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Types of pain in NMOSD patients including painful tonic muscle spasms, neuropathic pain, and sometimes pain due to excess loading and pain as a side effect of immunotherapy and in the context of comorbidities. Also, 46% of NMOSD patients in the current study experienced ongoing pain, and further binary logistic regression analysis showed that pain was positively correlated with the C5a level, with gender and EDSS score were identified as independent factors. Keywords: neuromyelitis optica spectrum disorders; remission; pain; C5a EN neuromyelitis optica spectrum disorders remission pain C5a 1039 1046 8 06/09/22 20220501 NES 220501 Introduction Neuromyelitis optica spectrum disorders (NMOSD) is a rare autoimmune inflammatory demyelinating disease of the central nervous system (CNS) characterized by recurrent inflammation of the optic nerve, spinal cord, and specific brain areas.[1] Compared to multiple sclerosis (MS) that primarily targets myelin, NMOSD induces irreparable neuronal cell death which leads to more severe disability and a poorer prognosis.[2] The clinical presentation of NMOSD includes severe episodes of optic neuritis that may lead to loss of vision, transverse myelitis causing paraplegia or paralysis, and sometimes brainstem encephalitis causing intractable vomiting or hiccups. Pain, which is highly prevalent in patients with NMOSD, can greatly impair quality of life.[18] In the present study, 46% of the patients with NMOSD during remission complained of current pain. [Extracted from the article]

Favorable effects exerted by long-term administration of fingolimod therapy in multiple sclerosis (MS) patients have been reported, but sporadic side effects, such as reversible macular edema, also have been recorded. The present study aimed to determine whether fingolimod therapy is beneficial to the visual system in experimental autoimmune encephalomyelitis (EAE) mice. A decrease in demyelination and axon loss in the optic nerve as well as cellular infiltration, especially the recruited macrophages, was observed in EAE with fingolimod treatment. Fingolimod administration diminished hypergliosis of macroglia, including astrocytes and Müller cells in the retina and optic nerve in EAE. Microglia were hyperactivated in the retina and optic nerve in the EAE mice compared to controls, which could be alleviated by fingolimod treatment. Moreover, apoptosis of retinal ganglion cells (RGC) and oligodendrocytes in the optic nerve was significantly reduced with fingolimod treatment compared to that in the untreated EAE mice. These results suggested that fingolimod exerts neuroprotective and anti-inflammatory effects on the retina and optic nerve in a mouse model of EAE. Considering the paradox of favorable and side effects of fingolimod on visual system, we speculate that side effects including macular oedema caused by fingolimod during MS treatment is tendency to be vasogenic rather than hypergliosis in optic nerve and retina which warrants further neuroophthalmological investigation. Our results show that fingolimod is a potential therapeutic approach to prevent EAE-induced visual impairment. Moreover, we show that the observed neuro-ophthalmological protective effects of fingolimod were dependent on hampering hyper-gliosis in the retina and optic nerve. [ABSTRACT FROM AUTHOR]

Background: A prominent pathological feature of neuromyelitis optica spectrum disorders (NMOSD) is markedly greater eosinophilic infiltration than that seen in other demyelinating diseases, like multiple sclerosis (MS). Eosinophils express the chemokine receptor CCR3, which is activated by eotaxins (CCL11/eotaxin-1, CCL24/eotaxin-2, CCL26/eotaxin-3) and CCL13 [monocyte chemoattractant protein (MCP)-4]. Moreover, CCL13 is part of the chemokine set that activates CCR2. The present study aimed to evaluate plasma levels of eotaxins (CCL11, CCL24, and CCL26) and MCPs (CCL13, CCL2, CCL8, and CCL7) in patients with NMOSD during remission. Methods: Healthy controls (HC; n = 30) and patients with MS (n = 47) and NMOSD (n = 58) in remission were consecutively enrolled in this study between January 2016 and August 2017. Plasma CCL11, CCL24, CCL26, CCL2, CCL8, CCL7, CCL13, tumor necrosis factor (TNF)-a, and interleukin (IL)-1ß levels were detected using the human cytokine multiplex assay. Results: Plasma CCL13, CCL11, and CCL26 levels were all significantly higher in patients with NMOSD than in HC and patients with MS. No significant differences were found in the CCL13, CCL11, or CCL26 levels between patients with NMOSD receiving and not receiving immunosuppressive therapy. The plasma levels of TNF-α and IL-1β, which stimulate the above chemokines, were higher in patients with NMOSD than in HC. There was no difference in CCL24 levels among the three groups. In most cases, the CCL7 levels were below the threshold value of the human cytokine multiplex assay, which is in line with other studies. Adjusted multiple regression analyses showed a positive association of CCL13 levels with the number of relapses after controlling gender, age, body mass index, and disease duration in patients with NMOSD. Conclusion: The study indicates that in NMOSD, the overproduction of cytokines such as IL-1ß and TNF-a during remission stimulates eosinophilic chemoattractants such as CCL13, CCL11, and CCL26, which in turn bind to their receptor (CCR3); this could lead to eosinophil hypersensitivity. These findings suggest that the elevated secretion of CCL13, CCL11, and CCL26 may be a critical step in eosinophil recruitment during NMOSD remission. [ABSTRACT FROM AUTHOR]