Autoantibodies Targeting Unknown Epitope Autoimmune Encephalitis and the Effect of Modified Electroconvulsive Therapy: Report of Three Cases.

Objective: Generally autoimmune encephalitis (AE) cases present with central nervous system symptoms. Many types of autoantibodies are associated with autoimmune encephalitis, with anti-N-methyl-D-aspartate receptor being the most commonly reported. However, autoimmune encephalitis cases with autoantibodies targeting unknown epitopes are increasingly recognized. This article aims to summarize the clinical experience and assess the feasibility of modified electroconvulsive therapy (MECT) as an adjunctive treatment method for autoimmune encephalitis patients with poor response to first-line immunotherapy and mainly displaying psychiatric symptoms. Methods: This work reports three cases of which two have been diagnosed as autoantibodies targeting unknown epitope autoimmune encephalitis while one has been diagnosed as anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and all were effectively treated with MECT. Results: All three cases that otherwise failed to respond to standard immunotherapy for controlling psychiatric symptoms exhibited excellent clinical outcomes following MECT. The underlying mechanism of action of MECT is unclear and whether such an effect involves a neurotransmitter rebalance in the brain remains uncertain. At present, we have observed only a small number of clinical cases, warranting further research among a larger number of clinical cases and more systematic multicenter retrospective analysis. Conclusions: It should be noted that, while our experience supports the utility of MECT in the treatment of certain cases of AE, this option should be regarded as an adjuvant therapy after standard immunosuppressive therapy. Clinicians must be aware that patients should be provided with psychiatric or neurological services for timely diagnosis along with timely and appropriate treatment.

Validation of the Clinical Assessment Scale in Autoimmune Encephalitis in Chinese Patients.

Background and Objectives: The Clinical Assessment Scale in Autoimmune Encephalitis (CASE) is a scale for assessing severity in autoimmune encephalitis. We aimed to validate the CASE score in a Chinese population and evaluate its clinical significance. Methods: Patients diagnosed with autoimmune encephalitis were recruited between June 2014 and May 2019 from two hospitals. CASE and modified Rankin Scale (mRS) scores were obtained. Data regarding clinical features, treatment, and available information were gathered from the hospital information system. Results: Of the 176 patients with autoimmune encephalitis, 11 died and 14 had tumors. Ten patients received second-line treatment. The CASE scores of patients receiving second-line treatment were significantly higher (median CASE: 15) than in those receiving first-line treatment (median CASE: 8) (p<0.001). Twenty-two patients had poor functional status (mRS>2). Areas under the curve of CASE on whether functional status was poor at 1 year were 0.89 (p<0.001). Sixty patients were admitted to the intensive care unit (ICU), and the CASE scores were positively correlated with days in the ICU (r=0.58, p<0.001). There was no statistically significant association between the CASE scores and relapse (p=0.39>0.05). Additionally, the CASE scores were positively associated with the mRS scores (r=0.85 p<0.001). Conclusions: The CASE score is suitable for the comprehensive assessment of Chinese patients with autoimmune encephalitis, which may help clinicians to select the appropriate intervention and estimate the disease severity and prognosis.

Dl-3-n-Butylphthalide promotes neovascularization and neurological recovery in a rat model of intracerebral hemorrhage.

BACKGROUND: Cerebral stroke occurs following ischemic and hemorrhagic lesions in the brain. Survival and recovery of stroke patients depend on the severity of the initial injury but also the therapeutic approaches applied for emergent lifesaving and continuing post-stroke management. Dl-3-n-Butylphthalide (NBP), an active compound derived from Chinese celery seeds, has shown clinical efficacy in the treatment of ischemic cerebral stroke. RESULTS: In the present study we explored the therapeutic effect of NBP in a rat model of intracerebral hemorrhage (ICH), focusing on its potential role in promoting neovascularization in the perihemorrhagic zone. ICH was induced in male Sprague-Dawley rats by unilateral injection of autologous blood into the globus pallidus, with sham-operated (Sham group), vehicle-treated (ICH) and NBP-treated (at 10 and 25 mg/kg/Bid, p.o., ICH + NBP10 and ICH + NBP25, respectively) groups examined behaviorally, macroscopically, histologically and biochemically at 1, 3, 7 and 15 days (d) post operation. Rats in the ICH + NBP10 and ICH + NBP25 groups showed reduced Longa's motor scores relative to the ICH groups at the 3 and 7d time points, while the hematoma volume was comparable in the two NBP relative to the ICH groups as measured at 7d and 15d. In the perihemorrhagic zone, the numeric density of blood vessels immunolabeled by CD34, an angiogenic marker, was greater in the ICH + NBP10 and ICH + NBP25 than ICH groups, more so in the higher dosage group, at 1, 3, 7 and 15d. Levels of the vascular endothelial growth factor (VEGF) and angiopoietins-2 (Ang-2) proteins were elevated in the NBP groups relative to the sham and vehicle controls in immunoblotting of tissue lysates from the injection region. CONCLUSION: These results suggest that NBP can alleviate neurological defects following experimentally induced local brain hemorrhage, which is associated with a potential role of this drug in promoting neovascularization surrounding the bleeding loci.

microRNA-200a functions as a tumor suppressor by targeting FOXA1 in glioma.

microRNAs (miRs) serve primary roles in certain human malignancies; however, the detailed regulatory mechanism of miR-200a in glioma progression is yet to be fully elucidated. The current study aimed to assess the expression of miR-200a in glioma as well as the regulatory mechanism of miR-200a in glioma cell proliferation, survival and invasion. RT-qPCR and western blotting were performed to examine mRNA and protein expression. An MTT assay, an EdU incorporation cell proliferation assay and a transwell assay were utilized to assess cell survival, proliferation and invasion. The results indicated that the miR-200a levels were significantly reduced in glioma tissues compared with normal brain tissues. Levels were also downregulated in glioma cell lines when compared with those in normal human astrocyte cells. Furthermore, low miR-200a expression was associated with advanced progression of glioma. The overexpression of miR-200a inhibited glioma cell proliferation, survival and invasion. Results also identified that FOXA1 was a target gene of miR-200a in glioma cells and that the increased expression of FOXA1 was negatively correlated to the decreased expression of miR-200a in glioma tissues. Furthermore, FOXA1 expression was negatively mediated by miR-200a in glioma cells and the overexpression of FOXA1 eliminated the inhibitory effects of miR-200a on the survival, proliferation and invasion of glioma cells. In conclusion, the current study demonstrated that miR-200a functions acts as a tumor suppressor in glioma by directly targeting FOXA1 and may thus be a potential candidate for the treatment of glioma.