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      Antibodies to myelin oligodendrocyte glycoprotein in bilateral and recurrent optic neuritis

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          Abstract

          Objective:

          We examined a cohort of adults with aquaporin-4 (AQP4) antibody–negative neuromyelitis optica/neuromyelitis optica spectrum disorder (NMO/NMOSD) for antibodies to myelin oligodendrocyte glycoprotein (MOG).

          Methods:

          We performed a flow cytometry cell-based assay using live human lentivirus–transduced cells expressing full-length surface MOG. Serum was tested in 23 AQP4 antibody–negative NMO/NMOSD patients with bilateral and/or recurrent optic neuritis (BON, n = 11), longitudinally extensive transverse myelitis (LETM, n = 10), and sequential BON and LETM (n = 2), as well as in patients with multiple sclerosis (MS, n = 76) and controls (n = 52).

          Results:

          MOG antibodies were detected in 9/23 AQP4 antibody–negative patients with NMO/NMOSD, compared to 1/76 patients with MS and 0/52 controls ( p < 0.001). MOG antibodies were detected in 8/11 patients with BON, 0/10 patients with LETM, and 1/2 patients with sequential BON and LETM. Six of 9 MOG antibody–positive patients had a relapsing course. MOG antibody–positive patients had prominent optic disc swelling and were more likely to have a rapid response to steroid therapy and relapse on steroid cessation than MOG antibody–negative patients ( p = 0.034 and p = 0.029, respectively). While 8/9 MOG antibody–positive patients had good follow-up visual acuity, one experienced sustained visual impairment, 3 had retinal nerve fiber layer thinning, and one had residual spinal disability.

          Conclusions:

          MOG antibodies have a strong association with BON and may be a useful clinical biomarker. MOG antibody–associated BON is a relapsing disorder that is frequently steroid responsive and often steroid dependent. Failure to recognize the disorder early and institute immunotherapy promptly may be associated with sustained impairment.

          Classification of evidence:

          This study provides Class II evidence that MOG antibodies are associated with AQP4 antibody–negative BON (sensitivity 69%, 95% confidence interval [CI] 42%–87%; specificity 99%, 95% CI 93.7%–99.8%).

          Related collections

          Most cited references26

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          Myelin-oligodendrocyte glycoprotein antibodies in adults with a neuromyelitis optica phenotype.

          Joanna Kitley, Mark Woodhall, Patrick Waters … (2012)
          To report an association of myelin-oligodendrocyte glycoprotein (MOG) antibodies with aquaporin-4 (AQP4) antibody-seronegative neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorder (NMOSD) in adults. We describe the clinical and serologic features of 4 adult patients with an NMO/NMOSD phenotype who had antibodies to MOG. Twenty-seven adult AQP4-seronegative NMO/NMOSD patients were tested for MOG antibodies. Four patients (3 male, 1 female) with severe optic neuritis and/or longitudinally extensive transverse myelitis were positive. All 4 made good recoveries with steroids or plasma exchange. Two patients experienced recurrence of symptoms when corticosteroids were withdrawn quickly but none have experienced further relapses over a mean follow-up of 12 months, although 3 patients remain on treatment. Imaging abnormalities resolved fully following clinical recovery and MOG antibody titers fell in all 4 patients. MOG antibodies were not found in 44 AQP4 antibody-positive NMO/NMOSD patients, 75 adult patients with multiple sclerosis, or 47 healthy individuals. MOG antibody-associated NMO/NMOSD could account for some cases thought previously to be AQP4-seronegative NMO/NMOSD. Our 4 patients appear to have more favorable clinical outcomes than those with typical AQP4 antibody-mediated disease. However, further studies of NMO/NMOSD and other demyelinating conditions are required to help clarify the diagnostic and prognostic relevance of MOG antibodies.
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            Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders

            Simone Mader, Viktoria Gredler, Kathrin Schanda … (2011)
            Background Serum autoantibodies against the water channel aquaporin-4 (AQP4) are important diagnostic biomarkers and pathogenic factors for neuromyelitis optica (NMO). However, AQP4-IgG are absent in 5-40% of all NMO patients and the target of the autoimmune response in these patients is unknown. Since recent studies indicate that autoimmune responses to myelin oligodendrocyte glycoprotein (MOG) can induce an NMO-like disease in experimental animal models, we speculate that MOG might be an autoantigen in AQP4-IgG seronegative NMO. Although high-titer autoantibodies to human native MOG were mainly detected in a subgroup of pediatric acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS) patients, their role in NMO and High-risk NMO (HR-NMO; recurrent optic neuritis-rON or longitudinally extensive transverse myelitis-LETM) remains unresolved. Results We analyzed patients with definite NMO (n = 45), HR-NMO (n = 53), ADEM (n = 33), clinically isolated syndromes presenting with myelitis or optic neuritis (CIS, n = 32), MS (n = 71) and controls (n = 101; 24 other neurological diseases-OND, 27 systemic lupus erythematosus-SLE and 50 healthy subjects) for serum IgG to MOG and AQP4. Furthermore, we investigated whether these antibodies can mediate complement dependent cytotoxicity (CDC). AQP4-IgG was found in patients with NMO (n = 43, 96%), HR-NMO (n = 32, 60%) and in one CIS patient (3%), but was absent in ADEM, MS and controls. High-titer MOG-IgG was found in patients with ADEM (n = 14, 42%), NMO (n = 3, 7%), HR-NMO (n = 7, 13%, 5 rON and 2 LETM), CIS (n = 2, 6%), MS (n = 2, 3%) and controls (n = 3, 3%, two SLE and one OND). Two of the three MOG-IgG positive NMO patients and all seven MOG-IgG positive HR-NMO patients were negative for AQP4-IgG. Thus, MOG-IgG were found in both AQP4-IgG seronegative NMO patients and seven of 21 (33%) AQP4-IgG negative HR-NMO patients. Antibodies to MOG and AQP4 were predominantly of the IgG1 subtype, and were able to mediate CDC at high-titer levels. Conclusions We could show for the first time that a subset of AQP4-IgG seronegative patients with NMO and HR-NMO exhibit a MOG-IgG mediated immune response, whereas MOG is not a target antigen in cases with an AQP4-directed humoral immune response.
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              Prognostic factors and disease course in aquaporin-4 antibody-positive patients with neuromyelitis optica spectrum disorder from the United Kingdom and Japan.

              Joanna Kitley, M Isabel Leite, Ichiro Nakashima … (2012)
              Neuromyelitis optica and neuromyelitis optica spectrum disorders have been recently associated with the disease-specific autoantibody aquaporin-4, thought to be pathogenic. Identifying this antibody has allowed the clinical phenotype to be broadened. It is clear that some patients with similar clinical features do not have this antibody and may have a different condition with different outcomes and prognosis. Previous clinical neuromyelitis optica and neuromyelitis optica spectrum disorder studies have included such patients. We investigated clinical outcomes and prognostic characteristics of 106 aquaporin-4 antibody-seropositive patients from the UK and Japan. We looked at predictors of disability outcomes, namely visual disability (permanent bilateral visual loss with visual acuity of <6/36 in the best eye), motor disability (permanent inability to walk further than 100 m unaided), wheelchair dependence and mortality. Data were collected largely retrospectively through review of case records. After median disease duration of 75 months, 18% had developed permanent bilateral visual disability, 34% permanent motor disability, 23% had become wheelchair dependent and 9% had died. Age at disease onset appeared to be an important predictor of disability type. Young-onset patients in the UK, but not the Japanese cohort, commonly presenting with optic neuritis, had a high risk of visual disability while older patients in both cohorts had a high risk of motor disability, regardless of their onset symptom. Genetic factors also appeared important. The UK cohort seemed to have more severe disease than the Japanese cohort, with more severe onset attacks, a higher relapse frequency and greater disability at follow-up, despite earlier immunosuppression. Moreover, within the UK cohort, there were important differences between ethnic groups, with Afro-Caribbean patients having a younger age at disease onset, more brain and multifocal attacks and higher likelihood of visual disability than Caucasian patients. Thus, age at disease onset and genetic factors are both likely to be important in determining clinical outcomes in aquaporin-4 disease. This has important implications for interpreting clinical neuromyelitis optica and neuromyelitis optica spectrum disorder studies, since clinical features and outcomes appear not to be generic across populations and may need to be tailored to individual groups. These factors need to be explored further in future prospective neuromyelitis optica and neuromyelitis optica spectrum disorder studies.
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                Author and article information

                Contributors
                Sudarshini Ramanathan:
                Comment :

                Scientific Advisory Boards:

                1. NONE

                Gifts:

                1. NONE

                Funding for Travel or Speaker Honoraria:

                1. NONE

                Editorial Boards:

                1. NONE

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. NONE

                Research Support, Academic Entities:

                1. Sudarshini Ramanathan has received a scholarship from the National Health and Medical Research Council (Australia)

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

                1. NONE

                Stock/Stock Options, Research Sponsor:

                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                Stephen W. Reddel:
                Comment :

                Scientific Advisory Boards:

                1. 1. CSL 2. Baxter 3. Genzyme 4. Biogen 5. National Immunoglobulin Governmental Advisory Council, Australia

                Gifts:

                1. NONE

                Funding for Travel or Speaker Honoraria:

                1. 1. CSL 2. Genzyme 3. Biogen

                Editorial Boards:

                1. NONE

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NSW Health, Australia

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. 1. Genzyme

                Research Support, Government Entities:

                1. NONE

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. Beeren Foundation

                Stock/Stock Options/Board of Directors Compensation:

                1. 1. Sydney Neurology 2. Medical Safety Systems

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

                1. NONE

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                1. NONE

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                1. NONE

                Legal Proceedings:

                1. NONE

                Andrew Henderson:
                Comment :

                Scientific Advisory Boards:

                1. NONE

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                1. NONE

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                1. NONE

                Editorial Boards:

                1. NONE

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. NONE

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

                Legal Proceedings:

                1. NONE

                John D.E. Parratt:
                Comment :

                Scientific Advisory Boards:

                1. 1. Commercial - Genzyme scientific advisory board 2. Commercial - Novartis scientific advisory board

                Gifts:

                1. NONE

                Funding for Travel or Speaker Honoraria:

                1. 1. Commercial - Honoraria from Biogen for educational meetings 2. Commercial - Honoraria from Genzyme/Sanofi for educational meetings 3. Commercial - Honoraria from Merck Serono for educational meetings.

                Editorial Boards:

                1. NONE

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. NONE

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. Multiple sclerosis research Australia Neil and Norma Hill inaugural junior practitioner fellowship

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

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                1. NONE

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                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                Michael Barnett:
                Comment :

                Scientific Advisory Boards:

                1. 1.Novartis, scientific advisory board 2.Genzyme-Sanofi, scientific advisory board

                Gifts:

                1. NONE

                Funding for Travel or Speaker Honoraria:

                1. NONE

                Editorial Boards:

                1. NONE

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. 1. Novartis, Research Grant support 2. Genzyme-Sanofi, Research Grant Support 3. Bio-CSL, Research Grant Support

                Research Support, Government Entities:

                1. 1. NSW Government (Australia), Paul Brock Fellowship, 2012- 2014

                Research Support, Academic Entities:

                1. 1. Multiple Sclerosis Research Australia, principal investigator 2009-2011

                Research Support, Foundations and Societies:

                1. Nerve Research Foundation, The University of Sydney

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

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                Prudence N. Gatt:
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                Vera Merheb:
                Comment :

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                Raani-Yogeeta Anusuiya Kumaran:
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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                Karrnan Pathmanandavel:
                Comment :

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

                Research Support, Foundations and Societies:

                1. Karrnan Pathmanandavel has received a scholarship from the Petre Foundation (Australia)

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                1. NONE

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                Nese Sinmaz:
                Comment :

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

                Research Support, Academic Entities:

                1. Australian Postgraduate Award (Australia)

                Research Support, Foundations and Societies:

                1. NONE

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                1. NONE

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                1. NONE

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                Mahtab Ghadiri:
                Comment :

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                1. NONE

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                1. NONE

                Funding for Travel or Speaker Honoraria:

                1. 1. Genzyme, funding for travel to the AAN annual meeting 2014 2. BioCSL, funding for travel to the ECTRIMS annaul meeting 2013 3. Biogen Idec, funding for travel to the AAN annual meeting 2013 4. Novartis, funding for travel to the PACTRIMS annual meeting 2012

                Editorial Boards:

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                Other Activities:

                1. 1. Novartis, received fellowship funding

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                Con Yiannikas:
                Comment :

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                1. (1)Commercial- Biogen Idec-BG12 Advisory board

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                1. NONE

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                1. Commercial-Novartis-Travel to ECTRIMs 2012 Biogen -Travel to AAN-2012 Novartis- MS symposium 2012

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                1. Consultant-Allergan

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                Steve Vucic:
                Comment :

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                1. Member of the scientific boards for Merck Serono Australia, Novartis, and Bayer Schering. Commercial entity

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. Medical consultant for Merck Serono Australia

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

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                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. NONE

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

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                Graeme Stewart:
                Comment :

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                1. SAB Actelion, Basel

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

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                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. Pfizer International : study on familial amyloidosis in Australia

                Research Support, Government Entities:

                1. National Health & Medical Research Council of Australia, project grant funding unrelated to the study in the submitted manuscript

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

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                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                Andrew F. Bleasel:
                Comment :

                Scientific Advisory Boards:

                1. NONE

                Gifts:

                1. NONE

                Funding for Travel or Speaker Honoraria:

                1. NONE

                Editorial Boards:

                1. NONE

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. NONE

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

                1. NONE

                Stock/Stock Options, Research Sponsor:

                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                David Booth:
                Comment :

                Scientific Advisory Boards:

                1. NONE

                Gifts:

                1. NONE

                Funding for Travel or Speaker Honoraria:

                1. Genzyme, speaker honoraria Biogen Idec, Merck Serono, Sanofi Aventis, and Pfizer.

                Editorial Boards:

                1. Plos One, editor, 2013-2014

                Patents:

                1. Prediction of response to therapy for hepatitis C

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. Pfizer, Research Grant on Amyloidosis (not related to this work)

                Research Support, Government Entities:

                1. National Health Medical Research Council, Australia (NHMRC), APP1049936, CI, 2013-2015 NHMRC, APP1050074, CI, 2013-2015 NHMRC,APP1065157, CI, 2014-2016 NHMRC,APP1067209, CI, 2014-2016

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. Multiple Sclerosis Research Australia (MSRA) Senior Research Fellowship (2010-2014) MSRA, APP10-029, 2011-2013 the Australian Research Council, Multiple Sclerosis Research Australia, and the Leukemia foundation

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

                1. NONE

                Stock/Stock Options, Research Sponsor:

                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                Victor S.C. Fung:
                Comment :

                Scientific Advisory Boards:

                1. Advisory Boards for Abbott, Allergan, Boehringer-Ingelheim, Hospira, Ipsen, Lundbeck, Novartis, Solvay and UCB.

                Gifts:

                1. NONE

                Funding for Travel or Speaker Honoraria:

                1. Boehringer-Ingelheim, Ipsen

                Editorial Boards:

                1. Movement Disorders Clinical Practice, Journal of Clinical Movement Disorders, Basal Ganglia, F1000 Research

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. Western Sydney Local Health Network, NSW, Australia

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. NONE

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

                1. NONE

                Stock/Stock Options, Research Sponsor:

                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                Russell C. Dale:
                Comment :

                Scientific Advisory Boards:

                1. Queensland Children's Medical Institute Research advisory committee. Not for profit.

                Gifts:

                1. NONE

                Funding for Travel or Speaker Honoraria:

                1. received an honoraria for lecturing from Biogen Idec

                Editorial Boards:

                1. Editorial advisory board member of MSARD Editorial board member of Neurology: Neuroimmunology and Neuroinflammation Editorial board member of European Journal of Paediatric Neurology

                Patents:

                1. NONE

                Publishing Royalties:

                1. Biogen Idec 1000 dollar honoria in 2008

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. NHMRC national grant in 2011 national grant for encephalitis study NHMRC practitioner fellowship 2014-8

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. NONE

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

                1. NONE

                Stock/Stock Options, Research Sponsor:

                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                Fabienne Brilot:
                Comment :

                Scientific Advisory Boards:

                1. NONE

                Gifts:

                1. NONE

                Funding for Travel or Speaker Honoraria:

                1. NONE

                Editorial Boards:

                1. (1)Journal of Visualized Experiments, associate editor, 1 year, no compensation received

                Patents:

                1. NONE

                Publishing Royalties:

                1. NONE

                Employment, Commercial Entity:

                1. NONE

                Consultancies:

                1. NONE

                Speakers' Bureaus:

                1. NONE

                Other Activities:

                1. NONE

                Clinical Procedures or Imaging Studies:

                1. NONE

                Research Support, Commercial Entities:

                1. NONE

                Research Support, Government Entities:

                1. (1) National Health and Medical Research Council Australia

                Research Support, Academic Entities:

                1. NONE

                Research Support, Foundations and Societies:

                1. (1) The Star Scientific Foundation Australia (2) The Trish Multiple Sclerosis Foundation Australia (3) Multiple Sclerosis Research Australia (4) Multiple Sclerosis Angels Melbourne Australia (5) Petre Foundation Australia

                Stock/Stock Options/Board of Directors Compensation:

                1. NONE

                License Fee Payments, Technology or Inventions:

                1. NONE

                Royalty Payments, Technology or Inventions:

                1. NONE

                Stock/Stock Options, Research Sponsor:

                1. NONE

                Stock/Stock Options, Medical Equipment & Materials:

                1. NONE

                Legal Proceedings:

                1. NONE

                Journal
                Journal ID (nlm-ta): Neurol Neuroimmunol Neuroinflamm
                Journal ID (iso-abbrev): Neurol Neuroimmunol Neuroinflamm
                Journal ID (hwp): nnn
                Journal ID (publisher-id): NEURIMMINFL
                Title: Neurology® Neuroimmunology & Neuroinflammation
                Publisher: Lippincott Williams & Wilkins (Hagerstown, MD )
                ISSN (Electronic): 2332-7812
                Publication date (Electronic): 29 October 2014
                Publication date Collection: December 2014
                Publication date PMC-release: 29 October 2014
                Volume: 1
                Issue: 4
                Electronic Location Identifier: e40
                Affiliations
                Authors' affiliations are listed at the end of the article.
                Author notes
                Correspondence to Dr. Brilot: Fabienne.brilot@ 123456sydney.edu.au

                Go to Neurology.org/nn for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was paid by the authors.

                Article
                Publisher ID: NEURIMMINFL2014001404
                DOI: 10.1212/NXI.0000000000000040
                PMC ID: 4215392
                PubMed ID: 25364774
                SO-VID: eeef41a5-2335-4821-a0fe-10bcf69ed625
                Copyright © © 2014 American Academy of Neurology
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution-Noncommercial No Derivative 3.0 License, which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.

                History
                Date received : 01 June 2014
                Date accepted : 11 September 2014
                Categories
                Subject: Article
                Custom metadata
                OPEN-ACCESS TRUE
                special-property triangle

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