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