Thursday, 31 December 2015

ResearchSpeak: lesions, relapses and disability outcomes

Do relapses matter more than silent MRI activity? #MSBlog #MSResearch #ResearchSpeak

"This relatively small study of 111 pwMS demonstrates that with intermediate-term follow-up (mean of 8 years) the presence of Gd-enhancing, or active, lesions at baseline correlated with the subsequent number of relapses, but not with disability. Interestingly, only relapses, and not Gd-enhancing lesions, correlated with subsequent disability."


"This study suggests that the detection of Gd-enhancing lesions may not be the best predictor of outcome and that relapses are more important. This raises the issue of whether or not clinically-silent Gd-enhancing lesions are different to lesions associated with relapses. I have always said that if you take a narrow EDSS-view of disability then you are biasing the results in favour of symptomatic lesions, i.e. what the EDSS measures. What about what the EDSS does not measure; for example cognition, mood, vision, etc.? It would therefore be interesting to know if Gd-enhancing lesions correlated with more sensitive measures of hidden disabilities, in particular cognitive impairment."

"Within the paper there was a correlation between MRI T2 & T1 lesion loads, and brain volume and the PASAT (paced auditory serial addition test) a cognitive test. This data indicates that focal MS lesions (T2/white blobs & T1/black holes), which almost all start their life out as Gd-enhancing lesions, is correlated with cognitive impairment. Hence the results of this study are consistent with what we know about the pathology of MS lesions and the lack of correlation between baseline Gd-enhancing lesions and intermediate term disability can almost certainly be explained by methodological issues; a relatively small study (n=111), treatment effects (79% received a DMT, which affects outcomes), use of  the EDSS as the primary disability measure (we know that the EDSS captures cognitive impairments poorly) and finally intermediate- (8 year) rather than long-term (>= 15 years), follow-up."

"Will these results change how we use the baseline MRI in clinical practice? No. High baseline lesion load (T2), the presence of T1 black holes, posterior fossa and spinal cord lesions, brain atrophy and Gd-enhancing lesions at baseline will still be used to indicate a relatively poor prognostic profile."


Epub: Stone et al. Relapse May Serve as a Mediator Variable in Longitudinal Outcomes in Multiple Sclerosis.  J Neuroimaging. 2015 Dec 21. doi: 10.1111/jon.12321.

BACKGROUND/PURPOSE: Contrast-enhancing lesions (CEL) on magnetic resonance imaging (MRI) are believed to represent inflammatory disease activity in multiple sclerosis (MS), but their relationship to subsequent long-term disability and progression is unclear, particularly at longer time periods such as 8-10 years.


METHODS: Between 1989 and 1994, 111 MS patients were seen at the National Institutes of Health for clinical evaluations and 3 monthly contrast-enhanced MRI scans. Of these, 94 patients were re-evaluated a mean of 8 years later (range 6.1-10.5 years) with a single MRI scan and clinical evaluation. CEL number and volume were determined at baseline and follow-up. The number of relapses was ascertained over the follow-up period and annualized relapse rates were calculated. Other MRI parameters, such as T2 hyperintensity volume, T1 volume, and brain parenchymal fraction, were also calculated.

RESULTS: While there was no direct correlation between CEL number or volume at baseline and disability status at follow-up, CEL measures at baseline did correlate with number of relapses observed in the subsequent years, and the number of relapses in turn correlated with subsequent disability as well as transition to progressive MS.

CONCLUSION: While number and volume of CEL at baseline do not directly correlate with disability in the longer term in MS, our data suggest that one route to disability involves relapses as a mediator variable in the causal sequence of MS progression from CEL to disability. Further studies using relapse as a mediator variable in a larger data set may be warranted.

5 comments:

  1. Haven't we known that lesions are a poor measure of activity as theinterferonsare good at inhibiting MRI and less good at stopping relapses

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  2. Sorry Prof G, I'm unable to follow your explanation and interpretation.
    What is your main point? in simple language

    The results and conclusion seem clear enough: Gd-enhancing lesions are co-related with relapses, relapses are co-related with disability

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  3. I know people who have many spinal cord and brain MRI lesions asymptomatic, even if asymptomatic. Then they ask "what does that mean?", I say "I do not know" why I really do not know ...

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  4. I don't understand: A correlates with B, B correlates with C, but A does not correlate with C?

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    Replies
    1. Well I guess it's a matter of degree. I can't read the paper to find any stats but I guess A to B and B to A are weak enough that A to C is so weak that it isn't statistically significant.

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