Semin Neurol 2013; 33(02): 083-090
DOI: 10.1055/s-0033-1348965
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Coma and Disorders of Consciousness: Scientific Advances and Practical Considerations for Clinicians

Olivier Bodart
1   Department of Neurology, Coma Science Group, Cyclotron Research Center, University of Liège, University Hospital of Liège, Liège, Belgium
,
Steven Laureys
1   Department of Neurology, Coma Science Group, Cyclotron Research Center, University of Liège, University Hospital of Liège, Liège, Belgium
,
Olivia Gosseries
1   Department of Neurology, Coma Science Group, Cyclotron Research Center, University of Liège, University Hospital of Liège, Liège, Belgium
› Author Affiliations
Further Information

Publication History

Publication Date:
25 July 2013 (online)

Abstract

Recently, neuroscientists and clinicians have seen the rapid evolution of diagnoses in disorders of consciousness. The unresponsive wakefulness syndrome–vegetative state, the minimally conscious state plus and minus, and the functional locked-in syndrome have been defined using new neuroimaging techniques. Diffusion tensor imaging, positron emission tomography, functional magnetic resonance imaging, electroencephalography, and transcranial magnetic stimulation techniques have all promoted important discoveries in the field of disorders of consciousness. This has led to a better understanding of these patients' condition and to the development of new prognosis, therapeutic, and communication tools. However, low sensitivity and artifacts problems need to be solved to bring these new technologies to the single-patient level; they also need to be studied in larger scale and randomized control trials. In addition, new ethics questions have arisen and need to be investigated.

 
  • References

  • 1 Giacino JT, Ashwal S, Childs N , et al. The minimally conscious state: definition and diagnostic criteria. Neurology 2002; 58 (3) 349-353
  • 2 Jennett B, Plum F. Persistent vegetative state after brain damage. A syndrome in search of a name. Lancet 1972; 1 (7753) 734-737
  • 3 The Multi-Society Task Force on PVS. Medical aspects of the persistent vegetative state (1). N Engl J Med 1994; 330 (21) 1499-1508
  • 4 The Multi-Society Task Force on PVS. Medical aspects of the persistent vegetative state (2). N Engl J Med 1994; 330 (22) 1572-1579
  • 5 Laureys S, Celesia GG, Cohadon F , et al; European Task Force on Disorders of Consciousness. Unresponsive wakefulness syndrome: a new name for the vegetative state or apallic syndrome. BMC Med 2010; 8: 68
  • 6 Bruno MA, Vanhaudenhuyse A, Thibaut A, Moonen G, Laureys S. From unresponsive wakefulness to minimally conscious PLUS and functional locked-in syndromes: recent advances in our understanding of disorders of consciousness. J Neurol 2011; 258 (7) 1373-1384
  • 7 Gosseries O, Bruno M-A, Vanhaudenhuyse A , et al. Consciousness in the locked-in syndrome. In: Laureys S, Tononi G, , eds. The Neurology of Consciousness: Cognitive Neuroscience and Neuropathology. Oxford, United Kingdom: Elsevier; 2009: 191-203
  • 8 Seel RT, Sherer M, Whyte J , et al; American Congress of Rehabilitation Medicine, Brain Injury-Interdisciplinary Special Interest Group, Disorders of Consciousness Task Force. Assessment scales for disorders of consciousness: evidence-based recommendations for clinical practice and research. Arch Phys Med Rehabil 2010; 91 (12) 1795-1813
  • 9 Giacino JT, Kalmar K, Whyte J. The JFK Coma Recovery Scale-Revised: measurement characteristics and diagnostic utility. Arch Phys Med Rehabil 2004; 85 (12) 2020-2029
  • 10 Seel RT, Sherer M, Whyte J , et al; American Congress of Rehabilitation Medicine, Brain Injury-Interdisciplinary Special Interest Group, Disorders of Consciousness Task Force. Assessment scales for disorders of consciousness: evidence-based recommendations for clinical practice and research. Arch Phys Med Rehabil 2010; 91 (12) 1795-1813
  • 11 Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet 1974; 2 (7872) 81-84
  • 12 Wijdicks EF, Bamlet WR, Maramattom BV, Manno EM, McClelland RL. Validation of a new coma scale: the FOUR score. Ann Neurol 2005; 58 (4) 585-593
  • 13 Bruno MA, Ledoux D, Lambermont B , et al. Comparison of the Full Outline of UnResponsiveness and Glasgow Liege Scale/Glasgow Coma Scale in an intensive care unit population. Neurocrit Care 2011; 15 (3) 447-453
  • 14 Schnakers C, Vanhaudenhuyse A, Giacino J , et al. Diagnostic accuracy of the vegetative and minimally conscious state: clinical consensus versus standardized neurobehavioral assessment. BMC Neurol 2009; 9: 35
  • 15 Gill-Thwaites H. Lotteries, loopholes and luck: misdiagnosis in the vegetative state patient. Brain Inj 2006; 20 (13-14) 1321-1328
  • 16 Godbolt AK, Stenson S, Winberg M, Tengvar C. Disorders of consciousness: preliminary data supports added value of extended behavioural assessment. Brain Inj 2012; 26 (2) 188-193
  • 17 Jennett B, Bond M. Assessment of outcome after severe brain damage. Lancet 1975; 1 (7905) 480-484
  • 18 Yanagawa Y, Tsushima Y, Tokumaru A , et al. A quantitative analysis of head injury using T2*-weighted gradient-echo imaging. J Trauma 2000; 49 (2) 272-277
  • 19 Kampfl A, Schmutzhard E, Franz G , et al. Prediction of recovery from post-traumatic vegetative state with cerebral magnetic-resonance imaging. Lancet 1998; 351 (9118) 1763-1767
  • 20 Firsching R, Woischneck D, Diedrich M , et al. Early magnetic resonance imaging of brainstem lesions after severe head injury. J Neurosurg 1998; 89 (5) 707-712
  • 21 Hoelper BM, Soldner F, Choné L, Wallenfang T. Effect of intracerebral lesions detected in early MRI on outcome after acute brain injury. Acta Neurochir Suppl (Wien) 2000; 76: 265-267
  • 22 Paterakis K, Karantanas AH, Komnos A, Volikas Z. Outcome of patients with diffuse axonal injury: the significance and prognostic value of MRI in the acute phase. J Trauma 2000; 49 (6) 1071-1075
  • 23 Karantanas A, Paterakis K. Magnetic resonance imaging and brainstem injury. J Neurosurg 2000; 92 (5) 896-897
  • 24 Weiss N, Galanaud D, Carpentier A , et al. A combined clinical and MRI approach for outcome assessment of traumatic head injured comatose patients. J Neurol 2008; 255 (2) 217-223
  • 25 Tshibanda L, Vanhaudenhuyse A, Galanaud D, Boly M, Laureys S, Puybasset L. Magnetic resonance spectroscopy and diffusion tensor imaging in coma survivors: promises and pitfalls. Prog Brain Res 2009; 177: 215-229
  • 26 Fernández-Espejo D, Bekinschtein T, Monti MM , et al. Diffusion weighted imaging distinguishes the vegetative state from the minimally conscious state. Neuroimage 2011; 54 (1) 103-112
  • 27 Huisman TA, Schwamm LH, Schaefer PW , et al. Diffusion tensor imaging as potential biomarker of white matter injury in diffuse axonal injury. AJNR Am J Neuroradiol 2004; 25 (3) 370-376
  • 28 Perlbarg V, Puybasset L, Tollard E, Lehéricy S, Benali H, Galanaud D. Relation between brain lesion location and clinical outcome in patients with severe traumatic brain injury: a diffusion tensor imaging study using voxel-based approaches. Hum Brain Mapp 2009; 30 (12) 3924-3933
  • 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 (7) 2005-2011
  • 30 Tommasino C, Grana C, Lucignani G, Torri G, Fazio F. Regional cerebral metabolism of glucose in comatose and vegetative state patients. J Neurosurg Anesthesiol 1995; 7 (2) 109-116
  • 31 Beuthien-Baumann B, Handrick W, Schmidt T , et al. Persistent vegetative state: evaluation of brain metabolism and brain perfusion with PET and SPECT. Nucl Med Commun 2003; 24 (6) 643-649
  • 32 Rudolf J, Ghaemi M, Ghaemi M, Haupt WF, Szelies B, Heiss WD. Cerebral glucose metabolism in acute and persistent vegetative state. J Neurosurg Anesthesiol 1999; 11 (1) 17-24
  • 33 Laureys S, Owen AM, Schiff ND. Brain function in coma, vegetative state, and related disorders. Lancet Neurol 2004; 3 (9) 537-546
  • 34 Laureys S, Goldman S, Phillips C , et al. Impaired effective cortical connectivity in vegetative state: preliminary investigation using PET. Neuroimage 1999; 9 (4) 377-382
  • 35 Nakayama N, Okumura A, Shinoda J, Nakashima T, Iwama T. Relationship between regional cerebral metabolism and consciousness disturbance in traumatic diffuse brain injury without large focal lesions: an FDG-PET study with statistical parametric mapping analysis. J Neurol Neurosurg Psychiatry 2006; 77 (7) 856-862
  • 36 Laureys S, Faymonville ME, Luxen A, Lamy M, Franck G, Maquet P. Restoration of thalamocortical connectivity after recovery from persistent vegetative state. Lancet 2000; 355 (9217) 1790-1791
  • 37 Thibaut A, Bruno MA, Chatelle C , et al. Metabolic activity in external and internal awareness networks in severely brain-damaged patients. J Rehabil Med 2012; 44 (6) 487-494
  • 38 Vanhaudenhuyse A, Noirhomme Q, Tshibanda LJ , et al. Default network connectivity reflects the level of consciousness in non-communicative brain-damaged patients. Brain 2010; 133 (Pt 1) 161-171
  • 39 Boly M, Tshibanda L, Vanhaudenhuyse A , et al. Functional connectivity in the default network during resting state is preserved in a vegetative but not in a brain dead patient. Hum Brain Mapp 2009; 30 (8) 2393-2400
  • 40 Norton L, Hutchison RM, Young GB, Lee DH, Sharpe MD, Mirsattari SM. Disruptions of functional connectivity in the default mode network of comatose patients. Neurology 2012; 78 (3) 175-181
  • 41 Babiloni C, Sarà M, Vecchio F , et al. Cortical sources of resting-state alpha rhythms are abnormal in persistent vegetative state patients. Clin Neurophysiol 2009; 120 (4) 719-729
  • 42 Gosseries O, Schnakers C, Ledoux D , et al. Automated EEG entropy measurements in coma, vegetative state/unresponsive wakefulness syndrome and minimally conscious state. Funct Neurol 2011; 26 (1) 25-30
  • 43 Friston KJ. Functional and effective connectivity: a review. Brain Connect 2011; 1 (1) 13-36
  • 44 Massimini M, Ferrarelli F, Murphy M , et al. Cortical reactivity and effective connectivity during REM sleep in humans. Cogn Neurosci 2010; 1 (3) 176-183
  • 45 Rosanova M, Gosseries O, Casarotto S , et al. Recovery of cortical effective connectivity and recovery of consciousness in vegetative patients. Brain 2012; 135 (Pt 4) 1308-1320
  • 46 Massimini M, Ferrarelli F, Huber R, Esser SK, Singh H, Tononi G. Breakdown of cortical effective connectivity during sleep. Science 2005; 309 (5744) 2228-2232
  • 47 Ferrarelli F, Massimini M, Sarasso S , et al. Breakdown in cortical effective connectivity during midazolam-induced loss of consciousness. Proc Natl Acad Sci U S A 2010; 107 (6) 2681-2686
  • 48 Boly M, Faymonville ME, Peigneux P , et al. Auditory processing in severely brain injured patients: differences between the minimally conscious state and the persistent vegetative state. Arch Neurol 2004; 61 (2) 233-238
  • 49 Schiff ND, Ribary U, Moreno DR , et al. Residual cerebral activity and behavioural fragments can remain in the persistently vegetative brain. Brain 2002; 125 (Pt 6) 1210-1234
  • 50 Giacino JT, Hirsch J, Schiff N, Laureys S. Functional neuroimaging applications for assessment and rehabilitation planning in patients with disorders of consciousness. Arch Phys Med Rehabil 2006; 87 (12) (Suppl. 02) S67-S76
  • 51 Laureys S, Faymonville ME, Peigneux P , et al. Cortical processing of noxious somatosensory stimuli in the persistent vegetative state. Neuroimage 2002; 17 (2) 732-741
  • 52 Boly M, Faymonville ME, Schnakers C , et al. Perception of pain in the minimally conscious state with PET activation: an observational study. Lancet Neurol 2008; 7 (11) 1013-1020
  • 53 Silva S, Alacoque X, Fourcade O , et al. Wakefulness and loss of awareness: brain and brainstem interaction in the vegetative state. Neurology 2010; 74 (4) 313-320
  • 54 Owen AM, Menon DK, Johnsrude IS , et al. Detecting residual cognitive function in persistent vegetative state. Neurocase 2002; 8 (5) 394-403
  • 55 Qin P, Di H, Liu Y , et al. Anterior cingulate activity and the self in disorders of consciousness. Hum Brain Mapp 2010; 31 (12) 1993-2002
  • 56 Di HB, Yu SM, Weng XC , et al. Cerebral response to patient's own name in the vegetative and minimally conscious states. Neurology 2007; 68 (12) 895-899
  • 57 Vanhaudenhuyse A, Laureys S, Perrin F. Cognitive event-related potentials in comatose and post-comatose states. Neurocrit Care 2008; 8 (2) 262-270
  • 58 Boly M, Garrido MI, Gosseries O , et al. Preserved feedforward but impaired top-down processes in the vegetative state. Science 2011; 332 (6031) 858-862
  • 59 Owen AM, Coleman MR, Boly M, Davis MH, Laureys S, Pickard JD. Detecting awareness in the vegetative state. Science 2006; 313 (5792) 1402
  • 60 Boly M, Coleman MR, Davis MH , et al. When thoughts become action: an fMRI paradigm to study volitional brain activity in non-communicative brain injured patients. Neuroimage 2007; 36 (3) 979-992
  • 61 Bekinschtein TA, Manes FF, Villarreal M, Owen AM, Della-Maggiore V. Functional imaging reveals movement preparatory activity in the vegetative state. Front Hum Neurosci 2011; 5: 5
  • 62 Bardin JC, Schiff ND, Voss HU. Pattern classification of volitional functional magnetic resonance imaging responses in patients with severe brain injury. Arch Neurol 2012; 69 (2) 176-181
  • 63 Monti MM, Vanhaudenhuyse A, Coleman MR , et al. Willful modulation of brain activity in disorders of consciousness. N Engl J Med 2010; 362 (7) 579-589
  • 64 Rodriguez Moreno D, Schiff ND, Giacino J, Kalmar K, Hirsch J. A network approach to assessing cognition in disorders of consciousness. Neurology 2010; 75 (21) 1871-1878
  • 65 Monti MM, Pickard JD, Owen AM. Visual cognition in disorders of consciousness: From V1 to top-down attention. Hum Brain Mapp 2013; 34 (6) 1245-1253
  • 66 Schnakers C, Perrin F, Schabus M , et al. Voluntary brain processing in disorders of consciousness. Neurology 2008; 71 (20) 1614-1620
  • 67 Cruse D, Chennu S, Chatelle C , et al. Bedside detection of awareness in the vegetative state: a cohort study. Lancet 2011; 378 (9809) 2088-2094
  • 68 Bekinschtein TA, Dehaene S, Rohaut B, Tadel F, Cohen L, Naccache L. Neural signature of the conscious processing of auditory regularities. Proc Natl Acad Sci U S A 2009; 106 (5) 1672-1677
  • 69 Cruse D, Owen AM. Consciousness revealed: new insights into the vegetative and minimally conscious states. Curr Opin Neurol 2010; 23 (6) 656-660
  • 70 Goldfine AM, Victor JD, Conte MM, Bardin JC, Schiff ND. Determination of awareness in patients with severe brain injury using EEG power spectral analysis. Clin Neurophysiol 2011; 122 (11) 2157-2168
  • 71 Sorger B, Reithler J, Dahmen B, Goebel R. A real-time fMRI-based spelling device immediately enabling robust motor-independent communication. Curr Biol 2012; 22 (14) 1333-1338
  • 72 Lulé D, Noirhomme Q, Kleih SC , et al. Probing command following in patients with disorders of consciousness using a brain-computer interface. Clin Neurophysiol 2013; 124 (1) 101-106
  • 73 Bardin JC, Fins JJ, Katz DI , et al. Dissociations between behavioural and functional magnetic resonance imaging-based evaluations of cognitive function after brain injury. Brain 2011; 134 (Pt 3) 769-782
  • 74 Soddu A, Vanhaudenhuyse A, Demertzi A , et al. Resting state activity in patients with disorders of consciousness. Funct Neurol 2011; 26 (1) 37-43
  • 75 Bruno MA, Vanhaudenhuyse A, Schnakers C , et al. Visual fixation in the vegetative state: an observational case series PET study. BMC Neurol 2010; 10: 35
  • 76 Vanhaudenhuyse A, Schnakers C, Brédart S, Laureys S. Assessment of visual pursuit in post-comatose states: use a mirror. J Neurol Neurosurg Psychiatry 2008; 79 (2) 223
  • 77 Vanhaudenhuyse A, Giacino J, Schnakers C , et al. Blink to visual threat does not herald consciousness in the vegetative state. Neurology 2008; 71 (17) 1374-1375
  • 78 Noé E, Olaya J, Navarro MD , et al. Behavioral recovery in disorders of consciousness: a prospective study with the Spanish version of the Coma Recovery Scale-Revised. Arch Phys Med Rehabil 2012; 93 (3) 428-433.e12
  • 79 Whyte J, Gosseries O, Chervoneva I , et al. Predictors of short-term outcome in brain-injured patients with disorders of consciousness. Prog Brain Res 2009; 177: 63-72
  • 80 Estraneo A, Moretta P, Loreto V, Lanzillo B, Santoro L, Trojano L. Late recovery after traumatic, anoxic, or hemorrhagic long-lasting vegetative state. Neurology 2010; 75 (3) 239-245
  • 81 Luauté J, Maucort-Boulch D, Tell L , et al. Long-term outcomes of chronic minimally conscious and vegetative states. Neurology 2010; 75 (3) 246-252
  • 82 Luauté J, Fischer C, Adeleine P, Morlet D, Tell L, Boisson D. Late auditory and event-related potentials can be useful to predict good functional outcome after coma. Arch Phys Med Rehabil 2005; 86 (5) 917-923
  • 83 Daltrozzo J, Wioland N, Mutschler V, Kotchoubey B. Predicting coma and other low responsive patients outcome using event-related brain potentials: a meta-analysis. Clin Neurophysiol 2007; 118 (3) 606-614
  • 84 Fischer C, Luauté J, Némoz C, Morlet D, Kirkorian G, Mauguière F. Improved prediction of awakening or nonawakening from severe anoxic coma using tree-based classification analysis. Crit Care Med 2006; 34 (5) 1520-1524
  • 85 Demertzi A, Schnakers C, Ledoux D , et al. Different beliefs about pain perception in the vegetative and minimally conscious states: a European survey of medical and paramedical professionals. Prog Brain Res 2009; 177: 329-338
  • 86 Demertzi A, Ledoux D, Bruno MA , et al. Attitudes towards end-of-life issues in disorders of consciousness: a European survey. J Neurol 2011; 258 (6) 1058-1065
  • 87 Schnakers C, Chatelle C, Vanhaudenhuyse A , et al. The Nociception Coma Scale: a new tool to assess nociception in disorders of consciousness. Pain 2010; 148 (2) 215-219
  • 88 Giacino JT, Whyte J, Bagiella E , et al. Placebo-controlled trial of amantadine for severe traumatic brain injury. N Engl J Med 2012; 366 (9) 819-826
  • 89 Brefel-Courbon C, Payoux P, Ory F , et al. Clinical and imaging evidence of zolpidem effect in hypoxic encephalopathy. Ann Neurol 2007; 62 (1) 102-105
  • 90 Clauss RP, Güldenpfennig WM, Nel HW, Sathekge MM, Venkannagari RR. Extraordinary arousal from semi-comatose state on zolpidem. A case report. S Afr Med J 2000; 90 (1) 68-72
  • 91 Whyte J, Myers R. Incidence of clinically significant responses to zolpidem among patients with disorders of consciousness: a preliminary placebo controlled trial. Am J Phys Med Rehabil 2009; 88 (5) 410-418
  • 92 Chew E, Zafonte RD. Pharmacological management of neurobehavioral disorders following traumatic brain injury—a state-of-the-art review. J Rehabil Res Dev 2009; 46 (6) 851-879
  • 93 Schiff ND, Giacino JT, Kalmar K , et al. Behavioural improvements with thalamic stimulation after severe traumatic brain injury. Nature 2007; 448 (7153) 600-603
  • 94 Gosseries O, Thonnard M, Laureys S. Pharmacological treatment. In: Schnakers C, Laureys S, , eds. Coma and disorders of consciousness. London, UK: Springer-Verlag; 2012: 121-138
  • 95 Larriviere D, Bonnie RJ. Terminating artificial nutrition and hydration in persistent vegetative state patients: current and proposed state laws. Neurology 2006; 66 (11) 1624-1628
  • 96 Bruno MA, Vanhaudenhuyse A, Thibaut A, Moonen G, Laureys S. From unresponsive wakefulness to minimally conscious PLUS and functional locked-in syndromes: recent advances in our understanding of disorders of consciousness. J Neurol 2011; 258 (7) 1373-1384
  • 97 Massimini M, Ferrarelli F, Murphy M , et al. Cortical reactivity and effective connectivity during REM sleep in humans. Cogn Neurosci 2010; 1 (3) 176-183