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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232 results found

Scalfari A, Lederer C, Daumer M, Nicholas R, Ebers GC, Muraro PAet al., 2016, The relationship of age with the clinical phenotype in multiple sclerosis, MULTIPLE SCLEROSIS JOURNAL, Vol: 22, Pages: 1750-1758, ISSN: 1352-4585

Journal article

Nicholas R, Magliozzi R, Campbell G, Mahad D, Reynolds Ret al., 2016, Temporal lobe cortical pathology and inhibitory GABA interneuron cell loss are associated with seizures in multiple sclerosis, Multiple Sclerosis Journal, Vol: 22, Pages: 25-35, ISSN: 1477-0970

Background: Seizures are recognised in multiple sclerosis (MS), but their true incidence and the mechanismby which they are associated with MS is unclear.Objective: The objective of this paper is to determine the lifetime frequency of seizures in the UnitedKingdom MS Tissue Bank (UKMSTB) population and any pathological features associated with seizures.Methods: We evaluated 255 individuals from the UKMSTB. A subset underwent analysis of corticalthickness, grey matter lesion (GML) (type and number) and cortical neuronal numbers (total and GABAergic).Results: A total of 37/255 patients had seizures (14.5% lifetime incidence); in 47% they were associatedwith concurrent infection. In those with seizures, death and wheelchair use occurred earlier and in 59%seizures developed after 15 years of disease. Seizures were associated with Type 1 GMLs and reducedcortical thickness in the middle temporal gyrus. Localised selective GABAergic interneuron loss in layersIV and VI was related to GMLs but was not explained by the presence of inflammation or by mitochondrial dysfunction within Type I GMLs. Conclusion: We confirm that seizure frequency rises in MS. Type I GMLs in the temporal lobe underlie a loss of inhibitory interneurons in cortical layers IV and VI and these changes could together with concurrent infection enhance susceptibility to seizures.

Journal article

Colasanti A, Guo, Giannetti P, Wall M, Newbould R, Bishop C, Onega M, Nicholas R, Ciccarelli O, Muraro PM, Malik O, Owen D, Young AH, Gunn R, Piccini P, Matthews P, Rabiner Eet al., 2015, Hippocampal neuroinflammation, functional connectivity and depressive symptoms in multiple sclerosis, Biological Psychiatry, Vol: 80, Pages: 62-72, ISSN: 1873-2402

BackgroundDepression, a condition commonly comorbid with multiple sclerosis (MS), is associated more generally with elevated inflammatory markers and hippocampal pathology. We hypothesized that neuroinflammation in the hippocampus is responsible for depression associated with MS. We characterized the relationship between depressive symptoms and hippocampal microglial activation in patients with MS using the 18-kDa translocator protein radioligand [18F]PBR111. To evaluate pathophysiologic mechanisms, we explored the relationships between hippocampal neuroinflammation, depressive symptoms, and hippocampal functional connectivities defined by resting-state functional magnetic resonance imaging.MethodsThe Beck Depression Inventory (BDI) was administered to 11 patients with MS and 22 healthy control subjects before scanning with positron emission tomography and functional magnetic resonance imaging. We tested for higher [18F]PBR111 uptake in the hippocampus of patients with MS relative to healthy control subjects and examined the correlations between [18F]PBR111 uptake, BDI scores, and hippocampal functional connectivities in the patients with MS.ResultsPatients with MS had an increased hippocampal [18F]PBR111 distribution volume ratio relative to healthy control subjects (p = .024), and the hippocampal distribution volume ratio was strongly correlated with the BDI score in patients with MS (r = .86, p = .006). Hippocampal functional connectivities to the subgenual cingulate and prefrontal and parietal regions correlated with BDI scores and [18F]PBR111 distribution volume ratio.ConclusionsOur results provide evidence that hippocampal microglial activation in MS impairs the brain functional connectivities in regions contributing to maintenance of a normal affective state. Our results suggest a rationale for the responsiveness of depression in some patients with MS to effective control of brain neuroinflammation. Our findings also lend support to further investigation of t

Journal article

Raffel J, Gafson A, Dahdaleh S, Nicholas Ret al., 2015, EARLY PREDICTION OF LONG-TERM RESPONSE TO NATALIZUMAB IN MULTIPLE SCLEROSIS, Annual Meeting of the Association-of-British-Neurologists (ABN), Publisher: BMJ PUBLISHING GROUP, ISSN: 0022-3050

Conference paper

McGuigan C, Craner M, Guadagno J, Kapoor R, Mazibrada G, Molyneux P, Nicholas R, Palace J, Pearson OR, Rog D, Young CAet al., 2015, Stratification and monitoring of natalizumab-associated progressive multifocal leukoencephalopathy risk: recommendations from an expert group, Journal of Neurology Neurosurgery and Psychiatry, Vol: 87, Pages: 117-125, ISSN: 1468-330X

The use of natalizumab for highly active relapsing-remitting multiple sclerosis (MS) is influenced by the occurrence of progressive multifocal leukoencephalopathy (PML). Through measurement of the anti-JCV antibody index, and in combination with the presence or absence of other known risk factors, it may be possible to stratify patients with MS according to their risk of developing PML during treatment with natalizumab and detect early suspected PML using MRI including a diffusion-weighted imaging sequence. This paper describes a practical consensus guideline for treating neurologists, based on current evidence, for the introduction into routine clinical practice of anti-JCV antibody index testing of immunosuppressant-naïve patients with MS, either currently being treated with, or initiating, natalizumab, based on their anti-JCV antibody status. Recommendations for the frequency and type of MRI screening in patients with varying index-associated PML risks are also discussed. This consensus paper presents a simple and pragmatic algorithm to support the introduction of anti-JCV antibody index testing and MRI monitoring into standard PML safety protocols, in order to allow some JCV positive patients who wish to begin or continue natalizumab treatment to be managed with a more individualised analysis of their PML risk.

Journal article

Raffel J, Gafson AR, Malik O, Nicholas Ret al., 2015, Anti-JC virus antibody titres increase over time with natalizumab treatment., Multiple Sclerosis Journal, Vol: 21, Pages: 1833-1838, ISSN: 1477-0970

BACKGROUND: Anti-JC virus antibody status is a risk factor for progressive multifocal leukoencephalopathy after natalizumab treatment in multiple sclerosis. Previous studies have used a cross-sectional approach to conclude that the presence and duration of natalizumab treatment does not influence anti-JCV Ab seropositivity. OBJECTIVES: Using a longitudinal approach, we measured change in anti-JCV Ab results after natalizumab treatment. METHODS: Anti-JCV Ab results (n = 1154) from the second-generation STRATIFY JCV™ DxSelect™ test were analysed from an observational cohort of MS patients on natalizumab (n = 485; n = 340 with repeat testing; n = 657 repeat tests on natalizumab). RESULTS: Across sequential paired tests, seroconversion rate was greater than seroreversion rate (40/364 (11.0%) versus 18/293 (6.1%); p < 0.05). Moreover, anti-JCV Ab index increased across longitudinal paired tests (mA-B 0.102; paired t(656) = 5.0; p < 0.0001). This magnitude of Ab level increase far exceeds that expected due to increasing age alone. CONCLUSION: Our data suggest that natalizumab therapy is associated with a significant and substantial increase in anti-JCV Ab index over time. Further work should focus on the underlying mechanisms of this phenomenon, and the clinical relevance to risk stratification.

Journal article

Howell OW, Schulz-Trieglaff EK, Carassiti D, Gentleman SM, Nicholas R, Roncaroli F, Reynolds Ret al., 2015, Extensive grey matter pathology in the cerebellum in multiple sclerosis is linked to inflammation in the subarachnoid space, NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol: 41, Pages: 798-813, ISSN: 0305-1846

Journal article

Datta G, Battaglini M, Scott G, Yaldizli O, Ribeiro AS, Wall MB, Gunn R, Rabiner EA, Ciccarelli O, Nicholas R, Stefano ND, Matthews PMet al., 2015, Positron emission tomography imaging in multiple sclerosis highlights a diffuse inflammatory response in brain that appears normal on conventional magnetic resonance imaging, 31st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE Publications (UK and US), Pages: 477-478, ISSN: 1477-0970

Conference paper

Colasanti A, Guo Q, Giannetti P, Wall M, Newbould RD, Bishop C, Onega M, Nicholas R, Ciccarelli O, Muraro P, Malik O, Owen D, Young AH, Gunn R, Piccini P, Matthews PM, Rabiner EAet al., 2015, Hippocampal inflammation and depression in multiple sclerosis: integrating evidence from TSPO PET and resting state fMRI, 31st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE Publications (UK and US), Pages: 492-493, ISSN: 1477-0970

Conference paper

Roever C, Nicholas R, Straube S, Friede Tet al., 2015, Changing EDSS Progression in Placebo Cohorts in Relapsing MS: A Systematic Review and Meta-Regression, PLOS One, Vol: 10, ISSN: 1932-6203

BackgroundRecent systematic reviews of randomised controlled trials (RCTs) in relapsing multiple sclerosis (RMS) revealed a decrease in placebo annualized relapse rates (ARR) over the past two decades. Furthermore, regression to the mean effects were observed in ARR and MRI lesion counts. It is unclear whether disease progression measured by the expanded disability status scale (EDSS) exhibits similar features.MethodsA systematic review of RCTs in RMS was conducted extracting data on EDSS and baseline characteristics. The logarithmic odds of disease progression were modelled to investigate time trends. Random-effects models were used to account for between-study variability; all investigated models included trial duration as a predictor to correct for unequal study durations. Meta-regressions were conducted to assess the prognostic value of a number of study-level baseline variables.ResultsThe systematic literature search identified 39 studies, including a total of 19,714 patients. The proportion of patients in placebo controls experiencing a disease progression decreased over the years (p<0.001). Meta-regression identified associated covariates including the size of the study and its duration that in part explained the time trend. Progression probabilities tended to be lower in the second year of a study compared to the first year with a reduction of 28% in progression odds from year 1 to year 2 (p = 0.017).ConclusionEDSS disease progression exhibits similar behaviour over time as the ARR and point to changes in trial characteristics over the years. This needs to be considered in comparisons between historical and recent trials.

Journal article

Nicholas R, Raffel J, Malik O, 2015, Progressive multifocal leukoencephalopathy presenting with posterior fossa radiological features in the context of natalizumab therapy in relapsing-remitting multiple sclerosis, 31st Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE PUBLICATIONS LTD, Pages: 585-585, ISSN: 1352-4585

Conference paper

Scalfari A, Lederer C, Daumer M, Nicholas R, Ebers G, Muraro Pet al., 2015, The influence of age on the disease phenotype preceding the onset of progressive multiple sclerosis, 1st Congress of the European-Academy-of-Neurology, Publisher: WILEY, Pages: 301-301, ISSN: 1351-5101

Conference paper

Scalfari A, Ebers G, Nicholas R, Muraro P, Calabrese Met al., 2015, Frequent early relapses and severe cortical damage characterize patients at high risk of early developing progressive multiple sclerosis, 1st Congress of the European-Academy-of-Neurology, Publisher: WILEY, Pages: 620-620, ISSN: 1351-5101

Conference paper

Nicholas RS, Kostadima V, Hanspal M, Wakerley BR, Sergeant R, Decuypere S, Malik O, Boyton RJ, Altmann DMet al., 2015, MS in South Asians in England: early disease onset and novel pattern of myelin autoimmunity., BMC Neurology, Vol: 15, ISSN: 1471-2377

BACKGROUND: Epidemiological studies describe a latitude gradient for increased MS prevalence and a preponderance of disease in Caucasian individuals. However, individuals from other ethnic backgrounds and low-risk regions can acquire a raised risk through migration. Nearly a fifth of the London population is of Asian/Asian-British origin and a significant proportion of referrals are from this group. METHODS: We investigated whether there were differences in timing, presentation, severity, and immunology of disease (with respect to CD4 myelin epitope recognition) between individuals in London with MS who were either of S. Asian or Caucasian origin. Individuals of S. Asian origin with MS were compared with healthy S. Asian controls, individuals with MS and of Caucasian origin and Caucasian controls. RESULTS: Age at MS onset is significantly lower in the S. Asian group, attributable to earlier onset specifically in UK-born individuals, though clinical presentation is similar. Analysis of CD4 autoimmunity to myelin antigens shows disease in S. Asian individuals to encompass recognition of novel epitopes; immunity to MBP116-130 in S. Asian individuals was highly disease-specific. CONCLUSIONS: These findings emphasize the need to define disease profiles across ethnicities and identify environmental triggers conferring acquired risk. Such findings must inform choices for immunotherapeutic interventions suitable for all, across ethnicities.

Journal article

Mattoscio M, Nicholas R, Sormani MP, Malik O, Lee JS, Waldman AD, Dazzi F, Muraro PAet al., 2015, Hematopoietic mobilization Potential biomarker of response to natalizumab in multiple sclerosis, NEUROLOGY, Vol: 84, Pages: 1473-1482, ISSN: 0028-3878

Journal article

Clay J, Kelsey P, Bell S, Lim C, Helen J, Nicholas R, Silber E, Malik O, Brex P, Muraro P, Sharrack B, Snowden J, Kazmi Met al., 2015, Autologous haematopoietic stem cell transplantation in aggressive multiple sclerosis: a UK cohort from two centres, 41st Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation, Publisher: NATURE PUBLISHING GROUP, Pages: S61-S61, ISSN: 0268-3369

Conference paper

Giovannonin G, de Jong B, Derfuss T, Izquierdo G, Mazibrada G, Molyneux P, Nicholas R, Overell J, Ziemssen T, Juliusson Get al., 2015, A pragmatic approach to dealing with fingolimod-related lynnphopaenia in Europe, MULTIPLE SCLEROSIS AND RELATED DISORDERS, Vol: 4, Pages: 83-84, ISSN: 2211-0348

Journal article

Sousa ADPA, Malmegrim KCR, Panepucci RA, Brum DS, Barreira AA, Dos Santos AC, Araujos AG, Covas DT, Oliveira MC, Moraes DA, Pieroni F, Barros GM, Simoes BP, Nicholas R, Burt RK, Voltarelli JC, Muraro PAet al., 2015, Autologous haematopoietic stem cell transplantation reduces abnormalities in the expression of immune genes in multiple sclerosis, CLINICAL SCIENCE, Vol: 128, Pages: 111-U57, ISSN: 0143-5221

Journal article

Nicholas RS, Friede T, Hollis S, Young CAet al., 2015, Anticholinergics for urinary symptoms in multiple sclerosis (Withdrawn Paper. 2015, Art. no. CD004193), COCHRANE DATABASE OF SYSTEMATIC REVIEWS, ISSN: 1469-493X

Journal article

Giannetti P, Politis M, Su P, Turkheimer FE, Malik O, Keihaninejad S, Wu K, Waldman A, Reynolds R, Nicholas R, Piccini Pet al., 2014, Increased PK11195-PET binding in normal-appearing white matter in clinically isolated syndrome, Brain, Vol: 138, Pages: 110-119, ISSN: 0006-8950

Journal article

Sousa ADPA, Nicholas R, Johnson K, Darko S, Price D, Douek D, Muraro P, Jacobson Set al., 2014, Deep sequencing of T-cell receptor repertoire reveals enrichment of highly expanded clonotypes in cerebrospinal fluid from multiple sclerosis, 12th International Congress of Neuroimmunology (ISNI), Publisher: ELSEVIER SCIENCE BV, Pages: 197-198, ISSN: 0165-5728

Conference paper

Nicholas R, Barkhof F, Cohen J, Radue E-W, Kappos L, Haering D, Sfikas N, von Rosenstiel P, Francis Get al., 2014, BRAIN VOLUME CHANGE AND DISABILITY IN FINGOLIMOD TRIALS, Annual Meeting of the Association-of-British-Neurologists, Publisher: BMJ PUBLISHING GROUP, ISSN: 0022-3050

Conference paper

Raffel J, Nicholas R, Roncaroli F, Reynolds Ret al., 2014, Astrocytes upregulate interleukin-17 receptor expression in white matter lesions in multiple sclerosis, Joint ACTRIMS-ECTRIMS Meeting, Publisher: SAGE PUBLICATIONS LTD, Pages: 366-367, ISSN: 1352-4585

Conference paper

Sousa ADPA, Nicholas R, Johnson K, Darko S, Price D, Douek DC, Jacobson S, Muraro PAet al., 2014, Deep sequencing of T-cell receptor repertoire reveals enrichment of highly expanded clonotypes in cerebrospinal fluid from multiple sclerosis patients, Joint ACTRIMS-ECTRIMS Meeting, Publisher: SAGE PUBLICATIONS LTD, Pages: 57-57, ISSN: 1352-4585

Conference paper

Colasanti A, Guo Q, Muhlert N, Giannetti P, Onega M, Newbould RD, Ciccarelli O, Rison S, Thomas C, Nicholas R, Muraro PA, Malik O, Owen DR, Piccini P, Gunn RN, Rabiner EA, Matthews PMet al., 2014, In Vivo Assessment of Brain White Matter Inflammation in Multiple Sclerosis with F-18-PBR111 PET, JOURNAL OF NUCLEAR MEDICINE, Vol: 55, Pages: 1112-1118, ISSN: 0161-5505

Journal article

Chataway J, Schuerer N, Alsanousi A, Chan D, MacManus D, Hunter K, Anderson V, Bangham CRM, Clegg S, Nielsen C, Fox NC, Wilkie D, Nicholas JM, Calder VL, Greenwood J, Frost C, Nicholas Ret al., 2014, Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial, LANCET, Vol: 383, Pages: 2213-2221, ISSN: 0140-6736

Journal article

Giannetti P, Politis M, Su P, Turkheimer F, Malik O, Keihaninejad S, Wu K, Reynolds R, Nicholas R, Piccini Pet al., 2014, Microglia activation in multiple sclerosis black holes predicts outcome in progressive patients: An in vivo [(11)C](R)-PK11195-PET pilot study, NEUROBIOLOGY OF DISEASE, Vol: 65, Pages: 203-210, ISSN: 0969-9961

Journal article

Papadopoulos D, Antoniou N, Tsimaratou K, Mitsikostas DD, Gorgoulis V, Nicholas Ret al., 2014, A quantitative histopathological study of the effects of arsenic oxides on inflammation, demyelination and neurodegeneration in multiple sclerosis, Joint Congress of European Neurology, Publisher: SPRINGER HEIDELBERG, Pages: S438-S438, ISSN: 0340-5354

Conference paper

Papadopoulos D, Antoniou N, Tsimaratou K, Mitsikostas DD, Gorgoulis V, Nicholas Ret al., 2014, A quantitative histopathological study of the effects of arsenic oxides on inflammation, demyelination and neurodegeneration in multiple sclerosis, Joint Congress of European Neurology, Publisher: WILEY-BLACKWELL, Pages: 677-677, ISSN: 1351-5101

Conference paper

Newbould RD, Nicholas R, Thomas CL, Quest R, Lee JSZ, Honeyfield L, Colasanti A, Malik O, Mattoscio M, Matthews PM, Sormani MP, Waldman AD, Muraroc PAet al., 2014, Age independently affects myelin integrity as detected by magnetization transfer magnetic resonance imaging in multiple sclerosis, NeuroImage: Clinical, Vol: 4, Pages: 641-648, ISSN: 2213-1582

BackgroundMultiple sclerosis (MS) is a heterogeneous disorder with a progressive course that is difficult to predict on a case-by-case basis. Natural history studies of MS have demonstrated that age influences clinical progression independent of disease duration.ObjectiveTo determine whether age would be associated with greater CNS injury as detected by magnetization transfer MRI.Materials and methodsForty MS patients were recruited from out-patient clinics into two groups stratified by age but with similar clinical disease duration as well as thirteen controls age-matched to the older MS group. Images were segmented by automated programs and blinded readers into normal appearing white matter (NAWM), normal appearing gray matter (NAGM), and white matter lesions (WMLs) and gray matter lesions (GMLs) in the MS groups. WML and GML were delineated on T2-weighted 3D fluid-attenuated inversion recovery (FLAIR) and T1 weighted MRI volumes. Mean magnetization transfer ratio (MTR), region volume, as well as MTR histogram skew and kurtosis were calculated for each region.ResultsAll MTR measures in NAGM and MTR histogram metrics in NAWM differed between MS subjects and controls, as expected and previously reported by several studies, but not between MS groups. However, MTR measures in the WML did significantly differ between the MS groups, in spite of no significant differences in lesion counts and volumes.ConclusionsDespite matching for clinical disease duration and recording no significant WML volume difference, we demonstrated strong MTR differences in WMLs between younger and older MS patients. These data suggest that aging-related processes modify the tissue response to inflammatory injury and its clinical outcome correlates in MS.

Journal article

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