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Diagnostic accuracy and prognostic value of the CRS-R modified score in patients with disorders of consciousness.

Maria Maddalena Filippini1*, Estelle Bonin1, Charlène Aubinet1, Manon Carrière1, Helena Cassol1, Olivia Gosseries1, Aurore Thibaut1, Alice Barra1, Audrey Wolff1, Leandro R. Sanz1, Charlotte Martial1, Steven Laureys1 and Camille Chatelle1
  • 1 Coma Science Group, University of Liège, Belgium

Background The Coma Recovery Scale – Revised (CRS-R) (Giacino et al., 2004) is currently the most reliable clinical tool for the differential diagnosis of disorders of consciousness (DOC) (Seel et al., 2010). If commonly used in research, the CRS-R total score (CRS-R TS), however, lacks sensitivity and specificity in the detection of conscious awareness (Bodien et al., 2016), which limits its use. An alternative scoring system for the CRS-R, the CRS-R modified score (CRS-R MS), has recently been proposed to overcome this limitation. Its calculation requires that all 23 items of the scale, dichotomised into "reflex behaviours" (RB) and "cognitively mediated behaviours" (CMB), are tested during each assessment. The final CRS-R MS is derived from the number of RB and CMB displayed by the patient by means of a calculation matrix, with an additional correction applied on the basis of the arousal subscale. CRS-R MS values range from 0 to 100 and the score of 8,34 has previously been suggested as the cut-off for recovery of at least one sign of consciousness, corresponding to a diagnosis of minimally conscious state (MCS) (Sattin et al., 2015). Among other neuroimaging techniques, Positron Emission Tomography (PET) seems to be highly sensitive to identify minimally conscious states and reliable in predicting recovery of patients with DOC (Stender et al., 2014). One previous PET study has found a positive correlation between the CRS-R TS and metabolic activity in bilateral fronto-parietal areas and in precuneus/posterior cingulate cortex (Thibaut et al., 2012). Objective The aim of this retrospective study was to test the diagnostic accuracy and prognostic value of the CRS-R MS and to explore its potential correlation with brain metabolic activity in a sample of acute and chronic brain-injured patients with DOC (i.e., patients in an unresponsive wakefulness syndrome – UWS – or in a MCS). Methods The CRS-R MSs of 124 patients (39 UWS and 85 MCS) were retrospectively calculated based on data extracted from medical records following the calculation procedure as reported in (Sattin et al., 2015). All the subjects were repeatedly evaluated by means of the CRS-R by experienced clinicians. All the items of the scale were tested during each evaluation. The best assessment (i.e. best CRS-R-based diagnosis) was selected for the calculation of the CRS-R MS. All patients underwent a PET examination during hospitalisation. Forty-five patients (18 UWS, 27 MCS) were assessed six and/or twelve months later via telephone structured interview using the Extended Glasgow Outcome Scale (GOSE) (Pettigrew et al., 2003). Spearman correlation was used to calculate the correlation between CRS-R TSs and CRS-R MSs. Additionally, receiver operating characteristics (ROC) curves were calculated to test the CRS-R TS and CRS-R MS diagnostic accuracy. The Spearman correlations between CRS-R TSs and MSs and GOSE scores at six and twelve months were also calculated. Finally, seventy-five patients were included in the analysis of brain metabolism; the remaining were excluded due to extensive brain damage (27 subjects), PET examination acquired in the acute stage (18 subjects) and incomplete data (4 subjects). We investigated which brain regions showed a correlation in metabolism with CRS-R TSs and CRS-R MSs. Statistical analysis was performed using Statistical Parametric Mapping (SPM12) and results were thresholded for significance at p < 0.05 corrected for multiple comparisons within a priori defined regions of interest (using a 8-mm radius spherical small volume correction in SPM—at voxel and cluster level) centered on a priori coordinates for areas previously identified as correlating with CRS-R TS in DOC patients (right and left lateral parietal cortex, right and left lateral prefrontal cortex, precuneus/cingulate cortex) (Thibaut et al., 2012). Results Demographic and clinical features of the patients are shown in table 1 (Supplementary material). CRS-R TSs between 5 and 8 (52 patients, 42% of the sample) were found unable to discriminate between unconscious and conscious patients. By contrast, no diagnostic overlap was seen for any value of the CRS-R MS (see fig. 1). We found a very strong correlation between CRS-R TS and CRS-R MS (ρ = .94; p < 0.001). A CRS-R TS of 8 or higher yielded a sensitivity of .96 for correct identification of patients in MCS and a specificity of .74 for correct identification of patients who did not meet criteria for this diagnosis (i.e., were diagnosed in UWS). The area under the ROC curve was .93. A CRS-R MS of 8.32 or higher yielded a sensitivity of 1 for correct identification of patients in MCS, and a specificity of 1 for correct identification of patients with UWS. The area under the ROC curve was 1 (see fig. 2). Both CRS-R TS and CRS-R MS showed a strong correlation with GOSE scores, both at six (ρTS = .67; p < 0.001 and ρMS = .69; p < 0.001) and twelve months (ρTS = .62; p < 0.001 and ρMS = .62; p < 0.001) (see fig. 3). Voxel-based parametric analysis of brain metabolism showed a significant positive correlation between both the CRS-R TS and the CRS-R MS and three brain areas: right lateral parietal cortex, right lateral prefrontal cortex and precuneus/posterior cingulate cortex (see Table 2 in the Supplementary material for additional information). No correlation was found with the left fronto-parietal network, for neither of the two scoring systems (see fig.4). Conclusion Our results suggest that the CRS-R MS is more sensitive than the CRS-R TS to discriminate between patients in UWS and MCS. Indeed, the CRS-R MS allowed a perfect distinction between UWS and MCS, together with a prognostic value similar to the CRS-R TS. The two scoring systems also showed a similar correlation with brain metabolic activity. Our data support previous findings and highlight the interest of using this modified score for research purposes and patient assessment. On the other hand, the necessity to administer the full CRS-R list of items in order to obtain the CRS-R MS and the rather complex calculation procedure represent major constraints, likely to hamper its use in routine clinical practice. Fig. 1. Scatter plot of CRS-R modified scores and CRS-R total scores, showing the positive correlation between the two scoring systems (solid black line). Dotted lines identify CRS-R total scores corresponding to overlapping diagnosis. UWS and MCS patients clearly spread out separately, respectively on the left and on the right of the cut-off line for MCS diagnosis (x = 8,32 - in red). CRS-R = Coma Recovery Scale - Revised, UWS = unresponsive wakefulness syndrome, MCS = minimally conscious state. Fig. 2. ROC curves showing sensitivity and specificity of CRS-R TS (left) and CRS-R MS (right). CRS-R MS demonstrated ideal levels of accuracy in differentiating patients in an unresponsive wakefulness syndrome from patients in a minimally conscious state (AUC = 1). ROC = receiver operating characteristics, CRS-R TS = Coma Recovery Scale - Revised total score, CRS-R MS = Coma Recovery Scale - Revised modified score, AUC = area under the curve. Fig. 3. Correlations between CRS-R total scores (left) and CRS-R modified scores (right) and outcome measures at six (upper row) and twelve (lower row) months. CRS-R = Coma Recovery Scale-Revised, GOSE = Glasgow Outcome Scale Extended Fig.4. Areas where metabolic activity correlated with Coma Recovery Scale-Revised (CRS-R) total scores (upper panel) and modified scores (lower panel; thresholded at p <0.05 false discovery rate correction for multiple comparisons).

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Acknowledgements

The study was supported by the University and University Hospital of Liège, the Belgian National Funds for Scientific Research (FRS-FNRS), and the European Union’s Horizon 2020 Framework Programme for Research and Innovation (Grant Agreement No. 720270 (Human Brain Project SGA1) and No. 785907 (Human Brain Project SGA2)). CA is research fellow, AT and OG are postdoctoral researchers and SL is research director at FNRS. CC is a Marie Sklodowska-Curie fellow (H2020-MSCA-IF-2016-ADOC- 752686).

References

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Keywords: Brain Injury, disorders of consciousness, Neurobehavioural assessment, Coma Recovery Scale-Revised, Diagnostic accuracy

Conference: Belgian Brain Congress 2018 — Belgian Brain Council, LIEGE, Belgium, 19 Oct - 19 Oct, 2018.

Presentation Type: e-posters

Topic: NOVEL STRATEGIES FOR NEUROLOGICAL AND MENTAL DISORDERS: SCIENTIFIC BASIS AND VALUE FOR PATIENT-CENTERED CARE

Citation: Filippini M, Bonin E, Aubinet C, Carrière M, Cassol H, Gosseries O, Thibaut A, Barra A, Wolff A, Sanz LR, Martial C, Laureys S and Chatelle C (2019). Diagnostic accuracy and prognostic value of the CRS-R modified score in patients with disorders of consciousness.. Front. Neurosci. Conference Abstract: Belgian Brain Congress 2018 — Belgian Brain Council. doi: 10.3389/conf.fnins.2018.95.00094

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Received: 30 Aug 2018; Published Online: 17 Jan 2019.

* Correspondence: MD. Maria Maddalena Filippini, Coma Science Group, University of Liège, Liège, Liège, 4000, Belgium, mmfilippini@uliege.be