Abstract
BackgroundBrain 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.ObjectivesTo examine whole and segmented gray, white, thalamic, and corpus callosum volume loss in stable patients receiving natalizumab for 2–5 years.MethodsThis 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.ResultsOver 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.ConclusionsThese results demonstrate that brain volume loss in MS is primarily driven by gray matter changes and may be independent of clinically effective treatment.
Highlights
Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system (CNS)
The competing interests as declared do not alter our adherence to PLOS ONE policies on sharing data and materials. These results demonstrate that brain volume loss in MS is primarily driven by gray matter changes and may be independent of clinically effective treatment
The mechanisms involved and the time course leading to permanent tissue loss continue to be defined, but focal and diffuse inflammation is an important factor in the disease pathology
Summary
Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system (CNS). It is characterized by demyelination in the white matter and substantially in the gray matter, as well as by axonal transection and neuronal loss.[1,2,3] Loss of tissue in the gray and white matter is associated with cognitive and physical disability. The mechanisms involved and the time course leading to permanent tissue loss continue to be defined, but focal and diffuse inflammation is an important factor in the disease pathology. [4] Current disease modifying treatments (DMTs) for MS target the inflammatory component of the disease with variable effectiveness in curtailing disability. Due to the difficulties of conducting long-term clinical trials, surrogate markers of disease activity, MRI, are essential for assessing disease status over time
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