Axonal loss in the pathology of MS: consequences for understanding the progressive phase of the disease
Open accessAbstract
Axonal degeneration has been identified as the major determinant of irreversible neurological disability in patients with multiple sclerosis (MS). Axonal injury begins at disease onset and correlates with the degree of inflammation within lesions, indicating that inflammatory demyelination influences axon pathology during relapsing-remitting MS (RR-MS). This axonal loss remains clinically silent for many years, and irreversible neurological disability develops when a threshold of axonal loss is reached and compensatory CNS resources are exhausted. Experimental support for this view-the axonal hypothesis-is provided by data from various animal models with primary myelin or axonal pathology, and from pathological or magnetic resonance studies on MS patients. In mice with experimental autoimmune encephalomyelitis (EAE), 15-30% of spinal cord axons can be lost before permanent ambulatory impairment occurs. During secondary progressive MS (SP-MS), chronically demyelinated axons may degenerate due to lack of myelin-derived trophic support. In addition, we hypothesize that reduced trophic support from damaged targets or degeneration of efferent fibers may trigger preprogrammed neurodegenerative mechanisms. The concept of MS as an inflammatory neurodegenerative disease has important clinical implications regarding therapeutic approaches, monitoring of patients, and the development of neuroprotective treatment strategies.
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- Authors
- Bjartmar, C., Wujek, J. R., & Trapp, B. D.
- Affiliations
- Cleveland Clinic (US)
- Corresponding author
- Trapp, B.D
- ORCID
- Trapp, B.D
- Venue
- Journal of the Neurological Sciences
- Publisher
- Elsevier BV
- Published
- 2003-02
- Volume
- 206
- Issue
- 2
- Pages
- 165-171
- ISSN
- 0022-510X (ISSN-L)
- OpenAlex
- W2025732446
- Cited by
- 573
- References
- 52
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 13 · 2023: 7 · 2022: 9 · 2021: 13 · 2020: 19 · 2019: 24 · 2018: 22 · 2017: 21 · 2016: 24 · 2015: 18 · 2014: 22 · 2013: 42 · 2012: 15
- FWCI
- 5.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of the Neurological Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Multiple Sclerosis Society
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS35058, NS38667, R01NS035058)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- multiple sclerosis, axonal degeneration, axonal loss, secondary progressive multiple sclerosis, relapsing-remitting multiple sclerosis, demyelination, neurodegeneration, experimental autoimmune encephalomyelitis, neurological deficit, neuroprotection
- MeSH terms
- Animals, Axons, Encephalomyelitis, Autoimmune, Experimental, Humans, Multiple Sclerosis, Nerve Degeneration, Severity of Illness Index, Spinal Cord, Disease Progression, Mice
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