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

View Article: PubMed Central - PubMed

ABSTRACT

Background: Multiple sclerosis (MS) is a chronic autoimmune disease characterized by inflammatory and neurodegenerative processes leading to irreversible neurological impairment. Brain atrophy occurs early in the course of the disease at a rate greater than the general population. Brain volume loss (BVL) is associated with disability progression and cognitive impairment in patients with MS; hence its value as a potential target in monitoring and treating MS is discussed.

Methods: 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. The panel used a voting system to reach a consensus and the votes were counted for the proposed set of questions for cognitive and brain atrophy assessments.

Results: The panel of experts was able to identify recent studies, which demonstrated the correlation between BVL and future worsening of disability and cognition. The current evidence revealed that reduction of BVL could be achieved with different disease-modifying therapies (DMTs). BVL provided a better treatment and monitoring strategy when it is combined to the composite measures of “no evidence of disease activity” (NEDA). The panel recommended a set of cognitive assessment tools and MRI methods and software applications that may help in capturing and measuring the underlying MS pathology with high degree of specificity.

Conclusion: BVL was considered to be a useful measurement to longitudinally assess disease progression and cognitive function in patients with MS. Brain atrophy measurement was recommended to be incorporated into the concept of NEDA. Consequently, a consensus recommendation was reached in anticipation for implementation of the use of cognitive assessment and brain atrophy measurements on a regional level.

No MeSH data available.


Illustration of a longitudinal effect of treatment on brain parenchymal fraction. (Source: Dr. Rovira; data on file)
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Fig1: Illustration of a longitudinal effect of treatment on brain parenchymal fraction. (Source: Dr. Rovira; data on file)

Mentions: The panel discussed incorporating BVL as a key measure and part of the treatment strategy, which focuses on achieving no evidence of disease activity (NEDA). The measures under NEDA-3 were focused on the composite measures of absence of relapses, disability progression (based on expanded disability status scale (EDSS) scores), and MRI activity (new or enlarging of T2 lesion) [30, 31]. As more evidence is accumulating with respect to the importance of brain atrophy during different stages of MS, absence of BVL may be incorporated to the NEDA measures to be a total of four measures (NEDA-4). Incorporating BVL in NEDA-4, allows a more comprehensive and balanced assessment, capturing both focal and diffuse disease activity [55, 56]. In the pooled analysis of the two FREEDOMS studies with fingolimod, patients on fingolimod were 4 times were more likely to achieve NEDA-4 than those who were on placebo at two years [57]. The advisors discussed the following case as an example of a patient who achieved a NEDA-4 during a period of 3 years. A 35-year old female was diagnosed with MS and had a highly active disease (more than 20 active lesions) at baseline. A disease modifying therapy was initiated in 2012. Over the 3-year longitudinal follow-up, there was no evidence of disease activity (absence of relapses, disease progression and MRI new/enlarging lesions). The change in the annualized brain volume change during the observational period was −0.089, which was below the threshold considered in NEDA 4 of −0.4% (Fig. 1).Fig. 1


A regional consensus recommendation on brain atrophy as an outcome measure in multiple sclerosis
Illustration of a longitudinal effect of treatment on brain parenchymal fraction. (Source: Dr. Rovira; data on file)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5121973&req=5

Fig1: Illustration of a longitudinal effect of treatment on brain parenchymal fraction. (Source: Dr. Rovira; data on file)
Mentions: The panel discussed incorporating BVL as a key measure and part of the treatment strategy, which focuses on achieving no evidence of disease activity (NEDA). The measures under NEDA-3 were focused on the composite measures of absence of relapses, disability progression (based on expanded disability status scale (EDSS) scores), and MRI activity (new or enlarging of T2 lesion) [30, 31]. As more evidence is accumulating with respect to the importance of brain atrophy during different stages of MS, absence of BVL may be incorporated to the NEDA measures to be a total of four measures (NEDA-4). Incorporating BVL in NEDA-4, allows a more comprehensive and balanced assessment, capturing both focal and diffuse disease activity [55, 56]. In the pooled analysis of the two FREEDOMS studies with fingolimod, patients on fingolimod were 4 times were more likely to achieve NEDA-4 than those who were on placebo at two years [57]. The advisors discussed the following case as an example of a patient who achieved a NEDA-4 during a period of 3 years. A 35-year old female was diagnosed with MS and had a highly active disease (more than 20 active lesions) at baseline. A disease modifying therapy was initiated in 2012. Over the 3-year longitudinal follow-up, there was no evidence of disease activity (absence of relapses, disease progression and MRI new/enlarging lesions). The change in the annualized brain volume change during the observational period was −0.089, which was below the threshold considered in NEDA 4 of −0.4% (Fig. 1).Fig. 1

View Article: PubMed Central - PubMed

ABSTRACT

Background: Multiple sclerosis (MS) is a chronic autoimmune disease characterized by inflammatory and neurodegenerative processes leading to irreversible neurological impairment. Brain atrophy occurs early in the course of the disease at a rate greater than the general population. Brain volume loss (BVL) is associated with disability progression and cognitive impairment in patients with MS; hence its value as a potential target in monitoring and treating MS is discussed.

Methods: 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. The panel used a voting system to reach a consensus and the votes were counted for the proposed set of questions for cognitive and brain atrophy assessments.

Results: The panel of experts was able to identify recent studies, which demonstrated the correlation between BVL and future worsening of disability and cognition. The current evidence revealed that reduction of BVL could be achieved with different disease-modifying therapies (DMTs). BVL provided a better treatment and monitoring strategy when it is combined to the composite measures of “no evidence of disease activity” (NEDA). The panel recommended a set of cognitive assessment tools and MRI methods and software applications that may help in capturing and measuring the underlying MS pathology with high degree of specificity.

Conclusion: BVL was considered to be a useful measurement to longitudinally assess disease progression and cognitive function in patients with MS. Brain atrophy measurement was recommended to be incorporated into the concept of NEDA. Consequently, a consensus recommendation was reached in anticipation for implementation of the use of cognitive assessment and brain atrophy measurements on a regional level.

No MeSH data available.