ReviewNeurology. Clinical practice2021
Multiple Sclerosis Phenotypes as a Continuum: The Role of Neurologic Reserve.
Review in Neurology. Clinical practice, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled 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.
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.
Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- Disease activity in primary progressive multiple sclerosis: a systematic review and meta-analysis.Frontiers in neurology · 2023Pooled it
- Effects of cognitive rehabilitation and exercise on brain structure in progressive multiple sclerosis: results from the CogEx trial.Journal of neurology · 2025Trial
- Multiple Sclerosis and Viruses: « Liaisons Dangereuses ».Reviews in medical virology · 2026Review
- Clinical trials in non-ambulatory people with progressive multiple sclerosis: can the nine hole peg test step up as primary outcome measure?Journal of neurology · 2026Article
- Rethinking prognosis in multiple sclerosis: a multiaxial perspective.Nature reviews. Neurology · 2026Review
- Infectious Agents in Multiple Sclerosis: Viral Triggers, Antibody-Mediated Autoimmunity, and Parasitic Immunomodulation.Biomolecules · 2026Review
- Smoking, Comorbidities, and Low Sun Exposure Are Associated with Clinical and Radiological Outcomes in Patients with Multiple Sclerosis-A Four-Year Observational Cohort Study.Journal of clinical medicine · 2026Article
- Deep learning-based neuroanatomical profiling reveals population-specific brain changes in multiple sclerosis: a large-scale Middle Eastern study.BMC medical imaging · 2026Observational
- From Phenotypes to Spectrum: Rethinking RRMS, SPMS and PPMS in the Era of PIRA-A Framework Integrating PIRA, Smouldering-Associated Worsening, and Neurologic Reserve to Facilitate Earlier Recognition of Progression.Neurology international · 2026Review
- Patient-reported gradual worsening reveals progression beyond MS subtypes.Journal of neurology · 2026Article
- Advancing Care in Myasthenia Gravis: What Can We Learn From the Multiple Sclerosis Community?Neurology and therapy · 2026Article
- Autologous haematopoietic stem cell transplantation affects long-term progression independent of relapse activity in aggressive multiple sclerosis: a comparative matched study.Journal of neurology, neurosurgery, and psychiatry · 2026Article
- Multiple sclerosis as an asynchronous neuroinflammatory system.Frontiers in immunology · 2026Review
- Assisted Reproduction Therapy in Patients with Multiple Sclerosis: Narrative Review and Practical Recommendations.Healthcare (Basel, Switzerland) · 2025Review
- Does Vitamin D Supplementation Slow Brain Volume Loss in Multiple Sclerosis? A 4-Year Observational Study.Nutrients · 2025Observational
- Multiple Sclerosis After the Age of 50 Years: A Comparative Analysis of Late Onset and Adult Onset.Journal of clinical neurology (Seoul, Korea) · 2025Article
- Healthcare use is elevated two decades before a first demyelinating event and differs by age and sex.Annals of clinical and translational neurology · 2025Article
- Multifaceted Biomarkers Suggest a Similar Profile of CNS Pathology in Relapsing and Progressive MS.European journal of neurology · 2025Article
- MRI versus relapse: optimal activity monitoring for management of progressive multiple sclerosis.Brain communications · 2025Article
- Depicting multiple sclerosis disease course using lesion parenchymal fraction: a quantified expression of the topographical model of multiple sclerosis.Brain communications · 2025Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purpose of reviewThis review presents the hypothesis that loss of neurologic reserve explains onset of progressive multiple sclerosis (PrMS). RECENT
findingsEvidence supporting the separate classification of PrMS and relapsing multiple sclerosis (RMS) is limited and does not explain PrMS or the response of these patients to therapy. SUMMARY: We argue that multiple sclerosis (MS) progresses along a continuum from RMS to PrMS, with differing levels of neurologic reserve accounting for phenotypic differences. In early MS, inflammation causes brain atrophy with symptoms buffered by neurologic reserve. As brain loss from normal aging and MS continues, reserve is depleted and effects of subclinical MS disease activity and aging are unmasked, manifesting as PrMS. Most therapies show limited benefit in PrMS; patients are older, have fewer inflammatory events, and the effects of aging cause continued loss of neurologic function, even if inflammation is terminated. Loss of neurologic reserve means patients with PrMS cannot recover function, unlike patients with RMS.
Identifiers
What OpenQuestion holds
Registered trials
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.