Antonio Scalfari1, Chiara Romualdi1, Richard S Nicholas1, Miriam Mattoscio1, Roberta Magliozzi1, Aldo Morra1, Salvatore Monaco1, Paolo A Muraro1, Massimiliano Calabrese2. 1. From the Division of Neuroscience (A.S., R.S.N., M.M., P.M.), Imperial College, London, UK; Biology Department (C.R.), University of Padua; Department of Neurological, Biomedicine and Movement Sciences (R.M., S.M., M.C.), University of Verona; and Neuroradiology Unit (A.M.), Euganea Medica, Padua, Italy. 2. From the Division of Neuroscience (A.S., R.S.N., M.M., P.M.), Imperial College, London, UK; Biology Department (C.R.), University of Padua; Department of Neurological, Biomedicine and Movement Sciences (R.M., S.M., M.C.), University of Verona; and Neuroradiology Unit (A.M.), Euganea Medica, Padua, Italy. calabresem@hotmail.it.
Abstract
OBJECTIVE: To investigate the relationship among cortical radiologic changes, the number of early relapses (ERs), and the long-term course of multiple sclerosis (MS). METHODS: In this cohort study, we assessed the number of cortical lesions (CLs) and white matter (WM) lesions and the cortical thickness (Cth) at clinical onset and after 7.9 mean years among 219 patients with relapsing remitting (RR) MS with 1 (Low-ER), 2 (Mid-ER), and ≥3 (High-ER) ERs during the first 2 years. Kaplan-Meier and Cox regression analyses investigated early factors influencing the risk of secondary progressive (SP) MS. RESULTS: Fifty-nine patients (27%) converted to SPMS in 6.1 mean years. A larger number of CLs at onset predicted a higher risk of SPMS (hazard ratio [HR] 2.16, 4.79, and 12.3 for 2, 5, and 7 CLs, respectively, p < 0.001) and shorter latency to progression. The High-ER compared to the Low-ER and Mid-ER groups had a larger volume of WM lesions and CLs at onset, accrued more CLs, experienced more severe cortical atrophy over time, and entered the SP phase more rapidly. In the multivariate model, older age at onset (HR 1.97, p < 0.001), a larger baseline CL (HR 2.21, p = 0.005) and WM lesion (HR 1.32, p = 0.03) volume, early changes of global Cth (HR 1.36, p = 0.03), and ≥3 ERs (HR 6.08, p < 0.001) independently predicted a higher probability of SP. CONCLUSIONS: Extensive cortical damage at onset is associated with florid inflammatory clinical activity and predisposes to a rapid occurrence of the progressive phase. Age at onset, the number of early attacks, and the extent of baseline focal cortical damage can identify groups at high risk of progression who may benefit from more active therapy.
OBJECTIVE: To investigate the relationship among cortical radiologic changes, the number of early relapses (ERs), and the long-term course of multiple sclerosis (MS). METHODS: In this cohort study, we assessed the number of cortical lesions (CLs) and white matter (WM) lesions and the cortical thickness (Cth) at clinical onset and after 7.9 mean years among 219 patients with relapsing remitting (RR) MS with 1 (Low-ER), 2 (Mid-ER), and ≥3 (High-ER) ERs during the first 2 years. Kaplan-Meier and Cox regression analyses investigated early factors influencing the risk of secondary progressive (SP) MS. RESULTS: Fifty-nine patients (27%) converted to SPMS in 6.1 mean years. A larger number of CLs at onset predicted a higher risk of SPMS (hazard ratio [HR] 2.16, 4.79, and 12.3 for 2, 5, and 7 CLs, respectively, p < 0.001) and shorter latency to progression. The High-ER compared to the Low-ER and Mid-ER groups had a larger volume of WM lesions and CLs at onset, accrued more CLs, experienced more severe cortical atrophy over time, and entered the SP phase more rapidly. In the multivariate model, older age at onset (HR 1.97, p < 0.001), a larger baseline CL (HR 2.21, p = 0.005) and WM lesion (HR 1.32, p = 0.03) volume, early changes of global Cth (HR 1.36, p = 0.03), and ≥3 ERs (HR 6.08, p < 0.001) independently predicted a higher probability of SP. CONCLUSIONS: Extensive cortical damage at onset is associated with florid inflammatory clinical activity and predisposes to a rapid occurrence of the progressive phase. Age at onset, the number of early attacks, and the extent of baseline focal cortical damage can identify groups at high risk of progression who may benefit from more active therapy.
Authors: Kathrine E Attfield; Lise Torp Jensen; Max Kaufmann; Manuel A Friese; Lars Fugger Journal: Nat Rev Immunol Date: 2022-05-04 Impact factor: 53.106
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Authors: Jiaen Liu; Erin S Beck; Stefano Filippini; Peter van Gelderen; Jacco A de Zwart; Gina Norato; Pascal Sati; Omar Al-Louzi; Hadar Kolb; Maxime Donadieu; Mark Morrison; Jeff H Duyn; Daniel S Reich Journal: Invest Radiol Date: 2021-07-01 Impact factor: 10.065
Authors: Max Kaufmann; Hayley Evans; Anna-Lena Schaupp; Jan Broder Engler; Gurman Kaur; Anne Willing; Nina Kursawe; Charlotte Schubert; Kathrine E Attfield; Lars Fugger; Manuel A Friese Journal: Med (N Y) Date: 2021-03-12
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Authors: Roshni A Desai; Andrew L Davies; Natalie Del Rossi; Mohamed Tachrount; Alex Dyson; Britta Gustavson; Pardis Kaynezhad; Lewis Mackenzie; Marieke A van der Putten; Daniel McElroy; Dimitra Schiza; Christopher Linington; Mervyn Singer; Andrew R Harvey; Ilias Tachtsidis; Xavier Golay; Kenneth J Smith Journal: Ann Neurol Date: 2020-05-06 Impact factor: 10.422