BACKGROUND AND OBJECTIVES:It is currently difficult to accurately predict who, after the index event of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), will develop relapsing disease (R-MOGAD). Several clinical features have been reported as possibly predictive, but none have been validated in clinical practice. We used a prospectively designed analysis to assess a combined model of reported clinical prognosticators for developing R-MOGAD in 101 patients with MOGAD (86% with onset in adulthood) from 3 UK specialist centers. METHODS:A multivariable binary logistic regression model using variables identified from a scoping literature review was fitted in a retrospective clinical data set of patients with MOGAD (Nottingham MS & Neuroinflammation Centre [NUH]), with validation analysis in 2 independent data sets (Walton NMOSD Specialist Centre [WSC]; Imperial College London [ICL]). Secondary analysis investigated time to first relapse using Cox proportional hazards on the combined cohort. Results from the significant variables from the initial analysis were further examined in a meta-analysis of relevant literature studies. RESULTS:In the Neuroinflammation - Nottingham University Hospitals NHS Trust data set (n = 33), treatment with steroids ≥10 mg for ≥ 3 months after the index event was significantly associated with a lower likelihood of developing R-MOGAD (p = 0.006) with sensitivity 83% (95% CI 59-96) and specificity 73% (95% CI 45-92). A persistently positive MOG-IgG status, age at onset, optic neuritis at onset, and sex were not significant predictors of developing R-MOGAD. To assess generalizability, this predictor was tested in 2 independent data sets. In Walton Centre Liverpool (n = 39), not receiving prednisolone ≥10 mg ≥ 3 months was associated with R-MOGAD (OR = 9.7; 95% CI 2.1-45.4; sensitivity 63%; 95% CI 38-84; specificity 85%; 95% CI 62-97). In ICL (n = 29), the association was directionally consistent but inconclusive, with wide confidence intervals crossing unity (OR = 2.7; 95% CI 0.5-13.4; sensitivity 73%; 95% CI 39-94; specificity 50%; 95% CI 26-74). For the combined cohort (n = 101), not receiving prednisolone ≥ 10 mg for ≥3 months was associated with increased odds of developing R-MOGAD (OR = 6.2; 95% CI 2.6-14.8; p < 0.0001). Conversely, prednisolone ≥10 mg ≥ 3 months was associated with a lower hazard of relapse (HR = 0.47; 95% CI 0.24-0.91; p = 0.024). Median follow-up for monophasic patients was 42 months (IQR: 17.5-64.5). DISCUSSION:Prednisolone ≥10 mg for ≥ 3 months after the index event was associated with a lower likelihood of relapsing MOGAD. This association was supported in first external cohort and directionally consistent but inconclusive in a second, smaller cohort. Further prospective multicenter studies are required to assess the reproducibility and clinical utility of this association.

BACKGROUND AND PURPOSE:Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a relatively recently described disease, most commonly presenting with optic neuritis and longitudinally extensive transverse myelitis. Cerebral cortical encephalitis is a rare manifestation of MOGAD. METHODS:We identified patients presenting with cerebral cortical encephalitis with positive MOG antibodies in serum across a large specialized service. Demographic and clinical information were collected. We describe clinical and laboratory characteristics, treatment response, and subsequent relapse risk in adults presenting with this phenotype. RESULTS:We identified eight patients meeting clinical criteria for cerebral cortical encephalitis with MOG antibodies. All had seizures; four had focal onset seizures with or without secondary generalization. Two patients exhibited encephalopathy, and six demonstrated focal neurological deficits at presentation. All had fluid-attenuated inversion recovery hyperintensities. Five of eight displayed cerebral swelling, and two of eight displayed leptomeningeal enhancement. Where cerebrospinal fluid (CSF) results were available, five of seven had CSF pleocytosis, protein was raised in two of seven, and one patient had oligoclonal bands unique to CSF. Median time to seizure control was 1.25 months, and all clinical features and magnetic resonance imaging abnormalities resolved. Four of eight patients (50%) had a clinical relapse, with a median time to relapse of 6.4 months. CONCLUSIONS:Cerebral cortical encephalitis appears to share similar CSF findings, steroid responsiveness, and risk of relapse with other clinical manifestations of MOGAD. This informs treatment decisions and patient counselling.

There are only a few studies exploring post-thymectomy outcome in patients with acetylcholine receptor antibody (AChR-Ab)-positive generalised myasthenia gravis (MG). To assess the predictors of outcome in patients with AChR-Ab-positive generalised MG who underwent thymectomy. A retrospective study of 53 patients from a single neuroscience centre in the UK. The mean disease duration from diagnosis was 6.2 ± 4.3 years. Pre-thymectomy, 37 patients had mild weakness affecting muscles other than ocular muscles, 11 patients had moderate weakness and 5 patients had severe weakness. 27/53 patients had thymoma. Post-thymectomy (mean duration of 5.7 ± 4.2 years), 34 patients (64

BackgroundAnnualized relapse rate (ARR) is used as an outcome measure in multiple sclerosis (MS) clinical trials. Previous studies demonstrated that ARR has reduced in placebo groups between 1990 and 2012. This study aimed to estimate real-world ARRs from contemporary MS clinics in the UK, in order to improve the feasibility estimations for clinical trials and facilitate MS service planning.MethodsA multicentre observational, retrospective study of patients with MS from 5 tertiary neuroscience centres in the UK. We included all adult patients with a diagnosis of MS that had a relapse between 01/04/2020 and 30/06/2020.ResultsOne hundred thirteen out of 8783 patients had a relapse during the 3-month study period. Seventy-nine percent of the patients with a relapse were female, the mean age was 39 years, and the median disease duration was 4.5 years; 36% of the patients that had a relapse were on disease-modifying treatment. The ARR from all study sites was estimated at 0.05. The ARR for relapsing remitting MS (RRMS) was estimated at 0.08, while the ARR for secondary progressive MS (SPMS) was 0.01.ConclusionsWe report a lower ARR compared to previously reported rates in MS.

Susac syndrome is a likely autoimmune microangiopathy affecting the brain, retina and inner ear. Due to the rarity of this condition, diagnosis and treatment can be challenging. Diagnosis is based on the presence of the clinical triad of central nervous system dysfunction, branch retinal artery occlusions and sensorineural hearing loss. Typical MRI findings of callosal and peri-callosal lesions may assist in diagnosis. Clinical course can be monophasic, polycyclic or chronic continuous. It is important to look out for red flags to attain an accurate diagnosis and follow a therapeutic algorithm based on severity of the disease and response to treatment. Patients are treated with steroids and immunosuppressive agents with a variable response. Early aggressive treatment especially in severe cases, may help in preventing relapses and morbidity/disability. This study highlights important diagnostic features and proposes a treatment algorithm based on clinical experience from management of 16 patients from 2 neuroscience centres in the UK since 2007, who were followed up over a long period of 3–15 years.

IntroductionMultiple sclerosis (MS) is an immune-mediated disorder of the CNS manifested by recurrent attacks of neurological symptoms (related to focal inflammation) and gradual disability accrual (related to progressive neurodegeneration and neuroinflammation). Sphingosine-1-phosphate-receptor (S1PR) modulators are a class of oral disease-modifying therapies (DMTs) for relapsing MS. The first S1PR modulator developed and approved for MS was fingolimod, followed by siponimod, ozanimod, and ponesimod. All are S1P analogues with different S1PR-subtype selectivity. They restrain the S1P-dependent lymphocyte egress from lymph nodes by binding the lymphocytic S1P-subtype-1-receptor. Depending on their pharmacodynamics and pharmacokinetics, they can also interfere with other biological functions.Areas coveredOur narrative review covers the PubMed English literature on S1PR modulators in MS until August 2022. We discuss their pharmacology, efficacy, safety profile, and risk management recommendations based on the results of phase II and III clinical trials. We briefly address their impact on the risk of infections and vaccines efficacy.Expert opinionS1PR modulators decrease relapse rate and may modestly delay disease progression in people with relapsing MS. Aside their established benefit, their place and timing within the long-term DMT strategy in MS, as well as their immunological effects in the new and evolving context of the post-COVID-19 pandemic and vaccination campaigns warrant further study.

Introduction: Annualized relapse rate (ARR) is routinely used as the primary outcome measure in MS clinical trials and is important in service planning. Most disease modifying therapies (DMTs) are prescribed in people with relapsing remitting MS (RRMS) and the ARR of secondary progressive MS (SPMS) and RRMS has not been accurately described in a modern clinical cohort. Recent treatment advances have led to more people with MS being effectively managed with early intensive medications, reducing the frequency of reported relapse rates in RRMS. Aims: To facilitate MS service planning and improve the feasibility estimations for clinical trials in MS. Objectives: To establish a current estimated ARR observed in a contemporary MS clinic in the UK. Methods: A retrospective cohort study examined all relapses recorded in a university hospital serving the local MS population. A random sample of 812 MS Nottingham patients from our database were reviewed for reported relapses from April 1 to June 30, 2020 and the same period in 2019, to account for potential reporting bias during the COVID-19 pandemic. The MS clinical database, nurse and admin registries, medical and telephone records for those individuals were reviewed at the end of 2020 for possible relapses during the study periods. Results: Among MS patients followed up in clinic, 60% had RRMS, 23% SPMS, 14% PPMS and 4% CIS. We identified 30 clinician confirmed relapses during the study period equating to an ARR of 0.15 for all MS patients treated and untreated. 70% of RRMS and 18% of SPMS were on DMTs. The ARR in RRMS and SPMS were the same (0.15). Validating this with pre-pandemic 2019 records found similar results. Conclusions: This contemporary UK-based study reports halving of the ARR previously reported in 2 similar studies in the UK 8 years ago. While relapse prevention has been achieved in RRMS, there appears to be significant unappreciated relapses occurring in the SPMS (pre-siponimod) cohort.

BACKGROUND:There are few studies exploring the prognostic factors in patients with aquaporin-4 (AQP4)-IgG positive neuromyelitis optica spectrum disorder (NMOSD). OBJECTIVE:To assess the predictors of outcome in patients with AQP4-antibody positive NMOSD from a United Kingdom (UK) population. METHODS:A retrospective study of 52 patients from 2 neuroscience centres in the UK Midlands. RESULTS:The most common initial presentations were acute myelitis and optic neuritis, with 22/52 cases (42.3%) each. Relapsing course was seen in 32 patients (61.5%) with mean annualised relapse rate of 0.43 (standard deviation 0.45) and a mean interval time to first relapse of 31 months (range 2-108). The median Expanded Disability Status Scale (EDSS) score at the last follow up was 4 (range 1-9). Age at onset was an independent predictor of disability in the whole cohort of patients with NMOSD. For every 10-year increase in age at disease onset, the risk of developing an EDSS score of ≥4 increased by 34%. Patients who presented initially with a longitudinally extensive transverse myelitis (LETM) showed a higher risk to develop disability, compared to other clinical presentations (median time of 4 years versus 13 years). Late onset (LO-NMOSD) patients were likely to reach an EDSS score of 4 more quickly, compared to early onset (EO-NMOSD) (median time of 7 years versus 13 years). Higher median EDSS score at last follow up was observed in LO-NMOSD compared to EO-NMOSD (6 versus 2). CONCLUSION:Increasing age at onset and LETM predict disability in AQP-4-IgG positive NMOSD patients.

Beta interferons (IFN-β) are pleiotropic cytokines with antiviral properties. They play important roles in the pathogenesis of multiple sclerosis (MS), an incurable immune-mediated disorder of the central nervous system. The clinical expression of MS is heterogeneous, with relapses of neuroinflammation and with disability accrual in considerable part unrelated to the attacks. The injectable recombinant IFN-β preparations are the first approved disease-modifying treatments for MS. They have moderate efficacy in reducing the frequency of relapses, but good long-term cost-efficacy and safety profiles, so are still widely used. They have some tolerability and adherence issues, partly mitigated in recent years by the introduction of a PEGylated formulation and use of 'smart' autoinjector devices. Their general impact on long-term disability is modest but could be further improved by developing accurate tools for identifying the patient profile of best responders to IFN-β. Here, we present the IFN-β-based immunomodulatory therapeutic approaches in MS, highlighting their place in the current coronavirus disease (COVID-19) pandemic. The potential role of IFN-β in the treatment of COVID-19 is also briefly discussed.

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative condition of the central nervous system. Its prevalence varies from 50–300 per 100 000 people, and it is estimated that around 2.3 million people worldwide live with MS.1 In 2020, Public Health England released new MS prevalence data from GP records. This revealed that the number of adults with MS in the UK has risen to 131 720.2 Each year there are on average 4950 new cases of MS diagnosed and recorded in UK primary care records.2 Treatment of MS comprises disease-modifying drugs (DMDs) that reduce the inflammation and management of MS relapses and symptoms. The clinical decisions about DMDs and their complex monitoring dominate consultations with MS specialists, leaving less time for the management of patients’ daily symptoms. Therefore, GPs currently have a unique role in managing patients’ symptoms in primary care. This article focuses on the most under-recognised symptoms of MS. Cognitive dysfunction, fatigue, and depression are often overlooked by healthcare professionals.3–8 These symptoms are linked and profoundly affect patients’ quality of life, especially at the early stages of the disease.3–8 ### Cognitive dysfunction Cognitive impairment is prevalent in up to 65% of patients with MS.4 The most common cognitive domains affected are processing speed and memory.4 Other cognitive symptoms include deficits in attention, executive functioning, and verbal fluency.4,5 There is a robust correlation between cognitive deficits and quality of life, including employment status in patients with MS.4,5 Patients’ self-reported cognitive function is not considered a reliable measure, as it correlates with depression, rather than cognition.4 An informant report about patients’ cognition correlates better with objectively measured cognitive function …

•MS has been associated with an increased risk for VTE.•In our cases, DMF was a possible triggering factor for PE.•High number of VTE cases was found on adverse event reporting systems.•Further work is needed to establish DMTs role in VTE.

Background The clinical spectrum of myelin oligodendrocyte glycoprotein (MOG)-antibody-associated disease is expanding. Objective To describe an unusual case of MOG-antibody-associated hypertrophic pachymeningitis (HP). Methods Case study. Results A 57-year-old female presented with a generalised seizure on a background of 3 months history of progressive cognitive decline and behavioural changes. Brain Magnetic Resonance Imaging (MRI) revealed widespread pachymeningeal enhancement and hyperintense signal in both hippocampi. Cerebrospinal Fluid (CSF) examination was normal. The patient was found positive for MOG-antibody. She clinically improved with steroids and the MRI abnormalities completely resolved. Conclusions Clinicians might consider testing for MOG-antibody in cases with HP.

IntroductionAntibodies to myelin oligodendrocyte glycoprotein (MOG) have been demonstrated in patients with optic neuritis (ON), encephalitis and myelitis.ObjectiveTo describe the clinical and paraclinical features in patients with MOG-associated demyelination, focusing on unusual cases, brain biopsy and concomitant autoimmunity.MethodsA single centre retrospective observational case series, analysing demographic, clinical, laboratory, histopathology and radiological data from MOG- positive patients.ResultsWe identified 20 adults. The male/female ratio was 1.5. Mean age at onset was 31.6 years and mean disease duration was 7.5 years. The most frequent presentation was myelitis (45%), followed by ON (30%). One case had simultaneous myelitis and ON. Two patients had a cortical syndrome, 1 patient had an encephalopathic presentation and 1 cryptogenic focal epilepsy. Anti-neutrophil cytoplasmic antibodies (ANCA) were found in 3 cases, while 1 patient had an antibody to glutamic acid decarboxylase (GAD). Brain biopsy was performed in 2 patients. Relapsing course was identified in 60% of patients. We also discuss 3 cases with atypical features, brain histopathology and concomitant autoimmunity.ConclusionMOG- associated demyelination represents a new disease entity. Unusual cases are reported, expanding the disease spectrum. Elucidating this further should be the focus of prospective studies.