with periventricular densities on sonograms.  AJNR. 2000;  21 852-861
    PubMedGoogle Scholar
  • 124 Garcia-Alix A, Cabanas F, Pellicer A. et al . Neuron-specific enolase and myelin-basic protein: relationship of cerebrospinal fluid concentrations to the neurologic condition of asphyxiated full-term infants.  Pediatrics. 1994;  93 234-240
    PubMedGoogle Scholar
  • 125 Block F, Schwarz M. Neuroprotektion beim Schlaganfall.  Nervenarzt. 1999;  70 101-110
    CrossrefPubMedGoogle Scholar
  • 126 Katsuta K, Nakanishi H, Shirakawa K. et al . The neuroprotective effect of the novel noncompetitive NMDA antagonist, FR115427, in focal cerebral ischemia in rats.  J Cereb Blood Flow Metab. 1995;  15 345-348
    PubMedGoogle Scholar
  • 127 Ozyurt E, Graham D I, Woodruff G N, McCulloch J. Protective effect of the glutamate antagonist, MK-801, in focal cerebral ischemia in the cat.  J Cereb Blood Flow Metab. 1988;  8 138-143
    PubMedGoogle Scholar
  • 128 Sauer D, Weber E, Lüöond G. et al . The competitive NMDA antagonist CGP 40116 permanently reduces brain damage after middle cerebral artery occlusion in rats.  J Cereb Blood Flow Metab. 1995;  15 602-610
    PubMedGoogle Scholar
  • 129 Valentino K, Newcom R, Gadbois T. et al . A selective N-type calcium channel antagonist protects against neuronal loss after global ischemia. Proc.  Natl acad Sci (USA). 1993;  90 7894-7897
    PubMedGoogle Scholar
  • 130 Giroux C, Scatton B. Ischemic stroke: treatment on the horizon.  Eur Neurol. 1996;  36 61-64
    PubMedGoogle Scholar
  • 131 Gillardon F, Kiprianova I, Sandkuhler J. et al . Inhibition of caspases prevents cell death of hippocampal CA1 neurons, but not impairment of hippocampal long-term potentiation following global ischemia.  Neuroscience. 1999;  93 1219-1222
    CrossrefPubMedGoogle Scholar
  • 132 Krep H, Brinker G, Schwindt W, Hossmann K A. Endothelin type A-antagonist improves long-term neurological recovery after cardiac arrest in rats.  Crit Care Med. 2000;  28 2873-2880
    PubMedGoogle Scholar
  • 133 Chan P H, Kawase M, Murakami K. et al . Overexpression of SOD1 in transgenic rats protects vulnerable neurons against ischemic damage after global cerebral ischemia and reperfusion.  J Neurosci. 1998;  18 8292-8299
    PubMedGoogle Scholar
  • 134 Crumrine R C, Bergstrand K, Cooper A T. et al . Lamotrigine protects hippocampal CA1 neurons from ischemic damage after cardiac arrest.  Stroke. 1997;  28 2230-2236
    PubMedGoogle Scholar
  • 135 Brain Resuscitation Clinical Trial I Study Group . Randomized clinical study of thiopental loading in comatose survivors of cardiac arrest.  N Engl J Med. 1986;  314 397-403
    PubMedGoogle Scholar
  • 136 Jastremski M, Sutton-Tyrrell K, Vaagenes P. et al . Glucocorticosteroid treatment does not improve neurologic recovery following cardiac arrest.  JAMA. 1989;  262 3427-3430
    CrossrefPubMedGoogle Scholar
  • 137 Brain Resuscitation Clinical Trial I Study Group . Brain Resuscitation Clinical Trial II Study Group. A randomized clinical study of a calcium-entry blocker (lidoflazine) in the treatment of comatose survivors of cardiac arrest.  N Engl J Med. 1991;  324 1225-1231
    PubMedGoogle Scholar
  • 138 Gelman B, Schleien C, Lohe A, Kuluz J W. Selective brain cooling in infant piglets after cardiac arrest and resuscitation.  Crit Care Med. 1996;  24 1009-1017
    PubMedGoogle Scholar
  • 139 Nedelcu J, Klein M A, Aguzzi A, Martin E. Resuscitative hypothermia protects the neonatal rat brain from hypoxic-ischemic injury.  Brain Pathol. 2000;  10 61-71
    PubMedGoogle Scholar
  • 140 Safar P, Klain M, Tisherman S. Selective brain cooling after cardiac arrest.  Crit Care Med. 1996;  24 911-914
    CrossrefPubMedGoogle Scholar
  • 141 Thoresen M, Bagenholm R, Loberg E M. et al . Posthypoxic cooling of neonatal rats provides protection against brain injury.  Arch Dis Child Fetal Neonatal Ed. 1996;  74 3-9
    PubMedGoogle Scholar
  • 142 Towfighi J, Housman C, Heitjan D F. et al . The effect of focal cerebral cooling on perinatal hypoxic-ischemic brain damage.  Acta Neuropathol (Berl). 1994;  87 598-604
    PubMedGoogle Scholar
  • 143 Yager J Y, Asselin J. Effect of mild hypothermia on cerebral energy metabolism during the evolution of hypoxic-ischemic brain damage in the immature rat.  Stroke. 1996;  27 919-925
    PubMedGoogle Scholar
  • 144 Bernard S A, MacJones B, Horne M K. Clinical trial of induced hypothermia in comatose survivors of out-of-hospital cardiac arrest.  Ann Emerg Med. 1997;  30 146-153
    CrossrefPubMedGoogle Scholar
  • 145 Yanakawa Y, Ishihara S, Norio H. et al . Preliminary clinical outcome study of mild resuscitative hypothermia after out-of-hospital cardiopulmonary arrest.  Resuscitation. 1998;  39 61-66
    CrossrefPubMedGoogle Scholar
  • 146 Bernard S A, Gray T W, Buist M D. et al . Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia.  New Engl J Med. 2002;  346 557-563
    CrossrefPubMedGoogle Scholar
  • 147 The Hypothermia after Cardiac Arrest Study Group . Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest.  New Engl J Med. 2002;  346 549-556
    CrossrefPubMedGoogle Scholar
  • 148 Spandou E, Karkavelas G, Soubasi V. et al . Effect of ketamine on hypoxic-ischemic brain damage in newborn rats.  Brain Res. 1999;  81 1-7
    PubMedGoogle Scholar
  • 149 Cortey A, Monin P, Hascoet J M. et al . Effects of Phenobarbital on cerebral blood flow during hypoxia.  Biol Neonate. 1994;  65 2396-2405
    PubMedGoogle Scholar
  • 150 Yuan S Z, Runold M, Hagberg H. et al . Hypoxic-ischemic brain damage in immature rats: effects of adrenoceptor modulation.  Europ J Paediatr Neurol. 2001;  5 29-35
    PubMedGoogle Scholar
  • 151 Trivedi M, Ridley S A. Intermediate outcome of medical patients after intensive care.  Anaesthesia. 2001;  56 841-846
    CrossrefPubMedGoogle Scholar
  • 152 Berek K, Jeschow M, Aichner F. The prognostication of cerebral hypoxia after out-of-hospital cardiac arrest in adults.  Eur Neurol. 1997;  37 135-145
    CrossrefPubMedGoogle Scholar
  • 153 Brunko E, Zegers de Beyl D. Prognostic value of early cortical somatosensory evoked potentials after resuscitation from cardiac arrest.  Electroencephalogr Clin Neurophysiol. 1987;  66 15-24
    PubMedGoogle Scholar
  • 154 Ganji S, Peters G, Frazier E. Somatosensory and brainstem auditory evoked potential studies in nontraumatic coma.  Clin Electroencephalogr. 1988;  19 55-67
    PubMedGoogle Scholar
  • 155 Haupt W F, Schumacher A. Medianus-SEP und Prognose in der neurologischen Intensivmedizin.  Z EEG EMG. 1988;  19 148-151
    PubMedGoogle Scholar
  • 156 Kano T, Shimoda O, Morioka T. et al . Evaluation of the central nervous function in resuscitated comatose patients by multilevel evoked potentials.  Resuscitation. 1992;  23 235-248
    CrossrefPubMedGoogle Scholar
  • 157 Madl C, Kramer L, Yegawehfar W. et al . Detection of nontraumatic comatose patients with no benefit from intensive care treatment by recording sensory evoked potentials.  Arch Neurol. 1996;  53 512-516
    PubMedGoogle Scholar
  • 158 Ragazzoni A, Cincotta M, Chiaramonti R. et al . Electrophysiological early predictors of outcome in patients with anoxic coma: EEG and SEPs.  Clin Neurophysiol. 1999;  10 (S1) 245-246
    PubMedGoogle Scholar
  • 159 Walser H, Mattle H, Keller H M, Janzer R. Early cortical median nerve somatosensory evoked potentials. Prognostic value in anoxic coma.  Arch Neurol. 1986;  42 32-38
    PubMedGoogle Scholar
  • 160 Walser H, Emre M, Janzer R. Somatosensory evoked potentials in comatose patients: correlation with outcome and neuropathological findings.  J Neurol. 1986;  223 34-40
    PubMedGoogle Scholar
  • 161 Zegers de Beyl D, Borenstein S, Dufaye P. et al . Irreversible cortical damage in acute postanoxic coma: predictive value of somatosensory evoked potentials.  Transplant Proc. 1984;  16 98-101
    PubMedGoogle Scholar
  • 162 Massey T H, Goe M R. Transient creatine kinase BB activity in serum or plasma after cardiac or respiratory arrest.  Clin Chem. 1984;  30 50-55
    PubMedGoogle Scholar

Dr. W. Müllges,
Prof. Dr. G. Stoll

Neurologische Universitätsklinik

Josef-Schneider-Straße 11

97080 Würzburg

Email: wolfgang.muellges@mail.uni-wuerzburg.de

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