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Low serum levels of 25-hydroxyvitamin D [25(OH)D] and low sunlight exposure are known risk factors for the development of multiple sclerosis. Add-on vitamin D supplementation trials in established multiple sclerosis have been inconclusive. The effects of vitamin D supplementation to prevent multiple sclerosis is unknown. We aimed to test the hypothesis that oral vitamin D3 supplementation in high-risk clinically isolated syndrome (abnormal MRI, at least three T2 brain and/or spinal cord lesions), delays time to conversion to definite multiple sclerosis, that the therapeutic effect is dose-dependent, and that all doses are safe and well tolerated. We conducted a double-blind trial in Australia and New Zealand. Eligible participants were randomized 1:1:1:1 to placebo, 1000, 5000 or 10 000 international units (IU) of oral vitamin D3 daily within each study centre (n = 23) and followed for up to 48 weeks. Between 2013 and 2021, we enrolled 204 participants. Brain MRI scans were performed at baseline, 24 and 48 weeks. The main study outcome was conversion to clinically definite multiple sclerosis based on the 2010 McDonald criteria defined as either a clinical relapse or new brain MRI T2 lesion development. We included 199 cases in the intention-to-treat analysis based on assigned dose. Of these, 116 converted to multiple sclerosis by 48 weeks (58%). Compared to placebo, the hazard ratios (95% confidence interval) for conversion were 1000 IU 0.87 (0.50, 1.50); 5000 IU 1.37 (0.82, 2.29); and 10 000 IU 1.28 (0.76, 2.14). In an adjusted model including age, sex, latitude, study centre and baseline symptom number, clinically isolated syndrome onset site, presence of infratentorial lesions and use of steroids, the hazard ratios (versus placebo) were 1000 IU 0.80 (0.45, 1.44); 5000 IU 1.36 (0.78, 2.38); and 10 000 IU 1.07 (0.62, 1.85). Vitamin D3 supplementation was safe and well tolerated. We did not demonstrate reduction in multiple sclerosis disease activity by vitamin D3 supplementation after a high-risk clinically isolated syndrome. [ABSTRACT FROM AUTHOR]

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.

Multiple sclerosis (MS) is a potentially life-changing immune mediated disease of the central nervous system. Until recently, treatment has been largely confined to acute treatment of relapses, symptomatic therapies and rehabilitation. Through persistent efforts of dedicated physicians and scientists around the globe for 160 years, a number of therapies that have an impact on the long term outcome of the disease have emerged over the past 20 years. In this three part series we review the practicalities, benefits and potential hazards of each of the currently available and emerging treatment options for MS. We pay particular attention to ways of abrogating the risks of these therapies and provide advice on the most appropriate indications for using individual therapies. In Part 1 we review the history of the development of MS therapies and its connection with the underlying immunobiology of the disease. The established therapies for MS are reviewed in detail and their current availability and indications in Australia and New Zealand are summarised. We examine the evidence to support their use in the treatment of MS., (Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.)

In this third and final part of our review of multiple sclerosis (MS) treatment we look at the practical day-to-day management issues that are likely to influence individual treatment decisions. Whilst efficacy is clearly of considerable importance, tolerability and the potential for adverse effects often play a significant role in informing individual patient decisions. Here we review the issues surrounding switching between therapies, and the evidence to assist guiding the choice of therapy to change to and when to change. We review the current level of evidence with regards to the management of women in their child-bearing years with regards to recommendations about treatment during pregnancy and whilst breast feeding. We provide a summary of recommended pre- and post-treatment monitoring for the available therapies and review the evidence with regards to the value of testing for antibodies which are known to be neutralising for some therapies. We review the occurrence of adverse events, both the more common and troublesome effects and those that are less common but have potentially much more serious outcomes. Ways of mitigating these risks and managing the more troublesome adverse effects are also reviewed. Finally, we make specific recommendations with regards to the treatment of MS. It is an exciting time in the world of MS neurology and the prospects for further advances in coming years are high., (Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.)

In Part 2 of this three part review of multiple sclerosis (MS) treatment with a particular focus on the Australian and New Zealand perspective, we review the newer therapies that have recently become available and emerging therapies that have now completed phase III clinical trial programs. We go on to compare the relative efficacies of these newer and emerging therapies alongside the existing therapies. The effectiveness of β-interferon in the treatment of different stages and the different disease courses of MS is critically reviewed with the conclusion that the absolute level of response in term of annualised relapse rates (where relapses occur) and MRI activity are similar, but are disappointing in terms of sustained disability progression for progressive forms of the disease. Finally we review the controversial area of combination therapy for MS. Whilst it remains the case that we have no cure or means of preventing MS, we do have a range of effective therapies that when used appropriately and early in the disease course can have a significant impact on short term and longer term outcomes., (Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.)