Intestinal perfusion of unacylated ghrelin alleviated metabolically associated fatty liver disease in rats via a central glucagon-like peptide-1 pathway.

Unacylated ghrelin (UAG), the unacylated form of ghrelin, accounts for 80%-90% of its circulation. Accumulated studies have pointed out that UAG may be used to treat metabolic disorders. This study aimed to investigate the effect of intestinal perfusion of UAG on metabolically associated fatty liver disease (MAFLD) induced by a high-fat diet and its possible mechanisms. Neuronal retrograde tracking combined with immunofluorescence, central administration of a glucagon-like peptide-1 receptor (GLP-1R) antagonist, and hepatic vagotomy was performed to reveal its possible mechanism involving a central glucagon-like peptide-1 (GLP-1) pathway. The results showed that intestinal perfusion of UAG significantly reduced serum lipids, aminotransferases, and food intake in MAFLD rats. Steatosis and lipid accumulation in the liver were significantly alleviated, and lipid metabolism-related enzymes in the liver were regulated. UAG upregulated the expression of GLP-1 receptor (GLP-1R) in the paraventricular nucleus (PVN) and GLP-1 in the nucleus tractus solitarii (NTS), as well as activated GLP-1 neurons in the NTS. Furthermore, GLP-1 fibers projected from NTS to PVN were activated by the intestinal perfusion of UAG. However, hepatic vagotomy and GLP-1R antagonists delivered into PVN before intestinal perfusion of UAG partially attenuated its alleviation of MAFLD. In conclusion, intestinal perfusion of UAG showed a therapeutic effect on MAFLD, which might be related to its activation of the GLP-1 neuronal pathway from NTS to PVN. The present results provide a new strategy for the treatment of MAFLD.NEW & NOTEWORTHY Intestinal perfusion of UAG, the unacylated form of ghrelin, has shown promising potential for treating MAFLD. This study unveils a potential mechanism involving the central GLP-1 pathway, with UAG upregulating GLP-1R expression and activating GLP-1 neurons in specific brain regions. These findings propose a novel therapeutic strategy for MAFLD treatment through UAG and its modulation of the GLP-1 neuronal pathway.

Short-term safety of inactivated SARS-Cov-2 vaccines in Chinese patients with central nervous system inflammatory demyelinating diseases.

Objective: This study aims to evaluate the short-term safety of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in Chinese patients with central nervous system inflammatory demyelinating diseases (CNS IDDs). Methods: A web-based survey was conducted among patients with CNS IDDs from April 15 to 19, 2022 in China. In total, 645 patients with CNS IDDs were identified, including 425 patients with multiple sclerosis (MS), 194 with neuromyelitis optica spectrum disorder (NMOSD), and 26 with other CNS IDDs. The questionnaire consisted of demographic data, clinical records, history of SARS-CoV-2 vaccination, and vaccination-related symptoms within one month after vaccination. The demographic data, clinical information, and relapse rates between vaccinated and non-vaccinated patients were compared. Results: Among 645 patients with CNS IDDs, 78 were vaccinated and 567 were non-vaccinated with the vaccination rate of 12.1 %. Compared to non-vaccinated group, a lower percentage of patients on DMDs therapy (41.0 % vs. 71.8 %, P < 0.001) and an increased proportion of patients with other vaccination in past 3 years (17.9 % vs. 4.8 %, P < 0.001) were observed in vaccinated group. Six patients experienced a relapse within 30 days of a vaccination. Additionally, vaccine-associated relapse rates in vaccinated patients did not significantly differ from these in non-vaccinated patients among 2020, 2021, and from January 1 to October 1, 2022. Conclusions: No increased risk of vaccination-associated relapses among Chinese patients with CNS IDDs indicated that inactivated SARS-CoV-2 vaccines appear to be safe for this population.

Rituximab at lower dose for neuromyelitis optica spectrum disorder: a multicenter, open-label, self-controlled, prospective follow-up study.

Objective: To address a novel lower-dose rituximab (RTX) therapy strategy based on our clinical experience and assess its efficacy and safety in neuromyelitis optica spectrum disorder (NMOSD). Methods: A multicenter, open-label, self-controlled, prospective follow-up study. Totally, 108 NMOSD patients were enrolled and a lower-dose RTX strategy was applied including 100 mg weekly for 3 weeks and then reinfusions every 6 months. Annualized relapse rate (ARR), the expanded disability status scale (EDSS) score and length of spinal cord lesions were included to evaluate the efficacy. Side effects were recorded to assess the safety profile. Results: Of 108 patients, 80 (74.1%) initiated low-dose RTX therapy immediately after acute attack treatment and 33 (30.6%) initiated it after the first attack. During a median treatment period of 35.5 (22.0-48.8) months, significant decreases were observed in median ARR (1.1 [0.8-2.0] versus 0 [0-0.2], p < 0.001), EDSS score (3.5 [2.5-4.0] versus 2.0 [1.0-3.0], p < 0.001) and spinal cord lesion segments (5.0 [4.0-8.0] versus 3.0 [1.0-6.0], p < 0.001). The cumulative risk of relapses significantly decreased during the post- versus pre-RTX period (HR 0.238, 95%CI 0.160-0.356, p < 0.001) and on early therapy initiated within 24 months after disease onset versus delayed therapy (HR 0.506, 95%CI 0.258-0.994, p = 0.041). No serious side effects were recorded and all the subjects did not discontinue treatment due to RTX-related side effects. Conclusion: Our research provided evidence supporting the lower-dose RTX strategy in treating NMOSD and reopened the issues of optimal dosage and therapy initiation timing.

Late-Onset Anti-GABAB Receptor Encephalitis: Clinical Characteristics and Outcomes Differing From Early-Onset Patients.

BACKGROUND AND OBJECTIVES: Existing evidence indicates anti-GABAB receptor encephalitis (GABABR-E) seems to occur more commonly later in life, yet the age-associated differences in clinical features and outcomes are not well determined. This study aims to explore the demographic, clinical characteristics, and prognostic differences between late-onset and early-onset GABABR-E and identify predictors of favorable long-term outcomes. METHODS: This is an observational retrospective study conducted in 19 centers from China. Data from 62 patients with GABABR-E were compared between late-onset (aged 50 years or older) and early-onset (younger than 50 years) groups and between groups with favorable outcomes (modified Rankin scale (mRS) ≤ 2) and poor outcomes (mRS >2). Logistic regression analyses were applied to identify factors affecting long-term outcomes. RESULTS: Forty-one (66.1%) patients experienced late-onset GABABR-E. A greater proportion of males, a higher mRS score at onset, higher frequencies of ICU admission and tumors, and a higher risk of death were demonstrated in the late-onset group than in the early-onset group. Compared with poor outcomes, patients with favorable outcomes had a younger onset age, a lower mRS score at onset, lower frequencies of ICU admission and tumors, and a greater proportion with immunotherapy maintenance for at least 6 months. On multivariate regression analysis, age at onset (OR, 0.849, 95% CI 0.739-0.974, p = 0.020) and the presence of underlying tumors (OR, 0.095, 95% CI 0.015-0.613, p = 0.013) were associated with poorer long-term outcomes, whereas immunotherapy maintenance for at least 6 months was associated with favorable outcomes (OR, 10.958, 95% CI 1.469-81.742, p = 0.020). DISCUSSION: These results demonstrate the importance of risk stratification of GABABR-E according to age at onset. More attention should be paid to older patients especially with underlying tumors, and immunotherapy maintenance for at least 6 months is recommended to achieve a favorable outcome.

Efficacy and safety of repeated low-dose rituximab therapy in relapsing-remitting multiple sclerosis: A retrospective case series study.

BACKGROUND: Rituximab (RTX) is an extensively used off-label drug for multiple sclerosis (MS), whereas the induction and maintenance regimens vary widely among studies. Few data are available on efficacy and safety of repeated low-dose RTX therapy in MS patients. OBJECTIVE: This study aimed to evaluate the efficacy and safety of repeated low-dose RTX therapy for relapsing-remitting MS (RRMS), the most common form of MS affecting approximately 85% of patients. METHODS: Nine RRMS patients were enrolled and the medical records were retrospectively reviewed. RTX at 100 mg per week for three consecutive weeks was used as induction therapy. Maintenance therapy was reinfusions of RTX at 100 mg every 6 months during the first year, followed by 100 mg every 6 to 12 months. Main outcome measures included annualized relapse rate (ARR), expanded disability status scale (EDSS) score, and T2 lesion burden on MRI for evaluating the efficacy of low-dose RTX regimen. Meanwhile, adverse events (AEs) were recorded to assess the safety of repeated RTX infusions. RESULTS: All patients were females with an average onset age of 25.4 ± 6.7 years. The median disease duration before the first RTX infusion was 56 (range, 3-108) months and the median follow-up period was 30 (range, 15-40) months. No relapses were recorded in all patients after RTX therapy. Repeated low-dose RTX therapy resulted in a dramatic reduction of median ARR (pre-RTX vs post-RTX, 1.1 vs 0, p = 0.012), median EDSS score (2.0 vs 0, p = 0.007), and the number of T2 lesions on MRI (35.6 ± 18.0 vs 29.4 ± 18.1, p = 0.001). A total of 35 episodes of AEs occurred during repeated low-dose RTX therapy, and all of them were mild and transient. CONCLUSION: Repeated low-dose RTX therapy is cost-effective for RRMS patients and shows a good safety profile. It may be a promising option for those having no access or poor response to first-line disease-modified drugs (DMDs), particularly in low- or middle-income countries.

Notch signaling dependent monocyte conversion alleviates immune-mediated neuropathies by regulating RBP-J/NR4A1 axis.

Monocytes in peripheral blood and sciatic nerves play vital roles in immune-mediated neuropathies such as Guillain-Barré syndrome (GBS). Different subpopulations of monocytes, including classical and non-classical, exhibit distinct functions as well as phenotypic conversion potentials. However, the mechanisms underlying their development during immune-mediated neuropathy remain unclear. Notch signaling participates in monocyte differentiation and function. In this study, we used a myeloid-specific Notch signaling activation transgenic mouse (NICcA) and investigated the role of Notch signaling in monocytes during experimental autoimmune neuritis (EAN) in a mouse model of GBS. Clinical score assessment and histopathological examination revealed that sciatic nerve injury was attenuated in NICcA EAN mice compared to that in control mice. Flow cytometry and immunofluorescence staining suggested that increasing Ly6Clo monocytes in the peripheral blood and nerve tissue might contribute to the alleviation of neuritis in NICcA mice. Meanwhile, an in vitro study suggested that bone marrow-derived monocytes from NICcA mice are more inclined toward Ly6Clo cells than Ly6Chi cells. Differential expression of monocyte development-associated genes was detected in NICcA and wild-type mice using RNA sequencing. The expression of Nr4a1 is upregulated remarkably when Notch signaling is activated. Treatment with Nr4a1 antagonist on NICcA mice-derived monocytes compromise their Ly6Clo tendency. Consistently, a relationship between monocyte conversion and disease severity was observed in blood samples from patients with GBS. In conclusion, our current study showed that monocyte conversion modulated by Notch signaling plays an essential role in the EAN mouse model.

Coexistence of Myelin Oligodendrocyte Glycoprotein Immunoglobulin G and Neuronal or Glial Antibodies in the Central Nervous System: A Systematic Review.

BACKGROUND: Myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) has been considered a diagnostic marker for patients with demyelinating disease, termed "MOG-IgG associated disorder" (MOGAD). Recently, the coexistence of MOG-IgG and other neuronal or glial antibodies has attracted extensive attention from clinicians. In this article, we systematically review the characteristics of MOG-IgG-related antibody coexistence syndrome. METHODS: Two authors independently searched PubMed for relevant studies published before October 2021. We also manually searched the references of each related article. The appropriateness of the included studies was assessed by reading the titles, abstracts, and full texts if necessary. RESULTS: Thirty-five relevant publications that met our inclusion criteria were finally included, of which fourteen were retrospective studies and twenty-one were case reports. A total of 113 patients were reported to show the coexistence of MOG-IgG and neuronal or glial antibodies. Additionally, 68.14% of patients were double positive for MOG-IgG and N-Methyl-D-Aspartate Receptor-IgG (NMDAR-IgG), followed by 23.01% of patients who were double positive for MOG-IgG and aquaporin4-IgG (AQP4-IgG). Encephalitis was the predominant phenotype when MOG-IgG coexisted with NMDAR-IgG, probably accompanied by imaging features of demyelination. Patients with dual positivity for MOG-IgG and AQP4-IgG experienced more severe disease and more frequent relapses. The coexistence of MOG-IgG and antibodies other than NMDAR-IgG and AQP4-IgG was extremely rare, and the clinical presentations were diverse and atypical. Except for patients who were double positive for MOG-IgG and AQP4-IgG, most patients with multiple antibodies had a good prognosis. CONCLUSIONS: MOG-IgG may coexist with neuronal or glial antibodies. Expanded screening for neuronal or glial antibodies should be performed in patients with atypical clinical and radiological features.

Atractylodes chinensis volatile oil up-regulated IGF-1 to improve diabetic gastroparesis in rats.

Objectives: Diabetic gastroparesis (DGP) is one of the main complications of diabetes, and more than half of diabetes cases are accompanied by gastroparesis. This study aims to explore the effect of Atractylodes chinensis volatile oil (ACVO) on DGP rats. Materials and Methods: The rats were injected with STZ combined with a high-sugar and high-fat diet in an irregular manner to establish the DGP model. ACVO at different doses (9.11 mg/kg, 18.23 mg/kg, and 36.45 mg/kg) were given by intragastric administration. A mixture of cisapride and metformin was used as the positive control. At the end of the experiment, gastric emptying and intestinal propulsion were determined. Then the tissue samples and blood were taken from each group for serum analysis, western blot and immunopathological examination. Results: After treatment with ACVO, body weight increased and blood glucose decreased when compared with rats in the DGP group. Gastric emptying and intestinal propulsion were accelerated, and gastric acid secretion increased. The serum insulin-like growth factor-1 (IGF-1) level was increased. Protein expressions and positive cells of IGF-1 receptor (IGF-1R), acetylcholine transferase (CHAT), and stem cell factors (SCF) in the stomach were significantly increased determined by western blot and immunofluorescence staining. The morphology and the number of interstitial cells of Cajal (ICCs) in the stomach were restored, determined by hematoxylin and eosin staining and immunohistochemical staining, respectively. Conclusion: ACVO effectively alleviated DGP in rats, and its mechanism may be related to the up-regulation of IGF-1/IGF-1R signaling.

Eugenol alleviated nonalcoholic fatty liver disease in rat via a gut-brain-liver axis involving glucagon-like Peptide-1.

Eugenol, an active ingredient of many medicinal aromatic plants, has been proved to have the hypolipidemic effect, but its potential mechanism of action is still unknown. This study aimed to investigate whether eugenol regulates liver lipid accumulation in high-fat diet (HFD) induced nonalcoholic fatty liver disease (NAFLD) rats via the gut-brain-liver axis involving glucagon-like peptide-1 (GLP-1). Hepatic vagotomy was performed in NAFLD rats to determine the role of eugenol in regulating hepatic lipid accumulation via vagus nerve. The results showed that after eight weeks of eugenol administration in NAFLD rats, serum total cholesterol (TC), triglyceride (TG) and hepatic TG decreased. However, eugenol showed no significant effect on the increased food intakes and weight gain caused by the HFD. Eugenol promoted the secretion of GLP-1 into the blood, increased GLP-1 receptor (GLP-1R) expression in the duodenum, liver, arcuate nucleus (ARC) and paraventricular nucleus (PVN), increased c-fos expression in the nucleus tractus solitarii (NTS), and promoted ZO-1 and occludin expression in duodenum. Furthermore, steatosis and lipid accumulation were significantly alleviated. Hepatic vagotomy partially attenuated the improvement of eugenol in hepatic lipid accumulation in NAFLD rats. In conclusion, eugenol regulates hepatic lipid metabolism via a gut-brain-liver axis involving in GLP-1, providing a new strategy for the treatment of NAFLD.

Association between serum low-density neutrophils and acute-onset and recurrent Guillain-Barré syndrome.

BACKGROUND AND AIM: Guillain-Barré syndrome (GBS) is one of the most common causes of acute flaccid paralysis. A timely assessment of this disease condition and its treatments are of vital importance to patients diagnosed with GBS. The purpose of this study is to investigate the variation trend of neutrophils along with disease courses and assess the prognostic value of serum low-density neutrophils (LDNs) in the acute-onset and recurrence of GBS. METHODS: A total of 176 GBS patients were recruited. Patients were evaluated with Medical Research Council (MRC) sum score and the Hughes Functional Grading Scale score upon admission. Peripheral blood samples were collected for routine testing. Flow cytometry analysis was performed to identify LDNs. All patients were followed up to collect disease condition data. RESULTS: The total neutrophil ratios and counts were significantly higher in patients with acute-onset GBS compared to healthy controls (HCs). These counts/ratios decreased during remission and re-elevated in recurrent GBS patients. However, no correlation was observed between the total neutrophil counts/ratios and the MRC sum score. The LDNs collected from different GBS courses were identified using flow cytometry. The counts and ratios were significantly higher in acute-onset GBS and recurrent GBS compared to HCs and patients in remission. The LDN counts/ratios displayed a negative correlation with the MRC sum scores in acute-onset GBS and recurrent GBS. CONCLUSION: Our findings suggest that LDN counts/ratios are positively correlated with the acute-onset and recurrence of GBS and its severity. Therefore, LDNs might serve as an accessible prognostic indicator for disease progression monitoring.

Case Report: Prominent Brainstem Involvement in Two Patients With Anti-CASPR2 Antibody-Associated Autoimmune Encephalitis.

Anti-contactin-associated protein-like 2 (CASPR2) antibody-associated autoimmune encephalitis is commonly characterized by limbic encephalitis with clinical symptoms of mental and behavior disorders, cognitive impairment, deterioration of memory, and epilepsy. The classical lesions reported are located at the medial temporal lobe or hippocampus, whereas prominent brainstem lesions have not been addressed to date. Herein, we reported two patients mimicking progressive brainstem infarction with severe neurological manifestations. On brain magnetic resonance imaging (MRI), prominent brainstem lesions were noted, although multifocal lesions were also shown in the juxtacortical and subcortical white matters, basal ganglia, hippocampus, and cerebellar hemisphere. Unexpectedly and interestingly, both cases had detectable CASPR2 antibodies in sera, and an exclusive IgG1 subclass was documented in the further analysis. They were treated effectively with aggressive immunosuppressive therapies including corticosteroids, intravenous immunoglobulin G, and rituximab, with the first case achieving a rapid remission and the other undergoing a slow but gradual improvement. To the best of our knowledge, this is the first report on prominent brainstem involvement with definite MRI lesions in anti-CASPR2 antibody-associated autoimmune encephalitis, which helps to expand the clinical spectrum of this rare autoimmune disease and update the lesion patterns in the CNS.

Hypertension management in elderly with severe intracerebral hemorrhage.

OBJECTIVE: To explore the effect of individualized blood pressure (BP)-lowering treatment on the outcomes of elderly patients with severe intracerebral hemorrhage (ICH). METHODS: We performed an exploratory analysis of Controlling Hypertension After Severe Cerebrovascular Event (CHASE) trial, which was a multicenter, randomized, controlled clinical trial. Patients with severe ischemic or hemorrhagic stroke (defined as GCS ≤ 12 or NIHSS ≥ 11) were randomized into individualized versus standard BP-lowering treatment in CHASE trial. In this exploratory analysis, patients with severe ICH were included. The primary outcome was the percentage of patients with 90-day functional independence defined as modified Rankin Scale (mRS) ≤2. RESULTS: We included 242 patients with severe ICH in the present analysis, consisting of 142 patients aged <65 years and 100 patients aged ≥65 years. There were significant differences between patients aged ≥65 years and <65 years in the proportion of functional independence (47.9% vs. 15.0%, P < 0.001) and good outcome (73.9% vs. 50.0%, P < 0.001) at day 90. In patients aged ≥65 years, the adjusted individualized BP-lowering treatment had an unequivocal effect on the functional independence at day 90 (21.6% vs. 8.2%, odds ratio [OR]: 4.309, 95% confidence interval [CI]: 1.040-17.859, P = 0.044) and improved the neurological deficits at discharge (∆ NIHSS ≥ 4: 64.7% vs. 34.7%, OR: 4.300, 95% CI: 1.599-11.563, P = 0.004). INTERPRETATION: Compared with the younger counterparts, the elderly patients (≥65 years) with acute severe ICH might benefit more from individualized BP-lowering treatment.

QKI 6 ameliorates CIRI through promoting synthesis of triglyceride in neuron and inhibiting neuronal apoptosis associated with SIRT1-PPARγ-PGC-1α axis.

BACKGROUND: The stroke induced by ischemia of brain remains high incidence and death rate. The study wanted to confirm the effects of Quaking 6 (QKI 6) on the protection role in neurons of rat model of cerebral ischemia/reperfusion injury (CIRI). MATERIAL AND METHODS: The rat model with CIRI induced by middle cerebral artery occlusion was well established and rat neurons were isolated to characterize the effects of QKI 6 mediated by sirtuin 1 (SIRT1) on synthesis of triglyceride in neuron and neuronal apoptosis via activation of SIRT1-peroxisome proliferater-activated receptor (PPAR)γ- peroxisome proliferator-activated receptor coactivator (PGC)-1α signaling pathway. RESULTS: The expression levels of SIRT1 or QKI 6, and acetylation level of QKI 6 were decreased in neurons of rat model with CIRI. QKI 6 deacetylated and mediated by SIRT1 that contributed to suppressing the progression of neuronal apoptosis in rat through promoting synthesis of triglyceride in vivo and in vitro via SIRT1-PPARγ-PGC-1α signaling pathway, then inhibiting CIRI. CONCLUSIONS: Our results demonstrated SIRT1 deacetylates QKI 6, the RNA-binding protein, that affects significantly the synthesis of triglyceride in neurons of CIRI rat model. Moreover, it activated transcription factor peroxisome proliferator-activated receptorγ coactivator-1α (PGC-1α) through post-transcriptional regulation of the expression of PPARγ, and further enhanced synthesis of triglyceride, thereby restrained the progression of neural apoptosis and CIRI.

Controlling Hypertension After Severe Cerebrovascular Event (CHASE): A randomized, multicenter, controlled study.

BACKGROUND: The optimal blood pressure lowering target in the acute phase of severe stroke is uncertain. Our aim was to compare the efficacy and safety of individualized blood pressure lowering with standard blood pressure lowering in severe stroke. METHODS: Five-hundred consecutive patients with acute severe stroke and elevated BP were recruited from 26 Chinese hospitals. Eligible patients were randomized into an individualized blood pressure lowering group (with 10-15% reduction in systolic blood pressure from admission level or standard blood pressure lowering group (with a target SBP of <200 mm Hg in acute ischemic stroke and <180 mm Hg in intracerebral hemorrhage). The primary outcome was the proportion of patients with a poor functional outcome at day 90 of enrolment. RESULTS: Of 483 participants included in the analysis, 242 received individualized blood pressure lowering treatment and 241 received standard treatment. The primary outcome event was observed in 71.1% of the participants in the individualized treatment group and in 73.4% of the standard treatment group (odds ratio with individualized treatment for primary outcome, 0.75; 95% confidence interval, 0.47 to 1.19; p = 0.222). The rates of serious adverse events in the two groups were similar (27.7% vs. 28.2%). CONCLUSIONS: In patients with acute severe stoke, individualized blood pressure lowering treatment did not significantly reduce the rate of three-month death or dependence. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02982655. Registered in 5 December 2016, https://clinicaltrials.gov/ct2/show/NCT02982655.

Blood pressure variability and outcome in acute severe stroke: A post hoc analysis of CHASE-A randomized controlled trial.

The influence of blood pressure variability (BPV) on outcomes in patients with severe stroke is still largely unsettled. Using the data of CHASE trial, the authors calculated the BPV during the acute phase and subacute phase of severe stroke, respectively. The primary outcome was to investigate the relationship between BPV and 90-day modified Rankin scale (mRS) ≥ 3. The BPV was assessed by eight measurements including standard deviation (SD), mean, maximum, minimum, coefficient of variation (CV), successive variation (SV), functional successive variation (FSV), and average real variability (ARV). Then, the SD of SBP was divided into quintiles and compared the quintile using logistic regression in three models. The acute phase included 442 patients, and the subacute phase included 390 patients. After adjustment, six measurements of BPV during the subacute phase rather than acute phase were strongly correlated with outcomes including minimum (odds ratio [OR]: 0.83, 95% confidence interval [CI]: 0.69-0.99, p = .037), SD (OR: 1.10, 95% CI: 1.03-1.17, p = .007), CV (OR: 1.12, 95% CI: 1.03-1.23, p = .012), ARV (OR: 1.13, 95% CI: 1.05-1.20, p < .001), SV (OR: 1.09, 95% CI: 1.04-1.15, p = .001), and FSV (OR: 1.12, 95% CI: 1.05-1.19, p = .001). In the logistic regression, the highest fifth of SD of SBP predicted poor outcome in all three models. In conclusion, the increased BPV was strongly correlated with poor outcomes in the subacute phase of severe stroke, and the magnitude of association was progressively increased when the SD of BP was above 12.

Possible coexistence of MOG-IgG-associated disease and anti-Caspr2 antibody-associated autoimmune encephalitis: a first case report.

Myelin oligodendrocyte glycoprotein antibody-associated disease has been proposed as a separate inflammatory demyelinating disease of the central nervous system (CNS) since the discovery of pathogenic antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG). Antibodies targeting contactin-associated protein-like 2 (Caspr2), a component of voltage-gated potassium channel (VGKC) complex, have been documented to be associated with a novel autoimmune synaptic encephalitis with a low incidence. Herein, we reported an adult female with initial presentation of decreased vision in the right eye and subsequent episodes of neuropsychiatric disturbance including hypersomnia, agitation, apatheia, and memory impairment. Magnetic resonance imaging (MRI) revealed multiple lesions scattered in brain, brainstem, and cervical and thoracic spinal cord, showing hypointensity on T1-weighted images, hyperintensity on T2-weighted and fluid attenuated inversion recovery (FLAIR) images. Heterogenous patchy or ring-like enhancement was observed in the majority of lesions. The detection of low-titer MOG-IgG exclusively in cerebrospinal fluid (CSF; titer, 1:1) and Caspr2-IgG in both serum and CSF (titers, 1:100 and 1:1) led to a possible diagnosis of coexisting MOG-IgG-associated disease (MOGAD) and anti-Caspr2 antibody-associated autoimmune encephalitis. The patient was treated with immunosuppressive agents including corticosteroids and immunoglobulin, and achieved a sustained remission. To the best of our knowledge, this is the first report on the possible coexistence of MOGAD and anti-Caspr2 antibody-associated autoimmune encephalitis, which advocates for the recommendation of a broad spectrum screening for antibodies against well-defined CNS antigens in suspected patients with autoimmune-mediated diseases of the CNS.

Prediction of generalization of ocular myasthenia gravis under immunosuppressive therapy in Northwest China.

BACKGROUND: It is well demonstrated that immunosuppressants can reduce, but not eliminate the risk of generalized development in ocular myasthenia gravis (OMG). In this study, we aimed to explore the predictive factors of generalized conversion of OMG patients who received immunosuppressive treatments. METHODS: OMG patients under immunosuppressive treatments in Tangdu Hospital from June 2008 to June 2012 were retrospectively reviewed. Baseline clinical characteristics were documented. Patients were followed up regularly by face-to-face interview and the main outcome measure was generalized conversion. The logistic regression analysis was performed to determine the predictive factors of generalization of OMG. RESULTS: Two hundred twenty-three eligible OMG patients completed the final follow-up visit and 38 (17.0%) progressed to generalized MG (GMG) at a median time to generalization of 0.9 year. Patients with adult onset and positive repetitive nerve stimulation (RNS) of facial or axillary nerve had higher conversion rate than those with juvenile onset and negative RNS (p = 0.001; p = 0.019; p = 0.015, respectively). Adult-onset patients converted earlier than juvenile-onset OMG patients (p = 0.014). Upon multivariate logistic regression analysis, age of onset (Odds ratio [OR] 1.023, 95% confidence interval [CI] 1.006-1.041, p = 0.007) and positive facial nerve RNS (OR 2.826, 95%CI 1.045-5.460, p = 0.038) were found to be positively associated with generalized development. Moreover, an obviously negative association was found for disease duration (OR 0.603, 95%CI 0.365-0.850, p = 0.019). CONCLUSIONS: Age of onset, disease duration and facial nerve RNS test can predict generalized conversion of OMG under immunosuppressive therapy. Adult-onset, shorter disease duration and facial nerve RNS-positive OMG patients have a higher risk of generalized development.

Overlapping syndrome of MOG-IgG-associated disease and autoimmune GFAP astrocytopathy.

Antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) have been considered to be closely relevant to an inflammatory demyelinating disease of the central nervous system (CNS). Glial fibrillary acidic protein (GFAP) immunoglobulin G (IgG) has been identified as a biomarker for a novel autoimmune astrocytopathy. However, coexistence of MOG-IgG and GFAP-IgG is extremely unusual and only one patient has been described with simultaneous presence of MOG-IgG in serum and GFAP-IgG in cerebrospinal fluid (CSF). Herein, we reported the first case of overlapping syndrome of MOG-IgG-associated disease (MOG-AD) and autoimmune GFAP astrocytopathy in whom MOG-IgG and GFAP-IgG were detected both in serum and CSF. A 20-year-old male patient was referred to our department with the presentation of decreased vision, diplopia and weakness of right limb with unknown reasons. Magnetic resonance imaging (MRI) revealed multiple intracranial lesions presenting hypointensity on T1-weighted images, hyperintensity on T2-weighted and FLAIR images and patchy contrast enhancement. MOG-IgG and GFAP-IgG were detected both in serum and CSF, and the titers of both antibodies fluctuated with the severity of disease. Treatment strategy employing intravenous methylprednisolone pulse therapy followed by oral prednisone with slow tapering resulted in an improvement of his symptoms and a sustained remission. Coexistence of MOG-IgG and GFAP-IgG with distinct underlying pathogeneses necessitates the recommendations to screen all recognized pathogenic antibodies against CNS antigens when an autoimmune disease is suspected, since it shows great significance for definite diagnosis of disease and treatment strategy options.

Azathioprine-induced pellagra in neuromyelitis optica: A case report and review of literature.

Neuromyelitis optica (NMO), also known as Devic's disease, is a classical autoimmune disorder of the central nervous system (CNS). The relapsing-remitting disease course contributes to application of a variety of immunosuppressants to prevent further relapses after high-dose methylprednisolone pulse therapy for acute attacks. Azathioprine is one of the most widely used immunosuppressive drugs during the remission stage of NMO due to its good efficacy and favorable side-effect profile. Even if, enough attention should be paid to some rare but devastating adverse events, such as pellagra. Herein, we reported that a well-nourished patient experienced serious pellagra while receiving oral azathioprine for treating her NMO. Moreover, literature on azathioprine-induced pellagra was reviewed to raise concerns regarding patient safety.

T Follicular Helper-Like Cells Are Involved in the Pathogenesis of Experimental Autoimmune Encephalomyelitis.

Multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) have been proved to be T cell-mediated autoimmune diseases. Recent researches indicate that humoral immunity is also involved in the pathogenesis of these disorders. T follicular helper (Tfh) cells are critical for B cell differentiation and antibody production. However, the role of Tfh cells in MS and EAE remains unclear. Here, we found elevated frequencies of CD4+CXCR5+PD-1+ Tfh-like cells in both MS patients and EAE. In EAE mice, Tfh-like cells, together with B cells, were found in the ectopic lymphoid structures in spinal cords. Moreover, Tfh-like cells promoted the antibody production via IL-21/IL-21R and CD40 ligand/CD40 interaction and the synergy effect of STAT3 and non-canonical NF-κB signaling pathway inside B cells. Moreover, adoptive transfer of Tfh-like cells could increase the severity and delay the remission of EAE. In conclusion, our data indicate that Tfh-like cells contribute to the pathogenesis of EAE.