A2 Refereed review article in a scientific journal

Smouldering multiple sclerosis: the 'real MS'




AuthorsGiovannoni Gavin, Popescu Veronica, Wuerfel Jens, Hellwig Kerstin, Iacobeus Ellen, Jensen Michael B., García-Domínguez José Manuel, Sousa Livia, De Rossi Nicola, Hupperts Raymond, Fenu Giuseppe, Bodini Benedetta, Kuusisto Hanna-Maija, Stankoff Bruno, Lycke Jan, Airas Laura, Granziera Cristina, Scalfari Antonio

PublisherSAGE PUBLICATIONS LTD

Publication year2022

JournalTherapeutic Advances in Neurological Disorders

Journal name in sourceTHERAPEUTIC ADVANCES IN NEUROLOGICAL DISORDERS

Journal acronymTHER ADV NEUROL DISO

Article number 17562864211066751

Volume15

Number of pages18

ISSN1756-2856

eISSN1756-2864

DOIhttps://doi.org/10.1177/17562864211066751(external)

Web address https://journals.sagepub.com/doi/10.1177/17562864211066751(external)

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/174780452(external)


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.

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