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Neuromyelitis optica spectrum disorders (NMOSD) are an inflammation of the central nervous system associated with autoantibodies to aquaporin-4. We have undertaken a clinic-based survey of NMOSD in the Australia and New Zealand populations with the aim of characterising the clinical features and establishing the value of recently revised diagnostic criteria. Cases of possible NMOSD and age and sex-matched controls with multiple sclerosis (MS) were referred from centres across Australia and New Zealand. Cases were classified as NMOSD if they met the 2015 IPND criteria and remained as suspected NMOSD if they did not. Clinical and paraclinical data were compared across the three groups. NMOSD was confirmed in 75 cases and 89 had suspected NMOSD. There were 101 controls with MS. Age at onset, relapse rates and EDSS scores were significantly higher in NMOSD than in MS. Lesions and symptoms referable to the optic nerve were more common in NMOSD whereas brainstem, cerebellar and cerebral lesions were more common in MS. Longitudinally extensive spinal cord lesions were seen in 48/71 (68%) of cases with NMOSD. Elevations of CSF, white cell count and protein were more common in NMOSD. We have confirmed a clinical pattern of NMOSD that has been seen in several geographical regions. We have demonstrated the clinical utility of the current diagnostic criteria. Distinct patterns of disease are evident in NMOSD and MS, but there remains a large number of patients with NMOSD-like features who do not meet the current diagnostic criteria for NMOSD and remain a diagnostic challenge.

Objectives: We have undertaken a clinic-based survey of neuromyelitis optica spectrum disorders (NMOSDs) in Australia and New Zealand to establish incidence and prevalence across the region and in populations of differing ancestry., Background: NMOSD is a recently defined demyelinating disease of the central nervous system (CNS). The incidence and prevalence of NMOSD in Australia and New Zealand has not been established., Methods: Centres managing patients with demyelinating disease of the CNS across Australia and New Zealand reported patients with clinical and laboratory features that were suspicious for NMOSD. Testing for aquaporin 4 antibodies was undertaken in all suspected cases. From this group, cases were identified who fulfilled the 2015 Wingerchuk diagnostic criteria for NMOSD. A capture-recapture methodology was used to estimate incidence and prevalence, based on additional laboratory identified cases., Results: NMOSD was confirmed in 81/170 (48%) cases referred. Capture-recapture analysis gave an adjusted incidence estimate of 0.37 (95% CI 0.35 to 0.39) per million per year and a prevalence estimate for NMOSD of 0.70 (95% CI 0.61 to 0.78) per 100 000. NMOSD was three times more common in the Asian population (1.57 (95% CI 1.15 to 1.98) per 100 000) compared with the remainder of the population (0.57 (95% CI 0.50 to 0.65) per 100 000). The latitudinal gradient evident in multiple sclerosis was not seen in NMOSD., Conclusions: NMOSD incidence and prevalence in Australia and New Zealand are comparable with figures from other populations of largely European ancestry. We found NMOSD to be more common in the population with Asian ancestry., Competing Interests: Competing interests: MHB has received honoraria for participation in advisory boards and travel sponsorship from Novartis, BioCSL, Genzyme and Biogen Idec. MBo has received travel sponsorship and honoraria from Sanofi-Genzyme, Teva, Novartis, BiogenIdec and Roche. BJB has received honoraria as a board member for GlaxoSmithKline, Biogen Idec, ViiV Healthcare and Merck Serono, has received speaker honoraria from ViiV Healthcare, Boehringer Ingelheim, Abbott, AbbVie and Biogen Idec, has received travel sponsorship from Abbott and ViiV Healthcare and has received research support funding from EIi Lilly, GlaxoSmithKline, ViiV Healthcare and Merck Serono. SAB has received honoraria for attendance at advisory boards and travel sponsorship from Bayer Schering Pharma, BiogenIdec, Merck Serono, Novartis and Sanofi-Genzyme, has received speaker honoraria from Biogen Idec and Genzyme, is an investigator in clinical trials sponsored by Biogen Idec, Novartis and Genzyme and was the recipient of an unencumbered research grant from Biogen Idec. HB has received honoraria for serving on scientific advisory boards for Biogen Idec, Novartis and Sanofi-Genzyme, has received conference travel sponsorship from Novartis and Biogen Idec, has received honoraria for speaking and acting as Chair at educational events organised by Novartis, Biogen Idec, Medscape and Merck Serono, serves on steering committees for trials conducted by Biogen Idec and Novartis, is chair (honorary) of the MSBase Foundation, which has received research support from Merck Serono, Novartis, Biogen Idec, Genzyme Sanofi and CSL Biopharma and has received research support form Merck Serono. WMC has been the recipient of travel sponsorship from, and provided advice to, Bayer Schering Pharma, BiogenIdec, Novartis, Genzyme, Sanofi-Aventis, BioCSL and Merck Serono. RCD has received research funding from the National Health and Medical Research Council, MS Research Australia, Star Scientific Foundation, Pfizer Neuroscience, Tourette Syndrome Association, University of Sydney and the Petre Foundation and has received honoraria from Biogen Idec and Bristol-Myers Squibb as an invited speaker. MjF-P has received travel sponsorship from Biogen Australia and New Zealand. RH has received honoraria, educational support and clinic funding from Novartis, Biogen Idec, Genzyme and BioCSL. AGK has received scientific consulting fees and/or lecture honoraria from Bayer, BioCSL, BiogenIdec, Genzyme, Merck, Novartis, Sanofi-Aventis and Teva. TJK has received travel sponsorship from Novartis, BioCSL, Novartis, Merck Serono and BiogenIdec, has received speaker honoraria from Biogen Idec, BioCSL, Merck Serono, Teva, Genzyme and Novartis, has received research support from Biogen Idec, Genzyme, GlaxoSmithKline, Bayer Schering Pharma and Merck Serono and has received scientific consulting fees from GlaxoSmithKline China, Biogen Idec and Novartis. JK has received remuneration for advisory board activities and presentations from Bayer Healthcare, Biogen Idec, BioCSL, Genzyme and Novartis. CK has received travel support, honoraria and advisory board payments from Biogen Idec, Bayer,Genzyme, Novartis and Serono. JL-S has received unencumbered funding as well as honoraria for presentations and membership on advisory boards from Sanofi-Aventis, Biogen Idec, Bayer Health Care, CSL, Genzyme, Merck Serono, Novartis Australia and Teva. RALM has received honoraria for attendance at advisory boards and travel sponsorship from Bayer Schering Pharma, Biogen Idec, CSL, Merck Serono, Novartis and Sanofi-Genzyme. MPMa has received travel sponsorship, honoraria, trial payments, research and clinical support from Bayer Schering Pharma, Biogen Idec, BioCSL, Genzyme, Novartis and Sanofi-Aventis Genzyme. DFM has received honoraria for attendance at advisory boards from Biogen Idec and Novartis, and travel sponsorship from Bayer Schering Pharma, Biogen Idec and Sanofi-Genzyme. PAMcC has received honoraria or travel sponsorship from Novartis, Sanofi-Aventis and Biogen Idec. JAP has received travel sponsorship, honoraria for presentations and membership on advisory boards from Biogen Idec and Novartis and Sanofi-Aventis. JDP has received honoraria for seminars or advisory boards from Teva, Biogen, Sanofi-Genzyme, Novartis, Merck, Bayer and research grants or fellowships from Merck, Novartis, Bayer, Biogen, Sanofi-Genzyme and Teva. SWR has received travel sponsorship, honoraria, trial payments, research and clinical support from Aspreva, Baxter, Bayer Schering Pharma, Biogen Idec, BioCSL, Genzyme, Novartis, Sanofi-Aventis Genzyme and Servier, and is a director of Medical Safety Systems Pty Ltd. CPS has received travel sponsorship from Biogen Idec, Novartis and Bayer Schering Pharma. IS has received remuneration for Advisory Board activities from Biogen, CSL and Bayer Schering Pharma and educational activities with Biogen, CSL and travel sponsorship from Biogen, Novartis and Bayer Schering Pharma. MS has received research support from Novartis, Biogen Idec and BioCSL. JSp has received honoraria for lectures and participation in advisory boards, and travel sponsorship from Novartis, BioCSL, Genzyme and Biogen Idec. BVT has received travel sponsorship from Novartis and Bayer Schering Pharma. AV and the University of Oxford hold patents and receive royalties for antibody testing. PW and the University of Oxford hold patents for antibody assays and have received royalties, has received speaker honoraria from Biogen Idec and Euroimmun AG and travel grants from the Guthy-Jackson Charitable Foundation. EW has received honoraria for participation in advisory boards from Biogen Idec and Novartis, travel sponsorship from Biogen Idec, Bayer Schering Pharma and Teva and is an investigator in clinical trials funded by Biogen Idec and Teva. DA, SBh, SBl, KB, MBr, WBr, WBu, CSB, CCM, LC, AC, CD, KD, DF, DG, SHa, APDH, SHe, SHo, SJ-S, AJK, M-WL, CL, CO’G, MPM, CS, RS, JSt, AV, SV, MWa, RJW, RCW, MWo and EMY report no disclosures., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Optic neuritis (ON) occurs in immune-mediated disorders including multiple sclerosis (MS), aquaporin-4 antibody-positive (AQP4) neuromyelitis optica spectrum disorder (AQP4-NMOSD) and myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination (MOGAD). Accurate determination of aetiology is critical for appropriate treatment and prognostication. Objective: To evaluate demyelination and axonal loss in MOG-ON to facilitate differentiation from MS-ON and AQP4-ON. Methods: 15 MOGAD patients with previous ON (25 eyes) underwent multifocal visual evoked potential (mfVEP) recordings and optical coherence tomography scans. Comparison was made to previously reported MS patients (n = 67, 69 eyes) and AQP4-NMOSD patients (n = 15, 23 eyes) with prior ON and healthy controls (n = 37, 74 eyes). Results: MOG-ON patients had less retinal nerve fibre layer (RNFL) loss than AQP4-ON patients (p < 0.05) and less mfVEP latency prolongation than MS-ON patients (p < 0.01). Number of ON episodes in MOGAD was associated with reduced RNFL thickness (global, p = 0.07; temporal, p < 0.001) and mfVEP amplitude (p < 0.001). There was no abnormality in non-ON eyes. Conclusions: Our study demonstrated a distinct pattern of damage in MOG-ON compared to AQP4-ON and MS-ON. ON in MOGAD produces less axonal loss than AQP4-NMOSD. Damage accumulates with relapses, supporting the role of maintenance immunosuppression to induce remission. Compared to MS, MOGAD causes less demyelination. [ABSTRACT FROM AUTHOR]

Objective: We characterised the clinical course, treatment and outcomes in 59 patients with relapsing myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination.Methods: We evaluated clinical phenotypes, annualised relapse rates (ARR) prior and on immunotherapy and Expanded Disability Status Scale (EDSS), in 218 demyelinating episodes from 33 paediatric and 26 adult patients.Results: The most common initial presentation in the cohort was optic neuritis (ON) in 54% (bilateral (BON) 32%, unilateral (UON) 22%), followed by acute disseminated encephalomyelitis (ADEM) (20%), which occurred exclusively in children. ON was the dominant phenotype (UON 35%, BON 19%) of all clinical episodes. 109/226 (48%) MRIs had no brain lesions. Patients were steroid responsive, but 70% of episodes treated with oral prednisone relapsed, particularly at doses <10 mg daily or within 2 months of cessation. Immunotherapy, including maintenance prednisone (P=0.0004), intravenous immunoglobulin, rituximab and mycophenolate, all reduced median ARRs on-treatment. Treatment failure rates were lower in patients on maintenance steroids (5%) compared with non-steroidal maintenance immunotherapy (38%) (P=0.016). 58% of patients experienced residual disability (average follow-up 61 months, visual loss in 24%). Patients with ON were less likely to have sustained disability defined by a final EDSS of ≥2 (OR 0.15, P=0.032), while those who had any myelitis were more likely to have sustained residual deficits (OR 3.56, P=0.077).Conclusion: Relapsing MOG antibody-associated demyelination is strongly associated with ON across all age groups and ADEM in children. Patients are highly responsive to steroids, but vulnerable to relapse on steroid reduction and cessation. [ABSTRACT FROM AUTHOR]

Background: Recognizing the cause of optic neuritis (ON) affects treatment decisions and visual outcomes. Objective: We aimed to define radiological features of first-episode demyelinating ON. Methods: We performed blinded radiological assessment of 50 patients presenting with first-episode myelin oligodendrocyte glycoprotein (MOG) antibody-associated ON (MOG-ON; n=19), aquaporin-4 (AQP4) antibody-associated ON (AQP4-ON; n=11), multiple sclerosis (MS)-associated ON (MS-ON; n=13), and unclassified ON (n=7). Results: Bilateral involvement was more common in MOG-ON and AQP4-ON than MS-ON (84% vs. 82% vs. 23%), optic nerve head swelling was more common in MOG-ON (53% vs. 9% vs. 0%), chiasmal involvement was more common in AQP4-ON (5% vs. 64% vs. 15%), and bilateral optic tract involvement was more common in AQP4-ON (0% vs. 45% vs. 0%). Retrobulbar involvement was more common in MOG-ON, whereas intracranial involvement was more common in AQP4-ON. MOG-ON and AQP4-ON had longer lesion lengths than MS-ON. The combination of two predictors, the absence of magnetic resonance imaging brain abnormalities and a higher lesion extent score, showed a good ability to discriminate between an autoantibody-associated ON (MOG or AQP4) and MS. AQP4-ON more frequently had severe and sustained visual impairment. Conclusion: MOG-ON and AQP4-ON are more commonly bilateral and longitudinally extensive. MOG-ON tends to involve the anterior optic pathway, whereas AQP4-ON the posterior optic pathway. [ABSTRACT FROM AUTHOR]

Lesions in the corpus callosum (CC) are important radiological clues to the diagnosis of multiple sclerosis (MS), but may also occur in other neuroinflammatory and non-neuroinflammatory conditions. In this article, we discuss the radiological features of lesions within the CC in MS and other central nervous system inflammatory and acquired demyelinating diseases. An understanding of the appearance and location of lesions in the CC is important not only for accurate diagnosis and treatment of these various conditions, but as it also provides insights into pathogenesis. [ABSTRACT FROM AUTHOR]