Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the CNS and affects women of childbearing age. Most patients with NMO have circulating Abs, termed NMO-IgG, against the astrocytic water channel protein aquaporin-4. In the CNS, NMO-IgG causes complement-mediated astrocyte damage, inflammatory cell infiltration, and myelin loss. In this study, we show that aquaporin-4 is expressed in the syncytiotrophoblast of human and mouse placenta. Placental aquaporin-4 expression is high during mid-gestation and progressively decreases with advancing pregnancy. Intraperitoneally injected NMO-IgG binds mouse placental aquaporin-4, activates coinjected human complement, and causes inflammatory cell infiltration into the placenta and placental necrosis. There was no damage to maternal organs that express aquaporin-4, including the brain, spinal cord, kidneys, and skeletal muscle. In control experiments, no placentitis was found in mice injected with NMO-IgG without complement, non–NMO-IgG with human complement, or in aquaporin-4 null mice injected with NMO-IgG and human complement. The infiltrating cells were primarily neutrophils with a few scattered eosinophils and macrophages. NMO-IgG and human complement–induced placentitis caused fetal death, but some fetuses were born normal when lower amounts of NMO-IgG and human complement were injected. Sivelestat, a neutrophil elastase inhibitor, and aquaporumab, a nonpathogenic IgG that competes with NMO-IgG for aquaporin-4 binding, significantly reduced NMO-IgG and human complement induced placentitis and fetal death. Our data suggest that NMO-IgG can cause miscarriage, thus challenging the concept that NMO affects only the CNS. These findings have implications for the management of NMO during pregnancy.

Neuromyelitis optica IgG causes placental inflammation and fetal death in mice

Neuromyelitis optica spectrum disorders (NMOSD) predominantly affect women who are of childbearing age. Understanding the interactions between pregnancy and NMOSD is important for clinical management. Aquaporin-4 (AQP4), the most common target antigen in NMOSD, is expressed on placenta in early pregnancy. A variety of immune and cytokine changes in pregnancy may impact pregnancy outcomes in NMOSD patients. Relapses continue during pregnancy and increase in frequency postpartum. Preeclampsia and fetal loss are more frequent in NMOSD than in controls. Transfer of AQP4-immunoglobulin G (IgG) from mother to baby occurs but appears not to cause disease. Several treatment options are relatively safe and mitigate the risk of relapse during pregnancy and postpartum. For patients with active NMOSD, it may be advisable to continue immunotherapy during pregnancy.

https://journals.sagepub.com/doi/pdf/10.1177/1352458517740215

Neuromyelitis optica spectrum disorders and pregnancy: Interactions and management.

Primary spinal astrocytoma is a subtype of glioma, the most common spinal cord tumor found in the intradural intramedullary compartment. Spinal astrocytomas account for 6-8% of all spinal cord tumors and are primarily low grade (World Health Organization grade I (WHO I) or WHO II). They are seen in both the adult and pediatric population with the most common presenting symptoms being back pain, sensory dysfunction, or motor dysfunction. Magnetic Resonance Imaging (MRI) with and without gadolinium is the imaging of choice, which usually reveals a hypointense T1 weighted and hyperintense T2 weighted lesion with a heterogeneous pattern of contrast enhancement. Further imaging which may aid in surgical planning includes computerized tomography, diffusion tensor imaging, and tractography. Median survival in spinal cord astrocytomas ranges widely. The factors most significantly associated with poor prognosis and shorter median survival are older age at initial diagnosis, higher grade lesion based on histology, and extent of resection. The mainstay of treatment for primary spinal cord astrocytomas is surgical resection, with the goal of preservation of neurologic function, guided by intraoperative neuromonitoring. Adjunctive radiation has been shown beneficial and may increase overall survival. The role of adjunctive chemotherapy is employed, however, its benefit has not been clearly defined. Primary spinal cord astrocytomas are rare and challenging to treat. The gold standard treatment is surgical resection. Second-line treatments include radiation and chemotherapy, although, the optimal regimen for adjunctive therapy has not yet been clearly defined.

Primary Spinal Astrocytomas: A Literature Review

Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory disorder of the central nervous system characterized by severe, antibody-mediated astrocyte loss with secondary demyelination and axonal damage, predominantly targeting optic nerves and the spinal cord. Recent publications have alluded to increased disease activity during pregnancy, and adverse maternal and fetal outcomes in patients with NMOSD. Our objective was to systematically review published literature to help counsel and manage women with NMOSD contemplating pregnancy. Methods: We searched five databases including MEDLINE and EMBASE, for English-language publications describing pregnancies in women with NMOSD. Article selection, data extraction, and risk-of-bias assessment using Joanna Briggs' critical appraisal tool for case reports and case series, were performed in duplicate. Pooled incidences were calculated where possible, and a narrative summary was provided. Results: Of 2,118 identified titles, 22 case reports and seven case series, representing 595 pregnancies in 389 women, were included. The mean maternal age was 28.12 ± 5.19 years. At least 20% of cases were first diagnosed during pregnancy. There were no maternal deaths. Pooled estimates for clinical outcomes could not be obtained due to inadequate reporting. NMOSD-related disability and relapses increased considerably during pregnancy and especially in the immediate postpartum period. Although a high proportion of early pregnancy losses were reported, an association with disease activity or therapeutic interventions could not be established. Apart from one publication which reported an increased risk of preeclampsia, there was no increase in adverse obstetric outcomes including preterm birth, fetal growth restriction or congenital malformations. Initial attacks and relapses were successfully managed with oral or intravenous corticosteroids and immunosuppressants, and refractory cases with immunoglobulin, plasma exchange and immunoadsorption. Conclusion: Increased NMOSD-related disability and relapses during pregnancy the postpartum period may respond to aggressive management with corticosteroids and immunosuppressants such as azathioprine, which are safely administered during pregnancy and lactation. Emerging safety data on monoclonal antibodies during pregnancy, make these attractive options, while intravenous immunoglobulin, plasma exchange and immunoadsorption can be safely used to treat severe relapses. The complex interplay between NMOSD and pregnancy outcomes would be best understood through prospective analysis of data collected through an international registry. Disclosure: Dalia Rotstein has served as a consultant or speaker for Alexion and Roche. She has received research support from Roche Canada. Rohan D'Souza has served as a consultant and speaker for Ferring Canada Inc and Ferring Global Inc, on topics unrelated to this manuscript. The other authors have no relevant relationships to disclose.

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Pregnancy and Neuromyelitis Optica Spectrum Disorder - Reciprocal Effects and Practical Recommendations: A Systematic Review.

Background and purpose Data on the pregnancy outcome of neuromyelitis optica spectrum disorder (NMOSD) remain limited, especially for woman who had received immunosuppressive treatment before becoming pregnant. The aim was to evaluate the outcome of pregnancy amongst patients with NMOSD who attempted to become pregnant after NMOSD onset and to identify risk factors that predict pregnancy-related attack. Methods Medical records from 29 patients who attempted to become pregnant after NMOSD onset were retrospectively evaluated and the patients were interviewed for pregnancy outcomes. Pregnancy-related attack was defined as an attack that occurred during pregnancy or within 1 year of delivery. Results Amongst the 29 patients, 26 had 33 pregnancies after NMOSD symptom onset. The 33 pregnancies after NMOSD onset resulted in 24 live births (healthy neonates except one with low birth weight), six miscarriages and three elective abortions. Pregnancy-related attack occurred in nine (75%) of 12 pregnancies before initiation of immunosuppressive therapy, but in only five (24%) of 21 pregnancies after initiation of immunosuppressive therapy (P = 0.009). Multivariable analysis indicated that pregnancy-related attack was negatively associated with pregnancy after initiation of rituximab (odds ratio 0.048, 95% confidence interval 0.004-0.546). Conclusion Successful pregnancy without maternal and neonatal complications may be feasible in patients with NMOSD. Rituximab treatment before pregnancy might help to prevent pregnancy-related attack in patients with NMOSD.

Outcome of pregnancies after onset of the neuromyelitis optica spectrum disorder

Effectiveness and safety of immunosuppressive therapy in neuromyelitis optica spectrum disorder during pregnancy.

Axial MR diffusion tensor imaging and tractography in clinical diagnosed and pathology confirmed cervical spinal cord astrocytoma

Stable binary nanohybrids based on all‐inorganic halide perovskite encapsulated in porphyrinic Zr‐MOF (PCN‐222) are constructed for photoinduced electron transfer‐reversible addition‐fragmentation chain transfer (PET‐RAFT) polymerization. The synergistic effect of perovskite and PCN‐222 endows the photocatalyst with high‐efficiency photogenic charge carrier separation and light absorption property. CsPbI3@PCN‐222 (20%) is finally screened out as the oxygen and solvent‐resistant photocatalyst for highly efficient photo‐controlled polymerization of conjugated and unconjugated monomers under red to near infrared (NIR) light with high monomer conversion and narrow molecular weight distribution well‐defined polymers (Đ < 1.20). Controllable polymers and ultrahigh molecular weight polymers (up to 1730000 g mol−1) are successfully obtained by chain extension and block copolymerization of various monomers. The constructed photocatalysts easily achieve excellent light and temporal control, and even show high MMA conversion with NIR light under a thick barrier.

Binary Hybridization Strategy toward Stable Porphyrinic Zr‐MOF Encapsulated Perovskites as High‐Performance Heterogeneous Photocatalysts for Red to NIR Light‐Induced PET‐RAFT Polymerization

Objective Rituximab (RTX), an anti-CD20 monoclonal antibody, has been demonstrated to be a useful maintenance therapy for neuromyelitis optica spectrum disorder (NMOSD). However, few patients may suffer from relapses shortly after RTX. In order to investigate the clinical features of RTX-related relapses and guide therapeutic strategy, 3 patients in our department were reported and literatures were reviewed. Methods We reported three NMOSD patients suffered from relapses shortly after rituximab treatment in our hospital and reviewed 13 patients reported in literatures. Their demographic characteristics, clinical features and therapeutic strategy were retrospectively analyzed. Results Sixteen patients, including three cases reported in this study, experienced 21 attacks within 1 month after RTX infusion. All of them were women with an age at onset of 34.0 ± 15.0 years. Fourteen patients were seropositive for aquaporin-4 antibody, and one was seropositive for myelin oligodendrocyte glycoprotein antibody. 57.1% (12/21) of RTX-related relapses occurred after the first use of RTX. Their clinical manifestations included optic neuritis (8/21), myelitis (11/21), and the other two relapses without detailed descriptions. Also, 62.5% (10/16) of patients had a history of prior relapses within 3 months before RTX infusions, and the location of nine relapses overlapped with previous relapses. RTX was given again after the first RTX-related relapse in eight patients, three of them with low-dosage RTX stayed stable for years, and five patients with full-dosage RTX experienced another RTX-related relapse. Conclusions Relapses may occur shortly after RTX treatment in NMOSD. RTX-related relapse did not necessarily mean that RTX was ineffective in low-dosage regimen. Timely and sufficient treatment of RTX is crucial to prevent a relapse. It may be more reasonable to monitor B cell repopulation so as to determine a re-treatment regimen. RTX-related relapse following full-dosage RTX may be a predictor for a second time RTX-related relapse and it may be reasonable to switch to other immunosuppressants in early stage.

Bingxin Shi

Papers

Effectiveness and safety of immunosuppressive therapy in neuromyelitis optica spectrum disorder during pregnancy.

Axial MR diffusion tensor imaging and tractography in clinical diagnosed and pathology confirmed cervical spinal cord astrocytoma

Binary Hybridization Strategy toward Stable Porphyrinic Zr‐MOF Encapsulated Perovskites as High‐Performance Heterogeneous Photocatalysts for Red to NIR Light‐Induced PET‐RAFT Polymerization

Relapses shortly after rituximab treatment in neuromyelitis optica spectrum disorder.

Cross-linked polymer modified layered double hydroxide nanosheet stabilized CsPbBr3 perovskite quantum dots for white light-emitting diode