Sleep patterns correlates with the efficacy of tDCS on post-stroke patients with prolonged disorders of consciousness.

BACKGROUND: The subclassification of prolonged disorders of consciousness (DoC) based on sleep patterns is important for the evaluation and treatment of the disease. This study evaluates the correlation between polysomnographic patterns and the efficacy of transcranial direct current stimulation (tDCS) in patients with prolonged DoC due to stroke. METHODS: In total, 33 patients in the vegetative state (VS) with sleep cycles or without sleep cycles were randomly assigned to either active or sham tDCS groups. Polysomnography was used to monitor sleep changes before and after intervention. Additionally, clinical scale scores and electroencephalogram (EEG) analysis were performed before and after intervention to evaluate the efficacy of tDCS on the patients subclassified according to their sleep patterns. RESULTS: The results suggest that tDCS improved the sleep structure, significantly prolonged total sleep time (TST) (95%CI: 14.387-283.527, P = 0.013) and NREM sleep stage 2 (95%CI: 3.157-246.165, P = 0.040) of the VS patients with sleep cycles. It also significantly enhanced brain function of patients with sleep cycles, which were reflected by the increased clinical scores (95%CI: 0.340-3.440, P < 0.001), the EEG powers and functional connectivity in the brain and the 6-month prognosis. Moreover, the changes in NREM sleep stage 2 had a significant positive correlation with each index of the ß band. CONCLUSION: This study reveals the importance of sleep patterns in the prognosis and treatment of prolonged DoC and provides new evidence for the efficacy of tDCS in post-stroke patients with VS patients subclassified by sleep pattern. Trial registration URL: https://www. CLINICALTRIALS: gov . Unique identifier: NCT03809936. Registered 18 January 2019.

Altered Intestinal Microbiomes and Lipid Metabolism in Patients With Prolonged Disorders of Consciousness.

The intestinal microbiota regulate the brain function of the host through the production of a myriad of metabolites and are associated with various neurological diseases. Understanding the intestinal microbiome of patients with prolonged disorders of consciousness (DoC) is important for the evaluation and treatment of the disease. To investigate the differences in the intestinal microbiome and short-chain fatty acids (SCFAs) among patients in a vegetative state (VS), a minimally conscious state (MCS), and emerged from MCS (EMCS), as well as the influence of antibiotics on these patients, 16S ribosomal RNA (16S rRNA) sequencing and targeted lipidomics were performed on fecal samples from patients; in addition, analysis of the electroencephalogram (EEG) signals was performed to evaluate the brain function of these patients. The results showed that the intestinal microbiome of the three groups differed greatly, and some microbial communities showed a reduced production of SCFAs in VS patients compared to the other two groups. Moreover, reduced microbial communities and five major SCFAs, along with attenuated brain functional connectivity, were observed in MCS patients who were treated with antibiotics compared to those who did not receive antibiotic treatment, but not in the other pairwise comparisons. Finally, three genus-level microbiota-Faecailbacterium, Enterococcus, and Methanobrevibacter-were considered as potential biomarkers to distinguish MCS from VS patients, with high accuracy both in the discovery and validation cohorts. Together, our findings improved the understanding of patients with prolonged DoC from the intestinal microbiome perspective and provided a new reference for the exploration of therapeutic targets.

Individualized Thalamic Parcellation Reveals Alterations in Shape and Microstructure of Thalamic Nuclei in Patients with Disorder of Consciousness.

The thalamus plays crucial roles in consciousness generation and information processing. Previous evidence suggests that disorder of consciousness (DOC) caused by severe brain injury, is potentially related to thalamic abnormalities. However, how the morphology and microstructure change in thalamic subfields and thalamocortical fiber pathways in patients with DOC, and the relationships between these changes and the consciousness status remain unclear. Here, we generated the individual-specific thalamic parcellation in 10 DOC patients and 10 healthy controls (HC) via a novel thalamic segmentation framework based on the fiber orientation distribution (FOD) derived from 7-Tesla diffusion MRI, and investigated the shape deformation of thalamic nuclei as well as the microstructural changes associated with thalamic nuclei and thalamocortical pathways in patients with DOC. Enlargement of dorsal posterior nucleus and atrophy of anterior nucleus in the right thalamus were observed in DOC cohort relative to the HCs, and the former was closely linked to the consciousness level of the patients. We also found significant reductions of fiber density, but not fiber bundle cross-section, within several thalamic nuclei and most of the thalamocortical fiber pathways, suggesting that loss of axons might take primary responsibility for the impaired thalamocortical connections in patients with DOC rather than the change in fiber-bundle morphology. Furthermore, the individual-specific thalamic parcellation achieved 80% accuracy in classifying patients at the minimally conscious state from the vegetative state, compared with ~60% accuracy based on group-level parcellations. Our findings provide the first evidence for the shape deformation of thalamic nuclei in DOC patients and the microstructural basis of the disrupted thalamocortical connections.

Neuromodulatory therapies for patients with prolonged disorders of consciousness.

BACKGROUND: Reviving patients with prolonged disorders of consciousness (DOCs) has always been focused and challenging in medical research. Owing to the limited effectiveness of available medicine, recent research has increasingly turned towards neuromodulatory therapies, involving the stimulation of neural circuits. We summarised the progression of research regarding neuromodulatory therapies in the field of DOCs, compared the differences among different studies, in an attempt to explore optimal stimulation patterns and parameters, and analyzed the major limitations of the relevant studies to facilitate future research. METHODS: We performed a search in the PubMed database, using the concepts of DOCs and neuromodulation. Inclusion criteria were: articles in English, published after 2002, and reporting clinical trials of neuromodulatory therapies in human patients with DOCs. RESULTS: Overall, 187 published articles met the search criteria, and 60 articles met the inclusion criteria. There are differences among these studies regarding the clinical efficacies of neurostimulation techniques for patients with DOCs, and large-sample studies are still lacking. CONCLUSIONS: Neuromodulatory techniques were used as trial therapies for DOCs wherein their curative effects were controversial. The difficulties in detecting residual consciousness, the confounding effect between the natural course of the disease and therapeutic effect, and the heterogeneity across patients are the major limitations. Large-sample, well-designed studies, and innovations for both treatment and assessment are anticipated in future research.

Prediction of poor outcome after hypoxic-ischemic brain injury by diffusion-weighted imaging: A systematic review and meta-analysis.

Accurate prediction of the neurological outcome following hypoxic-ischemic brain injury (HIBI) remains difficult. Diffusion-weighted imaging (DWI) can detect acute and subacute brain abnormalities following global cerebral hypoxia. Therefore, DWI can be used to predict the outcomes of HIBI. To this end, we searched the PubMed, EMBASE, and Cochrane Library databases for studies that examine the diagnostic accuracy of DWI in predicting HIBI outcomes in adult patients between January1995 and September 2019. Next, we conducted a comprehensive meta-analysis using the Meta-DiSc and several complementary techniques. Following the application of inclusion and exclusion criteria, a total of 28 studies were included with 98 data subsets. The overall sensitivity and specificity, with 95% confidence interval, were 0.613(0.599-0.628) and 0.958(0.947-0.967), respectively, and the area under the curve was 0.9090. Significant heterogeneity among the included studies and a threshold effect were observed (p<0.001). Different positive indices were the major sources for the heterogeneity, followed by the anatomical region examined, both of which significantly affected the prognostic accuracy. In conclusion, we demonstrated that DWI can be an instrumental modality in predicting the outcome of HIBI with good prognostic accuracy. However, the lack of clear and generally accepted positive indices limits its clinical application. Therefore, using more reliable positive indices and combining DWI with other clinical predictors may improve the diagnostic accuracy of HIBI.