BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently described demyelinating disorder, and children represent about 50% of all cases. Almost half of the patients experience relapses, but very few studies have evaluated predictors of relapse risk, challenging clinical management. The study aimed to identify predictors at MOGAD onset that are associated with a relapsing course.
METHODS: Prospectively collected data from paediatric patients with MOGAD seen by the US Network of Paediatric MS Centres were leveraged. Univariable and adjusted multivariable models were used to predict recurrent disease.
RESULTS: We identified 326 MOGAD cases (mean age at first event 8.9 years [SD 4.3], 57% female, 77% white and 74% non-Hispanic) and 46% relapsed during a mean follow-up of 3.9 years (SD 4.1). In the adjusted multivariable model, female sex (HR 1.66, 95% CI 1.17 to 2.36, p=0.004) and Hispanic/Latino ethnicity (HR 1.77, 95% CI 1.19 to 2.64, p=0.005) were associated with a higher risk of relapsing MOGAD. Maintenance treatment initiated before a second event with rituximab (HR 0.25, 95% CI 0.07 to 0.92, p=0.037) or intravenous immunoglobulin (IVIG) (HR 0.35, 95% CI 0.14 to 0.88, p=0.026) was associated with lower risk of a second event in multivariable analyses. Conversely, maintenance steroids were associated with a higher estimated relapse risk (HR 1.76, 95% CI 0.90 to 3.45, p=0.097).
CONCLUSIONS: Sex and ethnicity are associated with relapsing MOGAD. Use of rituximab or IVIG therapy shortly after onset is associated with a lower risk of the second event. Preventive treatment after a first event could be considered for those with a higher relapse risk.

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.
CONCLUSIONS: 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.

We report unusual cases of combined central and peripheral demyelination in two siblings related to pregnancy, each presenting with progressive tetraparesis and cranial nerve palsies. The elder sister had a relapsing-remitting course with optic nerve dysfunction and died during a relapse from respiratory insufficiency. The younger sister presented with disorientation and acute-onset limb and facial weakness. She responded well to corticosteroid therapy. Their clinical presentation, response to immunomodulatory therapy, nerve conduction studies, cerebrospinal fluid and histology supported an acquired demyelinating cause. Whole-exome sequencing identified variants in two genes not previously linked to this clinical phenotype. Serological tests for antibody-mediated demyelination were negative. Despite the undefined pathogenesis, these cases provide a platform to explore the confluence of genetic, immune and environmental factors in the context of acquired demyelination. We discuss the differential diagnosis and a diagnostic approach to such cases from the perspectives of neuroimmunology and neurogenetics.

Oligoclonal bands (OCBs) represent the presence of intrathecal immunoglobulin G (IgG) as detected by isoelectric focusing and immunofixation. Cerebrospinal fluid (CSF) analysed alongside a paired serum sample gives five different immunofixation patterns. These are: type 1-the normal physiological state with no intrathecal IgG synthesis; type 2-evidence for intrathecal IgG synthesis, with CSF-restricted OCBs; type 3-evidence for intrathecal IgG synthesis, with CSF-restricted OCBs, but with additional, identical bands in the CSF and serum; type 4-absence of intrathecal IgG synthesis, but with identical OCBs in CSF and serum; and type 5-absence of intrathecal IgG synthesis, with a monoclonal band in CSF and serum. Analysis of these patterns can help to diagnose a range of neurological conditions, including multiple sclerosis. However, it is important to interpret OCB results alongside other CSF tests and their clinical context.

This Commentary recounts an academic journey from dentistry to neuroimmunology, highlighting pivotal moments such as a PhD fraught with challenges and an unexpected postdoctoral experience in France. My decision to settle in Belgium for a postdoc and subsequent transition to an assistant professorship at KU Leuven reflects resilience, adaptability and a commitment to both scientific exploration and family life. Balancing career uncertainties, motherhood and academic achievements, it encapsulates a trajectory shaped by a passion for neuroimmunology.

Neuroimmunology is an interdisciplinary branch of biomedical science that emerges from the intersection of studies on the nervous system and the immune system. The complex interplay between the two systems has long been recognized. Research efforts directed at the underlying functional interface and associated pathophysiology, however, have garnered attention only in recent decades. In this narrative review, we highlight significant advances in research on neuroimmune interplay and modulation. A particular focus is on early- and middle-career neuroimmunologists in China and their achievements in frontier areas of \"neuroimmune interface\", \"neuro-endocrine-immune network and modulation\", \"neuroimmune interactions in diseases\", \"meningeal lymphatic and glymphatic systems in health and disease\", and \"tools and methodologies in neuroimmunology research\". Key scientific questions and future directions for potential breakthroughs in neuroimmunology research are proposed.

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Herein we describe a case of relapsing anti-GAD65-associated encephalitis which was responsive to the combination of thymoma resection, external beam radiotherapy, and immunomodulatory therapy. The case illustrates the value of remaining vigilant for the possibility of paraneoplastic syndromes in the context of anti-GAD65 antibodies and thymoma. It also illustrates that tumor-directed therapies may offer additional benefit beyond immunomodulatory therapy alone.

The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 revealed a huge number of problems as well as discoveries in medicine, notably, regarding the effects of the virus on the central nervous system (CNS) and peripheral nervous system (PNS). This paper is a narrative review that takes a deep dive into the complex interactions between COVID-19 and the NS. Therefore, this paper explains the broad range of neurological manifestations and neurodegenerative diseases caused by the virus. It carefully considers the routes through which SARS-CoV-2 reaches the NS, including the olfactory system and of course, the hematogenous route, which are also covered when discussing the virus\'s direct and indirect mechanisms of neuropathogenesis. Besides neurological pathologies such as stroke, encephalitis, Guillain-Barré syndrome, Parkinson\'s disease, and multiple sclerosis, the focus area is also given to the challenges of making diagnosis, treatment, and management of these conditions during the pandemic. The review also examines the strategic and interventional approaches utilized to prevent these disorders, as well as the ACE2 receptors implicated in the mediation of neurological effects caused by COVID-19. This detailed overview, which combines research outputs with case data, is directed at tackling this pandemic challenge, with a view toward better patient care and outcomes in the future.

UNASSIGNED: Recently, there have been a few reports of atypical post-coronavirus disease 2019 (COVID-19) myelopathy manifesting tract-specific lesions similar to those due to vitamin B12 deficiency. However, the precise characteristics of imaging or clinical course remain not well understood.
UNASSIGNED: A retrospective analysis of the clinical and imaging characteristics of four patients who were referred to our hospital with a unique post-COVID-19 myelopathy was performed.
UNASSIGNED: Four-to-six weeks following COVID-19 infection in the summer of 2023, four middle-aged men developed paraparesis, hypo/dysesthesia and bladder/bowel disturbance, suggesting myelopathy. Although spinal MRI showed no abnormalities in the early stages, tract-specific longitudinal lesions along the dorsal and lateral columns became apparent as the symptoms progressed. Owing to the lack of MRI findings at the early stage, all cases were challenging to diagnose. However, the patients remained partially responsive to aggressive immunosuppressive therapies, even in the advanced stage.
UNASSIGNED: We termed these tract-specific longitudinal lesions in the presented case series \'Grasshopper sign\' because brain coronal and spine axial MRI findings looked like a grasshopper\'s antennae and face. Early identification of the characteristic MRI abnormality could allow for early intervention using intensive immunosuppressive therapy, which could improve patient outcomes.