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Neurodegenerative disorders are progressive diseases that cause irreversible damage and loss to neurons in specific brain areas. Examples of these disorders include Parkinson's disease, Alzheimer's disease, Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS). These disorders share characteristics such as proteinopathies, selective neuronal vulnerability, and a complex interplay between genetic and environmental factors. The primary therapeutic goal for these conditions is...
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Updated: Oct 5, 2025

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Smouldering multiple sclerosis: the 'real MS'.

Gavin Giovannoni1, Veronica Popescu2, Jens Wuerfel3

  • 1Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark St., Whitechapel, London E1 2AT, UK.

Therapeutic Advances in Neurological Disorders
|January 31, 2022
PubMed
Summary
This summary is machine-generated.

Multiple sclerosis (MS) may be driven by a smoldering disease process, not just focal inflammation. Current treatments targeting only active inflammation may not prevent long-term disability progression in MS patients.

Keywords:
multiple sclerosisprogression independent of relapse activityprogressive multiple sclerosissmouldering multiple sclerosis

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Area of Science:

  • Neuroimmunology
  • Neuropathology
  • Clinical Neurology

Background:

  • The dominant view defines multiple sclerosis (MS) as a focal inflammatory central nervous system (CNS) disease.
  • This perspective relies heavily on clinico-radiological evidence, including relapses and MRI-detected focal activity.

Purpose of the Study:

  • To challenge the traditional clinico-radiological definition of MS.
  • To propose that MS is primarily driven by a smoldering pathological process.
  • To explore implications for MS management and therapeutic strategies.

Main Methods:

  • Philosophical approach and deductive reasoning.
  • Analysis of evidence from natural history studies and clinical trials.
  • Review of magnetic resonance imaging (MRI) findings and disability outcomes.

Main Results:

  • Relapses and focal MRI activity are poor predictors of long-term MS disease evolution and disability.
  • Progressive disability accumulation in MS can occur independently of relapse activity.
  • A diffuse, smoldering pathological process throughout the CNS may underlie MS progression.

Conclusions:

  • Therapeutic strategies should target the smoldering pathology in MS, not solely evident inflammatory activity.
  • Treatments aiming for 'no evident inflammatory disease activity' (NEIDA) may be insufficient.
  • A holistic approach, including managing systemic factors, is crucial for comprehensive MS care.