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Brain Injury
ISSN: 0269-9052 (Print) 1362-301X (Online) Journal homepage: http://www.tandfonline.com/loi/ibij20
Score on Coma Recovery Scale-Revised at
admission predicts outcome at discharge in
intensive rehabilitation after severe brain injury
Emilio Portaccio, Azzurra Morrocchesi, Anna Maria Romoli, Bahia Hakiki,
Maria Pia Taglioli, Elena Lippi, Martina Di Renzone, Antonello Grippo &
Claudio Macchi
To cite this article: Emilio Portaccio, Azzurra Morrocchesi, Anna Maria Romoli, Bahia Hakiki, Maria Pia Taglioli, Elena Lippi, Martina Di Renzone, Antonello Grippo & Claudio Macchi (2018): Score on Coma Recovery Scale-Revised at admission predicts outcome at discharge in intensive rehabilitation after severe brain injury, Brain Injury, DOI: 10.1080/02699052.2018.1440420
To link to this article: https://doi.org/10.1080/02699052.2018.1440420
Published online: 26 Feb 2018.
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Score on Coma Recovery Scale-Revised at admission predicts outcome at discharge
in intensive rehabilitation after severe brain injury
Emilio Portaccioa, Azzurra Morrocchesia, Anna Maria Romolia, Bahia Hakikia,b, Maria Pia Tagliolia, Elena Lippia,
Martina Di Renzonea, Antonello Grippoa, and Claudio Macchia,b
aIntensive Rehabilitation Unit IRCCS Don Gnocchi Foundation, Florence, Italy;bDepartment of Experimental and Clinical Medicine, University of Florence, Florence, Italy
ABSTRACT
Objective: To assess the prognostic utility of the Coma Recovery Scale-Revised (CRS-R) in rehabilitation of patients surviving from severe brain injury.
Methods: In this prospective cohort study, all patients consecutively admitted to an Italian Intensive Rehabilitation Unit, with a diagnosis of unresponsive wakefulness syndrome (UWS) or minimally con-scious state (MCS) due to acquired brain injury, underwent clinical evaluations using the Italian version of the CRS-R. At discharge, patients transitioning from UWS to MCS or emergence from MCS (E-MCS) and from MCS to E-MCS were classified as improved responsiveness (IR). Score on the Glasgow Outcome Scale (GOS) at discharge was recorded.
Results: In total, 137 (66 UWS, 71 MCS) subjects were enrolled. After a mean hospital stay of 5.3 ± 2.9 months, 81 (59.1%) patients achieved an IR. In the multivariable analysis, IR was associated with higher CRS-R score at admission (p = 0.002) and younger age at injury (p = 0.010). Moreover, higher GOS scores at discharge were related to younger age at injury (p = 0.018), shorter time post-onset (p = 0.003) and higher CRS-R score at admission (p < 0.001).
Conclusions: Higher CRS-R scores at admission in intensive rehabilitation unit can help differentiate patients with better outcome at discharge, providing information for rehabilitation planning and communication with patients and their caregivers.
ARTICLE HISTORY Received 28 July 2017 Revised 22 January 2018 Accepted 10 February 2018 Published online 23 February 2018 KEYWORDS Coma Recovery Scale-Revised; intensive rehabilitation; severe brain injury; prognosis
Introduction
The prediction of later outcome in patients with disorders of consciousness due to severe brain injury admitted to acute rehabilitation is still an unresolved issue. Over the last few decades, advances in intensive care technology and neurosur-gical procedures led to a significant increase in the number of survivors from severe brain injury, who eventually access inpatient rehabilitation units. After the coma phase, patients can transition to an unresponsive wakefulness syndrome (UWS), a minimally conscious state (MCS) or emerge from the MCS (E-MCS) and recover a full consciousness. The evolution of disorders of consciousness has a great interindi-vidual variability, depending on the aetiology of injury and other demographic, clinical and instrumental factors (1–9).
In the setting of inpatient rehabilitation unit, physicians face two main issues that are strictly intermingled: the accu-rate classification of consciousness level and the prediction of outcome. Estimates of consciousness misdiagnosis in this population consistently range from 30% to 45% (10–12). The errors derive from potential examiner, patient and envir-onmental biases. Recently, the American Congress of Rehabilitation Medicine (13) reviewed the available assess-ment tools for patients with disorders of consciousness. Among the 13 scales evaluated, the authors recommended
with minor reservations for the use in clinical practice only the Coma Recovery Scale-Revised (CRS-R) (14–16).
Regarding outcome prediction, although there is accumu-lating evidence on prognostic factors in the acute phase (17), there is limited information on the predictors of later out-come in patients with low levels of consciousness admitted to acute rehabilitation. In particular, there are a few small sample surveys providing preliminary indications on the role of CRS-R (18–20). With this background, the objective of the present study was to assess the prognostic utility of CRS-R performed at admission in intensive rehabilitation in low-awareness-state patients surviving from severe brain injury.
Materials and methods Participants and procedures
All patients consecutively admitted to the Intensive Rehabilitation Unit at the IRCCS Don Gnocchi Foundation (Florence, Italy) from August 2012 to December 2016 were screened. Inclusion criteria were diagnosis of UWS or MCS due to acquired brain injury (2,21) and age older than 18 years. Within 48 h from admission, all the patients underwent clinical evaluations using the Italian version of the CRS-R (22,23). Ratings were conducted by trained and experienced examiners
(neurolo-CONTACTEmilio Portaccio portilio@tin.it IRCCS Don Gnocchi Foundation, Via di Scandicci, 269, 50143 Florence, Italy.
https://doi.org/10.1080/02699052.2018.1440420
gists and speech therapists). Clinical assessment was performed in the absence of environmental interferences and of medical con-ditions that could have impacted patient alertness. The great majority of patients were assessed in their bed, with the chest raised up to increase arousal and avoid sleepiness. According to the CRS-R manual, at the beginning of each examination, spon-taneous movements were observed for at least 1 min and the arousal protocol was applied if the patient was drowsy. The total CRS-R score was recorded.
During the hospital stay, all patients underwent an indivi-dualized multidisciplinary rehabilitation treatment (1–2 h daily, six days a week). Rehabilitation and pharmacologic approaches were homogeneously planned over the study per-iod according to patient needs.
At discharge, the patient level of consciousness was classi-fied on the basis of clinical assessment (UWS, MCS, or E-MCS) (21). Patients transitioning from UWS to MCS or E-MCS and from MCS to E-MCS were classified as patients with improved responsiveness (IR). We also included in the IR group patients who recovered responsiveness and then died because of new aetiologic events. Moreover, the outcome of brain injury was assessed through the Glasgow Outcome Scale (GOS) at discharge (24,25).
The study was approved by the local ethics committee, and written consent was obtained from the legal guardians of all patients.
Statistical analysis
The main outcome measures were the behavioural classifica-tion and score on the GOS at final discharge.
Baseline characteristics were reported as frequency (per-centage) and mean ± standard deviation (SD) and compared with Pearson’s χ2, Student’s t and Mann–Whitney U tests when appropriate.
Possible predictors of outcome measures at discharge were measured using stepwise multivariable logistic and linear regression models. Model assumptions and goodness of fit were assessed through the Hosmer and Lemeshow test (for logistic regression) and through checking for multicollinear-ity, and the graphical test of standardized residual plots (for linear regression). Regarding behavioural classification (IR vs. not-IR), the multivariable logistic regression model included the following covariates: age at brain injury, sex, aetiology, time post-onset and CRS-R at admission. Regarding the GOS score at discharge, the multivariable linear regression model included the following covariates: age at brain injury, sex, aetiology, time post-onset and CRS-R at admission.
All analyses were performed using SPSS 23.0 software running on Windows (SPSS, Chicago, IL, USA).
Results
During the study period, a total of 215 patients were admitted to the Intensive Rehabilitation Unit at the IRCCS Don Gnocchi Foundation (Florence, Italy). Among those, 74 were classified as having full consciousness at admission, whereas four patients had incomplete data collection. The remaining 137 (66 UWS, 71 MCS) fulfilled the inclusion criteria and were included in the
analysis (Table 1). In comparison with minimally conscious sub-jects, patients diagnosed as UWS survived more frequently from anoxic injury (39.4% vs. 12.7%,p = 0.001;Table 1).
After a mean hospital stay of 5.3 ± 2.9 months, 81 (59.1%) patients achieved an IR. On the whole, 59 (43.4%) subjects emerged from the MCS (11 out of 66 UWS and 48 out of 70 MCS). Moreover, among the 66 subjects with UWS at admission, 21 transitioned to an MCS. Level of consciousness did not improve in the remaining 34 patients with UWS and 22 patients with MCS. Differences between patients with and without IR are reported in Table 2. IR was related with younger age at brain injury (56.7 ± 14.9 vs. 63.1 ± 14.9 years,p = 0.015), shorter median time post-onset (1.4 vs. 1.9 months,p = 0.002), higher median CRS-R score at admission (10.0 vs. 6.5,p = 0.001) and longer median hospital stay (5.3 vs. 4.1 months, p = 0.023). In the multivariable analysis, IR at discharge was confirmed to be asso-ciated with higher CRS-R score at admission (OR 1.12; 95%CI 1.04–1.21; p = 0.002) and younger age at brain injury (OR = 0.96; 95%CI 0.94–0.99; p = 0.010) (Table 3). The Hosmer and Lemeshow test was not significant (p = 0.978), confirming the goodness of fit for the regression model. Nagelkerke R-squared for the final model was 0.19.
Table 1.Characteristics of the study sample at admission. Total sample
(n 137) UWS (n 66) MCS (n 71) p Age at brain injury
(mean ± SD), years 59.3 ± 15.2 59.8 ± 14.6 58.8 ± 15.8 0.692 Sex (n/%) Women 54 (39.4) 26 (39.4) 28 (39.4) 0.996 Men 83 (60.6) 40 (60.6) 43 (60.6) Aetiology (n/%) Traumatic 40 (29.2) 18 (27.3) 22 (31.0) 0.001 Anoxic 35 (25.5) 26 (39.4) 9 (12.7) Vascular/other 62 (45.3) 22 (33.3) 40 (56.3) Time post-onset (mean ± SD, median), months 2.2 ± 2.3, 1.6 2.4 ± 2.9, 1.7 1.9 ± 1.4, 1.5 0.484 CRS-R at admission (mean ± SD, median) 9.3 ± 5.4, 8.0 4.5 ± 1.9, 4.0 13.7 ± 3.6, 13.0 <0.001 UWS: Unresponsive Wakefulness Syndrome
MCS: Minimally Conscious State SD: Standard Deviation
CRS-R: Coma Recovery Scale-Revised
Table 2.Characteristics of patients with or without improved responsiveness at discharge.
IR (n 81) Not-IR (n 56) P Age at brain injury
(mean ± SD), years 56.7 ± 14.9 63.1 ± 14.9 0.015 Sex (n/%) Women 28 (34.6) 26 (46.4) 0.163 Men 53 (65.4) 30 (53.6) Aetiology (n/%) Traumatic 25 (30.9) 15 (26.8) 0.170 Anoxic 16 (19.8) 19 (33.9) Vascular/other 40 (49.4) 22 (39.3) Time post-onset
(mean ± SD, median), months
1.9 ± 2.4, 1.4 2.5 ± 2.1, 1.9 0.002 CRS-R at admission
(mean ± SD, median)
10.5 ± 5.5, 10.0 7.5 ± 4.8, 6.5 0.001 Length of hospital stay
(mean ± SD, median), months
5.8 ± 2.8, 5.3 4.6 ± 3.0, 4.1 0.023 IR: Improved Responsiveness
SD: Standard Deviation
CRS-R: Coma Recovery Scale-Revised 2 E. PORTACCIO ET AL.
At discharge, the majority of patients (69, 50.4%) were classi-fied as severely impaired on the GOS, whereas independence (GOS scores 4–5) was obtained in 20 cases (14.6%). Thirty-four (34.8%) subjects did not emerge from the UWS. The remaining 14 cases (10.2%) died during the hospital stay. In the multi-variable analysis, higher GOS scores were related to younger age at brain injury (B =−0.01; 95%CI −0.19/-2.40; p = 0.018), shorter time post-onset (B =−0.09; 95%CI −0.24/-2.97; p = 0.003) and higher CRS-R score at admission (B = 0.050; 95%CI 0.32–4.03; p < 0.001) (Table 3). Multicollinearity and graphical testing of standardized residual plots confirmed the model assumptions. The R-squared value for the final model was 0.20.
Discussion
In this prospective cohort study, the CRS-R assessment of low-awareness-state patients entering the intensive rehabilitation phase allowed the accurate classification of consciousness level and contributed to the prediction of later outcome. In particular, higher CRS-R scores at admission to inpatient rehabilitation were associated with IR and lower disability levels at discharge.
As for consciousness classification, CRS-R is based on the diagnostic criteria for disorders of consciousness by the Aspen Workgroup (26) and is recommended by the Brain Injury– Interdisciplinary Special Interest Group of the American Congress of Rehabilitation Medicine since its use reduced the 30–45% consciousness misdiagnosis reported in previous assessments (12,13). On the other hand, the prognostic value of CRS-R still needs to be clarified (13). A few studies showed a relationship between CRS-R score at inclusion and patient outcomes, stronger than that observed with scales of func-tional level (such as the Disability Rating Scale) (18,19).
The present prospective study is, to our knowledge, the largest study assessing the role of CRS-R as a prognostic tool in survivors from severe brain injury entering the inpatient rehabilitation phase. Higher score on the CRS-R at admission was related to a higher probability of recovering responsive-ness or consciousresponsive-ness and to higher scores on the GOS at discharge. This relationship was independent of age, sex, aetiology and time post-onset.
These findings have important implications for prognosis definition in inpatient rehabilitation after severe brain injury. Assessment through the CRS-R should be performed early after a severe brain injury, even in the post-acute phase in the Intensive Care Unit and could be included in the panel of demographic, clinical, neuroradiological and electrophysiologi-cal parameters applied in the selection of patients who can
benefit from inpatient rehabilitation. Moreover, our results can assist physicians in the communication process with patients and caregivers. Indeed, families have identified information about prognosis as one of their most important needs after a severe brain injury (27–29), a need often gone unmet (30).
Another important predictor of outcome was younger age at brain injury. This finding is in line with previous publica-tions in which younger age was consistently associated with a better outcome in terms of recovery of responsiveness or consciousness (2,4,7,8,18).
Aetiology, another acknowledged prognostic factor, had a sig-nificant relationship with behavioural classification only at admis-sion in our rehabilitation unit. Indeed, the majority of patients with post-anoxic injury were in unresponsive wakefulness status at study entry. This relationship disappeared at the end of the follow-up and in all the multivariable analyses. This could be due, at least in part, to the higher relevance of aetiology in short-term prognosis. In a previous study, aetiology significantly predicted outcome on the Disability Rating Scale at six weeks after enrol-ment, whereas it lost its significance at 13 weeks (7). Moreover, in other studies assessing recovery from UWS in the long term, the rate of improvement was not related to aetiology (8,31).
Chronicity has been consistently recognized as a predictor of recovery in UWS (2,4,7,18). In terms of IR, in our study its effect was evident only in the univariate analysis, since patients who recovered responsiveness or consciousness had a shorter time post-onset at admission. However, this effect disappeared in the multivariable analysis, suggesting that the predictive role of CRS-R scores at entry was stronger. On the other hand, in terms of disability level at discharge, shorter time post-onset was con-firmed as an independent predictor of better outcome.
In interpreting the study findings, some possible issues should be taken into account. The analysis was based on the total score on the CRS-R, and the relevance of each subscale was not assessed. In previous studies (32,33), recovery of responsive-ness was associated with higher scores and improvement on the visual subscale. It is possible that in our sample, the prognostic role of the total CRS-R was mainly driven by the performance on the visual subset. However, this does not change the value of CRS-R assessment in the early phase of intensive rehabilitation in terms of outcome prediction. Moreover, the time of observa-tion was relatively short, and possible delayed recovery might have been missed. Finally, we did not take into account neuror-adiological and electrophysiological parameters (such as soma-tosensory-evoked potentials and electroencephalographic patterns) (34,35) and clinical complications (such as infections, hydrocephalus) that might have influenced the outcome inde-pendent of the level of consciousness. Indeed, the variance explained by our models is relatively low (20%), and other factors have to be taken into account. Regarding this, an analysis on the predictive role of CRS-R score change during the earliest phase of inpatient rehabilitation is under way in our sample.
Despite these limitations, our findings indicate the useful-ness of assessment on the CRS-R in subjects with severe brain injury entering inpatient rehabilitation. Patients with higher CRS-R scores have a higher probability of benefiting from rehabilitation and encountering a better outcome at discharge, providing information for rehabilitation planning and com-munication with patients and their caregivers. Further studies Table 3.Predictors of IR and higher GOS score at discharge.
OR (95%CI) p
IR at discharge
Younger age at brain injury 0.96 (0.94–0.99) 0.010 CRS-R at admission 1.12 (1.04–1.21) 0.002 GOS score at discharge
Younger age at brain injury −0.01 (−0.19/–2.40) 0.018 Shorter time post-onset −0.09 (−0.24/–2.97) 0.003 CRS-R at admission 0.05 (0.32–4.03) <0.001 IR: Improved Responsiveness
GOS: Glasgow Outcome Scale CRS-R: Coma Recovery Scale-Revised
are needed to confirm its relevance in the long term and on thorough disability measures.
Acknowledgements
The Intensive Rehabilitation Unit Study Group of the IRCCS Don Gnocchi Foundation, Florence, Italy:
Atzori Tiziana, Binazzi Barbara, Boni Roberta, Borsotti Marco, Carrai Riccardo, Castagnoli Chiara, Cecchi Francesca, Croci Loredana, Gallì Irene, Marella Andrea, Mazzucchi Anna, Molino Lova Raffaello, Sorbi Sandro, Tofani Ariela, Paperini Anita, Pasquini Guido, Scarpino Maenia, Vannetti Federica
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.
References
1. Hirschberg R, Giacino JT. The vegetative and minimally con-scious states: diagnosis, prognosis and treatment. Neurol Clin. 2011;29(4):773–86.
2. The Multi-Society Task Force on PVS. Medical aspects of the persistent vegetative state (2). N Engl J Med.1994;330(22):1572–79. 3. Giacino JT, Kalmar K. Diagnostic and prognostic guidelines for the vegetative and minimally conscious states. Neuropsychol Rehabil.2005;15(3–4):166–74.
4. Katz DI, 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. 2009;177:73–88.
5. Lammi MH, Smith VH, Tate RL, Taylor CM. The minimally conscious state and recovery potential: a follow-up study 2 to 5 years after traumatic brain injury. Arch Phys Med Rehabil. 2005;86(4):746–54.
6. Luauté J, Maucort-Boulch D, Tell L, Quelard F, Sarraf T, Iwaz J, Boisson D, Fischer C. Long-term outcomes of chronic mini-mally conscious and vegetative states. Neurology. 2010;75 (3):246–52.
7. Whyte J, Gosseries O, Chervoneva I, DiPasquale MC, Giacino J, Kalmar K, Katz D, Novak P, Long D, Childs N, et al. Predictors of short-term outcome in brain-injured patients with disorders of consciousness. Prog Brain Res.2009;177:63–72.
8. Estraneo A, Moretta P, Loreto V, Lanzillo B, Santoro L, Trojano L. Late recovery after traumatic, anoxic, or hemorrhagic long-lasting vegetative state. Neurology.2010;75(3):239–45.
9. Whyte J, Katz D, Long D, DiPasquale MC, Polansky M, Kalmar K, Giacino J, Childs N, Mercer W, Novak P, et al. Predictors of outcome in prolonged posttraumatic disorders of consciousness and assessment of medication effects: a multicenter study. Arch Phys Med Rehabil.2005;86(3):453–62.
10. Childs NL, Mercer WN, Childs HW. Accuracy of diagnosis of persistent vegetative state. Neurology.1993;43(8):1465–67. 11. Andrews K, Murphy L, Munday R, Littlewood C. Misdiagnosis of
the vegetative state: retrospective study in a rehabilitation unit. Bmj.1996;313(7048):13–16.
12. 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 ver-sus standardized neurobehavioral assessment. BMC Neurol. 2009;9:35.
13. Seel RT, Sherer M, Whyte J, Katz DI, Giacino JT, Rosenbaum AM, Hammond FM, Kalmar K, Pape TL, Zafonte R, et al. Assessment scales for disorders of consciousness: evidence-based
recommendations for clinical practice and research. Arch Phys Med Rehabil.2010;91(12):1795–813.
14. Giacino JT, Kalmar K, Whyte J. The JFK coma recovery scale-revised: measurement characteristics and diagnostic utility. Arch Phys Med Rehabil.2004;85(12):2020–29.
15. Løvstad M, Frøslie KF, Giacino JT, Skandsen T, Anke A, Schanke AK. Reliability and diagnostic characteristics of the JFK coma recovery scale-revised: exploring the influence of rater’s level of experience. J Head Trauma Rehabil. 2010;25 (5):349–56.
16. McDonnell E, Giacino JT, Kolakowsky-Hayner SA. A brief over-view of the coma recovery scale-revised: updates from the COMBI. J Head Trauma Rehabil.2015;30(2):143–45.
17. Eapen BC, Allred DB, O’Rourke J, Cifu DX. Rehabilitation of moderate-to-severe traumatic brain injury. Semin Neurol. 2015;35(1):e1–3.
18. Noé E, Olaya J, Navarro MD, Noguera P, Colomer C, García-Panach J, Rivero S, Moliner B, Ferri J. Behavioral recovery in disorders of consciousness: a prospective study with the Spanish version of the coma recovery scale-revised. Arch Phys Med Rehabil.2012;93(3):428–33.e12.
19. 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;80(5):464–70.
20. Pignat JM, Mauron E, Jöhr J, Gilart De Keranflec’h C, Van De Ville D, Preti MG, Meskaldji DE, Hömberg V, Laureys S, Draganski B, et al. Outcome prediction of consciousness disorders in the acute stage based on a complementary motor behavioural tool. PLoS One.2016;11(6):e0156882.
21. Bernat JL. Chronic disorders of consciousness. Lancet.2006;367 (9517):1181–92.
22. Lombardi F, Gatta G, Sacco S, Muratori A, Carolei A. The Italian version of the coma recovery scale-revised (CRS-R). Funct Neurol. 2007;22(1):47–61.
23. Estraneo A, Moretta P, De Tanti A, Gatta G, Giacino JT, Trojano L. An Italian multicentre validation study of the coma recovery scale-revised. Eur J Phys Rehabil Med.2015;51(5):627–34. 24. Jennett B, Bond M. Assessment of outcome after severe brain
damage. Lancet.1975;1(7905):480–84.
25. McMillan T, Wilson L, Ponsford J, Levin H, Teasdale G, Bond M. The Glasgow Outcome Scale– 40 years of application and refine-ment. Nat Rev Neurol.2016;12(8):477–85.
26. Giacino JT, Ashwal S, Childs N, Cranford R, Jennett B, Katz DI, Kelly JP, Rosenberg JH, Whyte J, Zafonte RD, et al. The minimally conscious state: definition and diagnostic criteria. Neurology. 2002;58(3):349–53.
27. Consensus conference. Rehabilitation of persons with traumatic brain injury. NIH consensus development panel on rehabilitation of persons with traumatic brain injury. Jama.1999;282(10):974–83. 28. Holland D, Shigaki CL. Educating families and caretakers of traumatically brain injured patients in the new health care envir-onment: a three phase model and bibliography. Brain Inj.1998;12 (12):993–1009.
29. Junqué C, Bruna O, Mataró M. Information needs of the trau-matic brain injury patient’s family members regarding the con-sequences of the injury and associated perception of physical, cognitive, emotional and quality of life changes. Brain Inj. 1997;11(4):251–58.
30. Lefebvre H, Levert MJ. Breaking the news of traumatic brain injury and incapacities. Brain Inj.2006;20(7):711–18.
31. Dolce G, Quintieri M, Serra S, Lagani V, Pignolo L. Clinical signs and early prognosis in vegetative state: a decisional tree, data-mining study. Brain Inj.2008;22(7–8):617–23.
32. Estraneo A, Moretta P, Cardinale V, De Tanti A, Gatta G, Giacino JT, Trojano L. A multicentre study of intentional behavioural responses measured using the coma recovery scale-revised in patients with minimally conscious state. Clin Rehabil. 2015;29 (8):803–08.
33. Bagnato S, Boccagni C, Sant’Angelo A, Fingelkurts AA, Galardi G. Longitudinal assessment of clinical signs of recovery in patients with unresponsive wakefulness syndrome after traumatic or non-traumatic brain injury. J Neurotrauma.2017;34(2):535–539. 34. Amantini A, Carrai R, Fossi S, Pinto F, Grippo A. The role of
early electroclinical assessment in improving the evaluation of
patients with disorders of consciousness. Funct Neurol.2011;26 (1):7–14.
35. Grippo A, Carrai R, Scarpino M, Spalletti M, Lanzo G, Cossu C, Peris A, Valente S, Amantini A. Neurophysiological prediction of neurological good and poor outcome in post-anoxic coma. Acta Neurol Scand.2017;135(6):641–648.
