Information of the Coma Recovery Scale-Revised for Neurobehavioral State and Recovery of Consciousness Prediction

Disorder of Consciousness Clinical Trial

— CRS-R_Info  

Official title:

An Analysis of the Information of the Coma Recovery Scale-Revised Providing the Most Reliable Prediction of the Neurobehavioral State and Recovery of Consciousness

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05819177
• Other study ID #: CRS-R_Info
• Status: Completed
• Start date: February 1, 2004
• Est. completion date: December 31, 2021

Study information

• Verified date: April 2023
• Source: Hospitales Nisa
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Background: The Coma Recovery Scale-Revised (CRS-R) is the most recommended instrument to examine the neurobehavioral condition of individuals with disorders of consciousness (DOCs). Different studies have investigated the prognostic value of the information provided by the conventional administration of the scale, while other measures derived from the scale have been proposed to improve the prognosis of DOCs. However, the heterogeneity of the data used in the different studies prevents a reliable comparison of the identified predictors and measures. Objectives: This study investigates which information derived from the CRS-R provides the most reliable prediction of both the neurobehavioral state and recovery of consciousness at the discharge of a long-term neurorehabilitation program. Methods: The clinical records of 171 individuals with DOCs admitted to an inpatient neurorehabilitation program for a minimum of 3 months were used to implement machine learning classifiers that were trained to predict the neurobehavioral state and recovery of consciousness at discharge.

Description:

Severe acquired brain injury, understood as any damage to the brain that causes coma for over 24 hours, can lead to a complex clinical condition characterized by impaired consciousness, commonly referred to as a disorder of consciousness (DOC). The concept of consciousness is multifaceted and complex and arises from the presence of both arousal, i.e. vigilance and wakefulness, and awareness, i.e. perception of the environment and self. Consequently, depending on the presence and nature of the behavioral responses to multisensory stimuli, individuals with DOC are diagnosed as either in an unresponsive wakefulness syndrome (UWS) or vegetative state (VS) if they only show reflexes, or in a minimally conscious state (MCS) if they show intentional responses. Two further subgroups have been proposed within this latter group that allow to categorize individuals in an MCS+ or in an MCS- according to the presence or absence of higher-level behaviors, respectively. Finally, individuals who show functional communication or functional use of objects are considered as emerging from the MCS. Diagnosis of DOCs, therefore, poses a clinical challenge, as it requires the accurate analysis of behavioral signs that can be weak or inconsistent. The Coma Recovery Scale-Revised (CRS-R) is the most recommended instrument worldwide for assessing the neurobehavioral condition of individuals with DOC and features multiple cross-cultural adaptations. The CRS-R investigates the presence of 23 neurobehavioral responses, grouped in 6 different subscales, which evaluate auditory, visual, motor, oromotor, communication, and arousal functions. For each subscale, the responses are hierarchically ordered and are evaluated from higher responses (cognitively-mediated responses) to lower responses (reflexes). The diagnostic utility of the scale was first analyzed in 2004, but it was not until 2010 that its interrater reliability, internal consistency, and prognostic or diagnostic validity supported its use for diagnosis. Additionally, although this has been only proven for traumatic etiology, the scale has demonstrated strong construct validity, with confirmed evidence of monotonicity, mutual independence, and invariant item ordering. In this regard, the hierarchy of the CRS-R has also shown a lack of invariance across relevant group factors including age, sex, etiology, enrollment facility, time since injury, and time between assessments. However, in spite that all these properties of the CRS-R contribute to reduce its diagnostic error in comparison to consensus-based tools, it is recommended that the diagnosis of DOCs is based on the clinical findings from five consecutive assessments and combined with imaging or electrophysiological-derived measures. Interestingly, some authors have proposed alternative indices and measures derived from the CRS-R, such as the CRS-R Modified Score and the CRS-R Index, pursuing an increase in the accuracy of the original version. The total score in the CRS-R has been also identified as an important predictor of recovery of responsiveness in non-traumatic individuals with UWS in Class I studies. In the case of mixed cohorts, however, the current guidelines neither confirm nor refuse the prognostic value of the CRS-R due to insufficient evidence. However, more recent studies highlight the relevance of the information provided by the CRS-R in the prediction of the recovery of consciousness. Measures derived from the CRS-R have been also proposed to improve prognosis of DOCs. Arnaldi and colleagues introduced the CRS+, a weighted score based on the CRS-R to investigate the prognostic value of sleep patterns in the recovery of consciousness. More recently, the Consciousness Domain Index was proposed, an unsupervised machine learning clustering technique based on information from the CRS-R sub-scales to improve the prediction of recovery of consciousness. However, although the information provided by the CRS-R might be essential to predict the clinical progress of individuals with DOCs and many attempts exist to find alternative measures that improve the predictive value of the original instrument, the heterogeneity of the data used in the different studies prevent a reliable comparison of the identified predictors and measures. Consequently, the aim of this study was to determine which information derived from the CRS-R provides the most reliable prediction of both the neurobehavioral state and recovery of consciousness at discharge of a long-term neurorehabilitation program.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 171
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Gender: All
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

• diagnosis with (Unresponsive Wakefulness Syndrome) UWS or Minimal Consciousness State (MCS) due to either a vascular, anoxic or traumatic origin

Exclusion Criteria:

• individuals who did not attended the program for at least three months

Related Conditions & MeSH terms

• Consciousness Disorders
• Disorder of Consciousness

Intervention

Other:
• Rehabilitation program
This group of patients underwent standard rehabilitation programs set by national guidelines.

Locations

Country	Name	City	State
Spain	Hospitales NISA	Valencia
Spain	Servicio de Neurorrehabilitación y Daño Cerebral de los Hospitales NISA	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Hospitales Nisa

Country where clinical trial is conducted

Spain, 

References & Publications (26)

'CRSR_GeneralGuidelines_20200812_v1.pdf'. Accessed: Jun. 09, 2022. [Online]. Available: https://www.sralab.org/sites/default/files/downloads/2020-09/CRSR_GeneralGuidelines_20200812_v1.pdf

American Congress of Rehabilitation Medicine, Brain Injury-Interdisciplinary Special Interest Group, Disorders of Consciousness Task Force; Seel RT, Sherer M, Whyte J, Katz DI, Giacino JT, Rosenbaum AM, Hammond FM, Kalmar K, Pape TL, Zafonte R, Biester RC, Kaelin D, Kean J, Zasler N. Assessment scales for disorders of consciousness: evidence-based recommendations for clinical practice and research. Arch Phys Med Rehabil. 2010 Dec;91(12):1795-813. doi: 10.1016/j.apmr.2010.07.218. — View Citation

Annen J, Filippini MM, Bonin E, Cassol H, Aubinet C, Carriere M, Gosseries O, Thibaut A, Barra A, Wolff A, Sanz LRD, Martial C, Laureys S, Chatelle C. Diagnostic accuracy of the CRS-R index in patients with disorders of consciousness. Brain Inj. 2019;33(11):1409-1412. doi: 10.1080/02699052.2019.1644376. Epub 2019 Jul 18. — View Citation

Arnaldi D, Terzaghi M, Cremascoli R, De Carli F, Maggioni G, Pistarini C, Nobili F, Moglia A, Manni R. The prognostic value of sleep patterns in disorders of consciousness in the sub-acute phase. Clin Neurophysiol. 2016 Feb;127(2):1445-1451. doi: 10.1016/j.clinph.2015.10.042. Epub 2015 Nov 6. — View Citation

Bruno MA, Vanhaudenhuyse A, Thibaut A, Moonen G, Laureys S. From unresponsive wakefulness to minimally conscious PLUS and functional locked-in syndromes: recent advances in our understanding of disorders of consciousness. J Neurol. 2011 Jul;258(7):1373-84. doi: 10.1007/s00415-011-6114-x. Epub 2011 Jun 16. — View Citation

Calabro RS, Naro A. Diagnosing Disorder of Consciousness: The Opening of Pandora's Box! Innov Clin Neurosci. 2016 Apr 1;13(3-4):10-1. eCollection 2016 Mar-Apr. No abstract available. — View Citation

Carriere M, Llorens R, Navarro MD, Olaya J, Ferri J, Noe E. Behavioral signs of recovery from unresponsive wakefulness syndrome to emergence of minimally conscious state after severe brain injury. Ann Phys Rehabil Med. 2022 Mar;65(2):101534. doi: 10.1016/j.rehab.2021.101534. Epub 2021 Nov 18. — View Citation

Estraneo A, Moretta P, Loreto V, Lanzillo B, Cozzolino A, Saltalamacchia A, Lullo F, Santoro L, Trojano L. Predictors of recovery of responsiveness in prolonged anoxic vegetative state. Neurology. 2013 Jan 29;80(5):464-70. doi: 10.1212/WNL.0b013e31827f0f31. Epub 2013 Jan 9. — View Citation

Gerrard P, Zafonte R, Giacino JT. Coma Recovery Scale-Revised: evidentiary support for hierarchical grading of level of consciousness. Arch Phys Med Rehabil. 2014 Dec;95(12):2335-41. doi: 10.1016/j.apmr.2014.06.018. Epub 2014 Jul 7. — View Citation

Giacino JT, Ashwal S, Childs N, Cranford R, Jennett B, Katz DI, Kelly JP, Rosenberg JH, Whyte J, Zafonte RD, Zasler ND. The minimally conscious state: definition and diagnostic criteria. Neurology. 2002 Feb 12;58(3):349-53. doi: 10.1212/wnl.58.3.349. — View Citation

Giacino JT, Kalmar K, Whyte J. The JFK Coma Recovery Scale-Revised: measurement characteristics and diagnostic utility. Arch Phys Med Rehabil. 2004 Dec;85(12):2020-9. doi: 10.1016/j.apmr.2004.02.033. — View Citation

Giacino JT, Katz DI, Schiff ND, Whyte J, Ashman EJ, Ashwal S, Barbano R, Hammond FM, Laureys S, Ling GSF, Nakase-Richardson R, Seel RT, Yablon S, Getchius TSD, Gronseth GS, Armstrong MJ. 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 Sep 4;91(10):450-460. doi: 10.1212/WNL.0000000000005926. Epub 2018 Aug 8. Erratum In: Neurology. 2019 Jul 16;93(3):135. — View Citation

Hirschberg R, Giacino JT. The vegetative and minimally conscious states: diagnosis, prognosis and treatment. Neurol Clin. 2011 Nov;29(4):773-86. doi: 10.1016/j.ncl.2011.07.009. — View Citation

J. T. Giacino, 'COMA RECOVERY SCALE-REVISED ©2004', p. 17, 2020.

Jox RJ, Bernat JL, Laureys S, Racine E. Disorders of consciousness: responding to requests for novel diagnostic and therapeutic interventions. Lancet Neurol. 2012 Aug;11(8):732-8. doi: 10.1016/S1474-4422(12)70154-0. Erratum In: Lancet Neurol. 2012 Oct;11(10):841. — View Citation

La Porta F, Caselli S, Ianes AB, Cameli O, Lino M, Piperno R, Sighinolfi A, Lombardi F, Tennant A. Can we scientifically and reliably measure the level of consciousness in vegetative and minimally conscious States? Rasch analysis of the coma recovery scale-revised. Arch Phys Med Rehabil. 2013 Mar;94(3):527-535.e1. doi: 10.1016/j.apmr.2012.09.035. Epub 2012 Nov 2. — View Citation

Laureys S, Owen AM, Schiff ND. Brain function in coma, vegetative state, and related disorders. Lancet Neurol. 2004 Sep;3(9):537-46. doi: 10.1016/S1474-4422(04)00852-X. — View Citation

Liuzzi P, Grippo A, Campagnini S, Scarpino M, Draghi F, Romoli A, Bahia H, Sterpu R, Maiorelli A, Macchi C, Cecchi F, Carrozza MC, Mannini A. Merging Clinical and EEG Biomarkers in an Elastic-Net Regression for Disorder of Consciousness Prognosis Prediction. IEEE Trans Neural Syst Rehabil Eng. 2022;30:1504-1513. doi: 10.1109/TNSRE.2022.3178801. Epub 2022 Jun 13. — View Citation

Magliacano A, Liuzzi P, Formisano R, Grippo A, Angelakis E, Thibaut A, Gosseries O, Lamberti G, Noe E, Bagnato S, Edlow BL, Lejeune N, Veeramuthu V, Trojano L, Zasler N, Schnakers C, Bartolo M, Mannini A, Estraneo A; IBIA DoC-SIG. Predicting Long-Term Recovery of Consciousness in Prolonged Disorders of Consciousness Based on Coma Recovery Scale-Revised Subscores: Validation of a Machine Learning-Based Prognostic Index. Brain Sci. 2022 Dec 27;13(1):51. doi: 10.3390/brainsci13010051. — View Citation

Martens G, Bodien Y, Sheau K, Christoforou A, Giacino JT. Which behaviours are first to emerge during recovery of consciousness after severe brain injury? Ann Phys Rehabil Med. 2020 Jul;63(4):263-269. doi: 10.1016/j.rehab.2019.10.004. Epub 2019 Nov 26. — View Citation

Noe E, Ferri J, Olaya J, Navarro MD, O'Valle M, Colomer C, Moliner B, Ippoliti C, Maza A, Llorens R. When, How, and to What Extent Are Individuals with Unresponsive Wakefulness Syndrome Able to Progress? Neurobehavioral Progress. Brain Sci. 2021 Jan 19;11(1):126. doi: 10.3390/brainsci11010126. — View Citation

Practice Guideline Update Recommendations Summary_ Disorders of Consciousness.pdf'.

Sattin D, Minati L, Rossi D, Covelli V, Giovannetti AM, Rosazza C, Bersano A, Nigri A, Leonardi M. The Coma Recovery Scale Modified Score: a new scoring system for the Coma Recovery Scale-revised for assessment of patients with disorders of consciousness. Int J Rehabil Res. 2015 Dec;38(4):350-6. doi: 10.1097/MRR.0000000000000135. — View Citation

Schnakers C, Vanhaudenhuyse A, Giacino J, Ventura M, Boly M, Majerus S, Moonen G, Laureys S. Diagnostic accuracy of the vegetative and minimally conscious state: clinical consensus versus standardized neurobehavioral assessment. BMC Neurol. 2009 Jul 21;9:35. doi: 10.1186/1471-2377-9-35. — View Citation

Sousa VD, Rojjanasrirat W. Translation, adaptation and validation of instruments or scales for use in cross-cultural health care research: a clear and user-friendly guideline. J Eval Clin Pract. 2011 Apr;17(2):268-74. doi: 10.1111/j.1365-2753.2010.01434.x. Epub 2010 Sep 28. — View Citation

Wannez S, Heine L, Thonnard M, Gosseries O, Laureys S; Coma Science Group collaborators. The repetition of behavioral assessments in diagnosis of disorders of consciousness. Ann Neurol. 2017 Jun;81(6):883-889. doi: 10.1002/ana.24962. — View Citation

* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recovery of consciousness	Described as Emergence from Minimal Consciousness State (MCS) or from Unresponsive Wakefulness Syndrome (UWS) (1) or presence of Disorder of Consciousness (DoC, 0)	At discharge from the rehabilitation hospital (median of 365 days)
Primary	Neurobehavioral state	Described as Minimal Consciousness State (MCS), Unresponsive Wakefulness Syndrome (UWS), or Emergence from Minimal Consciousness State (E-MCS)	At discharge from the rehabilitation hospital (median of 365 days)