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Understanding, detecting, and stimulating consciousness recovery in the ICU

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Abstract

Coma is a medical and socioeconomic emergency. Although underfunded, research on coma and disorders of consciousness has made impressive progress. Lesion-network-map** studies have delineated the precise brainstem regions that consistently produce coma when damaged. Functional neuroimaging has revealed how mechanisms like “communication through coherence” and “inhibition by gating” work in synergy to enable cortico-cortical processing and how this information transfer is disrupted in brain injury. On the cellular level, break-down of intracellular communication between the layer 5 pyramidal cell soma and the apical dendritic part impairs dendritic information integration, with up-stream effects on microcircuits in local neuronal populations and on large-scale fronto-parietal networks, which correlates with loss of consciousness. A breakthrough in clinical concepts occurred when fMRI, and later EEG, studies revealed that 15% of clinically unresponsive patients in acute and chronic settings are in fact awake and aware, as shown by their command following abilities revealed by brain activation during motor and locomotion imagery tasks. This condition is now termed “cognitive motor dissociation.” Furthermore, epidemiological data on coma were literally non-existent until recently because of difficulties related to case ascertainment with traditional methods, but crowdsourcing of family observations enabled the first estimates of how frequent coma is in the general population (pooled annual incidence of 201 coma cases per 100,000 population in the UK and the USA). Diagnostic guidelines on coma and disorders of consciousness by the American Academy of Neurology and the European Academy of Neurology provide ambitious clinical frameworks to accommodate these achievements. As for therapy, a broad range of medical and non-medical treatment options is now being tested in increasingly larger trials; in particular, amantadine and transcranial direct current stimulation appear promising in this regard. Major international initiatives like the Curing Coma Campaign aim to raise awareness for coma and disorders of consciousness in the public, with the ultimate goal to make more brain-injured patients recover consciousness after a coma. To highlight all these accomplishments, this paper provides a comprehensive overview of recent progress and future challenges related to understanding, detecting, and stimulating consciousness recovery in the ICU.

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Funding

DK received funding from Rigshospitalets Forskningspulje Q16 R143-A6132-B3632, Region Hovedstadens Forskningsfond til Sundhedsforskning 2019—A6597, Jascha Fonden 2019—7684, Offerfonden 19–610-00060, the Lundbeck Foundation R349-2020–658, and the Novo Nordisk Foundation NNF21OC0067769. MW received funding from Rigshospitalets Forskningspulje and MA from Offerfonden 19–610-00060, and EJW received a scholar ship from the Lundbeck Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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  1. Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100, Copenhagen, Denmark

    Daniel Kondziella, Moshgan Amiri, Marwan H. Othman & Elisabeth Waldemar Jakobsen

  2. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

    Daniel Kondziella & Kirsten Møller

  3. Department of Neuroanesthesiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

    Tejs Jansen & Kirsten Møller

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Kondziella, D., Amiri, M., Othman, M.H. et al. Understanding, detecting, and stimulating consciousness recovery in the ICU. Acta Neurochir 165, 809–828 (2023). https://doi.org/10.1007/s00701-022-05378-5

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  • DOI: https://doi.org/10.1007/s00701-022-05378-5

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