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Background: There is a need for biomarkers of disease progression and therapeutic response in multiple sclerosis (MS). This study aimed to identify cerebrospinal fluid (CSF) lipids that differentiate MS from other neuroinflammatory conditions and correlate with Expanded Disability Status Scale (EDSS) scores, gadolinium-enhancing lesions or inflammatory mediators., Methods: Lipids and inflammatory cytokines/chemokines were quantified with liquid chromatography-tandem mass spectrometry and multiplex ELISA, respectively, in CSF from people with untreated MS, neuromyelitis optica spectrum disorder (NMOSD), other inflammatory neurological diseases and non-inflammatory neurological diseases (NIND). Analytes were compared between groups using analysis of variance, and correlations were assessed with Pearson's analysis., Results: Twenty-five sphingolipids and four lysophosphatidylcholines were significantly higher in NMOSD compared with MS and NIND cases, whereas no lipids differed significantly between MS and NIND. A combination of three sphingolipids differentiated NMOSD from MS with the area under the curve of 0.92 in random forest models. Ninety-four lipids, including those that differentiated NMOSD from MS, were positively correlated with macrophage migration inhibitory factor (MIF) and 37 lipids were positively correlated with CSF protein in two independent MS cohorts. EDSS was inversely correlated with cholesterol ester CE(16:0) in both MS cohorts. In contrast, MIF and soluble triggering receptor expressed on myeloid cells 2 were positively associated with EDSS., Conclusions: CSF sphingolipids are positively correlated with markers of neuroinflammation and differentiate NMOSD from MS. The inverse correlation between EDSS and CE(16:0) levels may reflect poor clearance of cholesterol released during myelin break-down and warrants further investigation as a biomarker of therapeutic response., Competing Interests: Competing interests: TAH has received honoraria for talks, advisory boards or support for scientific meetings from Bayer-Schering, Biogen Idec, Novartis, Teva, Merck, Alexion, Briston Myers Squibb and Sanofi-Genzyme, and is a paid writer for Australian MS Research Review., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY. Published by BMJ Group.)

Background: Patients with refractory or high-risk myasthenia gravis (MG) respond poorly to conventional immunosuppressive therapy, requiring rescue therapies and often experiencing treatment toxicity. Rescue and injectable therapies do not induce remission and require repetitive administration leading to significant constraints on patients and the healthcare system. This long-term follow-up study demonstrates cyclophosphamide as a rapidly effective and safe treatment in patients with refractory or high-risk MG., Methods: Retrospective cohort study of MG patients treated with cyclophosphamide between January 2000 and June 2022 conducted at a quaternary neuroimmunology clinic in New South Wales, Australia., Results: 31 patients were treated: mean age of 64 years; median follow-up 3.6 years (5 months to 11 years); 94% seropositive to acetylcholine receptor (AChR) antibodies and 45% had thymoma. A reduced intensity cyclophosphamide induction protocol followed by oral antiproliferative maintenance is described.Median myasthenia gravis composite scores reduced by >50% after the third cycle of cyclophosphamide. Complete cessation of prednisolone was possible in 11 patients while 20 remained on prednisolone with a median daily dose of 5 mg. Plasma exchange was ceased in 62% of patients and intravenous immunoglobulin ceased in 55%. Cyclophosphamide was generally well tolerated with mild cytopenias. There were no malignancies or cases of haemorrhagic cystitis., Conclusion: We describe a large cohort of high-risk MG patients treated with cyclophosphamide in a retrospective single-clinic cohort. We suggest cyclophosphamide should be considered for rapid remission induction, corticosteroid reduction and long-term freedom from recurrent injectable therapies in selected patients, typically those with AChR antibodies., Competing Interests: Competing interests: SR has received research funding from the National Health and Medical Research Council (NHMRC, Australia), the Petre Foundation, the Brain Foundation (Australia), the Royal Australasian College of Physicians, and the University of Sydney. She is supported by an NHMRC Investigator Grant (GNT2008339). She serves as a consultant on an advisory board for UCB and Limbic Neurology. She has been an invited speaker for Biogen, Excemed, Alexion, Novartis and Limbic Neurology for research and education meetings. She is a non-remunerated member of the medical advisory board of The MOG Project and The Sumaira Foundation. SWR declares funds over the last 5 years including but not limited to travel support, honoraria, trial payments, research and clinical support to the neurology department or academic projects of which I am a member have been received from bodies and charities: NHMRC, MRFF, NBA, Myasthenia Alliance Australia, Lambert Initiative, Beeren foundation, anonymous donors; and from pharmaceutical/biological companies: Alexion, Biogen, CSL, Genzyme, Grifols, Merck, Novartis, Roche, Sandoz, Sanofi, UCB. Additional interests and potential conflicts of interest include:Co-founder/shareholder of RxPx health, National IVIG Governance Advisory Council & Specialist Working Group Australia (Neurology) (paid), Australian Medical Services Advisory Committee ad hoc subcommittee on IVIG (paid), Australian Technical Advisory Group on Immunisation Varicella Zoster working party (unpaid), Public Salary as a staff specialist neurologist from Concord Hospital Sydney Local Health District (paid), Private billings from patients and medicare Australia reimbursement as a private practice neurologist (paid), Medical advisor (unpaid) to various patient and advocacy groups. All other authors declare no competing interests for content., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We sought to identify an optimal oral corticosteroid regimen at the onset of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), which would delay time to first relapse while minimising cumulative corticosteroid exposure., Methods: In a retrospective multicentre cohort study, Cox proportional hazards models examined the relationship between corticosteroid course as a time-varying covariate and time to first relapse. Simon-Makuch and Kaplan-Meier plots identified an optimal dosing strategy., Results: We evaluated 109 patients (62 female, 57%; 41 paediatric, 38%; median age at onset 26 years, (IQR 8-38); median follow-up 6.2 years (IQR 2.6-9.6)). 76/109 (70%) experienced a relapse (median time to first relapse 13.7 months; 95% CI 8.2 to 37.9). In a multivariable model, higher doses of oral prednisone delayed time to first relapse with an effect estimate of 3.7% (95% CI 0.8% to 6.6%; p = 0.014) reduced hazard of relapse for every 1 mg/day dose increment. There was evidence of reduced hazard of relapse for patients dosed ≥12.5 mg/day (HR 0.21, 95% CI 0.07 to 0.6; p = 0.0036), corresponding to a 79% reduction in relapse risk. There was evidence of reduced hazard of relapse for those dosed ≥12.5 mg/day for at least 3 months (HR 0.12, 95% CI 0.03 to 0.44; p = 0.0012), corresponding to an 88% reduction in relapse risk compared with those never treated in this range. No patient with this recommended dosing at onset experienced a Common Terminology Criteria for Adverse Events grade >3 adverse effect., Conclusions: The optimal dose of 12.5 mg of prednisone daily in adults (0.16 mg/kg/day for children) for a minimum of 3 months at the onset of MOGAD delays time to first relapse., Competing Interests: Competing interests: BPT receives a University of Sydney postgraduate scholarship and a stipend from CIA Ramanathan’s Royal Australasian College of Physicians Research Establishment Fellowship. RCD has received research funding from the Star Scientific Foundation, The Trish Multiple Sclerosis Research Foundation, Multiple Sclerosis Research Australia, the Petre Foundation and the NHMRC (Australia; Investigator Grant). He has also received honoraria from Biogen Idec as an invited speaker, and is on the IDMC for a Roche RCT in paediatric MS. He is on the medical advisory board (non-remunerated position). TAH has received research funding from MS Australia, the NHMRC Medical Research Future Fund (Australia), the Brain Foundation and has received honoraria for talks, advisory boards or support for scientific meetings from Bayer-Schering, Novartis, Biogen Idec, Merck, Teva, Alexion, Bristol Myers Squibb and Sanofi-Genzyme. AVDW receives funding from MS Australia, the NHMRC and the Trish Foundation. She has received research support from Roche pharmaceuticals, Biogen, Novartis and Merck. She has received honoraria for talks, advisory boards, and travel support from Novartis and Merck. She serves as the COO of the MSBase Foundation. JLS received travel compensation from Biogen, Merck, Novartis; has been involved in clinical trials with Biogen, Novartis, Roche; her institution has received honoraria for talks and advisory board service from Biogen, Merck, Novartis, Roche. She is on the board of directors for MSPlus. HB has received institutional compensation (To Monash University) for advisory board or trial steering committee membership or speaker bureaus from Biogen, Merck, Novartis, Roche, and UCB Pharma. Institutional Research Support to Monash University or MSBase Foundation from Merck, Biogen, Roche, Novartis, UCB Pharma, Alexion, Teva, NMHRC (Australia), MRFF (Australia), MS Australia, TRISH MS Research Foundation, Pennycook Foundation and Monash University. SAB has received honoraria for attendance at advisory boards and travel sponsorship from Bayer-Schering, Biogen-Idec, Merck-Serono, Novartis, and Sanofi-Genzyme, has received speaker’s 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. MB received research grants from Genzyme-Sanofi, Novartis, Biogen, Merck and BMS; and is a Research Consultant for RxMx and Research Director for the Sydney Neuroimaging Analysis Centre. He is on the board of the Research Management Council of MS Australia, or the Trish Foundation Board. SWR has received travel support, honoraria, trial payments, research and clinical support to the neurology department or academic projects from NHMRC, MRFF, NBA, Myasthenia Alliance Australia, Lambert Initiative, Beeren foundation, anonymous donors; and from pharmaceutical / biological companies: Alexion, Biogen, CSL, Genzyme, Grifols, Merck, Novartis, Roche, Sandoz, Sanofi, UCB. He is cofounder/shareholder of RxPx health, National IVIG Governance Advisory Council & Specialist Working Group Australia (Neurology) (paid), Australian Medical Services Advisory Committee ad hoc subcommittee on IVIG (paid), Australian Technical Advisory Group on Immunisation Varicella Zoster working party (unpaid), Medical advisor (unpaid) to various patient and advocacy groups. Funds over the last 5 years including but not limited to travel support, honoraria, trial payments, research and clinical support to the neurology department or academic projects from: NHMRC, MRFF, NBA, Myasthenia Alliance Australia, Lambert Initiative, Beeren foundation, anonymous donors; and from pharmaceutical/biological companies: Alexion, Biogen, CSL, Genzyme, Grifols, Merck, Novartis, Roche, Sandoz, Sanofi, UCB. FB has received research funding from NSW Health, MS Australia, the NHMRC (Australia), the Medical Research Future Fund (Australia), The MOG Project (Apollo Grant) and Novartis. She was on an advisory board for Novartis and Merck, and has been an invited speaker for Biogen, Novartis and Limbic Neurology. She is on the medical advisory board (non-remunerated positions) of The MOG Project and the Sumaira Foundation. TK served on scientific advisory boards for MS International Federation and World Health Organisation, BMS, Roche, Janssen, Sanofi Genzyme, Novartis, Merck and Biogen, steering committee for Brain Atrophy Initiative by Sanofi Genzyme, received conference travel support and/or speaker honoraria from WebMD Global, Eisai, Novartis, Biogen, Roche, Sanofi-Genzyme, Teva, BioCSL and Merck and received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene and Merck. SR has received research funding from the National Health and Medical Research Council (NHMRC, Australia), the Petre Foundation, the Brain Foundation, the Royal Australasian College of Physicians, and the University of Sydney. She is supported by an NHMRC Investigator Grant (GNT2008339). She serves as a consultant on an advisory board for UCB and Limbic Neurology and has been an invited speaker for educational/research sessions coordinated by Biogen, Alexion, Novartis, Excemed and Limbic Neurology. She is on the medical advisory board (non-remunerated positions) of The MOG Project and the Sumaira Foundation. All other authors have no relevant disclosures., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

The triad of central nervous system symptoms, visual disturbance and hearing impairment is an oft-encountered clinical scenario. A number of immune-mediated diseases should be considered among the differential diagnoses including: Susac syndrome, Cogan syndrome or Vogt-Koyanagi-Harada disease; demyelinating conditions such as multiple sclerosis or neuromyelitis optica spectrum disorder; systemic diseases such as systemic lupus erythematosus, Sjögren syndrome or Behcet disease and granulomatous diseases such as sarcoidosis. In this article, we coin the term 'BEE syndromes' to draw attention to the various immune-mediated diseases that affect the brain, eye and ear. We present common disease manifestations and identify key clinical and investigation features., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Tumefactive lesions are an uncommon manifestation of demyelinating disease and can pose a diagnostic challenge in patients without a pre-existing diagnosis of multiple sclerosis. Choosing when to biopsy a tumefactive lesion to exclude alternative pathology can be difficult. Other questions include how best to treat an acute attack as well as the optimal timing of therapy to prevent relapse. This article aims to review the available literature for tumefactive demyelination and to propose an approach to diagnosis and management. We argue that disease modifying therapy should be considered for acute tumefactive demyelinating lesions only once criteria of dissemination in time and space are fulfilled and the diagnosis of multiple sclerosis is confirmed.