Correlating multiple MRI parameters with clinical features: an attempt to define a new strategy in multiple sclerosis

Tourbah, Ayman; Stievenart, J.L.; Abanou, A.; Fontaine, Bernard; Cabanis, E. A.; Lyon-Caen, O

doi:10.1007/s002340100547

Cited by 15 publications

(10 citation statements)

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“…This analysis shows for the first time that lesion load correlated strongly with disease severity. This is in line with a number of prospective MRI studies [ 7 , 11 , 42 ]. We also show for the first time that relapsing patients have a lower lesion load, and a higher proportion of remyelinated lesions and confirm that they have a lower proportion of mixed active/inactive lesions.…”

Section: Discussionsupporting

confidence: 89%

Progressive multiple sclerosis patients show substantial lesion activity that correlates with clinical disease severity and sex: a retrospective autopsy cohort analysis

et al. 2018

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Multiple sclerosis (MS) is a highly heterogeneous disease with large inter-individual differences in disease course. MS lesion pathology shows considerable heterogeneity in localization, cellular content and degree of demyelination between patients. In this study, we investigated pathological correlates of disease course in MS using the autopsy cohort of the Netherlands Brain Bank (NBB), containing 182 MS brain donors. Using a standardized autopsy procedure including systematic dissection from standard locations, 3188 tissue blocks containing 7562 MS lesions were dissected. Unbiased measurements of lesion load were made using the tissue from standard locations. Lesion demyelinating and innate inflammatory activity were visualized by immunohistochemistry for proteolipid protein and human leukocyte antigen. Lesions were classified into active, mixed active/inactive (also known as chronic active), inactive or remyelinated, while microglia/macrophage morphology was classified as ramified, amoeboid or foamy. The severity score was calculated from the time from first symptoms to EDSS-6. Lesion type prevalence and microglia/macrophage morphology were analyzed in relation to clinical course, disease severity, lesion load and sex, and in relation to each other. This analysis shows for the first time that (1) in progressive MS, with a mean disease duration of 28.6 ± 13.3 years (mean ± SD), there is substantial inflammatory lesion activity at time to death. 57% of all lesions were either active or mixed active/inactive and 78% of all patients had a mixed active/inactive lesion present; (2) patients that had a more severe disease course show a higher proportion of mixed active/inactive lesions (p = 6e−06) and a higher lesion load (p = 2e−04) at the time of death, (3) patients with a progressive disease course show a higher lesion load (p = 0.001), and a lower proportion of remyelinated lesions (p = 0.03) compared to patients with a relapsing disease course, (4) males have a higher incidence of cortical grey matter lesions (p = 0.027) and a higher proportion of mixed active/inactive lesions compared to females across the whole cohort (p = 0.007). We confirm that there is a higher proportion of mixed active/inactive lesions (p = 0.006) in progressive MS compared to relapsing disease. Identification of mixed active/inactive lesions on MRI is necessary to determine whether they can be used as a prognostic tool in living MS patients.Electronic supplementary materialThe online version of this article (10.1007/s00401-018-1818-y) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 89%

Progressive multiple sclerosis patients show substantial lesion activity that correlates with clinical disease severity and sex: a retrospective autopsy cohort analysis

et al. 2018

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“…Assessment of DTI has been intensely studied in MS in order to provide an objective outcome measure of microstructural brain damage for clinical trials (e.g., [8, 11, 41, 44]). The direct link to brain pathology makes DTI particularly compelling for assessing novel measures such as GFV; a similar strategy has recently been applied to provide evidence for a link of oculomotor deficits to changes in DTI [12].…”

Section: Discussionmentioning

confidence: 99%

“…Several MRI techniques have been established to assess disease burden in the brains of subjects with MS; diffusion tensor imaging (DTI) has evolved as a reliable method to detect and monitor microstructural brain tissue damage in MS (for review see [9]). DTI was previously shown to correlate to clinical disability in MS [34, 41, 44] and is considered a promising imaging endpoint for proof of concept studies [11]. A DTI measure of anisotropy frequently applied in neurology and particularly in MS is “fractional anisotropy” (FA) (e.g., [2, 5, 6, 9]), which was predefined as a primary DTI outcome measure in this study.…”

Section: Introductionmentioning

confidence: 99%

Grasping multiple sclerosis: do quantitative motor assessments provide a link between structure and function?

et al. 2012

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Motor disability in MS is commonly assessed by the Expanded Disability Status Scale (EDSS). Categorical rating scales are limited by subjective error and inter-rater variability. Therefore, objective and quantitative measures of motor disability may be useful to supplement the EDSS in the setting of clinical trials. It was previously shown that grip-force-variability (GFV) is increased in MS. We hypothesized that GFV may be an objective measure of motor disability in MS. To investigate whether the increase in GFV in MS is correlated to the clinical disability as assessed by the EDSS and to microstructural changes in the brain as assessed by diffusion tensor imaging, GFV was recorded in a grasping and lifting task in 27 MS patients and 23 controls using a grip-device equipped with a force transducer. The EDSS was assessed by neurologists experienced in MS. Patients underwent diffusion tensor imaging at 3T to assess the fractional anisotropy (FA) of the cerebral white matter as a measure of microstructural brain integrity. GFV was increased in MS and correlated to changes in the FA of white matter in the vicinity of the somatosensory and visual cortex. GFV also correlated with the EDSS. GFV may be a useful objective measure of motor dysfunction in MS linked to disability and structural changes in the brain. Our data suggests that GFV should be further explored as an objective measure of motor dysfunction in MS. It could supplement the EDSS, e.g., in proof of concept studies.

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“…When applied to patients across a broad range of clinical impairments, NAA/Cr ratios correlate moderately with disease duration and disability. 105,114 Patients with RR MS and advanced clinical disability, those with SP MS, and patients with long disease duration generally show the most severe loss of NAA. Some evidence supports a disproportionate increase in Cr in patients with PP MS compared with those with RR MS, 115 possibly reflecting more widespread gliosis in the former.…”

Section: Mr Spectroscopymentioning

confidence: 99%

Imaging of multiple sclerosis: Role in neurotherapeutics

Bakshi¹,

Minagar²,

Jaisani³

et al. 2005

Neurotherapeutics

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Summary:Magnetic resonance imaging (MRI) plays an everexpanding role in the evaluation of multiple sclerosis (MS). This includes its sensitivity for the diagnosis of the disease and its role in identifying patients at high risk for conversion to MS after a first presentation with selected clinically isolated syndromes. In addition, MRI is a key tool in providing primary therapeutic outcome measures for phase I/II trials and secondary outcome measures in phase III trials. The utility of MRI stems from its sensitivity to longitudinal changes including those in overt lesions and, with advanced MRI techniques, in areas affected by diffuse occult disease (the so-called normalappearing brain tissue). However, all current MRI methodology suffers from limited specificity for the underlying histopathology. Conventional MRI techniques, including lesion detection and measurement of atrophy from T1-or T2-weighted images, have been the mainstay for monitoring disease activity in clinical trials, in which the use of gadolinium with T1-weighted images adds additional sensitivity and specificity for areas of acute inflammation. Advanced imaging methods including magnetization transfer, fluid attenuated inversion recovery, diffusion, magnetic resonance spectroscopy, functional MRI, and nuclear imaging techniques have added to our understanding of the pathogenesis of MS and may provide methods to monitor therapies more sensitively in the future. However, these advanced methods are limited by their cost, availability, complexity, and lack of validation. In this article, we review the role of conventional and advanced imaging techniques with an emphasis on neurotherapeutics.

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Correlating multiple MRI parameters with clinical features: an attempt to define a new strategy in multiple sclerosis

Cited by 15 publications

References 0 publications

Progressive multiple sclerosis patients show substantial lesion activity that correlates with clinical disease severity and sex: a retrospective autopsy cohort analysis

Progressive multiple sclerosis patients show substantial lesion activity that correlates with clinical disease severity and sex: a retrospective autopsy cohort analysis

Grasping multiple sclerosis: do quantitative motor assessments provide a link between structure and function?

Imaging of multiple sclerosis: Role in neurotherapeutics

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