Recent advances in disorders of consciousness: Focus on the diagnosis

Abstract Background: Over the last two decades, there has been a considerable increase in knowledge of brain function in patients with disorders of consciousness following a coma. Differentiating between patients in unresponsive wakefulness syndrome and in minimally conscious state still represents a major clinical, legal and ethical challenge. Objectives: This review focuses on recent behavioural and neuroimaging studies in this specific population. Results: The growing interest in the use of neuroimaging techniques as new diagnostic tools has stimulated research in this area and created further challenges to clinical categorization and management. This study proposes a diagnostic procedure combining the use of behavioural scales and neuroimaging techniques. In cases of dissociation between behavioural and ancillary test results, it is suggested that a diagnostic label of ‘non-behavioural MCS’ (MCS*) be used to provide a more clinically accurate diagnosis (and, in theory, prognosis) when the bedside exam shows no evidence of consciousness, yet the neurodiagnostic work-up does. Conclusion: More neuroimaging research is needed before clinical implementation to reach the single-subject diagnosis level, as well as to address the sensitivity and specificity of each technique, whether single or combined.

[1]  Multi-Society Task Force on Pvs Medical aspects of the persistent vegetative state (2). , 1994, The New England journal of medicine.

[2]  L. Naccache,et al.  A combined clinical and MRI approach for outcome assessment of traumatic head injured comatose patients , 2008, Journal of Neurology.

[3]  S. Gevers Withdrawing life support from patients in a persistent vegetative state: the law in the Netherlands. , 2005, European journal of health law.

[4]  Valeria Della-Maggiore,et al.  Functional Imaging Reveals Movement Preparatory Activity in the Vegetative State , 2011, Front. Hum. Neurosci..

[5]  Laurie Zoloth,et al.  Willful modulations of brain activity in disorders of consciousness, by MM Monti, A Vanhaudenhuyse, MR Coleman, M Boly, JD Pickard, L Tshibanda, AM Owen, S Laureys: New England Journal of Medicine , 2010 .

[6]  Karl J. Friston,et al.  Preserved Feedforward But Impaired Top-Down Processes in the Vegetative State , 2011, Science.

[7]  G. B. Young,et al.  Predictors of recovery of responsiveness in prolonged anoxic vegetative state , 2013, Neurology.

[8]  Dominique Morlet,et al.  Late auditory and event-related potentials can be useful to predict good functional outcome after coma. , 2005, Archives of physical medicine and rehabilitation.

[9]  Multi-Society Task Force on Pvs Medical aspects of the persistent vegetative state (1). , 1994, The New England journal of medicine.

[10]  Carlo Miniussi,et al.  Vegetative versus Minimally Conscious States: A Study Using TMS-EEG, Sensory and Event-Related Potentials , 2013, PloS one.

[11]  N. Schiff,et al.  Dissociations between behavioural and functional magnetic resonance imaging-based evaluations of cognitive function after brain injury. , 2011, Brain : a journal of neurology.

[12]  S Laureys,et al.  Voluntary brain processing in disorders of consciousness , 2008, Neurology.

[13]  Andrew A Fingelkurts,et al.  Dissociation of Vegetative and Minimally Conscious Patients Based on Brain Operational Architectonics , 2013, Clinical EEG and neuroscience.

[14]  R. Seel,et al.  Specialized early treatment for persons with disorders of consciousness: program components and outcomes. , 2013, Archives of physical medicine and rehabilitation.

[15]  Martin H. Feldman Physiological observations in a chronic case of “locked‐in” syndrome , 1971, Neurology.

[16]  Steve Majerus,et al.  Volitional electromyographic responses in disorders of consciousness , 2014, Brain injury.

[17]  H. Gill-Thwaites Lotteries, loopholes and luck: Misdiagnosis in the vegetative state patient , 2006, Brain injury.

[18]  M. Boly,et al.  Monitoring epilepsy in the intensive care unit: Current state of facts and potential interest of high density EEG , 2014, Brain injury.

[19]  J. Giacino,et al.  The JFK Coma Recovery Scale-Revised: measurement characteristics and diagnostic utility. , 2004, Archives of physical medicine and rehabilitation.

[20]  M. Leonardi,et al.  Physical and mental health, anxiety and depressive symptoms in caregivers of patients in vegetative state and minimally conscious state. , 2014, Clinical psychology & psychotherapy.

[21]  Steven Laureys,et al.  Neuroimaging activation studies in the vegetative state: predictors of recovery? , 2008, Clinical medicine.

[22]  F. Gerstenbrand,et al.  Varieties of the locked-in syndrome , 1979, Journal of Neurology.

[23]  M. Estévez,et al.  A network approach to assessing cognition in disorders of consciousness , 2011, Neurology.

[24]  J. A. Cruzado,et al.  Caregivers of patients with disorders of consciousness: coping and prolonged grief , 2013, Acta neurologica Scandinavica.

[25]  A. Vanhaudenhuyse,et al.  Detection of visual pursuit in patients in minimally conscious state: A matter of stimuli and visual plane? , 2014, Brain injury.

[26]  O. Gosseries,et al.  Consciousness in the Locked-in Syndrome , 2016 .

[27]  Steve Majerus,et al.  Visual fixation in the vegetative state: an observational case series PET study , 2010, BMC neurology.

[28]  Steven Laureys,et al.  Automated EEG entropy measurements in coma, vegetative state/unresponsive wakefulness syndrome and minimally conscious state. , 2011, Functional neurology.

[29]  R. Goebel,et al.  Brain–computer interfaces for communication with nonresponsive patients , 2012, Annals of neurology.

[30]  S Laureys,et al.  vegetative state , 2008 .

[31]  Gustave Moonen,et al.  Cortical Processing of Noxious Somatosensory Stimuli in the Persistent Vegetative State , 2002, NeuroImage.

[32]  J. Calvet,et al.  [Meningitis of sinusoid origin with the form of coma vigil]. , 1959, Revue d'oto-neuro-ophtalmologie.

[33]  Justin L. Vincent,et al.  Intrinsic functional architecture in the anaesthetized monkey brain , 2007, Nature.

[34]  F. Plum,et al.  The diagnosis of stupor and coma. , 1972, Contemporary neurology series.

[35]  F. Gerstenbrand,et al.  The Vegetative State – A Syndrome in Search of a Name , 2012, Journal of medicine and life.

[36]  Bruce D. McCandliss,et al.  Possible axonal regrowth in late recovery from the minimally conscious state. , 2006, The Journal of clinical investigation.

[37]  Tao Yu,et al.  Global functional connectivity reveals highly significant differences between the vegetative and the minimally conscious state , 2013, Journal of Neurology.

[38]  Matthew H. Davis,et al.  Detecting awareness in the vegetative state. , 2006, Science.

[39]  Steven Laureys,et al.  BLINK TO VISUAL THREAT DOES NOT HERALD CONSCIOUSNESS IN THE VEGETATIVE STATE , 2008, Neurology.

[40]  Caroline Schnakers,et al.  Pain assessment and management in disorders of consciousness , 2007, Current opinion in neurology.

[41]  Habib Benali,et al.  Relation between brain lesion location and clinical outcome in patients with severe traumatic brain injury: A diffusion tensor imaging study using voxel‐based approaches , 2009, Human brain mapping.

[42]  C. Fischer,et al.  Improved prediction of awakening or nonawakening from severe anoxic coma using tree-based classification analysis* , 2006, Critical care medicine.

[43]  M. Boly,et al.  Auditory processing in severely brain injured patients: differences between the minimally conscious state and the persistent vegetative state. , 2004, Archives of neurology.

[44]  F. Fazio,et al.  Regional cerebral metabolism of glucose in comatose and vegetative state patients. , 1995, Journal of neurosurgical anesthesiology.

[45]  Walter G Sannita,et al.  Unresponsive wakefulness syndrome: a new name for the vegetative state or apallic syndrome , 2010, BMC medicine.

[46]  N. Zasler,et al.  Post-Traumatic Pain Disorders: Medical Assessment and Management , 2012 .

[47]  M. Boly,et al.  Default network connectivity reflects the level of consciousness in non-communicative brain-damaged patients. , 2010, Brain : a journal of neurology.

[48]  G. Borasio,et al.  How family caregivers' medical and moral assumptions influence decision making for patients in the vegetative state: a qualitative interview study , 2012, Journal of Medical Ethics.

[49]  Steven Laureys,et al.  Assessment of visual pursuit in post-comatose states: use a mirror , 2008, Journal of Neurology, Neurosurgery, and Psychiatry.

[50]  Marcello Massimini,et al.  Recovery of cortical effective connectivity and recovery of consciousness in vegetative patients , 2012, Brain : a journal of neurology.

[51]  Steven Laureys,et al.  Resting state activity in patients with disorders of consciousness. , 2011, Functional neurology.

[52]  A. Godbolt,et al.  Disorders of consciousness: Preliminary data supports added value of extended behavioural assessment , 2012, Brain injury.

[53]  J. Giacino,et al.  Medical complications during inpatient rehabilitation among patients with traumatic disorders of consciousness. , 2013, Archives of physical medicine and rehabilitation.

[54]  Steven Laureys,et al.  Abnormal Corticospinal Excitability in Patients with Disorders of Consciousness , 2022 .

[55]  B. Kotchoubey,et al.  Can mental imagery functional magnetic resonance imaging predict recovery in patients with disorders of consciousness? , 2013, Archives of physical medicine and rehabilitation.

[56]  R. Zorowitz,et al.  Measuring interconnection of the residual cortical functional islands in persistent vegetative state and minimal conscious state with EEG nonlinear analysis , 2011, Clinical Neurophysiology.

[57]  M. Boly,et al.  Willful modulation of brain activity in disorders of consciousness. , 2010, The New England journal of medicine.

[58]  M. Boly,et al.  Diagnostic accuracy of the vegetative and minimally conscious state: Clinical consensus versus standardized neurobehavioral assessment , 2009, BMC neurology.

[59]  J. A. Cruzado,et al.  Coping and distress in caregivers of patients with disorders of consciousness , 2013, Brain injury.

[60]  John Whyte,et al.  Placebo-controlled trial of amantadine for severe traumatic brain injury. , 2012, The New England journal of medicine.

[61]  S. Eickhoff,et al.  N400 predicts recovery from disorders of consciousness , 2013, Annals of neurology.

[62]  M. Boly,et al.  Functional connectivity in the default network during resting state is preserved in a vegetative but not in a brain dead patient , 2009, Human brain mapping.

[63]  Eva Grill,et al.  Rehabilitation outcome of anoxic-ischaemic encephalopathy survivors with prolonged disorders of consciousness. , 2013, Resuscitation.

[64]  Athena Demertzi,et al.  Two Distinct Neuronal Networks Mediate the Awareness of Environment and of Self , 2011, Journal of Cognitive Neuroscience.

[65]  Steve Majerus,et al.  Detecting Consciousness in a Total Locked-in Syndrome: an Active Event-related Paradigm Detecting Consciousness in a Total Lis , 2022 .

[66]  E. Kretschmer Das apallische Syndrom , 1940 .

[67]  C. Machado,et al.  Vegetative state is a pejorative term. , 2012, NeuroRehabilitation.

[68]  R. Clauss,et al.  Extraordinary arousal from semi-comatose state on zolpidem. A case report. , 2000, South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde.

[69]  Montserrat Bernabeu,et al.  Combination of diffusion tensor and functional magnetic resonance imaging during recovery from the vegetative state , 2010, BMC neurology.

[70]  John D Pickard,et al.  Visual cognition in disorders of consciousness: From V1 to top‐down attention , 2013, Human brain mapping.

[71]  Steven Laureys,et al.  Transcranial magnetic stimulation combined with high-density EEG in altered states of consciousness , 2014, Brain injury.

[72]  C. Schnakers,et al.  Disorders of consciousness: what's in a name? , 2011, NeuroRehabilitation.

[73]  Steven Laureys,et al.  Pain issues in disorders of consciousness , 2014, Brain injury.

[74]  G. Tipoe,et al.  Should we continue treatment for M? The benefits of living , 2013, Journal of Medical Ethics.

[75]  J. Giacino,et al.  Predictors of short-term outcome in brain-injured patients with disorders of consciousness. , 2009, Progress in brain research.

[76]  Carolina Colomer,et al.  Behavioral recovery in disorders of consciousness: a prospective study with the Spanish version of the Coma Recovery Scale-Revised. , 2012, Archives of physical medicine and rehabilitation.

[77]  T Sarraf,et al.  Long-term outcomes of chronic minimally conscious and vegetative states , 2010, Neurology.

[78]  N. Ferreira Latest legal and social developments in the euthanasia debate: bad moral consciences and political unrest. , 2007, Medicine and law.

[79]  Adrian M. Owen,et al.  Diffusion weighted imaging distinguishes the vegetative state from the minimally conscious state , 2011, NeuroImage.

[80]  C. Poser,et al.  The Diagnosis of Stupor and Coma , 1981 .

[81]  R. Goebel,et al.  A Real-Time fMRI-Based Spelling Device Immediately Enabling Robust Motor-Independent Communication , 2012, Current Biology.

[82]  B. Kotchoubey,et al.  Predicting coma and other low responsive patients outcome using event-related brain potentials: A meta-analysis , 2007, Clinical Neurophysiology.

[83]  Alberto Raggi,et al.  Burnout in healthcare professionals working with patients with disorders of consciousness. , 2013, Work.

[84]  C. Schnakers,et al.  CHAPTER 15 – Consciousness in the Locked-in Syndrome , 2009 .

[85]  Steven Laureys,et al.  Brain function in coma, vegetative state, and related disorders , 2004, The Lancet Neurology.

[86]  Steven Laureys,et al.  Spasticity after stroke: Physiology, assessment and treatment , 2013, Brain injury.

[87]  Steven Laureys,et al.  Self-consciousness in non-communicative patients , 2007, Consciousness and Cognition.

[88]  Steven Laureys,et al.  Probing command following in patients with disorders of consciousness using a brain–computer interface , 2013, Clinical Neurophysiology.

[89]  Steven Laureys,et al.  A European survey on attitudes towards pain and end-of-life issues in locked-in syndrome , 2014, Brain injury.

[90]  A. Owen,et al.  A multimodal approach to the assessment of patients with disorders of consciousness. , 2009, Progress in brain research.

[91]  G. Tononi,et al.  The neurology of consciousness : cognitive neuroscience and neuropathology , 2009 .

[92]  L. Santoro,et al.  Predictors of recovery of responsiveness in prolonged anoxic vegetative state , 2013, Neurology.

[93]  S. Ashwal,et al.  Medical aspects of the persistent vegetative state--a correction. The Multi-Society Task Force on PVS. , 1995, The New England journal of medicine.

[94]  S Laureys,et al.  Multimodal neuroimaging in patients with disorders of consciousness showing "functional hemispherectomy". , 2011, Progress in brain research.

[95]  Steven Laureys,et al.  Attitudes towards end-of-life issues in disorders of consciousness: a European survey , 2011, Journal of Neurology.

[96]  Steven Laureys,et al.  A sensitive scale to assess nociceptive pain in patients with disorders of consciousness , 2012, Journal of Neurology Neurosurgery & Psychiatry.

[97]  Dominique Cardebat,et al.  Clinical and imaging evidence of zolpidem effect in hypoxic encephalopathy , 2007, Annals of neurology.

[98]  C. Degueldre,et al.  Auditory processing in the vegetative state. , 2000, Brain : a journal of neurology.

[99]  Steven Laureys,et al.  Effect of zolpidem in chronic disorders of consciousness: a prospective open-label study. , 2014, Functional neurology.

[100]  J. Giacino,et al.  The minimally conscious state: Definition and diagnostic criteria , 2002, Neurology.

[101]  Srivas Chennu,et al.  Bedside detection of awareness in the vegetative state: a cohort study , 2011, The Lancet.

[102]  B. Kotchoubey,et al.  Event-related potentials predict the outcome of the vegetative state , 2007, Clinical Neurophysiology.

[103]  Andrea Soddu,et al.  Lies, damned lies and diagnoses: Estimating the clinical utility of assessments of covert awareness in the vegetative state , 2014, Brain injury.

[104]  Y. An,et al.  Brain metabolism in patients with vegetative state after post-resuscitated hypoxic-ischemic brain injury: statistical parametric mapping analysis of F-18 fluorodeoxyglucose positron emission tomography. , 2013, Chinese medical journal.

[105]  Steven Laureys,et al.  Limbic hyperconnectivity in the vegetative state , 2013, Neurology.

[106]  Xiaodan Jiang,et al.  Prediction of minimally conscious state with somatosensory evoked potentials in long-term unconscious patients after traumatic brain injury , 2012, The journal of trauma and acute care surgery.

[107]  Steven Laureys,et al.  Palliative sedation: Why we should be more concerned about the risks that patients experience an uncomfortable death , 2013, PAIN®.

[108]  Steven Laureys,et al.  From unresponsive wakefulness to minimally conscious PLUS and functional locked-in syndromes: recent advances in our understanding of disorders of consciousness , 2011, Journal of Neurology.

[109]  Steven Laureys,et al.  Perception of pain in the minimally conscious state with PET activation: an observational study , 2008, The Lancet Neurology.

[110]  Steven Laureys,et al.  Mismatch negativity to the patient’s own name in chronic disorders of consciousness , 2008, Neuroscience Letters.

[111]  Steven Laureys,et al.  Resting-state EEG study of comatose patients: a connectivity and frequency analysis to find differences between vegetative and minimally conscious states. , 2012, Functional neurology.

[112]  J. Giacino,et al.  Potential applications of concurrent transcranial magnetic stimulation and functional magnetic resonance imaging in acquired brain injury and disorders of consciousness , 2014, Brain injury.

[113]  S Laureys,et al.  Restoration of thalamocortical connectivity after recovery from persistent vegetative state , 2000, The Lancet.

[114]  J. Manning Withdrawal of life-sustaining treatment from a patient in a minimally conscious state. , 2012, Journal of law and medicine.

[115]  Steven Laureys,et al.  Assessment of localisation to auditory stimulation in post-comatose states: use the patient’s own name , 2013, BMC Neurology.

[116]  Athena Demertzi,et al.  Metabolic activity in external and internal awareness networks in severely brain-damaged patients. , 2012, Journal of rehabilitation medicine.

[117]  John Whyte,et al.  Incidence of Clinically Significant Responses to Zolpidem Among Patients with Disorders of Consciousness: A Preliminary Placebo Controlled Trial , 2009, American journal of physical medicine & rehabilitation.

[118]  Steven Laureys,et al.  Disorders : Correlation with High-Resolution Computed Tomography Ultrasound in the Assessment of Pulmonary Fibrosis in Connective Tissue , 2012 .

[119]  Francesco Piccione,et al.  Post-acute P300 predicts recovery of consciousness from traumatic vegetative state , 2009, Brain injury.

[120]  Athena Demertzi,et al.  Identifying the default‐mode component in spatial IC analyses of patients with disorders of consciousness , 2012, Human brain mapping.

[121]  Robyn L McClelland,et al.  Validation of a new coma scale: The FOUR score , 2005, Annals of neurology.

[122]  Donald H. Lee,et al.  Disruptions of functional connectivity in the default mode network of comatose patients , 2012, Neurology.

[123]  M. Leonardi,et al.  Burden and needs of 487 caregivers of patients in vegetative state and in minimally conscious state: Results from a national study , 2012, Brain injury.

[124]  Steve Majerus,et al.  Functional neuroanatomy underlying the clinical subcategorization of minimally conscious state patients , 2012, Journal of Neurology.

[125]  J. Whyte,et al.  Assessment of command-following in minimally conscious brain injured patients. , 1999, Archives of physical medicine and rehabilitation.

[126]  B. Kotchoubey,et al.  What kind of consciousness is minimal? , 2014, Brain injury.

[127]  C. Schnakers Clinical assessment of patients with disorders of consciousness. , 2012, Archives italiennes de biologie.

[128]  W D Heiss,et al.  Cerebral glucose metabolism in acute and persistent vegetative state. , 1999, Journal of neurosurgical anesthesiology.

[129]  Steven Laureys,et al.  Amantadine, apomorphine and zolpidem in the treatment of disorders of consciousness. , 2013, Current pharmaceutical design.

[130]  A. Karantanas,et al.  Outcome of patients with diffuse axonal injury: the significance and prognostic value of MRI in the acute phase. , 2000, The Journal of trauma.