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Updated: Mar 11, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Age-related small vessel disease: a potential contributor to neurodegeneration in multiple sclerosis
Ruth Geraldes1, Margaret M Esiri1, Gabriele C DeLuca1
1Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, UK.
Abstract:
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system wherein, after an initial phase of transient neurological defects, slow neurological deterioration due to progressive neuronal loss ensues. Age is a major determinant of MS progression onset and disability. Over the past years, several mechanisms have been proposed to explain the key drivers of neurodegeneration and disability accumulation in MS. However, the effect of commonly encountered age-related cerebral vessel disease, namely small vessel disease (SVD), has been largely neglected and constitutes the aim of this review. SVD shares some features with MS, that is, white matter demyelination and brain atrophy, and has been shown to contribute to the neuronal damage seen in vascular cognitive impairment. Several lines of evidence suggest that an interaction between MS and SVD may influence MS-related neurodegeneration. SVD may contribute to hypoperfusion, reduced vascular reactivity and tissue hypoxia, features seen in MS. Venule and endothelium abnormalities have been documented in MS but the role of arterioles and of other neurovascular unit structures, such as the pericyte, has not been explored. Vascular risk factors (VRF) have recently been associated with faster progression in MS, though the mechanisms are unclear since very few studies have addressed the impact of VRF and SVD on MS imaging and pathology outcomes. Therapeutic agents targeting the microvasculature and the neurovascular unit may impact both SVD and MS and may benefit patients with dual pathology.
Insights
Small vessel disease (SVD) is often overlooked in multiple sclerosis (MS) but may drive neurodegeneration. Targeting SVD and the neurovascular unit could benefit MS patients with this dual pathology.
Area of Science:
- Neurology
- Neuroscience
- Vascular Biology
Background:
- Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease characterized by neurological deficits and progressive neurodegeneration.
- Age significantly influences MS onset and disability progression.
- While neurodegeneration drivers in MS are studied, the role of age-related small vessel disease (SVD) remains largely unexplored.
Purpose of the Study:
- To review the impact of small vessel disease (SVD) on neurodegeneration and disability in multiple sclerosis (MS).
- To explore the potential interaction between MS and SVD, including shared pathological features and mechanisms.
- To highlight the underappreciated role of SVD and vascular risk factors (VRF) in MS progression.
Main Methods:
- Literature review synthesizing evidence on SVD, MS, and neurodegeneration.
- Analysis of shared pathological features between MS and SVD, such as white matter demyelination and brain atrophy.
- Examination of the neurovascular unit's role, including arterioles and pericytes, in the context of MS and SVD.
Main Results:
- SVD shares pathological similarities with MS and contributes to neuronal damage in vascular cognitive impairment.
- Evidence suggests SVD exacerbates MS neurodegeneration through hypoperfusion, reduced vascular reactivity, and hypoxia.
- Vascular risk factors (VRF) are linked to faster MS progression, but their impact on MS pathology and imaging outcomes requires further investigation.
Conclusions:
- The interaction between MS and SVD significantly influences neurodegeneration and disability accumulation.
- Further research into SVD's role in MS is crucial, particularly concerning arterioles and the broader neurovascular unit.
- Therapeutic strategies targeting the microvasculature and neurovascular unit may offer benefits for MS patients with co-existing SVD.
