Combining clinical and magnetic resonance imaging markers enhances prediction of 12-year disability in multiple sclerosis

Uher, Tomáš; Vaněčková, Manuela; Sobíšek, Lukáš; Týblová, Michaela; Seidl, Zdeněk; Krásenský, Jan; Ramasamy, Deepa P.; Zivadinov, Robert; Havrdová, Eva; Kalinčík, Tomáš; Horáková, Dana

doi:10.1177/1352458516642314

Cited by 46 publications

(47 citation statements)

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“…Intracranial volume was calculated as the sum of the total brain parenchymal volume and the total intraventricular and subarachnoidal cerebrospinal fluid volume. Normalized compartment volume was calculated as follows: (BPF) = whole‐brain parenchymal volume/intracranial volume 4, 28, 29…”

Section: Methodsmentioning

confidence: 99%

“…The clinical presentation of multiple sclerosis (MS) includes a wide range of physical, as well as cognitive, signs, and symptoms 1, 2, 3, 4. In particular, cognitive impairment has recently been increasingly recognized as an important determinant of employment status and associated societal costs,5, 6 negatively impacting social functioning, coping, quality of life, and treatment adherence among patients with MS 7…”

Section: Introductionmentioning

confidence: 99%

“…The clinical presentation of multiple sclerosis (MS) includes a wide range of physical, as well as cognitive, signs, and symptoms. [1][2][3][4] In particular, cognitive impairment has recently been increasingly recognized as an important determinant of employment status and associated societal costs, 5,6 negatively impacting social functioning, coping, quality of life, and treatment adherence among patients with MS. 7 In this context, associations between brain imaging measures and cognitive functioning have been observed This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.…”

Section: Introductionmentioning

confidence: 99%

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Cognitive clinico‐radiological paradox in early stages of multiple sclerosis

Uher

Krásenský

Sobíšek

et al. 2017

Ann Clin Transl Neurol

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ObjectiveTo investigate whether the strength of the association between magnetic resonance imaging (MRI) metrics and cognitive outcomes differs between various multiple sclerosis subpopulations.MethodsA total of 1052 patients were included in this large cross‐sectional study. Brain MRI (T1 and T2 lesion volume and brain parenchymal fraction) and neuropsychological assessment (Brief International Cognitive Assessment for Multiple Sclerosis and Paced Auditory Serial Addition Test) were performed.ResultsWeak correlations between cognitive domains and MRI measures were observed in younger patients (age≤30 years; absolute Spearman's rho = 0.05–0.21), with short disease duration (<2 years; rho = 0.01–0.21), low Expanded Disability Status Scale [EDSS] (≤1.5; rho = 0.08–0.18), low T2 lesion volume (lowest quartile; <0.59 mL; rho = 0.01–0.20), and high brain parenchymal fraction (highest quartile; >86.66; rho = 0.01–0.16). Stronger correlations between cognitive domains and MRI measures were observed in older patients (age>50 years; rho = 0.24–0.50), with longer disease duration (>15 years; rho = 0.26–0.53), higher EDSS (≥5.0; rho = 0.23–0.39), greater T2 lesion volume (highest quartile; >5.33 mL; rho = 0.16–0.32), and lower brain parenchymal fraction (lowest quartile; <83.71; rho = 0.13–0.46). The majority of these observed results were confirmed by significant interactions (P ≤ 0.01) using continuous variables.InterpretationThe association between structural brain damage and functional cognitive impairment is substantially weaker in multiple sclerosis patients with a low disease burden. Therefore, disease stage should be taken into consideration when interpreting associations between structural and cognitive measures in clinical trials, research studies, and clinical practice.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cognitive clinico‐radiological paradox in early stages of multiple sclerosis

Uher

Krásenský

Sobíšek

et al. 2017

Ann Clin Transl Neurol

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“…(2) Disease duration versus lesion volume —This may also reflect differences in the disease severity of the cohorts, given that the UCSF patients clearly developed more disability and more of them developed progressive disease on‐study. It is well known that cerebral lesion volume is related in part to disability change in MS . (3) BPF versus 5‐year EDSS score —This may again reflect the different on‐study change in disease severity of the cohorts.…”

Section: Discussionmentioning

confidence: 99%

Brain MRI Predicts Worsening Multiple Sclerosis Disability over 5 Years in the SUMMIT Study

Bakshi

Healy

Dupuy

et al. 2020

Journal of Neuroimaging

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BACKGROUND AND PURPOSE Brain MRI‐derived lesions and atrophy are related to multiple sclerosis (MS) disability. In the Serially Unified Multicenter MS Investigation (SUMMIT), from Brigham and Women's Hospital (BWH) and University of California, San Francisco (UCSF), we assessed whether MRI methodologic heterogeneity may limit the ability to pool multisite data sets to assess 5‐year clinical‐MRI associations. METHODS Patients with relapsing‐remitting (RR) MS (n = 100 from each site) underwent baseline brain MRI and baseline and 5‐year clinical evaluations. Patients were matched on sex (74 women each), age, disease duration, and Expanded Disability Status Scale (EDSS) score. MRI was performed with differences between sites in both acquisition (field strength, voxel size, pulse sequences), and postprocessing pipeline to assess brain parenchymal fraction (BPF) and T2 lesion volume (T2LV). RESULTS The UCSF cohort showed higher correlation than the BWH cohort between T2LV and disease duration. UCSF showed a higher inverse correlation between BPF and age than BWH. UCSF showed a higher inverse correlation than BWH between BPF and 5‐year EDSS score. Both cohorts showed inverse correlations between BPF and T2LV, with no between‐site difference. The pooled but not individual cohort data showed a link between a lower baseline BPF and the subsequent 5‐year worsening in disability in addition to other stronger relationships in the data. CONCLUSIONS MRI acquisition and processing differences may result in some degree of heterogeneity in assessing brain lesion and atrophy measures in patients with MS. Pooling of data across sites is beneficial to correct for potential biases in individual data sets.

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“…A relation between the inflammation and CD133 expression was noted in solid cancers (Karbanová et al, 2014; Rappa et al, 2015). Altogether, CD133 may serve as a surrogate marker for monitoring disease activity – similar to radiological findings – after initiation of immunomodulatory therapy (Harris and Sadiq, 2014; Khan et al, 2016; Uher et al, 2016; Zivadinov et al, 2016). …”

Section: Discussionmentioning

confidence: 99%

CD133-Positive Membrane Particles in Cerebrospinal Fluid of Patients with Inflammatory and Degenerative Neurological Diseases

Bobinger

May

Lücking

et al. 2017

Front. Cell. Neurosci.

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Background: Analysis of cerebrospinal fluid (CSF) is a frequently used diagnostic tool in a variety of neurological diseases. Recent studies suggested that investigating membrane particles enriched with the stem cell marker CD133 may offer new avenues for studying neurological disease. In this study, we evaluated the amount of membrane particle-associated CD133 in human CSF in neuroinflammatory and degenerative diseases.Methods: We compared the amount of membrane particle-associated CD133 in CSF samples collected from 45 patients with normal pressure hydrocephalus, parkinsonism, dementia, and cognitive impairment, chronic inflammatory diseases and 10 healthy adult individuals as controls. After ultracentrifugation of CSF, gel electrophoresis and immunoblotting using anti-CD133 monoclonal antibody 80B258 were performed. Antigen-antibody complexes were detected using chemiluminescence.Results: The amount of membrane particle-associated CD133 was significantly increased in patients with normal pressure hydrocephalus (p < 0.001), parkinsonism (p = 0.011) as well as in patients with chronic inflammatory disease (p = 0.008). Analysis of CSF of patients with dementia and cognitive impairment revealed no significant change compared with healthy individuals. Furthermore, subgroup analysis of patients with chronic inflammatory diseases demonstrated significantly elevated levels in individuals with relapsing-remitting multiple sclerosis (p = 0.023) and secondary progressive multiple sclerosis (SPMS; p = 0.010).Conclusion: Collectively, our study revealed elevated levels of membrane particle-associated CD133 in patients with normal pressure hydrocephalus, parkinsonism as well as relapsing-remitting and SPMS. Membrane glycoprotein CD133 may be of clinical value for several neurological diseases.

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Combining clinical and magnetic resonance imaging markers enhances prediction of 12-year disability in multiple sclerosis

Abstract: The combination of established MRI and clinical indices with MRI volumetric predictors improves the prediction of SDP over long-term follow-up and may provide valuable information for therapeutic decisions.

Cited by 46 publications

References 35 publications

Cognitive clinico‐radiological paradox in early stages of multiple sclerosis

Cognitive clinico‐radiological paradox in early stages of multiple sclerosis

Brain MRI Predicts Worsening Multiple Sclerosis Disability over 5 Years in the SUMMIT Study

CD133-Positive Membrane Particles in Cerebrospinal Fluid of Patients with Inflammatory and Degenerative Neurological Diseases

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