Evidence map›Paper›PMID 34732831›Full record

ReviewNature reviews. Neurology2022

Mechanism-based criteria to improve therapeutic outcomes in progressive multiple sclerosis.

Heather Y F Yong, V Wee Yong

Abstract readReview
PubMed Publisher
In one paragraph

Review in Nature reviews. Neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 2 pooled it
17.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

69 citing papers in PubMed, 2 syntheses or guidelines pooled it, 151 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Immune-mediated excitotoxicity in brain disorders.Nature reviews. Immunology · 2026
    Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Investigations of remibrutinib in models pertinent to multiple sclerosis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Bruton Tyrosine Kinase in Lesions of Multiple Sclerosis and 3 of Its Models.Neurology(R) neuroimmunology & neuroinflammation · 2025
    Article

9 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Heather Y F YongHotchkiss Brain Institute and the Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
V Wee YongHotchkiss Brain Institute and the Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. vyong@ucalgary.ca.ORCID http://orcid.org/0000-0002-2600-3563
University of Calgary · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In contrast to the multiple disease-modifying therapies that are available for relapsing-remitting multiple sclerosis (MS), the therapeutic options for progressive MS (PMS) are limited. Recent advances in our understanding of the neuroimmunology of PMS, including the mechanisms that drive slowly expanding lesions, have fuelled optimism for improved treatment of this condition. In this Review, we highlight the commonly observed neuropathology of PMS and discuss the associated mechanisms of CNS injury. We then apply this knowledge to formulate criteria for therapeutic efficacy in PMS, beginning with the need for early treatment owing to the substantial neuropathology that is already present at the initial clinical presentation. Other requirements include: antagonism of neuroaxonal injury mediators such as pro-inflammatory microglia and lymphocytes; remediation of oxidative stress resulting from iron deposition and mitochondrial dysfunction; and promotion of neuroprotection through remyelination. We consider whether current disease-modifying therapies for relapsing-remitting MS meet the criteria for successful therapeutics in PMS and suggest that the evidence favours the early introduction of sphingosine 1-phosphate receptor modulators. Finally, we weigh up emerging medications, including repurposed generic medications and Bruton's tyrosine kinase inhibitors, against these fundamental criteria. In this new therapeutic era in PMS, success depends collectively on understanding disease mechanisms, drug characteristics (including brain penetration) and rational use.

Indexed as

AnimalsHumansImmunosuppressive AgentsImmunotherapyMultiple Sclerosis, Chronic ProgressiveMultiple Sclerosis, Relapsing-RemittingTreatment OutcomeImmunosuppressive Agents

Identifiers

PMID34732831
OpenAlexW3208672684

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.