Cerebellar Atrophy in Multiple System Atrophy (Cerebellar Type) and Its Implication for Network Connectivity.

We sought to assess structural and functional patterns of cerebellum in multiple system atrophy (cerebellar type), and investigate the associations of structural and functional cerebellar gray matter abnormalities. We collected magnetic resonance imaging data of 18 patients with multiple system atrophy (cerebellar type) and 18 health control subjects. The gray matter loss across the motor and cognitive cerebellar territories in patients was assessed using voxel-based morphometry. And change in the connectivity between the cerebellum and large-scale cortical networks was assessed using resting-state functional MRI analysis. Furthermore, we assessed the relationship between the extent of cerebellar atrophy and reduced-activation in the cerebellar-cortical and subthalamo-cerebellar functional connectivities. We confirmed the gray matter loss across the motor and cognitive cerebellar territories in patients and found that the extent of cerebellar atrophy was correlated with decreased connectivity between the cerebellum and large-scale cortical networks, including the default, frontal parietal, and sensorimotor networks. The volume reduction in the motor cerebellum was closely associated with the clinical motor severity. A post hoc analysis showed reduced-activation in the subthalamo-cerebellar functional connectivity without the subthalamic nucleus atrophy. These results emphasized significant atrophy in the cerebellar subsystem and its association with the large-scale cortical networks in multiple system atrophy (cerebellar type), which may improve our understanding of the neural pathophysiology mechanisms of disease.

The efficacy and safety of the Xuesaitong soft capsule in the treatment of patients with ischemic stroke: systematic review and meta-analysis.

BACKGROUND: Ischaemic stroke is a common neurological disease and a leading cause of severe disability and death in developed countries. In most cases, stroke is thought to be a multifactorial disorder or complex trait for which classic patterns of inheritance cannot be shown. Xuesaitong is one of the most commonly used medicines for treating ischemic stroke in China. However, compared to the conventional therapy, the effectiveness and safety of Xuesaitong for ischemic stroke needs to be further systematically reviewed and determined. METHODS: Relevant randomized controlled trials (RCTs) examining the use of the Xuesaitong soft capsule in the treatment of patients with ischemic stroke were identified from databases, including the China National Knowledge Infrastructure, Wanfang, PubMed, Embase, and Web of Science databases. Next, 2 researchers independently extracted information from the included studies, analyzed the data using STATA 15.0 software, and evaluated the quality of the included studies using RevMan 5.3. RESULTS: A total of 17 RCTs (comprising 1,942 patients with ischemic stroke) were included in the meta-analysis. The meta-analysis results showed that the Xuesaitong soft capsule treatment increased patients' total effective rate compared to conventional or other drug treatments, and improved patients' Clinical Severity Score (CSS scores) or Barthel index (BI) score. A further subgroup analysis stratified by different treatment times showed that Xuesaitong soft capsule treatment at 4 and 8 weeks improved CSS scores more than treatment at 2 weeks in patients with ischemic stroke. Additionally, the Xuesaitong soft capsule also significantly improved plasma viscosity, whole-blood viscosity at high and low shear rates, fibrinogen, hematocrit, and the effect on traditional Chinese medicine (TCM) single symptoms or signs in patients with ischemic stroke. DISCUSSION: In summary, compared to conventional or other drug treatments, the Xuesaitong soft capsule treatment was beneficial in improving patients' TCM symptoms (e.g., crooked mouth and tongue, and dizziness) and various indicators. Further, Xuesaitong soft capsule may be a safe and effective drug for the treatment of ischemic stroke. And large-scale randomized clinical trials are needed to further confirm our findings.

Hemoglobin-binding α-synuclein levels in erythrocytes are elevated in patients with multiple system atrophy.

Previous studies have shown that α-synuclein (α-syn) accumulation in the normal aging brain is associated with a parallel increase in hemoglobin-binding α-syn (Hb-α-syn) in the brain and peripheral erythrocytes (ERCs), indicating that Hb-α-syn levels in ERCs may reflect the α-syn changes in the brain. However, if there is any change in ERC Hb-α-syn levels in disease condition is unclear. In this study, Hb-α-syn levels in ERCs from 149 Patients with multiple system atrophy (MSA) and 149 healthy controls (HCs) were measured by enzyme linked immunosorbent assay (ELISA). The results showed that Hb-α-syn levels in ERCs were significantly increased in MSA patients in comparison with those in HCs (777.84 ± 240.82 ng/mg vs 508.84 ± 162.57 ng/mg, P < 0.001). Receiver operating characteristic curve (ROC) indicated that increased Hb-α-syn in ERCs could discriminate MSA patients from HCs, with a sensitivity of 71.8%, a specificity of 80.5%, and an area under the curve (AUC) of 0.837. The positive and negative predictive values at a cut-off value of 616.12 ng/mg were 78.7% and 74.1%, respectively. However, the increase in Hb-α-syn levels did not show any association with the age of onset and consultation, disease duration, and UMSARS (I-IV) score. This pilot study suggests that ERC Hb-α-syn is increased in MSA patients and could evaluate α-syn accumulation in the brain of patients.

A study on the characteristics of cognitive function in patients with multiple system atrophy in China.

Nonmotor symptoms in patients with multiple system atrophy (MSA) have received an increasing amount of attention in recent years, but no research on MSA patients' cognitive characteristics has been conducted in China. To evaluate the cognitive function of MSA patients in China. Using a case-control study design, 256 MSA patients and 64 controls were evaluated by the Montreal cognitive assessment (MoCA) scale to characterize their cognitive function. Like the controls, 60.5% of the patients with MSA had cognitive impairment, but the characteristics of cognitive impairment between the two groups were different. The cognitive impairment in MSA patients was prominent in the cognitive domains of visuospatial/executive functions, naming, attention, and orientation; particularly, the visuospatial/executive functions were the most significantly impaired, while impairment in language function was mainly seen in the controls. Besides, impairments in visuospatial/executive functions, attention, language, and orientation were more prominent in MSA-P (MSA with predominant Parkinsonism) patients than in MSA-C (MSA with predominant cerebellar ataxia). The cognitive impairments were more severe in patients with probable MSA than in patients with possible MSA. In addition, the results showed that the level of cognitive function was negatively correlated with the severity of MSA. This study, which characterized the cognitive function of MSA patients with the largest sample size known so far in China, found that patients with MSA do have cognitive impairment and display specific characteristics. Therefore, the cognitive impairment of MSA should be paid more attention.The study has been registered in the Chinese Clinical Trial Registry (ChiCTR) (Registration No: ChiCTR1900022462).

Abnormal static and dynamic functional connectivity of resting-state fMRI in multiple system atrophy.

In order to explore the topological alterations in functional brain networks between multiple system atrophy (MSA) patients and healthy controls (HC), a new joint analysis method of static and dynamic functional connectivity (FC) is proposed in this paper. Twenty-four MSA patients and twenty HCs were enrolled in this study. We constructed static and dynamic brain networks from resting-state fMRI data and calculated four graph theory attributes. Statistical comparisons and correlation analysis were carried out for static and dynamic FC separately before combining both cases. We found decreased local efficiency (LE) and weighted degree (WD) in cerebellum from both static and dynamic graph attributes. For static FC alone, we identified increased betweenness centrality (BC) at left dorsolateral prefrontal cortex, left Cerebellum_Crus9 and decreased WD at Vermis_6. For dynamic FC alone, decreased BC, clustering coefficients and LE at several cortical regions and cerebellum were identified. All the features had significant correlation with total UMSARS scores. Receiver operating characteristic analysis showed that dynamic features had the highest area under the curve value. Our work not only added new evidence for the underlying neurobiology and disrupted dynamic disconnection syndrome of MSA, but also proved the possibility of disease diagnosis and progression tracking using rs-fMRI.