TY - JOUR
T1 - Multiple sclerosis progression
T2 - time for a new mechanism-driven framework
AU - International Advisory Committee on Clinical Trials in Multiple Sclerosis
AU - Kuhlmann, Tanja
AU - Moccia, Marcello
AU - Coetzee, Timothy
AU - Cohen, Jeffrey A.
AU - Correale, Jorge
AU - Graves, Jennifer
AU - Marrie, Ruth Ann
AU - Montalban, Xavier
AU - Yong, V. Wee
AU - Thompson, Alan J.
AU - Reich, Daniel S.
AU - Amato, Maria Pia
AU - Banwell, Brenda
AU - Barkhof, Frederik
AU - Chataway, Jeremy
AU - Chitnis, Tanuja
AU - Comi, Giancarlo
AU - Derfuss, Tobias
AU - Finlayson, Marcia
AU - Goldman, Myla
AU - Green, Ari
AU - Hellwig, Kerstin
AU - Kos, Daphne
AU - Miller, Aaron
AU - Mowry, Ellen
AU - Oh, Jiwon
AU - Salter, Amber
AU - Sormani, Maria Pia
AU - Tintore, Mar
AU - Tremlett, Helen
AU - Trojano, Maria
AU - van der Walt, Anneke
AU - Vukusic, Sandra
AU - Waubant, Emmaunelle
N1 - Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/1
Y1 - 2023/1
N2 - Traditionally, multiple sclerosis has been categorised by distinct clinical descriptors—relapsing-remitting, secondary progressive, and primary progressive—for patient care, research, and regulatory approval of medications. Accumulating evidence suggests that the clinical course of multiple sclerosis is better considered as a continuum, with contributions from concurrent pathophysiological processes that vary across individuals and over time. The apparent evolution to a progressive course reflects a partial shift from predominantly localised acute injury to widespread inflammation and neurodegeneration, coupled with failure of compensatory mechanisms, such as neuroplasticity and remyelination. Ageing increases neural susceptibility to injury and decreases resilience. These observations encourage a new consideration of the course of multiple sclerosis as a spectrum defined by the relative contributions of overlapping pathological and reparative or compensatory processes. New understanding of key mechanisms underlying progression and measures to quantify progressive pathology will potentially have important and beneficial implications for clinical care, treatment targets, and regulatory decision-making.
AB - Traditionally, multiple sclerosis has been categorised by distinct clinical descriptors—relapsing-remitting, secondary progressive, and primary progressive—for patient care, research, and regulatory approval of medications. Accumulating evidence suggests that the clinical course of multiple sclerosis is better considered as a continuum, with contributions from concurrent pathophysiological processes that vary across individuals and over time. The apparent evolution to a progressive course reflects a partial shift from predominantly localised acute injury to widespread inflammation and neurodegeneration, coupled with failure of compensatory mechanisms, such as neuroplasticity and remyelination. Ageing increases neural susceptibility to injury and decreases resilience. These observations encourage a new consideration of the course of multiple sclerosis as a spectrum defined by the relative contributions of overlapping pathological and reparative or compensatory processes. New understanding of key mechanisms underlying progression and measures to quantify progressive pathology will potentially have important and beneficial implications for clinical care, treatment targets, and regulatory decision-making.
UR - http://www.scopus.com/inward/record.url?scp=85143859963&partnerID=8YFLogxK
U2 - 10.1016/S1474-4422(22)00289-7
DO - 10.1016/S1474-4422(22)00289-7
M3 - Review article
C2 - 36410373
AN - SCOPUS:85143859963
SN - 1474-4422
VL - 22
SP - 78
EP - 88
JO - The Lancet Neurology
JF - The Lancet Neurology
IS - 1
ER -