PT  - JOURNAL ARTICLE
AU  - Chenyu Wang
AU  - Michael H. Barnett
AU  - Con Yiannikas
AU  - Joshua Barton
AU  - John Parratt
AU  - Yuyi You
AU  - Stuart L. Graham
AU  - Alexander Klistorner
TI  - Lesion activity and chronic demyelination are the major determinants of brain atrophy in MS
AID  - 10.1212/NXI.0000000000000593
DP  - 2019 Sep 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e593
VI  - 6
IP  - 5
4099  - http://nn.neurology.org/content/6/5/e593.short
4100  - http://nn.neurology.org/content/6/5/e593.full
SO  - Neurol Neuroimmunol Neuroinflamm2019 Sep 01; 6
AB  - Objective To evaluate the combined effect of lesion activity and pathologic processes occurring in both chronically demyelinated lesions and normal-appearing white matter (NAWM) on brain atrophy in MS.Methods Pre- and post-gadolinium T1, fluid attenuation inversion recovery, and diffusion tensor imaging images were acquired from 50 consecutive patients with relapsing-remitting MS (all, but one, on disease-modifying therapy) at baseline and 5 years. Brain atrophy was measured using structural image evaluation, using normalization of atrophy percent brain volume change (PBVC) analysis.Results During follow-up, brain volume diminished by 2.0% ± 1.1%. PBVC was not associated with patient age, disease duration, sex, or type of treatment. PBVC moderately correlated with baseline lesion load (r = −0.38, p = 0.016), but demonstrated strong association with new lesion activity (r = −0.63, p < 0.001). Brain atrophy was also strongly linked to the increase of water diffusion within chronic MS lesions (r = −0.62, p < 0.001). In normal-appearing white matter (NAWM), PBVC demonstrated a significant correlation with both baseline and longitudinal increase of demyelination as measured by radial diffusivity (RD, r = −0.44, p = 0.005 and r = −0.35, p = 0.026, respectively). Linear regression analysis explained 62% of the variance in PBVC. It confirmed the major role of new lesion activity (p = 0.002, standardized beta-coefficient −0.42), whereas change in diffusivity inside chronic lesions and NAWM RD at baseline also contributed significantly (p = 0.04 and 0.02, standardized beta-coefficient −0.31 and −0.29, respectively), increasing predictive power of the model by 55%.Conclusion In addition to new lesion activity, progressive loss of demyelinated axons in chronic lesions and the degree of demyelination in NAWM significantly contribute to accelerated loss of brain tissue in patients with MS receiving immunomodulatory therapy.AD=axial diffusivity; DTI=diffusion tensor imaging; EDSS=Expanded Disability Status Scale; FLAIR=fluid attenuation inversion recovery; FSL=Functional MRI of the Brain Software Library; GAD=gadolinium; MD=mean diffusivity; NAWM=normal-appearing white matter; PBVC=percent brain volume change; RD=radial diffusivity; ROI=region of interest; RRMS=relapsing-remitting MS