IntroductionDisorders 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.MethodsWe 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.ResultsUltimately, 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.ConclusionThese 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.Clinical trial registrationhttps://www.chictr.org.cn/edit.aspx?pid=175938&htm=4, identifier: ChiCTR2200066629.

Background: Neuronal damage is the main cause of neurological diseases. Neural stem cells (NSCs) have the functions of cell repair and replacement of neurons, secretion of neurotrophic factors, and immune regulation of the neural microenvironment. Objective: Previous study found that Orexin-A had a protective effect on neurons in the central nervous system, but it is lacking in making great efforts on the function of Orexin-A on NSCs. This study aimed to investigate the anti-inflammatory responses and signaling mechanisms of Orexin-A on lipopolysaccharide (LPS)-induced NSCs. Methods: Quantitative real-time polymerase chain reaction was used to detect the mRNA level. Signaling pathway-related protein expression was detected by Western blot. The proliferation and migration of NSCs were investigated by Cell Counting Kit-8 (CCK-8) detection kit and transwell assay. Besides, the staining of hematoxylin and eosin (HE) was performed to study the morphology of cell. Results: Orexin-A decreased the pro-inflammatory cytokines of IL-1β, TNF-α, and IL-6 induced by LPS by regulating nuclear factor-k-gene binding (NF-kB) and phosphorylation of P38/Erk-mitogen-activated protein kinases (MAPKs) pathways, but not p-JNK signaling. Conclusion:Our findings indicate that Orexin-A can alleviate the inflammatory response of NSC. It can provide beneficial help in neural stem cell therapy applications.

ObjectiveThis study aimed to establish and validate a prediction model for clinical outcomes in patients with prolonged disorders of consciousness (pDOC).MethodsA total of 170 patients with pDOC enrolled in our rehabilitation unit were included and divided into training (n = 119) and validation sets (n = 51). Independent predictors for improved clinical outcomes were identified by univariate and multivariate logistic regression analyses, and a nomogram model was established. The nomogram performance was quantified using receiver operating curve (ROC) and calibration curves in the training and validated sets. A decision curve analysis (DCA) was performed to evaluate the clinical usefulness of this nomogram model.ResultsUnivariate and multivariate logistic regression analyses indicated that age, diagnosis at entry, serum albumin (g/L), and pupillary reflex were the independent prognostic factors that were used to construct the nomogram. The area under the curve in the training and validation sets was 0.845 and 0.801, respectively. This nomogram model showed good calibration with good consistency between the actual and predicted probabilities of improved outcomes. The DCA demonstrated a higher net benefit in clinical decision-making compared to treating all or none.ConclusionSeveral feasible, cost-effective prognostic variables that are widely available in hospitals can provide an efficient and accurate prediction model for improved clinical outcomes and support clinicians to offer suitable clinical care and decision-making to patients with pDOC and their family members.

Purpose: 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). Methods: 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. Results: 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. Conclusion: 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. AGINGTable 1. Characteristics of patients with prolonged disorders of consciousness. VS MCS− MCS+ p value N 29 34 13 GCS 6.4 ± 2.0 7.4 ± 1.5 11.0 ± 2.0 <0.001 FOUR 8.8 ± 2.4 10.2 ± 1.7 12.4 ± 1.1 <0.001 CRS-R 5.1 ± 2.0 6.5 ± 1.4 8.5 ± 1.4 <0.001 Age (y.o) 53.0 ± 12.6 51.4 ± 18.2 48.6 ± 10.3 0.574 pDOC duration (days) 54.3 ± 36.2 46.5 ± 30.9 45.1 ± 28.2 0.544 Time to emergency (hours) 1.8 ± 2.3 1.2 ± 1.4 1.3 ± 1.3 0.419 Gender (female/male) 6/23 11/23 4/9 0.5650 Job (yes/no) 19/10 19/15 7/6 0.6742 Married (yes/no) 27/2 28/6 12/1 0.3695 Education level (elementary/middle/high) 13/13/3 15/11/8 6/6/1 0.5286 Etiology (TBI/Non-TBI) 12/17 18/16 6/7 0.4977 differences were observed between the three types of pDOC in age, pDOC duration, time to emergency, gender, job, married, education level, and etiology. Patients with MCS+ had the highest means total scores of Coma Recovery Scale-Revised (CRS-R), Glasgow Coma Scale (GCS), and Full Scale of Unresponsiveness (FOUR) scores. Differences in CBF, CBV, MTT, and TTP between the three types of pDOCAmong the three groups, patients with VS showed a significantly decreased CBF in the bilateral frontal lobe, thalamus, temporal lobe, occipital lobe, brainstem, and damaged part. CBV was significantly decreased in patients with VS in the bilateral frontal lobe, thalamus, temporal lobe, brainstem, and damaged part. The mean MTT significantly differed between the three types of pDOC in the bilateral thalamus, temporal lobe, occipital lobe, brainstem, and damaged part. No significa...

ObjectiveTo 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).Participants and methodsWe 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.ResultsBefore 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.ConclusionThe combination of MNS + rTMS was more efficacious in improving the level of consciousness than MNS alone or rTMS alone in patients with pDOC.