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Coma, Disorders of Consciousness, and Brain Death

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Emergency Neurology

Abstract

Accurate and competent assessment of the spectrum of disorders of consciousness, and an understanding of the neuroanatomical and neurophysiological mechanisms underlying them, is crucial for guiding treatment plans and prognostication. This chapter describes the various presentations seen in disorders of consciousness; the anatomical and physiological foundations of arousal failure; the clinical approach to a patient presenting with acute coma; treatments in acute and chronic coma; and the approach to a patient with suspected brain death. Impairments of consciousness are manifested by spectrum of clinical syndromes ranging from encephalopathy to coma. They are the final pathway for a broad range of diseases that share the common thread of pathophysiological derangement of the pons, midbrain, and thalamus or simultaneous damage to bilateral thalamocortical projections or bilateral cortices. Encephalopathy is an impairment of normal arousal in which the level of arousal fluctuates. Minimally conscious state is a syndrome where the patient is awake but in which there is only evidence of a minimal awareness of self or environment. Akinetic mutism is a rare form of arousal failure, characterized by an emotionless, frequently motionless state with intact visual tracking, and occurs commonly due to lesions in the bilateral anterior cingulate gyri. Unresponsive wakefulness syndrome, a new name for the previously described persistent vegetative state, is a syndrome where patients are awake (eyes open) but remain otherwise unresponsive, showing only reflexive movements. Coma is a state of complete unresponsiveness to external and internal stimuli, typified by a complete failure of normal arousal. Finally, brain death is defined as the irreversible cessation of clinical brain activity. Clinicians must take care to rule out mimics such as the locked-in syndrome and covert consciousness. In locked-in syndrome, patients have intact arousal and awareness but can only communicate through blinking and/or upward gaze due to severe injury in the ventral pons. Recent studies using EEG have also shown evidence of brain activation to commands in otherwise unresponsive patients, suggesting that there are patients with covert consciousness that don’t have the ability to communicate at all.

Physicians must be able to recognize these syndromes, as well as neurological emergencies associated with them. As needed, prompt application of advance cardiac life support (ACLS) and emergency neurological life support (ENLS) algorithms could dramatically impact the course of someone presenting with acute coma. Cerebral herniation associated with a comatose state may require the initiation of a brain code and administration of emergent therapies to decrease ICP including appropriate head of the bed and neck positioning; placement of central access as needed; controlled hyperventilation; and use of hypertonic saline or mannitol. For patients in coma over a longer period of time, new therapies are emerging and being investigated to stimulate patients and maximize their improvement.

The final section of this chapter discusses the diagnosis of brain death. It includes criteria and guidance for the clinical exams involved, and an overview of the various ancillary tests that can be done. It also discusses special considerations for patients undergoing targeted temperature management or on extracorporeal membrane oxygenation.

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References

  1. Posner JB, Plum F. Plum and Posner’s diagnosis of stupor and coma. 4th ed. Oxford: Oxford University Press; 2007.

    Google Scholar 

  2. Laureys S, Celesia GG, Cohadon F, et al. Unresponsive wakefulness syndrome: a new name for the vegetative state or apallic syndrome. BMC Med. 2010;8:68.

    PubMed  PubMed Central  Google Scholar 

  3. Giacino S, Ashwal N, Childs R, Cranford B, Jennett DI, Katz JP, Kelly JH, Rosenberg J, Whyte RD, et al. The minimally conscious state. Neurology. 2002;58(3):349–53.

    PubMed  Google Scholar 

  4. Thibaut A, Bodien YG, Laureys S, Giacino JT. Minimally conscious state “plus”: diagnostic criteria and relation to functional recovery. J Neurol. 2020;267:1245–54.

    PubMed  Google Scholar 

  5. Owen AM, Coleman MR, Boly M, Davis MH, Laureys S, Pickard JD. Detecting awareness in the vegetative state. Science. 2006;313:1402.

    CAS  PubMed  Google Scholar 

  6. Monti MM, Vanhaudenhuyse A, Coleman MR, Boly M, Pickard JD, Tshibanda L, et al. Willful modulation of brain activity in disorders of consciousness. N Engl J Med. 2010;362:579–89.

    CAS  PubMed  Google Scholar 

  7. Edlow BL, Claassen J, Schiff ND, Greer DM. Recovery from disorders of consciousness: mechanisms, prognosis and emerging therapies. Nat Rev Neurol. 2020;14:1–22.

    Google Scholar 

  8. Claasen J, Doyle K, Matory Am Couch C, et al. Detection of brain activation in unresponsive patients with acute brain injury. N Engl J Med. 2019;380:2497–505.

    Google Scholar 

  9. Steriade M. Corticothalamic resonance, states of vigilance and mentation. Neuroscience. 2000;101(2):243–76.

    CAS  PubMed  Google Scholar 

  10. Llinas RR, Steriade M. Bursting of thalamic neurons and states of vigilance. J Neurophysiol. 2006;95(6):3297–308.

    PubMed  Google Scholar 

  11. Hoesch RE, Koenig MA, Geocadin RG. Coma after global ischemic brain injury: pathophysiology and emerging therapies. Crit Care Clin. 2008;24(1):25–44. vii–viii

    PubMed  Google Scholar 

  12. Lindsley DB, Schreiner LH, Knowles WB, Magoun HW. Behavioral and EEG changes following chronic brain stem lesions in the cat. Electroencephalogr Clin Neurophysiol. 1950;2(4):483–98.

    CAS  PubMed  Google Scholar 

  13. Jones BE. Arousal systems. Front Biosci. 2003;8:s438–51.

    CAS  PubMed  Google Scholar 

  14. Starzl TE, Taylor CW, Magoun HW. Ascending conduction in reticular activating system, with special reference to the diencephalon. J Neurophysiol. 1951;14(6):461–77.

    CAS  PubMed  Google Scholar 

  15. Steriade M, Oakson G, Ropert N. Firing rates and patterns of midbrain reticular neurons during steady and transitional states of the sleep-waking cycle. Exp Brain Res. 1982;46(1):37–51.

    CAS  PubMed  Google Scholar 

  16. Jones EG. Thalamic circuitry and thalamocortical synchrony. Philos Trans R Soc Lond Ser B Biol Sci. 2002;357(1428):1659–73.

    Google Scholar 

  17. Groenewegen HJ, Berendse HW. The specificity of the ‘nonspecific’ midline and intralaminar thalamic nuclei. Trends Neurosci. 1994;17(2):52–7.

    CAS  PubMed  Google Scholar 

  18. Lin JS, Sakai K, Vanni-Mercier G, Jouvet M. A critical role of the posterior hypothalamus in the mechanisms of wakefulness determined by microinjection of muscimol in freely moving cats. Brain Res. 1989;479(2):225–40.

    CAS  PubMed  Google Scholar 

  19. Panula P, Yang HY, Costa E. Histamine-containing neurons in the rat hypothalamus. Proc Natl Acad Sci U S A. 1984;81(8):2572–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Jin CY, Kalimo H, Panula P. The histaminergic system in human thalamus: correlation of innervation to receptor expression. Eur J Neurosci. 2002;15(7):1125–38.

    CAS  PubMed  Google Scholar 

  21. Alexandre C, Andermann ML, Scammell TE. Control of arousal by the orexin neurons. Curr Opin Neurobiol. 2013;23(5):752–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Peyron C, Tighe DK, van den Pol AN, de Lecea L, Heller HC, Sutcliffe JG, Kilduff TS. Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci. 1998;18:9996–10015.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Saper CB, Scammell TE, Lu J. Hypothalamic regulation of sleep and circadian rhythms. Nature. 2005;437:1257–63.

    CAS  PubMed  Google Scholar 

  24. Rye DB, Wainer BH, Mesulam MM, Mufson EJ, Saper CB. Cortical projections arising from the basal forebrain: a study of cholinergic and noncholinergic components employing combined retrograde tracing and immunohistochemical localization of choline acetyltransferase. Neuroscience. 1984;13(3):627–43.

    CAS  PubMed  Google Scholar 

  25. Buzsaki G, Bickford RG, Ponomareff G, Thal LJ, Mandel R, Gage FH. Nucleus basalis and thalamic control of neocortical activity in the freely moving rat. J Neurosci. 1988;8(11):4007–26.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Szymusiak R, McGinty D. Sleep-related neuronal discharge in the basal forebrain of cats. Brain Res. 1986;370(1):82–92.

    CAS  PubMed  Google Scholar 

  27. Hinchey J, Chaves C, Appignani B, Breen J, Pao L, Wang A, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med. 1996;334(8):494–500.

    CAS  Google Scholar 

  28. McKinney AM, Jagadeesan BD, Truwit CL. Central-variant posterior reversible encephalopathy syndrome: brainstem or basal ganglia involvement lacking cortical or subcortical cerebral edema. AJR Am J Roentgenol. 2013;201:631–8.

    PubMed  Google Scholar 

  29. Hinduja A. Posterior reversible encephalopathy syndrome: clinical features and outcome. Front Neurol. 2020;11:71.

    PubMed  PubMed Central  Google Scholar 

  30. Ishii M. Endocrine emergencies with neurological manifestations. Continuum (Minneap Minn). 2017;23(3):778–801.

    Google Scholar 

  31. Krause M, Hocker S. Toxin-induced coma and central nervous system depression. Neurol Clin. 2020;38(4):825–41.

    PubMed  Google Scholar 

  32. McNicoll L, Pisani MA, Zhang Y, Ely EW, Siegel MD, Inouye SK. Delirium in the intensive care unit: occurrence and clinical course in older patients. J Am Geriatr Soc. 2003;51(5):591–8.

    PubMed  Google Scholar 

  33. Volpi-Abadie J, Kaye AM, Kaye AD. Serotonin syndrome. Oschsner J. 2013;13(4):533–40.

    Google Scholar 

  34. Oruch R, Pryme IF, Engelsen BA, Lund A. Neuroleptic malignant syndrome; an easily overlooked medical emergency. Neuropsychiatr Dis Treat. 2017;13:161–75.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Venkatasubramanian C, Lopez GA, O’Phelan KH, et al. Emergency neurological life support: fourth edition, updates in the approach to early management of a neurological emergency. Neurocrit Care. 2020;32:636–40.

    PubMed  Google Scholar 

  36. Fodstad H, Kelly PJ, Buchfelder M. History of the cushing reflex. Neurosurgery. 2006;59(5):1132–7. discussion 1137

    PubMed  Google Scholar 

  37. Wijdicks EF, Bamlet WR, Maramattom BV, Manno EM, McClelland RL. Validation of a new coma scale: the FOUR score. Ann Neurol. 2005;58(4):585–93.

    PubMed  Google Scholar 

  38. Iyer VN, Mandrekar JN, Danielson RD, Zubkov AY, Elmer JL, Wijdicks EF. Validity of the FOUR score coma scale in the medical intensive care unit. Mayo Clin Proc. 2009;84:694–701.

    PubMed  PubMed Central  Google Scholar 

  39. Anderson CS, Heeley E, Huang Y, Wang J, Stapf C, Delcourt C, INTERACT2 Investigators, et al. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med. 2013;368:2355–65.

    CAS  PubMed  Google Scholar 

  40. Hemphill JC, Greenberg SM, Anderson CS, Becker K, Bendok BR, Cushman M, et al. American Heart Association Stroke Council; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2015;46:2032–60.

    PubMed  Google Scholar 

  41. Farrokh S, Cho SM, Lefebvre AT, Zink EK, Schiavi A, Puttgen HA. Use of intraosseous hypertonic saline in critically ill patients. J Vasc Access. 2019;20(4):427–32.

    PubMed  Google Scholar 

  42. Qureshi AI, Geocadin RG, Suarez JI, Ulatowski JA. Long-term outcome after medical reversal of transtentorial herniation in patients with supratentorial mass lesions. Crit Care Med. 2000;28(5):1556–64.

    CAS  PubMed  Google Scholar 

  43. Koenig MA, Bryan M, Lewin JL, Mirski MA, Geocadin RG, Stevens RD. Reversal of transtentorial herniation with hypertonic saline. Neurology. 2008;70(13):1023–9.

    CAS  PubMed  Google Scholar 

  44. Brazis PW, Masdeu JC, Biller J. Localization in clinical neurology. 5th ed. Philadelphia: Lippincott Williams & Wilkins; 2007.

    Google Scholar 

  45. Liu GT, Ronthal M. Reflex blink to visual threat. J Clin Neuroophthalmol. 1992;12(1):47–56.

    CAS  PubMed  Google Scholar 

  46. Baloh RW, Yee RD, Honrubia V. Optokinetic nystagmus and parietal lobe lesions. Ann Neurol. 1980;7(3):269–76.

    CAS  PubMed  Google Scholar 

  47. Geocadin RG, Callaway CW, Fink EL, Golan E, Greer DM, Ko NU, Lang E, Licht DJ, Marino BS, McNair ND, Peberdy MA, Perman SM, Sims DB, Soar J, Sandroni C, American Heart Association Emergency Cardiovascular Care Committee. Standards for studies of neurological prognostication in comatose survivors of cardiac arrest: a scientific statement from the American Heart Association. Circulation. 2019;140(9):e517–42.

    PubMed  Google Scholar 

  48. Giacino JT, Kalmar K, White J. The JFK coma recovery scale – revised: measurement characteristics and diagnostic utility. Arch Phys Med Rehabil. 2004;85(12):2020–9.

    PubMed  Google Scholar 

  49. Thibaut A, Schiff N, Giacino J, Laureys S, Gosseries O. Therapeutic interventions in patients with prolonged disorders of consciousness. Lancet Neurol. 2019;18:600–14.

    PubMed  Google Scholar 

  50. Giacino JT, Katz D, Schiff N, et al. Practice guideline update recommendations summary: disorders of consciousness. Neurology. 2018;91:450–60.

    PubMed  PubMed Central  Google Scholar 

  51. Giacino JT, Whyte J, Bagiella E, Kalmar K, Childs N, Khademi A, Eifert B, Long D, Katz DI, Cho S, Yablon SA, Luther M, Hammond FM, Nordenbo A, Novak P, Mercer W, Maurer-Karattup P, Sherer M. Placebo-controlled trial of amantadine for severe traumatic brain injury. N Engl J Med. 2012;366:819–26.

    CAS  PubMed  Google Scholar 

  52. Schnakers C, Hustinx R, Vandewalle G, et al. Measuring the effect of amantadine in chronic anoxic minimally conscious state. J Neurol Neurosurg Psychiatry. 2008;79:225–7.

    CAS  PubMed  Google Scholar 

  53. Estraneo A, Pascarella A, Moretta P, Loreto V, Trojano L. Clinical and electroencephalographic on–off effect of amantadine in chronic non-traumatic minimally conscious state. J Neurol. 2015;262:1584–6.

    CAS  PubMed  Google Scholar 

  54. Herrold AA, Pape TLB, Guernon A, Mallinson T, Collins E, Jordan N. Prescribing multiple neurostimulants during rehabilitation for severe brain injury. Sci World J. 2014;2014:964578.

    Google Scholar 

  55. Gosseries O, Charland-Verville V, Thonnard M, Bodart O, Laureys S, Demertzi A. Amantadine, apomorphine and zolpidem in the treatment of disorders of consciousness. Curr Pharm Des. 2014;20:4167–84.

    CAS  PubMed  Google Scholar 

  56. Fridman EA, Calvar J, Bonetto M, Gamzu E, Krimchansky BZ, Meli F, et al. Fast awakening from minimally conscious state with apomorphine. Brain Inj. 2009;23:172–7.

    PubMed  Google Scholar 

  57. Fridman EA, Krimchansky BZ, Bonetto M, Galperin T, Gamzu ER, Leiguarda RC, et al. Continuous subcutaneous apomorphine for severe disorders of consciousness after traumatic brain injury. Brain Inj. 2010;24:636–461.

    PubMed  Google Scholar 

  58. Margetis K, Korfias SI, Gatzonis S, et al. Intrathecal baclofen associated with improvement of consciousness disorders in spasticity patients. Neuromodulation. 2014;17:699–704.

    PubMed  Google Scholar 

  59. Whyte J, Rajan R, Rosenbaum A, et al. Zolpidem and restoration of consciousness. Am J Phys Med Rehabil. 2014;93:101–13.

    PubMed  Google Scholar 

  60. Machado C, Estevez M, Rodriguez R, et al. Zolpidem arousing effect in persistent vegetative state patients: autonomic, EEG and behavioral assessment. Curr Pharm Des. 2014;20:4185–202.

    CAS  PubMed  Google Scholar 

  61. Calabrò RS, Aricò I, De Salvo S, Conti-Nibali V, Bramanti P. Transient awakening from vegetative state: is high-dose zolpidem more effective? Psychiatry Clin Neurosci. 2015;69:122–3.

    PubMed  Google Scholar 

  62. Thonnard M, Gosseries O, Demertzi A, et al. Effect of zolpidem in chronic disorders of consciousness: a prospective open-label study. Funct Neurol. 2014;28:259–64.

    PubMed Central  Google Scholar 

  63. Williams ST, Conte MM, Goldfine AM, et al. Common resting brain dynamics indicate a possible mechanism underlying zolpidem response in severe brain injury. elife. 2013;2:e01157.

    PubMed  PubMed Central  Google Scholar 

  64. Scott G, Carhart-Harris RL. Psychedelics as a treatment for disorders of consciousness. Neurosci Conscious. 2019;2019:niz003.

    PubMed  PubMed Central  Google Scholar 

  65. Varley TF, Carhart-Harris R, Roseman L, Menon DK, Stamatakis EA. Serotonergic psychedelics LSD & psilocybin increase the fractal dimension of cortical brain activity in spatial and temporal domains. NeuroImage. 2020;220:117049. https://doi.org/10.1016/j.neuroimage.2020.117049.

    Article  CAS  PubMed  Google Scholar 

  66. Thibaut A, Bruno M-A, Ledoux D, Demertzi A, Laureys S. tDCS in patients with disorders of consciousness: sham-controlled randomized double-blind study. Neurology. 2014;82:1112–8.

    PubMed  Google Scholar 

  67. Pape TL-B, Rosenow JM, Harton B, et al. Preliminary framework for Familiar Auditory Sensory Training (FAST) provided during coma recovery. J Rehabil Res Dev. 2012;49:1137.

    PubMed  Google Scholar 

  68. Mollaret P, Goulon M. Le coma depasse. Rev Neurol (Paris). 1959;101:3–15.

    CAS  Google Scholar 

  69. A definition of irreversible coma: report of the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death. JAMA. 1968;205:337–40.

    Google Scholar 

  70. President’s Commission for the Study of Ethical Problems in Medicine and Biomedical Behavioral Research. Defining Death: A Report on the Medical, Legal and Ethical Issues in the Determination of Death. President’s Council on Bioethics; 1981.

    Google Scholar 

  71. The Quality Standards Subcommittee of the American Academy of Neurology. Practice parameters for determining brain death in adults (summary statement). Neurology. 1995;45(5):1012–4.

    Google Scholar 

  72. Wijdicks EFM, Varelas PN, Gronseth GS, Greer DM. Evidence-based guideline update: determining brain death in adults—report of the quality standards subcommittee of the American Academy of Neurology. Neurology. 2010;74(23):1911–8.

    PubMed  Google Scholar 

  73. Greer DM, Varelas PN, Haque S, Wijdicks EFM. Variability of brain death determination guidelines in leading US neurologic institutions. Neurology. 2008;70(4):284–9.

    PubMed  Google Scholar 

  74. Greer DM, Shemie SD, Lewis A, Torrance S, Varelas P, Goldenberg FD, Bernat JL, Souter M, Topcuoglu MA, Alexandrov AW, Baldisseri M, Bleck T, Citerio G, Dawson R, Hoppe A, Jacobe S, Manara A, Nakagawa TA, Pope TM, Silvester W, Thomson D, Al Rahma H, Badenes R, Baker AJ, Cerny V, Chang C, Chang TR, Gnedovskaya E, Han MK, Honeybul S, Jimenez E, Kuroda Y, Liu G, Mallick UK, Marquevich V, Mejia-Mantilla J, Piradov M, Quayyum S, Shrestha GS, Su YY, Timmons SD, Teitelbaum J, Videtta W, Zirpe K, Sung G. Determination of brain death/death by neurologic criteria: the world brain death project. JAMA. 2020;324:1078–97.

    PubMed  Google Scholar 

  75. Lewis A, Bakkar A, Kreiger-Benson E, Kumpfbeck A, Liebman J, Shemie SD, Sung G, Torrance S, Greer D. Determination of death by neurologic criteria around the world. Neurology. 2020;95:e299–309.

    PubMed  Google Scholar 

  76. Machado C. Brain death: a reappraisal. New York: Springer Science+Business Media, LLC; 2007.

    Google Scholar 

  77. Machado C. Jahi McMath: a new state of disorder of consciousness. J Neurosurg Sci. 2021;65(2):211–3.

    PubMed  Google Scholar 

  78. Walter U, Fernandez-Torre JL, Kirschstein T, Laureys S. When is "brainstem death" brain death? The case for ancillary testing in primary infratentorial brain lesion. Clin Neurophysiol. 2018;129:2451–65.

    PubMed  Google Scholar 

  79. Machado C. Multimodality evoked potentials and electroretinography in a test battery for an early diagnosis of brain death. J Neurosurg Sci. 1993;37:125–31.

    CAS  PubMed  Google Scholar 

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Mathur, R., Balucani, C., Elmashala, A., Geocadin, R. (2021). Coma, Disorders of Consciousness, and Brain Death. In: Roos, K.L. (eds) Emergency Neurology. Springer, Cham. https://doi.org/10.1007/978-3-030-75778-6_17

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