Association of sex and age with in-hospital mortality and complications of patients with intracerebral hemorrhage: A study from the Chinese Stroke Center Alliance.

BACKGROUND AND PURPOSE: The impact of sex and age on prognosis in patients with intracerebral hemorrhage (ICH) in the Chinese population remains unclear. Our study aimed to investigate the relationship between sex and age of Chinese ICH patients and adverse prognosis. METHODS: We used the Chinese Stroke Center Alliance database with in-hospital mortality as the primary outcome and hospital complications as the secondary outcome. Patients were divided into four groups by sex and age. Logistic regression analyses were performed to assess the association between sex and age and the prognosis of ICH patients. RESULTS: We enrolled 60,911 ICH patients, including 22,284 young and middle-aged males, 15,651 older males, 11,948 young and middle-aged females, and 11,028 older females. After adjusting for variables, older male patients had a higher mortality rate (OR = 1.21, 95% CI 1.01-1.45), combined with more frequent hematoma expansion (OR = 1.14, 95% CI 1.03-1.26), pneumonia (OR = 1.91, 95% CI 1.81-2.03), and hydrocephalus (OR = 1.28, 95% CI 1.04-1.59). Young and middle-aged female patients had a lower mortality rate (OR = 0.74, 95% CI 0.58-0.95) and less frequent combined pneumonia (OR = 0.81, 95% CI 0.75-0.87). In-hospital mortality was not significantly different in older females compared with young and middle-aged males, but the odds of deep vein thrombosis, swallowing disorders, urinary tract infections, and gastrointestinal bleeding were significantly higher. CONCLUSION: Among young and middle-aged patients, females are related to a lower in-hospital mortality rate from ICH. Older patients are at an increased risk of ICH complications, with higher in-hospital mortality in older men.

Homocysteine and Clinical Outcomes in Intracerebral Hemorrhage Patients: Results from the China Stroke Center Alliance.

Objective: Elevated homocysteine (Hcy) levels play a detrimental role in ischemic stroke. Acute spontaneous intracerebral hemorrhage (ICH) accounts for nearly 25% of all stroke cases. However, the influence of Hcy levels and ICH severity on clinical outcomes is unclear. Participants and Study Location: Data were obtained from 85,705 ICH patients enrolled in the China Stroke Center Alliance (CSCA) study, a national, hospital-based, multicenter, voluntary, quality assessment and improvement initiative performed in China. Patients were divided into high and normal Hcy groups according to their Hcy levels observed at admission. Outcome Measures: The outcome indices included severe ICH, in-hospital mortality, and a poor functional outcome at discharge. Multivariable logistic regression was used to analyze the association of different Hcy levels with outcomes. Results: The final analysis included 55,793 ICH patients. High homocysteine (HHcy) levels had higher adjusted odds ratios for severe ICH (OR 1.09, 95% CI 1.01-1.10, P<0.0001) and a poor functional outcome at discharge (OR 1.06, 95% CI 1.01-1.10, P=0.0100) compared with normal Hcy levels. There was no significant difference between HHcy and in-hospital mortality. In the subgroup analysis, stratified by sex and history of hypertension, significant interactions were observed between HHcy and severe ICH (P for interactions was 0.0138 and 0.0120, respectively). HHcy levels exhibited greater associations for severe ICH in female patients (OR 1.07, 95% CI 1.02-1.12) and patients without hypertension (OR 1.20, 95% CI 1.09-1.33). Conclusion: An elevated Hcy level exhibited significant association with severe ICH on admission and a poor functional outcome at discharge. The relationship between HHcy and ICH severity on admission was more robust in female patients and patients without hypertension. Hcy might be a valuable biomarker for ICH patients to predict severity at onset and functional outcome at discharge.

Neuroimaging studies in persistent postural-perceptual dizziness and related disease: a systematic review.

BACKGROUND: Persistent Postural-Perceptual Dizziness (PPPD) is one of the most common types of chronic dizziness. The pathogenesis remains unclear. OBJECTIVE: This study aimed to systematically review neuroimaging literature for investigating the central mechanism of PPPD and related disorders. METHODS: PubMed, EMBASE, Medline, Cochrane, and Web of Science were searched by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The articles analyzing structural and functional neuroimaging features of PPPD and related disorders were selected according to eligibility criteria. RESULTS: Fifteen articles, including 4 structural, 10 functional, and 1 multimodal imaging, were eligible for inclusion in this review. The whiter matter alterations in PPPD are not entirely consistent. The changes of grey matter mainly in multisensory vestibular cortices, visual cortex, cerebellum, as well as anxiety-related network. Consistent with structural imaging, functional imaging conducted during the specific tasks or in the resting state has both found abnormal functional activation and connectivity in the vestibular cortex, especially in the parieto-insular vestibular cortex (PIVC), visual cortex, cerebellum, and anxiety-related network in PPPD and related disorder. CONCLUSIONS: The current review provides up-to-date knowledge and summarizes the possible central mechanism for PPPD and related disorders, and it is helpful to understanding the mechanism of PPPD.

Association Between Cumulative Exposure to Increased Low-Density Lipoprotein Cholesterol and the New Occurrence of Peripheral Artery Disease.

Background and Purpose: Peripheral artery disease (PAD) is a manifestation of systemic atherosclerosis with increased risk of severe cardiovascular and cerebrovascular events. The relationship between one-time measuring of low-density lipoprotein cholesterol (LDL-C) and PAD is inconsistent. Increasing evidence shows that the predictive value of non-high-density lipoprotein cholesterol (non-HDLC) on atherosclerosis disease is superior to LDL-C. We aimed to investigate the relationship between cumulative exposure to increased LDL-C and the risk of newly developed PAD and compare the predictive value of LDL-C with non-HDLC. Materials and Methods: In the Asymptomatic Polyvascular Abnormalities Community study, we enrolled 2,923 participants with LDL-C and non-HDLC measured every 2 years from 2006 to 2012. Cumulative exposure to increased LDL-C and non-HDLC, defined as LDL-C burden and non-HDLC burden, respectively, was calculated as the weighted sum of the difference between the measured value and the cutoff value. A new occurrence of PAD was identified through ankle brachial index measured in 2010 and 2012. Multivariate models were adopted to analyze the association of LDL-C burden and non-HDLC burden with the newly developed PAD. The receiver operating curve was drawn, and the area under the curve was calculated to compare the predictive performance of LDL-C burden with a single measure of LDL-C in 2006 and non-HDL-C burden adjusted with a model including traditional risk factors. Results: Of the 2,923 participants, 5.4% (158/2,923) were diagnosed as newly developed PAD. In the univariate analysis, the highest quartile of LDL-C burden was significantly associated with new occurrence of PAD [odds ratio (OR) 1.75, 95% confidence interval (CI) 1.13-2.73]. After adjustment for confounding factors, the same result was obtained (OR 1.59, 95%CI 1.01-2.49). The non-HDLC burden failed to show any statistical significance on the newly developed PAD (OR 1.31, 95% CI 0.84-2.04). Though LDL-C burden had a tendency to show better predictive performance than non-HDLC, it did not reach statistical significance (AUCLDL-C = 0.554 vs. AUCnon-HDLC = 0.544, P = 0.655). Conclusions: Cumulative exposure to increased LDL-C is an independent risk factor of newly developed PAD. The predictive value of non-HDLC burden was not revealed.

Association Between the Change of Coagulation Parameters and Clinical Prognosis in Acute Ischemic Stroke Patients After Intravenous Thrombolysis With rt-PA.

Acute ischemic stroke patients with intravenous (IV) recombinant tissue plasminogen activator (rt-PA) thrombolysis have different outcomes. The degree of thrombolysis depends largely on the delicate balance of coagulation and fibrinolysis. Thus, our study aimed to investigate the prognostic value of routine coagulation parameters in acute stroke patients treated with rt-PA. From December 2016 to October 2018, consecutive patients treated with standard-dose IV rt-PA within 4.5 h of stroke onset were collected in Beijing Tiantan Hospital. Routine coagulation parameters, including platelet count, mean platelet volume, platelet distribution width, prothrombin time (PT), activated partial thromboplastin time, thrombin time, and fibrinogen, were measured at baseline (h0) and 24 h (h24) after thrombolysis. The change of coagulation parameters was defined as the (h24-h0)/h0 ratio. The prognosis included short-term outcome at 24 h and functional outcome at 3 months. A total of 267 patients were investigated (188 men and 79 women) with a mean age of 60.88 ± 12.31 years. In total, 9 patients had early neurological deterioration within 24 h, and 99 patients had an unfavorable outcome at the 3-month visit. In multivariate logistic regression, the (h24-h0)/h0 of PT was associated with unfavorable functional outcomes at 3 months (odds ratio: 1.42, 95% confidence interval: 1.02-2.28). While the change of other coagulation parameters failed to show any correlation with short-term or long-term prognosis. In conclusion, the prolongation of PT from baseline to 24 h after IV rt-PA increases the risk of 3-month unfavorable outcomes in acute stroke patients.

Risk factors related balance disorder for patients with dizziness/vertigo.

BACKGROUND: When dizziness/vertigo patients presented with balance disorder, it will bring severe morbidity. There is currently lack of research to explore risk factor related balance disorder in dizziness patients, especially in those who walk independently. AIM: To investigate risk factors related balance disorder in dizziness/vertigo patients who walk independently. METHODS: Medical data of 1002 dizziness/vertigo patients registered in vertigo/balance disorder registration database were reviewed. The demographic data, medical history, and risk factors for atherosclerosis (AS) were collected. Enrolled dizziness/vertigo patients could walk independently, completed Romberg test, videonystagmography (VNG), and limits of stability (LOS). The subjective imbalance was patient complained of postural symptom when performing Romberg test. Multivariable logistic regression analyzed risk factors related balance disorder. The receiver operating characteristic (ROC) curve evaluated the utility of regression model. RESULTS: Five hundred fifty-three dizziness/vertigo patients who walk independently were included in the final analysis. According to LOS, patients were divided into 334 (60%) normal balance and 219 (40%) balance disorder. Compared with normal balance, patients with balance disorder were older (P = 0.045) and had more risk factors for AS (P<0.0001). The regression showed that risk factors for AS (OR 1.494, 95% CI 1.198-1.863), subjective imbalance (OR 4.835, 95% CI 3.047-7.673), and abnormality of optokinetic nystagmus (OR 8.308, 95% CI 1.576-43.789) were related to balance disorder. The sensitivity and specificity of model were 71 and 63% (P<0.0001). The area under the curve (AUC) was 0.721. CONCLUSIONS: Risk factors for AS, subjective imbalance, and abnormality of optokinetic nystagmus were predictors for balance disorder in patients with dizziness/vertigo who walk independently.

Body mass index and clinical outcomes in patients with intracerebral haemorrhage: results from the China Stroke Center Alliance.

BACKGROUND AND AIM: Obesity paradox has aroused increasing concern in recent years. However, impact of obesity on outcomes in intracerebral haemorrhage (ICH) remains unclear. This study aimed to evaluate association of body mass index (BMI) with in-hospital mortality, complications and discharge disposition in ICH. METHODS: Data were from 85 705 ICH enrolled in the China Stroke Center Alliance study. Patients were divided into four groups: underweight, normal weight, overweight and obese according to Asian-Pacific criteria. The primary outcome was in-hospital mortality. The secondary outcomes included non-routine discharge disposition and in-hospital complications. Discharge to graded II or III hospital, community hospital or rehabilitation facilities was considered non-routine disposition. Multivariable logistic regression analysed association of BMI with outcomes. RESULTS: 82 789 patients with ICH were included in the final analysis. Underweight (OR=2.057, 95% CI 1.193 to 3.550) patients had higher odds of in-hospital mortality than those with normal weight after adjusting for covariates, but no significant difference was observed for patients who were overweight or obese. No significant association was found between BMI and non-disposition. Underweight was associated with increased odds of several complications, including pneumonia (OR 1.343, 95% CI 1.138 to 1.584), poor swallow function (OR 1.351, 95% CI 1.122 to 1.628) and urinary tract infection (OR 1.532, 95% CI 1.064 to 2.204). Moreover, obese patients had higher odds of haematoma expansion (OR 1.326, 95% CI 1.168 to 1.504), deep vein thrombosis (OR 1.506, 95% CI 1.165 to 1.947) and gastrointestinal bleeding (OR 1.257, 95% CI 1.027 to 1.539). CONCLUSIONS: In patients with ICH, being underweight was associated with increased in-hospital mortality. Being underweight and obese can both increased risk of in-hospital complications compared with having normal weight.

Clinical Characteristics and Electrophysiological Biomarkers of Parkinson's Disease Developed From Essential Tremor.

Background and Objective: Parkinson's disease developed from essential tremor (ET-PD) is a distinct clinical syndrome that is different from essential tremor (ET) and Parkinson's disease (PD). There is currently a lack of research on ET-PD. Tremor characteristics (amplitude and frequency) are primary quantitative indexes for diagnosing and monitoring of tremors. In this study, we aimed to explore specific clinical and electrophysiological biomarkers for the identification of ET-PD. Methods: The study included patients with ET-PD (n = 22), ET (n = 42), and tremor-dominant PD (t-PD, n = 47). We collected demographic data, clinical characteristics (including motor and non-motor symptoms), and tremor analysis. The frequency, amplitude, contracting patterns of resting tremor and postural tremor were collected. The analysis of ET-PD and ET/t-PD was compared. The receiver operating characteristic (ROC) curve was used to analyze the electrophysiological features in distinguishing ET-PD from ET or t-PD. Results: Compared with ET, hyposmia, bradykinesia, rigidity, postural abnormality, and resting tremor were more common in the ET-PD group (P = 0.01, 0.003, 0.001, 0.001, 0.019, respectively). The postural tremor frequencies of the head, upper limbs, and lower limbs were significantly lower in the ET-PD than in the ET (P = 0.007, 0.003, 0.035, respectively), which were the most appropriate variables for distinguishing ET-PD from ET (AUC: 0.775, 0.727, and 0.701, respectively). Compared with t-PD, bradykinesia, rigidity, postural abnormality (both P < 0.001), and resting tremor (P = 0.024) were less common in the ET-PD. The postural tremor amplitudes of the head and upper limbs were significantly higher in the ET-PD than in the t-PD (P = 0.022, 0.001, respectively), which were the most appropriate variables for distinguishing ET-PD from t-PD (AUC: 0.793 and 0.716). Conclusions: Hyposmia and electrophysiological biomarkers (postural tremor frequencies and amplitudes) help early recognition of ET-PD.

Differential Diagnosis of Multiple System Atrophy-Parkinsonism and Parkinson's Disease Using α-Synuclein and External Anal Sphincter Electromyography.

Background and aim: Discriminating multiple system atrophy-parkinsonism (MSA-P) from Parkinson's disease (PD) is challenging. We aimed to provide a new method to make an identification between MSA-P and PD by combining biofluid marker with electrophysiology marker. Methods: The XYCQ EV Enrichment KIT was applied to extract extracellular vesicles (EVs) from saliva. The levels of α-syn which included total α-syn (α- synTotal), phosphorylated-ser129 α-syn (α-synPS129) and oligomeric α-syn (α-synOlig) in EVs of saliva were tested by new developed Electrochemiluminescence (ECL) assays. We collected multi-motor unit potential (MUP) of all participants who conducted external anal sphincter electromyography (EAS-EMG). The duration, phase, amplitude and satellite potential of EAS-EMG were analyzed. The Receiver operator characteristic (ROC) curve was adopted to analyze the diagnostic utility of α-syn in EVs of saliva, EAS-EMG for MSA-P. Results: In EVs of saliva, the α-synTotal concentrations were lower in MSA-P than PD (P = 0.003). No significant difference was shown in α-synOlig and α-synPS129. α-synTotal 4.46 pg/ng distinguished MSA-P from PD with area under the curve (AUC) 0.804. Compared with PD, the duration, phase and satellite potential of EAS-EMG in MSA-P were increased (P = 0.002, 0.008, 0.001). There was no significant difference in amplitude. ROC curve showed that the duration (AUC: 0.780), phase (AUC: 0.751), and satellite potential (AUC: 0.809) had both diagnostic value for MSA-P. The combination of α-synTotal in salivary EVs and EAS-EMG (including duration, phase and satellite potential) could efficiently make a differentiation between MSA-P and PD with sensitivity of 100% and specificity of 86%. The AUC value was 0.901. Conclusion: The study suggested the combination of α-synTotal in salivary EVs and EAS-EMG could help efficiently distinguish MSA-P from PD.

Seasonality and Cardio-Cerebrovascular Risk Factors for Benign Paroxysmal Positional Vertigo.

Background: Benign paroxysmal positional vertigo (BPPV) is the most common cause of vertigo, especially in the elderly. Several studies have revealed a possible seasonality to BPPV. However, whether the seasonality of BPPV also exists in China is unclear. The characteristics of cardio-cerebrovascular risk factors for BPPV in the cold season have not yet been investigated. Objectives: (1) To investigate the seasonality of BPPV; (2) To explore the relationship between cardio-cerebrovascular risk factors and seasonality of BPPV. Methods: A retrospective observational study was performed in Beijing Tiantan Hospital from Jan 2016 to Dec 2018. The study included 1,409 new-onset BPPV patients aged 18-88 years. The demographic data, onset time, and medical history of BPPV were collected. The meteorological data, including temperature, atmospheric pressure, rainfall, and insolation, was obtained from Beijing Meteorological service. The x 2 goodness of fit test was used to evaluate whether BPPV patients' numbers were significantly different among different months of the year. The Spearman correlation was used to detect the correlation between numbers of BPPV patients diagnosed monthly with each climatic parameter. The chi-square test for linear-by-linear association were used to investigate the relationship between cardio-cerebrovascular risk factor and seasonality of BPPV. Results: November to next March is the top 5 months with higher BPPV patient numbers (P < 0.001). The numbers of BPPV diagnosed monthly were conversely correlated with temperature and rainfall (r = -0.736, P = 0.010; r = -0.650, P = 0.022, respectively), positively correlated with atmospheric pressure (r = 0.708, P = 0.010), but no significant correlated with insolation. BPPV in the cold season (including January, February, March, November, and December) had a higher proportion, accounting for 54.2% of all BPPV patients. Among BPPV patients with ≥2, 1, and none cardio-cerebrovascular risk factors, the cold season accounted for 57.0, 56.0, 49.8%, respectively. As the number of cardio-cerebrovascular risk factors increased, the proportion of patients in the cold season of BPPV increased (P = 0.025). Conclusions: BPPV patients are seen more in the months with low temperature, low rainfall, and high atmospheric pressure. Compared with the non-cold season, BPPV patients have more risk factors for cardio-cerebrovascular diseases in the cold season.

Uric Acid and Clinical Outcomes Among Intracerebral Hemorrhage Patients: Results From the China Stroke Center Alliance.

Background and Purpose: The effect of uric acid (UA) levels on severity and prognosis of spontaneous intracerebral hemorrhage (ICH) remains controversial. We aimed to explore the association of admission UA levels with stroke severity and outcomes in ICH patients. Materials and Methods: The patients enrolled in this study were from the China Stroke Center Alliance study (CSCA). Patients were divided into four groups (Q1-Q4) according to the quartiles of UA levels at admission. The primary outcome was in-hospital mortality. The secondary outcomes included stroke severity, in-hospital complications, and discharge disposition. Multivariate logistic regression was adopted to explore the association of UA levels with outcomes after ICH. Results: Patients (84,304) with acute ICH were included in the final analysis; the median (interquartile range) of UA was 277 (210, 354) µmol/L. The four groups were defined as follows: Q1 ≤ 210 µmol/L, 210 µmol/L < Q2 ≤ 277 µmol/L, 277 µmol/L < Q3 ≤ 354 µmol/L, Q4 > 354 µmol/L. There was no significant evidence indicating that UA levels were correlated with the discharge disposition and in-hospital mortality after ICH. However, compared to Q1, the patients with higher UA levels had decreased odds of severe stroke (NIHSS ≥ 16) at admission (OR 0.89, 95% CI 0.86-0.92). An L-shaped association was found between UA and severe stroke. Among in-hospital complications, decrease in pneumonia, poor swallow function, gastrointestinal bleeding, and deep vein thrombosis (DVT) were significantly associated with higher UA levels compared to Q1 (P for trend < 0.0001). Conclusions: UA was a protective factor for stroke severity and in-hospital complications such as pneumonia, poor swallow function, gastrointestinal bleeding, and DVT. However, no significant evidence indicated that UA levels were predictive of the discharge disposition and in-hospital mortality after ICH.

Association of pre- and post-stroke glycemic status with clinical outcome in spontaneous intracerebral hemorrhage.

In this study, we aimed to disclose the association of pre- and post-stroke glycemic status with clinical outcome in patients with spontaneous intracerebral hemorrhage (sICH). It was a multicenter, prospective, observational cohort study, conducted in 13 hospitals in Beijing from January 2014 to September 2016. The association of admission random blood glucose (RBG), fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) with clinical outcome at 90 days after sICH onset were analyzed comprehensively. Poor outcome was defined as death or modified Rankin Scale (mRS) score >2. The results showed that elevated RBG and FBG were associated with larger hematoma volume, lower GCS, higher NIHSS (P < 0.001), and poor outcome, but HbA1c was not (P > 0.05). In stratified analysis, the association of poor outcome with elevated FBG or RBG retained statistical significance just in patients without diabetes. Kaplan-Meier curve and Cox regression showed that patients with elevated FBG or RBG had significantly higher risk of death within 90 days (P < 0.05). So we conclude that poststroke hyperglycemia was associated with larger hematoma volume, severe neurological damage and poor clinical outcome, but HbA1c was not relevant to hematoma volume or clinical outcome in patients with sICH.

Alpha-synuclein in erythrocyte membrane of patients with multiple system atrophy: A pilot study.

BACKGROUND: Multiple system atrophy(MSA) is a neurodegenerative disease characterized by intracellular α-synuclein deposits. There is an unmet need for blood-based biomarkers to diagnose MSA. Our previous studies have reported elevated α-synuclein levels in erythrocytes of MSA patients. However, α-synuclein protein in the membrane and cytoplasm of erythrocytes in MSA have not been investigated. METHODS: The membrane and cytoplasm were extracted from erythrocytes in 77 patients with MSA and 133 healthy controls. Levels of total and oligomeric α-synuclein were detected using Electrochemiluminescence assays. The correlations between α-synuclein levels and clinical characteristics were explored in MSA group. The diagnostic value of erythrocyte α-synuclein for MSA was determined by Receiver operator characteristic curve. RESULTS: α-synuclein levels in the erythrocyte membrane were significantly elevated in MSA patients compared with the healthy controls (total α-synuclein, p = 0.003; oligomeric α-synuclein/total α-synuclein, p = 0.033; oligomeric α-synuclein/protein, p < 0.001). The combination of total and oligomeric α-synuclein levels in erythrocyte membrane could efficiently distinguish MSA from healthy controls (sensitivity of 79.2%; specificity of 69.2%; area under the curve: 0.771). In contrast, no significant difference was found in erythrocyte cytoplasm α-synuclein levels. In the subgroup of 48 patients with probable MSA, there was a weakly negative correlation between oligomeric α-synuclein/protein in erythrocyte membrane and disease duration (r = -0.336; p = 0.009). CONCLUSION: Our pilot study suggests that the membrane fraction of α-synuclein levels in erythrocyte were elevated in patients with MSA, and these levels may be decreased with the development of disease.

α-Synuclein in salivary extracellular vesicles as a potential biomarker of Parkinson's disease.

BACKGROUND: Detection of α-synuclein (α-syn) in biological fluids such as saliva may serve as potential biomarker of PD. α-syn pertaining to extracellular vesicles (EVs) has been recently studied in plasma, but not in other biological fluids such as saliva. AIM: 1) To investigate the presence of exosomes in PD saliva; 2) to explore the value of α-syn in salivary EVs as potential biomarker in PD. METHODS: Saliva samples were obtained from 74 PD and 60 healthy controls (HCs). The EVs were extracted from saliva by XYCQ EV Enrichment KIT. Western blot and Nanosight 300 were used to validate the existence of exosomes in EVs and to analyze the size of salivary EVs. Salivary EVs α-syn levels, including total α-syn (α-synTotal), oligomeric α-syn (α-synOlig) and phosphorylated-ser129 α-syn (α-synPS129), were measured by Electrochemiluminescence (ECL) assays. Diagnostic value and clinical relevance of salivary EVs α-syn were assessed by Receiver Operator Characteristic (ROC) curve and Spearman correlation. RESULTS: Alix and CD9 positive EVs, representing the presence of exosomes, was detected in PD salivary samples. Size of salivary EVs was about 30-400 nm. The levels of α-synOlig and α-synOlig/α-synTotal in the salivary EVs were higher in PD than in HCs (10.39 ± 1.46 pg/ng vs.1.37 ± 0.24 pg/ng, p＜0.001;1.70 ± 0.52 pg/ng vs.0.67 ± 0.26 pg/ng, p＜0.001). There was no significant difference in α-synTotal、α-synPS129、 α-synPS129/α-synTotal ratio between PD and HCs (P = 0.723, 0.634, 0.734, respectively). α-synOlig 2.05 pg/ng distinguished PD from HCs with sensitivity 92% and specificity 86%; α-synOlig /α-synTotal 0.18 pg/ng differentiated PD from HCs with sensitivity 81% and specificity 71%. No significant correlation between salivary EVs α-synOlig, α-synOlig/α-synTotal and disease severity was found. CONCLUSIONS: Exosomes are present in PD saliva. The α-synOlig and α-synOlig/α-synTotal ratio in salivary EVs may serve as potential diagnostic biomarkers for PD.

Auricular Vagus Nerve Stimulation Exerts Antiinflammatory Effects and Immune Regulatory Function in a 6-OHDA Model of Parkinson's Disease.

According to epidemiologic studies, smoking appears to downregulate the prevalence of Parkinson's disease (PD), possibly due to antiinflammatory mechanisms via activation of α7 nicotinic acetylcholine receptors (α7 nAChRs). This receptor also appears to play a role in T-cell differentiation. Recently, it has become apparent that the innate immune system participates in PD pathogenesis. The aim of this study was to evaluate the effects of auricular vagus nerve stimulation (aVNS) on substantia nigra (SN) dopaminergic neurodegeneration and the associated neuroinflammation and immune responses in a rat PD model. Adult male Wistar rats were unilaterally administered 6-hydroxydopamine (6-OHDA) to the medial forebrain bundle, followed by aVNS treatment after surgery. Following motor behavioral tests, the expression of tyrosine hydroxylase (TH) in the SN and the levels of inflammatory cytokines in the ventral midbrain were evaluated. In addition, changes in the trends of subsets of CD4+ T lymphocytes in the SN were measured by immunofluorescence staining. Western blotting was used to evaluate the α7 nAChR protein level. Compared with 6-OHDA treats rats, aVNS treatment significantly improved motor deficits, increased TH and α7 nAChR expression, and reduced the levels of inflammatory cytokines (tumor necrosis factor-a (TNF-α) and interleukin-1ß (IL-1ß)) (p < 0.05). Additionally, aVNS increased the numbers of regulatory T (Treg) cells while decreasing T helper (Th)17 cells. aVNS exerted neuroprotective effects against dopaminergic damage, possibly by suppressing the evolution of inflammation and modulating innate immune responses. Thus, aVNS may be a potential promising therapy in the future.

Impaired brain network architecture in newly diagnosed Parkinson's disease based on graph theoretical analysis.

BACKGROUND: Resting state functional magnetic resonance imaging (rs-fMRI) has been applied to investigate topographic structure in Parkinson's disease (PD). Alteration of topographic architecture has been inconsistent in PD AIM: To investigate the network profile of PD using graph theoretical analysis. METHOD: Twenty six newly diagnosed PD and 19 age- and gender- matched healthy controls (HC) were included in our analysis. Small-world profile and topographic profiles (nodal degree, global efficiency, local efficiency, cluster coefficient, shortest path length, betweenness centrality) were measured and compared between groups, with age and gender as covariates. We also performed correlation analysis between topographic features with motor severity measured by UPDRS III. RESULTS: Small-world property was present in PD. Nodal degree, global efficiency, local efficiency and characteristic path length consistently revealed disruptive sensorimotor network, and visual network to a less degree in PD. By contrast, default mode network (DMN) and cerebellum in PD showed higher nodal degree, global efficiency and local efficiency, and lower characteristic path length. Global and local efficiency in the midbrain was higher in PD excluding substantia nigra. PD group also exhibited lower cluster coefficient in the subcortical motor network (thalamus and caudate nucleus). No significant correlation was found between topographic properties and motor severity. CONCLUSION: PD exhibited disruptive sensorimotor and visual networks in early disease stage. DMN, a certain areas in the cerebellum and midbrain may compensate for disruptive sensorimotor and visual network in PD. Disruptive network architecture may be an early alteration of PD pathophysiology but may not serve as a valid biomarker yet.