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Guidelines for the use of magnetic resonance techniques in monitoring the treatment of multiple sclerosis
Abstract
Because of the major difficulties in measuring clinical end points in multiple sclerosis (MS) treatment trials, there has been much enthusiasm for using magnetic resonance imaging (MRI) findings as an alternative outcome. To provide international consensus guidelines for the use of MRI in MS clinical trials, a task force of the US National MS Society was convened. The recommendations of the task force are presented in this review. Given the high sensitivity for detecting pathological activity in relapsing‐remitting and secondary progressive MS, monthly T2‐weighted and gadoliniumenhanced brain MRI is an excellent tool for short‐term exploratory trials of new agents where it serves as the primary end point; in particular, failure to demonstrate a reduction in lesion activity avoids the time, cost, and risks of a larger clinical end point study. However, conventional MRI findings have a limited correlation with disability in established MS. The primary end point of a definitive trial should therefore be clinical, although serial MRI at 6‐ to 12‐month intervals is a useful secondary end point in providing an index of pathological progression. In trials of patients presenting with clinically isolated syndromes suggestive of MS, MRI findings can be used in the entry criteria, and as a secondary outcome measure, but conversion to clinically definite MS should be the primary outcome. The pathological substrates of irreversible disability are demyelination and axonal loss. Putative magnetic resonance markers for these processes include decreased N‐acetylaspartate on proton magnetic resonance spectroscopy, decreased magnetization transfer ratios, hypointensity on T1‐weighted images, and loss of short T2 water fractions, some of which relate more closely to disability than conventional MRI findings. Further technical developments should lead to more accurate quantitation, greater pathological specificity, and stronger clinical correlations.
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“With regard to APOE genotype, our results are in agreement with those of Growdon et al [41, 42] who found that while the prevalence of APOE ∈4 was greater in AD patients than controls, the rate of clinical progression in patients with established AD was not different for ∈4 carriers vs ∈4 non-carriers.”
From Rate of medial temporal lobe atrophy in typical aging and Alzheimer's disease (1998) · cites this paper as [42]
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Metadata
- Authors
- Miller, D. H., Albert, P. S., Barkhof, F., Francis, G., Frank, J. A., Hodgkinson, S., Lublin, F. D., Paty, D. W., Reingold, S. C., & Simon, J.
- Affiliations
- UCL Queen Square Institute of Neurology (GB)
- National Institutes of Health (US)
- Montreal Neurological Institute and Hospital (CA)
- Liverpool Hospital (AU)
- University of British Columbia (CA)
- National Multiple Sclerosis Society (US)
- University of Colorado Health (US)
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 1996-01
- Volume
- 39
- Issue
- 1
- Pages
- 6-16
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2030792741
- Cited by
- 444
- References
- 83
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 2 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 4 · 2016: 3 · 2015: 2 · 2014: 6 · 2013: 5 · 2012: 9
- FWCI
- 56.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Health Sciences › Medicine › Oncology › Polyomavirus and related diseases
- Keywords
- multiple sclerosis, magnetic resonance imaging, treatment monitoring, clinical trial endpoints, relapsing-remitting multiple sclerosis, secondary progressive multiple sclerosis, clinically isolated syndrome, disability progression, demyelination, axonal loss, N-acetylaspartate, magnetization transfer ratio, T2-weighted MRI, gadolinium-enhanced MRI, MRI outcome measures
- MeSH terms
- Clinical Trials as Topic, Persons with Disabilities, Humans, Magnetic Resonance Imaging, Multiple Sclerosis, Magnetic Resonance Spectroscopy, Sensitivity and Specificity, Treatment Outcome, Disease Progression
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