Publications
316 results found
Simpson-Yap S, Pirmani A, Kalincik T, et al., 2022, Updated Results of the COVID-19 in MS Global Data Sharing Initiative: Anti-CD20 and Other Risk Factors Associated With COVID-19 Severity., Neurol Neuroimmunol Neuroinflamm, Vol: 9
BACKGROUND AND OBJECTIVES: Certain demographic and clinical characteristics, including the use of some disease-modifying therapies (DMTs), are associated with severe acute respiratory syndrome coronavirus 2 infection severity in people with multiple sclerosis (MS). Comprehensive exploration of these relationships in large international samples is needed. METHODS: Clinician-reported demographic/clinical data from 27 countries were aggregated into a data set of 5,648 patients with suspected/confirmed coronavirus disease 2019 (COVID-19). COVID-19 severity outcomes (hospitalization, admission to intensive care unit [ICU], requiring artificial ventilation, and death) were assessed using multilevel mixed-effects ordered probit and logistic regression, adjusted for age, sex, disability, and MS phenotype. DMTs were individually compared with glatiramer acetate, and anti-CD20 DMTs with pooled other DMTs and with natalizumab. RESULTS: Of 5,648 patients, 922 (16.6%) with suspected and 4,646 (83.4%) with confirmed COVID-19 were included. Male sex, older age, progressive MS, and higher disability were associated with more severe COVID-19. Compared with glatiramer acetate, ocrelizumab and rituximab were associated with higher probabilities of hospitalization (4% [95% CI 1-7] and 7% [95% CI 4-11]), ICU/artificial ventilation (2% [95% CI 0-4] and 4% [95% CI 2-6]), and death (1% [95% CI 0-2] and 2% [95% CI 1-4]) (predicted marginal effects). Untreated patients had 5% (95% CI 2-8), 3% (95% CI 1-5), and 1% (95% CI 0-3) higher probabilities of the 3 respective levels of COVID-19 severity than glatiramer acetate. Compared with pooled other DMTs and with natalizumab, the associations of ocrelizumab and rituximab with COVID-19 severity were also more pronounced. All associations persisted/enhanced on restriction to confirmed COVID-19. DISCUSSION: Analyzing the largest international real-world data set of people with MS with suspected/confirmed COVID-19 confirms that the use of anti-CD20 m
Simpson-Yap S, Pirmani A, De Brouwer E, et al., 2022, Severity of COVID19 infection among patients with multiple sclerosis treated with interferon-beta, MULTIPLE SCLEROSIS AND RELATED DISORDERS, Vol: 66, ISSN: 2211-0348
Owen D, 2022, Human pharmacokinetics of XBD173 and etifoxine distinguish their potential for pharmacodynamic effects mediated by TSPO, British Journal of Clinical Pharmacology, Vol: 88, Pages: 4230-4236, ISSN: 0306-5251
XBD173 and etifoxine are translocator protein (TSPO) ligands that modulate inflammatory responses in preclinical models. Limited human pharmacokinetic data is available for either molecule, and the binding affinity of etifoxine for human TSPO is unknown. To allow for design of human challenge experiments, we derived pharmacokinetic data for orally administered etifoxine (50 mg 3 times daily) and XBD173 (90 mg once daily) and determined the binding affinity of etifoxine for TSPO. For XBD173, maximum plasma concentration and free fraction measurements predicted a maximal free concentration of 1.0 nM, which is similar to XBD173 binding affinity. For etifoxine, maximum plasma concentration and free fraction measurements predicted a maximal free concentration of 0.31 nM, substantially lower than the Ki for etifoxine in human brain derived here (7.8 μM, 95% CI 4.5–14.6 μM). We conclude that oral XBD173 dosing at 90 mg once daily will achieve pharmacologically relevant TSPO occupancy. However, the occupancy is too low for TSPO mediated effects after oral dosing of etifoxine at 50 mg 3 times daily.
Young CA, Mills RJ, Langdon D, et al., 2022, Measuring coping in multiple sclerosis: The Coping Index-MS, MULTIPLE SCLEROSIS JOURNAL, ISSN: 1352-4585
Magliozzi R, Fadda G, Brown RA, et al., 2022, "Ependymal-in" Gradient of Thalamic Damage in Progressive Multiple Sclerosis, ANNALS OF NEUROLOGY, ISSN: 0364-5134
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- Citations: 1
Dobson R, Craner M, Ed Waddingham E, et al., 2022, Evaluating the feasibility of a real world pharmacovigilance study (OPTIMISE:MS), MULTIPLE SCLEROSIS AND RELATED DISORDERS, Vol: 63, ISSN: 2211-0348
Young CA, Mills R, Langdon D, et al., 2022, The four self-efficacy trajectories among people with multiple sclerosis: Clinical associations and implications, JOURNAL OF THE NEUROLOGICAL SCIENCES, Vol: 436, ISSN: 0022-510X
Rodgers J, Friede T, Vonberg FW, et al., 2022, The impact of smoking cessation on multiple sclerosis disease progression, BRAIN, Vol: 145, Pages: 1368-1378, ISSN: 0006-8950
Choi S, Hill D, Guo L, et al., 2022, Automated characterisation of microglia in ageing mice using image processing and supervised machine learning algorithms, Scientific Reports, Vol: 12, ISSN: 2045-2322
The resident macrophages of the central nervous system, microglia, are becoming increasingly implicated as active participants in neuropathology and ageing. Their diverse and changeable morphology is tightly linked with functions they perform, enabling assessment of their activity through image analysis. To better understand the contributions of microglia in health, senescence, and disease, it is necessary to measure morphology with both speed and reliability. A machine learning approach was developed to facilitate automatic classification of images of retinal microglial cells as one of five morphotypes, using a support vector machine (SVM). The area under the receiver operating characteristic curve for this SVM was between 0.99 and 1, indicating strong performance. The densities of the different microglial morphologies were automatically assessed (using the SVM) within wholemount retinal images. Retinas used in the study were sourced from 28 healthy C57/BL6 mice split over three age points (2, 6, and 28-months). The prevalence of ‘activated’ microglial morphology was significantly higher at 6- and 28-months compared to 2-months (p < .05 and p < .01 respectively), and ‘rod’ significantly higher at 6-months than 28-months (p < 0.01). The results of the present study propose a robust cell classification SVM, and further evidence of the dynamic role microglia play in ageing.
Papadopoulos D, Gklinos P, Psarros G, et al., 2022, Disease-modifying treatments for multiple sclerosis have not affected the incidence of neoplasms in clinical trials over 3 decades: a meta-analysis with meta-regression, JOURNAL OF NEUROLOGY, Vol: 269, Pages: 3226-3237, ISSN: 0340-5354
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- Citations: 1
Jacobs SAH, Muraro PA, Cencioni MT, et al., 2022, Worse Physical Disability Is Associated With the Expression of PD-1 on Inflammatory T-Cells in Multiple Sclerosis Patients With Older Appearing Brains, FRONTIERS IN NEUROLOGY, Vol: 12, ISSN: 1664-2295
Das J, Rog DJ, Middleton R, et al., 2022, The association between deprivation and the access to disease modifying therapies for multiple sclerosis: An England wide community-based study in the UK MS Register, MULTIPLE SCLEROSIS AND RELATED DISORDERS, Vol: 57, ISSN: 2211-0348
Garjani A, Middleton RM, Nicholas R, et al., 2022, Recovery From COVID-19 in Multiple Sclerosis: A Prospective and Longitudinal Cohort Study of the United Kingdom Multiple Sclerosis Register, NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION, Vol: 9, ISSN: 2332-7812
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- Citations: 5
Koffman J, Penfold C, Cottrell L, et al., 2022, "I wanna live and not think about the future" what place for advance care planning for people living with severe multiple sclerosis and their families? A qualitative study., PLoS One, Vol: 17
BACKGROUND: Little is known about how people with multiple sclerosis (MS) and their families comprehend advance care planning (ACP) and its relevance in their lives. AIM: To explore under what situations, with whom, how, and why do people with MS and their families engage in ACP. METHODS: We conducted a qualitative study comprising interviews with people living with MS and their families followed by an ethical discussion group with five health professionals representing specialties working with people affected by MS and their families. Twenty-seven people with MS and 17 family members were interviewed between June 2019 and March 2020. Interviews and the ethical discussion group were audio-recorded and transcribed verbatim. Data were analysed using the framework approach. RESULTS: Participants' narratives focused on three major themes: (i) planning for an uncertain future; (ii) perceived obstacles to engaging in ACP that included uncertainty concerning MS disease progression, negative previous experiences of ACP discussions and prioritising symptom management over future planning; (iii) Preferences for engagement in ACP included a trusting relationship with a health professional and that information then be shared across services. Health professionals' accounts from the ethical discussion group departed from viewing ACP as a formal document to that of an ongoing process of seeking preferences and values. They voiced similar concerns to people with MS about uncertainty and when to initiate ACP-related discussions. Some shared concerns of their lack of confidence when having these discussions. CONCLUSION: These findings support the need for a whole system strategic approach where information about the potential benefits of ACP in all its forms can be shared with people with MS. Moreover, they highlight the need for health professionals to be skilled and trained in engaging in ACP discussions and where information is contemporaneously and seamlessly shared across servic
Simpson-Yap S, De Brouwer E, Kalincik T, et al., 2021, Associations of Disease-Modifying Therapies With COVID-19 Severity in Multiple Sclerosis, NEUROLOGY, Vol: 97, Pages: E1870-E1885, ISSN: 0028-3878
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- Citations: 58
Dobson R, Craner M, Waddingham E, et al., 2021, OPTIMISE: MS study protocol: a pragmatic, prospective observational study to address the need for, and challenges with, real world pharmacovigilance in multiple sclerosis, BMJ OPEN, Vol: 11, ISSN: 2044-6055
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- Citations: 3
Middleton RM, Craig EM, Rodgers WJ, et al., 2021, COVID-19 in Multiple Sclerosis: Clinically reported outcomes from the UK Multiple Sclerosis Register, MULTIPLE SCLEROSIS AND RELATED DISORDERS, Vol: 56, ISSN: 2211-0348
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- Citations: 4
Nicholas R, Nicholas E, Hannides M, et al., 2021, Influence of individual, illness and environmental factors on place of death among people with neurodegenerative diseases: a retrospective, observational, comparative cohort study, BMJ SUPPORTIVE & PALLIATIVE CARE, ISSN: 2045-435X
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- Citations: 1
Nicholas RS, Rhone EE, Mariottini A, et al., 2021, Autologous Hematopoietic Stem Cell Transplantation in Active Multiple Sclerosis A Real-world Case Series, NEUROLOGY, Vol: 97, Pages: E890-E901, ISSN: 0028-3878
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- Citations: 5
Huang Y, Rodgers WJ, Middleton RM, et al., 2021, Willingness to receive a COVID-19 vaccine in people with multiple sclerosis - UK MS Register survey, MULTIPLE SCLEROSIS AND RELATED DISORDERS, Vol: 55, ISSN: 2211-0348
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- Citations: 5
Pitteri M, Magliozzi R, Nicholas R, et al., 2021, Cerebrospinal fluid inflammatory profile of cognitive impairment in newly diagnosed multiple sclerosis patients, MULTIPLE SCLEROSIS JOURNAL, Vol: 28, Pages: 768-777, ISSN: 1352-4585
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- Citations: 2
Garjani A, Middleton RM, Nicholas R, et al., 2021, Pre-existing anxiety, depression, and neurological disability is associated with long COVID: A prospective and longitudinal cohort of the United Kingdom Multiple Sclerosis Register
<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Objectives</jats:title><jats:p>To assess the prevalence of long COVID among people with multiple sclerosis (MS) and its predictors, including their pre-COVID-19 functional status.</jats:p></jats:sec><jats:sec><jats:title>Design</jats:title><jats:p>Community-based prospective and longitudinal cohort study</jats:p></jats:sec><jats:sec><jats:title>Setting</jats:title><jats:p>The United Kingdom (UK) MS Register (UKMSR) COVID-19 study</jats:p></jats:sec><jats:sec><jats:title>Participants</jats:title><jats:p>A national cohort of people with MS and COVID-19</jats:p></jats:sec><jats:sec><jats:title>Main outcome measures</jats:title><jats:p>Participants used the online questionnaire-based platform of the UKMSR to update their COVID-19 symptoms, recovery status, and duration of symptoms for those who had fully recovered. Questionnaires were date-stamped for estimation of COVID-19 symptom duration for those who had not recovered at their last follow-up. The UKMSR holds demographic and up-to-date clinical data on participants as well as their web-based Expanded Disability Status Scale (a measure of physical disability in MS) and Hospital Anxiety and Depression Scale scores. The association between these factors and recovery from COVID-19 was assessed using multivariable Cox regression analysis.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Out of 7,977 people with MS who participated in the UKMSR COVID-19 study, 599 had COVID-19 and updated their recovery status prospectively. At least 181 participants (31.1%) had long-standing COVID-19 symptoms for ≥4 weeks and 76 (13.1 %) for ≥12 weeks. Participants with higher levels of pre-COVID-19 physical disability, participants with anxiety a
Pienaar IS, Mohammed R, Courtley R, et al., 2021, Investigation of the correlation between mildly deleterious mtDNA Variations and the clinical progression of multiple sclerosis, MULTIPLE SCLEROSIS AND RELATED DISORDERS, Vol: 53, ISSN: 2211-0348
Garjani A, Hunter R, Law GR, et al., 2021, Mental health of people with multiple sclerosis during the COVID-19 outbreak: A prospective cohort and cross-sectional case-control study of the UK MS Register, MULTIPLE SCLEROSIS JOURNAL, Vol: 28, Pages: 1060-1071, ISSN: 1352-4585
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- Citations: 7
Choi S, Hill D, Guo L, et al., 2021, Automated Characterisation of Retinal Microglia in a Multiple Sclerosis Mouse Model and Age-Matched Controls, Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404
Garjani A, Middleton RM, Hunter R, et al., 2021, COVID-19 is associated with new symptoms of multiple sclerosis that are prevented by disease modifying therapies, MULTIPLE SCLEROSIS AND RELATED DISORDERS, Vol: 52, ISSN: 2211-0348
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- Citations: 12
Magliozzi R, Pitteri M, Ziccardi S, et al., 2021, CSF parvalbumin levels reflect interneuron loss linked with cortical pathology in multiple sclerosis, Annals of Clinical and Translational Neurology, Vol: 8, Pages: 534-547, ISSN: 2328-9503
INTRODUCTION AND METHODS: In order to verify whether parvalbumin (PVALB), a protein specifically expressed by GABAergic interneurons, could be a MS-specific marker of grey matter neurodegeneration, we performed neuropathology/molecular analysis of PVALB expression in motor cortex of 40 post-mortem progressive MS cases, with/without meningeal inflammation, and 10 control cases, in combination with cerebrospinal fluid (CSF) assessment. Analysis of CSF PVALB and neurofilaments (Nf-L) levels combined with physical/cognitive/3TMRI assessment was performed in 110 naïve MS patients and in 32 controls at time of diagnosis. RESULTS: PVALB gene expression was downregulated in MS (fold change = 3.7 ± 1.2, P < 0.001 compared to controls) reflecting the significant reduction of PVALB+ cell density in cortical lesions, to a greater extent in MS patients with high meningeal inflammation (51.8, P < 0.001). Likewise, post-mortem CSF-PVALB levels were higher in MS compared to controls (fold change = 196 ± 36, P < 0.001) and correlated with decreased PVALB+ cell density (r = -0.64, P < 0.001) and increased MHC-II+ microglia density (r = 0.74, P < 0.01), as well as with early age of onset (r = -0.69, P < 0.05), shorter time to wheelchair (r = -0.49, P < 0.05) and early age of death (r = -0.65, P < 0.01). Increased CSF-PVALB levels were detected in MS patients at diagnosis compared to controls (P = 0.002). Significant correlation was found between CSF-PVALB levels and cortical lesion number on MRI (R = 0.28, P = 0.006) and global cortical thickness (R = -0.46, P < 0.001), better than Nf-L levels. CSF-PVALB levels increased in MS patients with severe cognitive impairment (mean ± SEM:25.2 ± 7.5
Evangelou N, Garjani A, dasNair R, et al., 2021, Self-diagnosed COVID-19 in people with multiple sclerosis: a community-based cohort of the UK MS Register, JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, Vol: 92, Pages: 107-+, ISSN: 0022-3050
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- Citations: 25
das Nair R, Hunter R, Garjani A, et al., 2021, Challenges of developing, conducting, analysing and reporting a COVID-19 study as the COVID-19 pandemic unfolds: an online co-autoethnographic study, BMJ OPEN, Vol: 11, ISSN: 2044-6055
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- Citations: 3
Middleton R, Evangelou N, Garjani A, et al., 2020, Clinical COVID19 data collection from the uk multiple sclerosis register, 8th Joint ACTRIMS-ECTRIMS Meeting (MSVirtual), Publisher: SAGE PUBLICATIONS LTD, Pages: 63-64, ISSN: 1352-4585
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