Characteristics of recurrence risk perception and coping strategies in patients with neuromyelitis optica spectrum disorder: A qualitative study.

BACKGROUND: Although neuromyelitis optica spectrum disorder (NMOSD) has high recurrence and disability rates, cases of relapses can be recognized, and timely intervention can be provided if the risk of relapse is properly perceived. However, there have been no studies to explore patients' perceptions of recurrence risk and coping strategies. This study aimed to explore the characteristics of relapse risk perception and coping strategies of patients with NMOSD. METHODS: We adopted the phenomenological method of qualitative research. Face-to-face, semi-structured in-depth interviews were conducted with 15 patients with NMOSD. The interview data were then analyzed using the Colaizzi seven-step analysis. RESULTS: The analysis revealed five major themes. The first theme was the 'perception of possibility of relapse', which included subjectively underestimating the likelihood of relapse and shifted from underestimation to overestimation; the second theme was 'relapse warning signs perception'; the third theme was 'perception of relapse triggers', which included understanding relapse triggers, potential misconceptions about relapse triggers, and no identifiable cause of recurrence; the fourth theme was 'perception of the relapse consequences', encompassing severe impairment of body structure and function, prominent psychological problems, limited family roles and social functions, and heavy financial burden; and the final theme was 'relapse risk coping strategies', which included actively yearning for and seeking information support, recurrence risk prevention/management, limitations of coping strategies. CONCLUSIONS: This study's findings revealed that newly diagnosed patients as well as those who relapsed subjectively underestimated the likelihood of relapse before they had experienced multiple (two or more) relapses. In contrast, patients who had experienced multiple relapses had transitioned from initial underestimation to subsequent overestimation. Additionally, patients' compliance with medication was identified as a relapse-risk behaviors that was very manageable. The occurrence of relapse is associated with significant and extensive adverse effects on patients. Consequently, patients are eager to communicate with their healthcare providers regarding treatment planning and relapse management.

Cerebrospinal fluid uric acid levels associated with disease severity in patients with anti-N-methyl-d-aspartate receptor encephalitis.

INTRODUCTION: Uric acid (UA) is an important natural antioxidant and strong peroxynitrite scavenger, but little is known about central nervous system (CNS) levels of UA in patients with anti-N-methyl-d-aspartate receptor encephalitis (NMDARE). METHODS: Cerebrospinal fluid (CSF) and serum levels of UA were determined in 72 patients with anti-NMDARE and 111 controls with non-inflammatory neurological diseases (NINDs). Serum UA levels were also evaluated in 132 healthy controls (HCs). CSF neuron-specific enolase (NSE) and blood-brain barrier (BBB) index were evaluated in patients with anti-NMDARE. The association of CSF UA levels with anti-NMDARE and its clinical parameters were evaluated in the patients. RESULTS: CSF UA levels were lower in patients with anti-NMDARE than in patients with NINDs, especially in patients with severe impairments (modified Rankin Scale [mRS] scores >3 vs. ≤ 3, p = 0.006). Furthermore, serum UA levels in patients with anti-NMDARE were significantly lower than in patients with NINDs and HCs. CSF UA levels were significantly associated with mRS scores, and serum UA levels in patients with anti-NMDARE. Furthermore, CSF/serum UA ratio was significantly associated with BBB index. CONCLUSIONS: CSF UA levels associated with disease severity and serum UA levels in patients with anti-NMDARE. And CSF/serum UA ratio correlated with BBB index, indicating that CSF and serum UA levels change similarly with BBB permeability in anti-NMDARE patients.

Gut microbes exacerbate systemic inflammation and behavior disorders in neurologic disease CADASIL.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebral small vessel disease that carries mutations in NOTCH3. The clinical manifestations are influenced by genetic and environmental factors that may include gut microbiome. RESULTS: We investigated the fecal metagenome, fecal metabolome, serum metabolome, neurotransmitters, and cytokines in a cohort of 24 CADASIL patients with 28 healthy household controls. The integrated-omics study showed CADASIL patients harbored an altered microbiota composition and functions. The abundance of bacterial coenzyme A, thiamin, and flavin-synthesizing pathways was depleted in patients. Neurotransmitter balance, represented by the glutamate/GABA (4-aminobutanoate) ratio, was disrupted in patients, which was consistent with the increased abundance of two major GABA-consuming bacteria, Megasphaera elsdenii and Eubacterium siraeum. Essential inflammatory cytokines were significantly elevated in patients, accompanied by an increased abundance of bacterial virulence gene homologs. The abundance of patient-enriched Fusobacterium varium positively correlated with the levels of IL-1ß and IL-6. Random forest classification based on gut microbial species, serum cytokines, and neurotransmitters showed high predictivity for CADASIL with AUC = 0.89. Targeted culturomics and mechanisms study further showed that patient-derived F. varium infection caused systemic inflammation and behavior disorder in Notch3R170C/+ mice potentially via induction of caspase-8-dependent noncanonical inflammasome activation in macrophages. CONCLUSION: These findings suggested the potential linkage among the brain-gut-microbe axis in CADASIL. Video Abstract.

Identification of fecal microbiome signatures associated with familial longevity and candidate metabolites for healthy aging.

Gut microbiota associated with longevity plays an important role in the adaptation to damaging stimuli accumulated during the aging process. The mechanism by which the longevity-associated microbiota protects the senescent host remains unclear, while the metabolites of the gut bacteria are of particular interest. Here, an integrated analysis of untargeted metabolomics and 16S rRNA gene sequencing was used to characterize the metabolite and microbiota profiles of long-lived individuals (aged ≥90 years) in comparison to old-elderly (aged 75-89 years), young-elderly (aged 60-74 years), and young to middle-aged (aged ≤59 years) individuals. This novel study constructed both metabolite and microbiota trajectories across aging in populations from Jiaoling county (the seventh longevity town of the world) in China. We found that the long-lived group exhibited remarkably differential metabolomic signatures, highlighting the existence of metabolic heterogeneity with aging. Importantly, we also discovered that long-lived individuals from the familial longevity cohort harbored a microbiome distinguished from that of the general population. Specifically, we identified that the levels of a candidate metabolite, pinane thromboxane A2 (PTA2), which is positively associated with aging, were consistently higher in individuals with familial longevity and their younger descendants than in those of the general population. Furtherly, functional analysis revealed that PTA2 potentiated the efficiency of microglial phagocytosis of ß-amyloid 40 and enhanced an anti-inflammatory phenotype, indicating a protective role of PTA2 toward host health. Collectively, our results improve the understanding of the role of the gut microbiome in longevity and may facilitate the development of strategies for healthy aging.

Natural Killer Cells Disrupt Nerve Fibers by Granzyme H in Atheriosclerotic Cerebral Small Vessel Disease.

Natural killer (NK) cells are enriched in the central nervous system in aging-related atheriosclerotic cerebral small vessel disease (aCSVD), but their roles and underlying mechanism remain to be elucidated. To identify potential cytotoxic molecules released by NK cells in aCSVD lesions, proteomic analysis of cerebrospinal fluid (CSF), plasma, and peripheral NK cells from patients with aCSVD were performed. We found that integrin ß2 (ITGB2), cathepsin D (CTSD), and granzyme H (GZMH) were highly expressed in NK cells. ITGB2 interacted with intercellular adhesion molecule 1 in vascular endothelial cells. As assessed by immunofluorescence and scanning electron microscopy of the blood-brain barrier model, transwell membranes covered with primary human brain microvascular endothelial cells and astrocytes, we demonstrated that the CTSD-mediated degradation of collagen in the blood-brain barrier depended on the cytotoxicity of NK cells in aCSVD. With the immunostaining in vitro and in vivo, GZMH disruption of demyelinated nerve fibers was reversed by cotreatment with the inhibitor 3,4-DCIC during white matter hyperintensity (WMH) in aCSVD. Our results indicate that NK cells contribute to CTSD-induced damage to the blood-brain barrier and GZMH-induced disruption of nerve fibers during WMH in aCSVD.

Factors Influencing Social Participation Among Persons With Neuromyelitis Optica Spectrum Disorders: A Cross-Sectional Study.

Background: Neuromyelitis optica spectrum disorders seriously hinder social participation. Only clarifying the status of social participation and the factors most strongly influencing it can promote better-targeted support for those with neuromyelitis optica spectrum disorders. Objectives: To explore the factors influencing social participation among persons with neuromyelitis optica spectrum disorders. Methods: 138 persons with neuromyelitis optica were recruited by convenience sampling. They completed the Impact on Participation and Autonomy Questionnaire, and were rated using the Barthel index, the Beck Anxiety Inventory and the Beck Depression Inventory. The data were used to evaluate a generalized linear model predicting social participation. Results: The respondents mostly perceived good or very good possibilities of social participation, but participation outdoors and in social relations were considered more restricted. Ability in the activities of daily living, education level, bladder and bowel dysfunction, and depression were four significant predictors of social participation. Conclusions: Strengthening training in the activities of daily living, continuing education, giving positive psychological support and helping with bladder and bowel problems may help to promote social participation among those with neuromyelitis optica spectrum disorders.

Experiences of social isolation among patients with neuromyelitis optica spectrum disorder in China: A qualitative study.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory demyelinating disease of the central nervous system, which mainly involves the optic nerve and spinal cord and has high recurrence and disability rates. Patients with this condition are prone to social isolation, which has not been widely assessed. The purpose of this study was to investigate the experience of social isolation in patients with NMOSD. METHODS: A qualitative descriptive approach was used to conduct in-depth, face-to-face, semi-structured interviews. Data were analyzed using thematic analysis. RESULTS: A total of 20 patients (19 females, 1 male) completed the interview. Patients ranged in age from 14 to 68 years, with disease duration from 1 month to 30 years and Expanded Disability Status Scale scores from 2.0 to 8.0; 60% of patients were unemployed. Four major themes were identified: (1) perception of social isolation, (2) reasons for isolation, (3) impacts of isolation, and (4) potential solutions. CONCLUSIONS: Social isolation affects patients of all ages with different levels of disability and duration of NMOSD. Isolation occurs as a result of multiple interactions between physiological, cognitive-psychological, and environmental factors. The effects of social isolation mainly involve physical, psychological, and family-society aspects. Comprehensive interventions to improve social isolation should be carried out based on these multidimensional influencing factors.

Comparisons of Stroke Knowledge and Health Behaviors in Patients With Hypertensive Stroke at Different Recurrence Risk Strata: The Comprehensive Reminder System Based on the Health Belief Model Study.

BACKGROUND: Risk factor management via behavioral change contributes substantially to secondary stroke prevention. The health belief model identified self-perceived risk as a significant factor in behavior change. In previous studies, people have tended to incorrectly estimate their risk of stroke. Little is known about the differences in stroke knowledge and health behaviors in patients who have had a stroke with different risks of stroke recurrence in China. OBJECTIVE: The aims of this study were to determine the accuracy of self-perceived risk of stroke recurrence and to compare stroke knowledge and health behaviors in patients with hypertensive stroke at different recurrence risk strata. METHODS: Baseline data from 174 patients in the Comprehensive Reminder System based on the Health Belief Model (CRS-HBM) study were used. Self-perceived risk was assessed via the susceptibility subcategory of the Short-Form Health Belief Model Scale, and actual risk was stratified using the Essen Stroke Risk Score. RESULTS: Only 27.0% of the patients estimated their risks of stroke recurrence accurately. Patients who perceived themselves to be at higher risk had better knowledge of warning signs. Compared with patients who underestimated their risk of stroke recurrence, those who accurately estimated or overestimated their risk less likely to smoke. CONCLUSIONS: Most patients incorrectly estimated their risk of stroke recurrence. Communicating with patients about their future risk of recurrent stroke may help improve their stroke knowledge and health behaviors. Implementation of the Comprehensive Reminder System based on the Health Belief Model focusing on risk education aimed at prevention of stroke recurrence is warranted in China.

Social participation and quality of life among patients with neuromyelitis optica spectrum disorders: The mediating effects of depression.

BACKGROUND: Depression is one of the most common and important symptoms of patients with neuromyelitis optica spectrum disorders. Depression is an important aspect of mental health which would be expected to affect a person's social participation. Studies have shown that depression and social participation are independent predictors of health-related quality of life. Depression especially affects its mental component and social participation especially affects its physical aspects. This study was designed to explore to what extent depression may regulate the relationship between social participation and quality of life. METHODS: A convenience sample of 138 discharged patients with neuromyelitis optica spectrum disorders were surveyed. They were asked about their demographic characteristics and disease-related information. Their ability in the activities of daily living was quantified using the Barthel Index. The 36-item short-form health survey, the Beck Depression Inventory and the Impact on Participation and Autonomy questionnaire were also administered. Univariate analysis and Pearson correlations were used to test for any significant relationships between the variables and quality of life. The mediating effect of depression on the association between social participation and life quality was examined using structural equation modeling. RESULTS: The structural equation models provided an excellent fit for the data. Social participation and the physical aspects of life quality were found to be strongly associated. And depression was of course strongly related to the mental aspects. Depression was not a mediator in the significant relationship between social participation and the physical aspects of life quality, but depression was found to be a strong and significant meditator in the association between social participation and the mental aspects of life quality. CONCLUSION: These findings help to clarify the direct and indirect effects of depression and social participation on the life quality of patients with neuromyelitis optica spectrum disorders. While helping and encouraging patients to actively participate in social life should be supplemented by monitoring them for signs of depression and providing appropriate treatment.

Protein A immunoadsorption for the treatment of refractory anti-N-methyl-d-aspartate receptor encephalitis: A single-center prospective study.

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of protein A immunoadsorption (IA) for anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis resistant to intravenous methylprednisolone (IVMP) and intravenous immunoglobulin (IVIG). METHODS: We prospectively evaluated patients with refractory anti-NMDAR encephalitis, treated with protein A IA. Demographic data, clinical characteristics, modified Rankin Score (mRS), and anti-NMDAR antibodies were documented before and after IA and at follow-up. Clinical improvement was defined as a decrease of mRS ≥1. Adverse events were recorded throughout the study. RESULTS: Ten patients with mRS ≥3 were enrolled and treated with protein A IA; treatment was performed for an average of 5.2 times per patient. Among the nine patients with positive serum anti-NMDAR, the titer decreased in seven patients, of which two became negative. The cerebrospinal fluid (CSF) anti-NMDAR titer decreased in all patients, and one became negative. Anti-NMDAR levels were tested in two patients at follow-up and found to have declined continuously. All patients exhibited clinical improvement with a mRS decline ≥1 after IA treatment (median mRS: 5.0 [range, 3.0-5.0] vs. 4.0 [range, 2.0-4.0], p = 0.014), and the median mRS decreased to 1.0 (range, 0-3.0) at follow-up. After IA, all patients exhibited accelerated recovery. No adverse events were observed during IA treatment. CONCLUSION: Protein A IA may be effective for treating IVMP/IVIG-resistant anti-NMDAR encephalitis and well tolerated. It is necessary to initiate larger-scale prospective controlled studies to validate the efficacy and safety of protein A IA in anti-NMDAR encephalitis.

Gender Difference in the Association Between Stroke Knowledge and Health Behavior Before the Onset of Stroke Among Chinese Hypertensive Patients.

ABSTRACT: BACKGROUND: Previous research has shown that men and women have different levels of stroke knowledge and differing health behaviors, which are important factors affecting blood pressure, as hypertension is a key risk factor for stroke occurrence. There has been little research on the effects of sex on the association between these 2 variables before the onset of stroke among Chinese hypertensive patients. METHODS: A cross-sectional study and a convenience sampling method were used. 272 male and 118 female hypertensive stroke patients were recruited. Each patient completed the Stroke Knowledge Questionnaire and the Health Behavior Scale for stroke patients. RESULTS: Compared with female patients, male patients had greater stroke knowledge and worse prestroke health behavior. The Pearson correlation coefficient between stroke knowledge and prestroke health behavior was 0.149 and 0.223 in male and female participants, respectively, P < .05. The results of a multiple regression analysis showed that Chinese hypertensive stroke patients' prestroke health behavior was significantly influenced by sex and stroke knowledge. CONCLUSION: Chinese male and female hypertensive stroke patients had disparities in stroke knowledge and prestroke health behavior; moreover, the correlation between these 2 variables before experiencing a hypertensive stroke was different between men and women. Men with hypertension should be considered at a higher risk for an initial or recurrent stroke. Developing sex-specific intervention for primary or secondary stroke prevention in China is essential.

Gut microbiota from patients with arteriosclerotic CSVD induces higher IL-17A production in neutrophils via activating RORγt.

The intestinal microbiota shape the host immune system and influence the outcomes of various neurological disorders. Arteriosclerotic cerebral small vessel disease (aCSVD) is highly prevalent among the elderly with its pathological mechanisms yet is incompletely understood. The current study investigated the ecology of gut microbiota in patients with aCSVD, particularly its impact on the host immune system. We reported that the altered composition of gut microbiota was associated with undesirable disease outcomes and exacerbated inflammaging status. When exposed to the fecal bacterial extracts from a patient with aCSVD, human and mouse neutrophils were activated, and capacity of interleukin-17A (IL-17A) production was increased. Mechanistically, RORγt signaling in neutrophils was activated by aCSVD-associated gut bacterial extracts to up-regulate IL-17A production. Our findings revealed a previously unrecognized implication of the gut-immune-brain axis in aCSVD pathophysiology, with therapeutic implications.

Triglyceride-Glucose Index Linked to Hospital Mortality in Critically Ill Stroke: An Observational Multicentre Study on eICU Database.

Objective: The triglyceride-glucose (TyG) index is a reliable surrogate of insulin resistance and a marker for ischemic stroke (IS) incident. Whether the TyG index predicts stroke outcome remains uncertain. This study investigated the prognostic value of the TyG index in critically ill stroke patients. Methods: This was a retrospective observational study that included stroke patients, and all data were extracted from the eICU Collaborative Research Database. The TyG index was calculated as the ln [fasting glucose level (mg/dL) × triglyceride level (mg/dL)/2]. Outcomes included the hospital and intensive care unit (ICU) death. Multivariate logistic regression was used to determine independent risk factors. The smoothing curves and forest plots were illustrated. Results: A total of 4,570 eligible subjects were enrolled. The mean level of TyG index was 9.1 ± 0.7. The hospital and ICU mortality rate were 10.3 and 5.0%, respectively. TyG index as a continuous variable was associated hospital mortality in univariate analysis (OR 1.723, 95% CI 1.524-1.948, P < 0.001), adjusted model 1 (OR 1.861, 95% CI 1637-2.116, P < 0.001), and adjusted model 2 (OR 2.543, 95% CI 1.588-4.073, P < 0.001). TyG was also associated ICU mortality in univariate analysis (OR 2.146, 95% CI 1.826-2.523, P < 0.001), adjusted model 1 (OR 2.183, 95% CI 1.847-2.580, P < 0.001), and adjusted model 2 (OR 2.672, 95% CI 1.376-5.188, P < 0.001). The smoothing curves observed a continuous linear association after adjusting all covariates both in hospital and ICU mortality. Subgroup analysis demonstrated TyG index was associated with increased risk of hospital and ICU death in critically ill IS (P < 0.05), but not in hemorrhage stroke (P > 0.05). Conclusion: The TyG index is a potential predictor for hospital and ICU mortality in critically ill stroke patients, especially in IS patients.

Different magnetic resonance imaging features between MOG antibody- and AQP4 antibody-mediated disease: A Chinese cohort study.

Few studies have compared radiological features obtained on magnetic resonance imaging (MRI) between myelin oligodendrocyte glycoprotein antibody (MOG-ab)- and aquaporin 4 antibody (AQP4-ab)-positive patients. In this study, 77 MOG-ab and 92 AQP4-ab patients were enrolled. The results demonstrated that the brain MRI-based incidence of subcortical white matter lesions was higher in MOG-ab patients (p < .000) than in AQP4-ab patients and that the former therefore had a higher incidence of periventricular lesions (p = .003). The posterior limb of the internal capsule was more prone to lesions in MOG-ab patients (p = .019). Large lesions and U- or S-shaped lesions were also more frequent in MOG-ab (p < .000 and p = .013, respectively). Half of the MOG-ab patients had spinal cord involvement, and 36.5% presented with longitudinally extensive transverse myelitis (LETM). However, among the MOG-ab and AQP4-ab patients with spinal attack, there was no significant difference in the proportion with LETM (p = .057). In conclusion, a higher proportion of MOG-ab patients than AQP4-ab patients had brain lesions in white matter. Among MOG-ab patients who had an attack in the spinal cord, 65.5% also had LETM during the disease course. Conus medullaris lesions were rare in Chinese MOG-ab patients.

The Efficacy of a Comprehensive Reminder System to Improve Health Behaviors and Blood Pressure Control in Hypertensive Ischemic Stroke Patients: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVE: The health behaviors of hypertensive stroke patients in China are not satisfactory. In this study, we tested the effect of a Health Belief Model Comprehensive Reminder System on health behaviors and blood pressure control in hypertensive ischemic stroke patients after occurrence and hospital discharge. METHODS: A randomized, parallel-group, assessor-blinded experimental design yielded participation of 174 hospitalized hypertensive ischemic stroke patients. The intervention consisted of face-to-face and telephone health belief education, a patient calendar handbook, and weekly automated short-message services. Data were collected at baseline and 3 months after discharge. RESULTS: Three months after discharge, the intervention group showed statistically, significantly better health behaviors for physical activity, nutrition, low-salt diet, and medication adherence. The intervention group also had statistically, significantly decreased systolic blood pressure and increased blood pressure control rate. Smoking and alcohol use behaviors were not affected. CONCLUSION: At 3 months, use of the Comprehensive Reminder System based on the Health Belief Model, yielded improvement in most health behaviors and blood pressure control in hypertensive ischemic stroke patients. Continued implementation of this intervention protocol is warranted to determine the long-term effect. Smoking and alcohol use behaviors need to be targeted with a different intervention.

Stroke prevention knowledge and prestroke health behaviors among hypertensive stroke patients in mainland China.

BACKGROUND AND OBJECTIVES: Individuals with hypertension are at risk of stroke, and patients with stroke histories are at risk of experiencing another stroke. At this time, however, only a few studies have reported on stroke prevention knowledge and health behaviors among hypertensive patients who have had an initial stroke. The purpose of this study was to determine stroke prevention knowledge and health behaviors and to analyze the association between these 2 variables among hypertensive stroke patients who have had an initial stroke. SUBJECTS AND METHODS: With the use of a descriptive correlational design, a sample of 112 hypertensive stroke patients was recruited from the departments of neurology of 3 hospitals in Guangzhou, China. Each patient completed 2 reliable, validated questionnaires, the Stroke Prevention Knowledge Questionnaire and the Health Promoting Lifestyle Profile II. Data were collected during patients' hospital admission for stroke, within 2 days of stroke onset, and before they received stroke education. Pearson correlation coefficient was used to examine the correlations between the study variables. Multiple stepwise regression analysis was used to predict both the level of knowledge relating to stroke prevention and health behaviors. RESULTS AND CONCLUSIONS: The participants showed a relatively low level of stroke prevention knowledge and a moderate level of engagement in healthy behaviors. Pearson correlation coefficient between these 2 variables was 0.423 (P < .001). The results of multiple regression analysis showed that stroke prevention knowledge was positively influenced by education level; health behaviors were positively influenced by both gender and stroke prevention knowledge. Findings suggest that male hypertensive patients and those with a lower education level need targeted stroke education. Because knowledge was unrelated to behavior with respect to smoking, alcohol use, and low-salt diet, behavioral interventions should be explored to address these important risk factors among patients at risk for stroke.

Combined therapy with methylprednisolone and ulinastatin in experimental autoimmune encephalomyelitis.

BACKGROUND: Our previous study had demonstrated that ulinastatin (UTI) had a neuroprotective effect in experimental autoimmune encephalomyelitis (EAE). Methylprednisolone has been recommended to be a standard drug in multiple sclerosis (MS) therapies. The present study was to investigate the protective effects of UTI combined methylprednisolone in EAE. METHODS: Mice were divided into a UTI treatment group, a methylprednisolone treatment group, a combined treatment group with UTI and methylprednisolone, a normal saline treatment group, and a normal control group. EAE mice were induced in groups receiving different combined treatments, or respective monotherapies. Demyelination was evaluated by Solochrome cyanin staining. 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP)/ myelin basic protein (MBP)/ the precursor form of nerve growth factor (proNGF)/p75/ inducible nitric oxide synthase (iNOS) proteins in cerebral cortex of EAE were detected by Western blotting. RESULTS: The combined treatment group had a lower clinical score (0.61 ± 0.06) and demyelinating score (1.33 ± 0.33) than the groups with normal saline (clinical score: 1.39 ± 0.08, P < 0.001; demyelinating score: 2.75 ± 0.49, P < 0.05) or monotheraphies. Compared with the saline treated EAE group, UTI combined methylprednisolone significantly increased expressions of CNP (1.14 ± 0.06 vs. 0.65 ± 0.04, P < 0.001), MBP (1.28 ± 0.14 vs. 0.44 ± 0.17, P < 0.001), and decreased expressions of proNGF (1.08 ± 0.10 vs. 2.32 ± 0.12, P < 0.001), p75 (1.13 ± 0.13 vs. 2.33 ± 0.17, P < 0.001), and iNOS (1.05 ± 0.31 vs. 2.17 ± 0.13, P < 0.001) proteins in EAE. Furthermore, UTI combined methylprednisolone could significantly upregulate MBP (1.28 ± 0.14 vs. 1.01 ± 0.15, P < 0.05) expression and downregulate iNOS (1.05 ± 0.31 vs. 1.35 ± 0.14, P < 0.05) expression compared to methylprednisolone treatment EAE group. And proNGF expression was significantly lower in combined treatment (1.08 ± 0.10) than that in UTI (1.51 ± 0.24, P < 0.05) or methylprednisolone (1.31 ± 0.04, P < 0.05) treatment group. CONCLUSION: Combination treatment of UTI with methylprednisolone was shown to protect EAE, suggesting that combination therapy is a potential novel treatment in MS.