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Title: Smouldering multiple sclerosis: the 'real MS'
Authors: Giovannoni, Gavin
Popescu, Veronica
Wuerfel, Jens
Hellwig, Kerstin
Iacobaeus, Ellen
Jensen, Michael B
García-Domínguez, José Manuel
Sousa, Lívia 
De Rossi, Nicola
Hupperts, Raymond
Fenu, Giuseppe
Bodini, Benedetta
Kuusisto, Hanna-Maija
Stankoff, Bruno
Lycke, Jan
Airas, Laura
Granziera, Cristina
Scalfari, Antonio
Keywords: multiple sclerosis; smouldering multiple sclerosis; progression independent of relapse activity; progressive multiple sclerosis
Issue Date: 2022
Publisher: SAGE Publications Ltd
Project: Sanofi Genzyme 
Serial title, monograph or event: Therapeutic Advances in Neurological Disorders
Volume: 15
Abstract: Using a philosophical approach or deductive reasoning, we challenge the dominant clinico-radiological worldview that defines multiple sclerosis (MS) as a focal inflammatory disease of the central nervous system (CNS). We provide a range of evidence to argue that the 'real MS' is in fact driven primarily by a smouldering pathological disease process. In natural history studies and clinical trials, relapses and focal activity revealed by magnetic resonance imaging (MRI) in MS patients on placebo or on disease-modifying therapies (DMTs) were found to be poor predictors of long-term disease evolution and were dissociated from disability outcomes. In addition, the progressive accumulation of disability in MS can occur independently of relapse activity from early in the disease course. This scenario is underpinned by a more diffuse smouldering pathological process that may affect the entire CNS. Many putative pathological drivers of smouldering MS can be potentially modified by specific therapeutic strategies, an approach that may have major implications for the management of MS patients. We hypothesise that therapeutically targeting a state of 'no evident inflammatory disease activity' (NEIDA) cannot sufficiently prevent disability accumulation in MS, meaning that treatment should also focus on other brain and spinal cord pathological processes contributing to the slow loss of neurological function. This should also be complemented with a holistic approach to the management of other systemic disease processes that have been shown to worsen MS outcomes.
ISSN: 1756-2856
DOI: 10.1177/17562864211066751
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais

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