A regional consensus recommendation on brain atrophy as an outcome measure in multiple sclerosis

Alroughani, Raed; Deleu, Dirk; Salem, Khalid El; Al-Hashel, Jasem; Alexander, K J; Abdelrazek, Mohamed A; Al-Jishi, Adel; Alkhaboori, Jaber; Azri, Faisal Al; Zadjali, Nahida Al; Hbahbih, Majed; Sokrab, Tag-Eldin O.; Said, Marwa

doi:10.1186/s12883-016-0762-5

Cited by 16 publications

(11 citation statements)

References 56 publications

(77 reference statements)

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“…However, current methods provide sufficient precision for cohort studies, but are not adequate for confidently assessing changes in individual patients. Advancing in imaging and processing techniques will enable neurologists to probe BVL along with the clinical endpoints in RRMS and ultimately improve treatment (34).…”

Section: Discussionmentioning

confidence: 99%

Prospective Assessment of No Evidence of Disease Activity-4 Status in Early Disease Stages of Multiple Sclerosis in Routine Clinical Practice

et al. 2019

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Background: In relapsing-remitting multiple sclerosis, no evidence of disease activity-3 (NEDA-3) is defined as no relapses, no disability progression and no MRI activity. NEDA-4 status is defined as meeting all NEDA-3 criteria plus having an annualized brain volume loss (a-BVL) of ≤0.4%. Prospective real-world studies presenting data on NEDA-4 are scarce. Objective: To determine the proportion of patients failing to meet one or more NEDA-4 criteria and the contribution of each component to this failure. Methods: Forty-eight patients were followed for 12 months. Structural image evaluation, using normalization, of atrophy was used to assess a-BVL. Results: The patients had a mean age of 33.0 years (range 18–57), disease duration of 1.7 years (0.4–4) and Expanded Disability Status Scale score of 1.3 (0–4); 71% were women. All patients were on disease-modifying therapies. During follow-up, 21% of the patients had at least one relapse, 21% had disability progression, 8% had new T2 lesions, and 10% had gadolinium-enhanced lesions. Fifty-eight percent (28/48) achieved NEDA-3 status. a-BVL of >0.4% was observed in 52% (25/48). Only 29% (14/48) achieved NEDA-4 status. Conclusion: a-BVL is a good marker to detect subclinical disease activity. a-BVL is parameter to continue investigating for guiding clinical practice in relapsing-remitting multiple sclerosis.

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Section: Discussionmentioning

confidence: 99%

Prospective Assessment of No Evidence of Disease Activity-4 Status in Early Disease Stages of Multiple Sclerosis in Routine Clinical Practice

et al. 2019

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“…Indeed, in a meta-analysis of data from 13 trials (including >13,500 patients with RRMS), treatment effects on disability progression were correlated with treatment effects both on brain atrophy and on active MRI lesions ( 134 ). At a recent expert panel meeting, a group of MS neurologists and neuro-radiologists reviewed the current literature on brain atrophy and discussed the challenges in assessing and implementing brain atrophy measurements in clinical practice ( 136 ). Brain volume loss was considered a useful longitudinal measure of disease progression and cognitive function in patients with MS ( 136 ).…”

Section: Discussionmentioning

confidence: 99%

“…At a recent expert panel meeting, a group of MS neurologists and neuro-radiologists reviewed the current literature on brain atrophy and discussed the challenges in assessing and implementing brain atrophy measurements in clinical practice ( 136 ). Brain volume loss was considered a useful longitudinal measure of disease progression and cognitive function in patients with MS ( 136 ). However, at present, methodological constraints (e.g., standardization of acquisition, lack of robust post-processing procedures) and physiological confounding factors (e.g., degree of hydration, other medical conditions) mean that brain atrophy measurement, although sufficiently precise for cohort studies, is not suitable for confidently predicting changes in individual patients ( 19 ).…”

Section: Discussionmentioning

confidence: 99%

The Role of T1-Weighted Derived Measures of Neurodegeneration for Assessing Disability Progression in Multiple Sclerosis

2017

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IntroductionMultiple sclerosis (MS) is characterised by the accumulation of permanent neurological disability secondary to irreversible tissue loss (neurodegeneration) in the brain and spinal cord. MRI measures derived from T1-weighted image analysis (i.e., black holes and atrophy) are correlated with pathological measures of irreversible tissue loss. Quantifying the degree of neurodegeneration in vivo using MRI may offer a surrogate marker with which to predict disability progression and the effect of treatment. This review evaluates the literature examining the association between MRI measures of neurodegeneration derived from T1-weighted images and disability in MS patients.MethodsA systematic PubMed search was conducted in January 2017 to identify MRI studies in MS patients investigating the relationship between “black holes” and/or atrophy in the brain and spinal cord, and disability. Results were limited to human studies published in English in the previous 10 years.ResultsA large number of studies have evaluated the association between the previous MRI measures and disability. These vary considerably in terms of study design, duration of follow-up, size, and phenotype of the patient population. Most, although not all, have shown that there is a significant correlation between disability and black holes in the brain, as well as atrophy of the whole brain and grey matter. The results for brain white matter atrophy are less consistently positive, whereas studies evaluating spinal cord atrophy consistently showed a significant correlation with disability. Newer ways of measuring atrophy, thanks to the development of segmentation and voxel-wise methods, have allowed us to assess the involvement of strategic regions of the CNS (e.g., thalamus) and to map the regional distribution of damage. This has resulted in better correlations between MRI measures and disability and in the identification of the critical role played by some CNS structures for MS clinical manifestations.ConclusionThe evaluation of MRI measures of atrophy as predictive markers of disability in MS is a highly active area of research. At present, measurement of atrophy remains within the realm of clinical studies, but its utility in clinical practice has been recognized and barriers to its implementation are starting to be addressed.

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“…In the ALLEGRO clinical trial, after adjusting for baseline active inflammation, laquinimod markedly reduced BVL as compared to the placebo [157]. Positive effects on PBVC are replicated in one active comparator trial [BRAVO] versus im IFN-β-1a [158,159]. At present, the agent is further investigated in RRMS [CONCERTO] and PPMS patients [ARPEGGIO].…”

Section: Emerging Dmts and Their Effect On Pbvcmentioning

confidence: 99%

Brain atrophy in multiple sclerosis: mechanisms, clinical relevance and treatment options

Andravizou

Dardiotis

Artemiadis

et al. 2019

Autoimmun Highlights

114

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Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system characterized by focal or diffuse inflammation, demyelination, axonal loss and neurodegeneration. Brain atrophy can be seen in the earliest stages of MS, progresses faster compared to healthy adults, and is a reliable predictor of future physical and cognitive disability. In addition, it is widely accepted to be a valid, sensitive and reproducible measure of neurodegeneration in MS. Reducing the rate of brain atrophy has only recently been incorporated as a critical endpoint into the clinical trials of new or emerging disease modifying drugs (DMDs) in MS. With the advent of easily accessible neuroimaging softwares along with the accumulating evidence, clinicians may be able to use brain atrophy measures in their everyday clinical practice to monitor disease course and response to DMDs. In this review, we will describe the different mechanisms contributing to brain atrophy, their clinical relevance on disease presentation and course and the effect of current or emergent DMDs on brain atrophy and neuroprotection. which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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A regional consensus recommendation on brain atrophy as an outcome measure in multiple sclerosis

Cited by 16 publications

References 56 publications

Prospective Assessment of No Evidence of Disease Activity-4 Status in Early Disease Stages of Multiple Sclerosis in Routine Clinical Practice

Prospective Assessment of No Evidence of Disease Activity-4 Status in Early Disease Stages of Multiple Sclerosis in Routine Clinical Practice

The Role of T1-Weighted Derived Measures of Neurodegeneration for Assessing Disability Progression in Multiple Sclerosis

Brain atrophy in multiple sclerosis: mechanisms, clinical relevance and treatment options

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