Analyzing serum levels of TJ proteins, like CLDN5, OCLN, and CLDN5/ZO1 ratio, as well as S100B and VEGF, is an effective way to screen for clinical deterioration caused by HT in ischemic stroke patients, both within and after the IV thrombolysis time window.

Myelin oligodendrocyte glycoprotein (MOG)-associated disease (MOGAD) is a rare, antibody-mediated inflammatory demyelinating disorder of the central nervous system (CNS) with various phenotypes starting from optic neuritis, via transverse myelitis to acute demyelinating encephalomyelitis (ADEM) and cortical encephalitis. Even though sometimes the clinical picture of this condition is similar to the presentation of neuromyelitis optica spectrum disorder (NMOSD), most experts consider MOGAD as a distinct entity with different immune system pathology. MOG is a molecule detected on the outer membrane of myelin sheaths and expressed primarily within the brain, spinal cord and also the optic nerves. Its function is not fully understood but this glycoprotein may act as a cell surface receptor or cell adhesion molecule. The specific outmost location of myelin makes it a potential target for autoimmune antibodies and cell-mediated responses in demyelinating processes. Optic neuritis seems to be the most frequent presenting phenotype in adults and ADEM in children. In adults, the disease course is multiphasic and subsequent relapses increase disability. In children ADEM usually presents as a one-time incident. Luckily, acute immunotherapy is very effective and severe disability (ambulatory and visual) is less frequent than in NMOSD. A critical element of reliable diagnosis is detection of pathogenic serum antibodies MOG with accurate, specific and sensitive methods, preferably with optimized cell-based assay (CBA). MRI imaging can also help in differentiating MOGAD from other neuro-inflammatory disorders. Reports on randomised control trials are limited, but observational open-label experience suggests a role for high-dose steroids and plasma exchange in the treatment of acute attacks, and for immunosuppressive therapies, such as steroids, oral immunosuppressants and rituximab as maintenance treatment. In this review, we present up-to-date clinical, immunological, radiographic, histopathological data concerning MOGAD and summarize the practical aspects of diagnosing and managing patients with this disease.

Neuromyelitis optica (NMO) is an autoimmune, demyelinating disorder of the central nervous system (CNS) with typical clinical manifestations of optic neuritis and acute transverse myelitis attacks. Previously believed to be a variant of multiple sclerosis (MS), it is now considered an independent disorder which needs to be differentiated from MS. The discovery of autoantibodies against aquaporin-4 (AQP4-IgGs) changed our understanding of NMO immunopathogenesis and revolutionized the diagnostic process. AQP4-IgG is currently regarded as a specific biomarker of NMO and NMO spectrum disorders (NMOsd) and a key factor in its pathogenesis. Nevertheless, AQP4-IgG seronegativity in 10%–25% of NMO patients suggests that there are several other factors involved in NMO immunopathogenesis, i.e., autoantibodies against aquaporin-1 (AQP1-Abs) and antibodies against myelin oligodendrocyte glycoprotein (MOG-IgGs). This manuscript reviews current knowledge about NMO immunopathogenesis, pointing out the controversial issues and showing potential directions for future research. Further efforts should be made to broaden our knowledge of NMO immunology which could have important implications for clinical practice, including the use of potential novel biomarkers to facilitate an early and accurate diagnosis, and modern treatment strategies improving long-term outcome of NMO patients.

Small Heat shock proteins (sHsp) are a group of chaperone proteins. Under conditions of stress, the expression of sHsp is increased. Therefore, they are implicated in the pathogenesis of various autoimmune-mediated disorders and cancer. The purpose of this study was to analyze sHsp expression in exosomes from patients with gynecologic cancers and correlate these results with markers of cytotoxic immune response. The study group included patients with ovarian cancer, endometrial cancer, and patients with endometriosis. The levels of sHsps and cytotoxic markers were analyzed in serum, peritoneal fluid and exosomes using ELISA method. We found the highest levels of sHsp in exosomes from patients with ovarian cancer, but they were also elevated in patients with endometrial cancer and endometriosis. Moreover, we identified the presence of small Hsps in serum and peritoneal fluid in all study groups, but again the highest level was in patients with ovarian cancer. Small Hsps expression levels were positively correlated with markers of cytotoxic immune response.

IntroductionParaneoplastic neurological syndromes (PNS) are neurologic deficits triggered by an underlying remote tumor. PNS can antedate clinical manifestation of ovarian malignancy and enable its diagnosis at an early stage. Interestingly, neoplasms associated with PNS are less advanced and metastasize less commonly than those without PNS. This suggests that PNS may be associated with a naturally occurring antitumor response.MethodsWe review the literature on the diagnosis, pathogenesis and management of PNS associated with ovarian tumors: paraneoplastic cerebellar degeneration (PCD) and anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis. An approach to the diagnostic workup of underlying tumors is discussed.ResultsPCD can precede the manifestation of ovarian carcinoma. Anti-NMDAR encephalitis in young women appears often as a result of ovarian teratoma. Since ovarian tumors and nervous tissue share common antigens (e.g., cdr2, NMDAR), autoimmune etiology is a probable mechanism of these neurologic disorders. The concept of cross-presentation, however, seems insufficient to explain entirely the emergence of PNS. Early resection of ovarian tumors is a significant part of PNS management and improves the outcome.ConclusionsThe diagnosis of PNS potentially associated with ovarian tumor indicates a need for a thorough diagnostic procedure in search of the neoplasm. In some patients, explorative laparoscopy/laparotomy can be considered.

Aim: The aim of this study was to evaluate the role of the serum osteopontin (OPN) level as a biomarker for discriminating between malignant and benign ovarian tumors. Furthermore, comparisons with the diagnostic usefulness of the other tests were performed. Methods: The study included 114 consecutive women with ovarian tumors (82 benign and 32 malignant) who were referred to our division. Results: A cut-off level of 28.0 ng/mL for OPN showed a sensitivity of 71.87% and a specificity of 89.02%. The area under the receiver-operator curve (ROC) was 0.812. There were no differences in diagnostic utility between OPN and the other studied tests. OPN levels were lower in patients with endometriotic ovarian cysts than in those with other benign ovarian tumors (14.00 vs 19.50 ng/mL; P = 0.018). The difference between the median OPN level in patients with endometriotic cysts (14.0 ng/mL) and those with malignant tumors (40.85 ng/mL) was also statistically significant (P < 0.0001). The calculated OPN/CA-125 ratio was significantly different between patients with endometriotic cysts (median, 0.36; range, 0.05-2.89) and those with other benign tumors (median, 1.25; range, 0.05-5.70) (P = 0.0002). There was also a statistically significant difference in the median OPN/CA-125 ratio between patients with endometrial cysts (median, 0.36; range, 0.05-2.89) and those with malignant tumors (median, 0.12; range, 0.01-3.39) (P = 0.004). Conclusion:The diagnostic utility of OPN is similar to that of ultrasonographic evaluation and CA-125 level assessment. Thus, OPN may be useful in differential diagnosis for less experienced ultrasonographers and is especially valuable for differential diagnosis of endometriotic cysts.

No abstract

Paraneoplastic neurological syndromes (PNS) are disorders of the nervous system that are associated with remote effects of malignancy. PNS are considered to have an autoimmune pathology. It has been suggested that immune antitumor responses are the origin of improved outcome in PNS. We describe cell-mediated immune responses in PNS and their potential contributions to antitumor reactions. Experimental and neuropathological studies have revealed infiltrates in nervous tissue and disturbances in lymphocyte populations in both cerebrospinal fluid and peripheral blood. A predominance of cytotoxic T lymphocytes (CTLs) over T helper cells has been observed. CTLs can be specifically aggressive against antigens shared by tumors and nervous tissue. Based on genetic studies, a common clonal origin of lymphocytes from blood, tumor, and nervous tissue is suggested. Suppressive regulatory T (Treg) lymphocytes are dysfunctional. Simultaneously, in tumor tissue, more intense cell-mediated immune responses are observed, which often coincide with a less aggressive course of neoplastic disease. An increased titer of onconeural antibodies is also related to better prognoses in patients without PNS. The evaluation of onconeural and neuronal surface antibodies was recommended in current guidelines. The link between PNS emergence and antitumor responses may result from more active CTLs and less functional Treg lymphocytes.