For those who want more background on the importance of loss of gray matter in MS disease progression, here are some recent papers with explanation.
Gray matter atrophy means the loss of gray matter in the brain. It is a "wasting away" or death of brain tissue. This can be seen on MRI. The death of gray matter is directly related to disease progression and disability levels in MS.
What's most important to understand is that gray matter atrophy happens independent of white matter lesions. That's why Jeff has over 20 white matter lesions, but has had a reversal of gray matter atrophy since his CCSVI venoplasty almost 3 years ago. His gray matter is plumper on his last MRI---it actually looks "normal." And that gives us reason to celebrate.
People with MS should ask their neurologists "How does my gray matter look?"
If disease progression and disability are more closely linked to the rate of gray matter atrophy, it will give patients a better understanding of their own disease progression.
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From the Cleveland Clinic in 2008--a 4 year longitudinal study of gray matter atrophy.
To determine gray matter (GM) atrophy rates in multiple sclerosis (MS) patients at all stages of disease, and to identify predictors and clinical correlates of GM atrophy.
METHODS:
MS patients and healthy control subjects were observed over 4 years with standardized magnetic resonance imaging (MRI) and neurological examinations. Whole-brain, GM, and white matter atrophy rates were calculated. Subjects were categorized by disease status and disability progression to determine the clinical significance of atrophy. MRI predictors of atrophy were determined through multiple regression.
RESULTS:
Subjects included 17 healthy control subjects, 7 patients with clinically isolated syndromes, 36 patients with relapsing-remitting MS (RRMS), and 27 patients with secondary progressive MS (SPMS). Expressed as fold increase from control subjects, GM atrophy rate increased with disease stage, from 3.4-fold normal in clinically isolated syndromes patients converting to RRMS to 14-fold normal in SPMS. In contrast, white matter atrophy rates were constant across all MS disease stages at approximately 3-fold normal. GM atrophy correlated with disability. MRI measures of focal and diffuse tissue damage accounted for 62% of the variance in GM atrophy in RRMS, but there were no significant predictors of GM atrophy in SPMS.
INTERPRETATION:
Gray matter tissue damage dominates the pathological process as MS progresses, and underlies neurological disabillity. Imaging correlates of gray matter atrophy indicate that mechanisms differ in RRMS and SPMS. These findings demonstrate the clinical relevance of gray matter atrophy in MS, and underscore the need to understand its causes.
http://www.ncbi.nlm.nih.gov/pubmed/18661561
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Here's a study on gray matter loss in clinically isolated syndrome (CIS), or patients that have had one MS event, but are not officially diagnosed. What the researchers noted was that gray matter atrophy was not relevent and was about the same as normal controls at the very beginnings of the disease, but became significant when patients converted to MS.
Methods: A total of 105 patients presenting with CIS and 42 normal controls (NC) were studied. At baseline, 65/105 patients with CIS met the criterion of dissemination in space of lesions (DIS+). All patients were clinically assessed by means of the Expanded Disability Status Scale every 6 months and underwent MRI evaluation at study entry and then annually for 4 years. Global and regional cortical thickness and deep GM atrophy were assessed using Freesurfer.
Results: No significant reduction in GM atrophy was observed between the entire CIS group and the NC, excepting for the cerebellum cortical volume. When the 59 patients with CIS (46 DIS+, 13 DIS-) who converted to MS during the follow-up were compared to the NC, a significant atrophy in the precentral gyrus, superior frontal gyrus, thalamus, and putamen was observed (p ranging from 0.05 to 0.001). The multivariate analysis identified the atrophy of superior frontal gyrus, thalamus, and cerebellum as independent predictors of conversion to MS. CIS with atrophy of such areas had a double risk of conversion compared to DIS+ (odds ratio 9.6 vs 5.0).
Conclusion: Selective GM atrophy is relevant in patients with CIS who convert early to MS. The inclusion of GM analysis in the MS diagnostic workup is worthy of further investigation.
http://www.neurology.org/content/77/3/257
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In contrast to CIS, early PPMS shows obvious gray matter atrophy.
Here's a study looking at gray matter atrophy in PPMS.
Background: Gray matter (GM) atrophy has been reported in multiple sclerosis (MS). However, little is known about its regional distribution.
Objective: To investigate the regional distribution of GM atrophy in clinically early primary progressive MS (PPMS).
Design and Patients: Thirty-one patients with PPMS within 5 years of symptom onset (mean age, 43.2 years; median Expanded Disability Status Scale score, 4.5) and 15 healthy control subjects (mean age, 43.7 years) were studied. All subjects underwent a 3-dimensional inversion- recovery fast spoiled gradient-recalled echo sequence that was repeated after 1 year in patients only. Magnetic resonance images underwent an optimized voxel-based mor- phometric analysis that segments magnetic resonance data volumes in a normalized space and quantifies tissue at- rophy on a voxel-by-voxel basis. A lesion mask was created for each patient and used in normalization and seg-
Results: At baseline, patients with PPMS displayed bi- lateral thalamic atrophy compared with controls. In addition, a significant association between lesion load and decreased GM volume was found for the thalami. Loss of GM in the putamen, caudate, thalami, and cortical and infratentorial areas was observed in patients after 1 year of follow-up.
Conclusions: Atrophy is most obvious in deep GM in clinically early PPMS. This may reflect increased sensi- tivity of these regions to neurodegeneration. Cortical and infratentorial atrophy developed as the disease evolved.
http://archneur.ama-assn.org/cgi/reprint/63/8/1175.pdf
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Hope this information helps you understand your own disease.
Maybe we can get Marie to chime in with her thoughts on gray matter and info on this from her book....
Joan
