Gray Matter Atrophy in Multiple Sclerosis May Occur Independently of Clinically Effective Treatment


Once thought to be a disease only of white matter, the myelin sheath of oligoglia, it is now accepted that multiple sclerosis (MS) affects nerve cells themselves, the gray matter of the brain. Injury to neurons in multiple sclerosis can occur independently from myelin damage and a type of MS in which only gray matter damage is seen was recently identified in neuropathologic studies. 

Damage to both oligoglia and neurons results in brain atrophy that has become an important surrogate marker for assessing efficacy of disease-modifying treatments DMTs in reducing disability for patients with MS. The contributions of gray matter vs white matter loss to brain atrophy, however, is undetermined. 

In a retrospective study published in the journal PLOS One, researchers measured whole brain atrophy as well as the loss of gray or white matter specifically in 20 patients with MS who were being treated with the DMT natalizumab (Tysabri; Biogen, Cambridge, MA). All patients remained clinically stable during the study. Volume loss in the corpus collusum and thalamic regions were also specifically measured. 

Over a mean period of 36.6 months, patients had a decline in gray matter (P = .001), but not white matter (P = .06) and a median percent brain volume change (PBVC) of -2.0% (IQR 0.99–2.99). Brain volume loss occurred in the thalamic regions (P = 0.01) but not the corpus callosum (P = 0.09). Interestingly, the patients disease duration and base line T2 lesion volume did not correlate with PBVC, but the patients age did (P = .010, multivariate regression). 


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