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Hypoxic-ischemic brain injury: Evaluation and prognosis

INTRODUCTION

Hypoxic-ischemic brain injury most often results from insults such as cardiac arrest, vascular catastrophe, poisoning (such as carbon monoxide intoxication or drug overdose), or head trauma. While many patients expire without recovering awareness, improved techniques in resuscitation and artificial life support have resulted in greater numbers of patients surviving with variable degrees of brain injury. The evolution of hypothermic treatment for comatose survivors of cardiac arrest has furthered the potential to improve neurologic morbidity and lessen mortality following anoxic brain injury [1-3].

While progress has also been made in the early identification of patients at greatest risk of poor neurologic outcome after cardiac arrest, reliable prediction of good outcomes, with intact memory and independence, has lagged. The evaluation and prognosis of patients with non-traumatic hypoxic-ischemic brain injury are reviewed here.

NOMENCLATURE

Coma is defined as a state of pathologic unconsciousness; patients are unaware of their environment and are unarousable. It is caused by either dysfunction of the reticular activating system above the level of the mid-pons, or dysfunction of both cerebral hemispheres. Physical examination permits localization of the level of central nervous system dysfunction (see 'Clinical assessment' below) [4,5].

Coma must be distinguished from the persistent vegetative state, which is also characterized by unawareness, but in which patients have normal sleep-wake cycles and are arousable. Patients in a coma may progress to a vegetative state, but this may not be associated with an improvement in their overall functional outcome. Both coma and persistent vegetative states must be distinguished from brain death, locked-in syndrome (a condition in which the patient is awake and aware but cannot move or communicate due to muscle paralysis), akinetic mutism (a condition resulting from frontal lobe injury in which the patient does not initiate speech or movements), and dementia (table 1) [4,6]. (See "Stupor and coma in adults", section on 'Conditions mistaken for coma'.)

The vegetative and minimally conscious states are clinically defined syndromes. Importantly, prognosis for recovery can vary depending on the underlying etiology and differs between patients who have hypoxic ischemic versus traumatic brain injury [7].

                   

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Literature review current through: Aug 2014. | This topic last updated: Aug 29, 2013.
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References
Top
  1. Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002; 346:549.
  2. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002; 346:557.
  3. Mateen FJ, Josephs KA, Trenerry MR, et al. Long-term cognitive outcomes following out-of-hospital cardiac arrest: a population-based study. Neurology 2011; 77:1438.
  4. Laureys S, Owen AM, Schiff ND. Brain function in coma, vegetative state, and related disorders. Lancet Neurol 2004; 3:537.
  5. Plum, F, Posner, JB. The Diagnosis of Stupor and Coma. 3rd ed, FA Davis Company, Philadelphia 1980. p.103.
  6. Medical aspects of the persistent vegetative state (1). The Multi-Society Task Force on PVS. N Engl J Med 1994; 330:1499.
  7. Bernat JL. The natural history of chronic disorders of consciousness. Neurology 2010; 75:206.
  8. Saposnik G, Maurino J, Saizar R, Bueri JA. Spontaneous and reflex movements in 107 patients with brain death. Am J Med 2005; 118:311.
  9. Jennett B, Bond M. Assessment of outcome after severe brain damage. Lancet 1975; 1:480.
  10. Levy DE, Bates D, Caronna JJ, et al. Prognosis in nontraumatic coma. Ann Intern Med 1981; 94:293.
  11. Jennett B, Plum F. Persistent vegetative state after brain damage. A syndrome in search of a name. Lancet 1972; 1:734.
  12. Medical aspects of the persistent vegetative state (2). The Multi-Society Task Force on PVS. N Engl J Med 1994; 330:1572.
  13. Luauté J, Maucort-Boulch D, Tell L, et al. Long-term outcomes of chronic minimally conscious and vegetative states. Neurology 2010; 75:246.
  14. Estraneo A, Moretta P, Loreto V, et al. Late recovery after traumatic, anoxic, or hemorrhagic long-lasting vegetative state. Neurology 2010; 75:239.
  15. Monti MM, Vanhaudenhuyse A, Coleman MR, et al. Willful modulation of brain activity in disorders of consciousness. N Engl J Med 2010; 362:579.
  16. Owen AM, Coleman MR, Boly M, et al. Detecting awareness in the vegetative state. Science 2006; 313:1402.
  17. Rodriguez Moreno D, Schiff ND, Giacino J, et al. A network approach to assessing cognition in disorders of consciousness. Neurology 2010; 75:1871.
  18. Yu T, Lang S, Vogel D, et al. Patients with unresponsive wakefulness syndrome respond to the pain cries of other people. Neurology 2013; 80:345.
  19. Faugeras F, Rohaut B, Weiss N, et al. Probing consciousness with event-related potentials in the vegetative state. Neurology 2011; 77:264.
  20. Cruse D, Chennu S, Chatelle C, et al. Bedside detection of awareness in the vegetative state: a cohort study. Lancet 2011; 378:2088.
  21. Cruse D, Chennu S, Chatelle C, et al. Relationship between etiology and covert cognition in the minimally conscious state. Neurology 2012; 78:816.
  22. Ropper, AH. Cogito ergo sum by MRI. N Eng J Med 2010; 362:648.
  23. Giacino JT, Ashwal S, Childs N, et al. The minimally conscious state: definition and diagnostic criteria. Neurology 2002; 58:349.
  24. Landsness E, Bruno MA, Noirhomme Q, et al. Electrophysiological correlates of behavioural changes in vigilance in vegetative state and minimally conscious state. Brain 2011; 134:2222.
  25. La Porta F, Caselli S, Ianes AB, et al. Can we scientifically and reliably measure the level of consciousness in vegetative and minimally conscious States? Rasch analysis of the coma recovery scale-revised. Arch Phys Med Rehabil 2013; 94:527.
  26. Giacino JT, Kalmar K, Whyte J. The JFK Coma Recovery Scale-Revised: measurement characteristics and diagnostic utility. Arch Phys Med Rehabil 2004; 85:2020.
  27. Laureys S, Perrin F, Faymonville ME, et al. Cerebral processing in the minimally conscious state. Neurology 2004; 63:916.
  28. Coleman MR, Menon DK, Fryer TD, Pickard JD. Neurometabolic coupling in the vegetative and minimally conscious states: preliminary findings. J Neurol Neurosurg Psychiatry 2005; 76:432.
  29. Voss HU, Uluç AM, Dyke JP, et al. Possible axonal regrowth in late recovery from the minimally conscious state. J Clin Invest 2006; 116:2005.
  30. Whyte J, Katz D, Long D, et al. Predictors of outcome in prolonged posttraumatic disorders of consciousness and assessment of medication effects: A multicenter study. Arch Phys Med Rehabil 2005; 86:453.
  31. Lammi MH, Smith VH, Tate RL, Taylor CM. The minimally conscious state and recovery potential: a follow-up study 2 to 5 years after traumatic brain injury. Arch Phys Med Rehabil 2005; 86:746.
  32. Guldenmund P, Stender J, Heine L, Laureys S. Mindsight: diagnostics in disorders of consciousness. Crit Care Res Pract 2012; 2012:624724.
  33. Fernández-Espejo D, Bekinschtein T, Monti MM, et al. Diffusion weighted imaging distinguishes the vegetative state from the minimally conscious state. Neuroimage 2011; 54:103.
  34. Estraneo A, Moretta P, Loreto V, et al. Predictors of recovery of responsiveness in prolonged anoxic vegetative state. Neurology 2013; 80:464.
  35. Godbolt AK, Stenson S, Winberg M, Tengvar C. Disorders of consciousness: preliminary data supports added value of extended behavioural assessment. Brain Inj 2012; 26:188.
  36. Wijdicks EF, Hijdra A, Young GB, et al. Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2006; 67:203.
  37. Rossetti AO, Oddo M, Logroscino G, Kaplan PW. Prognostication after cardiac arrest and hypothermia: a prospective study. Ann Neurol 2010; 67:301.
  38. Sunde K, Dunlop O, Rostrup M, et al. Determination of prognosis after cardiac arrest may be more difficult after introduction of therapeutic hypothermia. Resuscitation 2006; 69:29.
  39. Perman SM, Kirkpatrick JN, Reitsma AM, et al. Timing of neuroprognostication in postcardiac arrest therapeutic hypothermia*. Crit Care Med 2012; 40:719.
  40. Berek K, Jeschow M, Aichner F. The prognostication of cerebral hypoxia after out-of-hospital cardiac arrest in adults. Eur Neurol 1997; 37:135.
  41. de Vos R, Koster RW, De Haan RJ, et al. In-hospital cardiopulmonary resuscitation: prearrest morbidity and outcome. Arch Intern Med 1999; 159:845.
  42. Saklayen M, Liss H, Markert R. In-hospital cardiopulmonary resuscitation. Survival in 1 hospital and literature review. Medicine (Baltimore) 1995; 74:163.
  43. Booth CM, Boone RH, Tomlinson G, Detsky AS. Is this patient dead, vegetative, or severely neurologically impaired? Assessing outcome for comatose survivors of cardiac arrest. JAMA 2004; 291:870.
  44. Levy DE, Caronna JJ, Singer BH, et al. Predicting outcome from hypoxic-ischemic coma. JAMA 1985; 253:1420.
  45. Mullie A, Verstringe P, Buylaert W, et al. Predictive value of Glasgow coma score for awakening after out-of-hospital cardiac arrest. Cerebral Resuscitation Study Group of the Belgian Society for Intensive Care. Lancet 1988; 1:137.
  46. 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.
  47. Zandbergen EG, de Haan RJ, Stoutenbeek CP, et al. Systematic review of early prediction of poor outcome in anoxic-ischaemic coma. Lancet 1998; 352:1808.
  48. Al Thenayan E, Savard M, Sharpe M, et al. Predictors of poor neurologic outcome after induced mild hypothermia following cardiac arrest. Neurology 2008; 71:1535.
  49. Fugate JE, Wijdicks EF, Mandrekar J, et al. Predictors of neurologic outcome in hypothermia after cardiac arrest. Ann Neurol 2010; 68:907.
  50. Bouwes A, Binnekade JM, Kuiper MA, et al. Prognosis of coma after therapeutic hypothermia: a prospective cohort study. Ann Neurol 2012; 71:206.
  51. Wijdicks EF, Parisi JE, Sharbrough FW. Prognostic value of myoclonus status in comatose survivors of cardiac arrest. Ann Neurol 1994; 35:239.
  52. Zandbergen EG, Hijdra A, Koelman JH, et al. Prediction of poor outcome within the first 3 days of postanoxic coma. Neurology 2006; 66:62.
  53. Wijdicks EF, Young GB. Myoclonus status in comatose patients after cardiac arrest. Lancet 1994; 343:1642.
  54. Crepeau AZ, Rabinstein AA, Fugate JE, et al. Continuous EEG in therapeutic hypothermia after cardiac arrest: prognostic and clinical value. Neurology 2013; 80:339.
  55. Young GB, Gilbert JJ, Zochodne DW. The significance of myoclonic status epilepticus in postanoxic coma. Neurology 1990; 40:1843.
  56. Arnoldus EP, Lammers GJ. Postanoxic coma: good recovery despite myoclonus status. Ann Neurol 1995; 38:697.
  57. Harper SJ, Wilkes RG. Posthypoxic myoclonus (the Lance-Adams syndrome) in the intensive care unit. Anaesthesia 1991; 46:199.
  58. Krumholz A, Stern BJ, Weiss HD. Outcome from coma after cardiopulmonary resuscitation: relation to seizures and myoclonus. Neurology 1988; 38:401.
  59. Rossetti AO, Oddo M, Liaudet L, Kaplan PW. Predictors of awakening from postanoxic status epilepticus after therapeutic hypothermia. Neurology 2009; 72:744.
  60. Carter BG, Butt W. Review of the use of somatosensory evoked potentials in the prediction of outcome after severe brain injury. Crit Care Med 2001; 29:178.
  61. Chen R, Bolton CF, Young B. Prediction of outcome in patients with anoxic coma: a clinical and electrophysiologic study. Crit Care Med 1996; 24:672.
  62. Robinson LR, Micklesen PJ, Tirschwell DL, Lew HL. Predictive value of somatosensory evoked potentials for awakening from coma. Crit Care Med 2003; 31:960.
  63. Pohlmann-Eden B, Dingethal K, Bender HJ, Koelfen W. How reliable is the predictive value of SEP (somatosensory evoked potentials) patterns in severe brain damage with special regard to the bilateral loss of cortical responses? Intensive Care Med 1997; 23:301.
  64. Zandbergen EG, Koelman JH, de Haan RJ, et al. SSEPs and prognosis in postanoxic coma: only short or also long latency responses? Neurology 2006; 67:583.
  65. Lee YC, Phan TG, Jolley DJ, et al. Accuracy of clinical signs, SEP, and EEG in predicting outcome of hypoxic coma: a meta-analysis. Neurology 2010; 74:572.
  66. Zandbergen EG, Hijdra A, de Haan RJ, et al. Interobserver variation in the interpretation of SSEPs in anoxic-ischaemic coma. Clin Neurophysiol 2006; 117:1529.
  67. 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.
  68. Bouwes A, Binnekade JM, Zandstra DF, et al. Somatosensory evoked potentials during mild hypothermia after cardiopulmonary resuscitation. Neurology 2009; 73:1457.
  69. Leithner C, Ploner CJ, Hasper D, Storm C. Does hypothermia influence the predictive value of bilateral absent N20 after cardiac arrest? Neurology 2010; 74:965.
  70. Steppacher I, Eickhoff S, Jordanov T, et al. N400 predicts recovery from disorders of consciousness. Ann Neurol 2013; 73:594.
  71. Rossetti AO, Logroscino G, Liaudet L, et al. Status epilepticus: an independent outcome predictor after cerebral anoxia. Neurology 2007; 69:255.
  72. Young GB. The EEG in coma. J Clin Neurophysiol 2000; 17:473.
  73. Rossetti AO, Carrera E, Oddo M. Early EEG correlates of neuronal injury after brain anoxia. Neurology 2012; 78:796.
  74. Thenayan EA, Savard M, Sharpe MD, et al. Electroencephalogram for prognosis after cardiac arrest. J Crit Care 2010; 25:300.
  75. Hovland A, Nielsen EW, Klüver J, Salvesen R. EEG should be performed during induced hypothermia. Resuscitation 2006; 68:143.
  76. Vaagenes P, Kjekshus J, Torvik A. The relationship between cerebrospinal fluid creatine kinase and morphologic changes in the brain after transient cardiac arrest. Circulation 1980; 61:1194.
  77. Kärkelä J, Pasanen M, Kaukinen S, et al. Evaluation of hypoxic brain injury with spinal fluid enzymes, lactate, and pyruvate. Crit Care Med 1992; 20:378.
  78. Tirschwell DL, Longstreth WT Jr, Rauch-Matthews ME, et al. Cerebrospinal fluid creatine kinase BB isoenzyme activity and neurologic prognosis after cardiac arrest. Neurology 1997; 48:352.
  79. Müllner M, Sterz F, Domanovits H, et al. The association between blood lactate concentration on admission, duration of cardiac arrest, and functional neurological recovery in patients resuscitated from ventricular fibrillation. Intensive Care Med 1997; 23:1138.
  80. 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.
  81. 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.
  82. Edgren E, Terent A, Hedstrand U, Ronquist G. Cerebrospinal fluid markers in relation to outcome in patients with global cerebral ischemia. Crit Care Med 1983; 11:4.
  83. Zandbergen EG, de Haan RJ, 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.
  84. Meynaar IA, Oudemans-van Straaten HM, van der Wetering J, et al. Serum neuron-specific enolase predicts outcome in post-anoxic coma: a prospective cohort study. Intensive Care Med 2003; 29:189.
  85. Zingler VC, Krumm B, Bertsch T, et al. Early prediction of neurological outcome after cardiopulmonary resuscitation: a multimodal approach combining neurobiochemical and electrophysiological investigations may provide high prognostic certainty in patients after cardiac arrest. Eur Neurol 2003; 49:79.
  86. Tiainen M, Roine RO, Pettilä V, Takkunen O. Serum neuron-specific enolase and S-100B protein in cardiac arrest patients treated with hypothermia. Stroke 2003; 34:2881.
  87. Steffen IG, Hasper D, Ploner CJ, et al. Mild therapeutic hypothermia alters neuron specific enolase as an outcome predictor after resuscitation: 97 prospective hypothermia patients compared to 133 historical non-hypothermia patients. Crit Care 2010; 14:R69.
  88. Cronberg T, Rundgren M, Westhall E, et al. Neuron-specific enolase correlates with other prognostic markers after cardiac arrest. Neurology 2011; 77:623.
  89. Wijman CA, Mlynash M, Caulfield AF, et al. Prognostic value of brain diffusion-weighted imaging after cardiac arrest. Ann Neurol 2009; 65:394.
  90. Wu O, Sorensen AG, Benner T, et al. Comatose patients with cardiac arrest: predicting clinical outcome with diffusion-weighted MR imaging. Radiology 2009; 252:173.
  91. Rutherford M, Pennock J, Schwieso J, et al. Hypoxic-ischaemic encephalopathy: early and late magnetic resonance imaging findings in relation to outcome. Arch Dis Child Fetal Neonatal Ed 1996; 75:F145.
  92. Laureys S, Antoine S, Boly M, et al. Brain function in the vegetative state. Acta Neurol Belg 2002; 102:177.
  93. Wartenberg KE, Patsalides A, Yepes MS. Is magnetic resonance spectroscopy superior to conventional diagnostic tools in hypoxic-ischemic encephalopathy? J Neuroimaging 2004; 14:180.
  94. Mlynash M, Campbell DM, Leproust EM, et al. Temporal and spatial profile of brain diffusion-weighted MRI after cardiac arrest. Stroke 2010; 41:1665.
  95. Coleman MR, Davis MH, Rodd JM, et al. Towards the routine use of brain imaging to aid the clinical diagnosis of disorders of consciousness. Brain 2009; 132:2541.
  96. Grubb NR. Managing out-of-hospital cardiac arrest survivors: 1. Neurological perspective. Heart 2001; 85:6.
  97. Patel R, Jha S. Intravenous valproate in post-anoxic myoclonic status epilepticus: a report of ten patients. Neurol India 2004; 52:394.
  98. Thömke F, Weilemann SL. Poor prognosis despite successful treatment of postanoxic generalized myoclonus. Neurology 2010; 74:1392.