Coma Recovery Scale-Revised Total Score Research Articles

Controlled clinical trial of repeated prefrontal tDCS in patients with chronic minimally conscious state

ABSTRACTObjectives: To assess the effects of repeated transcranial direct current stimulation (tDCS) sessions on the level of consciousness in chronic patients in minimally conscious state (MCS).Methods: In this randomized double-blind sham-controlled crossover study, we enrolled 16 patients in chronic MCS. For 5 consecutive days, each patient received active or sham tDCS over the left prefrontal cortex (2 mA during 20 min). Consciousness was assessed with the Coma Recovery Scale-Revised (CRS-R) before the first stimulation (baseline), after each stimulation (day 1–day 5) and 1 week after the end of each session (day 12).Results: A treatment effect (p = 0.013; effect size = 0.43) was observed at the end of the active tDCS session (day 5) as well as 1 week after the end of the active tDCS session (day 12; p = 0.002; effect size = 0.57). A longitudinal increase of the CRS-R total scores was identified for the active tDCS session (p < 0.001), while no change was found for the sham session (p = 0.64). Nine patients were identified as responders (56%).Conclusion: Our results suggest that repeated (5 days) left prefrontal tDCS improves the recovery of consciousness in some chronic patients in MCS, up to 1 week after the end of the stimulations.

40Hz auditory steady-state responses in patients with disorders of consciousness: Correlation between phase-locking index and Coma Recovery Scale-Revised score.

We aimed to elucidate whether 40Hz auditory steady-state response (ASSR) could be sensitive to the state of patients with disorders of consciousness (DOC) as estimated with Coma Recovery Scale-Revised (CRS-R) diagnostic tool. Fifteen DOC patients and 24 healthy controls took part in the study. The 40Hz click trains were used to evoke ASSRs. Mean evoked amplitude (EA) and phase-locking index (PLI) within 38-42Hz window were calculated for 100ms bins, starting from -200 to 700ms relative to stimulus onset. The PLI values from the patient group in the period of 200-500ms after the stimulus onset positively correlated with the CRS-R total score and with the scores of the Auditory and Visual subscales. The phase-locking index of 40Hz auditory steady-state responses can be an indicator of the level of dysfunction of the central nervous system in DOC. Our results emphasize the role of central auditory system integrity in determining the level of functioning of DOC patients and suggest the possibility to use the ASSR protocol as an objective diagnostic method in DOC patients.

Utility of the Coma Recovery Scale-Revised Total Score in Detecting Conscious Awareness

Utility of the Coma Recovery Scale-Revised Total Score in Detecting Conscious Awareness

Sensitivity and Specificity of the Coma Recovery Scale–Revised Total Score in Detection of Conscious Awareness

ObjectiveTo describe the sensitivity and specificity of Coma Recovery Scale–Revised (CRS-R) total scores in detecting conscious awareness. DesignData were retrospectively extracted from the medical records of patients enrolled in a specialized disorders of consciousness (DOC) program. Sensitivity and specificity analyses were completed using CRS-R–derived diagnoses of minimally conscious state (MCS) or emerged from minimally conscious state (EMCS) as the reference standard for conscious awareness and the total CRS-R score as the test criterion. A receiver operating characteristic curve was constructed to demonstrate the optimal CRS-R total cutoff score for maximizing sensitivity and specificity. SettingSpecialized DOC program. ParticipantsPatients enrolled in the DOC program (N=252, 157 men; mean age, 49y; mean time from injury, 48d; traumatic etiology, n=127; nontraumatic etiology, n=125; diagnosis of coma or vegetative state, n=70; diagnosis of MCS or EMCS, n=182). InterventionsNot applicable. Main Outcome MeasuresSensitivity and specificity of CRS-R total scores in detecting conscious awareness. ResultsA CRS-R total score of 10 or higher yielded a sensitivity of .78 for correct identification of patients in MCS or EMCS, and a specificity of 1.00 for correct identification of patients who did not meet criteria for either of these diagnoses (ie, were diagnosed with vegetative state or coma). The area under the curve in the receiver operating characteristic curve analysis is .98. ConclusionsA total CRS-R score of 10 or higher provides strong evidence of conscious awareness but resulted in a false-negative diagnostic error in 22% of patients who demonstrated conscious awareness based on CRS-R diagnostic criteria. A cutoff score of 8 provides the best balance between sensitivity and specificity, accurately classifying 93% of cases. The optimal total score cutoff will vary depending on the user's objective.

Poster 45 Utility of the Coma Recovery Scale-Revised Total Score in Detecting Conscious Awareness

Poster 45 Utility of the Coma Recovery Scale-Revised Total Score in Detecting Conscious Awareness

Intrinsic functional connectivity differentiates minimally conscious from unresponsive patients.

Despite advances in resting state functional magnetic resonance imaging investigations, clinicians remain with the challenge of how to implement this paradigm on an individualized basis. Here, we assessed the clinical relevance of resting state functional magnetic resonance imaging acquisitions in patients with disorders of consciousness by means of a systems-level approach. Three clinical centres collected data from 73 patients in minimally conscious state, vegetative state/unresponsive wakefulness syndrome and coma. The main analysis was performed on the data set coming from one centre (Liège) including 51 patients (26 minimally conscious state, 19 vegetative state/unresponsive wakefulness syndrome, six coma; 15 females; mean age 49 ± 18 years, range 11-87; 16 traumatic, 32 non-traumatic of which 13 anoxic, three mixed; 35 patients assessed >1 month post-insult) for whom the clinical diagnosis with the Coma Recovery Scale-Revised was congruent with positron emission tomography scanning. Group-level functional connectivity was investigated for the default mode, frontoparietal, salience, auditory, sensorimotor and visual networks using a multiple-seed correlation approach. Between-group inferential statistics and machine learning were used to identify each network's capacity to discriminate between patients in minimally conscious state and vegetative state/unresponsive wakefulness syndrome. Data collected from 22 patients scanned in two other centres (Salzburg: 10 minimally conscious state, five vegetative state/unresponsive wakefulness syndrome; New York: five minimally conscious state, one vegetative state/unresponsive wakefulness syndrome, one emerged from minimally conscious state) were used to validate the classification with the selected features. Coma Recovery Scale-Revised total scores correlated with key regions of each network reflecting their involvement in consciousness-related processes. All networks had a high discriminative capacity (>80%) for separating patients in a minimally conscious state and vegetative state/unresponsive wakefulness syndrome. Among them, the auditory network was ranked the most highly. The regions of the auditory network which were more functionally connected in patients in minimally conscious state compared to vegetative state/unresponsive wakefulness syndrome encompassed bilateral auditory and visual cortices. Connectivity values in these three regions discriminated congruently 20 of 22 independently assessed patients. Our findings point to the significance of preserved abilities for multisensory integration and top-down processing in minimal consciousness seemingly supported by auditory-visual crossmodal connectivity, and promote the clinical utility of the resting paradigm for single-patient diagnostics.

Impact of Aphasia on Consciousness Assessment

Background. Previous findings suggest that language disorders may occur in severely brain-injured patients and could interfere with behavioral assessments of consciousness. However, no study investigated to what extent language impairment could affect patients’ behavioral responses. Objective. To estimate the impact of receptive and/or productive language impairments on consciousness assessment. Methods. Twenty-four acute and subacute stroke patients with different types of aphasia (global, n = 11; Broca, n = 4; Wernicke, n = 3; anomic, n = 4; mixed, n = 2) were recruited in neurology and neurosurgery units as well as in rehabilitation centers. The Coma Recovery Scale–Revised (CRS-R) was administered. Results. We observed that 25% (6 out of 24) of stroke patients with a diagnosis of aphasia and 54% (6 out of 11) of patients with a diagnosis of global aphasia did not reach the maximal CRS-R total score of 23. An underestimation of the consciousness level was observed in 3 patients with global aphasia who could have been misdiagnosed as being in a minimally conscious state, even in the absence of any documented period of coma. More precisely, lower subscores were observed on the communication, motor, oromotor, and arousal subscales. Conclusion. Consciousness assessment may be complicated by the co-occurrence of severe language deficits. This stresses the importance of developing new tools or identifying items in existing scales, which may allow the detection of language impairment in severely brain-injured patients.

TDCS in patients with disorders of consciousness

We assessed the effects of left dorsolateral prefrontal cortex transcranial direct current stimulation (DLPF-tDCS) on Coma Recovery Scale-Revised (CRS-R) scores in severely brain-damaged patients with disorders of consciousness. In a double-blind sham-controlled crossover design, anodal and sham tDCS were delivered in randomized order over the left DLPF cortex for 20 minutes in patients in a vegetative state/unresponsive wakefulness syndrome (VS/UWS) or in a minimally conscious state (MCS) assessed at least 1 week after acute traumatic or nontraumatic insult. Clinical assessments were performed using the CRS-R directly before and after anodal and sham tDCS stimulation. Follow-up outcome data were acquired 12 months after inclusion using the Glasgow Outcome Scale-Extended. Patients in MCS (n = 30; interval 43 ± 63 mo; 19 traumatic, 11 nontraumatic) showed a significant treatment effect (p = 0.003) as measured by CRS-R total scores. In patients with VS/UWS (n = 25; interval 24 ± 48 mo; 6 traumatic, 19 nontraumatic), no treatment effect was observed (p = 0.952). Thirteen (43%) patients in MCS and 2 (8%) patients in VS/UWS further showed postanodal tDCS-related signs of consciousness, which were observed neither during the pre-tDCS evaluation nor during the pre- or post-sham evaluation (i.e., tDCS responders). Outcome did not differ between tDCS responders and nonresponders. tDCS over left DLPF cortex may transiently improve signs of consciousness in MCS following severe brain damage as measured by changes in CRS-R total scores. This study provides Class II evidence that short-duration tDCS of the left DLPF cortex transiently improves consciousness as measured by CRS-R assessment in patients with MCS.

Effect of zolpidem in chronic disorders of consciousness: a prospective open-label study

Zolpidem has been reported as an "awakening drug" in some patients with disorders of consciousness (DOC). We here present the results of a prospective openlabel study in chronic DOC patients. Sixty patients (35±15 years; 18 females; mean time since insult ± SD: 4±5.5 years; 31 with traumatic etiology) with a diagnosis of vegetative state/unresponsive wakefulness syndrome (n=28) or minimally conscious state (n=32) were behaviorally assessed using the Coma Recovery Scale-Revised (CRS-R) before and one hour after administration of 10 mg of zolpidem. At the group level, the diagnosis did not change after intake of zolpidem (p=0.10) and CRS-R total scores decreased (p=0.01). Twelve patients (20%) showed improved behaviors and/or CRS-R total scores after zolpidem administration but in only one patient was the diagnosis after zolpidem intake found to show a significant improvement (functional object use), which suggested a change of diagnosis. However, in this patient, a double-blind placebo-controlled trial was performed in order to better specify the effects of zolpidem, but the patient, on this trial, failed to show any clinical improvements. The present open-label study therefore failed to show any clinically significant improvement (i.e., change of Effect of zolpidem in chronic disorders of consciousness: a prospective open-label study diagnosis) in any of the 60 studied chronic DOC patients.

Can We Scientifically and Reliably Measure the Level of Consciousness in Vegetative and Minimally Conscious States? Rasch Analysis of the Coma Recovery Scale-Revised

Objectives(1) To appraise, by the means of Rasch analysis, the internal validity and reliability of the Coma Recovery Scale-Revised (CRS-R) in a sample of patients with disorder of consciousness (DOC); and (2) to provide information about the comparability of CRS-R scores across persons with DOC across different settings and groups, including different etiologies. DesignMulticenter observational prospective study. SettingTwo rehabilitation wards, 1 intermediate care facility, and 2 nursing homes in Italy. ParticipantsConsecutively admitted patients (N=129) for which assessments at 2 different time points were available, giving a total sample of 258 observations. InterventionsNot applicable. Main Outcome MeasureCRS-R. ResultsAfter controlling for any possible dependency between persons’ measures collected at different time points, and for uniform differential item functioning by etiology showed by the visual subscale, Rasch analysis demonstrated adequate satisfaction of all the model’s requirements, including adequate ordering of scoring categories, unidimensionality, local independence, invariance (χ221=27.798, P=.146), and absence of differential item functioning across patients’ sex, age, time, and setting. The reliability (person separation index=.896) was adequate for individual person measurement. We devised a practical raw score to measure conversion tables based on the CRS-R calibrations. ConclusionsThe CRS-R is a psychometrically sound and robust measurement tool. The linear measures of ability derived from the CRS-R total scores do satisfy all the principles of scientific measurement and are sufficiently reliable for high stakes assessments, such as the diagnosis of the level of consciousness in individual patients. Future studies are needed to directly explore the capabilities of the CRS-R measures to reduce the risk of vegetative state misdiagnosis.

Metabolic activity in external and internal awareness networks in severely brain-damaged patients

An extrinsic cerebral network (encompassing lateral frontoparietal cortices) related to external/sensory awareness and an intrinsic midline network related to internal/self-awareness have been identified recently. This study measured brain metabolism in both networks in patients with severe brain damage. Prospective [18F]-fluorodeoxyglucose-positron emission tomography and Coma Recovery Scale-Revised assessments in a university hospital setting. Healthy volunteers and patients in vegetative state/unresponsive wakefulness syndrome (VS/UWS), minimally conscious state (MCS), emergence from MCS (EMCS), and locked-in syndrome (LIS). A total of 70 patients were included in the study: 24 VS/UWS, 28 MCS, 10 EMCS, 8 LIS and 39 age-matched controls. VS/UWS showed metabolic dysfunction in extrinsic and intrinsic networks and thalami. MCS showed dysfunction mostly in intrinsic network and thalami. EMCS showed impairment in posterior cingulate/retrosplenial cortices. LIS showed dysfunction only in infratentorial regions. Coma Recovery Scale-Revised total scores correlated with metabolic activity in both extrinsic and part of the intrinsic network and thalami. Progressive recovery of extrinsic and intrinsic awareness network activity was observed in severely brain-damaged patients, ranging from VS/UWS, MCS, EMCS to LIS. The predominance of intrinsic network impairment in MCS could reflect altered internal/self-awareness in these patients, which is difficult to quantify at the bedside.

Nociception Coma Scale-Revised total scores correlate with anterior cingulate cortex as measured by FDG-PET in patients with disorders of consciousness

Event Abstract Back to Event Nociception Coma Scale-Revised total scores correlate with anterior cingulate cortex as measured by FDG-PET in patients with disorders of consciousness Camille Chatelle1*, Aurore Thibaut1, Marie-Aurélie Bruno1, Melanie Boly1, Claire Bernard2, Roland Hustinx2, Caroline Schnakers1 and Steven Laureys1 1 University of Liège, Cyclotron Research Centre, Belgium 2 University Hospital of Liège, Nuclear Medicine Dept, Belgium Introduction. The Nociception Coma Scale-Revised was recently validated to assess possible pain perception in patients with disorders of consciousness (i.e., vegetative state/unresponsive wakefulness syndrome and minimally conscious state [1,2,3]). We here aim to identify correlations between cerebral glucose metabolism and Nociception Coma Scale-Revised total scores in disorders of consciousness. Methods. [18F]-fluorodeoxyglucose-PET was performed in 42 patients with disorders of consciousness (29 males, aged 42±17 years; 26 minimally conscious state; 19 post-traumatic; 22 in the acute/subacute setting (i.e., < 1 year post insult). All patients had Coma Recovery Scale-Revised [4] and Nociception Coma Scale-Revised assessment on the day of PET imaging. Data preprocessing and analyses employed statistical parametric mapping (SPM8) and results were considered significant at small-volume corrected p<0.05 for a priori identified coordinates of the pain matrix (Boly et al., 2008 [5]) (i.e., thalamus, primary and secondary somatosensory cortex, insula and anterior cingulate cortex). Results. Anterior cingulate cortex metabolism showed a positive linear correlation with Nociception Coma Scale-Revised total scores and not with Coma Recovery Scale-Revised total scores (corrected p= 0.018; x=20, y=16, z=36). The observed effect showed no significant difference depending on etiology or duration. Conclusions. Nociception Coma Scale-Revised scores (and not Coma Recovery Scale-Revised scores) correlated with metabolic activity of anterior cingulate cortex, known to be involved in the affective emotional component of pain perception. Our data support the hypothesis that Nociception Coma Scale-Revised assessment in non-communicative patients with disorders of consciousness indeed reflects possible pain perception, permitting clinicians to treat adequately and optimize the clinical management of this challenging patient population [6]. Figure 1 Acknowledgements CC is Research Fellow; MAB, MB and CS are Postdoctoral Researcher and SL is Research Director at the Fonds National de la Recherche Scientifique de Belgique (FNRS). This research was supported by FNRS, University and University Hospital of Liège, European Commission, James S. McDonnell Foundation, Mind Science Foundation, Concerted Research Action and Fondation Léon Frédéricq.

Reliability and Diagnostic Characteristics of the JFK Coma Recovery Scale–Revised

To confirm the reliability and diagnostic validity of the JFK Coma Recovery Scale-Revised (CRS-R) across raters with varying levels of experience. Thirty-one patients with disorders of consciousness were recruited from 6 Norwegian hospitals. CRS-R and the Disability Rating Scale. Reliability measures were good for the CRS-R total scores and moderate to good for its subscales. Diagnostic agreement among examiners was good. Raters' experience with the CRS-R favorably influenced reliability. Sensitivity and specificity analyses demonstrated better detection of patients in minimally conscious state on the CRS-R relative to the Disability Rating Scale. The CRS-R is a reliable tool for diagnosing vegetative state and minimally conscious state. Raters' level of experience influences the reliability of the CRS-R scores.

A French validation study of the Coma Recovery Scale-Revised (CRS-R)

Primary objective: The aim of the present study was to explore the concurrent validity, inter-rater agreement and diagnostic sensitivity of a French adaptation of the Coma Recovery Scale–Revised (CRS-R) as compared to other coma scales such as the Glasgow Coma Scale (GCS), the Full Outline of UnResponsiveness scale (FOUR) and the Wessex Head Injury Matrix (WHIM).Research design: Multi-centric prospective study.Method and procedures: To test concurrent validity and diagnostic sensitivity, the four behavioural scales were administered in a randomized order in 77 vegetative and minimally conscious patients. Twenty-four clinicians with different professional backgrounds, levels of expertise and CRS-R experience were recruited to assess inter-rater agreement.Main outcomes and results: Good concurrent validity was obtained between the CRS-R and the three other standardized behavioural scales. Inter-rater reliability for the CRS-R total score and sub-scores was good, indicating that the scale yields reproducible findings across examiners and does not appear to be systematically biased by profession, level of expertise or CRS-R experience. Finally, the CRS-R demonstrated a significantly higher sensitivity to detect MCS patients, as compared to the GCS, the FOUR and the WHIM.Conclusion: The results show that the French version of the CRS-R is a valid and sensitive scale which can be used in severely brain damaged patients by all members of the medical staff.

The JFK Coma Recovery Scale-Revised: Measurement characteristics and diagnostic utility

Giacino JT, Kalmar K, Whyte J. The JFK Coma Recovery Scale-Revised: measurement characteristics and diagnostic utility. Objective To determine the measurement properties and diagnostic utility of the JFK Coma Recovery Scale-Revised (CRS-R). Design Analysis of interrater and test-retest reliability, internal consistency, concurrent validity, and diagnostic accuracy. Setting Acute inpatient brain injury rehabilitation hospital. Participants Convenience sample of 80 patients with severe acquired brain injury admitted to an inpatient Coma Intervention Program with a diagnosis of either vegetative state (VS) or minimally conscious state (MCS). Interventions Not applicable. Main outcome measures The CRS-R, the JFK Coma Recovery Scale (CRS), and the Disability Rating Scale (DRS). Results Interrater and test-retest reliability were high for CRS-R total scores. Subscale analysis showed moderate to high interrater and test-retest agreement although systematic differences in scoring were noted on the visual and oromotor/verbal subscales. CRS-R total scores correlated significantly with total scores on the CRS and DRS indicating acceptable concurrent validity. The CRS-R was able to distinguish 10 patients in an MCS who were otherwise misclassified as in a VS by the DRS. Conclusions The CRS-R can be administered reliably by trained examiners and repeated measurements yield stable estimates of patient status. CRS-R subscale scores demonstrated good agreement across raters and ratings but should be used cautiously because some scores were underrepresented in the current study. The CRS-R appears capable of differentiating patients in an MCS from those in a VS.