Coma Recovery Research Articles

Effectiveness of coma arousal therapy on patients with disorders of consciousness - A systematic review and meta-analysis.

Disorders of consciousness (DOC) incorporate stages of awareness and arousal. Through coma arousal therapy sensory deprivation experienced by patients with DOC can be mitigated. Nevertheless, consensus concerning its effectiveness on these patients is still fractional. This review aims to investigate the effectiveness of coma arousal therapies on patients with DOC. A meta-analysis was performed by searching electronic databases using search terms, the studies investigating the effect of coma arousal therapy in patients with DOC using the Coma Recovery Scale-Revised and Glasgow Coma Scale as outcome measures were included. The risk of bias was assessed, using Cochrane and Joanna Briggs Institute critical appraisal tools. Further, analysis was conducted for the included studies. Out of 260 studies, 45 trials were reviewed and assessed for bias, with 31 studies included for analysis. The analysis demonstrates a significant difference in pre- and post - sensory stimulation, vagus nerve stimulation, transcranial magnetic stimulation, and transcranial direct current stimulation. Sensory stimulation showed the greatest mean difference of -4.96; 95% CI = -5.76 to - 4.15. The patients who underwent intervention after 3 months of illness showed significant improvement. The result shows that sensory stimulation, transcranial magnetic stimulation, and transcranial direct stimulation can improve behavioral outcomes of patients with DOC, wherein sensory stimulation is found to be more effective.

Indices of Responsiveness for the Coma Recovery Scale - Revised in a Clinical Trial of Amantadine for Patients with Disorders of Consciousness

Indices of Responsiveness for the Coma Recovery Scale - Revised in a Clinical Trial of Amantadine for Patients with Disorders of Consciousness

Feasibility and Validity of the Coma Recovery Scale-Revised For Accelerated Standardized Testing (CRSR-FAST): A Practical Assessment Scale for Detecting Consciousness in the Intensive Care Unit

Feasibility and Validity of the Coma Recovery Scale-Revised For Accelerated Standardized Testing (CRSR-FAST): A Practical Assessment Scale for Detecting Consciousness in the Intensive Care Unit

439 Optimal Targets, Connectivity, and Tissue Integrity for Deep Brain Stimulation in Patients With Disorders of Consciousness

INTRODUCTION: Disorders of consciousness (DOC) are characterized by alterations in arousal and/or awareness resulting from brain injuries. Deep brain stimulation (DBS) is an emerging treatment to restore arousal/awareness in DOC. However, little is known about optimal targets and whether outcomes depend on brain connectivity, tissue integrity, or reorganization potential. METHODS: Retrospective analysis of 38 patients with DOC who underwent unilateral DBS targeting thalamic centromedian nucleus (ages = 12-65 years). DOC resulted from anoxic (n = 26) or traumatic (n = 12) injuries. Patients were classified as ‘responders’ or ‘non-responders’ using Coma/Near Coma and Coma Recovery Scales. Volumes of tissue activated (VTAs) assessed DBS locations associated with favorable response. Correlations were also performed with age, regional brain volumes from pre-operative MRI, and structural connectivity calculated from patients’ VTAs using normative diffusion MRI. RESULTS: 8/38 patients were responders and 24/38 non-responders; outcomes are pending in 6/38 patients due to <3 months follow-up. Favorable response was associated with younger age (median age = 19 years in responders, 42 years in non-responders) and greater volumes of whole-brain grey matter and subcortical regions including putamen, pallidum, caudate, and cerebellum. Responders also tended to have deeper and more medial implantations, with VTAs engaging parafascicular nucleus, reticular nucleus, and peri-midbrain red nucleus. In responders, VTA connectivity was higher with superior frontal gyrus, caudate, pallidum, and cerebellum, and lower with sensorimotor and occipital cortex. CONCLUSIONS: Efficacious DBS for DOC is linked to younger age, greater preservation of whole-brain grey-matter, greater volumes of and connectivity with select subcortical areas (pallidum, caudate, cerebellum), stronger connectivity with superior frontal gyrus, and stimulation of locations inferomedial to the centromedian nucleus. Findings may assist with optimizing patient selection, DBS targeting, and post-implantation programming.

237 SeeMe: An Automated Methodology to Detect Early Signs of Recovery After Acute Brain Injury

INTRODUCTION: Assessing the functional state of the brain and predicting recovery after acute brain injury (ABI) remains a major unsolved problem. At present, physicians make predictions using clinical examination, traditional scoring systems, and statistical models, which have significant shortcomings and lack the ability to forecast recovery on an individual basis. METHODS: SeeMe is based on analyzing subtle facial expressions in response to auditory commands (i.e., “open your eyes,” “make a smile”) over time and compares the results to a pre-stimulus baseline. These subtle motions are often not detectable by the naked eye. We enrolled 26 comatose ABI patients and 16 healthy volunteers to test this tool. Command-evoked eye-opening movements were compared to clinical observation and the JFK Coma Recovery Scale-Revised (CRS-R). RESULTS: In our study, 22 of 26 (85%) patients recovered consciousness during hospitalization after ABI. On average, SeeMe detected command-evoked eye opening ∼9 days before clinical assessment using the CRS-R and ∼3 days before blinded human raters who observed the recorded videos using the naked eye.Using the optimally identified decision threshold, SeeMe demonstrated the following performance metrics on ABI patients with no eye opening to command (auditory CRS subscale = 2): sensitivity = 74.1%, specificity = 66.6%, positive predictive value = 16.8%, and negative predictive value = 96.6%. CONCLUSIONS: These findings demonstrate the high predictive performance of SeeMe in assessing consciousness in ABI patients and provide a quantitative tool for studying neural circuits and developing novel therapeutic approaches. SeeMe's ability to detect low-amplitude motor movements opens new avenues for understanding and facilitating recovery of consciousness in patients with ABI.

Geographic variation in larval cold tolerance and exposure across the invasion front of a widely established forest insect.

Under global climate change, high and low temperature extremes can drive shifts in species distributions. Across the range of a species, thermal tolerance is based on acclimatization, plasticity, and may undergo selection, shaping resilience to temperature stress. In this study, we measured variation in cold temperature tolerance of early instar larvae of an invasive forest insect, Lymantria dispar dispar L. (Lepidoptera: Erebidae), using populations sourced from a range of climates within the current introduced range in the Eastern United States. We tested for population differences in chill coma recovery (CCR) by measuring recovery time following a period of exposure to a nonlethal cold temperature in 2 cold exposure experiments. A 3rd experiment quantified growth responses after CCR to evaluate sublethal effects. Our results indicate that cold tolerance is linked to regional climate, with individuals from populations sourced from colder climates recovering faster from chill coma. While this geographic gradient is seen in many species, detecting this pattern is notable for an introduced species founded from a single point-source introduction. We demonstrate that the cold temperatures used in our experiments occur in nature during cold spells after spring egg hatch, but impacts to growth and survival appear low. We expect that population differences in cold temperature performance manifest more from differences in temperature-dependent growth than acute exposure. Evaluating intraspecific variation in cold tolerance increases our understanding of the role of climatic gradients on the physiology of an invasive species, and contributes to tools for predicting further expansion.

Neck muscle spasticity in patients with disorder of consciousness: a pilot study.

Disorder of consciousness (DOC) is a state of prolonged altered consciousness due to severe acquired brain injury (ABI). DOC can be differentiated into coma, unresponsive wakefulness syndrome (UWS), or minimally conscious state (MCS) depending on the behavioral features observed and their relationship to the level of consciousness. Spasticity is one of the most frequently reported medical comorbidities in DOC patients. Since there is a critical lack of spasticity-focused studies and, in turn, of target treatment, we designed this pilot prospective study to evaluate cervical spine muscle spasticity and its effect on rehabilitation outcome in a large cohort of patients followed from the post-acute phase to 6 months after severe ABI. To evaluate neck muscle spasticity and investigate its impact on neurological and functional outcome in a large cohort of adult patients with DOC followed from post-acute to 6 months after severe ABI. Single-center prospective pilot study. Highly specialized inpatient neurorehabilitation clinic. Patients with severe ABI admitted within 3 months after the acute event to our Neurorehabilitation Unit between May 21st, 2019 and April 23rd, 2020 for treatment of DOC as a part of their rehabilitation program. In this single-center prospective pilot study demographic data, etiology of ABI (traumatic versus non-traumatic), DOC evaluated with the revised Coma Recovery Scale (CRS-R), and neurological and functional outcome assessed respectively with the Glasgow Coma Scale (GCS) and Functional Independence Measure (FIM) were considered. During cervical examination, we assessed spasticity with the Modified Ashworth Scale (MAS), deviation of head alignment with a goniometer, and pain with the Nociception Coma Scale-Revised (NCS-R). Of the 48 patients, 41.7% were diagnosed with UWS and 58.3% were in a minimally conscious state (MCS). We found spasticity of neck muscles in 91.7% of patients, with no difference in severity (assessed with MAS) between UWV and MCS. The NCS-R score at cervical spine examination was lower in UWS than MCS. Spasticity was severer in patients with traumatic brain injury (TBI) compared to non-traumatic. At multiple linear regression analysis, younger age, hemisyndrome, and tetraparesis were independent predictors of severity of neck muscle spasticity in MCS. More severe spasticity was a predictor of worse neurological and functional outcome at discharge in UWS patients, independently of the other confounding variables at admission (e.g., age, severity of brain injury, functional assessment, and pain). Spasticity of neck muscles frequently develops in patients with DOC and is more severe in those after TBI. UWV and MCS have different spasticity profiles as regards risk factors and neurological and functional outcome. Severity of neck muscle spasticity in UWV patients may represent an early indicator of worse neurological and functional outcome after inpatient rehabilitation. Our findings could prompt clinicians to redefine the rehabilitation aims regarding spasticity and to estimate the functional outcome in patients undergoing intensive rehabilitation after severe ABI.

Assessment of Frequency and Predictive Value of Comorbidities in Patients With Disorders of Consciousness in the Acute Setting.

Medical comorbidities are frequent in patients with disorders of consciousness (DoC) and their impact on outcomes is under investigation. The aim of this study was to investigate patients with DoC in the acute stage and the influence of comorbidities. Patients admitted to intensive care units and neurological units with a diagnosis of coma, vegetative state/unresponsive wakefulness syndrome (VS/UWS), and minimally conscious state (MCS) were investigated through the Glasgow Coma Scale (GCS), the Coma Recovery Scale - Revised (CRS-R) and the Comorbidities Coma Scale (CoCos). Forty-three patients (21 men and 22 women; mean age at admission: 60.4 ± 21.0) were included in the study. The most frequent diagnosis at admission was coma (72%) followed by VS/UWS (14%) and MCS (14%). The most frequent brain injury was subarachnoid hemorrhage (46%). At the 6-month follow-up, 19 patients had died (44%), 15 showed a full recovery of consciousness (35%), 7 were in a condition of emergence from MCS (16%), and 2 showed a persistent VS/UWS (5%). Forty-two (98%) patients showed at least one comorbidity: presence of life-support device (92.9%), anemia (76.2%), arterial hypertension (66,7%), hydrocephalus (45.3%), and respiratory infections (45.2%) were those most frequently reported. At the Multivariable Cox regression, the presence of renal disease (hazard ratio [HR] 33.37; p = 0.033) and malnutrition (HR 14.52; p = 0.001) were predictors of missed recovery of full consciousness. Although adverse outcomes are generally predicted by the severity of brain damage, the presence of medical comorbidities in an acute phase could influence outcomes and long-term prognosis.

The Prognostic Role of Candidate Serum Biomarkers in the Post-Acute and Chronic Phases of Disorder of Consciousness: A Preliminary Study.

Serum biomarkers, such as Neurofilament Light (NF-L), Glial Fibrillary Acidic Protein (GFAP), Ubiquitin C-terminal Hydrolase (UCH-L1), and Total-tau (T-Tau) have been proposed for outcome prediction in the acute phase of severe traumatic brain injury, but they have been less investigated in patients with prolonged DoC (p-DoC). We enrolled 25 p-DoC patients according to the Coma Recovery Scale-Revised (CRS-R). We identified different time points: injury onset (t0), first blood sampling at admission in Neurorehabilitation (t1), and second blood sampling at discharge (t2). Patients were split into improved (improved level of consciousness from t1 to t2) and not-improved (unchanged or worsened level of consciousness from t1 to t2). All biomarker levels decreased over time, even though each biomarker reveals typical features. Serum GFAP showed a weak correlation between t1 and t2 (p = 0.001), while no correlation was observed for serum NF-L (p = 0.955), UCH-L1 (p = 0.693), and T-Tau (p = 0.535) between t1 and t2. Improved patients showed a significant decrease in the level of NF-L (p = 0.0001), UCH-L1 (p = 0.001), and T-Tau (p = 0.002), but not for serum GFAP (p = 0.283). No significant statistical differences were observed in the not-improved group. A significant correlation was found between the level of consciousness improvement and decreased NF-L, UCH-L1, and T-Tau levels. Future studies on the association of serum biomarkers with neurophysiological and neuroimaging prognostic indicators are recommended.

The safety and feasibility of transcranial direct current stimulation for patients with chronic severe traumatic brain injury in Japan, a phase I study

BackgroundDespite evidence regarding the benefits of transcranial direct current stimulation (tDCS) in patients with severe traumatic brain injury, few trials have examined the treatment safety. Therefore, we created a phase I trial in Japan to investigate the safety of tDCS after severe brain injury. MethodsWe verified the safety of tDCS through constant left frontal anodal stimulation at 2 mA for 20 min for 5 consecutive days. Additionally, we added a variable stimuli period to explore the effects of stimulus intensity, location, and duration. We adapted a traditional 3 + 3 study design. We assessed the rate of adverse effects, including skin burns and clinical seizure. Changes in neurological symptoms were evaluated using the Glasgow Coma Scale, Coma Recovery Scale-Revised, and 4 states of consciousness (coma, unresponsive wakefulness syndrome, minimally conscious state, and severe disability). ResultsSix patients completed the study. No obvious adverse events were observed during the constant stimulation period or the variable stimulation period (right frontal anodal stimulation, stimulation frequency 2–4 mA, 1 or 5 times per week for a period of 4 weeks). Regarding the Coma Recovery Scale-Revised, patients in 4 out of 6 instances (66.7 %) improved by more than 1 point. ConclusionOur phase I safety study indicated that a single course of tDCS was safe in patients with severe traumatic brain injury. The next step is a phase II trial to investigate the preliminary efficacy and safety of tDCS at 2 mA (in comparison with sham stimulation).

Feasibility of overground exoskeleton gait training during inpatient rehabilitation after severe acquired brain injury

ABSTRACT Objective To describe the safety, feasibility, and tolerability of overground exoskeleton gait training (OEGT) integrated into clinical practice for patients after severe acquired brain injury (ABI). Setting Inpatient rehabilitation hospital. Participants Eligible patients with severe ABI met the following criteria: age > 18, medically stable, met exoskeleton frame limitations, and a score of ≤ 3 on the motor function portion of the Coma Recovery Scale – Revised (CRS-R). Presence of consciousness disorder was not exclusionary. Design Prospective observational study. Main Measures Outcomes examined safety (adverse events), feasibility (session count and barriers to session completion), and tolerability of OEGT (session metrics and heart rate). Results Ten patients with ABI completed 10.4 ± 4.8 OEGT sessions with no adverse events. Barriers to session completion included clinical focus on prioritized interventions. Sessions [median up time = 17 minutes, (IQR: 7); walk time = 13 minutes, (IQR: 9); step count = 243, (IQR: 161); device assist = 74, (IQR: 28.0)] were primarily spent in Very Light to Light heart rate intensities [89%, (IQR: 42%) and 9%, (IQR: 33%), respectively]. Conclusion OEGT incorporated into the rehabilitation plan of care during inpatient rehabilitation after severe ABI was observed to be safe, feasible, and tolerable. However, intentional steps must be taken to facilitate patient safety.

Brain activation during processing of mouth actions in patients with disorders of consciousness.

In the past 2 decades, several attempts have been made to promote a correct diagnosis and possible restorative interventions in patients suffering from disorders of consciousness. Sensory stimulation has been proved to be useful in sustaining the level of arousal/awareness and to improve behavioural responsiveness with a significant effect on oro-motor functions. Recently, action observation has been proposed as a stimulation strategy in patients with disorders of consciousness, based on neurophysiological evidence that the motor cortex can be activated not only during action execution but also when actions are merely observed in the absence of motor output, or during listening to action sounds and speech. This mechanism is provided by the activity of mirror neurons. In the present study, a group of patients with disorders of consciousness (11 males, 4 females; median age: 55 years; age range: 19-74 years) underwent task-based functional MRI in which they had, in one condition, to observe and listen to the sound of mouth actions, and in another condition, to listen to verbs with motor or abstract content. In order to verify the presence of residual activation of the mirror neuron system, the brain activations of patients were compared with that of a group of healthy individuals (seven males, eight females; median age: 33.4 years; age range: 24-65 years) performing the same tasks. The results show that brain activations were lower in patients with disorders of consciousness compared with controls, except for primary auditory areas. During the audiovisual task, 5 out of 15 patients with disorders of consciousness showed only residual activation of low-level visual and auditory areas. Activation of high-level parieto-premotor areas was present in six patients. During the listening task, three patients showed only low-level activations, and six patients activated also high-level areas. Interestingly, in both tasks, one patient with a clinical diagnosis of vegetative state showed activations of high-level areas. Region of interest analysis on blood oxygen level dependent signal change in temporal, parietal and premotor cortex revealed a significant linear relation with the level of clinical functioning, assessed with coma recovery scale-revised. We propose a classification of the patient's response based on the presence of low-level and high-level activations, combined with the patient's functional level. These findings support the use of action observation and listening as possible stimulation strategies in patients with disorders of consciousness and highlight the relevance of combined methods based on functional assessment and brain imaging to provide more detailed neuroanatomical specificity about residual activated areas at both cortical and subcortical levels.

Variability of large timescale functional networks in patients with disorders of consciousness.

Most brain function assessments for disorders of consciousness (DOC) utilized quantified characteristics, measured only once, ignoring the variation of patients' brain states. The study aims to investigate the brain activities of patients with DOC from a new perspective: variability of a large timescale functional network. Forty-nine patients were enrolled in this study and performed a 1-week behavioral assessment. Subsequently, each patient received electroencephalography (EEG) recordings five times daily at 2-h intervals. Functional connectivity and networks were measured by weighted phase lag index and complex network parameters (characteristic path length, cluster coefficient, and betweenness centrality). The relative coefficient of variation (CV) of network parameters was measured to evaluate functional network variability. Functional networks of patients with vegetative state/unresponsive wakefulness syndrome (VS/UWS) showed significantly higher segregation (characteristic path length) and lower centrality (betweenness centrality) than emerging from the minimal conscious state (EMCS) and minimal conscious state (MCS), as well as lower integration (cluster coefficient) than MCS. The functional networks of VS/UWS patients consistently presented the highest variability in segregation and integration (i.e., highest CV values of characteristic path length and cluster coefficient) on a larger time scale than MCS and EMCS. Moreover, the CV values of characteristic path length and cluster coefficient showed a significant inverse correlation with the Coma Recovery Scale-Revised scores (CRS-R). The CV values of network betweenness centrality, particularly of the cento-parietal region, showed a positive correlation with the CRS-R. The functional networks of VS/UWS patients present the most invariant segregation and integration but divergent centrality on the large time scale networks than MCS and EMCS. The variations observed within large timescale functional networks significantly correlate with the degree of consciousness impairment. This finding augments our understanding of the neurophysiological mechanisms underpinning disorders of consciousness.

Reliability and validation of the Japanese version of the coma recovery scale-revised (CRS-R)

ABSTRACT Primary objective This study aimed to verify the reliability and validity of the Japanese version of the Coma Recovery Scale-Revised (CRS-R). Methods Subjects included 59 patients with disorders of consciousness (DOC) due to acquired brain injury. To validate test-retest reliability, Evaluator A assessed the CRS-R twice on the same day (A1, A2). To examine inter-rater reliability, Evaluators A (A2) and B (B) assessed the CRS-R without a time interval. To test concurrent validity, Evaluator A (A1) assessed the CRS-R, Japan Coma Scale (JCS), and the Glasgow Coma Scale (GCS) consecutively. To validate diagnostic accuracy, we evaluated the degree of agreement between A1 and A2 and between A2 and B in their diagnosis of DOC by CRS-R. Results The test-retest (ρ = 0.92) and inter- (ρ = 0.98) reliability of CRS-R were excellent” and Concurrent validity of CRS-R with JCS (ρ = −0.82) and GCS (ρ = 0.92) were high. Results of DOC diagnosis were consistent for 48/59 cases (κ = 0.82) for A1 and A2 and for 54/59 cases (κ = 0.92) for A2 and B. Conlcusion The Japanese version of the CRS-R may be as reliable and valid as the original English and other language versions.

Family caregivers improve the diagnostic accuracy of disorders of consciousness: from remote to near-bed auditory stimulation.

Family caregivers (FC) contribute to reducing the misdiagnosis rate in patients with disorders of consciousness (DOC). Unfortunately, the recent pandemic of COVID-19 imposed drastic restrictions that limited the access of FC to the sensory/cognitive stimulation protocols. Telemedicine approaches have been implemented to avoid discontinuity in care pathways and to ensure caregivers involvement in rehabilitation programs. The aim was to investigate whether the presence of FC remotely connected might help clinicians in eliciting higher cortically mediated behavioral responses in patients with DOC. Cross-sectional study. Post-acute Unit of Neurorehabilitation. DOC due to severe brain injury. Consecutive patients with DOC were assessed by means of the Coma Recovery Scale-Revised (CRS-R) by two expert examiners. Each patient underwent to five assessments in two weeks in three different conditions: 1) by the examiner only (standard); 2) with the verbal stimulation given by the FC remotely connected by PC tablet (caregiver in remote); and 3) with the verbal stimulation given by the FC physically present (caregiver in presence). Thirty patients with DOC (VS/UWS=10; MCS=20; mean age: 51, range: 21-79; vascular: 16; anoxic: 6; TBI=8) and their FC were enrolled. Higher total scores of CRS-R were recorded both in "caregiver in remote" and in "caregiver in presence" than in standard condition (standard vs. remote, Z=2.942, P=0.003; standard vs. presence, Z=3.736, P<0.001). Furthermore, the administration of the CRS-R with a FC, elicited higher levels of behavioral responses in MCS patients, than CRS-R performed in standard condition. In particular, 2 patients out of 30 (6.66%) showed higher scores and better diagnosis when the CRS-R was administered with FC in remote. Similarly, 5 out of 30 patients (16.66%) showed better diagnoses when the CRS-R was administered with FC in presence. Five patients changed diagnosis between standard and presence conditions (3 MCS- were diagnosed as MCS+; 2 MCS+ were diagnosed as conscious). Our findings add new evidence regarding the beneficial role of family members in the diagnosis of DOC, even mediated by telemedicine approach. In future guidelines, FC should have an active and supporting role in the diagnostic and rehabilitative process of DOC.

Long-term repetitive transcranial direct current stimulation in patients with disorders of consciousness: a preliminary study

ABSTRACT Objectives To investigate the effects of long-term repetitive transcranial direct current stimulation on patients with DOC in the subacute phase. Methods In a randomized, double-blind, controlled study, 33 patients were randomly assigned to the active or sham group, and 28 patients completed the study. Patients in the active group received anodal stimulation over the DLPFC, while patients in the sham group received placebo stimulation (20 min/day, 5 days/week, for 4 weeks). The level of consciousness among patients was assessed with the Coma Recovery Scale-Revised (CRS-R) at baseline and at the end of every week from the first to the fourth week. Results The CRS-R scores of both the active and sham groups showed a consistent increasing trend over time; however, the treatment effect of the active group was better than that of the sham group. In addition, there was a statistically significant difference in the total CRS-R score between the two groups at weeks 1, 2, 3 and 4. Moreover, 10 patients (71.4%) in the active group and 3 patients (21.4%) in the sham group were regarded as responders. Conclusion Long-term tDCS could improve the level of consciousness of patients with DOC in the subacute stage.

Central autonomic network and early prognosis in patients with disorders of consciousness

The central autonomic network (CAN) plays a crucial role in modulating the autonomic nervous system. Heart rate variability (HRV) is a valuable marker for assessing CAN function in disorders of consciousness (DOC) patients. We used HRV analysis for early prognosis in 58 DOC patients enrolled within ten days of hospitalization. They underwent a five-minute electrocardiogram during baseline and acoustic/visual stimulation. The coma recovery scale-revised (CRS-R) was used to define the patient’s consciousness level and categorize the good/bad outcome at three months. The high-frequency Power Spectrum Density and the standard deviation of normal-to-normal peaks in baseline, the sample entropy during the stimulation, and the time from injury features were used in the support vector machine analysis (SVM) for outcome prediction. The SVM predicted the patients’ outcome with an accuracy of 96% in the training test and 100% in the validation test, underscoring its potential to provide crucial clinical information about prognosis.

Diagnosing awareness in disorders of consciousness with gamma-band auditory responses.

The prolonged disorders of consciousness (pDOC) describe a group of neurological conditions characterized by severe impairment of consciousness resulting from the injury of the central nervous system. As the behavioral diagnosis of pDOC remains challenging, the methods based on observing brain activity appear as promising alternatives. One of these methods is electroencephalography, which allows for noninvasive assessment of brain function. In this study, we evaluated evoked auditory responses to the chirp-modulated auditory stimulation as a potential biomarker of awareness in pDOC. Chirp-modulated stimulation is based on the repetitive presentation of auditory stimuli with a changing frequency over time. Two protocols were tested: amplitude-modulated narrow-band chirps (frequency range 25-55 Hz) and click-based wide-band chirps (30-100 Hz). The studied pDOC patient group included 62 patients (19 females and 43 males, mean age 40.72 years) diagnosed with Coma Recovery Scale-Revised. Envelope-following responses to stimulation were examined using the intertrial phase clustering coefficient. For both types of stimulation, the strength of the response in the low-gamma range (around 40 Hz) was related to the diagnosis of pDOC. Patients diagnosed with unresponsive wakefulness syndrome exhibited diminished responses, while more favorable diagnoses, suggesting awareness (minimally conscious state or emergence from the minimally conscious state), showed elevated responses. The variations in the integrity of the auditory pathway and the etiology of brain injury altered the observed response strength. Narrow-band stimulation yielded a more systematic relationship between low-gamma response and pDOC diagnosis. The results suggest the potential role of low gamma-band responses to chirp-modulated stimulation as the supportive diagnostic tool to detect awareness in the pDOC patient group.

Musical and electrical stimulation as intervention in disorder of consciousness (DOC) patients: A randomised cross-over trial.

Disorders of consciousness (DOC), i.e., unresponsive wakefulness syndrome (UWS) or vegetative state (VS) and minimally conscious state (MCS), are conditions that can arise from severe brain injury, inducing widespread functional changes. Given the damaging implications resulting from these conditions, there is an increasing need for rehabilitation treatments aimed at enhancing the level of consciousness, the quality of life, and creating new recovery perspectives for the patients. Music may represent an additional rehabilitative tool in contexts where cognition and language are severely compromised, such as among DOC patients. A further type of rehabilitation strategies for DOC patients consists of Non-Invasive Brain Stimulation techniques (NIBS), including transcranial electrical stimulation (tES), affecting neural excitability and promoting brain plasticity. We here propose a novel rehabilitation protocol for DOC patients that combines music-based intervention and NIBS in neurological patients. The main objectives are (i) to assess the residual neuroplastic processes in DOC patients exposed to music, (ii) to determine the putative neural modulation and the clinical outcome in DOC patients of non-pharmacological strategies, i.e., tES(control condition), and music stimulation, and (iii) to evaluate the putative positive impact of this intervention on caregiver's burden and psychological distress. This is a randomised cross-over trial in which a total of 30 participants will be randomly allocated to one of three different combinations of conditions: (i) Music only, (ii) tES only (control condition), (iii) Music + tES. The music intervention will consist of listening to an individually tailored playlist including familiar and self-relevant music together with fixed songs; concerning NIBS, tES will be applied for 20 minutes every day, 5 times a week, for two weeks. After these stimulations two weeks of placebo treatments will follow, with sham stimulation combined with noise for other two weeks. The primary outcomes will be clinical, i.e., based on the differences in the scores obtained on the neuropsychological tests, such as Coma Recovery Scale-Revised, and neurophysiological measures as EEG, collected pre-intervention, post-intervention and post-placebo. This study proposes a novel rehabilitation protocol for patients with DOC including a combined intervention of music and NIBS. Considering the need for rigorous longitudinal randomised controlled trials for people with severe brain injury disease, the results of this study will be highly informative for highlighting and implementing the putative beneficial role of music and NIBS in rehabilitation treatments. ClinicalTrials.gov identifier: NCT05706831, registered on January 30, 2023.

Which information derived from the Coma Recovery Scale-Revised provides the most reliable prediction of clinical diagnosis and recovery of consciousness? A comparative study using machine learning techniques.

The Coma Recovery Scale-Revised (CRS-R) is the most recommended clinical tool to examine the neurobehavioral condition of individuals with disorders of consciousness (DOCs). Different studies have investigated the prognostic value of the information provided by the conventional administration of the scale, while other measures derived from the scale have been proposed to improve the prognosis of DOCs. However, the heterogeneity of the data used in the different studies prevents a reliable comparison of the identified predictors and measures. This study investigates which information derived from the CRS-R provides the most reliable prediction of both the clinical diagnosis and recovery of consciousness at the discharge of a long-term neurorehabilitation program. Retrospective observational multisite study. The enrollment was performed in three neurorehabilitation facilities of the same hospital network. A total of 171 individuals with DOCs admitted to an inpatient neurorehabilitation program for a minimum of 3 months were enrolled. Machine learning classifiers were trained to predict the clinical diagnosis and recovery of consciousness at discharge using clinical confounders and different metrics extracted from the CRS-R scale. Results showed that the neurobehavioral state at discharge was predicted with acceptable and comparable predictive value with all the indices and measures derived from the CRS-R, but for the clinical diagnosis and the Consciousness Domain Index, and the recovery of consciousness was predicted with higher accuracy and similarly by all the investigated measures, with the exception of initial clinical diagnosis. Interestingly, the total score in the CRS-R and, especially, the total score in its subscales provided the best overall results, in contrast to the clinical diagnosis, which could indicate that a comprehensive measure of the clinical diagnosis rather than the condition of the individuals could provide a more reliable prediction of the neurobehavioral progress of individuals with prolonged DOC. The results of this work have important implications in clinical practice, offering a more accurate prognosis of patients and thus giving the possibility to personalize and optimize the rehabilitation plan of patients with DoC using low-cost and easily collectable information.