Exosomal miR-23a-3p derived from human umbilical cord mesenchymal stem cells promotes remyelination in central nervous system demyelinating diseases by targeting Tbr1/Wnt pathway.

Oligodendrocyte precursor cells are present in the adult central nervous system, and their impaired ability to differentiate into myelinating oligodendrocytes can lead to demyelination in patients with multiple sclerosis, accompanied by neurological deficits and cognitive impairment. Exosomes, small vesicles released by cells, are known to facilitate intercellular communication by carrying bioactive molecules. In this study, we utilized exosomes derived from human umbilical cord mesenchymal stem cells (HUMSCs-Exos). We performed sequencing and bioinformatics analysis of exosome-treated cells to demonstrate that HUMSCs-Exos can stimulate myelin gene expression in oigodendrocyte precursor cells. Functional investigations revealed that HUMSCs-Exos activate the Pi3k/Akt pathway and regulate the Tbr1/Wnt signaling molecules through the transfer of miR-23a-3p, promoting oligodendrocytes differentiation and enhancing the expression of myelin-related proteins. In an experimental autoimmune encephalomyelitis model, treatment with HUMSCs-Exos significantly improved neurological function and facilitated remyelination. This study provides cellular and molecular insights into the use of cell-free exosome therapy for central nervous system demyelination associated with multiple sclerosis, demonstrating its great potential for treating demyelinating and neurodegenerative diseases.

Clinical characteristics and prognosis in patients with neuronal surface antibody-mediated autoimmune encephalitis: a single-center cohort study in China.

Objective: This retrospective observational study primarily aimed to analyse the clinical characteristics of patients with neuronal surface antibody-mediated autoimmune encephalitis (AE) in China and report their prognosis after immunotherapy. Methods: Clinical characteristics, laboratory or imaging examinations, and treatment outcomes of 103 patients diagnosed with AE between 1 September 2014 and 31 December 2020 were collected. Univariate and multivariate logistic regression analyses were performed to determine the predictors of poor prognosis. Results: Overall, 103 patients were enrolled in the study. The main clinical symptoms included seizures (74.8%), psychiatric and behavior disorders (66.0%), cognitive deficits (51.5%), disturbances of consciousness (45.6%), and movement disorders/involuntary movements (26.2%). The distribution of clinical syndromes also differed for different AE subtypes. The efficacy rates of first-line immunotherapy for anti-NMDAR, anti-LGI1, anti-GABABR, and anti-CASPR2 encephalitis were 70.2%, 92.3%, 70%, and 83.3%, respectively, and rituximab was administered to 21 patients as second-line immunotherapy, including 14 patients with anti-NMDAR encephalitis, 4 with anti-LGI1 encephalitis, 2 with anti-GABABR encephalitis, and 1 with anti-CASPR2 encephalitis. Five patients with poor effect of the second-line treatment received bortezomib. According to the results of the last follow-up, 78 patients had a good prognosis (mRS 0-2), and 21 patients had a poor prognosis (mRS 3-6). The proportion of patients with a poor prognosis was significantly higher in anti-GABABR encephalitis compared to the other AE subtypes (p<0.001). Multivariate analysis indicated that elevated neutrophil-to-lymphocyte ratio (NLR) and tumour presence were independent risk factors for poor prognosis. The regression equation of the model was logit(P)=-3.480 + 0.318 NLR+2.434 with or without tumour (with assignment =1, without assignment =0). The prediction probability generated by the regression model equation was used as the independent variable for receiver operating curve (ROC) analysis. The results showed that the area under the curve (AUC) of the prediction probability was 0.847 (95% CI, 0.733-0.961; p < 0.001). Conclusions: Different AE subtypes demonstrated different clinical symptom spectra throughout the disease stage. Anti-LGI1 encephalitis and anti-CASPR2 encephalitis were more sensitive to first-line and second-line treatments. Anti-GABABR encephalitis had the worst prognosis among the abovementioned subtypes. The regression equation constructed using NLR and tumour presence effectively predicted the poor prognosis.

Long-term efficacy and safety of different corticosteroid courses plus mycophenolate mofetil for autoimmune encephalitis with neuronal surface antibodies without tumor.

Objective: To compare the efficacy and safety of different-course corticosteroids plus mycophenolate mofetil (MMF) as maintenance therapy in autoimmune encephalitis (AE) with neuronal surface antibodies (NSAbs) without tumor and explore the optimal course of corticosteroids. Methods: Fifty-five patients with definite AE without tumor were enrolled consecutively between June 2015 and November 2020 and retrospectively divided three groups according to the course of treatment with corticosteroid, i.e., a group of patients with a course of 3-6 months (Group 3-6mo), 6-12 months (Group 6-12mo), and >12 months (Group >12mo). Demographic data, clinical manifestation and ancillary tests results were recorded. The dosage and courses of corticosteroid treatment, the recovery of neurological function, the occurrence of adverse effects, and relapses were followed up. Results: A total of 55 patients were included in the final analysis. The numbers of patients in Group 3-6 mo, Group 6-12 mo, and Group >12 mo was 14, 17, and 24, respectively. A significantly higher proportion of patients in Group >12 mo showed a decreased level of consciousness at the onset (12, 50%) than in Group 3-6 mo and Group 6-12 mo (2,14.3%; 3, 17.6%) (p = 0.033). The incidence of MRI abnormalities was significantly higher in Group 6-12 mo and Group >12 mo (10, 58.8%; 16, 66.7%) than in Group 3-6 mo (3, 21.4%) (P=0.023). Ordinal regression analysis indicated that decreased level of consciousness was associated with the course of corticosteroid (OR=3.838, 95% CI: 1.103-13.323, P=0.035). No significant difference was observed between the three groups regarding the cumulative dose of corticosteroids administered during the first three months of long-term treatment (P>0.05). Additionally, no significant difference in the cumulative dosage of corticosteroids was found between patients in Group 6-12 months and Group >12 months during the first 6 months after beginning long-term treatment. The mRS scores of the three groups were not statistically significant before and after first-line treatment or at the last follow-up. Bonferroni multiple comparison test indicated that the mRS scores of patients in Group 6-12 months and Group >12 months were not statistically significant at 3 months and 12 months after the start of long-term treatment. During the follow-up, 50 (90.9%) patients achieved satisfactory neurological function (mRS score ≤2). Five patients (9.1%) experienced a first relapse and 2 of them were overlapped with both anti-NMDA receptor and glial antibodies. The incidence of adverse effects was significantly higher in Group >12 mo (17, 70.8%) than in Group 3-6 mo (3, 21.4%) and Group 6-12 mo (5, 29.4%) (P=0.003). Conclusions: The beneficial effects of oral corticosteroid treatment may do not persist beyond 12 months and may even contribute to an increased incidence of adverse effects. In order to optimize the effectiveness and safety of treatment, we recommend a corticosteroid course of 3-12 months. Patients with reduced levels of consciousness may be more inclined to choose longer courses of corticosteroids for long-term treatment. Patients with an "overlapping syndrome" may require more intense immunotherapy to prevent relapse.

Clinical Features, Treatment, and Prognostic Factors in Neuronal Surface Antibody-Mediated Severe Autoimmune Encephalitis.

Objective: This study aimed to determine the clinical characteristics and evaluate the efficacy of immunotherapy and the long-term prognosis of severe autoimmune encephalitis (AE) in China. Methods: Clinical features, laboratory or radiological findings, and treatment outcomes of 60 severe patients with AE from January 1, 2014, to December 31, 2020, were collected. Continuous variables were compared using the t-test and the nonparametric Mann-Whitney U test, as appropriate. Univariate and multivariable logistic regression analyses were performed to assess the correlations between factors, treatment responses, and prognosis of severe AE. Results: The median age of symptom onset was 35 years. Tumors were identified in 23.3% of patients, and 36/60 (60%) patients responded to first-line immunotherapy. Second-line immunotherapy was implemented in 26/60 (43.3%) patients. A significant clinical benefit was observed in 19/26 (73.1%) patients treated with lower dosage rituximab; seven patients were still refractory and received bortezomib as an add-on therapy. During the last follow-up, 48/60 (80%) patients achieved good outcomes (mRS, 0-2), and 10 died. Seventeen patients experienced relapses. A high CD19+ B-cell count (OR, 1.197; 95% CI [1.043-1.496]; p = 0.041) and a lower neutrophil-to-lymphocyte ratio (NLR; OR, 0.686; 95% CI [0.472-0.884]; p = 0.015) predict the response to first-line treatment and good prognosis, respectively. Conclusions: Patients with severe AE were in critical condition at baseline but could be salvaged after effective rescue immunotherapy. A lower dosage of rituximab could be an optimal option for severe AE. CD19+ B-cell count and NLR may provide prognostic information for predicting treatment response and outcome of severe AE.

Low high-density lipoprotein cholesterol and apolipoprotein A-I levels are associated with poor outcome and relapse in autoimmune encephalitis.

BACKGROUND: Growing evidence suggests an association between dyslipidemia and autoimmune diseases. This study aimed to investigate the relationship between lipid profiles and prognosis of autoimmune encephalitis (AE) patients. METHODS: This retrospective study consisted of 114 AE patients from September 2014 to September 2020. Data of clinical parameters, including age, sex, body mass index (BMI), clinical features, comorbidities, therapeutic management, lipid profiles, modified Rankin scale (mRS) scores, outcomes, and relapses were collected. Logistic regression models were used to examine the associations between lipid profiles and outcomes of AE. Correlations between lipid profiles and C-reactive protein (CRP), which is an inflammatory marker, were assessed. RESULTS: In the univariate logistic analysis, sex (P = 0.030), mental behavior disorder (P = 0.004), disturbance of consciousness (P = 0.002), mRS at study entry (P = 0.020), tumor comorbidity (P = 0.028), high-density lipoprotein cholesterol (HDL-C) (P = 0.029), apolipoprotein A-I (apoA-I) (P = 0.012), apolipoprotein B (apoB) (P = 0.036) and apoA-I/apoB (P = 0.001) levels were all associated with the unfavorable outcomes of patients. After adjustment for age, sex and mRS at study entry, lower apoA-I and apoA-I /apoB levels were still significantly associated with the unfavorable outcomes of patients. Low HDL-C (P = 0.048) and apoA-I levels (P = 0.026) were also significantly associated with the relapse of AE patients. HDL-C and apoA-I levels were negatively correlated with CRP levels in correlation analysis. CONCLUSIONS: Lipid profiles, especially low HDL-C and apoA-I levels, are significantly associated with the poor outcomes and relapse of AE patients, and seem associated with inflammatory responses. HDL-C and apoA-I levels may be good candidates for predicting prognosis of AE patients.

Eculizumab treatment for myasthenia gravis subgroups: 2021 update.

Eculizumab is a recombinant humanized monoclonal antibody that targets the complement protein C5, inhibiting its cleavage into C5a and C5b and ultimately preventing the formation of C5b-9 membrane attack complex (MACs), thereby protecting the neuromuscular junction from the damage of complement activation. In 2017, eculizumab became the second FDA-approved medication for AchR-positive generalized myasthenia gravis (gMG) patients based on the successful results of a randomized, double-blinded, placebo-controlled, phase 2, phase 3 study (the REGAIN trial) and its open-label extension study. Despite the efficacy of eculizumab in treating AchR antibody-positive refractory gMG was demonstrated in the REGAIN study, there is few information on its efficacy in other subgroup of MG patients including seronegative MG, thymoma-associated MG and MG crisis. This narrative review summarizes current clinical studies of eculizumab in these refractory gMG patients, with a focus on the therapeutic efficacy and tolerability in different subgroup of MG.

Efficacy and safety of bortezomib in rituximab-resistant anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis as well as the clinical characteristics: An observational study.

Treatment resistance leads to physiological, psychological, and economical effects among patients with anti-N-methyl d-aspartate receptor (anti-NMDAR) encephalitis, and the clinical and immune characteristics of these patients remain to be described. According to our clinical experience, bortezomib may be effective due to its plasma-cells depletion ability. Herein, the clinical presentations and immune parameters, including B cell and antibody secreting cell (ASC) abundance, of 5 enrolled treatment-resistant patients are described. When compared with 5 treatment-sensitive cases, the patients had serious clinical presentations but comparable B cells and ASCs. After receiving bortezomib, the ASC count and anti-NMDAR antibody titers decreased effectively. All 5 patients had a favorable prognosis (mRS ≤ 2) with a median follow-up of 31 months without severe side effects or relapse.

Complement C3 polymorphism is associated with the susceptibility of myasthenia gravis in Chinese adult patients.

Complement component 3 (C3) had been proved to be involved in the pathogenesis and exacerbation of both myasthenia gravis (MG) patients and experimental autoimmune myasthenia gravis (EAMG) models. We evaluated the underlying association between five SNPs (rs344555, rs7951, rs3745568, rs366510 and rs163913) in C3 gene and Chinese adult MG patients. Our study consisted of 409 adult MG patients and 487 healthy controls. Subgroups were classified by gender, onset age, thymoma, anti-AChR antibody, onset muscle involvement (ocular/generalized) and severity (Oosterhuis score at the maximal severity during the initial two years after the onset of MG). We found significant differences in allele frequencies between MG and the control group, between various MG subgroups and the control group in rs344555 and rs3745568. There were significant differences in genotype frequencies between MG group and the control group, between MG subgroups and the control group under the codominant and additive inheritance models in rs344555 and rs3745568. No association was found between the frequencies of these SNPs and the severity of MG. We also used a comprehensive classification which was close to the clinical scenario to minimize the interaction among clinical features. In rs344555, the T allele frequency in thymoma (-) AChR-Ab (+) subgroup was significantly higher than that in the control group. Our results indicated that rs344555 was associated with the susceptibility of Chinese adult MG patients; rs3745568 was probably associated with the susceptibility of Chinese adult MG patients. No association was found between the frequencies of these SNPs and the severity of MG.

High serum creatinine is associated with reduction of psychiatric symptoms in female patients with anti-NMDAR encephalitis.

OBJECTIVE: Serum creatinine (SCR) has been shown to be associated with many neurodegenerative diseases. In this study, we investigated the relationship between SCR levels and the incidence of psychiatric symptoms in patients with anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis. METHODS: The SCR levels were tested in 69 patients with anti-NMDAR encephalitis at admission. Clinical characteristics and blood and CSF parameters were compared between the group of patients with psychiatric symptoms (P + group) and the group of those without psychiatric symptoms (P- group). The association between SCR and the incidence of psychiatric symptoms was determined by multivariate-adjusted linear regression analyses. RESULTS: The SCR levels in the P + group were significantly lower than those in the P- group (P < 0.001). In the female subgroup, the SCR levels in the P + group were significantly lower compared to the P- group (P < 0.001), whereas in the male subgroup, the SCR levels did not differ between the two groups (P = 0.084). Furthermore, the highest SCR tercile overall had a significantly lower incidence of psychiatric symptoms than the lowest tercile (P < 0.001), and a significant negative correlation between the SCR levels and the occurrence of psychiatric symptoms was observed (r = -0.392, P < 0.001). Multivariate logistic regression analysis showed that the association was independent after adjusting for age, cystatin C and the modified Rankin Scale (mRS) score (P = 0.001). A similar result was found in the female subgroup (P = 0.010), but not in the male subgroup (P = 0.225). CONCLUSION: Our study indicated that the SCR level was negatively correlated with incidence of psychiatric symptoms in female patients, and higher SCR level could be a protective factor for psychiatric symptoms in female patients with anti-NMDAR encephalitis.

Follow-up of a Rickettsia felis encephalitis: Some new insights into clinical and imaging features.

Rickettsia felis (R. felis) infection is a cause of unspecified encephalitis. However, the incidence has been underestimated due to the intracellular features of the pathogen and insufficient understanding of its clinical picture. This study reported a case of R. felis infection in a 26-year-old female who only manifested with certain neurological symptoms. With a lack of specific systemic inflammatory symptoms, the diagnosis was initially misdiagnosed as a brain glioma. However, a brain tissue biopsy showed prominent perivascular inflammatory infiltrations, which indicated inflammatory disease. Spinal fluid metagenomic next-generation sequencing (mNGS) was taken after ruling out other common infectious and autoimmune diseases. The results suggested R. felis infection, which was also supported by Weil-Felix reaction in the serum. After the diagnosis was corrected as R. felis encephalitis, the patient was successfully treated with doxycycline and had a good prognosis at the 1-year follow-up.

A Retrospective Study of Patients with GABABR Encephalitis: Therapy, Disease Activity and Prognostic Factors.

PURPOSE: To explore the effects of immunotherapy and tumour treatment on patients with GABABR encephalitis, evaluate the correlation between immune cell subsets and disease activity, and investigate effective prognostic factors. PATIENTS AND METHODS: Twenty patients with γ-aminobutyric acid B receptor (GABABR) encephalitis were enrolled from December 2015 to April 2020. The clinical data, modified Rankin Scale (mRS) score, prognosis and percentage of serum lymphocytes were recorded. RESULTS: All patients received first-line immunotherapy. The median mRS scores were 4 and 3 before and after first-line immunotherapy (P<0.01). Seven patients received second-line immunotherapy and had median mRS scores of 3 and 2 before and after second-line immunotherapy (P=0.015). Small-cell lung cancer was detected in twelve patients. Among the patients who died because of tumours, patients who received tumour treatment lived longer than patients who did not receive tumour treatment (P=0.025). All four surviving patients who received tumour treatment had good outcomes (mRS≤2). The median serum CD19+B cell percentage in sixteen patients were 20.00% and 13.42% prior first-line immunotherapy and at the last follow-up (P<0.01). After a maximum follow-up of 54 months (median: 12; range: 3-54), eleven patients (55%) had a poor prognosis (mRS>2). Predictors of a poor prognosis were older age (P=0.031), delayed initial improvement after immunotherapy (>4 weeks) (P=0.038) and respiratory failure (P=0.038). CONCLUSION: Aggressive immunotherapy and tumour treatment contribute to improvements in neurological function and a better prognosis of patients with GABABR encephalitis. The serum CD19+B cell percentage may be an indicator of disease activity. Older age, delayed initial improvement after immunotherapy, and respiratory failure may be associated with poor outcomes.

Lipid profiles and their potential inflammatory effects in anti-N-methyl-D-aspartate receptor encephalitis.

BACKGROUND: Growing evidence suggests an association between dyslipidemia and autoimmune diseases. This study aimed to perform a preliminary analysis to investigate the role of lipid profiles in anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis and to preliminarily explore the potential inflammatory effects of lipids on this disease by analyzing the association of lipid profiles with different inflammatory markers. METHODS: This retrospective study consisted of 40 anti-NMDAR encephalitis patients and 74 healthy controls. Serum lipid profiles and different inflammatory markers were analyzed upon admission and at each follow-up. Lipid profiles were compared among subgroups of patients, which were divided according to clinical characteristics. Correlations between lipid profiles and different inflammatory markers were assessed. RESULTS: The results showed that lipid profiles were abnormal and were correlated with both disease severity and prognosis in patients with anti-NMDAR encephalitis. Correlations between lipid profiles and different inflammatory markers were observed. After 12 months of treatment, inflammatory markers changed with lipid profiles, and these changes were significantly correlated. CONCLUSIONS: Lipid profiles are associated with pathogenesis and progression of anti-NMDAR encephalitis, and they are significantly correlated with different inflammatory markers, suggesting that the association of lipids with the disease might be influenced by the inflammatory response.

An unusual case of recurrent episodes of muscle weakness: Co-occurrence of Andersen-Tawil syndrome and glycogen storage disease type IXd.

A 25-year-old male patient presented with periodic paralysis that increased in severity and frequency with age, accompanied with muscle pain and significantly elevated creatine kinase (CK) levels. Initial clinical and genetic examination confirmed Andersen-Tawil syndrome. Although his father carried the same genetic mutation (p.G300A), he experienced minor and infrequent attacks of paralysis. A change in the patient's symptoms, such as accompanying pain, contracture, and significant CK elevation, lead to a reconsideration of the diagnosis. A muscle biopsy of the biceps brachii in the patient revealed glycogen storage, but no tubular aggregates. Analysis of the phosphorylase kinase regulatory subunit alpha 1 (PHKA1) gene revealed a pathogenic mutation (p.C1082X), indicating glycogen storage disease type Ⅸd. The case demonstrates that co-occurrence of glycogen storage disease type Ⅸd may prolong attacks of muscle weakness, and cause serious muscle pain in patients with Andersen-Tawil syndrome.

Cerebellar ataxia as the initial symptom with lesions involving the cerebellum in patient with anti-NMDAR encephalitis: A rare case report and literature review.

Cerebellar ataxia is an atypical presentation of anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis. In patients with anti-NMDAR encephalitis, cerebellar ataxia often develops simultaneously or sequentially with clinical features of demyelinating disorders, paraneoplastic neurologic syndromes, despite unremarkable brain magnetic resonance imagerying (MRI) findings. Herein, we report a patient with anti-NMDAR encephalitis who developed dizziness and gait ataxia as the initial symptoms, simultaneously showing MRI hyperintensities involving the cerebellum, even before manifesting behavioral and cognitive symptoms. We excluded the co-occurrence of other autoantibodies using cell- and tissue-based assays to establish a confirmed diagnosis of definite anti-NMDAR encephalitis.

Thyroid Function and Autoimmune Indications in Patients with Anti-N-Methyl-D-Aspartate Receptor Encephalitis.

OBJECTIVE: Previous studies have shown that functional abnormalities of the thyroid are associated with the pathogenesis of several neurological diseases. However, their relationship in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis remains to be defined. METHODS: Forty-three patients with anti-NMDAR encephalitis were examined for thyroid function and autoimmune indications, in comparison with 225 healthy controls (CTL). Patients were further classified into 2 subgroups based on their free tri-iodothyronine (fT3) levels. Moreover, fT3 levels were also investigated after at least three months of follow-up. The clinical characteristics of the patients and CTL were described in detail. RESULTS: Serum levels of fT3 and thyroid-stimulating hormone (TSH) were found to be relatively lower in patients with anti-NMDAR encephalitis than in CTL (both p < 0.001). Low T3 syndrome also occurred more frequently in anti- NMDAR encephalitis (25.6 vs. 0.4%, p < 0.001). However, no statistical differences were detected between patients and CTL in terms of the positive rate of thyroid antibodies and other types of thyroid dysfunction. Patients with low T3 levels tended to have a longer hospital stay (p = 0.006), a higher rate of abnormal brain magnetic resonance imaging (MRI) findings (p = 0.033), a higher frequency of consciousness declination (p = 0.029), and a higher modified Rankin scale (mRS) score during hospitalization. Low fT3 levels were also associated with abnormal MRI findings, a decline in consciousness, and the mRS score on admission. In addition, fT3 seemed to gradually return to normal levels upon improvement of the mRS score (r = -0.649, p = 0.002). CONCLUSIONS: Low T3 syndrome often copresents in anti-NMDAR encephalitis and indicates a longer hospitalization, abnormal MRI findings, consciousness declination, and a higher clinical severity. However, fT3 levels do not seem to influence the prognosis of anti-NMDAR encephalitis.

Lower dosages of rituximab used successfully in the treatment of anti-NMDA receptor encephalitis without tumour.

OBJECTIVE: The aim of this study was to evaluate the use and efficacy of lower dosages of rituximab for treating anti N-methyl-d-aspartate receptor (NMDAR) encephalitis without tumour. METHODS: We performed a prospective study of 10 patients with anti-NMDAR encephalitis who did not respond to 10 to 14days first-line immunotherapy and received rituximab administered intravenously (IV) at a dosage of 100mg once per week for 4 consecutive weeks. Reinfusion of rituximab was given when CD19+ B-cell counts of total lymphocytes in peripheral blood >1%. The annualized relapse rate (ARR), modified Rankin scale (mRS) and CD19+ B-cell counts were measured every 4 to 10weeks after initial rituximab treatment in order to assess the clinical outcome and efficacy of rituximab. RESULTS: Lower dosages of rituximab led to a significant reduction of mRS and CD19+ B-cells when compared with before the rituximab infusion (P<0.05) and allowed 9 (90%) patients to maintain a stabilised neurological status. One patient experienced a relapse at 19weeks after initial rituximab infusion. Although ARR reduction of all 10 patients did not achieve statistical significance (P>0.05), in the 4 patients who had relapses before rituximab treatment there was an apparent reduction in ARR over 56weeks. At the last follow up, 9 patients (90%) had a good outcome (mRS≤2) including 3 patients (30%) who recovered completely (mRS=0). Transient infusion adverse events occurred in 2 patients. We observed no serious delayed adverse events during the 56weeks follow-up. CONCLUSIONS: In patients with anti-NMDAR encephalitis who did not respond to first-line immunotherapy, early application of lower dosages of rituximab could efficiently reduce CD19+ B-cell counts of peripheral blood and improve the prognosis of anti-NMDAR encephalitis.

Protection against cerebral infarction by Withaferin A involves inhibition of neuronal apoptosis, activation of PI3K/Akt signaling pathway, and reduced intimal hyperplasia via inhibition of VSMC migration and matrix metalloproteinases.

PURPOSE: Stroke is a major public health concern with high rates of morbidity and mortality worldwide. Cerebral ischemia and infarction are commonly associated with stroke. Currently used medications, though effective, are also associated with adverse effects. Development of effective neuroprotective agents with fewer side effects would be of clinical value. We evaluated the effects of Withaferin A (WA), a steroidal lactone derived from the plant Withania somnifera, on experimentally induced cerebral infarction. MATERIALS AND METHODS: The ability of WA to inhibit neuroapoptosis and modulate vascular smooth muscle cell (VSMC) migration and PI3K/Akt signaling was assessed. Separate groups of Sprague Dawley rats were subjected to cerebral occlusion and reperfused for 24h. RESULTS: WA treatment (25, 50 or 100mg/kg bodyweight) significantly reduced the infarct area in a carotid ligation model; WA reduced intimal hyperplasia and proliferating cell nuclear antigen (PCNA)-positive cell counts. Western blotting analysis revealed significantly suppressed PI3K/Akt signaling following cerebral ischemia/reperfusion injury. WA supplementation was found to downregulate apoptotic pathway proteins. WA suppressed PTEN and enhanced p-Akt and GSK-3ß levels and elevated mTORc1, cyclinD1 and NF-κB p65 expression, suggesting activation of the PI3K/Akt pathway. In vitro studies with PDGF-stimulated A7r5 cells revealed that WA exposure severely downregulated matrix metalloproteinases (MMP)-2 and -9 and inhibited migration of A7r5 cells. Additionally, WA reduced the proliferation of A7r5 cells significantly. CONCLUSIONS: WA exerted neuroprotective effects by activating the PI3K/Akt pathway, modulating the expression of MMPs, and inhibiting the migration of VSMCs.

Relationship between dyslipidemia and carotid plaques in a high-stroke-risk population in Shandong Province, China.

INTRODUCTION: The precise associations between stroke and carotid plaques and dyslipidemia are unclear. This population-based study aimed to examine the relationship between carotid plaques and dyslipidemia in a high-stroke-risk population. METHODS: Ultrasonography of left and right carotid arteries was conducted in 22,222 participants in a second screening survey of individuals with high stroke risk. Subjects were divided into two groups according to the presence or absence of carotid plaques. Blood TC (total cholesterol), TG (total triglycerides), and LDL-C (low-density lipoprotein cholesterol) levels were recorded. RESULTS: Multivariate logistic regression analysis, controlled for gender, age, education, geographic region, smoking, exercise, and overweight (Model 2), identified TG as a predictor of carotid-plaque risk (odds ratio [OR] = 1.109, 95% confidence interval [CI]: 1.038-1.185, P = 0.002), and the association between carotid plaques and LDL-C (OR = 0.967, 95%CI: 0.949-0.994, P = 0.019) was less significant, whereas there was no association between carotid plaques and TC (OR = 1.002, 95%CI: 0.932-1.007, P = 0.958). After additional adjustment for hypertension, diabetes, and atrial fibrillation (Model 3), TG remained a risk factor for carotid plaques (OR = 1.086, 95%CI: 1.016-1.161, P = 0.015), but no associations were observed between carotid plaques and LDL-C (OR = 0.972, 95%CI: 0.910-1.038, P = 0.394) or TC (OR = 1.003, 95%CI: 0.933-1.079, P = 0.928). Only the association between TG and carotid plaques (OR = 1.084, 95%CI: 1.014-1.159, P = 0.017) was independent of all covariates (covariates in Model 3 plus history of stroke or transient ischemic attack, and stroke family history) in Model 4. CONCLUSION: These findings indicate that TG was an independent risk factor for carotid plaques in high-risk population for stroke, whereas LDL-C and TC were not associated with the appearance of carotid plaques independently.