Publications
385 results found
Rhone E, Silber E, Mccormick J, et al., 2017, Autologous haematopoietic stem cell transplant in multiple sclerosis: Updated results from the Pan-London MS group, 43rd Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation (EBMT), Publisher: NATURE PUBLISHING GROUP, Pages: S482-S483, ISSN: 0268-3369
Monsalvo S, Gabriel I, Sevillano B, et al., 2017, Exacerbation of multiple sclerosis symptoms in patients undergoing autologous stem cell transplantation, 43rd Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation (EBMT), Publisher: NATURE PUBLISHING GROUP, Pages: S419-S420, ISSN: 0268-3369
Rhone E, Silber E, Mccormick J, et al., 2017, Investigating frequency of EBV reactivation following autologous HSCT in patients with multiple sclerosis, 43rd Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation (EBMT), Publisher: NATURE PUBLISHING GROUP, Pages: S495-S495, ISSN: 0268-3369
Muraro PA, Martin R, Mancardi GL, et al., 2017, Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis, Nature Reviews Neurology, Vol: 13, Pages: 391-405, ISSN: 1759-4758
Autologous haematopoietic stem cell transplantation (AHSCT) is a multistep procedure that enables destruction of the immune system and its reconstitution from haematopoietic stem cells. Originally developed for the treatment of haematological malignancies, the procedure has been adapted for the treatment of severe immune-mediated disorders. Results from ~20 years of research make a compelling case for selective use of AHSCT in patients with highly active multiple sclerosis (MS), and for controlled trials. Immunological studies support the notion that AHSCT causes qualitative immune resetting, and have provided insight into the mechanisms that might underlie the powerful treatment effects that last well beyond recovery of immune cell numbers. Indeed, studies have demonstrated that AHSCT can entirely suppress MS disease activity for 4–5 years in 70–80% of patients, a rate that is higher than those achieved with any other therapies for MS. Treatment-related mortality, which was 3.6% in studies before 2005, has decreased to 0.3% in studies since 2005. Current evidence indicates that the patients who are most likely to benefit from and tolerate AHSCT are young, ambulatory and have inflammatory MS activity. Clinical trials are required to rigorously test the efficacy, safety and cost-effectiveness of AHSCT against highly active MS drugs.
Chan D, Binks S, Nicholas JM, et al., 2017, Effect of high-dose simvastatin on cognitive, neuropsychiatric, and health-related quality-of-life measures in secondary progressive multiple sclerosis: secondary analyses from the MS-STAT randomised, placebo-controlled trial, Lancet Neurology, Vol: 16, Pages: 591-600, ISSN: 1474-4422
BackgroundIn the 24-month MS-STAT phase 2 trial, we showed that high-dose simvastatin significantly reduced the annualised rate of whole brain atrophy in patients with secondary progressive multiple sclerosis (SPMS). We now describe the results of the MS-STAT cognitive substudy, in which we investigated the treatment effect on cognitive, neuropsychiatric, and health-related quality-of-life (HRQoL) outcome measures.MethodsWe did a secondary analysis of MS-STAT, a 24-month, double-blind, controlled trial of patients with SPMS done at three neuroscience centres in the UK between Jan 28, 2008, and Nov 4, 2011. Patients were randomly assigned (1:1) to either 80 mg simvastatin (n=70) or placebo (n=70). The cognitive assessments done were the National Adult Reading Test, Wechsler Abbreviated Scale of Intelligence, Graded Naming Test, Birt Memory and Information Processing Battery (BMIPB), Visual Object and Space Perception battery (cube analysis), Frontal Assessment Battery (FAB), and Paced Auditory Serial Addition Test. Neuropsychiatric status was assessed using the Hamilton Depression Rating Scale and the Neuropsychiatric Inventory Questionnaire. HRQoL was assessed using the self-reported 36-Item Short Form Survey (SF-36) version 2. Assessments were done at study entry, 12 months, and 24 months. Patients, treating physicians, and outcome assessors were masked to treatment allocation. Analyses were by intention to treat. MS-STAT is registered with ClinicalTrials.gov, number NCT00647348.FindingsBaseline assessment revealed impairments in 60 (45%) of 133 patients on the test of frontal lobe function (FAB), and in between 13 (10%) and 43 (33%) of 130 patients in tests of non-verbal and verbal memory (BMIPB). Over the entire trial, we noted significant worsening on tests of verbal memory (T score decline of 5·7 points, 95% CI 3·6–7·8; p<0·0001) and non-verbal memory (decline of 6·8 points, 4·8–8·7; p<0·
Houston S, Nandoskar A, Nicholas R, et al., 2017, Microvascular Abnormalities and Inner Retinal Thickness in Multiple Sclerosis, Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404
Montgomery SM, Maruszczak MJ, Slater D, et al., 2017, A discrete event simulation to model the cost-utility of fingolimod and natalizumab in rapidly evolving severe relapsing-remitting multiple sclerosis in the UK, JOURNAL OF MEDICAL ECONOMICS, Vol: 20, Pages: 474-482, ISSN: 1369-6998
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- Citations: 13
Nandoskar A, Raffel J, Scalfari AS, et al., 2017, Pharmacological Approaches to the Management of Secondary Progressive Multiple Sclerosis, DRUGS, Vol: 77, Pages: 885-910, ISSN: 0012-6667
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- Citations: 16
Raffel J, Cole J, Record C, et al., 2017, Brain Age: A novel approach to quantify the impact of multiple sclerosis on the brain, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0028-3878
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- Citations: 3
Nicholas R, Dubis A, Nandoskar A, et al., 2017, Changes in Retinal Vessel Architecture and Blood Flow in Multiple Sclerosis, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0028-3878
Papadopoulos D, Karamita M, Mitsikostas DD, et al., 2017, Accelerated cellular senescence in a model of multiple sclerosis, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0028-3878
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- Citations: 1
Raffel J, Sridharan S, Nicholas R, 2017, [C-11]PBR-28 positron emission tomography in multiple sclerosis: Neuroinflammation or otherwise?, Annals of Neurology, Vol: 81, Pages: 323-324, ISSN: 0364-5134
Raffel J, Gafson AR, Dahdaleh S, et al., 2017, Inflammatory Activity on Natalizumab Predicts Short-term but not Long-term Disability in Multiple Sclerosis, PLOS One, Vol: 12, ISSN: 1932-6203
BACKGROUND: In people with multiple sclerosis treated with interferon-beta or glatiramer acetate, new MRI lesions and relapses during the first year of treatment predict a poor prognosis. OBJECTIVE: To study this association in those receiving natalizumab. METHODS: Data were collected on relapses, new MRI activity, and Modified Rio Score after initiation of natalizumab in an observational cohort of 161 patients with high baseline disability. These were correlated with Expanded Disability Status Scale (EDSS) progression at years 1, 2, 3, and 3-7 after treatment initiation, versus pre-treatment baseline. RESULTS: 46/161 patients had a relapse in the first year and 44/161 had EDSS progression by year 2. Relapses and Modified Rio Score in the first year of treatment predicted EDSS progression at year 1 and 2 after treatment initiation. However, this effect disappeared with longer follow-up. Paradoxically, there was a trend towards inflammatory activity on treatment (first year Modified Rio Score, relapses, and MRI activity) predicting a lower risk of EDSS progression by years 3-7, although this did not reach statistical significance. Those with and without EDSS progression did not differ in baseline age, EDSS, or pre-treatment relapse rate. Relapses in year 0-1 predicted further relapses in years 1-3. CONCLUSIONS: Breakthrough inflammatory activity after natalizumab treatment is predictive of short-term outcome measures of relapses or EDSS progression, but does not predict longer term EDSS progression, in this cohort with high baseline disability.
Datta G, Violante IR, Scott G, et al., 2016, Translocator positron-emission tomography and magnetic resonance spectroscopic imaging of brain glial cell activation in multiple sclerosis., Multiple Sclerosis, Vol: 23, Pages: 1469-1478, ISSN: 1352-4585
BACKGROUND: Multiple sclerosis (MS) is characterised by a diffuse inflammatory response mediated by microglia and astrocytes. Brain translocator protein (TSPO) positron-emission tomography (PET) and [myo-inositol] magnetic resonance spectroscopy (MRS) were used together to assess this. OBJECTIVE: To explore the in vivo relationships between MRS and PET [(11)C]PBR28 in MS over a range of brain inflammatory burden. METHODS: A total of 23 patients were studied. TSPO PET imaging with [(11)C]PBR28, single voxel MRS and conventional magnetic resonance imaging (MRI) sequences were undertaken. Disability was assessed by Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC). RESULTS: [(11)C]PBR28 uptake and [ myo-inositol] were not associated. When the whole cohort was stratified by higher [(11)C]PBR28 inflammatory burden, [ myo-inositol] was positively correlated to [(11)C]PBR28 uptake (Spearman's ρ = 0.685, p = 0.014). Moderate correlations were found between [(11)C]PBR28 uptake and both MRS creatine normalised N-acetyl aspartate (NAA) concentration and grey matter volume. MSFC was correlated with grey matter volume (ρ = 0.535, p = 0.009). There were no associations between other imaging or clinical measures. CONCLUSION: MRS [ myo-inositol] and PET [(11)C]PBR28 measure independent inflammatory processes which may be more commonly found together with more severe inflammatory disease. Microglial activation measured by [(11)C]PBR28 uptake was associated with loss of neuronal integrity and grey matter atrophy.
Lewin A, Hamilton S, Witkover A, et al., 2016, Free serum haemoglobin is associated with brain atrophy in secondary progressive multiple sclerosis [version 1; peer review: 1 approved, 2 approved with reservations], Wellcome Open Research, Vol: 1, ISSN: 2398-502X
Background A major cause of disability in secondary progressive multiple sclerosis (SPMS) is progressive brain atrophy, whose pathogenesis is not fully understood. The objective of this study was to identify protein biomarkers of brain atrophy in SPMS. Methods We used surface-enhanced laser desorption-ionization time-of-flight mass spectrometry to carry out an unbiased search for serum proteins whose concentration correlated with the rate of brain atrophy, measured by serial MRI scans over a 2-year period in a well-characterized cohort of 140 patients with SPMS. Protein species were identified by liquid chromatography-electrospray ionization tandem mass spectrometry. Results There was a significant (p<0.004) correlation between the rate of brain atrophy and a rise in the concentration of proteins at 15.1 kDa and 15.9 kDa in the serum. Tandem mass spectrometry identified these proteins as alpha-haemoglobin and beta-haemoglobin, respectively. The abnormal concentration of free serum haemoglobin was confirmed by ELISA (p<0.001). The serum lactate dehydrogenase activity was also highly significantly raised (p<10(-12)) in patients with secondary progressive multiple sclerosis. Conclusions An underlying low-grade chronic intravascular haemolysis is a potential source of the iron whose deposition along blood vessels in multiple sclerosis plaques contributes to the neurodegeneration and consequent brain atrophy seen in progressive disease. Chelators of free serum iron will be ineffective in preventing this neurodegeneration, because the iron (Fe(2+)) is chelated by haemoglobin.
Newbould R, Muraro P, Bishop C, et al., 2016, Analysis of ageing-associated grey matter volume in patients with multiple sclerosis shows excess atrophy in subcortical regions, NeuroImage-Clinical, Vol: 13, Pages: 9-15, ISSN: 2213-1582
Age of onset in multiple sclerosis (MS) exerts an influence on the course of disease. This study examined whether global and regional brain volumes differed between “younger” and “older” onset MS subjects who were matched for short disease duration, mean 1.9 years and burden as measured by the MS Severity Score and relapses.21 younger-onset MS subjects (age 30.4 ± 3.2 years) were compared with 17 older-onset (age 48.7 ± 3.3 years) as well as age-matched controls (n = 31, 31.9 ± 3.5 years and n = 21, 47.3 ± 4.0 years). All subjects underwent 3D volumetric T1 and T2-FLAIR imaging. White matter (WM) and grey matter (GM) lesions were outlined manually. Lesions were filled prior to tissue and structural segmentation to reduce classification errors.Volume loss versus control was predominantly in the subcortical GM, at > 13% loss. Younger and older-onset MS subjects had similar, strong excess loss in the putamen, thalamus, and nucleus accumbens. No excess loss was detected in the amygdala or pallidum. The hippocampus and caudate showed significant excess loss in the younger group (p < 0.001) and a strong trend in the older-onset group.These results provide a potential imaging correlate of published neuropsychological studies that reported the association of younger age at disease onset with impaired cognitive performance, including decreased working memory.
Record C, De Simoni S, Feeney C, et al., 2016, Improved cerebral blood flow after natalizumab treatment in multiple sclerosis, 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE Publications, Pages: 669-669, ISSN: 1352-4585
Raffel J, Wakerley B, Nicholas R, 2016, Multiple sclerosis, Medicine (United Kingdom), Vol: 44, Pages: 537-541, ISSN: 1357-3039
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) and the most common cause of disability among young adults. Most patients present with a relapsing–remitting illness, characterized by discrete episodes of focal neurological deficit with temporal and anatomical dispersion in the CNS. The introduction of diagnostic criteria integrating magnetic resonance imaging has enabled earlier diagnosis and guides earlier intervention in this chronic disease. Although the underlying cause of MS remains unknown, recent advances in molecular immunology have brought about a new wave of immunotherapies that can stop relapses and may delay progression. Given the emergence of more effective therapies, the recognition of relapses and the symptom management of continuing complications are important roles for all clinicians who encounter patients with MS.
Dubis AM, Nandoskar A, Kalitzeos A, et al., 2016, Retinal Vessel Architecture and Blood Flow in Multiple Sclerosis, Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC, ISSN: 0146-0404
Mitchell B, Raffel J, Nicholas R, 2016, Increasing area level deprivation in England impacts age of progression and wheelchair use in multiple sclerosis, 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE PUBLICATIONS LTD, Pages: 503-503, ISSN: 1352-4585
Connell L, Daws R, Hampshire A, et al., 2016, Validating a participant-led computerised cognitive battery in people with multiple sclerosis, 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE PUBLICATIONS LTD, Pages: 140-141, ISSN: 1352-4585
Chan D, Binks S, Nicholas J, et al., 2016, Effect of high-dose simvastatin on cognition in secondary progressive multiple sclerosis (MS-STAT cognitive): a randomised, placebo-controlled, Phase 2 trial., 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE PUBLICATIONS LTD, Pages: 82-83, ISSN: 1352-4585
Bermel R, Comi G, Eralinna J-P, et al., 2016, Design of two phase III open-label trials evaluating ocrelizumab in patients with relapsing-remitting multiple sclerosis and suboptimal response to disease-modifying treatment, 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE PUBLICATIONS LTD, Pages: 615-616, ISSN: 1352-4585
Gafson AR, Nicholas R, Giovannoni G, et al., 2016, Plasma cytokine concentration changes in multiple sclerosis patients after treatment with dimethyl fumarate, 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE PUBLICATIONS LTD, Pages: 670-671, ISSN: 1352-4585
Datta G, Colasanti A, Kalk NJ, et al., 2016, <i>In vivo</i> translocator protein positron emission tomography imaging detects a heterogeneity of lesion inflammatory activity in multiple sclerosis not evident by MRI., 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE PUBLICATIONS LTD, Pages: 36-37, ISSN: 1352-4585
Wallace A, Raffel J, Reynolds R, et al., 2016, Increased multiple sclerosis impact scale-29 score is associated with reduced survival in multiple sclerosis, 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE PUBLICATIONS LTD, Pages: 455-456, ISSN: 1352-4585
Dorsey-Campbell RJ, Quinn T, Felongco T, et al., 2016, Pharmacy-led monitoring of disease modifying treatments in multiple sclerosis improves the quality of monitoring and improves patient satisfaction, 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE PUBLICATIONS LTD, Pages: 792-792, ISSN: 1352-4585
Scalfari A, Romualdi C, Mattoscio M, et al., 2016, Early relapses and cortical damage predict the risk of developing secondary progressive MS, 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE PUBLICATIONS LTD, Pages: 197-198, ISSN: 1352-4585
Peress L, Violante IR, Scott G, et al., 2016, Thalamic magnetic resonance spectroscopy in highly active multiple sclerosis, 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE PUBLICATIONS LTD, Pages: 210-211, ISSN: 1352-4585
Lema A, Bishop C, Malik O, et al., 2016, A compararison of magnetization transfer methods to assess brain and cervical cord microstructure in multiple sclerosis, Journal of Neuroimaging, Vol: 27, Pages: 221-226, ISSN: 1552-6569
BACKGROUND: Demyelination is a core pathological feature of multiple sclerosis (MS) and spontaneous remyelination appears to be an important mechanism for repair in the disease. Magnetization transfer ratio imaging (MTR) has been used extensively to evaluate demyelination, although limitations to its specificity are recognized. MT saturation imaging (MTsat) removes some of the T1 dependence of MTR. We have performed a comparative evaluation of MTR and MTsat imaging in a mixed group of subjects with active MS, to explore their relative sensitivity to pathology relevant to explaining clinical outcomes. METHODS: A total of 134 subjects underwent MRI of their brain and cervical spinal cord. Isotropic 3-dimensional pre- and postcontrast T1-weighted and T2-weighted fluid-attenuated inversion recovery (FLAIR) volumes were segmented into brain normal appearing white matter (NAWM), brain WM lesions (WML), normal appearing spinal cord (NASC), and spinal cord lesions. Volumes and metrics for MTR and MTsat histograms were calculated for each region. RESULTS: Significant Spearman correlations were found with the Expanded Disability Status Scale and timed 25-foot walk for the whole brain and WML MTR, but not in that from the NAWM or any cervical spinal cord region. By contrast, the MTsat was correlated with both disability metrics in all these regions in both the brain and spine. CONCLUSIONS: This study extends prior work relating atrophy and lesion load with disability, by characterization of MTsat parameters. MTsat is practical in routine clinical applications and may be more sensitive to tissue damage than MTR for both brain and cervical spinal cord.
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