AUTHOR=Rothstein Ted L. TITLE=Gray Matter Matters: A Longitudinal Magnetic Resonance Voxel-Based Morphometry Study of Primary Progressive Multiple Sclerosis JOURNAL=Frontiers in Neurology VOLUME=Volume 11 - 2020 YEAR=2020 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.581537 DOI=10.3389/fneur.2020.581537 ISSN=1664-2295 ABSTRACT=Background: Multiple Sclerosis (MS) lesions in white matter (WM) are easily detected with conventional MRI which induce inflammation thereby generating contrast. WM lesions do not consistently explain the extent of clinical disability, cognitive impairment, or the source of an exacerbation. Grey matter (GM) structures including the cerebral cortex and various deep nuclei are known to be affected early in Primary Progressive Multiple Sclerosis (PPMS) and drive disease progression, disability, fatigue, and cognitive dysfunction. However, little is known about how rapidly GM lesions develop and accumulate over time. Objective: The purpose of this study is to analyze the degree and rate of progression in 24 patients with PPMS using voxel based automated volumetric quantitation. Methods: This is a retrospective single-center study which includes a cohort of 24 patients with PPMS scanned utilizing NeuroQuant® 3 dimensional voxel-based morphometry (3D VBM) automated analysis and database and restudied after one year. Comparisons with normative data were acquired for whole brain, forebrain parenchyma, cortical GM, hippocampus, thalamus, superior and inferior lateral ventricles. GM volume changes were correlated with their clinical motor and cognitive scores using Extended Disability Status Scales (EDSS) and Montreal Cognitive Assessments (MoCA). Results: Steep reductions occurred in cerebral cortical GM and deep GM nuclei volumes which correlated with each patient’s clinical and cognitive impairment. The median observed percentile volume losses were statistically significant compared with the 50th percentile for each GM component. Longitudinal assessment showed prominent losses occurring over one year in Cortical GM and hippocampus. Conclusions: Knowledge of the degree and rapidity with which cortical atrophy and deep GM volume loss develops clarifies the source of progressive cognitive and clinical decline in PPMS