Abstract

Multiple sclerosis is a chronic autoimmune disease of the central nervous system that results in varying degrees of disability. Progressive multiple sclerosis, characterized by a steady increase in neurological disability independently of relapses, can occur from onset (primary progressive) or after a relapsing–remitting course (secondary progressive). As opposed to active inflammation seen in the relapsing–remitting phases of the disease, the gradual worsening of disability in progressive multiple sclerosis results from complex immune mechanisms and neurodegeneration. A few anti-inflammatory disease-modifying therapies with a modest but significant effect on measures of disease progression have been approved for the treatment of progressive multiple sclerosis. The treatment effect of anti-inflammatory agents is particularly observed in the subgroup of patients with younger age and evidence of disease activity. For this reason, a significant effort is underway to develop molecules with the potential to induce myelin repair or halt the degenerative process. Appropriate trial methodology and the development of clinically meaningful disability outcome measures along with imaging and biological biomarkers of progression have a significant impact on the ability to measure the efficacy of potential medications that may reverse disease progression. In this issue, we will review current evidence on the physiopathology, diagnosis, measurement of disability, and treatment of progressive multiple sclerosis.

Highlights

  • Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that affects over 2.3 million people globally, with an estimated prevalence of approximately 310 per100,000 population in the United States [1,2]

  • Approved disease-modifying therapies (DMTs) target the inflammatory component of the disease, and strong evidence support their effectiveness in Relapsing–remitting MS (RRMS)

  • The goal of this review is to provide a comprehensive overview on the current knowledge of the pathogenesis, diagnosis, and treatment of progressive MS, as well as future directions in the field

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Summary

Introduction

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that affects over 2.3 million people globally, with an estimated prevalence of approximately 310 per. Most patients (~90%) have relapsing–remitting disease at onset, which typically is followed by a secondary progressive course, while a minority of patients have a primary progressive course from onset (~10%). Relapsing–remitting MS (RRMS) is characterized by frequent formation of inflammatory lesions in the brain and spinal cord. Approved disease-modifying therapies (DMTs) target the inflammatory component of the disease, and strong evidence support their effectiveness in RRMS. Trials evaluating their efficacy in slowing disease progression have shown mixed results, or have shown only modest effects in slowing progression. The goal of this review is to provide a comprehensive overview on the current knowledge of the pathogenesis, diagnosis, and treatment of progressive MS, as well as future directions in the field

Pathogenesis
Diagnostic Criteria and Disease Course Definitions
Disability Outcome Measures
Measuring Disease Progression
Approved Therapies
Therapies with Negative or Weak Effect in Progressive MS
Remyelination and Neuroprotection in Progressive MS
Results
Symptomatic Management
Challenges in Progressive MS Treatment and Research
Conclusions
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