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Optical coherence tomography in neuromyelitis optica spectrum disorders: potential advantages for individualized monitoring of progression and therapy

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      Abstract

      Neuromyelitis optica spectrum disorders (NMOSD) are mostly relapsing inflammatory disorders of the central nervous system (CNS). Optic neuritis (ON) is the first NMOSD-related clinical event in 55% of the patients, which causes damage to the optic nerve and leads to visual impairment. Retinal optical coherence tomography (OCT) has emerged as a promising method for diagnosis of NMOSD and potential individual monitoring of disease course and severity. OCT not only detects damage to the afferent visual system caused by ON but potentially also NMOSD-specific intraretinal pathology, i.e. astrocytopathy. This article summarizes retinal involvement in NMOSD and reviews OCT methods that could be used now and in the future, for differential diagnosis, for monitoring of disease course, and in clinical trials.

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      Optical coherence tomography

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        A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis.

        Neuromyelitis optica is an inflammatory demyelinating disease with generally poor prognosis that selectively targets optic nerves and spinal cord. It is commonly misdiagnosed as multiple sclerosis. Neither disease has a distinguishing biomarker, but optimum treatments differ. The relation of neuromyelitis optica to optic-spinal multiple sclerosis in Asia is uncertain. We assessed the capacity of a putative marker for neuromyelitis optica (NMO-IgG) to distinguish neuromyelitis optica and related disorders from multiple sclerosis. Indirect immunofluorescence with a composite substrate of mouse tissues identified a distinctive NMO-IgG staining pattern, which we characterised further by dual immunostaining. We tested masked serum samples from 102 North American patients with neuromyelitis optica or with syndromes that suggest high risk of the disorder, and 12 Japanese patients with optic-spinal multiple sclerosis. Control patients had multiple sclerosis, other myelopathies, optic neuropathies, and miscellaneous disorders. We also established clinical diagnoses for 14 patients incidentally shown to have NMO-IgG among 85000 tested for suspected paraneoplastic autoimmunity. NMO-IgG outlines CNS microvessels, pia, subpia, and Virchow-Robin space. It partly colocalises with laminin. Sensitivity and specificity were 73% (95% CI 60-86) and 91% (79-100) for neuromyelitis optica and 58% (30-86) and 100% (66-100) for optic-spinal multiple sclerosis. NMO-IgG was detected in half of patients with high-risk syndromes. Of 14 seropositive cases identified incidentally, 12 had neuromyelitis optica or a high-risk syndrome for the disease. NMO-IgG is a specific marker autoantibody of neuromyelitis optica and binds at or near the blood-brain barrier. It distinguishes neuromyelitis optica from multiple sclerosis. Asian optic-spinal multiple sclerosis seems to be the same as neuromyelitis optica.
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          The clinical course of neuromyelitis optica (Devic's syndrome).

          To evaluate the spectrum of neuromyelitis optica (NMO), including characteristics of the index events (optic neuritis [ON]) and myelitis), neuroimaging, CSF, and serologic studies, and to evaluate the long-term course. Review of 71 patients with NMO evaluated at the Mayo Clinic between 1950 and 1997. NMO was either monophasic or relapsing. Patients with a monophasic course (n = 23) usually presented with rapidly sequential index events (median 5 days) with moderate recovery. Most with a relapsing course (n = 48) had an extended interval between index events (median 166 days) followed within 3 years by clusters of severe relapses isolated to the optic nerves and spinal cord. Most relapsing patients developed severe disability in a stepwise manner, and one-third died because of respiratory failure. Features of NMO distinct from "typical" MS included >50 cells/mm3 in CSF (often polymorphonuclear), normal initial brain MRI, and lesions extending over three or more vertebral segments on spinal cord MRI. Clinical, laboratory, and imaging features generally distinguish neuromyelitis optica from MS. Patients with relapsing optic neuritis and myelitis may have neuromyelitis optica rather than MS. Patients with a relapsing course of neuromyelitis optica have a poor prognosis and frequently develop respiratory failure during attacks of cervical myelitis.
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            Author and article information

            Affiliations
            [1 ]NeuroCure Clinical Research Center, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany
            [2 ]Department of Neurology, Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
            [3 ]ISNI 0000 0001 1014 0849, GRID grid.419491.0, Experimental and Clinical Research Center, , Max-Delbrück-Centrum für Molekulare Medizin und Charité—Universitätsmedizin Berlin, ; Berlin, Germany
            Contributors
            frederike-cosima.oertel@charite.de
            hanna.zimmermann@charite.de
            friedemann.paul@charite.de
            +49-30-450-539757 , alexander.brandt@charite.de
            Journal
            EPMA J
            EPMA J
            The EPMA Journal
            Springer International Publishing (Cham )
            1878-5077
            1878-5085
            22 December 2017
            22 December 2017
            March 2018
            : 9
            : 1
            : 21-33
            5833887 123 10.1007/s13167-017-0123-5
            © The Author(s) 2017

            Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

            Funding
            Funded by: German Ministry for Education and Research
            Funded by: FundRef http://dx.doi.org/10.13039/501100001659, Deutsche Forschungsgemeinschaft;
            Award ID: Exc. 257
            Award Recipient :
            Funded by: FundRef http://dx.doi.org/10.13039/100008087, Guthy-Jackson Charitable Foundation;
            Funded by: FundRef http://dx.doi.org/10.13039/100000890, National Multiple Sclerosis Society;
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            © European Association for Predictive, Preventive and Personalised Medicine (EPMA) 2018

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