Biomarkers; Coma; Consciousness; Electrophysiology; Magnetic resonance imaging
Abstract :
[en] Coma and disorders of consciousness (DoC) are highly prevalent and constitute a burden for patients, families, and society worldwide. As part of the Curing Coma Campaign, the Neurocritical Care Society partnered with the National Institutes of Health to organize a symposium bringing together experts from all over the world to develop research targets for DoC. The conference was structured along six domains: (1) defining endotype/phenotypes, (2) biomarkers, (3) proof-of-concept clinical trials, (4) neuroprognostication, (5) long-term recovery, and (6) large datasets. This proceedings paper presents actionable research targets based on the presentations and discussions that occurred at the conference. We summarize the background, main research gaps, overall goals, the panel discussion of the approach, limitations and challenges, and deliverables that were identified.
Disciplines :
Neurology
Author, co-author :
Claassen, Jan
Akbari, Yama
Alexander, Sheila
Bader, Mary Kay
Bell, Kathleen
Bleck, Thomas P.
Boly, Melanie
Brown, Jeremy
Chou, Sherry H.-Y.
Diringer, Michael N.
Edlow, Brian L.
Foreman, Brandon
Giacino, Joseph T.
Gosseries, Olivia ; Université de Liège - ULiège > GIGA Consciousness - Coma Science Group
Provencio JJ, Hemphill JC, Claassen J, et al. The Curing Coma Campaign: framing initial scientific challenges—proceedings of the first Curing Coma Campaign Scientific Advisory Council Meeting. Neurocrit Care. 2020;33(1):1–12. DOI: 10.1007/s12028-020-01028-9
Geurts M, Macleod MR, van Thiel GJMW, van Gijn J, Kappelle LJ, van der Worp HB. End-of-life decisions in patients with severe acute brain injury. Lancet Neurol. 2014;13(5):515–24. DOI: 10.1016/S1474-4422(14)70030-4
Schmidt-Pogoda A, Bonberg N, Koecke MHM, et al. Why most acute stroke studies are positive in animals but not in patients: a systematic comparison of preclinical, early phase, and phase 3 clinical trials of neuroprotective agents. Ann Neurol. 2020;87(1):40–51. DOI: 10.1002/ana.25643
Menon DK, Maas AIR. Traumatic brain injury in 2014: progress, failures and new approaches for TBI research. Nat Rev Neurol. 2015;11(2):71–2. DOI: 10.1038/nrneurol.2014.261
Agoston DV. Bench-to-bedside and bedside back to the bench; seeking a better understanding of the acute pathophysiological process in severe traumatic brain injury. Front Neurol. 2015;6:47. DOI: 10.3389/fneur.2015.00047
Manley GT, Mac Donald CL, Markowitz AJ, et al. The Traumatic Brain Injury Endpoints Development (TED) Initiative: progress on a public–private regulatory collaboration to accelerate diagnosis and treatment of traumatic brain injury. J Neurotrauma. 2017;34(19):2721–30. DOI: 10.1089/neu.2016.4729
Monti MM, Vanhaudenhuyse A, Coleman MR, et al. Willful modulation of brain activity in disorders of consciousness. N Engl J Med. 2010;362(7):579–89. DOI: 10.1056/NEJMoa0905370
Owen AM, Coleman MR, Boly M, Davis MH, Laureys S, Pickard JD. Detecting awareness in the vegetative state. Science. 2006;313(5792):1402. DOI: 10.1126/science.1130197
Edlow BL, Chatelle C, Spencer CA, et al. Early detection of consciousness in patients with acute severe traumatic brain injury. Brain. 2017;140(9):2399–414. DOI: 10.1093/brain/awx176
Claassen J, Doyle K, Matory A, et al. Detection of brain activation in unresponsive patients with acute brain injury. N Engl J Med. 2019;380(26):2497–505. DOI: 10.1056/NEJMoa1812757
Lauer S, Renz H. The advance of personalized and stratified therapies in bronchial asthma: phenotypes–endotypes–biomarkers. EJIFCC. 2013;24(3):113–25.
Biankin AV, Piantadosi S, Hollingsworth SJ. Patient-centric trials for therapeutic development in precision oncology. Nature. 2015;526(7573):361–70. DOI: 10.1038/nature15819
Eckel-Passow JE, Lachance DH, Molinaro AM, et al. Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med. 2015;372(26):2499–508. DOI: 10.1056/NEJMoa1407279
Siafakas N, Corlateanu A, Fouka E. Phenotyping before starting treatment in COPD? COPD. 2017;14(3):367–74. DOI: 10.1080/15412555.2017.1303041
Kucuksezer UC, Ozdemir C, Akdis M, Akdis CA. Precision/personalized medicine in allergic diseases and asthma. Arch Immunol Ther Exp (Warsz). 2018;66(6):431–42. DOI: 10.1007/s00005-018-0526-6
Edwards BA, Redline S, Sands SA, Owens RL. More than the sum of the respiratory events: personalized medicine approaches for obstructive sleep apnea. Am J Respir Crit Care Med. 2019;200(6):691–703. DOI: 10.1164/rccm.201901-0014TR
Bayar Muluk N, Cingi C, Scadding GK, Scadding G. Chronic rhinosinusitis—could phenotyping or endotyping aid therapy? Am J Rhinol Allergy. 2019;33(1):83–93. DOI: 10.1177/1945892418807590
Seymour CW, Kennedy JN, Wang S, et al. Derivation, validation, and potential treatment implications of novel clinical phenotypes for sepsis. JAMA. 2019;321(20):2003–17. DOI: 10.1001/jama.2019.5791
Schoettler N, Strek ME. Recent advances in severe asthma: from phenotypes to personalized medicine. Chest. 2020;157(3):516–28. DOI: 10.1016/j.chest.2019.10.009
Ruffner MA, Cianferoni A. Phenotypes and endotypes in eosinophilic esophagitis. Ann Allergy Asthma Immunol. 2020;124(3):233–9. DOI: 10.1016/j.anai.2019.12.011
Threlkeld ZD, Bodien YG, Rosenthal ES, et al. Functional networks reemerge during recovery of consciousness after acute severe traumatic brain injury. Cortex. 2018;106:299–308. DOI: 10.1016/j.cortex.2018.05.004
Chatelle C, Rosenthal ES, Bodien YG, Spencer-Salmon CA, Giacino JT, Edlow BL. EEG correlates of language function in traumatic disorders of consciousness. Neurocrit Care. 2020;33(2):449–57. DOI: 10.1007/s12028-019-00904-3
Pan J, Xie Q, Qin P, et al. Prognosis for patients with cognitive motor dissociation identified by brain–computer interface. Brain. 2020;143(4):1177–89. DOI: 10.1093/brain/awaa026
Nielson JL, Cooper SR, Yue JK, et al. Uncovering precision phenotype–biomarker associations in traumatic brain injury using topological data analysis. PLoS ONE. 2017;12(3):e0169490. DOI: 10.1371/journal.pone.0169490
Gravesteijn BY, Sewalt CA, Ercole A, et al. Toward a new multi-dimensional classification of traumatic brain injury: a collaborative European neurotrauma effectiveness research for traumatic brain injury study. J Neurotrauma. 2020;37(7):1002–10. DOI: 10.1089/neu.2019.6764
Hinson HE, Puybasset L, Weiss N, et al. Neuroanatomical basis of paroxysmal sympathetic hyperactivity: a diffusion tensor imaging analysis. Brain Inj. 2015;29(4):455–61. DOI: 10.3109/02699052.2014.995229
Rosenthal ES, Biswal S, Zafar SF, et al. Continuous electroencephalography predicts delayed cerebral ischemia after subarachnoid hemorrhage: a prospective study of diagnostic accuracy. Ann Neurol. 2018;83(5):958–69. DOI: 10.1002/ana.25232
Rubin DB, Angelini B, Shoukat M, et al. Electrographic predictors of successful weaning from anaesthetics in refractory status epilepticus. Brain. 2020;143(3):1143–57.
Froese L, Dian J, Batson C, et al. The Impact of vasopressor and sedative agents on cerebrovascular reactivity and compensatory reserve in traumatic brain injury: an exploratory analysis. Neurotrauma Rep. 2020;1(1):157–68. DOI: 10.1089/neur.2020.0028
Froese L, Dian J, Batson C, Gomez A, Unger B, Zeiler FA. The impact of hypertonic saline on cerebrovascular reactivity and compensatory reserve in traumatic brain injury: an exploratory analysis. Acta Neurochir (Wien). 2020;162(11):2683–93. DOI: 10.1007/s00701-020-04579-0
Jain A, Jain M, Bellolio MF, Schears RM, Rabinstein AA, Ganti L. Is early DNR a self-fulfilling prophecy for patients with spontaneous intracerebral hemorrhage? Neurocrit Care. 2013;19(3):342–6. DOI: 10.1007/s12028-013-9878-2
Cho S, Mulder M, Geocadin RG. Early electroencephalogram for neurologic prognostication: a self-fulfilling prophecy? Ann Neurol. 2019;86(3):473–4. DOI: 10.1002/ana.25539
McCracken DJ, Lovasik BP, McCracken CE, et al. The intracerebral hemorrhage score: a self-fulfilling prophecy? Clin Neurosurg. 2019;84(3):741–7. DOI: 10.1093/neuros/nyy193
Turgeon AF, Lauzier F, Simard J-F, et al. Mortality associated with withdrawal of life-sustaining therapy for patients with severe traumatic brain injury: a Canadian multicentre cohort study. Can Med Assoc J. 2011;183(14):1581–8. DOI: 10.1503/cmaj.101786
Atkinson AJ, Colburn WA, DeGruttola VG, et al. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69(3):89–95. DOI: 10.1067/mcp.2001.113989
Giacino JT, Sherer M, Christoforou A, et al. Behavioral recovery and early decision making in patients with prolonged disturbance in consciousness after traumatic brain injury. J Neurotrauma. 2020;37(2):357–65. DOI: 10.1089/neu.2019.6429
Edlow BL, Claassen J, Schiff ND, Greer DM. Recovery from disorders of consciousness: mechanisms, prognosis and emerging therapies. Nat Rev Neurol. 2021;17(3):135–56. DOI: 10.1038/s41582-020-00428-x
Izzy S, Compton R, Carandang R, Hall W, Muehlschlegel S. Self-fulfilling prophecies through withdrawal of care: do they exist in traumatic brain injury, too? Neurocrit Care. 2013;19(3):347–63. DOI: 10.1007/s12028-013-9925-z
Elmer J, Torres C, Aufderheide TP, et al. Association of early withdrawal of life-sustaining therapy for perceived neurological prognosis with mortality after cardiac arrest. Resuscitation. 2016;102:127–35. DOI: 10.1016/j.resuscitation.2016.01.016
Cruse D, Chennu S, Chatelle C, et al. Bedside detection of awareness in the vegetative state: a cohort study. Lancet. 2011;378(9809):2088–94. DOI: 10.1016/S0140-6736(11)61224-5
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):2157–68. DOI: 10.1016/j.clinph.2011.03.022
Schiff ND. Cognitive motor dissociation following severe brain injuries. JAMA Neurol. 2015;72(12):1413. DOI: 10.1001/jamaneurol.2015.2899
Kondziella D, Friberg CK, Frokjaer VG, Fabricius M, Møller K. Preserved consciousness in vegetative and minimal conscious states: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2016;87(5):485–92. DOI: 10.1136/jnnp-2015-310958
Sokoliuk R, Degano G, Banellis L, et al. Covert speech comprehension predicts recovery from acute unresponsive states. Ann Neurol. 2020;89(4):646–56. DOI: 10.1002/ana.25995
Chou SH-Y, Robertson CS, Participants in the International Multi-disciplinary Consensus Conference on the Multimodality Monitoring. Monitoring biomarkers of cellular injury and death in acute brain injury. Neurocrit Care. 2014;21(Suppl 2):S187–214. DOI: 10.1007/s12028-014-0039-z
Hillered L, Vespa PM, Hovda DA. Translational neurochemical research in acute human brain injury: the current status and potential future for cerebral microdialysis. J Neurotrauma. 2005;22(1):3–41. DOI: 10.1089/neu.2005.22.3
Hutchinson P, O’Phelan K, Participants in the International Multidisciplinary Consensus Conference on Multimodality Monitoring. International multidisciplinary consensus conference on multimodality monitoring: cerebral metabolism. Neurocrit Care. 2014;21(Suppl 2):S148–58. DOI: 10.1007/s12028-014-0035-3
Chou SHY, Macdonald RL, Keller E, et al. Biospecimens and molecular and cellular biomarkers in aneurysmal subarachnoid hemorrhage studies: common data elements and standard reporting recommendations. Neurocrit Care. 2019;30(Suppl 1):46–59. DOI: 10.1007/s12028-019-00725-4
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):161–71. DOI: 10.1093/brain/awp313
Demertzi A, Antonopoulos G, Heine L, et al. Intrinsic functional connectivity differentiates minimally conscious from unresponsive patients. Brain. 2015;138(Pt 9):2619–31. DOI: 10.1093/brain/awv169
Wu X, Zou Q, Hu J, et al. Intrinsic functional connectivity patterns predict consciousness level and recovery outcome in acquired brain injury. J Neurosci. 2015;35(37):12932–46. DOI: 10.1523/JNEUROSCI.0415-15.2015
Demertzi A, Tagliazucchi E, Dehaene S, et al. Human consciousness is supported by dynamic complex patterns of brain signal coordination. Sci Adv. 2019;5(2):eaat7603. DOI: 10.1126/sciadv.aat7603
Kondziella D, Fisher PM, Larsen VA, et al. Functional MRI for assessment of the default mode network in acute brain injury. Neurocrit Care. 2017;27(3):401–6. DOI: 10.1007/s12028-017-0407-6
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):175–81. DOI: 10.1212/WNL.0b013e31823fcd61
Qin P, Wu X, Huang Z, et al. How are different neural networks related to consciousness? Ann Neurol. 2015;78(4):594–605. DOI: 10.1002/ana.24479
Jenkins PO, De Simoni S, Bourke NJ, et al. Stratifying drug treatment of cognitive impairments after traumatic brain injury using neuroimaging. Brain. 2019;142(8):2367–79. DOI: 10.1093/brain/awz149
Fridman EA, Osborne JR, Mozley PD, Victor JD, Schiff ND. Presynaptic dopamine deficit in minimally conscious state patients following traumatic brain injury. Brain. 2019;142(7):1887–93. DOI: 10.1093/brain/awz118
Edlow BL, Barra ME, Zhou DW, et al. Personalized connectome mapping to guide targeted therapy and promote recovery of consciousness in the intensive care unit. Neurocrit Care. 2020;33(2):364–75. DOI: 10.1007/s12028-020-01062-7
Comanducci A, Boly M, Claassen J, 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. 2020;131(11):2736–65. DOI: 10.1016/j.clinph.2020.07.015
Curley WH, Forgacs PB, Voss HU, Conte MM, Schiff ND. Characterization of EEG signals revealing covert cognition in the injured brain. Brain. 2018;141(5):1404–21. DOI: 10.1093/brain/awy070
Braiman C, Fridman EA, Conte MM, et al. Cortical response to the natural speech envelope correlates with neuroimaging evidence of cognition in severe brain injury. Curr Biol. 2018;28(23):3833-9.e3. DOI: 10.1016/j.cub.2018.10.057
Forgacs PB, Frey HP, Velazquez A, et al. Dynamic regimes of neocortical activity linked to corticothalamic integrity correlate with outcomes in acute anoxic brain injury after cardiac arrest. Ann Clin Transl Neurol. 2017;4(2):119–29. DOI: 10.1002/acn3.385
Claassen J, Velazquez A, Meyers E, et al. Bedside quantitative electroencephalography improves assessment of consciousness in comatose subarachnoid hemorrhage patients. Ann Neurol. 2016;80(4):541–53. DOI: 10.1002/ana.24752
Forgacs PB, Devinsky O, Schiff ND. Independent functional outcomes after prolonged coma following cardiac arrest: a mechanistic hypothesis. Ann Neurol. 2020;87(4):618–32. DOI: 10.1002/ana.25690
Tononi G, Boly M, Massimini M, Koch C. Integrated information theory: from consciousness to its physical substrate. Nat Rev Neurosci. 2016;17(7):450–61. DOI: 10.1038/nrn.2016.44
Sarasso S, Rosanova M, Casali AG, et al. Quantifying cortical EEG responses to TMS in (Un)consciousness. Clin EEG Neurosci. 2014;45(1):40–9. DOI: 10.1177/1550059413513723
Casali AG, Gosseries O, Rosanova M, et al. A theoretically based index of consciousness independent of sensory processing and behavior. Sci Transl Med. 2013;5(198):198ra105. DOI: 10.1126/scitranslmed.3006294
Casarotto S, Comanducci A, Rosanova M, et al. Stratification of unresponsive patients by an independently validated index of brain complexity. Ann Neurol. 2016;80(5):718–29. DOI: 10.1002/ana.24779
Comolatti R, Pigorini A, Casarotto S, et al. A fast and general method to empirically estimate the complexity of brain responses to transcranial and intracranial stimulations. Brain Stimul. 2019;12(5):1280–9. DOI: 10.1016/j.brs.2019.05.013
Committee on the Review of Omics-Based Tests for Predicting Patient Outcomes in Clinical Trials; Board on Health Care Services; Board on Health Sciences Policy; Institute of Medicine. Evolution of translational omics: lessons learned and the path forward. Micheel CM, Nass SJ, Omenn GS, editors. Washington (DC): National Academies Press; 2012.
Moore HM, Kelly AB, Jewell SD, et al. Biospecimen Reporting for Improved Study Quality (BRISQ). J Proteome Res. 2011;10(8):3429–38. DOI: 10.1021/pr200021n
Thibaut A, Schiff N, Giacino J, Laureys S, Gosseries O. Therapeutic interventions in patients with prolonged disorders of consciousness. Lancet Neurol. 2019;18(6):600–14. DOI: 10.1016/S1474-4422(19)30031-6
Olson DWM, Ortega-Pérez S. The cue-response theory and nursing care of the patient with acquired brain injury. J Neurosci Nurs. 2019;51(1):43–7. DOI: 10.1097/JNN.0000000000000426
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):819–26. DOI: 10.1056/NEJMoa1102609
Whyte J, Rajan R, Rosenbaum A, et al. Zolpidem and restoration of consciousness. Am J Phys Med Rehabil. 2014;93(2):101–13. DOI: 10.1097/PHM.0000000000000069
Machado C, Estévez M, Rodríguez R, et al. Zolpidem arousing effect in persistent vegetative state patients: autonomic, EEG and behavioral assessment. Curr Pharm Des. 2014;20(26):4185–202.
Cincotta M, Giovannelli F, Chiaramonti R, et al. No effects of 20 Hz-rTMS of the primary motor cortex in vegetative state: a randomised, sham-controlled study. Cortex. 2015;71:368–76. DOI: 10.1016/j.cortex.2015.07.027
Liu P, Gao J, Pan S, et al. Effects of High-frequency repetitive transcranial magnetic stimulation on cerebral hemodynamics in patients with disorders of consciousness: a sham-controlled study. Eur Neurol. 2016;76(1–2):1–7. DOI: 10.1159/000447325
He F, Wu M, Meng F, et al. Effects of 20 Hz repetitive transcranial magnetic stimulation on disorders of consciousness: a resting-state electroencephalography study. Neural Plast. 2018;2018:5036184. DOI: 10.1155/2018/5036184
Zhao H, Qiao L, Fan D, et al. Modulation of brain activity with noninvasive transcranial direct current stimulation (tDCS): clinical applications and safety concerns. Front Psychol. 2017;8:685. DOI: 10.3389/fpsyg.2017.00685
Naro A, Russo M, Leo A, Bramanti P, Quartarone A, Calabrò RS. A single session of repetitive transcranial magnetic stimulation over the dorsolateral prefrontal cortex in patients with unresponsive wakefulness syndrome: preliminary results. Neurorehabil Neural Repair. 2015;29(7):603–13. DOI: 10.1177/1545968314562114
Pisani LR, Naro A, Leo A, et al. Repetitive transcranial magnetic stimulation induced slow wave activity modification: a possible role in disorder of consciousness differential diagnosis? Conscious Cogn. 2015;38:1–8. DOI: 10.1016/j.concog.2015.09.012
Pape TLB, Rosenow JM, Patil V, et al. RTMS safety for two subjects with disordered consciousness after traumatic brain injury. Brain Stimul. 2014;7(4):620–2. DOI: 10.1016/j.brs.2014.03.007
Xia X, Bai Y, Zhou Y, et al. Effects of 10 Hz repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex in disorders of consciousness. Front Neurol. 2017;8:182. DOI: 10.3389/fneur.2017.00182
Thibaut A, Bruno MA, Ledoux D, Demertzi A, Laureys S. TDCS in patients with disorders of consciousness: sham-controlled randomized double-blind study. Neurology. 2014;82(13):1112–8. DOI: 10.1212/WNL.0000000000000260
Thibaut A, Wannez S, Donneau AF, et al. Controlled clinical trial of repeated prefrontal tDCS in patients with chronic minimally conscious state. Brain Inj. 2017;31(4):466–74. DOI: 10.1080/02699052.2016.1274776
Estraneo A, Pascarella A, Moretta P, et al. Repeated transcranial direct current stimulation in prolonged disorders of consciousness: a double-blind cross-over study. J Neurol Sci. 2017;375:464–70. DOI: 10.1016/j.jns.2017.02.036
Martens G, Lejeune N, O’Brien AT, et al. Randomized controlled trial of home-based 4-week tDCS in chronic minimally conscious state. Brain Stimul. 2018;11(5):982–90. DOI: 10.1016/j.brs.2018.04.021
Huang W, Wannez S, Fregni F, et al. Repeated stimulation of the posterior parietal cortex in patients in minimally conscious state: a sham-controlled randomized clinical trial. Brain Stimul. 2017;10(3):718–20. DOI: 10.1016/j.brs.2017.02.001
Hermann B, Raimondo F, Hirsch L, et al. Combined behavioral and electrophysiological evidence for a direct cortical effect of prefrontal tDCS on disorders of consciousness. Sci Rep. 2020;10(1):4323. DOI: 10.1038/s41598-020-61180-2
Thibaut A, Chatelle C, Vanhaudenhuyse A, et al. Transcranial direct current stimulation unveils covert consciousness. Brain Stimul. 2018;11(3):642–4. DOI: 10.1016/j.brs.2018.02.002
Legostaeva L, Poydasheva A, Iazeva E, et al. Stimulation of the angular gyrus improves the level of consciousness. Brain Sci. 2019;9(5):103. DOI: 10.3390/brainsci9050103
Schiff ND, Giacino JT, Kalmar K, et al. Behavioural improvements with thalamic stimulation after severe traumatic brain injury. Nature. 2007;448(7153):600–3. DOI: 10.1038/nature06041
Krewer C, Luther M, Koenig E, Möller F. Tilt table therapies for patients with severe disorders of consciousness: a randomized, controlled trial. PLoS ONE. 2015;10(12):e0143180. DOI: 10.1371/journal.pone.0143180
Pape TLB, Rosenow JM, Steiner M, et al. Placebo-controlled trial of familiar auditory sensory training for acute severe traumatic brain injury. Neurorehabil Neural Repair. 2015;29(6):537–47. DOI: 10.1177/1545968314554626
Corazzol M, Lio G, Lefevre A, et al. Restoring consciousness with vagus nerve stimulation. Curr Biol. 2017;27(18):R994–6. DOI: 10.1016/j.cub.2017.07.060
Mancuso M, Abbruzzese L, Canova S, Landi G, Rossi S, Santarnecchi E. Transcranial random noise stimulation does not improve behavioral and neurophysiological measures in patients with subacute vegetative-unresponsive wakefulness state (VS-UWS). Front Hum Neurosci. 2017;11:524. DOI: 10.3389/fnhum.2017.00524
Angus DC, Derde L, Al-Beidh F, et al. Effect of hydrocortisone on mortality and organ support in patients with severe COVID-19: the REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial. JAMA. 2020;324(13):1317–29. DOI: 10.1001/jama.2020.17022
Suarez JI, Martin RH, Bauza C, et al. Worldwide organization of neurocritical care: results from the PRINCE study part 1. Neurocrit Care. 2020;32(1):172–9. DOI: 10.1007/s12028-019-00750-3
Venkatasubba Rao CP, Suarez JI, Martin RH, et al. Global survey of outcomes of neurocritical care patients: analysis of the PRINCE study part 2. Neurocrit Care. 2020;32(1):88–103. DOI: 10.1007/s12028-019-00835-z
Rubin M, Bonomo J, Hemphill JC. Intersection of prognosis and palliation in neurocritical care. Curr Opin Crit Care. 2017;23(2):134–9. DOI: 10.1097/MCC.0000000000000396
Bodien YG, Carlowicz CA, Chatelle C, Giacino JT. Sensitivity and specificity of the coma recovery scale–revised total score in detection of conscious awareness. Arch Phys Med Rehabil. 2016;97(3):490-492.e1. DOI: 10.1016/j.apmr.2015.08.422
Becker KJ, Baxter AB, Cohen WA, et al. Withdrawal of support in intracerebral hemorrhage may lead to self-fulfilling prophecies. Neurology. 2001;56(6):766–72. DOI: 10.1212/WNL.56.6.766
Albaeni A, Chandra-Strobos N, Vaidya D, Eid SM. Predictors of early care withdrawal following out-of-hospital cardiac arrest. Resuscitation. 2014;85(11):1455–61. DOI: 10.1016/j.resuscitation.2014.08.030
Williamson T, Ryser MD, Ubel PA, et al. Withdrawal of life-supporting treatment in severe traumatic brain injury. JAMA Surg. 2020;155(8):723–31. DOI: 10.1001/jamasurg.2020.1790
Lazaridis C. Withdrawal of life-sustaining treatments in perceived devastating brain injury: the key role of uncertainty. Neurocrit Care. 2019;30(1):33–41. DOI: 10.1007/s12028-018-0595-8
Menon DK, Kolias AG, Servadei F, Hutchinson PJ. Survival with disability. Whose life is it, anyway? Br J Anaesth. 2017;119(5):1062–3. DOI: 10.1093/bja/aex374
Needham DM, Davidson J, Cohen H, et al. Improving long-term outcomes after discharge from intensive care unit: report from a stakeholders’ conference. Crit Care Med. 2012;40(2):502–9. DOI: 10.1097/CCM.0b013e318232da75
Bautista CA, Nydahl P, Bader MK, Livesay S, Cassier-Woidasky AK, Olson DWM. Executive summary: post-intensive care syndrome in the neurocritical intensive care unit. J Neurosci Nurs. 2019;51(4):158–61. DOI: 10.1097/JNN.0000000000000438
Turnbull AE, Rabiee A, Davis WE, et al. Outcome measurement in ICU survivorship research from 1970 to 2013: a scoping review of 425 publications. Crit Care Med. 2016;44(7):1267–77. DOI: 10.1097/CCM.0000000000001651
Schlichter E, Lopez O, Scott R, et al. Feasibility of nurse-led multidimensional outcome assessments in the neuroscience intensive care unit. Crit Care Nurse. 2020;40(3):e1-8. DOI: 10.4037/ccn2020681
Katzan IL, Schuster A, Newey C, Uchino K, Lapin B. Patient-reported outcomes across cerebrovascular event types: more similar than different. Neurology. 2018;91(23):E2182–91. DOI: 10.1212/WNL.0000000000006626
Quinn T, Moskowitz J, Khan MW, et al. What families need and physicians deliver: contrasting communication preferences between surrogate decision-makers and physicians during outcome prognostication in critically ill TBI patients. Neurocrit Care. 2017;27(2):154–62. DOI: 10.1007/s12028-017-0427-2
Christakis NA, Iwashyna TJ. Attitude and self-reported practice regarding prognostication in a national sample of internists. Arch Intern Med. 1998;158(21):2389–95. DOI: 10.1001/archinte.158.21.2389
Edlow BL, Fins JJ. Assessment of covert consciousness in the intensive care unit: clinical and ethical considerations. J Head Trauma Rehabil. 2018;33(6):424–34. DOI: 10.1097/HTR.0000000000000448
Hwang DY, Dell CA, Sparks MJ, et al. Clinician judgment versus formal scales for predicting intracerebral hemorrhage outcomes. Neurology. 2016;86(2):126–33. DOI: 10.1212/WNL.0000000000002266
Gravesteijn BY, Nieboer D, Ercole A, et al. Machine learning algorithms performed no better than regression models for prognostication in traumatic brain injury. J Clin Epidemiol. 2020;122:95–107. DOI: 10.1016/j.jclinepi.2020.03.005
Dijkland SA, Foks KA, Polinder S, et al. Prognosis in moderate and severe traumatic brain injury: a systematic review of contemporary models and validation studies. J Neurotrauma. 2020;37(1):1–13. DOI: 10.1089/neu.2019.6401
Foreman B. Neurocritical care: bench to bedside (eds. Claude Hemphill, Michael James) integrating and using big data in neurocritical care. Neurotherapeutics. 2020;17(2):593–605. DOI: 10.1007/s13311-020-00846-1
Yeatts SD, Martin RH, Meurer W, et al. Sliding scoring of the glasgow outcome scale-extended as primary outcome in traumatic brain injury trials. J Neurotrauma. 2020;37(24):2674–9. DOI: 10.1089/neu.2019.6969
Mitchell P. Adaptive preferences, adapted preferences. Mind. 2018;127(508):1003–25. DOI: 10.1093/mind/fzy020
Rahme R, Zuccarello M, Kleindorfer D, Adeoye OM, Ringer AJ. Decompressive hemicraniectomy for malignant middle cerebral artery territory infarction: is life worth living? J Neurosurg. 2012;117(4):749–54. DOI: 10.3171/2012.6.JNS111140
Corral L, Javierre CF, Ventura JL, Marcos P, Herrero JI, Mañez R. Impact of non-neurological complications in severe traumatic brain injury outcome. Crit Care. 2012;16(2):R44. DOI: 10.1186/cc11243
Muehlschlegel S, Carandang R, Ouillette C, Hall W, Anderson F, Goldberg R. Frequency and impact of intensive care unit complications on moderate–severe traumatic brain injury: early results of the outcome prognostication in traumatic brain injury (OPTIMISM) study. Neurocrit Care. 2013;18(3):318–31. DOI: 10.1007/s12028-013-9817-2
Wartenberg KE, Schmidt JM, Claassen J, et al. Impact of medical complications on outcome after subarachnoid hemorrhage. Crit Care Med. 2006;34(3):617–23. DOI: 10.1097/01.CCM.0000201903.46435.35
Sasannejad C, Ely EW, Lahiri S. Long-term cognitive impairment after acute respiratory distress syndrome: a review of clinical impact and pathophysiological mechanisms. Crit Care. 2019;23(1):352. DOI: 10.1186/s13054-019-2626-z
Sharrief AZ, Sánchez BN, Lisabeth LD, et al. The impact of pre-stroke depressive symptoms, fatalism, and social support on disability after stroke. J Stroke Cerebrovasc Dis. 2017;26(11):2686–91. DOI: 10.1016/j.jstrokecerebrovasdis.2017.06.039
Colantuoni E, Scharfstein DO, Wang C, et al. Statistical methods to compare functional outcomes in randomized controlled trials with high mortality. BMJ. 2018;360:j5748. DOI: 10.1136/bmj.j5748
Hemphill JC III, White DB. Clinical nihilism in neuroemergencies. Emerg Med Clin North Am. 2009;27(1):27–37, vii–viii. DOI: 10.1016/j.emc.2008.08.009
Kulkarni SS, Briggs A, Sacks OA, et al. Inner deliberations of surgeons treating critically-ill emergency general surgery patients: a qualitative analysis. Ann Surg. 2019. 10.1097/SLA.0000000000003669. DOI: 10.1097/SLA.0000000000003669
Turgeon AF, Dorrance K, Archambault P, et al. Factors influencing decisions by critical care physicians to withdraw life-sustaining treatments in critically ill adult patients with severe traumatic brain injury. CMAJ. 2019;191(24):E652–63. DOI: 10.1503/cmaj.190154
Kon AA, Davidson JE, Morrison W, Danis M, White DB. Shared decision making in ICUs: an American college of critical care medicine and American thoracic society policy statement. Crit Care Med. 2016;44(1):188–201. DOI: 10.1097/CCM.0000000000001396
White DB, Malvar G, Karr J, Lo B, Curtis JR. Expanding the paradigm of the physician’s role in surrogate decision-making: an empirically derived framework. Crit Care Med. 2010;38(3):743–50. DOI: 10.1097/CCM.0b013e3181c58842
Davidson JE, Aslakson RA, Long AC, et al. Guidelines for family-centered care in the neonatal, pediatric, and adult ICU. Crit Care Med. 2017;45(1):103–28. DOI: 10.1097/CCM.0000000000002169
Institute of Medicine (US) Committee on Quality of Health Care in America. Crossing the quality chasm: a new health system for the 21st century. Washington: National Academies Press; 2001.
Zier LS, Burack JH, Micco G, et al. Doubt and belief in physicians’ ability to prognosticate during critical illness: the perspective of surrogate decision makers. Crit Care Med. 2008;36(8):2341–7. DOI: 10.1097/CCM.0b013e318180ddf9
This finding resulted from the robust exploration of existing knowledge and knowledge gaps related to the experiences of family members of victims of cardiac arrest and severe neurotrauma, conducted in form of a workshop on 11/19/2020, funded by the administrative supplement to SIREN U24 (NS100659 02S1) titled “Understanding Paramedic, Trial Network, and Patient’s Family Experiences in Emergency Research Clinical Trials”. This workshop included family members and survivors of cardiac arrest and severe neurotrauma, as well as multidisciplinary clinicians.
Donovan AL, Matthew Aldrich J, Kendall Gross A, et al. Interprofessional care and teamwork in the ICU. Crit Care Med. 2018;46(6):980–90. DOI: 10.1097/CCM.0000000000003067
Au SS, Roze des Ordons AL, Blades KG, Stelfox HT. Best practices toolkit for family participation in ICU rounds. J Eval Clin Pract. 2020. 10.1111/jep.13517. DOI: 10.1111/jep.13517
Roze des Ordons AL, Stelfox HT, Grindrod-Millar K, Sinuff T, Smiechowski J, Sinclair S. Challenges and enablers of spiritual care for family members of patients in the intensive care unit. J Pastoral Care Counsel. 2020;74(1):12–21. DOI: 10.1177/1542305019890120
Dew MA, DiMartini AF, Dobbels F, et al. The 2018 ISHLT/APM/AST/ICCAC/STSW recommendations for the psychosocial evaluation of adult cardiothoracic transplant candidates and candidates for long-term mechanical circulatory support. J Hear Lung Transplant. 2018;37(7):803–23. DOI: 10.1016/j.healun.2018.03.005
Dhand A, Luke DA, Lang CE, Lee JM. Social networks and neurological illness. Nat Rev Neurol. 2016;12(10):605–12. DOI: 10.1038/nrneurol.2016.119
Carney N, Totten AM, O’Reilly C, et al. Guidelines for the management of severe traumatic brain injury, fourth edition. Neurosurgery. 2017;80(1):6–15. DOI: 10.1227/NEU.0000000000001432
Spaite DW, Bobrow BJ, Keim SM, et al. Association of statewide implementation of the prehospital traumatic brain injury treatment guidelines with patient survival following traumatic brain injury: the Excellence in Prehospital Injury Care (EPIC) Study. JAMA Surg. 2019;154(7):191152. DOI: 10.1001/jamasurg.2019.1152
Nakashima T, Noguchi T, Tahara Y, et al. Public-access defibrillation and neurological outcomes in patients with out-of-hospital cardiac arrest in Japan: a population-based cohort study. Lancet. 2019;394(10216):2255–62. DOI: 10.1016/S0140-6736(19)32488-2
Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346(8):549–56. DOI: 10.1056/NEJMoa012689
Giacino JT, Katz DI, Schiff ND, et al. Practice guideline update recommendations summary: disorders of consciousness. Neurology. 2018;91(10):450–60. DOI: 10.1212/WNL.0000000000005926
Multi-Society Task Force on PVS. Medical aspects of the persistent vegetative state (1). N Engl J Med. 1994;330(21):1499–508. DOI: 10.1056/NEJM199405263302107
Whyte J, Nordenbo AM, Kalmar K, et al. Medical complications during inpatient rehabilitation among patients with traumatic disorders of consciousness. Arch Phys Med Rehabil. 2013;94(10):1877–83. DOI: 10.1016/j.apmr.2012.12.027
Weppner JL, Wagner A, Galang GF, Franzese K, Didesch M, Linsenmeyer M. More than just “Dispo”: effects of an acute care brain injury medicine continuity service on healthcare utilization and rehabilitation outcomes [abstract]. PM R. 2019;11 Suppl 2. https://pmrjabstracts.org/abstract/more-than-just-dispo-effects-of-an-acute-care-brain-injury-medicine-continuity-service-on-healthcare-utilization-and-rehabilitation-outcomes/. Accessed 27 Dec 2020.
Nakase-Richardson R, Whyte J, Giacino JT, et al. Longitudinal outcome of patients with disordered consciousness in the NIDRR TBI Model Systems Programs. J Neurotrauma. 2012;29(1):59–65. DOI: 10.1089/neu.2011.1829
Hammond FM, Giacino JT, Nakase Richardson R, et al. Disorders of consciousness due to traumatic brain injury: functional status ten years post-injury. J Neurotrauma. 2019;36(7):1136–46. DOI: 10.1089/neu.2018.5954
Giacino JT, Katz DI, Schiff ND, et al. Practice guideline update recommendations summary: disorders of consciousness: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology; the American Congress of Rehabilitation Medicine; and the National Institute on Disability, Independent Living, and Rehabilitation Research. Neurology. 2018;91(10):450–60. DOI: 10.1212/WNL.0000000000005926
Multi-Society Task Force on PVS. medical aspects of the persistent vegetative state (2). N Engl J Med. 1994;330(22):1572–9. Erratum in: N Engl J Med. 1995;333(2):130.
Suarez JI, Macdonald RL. The end of the tower of babel in subarachnoid hemorrhage: common data elements at last. Neurocrit Care. 2019;30(Suppl 1):1–3. DOI: 10.1007/s12028-019-00751-2
Kumar A, Niknam K, Lumba-Brown A, et al. Practice variation in the diagnosis of aneurysmal subarachnoid hemorrhage: a survey of us and canadian emergency medicine physicians. Neurocrit Care. 2019;31(2):321–8. DOI: 10.1007/s12028-019-00679-7
McNett M, Fink EL, Schober M, et al. The global consortium study of neurological dysfunction in COVID-19 (GCS-NeuroCOVID): development of case report forms for global use. Neurocrit Care. 2020;33(3):793–828. DOI: 10.1007/s12028-020-01100-4
Huijben JA, Wiegers EJA, Lingsma HF, et al. Changing care pathways and between-center practice variations in intensive care for traumatic brain injury across Europe: a CENTER-TBI analysis. Intensive Care Med. 2020;46(5):995–1004. DOI: 10.1007/s00134-020-05965-z
Dijkland SA, Jaja BNR, van der Jagt M, et al. Between-center and between-country differences in outcome after aneurysmal subarachnoid hemorrhage in the subarachnoid hemorrhage international trialists (SAHIT) repository. J Neurosurg. 2020;133(4):1132–40. DOI: 10.3171/2019.5.JNS19483
Taran S, Trivedi V, Singh JM, English SW, McCredie VA. The use of standardized management protocols for critically ill patients with non-traumatic subarachnoid hemorrhage: a systematic review. Neurocrit Care. 2020;32(3):858–74. DOI: 10.1007/s12028-019-00867-5
Wartenberg KE, Hwang DY, Haeusler KG, et al. Gap analysis regarding prognostication in neurocritical care: a joint statement from the German Neurocritical Care Society and the Neurocritical Care Society. Neurocrit Care. 2019;31(2):231–44. DOI: 10.1007/s12028-019-00769-6
Vaccarino AL, Dharsee M, Strother S, et al. Brain-CODE: a secure neuroinformatics platform for management, federation, sharing and analysis of multi-dimensional neuroscience data. Front Neuroinform. 2018;12:28. DOI: 10.3389/fninf.2018.00028
Mori S, Wu D, Ceritoglu C, et al. MRICloud: delivering high-throughput MRI neuroinformatics as cloud-based software as a service. Comput Sci Eng. 2016;18(5):21–35. DOI: 10.1109/MCSE.2016.93
Framingham Heart Study. https://framinghamheartstudy.org/. Accessed 18 Jan 2021.
Mueller SG, Weiner MW, Thal LJ, et al. The Alzheimer’s disease neuroimaging initiative. Neuroimaging Clin N Am. 2005;15(4):869–77. DOI: 10.1016/j.nic.2005.09.008
Yue JK, Vassar MJ, Lingsma HF, et al. Transforming research and clinical knowledge in traumatic brain injury pilot: multicenter implementation of the common data elements for traumatic brain injury. J Neurotrauma. 2013;30(22):1831–44. DOI: 10.1089/neu.2013.2970
Adhikari NKJ, Arali R, Attanayake U, et al. Implementing an intensive care registry in India: preliminary results of the case-mix program and an opportunity for quality improvement and research. Wellcome Open Res. 2020;5:182. DOI: 10.12688/wellcomeopenres.16152.2
Transforming research and clinical knowledge in traumatic brain injury (TRACK-TBI) precision medicine phase 2 option 1. https://clinicaltrials.gov/ct2/show/NCT04602806?term=track-tbi&draw=2&rank=1. Accessed 1 Feb 2021.
Maas AIR, Menon DK, Steyerberg EW, et al. Collaborative European neurotrauma effectiveness research in traumatic brain injury (CENTER-TBI): a prospective longitudinal observational study. Neurosurgery. 2015;76(1):67–80. DOI: 10.1227/NEU.0000000000000575
CENTER-TBI: collaborative European neurotrauma effectiveness research in TBI (CENTER-TBI). https://clinicaltrials.gov/ct2/show/NCT02210221?term=Center+TBI&draw=2&rank=1. Accessed 1 Feb 2021.
Prognosis of brain reflexes (PRORETRO). https://clinicaltrials.gov/ct2/show/NCT02395861?term=ProReTro&draw=2&rank=1. Accessed 1 Feb 2021.
Velly L, Perlbarg V, Boulier T, et al. Use of brain diffusion tensor imaging for the prediction of long-term neurological outcomes in patients after cardiac arrest: a multicentre, international, prospective, observational, cohort study. Lancet Neurol. 2018;17(4):317–26. DOI: 10.1016/S1474-4422(18)30027-9
Multimodal resonance imaging for outcome prediction on coma patients (MRI-Coma). https://clinicaltrials.gov/ct2/show/NCT00577954?term=MRI-COMA&draw=2&rank=1. Accessed 1 Feb 2021.
Recovery of consciousness following intracerebral hemorrhage (RECONFIG). https://clinicaltrials.gov/ct2/show/NCT03990558?term=RECONFIG&draw=2&rank=1. Accessed 1 Feb 2021.
Resting and stimulus-based paradigms to detect organized networks and predict emergence of consciousness (RESPONSE 2). https://clinicaltrials.gov/ct2/show/NCT03504709?term=RESPONSE+edlow&draw=2&rank=1. Accessed 1 Feb 2021.
Wang J, Alotaibi NM, Akbar MA, et al. Loss of consciousness at onset of aneurysmal subarachnoid hemorrhage is associated with functional outcomes in good-grade patients. World Neurosurg. 2017;98:308–13. DOI: 10.1016/j.wneu.2016.10.099
TBI Endpoints Development (TED) Initiative. https://tbiendpoints.ucsf.edu/. Accessed 1 Feb 2021.
