Smouldering multiple sclerosis: the ‘real MS’

• 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. © The Author(s), 2022.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

multiple sclerosis

progression independent of relapse activity

progressive multiple sclerosis

smouldering multiple sclerosis

alemtuzumab

antioxidant

ascorbic acid

biological marker

Bruton tyrosine kinase

carrier protein

CD68 antigen

deferoxamine

Fc receptor

glutathione

immunoglobulin enhancer binding protein

iron

natalizumab

nitric oxide synthase

ocrelizumab

protein p22

reactive oxygen metabolite

rituximab

thioctic acid

Alzheimer disease

amyotrophic lateral sclerosis

brain atrophy

brain damage

brain size

cellular immunity

central nervous system

clinical outcome

degenerative disease

demyelination

diffusion tensor imaging

disease activity

disease course

disease duration

disease exacerbation

edema

Epstein Barr virus

Expanded Disability Status Scale

gliosis

hematopoietic stem cell transplantation

homeostasis

human

Human endogenous retrovirus

imaging

inflammation

innate immunity

iron chelation

memory B lymphocyte

microglia

myelooptic neuropathy

nerve degeneration

neuroprotection

nuclear magnetic resonance imaging

optic neuritis

oxidative stress

phenotype

positron emission tomography

relapse

Review

rheumatoid arthritis

scoring system

T1 weighted imaging

tissue injury

upregulation

white matter

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)