Imperial College London

DrRichardNicholas

Faculty of MedicineDepartment of Brain Sciences

Professor of Practice (Neurology)
 
 
 
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r.nicholas

 
 
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12L12CLab BlockCharing Cross Campus

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Publications

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292 results found

Garjani A, Middleton RM, Nicholas R, Evangelou Net al., 2022, Recovery From COVID-19 in Multiple Sclerosis: A Prospective and Longitudinal Cohort Study of the United Kingdom Multiple Sclerosis Register., Neurol Neuroimmunol Neuroinflamm, Vol: 9

BACKGROUND AND OBJECTIVES: To understand the course of recovery from coronavirus disease 2019 (COVID-19) among patients with multiple sclerosis (MS) and to determine its predictors, including patients' pre-COVID-19 physical and mental health status. METHODS: This prospective and longitudinal cohort study recruited patients with MS who reported COVID-19 from March 17, 2020, to March 19, 2021, as part of the United Kingdom MS Register (UKMSR) COVID-19 study. Participants used online questionnaires to regularly update their COVID-19 symptoms, recovery status, and duration of symptoms for those who 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 (web-EDSS) and Hospital Anxiety and Depression Scale (HADS) scores. The association between these factors and recovery from COVID-19 was assessed using multivariable Cox regression analysis. RESULTS: Of the 7,977 patients with MS who participated in the UKMSR COVID-19 study, 599 reported COVID-19 and prospectively updated their recovery status. Twenty-eight hospitalized participants were excluded. At least 165 participants (29.7%) had long-standing COVID-19 symptoms for ≥4 weeks and 69 (12.4%) for ≥12 weeks. Participants with pre-COVID-19 web-EDSS scores ≥7, participants with probable anxiety and/or depression (HADS scores ≥11) before COVID-19 onset, and women were less likely to report recovery from COVID-19. DISCUSSION: Patients with MS are affected by postacute sequelae of COVID-19. Preexisting severe neurologic impairment or mental health problems appear to increase this risk. These findings can have implications in tailoring their post-COVID-19 rehabilitation.

Journal article

Simpson-Yap S, De Brouwer E, Kalincik T, Rijke N, Hillert JA, Walton C, Edan G, Moreau Y, Spelman T, Geys L, Parciak T, Gautrais C, Lazovski N, Pirmani A, Ardeshirdavanai A, Forsberg L, Glaser A, McBurney R, Schmidt H, Bergmann AB, Braune S, Stahmann A, Middleton R, Salter A, Fox RJ, van der Walt A, Butzkueven H, Alroughani R, Ozakbas S, Rojas J, van der Mei I, Nag N, Ivanov R, do Olival GS, Dias AE, Magyari M, Brum D, Mendes MF, Alonso RN, Nicholas RS, Bauer J, Chertcoff AS, Zabalza A, Arrambide G, Fidao A, Comi G, Peeters Let al., 2021, Associations of Disease-Modifying Therapies With COVID-19 Severity in Multiple Sclerosis, NEUROLOGY, Vol: 97, Pages: E1870-E1885, ISSN: 0028-3878

Journal article

Middleton RM, Craig EM, Rodgers WJ, Tuite-Dalton K, Garjani A, Evangelou N, das Nair R, Hunter R, Tallantyre EC, Cauchi M, Cairn C, Paling D, Fuller S, McDonnell G, Petheram K, Liu B, Nock U, Ingram G, Brownlee W, Taylor J, Nicholas Ret 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

Journal article

Rodgers WJ, Friede T, Vonberg FW, Constantinescu CS, Coles A, Chataway J, Emsley H, Ford H, Fisniku L, Galea I, Harrower T, Hobart J, Huseyin H, Kipps C, Marta M, McDonnell G, McLean B, Pearson OR, Rog D, Schmierer K, Sharrack B, Straukiene A, Wilson H, Middleton R, Ford DV, Nicholas Ret al., 2021, The impact of smoking cessation on multiple sclerosis disease progression, MULTIPLE SCLEROSIS JOURNAL, Vol: 27, Pages: 41-42, ISSN: 1352-4585

Journal article

Huang Y, Rodgers WJ, Middleton RM, Baheerathan A, Tuite-Dalton KA, Ford D, Nicholas Ret 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

Journal article

Nicholas R, Nicholas E, Hannides M, Gautam V, Friede T, Koffman Jet 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

Journal article

Nicholas RS, Rhone EE, Mariottini A, Silber E, Malik O, Singh-Curry V, Turner B, Scalfari A, Ciccarelli O, Sormani MP, Olavarria E, Mehra V, Gabriel I, Kazmi MA, Muraro Pet 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

Journal article

Pienaar IS, Mohammed R, Courtley R, Gledson MR, Reynolds R, Nicholas R, Elson JLet 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

Journal article

Pitteri M, Magliozzi R, Nicholas R, Ziccardi S, Pisani AI, Pezzini F, Marastoni D, Calabrese Met al., 2021, Cerebrospinal fluid inflammatory profile of cognitive impairment in newly diagnosed multiple sclerosis patients, MULTIPLE SCLEROSIS JOURNAL, ISSN: 1352-4585

Journal article

Garjani A, Middleton RM, Hunter R, Tuite-Dalton KA, Coles A, Dobson R, Duddy M, Hughes S, Pearson OR, Rog D, Tallantyre EC, das Nair R, Nicholas R, Evangelou Net 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

Journal article

Garjani A, Hunter R, Law GR, Middleton RM, Tuite-Dalton KA, Dobson R, Ford D, Hughes S, Pearson OR, Rog D, Tallantyre EC, Nicholas R, Morriss R, Evangelou N, das Nair Ret 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, ISSN: 1352-4585

Journal article

Choi S, Hill D, Guo L, Luong V, Papadopoulos D, Nicholas R, Cordeiro MFet 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

Conference paper

Magliozzi R, Pitteri M, Ziccardi S, Pisani AI, Montibeller L, Marastoni D, Rossi S, Mazziotti V, Guandalini M, Dapor C, Schiavi G, Tamanti A, Nicholas R, Reynolds R, Calabrese Met 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

Journal article

das Nair R, Hunter R, Garjani A, Middleton RM, Tuite-Dalton KA, Nicholas RS, Evangelou Net 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

Journal article

Evangelou N, Garjani A, dasNair R, Hunter R, Tuite--Dalton KA, Craig EM, Rodgers WJ, Coles A, Dobson R, Duddy M, Ford DV, Hughes S, Pearson O, Middleton LA, Rog D, Tallantyre EC, Friede T, Middleton RM, Nicholas Ret 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

Journal article

Middleton R, Evangelou N, Garjani A, Das Nair R, Hunter R, Tuite-Dalton K, Craig E, Ford D, Nicholas Ret 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

Conference paper

Glaser A, Forsberg L, Manouchehrinia A, Ramanujam R, Spelman T, Klyve P, Drahota J, Horakova D, Joensen H, Magyari M, Ellenberger D, Stahmann A, Van der Walt A, Rodgers J, Middleton R, Nicholas R, Bezlyak V, Adlard N, Hach T, Lines C, Hillert Jet al., 2020, Objective classification methods result in an increased proportion of secondary progressive multiple sclerosis in five patient registries, 8th Joint ACTRIMS-ECTRIMS Meeting (MSVirtual), Publisher: SAGE PUBLICATIONS LTD, Pages: 348-348, ISSN: 1352-4585

Conference paper

Nicholas R, Dobay P, Lacinova K, Brennan R, Ziehn M, Lines C, Adlard Net al., 2020, ENTIMOS: A discrete event simulation model for maximizing efficiency of infusion suites in centres treating multiple sclerosis patients, 8th Joint ACTRIMS-ECTRIMS Meeting (MSVirtual), Publisher: SAGE PUBLICATIONS LTD, Pages: 121-122, ISSN: 1352-4585

Conference paper

Forsberg L, Glaser A, Manouchehrinia A, Ramanujam R, Spelman T, Klyve P, Drahota J, Horakova D, Joensen H, Magyari M, Ellenberger D, Stahmann A, Van der Walt A, Rodgers J, Middleton R, Nicholas R, Bezlyak V, Adlard N, Hach T, Lines C, Hillert Jet al., 2020, Validation of three secondary progressive multiple sclerosis classification methods in five registries within the SPMS research collaboration network Pharmacological management of progressive MS, 8th Joint ACTRIMS-ECTRIMS Meeting (MSVirtual), Publisher: SAGE PUBLICATIONS LTD, Pages: 19-19, ISSN: 1352-4585

Conference paper

Das J, Nicholas R, Middleton R, Rodgers J, Rog Det al., 2020, The impact of socioeconomic status on the access to disease modifying therapy in people with multiple sclerosis, 8th Joint ACTRIMS-ECTRIMS Meeting (MSVirtual), Publisher: SAGE PUBLICATIONS LTD, Pages: 357-358, ISSN: 1352-4585

Conference paper

Di Bella C, Trender W, Hellyer P, Knowles S, Hill J, Sandrone S, Nicholas R, Hampshire Aet al., 2020, Evaluating cognitive functioning in multiple sclerosis, compared to other neurological disorders, using an online cognitive battery, 8th Joint ACTRIMS-ECTRIMS Meeting (MSVirtual), Publisher: SAGE PUBLICATIONS LTD, Pages: 502-503, ISSN: 1352-4585

Conference paper

Rahn AC, Solari A, Beckerman H, Nicholas R, Wilkie D, Heesen C, Giordano Aet al., 2020, 'I will respect the autonomy of my patient': current stage of research to facilitate shared decision-making in multiple sclerosis, RIMS Digital Conference, Publisher: SAGE PUBLICATIONS LTD, Pages: 39-39, ISSN: 1352-4585

Conference paper

Barritt A, Das E, Morley N, Seymour M, Saha R, Vera J, Vundavalli S, Dizdarevic S, Nicholas R, Berger J, Fisniku Let al., 2020, Novel treatment approach for fingolimod-associated progressive multifocal leukoencephalopathy in a patient with relapsing remitting multiple sclerosis, 8th Joint ACTRIMS-ECTRIMS Meeting (MSVirtual), Publisher: SAGE PUBLICATIONS LTD, Pages: 294-294, ISSN: 1352-4585

Conference paper

Hillert J, Forsberg L, Manouchehrinia A, Ramanujam R, Spelman T, Klyve P, Drahota J, Horakova D, Joensen H, Magyari M, Ellenberger D, Stahmann A, Van der Walt A, Rodgers J, Nicholas R, Middleton R, Bezlyak V, Adlard N, Hach T, Lines C, Glaser Aet al., 2020, Ongoing disease modifying treatment associated with mis-classification of secondary progressive as relapsing-emitting multiple sclerosis Pharmacological management of progressive MS, 8th Joint ACTRIMS-ECTRIMS Meeting (MSVirtual), Publisher: SAGE PUBLICATIONS LTD, Pages: 20-21, ISSN: 1352-4585

Conference paper

Monaco S, Nicholas R, Reynolds R, Magliozzi Ret al., 2020, Intrathecal inflammation in progressive multiple sclerosis, International Journal of Molecular Sciences, Vol: 21, Pages: 1-11, ISSN: 1422-0067

Progressive forms of multiple sclerosis (MS) are associated with chronic demyelination, axonal loss, neurodegeneration, cortical and deep gray matter damage, and atrophy. These changes are strictly associated with compartmentalized sustained inflammation within the brain parenchyma, the leptomeninges, and the cerebrospinal fluid. In progressive MS, molecular mechanisms underlying active demyelination differ from processes that drive neurodegeneration at cortical and subcortical locations. The widespread pattern of neurodegeneration is consistent with mechanisms associated with the inflammatory molecular load of the cerebrospinal fluid. This is at variance with gray matter demyelination that typically occurs at focal subpial sites, in the proximity of ectopic meningeal lymphoid follicles. Accordingly, it is possible that variations in the extent and location of neurodegeneration may be accounted for by individual differences in CSF flow, and by the composition of soluble inflammatory factors and their clearance. In addition, “double hit” damage may occur at sites allowing a bidirectional exchange between interstitial fluid and CSF, such as the Virchow–Robin spaces and the periventricular ependymal barrier. An important aspect of CSF inflammation and deep gray matter damage in MS involves dysfunction of the blood–cerebrospinal fluid barrier and inflammation in the choroid plexus. Here, we provide a comprehensive review on the role of intrathecal inflammation compartmentalized to CNS and non-neural tissues in progressive MS.

Journal article

Cottrell L, Economos G, Evans C, Silber E, Burman R, Nicholas R, Farsides B, Ashford S, Koffman JSet al., 2020, A realist review of advance care planning for people with multiple sclerosis and their families, PLOS ONE, Vol: 15, ISSN: 1932-6203

Journal article

Wilkie D, Solari A, Nicholas R, 2020, The impact of the face-to-face consultation on decisional conflict in complex decision-making in multiple sclerosis: a pilot study, Multiple Sclerosis Journal - Experimental, Translational and Clinical, Vol: 6, Pages: 1-11, ISSN: 2055-2173

BackgroundThe role of face-to-face consultations in medicine is increasingly being challenged. Disease activity, national guidelines, life goals e.g. pregnancy, multiple therapies and side effects need to be considered on starting disease modifying treatments (DMTs) in people with multiple sclerosis (pwMS). ObjectivesWe studied the impact of a face-to-face consultation on decision making, using decisional conflict (DC) as the primary outcome. MethodsProspective cohort study of 73 pwMS attending clinics who were making decisions about DMTs followed for one year. Prerequisites and consultation features were measured with the SURE scale for DC used as the primary outcome at baseline and at one year.ResultsThe patient activation measure (PAM) was the only driver prior to the consultation associated with DC (p=0.02) showing those less engaged were more likely to have DC. Overall, 51/73 (70%) of people made their treatment decision or reinforced a former decision during the consultation. We found making a treatment decision between the original consultation and the follow-up was associated with resolving DC (p=0.008).Conclusions Patient engagement impacts DC but the HCP delivering the optimal Shared Decision Making (SDM) approach is additionally significant in reducing DC. In complex decisions there is a clear role for face-to-face consultations in current practice.

Journal article

Middleton RM, Pearson OR, Ingram G, Craig EM, Rodgers WJ, Downing-Wood H, Hill J, Tuite-Dalton K, Roberts C, Watson L, Ford D, Nicholas Ret al., 2020, A Rapid Electronic Cognitive Assessment Measure for Multiple Sclerosis: Validation of Cognitive Reaction, an Electronic Version of the Symbol Digit Modalities Test, JOURNAL OF MEDICAL INTERNET RESEARCH, Vol: 22, ISSN: 1438-8871

Journal article

Cencioni MT, Ali R, Nicholas R, Muraro PAet al., 2020, Defective CD19+CD24(hi)CD38(hi)transitional B-cell function in patients with relapsing-remitting MS, MULTIPLE SCLEROSIS JOURNAL, Vol: 27, Pages: 1187-1197, ISSN: 1352-4585

Journal article

Martin N, Sovetkina A, Nadir R, Scalfari A, Tona F, Murphy K, Rigoni E, Dorsey R, Malik O, Nandoskar A, Singh-Curry V, Nicholas Ret al., 2020, Development of autoimmune thyroid disease in multiple sclerosis patients post-alemtuzumab improves treatment response, The Journal of Clinical Endocrinology & Metabolism, Vol: 105, Pages: e3392-e3399, ISSN: 0021-972X

ContextAlemtuzumab is an anti-CD52 monoclonal antibody used in the treatment of relapsing-remitting multiple sclerosis (MS). Between 20-40% of alemtuzumab-treated MS patients develop autoimmune thyroid disease (AITD) as a side effect.ObjectiveTo determine whether MS disease progression following alemtuzumab treatment differs in patients that develop AITD compared to those who do not.Design, setting and patientsA retrospective analysis of 126 patients with relapsing-remitting MS receiving alemtuzumab from 2012 to 2017 at a tertiary referral centre.Main outcome measuresThyroid status, new relapses, Expanded Disability Status Score (EDSS) change and disability progression following alemtuzumab were evaluated.ResultsTwenty-six percent (33 out of 126, 25 female, 8 male) of alemtuzumab-treated patients developed AITD, 55% of which was Graves’ disease. EDSS score following alemtuzumab was reduced in patients who developed AITD compared to those who did not (median [IQR]; AITD: -0.25 [-1 - 0.5] vs non-AITD: 0 [1 - 0]. P=0.007]. Multivariate regression analysis confirmed that the development of AITD was independently associated with EDSS score improvement (p=0.011). Moreover, AITD patients had higher relapse-free survival following alemtuzumab (p=0.023). There was no difference in the number of new focal T2-lesions and contrast-enhancing MRI lesions developed following alemtuzumab between the two groups.ConclusionGraves’ disease was the most common form of AITD developed by MS patients following alemtuzumab. This study suggests that MS patients who develop AITD may have an improved response to alemtuzumab, as measured by reduced disability and lower relapse rate.

Journal article

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