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Slowly evolving lesions and relation to disability in a SPMS cohort
ECTRIMS Online Library. Calvi A. Oct 12, 2018; 232040
Alberto Calvi
Alberto Calvi
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Abstract: 287

Type: Scientific Session

Abstract Category: Pathology and pathogenesis of MS - MRI and PET

Introduction: Slowly evolving lesions (SELs) have been identified on MRI in longitudinal trials of primary progressive MS (PPMS) through non-linear registration-based analysis techniques.
Objectives: To identify SELs in a cohort of secondary progressive MS (SPMS) patients and explore the relationship between the presence of SELs and physical and cognitive disability.
Methods: At the time of this analysis data were available for 79 out of 176 SPMS patients from the MS-SMART trial (NCT01912059). This cohort underwent brain FLAIR and 3D T1-weighted imaging at baseline, 24 and 96 weeks were studied. “Candidate” SELs showing positive Jacobian expansion were extracted. Within candidates, definite SELs were selected through a sum of their concentricity and constancy scores. Associations between the presence of SELs during the follow-up and disability and cognitive measures at baseline were examined using multiple linear regressions models, correcting for total T2 lesion volume.
Results: Main clinical characteristics of this cohort (presented as mean[SD] or median[range]) were: age 54.2 yrs [7.1] gender 47F: 32M, disease duration 23.3 yrs [9.6], Expanded Disability Status Scale (EDSS) 6 [4.0-6.5], Multiple Sclerosis Functional Composite (MSFC) 0.24 [0.53], Symbol Digit Modalities Test (SDMT) 48 [20-70].
Out of 4756 T2 lesions screened, 1140 lesions were identified as candidates and 140 were classified as SELs (2.9%). In the overall cohort, the ratio of SEL volume to total lesion load was 0.29.
There were 61 SEL-positive patients (77%); the remaining 18 subjects (23%) were SEL-negative. In the SEL-positive group, the median SEL volume per patient was 1.84 mL.
SEL-positive patients showed higher physical disability, as measured by the MSFC score (adjusted difference = -0.42; 95% Confidence Intervals (CI) -0.70, -0.14; p=0.004) and worse cognitive performance, as measured by the SDMT (adjusted difference = -6.04; 95% CI -11.75, -0.32; p=0.04) at baseline than SELs-negative patients. Baseline EDSS did not differ between the two groups.
Conclusions: Patients developing SELs at follow-up are prone to present at baseline with higher physical and cognitive disability. The next steps are to extend this analysis to all trial patients and investigate the association between the development of SELs and progression of disability over time.
Disclosure: Acknowledgements/source of funding
MS-SMART is an investigator led project sponsored by University College London (UCL). This independent research is awarded by the Efficacy and Mechanism Evaluation Programme (EME) and funded by the Medical Research Council (MRC), the UK Multiple Sclerosis Society and the National Multiple Sclerosis Society (US NMSS) and managed by the National Institute for Health Research (NIHR) on behalf of the MRC-NIHR partnership. Additional support comes from the University of Edinburgh; the National Institute for Health Research University College London Hospitals (NIHR-UCLH) Biomedical Research Centre (BRC) and University College London; NIHR Leeds CRF (DenTCRU). CJW and RP were supported in this work by NHS Lothian via the Edinburgh Clinical Trials Unit.
We thank Emeritus Professor David Miller, Lorraine Smith, Marios Yiannakas, Rebecca Samson, Bhavana Solanky, Marcello Moccia, Tim Friede, Michael Hutchinson, Stanley Hawkins, Robert Swingler, John Thorpe, John O'Brien, Patricia Prestage, Allan Walker.
Disclosures: AC, FDA, JS, AD, NJ, DMCM, declare no conflict of interests with respect to this work.
FP receives a Guarantors of Brain fellowship.
CT has received an ECTRIMS Post-doctoral Research Fellowship in 2015. She has also received honoraria and support from travelling from Merck Serono, Sanofi, Roche, TEVA Pharmaceuticals, Novartis, Biogen, Bayer, Ismar Healthcare
OC received research funding from: UK and National MS Societies, Rosetrees trust, NIHR UCLH BRC. She is consultant for Novartis, Roche, and Teva. She is an Associate Editor for Neurology.
FB serves on the editorial boards of Brain, European Radiology, Journal of Neurology, Neurosurgery & Psychiatry, Neurology, Multiple Sclerosis, and Neuroradiology, and serves as consultant for Bayer Shering Pharma, Sanofi-Aventis, Biogen-Idec, TEVA Pharmaceuticals, Genzyme, Merck-Serono, Novartis, Roche, Synthon, Jansen Research, and Lundbeck.
CGKW receives research grants (PI and co-applicant) from Spinal Research, Craig H. Neilsen Foundation, EPSRC, Wings for Life, UK MS Society, Horizon2020, NIHR/MRC.
JC has received support from the Efficacy and Mechanism Evaluation Programme and Health Technology Assessment Programme (NIHR); UK Multiple Sclerosis Society and National Multiple Sclerosis Society. In the last three years, he has been a local principal investigator for trials in multiple sclerosis funded by: Receptos, Novartis and Biogen Idec, and has received an investigator grant from Novartis outside this work. He has taken part in Advisory Boards/consultancy for Roche, Merck, MedDay, Biogen and Celgene.
The MS-SMART investigators are: Queen Square Multiple Sclerosis Centre, University College London Hospitals NHS Foundation Trust, London: Jeremy Chataway, Claudia Gandini Wheeler-Kingshott, Floriana De Angelis, Tiggy Beyene, Vanessa Bassan, Domenico Plantone, Anisha Doshi, Alvin Zapata, Nevin John, Thomas Williams, Marie Braisher, Laura Cecconi; NHS Lothian, Anne Rowling Regenerative Neurology Clinic, Royal Infirmary of Edinburgh, Edinburgh: Siddharthan Chandran; Peter Connick, Dawn Lyle, James Cameron, Daisy Mollison; ECTU: Christopher J Weir, Richard Parker, Moira Ross, Gina Cranswick; Barts and the London, London: Gavin Giovannoni, Sharmilee Gnanapavan; Imperial College, London: Richard Nicholas; Brighton and Sussex University Hospitals: Waqar Rashid, Julia Aram; Leeds General Infirmary, Leeds: Helen Ford; Dental Translational Clinical Research Unit, University of Leeds: Sue Pavitt; Southern General Hospital, Glasgow: James Overell; The Walton Centre, Liverpool: Carolyn Young, Heinke Arndt; The Royal Victoria Infirmary, Newcastle: Martin Duddy, Joe Guadagno; Queens Medical Centre, Nottingham: Nikolaos Evangelou; John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford: Matthew Craner, Jacqueline Palace; Derriford Hospital, Plymouth: Jeremy Hobart; Royal Hallamshire Hospital, Sheffield: Basil Sharrack, David Paling; University Hospital of North Staffordshire, Stoke-on-Trent: Clive Hawkins, Seema Kalra; Royal Cornwall Hospital, Truro: Brendan McLean. Statistics and Epidemiology, Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry: Nigel Stallard. Patient Representative: Roger Bastow.

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