Explaining brain shrinkage

Steenwijk MD, Daams M, Pouwels PJ, Balk LJ, Tewarie PK, Killestein J, Uitdehaag BM, Geurts JJ, Barkhof F, Vrenken H.
What Explains Gray Matter Atrophy in Long-standing Multiple Sclerosis? Radiology. 2014:132708. [Epub ahead of print]

Purpose To identify the measures of focal and diffuse white matter (WM) abnormalities that are related to whole-brain, deep, and cortical gray matter (GM) atrophy in long-standing multiple sclerosis (MS). 

Materials and Methods  Magnetic resonance (MR) imaging was performed at 3 T in 208 patients with MS of long-standing duration (disease duration ≥ 10 years) and in 60 healthy control subjects. Normalized GM volume (NGMV), normalized WM volume (NWMV), normalized deep GM volume (NDGMV), cortical thickness, and normalized lesion volume (NLV) were quantified. Tissue integrity of normal-appearing WM (NAWM) and lesions was measured by using diffusion-tensor MR imaging.  
Results NGMV, NDGMV, and cortical thickness were reduced in people with MS (all P < .001). The final model for NGMV consisted of NWMV, NLV, and patient age and sex (R2 = 0.58, P < .001). NWMV, NLV, and patient sex were the explanatory variables for NDGMV (R2 = 0.75, P < .001). The model for cortical thickness consisted of fractional anisotropy of NAWM, NLV, and patient age and sex (R2 = 0.32, P < .001). The relationship between GM atrophy and WM abnormalities was weaker in primary and secondary progressive disease than in relapsing-remitting disease. Conclusion Whole-brain and deep GM atrophy were particularly explained by WM atrophy and lesion volume, while cortical atrophy was associated with NAWM integrity loss. The weaker relationship between GM atrophy and WM abnormalities in patients with progressive disease might indicate a more independent neurodegenerative disease process in these patients.
This study tries to relate changes in different compartments of the brain and suggests that there are changes in white and Grey matter size compared to non-MSers, Furthermore loss of Grey matter neurons (nerve heads) may be related and explained by white matter (axonal changes) and lesion load (nerve body). So damage to the white matter may precipitate downstream grey matter changes. However, whilst the p values are not bad, the correlation markers are not particularly convincing in terms of a causal relationship, which is often the case with MRI correlations to real pathology. However in progressive MS the results are less clear.Is it a more independent process or that the MRI cannot see the wood for the trees as cell damage is replaced by scarring and  swelling and atrophy is masked.

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