Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Perspective
  • Published:

Neuroprognostication: a conceptual framework

Nature Reviews Neurology volume 18, pages 419–427 (2022)Cite this article

Subjects

Abstract

Neuroprognostication, or the prediction of recovery from disorders of consciousness caused by severe brain injury, is as critical as it is complex. With profound implications for mortality and quality of life, neuroprognostication draws upon an intricate set of biomedical, probabilistic, psychosocial and ethical factors. However, the clinical approach to neuroprognostication is often unsystematic, and consequently, variable among clinicians and prone to error. Here, we offer a stepwise conceptual framework for reasoning through neuroprognostic determinations — including an evaluation of neurological function, estimation of a recovery trajectory, definition of goals of care and consideration of patient values — culminating in a clinically actionable formula for weighing the risks and benefits of life-sustaining treatment. Although the complexity of neuroprognostication might never be fully reducible to arithmetic, this systematic approach provides structure and guidance to supplement clinical judgement and direct future investigation.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Schematization of neuroprognostication: steps 1 and 2.
Fig. 2: Sources of information about a patient’s goals of care.
Fig. 3: Schematization of neuroprognostication: steps 3 and 4.
Fig. 4: Schematization of neuroprognostication: steps 5 and 6.

Similar content being viewed by others

References

  1. Greer, D. M., Rosenthal, E. S. & Wu, O. Neuroprognostication of hypoxic-ischaemic coma in the therapeutic hypothermia era. Nat. Rev. Neurol. 10, 190–203 (2014).

    Article  CAS  PubMed  Google Scholar 

  2. Giacino, J. T. et al. Practice guideline update recommendations summary: disorders of consciousness. Neurology 99, 1699–1709 (2018).

    Google Scholar 

  3. Elmer, J. et al. Association of early withdrawal of life-sustaining therapy for perceived neurological prognosis with mortality after cardiac arrest. Resuscitation 102, 127–135 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Turgeon, A. F. et al. Determination of neurologic prognosis and clinical decision making in adult patients with severe traumatic brain injury. Crit. Care Med. 41, 1086–1093 (2013).

    Article  PubMed  Google Scholar 

  5. Turgeon, A. F. et al. Mortality associated with withdrawal of life-sustaining therapy for patients with severe traumatic brain injury: a Canadian multicentre cohort study. CMAJ 183, 1581–1588 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Becker, K. J. et al. Withdrawal of support in intracerebral hemorrhage may lead to self-fulfilling prophecies. Neurology 56, 766–772 (2001).

    Article  CAS  PubMed  Google Scholar 

  7. Leblanc, G. et al. Incidence and impact of withdrawal of life-sustaining therapies in clinical trials of severe traumatic brain injury: a systematic review. Clin. Trials 15, 398–412 (2018).

    Article  PubMed  Google Scholar 

  8. Williamson, T. et al. Withdrawal of life-supporting treatment in severe traumatic brain injury. JAMA Surg. 27710, E1–E8 (2020).

    Google Scholar 

  9. McCredie, V. A. et al. Timing of withdrawal of life-sustaining therapies in severe traumatic brain injury: Impact on overall mortality. J. Trauma. Acute Care Surg. 80, 484–491 (2016).

    Article  PubMed  Google Scholar 

  10. van Veen, E. et al. End-of-life practices in traumatic brain injury patients: report of a questionnaire from the CENTER-TBI study. J. Crit. Care 58, 78–88 (2020).

    Article  PubMed  Google Scholar 

  11. Avidan, A. et al. Variations in end-of-life practices in intensive care units worldwide (Ethicus-2): a prospective observational study. Lancet Respir. Med. 9, 1101–1110 (2021).

    Article  PubMed  Google Scholar 

  12. Pratt, A. K., Chang, J. J. & Sederstrom, N. O. A fate worse than death. Crit. Care Med. 47, 591–598 (2019).

    Article  PubMed  Google Scholar 

  13. Edlow, B. L., Claassen, J., Schiff, N. D. & Greer, D. M. Recovery from disorders of consciousness: mechanisms, prognosis and emerging therapies. Nat. Rev. Neurol. 17, 135–156 (2021).

    Article  PubMed  Google Scholar 

  14. Giacino, J. T. The vegetative and minimally conscious states: consensus-based criteria for establishing diagnosis and prognosis. NeuroRehabilitation 19, 293–298 (2004).

    Article  PubMed  Google Scholar 

  15. Laureys, S. et al. Unresponsive wakefulness syndrome: a new name for the vegetative state or apallic syndrome. BMC Med 8, 68 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Posner, J. B., Saper, C. B., Schiff, N. D. & Claassen, J. Plum and Posner’s Diagnosis and Treatment of Stupor and Coma (Oxford Univ. Press, 2019).

  17. Giacino, J. T. et al. Behavioral assessment in patients with disorders of consciousness: gold standard or fool’s gold? Prog. Brain Res 177, 33–48 (2009).

    Article  PubMed  Google Scholar 

  18. Giacino, J. T. & Kalmar, K. Diagnostic and prognostic guidelines for the vegetative and minimally conscious states. Neuropsychol. Rehabil. 15, 166–174 (2005).

    Article  PubMed  Google Scholar 

  19. Giacino, J. T., Kalmar, K. & Whyte, J. The JFK coma recovery scale-revised: measurement characteristics and diagnostic utility. Arch. Phys. Med. Rehabil. 85, 2020–2029 (2004).

    Article  PubMed  Google Scholar 

  20. Faugeras, F. et al. Survival and consciousness recovery are better in the minimally conscious state than in the vegetative state. Brain Inj. 32, 72–77 (2018).

    Article  PubMed  Google Scholar 

  21. Giacino, J. & Kalmar, K. The vegetative and minimally conscious states: a comparison of clinical features and functional outcome. J. Head. Trauma. Rehabil. 12, 36–51 (1997).

    Article  Google Scholar 

  22. Katz, D. I., Polyak, M., Coughlan, D., Nichols, M. & Roche, A. Natural history of recovery from brain injury after prolonged disorders of consciousness: outcome of patients admitted to inpatient rehabilitation with 1-4 year follow-up. Prog. Brain Res. 177, 73–88 (2009).

    Article  PubMed  Google Scholar 

  23. Fins, J. J. Rights Come to Mind: Brain Injury, Ethics, and the Struggle for Consciousness (Cambridge Univ. Press, 2015).

  24. Fischer, D. B. & Truog, R. D. What is a reflex? A guide for understanding disorders of consciousness. Neurology 85, 543–548 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  25. Fischer, D. B. & Truog, R. D. The problems with fixating on consciousness in disorders of consciousness. Am. J. Bioeth. Neurosci. 8, 135–140 (2017).

    Google Scholar 

  26. Fischer, D. B. & Truog, R. D. Conscientious of the conscious: interactive capacity as a threshold marker for consciousness. Am. J. Bioeth. Neurosci. 4, 26–33 (2013).

    Google Scholar 

  27. Kondziella, D., Friberg, C. K., Frokjaer, V. G., Fabricius, M. & Møller, K. Preserved consciousness in vegetative and minimal conscious states: systematic review and meta-analysis. J. Neurol. Neurosurg. Psychiatry 87, 485–492 (2016).

    Article  PubMed  Google Scholar 

  28. Schnakers, C. et al. Covert cognition in disorders of consciousness: a meta-analysis. Brain Sci. 10, 930 (2020).

    Article  PubMed Central  Google Scholar 

  29. Schiff, N. D. Cognitive motor dissociation following severe brain injuries. JAMA Neurol. 72, 1413–1415 (2015).

    Article  PubMed  Google Scholar 

  30. Kondziella, D. et al. European Academy of Neurology guideline on the diagnosis of coma and other disorders of consciousness. Eur. J. Neurol. 27, 741–756 (2020).

    Article  CAS  PubMed  Google Scholar 

  31. Comanducci, A. et al. Clinical and advanced neurophysiology in the prognostic and diagnostic evaluation of disorders of consciousness: review of an IFCN-endorsed expert group. Clin. Neurophysiol. 131, 2736–2765 (2020).

    Article  CAS  PubMed  Google Scholar 

  32. Naccache, L. Minimally conscious state or cortically mediated state? Brain 141, 949–960 (2018).

    Article  PubMed  Google Scholar 

  33. Kondziella, D. et al. A precision medicine framework for classifying patients with disorders of consciousness: advanced classification of consciousness endotypes (ACCESS). Neurocrit. Care 35, 27–36 (2021).

    Article  PubMed  Google Scholar 

  34. Threlkeld, Z. D. et al. Functional networks reemerge during recovery of consciousness after acute severe traumatic brain injury. Cortex 106, 299–308 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  35. Sair, H. I. et al. Early functional connectome integrity and 1-year recovery in comatose survivors of cardiac arrest. Radiology 287, 247–255 (2018).

    Article  PubMed  Google Scholar 

  36. Chennu, S. et al. Brain networks predict metabolism, diagnosis and prognosis at the bedside in disorders of consciousness. Brain 140, 2120–2132 (2017).

    Article  PubMed  Google Scholar 

  37. Vanhaudenhuyse, A. et al. Default network connectivity reflects the level of consciousness in non-communicative brain-damaged patients. Brain 133, 161–171 (2010).

    Article  PubMed  Google Scholar 

  38. Sokoliuk, R. et al. Covert speech comprehension predicts recovery from acute unresponsive states. Ann. Neurol. 89, 646–656 (2020).

    Article  Google Scholar 

  39. Wang, F. et al. Cerebral response to subject’s own name showed high prognostic value in traumatic vegetative state. BMC Med 13, 83 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Coleman, M. R. et al. Towards the routine use of brain imaging to aid the clinical diagnosis of disorders of consciousness. Brain 132, 2541–2552 (2009).

    Article  CAS  PubMed  Google Scholar 

  41. Owen, A. M. et al. Detecting awareness in the vegetative state. Science 313, 1402 (2006).

    Article  CAS  PubMed  Google Scholar 

  42. Monti, M. M. et al. Willful modulation of brain activity in disorders of consciousness. N. Engl. J. Med 362, 579–589 (2010).

    Article  CAS  PubMed  Google Scholar 

  43. Edlow, B. L. et al. Early detection of consciousness in patients with acute severe traumatic brain injury. Brain 140, 2399–2414 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  44. Claassen, J. et al. Detection of brain activation in unresponsive patients with acute brain injury. N. Engl. J. Med. 380, 2497–2505 (2019).

    Article  PubMed  Google Scholar 

  45. Wannez, S., Heine, L., Thonnard, M., Gosseries, O. & Laureys, S. The repetition of behavioral assessments in diagnosis of disorders of consciousness. Ann. Neurol. 81, 883–889 (2017).

    Article  PubMed  Google Scholar 

  46. Rundgren, M. et al. Neuron specific enolase and S-100B as predictors of outcome after cardiac arrest and induced hypothermia. Resuscitation 80, 784–789 (2009).

    Article  CAS  PubMed  Google Scholar 

  47. Tiainen, M., Roine, R. O., Pettilä, V. & Takkunen, O. Serum neuron-specific enolase and S-100B protein in cardiac arrest patients treated with hypothermia. Stroke 34, 2881–2886 (2003).

    Article  CAS  PubMed  Google Scholar 

  48. Sandroni, C. et al. Prognostication in comatose survivors of cardiac arrest: an advisory statement from the European Resuscitation Council and the European Society of Intensive Care Medicine. Intensive Care Med. 40, 1816–1831 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  49. Scarpino, M. et al. Does a combination of ≥2 abnormal tests vs. the ERC-ESICM stepwise algorithm improve prediction of poor neurological outcome after cardiac arrest? A post-hoc analysis of the ProNeCA multicentre study. Resuscitation 160, 158–167 (2021).

    Article  PubMed  Google Scholar 

  50. Nolan, J. P. et al. European Resuscitation Council and European Society of Intensive Care Medicine guidelines for post-resuscitation care 2015. Section 5 of the European Resuscitation Council guidelines for resuscitation 2015. Resuscitation 95, 202–222 (2015).

    Article  PubMed  Google Scholar 

  51. Forsyth, R. J., Salorio, C. F. & Christensen, J. R. Modelling early recovery patterns after paediatric traumatic brain injury. Arch. Dis. Child. 95, 266–270 (2010).

    PubMed  Google Scholar 

  52. Christensen, B. K. et al. Recovery of cognitive function after traumatic brain injury: a multilevel modeling analysis of Canadian outcomes. Arch. Phys. Med. Rehabil. 89, S3–S15 (2008).

    Article  PubMed  Google Scholar 

  53. Hart, T. et al. Functional recovery after severe traumatic brain injury: an individual growth curve approach. Arch. Phys. Med. Rehabil. 95, 2103–2110 (2014).

    Article  PubMed  Google Scholar 

  54. Muehlschlegel, S. et al. Goals-of-care decision aid for critically ill patients with TBI: development and feasibility testing. Neurology 95, E179–E193 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  55. Jox, R. J. et al. Diagnosis and decision making for patients with disorders of consciousness: a survey among family members. Arch. Phys. Med. Rehabil. 96, 323–330 (2015).

    Article  PubMed  Google Scholar 

  56. Reynolds, J. M. The ableism of quality of life judgments in disorders of consciousness: who bears epistemic responsibility? Am. J. Bioeth. Neurosci. 7, 59–61 (2016).

    Google Scholar 

  57. Wilson, M., Staniforth, A., Till, R., Das Nair, R. & Vesey, P. The psychosocial outcomes of anoxic brain injury following cardiac arrest. Resuscitation 85, 795–800 (2014).

    Article  PubMed  Google Scholar 

  58. Bruno, M. A. et al. A survey on self-assessed well-being in a cohort of chronic locked-in syndrome patients: happy majority, miserable minority. BMJ Open 1, e000039 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  59. Albrecht, G. L. & Devlieger, P. J. The disability paradox: high quality of life against all odds. Soc. Sci. Med. 48, 977–988 (1999).

    Article  CAS  PubMed  Google Scholar 

  60. Giovannetti, A. M., Covelli, V., Sattin, D. & Leonardi, M. Caregivers of patients with disorder of consciousness: burden, quality of life and social support. Acta Neurol. Scand. 132, 259–269 (2015).

    Article  CAS  PubMed  Google Scholar 

  61. Chiambretto, P., Ferrario, S. R. & Zotti, A. M. Patients in a persistent vegetative state: caregiver attitudes and reactions. Acta Neurol. Scand. 104, 364–368 (2001).

    Article  CAS  PubMed  Google Scholar 

  62. Chinner, A., Pauli, R. & Cruse, D. The impact of prolonged disorders of consciousness on family caregivers’ quality of life–a scoping review. Neuropsychol. Rehabil. https://doi.org/10.1080/09602011.2021.1922463 (2021).

    Article  PubMed  Google Scholar 

  63. Edlow, B. L. & Fin, J. J. Assessment of covert consciousness in the intensive care unit: clinical and ethical considerations. J. Head. Truma Rehabil. 33, 424–434 (2018).

    Article  Google Scholar 

  64. Souter, M. J. et al. Recommendations for the critical care management of devastating brain injury: prognostication, psychosocial, and ethical management: a position statement for healthcare professionals from the Neurocritical Care Society. Neurocrit. Care 23, 4–13 (2015).

    Article  PubMed  Google Scholar 

  65. Gigerenzer, G., Gaissmaier, W., Kurz-Milcke, E., Schwartz, L. M. & Woloshin, S. Helping doctors and patients make sense of health statistics. Psychol. Sci. Public. Interest 8, 53–96 (2007).

    Article  PubMed  Google Scholar 

  66. Lee Char, S. J., Evans, L. R., Malvar, G. L. & White, D. B. A randomized trial of two methods to disclose prognosis to surrogate decision makers in intensive care units. Am. J. Respir. Crit. Care Med. 182, 905–909 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  67. Muehlschlegel, S., Shutter, L., Col, N. & Goldberg, R. Decision aids and shared decision-making in neurocritical care: an unmet need in our neuroICUs. Neurocrit. Care 23, 127–130 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  68. Wiegand, D. In their own time: the family experience during the process of withdrawal of life-sustaining therapy. J. Palliat. Med. 11, 1115–1121 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  69. Searight, H. R. Ethical Challenges in Multi-Cultural Patient Care: Cross Cultural Issues at the End of Life 85–99 (Springer, 2019).

  70. Jones, K., Quinn, T., Mazor, K. M. & Muehlschlegel, S. Prognostic uncertainty in critically ill patients with traumatic brain injury: a multicenter qualitative study. Neurocrit. Care 35, 311–321 (2021).

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors have received funding from the NIH National Institute of Neurological Disorders and Stroke (R25NS06574309, R21NS109627), the NIH Director’s Office (DP2HD101400), James S. McDonnell Foundation, the Tiny Blue Dot Foundation, and the National Institute on Disability, Independent Living and Rehabilitation Research (90DPTB0011).

Author information

Author notes

  1. These authors contributed equally: Brian L. Edlow, Joseph T. Giacino and David M. Greer.

Authors and Affiliations

  1. Center for Neurotechnology and Neurorecovery, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    David Fischer & Brian L. Edlow

  2. Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    David Fischer

  3. Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Brian L. Edlow

  4. Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Charlestown, MA, USA

    Joseph T. Giacino

  5. Department of Neurology, Boston University School of Medicine and Boston Medical Center, Boston, MA, USA

    David M. Greer

Authors
  1. David Fischer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brian L. Edlow
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joseph T. Giacino
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. David M. Greer
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The authors contributed equally to all aspects of the article.

Corresponding author

Correspondence to David Fischer.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Neurology thanks James Bernat, Johanna Horn, Niklas Nielsen and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Glossary

Advance directives

Legal documents that individuals prepare to specify their preferences about medical care, to be used if they are unable to make those decisions themselves in the future.

Surrogates

Individuals who have been designated to make decisions on a patient’s behalf, if the patient is unable to make those decisions themselves.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fischer, D., Edlow, B.L., Giacino, J.T. et al. Neuroprognostication: a conceptual framework. Nat Rev Neurol 18, 419–427 (2022). https://doi.org/10.1038/s41582-022-00644-7

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41582-022-00644-7

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing