Coma Recovery Scale-Revised Score Research Articles

Cortical responses to auditory stimulation predict the prognosis of patients with disorders of consciousness

ObjectiveThis study aimed to assess the prognosis of patients with disorders of consciousness (DoC) using auditory stimulation with electroencephalogram (EEG) recordings. MethodsWe enrolled 72 patients with DoC in the study, which involved subjecting patients to auditory stimulation while EEG responses were recorded. Coma Recovery Scale–Revised (CRS-R) scores and Glasgow Outcome Scale (GOS) were determined for each patient and followed up for three months. A frequency spectrum analysis was performed on the EEG recordings. Finally, the power spectral density (PSD) index was used to predict the prognosis of patients with DoC based on a support vector machine (SVM) model. ResultsPower spectral analyses revealed that the cortical response to auditory stimulation showed a decreasing trend with decreasing consciousness levels. Auditory stimulation-induced changes in absolute PSD at the delta and theta bands were positively correlated with the CRS-R and GOS scores. Furthermore, these cortical responses to auditory stimulation had a good ability to discriminate between good and poor prognoses of patients with DoC. ConclusionsAuditory stimulation-induced changes in the PSD were highly predictive of DoC outcomes. SignificanceOur findings showed that cortical responses to auditory stimulation may be an important electrophysiological indicator of prognosis in patients with DoC.

Prognosis prediction for impaired consciousness recovery in stroke patients using videofluoroscopic swallowing study: A retrospective observational study.

Prognosis prediction of impaired consciousness is clinically important for establishing therapeutic strategies, determining a rehabilitative goal and functional outcome, and estimating rehabilitative therapy duration. In this study, we investigated the prognosis prediction value of videofluoroscopic swallowing study (VFSS) in recovery of impaired consciousness in stroke patients. Fifty-one patients with impaired consciousness who underwent VFSS during the early stage of stroke between 2017 and 2021 were recruited in this retrospective study. VFSS were performed using modified Logemann protocol, and bonorex was used as the liquid contrast medium. The penetration-aspiration scale (PAS) was graded for all patients, and they were classified into 2 groups depending on the presence of aspiration on liquid material: the aspiration-positive group with a PAS score ≥ 6, and the aspiration-negative group with a PAS score < 6. The coma recovery scale-revised (CRS-R) was used to evaluate patients' conscious state at the time of VFSS and 3 months after. Statistical analysis was performed using independent t test and Pearson's correlation. The increase in total CRS-R score from time of VFSS to 3 months later was greater in aspiration-negative group than in aspiration-positive group (P < .05). A moderate negative correlation was observed between liquid PAS score and the increase in total CRS-R score (r = -0.499, P < .05). Among 6 CRS-R subscales, a strong negative correlation was observed between liquid PAS score and the communication score increase (r = -0.563, P < .05), while moderate negative correlations were detected between liquid PAS score and the increases in auditory (r = -0.465, P < .05), motor (r = -0.372, P < .05), oromotor (r = -0.426, P < .05), and arousal (r = -0.368, P < .05) scores. We observed that patients without aspiration on videofluoroscopic swallowing study showed better recovery of impaired consciousness, and the degree of penetration and aspiration had a predictive value for impaired consciousness prognosis in the early stage of stroke.

Effect of Transcranial Direct Current Stimulation on Patients With Disorders of Consciousness: A Systematic Review and Meta-analysis.

The aims of this study are to evaluate the efficacy of transcranial direct current stimulation for improving disorders of consciousness and to compare efficacy of the different etiologies of disorders of consciousness. Randomized controlled trials or crossover trials examining effects of transcranial direct current stimulation in patients with disorders of consciousness were searched in PubMed, Embase, Cochrane Library, and Web of Science. The sample characteristics, etiology, transcranial direct current stimulation treatment characteristics, and outcomes were extracted. Meta-analysis was performed using the RevMan software. We included nine trials providing data with 331 participants and found that transcranial direct current stimulation improved the Coma Recovery Scale-Revised score of disorders of consciousness patients. We found a significant improvement of Coma Recovery Scale-Revised score in the minimally conscious state group (weighted mean difference = 0.77, 95% confidence interval = 0.30-1.23, P = 0.001), but not in the vegetative state or unresponsive wakefulness syndrome group. The effects of transcranial direct current stimulation are related to etiology, as the Coma Recovery Scale-Revised score was improved in the traumatic brain injury group (weighted mean difference = 1.18, 95% confidence interval = 0.60-1.75, P < 0.001), but not in vascular accident and anoxia groups. This meta-analysis revealed the evidence for positive effects of transcranial direct current stimulation on disorders of consciousness without adverse effects observed in minimally conscious state patients. In particular, transcranial direct current stimulation may be an effective treatment in rehabilitating cognitive functions in people with traumatic brain injury.

Trigeminal nerve stimulation for prolonged disorders of consciousness: A randomized double-blind sham-controlled study

BackgroundTrigeminal nerve stimulation (TNS) has been proposed as a promising intervention for coma awakening. However, the effect of TNS on patients with prolonged disorders of consciousness (pDoC) is still unclear. ObjectiveThis study aimed to investigate the therapeutic effects of TNS in pDoC caused by stroke, trauma, and anoxia. MethodsA total of 60 patients (male =25, female =35) aged over 18 who were in a vegetative state or minimally conscious state were randomly assigned to the TNS (N = 30) or sham TNS (N = 30) groups. 4 weeks of intervention and a followed up for 8 weeks were performed. The Glasgow Coma Scale (GCS) and Coma Recovery Scale-Revised (CRS-R) scores as primary outcomes were assessed at baseline and at 2, 4, 8, and 12 weeks. ResultsThe score changes in the TNS group over time for CRS-R (2-week: mean difference = 0.9, 95% CI = [0.3, 1.5], P = 0.006; 4-week: 1.6, 95% CI = [0.8, 2.5], P < 0.001; 8-week: mean difference = 2.4, 95% CI = [1.3, 3.5], P < 0.001; 12-week: mean difference = 2.3, 95% CI = [1.1, 3.4], P < 0.001) and GCS (4-week: mean difference = 0.7, 95% CI = [0.3, 1.2], P = 0.002; 8-week: mean difference = 1.1, 95% CI = [0.6, 1.7], P < 0.001; 12-week: 1.1, 95% CI = [0.5, 1.7], P = 0.003) were higher than those in the sham group. 18-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) revealed that the metabolism of the right parahippocampal cortex, right precuneus, and bilateral middle cingulate cortex was significantly increased in TNS group. ConclusionThe results of this study indicate that TNS could increase local brain metabolism and may promote functional recovery in patients with prolonged disorders of consciousness. Registration informationName of the registry: Chinese Clinical Trial Registry. Registration number: ChiCTR1900025573. The date that the study was submitted to a registry: 2019-09-01. The date when the first patient was enrolled was 2021-01-20.

Resting State fMRI for Neuroprognostication in Traumatic Brain Injury: Clinical Experience of Evaluation for Covert Consciousness and Epileptogenic Networks in Acute Coma (P14-7.005)

<h3>Objective:</h3> To report the <b><i>clinical</i></b> experience of resting state fMRI (rs-fMRI) for neuroprognostication, consciousness recovery, and epileptogenic networks in acute coma. <h3>Background:</h3> Diagnosis and prognosis in acute disorders of consciousness (DoC) remains a challenge. Early withdrawal of care for traumatic brain injury (TBI) patients with recovery potential and continuation of care for patients with devastating prognosis due to misdiagnosis of DoC have both been reported. The rs-fMRI is an innovative tool that has shown promise in diagnosis and prognosis of DoC but has yet to see widespread clinical use. <h3>Design/Methods:</h3> Case Report. <h3>Results:</h3> We present a case of a previously healthy 38-year-old man who received clinical rs-fMRI in acute coma due to TBI. Initial exam: nonreactive pupils, intact corneal reflexes, absent cough and gag reflexes and no motor response. His Glasgow Coma Scale (GCS) was 3 and Coma Recovery Scale-Revised (CSR-R) score was 0. CT head showed acute left subdural hematoma, rightward midline shift, and uncal herniation. After undergoing emergent hemicraniectomy, MRI brain showed evolving Grade III diffuse axonal injury, severe ventriculomegaly, and protrusion of cortex through the hemicraniectomy. EEG demonstrated bilateral slowing but no seizures. Rs-fMRI (hospital day 36) demonstrated no epileptogenic networks, preserved default mode network, language and subcortical motor networks with moderate impairment. These findings supported return of consciousness, lower-level language comprehension, and motor impairment. Despite the patient’s poor initial examination, the rs-fMRI was useful in supporting the family’s decision to continue care. At three months, the patient’s CSR-R improved to 9, including regained localization to sound, visual fixation, flexion withdrawal, oral reflexive movements, no communication, and eye opening without stimulation, which is consistent with minimally conscious state minus. <h3>Conclusions:</h3> Clinical utilization of rs-fMRI has limitations but can aid in clinical decision-making when evaluating for epileptogenic networks, potential for consciousness recovery, and overall functional outcome in patients with DoC and severe TBI. <b>Disclosure:</b> Dr. Aseem has nothing to disclose. Dr. Strohm has nothing to disclose. Dr. Carlson has nothing to disclose. Dr. Karazanashvili has nothing to disclose. Dr. Gilbert has nothing to disclose. Ms. Gillette has nothing to disclose. Dr. Boerwinkle has nothing to disclose.

Effect of single and combined median nerve stimulation and repetitive transcranial magnetic stimulation in patients with prolonged disorders of consciousness: a prospective, randomized, single-blinded, controlled trial.

To investigate the efficacy of median nerve stimulation (MNS) combined with repetitive transcranial magnetic stimulation (rTMS), MNS alone, and rTMS alone in elevating the level of consciousness in patients with prolonged disorders of consciousness (pDOC). We enrolled 75 eligible inpatients suffering from pDOC as a result of traumatic or non-traumatic brain injury. Participants were randomly assigned to one of the following three treatment groups: (1) rTMS+sham-MNS; (2) MNS + sham-rTMS; or (3) MNS + rTMS. The rTMS protocol involved stimulation above the left dorsolateral prefrontal cortex at a 10 Hz frequency and 90% resting motor threshold. The MNS protocol involved the delivery of a 15-20 mA current at the median nerve point 2 cm from the wrist crease of the right distal forearm. The primary outcome was the change from baseline of the Coma Recovery Scale-Revised (CRS-R) score after treatment. Secondary outcomes included post-treatment changes from baseline of the Glasgow Coma Scale (GCS) score, awaken ratio, electroencephalography (EEG) scores, and the latency and amplitude of N20 on somatosensory evoked potentials. Before the intervention, there were no significant differences between groups in the CRS-R, GCS scores, age, duration of pDOC, clinical diagnosis, EEG scores, latency and amplitude of N20, sex, job, marital status, education level, or disease etiology. Within the three groups, the total CRS-R, GCS scores and amplitude of N20 on both side significantly increased and latency of N20 on poor side significantly decreased post-intervention. Significantly greater improvement in CRS-R, GCS total scores, amplitude of N20 on both side and latency of N20 on the poor side were observed in the MNS + TMS group compared to those of the groups receiving rTMS alone or MNS alone. The patients receiving TMS and MNS intervention showed a greater EEG activity improvement, and the EEG activity improved ratio significantly differ between groups, while there were no significant differences in the awakening ratios between the three groups. The combination of MNS + rTMS was more efficacious in improving the level of consciousness than MNS alone or rTMS alone in patients with pDOC.

Relationship between Coma Recovery Scale-Revised and the Thalamocortical Tract of Ascending Reticular Activating System in Hypoxic-Ischemic Brain Injury: A Pilot Study.

This pilot study examined the relationship between the Coma Recovery Scale-Revised (CRS-R) and the five subparts of the thalamocortical tract in chronic patients with hypoxic-ischemic brain injury by diffusion tensor tractography (DTT). Seventeen consecutive chronic patients with hypoxic-ischemic brain injury were recruited. The consciousness state was evaluated using CRS-R. The five subparts of the thalamocortical tract (the prefrontal cortex, the premotor cortex, the primary motor cortex, the primary somatosensory cortex, and the posterior parietal cortex) were reconstructed using DTT. Fractional anisotropy and the tract volume of each subpart of the thalamocortical tract were estimated. The CRS-R score showed a moderate positive correlation with the tract volume of the prefrontal cortex part of the thalamocortical tract (p < 0.05). In addition, the tract volume of the prefrontal cortex component of the thalamocortical tract could explain the variability in the CRS-R score (p < 0.05). The prefrontal cortex part was closely related to the CRS-R score in chronic patients with hypoxic-ischemic brain injury. In addition, the change in the remaining number of neural fibers of the prefrontal cortex part appeared to be related to the change in conscious state.

Evaluation of residual cognition in patients with disorders of consciousness based on functional near-infrared spectroscopy.

Accurate evaluation of consciousness in patients with prolonged disorders of consciousness (DOC) is critical for designing therapeutic plans, determining rehabilitative services, and predicting prognosis. Effective ways for detecting consciousness in patients with DOC are still needed. Evaluation of the residual awareness in patients with DOC and investigation of the spatiotemporal differences in the hemodynamic responses between the minimally conscious state (MCS) and the unresponsive wakefulness syndrome (UWS) groups using active command-driven motor imagery (MI) tasks. In this study, functional near-infrared spectroscopy (fNIRS) was used to measure the changes of hemodynamic responses in 19 patients with DOC (9 MCS and 10 UWS) using active command-driven MI tasks. The characteristics of the hemodynamic responses were extracted to compare the differences between the MCS and UWS groups. Moreover, the correlations between the hemodynamic responses and the clinical behavioral evaluations were also studied. The results showed significant differences in the spatiotemporal distribution of the hemodynamic responses between the MCS and UWS groups. For the patients with MCS, significant increases in task-evoked hemodynamic responses occurred during the "YES" questions of the command-driven MI tasks. Importantly, these changes were significantly correlated with their coma-recovery scale-revised (CRS-R) scores. However, for the patients with UWS, no significant changes of the hemodynamic responses were found. Additionally, the results did not show any statistical correlation between the hemodynamic responses and their CRS-R scores. The fNIRS-based command-driven MI tasks can be used as a promising tool for detecting residual awareness in patients with DOC. We hope that the findings and the active paradigm used in this study will provide useful insights into the diagnosis, therapy, and prognosis of this challenging patient population.

EEG complexity correlates with residual consciousness level of disorders of consciousness

Background and objectiveElectroencephalography (EEG) and neuroimaging measurements have been highly encouraged to be applied in clinics of disorders of consciousness (DOC) to improve consciousness detection. We tested the relationships between neural complexity measured on EEG and residual consciousness levels in DOC patients.MethodsResting-state EEG was recorded from twenty-five patients with DOC. Lempel–Ziv complexity (LZC) and permutation Lempel–Ziv complexity (PLZC) were measured on the EEG, and their relationships were analyzed with the consciousness levels of the patients.ResultsPLZC and LZC values significantly distinguished patients with a minimally conscious state (MCS), vegetative state/unresponsive wakefulness syndrome (VS/UWS), and healthy controls. PLZC was significantly correlated with the Coma Recovery Scale-Revised (CRS-R) scores of DOC patients in the global brain, particularly in electrodes locating in the anterior and posterior brain regions. Patients with higher CRS-R scores showed higher PLZC values. The significant difference in PLZC values between MCS and VS/UWS was mainly located in the bilateral frontal and right hemisphere regions.ConclusionNeural complexity measured on EEG correlates with residual consciousness levels of DOC patients. PLZC showed higher sensitivity than LZC in the classification of consciousness levels.

Clinical effect of short-term spinal cord stimulation in the treatment of patients with primary brainstem hemorrhage-induced disorders of consciousness.

Recently, short-term spinal cord stimulation (st-SCS) has been used in neurorehabilitation and consciousness recovery. However, little is known about its effects on primary brainstem hemorrhage (PBSH)-induced disorders of consciousness (DOC). In this study, we examined the therapeutic effects of st-SCS in patients with PBSH-induced DOC. Fourteen patients received a 2-week st-SCS therapy. Each patient's state of consciousness was evaluated using the Coma Recovery Scale-Revised (CRS-R). CRS-R evaluation scores were recorded at the baseline (before SCS implantation) and 14 days later. Over 70% (10/14) of the patients (CRS-R score increased to ≥2 points) responded to the SCS stimulation after 14 days of st-SCS treatment. All items included in the CRS-R exhibited a significant increase post-treatment compared with pretreatment. After 2 weeks of st-SCS treatment, seven patients showed diagnostic improvement, resulting in a 50% (7/14) overall effective rate. Approximately 75% (3/4) of patients with minimally conscious state plus (MCS+) improved to emergence from MCS (eMCS), and 50% (1/2) of patients with vegetative state or unresponsive wakefulness syndrome (VS/UWS) improved to MCS+. In PBSH-induced DOC, st-SCS is a safe and effective treatment. The clinical behavior of the patients improved significantly following the st-SCS intervention, and their CRS-R scores markedly increased. This was most effective for MCS+.

Optimizing the modulation paradigm of transcutaneous auricular vagus nerve stimulation in patients with disorders of consciousness: A prospective exploratory pilot study protocol.

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique. Several studies have reported the effectiveness of taVNS in patients with disorders of consciousness (DOC); however, differences in the modulation paradigm have led to inconsistent treatment outcomes. This prospective exploratory trial will include 15 patients with a minimally conscious state (MCS) recruited according to the coma recovery scale-revised (CRS-R). Each patient will receive 5 different frequencies of taVNS (1, 10, 25, 50, and 100 Hz); sham stimulation will be used as a blank control. The order of stimulation will be randomized, and the patients' CRS-R scores and resting electroencephalography (EEG) before and after stimulation will be recorded. The overall study of taVNS used in treating patients with DOC is still in the preliminary stage of exploration. Through this experiment, we aim to explore the optimal stimulation frequency parameters of taVNS for the treatment of DOC patients. Furthermore, we expect to achieve a stable improvement of consciousness in DOC patients by continuously optimizing the neuromodulation paradigm of taVNS for the treatment of DOC patients. https://www.chictr.org.cn/index.aspx, identifier ChiCTR 2200063828.

Transauricular vagus nerve stimulation for patients with disorders of consciousness: A randomized controlled clinical trial.

Disorders of consciousness (DoCs) are a frequent complication of brain injury disease, and effective treatments are currently lacking. Transauricular vagus nerve stimulation (tVNS) has been proposed as a promising therapeutic method for neurological disorders such as epilepsy and depression. In our previous study, we demonstrated that vagus nerve stimulation promoted recovery in rats with DoCs caused by traumatic brain injury. However, the clinical effect of vagus nerve stimulation on consciousness disorders is unclear. We aimed to investigate the therapeutic efficacy and safety of tVNS in patients with DoCs. We conducted a randomized, double-blinded, sham-controlled trial. Patients (N = 60) with DoCs, including minimally conscious state (MCS) and vegetative state/unresponsive wakefulness syndrome, were enrolled and randomized to groups receiving either active or sham tVNS. A frequency of 20 Hz and pulse wave of 200 us was used in the active-tVNS protocol, which was performed in the auricular branch of the vagus nerve in the left outer ear. The sham-tVNS protocol was the same as the active-tVNS protocol although without current input. Both groups of patients also received conventional treatments. Consciousness was evaluated according to the Coma Recovery Scale-Revised before and after the 4-week intervention. We also recorded the type and number of behavioral responses. Safety was primarily assessed according to the incidence of treatment-emergent adverse events. Each patient's heart rate and blood pressure were monitored during all treatment sessions. Ultimately, 57 patients completed the study: 28 patients underwent active tVNS and 29 patients underwent sham tVNS. No significant differences were observed in Coma Recovery Scale-Revised scores between the active- and sham-tVNS groups before the tVNS sessions. Compared with patients in the sham-tVNS group (9.28 ± 4.38), patients with DoCs treated with active tVNS showed improved consciousness (10.93 ± 4.99), although not statistically significant. Further analysis revealed obvious differences between patients with MCS receiving active and sham tVNS, but no significant difference in patients with vegetative state/unresponsive wakefulness syndrome in both groups. All side effects were considered common medical conditions with no obvious correlation to tVNS. These preliminary data provide early evidence that tVNS may be an effective and safe approach for promoting the recovery of consciousness, especially in patients with MCS. https://www.chictr.org.cn/edit.aspx?pid=175938&htm=4, identifier: ChiCTR2200066629.

Relationship between the Consciousness State and the Default Mode Network in Traumatic Brain Injury

This study investigated the relationship between Coma Recovery Scale-Revised (CRS-R) and the neural networks between the medial prefrontal cortex (mPFC) and precuneus (PCun)/posterior cingulate cortex (PCC) in disorders of consciousness (DOC) patients with a traumatic brain injury (TBI) using diffusion tensor tractography (DTT). Twenty-five consecutive patients with TBI admitted to the rehabilitation department of a university hospital were enrolled in this study. The Coma Recovery Scale-Revised (CRS-R) was used to evaluate the consciousness state. The pathway of the neural networks between the mPFC and the PCun (mPFC-PCun DMN)/PCC (mPFC-PCC DMN) were reconstructed using DTT. Fractional anisotropy (FA) and the tract volume (TV) were obtained to assess the diffusion tensor imaging parameters. The CRS-R score had strong positive correlations with the FA value and TV of the mPFC-PCun DMN (p < 0.05), while it showed a moderate positive correlation with the TV of the mPFC-PCC DMN (p < 0.05). In addition, the FA value of the mPFC-Pcun DMN showed that it could explain the variability in the CRS-R score. The close correlation was noted between the consciousness state and the mPFC-PCun DMN and mPFC-PCC DMN in DOC patients with TBI. On the other hand, the mPFC-PCun DMN appeared to be more closely correlated with the consciousness state than the mPFC-PCC DMN.

Coma Recovery Scale-Revised Predicts Disability Rating Scale in Acute Rehabilitation of Severe Traumatic Brain Injury

ObjectiveTo explore the prognostic value of the Coma Recovery Scale-Revised (CRS-R) in predicting disability outcomes in patients with severe traumatic brain injury using the Disability Rating Scale (DRS). DesignSecondary analysis including linear and logistic regressions were performed. SettingData were collected in a previous clinical trial. ParticipantsOne hundred eighty-four participants across 3 countries (N=184). Main Outcome MeasuresDisability Rating Scales. ResultsAnalyses showed an inverse relation between CRS-R scores obtained at baseline and change in DRS scores at 6 weeks. Similarly, changes in CRS-R scores between baseline and 4 weeks were also found to have an inverse relation to change in DRS scores at 6 weeks. ConclusionsThis study generates a tool that can be used to predict the probability that a patient with severe traumatic brain injury lands in 1 of 3 disability categories. The CRS-R may be useful in prognostication of disability in patients with severe traumatic brain injury.

FNIRS-based functional connectivity signifies recovery in patients with disorders of consciousness after DBS treatment

ObjectiveWhile deep brain stimulation (DBS) has proved effective for certain patients with disorders of consciousness (DOC), the working neural mechanism is not clear, the response varies for patients, and the assessment is inadequate. This paper aims to quantify the DBS-induced changes of consciousness in DOC patients at the neural functional level. MethodsTen DOC patients were included for DBS surgery. The DBS target was the right centromedian-parafascicular (CM-pf) nuclei for four patients and the bilateral CM-pf nuclei for six patients. Functional near-infrared spectroscopy (fNIRS) was taken to measure the neural activation of patients, in parallel with Coma Recovery Scale-Revised (CRS-R), before the DBS surgery and one month after. The fNIRS signals were recorded from the frontal, parietal, and occipital lobes. Functional connectivity analysis quantified the communication between brain regions, area communication strength, and global communication efficiency. Linear regression analysis was conducted between the changes of indices based on functional connectivity analysis and the changes of the CRS-R index. ResultsPatients with trauma (n = 4) exhibited a greater increase of CRS-R scores after DBS treatment compared with patients with hemorrhage (n = 4) and brainstem infarction (n = 2). Global communication efficiency changed consistently with the CRS-R index (slope = 57.384, p < 0.05, R2=0.483). No significant relationship was found between the changes of area communication strength of six brain lobes and the changes of the CRS-R index. ConclusionsThe cause of DOC is essential for the outcome of DBS treatment, and brain communication efficiency is a promising functional marker for DOC recovery. SignificancefNIRS-based functional connectivity analysis on brain network signifies changes of consciousness in DOC patients after DBS treatment.

Relationship between consciousness level and perfusion computed tomography in patients with prolonged disorders of consciousness.

We assessed the relationship between consciousness level and values of cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and time to peak (TTP) obtained by whole-brain perfusion computed tomography (pCT) in patients with prolonged disorders of consciousness (pDOC). This study included 29 patients in vegetative state (VS), 34 with minimally consciousness state minus (MCS-), and 13 with minimally consciousness state plus (MCS+). All patients were evaluated using the Coma Recovery Scale-Revised (CRS-R), the Glasgow Coma Scale (GCS), and the Full Outline of UnResponsiveness (FOUR). The values of CBF, CBV, MTT, and TTP were obtained from patients who underwent pCT. Differences in CBF, CBV, MTT, and TTP were compared between the three types of pDOC. Correlations between the CRS-R, GCS, and FOUR scores and the pCT results were analyzed. Among the three groups, patients in VS showed a significantly decreased CBF in the bilateral frontal lobe, thalamus, temporal lobe, occipital lobe, brainstem, and damaged part. CBV was significantly reduced in patients with VS in the bilateral frontal lobe, thalamus, temporal lobe, brainstem, and damaged part. The total CRS-R, GCS, and FOUR scores were positively correlated with CBF, CBV, and TTP in almost all regions of interest. Reductions in CBF and CBV calculated with pCT are associated with impaired consciousness and perfusion CT could be a promising tool in evaluating the conscious level in patients with pDOC.

Influence of High-Frequency Repetitive Transcranial Magnetic Stimulation on Neurobehavioral and Electrophysiology in Patients with Disorders of Consciousness.

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has been proposed as a promising therapeutic intervention for patients with disorders of consciousness (DOC). However, its therapeutic effects in the literature are inconsistently documented. The primary aim of this study was to explore the alterations in neural connectivity and neurobehavioral reactivity during rTMS modulation in patients with DOC. In addition, safety was investigated as a secondary aim. The presence of bilateral N20 components in DOC patients was determined by somatosensory-evoked potential (SEP) before enrollment in the study. A total of 64 patients were enrolled and randomly placed into the active and sham groups. Ultimately, 50 patients completed the study. Twenty-five patients in the active group underwent real HF-rTMS, and 25 patients in the sham group underwent sham HF-rTMS, which was delivered over the left dorsolateral prefrontal cortex (DLPFC). The outcome measures of performed pre- and postintervention included the latencies of the N20 and N20-P25 amplitudes of SEP, brainstem auditory-evoked potential (BAEP) grade, JFK Coma Recovery Scale-Revised (CRS-R) score, and Glasgow Coma Scale (GCS) score; any adverse events were recorded at any time during the intervention. Following six weeks of treatment, a significant increase was observed in the total CRS-R and GCS scores, and the N20-P25 amplitudes of patients in the two groups were compared with that obtained from preintervention (all p values < 0.05). The waves of BAEP in the two groups also showed a trend toward normalized activity compared with preintervention grades (p values < 0.05). A significant decrease in the latencies of N20 (p values < 0.001) was observed in the active group compared with measurements obtained from preintervention, whereas no significant decrease was observed in the sham group (p values = 0.013). The improvement in total CRS-R scores (p values = 0.002), total GCS scores (p values = 0.023), and N20-P25 amplitudes (p values = 0.011) as well as the decrease in latencies of N20 (p values = 0.018) and change in BAEP grades (p values = 0.013) were significantly different between the two groups. The parameters in neural connectivity (N20-P25 amplitudes, N20 latencies, and BAEP grades) were significantly correlated with the total CRS-R and GCS scores at postintervention, and the changes of CRS-R before and after interventions have a positive relationship with N20-P25 amplitudes. No adverse events related to the rTMS protocol were recorded. Neural connectivity levels are affected by HF-rTMS and are significantly related to clinical responses in DOC patients with the presence of bilateral N20. The elevation of neural connectivity levels may lay a foundation for successful HF-rTMS treatment for DOC patients.

Neuropsychological assessment through Coma Recovery Scale-Revised and Coma/Near Coma Scale in a sample of pediatric patients with disorder of consciousness

BackgroundThe Coma Recovery Scale-Revised (CRS-R) has become a standard tool in assessing Disorders of consciousness (DoC) in adults. However, its measurement validity in pediatrics has only been ascertained in healthy cases. Increasing use of CRS-R in children with DoC imposes appropriate comparison against previously validated tools. The aims of the study were to describe the emergence to a conscious state (eMCS) in pediatric acquired brain injury (ABI); to explore the agreement between the CRS-R and Coma Near Coma Scale (CNCS) and to discuss the advantage of administering the CRS-R in pediatric age.Materials and methodsIn this observational prospective study, 40 patients were recruited. Inclusion criteria were age 5 to 18 years, Glasgow Coma Scale (GCS) score ≤ 8 at the insult, and unresponsive wakefulness syndrome (UWS) or minimally conscious state (MCS) at admission. Patients were assessed with CRS-R, and CNCS was used as standard.ResultsThe agreement between scales was moderate (r = − 0.71). The analysis of the CRS-R domain scores also confirmed that decreasing CNCS levels (from a coma to eMCS) corresponded to concurrent increas of CRS-R scores in all domains. Moreover, CRS-R better defined patients’ status in the emergency phase from MCS. Conversely, CRS-R had lower DoC scoring ability in the presence of severe motor impairment.ConclusionWe show that CRS-R can track changes in DoC in children as young as 5 years old, and we provide evidence that the agreement with CNCS scores is good.

Relationship between the consciousness level and the structural neural connectivity of the medial prefrontal cortex in hypoxic-ischemic brain injury: a pilot study.

This pilot study investigated the relationship between the consciousness level and the structural neural connectivity of the medial prefrontal cortex (mPFC SNC) in patients with hypoxic-ischemic brain injury (HI-BI), using diffusion tensor tractography (DTT). Twenty-three patients with HI-BI were recruited into the study based on predefined inclusion criteria. Their consciousness levels were evaluated using the Glasgow Coma Scale (GCS) and the Coma Recovery Scale-Revised (CRS-R). Using DTT, the mPFC SNC was reconstructed for each patient. The average of the fractional anisotropy (FA), apparent diffusion coefficient (ADC), and voxel number (VN) for the mPFC SNC in both hemispheres were determined. The GCS score showed moderate positive correlations with the FA value and VN of the mPFC SNC [(FA) r = 0.439; (VN) r = 0.466; P < 0.05], and a strong negative correlation with ADC value ( r = -0.531; P < 0.05). The CRS-R score had a strong positive and negative correlation with the FA and ADC values of the mPFC SNC, respectively, [(FA) r = 0.540; (ADC) r = -0.614; P < 0.05] and a moderate positive correlation with the VN of the mPFC SNC ( r = 0.488; P < 0.05). We found that the severity of the injury to the mPFC SNC was closely related to the consciousness level. Our results suggest that the mPFC SNC appears to be a neural correlate for the control of consciousness in patients with HI-BI. Based on these results, we believe that the mPFC could be a target area for noninvasive neurostimulation therapies for patients with impaired consciousness following HI-BI.

Quantitative analysis of early-stage EEG reactivity predicts awakening and recovery of consciousness in patients with severe brain injury

BackgroundDecisions of withdrawal of life-sustaining therapy for patients with severe brain injury are often based on prognostic evaluations such as analysis of electroencephalography (EEG) reactivity (EEG-R). However, EEG-R usually relies on visual assessment, which requires neurophysiological expertise and is prone to inter-rater variability. We hypothesised that quantitative analysis of EEG-R obtained 3 days after patient admission can identify new markers of subsequent awakening and consciousness recovery. MethodsIn this prospective observational study of patients with severe brain injury requiring mechanical ventilation, quantitative EEG-R was assessed using standard 11-lead EEG with frequency-based (power spectral density) and functional connectivity-based (phase-lag index) analyses. Associations between awakening in the intensive care unit (ICU) and reactivity to auditory and nociceptive stimulations were assessed with logistic regression. Secondary outcomes included in-ICU mortality and 3-month Coma Recovery Scale-Revised (CRS-R) score. ResultsOf 116 patients, 86 (74%) awoke in the ICU. Among quantitative EEG-R markers, variation in phase-lag index connectivity in the delta frequency band after noise stimulation was associated with awakening (adjusted odds ratio=0.89, 95% confidence interval: 0.81–0.97, P=0.02 corrected for multiple tests), independently of age, baseline severity, and sedation. This new marker was independently associated with improved 3-month CRS-R (adjusted β=−0.16, standard error 0.075, P=0.048), but not with mortality (adjusted odds ratio=1.08, 95% CI: 0.99–1.18, P=0.10). ConclusionsAn early-stage quantitative EEG-R marker was independently associated with awakening and 3-month level of consciousness in patients with severe brain injury. This promising marker based on functional connectivity will need external validation before potential integration into a multimodal prognostic model.