eprintid: 10072582
rev_number: 35
eprint_status: archive
userid: 608
dir: disk0/10/07/25/82
datestamp: 2019-04-24 07:06:13
lastmod: 2021-09-17 22:08:41
status_changed: 2019-09-16 09:10:35
type: article
metadata_visibility: show
creators_name: Brownlee, WJ
creators_name: Altmann, DR
creators_name: Prados Carrasco, F
creators_name: Miszkiel, KA
creators_name: Eshaghi, A
creators_name: Wheeler-Kingshott, C
creators_name: Barkhof, F
creators_name: Ciccarelli, O
title: Early imaging predictors of long-term outcomes in relapse-onset multiple sclerosis
ispublished: pub
subjects: UCH
divisions: UCL
divisions: B02
divisions: C07
divisions: D07
divisions: F82
divisions: F87
divisions: B04
divisions: C05
divisions: F42
keywords: multiple sclerosis, clinically isolated syndrome, prognosis, magnetic resonance imaging
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
abstract: The clinical course of relapse-onset multiple sclerosis is highly variable. Demographic factors, clinical features and global brain T2 lesion load have limited value in counselling individual patients. We investigated early MRI predictors of key long-term outcomes including secondary progressive multiple sclerosis, physical disability and cognitive performance, 15 years after a clinically isolated syndrome. A cohort of patients with clinically isolated syndrome (n = 178) was prospectively recruited within 3 months of clinical disease onset and studied with MRI scans of the brain and spinal cord at study entry (baseline) and after 1 and 3 years. MRI measures at each time point included: supratentorial, infratentorial, spinal cord and gadolinium-enhancing lesion number, brain and spinal cord volumetric measures. The patients were followed-up clinically after ∼15 years to determine disease course, and disability was assessed using the Expanded Disability Status Scale, Paced Auditory Serial Addition Test and Symbol Digit Modalities Test. Multivariable logistic regression and multivariable linear regression models identified independent MRI predictors of secondary progressive multiple sclerosis and Expanded Disability Status Scale, Paced Auditory Serial Addition Test and Symbol Digit Modalities Test, respectively. After 15 years, 166 (93%) patients were assessed clinically: 119 (72%) had multiple sclerosis [94 (57%) relapsing-remitting, 25 (15%) secondary progressive], 45 (27%) remained clinically isolated syndrome and two (1%) developed other disorders. Physical disability was overall low in the multiple sclerosis patients (median Expanded Disability Status Scale 2, range 0–10); 71% were untreated. Baseline gadolinium-enhancing (odds ratio 3.16, P < 0.01) and spinal cord lesions (odds ratio 4.71, P < 0.01) were independently associated with secondary progressive multiple sclerosis at 15 years. When considering 1- and 3-year MRI variables, baseline gadolinium-enhancing lesions remained significant and new spinal cord lesions over time were associated with secondary progressive multiple sclerosis. Baseline gadolinium-enhancing (β = 1.32, P < 0.01) and spinal cord lesions (β = 1.53, P < 0.01) showed a consistent association with Expanded Disability Status Scale at 15 years. Baseline gadolinium-enhancing lesions was also associated with performance on the Paced Auditory Serial Addition Test (β = − 0.79, P < 0.01) and Symbol Digit Modalities Test (β = −0.70, P = 0.02) at 15 years. Our findings suggest that early focal inflammatory disease activity and spinal cord lesions are predictors of very long-term disease outcomes in relapse-onset multiple sclerosis. Established MRI measures, available in routine clinical practice, may be useful in counselling patients with early multiple sclerosis about long-term prognosis, and personalizing treatment plans.
date: 2019-08
date_type: published
publisher: Oxford University Press (OUP)
official_url: https://doi.org/10.1093/brain/awz156
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1649677
doi: 10.1093/brain/awz156
lyricists_name: Barkhof, Frederik
lyricists_name: Brownlee, Wallace
lyricists_name: Ciccarelli, Olga
lyricists_name: Eshaghi, Arman
lyricists_name: Prados Carrasco, Ferran
lyricists_name: Wheeler-Kingshott, Claudia
lyricists_id: FBARK32
lyricists_id: WBROW41
lyricists_id: OCICC52
lyricists_id: AESHA15
lyricists_id: FPRAD65
lyricists_id: CWHEE14
actors_name: Novi, Maya
actors_id: MNOVI52
actors_role: owner
full_text_status: public
publication: Brain
volume: 142
number: 8
pagerange: 2276-2287
issn: 0006-8950
citation:        Brownlee, WJ;    Altmann, DR;    Prados Carrasco, F;    Miszkiel, KA;    Eshaghi, A;    Wheeler-Kingshott, C;    Barkhof, F;           Brownlee, WJ;  Altmann, DR;  Prados Carrasco, F;  Miszkiel, KA;  Eshaghi, A;  Wheeler-Kingshott, C;  Barkhof, F;  Ciccarelli, O;   - view fewer <#>    (2019)    Early imaging predictors of long-term outcomes in relapse-onset multiple sclerosis.                   Brain , 142  (8)   pp. 2276-2287.    10.1093/brain/awz156 <https://doi.org/10.1093/brain%2Fawz156>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10072582/3/Brownlee_CIS_Predictors%20of%20long%20term%20outcomes_Revision%201_Final_Clean%20copy.pdf