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  1. Article ; Online: Multiple sclerosis, a treatable disease .

    Doshi, Anisha / Chataway, Jeremy

    Clinical medicine (London, England)

    2017  Volume 17, Issue 6, Page(s) 530–536

    Abstract: This article reviews our current understanding and modern treatment of multiple sclerosis (MS). MS is a disabling condition resulting in devastating social and economic impacts. As MS can affect any part of the central nervous system, the presentation is ...

    Abstract This article reviews our current understanding and modern treatment of multiple sclerosis (MS). MS is a disabling condition resulting in devastating social and economic impacts. As MS can affect any part of the central nervous system, the presentation is often diverse; however, there are key features that can be useful in the clinic. We comment on the diagnostic criteria and review the main subtypes of MS, including clinically isolated syndrome, relapsing remitting MS, secondary progressive MS and primary progressive MS. Although the underlying aetiology of MS is still not known, we summarise those with most evidence of association. Finally, we aim to present treatment strategies for managing the acute relapse, disease-modifying therapies and MS symptoms. This review highlights that progressive MS is an area where there is currently a paucity of available disease-modifying treatments and this will be a major focus for future development.
    MeSH term(s) Adjuvants, Immunologic/therapeutic use ; Alemtuzumab/therapeutic use ; Crotonates/therapeutic use ; Demyelinating Diseases/drug therapy ; Dimethyl Fumarate/therapeutic use ; Fingolimod Hydrochloride/therapeutic use ; Glatiramer Acetate/therapeutic use ; Glucocorticoids/therapeutic use ; Humans ; Hydroxybutyrates ; Immunologic Factors/therapeutic use ; Immunosuppressive Agents/therapeutic use ; Interferon beta-1a/therapeutic use ; Interferon beta-1b/therapeutic use ; Mitoxantrone/therapeutic use ; Multiple Sclerosis/drug therapy ; Multiple Sclerosis, Chronic Progressive/drug therapy ; Multiple Sclerosis, Relapsing-Remitting/drug therapy ; Natalizumab/therapeutic use ; Nitriles ; Toluidines/therapeutic use
    Chemical Substances Adjuvants, Immunologic ; Crotonates ; Glucocorticoids ; Hydroxybutyrates ; Immunologic Factors ; Immunosuppressive Agents ; Natalizumab ; Nitriles ; Toluidines ; Interferon beta-1b (145155-23-3) ; teriflunomide (1C058IKG3B) ; Alemtuzumab (3A189DH42V) ; Glatiramer Acetate (5M691HL4BO) ; Mitoxantrone (BZ114NVM5P) ; Dimethyl Fumarate (FO2303MNI2) ; Fingolimod Hydrochloride (G926EC510T) ; Interferon beta-1a (XRO4566Q4R)
    Language English
    Publishing date 2017-11-29
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2048646-7
    ISSN 1473-4893 ; 1470-2118
    ISSN (online) 1473-4893
    ISSN 1470-2118
    DOI 10.7861/clinmedicine.17-6-530
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  2. Article ; Online: Multiple sclerosis, a treatable disease.

    Doshi, Anisha / Chataway, Jeremy

    Clinical medicine (London, England)

    2016  Volume 16, Issue Suppl 6, Page(s) s53–s59

    Abstract: This article reviews our current understanding and modern treatment of multiple sclerosis (MS). MS is a disabling condition resulting in devastating social and economic impacts. As MS can affect any part of the central nervous system, the presentation is ...

    Abstract This article reviews our current understanding and modern treatment of multiple sclerosis (MS). MS is a disabling condition resulting in devastating social and economic impacts. As MS can affect any part of the central nervous system, the presentation is often diverse; however, there are key features that can be useful in the clinic. We comment on the diagnostic criteria and review the main subtypes of MS, including clinically isolated syndrome, relapsing remitting MS, secondary progressive MS and primary progressive MS. Although the underlying aetiology of MS is still not known, we summarise those with most evidence of association. Finally, we aim to present treatment strategies for managing the acute relapse, disease-modifying therapies and MS symptoms. This review highlights that progressive MS is an area where there is currently a paucity of available disease-modifying treatments and this will be a major focus for future development.
    MeSH term(s) Humans ; Multiple Sclerosis/diagnosis ; Multiple Sclerosis/epidemiology ; Multiple Sclerosis/therapy
    Language English
    Publishing date 2016-12-12
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2048646-7
    ISSN 1473-4893 ; 1470-2118
    ISSN (online) 1473-4893
    ISSN 1470-2118
    DOI 10.7861/clinmedicine.16-6-s53
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  3. Article ; Online: Serum neurofilament light and MRI predictors of cognitive decline in patients with secondary progressive multiple sclerosis: Analysis from the MS-STAT randomised controlled trial.

    Williams, Thomas / Tur, Carmen / Eshaghi, Arman / Doshi, Anisha / Chan, Dennis / Binks, Sophie / Wellington, Henny / Heslegrave, Amanda / Zetterberg, Henrik / Chataway, Jeremy

    Multiple sclerosis (Houndmills, Basingstoke, England)

    2022  Volume 28, Issue 12, Page(s) 1913–1926

    Abstract: Background: Cognitive impairment affects 50%-75% of people with secondary progressive multiple sclerosis (PwSPMS). Improving our ability to predict cognitive decline may facilitate earlier intervention.: Objective: The main aim of this study was to ... ...

    Abstract Background: Cognitive impairment affects 50%-75% of people with secondary progressive multiple sclerosis (PwSPMS). Improving our ability to predict cognitive decline may facilitate earlier intervention.
    Objective: The main aim of this study was to assess the relationship between longitudinal changes in cognition and baseline serum neurofilament light chain (sNfL) in PwSPMS. In a multi-modal analysis, MRI variables were additionally included to determine if sNfL has predictive utility beyond that already established through MRI.
    Methods: Participants from the MS-STAT trial underwent a detailed neuropsychological test battery at baseline, 12 and 24 months. Linear mixed models were used to assess the relationships between cognition, sNfL, T2 lesion volume (T2LV) and normalised regional brain volumes.
    Results: Median age and Expanded Disability Status Score (EDSS) were 51 and 6.0. Each doubling of baseline sNfL was associated with a 0.010 [0.003-0.017] point per month faster decline in WASI Full Scale IQ Z-score (
    Conclusion: Elevated sNfL is associated with faster cognitive decline, independent of T2LV and regional normalised volumes.
    MeSH term(s) Biomarkers ; Cognitive Dysfunction/diagnostic imaging ; Cognitive Dysfunction/etiology ; Humans ; Intermediate Filaments/pathology ; Magnetic Resonance Imaging/methods ; Multiple Sclerosis/pathology ; Multiple Sclerosis, Chronic Progressive/complications ; Multiple Sclerosis, Chronic Progressive/diagnostic imaging ; Neurofilament Proteins
    Chemical Substances Biomarkers ; Neurofilament Proteins
    Language English
    Publishing date 2022-08-09
    Publishing country England
    Document type Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 1290669-4
    ISSN 1477-0970 ; 1352-4585
    ISSN (online) 1477-0970
    ISSN 1352-4585
    DOI 10.1177/13524585221114441
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  4. Article ; Online: A Systematic Review of Resting-State Functional MRI Connectivity Changes and Cognitive Impairment in Multiple Sclerosis.

    Jandric, Danka / Doshi, Anisha / Scott, Richelle / Paling, David / Rog, David / Chataway, Jeremy / Schoonheim, Menno M / Parker, Geoff / Muhlert, Nils

    Brain connectivity

    2021  Volume 12, Issue 2, Page(s) 112–133

    Abstract: Introduction: ...

    Abstract Introduction:
    MeSH term(s) Adult ; Brain ; Brain Mapping ; Cognitive Dysfunction/diagnostic imaging ; Cognitive Dysfunction/etiology ; Humans ; Magnetic Resonance Imaging/methods ; Multiple Sclerosis/complications ; Multiple Sclerosis/diagnostic imaging
    Language English
    Publishing date 2021-10-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review ; Systematic Review
    ZDB-ID 2609017-X
    ISSN 2158-0022 ; 2158-0014
    ISSN (online) 2158-0022
    ISSN 2158-0014
    DOI 10.1089/brain.2021.0104
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  5. Article ; Online: Optimising recruitment in clinical trials for progressive multiple sclerosis: observational analysis from the MS-SMART and MS-STAT2 randomised controlled trials.

    Williams, Thomas / Alexander, Sarah / Blackstone, James / De Angelis, Floriana / John, Nevin / Doshi, Anisha / Beveridge, Judy / Braisher, Marie / Gray, Emma / Chataway, Jeremy

    Trials

    2022  Volume 23, Issue 1, Page(s) 644

    Abstract: Background: Slower than planned recruitment is a major factor contributing to the delay or failure of randomised controlled trials to report on time. There is a limited evidence base regarding the optimisation of recruitment strategies. Here we ... ...

    Abstract Background: Slower than planned recruitment is a major factor contributing to the delay or failure of randomised controlled trials to report on time. There is a limited evidence base regarding the optimisation of recruitment strategies. Here we performed an observational review of our experience in recruitment for two large randomised controlled trials for people with secondary progressive multiple sclerosis. We aimed to explicitly determine those factors which can facilitate trial recruitment in progressive neurodegenerative disease.
    Methods: Recruitment data from the sequential MS-SMART [NCT01910259] and MS-STAT2 [NCT03387670] UK randomised controlled trials was reviewed from the largest recruiting site, University College London (UCL). The trial population was similar which allowed comparison over the two recruitment periods of 2015-2016 and 2018-2021. This included sources of referral, progress through stages of recruitment, reasons for participant ineligibility and the impact of publicity events upon recruitment.
    Results: In MS-SMART, 18% of patients contacted were enrolled, compared to 27% for MS-STAT2. Online registration of interest portals provided the greatest number of referrals (76% in MS-SMART, and 51% in MS-STAT2), with publicity in national media outlets producing a demonstrable increase in the number of potential participants. The introduction of an online self-screening questionnaire for MS-STAT2 resulted in 67% of potential participants (3080 of 4605) automatically determining their own ineligibility. In both studies, however, around 60% of those directly telephoned to discuss the study were not eligible, with difficulties related to travel to trial visits, or excluded medication, being the most common issues. Eighty-four percent of those deemed potentially eligible following telephone calls were enrolled in the MS-STAT2 study, compared to only 55% for MS-SMART.
    Conclusions: Through a detailed review of recruiting participants at the largest centre into two large randomised controlled trials with similar entry criteria, we have identified a number of approaches that may improve recruitment efficiency. We highlight here the importance of mandatory online self-screening questionnaires, a coordinated publicity campaign, and simple interventions such as eligibility checklists and appointment reminders. Recruitment approaches should be further assessed through a studies within a trial (SWAT) design.
    Trial registration: MS-SMART: NCT01910259

    registered July 2013 and MS-STAT2: NCT03387670

    registered Jan 2018.
    MeSH term(s) Humans ; London ; Multiple Sclerosis/diagnosis ; Multiple Sclerosis/drug therapy ; Multiple Sclerosis, Chronic Progressive/diagnosis ; Multiple Sclerosis, Chronic Progressive/drug therapy ; Neurodegenerative Diseases ; Randomized Controlled Trials as Topic ; STAT2 Transcription Factor ; Telephone
    Chemical Substances STAT2 Transcription Factor ; STAT2 protein, human
    Language English
    Publishing date 2022-08-09
    Publishing country England
    Document type Journal Article
    ZDB-ID 2040523-6
    ISSN 1745-6215 ; 1468-6694 ; 1745-6215
    ISSN (online) 1745-6215
    ISSN 1468-6694 ; 1745-6215
    DOI 10.1186/s13063-022-06588-z
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  6. Article: Dimethyl fumarate may still have a role in progressive multiple sclerosis.

    Plantone, Domenico / De Angelis, Floriana / Doshi, Anisha / Chataway, Jeremy

    Therapeutic advances in neurological disorders

    2016  Volume 9, Issue 4, Page(s) 344–345

    Language English
    Publishing date 2016-04-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 2442245-9
    ISSN 1756-2864 ; 1756-2856
    ISSN (online) 1756-2864
    ISSN 1756-2856
    DOI 10.1177/1756285616640396
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  7. Article ; Online: Secondary Progressive Multiple Sclerosis: Definition and Measurement.

    Plantone, Domenico / De Angelis, Floriana / Doshi, Anisha / Chataway, Jeremy

    CNS drugs

    2016  Volume 30, Issue 6, Page(s) 517–526

    Abstract: Secondary progressive multiple sclerosis (SPMS) is diagnosed retrospectively and involves a clinical course characterized by a progressive accumulation of neurological disability, independent of relapses, following an initial relapsing-remitting (RR) ... ...

    Abstract Secondary progressive multiple sclerosis (SPMS) is diagnosed retrospectively and involves a clinical course characterized by a progressive accumulation of neurological disability, independent of relapses, following an initial relapsing-remitting (RR) phase. Our incomplete understanding of the pathological mechanisms underlying neurodegeneration in multiple sclerosis (MS) may explain why, to date, there is no definitive imaging or laboratory test that is able to inform us when the disease is clearly entering into a progressive phase and why the vast majority of clinical trials testing immunosuppressant and immunomodulating drugs in SPMS patients has so far yielded disappointing or mixed results. Here we discuss the definition(s) of SPMS and how it may vary, outcome measurements (current and emerging) and modern trial design.
    MeSH term(s) Disease Progression ; Humans ; Immunosuppressive Agents/administration & dosage ; Immunosuppressive Agents/therapeutic use ; Multiple Sclerosis/diagnosis ; Multiple Sclerosis/drug therapy ; Recurrence ; Retrospective Studies ; Treatment Outcome
    Chemical Substances Immunosuppressive Agents
    Language English
    Publishing date 2016
    Publishing country New Zealand
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1203800-3
    ISSN 1179-1934 ; 1172-7047
    ISSN (online) 1179-1934
    ISSN 1172-7047
    DOI 10.1007/s40263-016-0340-9
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  8. Article ; Online: Association of Slowly Expanding Lesions on MRI With Disability in People With Secondary Progressive Multiple Sclerosis.

    Calvi, Alberto / Carrasco, Ferran Prados / Tur, Carmen / Chard, Declan T / Stutters, Jonathan / De Angelis, Floriana / John, Nevin / Williams, Thomas / Doshi, Anisha / Samson, Rebecca S / MacManus, David / Gandini Wheeler-Kingshott, Claudia A / Ciccarelli, Olga / Chataway, Jeremy / Barkhof, Frederik

    Neurology

    2022  Volume 98, Issue 17, Page(s) e1783–e1793

    Abstract: Background and objective: To explore the relationship between slowly expanding lesions (SELs) on MRI and disability in secondary progressive multiple sclerosis (SPMS).: Methods: We retrospectively studied 345 patients with SPMS enrolled in the MS- ... ...

    Abstract Background and objective: To explore the relationship between slowly expanding lesions (SELs) on MRI and disability in secondary progressive multiple sclerosis (SPMS).
    Methods: We retrospectively studied 345 patients with SPMS enrolled in the MS-SMART trial. They underwent brain MRI at baseline and at 24 and 96 weeks. Definite SELs were defined as concentrically expanding T2 lesions, as assessed by nonlinear deformation of volumetric T1-weighted images. Associations of SEL volumes with other MRI metrics and disability were assessed through Pearson correlations and regression analyses.
    Results: Averaged across patients, 29% of T2 lesions were classified as being definite SELs. A greater volume of definite SELs correlated with a higher total baseline T2 lesion volume (
    Discussion: Definite SELs represent almost one-third of T2 lesions in SPMS. They are associated with neurodegenerative MRI markers and related to clinical worsening, suggesting that they may contribute to disease progression and be a new target for therapeutic interventions.
    MeSH term(s) Brain/pathology ; Humans ; Magnetic Resonance Imaging/methods ; Multiple Sclerosis ; Multiple Sclerosis, Chronic Progressive/complications ; Multiple Sclerosis, Chronic Progressive/diagnostic imaging ; Multiple Sclerosis, Chronic Progressive/drug therapy ; Retrospective Studies
    Language English
    Publishing date 2022-03-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 207147-2
    ISSN 1526-632X ; 0028-3878
    ISSN (online) 1526-632X
    ISSN 0028-3878
    DOI 10.1212/WNL.0000000000200144
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    Zs.MG 18: Show issues
    Zs.MO 374: Show issues

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  9. Article ; Online: Just a graze? Cephalic tetanus presenting as a stroke mimic.

    Doshi, Anisha / Warrell, Clare / Dahdaleh, Dima / Kullmann, Dimitri

    Practical neurology

    2013  Volume 14, Issue 1, Page(s) 39–41

    MeSH term(s) Aged ; Diagnosis, Differential ; Female ; Humans ; Stroke/diagnosis ; Tetanus/diagnosis ; Tetanus/physiopathology
    Language English
    Publishing date 2013-09-19
    Publishing country England
    Document type Case Reports ; Journal Article
    ZDB-ID 2170881-2
    ISSN 1474-7766 ; 1474-7758
    ISSN (online) 1474-7766
    ISSN 1474-7758
    DOI 10.1136/practneurol-2013-000541
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  10. Article ; Online: Longitudinal Metabolite Changes in Progressive Multiple Sclerosis: A Study of 3 Potential Neuroprotective Treatments.

    John, Nevin A / Solanky, Bhavana S / De Angelis, Floriana / Parker, Richard A / Weir, Christopher J / Stutters, Jonathan / Carrasco, Ferran Prados / Schneider, Torben / Doshi, Anisha / Calvi, Alberto / Williams, Thomas / Plantone, Domenico / Monteverdi, Anita / MacManus, David / Marshall, Ian / Barkhof, Frederik / Gandini Wheeler-Kingshott, Claudia A M / Chataway, Jeremy

    Journal of magnetic resonance imaging : JMRI

    2023  Volume 59, Issue 6, Page(s) 2192–2201

    Abstract: Background: 1: Purpose: To assess the effect on neurometabolites from three candidate drugs after 96-weeks as seen by : Study-type: Longitudinal.: Population: 108 participants with SPMS randomized to receive neuroprotective drugs amiloride [ ... ...

    Abstract Background: 1
    Purpose: To assess the effect on neurometabolites from three candidate drugs after 96-weeks as seen by
    Study-type: Longitudinal.
    Population: 108 participants with SPMS randomized to receive neuroprotective drugs amiloride [mean age 55.4 (SD 7.4), 61% female], fluoxetine [55.6 (6.6), 71%], riluzole [54.6 (6.3), 68%], or placebo [54.8 (7.9), 67%].
    Field strength/sequence: 3-Tesla. Chemical-shift-imaging 2D-point-resolved-spectroscopy (PRESS), 3DT1.
    Assessment: Brain metabolites in normal appearing white matter (NAWM) and gray matter (GM), brain volume, lesion load, nine-hole peg test (9HPT), and paced auditory serial addition test were measured at baseline and at 96-weeks.
    Statistical tests: Paired t-test was used to analyze metabolite changes in the placebo arm over 96-weeks. Metabolite differences between treatment arms and placebo; and associations between baseline metabolites and upper limb function/information processing speed at 96-weeks assessed using multiple linear regression models. P-value<0.05 was considered statistically significant.
    Results: In the placebo arm, tCho increased in GM (mean difference = -0.32 IU) but decreased in NAWM (mean difference = 0.13 IU). Compared to placebo, in the fluoxetine arm, mIns/tCr was lower (β = -0.21); in the riluzole arm, GM Glx (β = -0.25) and Glx/tCr (β = -0.29) were reduced. Baseline tNAA(β = 0.22) and tNAA/tCr (β = 0.23) in NAWM were associated with 9HPT scores at 96-weeks.
    Data conclusion: 1
    Level of evidence: 1 TECHNICAL EFFICACY: Stage 4.
    MeSH term(s) Humans ; Female ; Male ; Middle Aged ; Neuroprotective Agents ; Longitudinal Studies ; Multiple Sclerosis, Chronic Progressive/diagnostic imaging ; Multiple Sclerosis, Chronic Progressive/drug therapy ; Multiple Sclerosis, Chronic Progressive/metabolism ; Riluzole ; Adult ; Fluoxetine ; Brain/diagnostic imaging ; Brain/metabolism ; Inositol/metabolism ; Creatine/metabolism ; Aspartic Acid/analogs & derivatives ; Aspartic Acid/metabolism ; Choline/metabolism ; Magnetic Resonance Spectroscopy ; Proton Magnetic Resonance Spectroscopy ; Glutamine/metabolism ; Glutamic Acid/metabolism ; Magnetic Resonance Imaging/methods ; Gray Matter/diagnostic imaging ; Gray Matter/metabolism
    Chemical Substances Neuroprotective Agents ; Riluzole (7LJ087RS6F) ; Fluoxetine (01K63SUP8D) ; Inositol (4L6452S749) ; Creatine (MU72812GK0) ; Aspartic Acid (30KYC7MIAI) ; Choline (N91BDP6H0X) ; N-acetylaspartate (997-55-7) ; Glutamine (0RH81L854J) ; Glutamic Acid (3KX376GY7L)
    Language English
    Publishing date 2023-10-03
    Publishing country United States
    Document type Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 1146614-5
    ISSN 1522-2586 ; 1053-1807
    ISSN (online) 1522-2586
    ISSN 1053-1807
    DOI 10.1002/jmri.29017
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