COVID-19 vaccination for patients with epilepsy: A Chinese expert consensus.

Coronavirus disease-2019 (COVID-19) first emerged in late 2019 and has since spread worldwide. More than 600 million people have been diagnosed with COVID-19, and over 6 million have died. Vaccination against COVID-19 is one of the best ways to protect humans. Epilepsy is a common disease, and there are approximately 10 million patients with epilepsy (PWE) in China. However, China has listed "uncontrolled epilepsy" as a contraindication for COVID-19 vaccination, which makes many PWE reluctant to get COVID-19 vaccination, greatly affecting the health of these patients in the COVID-19 epidemic. However, recent clinical practice has shown that although a small percentage of PWE may experience an increased frequency of seizures after COVID-19 vaccination, the benefits of COVID-19 vaccination for PWE far outweigh the risks, suggesting that COVID-19 vaccination is safe and recommended for PWE. Nonetheless, vaccination strategies vary for different PWE, and this consensus provides specific recommendations for PWE to be vaccinated against COVID-19.

Genetic origin of sporadic cases and RNA toxicity in neuronal intranuclear inclusion disease.

BACKGROUND: GGC repeat expansion in NOTCH2NLC has been recently linked to neuronal intranuclear inclusion disease (NIID) via unknown disease mechanisms. Herein, we explore the genetic origin of the sporadic cases and toxic RNA gain-of-function mechanism in NIID. METHODS: Multiple genetic screenings were performed on NIID individuals and their available family members. Methylation status of blood DNA, NOTCH2NLC mRNA level from muscle biopsies and RNA foci from skin biopsies of NIID individuals or asymptomatic carriers were evaluated and compared. RESULTS: In two sporadic NIID families, we identified two clinically and pathologically asymptomatic fathers carrying large GGC repeat expansion, above 300 repeats, with offspring repeat numbers of 172 and 148, respectively. Further evaluation revealed that the GGC repeat numbers in the sperm from two asymptomatic fathers were only 63 and 98, respectively. The CpG island in NOTCH2NLC of the asymptomatic carriers was hypermethylated, and accordingly, the NOTCH2NLC mRNA levels were decreased in the asymptomatic fathers. GGC repeat expansion RNA formed RNA foci and sequestered RNA binding proteins into p62 positive intranuclear inclusions in NIID individuals but not in the control or asymptomatic carrier. CONCLUSION: Our study suggested the GGC repeat expansion in NOTCH2NLC might have a disease-causing number ranging from ~41 to ~300 repeats. The contraction of GGC repeat expansion in sperm could be a possible mechanism for the paternal-biased origin in some sporadic or recessive inherited NIID individuals. The toxic RNA gain-of-function mechanism was identified to be involved in the pathogenicity of this disease.

Changes of B cell subsets in central pathological process of autoimmune encephalomyelitis in mice.

BACKGROUND: Multiple sclerosis is a demyelinating and autoimmune disease and its immune response is not fully elucidated. This study was conducted to examine the pathological changes and B cell subsets in experimental autoimmune encephalomyelitis (EAE) mice, and analyze the expression of triosephosphate isomerase (TPI) and GADPH to define the role of B cell subsets in the disease. RESULTS: Female C57BL/6 mice were randomly divided into EAE group (n = 18) and control (n = 18). During the experiments, the weight and nerve function scores were determined. The proportions of B cell subsets in the peripheral blood were measured by flow cytometry. Seven, 18 and 30 days after immunization, the brain and spinal cord tissues were examined for the infiltration of inflammatory cells using hematoxylin-eosin (HE) HE staining and the demyelination using Luxol fast blue staining. The expression of B cell-related proteins was detected immunohistochemistrially and the expression of antigenic TPI and GADPH was analyzed using enzyme-linked immunosorbent assay (ELISA). HE staining showed that mice had more severe EAE 18 d than 7 d after modelling, while the symptoms were significantly relieved at 30 d. The results were consistent with the weight measurements and neural function scores. Immunohistochemistry studies showed that B cells aggregated in the spinal cord, but not much in the brain. Flow cytometry studies showed that there were more B cells in control than in EAE models from day 7 and the difference was narrowed at day 30. The level of plasma cells increased continuously, reached the top at day 21 and obviously declined at day 30. On other hand, the numbers of memory B cells increased gradually over the experimental period. The numbers of plasma and memory B cells were similar between the control and EAE mice. ELISA data revealed that the brain contents of TPI and GAPDH were higher in EAE mice than in control at day 7, while at day 18, the levels were reversed. CONCLUSIONS: In the central pathological process of EAE mice, B cells exert role through the mechanism other than producing antibodies and the levels of brain TPI and GADPH are related to the severity of autoimmune induced-damage.

Application of quantitative EEG in acute ischemic stroke patients who underwent thrombectomy: A comparison with CT perfusion.

OBJECTIVE: This study aimed to evaluate the predictive value of quantitative electroencephalography (QEEG) in the outcome of patients with acute ischemic stroke (AIS) who underwent mechanical thrombectomy (MT) and to assess the correlation between clinical outcome and QEEG and CT perfusion (CTP) data. METHODS: Twenty-nine MT patients were included in this prospective study. Continuous electroencephalography (EEG) monitoring was performed, in which delta power, the δ/α ratio (DAR), and the (θ + Î´)/(α + ß) ratio (DTABR) were calculated. The clinical scores at different points were recorded. Based on the modified Ranking scale, the patients were divided into good and poor outcome groups. Several CTP parameters were recorded before MT. The correlation between QEEG, CTP parameters, and clinical scores was analyzed using the Spearman correlation analysis. The predictive value of QEEG indices and CTP parameters for the 3-month outcome was compared using the receiver operating characteristic (ROC) curve. RESULTS: Delta power except for 7 days after MT, DAR, DATBR, and several CTP parameters were all significantly associated with the clinical scores. Although some CTP parameters were associated with the clinical scores, they were less powerful than QEEG in predicting a good or poor outcome at 3 months. Among the different explored EEG indicators, the predictive value of delta 24 h after MT was the highest. CONCLUSIONS: QEEG indices may have a certain predictive value for the outcome of AIS patients who underwent MT. SIGNIFICANCE: QEEG may become a new prognostic tool in AIS patients who underwent MT, facilitating the planning and management of related rehabilitation plans.

Reduction of Peripheral Blood iNKT and γδT Cells in Patients With Parkinson's Disease: An Observational Study.

Objective: To investigate the frequencies and numbers of invariant natural killer T (iNKT) cells and γδT cells in the peripheral blood of patients with the Parkinson's disease (PD), and to examine their association with the PD severity. Methods: Peripheral blood samples from 47 PD patients (PD group) and 47 age-matched healthy control subjects (HC group) were collected. The frequencies and the absolute cell numbers were analyzed by flow cytometry. Mann-Whitney U-test was used to test the difference between two groups, where P < 0.05 was considered as significant. An ordered probit regression method was used to examine the association of the iNKT and γδT cells with severity of PD. Results: Patients in the PD group showed significantly lower frequencies (0.039 vs. 0.139%; P = 0) and cell counts (308/mL vs. 1,371/mL; P = 0) of iNKT cells compared to the HC group. Moreover, the percentages and absolute numbers of γδT cells were significantly decreased in the PD group compared to the HC group (3.69 vs. 7.95% and 30/µL vs. 66/µL; P = 0). The iNKT cells were significantly reduced in PD patients with higher Unified Parkinson's Disease Rating Scale (UPDRS) scores or cognitive decline. Conclusions: Cell frequencies and absolute numbers of iNKT cells and γδT cells are significantly reduced in the peripheral blood samples of PD patients. Patients with high UPDRS scores or cognitive decline also showed significant reduction of iNKT cells. Our results suggest that iNKT cells and γδT cells may contribute to the development of PD.

Functions of T-cell subsets and their related cytokines in the pathological processes of autoimmune encephalomyelitic mice.

OBJECTIVE: This study aims to observe the pathological changes of the brain and spinal cord in an experimental allergic encephalitis (EAE) mice model in the early onset, peak and remission periods of the disease, to detect the changes in the T-cell subsets and cytokine levels, to analyze the types of immune response and related principles in the different stages of the disease. METHODS: C57BL/6 mice were randomly divided into two groups: the EAE group (n = 18) and the control group (n = 18). C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein (MOG) 35-55 polypeptide/complete Freund's adjuvant (CFA) to establish the EAE mouse model. In the control group, the mice were treated with normal saline. The weights of the mice were recorded during the experiment. Peripheral blood was collected on the 0 day, 3rd day, 7th day, 14th day and 21st day after immunization, and the levels of T-cell subsets were detected by flow cytometry. The brain and spinal cord were taken on the 7th day (early onset), 18th day (peak) and 30th day (remission) after immunization. HE staining was used to observe the infiltration of inflammatory cells, and LFB staining was used to observe the loss of the myelin sheath. The immunohistochemical method was used to detect the T cells and B cell related proteins, and an ELISA assay was used to detect the changes of IL-4, IL-6, IL-10, IL-12, IL-17, IL-23, TNF-α, IFN-γ and TGF-ß in mouse brain tissue. The interactions between the T cell subsets and cytokines, the types of immune responses of the EAE mice in different stages of the disease, and their related principles were analyzed. RESULTS: The symptoms of the EAE mice after treatment for 18 d were more severe than those at 7 d in the mice, while the symptoms were significantly relieved at 30 d. These findings coincide with the results of the weight measurement in mice. The immunohistochemical detection of T-cell and B-cell subset related factors showed that T cells accumulated in the brains of the EAE mice. In contrast, there was no obvious aggregation of B cells. The Th17 and Th2 levels in the T cell subsets in the EAE group were higher than those in the control group from the beginning of the treatment to the twenty-first day after the treatment. The level of Th1 in the EAE group was higher than it was in the control group on the seventh day after the treatment, and it was lower during the rest of the time than it was in the control group. There was no significant difference in the level of γδT between the control group and the EAE group. ELISA results showed that the cytokines in the EAE group were higher than they were in the control group on the seventh day after treatment, but the levels of IFN-γ, IL-12, TGF-ß, and IL-23 in EAE group were lower than they were in the control group on the 18th day after the treatment. There was no significant difference in the levels of cytokines between the two groups on the 30th day after the treatment. CONCLUSIONS: At the different disease stages of the EAE mice, the balance between Th1 and Th2 and the balance of Th17 differentiation changed. Th17 promoted the development of the disease, and Th2 was more effective in restoring health.

Relationship of atopic dermatitis with stroke and myocardial infarction: A meta-analysis.

BACKGROUND: Lots of previous reports have suggested a potential association of atopic dermatitis (AD) with stroke and myocardial infarction (MI). However, the result is still controversial, Consequently, we conducted this meta-analysis to estimate the relationship of AD with Stroke and MI. METHODS: PubMed, Embase, and Web of Science databases were searched from inception to June 2018. Stroke and MI were considered as a composite endpoint. We calculated pooled hazard ratios (HRs) with 95% confidence intervals (CIs). Subgroup and sensitivity analysis were performed to assess the potential sources of heterogeneity of the pooled estimation. RESULTS: A total of 12 articles with 15 studies involving 3,701,199 participants were included in this meta-analysis. Of these, 14 studies on stroke and 12 on MI. Pooled analysis showed participants with AD experienced a significant increased risk of stroke (combined HR, 1.15; 95% CI, 1.08-1.22; P = .000) and MI (combined HR, 1.13; 95% CI, 1.02-1.24; P = .014), compared with participants without AD. The risk of stroke and MI was significant both in male subjects (stroke: HR: 1.33, 95% CI: 1.14-1.56; MI: HR: 2.01, 95% CI: 1.31-3.08), but not in female subjects (HR: 1.02, 95% CI: 0.77-1.35; MI: HR: 0.98, 95% CI: 0.72-1.32). The results were more pronounced for ischemic stroke (HR: 1.16, 95% CI: 1.13-1.19) in the stratified with stroke type. Stratifying by AD type, the risk of stroke was significant in severe AD (HR: 1.29, 95% CI: 1.08-1.54) and moderate AD (HR: 1.11, 95% CI: 1.01-1.22) for MI. CONCLUSIONS: AD is independently associated with an increased risk of stroke and MI, especially in male subjects and ischemic stroke and the risk is associated with the severity of AD.

Effect of glycated hemoglobin index and mean arterial pressure on acute ischemic stroke prognosis after intravenous thrombolysis with recombinant tissue plasminogen activator.

To determine whether glycated hemoglobin and mean arterial pressure (MAP) during thrombolysis are prognostic factors of intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) for acute ischemic stroke (AIS).A total of 125 AIS patients, who received rt-PA intravenous thrombolysis in our hospital, were included into the present study, and divided into good prognosis group and poor prognosis group. Univariate and multivariate logistic regression analyses were used to determine the prognostic factors of AIS treated by rt-PA thrombolysis, Spearman correlation analysis was used to analyze the correlation of the accumulated cigarette consumption in the smoking subgroup and glycated hemoglobin in the diabetic subgroup with the prognosis after intravenous thrombolysis and the symptomatic intracranial hemorrhage (sICH).Univariate analysis revealed that the interval from onset to thrombolysis, baseline National Institutes of Health Stroke Scale (NIHSS) score, MAP during thrombolysis and DRAGON score were prognostic factors. Multivariate logistic regression analysis revealed that baseline NIHSS score and MAP during thrombolysis were independent prognostic factors for rt-PA thrombolysis. Furthermore, the glycated hemoglobin index was positively correlated with the incidence of sICH.The NIHSS score before thrombolysis and MAP during thrombolysis were independent factors for the prognosis of AIS treated by thrombolysis. The higher the glycated hemoglobin index of diabetic patients, the more likely they are to develop sICH, the glycated hemoglobin index was negatively correlated with the prognosis after intravenous thrombolysis. The accumulated cigarette consumption was negatively correlated with the prognosis after intravenous thrombolysis.

Comparisons of the therapeutic effects of three different routes of bone marrow mesenchymal stem cell transplantation in cerebral ischemic rats.

Bone marrow mesenchymal stem cells (BMSCs) are mainly administered via three routes: intra-arterial, intravenous and intracerebral. It has been reported that BMSC administration via each route ameliorates the functional deficits after cerebral ischemia. However, there have been no comparisons of the therapeutic benefits of BMSC administration through different delivery routes. In this study, we injected BMSCs into a rat model of transient middle cerebral artery occlusion (MCAO) through the intra-arterial, intravenous, or intracerebral route at day 7 after MCAO. Control animals received only the vehicle. Neurological function was assessed at post-ischemic days (PIDs) 1, 7, 14, 21, 28 and 35 using behavioral tests (modified Neurological Severity Score (mNSS) and the adhesive removal test). At PID 35, the rat brain tissues were processed for histochemical and immunohistochemical staining. Our results showed that BMSC transplantation via the intra-arterial, intravenous, and intracerebral routes induced greater improvement in neurological functions than the control treatments; furthermore, the intra-arterial route showed the greatest degree and speed of neurological functional recovery. Moreover, BMSCs treatment through each route enhanced reconstruction of axonal myelination in the area of the corpus callosum on the infarct side of the cerebral hemisphere, increased the expression of SYN and Ki-67, and decreased the expression of Nogo-A in the brain. These effects were more apparent in the intra-arterial group than in the intravenous and intracerebral groups. These data suggest that BMSCs transplantation, especially through intra-arterial delivery, can effectively improve neurological function intra-arterial. The underlying mechanism may include the promotion of synaptogenesis, endogenous cell proliferation, and axonal regeneration.

[Association of HLA-DRB1 and -DPB1 allele polymorphism with multiple sclerosis in Chinese Han population from Southern areas].

OBJECTIVE: To examine the correlation between multiple sclerosis (MS) in Chinese Southern Han population and the polymorphism of HLA-DRB1 and -DPB1 alleles, and compare it to the reports of Western, Japanese and Northern Chinese populations. METHODS: The HLA-DRB1 and -DPB1 alleles of 26 patients with conventional MS (C-MS), 13 patients with optic-spinal form of MS (OS-MS), and 50 normal controls were determined by sequence-based typing (SBT) method. The frequency of the HLA alleles was compared between the 2 MS subtypes and the MS subtypes and the controls by chi(2) or Fisher exact probability test. The P values were corrected according to Bonferroni's method to calculate corrected the P values (Pc). RESULTS: A total of 27 HLA-DRB1 alleles and 13 HLA-DPB1 alleles were identified in the 39 MS patients and 50 controls. The frequencies of DRB1(*)0406 (P = 0.014, OR = 2.09) and DRB1(*)1302 alleles (P = 0.007, OR = 2.84) were higher in the OS-MS patients than in the controls. In addition, the DRB1(*)120201 allele was more frequent in the C-MS patients than in the controls, and the frequency of DPB1(*)2101 was higher in the OS-MS patients than in the controls. However, all the differences were of no significance since the corrected P values (Pc) were all > 0.1. There was no correlation between the MS subtypes and the HLA-DRB1(*)1501 or DPB1(*)0501 as reported in Western and Japanese populations (all P > 0.1). CONCLUSION: The correlation between HLA-DRB1 and -DPB1 in Southern Han MS population is different from that in the Western, Japanese, and Northern Chinese populations. Southern Han MS patients may be linked to the HLA-DRB1(*)0406, DRB1(*)1302, DRB1(*)120201 and DPB1(*)2101, but not to the HLA-DRB1(*)1501 or DPB1(*)0501 alleles as reported in the above populations.

Balo's disease showing benign clinical course and co-existence with multiple sclerosis-like lesions in Chinese.

Baló's concentric sclerosis (BCS) is a rare demyelinating disorder usually considered a variant of multiple sclerosis (MS). However, its pathogenesis and its correlation with MS remains unclear and controversial. This report presents seven Hans Chinese subjects diagnosed as BCS on the basis of the pathognomonic MR (magnetic resonance) findings. Upon diagnosis, all the cases displayed good responses to corticosteroids and showed an overall benign prognosis during a follow-up period of 4-13.5 years, although three relapsed later. MR findings suggest that the characteristic concentric lesions of BCS frequently (5/7) coexist with multiple sclerosis-like lesions. During follow-up, the Baló-like lesions may either dissolve over time or transform into an MS-like lesion. Moreover, the Balóand MS-like lesions occurred one after another at the onset and relapse phases of the same patient in two cases. These clinical features suggest that Baló's disease showing benign clinical course and co-existence of multiple sclerosis (MS)-like lesion is not rare among the Chinese, and strengthens the notion that BCS correlates intrinsically with MS.