Smouldering multiple sclerosis: the "real MS"

Publikation: Bidrag til tidsskriftReviewForskningfagfællebedømt


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

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.

TidsskriftTherapeutic Advances in Neurological Disorders
Antal sider18
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Sanofi Genzyme kindly provided financial support to help adapt and design the figures and for a third party to help coordinate the submission of the manuscript.

Publisher Copyright:
© The Author(s), 2022.

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