To investigate the effect and mechanisms of carbamazepine (CBZ) on the onset and progression of amyotrophic lateral sclerosis (ALS) in SOD1-G93A mouse model.Starting from 64 days of age, SOD1-G93A mice were orally administered with CBZ at 200 mg/kg once daily until death. The disease onset and life span of SOD1-G93A mice were recorded. Motor neurons (MNs) in anterior horn of spinal cord were quantified by Nissl staining and SMI-32 immunostaining. Hematoxylin and eosin (H&E), nicotinamide adenine dinucleotide hydrogen (NADH), modified Gomori trichrome (MGT), and α-bungarotoxin-ATTO-488 staining were also performed to evaluate muscle and neuromuscular junction (NMJ) damage. Expressions of aggregated SOD1 protein and autophagy-related proteins were further detected by Western blot and immunofluorescent staining.Carbamazepine treatment could delay the disease onset and extend life span of SOD1-G93A mice by about 14.5% and 13.9%, respectively. Furthermore, CBZ treatment reduced MNs loss by about 46.6% and ameliorated the altered muscle morphology and NMJ. Much more interestingly, mechanism study revealed that CBZ treatment activated autophagy via AMPK-ULK1 pathway and promoted the clearance of mutant SOD1 aggregation.Our findings uncovered the therapeutic effects of CBZ against disease pathogenesis in SOD1-G93A mice, indicating a promising clinical utilization of CBZ in ALS therapy.
SARS-CoV-2 vaccine has considered being the most effective method to prevent SARS-CoV-2 infection. The safety and effectiveness of the SARS-CoV-2 vaccine has been confirmed. However, in very rare cases, autoimmune neurological diseases may occur. In this article, we report three rare cases of autoimmune encephalitis with definite auto-antibody after SARS-CoV-2 vaccination. They all have good prognosis after treatment. In addition, we first use 18F-DPA-714 PET/MRI to evaluate microglia activation in our patients. We found that 18F-DPA-714 PET/MRI may be a powerful tool for quantitative analysis of neuroinflammation in patients of autoimmune encephalitis. Finally, although rare complications may happen after vaccination, we still consider the benefits of vaccination far outweigh the risks. People without contraindications should be vaccinated without delay to prevent infection in current outbreak situation.
Abstract Background We conducted this study to describe detailed the clinical characteristics, ancillary test results and treatment response of a group of Chinese patients with anti‐IgLON5 disease. Methods We recruited 13 patients with positive IgLON5 antibodies in serum and/or cerebrospinal fluid from nine tertiary referral centers. Patients were enrolled from February 2017 to July 2021. We retrospectively collected information on the presenting and main symptoms, treatment response and follow‐up outcomes. Results The median age of onset for symptoms was 60 (range: 33–73) years and six of the 13 patients were females. The predominant clinical presentations included sleep disturbance (eight patients) and cognitive impairment (seven patients), followed by movement disorders (six patients). Parainfectious cause seemed plausible. Notably, we identified the first case of possible Epstein‐Barr virus (EBV)‐related anti‐IgLON5 disease. Coexisting neural autoantibodies were identified in two patients. Furthermore, two patients had other autoimmune diseases. The IgG subclass was determined in four patients, including two with dominant IgG4 subtype and two with dominant IgG1 subtype. Additionally, 10 patients were treated with immunotherapy and four patients exhibited improvement. Overall, six of 10 patients for whom follow‐up results were assessable had favorable clinical outcomes (modified Rankin Scale score ≤2). Conclusions The clinical spectrum of anti‐IgLON5 disease is variable. Our results highlight a boarder spectrum of anti‐IgLON5 disease.
Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that can virtually involve any organ system of the body. Many efforts have been made to elucidate the pathogeny, but the molecular mechanisms are still not understood. Lymphocytes are considered to play an important role in SLE pathogenesis. Aberrantly activated T cells mediate inflammatory responses and activate B cells to differentiate and produce autoantibodies, resulting in multisystem manifestations [1, 2]. With the wide use of gene technique, more genetic studies on SLE were performed and differentially expressed genes (DEGs) were identified. Integrating and re-analyzing these data can help us understand the molecular mechanisms and identify diagnostic and therapeutic targets of SLE. Objectives: In this study, we downloaded the microarray datasets GSE4588 and GSE10325 from Gene Expression Omnibus (GEO) database to identify the candidate genes in T and B cells respectively. Methods: Datasets GSE4588 and GSE10325 were downloaded from GEO ( http://www.ncbi.nlm.nih.gov/geo ). The DEGs between T or B cells and control samples were screened using GEO2R ( http://www.ncbi.nlm.nih.gov/geo/geo2r ). logFC |fold change| >1 and P-value <0.05 were considered statistically significant. To analyze the function of DEGs, biological analyses were performed using DAVID database ( http://david.ncifcrf.gov ). P<0.05 was considered statistically significant. The PPI networks of DEGs were constructed using STRING database, and an interaction with a combined score >0.4 was considered statistically significant. The PPI networks were drawn using Cytoscape and the most significant module was identified using MCODE. The criteria for selection were: MCODE scores >5, degree cut-off=2, node score cut-off=0.2, Max depth=100 and k-score=2. The hub genes were selected with degrees ≥10. Results: After standardization of the microarray results, DEGs in T and B cells were identified respectively (Fig. 1). Changes in biological processes in T and B cells were both mainly enriched in type I interferon signalling pathway, defense response to virus, and negative regulation of viral genome replication. Changes in cell component in T cells was enriched in the cytosol while in B cells it was in cytoplasm. KEGG pathway analysis revealed that the DEGs of T cells were mainly enriched in influenza A, measles, herpes simplex infection and hepatitis C, while DEGs of B cells were mainly enriched in measles. Changes in molecular function were not listed because the p values were ≥0.05. 4 genes were identified as hub genes (2 in each cell population). In T cells, the hub genes are PLSCR1 and GINS2. PLSCR1 may contribute to the prothrombotic tendency in SLE. GINS2 is involved in the initiation of DNA replication and cell cycle progression. In B cells, the hub genes are ISG15 and TOP2A. Increased ISG15 is correlated with lymphocytopenia in SLE patients. TOP2A encodes a DNA topoisomerase and anti-topoisomerase II antibody could be found in SLE. Conclusion: In our study, 2 mRNA microarray datasets were analyzed to obtain DEGs between SLE T and B cells versus healthy controls. A total of 56 DEGs were identified in T cells and 83 in B cells. Most of the DEGs were upregulated. Changes in biological processes in T and B cells were mainly related to type I interferon signalling pathway and anti-virus function. KEGG also showed the same. PLSCR1 and GINS2 were hub genes in T cells while ISG15 and TOP2A were hub genes in B cells. Overexpression of these genes might play an important role in the pathogenesis of SLE. References: [1]Ohl, K. and K. Tenbrock, Regulatory T cells in systemic lupus erythematosus. Eur J Immunol, 2015. 45 (2): p. 344-55. [2]Moulton, V.R. and G.C. Tsokos, T cell signaling abnormalities contribute to aberrant immune cell function and autoimmunity. J Clin Invest, 2015. 125 (6): p. 2220-7. Disclosure of Interests: None declared
Neuronal intranuclear inclusion disease (NIID) is a rare slowly progressive neurodegenerative disorder that is characterized pathologically by the presence of eosinophilic intranuclear inclusions. NIID is a heterogeneous disease with diverse clinical manifestations, making diagnosis difficult. Here, we analyzed the clinical, pathological, and radiological features of Chinese NIID patients to improve our understanding of NIID.A total of 17 patients with sporadic NIID were recruited from the Ruijin Hospital Database between 2014 and 2021. Clinical patient information and brain MRI data were collected. All of the patients underwent standard skin biopsy procedures.The average age of onset for symptoms was 60.18 years, and the average duration of illness was 4.06 years. All patients were diagnosed with NIID due to the presence of intranuclear inclusions confirmed by skin biopsy. Tremor was the most common initial symptom. The average ages at onset and at diagnosis were both lower in patients with tremor than in patients without tremor. NIID may be a systemic disease that affects multiple organs, for one patient had a history of chronic renal insufficiency for more than 10 years. In addition to high-intensity U-fibers signals on diffusion-weighted imaging, there were several other MRI findings, such as focal leukoencephalopathy and cortical swelling. Encephalitic episodes followed by reversible leukoencephalopathy was another important imaging feature of NIID.The clinical manifestations of NIID are highly variable. Tremor may be the most common initial symptom in certain cohorts. Encephalitic episodes followed by reversible asymmetric leukoencephalopathy may also indicate this disease.
Paraneoplastic amyotrophic lateral sclerosis (ALS) is a rare and special type of ALS. The pathogenesis, clinical presentation, treatment and prognosis remain poorly understood. We herein presented three cases of paraneoplastic ALS. In case 1, we first reported an ALS patient with the positive serum antibodies against both Sry-like high mobility group box 1 (SOX1) and glutamic acid decarboxylase 65 (GAD65). However, immunotherapy did not improve his neurological symptoms. We also reported two ALS patients with renal clear cell carcinoma and chronic myelogenous leukemia. No positive paraneoplastic antibodies were detected in either the serum or the cerebrospinal fluid of the two patients, and their clinical symptoms progressed slowly after tumor treatment. The three cases enriched the existing case pool of this rare disorder. In addition, we have comprehensively reviewed the literature of paraneoplastic ALS. The clinical features, treatment effect and prognosis were summarized to broaden our understanding of paraneoplastic ALS.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)