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.

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.

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.

[Safety evaluation and risk control measures of Psoralea corylifolia].

Through a systematic and comprehensive study of domestic and foreign literatures and information, this study aims to trace the herbal origin and the toxicity recorded in ancient and current documents, analyze the safety case reports of Psoralea corylifolia and experimental studies on toxicity in recent years, and make a preliminary summary about the clinical characteristics and potential risk factors of cases related to the safety of P. corylifolia and its preparations. The study involved 84 patients in the safety case reports of P. corylifolia. The adverse events were mainly liver damage (55.95%) and light toxic contact dermatitis (38.10%), sugguesting that P. corylifolia may lead to liver damage and photo toxicity. However, reproductive toxicity and renal damage were only reported in animal studies, but not in clinical reports. Because of its complicated ingredients, the toxic components and mechanisms of P. corylifolia have not been clear at present. Therefore, the authors proposed to strictly apply P. corylifolia in clinic, use it rationally and combine it with other medications. Besides, efforts shall be made to strength the guidance for doctors, the safety monitoring of P. corylifolia and relevant preparations, and actively carry out safety-related basic and clinical studies, so as to give a better guidance to safe medication, full exert the efficacy and avoid the medication risk.