Coma Recovery Research Articles

Extracerebral Normalization of 18F-FDG PET Imaging Combined with Behavioral CRS-R Scores Predict Recovery from Disorders of Consciousness.

Identifying patients likely to regain consciousness early on is a challenge. The assessment of consciousness levels and the prediction of wakefulness probabilities are facilitated by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET). This study aimed to develop a prognostic model for predicting 1-year postinjury outcomes in prolonged disorders of consciousness (DoC) using 18F-FDG PET alongside clinical behavioral scores. Eighty-seven patients with prolonged DoC newly diagnosed with behavioral Coma Recovery Scale-Revised (CRS-R) scores and 18F-FDG PET/computed tomography (18F-FDG PET/CT) scans were included. PET images were normalized by the cerebellum and extracerebral tissue, respectively. Images were divided into training and independent test sets at a ratio of 5:1. Image-based classification was conducted using the DenseNet121 network, whereas tabular-based deep learning was employed to train depth features extracted from imaging models and behavioral CRS-R scores. The performance of the models was assessed and compared using the McNemar test. Among the 87 patients with DoC who received routine treatments, 52 patients showed recovery of consciousness, whereas 35 did not. The classification of the standardized uptake value ratio by extracerebral tissue model demonstrated a higher specificity and lower sensitivity in predicting consciousness recovery than the classification of the standardized uptake value ratio by cerebellum model. With area under the curve values of 0.751 ± 0.093 and 0.412 ± 0.104 on the test sets, respectively, the difference is not statistically significant (P = 0.73). The combination of standardized uptake value ratio by extracerebral tissue and computed tomography depth features with behavioral CRS-R scores yielded the highest classification accuracy, with area under the curve values of 0.950 ± 0.027 and 0.933 ± 0.015 on the training and test sets, respectively, outperforming any individual mode. In this preliminary study, a multimodal prognostic model based on 18F-FDG PET extracerebral normalization and behavioral CRS-R scores facilitated the prediction of recovery in DoC.

A new ICT system coupling electromyography and coma recovery scale-revised to support the diagnostic process in disorders of consciousness

The Coma Recovery Scale-revised (CRS-r) is the gold standard for the behavioral assessment of patients with Disorders of Consciousness (DoCs). However, the misdiagnosis rate is around 40%. For this reason, recent guidelines suggested enhancing the assessment with neurophysiological measures: among these, surface electromyography (sEMG) represents a convenient bedside solution. This work presents the use of the STRIVEfc system, a wearable device that allows CRS-r administration while recording four sEMG signals. STRIVEfc was employed in 40 sessions on 33 DoCs patients and the sEMG was analyzed to look for voluntary and consistent over threshold (OT) muscular activities. Their duration, amplitude, and number were retained and compared between patients in Unresponsive Wakefulness Syndrome (UWS) and Minimally Conscious State (MCS), revealing more numerous and significantly longer OTs in the latter group. Lastly, the EMG information was exploited to enrich the behavioral assessment by building the instrumented CRS-r score (ICRS-r). In 9/16 UWS sessions, the ICRS-r score suggested a higher-level functioning, not translated into a behavioral response, compatible with MCS diagnosis. Overall, the use of STRIVEfc allows to reveal hidden muscular patterns not detectable by the clinician, thus improving the characterization of DoCs patient’s functional capabilities and supporting the diagnostic process.

Can Eye Tracking Help Assess the State of Consciousness in Non-Verbal Brain Injury Patients?

Background/Objectives: Developments in eye-tracking technology are opening up new possibilities for diagnosing patients in a state of minimal consciousness because they can provide information on visual behavior, and the movements of the eyeballs are correlated with the patients' level of consciousness. The purpose of this study was to provide validation of a tool, based on eye tracking by comparing the results obtained with the assessment obtained using the Coma Recovery Scale-Revised (CRS-R). Methods: The mul-ti-center clinical trial was conducted in Poland in 2022-2023. The results of 46 patients who were not able to communicate verbally due to severe brain injury were analyzed in this study. The state of consciousness of patients was assessed using the Minimally Conscious State Detection test (MCSD), installed on an eye tracker and compared to CRS-R. The examinations consisted of performing the MCSD test on patients five times (T1-T5) within 14 days. Collected data were processed based on the FDA and GCP's regulatory requirements. Depending on the nature of the data, the mean and standard deviation, median and lower and upper quartiles, and maximum and minimum values were calculated. Passing-Bablok regression analysis was used to assess the measurement equiva-lence of the methods used. Results: There was no difference between the MCSD and CRS-R in the raw change between T5 and T1 time points, as well as in the total % of points from all time points. The MCSD results from each time point show that at least the first two measurements serve to famil-iarize and adapt the patient to the measurement process, and the third and next measurement should be considered reliable. Conclusions: The results indicated a significant relationship be-tween the scores obtained with MCSD and CRS-R. The results suggest that it seems reasonable to introduce an assessment of the patient's state of consciousness based on eye-tracking technology. The use of modern technology to assess a patient's state of consciousness opens up the opportunity for greater objectivity, as well as a reduction in the workload of qualified personnel.

Conventional structural magnetic resonance imaging in differentiating chronic disorders of consciousness

BACKGROUND: Differential diagnosis of chronic disorders of consciousness remains one of the most difficult problems even for experienced clinicians. AIM: To evaluate the inter-expert consistency and capacity of the researcher-developed structural scale based on magnetic resonance imaging to differentiate chronic disorders of consciousness, named, DOC-MRIDS, on a larger sample of patients. MATERIALS AND METHODS: Sixty patients with a clinically stable status diagnosed with consciousness disorders (vegetative state, n=32; minimally conscious state, n=28) were enrolled. The revised coma recovery scale (CRS-R) was included in the clinical assessment. All patients underwent structural magnetic resonance imaging with 3.0-T Siemens scanners including T2 and T1 sequences. Structural changes were assessed using the DOC-MRIDS scale and included the following features: diffuse cortical atrophy, ventricular enlargement, gyri dilatation, leukoaraiosis, brainstem and/or thalamic degeneration, corpus callosum degeneration, and focal corpus callosum lesions. A total score was calculated. Magnetic resonance imaging data were analyzed by three neuroradiologists, and inter-observer agreement (Krippendorf’s alpha) was assessed. RESULTS: A high inter-examiner agreement of the DOC-MRIDS scale score was found, with α=0.806 (95% confidence interval 0.757–0.849). The vegetative state group had a higher DOC-MRIDS score than the minimally conscious state group (p 0.005). A negative correlation was obtained between CRS-R and DOC-MRIDS scale scores (ρ=–0.457, p 0.0001), individual clinical scale domains, and magnetic resonance imaging features. CONCLUSION: When assessing structural changes in patients with chronic consciousness disorders, the use of the DOC-MRIDS scale helps differentiate the type of such disorders with sufficient specificity, sensitivity, and inter-rater agreement. This scale can be used in clinical practice as an additional differential diagnostic tool.

Perturbational complexity index in assessing responsiveness to rTMS treatment in patients with disorders of consciousness: a cross-over randomized controlled trial study

BackgroundDisorders of Consciousness (DoC) caused by severe brain injuries represent a challenging clinical entity, which is easy to misdiagnosis and lacks effective treatment options. Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive neuroelectric stimulation method that shows promise in improving consciousness for DoC, especially in minimally conscious state (MCS). However, there is little evidence of its effectiveness, especially in RCT studies.MethodsTwenty MCS patients participated in a double-blind, randomized, crossover, sham-controlled clinical study to evaluate the safety and efficacy of rTMS for MCS. Subjects were randomized into two groups: one group received rTMS-active for 10 consecutive days (n = 10), and the other group received rTMS-sham for 10 consecutive days (n = 10). After a 10-day washout period, the two groups were crossed over and received the opposite treatment. the rTMS protocol consisted of 2,000 pulses per day in the left dorsolateral prefrontal cortex (L-DLPFC), sent at 10 Hz. The stimulation intensity was 90% of the resting motor threshold. Coma Recovery Scale Revised (CRS-R), the main evaluation index, was evaluated before and after each phase in a double-blind manner. Meanwhile RS-EEG and TMS-EEG data were acquired and relative alpha power (RAP), and perturbational complexity index based on state transitions (PCIst) were caculated.ResultsOne-way ANOVA revealed significantly higher scores in rTMS-active treatment compared to rTMS-sham across various measures, including CRS-R total score, RAP, PCIst (all P < 0.05). Among the 20 MCS patients, 7 (35%) were identified as responders following rTMS treatment. Compared to rTMS-sham, responder scores for CRS-R, RAP, and PCIst (all P < 0.05) were significantly elevated after rTMS-active treatment. Conversely, there was no significant difference observed in non-responders. Furthermore, post-hoc analysis revealed that baseline PCIst was significantly higher in responders than non-responders. Upon a 6-month follow-up, CRS-R scores significantly increased in all 20 patients (P = 0.026). However, the responder group exhibited a more favorable prognosis compared to the non-responder group (P = 0.031).ConclusionsApplying 10 Hz rTMS to L-DLPFC significantly increased consciousness level in MCS patients. PCIst is a neurophysiological index that has the potential to evaluate and predict therapeutic efficacy.Trial registrationwww.ClinicalTrials.gov, identifier: NCT05187000.

Nociception Coma Scale-Revised with Personalized Painful Stimulus Versus Standard Stimulation in Persons with Disorders of Consciousness: An International Multicenter Study.

Background/Objectives: Persons with disorders of consciousness (DoCs) may perceive pain without being able to communicate their discomfort. The Nociception Coma Scale (NCS) and its revised form (NCS-R) have been proposed to assess nociception in persons with DoCs. The main aim of this international multicenter study was to confirm (or not) our preliminary results and compare the NCS-R scores of standard stimulus (NCS-R-SS) to scores of personalized painful stimuli (NCS-R-PS). A secondary aim of the study was to verify possible correlations between the NCS-R-PS and Coma Recovery Scale-Revised (CRS-R) and to estimate convergent validity. Methods: Sixty-one patients with prolonged DoCs (pDoCs) were enrolled from seven European post-acute rehabilitation centers. Responsiveness and pain perception were assessed by CRS-R and NCS-R with standard stimulus (NCS-R-SS) and personalized stimulation (NCS-R-PS). ClinicalTrials.gov Identifier: NCT06012357. Results: our results support our prior findings on the superiority and the validity of the personalized painful stimulus approach in assessment of pain in persons with DoCs in comparison with the standardized pain assessment methodology. Conclusions: A more in-depth and tailored assessment of pain perception in persons with a DoC may lead to better acknowledgment of its presence and by extension an objective foundation for more aggressive and appropriate pain management.

Pain anticipation is a new behavioural sign of minimally conscious state.

Probing cognition and consciousness in the absence of functional communication remains an extremely challenging task. In this perspective, we imagined a basic clinical procedure to explore pain anticipation at bedside. In a series of 61 patients with a disorder of consciousness, we tested the existence of a nociceptive anticipation response by pairing a somaesthetic stimulation with a noxious stimulation. We then explored how nociceptive anticipation response correlated with (i) clinical status inferred from Coma Recovery Scale-Revised scoring, (ii) with an EEG signature of stimulus anticipation-the contingent negative variation-and (iii) how nociceptive anticipation response could predict consciousness outcome at 6 months. Proportion of nociceptive anticipation response differed significantly according to the state of consciousness: nociceptive anticipation response was present in 5 of 5 emerging from minimally conscious state patients (100%), in 10 of 11 minimally conscious state plus patients (91%), but only in 8 of 17 minimally conscious state minus patients (47%), and only in 1 of 24 vegetative state/unresponsive wakefulness syndrome patients (4%) (χ 2 P < 0.0001). Nociceptive anticipation response correlated with the presence of a contingent negative variation, suggesting that patients with nociceptive anticipation response were more prone to actively expect and anticipate auditory stimuli (Fisher's exact test P = 0.05). However, nociceptive anticipation response presence did not predict consciousness recovery. Nociceptive anticipation response appears as a new additional behavioural sign that can be used to differentiate minimally conscious state from vegetative state/unresponsive wakefulness syndrome patients. As most behavioural signs of minimally conscious state, the nociceptive anticipation response seems to reveal the existence of a cortically mediated state that does not necessarily reflect residual conscious processing.

The effect of cranioplasty on outcomes and complications of unresponsive wakefulness syndrome and minimally responsive state.

Background Studies that have shown neurological improvement following cranioplasty (CP) after decompressive craniectomy (DC) in patients with unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) did not include control groups. The aim of this study was to assess the justification of CP for these patients. Methods Data were collected from medical records of inpatients with UWS and MCS admitted between 2002 and 2018. Results Of the 144 participants (mean age 40 years, 76% males, 75% in UWS), 37% had CP following DC. The Loewenstein Communication Scale (LCS) gain was 12±17 and 16±17 for the control and study patients, respectively. The corresponding consciousness recovery rate (based on Coma Recovery Scale-Revised scores) was 51% and 53%, respectively. One-year survival rates were 0.80 and 0.93, and 5-year survival rates were 0.67 and 0.73, respectively. Mean outcome values were higher for the study group, but the differences between the groups did not reach statistical significance. Conclusions The study did not demonstrate that CP increases brain recovery or survival. Nevertheless, it showed that CP did not decrease them either, and it did not increase complications rate. The findings, therefore, support offering CP to patients with UWS and MCS as CP does not increase risks and can achieve additional goals for these patients.

Rasch Analysis of the Chinese Version of the Nociception Coma Scale–Revised in Patients with Prolonged Disorders of Consciousness

Objectives The aim of this study was to analyze the Chinese version of the Nociception Coma Scale–Revised in patients with prolonged disorders of consciousness within the framework of Rasch modeling, including investigating the invariance of total scores across different etiologies of disorders of consciousness. Design Prospective psychometric study. Participants Patients with prolonged disorders of consciousness from the Rehabilitation and Neurology units in hospital. Interventions None. Main Outcome Measure The Nociception Coma Scale–Revised was undertaken by trained raters and the Coma Recovery Scale-Revised was used to assess patients’ consciousness. The psychometric properties within the Rasch model including item-person targeting, reliability and separation, item fit, unidimensionality, and differential item functioning were assessed. Results 84 patients with prolonged disorders of consciousness (mean age 53 years; mean injury 5 months; 42 with Minimally Conscious State and 42 with Unresponsive Wakefulness Syndrome) of 252 observations were enrolled in the study. Through the procedure of repeated assessment and differential item function, a lower item bias Rasch set was purified. The Rasch model assumptions were examined and met, with item reliability and validity meeting the recommended threshold. Conclusions The Chinese version of the Nociception Coma Scale–Revised demonstrated unidimensionality, good reliability and separation, and good item fit, but dissatisfied person fit and item-person targeting. The verbal subscale showed a notable discrepancy between person responses and the difficulty of the items, suggesting limited clinical significance.

Modulation of electroencephalogram brain activity dynamics by 10 Hz parietal repetitive transcranial magnetic stimulation: Implications for recovery of the minimally conscious state

Background and objectivesDespite the fact that the parietal cortex is associated with consciousness, the underlying mechanisms of parietal repetitive transcranial magnetic stimulation (rTMS) have not yet been specifically investigated. The present study aims to examine the effects of parietal rTMS on patients with disorders of consciousness (DoC) and identify a novel potential target. MethodsTwenty minimally conscious state (MCS) patients were stochastically assigned to a real or sham rTMS group in a controlled trial. The real rTMS group was administered over the parietal cortex, with a frequency of 10 Hz and a rest motor threshold of 90 %. The sham rTMS group was identical to the real rTMS group without magnetic stimulation over the cortex. Pre- and post-treatment resting-state electrophysiological (EEG) data and coma recovery scale-revised (CRS-R) score were gathered. Microstate analyses were calculated to evaluate the brain activity dynamics. ResultsThe real rTMS treatment improved the CRS-R scores. There were notable alterations in the mean microstate duration (MMD) of microstate B in the real rTMS group. The sham rTMS group did not exhibit such changes in CRS-R score or EEG results, which were not statistically significant. Furthermore, the MMD and RTC of microstate E were found to be negatively correlated with baseline CRS-R scores. ConclusionParietal rTMS can induce behavioral improvement and brain activity dynamics in patients with MCS. EEG microstates can be used as a valuable method to study neurophysiological mechanisms behind MCS. And the parietal cortex represents an alternative for rTMS therapy protocols.

Seizure Risk Associated With the Use of Transcranial Magnetic Stimulation for Coma Recovery in Individuals With Disordered Consciousness After Severe Traumatic Brain Injury.

Repetitive Transcranial Magnetic Stimulation (rTMS) is emerging as a promising treatment for persons with disorder of consciousness (DoC) following traumatic brain injury (TBI). Clinically, however, there are concerns about rTMS exacerbating baseline seizure risk. To advance understanding of risks, this article reports evidence of DoC-TBI rTMS-related seizure risk. Acute and sub-acute hospitals. Persons in states of DoC 6.5months to 15years after TBI (n=20) who received active rTMS (n=17) or placebo rTMS (n=3). After completing placebo procedures, placebo participants completed active rTMS procedures. These 3 participants are included in the active group. Meta-analysis of data from 3 clinical trials; 2 within-subject, 1 double blind randomized placebo-controlled. Each trial used the same rTMS protocol, provided at least 30 rTMS sessions, and delivered rTMS to the dorsolateral prefrontal cortex. During each study's rTMS treatment phase, seizure occurrences were compared between active and placebo groups using logistic regression. After stratifying active group by presence/absence of seizure occurrences, sub-groups were compared using contingency chi-square tests of independence and relative risk (RR) ratios. Two unique participants experienced seizures (1 active, 1 placebo). Post seizure, both participants returned to baseline neurobehavioral function. Both participants received antiepileptics during remaining rTMS sessions, which were completed without further seizures. rTMS-related seizure incidence rate is 59 per 1000 persons. Logistic regression revealed no difference in seizure occurrence by treatment condition (active vs placebo) or when examined with seizure risk factors (P >.1). Presence of ventriculoperitoneal shunt elevated seizure risk (RR=2.0). Collectively, findings indicate a low-likelihood that the specified rTMS protocol exacerbates baseline seizure rates in persons with DoC after TBI. In presence of VP shunts, however, rTMS likely elevates baseline seizure risk and mitigation of this increased risk with pharmacological seizure prophylaxis should be considered.

Acupuncture-assisted therapy for prolonged disorders of consciousness: study protocol for a randomized, conventional-controlled, assessor-and-statistician-blinded trial.

Acupuncture is a promising non-pharmaceutical complementary therapy in treating prolonged Disorders of consciousness (pDOC), but solid evidence to support its effectiveness and safety is still lacking. Thus, the purpose of this study is to investigate the efficacy and safety of acupuncture-assisted therapy for pDOC patients. A single-center, prospective, randomized, conventional-controlled, assessor-and-statistician-blinded trial has been designed and is being conducted at West China Hospital of Sichuan University. A total of 110 participants will be randomly assigned to the experimental group and the control group in a 1:1 allocation ratio and evaluated using Coma Recovery Scale-Revised (CRS-R) at 8 a.m., 12 p.m., and 4 p.m. on 2 consecutive days before enrollment to determine the consciousness level. The experimental group will receive acupuncture combined with conventional treatment, while the control group will receive only conventional treatment during the trial observation period. The treatment duration of both groups will be 20 days. Among them, the frequency of acupuncture-assisted therapy is once a day, with 10 consecutive sessions followed by a day's rest for a total of 24 days. Data will be collected separately during baseline and after the final treatment. For data analysis, both Full Analysis Set (FAS) and Per Protocol Set (PPS) principles will be performed together by applying SPSS 27.0 software. The primary outcome measures are the changes of CRS-R before and after treatment, while the secondary outcome measures are the changes of Full Outline of Unresponsiveness Scale (FOUR), the changes of Nociception Coma Scale-Revised (NCS-R), the changes of Disability Rating Scale (DRS), the changes of Mismatch Negativity (MMN) and P300 before and after treatment, respectively. This trial aims to rationally assess the consciousness level from multiple 2 perspectives through subjective evaluation and objective detection by selecting several standardized clinical scales combined with Event-Related Potential (ERP) detection technology. In this way, we will be able to reduce the subjectivity of consciousness assessment and objectively evaluate the clinical efficacy of acupuncture-assisted therapy for pDOC. The study, if proven to be effective and safe enough, will provide a favorable evidence to guide medical decision-making choices and future researches. https://www.chictr.org.cn/, identifier ChiCTR2300076180.

Association of total bilirubin and prognosis in disorders of consciousness

Accurate prediction of the recovery of Disorders of Consciousness (DoC) is of paramount significance for clinicians and families. Serum total bilirubin (TBIL) formed by activation of heme oxygenase 2, is associated with incidence and prognosis of cardiovascular and cerebrovascular diseases. However, studies that based TBIL and DoC are limited. The study attempted to examine the association between serum TBIL levels and prognosis in patients with DoC. One hundred and sixty-eight patients with DoC in the Second hospital of Shandong University from June 2021 to June 2023 were recruited. The clinical characteristics and venous blood samples were collected within 24 h after admission. The diagnosis of DoC was determined by two skilled investigators employing various behavioral evaluations along the coma recovery scale-revised (CRS-R) and the investigators conducted follow-up assessments of diagnosis at 1, 3, and 6 months after admission. For statistical analysis, we categorized patients with an improvement in clinical diagnosis from study entry as having a “good outcome”. In total, 139 individuals enrolled in the study. The median TBIL level was 8.2 μmol/L. Good recovery of DoC at 1, 3, and 6 months occurred in 25 (18.0%), 41 (29.5%), and 56 (40.3%) patients, respectively. After full adjustment, a significant association was found between TBIL levels and the prognosis of DoC at 1, 3, and 6 months. When TBIL levels were analyzed as categorical variables, an increasing trend in the tertiles of TBIL levels demonstrated a significant positive association with the recovery of DoC at 1, 3, and 6 months. Stratified analysis revealed that the association between serum TBIL levels and the recovery of DoC remained consistent across different sub-populations. A high serum TBIL level is associated with an improved likelihood of recovery of DoC. Additional research is required to elucidate the underlying pathophysiological causal association between TBIL levels and DoC.

Quantitative and Radiological Assessment of Post-cardiac-Arrest Comatose Patients with Diffusion-Weighted Magnetic Resonance Imaging.

Although magnetic resonance imaging, particularly diffusion-weighted imaging, has increasingly been used as part of a multimodal approach to prognostication in patients who are comatose after cardiac arrest, the performance of quantitative analysis of apparent diffusion coefficient (ADC) maps, as compared to standard radiologist impression, has not been well characterized. This retrospective study evaluated quantitative ADC analysis to the identification of anoxic brain injury by diffusion abnormalities on standard clinical magnetic resonance imaging reports. The cohort included 204 previously described comatose patients after cardiac arrest. Clinical outcome was assessed by (1) 3-6 month post-cardiac-arrest cerebral performance category and (2) coma recovery to following commands. Radiological evaluation was obtained from clinical reports and characterized as diffuse, cortex only, deep gray matter structures only, or no anoxic injury. Quantitative analyses of ADC maps were obtained in specific regions of interest (ROIs), whole cortex, and whole brain. A subgroup analysis of 172 was performed after eliminating images with artifacts and preexisting lesions. Radiological assessment outperformed quantitative assessment over all evaluated regions (area under the curve [AUC] 0.80 for radiological interpretation and 0.70 for the occipital region, the best performing ROI, p = 0.011); agreement was substantial for all regions. Radiological assessment still outperformed quantitative analysis in the subgroup analysis, though by smaller margins and with substantial to near-perfect agreement. When assessing for coma recovery only, the difference was no longer significant (AUC 0.83 vs. 0.81 for the occipital region, p = 0.70). Although quantitative analysis eliminates interrater differences in the interpretation of abnormal diffusion imaging and avoids bias from other prediction modalities, clinical radiologist interpretation has a higher predictive value for outcome. Agreement between radiological and quantitative analysis improved when using high-quality scans and when assessing for coma recovery using following commands. Quantitative assessment may thus be more subject to variability in both clinical management and scan quality than radiological assessment.

Cognitive Motor Dissociation in Disorders of Consciousness

BackgroundPatients with brain injury who are unresponsive to commands may perform cognitive tasks that are detected on functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). This phenomenon, known as cognitive motor dissociation, has not been systematically studied in a large cohort of persons with disorders of consciousness.MethodsIn this prospective cohort study conducted at six international centers, we collected clinical, behavioral, and task-based fMRI and EEG data from a convenience sample of 353 adults with disorders of consciousness. We assessed the response to commands on task-based fMRI or EEG in participants without an observable response to verbal commands (i.e., those with a behavioral diagnosis of coma, vegetative state, or minimally conscious state–minus) and in participants with an observable response to verbal commands. The presence or absence of an observable response to commands was assessed with the use of the Coma Recovery Scale–Revised (CRS-R).ResultsData from fMRI only or EEG only were available for 65% of the participants, and data from both fMRI and EEG were available for 35%. The median age of the participants was 37.9 years, the median time between brain injury and assessment with the CRS-R was 7.9 months (25% of the participants were assessed with the CRS-R within 28 days after injury), and brain trauma was an etiologic factor in 50%. We detected cognitive motor dissociation in 60 of the 241 participants (25%) without an observable response to commands, of whom 11 had been assessed with the use of fMRI only, 13 with the use of EEG only, and 36 with the use of both techniques. Cognitive motor dissociation was associated with younger age, longer time since injury, and brain trauma as an etiologic factor. In contrast, responses on task-based fMRI or EEG occurred in 43 of 112 participants (38%) with an observable response to verbal commands.ConclusionsApproximately one in four participants without an observable response to commands performed a cognitive task on fMRI or EEG as compared with one in three participants with an observable response to commands. (Funded by the James S. McDonnell Foundation and others.)

The integrity of thalamo-dorsolateral prefrontal cortex tract: a key factor in residual consciousness in disorders of consciousness patients.

The mesocircuit model describes a complex network that includes the prefrontal cortical-striatopallidal-thalamo-cortical loop systems and is involved in the mechanism underlying consciousness in patients with disorders of consciousness (DoC). Inhibitory signals to the thalamus become hyperactive in DoC patients, leading to a loss of consciousness. Reactivating this mesocircuit system is important for recovering consciousness in these patients. We investigated how the residual integrity of the thalamo-dorsolateral prefrontal cortex tract (TDLPFCT) influences consciousness in patients with DoC. This retrospective case-control study included three groups: prolonged DoC (n = 20), stroke without DoC (n = 20), and healthy controls (n = 20). Diffusion tensor imaging (DTI) was performed at least 4 weeks after the onset. Thalamo-DLPFC tracts were reconstructed using diffusion tensor tractography, and fractional anisotropy (FA) and tract volume (TV) were measured for each hemisphere. Consciousness was assessed using the revised coma recovery scale (CRS-R) within a week of brain imaging. Significant differences in DLPFCT TV were observed across all three groups, in both affected and less-affected lobes, with the DoC group showing the greatest reduction. A significant correlation was found between the TV of the less-affected TDLPFCT and CRS-R score. The integrity of the TDLPFCT, particularly in the less affected hemisphere, is associated with consciousness levels in patients with prolonged DoC. This finding suggests its potential importance in assessing prognosis and further developing therapeutic strategies for patients with DoC.

Altered Mental Status at the Extreme: Behavioral Evaluation of Disorders of Consciousness.

Disorders of consciousness represent altered mental status at its most severe, comprising a continuum between coma, the vegetative state/unresponsive wakefulness syndrome, the minimally conscious state, and emergence from the minimally conscious state. Patients often transition between these levels throughout their recovery, and determining a patient's current level can be challenging, particularly in the acute care setting. Although healthcare providers have classically relied on a bedside neurological exam or the Glasgow Coma Scale to aid with assessment of consciousness, studies have identified multiple limitations of doing so. Neurobehavioral assessment measures, such as the Coma Recovery Scale-Revised, have been developed to address these shortcomings. Each behavioral metric has strengths as well as weaknesses when applied in the acute care setting. In this review, we appraise common assessment approaches, outline alternative measures for fine-tuning these assessments in the acute care setting, and highlight strategies for implementing these practices in an interdisciplinary manner.

Reviving Consciousness: The Impact of Short-Term Spinal Cord Stimulation on Patients with Early-Onset Prolonged Disorders of Consciousness

IntroductionManaging prolonged disorders of consciousness (pDoC) presents a significant clinical challenge despite numerous available therapies. While short-term spinal cord stimulation (st-SCS) for over 3 months has been recognized as an effective treatment for pDoC, its efficacy within the first 3 months remains unclear. This study explores st-SCS's impact on patients with pDoC for less than 3 months. Material and MethodsWe enrolled 141 pDoC patients within 3 months of onset; 104 received st-SCS, and 37 underwent conservative treatment. Consciousness levels were assessed using the Coma Recovery Scale-Revised (CRS-R) before treatment, 2 weeks after, and at 3-month follow-up. ResultsComparing the data from the 3-month follow-up, we found that, the st-SCS group showed significantly greater improvement in CRS-R scores compared to the control group (p < 0.01), with more patients showing symptom amelioration (51/104 (49%)). Further analysis of the st-SCS treatment group showed significant improvement in CRS-R scores after 2 weeks (T1) and at the 3-month follow-up (T2) compared to baseline (T0). Both consciousness levels and specific CRS-R items improved notably post-treatment. Younger patients (<40 years) with traumatic brain injury and higher initial CRS-R scores were more likely to experience positive outcomes. Additionally, multivariate logistic regression identified etiology, time since injury, and initial CRS-R score as significant predictors of the 3-month outcome (p < 0.05). Conclusionsst-SCS is an effective treatment for pDoC within 3 months of onset, particularly for younger patients and those with trauma-induced conditions, significantly improving consciousness and outcomes.

Examining the Motor Scale Items From the Coma Recovery Scale–Revised

Abstract Date Presented 03/23/24 We provide an empirical evaluation of the item hierarchy within the Coma Recover Scale–Revised (CRS–R), an assessment used with patients with disorders of consciousness.This evaluation is critical for determining whether the challenge of the items aligns with the order in which they are presented in the assessment. Primary Author and Speaker: Jill Calvani Additional Authors and Speakers: Trudy Mallinson, Jennifer Weaver Contributing Authors: Katherine O’Brien

Analyzing brain-activation responses to auditory stimuli improves the diagnosis of a disorder of consciousness by non-linear dynamic analysis of the EEG

Although auditory stimuli benefit patients with disorders of consciousness (DOC), the optimal stimulus remains unclear. We explored the most effective electroencephalography (EEG)-tracking method for eliciting brain responses to auditory stimuli and assessed its potential as a neural marker to improve DOC diagnosis. We collected 58 EEG recordings from patients with DOC to evaluate the classification model’s performance and optimal auditory stimulus. Using non-linear dynamic analysis (approximate entropy [ApEn]), we assessed EEG responses to various auditory stimuli (resting state, preferred music, subject’s own name [SON], and familiar music) in 40 patients. The diagnostic performance of the optimal stimulus-induced EEG classification for vegetative state (VS)/unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) was compared with the Coma Recovery Scale-Revision in 18 patients using the machine learning cascade forward backpropagation neural network model. Regardless of patient status, preferred music significantly activated the cerebral cortex. Patients in MCS showed increased activity in the prefrontal pole and central, occipital, and temporal cortices, whereas those in VS/UWS showed activity in the prefrontal and anterior temporal lobes. Patients in VS/UWS exhibited the lowest preferred music-induced ApEn differences in the central, middle, and posterior temporal lobes compared with those in MCS. The resting state ApEn value of the prefrontal pole (0.77) distinguished VS/UWS from MCS with 61.11% accuracy. The cascade forward backpropagation neural network tested for ApEn values in the resting state and preferred music-induced ApEn differences achieved an average of 83.33% accuracy in distinguishing VS/UWS from MCS (based on K-fold cross-validation). EEG non-linear analysis quantifies cortical responses in patients with DOC, with preferred music inducing more intense EEG responses than SON and familiar music. Machine learning algorithms combined with auditory stimuli showed strong potential for improving DOC diagnosis. Future studies should explore the optimal multimodal sensory stimuli tailored for individual patients.Trial registration: The study is registered in the Chinese Registry of Clinical Trials (Approval no: KYLL-2023-414, Registration code: ChiCTR2300079310).