Gray matter atrophy

A board to discuss the newly-released drug Tysabri, (formerly known as Antegren) as a treatment for Multiple Sclerosis
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Petr75
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Gray matter atrophy

Post by Petr75 »

2018 Dec 21
Division of Clinical Neurosciences, Turku University Hospital and University of Turku, Turku, Finland.
Department of Neurology, Oregon Health Science University, Portland, Oregon, United States of America ..
Gray matter atrophy in multiple sclerosis despite clinical and lesion stability during natalizumab treatment.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303064/

Abstract
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.
https://www.ncbi.nlm.nih.gov/pubmed/30576361
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vesta
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Re: Gray matter atrophy

Post by vesta »

Petr75 wrote: Fri Jan 11, 2019 1:08 pm 2018 Dec 21
Division of Clinical Neurosciences, Turku University Hospital and University of Turku, Turku, Finland.
Department of Neurology, Oregon Health Science University, Portland, Oregon, United States of America ..
Gray matter atrophy in multiple sclerosis despite clinical and lesion stability during natalizumab treatment.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303064/

Abstract
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.
https://www.ncbi.nlm.nih.gov/pubmed/30576361
Thanks for posting this excellent article. Besides the drug being in itself dangerous, it doesn't "work" if grey matter atrophy continues, therefore potential handicap. Time to forget the drug approach and consider the CNS fluid circulation pathology in MS.

Best regards, Vesta
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Petr75
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Re: Gray matter atrophy

Post by Petr75 »

2018 Feb 15
Department of Biofunctional Imaging, Preeminent Medical Photonics Education & Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan
Neuroinflammation following disease modifying therapy in multiple sclerosis: A pilot positron emission tomography study.
https://www.ncbi.nlm.nih.gov/pubmed/29406909

Abstract
INTRODUCTION:
Chronic activation of microglia accelerates the neurodegenerative process in multiple sclerosis (MS). Although disease modifying therapy (DMT) is reportedly effective for neuroinflammatory responses in MS, the progression of neuroinflammation after DMT remains unclear.
METHODS:
We evaluated microglial activation in six clinically stable relapsing-remitting MS patients after DMT by quantifying changes in translocator protein (TSPO) density using PET with [11C]DPA713, a selective TSPO tracer for microglial activation. All patients underwent [11C]DPA713 PET scans twice, and the scans were conducted one year apart. The binding potential (BPND) of the tracer was estimated using a simplified reference tissue model.
RESULTS:
[11C]DPA713 BPND measured at 6months after DMT was significantly higher in the MS group than that in the control group. Compared with the first PET measurement, the one-year PET measurement revealed significantly elevated [11C]DPA713 BPND in broader brain regions covering the temporal and parietal cortices after one year of DMT.
CONCLUSIONS:
The current results indicate that microglial activation may proceed in the entire brain of clinically stable MS patients even after receiving DMT.
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kevin4apenny
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Re: Gray matter atrophy

Post by kevin4apenny »

As a Retired senior nurse diagnosed 2001 but with presenting symptoms since age 16 (1975), I have been particularly interested an disturbed by the level of research dedicated to PML as a known side-effect of Tysabri nd the fact that the drug was withdrawn at least TWICE but reinstated purely because of the economic impacts u the pharmaceutical producers of this dangerous substance.
I wold be grateful for any responses to this as more than one friends have been severely affected.

Regards

Kevin Campbell RMN
admin www.vital-now.org organiser 2011 UK CCSVI Conference
email kkevvn@yahoo.com
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Scott1
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Re: Gray matter atrophy

Post by Scott1 »

Hi Kevin,

It's more than one drug that can cause this. As I understand it, the assumption is our T cells control JCV infection. Some MS drugs disable the T cells so JCV can then aggressively replicate in the oligodendrocytes and that stops myelination. It staggers me that the choice of DMD is often left to the patient as a default decision. The testing for JCV infection isn't part of the drug selection process. It doesn't seem that the testing for JCV is a mandatory step. You would think it should be, as MS is not a risk factor for JCV conversion to PML, but, obviously, some MS drugs are.
Regards,
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NHE
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Re: Gray matter atrophy

Post by NHE »

Scott1 wrote: Wed Jul 22, 2020 6:02 pmThe testing for JCV infection isn't part of the drug selection process. It doesn't seem that the testing for JCV is a mandatory step. You would think it should be, as MS is not a risk factor for JCV conversion to PML, but, obviously, some MS drugs are.
The JC virus is fairly common among the general population. You could test negative today, but be JCV positive a week later.

https://www.webmd.com/brain/jc-virus#1

https://www.healthline.com/health/multi ... patients#1
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Petr75
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Re: Gray matter atrophy

Post by Petr75 »

2021 Feb 2
Department of Radiology, Research Imaging Institute , Joe R. and Teresa Lozano Long School of Medicine , R.S.R., B.T., P.T.F.), and Department of Neurology (R.S.R., P.T.F.), The University of Texas Health Scienc ..
Disruption of the Atrophy-based Functional Network in Multiple Sclerosis Is Associated with Clinical Disability: Validation of a Meta-Analytic Model in Resting-State Functional MRI
https://pubmed.ncbi.nlm.nih.gov/33529135/


Abstract

Background In multiple sclerosis (MS), gray matter (GM) atrophy exhibits a specific pattern, which correlates strongly with clinical disability. However, the mechanism of regional specificity in GM atrophy remains largely unknown. Recently, the network degeneration hypothesis (NDH) was quantitatively defined (using coordinate-based meta-analysis) as the atrophy-based functional network (AFN) model, which posits that localized GM atrophy in MS is mediated by functional networks. Purpose To test the NDH in MS in a data-driven manner using the AFN model to direct analyses in an independent test sample. Materials and Methods Model fit testing was conducted with structural equation modeling, which is based on the computation of semipartial correlations. Model verification was performed in coordinate-based data of healthy control participants from the BrainMap database (https://www.brainmap.org). Model validation was conducted in prospectively acquired resting-state functional MRI in participants with relapsing-remitting MS who were recruited between September 2018 and January 2019. Correlation analyses of model fit indices and volumetric measures with Expanded Disability Status Scale (EDSS) scores and disease duration were performed. Results Model verification of healthy control participants included 80 194 coordinates from 9035 experiments. Model verification in healthy control data resulted in excellent model fit (root mean square error of approximation, 0.037; 90% CI: 0.036, 0.039). Twenty participants (mean age, 36 years ± 9 [standard deviation]; 12 women) with relapsing-remitting MS were evaluated. Model validation in resting-state functional MRI in participants with MS resulted in deviation from optimal model fit (root mean square error of approximation, 0.071; 90% CI: 0.070, 0.072), which correlated with EDSS scores (r = 0.68; P = .002). Conclusion The atrophy-based functional network model predicts functional network disruption in multiple sclerosis (MS), thereby supporting the network degeneration hypothesis. On resting-state functional MRI scans, reduced functional network integrity in participants with MS had a strong positive correlation with clinical disability. © RSNA, 2021 Online supplemental material is available for this article.
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