Coma Recovery Scale-Revised Score Research Articles

Interpreting Change in Disorders of Consciousness Using the Coma Recovery Scale-Revised.

The purpose of this study was to differentiate clinically meaningful improvement or deterioration from normal fluctuations in patients with disorders of consciousness (DoC) following severe brain injury. We computed indices of responsiveness for the Coma Recovery Scale-Revised (CRS-R) using data from a clinical trial of 180 participants with DoC. We used CRS-R scores from baseline (enrollment in a clinical trial) and a 4-week follow-up assessment period for these calculations. To improve precision, we transformed ordinal CRS-R total scores (0-23 points) to equal-interval measures on a 0-100 unit scale using Rasch Measurement theory. Using the 0-100 unit total Rasch measures, we calculated distribution-based 0.5 standard deviation (SD) minimal clinically important difference, minimal detectable change using 95% confidence intervals, and conditional minimal detectable change using 95% confidence intervals. The distribution-based minimal clinically important difference evaluates group-level changes, whereas the minimal detectable change values evaluate individual-level changes. The minimal clinically important difference and minimal detectable change are derived using the overall variability across total measures at baseline and 4 weeks. The conditional minimal detectable change is generated for each possible pair of CRS-R Rasch person measures and accounts for variation in standard error across the scale. We applied these indices to determine the proportions of participants who made a change beyond measurement error within each of the two subgroups, based on treatment arm (amantadine hydrochloride or placebo) or categorization of baseline Rasch person measure to states of consciousness (i.e., unresponsive wakefulness syndrome and minimally conscious state). We compared the proportion of participants in each treatment arm who made a change according to the minimal detectable change and determined whether they also changed to another state of consciousness. CRS-R indices of responsiveness (using the 0-100 transformed scale) were as follows: 0.5SD minimal clinically important difference = 9 units, minimal detectable change = 11 units, and the conditional minimal detectable change ranged from 11 to 42 units. For the amantadine and placebo groups, 70% and 58% of participants showed change beyond measurement error using the minimal detectable change, respectively. For the unresponsive wakefulness syndrome and minimally conscious state groups, 54% and 69% of participants changed beyond measurement error using the minimal detectable change, respectively. Among 115 participants (64% of the total sample) who made a change beyond measurement error, 29 participants (25%) did not change state of consciousness. CRS-R indices of responsiveness can support clinicians and researchers in discerning when behavioral changes in patients with DoC exceed measurement error. Notably, the minimal detectable change can support the detection of patients who make a "true" change within or across states of consciousness. Our findings highlight that the continued use of ordinal scores may result in incorrect inferences about the degree and relevance of a change score.

Effects of parietal repetitive transcranial magnetic stimulation in prolonged disorders of consciousness: A pilot study

ObjectiveAlthough the parietal cortex is related to consciousness, the dorsolateral prefrontal and primary motor cortices are the usual targets for repetitive transcranial magnetic stimulation (rTMS) for prolonged disorders of consciousness (pDoC). Herein, we applied parietal rTMS to patients with pDoC, to verify its neurobehavioral effects and explore a new potential rTMS target. Materials and methodsTwenty-six patients with pDoC were assigned to a rTMS or sham group. The rTMS group received 10 sessions of parietal rTMS; the sham group received 10 sessions of sham stimulation. The Coma Recovery Scale-Revised (CRS-R) and event-related potential (ERP) were collected before and after the 10 sessions or sham sessions. ResultsAfter the 10 sessions, the rTMS group showed: a significant CRS-R score increase; ERP appearance of a P300 waveform and significantly increased Fz amplitudes; increased potentials on topographic mapping, especially in the left prefrontal cortex; and an increase in delta and theta band powers at Fz, Cz, and Pz. The sham group did not show such changes in CRS-R score or ERP results statistically. ConclusionParietal rTMS shows promise as a novel intervention in the recovery of consciousness in pDoC. It showed neurobehavioral enhancement of residual brain function and may promote frontal activity by enhancing frontal–parietal connections. The parietal cortex may thus be an alternative for rTMS therapy protocols.

Correlation between Thalamocortical Tract and Default Mode Network with Consciousness Levels in Hypoxic-Ischemic Brain Injury Patients: A Comparative Study Using the Coma Recovery Scale-Revised.

BACKGROUND The thalamocortical tract (TCT) links nerve fibers between the thalamus and cerebral cortex, relaying motor/sensory information. The default mode network (DMN) comprises bilateral, symmetrical, isolated cortical regions of the lateral and medial parietal and temporal brain cortex. The Coma Recovery Scale-Revised (CRS-R) is a standardized neurobehavioral assessment of disorders of consciousness (DOC). In the present study, 31 patients with hypoxic-ischemic brain injury (HI-BI) were compared for changes in the TCT and DMN with consciousness levels assessed using the CRS-R. MATERIAL AND METHODS In this retrospective study, 31 consecutive patients with HI-BI (17 DOC,14 non-DOC) and 17 age- and sex-matched normal control subjects were recruited. Magnetic resonance imaging was used to diagnose HI-BI, and the CRS-R was used to evaluate consciousness levels at the time of diffusion tensor imaging (DTI). The fractional anisotropy (FA) values and tract volumes (TV) of the TCT and DMN were compared. RESULTS In patients with DOC, the FA values and TV of both the TCT and DMN were significantly lower compared to those of patients without DOC and the control subjects (p<0.05). When comparing the non-DOC and control groups, the TV of the TCT and DMN were significantly lower in the non-DOC group (p<0.05). Moreover, the CRS-R score had strong positive correlations with the TV of the TCT (r=0.501, p<0.05), FA of the DMN (r=0.532, p<0.05), and TV of the DMN (r=0.501, p<0.05) in the DOC group. CONCLUSIONS This study suggests that both the TCT and DMN exhibit strong correlations with consciousness levels in DOC patients with HI-BI.

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.

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.

The effects of non-invasive brain stimulation on disorder of consciousness in patients with brain injury: A systematic review and meta-analysis of randomized controlled trial

IntroductionDisorders of consciousness (DOC) result from neural system injury and manifest as changes in arousal or awareness. This systematic review and meta-analysis aimed to investigate the therapeutic effects of non-invasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), on consciousness dysfunction in patients with brain disorders. MethodsLiterature was systematically searched in Medline, Embase, Cochrane database, Web of Science, EBSCO from inception to May 2023. Only randomized controlled trial with NIBS as an intervention and participants with DOC were included. ResultsA total of 7 studies with 313 participants were included for meta-analysis. Compared with sham- or placebo-stimulation, NIBS can improve the Coma Recovery Scale-Revised scores significantly (mean difference [MD] = 1.96, 95 % confidence interval [CI] = [1.49; 2.43], P <.0001). ConclusionNIBS has a significant positive effect in enhancing the symptoms of DOC. Nevertheless, it is imperative for further investigations comprising high-quality research designs and larger sample sizes in order to comprehensively elucidate the effects of NIBS techniques on diverse targets of stimulation within the population of individuals suffering from DOC.

Hypothalamic Injury and Clinical Outcomes in Patients with Post-Traumatic Hyponatremia: A Diffusion Tensor Imaging Case-Control Study.

BACKGROUND Diffusion tensor imaging (DTI) is an advanced magnetic resonance imaging (MRI) method used to identify changes in microstructures in the brain's white matter. Severe brain injuries after trauma are associated with disorders of consciousness (DOC) and may result in hyponatremia due to damage to the hypothalamus. This case-control study aimed to use DTI to evaluate the hypothalamus in 36 patients with hyponatremia and DOC due to severe brain injuries. MATERIAL AND METHODS Thirty-six patients with DOC after traumatic brain injury (TBI) and 36 healthy control subjects were enrolled in this study. The diagnosis of DOC was based on the coma recovery scale-revised (CRS-R). The 36 patients were divided into 2 groups: Group A (18 with hyponatremia, serum sodium level <135 mmol/L) and group B (18 without hyponatremia). The DTI scans were conducted using a 6-channel head coil on a 1.5T Philips Gyroscan Intera scanner. Among the DTI data, fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) of the hypothalamus were analyzed. RESULTS Patient group A had a lower FA value (P=0.044) and higher ADC value (P=0.004) of the hypothalamus and showed a longer length of hospital stay (P=0.03), lower CRS-R score at discharge (P=0.01), and less change in CRS-R score (P=0.004) compared to patient group B. The improvements in the CRS-R score revealed a moderate negative correlation (r=-0.467) with the severity of the hyponatremia (P=0.004). CONCLUSIONS Post-traumatic hyponatremia was associated with hypothalamic injury and the presence and severity of hyponatremia were associated with poor clinical outcomes in DOC patients.

Behavioral Effects of Repetitive Transcranial Magnetic Stimulation in Disorders of Consciousness: A Systematic Review and Meta-Analysis.

Traumatic brain injury, cardiac arrest, intracerebral hemorrhage, and ischemic stroke may cause disorders of consciousness (DoC). Repetitive transcranial magnetic stimulation (rTMS) has been used to promote the recovery of disorders of consciousness (DoC) patients. In this meta-analysis, we examined whether rTMS can relieve DoC patient symptoms. We searched through journal articles indexed in PubMed, the Web of Science, Embase, Scopus, and the Cochrane Library until 20 April 2023. We assessed whether studies used rTMS as an intervention and reported the pre- and post-rTMS coma recovery scale-revised (CRS-R) scores. A total of 207 patients from seven trials were included. rTMS significantly improved the recovery degree of patients; the weighted mean difference (WMD) of the change in the CRS-R score was 1.89 (95% confidence interval (CI): 1.39-2.39; p < 0.00001) in comparison with controls. The subgroup analysis showed a significant improvement in CRS-R scores in rTMS over the dorsolateral prefrontal cortex (WMD = 2.24; 95% CI: 1.55-2.92; p < 0.00001; I2 = 31%) and the primary motor cortex (WMD = 1.63; 95% CI: 0.69-2.57; p = 0.0007; I2 = 14%). Twenty-hertz rTMS significantly improved CRS-R scores in patients with DoC (WMD = 1.61; 95% CI: 0.39-2.83; p = 0.010; I2 = 31%). Furthermore, CRS-R scores in rTMS over 20 sessions significantly improved (WMD = 1.75; 95% CI: 0.95-2.55; p < 0.0001; I2 = 12%). rTMS improved the symptoms of DoC patients; however, the available evidence remains limited and inadequate.

Breakdown of oscillatory effective networks in disorders of consciousness.

Combining transcranial magnetic stimulation with electroencephalography (TMS-EEG), oscillatory reactivity can be measured, allowing us to investigate the interaction between local and distant cortical oscillations. However, the extent to which human consciousness is related to these oscillatory effective networks has yet to be explored. We tend to investigate the link between oscillatory effective networks and brain consciousness, by monitoring the global transmission of TMS-induced oscillations in disorders of consciousness (DOC). A cohort of DOC patients was included in this study, which included 28 patients with a minimally conscious state (MCS) and 20 patients with vegetative state/unresponsive wakefulness syndrome (VS/UWS). Additionally, 25 healthy controls were enrolled. The oscillatory reactivity to single-pulse TMS of the frontal, sensorimotor and parietal cortex was measured using event-related spectral perturbation of TMS-EEG. The temporal-spatial properties of the oscillatory reactivity were illustrated through life time, decay gradients and accumulative power. In DOC patients, an oscillatory reactivity was observed to be temporally and spatially suppressed. TMS-EEG of DOC patients showed that the oscillations did not travel as far in healthy controls, in terms of both temporal and spatial dimensions. Moreover, cortical theta reactivity was found to be a reliable indicator in distinguishing DOC versus healthy controls when TMS of the parietal region and in distinguishing MCS versus VS/UWS when TMS of the frontal region. Additionally, a positive correlation was observed between the Coma Recovery Scale-Revised scores of the DOC patients and the cortical theta reactivity. The findings revealed a breakdown of oscillatory effective networks in DOC patients, which has implications for the use of TMS-EEG in DOC evaluation and offers a neural oscillation viewpoint on the neurological basis of human consciousness.

A Comparison of the Neuromodulation Effects of Frontal and Parietal Transcranial Direct Current Stimulation on Disorders of Consciousness.

Frontal transcranial direct current stimulation (tDCS) and parietal tDCS are effective for treating disorders of consciousness (DoC); however, the relative efficacies of these techniques have yet to be determined. This paper compares the neuromodulation effects of frontal and parietal tDCS on DoC. Twenty patients with DoC were recruited and randomly assigned to two groups. One group received single-session frontal tDCS and single-session sham tDCS. The other group received single-session parietal tDCS and single-session sham tDCS. Before and after every tDCS session, we recorded coma recovery scale-revised (CRS-R) values and an electroencephalogram. CRS-R was also used to evaluate the state of consciousness at 9-12-month follow-up. Both single-session frontal and parietal tDCS caused significant changes in the genuine permutation cross-mutual information (G_PCMI) of local frontal and across brain regions (p < 0.05). Furthermore, the changes in G_PCMI values were significantly correlated to the CRS-R scores at 9-12-month follow-up after frontal and parietal tDCS (p < 0.05). The changes in G_PCMI and CRS-R scores were also correlated (p < 0.05). Both frontal tDCS and parietal tDCS exert neuromodulatory effects in DoC and induce significant changes in electrophysiology. G_PCMI can be used to evaluate the neuromodulation effects of tDCS.

Impact of Sensory Stimulation on Perception and Performance among the Comatose: A Pilot Study

Adult brains in good health are capable of processing a variety of intricate sensory data. The faces of the object and the people are recognised, and the location, depth, and distance of the object and the people are identified. These basic and complex perceptual abilities may be impacted by a stroke or other acquired brain injury, such as a head injury. Being unaware of one's surroundings, as when sleeping, or being unresponsive to stimulation are both symptoms of being unconscious. In the area of neurorehabilitation, sensory stimulation programmes (SSP) have received the most research. A healthcare provider or a family member systematically stimulates the patient's five sensory modalities as part of sensory stimulation, a form of therapy that may improve the patient's responsiveness. In order to analyse the impact of sensory stimulation on perception and performance among comatose, double- blinded randomized clinical trial was conducted on 12 comatose patients with Glasgow Coma Scale score 3-8 and diagnosed with traumatic brain injury and cerebrovascular accidents. The patients were randomly assigned into two groups of experimental and control. The comatose patients were recruited via random sampling from various Intensive Care Units of AJ Institute of Medical Sciences, Mangalore. The experimental group was given sensory stimulation twice daily for seven consecutive days, with each session lasting 25 minutes. By contrast, the control group only received routine care from the hospital. Data was collected via demographic and clinical proforma and level of conscious was measured by Coma Recovery Scale-Revised (CRS-R). For statistical analysis, independent t test and ANOVA were computed. There was a significant increase in the post-test scores of CRS-R for experimental group which revealed that multimodal sensory stimulation effectively increased the CRS-R scores among unconscious patients in the experimental group. Nurses can use this intervention to improve sensory scores among unconscious patients in the Intensive Care Unit.

EEG dynamics induced by zolpidem forecast consciousness evolution in prolonged disorders of consciousness

ObjectiveTo explore whether the EEG dynamics induced by zolpidem can predict consciousness evolution in patients with prolonged disorders of consciousness (PDOC). MethodsWe conducted a prospective explorative analysis on thirty-six patients with PDOC and eleven healthy controls. The EEG power spectrum was analyzed and categorized into ‘ABCD’ patterns at baseline and one hour after zolpidem administration at 10 mg. The clinical outcome was defined as consciousness improvement and no improvement six months after enrollment using the Coma Recovery Scale-Revised (CRS-R) score. ResultsZolpidem administration significantly increased the EEG power in the delta & theta bands and decreased EEG power in the beta bands in healthy controls. Further follow-up studies indicated that the increased EEG beta-band power induced by zolpidem can predict an improved consciousness six months after enrollment with an area under the receiver operating characteristic curve (AUC) of 0.829, the sensitivity of 94.38% and an accuracy of 81.48%. ConclusionsOur work revealed that the specific EEG responses to zolpidem can predict consciousness recovery in PDOC patients. SignificanceThe zolpidem-induced specific EEG responses could potentially predict the recovery of PDOC patients, which may help clinicians and patients’ families in their decision-making process.

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.