Autoimmune nodopathy with anti-contactin 1 antibody characterized by cerebellar dysarthria: a case report and literature review.

Background: Autoimmune nodopathy (AN) has emerged as a novel diagnostic category that is pathologically different from classic chronic inflammatory demyelinating polyneuropathy. Clinical manifestations of AN include sensory or motor neuropathies, sensory ataxia, tremor, and cranial nerve involvement. AN with a serum-positive contactin-1 (CNTN1) antibody usually results in peripheral nerve demyelination. In this study, we reported a rare case of AN with CNTN1 antibodies characterized by the presence of CNTN1 antibodies in both serum and cerebrospinal fluid, which is associated with cerebellar dysarthria. Methods: A 25-year-old man was admitted to our hospital due to progressive dysarthria with limb tremors. The patient was initially diagnosed with peripheral neuropathy at a local hospital. Three years after onset, he was admitted to our hospital due to dysarthria, apparent limb tremor, and limb weakness. At that time, he was diagnosed with spinocerebellar ataxia. Eight years post-onset, during his second admission, his condition had notably deteriorated. His dysarthria had evolved to typical distinctive cerebellar characteristics, such as tremor, loud voice, stress, and interrupted articulation. Additionally, he experienced further progression in limb weakness and developed muscle atrophy in the distal limbs. Magnetic resonance imaging (MRI), nerve conduction studies (NCS), and autoimmune antibody tests were performed. Results: The results of the NCS suggested severe demyelination and even axonal damage to the peripheral nerves. MRI scans revealed diffuse thickening of bilateral cervical nerve roots, lumbosacral nerve roots, cauda equina nerve, and multiple intercostal nerve root sheath cysts. Furthermore, anti-CNTN1 antibody titers were 1:10 in the cerebrospinal fluid (CSF) and 1:100 in the serum. After one round of rituximab treatment, the patient showed significant improvement in limb weakness and dysarthria, and the CSF antibodies turned negative. Conclusion: Apart from peripheral neuropathies, cerebellar dysarthria (central nervous system involvement) should not be ignored in AN patients with CNTN1 antibodies.

Anti-NMDAR antibodies, the blood-brain barrier, and anti-NMDAR encephalitis.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an antibody-related autoimmune encephalitis. It is characterized by the existence of antibodies against NMDAR, mainly against the GluN1 subunit, in cerebrospinal fluid (CSF). Recent research suggests that anti-NMDAR antibodies may reduce NMDAR levels in this disorder, compromising synaptic activity in the hippocampus. Although anti-NMDAR antibodies are used as diagnostic indicators, the origin of antibodies in the central nervous system (CNS) is unclear. The blood-brain barrier (BBB), which separates the brain from the peripheral circulatory system, is crucial for antibodies and immune cells to enter or exit the CNS. The findings of cytokines in this disorder support the involvement of the BBB. Here, we aim to review the function of NMDARs and the relationship between anti-NMDAR antibodies and anti-NMDAR encephalitis. We summarize the present knowledge of the composition of the BBB, especially by emphasizing the role of BBB components. Finally, we further provide a discussion on the impact of BBB dysfunction in anti-NMDAR encephalitis.

Activated neutrophil-derived exosomes contribute to blood-brain barrier damage and hemorrhagic transformation after cerebral ischemia/reperfusion.

BACKGROUND: Hemorrhagic transformation (HT) caused by blood-brain barrier (BBB) damage is closely correlated with the poor prognosis of ischemic stroke. Neutrophils are proven to mediate BBB injury after ischemic stroke, but the mechanism remains to be further investigated. Therefore, the present study aims to investigate the effect of neutrophil-derived exosomes on BBB integrity. METHOD: A tMCAO-HT model was constructed to assess neutrophil infiltration and its co-localization with brain microvascular endothelial cells (BMEC). After using quiet (Q-Neu) and activated neutrophil (A-Neu) and their exosomes to treat the BBB model in vitro, TEER and permeability were assayed to assess the BBB integrity. Small RNA sequencing was performed to identify differentially expressed miRNAs (DE-miRNAs) in A-Neu- and Q-Neu-derived exosomes, and the function and pathways of DE-miRNA targets were analyzed by GO and KEGG enrichment. RESULT: Different degrees of cerebral hemorrhage were observed in the tMCAO-HT model. The expression of the neutrophil marker Ly6G was significantly increased in tMCAO-HT model compared to the sham group, and co-localized with the BMEC marker CD31. Notably, Ly6G expression was positively correlated with hemoglobin content in brain tissue. A-Neu and its derived exosomes reduced TEER and elevated permeability in the BBB model in vitro. Moreover, BBB-related proteins Claudin 5, Occludin and ZO-1 expression were significantly reduced in BMEC after treatment with A-Neu and its derived exosomes. Nevertheless, Q-Neu and its exosomes had no significant effect on BBB integrity. A total of 84 DE-miRNAs are present in Q-Neu- and A-Neu-derived exosomes, and their target genes are involved in the regulation of "positive regulation of establishment of endothelial barrier", "cell junction", "ECM-receptor interaction" and "VEGF signaling pathway". Moreover, RT-qPCR revealed that the expression trends of miR-409-3p, miR-6909-5p, miR-3473d, miR-370-3p and miR-6904-5p in exosomes were consistent with the sequencing results. CONCLUSION: Neutrophils are abnormally recruited in HT after ischemic stroke, and are associated with cerebral hemorrhage. In vitro, A-Neu-derived exosomes facilitate BBB injury, which may be accomplished by exosomal transport of miRNAs.

Diagnostic Accuracy of MRI for Detecting Cervical Invasion in Patients with Endometrial Carcinoma: A Meta-Analysis.

Objectives: To evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) in the preoperative assessment of cervical invasion and to analyse the influence of different imaging protocols in patients with endometrial carcinoma. Methods: An extensive search of articles about MRI for assessing cervical invasion in patients with endometrial carcinoma was performed on PubMed, Embase, Web of Science, Cochrane Library, and Clinical Trials from January 2000 to July 2020. Two reviewers independently evaluated the methodological quality of each study by using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Diagnostic accuracy results and additional useful information were extracted. The pooled estimation data was obtained by statistical analysis. Results: A total of 42 eligible studies were included in the meta-analysis. Significant evidence of heterogeneity was found for detecting cervical invasion (I2 = 74.1%, P = 0.00 for sensitivity and I2 = 56.2%, P = 0.00 for specificity). The pooled sensitivity and specificity of MRI were 0.58 and 0.95 respectively. The use of higher field strength (3.0 T) demonstrated higher pooled sensitivity (0.74). Using diffusion weighted imaging (DWI) alone presented higher pooled sensitivity (0.86) than using other sequences. The studies that used dynamic contrast-enhanced MRI (DCE-MRI) alone showed higher sensitivity (0.80) and specificity (0.96) than those that used T2-weighted imaging (T2WI) alone. Conclusions: MRI shows high specificity for detecting cervical infiltration in endometrial carcinoma. Using DWI or a 3.0-T device may improve the pooled sensitivity. DCE-MRI demonstrates higher pooled sensitivity and specificity than T2WI.

The preventive effect of phenolic-rich extracts from Chinese sumac fruits against nonalcoholic fatty liver disease in rats induced by a high-fat diet.

The objective of this study is to investigate the preventive effect of phenolic-rich extracts from Chinese sumac (Rhus chinensis Mill.) fruits against nonalcoholic fatty liver disease (NAFLD) in rats induced by a high-fat diet and to clarify the underlying mechanisms. The results showed that the phenolic-rich extract remarkably improved some critical biochemical indexes, including TG, TC, MDA, ALT, AST, and endogenous antioxidant enzymes. The results of immunofluorescence and TUNEL assay showed that the extract obviously reduced the level of NF-κB in cell nuclei and suppressed hepatocyte apoptosis. Moreover, immunohistochemistry and western blot analyses further revealed that the phenolic-rich extract can improve NAFLD in high-fat diet induced rats by regulating several key proteins related to lipid metabolism, inflammation and apoptosis of hepatocytes, namely upregulating the expression levels of p-AMPK, PPAR-α, CPT1 and Bcl-2, and downregulating the levels of PPAR-γ, CYP2E1, p-P38, p-NF-κB, iNOS, COX-2, caspase-3D and Bax. These results indicate that the phenolic-rich extract from Chinese sumac fruits could prevent NAFLD in rats by regulating some critical proteins in several signalling pathways and may be provided as a new natural ingredient for developing functional foods and/or nutraceuticals to prevent NAFLD.