The natural history of multiple sclerosis
Open accessAbstract
The course of multiple sclerosis (MS) results from the interplay of two clinical processes, relapses and progression. Three main clinical forms may be identified as relapsing-remitting, secondary progressive and primary progressive. The disease appears on average at the age of 30 and follows a remitting or a progressive course in 85% and 15% of the cases, respectively. Initial symptoms are related to an isolated or combined disturbance(s) of the long tracts of the central nervous system, of the brainstem, or of the optic nerve in 70%, 20% and 25% of the cases, respectively. The relapse rate is one relapse on average every other year. After an exacerbating-remitting onset of MS, secondary progression appears after 19 years on average. The median time to reach the landmarks of irreversible disability are 8 years regarding limitation of ambulation, 20 years for walking with a stick, and 30 years for wheel-chair dependency. In fact, MS prognosis is highly variable depending on individuals. All the intermediate types do exist between malignant forms, possibly lethal, and benign forms (circa 30% of the cases) that allow normal daily life. The clinical and paraclinical predictive factors identified so far have been acknowledged statistically. They provide little help however, if any, when an individual is concerned. Recent research has showed that relapses have only a marginal effect, relatively to progression, on the accumulation of irreversible neurological disability. Furthermore, the age when reaching the landmarks of irreversible disability is essentially similar whatever the mode of onset of MS, be it exacerbating-remitting or progressive. In spite of the outstanding clinical polymorphism of MS, a unifying concept of the disease ("complexity vs heterogeneity") can be put forward.
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The largest single risk factor for MS is biological sex, with >75% of patients being female.
“The largest single risk factor for MS is biological sex, with > 75% of patients being female – but the causes for this discrepancy in incidence are unknown.73”
From Genome‐wide association studies of multiple sclerosis (2018) · cites this paper as [73]
The section “The sex ratio in multiple sclerosis” (page unavailable) confirms female predominance, but reports a usual ratio of two females to one male and says the highest reported female proportion is 71%. That directly contradicts the claim that more than 75% of patients are female; the passage also does not rank sex as the largest single risk factor. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe causes for the female predominance in MS incidence are unknown.
“The largest single risk factor for MS is biological sex, with > 75% of patients being female – but the causes for this discrepancy in incidence are unknown.73”
From Genome‐wide association studies of multiple sclerosis (2018) · cites this paper as [73]
The section ‘The sex ratio in multiple sclerosis’ (page unavailable) confirms female predominance, but reports a usual ratio of two females to one male and a highest reported female proportion of 71%, not >75%. It does not say that the causes of the predominance are unknown. (LLM, conf=0.85)
Experimental — accuracy not yet measuredMS is a remarkably heterogeneous disease, with some patients declining rapidly and others showing few or no symptoms for decades.
“MS is also a remarkably heterogeneous disease, with some patients declining rapidly and others showing few or no symptoms for decades.73”
From Genome‐wide association studies of multiple sclerosis (2018) · cites this paper as [73]
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Huang, Y.-C., Chien, W., Chung, C., Chang, H., Kao, Y., Wan, F.-J., Huang, S.-H., Chung, R., Wang, R. S., Wang, B., et al. (2021) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s268360 · Cited by 12 · see citing works
Should we rebrand multiple sclerosis a dementia?
Giovannoni, G. (2017) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2017.01.008 · Cited by 12 · see citing works
Prognostication and contemporary management of clinically isolated syndrome
Allen, C. M., Mowry, E. M., Tintoré, M., & Evangelou, N. (2020) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2020-323087 · Cited by 13 · see citing works
Cost-effectiveness lessons from disease-modifying drugs in the treatment of multiple sclerosis
Hoch, J. S. (2004) · Expert Review of Pharmacoeconomics & Outcomes Research · doi:10.1586/14737167.4.5.537 · Cited by 12 · see citing works
Oral versus Intravenous Steroids for Treatment of Relapses in Multiple Sclerosis
Burton, J., O'Connor, P. W., Hohol, M. J., & Beyene, J. (2008) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd006921 · Cited by 12 · see citing works
Pyroptosis the Emerging Link Between Gut Microbiota and Multiple Sclerosis
Fan, H., Shen, R., Yan, J., Bai, Y., Fu, Q., Shi, X., Du, G., & Wang, D. (2024) · Drug Design Development and Therapy · doi:10.2147/dddt.s489454 · Cited by 12 · see citing works
MS, exercise, and the potential for older adults
Horton, S., MacDonald, D. J., & Erickson, K. T. (2010) · European Review of Aging and Physical Activity · doi:10.1007/s11556-010-0062-9 · Cited by 11 · see citing works
- Authors
- Confavreux, C., & Compston, A.
- Affiliations
- Inserm (FR)
- ORCID
- Compston, Alastair
- Venue
- McAlpine's Multiple Sclerosis
- Publisher
- Elsevier
- Published
- 2006
- Volume
- 56
- Issue
- 12
- Pages
- 183-272
- PMC
- PMC7173457
- OpenAlex
- W111819890
- Cited by
- 166
- References
- 0
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 12 · 2023: 1 · 2022: 6 · 2021: 2 · 2020: 5 · 2019: 7 · 2018: 8 · 2017: 7 · 2016: 15 · 2015: 9 · 2014: 11 · 2013: 7 · 2012: 7
- FWCI
- 62.74
- Type
- book chapter
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Elsevier eBooks (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Oncology › Polyomavirus and related diseases
- Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
- Keywords
- multiple sclerosis, clinical course, relapse, disease progression, relapsing-remitting multiple sclerosis, secondary progressive multiple sclerosis, primary progressive multiple sclerosis, disability progression, prognosis, predictive factors, disease heterogeneity
- MeSH terms
- Humans, Multiple Sclerosis, Prognosis, Disease Progression
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