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A Precision Medicine Framework for Classifying Patients with Disorders of Consciousness: Advanced Classification of Consciousness Endotypes (ACCESS)

  • The Curing Coma Campaign
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Abstract

Background

Consciousness in patients with brain injury is traditionally assessed based on semiological evaluation at the bedside. This classification is limited because of low granularity, ill-defined and rigid nomenclatures incompatible with the highly fluctuating nature of consciousness, failure to identify specific brain states like cognitive motor dissociation, and neglect for underlying biological mechanisms. Here, the authors present a pragmatic framework based on consciousness endotypes that combines clinical phenomenology with all essential physiological and biological data, emphasizing recovery trajectories, therapeutic potentials and clinical feasibility.

Methods

The Neurocritical Care Society’s Curing Coma Campaign identified an international group of experts who convened in a series of online meetings between May and November 2020 to discuss and propose a novel framework for classifying consciousness.

Results

The expert group proposes Advanced Classification of Consciousness Endotypes (ACCESS), a tiered multidimensional framework reflecting increasing complexity and an aspiration to consider emerging and future approaches. Tier 1 is based on clinical phenotypes and structural imaging. Tier 2 adds functional measures including EEG, PET and functional MRI, that can be summarized using the Arousal, Volition, Cognition and Mechanisms (AVCM) score (where “Volition” signifies volitional motor responses). Finally, Tier 3 reflects dynamic changes over time with a (theoretically infinite) number of physiologically distinct states to outline consciousness recovery and identify opportunities for therapeutic interventions.

Conclusions

Whereas Tiers 1 and 2 propose an approach for low-resource settings and state-of-the-art expertise at leading academic centers, respectively, Tier 3 is a visionary multidimensional consciousness paradigm driven by continuous incorporation of new knowledge while addressing the Curing Coma Campaign’s aspirational goals.

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Acknowledgements

This effort was underpinned by the Curing Coma Campaign [30] and draws on important insights provided by the publications “Practice Guideline Update Recommendations Summary: Disorders of Consciousness: Report of…the American Academy of Neurology; the American Congress of Rehabilitation Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research” [28 and “European Academy of Neurology Guideline on the Diagnosis of Coma and Other Disorders of Consciousness” [29]. Contributing collaborators of the Curing Coma Campaign are as follows: Jan Claassen, Brian Edlow, Jed Hartings, Claude Hemphill, Theresa Human, Molly McNett, DaiWai Olson, Adrian Owen, Len Polizzotto, Javier Provencio, Louis Puybasset, Eric Rosenthal, Amy Wagner, John Whyte, and Wendy Ziai. Other campaign participants are listed in Supplementary Table 1. Figures 1, 2 and 3 were created with biorender.com.

Author information

Author notes

  1. Daniel Kondziella and David K. Menon have contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Inge Lehmanns Vej 8, 2100, Copenhagen, Denmark

    Daniel Kondziella & Marwan H. Othman

  2. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Daniel Kondziella

  3. Division of Anaesthesia, University of Cambridge, Cambridge, CB2 0NU, UK

    David K. Menon

  4. Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria

    Raimund Helbok & Verena Rass

  5. PICNIC Lab Team, INSERM, U 1127, CNRS UMR 7225, Faculté de Médecine de Sorbonne Université, UMR S 1127 Institut du Cerveau et de la Moelle épinière, ICM, Hôpital Pitié-Salpêtrière, Paris, France

    Lionel Naccache

  6. APHP, Departments of Neurology and of Clinical Neurophysiology, Hôpital de la Salpêtriere, Paris, France

    Lionel Naccache

  7. Sorbonne Université, Faculté de Médecine Pitié-Salpêtrière, Paris, France

    Benjamin Rohaut

  8. Brain institute - ICM, Sorbonne Université, Inserm U1127, CNRS UMR 7225, Hôpital Pitié-Salpêtrière, Paris, France

    Benjamin Rohaut

  9. Department of Neurology, Neuro ICU, Groupe Hospitalier Universitaire APHP-Sorbonne Université, site Pitié-Salpêtrière, Paris, France

    Benjamin Rohaut

  10. Washington University in St. Louis, Saint Louis, MO, USA

    Michael N. Diringer

  11. Departments of Anesthesiology, Critical Care Medicine, Neurology, and Neurosurgery, School of Medicine, Johns Hopkins University, Baltimore, MD, USA

    Robert D. Stevens

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  1. Daniel Kondziella
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  2. David K. Menon
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  6. Verena Rass
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Consortia

The contributing collaborators of the Curing Coma Campaign

  • Jan Claassen
  • , Brian Edlow
  • , Jed Hartings
  • , Claude Hemphill
  • , Theresa Human
  • , Molly McNett
  • , DaiWai Olson
  • , Adrian Owen
  • , Len Polizzotto
  • , Javier Provencio
  • , Louis Puybasset
  • , Eric Rosenthal
  • , Amy Wagner
  • , John Whyte
  •  & Wendy Ziai

Contributions

All authors have reviewed and approved the text.

Corresponding authors

Correspondence to Daniel Kondziella or David K. Menon.

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Source of support

Individual authors were supported in these efforts by specific funders, including the James S. McDonnell Foundation (DKM and LN); the Brain, Mind and Consciousness program of the Canadian Institute for Advanced Research (DKM); the Lundbeck Foundation (DK); and Rådet for Offerfonden (DK).

Conflicts of interest

The authors declare no conflicts of interest.

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This article is part of the collection “Curing Coma Campaign”.

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Kondziella, D., Menon, D.K., Helbok, R. et al. A Precision Medicine Framework for Classifying Patients with Disorders of Consciousness: Advanced Classification of Consciousness Endotypes (ACCESS). Neurocrit Care 35 (Suppl 1), 27–36 (2021). https://doi.org/10.1007/s12028-021-01246-9

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  • DOI: https://doi.org/10.1007/s12028-021-01246-9

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