Tysabri doesn't help gray matter atrophy

[SuzE-Q]

At least in the few patients examined.

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PLoS One. 2018 Dec 21;13(12):e0209326. doi: 10.1371/journal.pone.0209326. eCollection 2018.

Gray matter atrophy in multiple sclerosis despite clinical and lesion stability during natalizumab treatment.

Koskimäki F1, Bernard J2, Yong J3, Arndt N4, Carroll T5, Lee SK5, Reder AT4, Javed A4.

BACKGROUND:
Brain volume loss is an important surrogate marker for assessing disability in MS; however, contribution of gray and white matter to the whole brain volume loss needs further examination in the context of specific MS treatment.

OBJECTIVES:
To examine whole and segmented gray, white, thalamic, and corpus callosum volume loss in stable patients receiving natalizumab for 2-5 years.

METHODS:
This was a retrospective study of 20 patients undergoing treatment with natalizumab for 24-68 months. Whole brain volume loss was determined with SIENA. Gray and white matter segmentation was done using FAST. Thalamic and corpus callosum volumes were determined using Freesurfer. T1 relaxation values of chronic hypointense lesions (black holes) were determined using a quantitative, in-house developed method to assess lesion evolution.

RESULTS:
Over a mean of 36.6 months, median percent brain volume change (PBVC) was -2.0% (IQR 0.99-2.99). There was decline in gray (p = 0.001) but not white matter (p = 0.6), and thalamic (p = 0.01) but not corpus callosum volume (p = 0.09). Gray matter loss correlated with PBVC (Spearman's r = 0.64, p = 0.003) but not white matter (Spearman's r = 0.42, p = 0.07).

Age significantly influenced whole brain volume loss (p = 0.010, multivariate regression), but disease duration and baseline T2 lesion volume did not. There was no change in T1 relaxation values of lesions or T2 lesion volume over time. All patients remained clinically stable.

CONCLUSIONS:
These results demonstrate that brain volume loss in MS is primarily driven by gray matter changes and may be independent of clinically effective treatment.

[Sunshine]

I wonder if there was a comparison group of MSers controlled for other factors oFf Tysabri. LIke compare to MSers on no DMTs, vs Tysabri, vs some other DMT, vs Non MSers with similar age , gender, SES, BMI etc?

[agate]

It looks as if this study didn't involve a comparison group. Here's the whole article. I plan to look at it more carefully soon.

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[SuzE-Q]

It looks as if this study didn't involve a comparison group. Here's the whole article. I plan to look at it more carefully soon.

Only registered and activated users can see links., Click Here To Register...

The BARTS MS blog states that gray matter loss for those on Tysabri was greater than normal aging loss:

Monday, 24 December 2018
Natalizumab is unable to stop the shredder
Is the treatment aim of 'maximising the lifelong brain health of every person with MS' realistic?

In this study below pwMS stable on natalizumab (one of our most effective DMTs) are still losing brain volume way and above what you would expect for age. Is this premature ageing or is this the slowly expanding chronically active lesion shredding the brain?

We know that over many years brain volume loss, or brain atrophy, correlates with poor outcome; i.e. cognitive impairment and physical disability. What this study indicates that we clearly need something additional to an anti-inflammatory to treat MS and prevent end-organ damage. What it is telling me is that we are going to need additional add-on treatments to really make a difference for pwMS. What these add-on treatments turn out to be is speculative. At the moment we talk about add-on neuroprotective, remyelinating and neurorestorative therapies when what we may need are antivirals to suppress EBV and HERVs that are driving the slow burn and gradual loss of brain and spinal cord.

It is clear that unless we normalise brain volume loss in pwMS they will not be able to age normally and nor will be able to 'maximise' their brain health.

One interpretation of this data is that the focal inflammatory lesion, and relapses, are not MS, but are simply the body's response to what is really causing the disease. We need to ask the question what is MS and what is driving this accelerated brain volume loss in the absence of focal inflammation?

Natalizumab continues to make me think about MS and continues to challenge the scientific dogma that MS is simply an organ-specific autoimmune disease. MS is clearly not an organ-specific autoimmune disease; it is a whole lot more complex than that.

For more information please read my recent blog post 'explaining why you get worse despite being NEDA'.

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[Lazarus]

The BARTS MS blog states that gray matter loss for those on Tysabri was greater than normal aging loss:



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Oi-vez!!!!!!!!!

[Sunshine]

What’s your understanding of the gray matter as distinct from white matter. Besides color.

If the grey is compromised, but not the white, what do you see clinically or experientially
And, if the white matter is compromised but not grey, what do you see clinically or experienctially
Or what if both are affected?